A subset of the diverse COG0523 family of putative metal chaperones is linked to zinc homeostasis in all kingdoms of life.
COG0523 proteins are, like the nickel chaperones of the UreG family, part of the G3E family of GTPases linking them to metallocenter biosynthesis. Even though the first COG0523-encoding gene, cobW, was identified almost 20 years ago, little is known concerning the function of other members belonging to this ubiquitous family. Based on a combination of comparative genomics, literature and phylogenetic analyses and experimental validations, the COG0523 family can be separated into at least fifteen subgroups. The CobW subgroup involved in cobalamin synthesis represents only one small sub-fraction of the family. Another, larger subgroup, is suggested to play a predominant role in the response to zinc limitation based on the presence of the corresponding COG0523-encoding genes downstream from putative Zur binding sites in many bacterial genomes. Zur binding sites in these genomes are also associated with candidate zinc-independent paralogs of zinc-dependent enzymes. Finally, the potential role of COG0523 in zinc homeostasis is not limited to Bacteria. We have predicted a link between COG0523 and regulation by zinc in Archaea and show that two COG0523 genes are induced upon zinc depletion in a eukaryotic reference organism, Chlamydomonas reinhardtii. This work lays the foundation for the pursuit by experimental methods of the specific role of COG0523 members in metal trafficking. Based on phylogeny and comparative genomics, both the metal specificity and the protein target(s) might vary from one COG0523 subgroup to another. Additionally, Zur-dependent expression of COG0523 and putative paralogs of zinc-dependent proteins may represent a mechanism for hierarchal zinc distribution and zinc sparing in the face of inadequate zinc nutrition.


Physical and functional interactions between p53 and cell cycle co-operating transcription factors, E2F1 and DP1.
One way in which wild-type p53 is able to regulate cell cycle progression is thought to be via the induction of its downstream target gene Waf1/CIP1, thus indirectly regulating the transcriptional activity of E2F. The E2F transcription factors are known to be key effectors of the cell cycle. We report here that there is a physical and functional interaction between p53 and two of the components of the E2F transcription factors, E2F1 and DP1. The expression of wild-type p53 can inhibit the transcriptional activity of E2F, and the expression of both E2F1 and DP1 can also downregulate p53-dependent transcription. The transcriptional activity of p53 is known to be inhibited by the direct binding of mdm2, but we demonstrate here that both E2F1 and DP1 can inhibit p53 transcriptional activity independently of mdm2. Detailed studies of protein-protein interactions have provided evidence that E2F1 and its co-operating factor DP1 can complex with p53 both in vitro and in vivo.


Integrated electronic platforms for weight loss.
What can be done to build effective weight loss solutions for the 1.5 billion people with obesity? It is self-evident that no one good solution exists for people who are overweight or obese, otherwise it would have been applied across the people who need it worldwide. There is, therefore, an urgent need for approaches that will afford weight loss; what is more, such approaches need to be scalable. For that reason, it is attractive to consider electronic platforms as an avenue for scalable weight loss solutions. Such platforms often do not require substantial investments but rather the integration of pre-existing off-the-shelf components. In this article we explore the concepts and design challenges for electronic platforms that precipitate weight loss.


Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.
Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor.


The environmental price tag on a ton of mountaintop removal coal.
While several thousand square kilometers of land area have been subject to surface mining in the Central Appalachians, no reliable estimate exists for how much coal is produced per unit landscape disturbance. We provide this estimate using regional satellite-derived mine delineations and historical county-level coal production data for the period 1985-2005, and further relate the aerial extent of mining disturbance to stream impairment and loss of ecosystem carbon sequestration potential. To meet current US coal demands, an area the size of Washington DC would need to be mined every 81 days. A one-year supply of coal would result in ∼2,300 km of stream impairment and a loss of ecosystem carbon sequestration capacity comparable to the global warming potential of >33,000 US homes. For the first time, the environmental impacts of surface coal mining can be directly scaled with coal production rates.


Blind image deconvolution using machine learning for three-dimensional microscopy.
In this work, we propose a novel method for the regularization of blind deconvolution algorithms. The proposed method employs example-based machine learning techniques for modeling the space of point spread functions. During an iterative blind deconvolution process, a prior term attracts the point spread function estimates to the learned point spread function space. We demonstrate the usage of this regularizer within a Bayesian blind deconvolution framework and also integrate into the latter a method for noise reduction, thus creating a complete blind deconvolution method. The application of the proposed algorithm is demonstrated on synthetic and real-world three-dimensional images acquired by a wide-field fluorescence microscope, where the need for blind deconvolution algorithms is indispensable, yielding excellent results.


Performance evaluation of partial differential equation models in electronic speckle pattern interferometry and the delta-mollification phase map method.
The ordinary differential equation (ODE) and partial differential equation (PDE) image- processing methods have been applied to reduce noise and enhance the contrast of electronic speckle pattern interferometry fringe patterns. We evaluate the performance of a few representative PDE denoising models quantitatively with two parameters called image fidelity and speckle index, and then we choose a good denoising model. Combining this denoising model with the ODE enhancement method, we make it possible to perform contrast enhancement and denoising simultaneously. Second, we introduce the delta-mollification method to smooth the unwrapped phase map. Finally, based on PDE image processing, delta mollification and some traditional techniques, an approach of phase extraction from a single fringe pattern is tested for computer-simulated and experimentally obtained fringe patterns. The method works well under a high noise level and limited visibility and can extract accurate phase values.


Arabidopsis MAP3K16 and Other Salt-Inducible MAP3Ks Regulate ABA Response Redundantly.
In the Arabidopsis genome, approximately 80 MAP3Ks (mitogen-activated protein kinase kinase kinases) have been identified. However, only a few of them have been characterized, and the functions of most MAP3Ks are largely unknown. In this paper, we report the function of MAP3K16 and several other MAP3Ks, MAP3K14/15/17/18, whose expression is salt-inducible. We prepared MAP3K16 overexpression (OX) lines and analyzed their phenotypes. The result showed that the transgenic plants were ABA-insensitive during seed germination and cotyledon greening stage but their root growth was ABA-hypersensitive. The OX lines were more susceptible to water-deficit condition at later growth stage in soil. A MAP3K16 knockout (KO) line, on the other hand, exhibited opposite phenotypes. In similar transgenic analyses, we found that MAP3K14/15/17/18 OX and KO lines displayed similar phenotypes to those of MA3K16, suggesting the functional redundancy among them. MAP3K16 possesses in vitro kinase activity, and we carried out two-hybrid analyses to identify MAP3K16 substrates. Our results indicate that MAP3K16 interacts with MKK3 and the negative regulator of ABA response, ABR1, in yeast. Furthermore, MAP3K16 recombinant protein could phosphorylate MKK3 and ABR1, suggesting that they might be MAP3K16 substrates. Collectively, our results demonstrate that MAP3K16 and MAP3K14/15/17/18 are involved in ABA response, playing negative or positive roles depending on developmental stage and that MAP3K16 may function via MKK3 and ABR1.


Extra-abdominal pneumodissection after laparoscopic antireflux surgery.
The presence of pneumoperitoneum during laparoscopic antireflux surgery can lead to the dissection of carbon dioxide into the mediastinum, retroperitoneum, subcutaneous tissues, and neck (pneumodissection). The purpose of this study is to describe the incidence, extent, duration and pathways of pneumodissection during laparoscopic antireflux surgery. Twenty patients who underwent laparoscopic antireflux surgery from August 1998 through May 1999 were studied. Physical examination and chest radiographs were performed in the recovery room and each day postoperatively. Noncontrast computerized tomography (CT) of the neck, chest, and upper abdomen was also performed on postoperative day one. Subcutaneous emphysema and radiologic evidence of pneumodissection occurred commonly and typically resolved within 4 days postoperatively. The incidence of pneumomediastinum (85%) seen on CT scan was similar to that of pneumodissection into the neck (80%). The most common pathway of dissection of gas was through the anterior mediastinum and into the neck through the carotid space. Other findings on CT scan revealed pneumoperitoneum in 70 per cent, pneumoretroperitoneum in 10 per cent, and pneumothorax in 0 per cent. The dissection of gas into the mediastinum, neck, and subcutaneous tissues is very common after laparoscopic antireflux surgery. Subcutaneous emphysema on physical examination and radiographic pneumodissection typically resolves within 3 to 4 days. After this time one should consider the presence of any substantial amount of gas as a potential complication related to the procedure.


Expression profile and chromosomal location of cDNA clones, identified from an enriched adult retina library.
To delineate the profile of genes expressed in the adult human retina and assign chromosomal location of cDNA clones. The end-sequence of random clones from an enriched human retinal cDNA library was analyzed by NCBI database search. Expression profile was established by northern blot analysis, database search, or both. Selected cDNA clones were localized to human chromosomes by somatic cell hybrid analysis, in situ hybridization to metaphase chromosomes, or both. Chromosomal location was also obtained by searching the databases. One hundred and thirty-seven clones were isolated from the subtracted retinal library. Fifty-one clones were identical with 35 known human genes in GenBank, and 24 clones corresponded to 23 uncharacterized human expressed sequenced tags (ESTs), novel genes, or both. The remaining 59 clones were not pursued further because they contained bacterial sequences or repetitive elements. Several clones indicated a restricted pattern of expression with high levels of transcripts in the retina. Chromosomal location of novel retinal ESTs is also reported. This study provides a profile of genes expressed in the adult human retina. One round of subtraction eliminated most constitutively expressed genes and permitted partial normalization of the retinal library. Twenty-three novel genes were identified. The combined information obtained from expression analysis and chromosomal localization of retinal cDNAs should be valuable in identifying candidate genes for diseases involving retinal dysfunction.


Characterization of active R2 retrotransposition in the rDNA locus of Drosophila simulans.
The rRNA gene (rDNA) loci of all arthropod lineages contain non-LTR retrotransposable elements that have evolved to specifically insert into the 28S rRNA genes. Extensive in vitro experiments have been conducted to investigate the mechanism of R2 retrotransposition but little is known of the insertion frequency or cellular factors that might regulate R2 activity. In this article, isofemale lines obtained from a population of Drosophila simulans were surveyed for recent R2 insertions. Within most lines, all individuals showed the same collection of R2 insertions, providing no evidence for recent R2 activity. However, in a few of the isofemale lines, virtually all individuals differed in their R2 insertion profiles. The descendants of individual pairs of flies from these "active lines" rapidly accumulated new insertions. The frequent insertion of new R2 elements was associated with the elimination of old R2 elements from the rDNA locus. The existence of lines in which R2 retrotransposes frequently and lines in which the elements appear dormant suggests that cellular mechanisms that can regulate the activity of R2 exist. Retrotransposition activity was correlated with the number of full-length R2 elements but not with the size of the rDNA locus or the number of uninserted units.


Functional redundancy of type II BMP receptor and type IIB activin receptor in BMP2-induced osteoblast differentiation.
Signaling pathways for bone morphogenetic proteins (BMPs) are important in osteoblast differentiation. Although the precise function of type I BMP receptors in mediating BMP signaling for osteoblast differentiation and bone formation has been characterized previously, the role of type II BMP receptors in osteoblasts is to be well clarified. In this study, we investigated the role of type II BMP receptor (BMPR-II) and type IIB activin receptor (ActR-IIB) in BMP2-induced osteoblast differentiation. While osteoblastic 2T3 cells expressed BMPR-II and ActR-IIB, loss-of-function studies, using dominant negative receptors and siRNAs, showed that BMPR-II and ActR-IIB compensated each other functionally in mediating BMP2 signaling and BMP2-induced osteoblast differentiation. This was evidenced by two findings. First, unless there was loss of function of both type II receptors, isolated disruption of either BMPR-II or ActR-IIB did not remove BMP2 activity. Second, in cells with loss of function of both receptors, restoration of function of either BMPR-II or ActR-IIB by transfection of the wild-type forms, restored BMP2 activity. These findings suggest a functional redundancy between BMPR-II and ActR-IIB in osteoblast differentiation. Results from experiments to test the effects of transforming growth factor β (TGF-β), activin, and fibroblast growth factor (FGF) on osteoblast proliferation and differentiation suggest that inhibition of receptor signaling by double-blockage of BMPR-II and ActR-IIB is BMP-signaling specific. The observed functional redundancy of type II BMP receptors in osteoblasts is novel information about the BMP signaling pathway essential for initiating osteoblast differentiation.


A cyanobacterial gene family coding for single-helix proteins resembling part of the light-harvesting proteins from higher plants.
In the cyanobacterium Synechocystis sp. PCC 6803 five genes were identified with significant sequence similarity to regions of members of the eukaryotic chlorophyll a/b binding gene family (Cab family) and to hliA, a gene coding for a small high-light-induced protein in Synechococcus sp. PCC 7942. Four of these five genes are 174-213 bp in length and code for small proteins predicted to have a single transmembrane helix. The fifth Cab-like gene in Synechocystis sp. PCC 6803 is much longer and codes for a protein of which the N-terminal 80% resemble ferrochelatase but the C-terminal domain has similarity to Cab regions. The small genes were expressed preferentially in the absence of photosystem I, but gene expression was not significantly enhanced at moderately high light intensity. Therefore they were not designated as hli (high-light-induced) as was done for the Synechococcus sp. PCC 7942 homolog. Instead, the genes have been named scp, as the corresponding polypeptides of Synechocystis sp. PCC 6803 are small Cab-like proteins (SCP). The scpA gene, which codes for ferrochelatase with a C-terminal Cab-like extension, was interrupted by the insertion of a kanamycin-resistance cassette between the ferrochelatase and Cab-like gene domains. In the PS I-less background, interruption of scpA was found to lead to increased tolerance to high light intensity and to the requirement of a slightly higher light intensity to drive photosystem II electron transfer, suggestive of decreased light-harvesting efficiency in the absence of the C-terminal extension of ScpA. Immunodetection of ScpC and ScpD indicated that either or both accumulated in PS I-less strains. These proteins were also detected in bands of more than 45 kDa on denaturing gels, raising the possibility that they may occur as stable oligomers. The SCPs represent a new group of cyanobacterial proteins that, in view of their primary structure and response to deletion of photosystem I, are likely to be involved in transient pigment binding.


The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis.
There is growing evidence that implicates a role for Sonic hedgehog (SHH) in morphogenesis of the craniofacial complex. Mutations in human and murine SHH cause midline patterning defects that are manifested in the head as holoprosencephaly and cyclopia. In addition, teratogens such as jervine, which inhibit the response of tissues to SHH, also produce cyclopia. Thus, the loss of SHH signaling during early stages of neural plate patterning has a profound influence of craniofacial morphogenesis. However, the severity of these defects precludes analyses of SHH function during later stages of craniofacial development. We have used an embryonic chick system to study the role of SHH during these later stages of craniofacial development. Using a combination of surgical and molecular experiments, we show here that SHH is essential for morphogenesis of the frontonasal and maxillary processes (FNP and MXPs), which give rise to the mid- and upper face. Transient loss of SHH signaling in the embryonic face inhibits growth of the primordia and results in defects analogous to hypotelorism and cleft lip/palate, characteristics of the mild forms of holoprosencephaly. In contrast, excess SHH leads to a mediolateral widening of the FNP and a widening between the eyes, a condition known as hypertelorism. In severe cases, this widening is accompanied by facial duplications. Collectively, these experiments demonstrate that SHH has multiple and profound effects on the entire spectrum of craniofacial development, and perturbations in SHH signaling are likely to underlie a number of human craniofacial anomalies.


Sexual orientation and psychiatric vulnerability: a twin study of neuroticism and psychoticism.
Recent evidence indicates that homosexuals and bisexuals are, on average, at greater risk for psychiatric problems than heterosexuals. It is assumed with some supporting evidence that prejudice often experienced by nonheterosexuals makes them more vulnerable to psychiatric disorder, but there has been no investigation of alternative explanations. Here we used Eysenck's Neuroticism and Psychoticism scales as markers for psychiatric vulnerability and compared heterosexuals with nonheterosexuals in a community-based sample of identical and nonidentical twins aged between 19 and 52 years (N = 4904). Firstly, we tested whether apparent sexual orientation differences in psychiatric vulnerability simply mirrored sex differences-for our traits, this would predict nonheterosexual males having elevated Neuroticism scores as females do, and nonheterosexual females having elevated Psychoticism scores as males do. Our results contradicted this idea, with nonheterosexual men and women scoring significantly higher on Neuroticism and Psychoticism than their heterosexual counterparts, suggesting an overall elevation of psychiatric risk in nonheterosexuals. Secondly, we used our genetically informative sample to assess the viability of explanations invoking a common cause of both nonheterosexuality and psychiatric vulnerability. We found significant genetic correlation between sexual orientation and both Neuroticism and Psychoticism, but no corresponding environmental correlations, suggesting that if there is a common cause of both nonheterosexuality and psychiatric vulnerability it is likely to have a genetic basis rather than an environmental basis.


An Argument for Adolescent and Young Adult Cancer Registry: One Model.
Over the last several years, there has been increasing awareness around the unique challenges faced by adolescent and young adult (AYA) cancer patients. More cancer centers across the United States are introducing AYA-specific programs to help improve outcomes for these patients. However, given the nature of the United States health care system, there is little ability to track the efficacy of these programs and identify important variables with respect to both interdisciplinary interventions offered and medical and psychosocial outcomes. One program offers an argument as to why tracking these data is important, with a description of the registry they have developed.


Partnership selection and formation: a case study of developing adolescent health community-researcher partnerships in fifteen U.S. communities.
This study describes the partner selection process in 15 U.S. communities developing community-researcher partnerships for the Connect to Protect (C2P): Partnerships for Youth Prevention Interventions, an initiative of the Adolescent Trials Network for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Interventions. Each site generated an epidemiological profile of urban youth in their community, selected a focus population and geographic area of youth at risk for HIV, conducted a series of successive structured interviews, and engaged in a process of relationship-building efforts culminating in a collaborative network of community agencies. Sites chose as their primary target population young women who have sex with men (n = 8 sites), young men who have sex with men (n = 6), and intravenous drug users (n = 1). Of 1162 agencies initially interviewed, 281 of 335 approached (84%) agreed to join the partnership (average 19/site). A diverse array of community agencies were represented in the final collaborative network; specific characteristics included: 93% served the sites' target population, 54% were predominantly youth oriented, 59% were located in the geographical area of focus, and 39% reported provision of HIV/STI (sexually transmitted infection) prevention services. Relationship-building activities, development of collaborative relationships, and lessons learned, including barriers and facilitators to partnership, are also described. Study findings address a major gap in the community partner research literature. Health researchers and policymakers need an effective partner selection framework whereby community-researcher partnerships can develop a solid foundation to address public health concerns.


RAIN: A Bio-Inspired Communication and Data Storage Infrastructure.
We summarize the results and perspectives from a companion article, where we presented and evaluated an alternative architecture for data storage in distributed networks. We name the bio-inspired architecture RAIN, and it offers file storage service that, in contrast with current centralized cloud storage, has privacy by design, is open source, is more secure, is scalable, is more sustainable, has community ownership, is inexpensive, and is potentially faster, more efficient, and more reliable. We propose that a RAIN-style architecture could form the backbone of the Internet of Things that likely will integrate multiple current and future infrastructures ranging from online services and cryptocurrency to parts of government administration.


Probiotics and Disease: A Comprehensive Summary-Part 7, Immune Disorders.
This article series provides a literature review of the disease-specific probiotic strains associated with immune and autoimmune conditions that have been studied in published clinical trials in humans and animals. This is not an exhaustive review. The table design allows for quick access to supportive data and will be helpful as a guide for both researchers and clinicians. The goal of the probiotics and disease series is to provide clinically useful tools. The first article (part 1) focused on mental health and neurological conditions, and the second article (part 2) explored cultured and fermented foods that are commonly available in the United States. The third article (part 3) explored the relationship between bacterial strains and 2 of the most prevalent diseases we have in modern society: cardiometabolic disease and fatigue syndromes. The fourth article (part 4) elucidated the role of the microbiome in infectious diseases, and the fifth article (part 5) examined respiratory conditions of the ears, nose, and throat. The sixth article (part 6) explored the relationship between beneficial microbiota and skin disorders. This seventh article (part 7) reviews the relationship between beneficial microbiota and autoimmune diseases, allergies, asthma, and other immunity-related disorders. Future articles will review the relationship between probiotics and skin disorders, the influence of the microbiome on cancer development and prognosis, and gastrointestinal and genitourinary diseases associated with dysbiosis, followed by an article focused on probiotic supplements. This literature review is specific to disease condition, probiotic classification, and individual strain.


The effect of colchicine on alveolar bone loss in ligature-induced periodontitis.
Colchicine is widely used in the treatment of several inflammatory diseases due to its anti-inflammatory effect, but effects on bone metabolism are unclear. The aim of this study was to evaluate the effects of systemically-administered colchicine on healthy periodontium and experimentally-induced periodontitis. In total, 42 male Wistar rats were included in this study. A non-ligated group constituting the negative control group (Control, C, n = 6) and a ligature-only group forming the positive control group (LO, n = 12) were created separately. Twelve rats were treated with 0.4 mg/kg colchicine and another 12 with 1 mg/kg colchicine. In the colchicine-administered groups, right mandibles constituted the ligated groups (1 mgC-L or 0.4 mgC-L) and left mandibles formed the corresponding non-ligated controls (1mgC or 0.4mgC). Silk ligatures were placed at the gingival margin of the lower first molars. The animals were euthanized at different time-points of healing (11 or 30 days). Alveolar bone loss was clinically measured and TRAP+ osteoclasts, osteoblastic activity, and MMP-1 expression were examined histologically. There was no increase in alveolar bone loss with either colchicine dose in healthy periodontium (p > 0.05) and the highest level of alveolar bone loss, TRAP+ osteoclast number, and MMP-1 expression were measured in the LO group (p < 0.05). The 0.4 mgC-L group showed less alveolar bone loss at 11 days (p < 0.05), but greater loss at 30 days. The 1 mgC-L group showed higher osteoblast number than the other ligated groups (p < 0.05) at both time-points. In summary, colchicine did not increase alveolar bone loss in healthy periodontium and also may tend to reduce periodontitis progression. However, further extensive study is necessary to understand the mechanism of colchicine action on alveolar bone loss in periodontitis.


Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas--possible role of Cannabis inhalation.
Spontaneous regression of pilocytic astrocytoma after incomplete resection is well recognized, especially for cerebellar and optic pathway tumors, and tumors associated with Neurofibromatosis type-1 (NF1). The purpose of this report is to document spontaneous regression of pilocytic astrocytomas of the septum pellucidum and to discuss the possible role of cannabis in promoting regression. We report two children with septum pellucidum/forniceal pilocytic astrocytoma (PA) tumors in the absence of NF-1, who underwent craniotomy and subtotal excision, leaving behind a small residual in each case. During Magnetic Resonance Imaging (MRI) surveillance in the first three years, one case was dormant and the other showed slight increase in size, followed by clear regression of both residual tumors over the following 3-year period. Neither patient received any conventional adjuvant treatment. The tumors regressed over the same period of time that cannabis was consumed via inhalation, raising the possibility that the cannabis played a role in the tumor regression. We advise caution against instituting adjuvant therapy or further aggressive surgery for small residual PAs, especially in eloquent locations, even if there appears to be slight progression, since regression may occur later. Further research may be appropriate to elucidate the increasingly recognized effect of cannabis/cannabinoids on gliomas.


Obesity and associated risk of coronary artery disease among patients of primary health care centers in abha, saudi arabia.
To estimate the magnitude of obesity and its relation to the 10 year probability of developing coronary artery disease (CAD) in patients attending primary health care centers (PHCCs) in Abha, southern Saudi Arabia. Saudi patients aged between 30-70 years who had attended three PHCCs in Abha city over a 6-month period (January to June 1998) and agreed to participate in the study were enrolled. All such patients had their weights and heights measured, body mass index (BMI) was calculated and they were screened for risk factors of CAD and requested to provide a fasting venous sample for lipoprotein analysis. The probability of developing coronary artery disease (PCAD) over the next ten years was calculated for each patient by means of the computer model based on Framingham heart study.2 A total of 858 subjects were studied: 46% males and 54% females. The percentage of obesity was 49% and overweight 35%; Females were dominantly obese while overweight was more prevalent in males. Of the study subjects 11.5% were hypertensive with significantly higher BMI than normotensives (P=<0.001); diabetes mellitus was represented in 29.6% with no significant difference in their BMI from nondiabetics. Smokers were 4.2% and they had a significantly lower BMI than non-smokers. Individuals with high-risk threshold of TC/HDL-c ratio (≥ 5.6% for women and ≥ 6.4% for men) represented 70.48% and had significantly higher BMI than those with low risk threshold. There was no direct relationship between BMI and PCAD10 (r(2)=0.007, p<0.12). (1) Obesity is an epidemic health problem with an expected upward trend in Saudi Arabia similar to that of LISA and Western Europe. (2) The risk factors for CAD were highly prevalent among the PHCC patients and had a strong significant association with obesity; thus weight control should be an integral part of the prevention of CAD at PHCCs level. (3) Although obesity was found to have a significant individual association with CAD risk factors, obesity per se had no significant direct relationship with the probability of CAD at 10 years. This confirms the conclusion reached by NCEP 11 that obesity caused CAD through the associated risk factors.


The relationship of cumulative motor asymmetries to scoliosis in Rett syndrome.
Interrelationships between Rett syndrome scoliosis and symmetric and asymmetric motor pull, ambulation, and advancement of age were investigated in order to provide a treatment rationale for slowing the progression of scoliosis. Questionnaires (N = 262) completed by International Rett Syndrome Association families were analyzed with logistic regression, odds ratio, Kruskal-Wallis one-way, and Fisher's exact test analyses. Rett syndrome scoliosis was found to be significantly related to orthopedic risk factors of asymmetric movements and positions (odds ratio = 4.5, p < .001). The odds ratio for asymmetric upper-body positioning (4.4), nonambulation (3.1), and age advancement (14.1) indicated that each was a significant predictor of scoliosis by logistic regression analysis. Univariate Kruskal-Wallis one-way analysis identified a significant relationship between scoliosis and asymmetric higher shoulder positioning (p < .001) and bodyside movements (p = .03). Hemisyndrome aspects of Rett syndrome were identified as the increased prevalence of symptoms in either right or left bodyside. A significant relationship was found between the prevalence of Rett syndrome scoliosis and orthopedic risk factors. These findings suggest a treatment approach for Rett syndrome scoliosis that focuses on balancing bilateral muscular pull.


Factors influencing postnatal Option B+ participation and breastfeeding duration among HIV-positive women in Lilongwe District, Malawi: A qualitative study.
To ensure the health of mothers and children, prevention of mother-to-child HIV transmission (PMTCT) programs test women for HIV, engage HIV-positive women in care, and promote recommended breastfeeding practices. Under Malawi's Option B+ PMTCT program, ~20% of women are lost-to-follow-up (LTFU) and little is known about their breastfeeding practices. The purpose of this study is to describe facilitators and barriers to Option B+ participation and how participation influences breastfeeding duration. We conducted in-depth interviews with HIV-positive women in Option B+ (n = 32) or LTFU from Option B+ (n = 32). They were recruited from four government clinics in Lilongwe District and had a child aged 0-23 months. Women in Option B+ had better disclosure experiences and more social support than LTFU women. The most common reasons for LTFU were fear of HIV disclosure, anticipated or experienced stigma, and insufficient social support. Other reasons included: non-acceptance of HIV status, antiretroviral therapy (ART) side effects, lack of funds for transport, and negative experiences with clinic staff. Worries about possible transmission, even while on ART, influenced timing of weaning for some women in Option B+. Despite their knowledge of the risk of HIV transmission to the child, most LTFU women continued to breastfeed after stopping ART because they considered breastmilk to be an important source of nutrients for the child. Given that HIV-positive Malawian women LTFU from Option B+ breastfeed in the absence of ART, efforts are needed to use evidence-based strategies to address the barriers to Option B+ participation and avert preventable transmission through breastmilk.


The effects of ankle supports on gait in adults: A randomized cross-over study.
We aimed to compare the effects of different ankle supports used after ankle injury/surgery on temporo-spatial gait characteristics. We conducted a randomized cross-over study including adult participants with no previous lower limb or neurological pathology, who underwent gait analysis on an electronic walkway in three different ankle supports, Tubigrip(®), a stirrup brace and a walker boot. The 18 participants were an average age of 42 (SD 13, range 24-62) years and 14 (88%) were female. Compared to Tubigrip(®), gait in the walker boot was slower (-0.19 m/s, 95%CI -0.23 to -0.16, P < 0.001), step length asymmetry was 10% (95%CI 9-12, P < 0.001) worse, single support time asymmetry was 5% (95%CI 3-7, P < 0.001) worse and participants also adopted a wider step width (4.1 cm, 95%CI 3.7-4.5, P < 0.001). There were no important differences in gait between the Tubigrip(®) and stirrup brace. The findings of this study suggest that there is a limit to the degree of normal walking characteristics in a walker boot in the absence of lower limb impairment. Further research is required to directly compare the effects of these ankle supports in clinical populations.


Influencing public health policy with data-informed mathematical models of infectious diseases: Recent developments and new challenges.
Modern data and computational resources, coupled with algorithmic and theoretical advances to exploit these, allow disease dynamic models to be parameterised with increasing detail and accuracy. While this enhances models' usefulness in prediction and policy, major challenges remain. In particular, lack of identifiability of a model's parameters may limit the usefulness of the model. While lack of parameter identifiability may be resolved through incorporation into an inference procedure of prior knowledge, formulating such knowledge is often difficult. Furthermore, there are practical challenges associated with acquiring data of sufficient quantity and quality. Here, we discuss recent progress on these issues.


Sleep and Circadian Rhythms in Survivors of Acute Respiratory Failure.
Background: Little is known about sleep and circadian rhythms in survivors of acute respiratory failure (ARF) after hospital discharge. Objectives: To examine sleep and rest-activity circadian rhythms in ARF survivors 3 months after hospital discharge, and to compare them with a community-dwelling population. Methods: Sleep diary, actigraphy data, and insomnia symptoms were collected in a pilot study of 14 ARF survivors. Rest-activity circadian rhythms were assessed with wrist actigraphy and sleep diary for 9 days, and were analyzed by cosinor and non-parametric circadian rhythm analysis. Results: All participants had remarkable actigraphic sleep fragmentation, 71.5% had subclinical or clinical insomnia symptoms. Compared to community-dwelling adults, this cohort had less stable rest-activity circadian rhythms (p < 0.001), and weaker circadian strength (p < 0.001). Conclusion: Insomnia and circadian disruption were common in ARF survivors. Sleep improvement and circadian rhythm regularity may be a promising approach to improve quality of life and daytime function after ARF.


Ecstasy intoxication: the toxicological basis for treatment.
Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.


Deficient selenium status of a healthy adult Spanish population.
Selenium is an essential micronutrient for human health, being a cofactor for enzymes with antioxidant activity that protect the organism from oxidative damage. An inadequate intake of this mineral has been associated with the onset and progression of chronic diseases such as hypertension, diabetes, coronary diseases, asthma, and cancer. For this reason, knowledge of the plasma and erythrocyte selenium levels of a population makes a relevant contribution to assessment of its nutritional status. The objective of the present study was to determine the nutritional status of selenium and risk of selenium deficiency in a healthy adult population in Spain by examining food and nutrient intake and analyzing biochemical parameters related to selenium metabolism, including plasma and erythrocyte levels and selenium-dependent glutathione peroxidase (GPx) enzymatic activity. We studied 84 healthy adults (31 males and 53 females) from the province of Granada, determining their plasma and erythrocyte selenium concentrations and the association of these levels with the enzymatic activity of glutathione peroxidase (GPx) and with life style factors. We also gathered data on their food and nutrient intake and the results of biochemical analyses. Correlations were studied among all of these variables. The mean plasma selenium concentration was 76.6 ± 17.3 μg/L (87.3 ± 17.4 μg/L in males, 67.3 ± 10.7 μg/L in females), whereas the mean erythrocyte selenium concentration was 104.6 μg/L (107.9 ± 26.1 μg/L in males and 101.7 ± 21.7 μg/L in females). The nutritional status of selenium was defined by the plasma concentration required to reach maximum GPx activity, establishing 90 μg/L as reference value. According to this criterion, 50% of the men and 53% of the women were selenium deficient. Selenium is subjected to multiple regulation mechanisms. Erythrocyte selenium is a good marker of longer term selenium status, while plasma selenium appears to be a marker of short-term nutritional status. The present findings indicate a positive correlation between plasma selenium concentration and the practice of physical activity. Bioavailability studies are required to establish appropriate reference levels of this mineral for the Spanish population.


Temporal trends in misclassification patterns of measured and self-report based body mass index categories--findings from three population surveys in Ireland.
As the use of self-reported data to classify obesity continues, the temporal change in the accuracy of self-report measurement when compared to clinical measurement remains unclear. The objective of this study was to examine temporal trends in misclassification patterns, as well as sensitivity and specificity, of clinically measured versus self-report based body mass index (BMI) from three national lifestyle surveys over a 10-year period. The Surveys of Lifestyle Attitudes and Nutrition (SLÁN) were interview based cross-sectional survey/measurements involving nationally representative samples in 1998, 2002 and 2007. Data from a subsample of both self-reported and measured height and weight were available from 66 men and 142 women in 1998, 147 men and 184 women in 2002 and 909 men and 1128 women in 2007. Respondents were classified into the BMI categories normal (< 25 kg m⁻²), overweight (25- < 30 kg m⁻²) and obese (≥ 30 kg m⁻²). Underreporting of BMI increased across the three surveys (14%→21%→24%; p = 0.002). Sensitivity scores for the normal category exceeded 94% in all three surveys but decreased for the overweight (75%→68%→66%) and obese categories (80%→64%→53%). Simultaneously, specificity levels remained high. BMI values based on self-reported determinations of height and weight in population samples are underestimating the true prevalence of the obesity epidemic and this underestimation is increasing with time. The decreased sensitivity and consistently high specificity scores in the obese category across time, highlights the limitation of self-report based BMI classifications and the need for simple, readily comprehensible indicators of obesity.


[Care to mastectomized woman: discussing ontic aspects and the ontological dimension in nurses performance at a Cancer Hospital].
This reflection approaches aspects related to the ontic and ontological dimensions that constitute and, therefore, permeate nursing care delivered to the client with breast cancer submitted to mastectomy. This reflexive analysis was developed considering the author's professional experience as a clinical nurse at the Cancer Hospital III and at the National Cancer Institute (INCA) as well as using the theoretical frameworks studied during her master and doctoral courses. Through a comprehensive attitude and using phenomenological interpretation, this study aimed at reflecting about nurse's clinical actions in the routine of an institution, pointing out possibilities for a care based on the existential dimension of the involved persons. Therefore, the author emphasizes nurse's performance with the client that is not only translated in the application of scientific techniques, orientations and information but also considering the perception, understanding and care provided by a human being in his/her singularity.


The epidemiology of erectile dysfunction.
During the last two decades, significant advances have been made in the understanding of male sexual dysfunction. Concomitantly, a marked increase in both clinical and research activity in the field of male erectile dysfunction has led to a better evaluation and more treatment options. The prevalence and incidence are dependent on the definitions used, the diagnostic tolls, and the treatment options. Using standard definitions as suggested by the NIH Consensus Conference and improving our diagnostic and treatment options will have a major impact on the epidemiology of ED. A summary of the risk factors for ED is presented in Table 3. Still more epidemiologic research is essential to further understand the distribution as well as the prevalence of ED in certain ethnic groups, chronic conditions, and as a result of surgery and trauma. These studies will help us improve our diagnostic skills as well as our therapeutic options.


Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes.
Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17, frequently are observed as targets of tumor infiltrating lymphocytes (TIL) originated from HLA-A*0201-expressing patients with melanoma. Furthermore, particular clinical relevance was attributed to gp100/pMel17 based on the impression that the adoptive transfer of gp100-recognizing TIL was associated with clinical responses in a small group of patients. However, the actual frequency of specific T cells for these melanoma differentiation antigens has never been directly enumerated in ex vivo or in vitro expanded TIL cultures. Here, we enumerated melanoma differentiation antigen-specific T-cell precursor frequency in TIL using tetrameric HLA/epitope complexes, functionally characterizing their responsiveness to cognate epitope by cytokine release assay. T-cell precursor frequencies were enumerated in 11 fresh-tumor preparations and 17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100-specific T cells could be detected respectively in 5 and 2 of the 11 fresh preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one exception, melanoma differentiation antigen-specific T-cell precursor frequency in fresh material and TIL ranged between 5,000 to 21,000/10(6) CD8+ T cells. T-cell precursor frequency was not significantly higher in TIL whose administration was associated with clinical response. These data provide direct enumeration of MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of HLA-A*0201.


Efficient quenching of TGA-capped CdTe quantum dot emission by a surface-coordinated europium(III) cyclen complex.
Extremely efficient quenching of the excited state of aqueous CdTe quantum dots (QDs) by photoinduced electron transfer to a europium cyclen complex is facilitated by surface coordination to the thioglycolic acid capping ligand. The quenching dynamics are elucidated using steady-state emission and picosecond transient absorption.


Economic motivation for raising coastal flood defenses in Europe.
Extreme sea levels (ESLs) in Europe could rise by as much as one metre or more by the end of this century due to climate change. This poses significant challenges to safeguard coastal communities. Here we present a comprehensive analysis of economically efficient protection scenarios along Europe's coastlines during the present century. We employ a probabilistic framework that integrates dynamic simulations of all ESL components and flood inundation, impact modelling and a cost-benefit analysis of raising dykes. We find that at least 83% of flood damages in Europe could be avoided by elevating dykes in an economically efficient way along 23.7%-32.1% of Europe's coastline, specifically where high value conurbations exist. The European mean benefit to cost ratio of the investments varies from 8.3 to 14.9 while at country level this ranges between 1.6 and 34.3, with higher efficiencies for a scenario with high-end greenhouse gas emissions and strong socio-economic growth.


Contribution of case reports to brain metastases research: systematic review and analysis of pattern of citation.
Research activity related to different aspects of prevention, prediction, diagnosis and treatment of brain metastases has increased during recent years. One of the major databases (Scopus) contains 942 scientific articles that were published during the 5-year time period 2006-2010. Of these, 195 (21%) reported on single patient cases and 12 (1%) were reports of 2 cases. Little is known about their influence on advancement of the field or scientific merits. Do brain metastases case reports attract attention and provide stimuli for further research or do they go largely unrecognized? Different measures of impact, visibility and quality of published research are available, each with its own pros and cons. For the present evaluation, article citation rate was chosen. The median number of citations overall and stratified by year of publication was 0, except for the year 2006 when it was 2. As compared to other articles, case reports remained more often without citation (p<0.05 except for 2006 data). All case reports with 10 or more citations (n = 6) reported on newly introduced anticancer drugs, which commonly are prescribed to treat extracranial metastases, and the responses observed in single patients with brain metastases. Average annual numbers of citations were also calculated. The articles with most citations per year were the same six case reports mentioned above (the only ones that obtained more than 2.0 citations per year). Citations appeared to gradually increase during the first two years after publication but remained on a generally low or modest level. It cannot be excluded that case reports without citation provide interesting information to some clinicians or researchers. Apparently, case reports describing unexpected therapeutic success gain more attention, at least in terms of citation, than others.


Drug-induced gingival overgrowth: a case with auto-correction of incisor drifting.
Drug-induced gingival overgrowth is an iatrogenic clinical condition, which affects a proportion of patients medicated for conditions such as hypertension, epilepsy and the prevention of organ transplant rejection. Clinical manifestation can vary in severity from minor problems to complete coverage of the standing teeth. Drifting of teeth can also occur, producing further aesthetic and functional problems for the patient. This report documents a case of a renal transplant patient in whom drifting of the upper incisor teeth spontaneously resolved following surgical reduction of the overgrown gingivae. Clinical issues relating to the management of gingival overgrowth are also discussed.


An overview of tests for animal tissues in feeds applied in response to public health concerns regarding bovine spongiform encephalopathy.
Enforcing the ban on meat-and-bone meal in feed for farmed animals, and especially ruminants, is considered an important measure to prevent the spread of bovine spongiform encephalopathy. The authors describe current analytical methods for the detection and identification of animal tissues in feed. In addition, recently approved requirements, such as the ban of intra-species recycling (practice of feeding an animal species with proteins derived from the bodies, or parts of bodies, of the same species) are described. In principle, four different approaches are currently applied, i.e. microscopic analysis, polymerase chain reaction, immunoassay analysis and near infrared spectroscopy or microscopy. The principal performance characteristics of these methods are presented and compared, and their specific advantages and disadvantages described. Special emphasis is also placed on the impact of rendering conditions, particularly high temperatures and on the use of molecular biology techniques.


Aromaticity effects on the profiles of the lowest triplet-state potential-energy surfaces for rotation about the C=C bonds of olefins with five-membered ring substituents: an example of the impact of Baird's rule.
A density functional theory study on olefins with five-membered monocyclic 4n and 4n+2 π-electron substituents (C4H3X; X=CH(+), SiH(+), BH, AlH, CH2, SiH2, O, S, NH, and CH(-)) was performed to assess the connection between the degree of substituent (anti)aromaticity and the profile of the lowest triplet-state (T1) potential-energy surface (PES) for twisting about olefinic C=C bonds. It exploited both Hückel's rule on aromaticity in the closed-shell singlet ground state (S0) and Baird's rule on aromaticity in the lowest ππ* excited triplet state. The compounds CH2=CH(C4H3X) were categorized as set A and set B olefins depending on which carbon atom (C2 or C3) of the C4H3X ring is bonded to the olefin. The degree of substituent (anti)aromaticity goes from strongly S0 -antiaromatic/T1 -aromatic (C5H4 (+)) to strongly S0 -aromatic/T1- antiaromatic (C5H4(-)). Our hypothesis is that the shapes of the T1 PESs, as given by the energy differences between planar and perpendicularly twisted olefin structures in T1 [ΔE(T1)], smoothly follow the changes in substituent (anti)aromaticity. Indeed, correlations between ΔE(T1) and the (anti)aromaticity changes of the C4 H3 X groups, as measured by the zz-tensor component of the nucleus-independent chemical shift ΔNICS(T1;1)zz , are found both for sets A and B separately (linear fits; r(2) =0.949 and 0.851, respectively) and for the two sets combined (linear fit; r(2) =0.851). For sets A and B combined, strong correlations are also found between ΔE(T1) and the degree of S0 (anti)aromaticity as determined by NICS(S0,1)zz (sigmoidal fit; r(2) =0.963), as well as between the T1 energies of the planar olefins and NICS(S0,1)zz (linear fit; r(2) =0.939). Thus, careful tuning of substituent (anti)aromaticity allows for design of small olefins with T1 PESs suitable for adiabatic Z/E photoisomerization.


Association of intraoperative blood pressure instability with adverse outcomes after liver transplantation.
Blood pressure derangements are common in orthotopic liver transplantation (OLT), and are potentially associated with adverse outcomes if they are sustained. While this concept is often believed to be true, few have rigorously demonstrated the validity of this claim, especially in likely vulnerable OLT patients. We retrospectively investigated 827 patients who underwent OLT to determine the magnitude of these hemodynamic associations with adverse outcomes. The median value of the mean arterial pressure (MAP) and the fractional change in the median MAP between subsequent epochs (FCM) were calculated for every 5-minute epoch intraoperatively. Epochs were classified according to prespecified ranges of MAP and fractional changes in MAP (lability) between epochs. Multivariate stepwise logistic regression was used to model associations of risk factors and epochs of intraoperative blood pressure (BP) instability with primary (30-day mortality and/or graft failure) and secondary adverse outcomes. Primary adverse outcomes occurred in 10.9% and 12.2% of patients for 30-day mortality and 30-day graft failure, respectively. Independent hemodynamic predictors for 30-day mortality and graft failure included sustained periods of MAP <50 mmHg and BP lability where the MAP changed >25%. All of these values were statistically significant. Although severe intraoperative hypotension and BP lability during OLT are often observed in current practice as consequences of major surgical manipulations and patient vulnerability, these are likely not benign conditions based on this retrospective analysis. Prospective trials are warranted to investigate the possibility that interventions tailored to avoidance of hypotension and BP lability may improve outcomes.


Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.
Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.


Conductance of fully equilibrated quantum wires.
We study the conductance of a quantum wire in the presence of weak electron-electron scattering. In a sufficiently long wire the scattering leads to full equilibration of the electron distribution function in the frame moving with the electric current. At nonzero temperature this equilibrium distribution differs from the one supplied by the leads. As a result the contact resistance increases, and the quantized conductance of the wire acquires a quadratic in temperature correction. The magnitude of the correction is found by analysis of the conservation laws of the system and does not depend on the details of the interaction mechanism responsible for equilibration.


Robertsonian translocation and their role in pathogenesis of recurrent in vitro fertilization failure.
Chromosomal anomalies have been postulated to be one of the principal genetic factors in reproductive failure. The principal structural anomalies are Robertsonian translocations which occur at a total frequency of rate 1.23 per thousand in newborns. Since most infertile men with Robertsonian translocation are oligospermic, they are good candidates for assisted reproduction like in vitro fertilization and intracytoplasmic sperm injection. However, a large number of such men/couples experience recurrent assisted procreation failure. The aim of the study was to diagnose the genetic basis of recurrent assisted reproductive failure (in vitro fertilization /intracytoplasmic sperm injection) in infertile men. One hundred twenty infertile men with idiopathic infertility who experienced recurrent assisted procreation techniques failure were recruited into this study after giving informed consent and after ethical clearance had been obtained. Semen and cytogenetic analyses were done to assess the semen status and cytogenetic profile of these men. Robertsonian translocations were found in 6 of 120 participants (5%). The men with Robertsonian translocation had recurrent assisted procreation techniques failure (>4 failed attempts; 3 in vitro fertilization and at least 1 unsuccessful intracytoplasmic sperm injection). In comparison, the men with a Yq microdeletion and other chromosomal abnormalities conceived after 1 to 2 in vitro fertilization cycles. These chromosomal anomalies may be the basis of failure of these assisted-reproductive procreation techniques. These results highlight the need for genetic investigations in all infertile men experiencing recurrent assisted procreation techniques failure.


Control of the adaptive response of the heart to stress via the Notch1 receptor pathway.
In the damaged heart, cardiac adaptation relies primarily on cardiomyocyte hypertrophy. The recent discovery of cardiac stem cells in the postnatal heart, however, suggests that these cells could participate in the response to stress via their capacity to regenerate cardiac tissues. Using models of cardiac hypertrophy and failure, we demonstrate that components of the Notch pathway are up-regulated in the hypertrophic heart. The Notch pathway is an evolutionarily conserved cell-to-cell communication system, which is crucial in many developmental processes. Notch also plays key roles in the regenerative capacity of self-renewing organs. In the heart, Notch1 signaling takes place in cardiomyocytes and in mesenchymal cardiac precursors and is activated secondary to stimulated Jagged1 expression on the surface of cardiomyocytes. Using mice lacking Notch1 expression specifically in the heart, we show that the Notch1 pathway controls pathophysiological cardiac remodeling. In the absence of Notch1, cardiac hypertrophy is exacerbated, fibrosis develops, function is altered, and the mortality rate increases. Therefore, in cardiomyocytes, Notch controls maturation, limits the extent of the hypertrophic response, and may thereby contribute to cell survival. In cardiac precursors, Notch prevents cardiogenic differentiation, favors proliferation, and may facilitate the expansion of a transient amplifying cell compartment.


Effect of electromagnetic radiations from mobile phone base stations on general health and salivary function.
Cell phones use electromagnetic, nonionizing radiations in the microwave range, which some believe may be harmful to human health. The present study aimed to determine the effect of electromagnetic radiations (EMRs) on unstimulated/stimulated salivary flow rate and other health-related problems between the general populations residing in proximity to and far away from mobile phone base stations. A total of four mobile base stations were randomly selected from four zones of Jaipur, Rajasthan, India. Twenty individuals who were residing in proximity to the selected mobile phone towers were taken as the case group and the other 20 individuals (control group) who were living nearly 1 km away in the periphery were selected for salivary analysis. Questions related to sleep disturbances were measured using Pittsburgh Sleep Quality Index (PSQI) and other health problems were included in the questionnaire. Chi-square test was used for statistical analysis. It was unveiled that a majority of the subjects who were residing near the mobile base station complained of sleep disturbances, headache, dizziness, irritability, concentration difficulties, and hypertension. A majority of the study subjects had significantly lesser stimulated salivary secretion (P < 0.01) as compared to the control subjects. The effects of prolonged exposure to EMRs from mobile phone base stations on the health and well-being of the general population cannot be ruled out. Further studies are warranted to evaluate the effect of electromagnetic fields (EMFs) on general health and more specifically on oral health.


Neopterin and prognosis in patients with adenocarcinoma of the colon.
Concentrations of neopterin, a sensitive indicator for the activation of cellular immunity, were measured in urine samples of 44 patients with adenocarcinoma of the colon at diagnosis. To judge the relative predictive value of neopterin concentrations, other routine clinical and laboratory variables were concomitantly determined. The patients were then followed up to 10 yr, and the abilities of all variables to predict death from cancer were assessed. Neopterin concentrations were not correlated with either tumor stage or Dukes' stage. In univariate analyses using the product-limit approach, four variables were significant indicators of poor prognosis: presence of distant metastases (P = 0.0001); high Dukes' stage (P = 0.0009); high urinary neopterin concentration (P = 0.0034); and advanced stage (P = 0.030). Presence versus absence of lymph node metastases was not associated with prognosis. Multivariate survival analyses by the proportional hazards technique demonstrated that neopterin provided statistically independent predictive information in addition to either presence versus absence of distant metastases or Dukes' stage. When neopterin and tumor stage were investigated for joint prediction, stage failed to be included in the model. Thus, neopterin concentrations provide valuable and statistically independent prognostic information in patients with adenocarcinoma of the colon.


Ibogaine interferes with motivational and somatic effects of naloxone-precipitated withdrawal from acutely administered morphine.
It has been reported that ibogaine interferes with somatic withdrawal reactions in rats chronically treated with morphine. The present experiments demonstrated that ibogaine also interferes with motivational withdrawal reactions and somatic withdrawal reactions in rats treated with morphine on only two occasions. On each of two conditioning trials, naloxone was administered 24 h following an injection of morphine. Four hours prior to each naloxone administration, rats were injected with either ibogaine or saline. In two experiments, ibogaine interfered with naloxone-precipitated withdrawal. In Experiment 1, ibogaine-treated rats displayed a weaker aversion to the withdrawal-paired chamber, and in Experiment 2, ibogaine-treated rats displayed fewer somatic withdrawal reactions than did saline treated rats.


Predicting functional upstream open reading frames in Saccharomyces cerevisiae.
Some upstream open reading frames (uORFs) regulate gene expression (i.e., they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not yet fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of experimentally verified functional uORFs are needed. Unfortunately, wet-experiments to verify that uORFs are functional are expensive. In this paper, a new computational approach to predicting functional uORFs in the yeast Saccharomyces cerevisiae is presented. Our approach is based on inductive logic programming and makes use of a novel combination of knowledge about biological conservation, Gene Ontology annotations and genes' responses to different conditions. Our method results in a set of simple and informative hypotheses with an estimated sensitivity of 76%. The hypotheses predict 301 further genes to have 398 novel functional uORFs. Three (RPC11, TPK1, and FOL1) of these 301 genes have been hypothesised, following wet-experiments, by a related study to have functional uORFs. A comparison with another related study suggests that eleven of the predicted functional uORFs from genes LDB17, HEM3, CIN8, BCK2, PMC1, FAS1, APP1, ACC1, CKA2, SUR1, and ATH1 are strong candidates for wet-lab experimental studies. Learning based prediction of functional uORFs can be done with a high sensitivity. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help to elucidate the regulatory roles of uORFs.


Development of quality indicators to evaluate the monitoring of SLE patients in routine clinical practice.
The assessment of systemic lupus erythematosus (SLE) patients in routine clinical practice is mainly based on the experience of the treating physician. This carries the risk of unwanted variability. Variability may have an impact on the quality of care offered to SLE patients, thereby affecting outcomes. Recommendations represent systematically developed statements to help practitioners in reducing variability. However, major difficulties arise in the application of recommendations into clinical practice. In this respect, the use of quality indicators may raise the awareness among rheumatologists regarding potential deficiencies in services and improve the quality of health care. The aim of this study was to develop a set of quality indicators (QI) for SLE by translating into QIs the recently developed EULAR Recommendations for monitoring SLE patients in routine clinical practice and observational studies. Eleven QIs have been developed referring to the use of validated activity and damage indices in routine clinical practice, general evaluation of drug toxicity, evaluation of comorbidities, eye evaluation, laboratory assessment, evaluation of the presence of chronic viral infections, documentation of vaccination and of antibody testing at baseline. A disease specific set of quality assessment tools should help physicians deliver high quality of care across populations. Routine updates will be needed.


Adverse moisture events predict seasonal abundance of Lyme disease vector ticks (Ixodes scapularis).
Lyme borreliosis (LB) is the most commonly reported vector-borne disease in north temperate regions worldwide, affecting an estimated 300,000 people annually in the United States alone. The incidence of LB is correlated with human exposure to its vector, the blacklegged tick (Ixodes scapularis). To date, attempts to model tick encounter risk based on environmental parameters have been equivocal. Previous studies have not considered (1) the differences between relative humidity (RH) in leaf litter and at weather stations, (2) the RH threshold that affects nymphal blacklegged tick survival, and (3) the time required below the threshold to induce mortality. We clarify the association between environmental moisture and tick survival by presenting a significant relationship between the total number of tick adverse moisture events (TAMEs - calculated as microclimatic periods below a RH threshold) and tick abundance each year. We used a 14-year continuous statewide tick surveillance database and corresponding weather data from Rhode Island (RI), USA, to assess the effects of TAMEs on nymphal populations of I. scapularis. These TAMEs were defined as extended periods of time (>8 h below 82% RH in leaf litter). We fit a sigmoid curve comparing weather station data to those collected by loggers placed in tick habitats to estimate RH experienced by nymphal ticks, and compiled the number of historical TAMEs during the 14-year record. The total number of TAMEs in June of each year was negatively related to total seasonal nymphal tick densities, suggesting that sub-threshold humidity episodes >8 h in duration naturally lowered nymphal blacklegged tick abundance. Furthermore, TAMEs were positively related to the ratio of tick abundance early in the season when compared to late season, suggesting that lower than average tick abundance for a given year resulted from tick mortality and not from other factors. Our results clarify the mechanism by which environmental moisture affects blacklegged tick populations, and offers the possibility to more accurately predict tick abundance and human LB incidence. We describe a method to forecast LB risk in endemic regions and identify the predictive role of microclimatic moisture conditions on tick encounter risk.


Cellular drug resistance in acute myeloid leukemia: literature review and preliminary analysis of an ongoing collaborative study.
Cellular drug resistance is one of the main causes of the frequent ultimate failure of chemotherapy in childhood acute myeloid leukemia (AML). We here summarize the results of a literature review on in vitro drug resistance in childhood AML, focusing on studies using so-called cell culture assays. We also briefly describe some results of an ongoing collaborative study between the Research Laboratory of Pediatric Oncology in Amsterdam (University Hospital Vrije Universiteit) and the German BFM-AML Group. In general, the literature and our preliminary data on in vitro cellular drug resistance in AML are promising in terms of clinical relevance. Cell biological features and clinical response to chemotherapy are related to in vitro drug resistance. However, a large study including multivariate analysis is required to more firmly establish the clinical value of cellular drug resistance testing in childhood AML, and the collaborative study will therefore be continued. Possible applications of cell culture assays include risk-group stratification, rational improvements of current treatment protocols for subgroups of patients based on specific drug resistance profiles, individualised tailored therapy, the study of cross-resistance patterns between drugs, the study of possibilities to modulate or circumvent drug resistance, the study of drug interactions, selection of patients for clinical phase II studies and drug screening.


Neovascular age-related macular degeneration management in the third year: final results from the TREX-AMD randomised trial.
Prospectively evaluate outcomes in the third year of neovascular age-related macular degeneration (AMD) management using ranibizumab with continued treat and extend (TREX) dosing compared with monthly visits with retreatment upon evidence of exudative disease activity (PRN, pro re nata). Subjects with treatment-naïve neovascular AMD were randomised 1:2 to Monthly or TREX and managed through 2 years. In the third year, subjects randomised to Monthly were managed PRN while subjects randomised to TREX were continued on TREX dosing or transitioned to PRN after achieving an interval of 12 weeks between visits. Sixty subjects enrolled and 46 (77%) completed month 36 (M36). Transition from Monthly to PRN was associated with a decline in best corrected visual acuity (BCVA) (+10.5 letters (month 24) to +5.4 (M36, p=0.09)); three (15%) subjects required no dosing during year 3, and 47% (114/243) of possible PRN injections were delivered, yielding a mean of 6.1 injections during year 3. Among the 9 (23%) TREX subjects transitioned to PRN, the need for ongoing anti-vascular endothelial growth factor retreatments was small, with 4 (4%) intravitreal injections being delivered among 106 PRN visits; this subgroup displayed an inferior BCVA trajectory compared with the remainder of subjects. Outcomes among subjects continued on TREX were more favourable, with a mean gain of +5.0 letters at M36. Upon transition to PRN, subjects randomised to monthly dosing experienced a decline in BCVA. Among subjects initially randomised to TREX who transitioned to PRN after achieving a 12-week interval between visits, the overall need for additional treatment was low. NCT01748292, Results.


Practices of rural Egyptian birth attendants during the antenatal, intrapartum and early neonatal periods.
Neonatal deaths account for almost two-thirds of infant mortality worldwide; most deaths are preventable. Two-thirds of neonatal deaths occur during the first week of life, usually at home. While previous Egyptian studies have identified provider practices contributing to maternal mortality, none has focused on neonatal care. A survey of reported practices of birth attendants was administered. Chi-square tests were used for measuring the statistical significance of inter-regional differences. In total, 217 recently-delivered mothers in rural areas of three governorates were interviewed about antenatal, intrapartum and postnatal care they received. This study identified antenatal advice of birth attendants to mothers about neonatal care and routine intrapartum and postpartum practices. While mothers usually received antenatal care from physicians, traditional birth attendants (dayas) conducted most deliveries. Advice was rare, except for breastfeeding. Routine practices included hand-washing by attendants, sterile cord-cutting, prompt wrapping of newborns, and postnatal home visits. Suboptimal practices included lack of disinfection of delivery instruments, unhygienic cord care, lack of weighing of newborns, and lack of administration of eye prophylaxis or vitamin K. One-third of complicated deliveries occurred at home, commonly attended by relatives, and the umbilical cord was frequently pulled to hasten delivery of the placenta. In facilities, mothers reported frequent use of forceps, and asphyxiated neonates were often hung upside-down during resuscitation. Consequently, high rates of birth injuries were reported. Priority areas for behaviour change and future research to improve neonatal health outcomes were identified, specific to type of provider (physician, nurse, or daya) and regional variations in practices.


Does Whole-Body Vibration Improve the Functional Exercise Capacity of Subjects With COPD? A Meta-Analysis.
Whole-body vibration (WBV) is considered a type of physical activity based on the assumption that it results in an increase in muscle strength and performance and, therefore, may be a promising way to exercise patients with COPD. A comprehensive database search (PubMed/MEDLINE, LILACS, CINAHL, Web of Science, Scopus, and COCHRANE Library) for randomized trials, including original articles, that compared WBV groups versus control groups was conducted and studies were selected for comparison. The effect of WBV treatment was compared for minimum clinically important differences. The statistical heterogeneity among the studies was assessed using the I2 statistic; the results are expressed as percentages. Inconsistencies of up to 25% were considered low, those between 50 and 75% were considerate moderate, and those > 75% were considered high. Risk of bias was classified based on the Cochrane Collaboration tool, the meta-analysis was conducted using RevMan 5.3 software, and the level of evidence was assessed using the GRADE system. The primary outcome was functional exercise capacity. Secondary outcomes were quality of life, performance in activities of daily living, muscle strength of the lower limbs, and possible adverse effects assessed clinically or by subject reports. We included 4 articles involving 185 subjects for analysis. All subjects in the groups undergoing WBV showed improvement in distance walked in the 6-min walk test compared with the control group (57.85 m, 95% CI 16.36-99.33 m). Regarding the secondary end points, just one article reported improved quality of life and activities of daily living. The only article that assessed muscle strength found no difference between the groups. The quality of evidence for functional exercise capacity outcome was considered moderate. WBV seems to benefit subjects with COPD by improving their functional exercise capacity, without producing adverse effects. The quality of evidence is moderate, but the degree of recommendation is strong. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero, 2015:CRD42015027659.).


Activation of nicotinic acetylcholine receptors enhances a slow calcium-dependent potassium conductance and reduces the firing of stratum oriens interneurons.
A large variety of distinct locally connected GABAergic cells are present in the hippocampus. By releasing GABA into principal cells and interneurons, they exert a powerful control on neuronal excitability and are responsible for network oscillations crucial for information processing in the brain. Here, whole-cell patch clamp recordings in current and voltage clamp mode were used to study the functional role of nicotinic acetylcholine receptors (nAChRs) on the firing properties of stratum oriens interneurons in hippocampal slices from transgenic mice expressing enhanced green fluorescent protein in a subpopulation of GABAergic cells containing somatostatin (GIN mice). Unexpectedly, activation of nAChRs by nicotine or endogenously released acetylcholine strongly enhanced spike frequency adaptation. This effect was blocked by apamin, suggesting the involvement of small calcium-dependent potassium channels (SK channels). Nicotine-induced reduction in firing frequency was dependent on intracellular calcium rise through calcium-permeable nAChRs and voltage-dependent calcium channels activated by the depolarizing action of nicotine. Calcium imaging experiments directly showed that nicotine effects on firing rate were correlated with large increases in intracellular calcium. Furthermore, blocking ryanodine receptors with ryanodine or sarcoplasmic-endoplasmic reticulum calcium ATPase with thapsygargin or cyclopiazonic acid fully prevented the effects of nicotine, suggesting that mobilization of calcium from the internal stores contributed to the observed effects. By regulating cell firing, cholinergic signalling through nAChRs would be instrumental for fine-tuning the output of stratum oriens interneurons and correlated activity at the network level.


Partial neurorescue effects of DHA following a 6-OHDA lesion of the mouse dopaminergic system.
Pre-clinical data collected in mouse models of Parkinson's disease (PD) support the neuroprotective potential of omega-3 polyunsaturated fatty acids (n-3 PUFA)-enriched diet on the dopaminergic (DAergic) system. In this study, we investigated the effects of an n-3 PUFA-rich diet using a neurorescue/neurorestorative paradigm. C57BL/6 adult mice were submitted to a striatal stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA) to induce striatal DAergic denervation and subsequent nigral DAergic cell loss. Three weeks post-lesion, mice received either a docosahexaenoic acid (DHA)-enriched or a control diet for a period of 6 weeks. HPLC analyses revealed a 111% post-lesion increase in striatal dopamine levels in the DHA-fed animals compared to controls (ctrl, P<0.05), although no improvement in the motor behavior was observed. DHA treatment led to a 89% rise in tyrosine-hydroxylase (TH)-immunoreactive terminals within the striatum (P<0.05) in lesioned animals. Despite the fact that DHA did not change the number of TH+ neurons in the substantia nigra pars compacta (SNpc), morphological analyses revealed an increased in perimeters (+7%) and areas (+21%) of DAergic cell bodies in treated animals. Collectively, our results suggest that DHA induces a partial neurorescue/neurorestoration of the DAergic system and support further studies to investigate the potential of a diet-based intervention, or at least the combination of such approach, to current treatments in PD.


An Investigative Approach to Treatment Modalities for Squamous Cell Carcinoma of Skin.
Squamous cell carcinoma of skin has become an important matter of discussion worldwide due to high number of deaths. Treatment of such cancer involves use of drugs (chemotherapy) along with surgery or radiation therapy. The combination chemotherapy is preferred over single treatment modality may be due to synergistic effect of targeting agent resulting in reduced drug dose, reduced cytotoxic effect and improved efficacy and survival rate. The objective of this work is to provide insight into the squamous cell carcinoma of skin; the various approaches and challenges adapted to surmount the cancer malignancies. Research evidence shows that nanoparticle based therapeutic delivery to squamous cell carcinoma is equanimous to lead therapeutic approaches for intervention of cancer growth. Active chemotherapeutic approach is one of the leading therapies to such cancer cells due specific selectivity towards the EGFR-receptors over-expressed in tumor cells. Review of numerous research publications revealed innate toxicity of chemotherapeutic agents, and substantiated active receptor mediated drug targeting for therapeutic regime. These actively functionalized nanoparticles have been delivered to the targeted cells with higher selectivity, minimal toxicity and better retention in the cell. Numerous approaches and strategies have been designed till date for successful delivery of drug to cancer cells. The techniques have shown tremendous improvement in getting normalcy of carcinomas but a few have been marketed so far. Indeed, receptor based drug targeting approach through molecular signal transduction pathways involved in skin cancer development will provide insight into squamous carcinoma. Despite of these, other such challenges in drug delivery to squamous cell carcinoma need further clarification.


Purple sweet potato anthocyanin exerts antitumor effect in bladder cancer.
Bladder cancer (BC) is the most common malignant disease. The developing of economically sustainable and available agents for the treatment of BC is required. Purple sweet potato anthocyanin (PSPA) has been shown to have antitumor abilities. The present study aimed to evaluate the potential role of PSPA in BC treatment. CCK-8 assay was used to assess the viability of BC cells. Flow cytometry assays were performed to evaluate the mitochondrial membrane potential (MMP), cell apoptosis and cell-cycle distribution. Real-time PCR (RT-PCR) and western blot analysis were performed to determine the expression of the target genes. The results of this study revealed that PSPA reduced the viability of BC in a dose-dependent manner. The MMP collapse was aggravated by the PSPA treatment. The apoptosis rate was higher in the PSPA groups than that in the control group. The expression of the pro-apoptosis genes, including cleaved caspase-3, Fas, Fasl, Bcl-2-associated X proteins (Bax) and anti-apoptotic gene (Bcl-2) was induced and decreased by PSPA, respectively. The cell-cycle progression was suppressed by the presence of PSPA. The activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt (PI3K/Akt) signaling pathway was suppressed by PSPA treatment during BC treatment. The PI3K/Akt signaling was closely related to the antitumor effect of PSPA in BC. The present study provided evidence regarding the treatment of BC and enhanced the understanding of the potential role that PSPA plays in cancer prevention.


Measurement-induced dynamics and stabilization of spinor-condensate domain walls.
Weakly measuring many-body systems and allowing for feedback in real time can simultaneously create and measure new phenomena in quantum systems. We theoretically study the dynamics of a continuously measured two-component Bose-Einstein condensate (BEC) potentially containing a domain wall and focus on the tradeoff between usable information obtained from measurement and quantum backaction. Each weakly measured system yields a measurement record from which we extract real-time dynamics of the domain wall. We show that quantum backaction due to measurement causes two primary effects: domain-wall diffusion and overall heating. The system dynamics and signal-to-noise ratio depend on the choice of measurement observable. We propose a feedback protocol to dynamically create a stable domain wall in the regime where domain walls are unstable, giving a prototype example of Hamiltonian engineering using measurement and feedback.


Measurement of average atmospheric temperature using a CO(2) laser radar.
A single-ended CO(2) lidar system has been used to measure the average temperature over a path between the lidar and the foothills located 5 km away. The CO(2) lidar was used to measure the ratio of transmission of the P(38) to the P(20) lines in the 10-microm band of CO(2). This ratio of transmission is directly related to temperature. Good correlation was obtained between the lidar-measured temperature and the thermometermeasured values.


Spatiotemporal information during unsupervised learning enhances viewpoint invariant object recognition.
Recognizing objects is difficult because it requires both linking views of an object that can be different and distinguishing objects with similar appearance. Interestingly, people can learn to recognize objects across views in an unsupervised way, without feedback, just from the natural viewing statistics. However, there is intense debate regarding what information during unsupervised learning is used to link among object views. Specifically, researchers argue whether temporal proximity, motion, or spatiotemporal continuity among object views during unsupervised learning is beneficial. Here, we untangled the role of each of these factors in unsupervised learning of novel three-dimensional (3-D) objects. We found that after unsupervised training with 24 object views spanning a 180° view space, participants showed significant improvement in their ability to recognize 3-D objects across rotation. Surprisingly, there was no advantage to unsupervised learning with spatiotemporal continuity or motion information than training with temporal proximity. However, we discovered that when participants were trained with just a third of the views spanning the same view space, unsupervised learning via spatiotemporal continuity yielded significantly better recognition performance on novel views than learning via temporal proximity. These results suggest that while it is possible to obtain view-invariant recognition just from observing many views of an object presented in temporal proximity, spatiotemporal information enhances performance by producing representations with broader view tuning than learning via temporal association. Our findings have important implications for theories of object recognition and for the development of computational algorithms that learn from examples.


Whole cell biosynthesis of a functional oligosaccharide, 2'-fucosyllactose, using engineered Escherichia coli.
2'-Fucosyllactose (2-FL) is a functional oligosaccharide present in human milk which protects against the infection of enteric pathogens. Because 2-FL can be synthesized through the enzymatic fucosylation of lactose with guanosine 5'-diphosphate (GDP)-l-fucose by α-1,2-fucosyltransferase (FucT2), an 2-FL producing Escherichia coli can be constructed through overexpressing genes coding for endogenous GDP- l-fucose biosynthetic enzymes and heterologous fucosyltransferase. The gene for FucT2 from Helicobacter pylori was introduced to the GDP-l-fucose producing recombinant E. coli BL21 star(DE3) strain. However, only small amount of 2-FL was produced in a batch fermentation because the E. coli BL21star(DE3) strain assimilated lactose instead of converting to 2-FL. As an alternative host, the E. coli JM109(DE3) strain which is incapable of assimilating lactose was chosen as a 2-FL producer. Whole cell biosynthesis of 2-FL from lactose was investigated in a series of batch fermentations using various concentrations of lactose. The results of batch fermentations showed that lactose was slowly assimilated by the engineered E. coli JM109(DE3) strain and 2-FL was synthesized without supplementation of another auxiliary sugar for cell growth. A maximum 2-FL concentration of 1.23 g/l was obtained from a batch fermentation with 14.5 g/l lactose. The experimentally obtained yield (g 2-FL/g lactose) corresponded to 20% of the theoretical maximum yield estimated by the elementary flux mode (EFM) analysis. The experimental 2-FL yield in this study corresponded to about 20% of the theoretical maximum yield, which suggests further modifications via metabolic engineering of a host strain or optimization of fermentation processes might be carried out for improving 2-FL yield. Improvement of microbial production of 2-FL from lactose by engineered E. coli would increase the feasibility of utilizing 2-FL as a prebiotic in various foods.


A Biophysical and Computational Study of Concanavalin A Immobilized Zinc Oxide Nanoparticles.
Con A, a lectin extract from jackbean Canavalia ensiformis is known for its agglutination activity. ZnO nanoparticles promote the faster electron transfer between the lectin immobilized and the target cells. Hence, Con A immobilized on ZnO nanoparticles will agglutinate cells more effectively than the native protein. Concanavalin A (Con A), a lectin was immobilized on the hexagonal zinc oxide (ZnO) nanoparticles to monitor its activity on RBCs and lymphocytes. The immobilization of Con A and zinc oxide nanoparticles has been studied by molecular docking, microscopic and genotoxicity assessment techniques. Qualitative assessment using various techniques like atomic force microscopy, scanning electron microscopy and X-ray diffraction showed minor changes in morphology of Con A and ZnO nanoparticles. FT-IR spectroscopy confirmed the linking of Con A amino groups with ZnO nanoparticles. Con A immobilized nanoparticles in contrast to native lectin showed minor changes in hemagglutination activity as confirmed by pH dependence studies using fluorimetry. Con Aimmobilized nanoparticles retained the agglutination activity, this can be indicative of their potential application in detection of virus transformed and neoplastic cells. The Con A immobilized ZnO nanoparticles did not induce any significant but minor damage to whole cell DNA as revealed from comet assay or plasmid DNA. Con A immobilized on ZnO nanoparticles showed minor changes in the structure of ZnO nanoparticles and in the conformational of native Con A. However, Con A immobilized ZnO nanoparticles interestingly, showed pH resistance and better hemagglutination activity as well as minor DNA damage to whole cell lymphocytes. Thus, this novel bioaffinity support has prospective clinical implications.


Tuberculin skin testing in white-tailed deer (Odocoileus virginianus).
The comparative cervical skin test for antemortem diagnosis of tuberculosis was done 169 times on 116 different white-tailed deer of known Mycobacterium bovis infection status. The sensitivity and specificity were 97 and 81%, respectively. The magnitude of change in skin thickness at test sites was not significantly influenced by dosage of inoculum, dissemination of the disease process, or repeated skin testing. However, the magnitude of change in skin thickness was significantly greater in deer infected for less than 109 days than in deer infected for more than 109 days. As used in the present study, the comparative cervical skin test is a sensitive method of antemortem diagnosis of M. bovis infection in white-tailed deer.


Short-Root regulates primary, lateral, and adventitious root development in Arabidopsis.
Short-Root (SHR) is a well-characterized regulator of radial patterning and indeterminacy of the Arabidopsis (Arabidopsis thaliana) primary root. However, its role during the elaboration of root system architecture remains unclear. We report that the indeterminate wild-type Arabidopsis root system was transformed into a determinate root system in the shr mutant when growing in soil or agar. The root growth behavior of the shr mutant results from its primary root apical meristem failing to initiate cell division following germination. The inability of shr to reactivate mitotic activity in the root apical meristem is associated with the progressive reduction in the abundance of auxin efflux carriers, PIN-FORMED1 (PIN1), PIN2, PIN3, PIN4, and PIN7. The loss of primary root growth in shr is compensated by the activation of anchor root primordia, whose tissues are radially patterned like the wild type. However, SHR function is not restricted to the primary root but is also required for the initiation and patterning of lateral root primordia. In addition, SHR is necessary to maintain the indeterminate growth of lateral and anchor roots. We conclude that SHR regulates a wide array of Arabidopsis root-related developmental processes.


The Diagnosis of Delirium Superimposed on Dementia: An Emerging Challenge.
Delirium occurring in patients with dementia is referred to as delirium superimposed on dementia (DSD). People who are older with dementia and who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision are considered the standard reference for the diagnosis of delirium and include criteria of impairments in cognitive processes such as attention, additional cognitive disturbances, or altered level of arousal. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision does not provide guidance regarding specific tests for assessment of the cognitive process impaired in delirium. Importantly, the assessment or inclusion of preexisting cognitive impairment is also not addressed by these standards. The challenge of DSD gets more complex as types of dementia, particularly dementia with Lewy bodies, which has features of both delirium and dementia, are considered. The objective of this article is to critically review key elements for the diagnosis of DSD, including the challenge of neuropsychological assessment in patients with dementia and the influence of particular tests used to diagnose DSD. To address the challenges of DSD diagnosis, we present a framework for guiding the focus of future research efforts to develop a reliable reference standard to diagnose DSD. A key feature of a reliable reference standard will improve the ability to clinically diagnose DSD in facility-based patients and research studies.