Iterative point-wise reinforcement learning for highly accurate indoor visible light positioning.
Iterative point-wise reinforcement learning (IPWRL) is proposed for highly accurate indoor visible light positioning (VLP). By properly updating the height information in an iterative fashion, the IPWRL not only effectively mitigates the impact of non-deterministic noise but also exhibits excellent tolerance to deterministic errors caused by the inaccurate a priori height information. The principle of the IPWRL is explained, and the performance of the IPWRL is experimentally evaluated in a received signal strength (RSS) based VLP system and compared with other positioning algorithms, including the conventional RSS algorithm, the k-nearest neighbors (KNN) algorithm and the PWRL algorithm where iterations exclude. Unlike the supervised machine learning method, e.g., the KNN, whose performance is highly dependent on the training process, the proposed IPWRL does not require training and demonstrates robust positioning performance for the entire tested area. Experimental results also show that when a large height information mismatch occurs, the IPWRL is able to first correct the height information and then offers robust positioning results with a rather low positioning error, while the positioning errors caused by the other algorithms are significantly higher.


The Importance of Understanding Parental Perception When Treating Primary Nocturnal Enuresis: A Topic Review and an Institutional Experience.
Primary nocturnal enuresis (PNE) is a common childhood disorder that adversely affects a child's mental well-being and social life. Our clinical experience showed parents and their child often have significantly different perspective of enuresis, and these differences can affect family dynamics, treatment approaches, and treatment success. Parents' perception of PNE also influences the likelihood of seeking medical treatment, and we found parents of children with enuresis have markedly different beliefs regarding bedwetting than those of physicians. Because achieving remission for PNE requires parents and their child to actively participate in treatment, assessing their expectancy of success and their beliefs will allow clinicians to adjust treatment goals as necessary. When treating PNE, guidelines consistently recommend incorporating bed alarms as part of the therapy. However, through interviewing parents and treating their children, we found parents preferred medications or other behavioral strategies, such as limiting water intake, because of their convenience. Many parents would complain bed alarms woke them up instead of their child, and they would soon give up on bed alarms. Part of assessing their beliefs includes assessing their confidence in their child being able to wake up to alarms and to persist with treatment. Understanding how they manage and approach setbacks will also determine the treatment modality suited for their child. In this review paper, we detailed our experiences interviewing parents and treating their child with NE with urodynamics and medications at the Changhua Christian Hospital in Taiwan.


Two loci on wheat chromosome 5A regulate the differential cold-dependent expression of the cor14b gene in frost-tolerant and frost-sensitive genotypes.
Although cold acclimation in cereals involves the expression of many cold-regulated genes, genetic studies have shown that only very few chromosomal regions carry loci that play an important role in frost tolerance. To investigate the genetic relationship between frost tolerance and the expression of cold-regulated genes, the expression and regulation of the wheat homolog of the barley cold-regulated gene cor14b was studied at various temperatures in frost-sensitive and frost-tolerant wheat genotypes. At 18/15 degrees C (day/night temperatures) frost-tolerant plants accumulated cor14b mRNAs and expressed COR14b proteins, whereas the sensitive plants did not. This result indicates that the threshold temperature for induction of the wheat cor14b homolog is higher in frost-resistant plants, and allowed us to use this polymorphism in a mapping approach. Studies made with chromosome substitution lines showed that the polymorphism for the threshold induction temperature of the wheat cor14b homolog is controlled by a locus(i) located on chromosome 5A of wheat, while the cor14b gene was mapped in Triticum monococcum on the long arm of chromosome 2Am. The analysis of single chromosome recombinant lines derived from a cross between Chinese Spring/Triticum spelta 5A and Chinese Spring/Cheyenne 5A identified two loci with additive effects that are involved in the genetic control of cor14b mRNA accumulation. The first locus was tightly linked to the marker psr911, while the second one was located between the marker Xpsr2021 and Frost resistance 1 (Fr1).


Diagnostic Impacts of Clinical Laboratory Based p2PSA Indexes on any Grade, Gleason Grade Group 2 or Greater, or 3 or Greater Prostate Cancer and Prostate Specific Antigen below 10 ng/ml.
The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml. Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer. Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy. Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.


Genome-wide association study of extreme longevity in Drosophila melanogaster.
Human genome-wide association studies (GWAS) of longevity attempt to identify alleles at different frequencies in the extremely old, relative to a younger control sample. Here, we apply a GWAS approach to "synthetic" populations of Drosophila melanogaster derived from a small number of inbred founders. We used next-generation DNA sequencing to estimate allele and haplotype frequencies in the oldest surviving individuals of an age cohort and compared these frequencies with those of randomly sampled individuals from the same cohort. We used this case-control strategy in four independent cohorts and identified eight significantly differentiated regions of the genome potentially harboring genes with relevance for longevity. By modeling the effects of local haplotypes, we have more power to detect regions enriched for longevity genes than marker-based GWAS. Most significant regions occur near chromosome ends or centromeres where recombination is infrequent, consistent with these regions harboring unconditionally deleterious alleles impacting longevity. Genes in regions of normal recombination are enriched for those relevant to immune function and a gene family involved in oxidative stress response. Genetic differentiation between our experimental cohorts is comparable to that between human populations, suggesting in turn that our results may help explain heterogeneous signals in human association studies of extreme longevity when panels have diverse ancestry.


Cardioprotection and myocardial reperfusion: pitfalls to clinical application.
With the advent of thrombolytic therapy and angioplasty, it has become possible to reduce myocardial infarct size through early reperfusion. Enormous effort has been expended to find therapies that can further reduce infarct size after early intervention. Animal studies have identified many cardioprotective pathways that have the potential to reduce infarct size if activated before the onset of ischemia. More recently, interventions effective at the onset of reperfusion have been described. Although basic research has identified many targets, most has been conducted in rodent models which may not be directly applicable to human disease and even promising agents have been disappointing in large-scale clinical trials. There are many potential explanations for this failure which is the subject of this review. Potential factors include (1) the variability inherent in the patient population, whereas animal studies usually use single sex homogeneous groups maintained on standard diets in carefully controlled environments; (2) the duration of ischemia is generally shorter in animal studies, resulting in potentially more salvageable myocardium than is often the case in patients; (3) that the animals are usually young without comorbidities, whereas the patient population is generally older and has significant comorbidities; (4) animals are not treated with medications a priori, whereas the patient population is often taking medications that may affect ischemic injury; and (5) animal studies may not involve thorough assessment of effects on organs other than the heart, whereas patients can experience adverse effects of treatment in other organs that can preclude clinical use.


Community treatment orders and associations with readmission rates and duration of psychiatric hospital admission: a controlled electronic case register study.
Limited evidence is available regarding the effect of community treatment orders (CTOs) on mortality and readmission to psychiatric hospital. We compared clinical outcomes between patients placed on CTOs to a control group of patients discharged to voluntary community mental healthcare. An observational study using deidentified electronic health record data from inpatients receiving mental healthcare in South London using the Clinical Record Interactive Search (CRIS) system. Data from patients discharged between November 2008 and May 2014 from compulsory inpatient treatment under the Mental Health Act were analysed. 830 participants discharged on a CTO (mean age 40 years; 63% male) and 3659 control participants discharged without a CTO (mean age 42 years; 53% male). The number of days spent in the community until readmission, the number of days spent in inpatient care in the 2 years prior to and the 2 years following the index admission and mortality. The mean duration of a CTO was 3.2 years. Patients receiving care from forensic psychiatry services were five times more likely and patients receiving a long-acting injectable antipsychotic were twice as likely to be placed on a CTO. There was a significant association between CTO receipt and readmission in adjusted models (HR: 1.60, 95% CI 1.42 to 1.80, p<0.001). Compared with controls, patients on a CTO spent 17.3 additional days (95% CI 4.0 to 30.6, p=0.011) in a psychiatric hospital in the 2 years following index admission and had a lower mortality rate (HR: 0.66, 95% CI 0.50 to 0.88, p=0.004). Many patients spent longer on CTOs than initially anticipated by policymakers. Those on CTOs are readmitted sooner, spend more time in hospital and have a lower mortality rate. These findings merit consideration in future amendments to the UK Mental Health Act.


'What's she doing here?' Overcoming barriers to the implementation of Expert by Experience positions in academia.
Experts by Experience involvement in the education of health professionals has gained momentum as an important strategy in ensuring quality, person-centred education. Despite being a requirement for occupational therapy programs in Australia and internationally, involvement is variable and limited. Barriers to the implementation of academic roles have been identified, including negative attitudes of colleagues, systemic barriers, and insufficient evidence of their value. Mental health academics who do not identify as having lived experience (referred to as allies) have provided crucial support for Experts by Experience. Understanding their perspectives on implementation barriers and how they can be addressed is crucial to facilitating a broader level of meaningful involvement. A qualitative exploratory research project was conducted, involving in-depth interviews with mental health academic allies (n = 16) from Australia, Ireland, and New Zealand. Participants were from the disciplines of nursing, occupational therapy, social work, and psychiatry. Data were analysed thematically. Two main themes were identified from the data analysis process: convincing colleagues and dealing with university barriers. Participants described varying attitudes from colleagues towards Experts by Experience, with many not understanding or appreciating their contribution to education and student outcomes. At the university level, reluctance to embrace innovation and funding and other resource shortages presented impediments to the implementation of Expert by Experience roles. Participants described using creative measures to overcome institutional barriers and encourage greater acceptance of such roles by colleagues. This research describes how allies experienced and overcame barriers they faced when supporting the implementation of academic positions for Experts by Experience. Allies have an important role to play in overcoming systemic barriers, and the approaches they have taken to achieve this may be an important source of learning for others with similar aspirations.


Glutamine metabolism in a holostean (Amia calva) and teleost fish (Salvelinus namaycush).
Amino acid metabolism was examined in mitochondria from the lateral red muscle of a teleost (lake char, Salvelinus namaycush) and a nonteleost fish (bowfin, Amia calva). Isolated mitochondria oxidize a wide variety of substrates and have high respiratory control ratios. In both species, glutamine is oxidized more rapidly than any other amino acid. The rate of glutamine oxidation by bowfin mitochondria exceeds that of lake char mitochondria, and the bowfin displays correspondingly higher levels of mitochondrial phosphate-dependent glutaminase. It is suggested that amino acids in general, and glutamine in particular, are important oxidative substrates for nonteleost red muscle. The teleost red muscle, however, may rely on both glutamine and fatty acids as oxidative substrates. It appears that glutamate derived from glutamine is oxidized primarily via glutamate dehydrogenase, whereas exogenous glutamate is oxidized primarily via aspartate aminotransferase. Complete oxidation of glutamine may be accomplished in the absence of other substrates by conversion of glutamine-derived malate to pyruvate via malic enzyme. To assess the relative abilities of various tissues to synthesize and oxidize glutamine, the activities of glutamine synthetase and glutaminase were measured. The results of these studies indicate that the organization of glutamine metabolism of fish differs markedly from that in mammals.


Parent-progeny sequencing indicates higher mutation rates in heterozygotes.
Mutation rates vary within genomes, but the causes of this remain unclear. As many prior inferences rely on methods that assume an absence of selection, potentially leading to artefactual results, we call mutation events directly using a parent-offspring sequencing strategy focusing on Arabidopsis and using rice and honey bee for replication. Here we show that mutation rates are higher in heterozygotes and in proximity to crossover events. A correlation between recombination rate and intraspecific diversity is in part owing to a higher mutation rate in domains of high recombination/diversity. Implicating diversity per se as a cause, we find an ∼3.5-fold higher mutation rate in heterozygotes than in homozygotes, with mutations occurring in closer proximity to heterozygous sites than expected by chance. In a genome that is a patchwork of heterozygous and homozygous domains, mutations occur disproportionately more often in the heterozygous domains. If segregating mutations predispose to a higher local mutation rate, clusters of genes dominantly under purifying selection (more commonly homozygous) and under balancing selection (more commonly heterozygous), might have low and high mutation rates, respectively. Our results are consistent with this, there being a ten times higher mutation rate in pathogen resistance genes, expected to be under positive or balancing selection. Consequently, we do not necessarily need to evoke extremely weak selection on the mutation rate to explain why mutational hot and cold spots might correspond to regions under positive/balancing and purifying selection, respectively.


Profound deafness and the acquisition of spoken language in children.
Profound congenital sensorineural hearing loss (SNHL) is not so infrequent, affecting 1 to 2 of every 1000 newborns in western countries. Nevertheless, universal hearing screening programs have not been widely applied, although such programs are already established for metabolic diseases. The acquisition of spoken language is a time-dependent process, and some form linguistic input should be present before the first 6 mo of life for a child to become linguistically competent. Therefore, profoundly deaf children should be detected early, and referred timely for the process of auditory rehabilitation to be initiated. Hearing assessment methods should reflect the behavioural audiogram in an accurate manner. Additional disabilities also need to be taken into account. Profound congenital SNHL is managed by a multidisciplinary team. Affected infants should be bilaterally fitted with hearing aids, no later than 3 mo after birth. They should be monitored until the first year of age. If they are not progressing linguistically, cochlear implantation can be considered after thorough preoperative assessment. Prelingually deaf children develop significant speech perception and production abilities, and speech intelligibility over time, following cochlear implantation. Age at intervention and oral communication, are the most important determinants of outcomes. Realistic parental expectations are also essential. Cochlear implant programs deserve the strong support of community members, professional bodies, and political authorities in order to be successful, and maximize the future earnings of pediatric cochlear implantation for human societies.


Advances in Treatment of Wilson Disease.
Wilson disease (WD) is an inherited neurometabolic disorder that results in excessive copper deposition in the liver and the brain, affecting children and young adults. Without treatment the disease is invariably fatal. Though treatments for WD have been available since the 1950s, the disease continues to be associated with considerable morbidity and mortality because of missed diagnosis, and delayed or inadequate treatment. In this paper we survey WD-related literature in order to review recent advances in WD treatment. We performed a literature search using the PubMed database for articles relating to WD and its medical treatment. We reviewed the articles, and cross-references of relevant articles, to summarize the current practices for treatment of WD. The survey shows that if WD is properly treated, in most patients the liver can be stabilized, even severe neurological disability reversed, and patients can resume normal lives. Medical treatment for WD includes use of copper chelators (penicillamine, trientine, dimercaprol, dimercaptopropane sulfonate, and ammonium tetrathiomolybdate) and drugs that decrease gastrointestinal copper absorption. Our knowledge of the treatment approaches has benefited from the large systematic clinical studies that have been conducted over the last decade. For each drug used to treat WD, we surveyed its development, indication for use, dosing, efficacy, and adverse effects.


Communication of information in the homecare context.
Organizing the Homecare with new information technologies is nowadays an important challenge. Indeed, some medical evolutions as the improvement of the duration of life, the number of chronic diseases and some social evolutions, such as the quality of patient life, or economic evolutions, such as the reduction of hospitalisation costs, could benefit from homecare. In this paper, we present the problem of the communication of information in the homecare context. Some main phases have been described that compose the two homecare processes: a logistic process and a care process. The communication of information during homecare depends on the concerned phases: first, some exchanges of information from existing Information System to the Homecare Information System; then, some exchanges between the homecare system and the mobile health care actors; and then, some mails during the outcome phase. Coordination architecture is briefly described, and two different implementations for the communication of information during homecare are presented: one is using XML messages to exchange information between Information Systems; the other is using mobile tools for communicating with mobile actors.


High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations.
Thymocyte selection-associated high-mobility group box (TOX) is a DNA-binding factor that is able to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. TOX has multiple roles in the development of the adaptive immune system including development of CD4 T cells, NK cells and lymph node organogenesis. However very few antibodies recognizing this molecule have been reported and no extensive study of the expression of TOX in reactive and neoplastic lymphoid tissue has been performed to date. In the present study, we have investigated TOX expression in normal and neoplastic lymphoid tissues using a novel rat monoclonal antibody that recognizes its target molecule in paraffin-embedded tissue sections. A large series of normal tissues and B- and T-cell lymphomas was studied, using whole sections and tissue microarrays. We found that the majority of precursor B/T lymphoblastic, follicular and diffuse large B-cell lymphomas, nodular lymphocyte-predominant Hodgkin lymphomas and angioimmunoblastic T-cell lymphomas strongly expressed the TOX protein. Burkitt and mantle cell lymphomas showed TOX expression in a small percentage of cases. TOX was not found in the majority of chronic lymphocytic leukemia, myelomas, marginal zone lymphomas and classical Hodgkin lymphomas. In conclusion, we describe for the first time the expression of TOX in normal and neoplastic lymphoid tissues. The co-expression of TOX and PD-1 identified in normal and neoplastic T cells is consistent with recent studies identifying TOX as a critical regulator of T-cell exhaustion and a potential immunotherapy target. Its differential expression may be of diagnostic relevance in the differential diagnosis of follicular lymphoma, the identification of the phenotype of diffuse large B-cell lymphoma and the recognition of peripheral T-cell lymphoma with a follicular helper T phenotype.


Tailoring subtractive cell biopanning to identify diffuse gastric adenocarcinoma-associated antigens via human scFv antibodies.
Among various solid tumours, gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Expansion into the peritoneal cavity, which results from dissemination of diffuse cancer cells, is the main cause of mortality in gastric adenocarcinoma patients. Therefore, investigation of putative biomarkers involved in metastasis is prerequisite for GC management. In an effort to discover potential tumour markers associated with peritoneal metastasis of GC, a semi-synthetic human scFv library (Tomlinson I) was used to isolate novel antibody fragments recognizing MKN-45, a poorly differentiated diffuse gastric adenocarcinoma cell line. Four rounds of subtractive selection each consisting of extensive pre-absorption of phage library with NIH-3T3 murine embryonic fibroblasts and AGS (a well-differentiated intestinal gastric adenocarcinoma) cell line were carried out prior to positive selection on MKN-45 target cells. ELISA-based screening of 192 phage-displayed scFv clones indicated 21 high-affinity binders with specific staining of MKN-45 compared with AGS cells. Diversity analysis of the selected phage-scFvs resulted in five distinct sequences with multiple frequency. Further analysis by ELISA and flow cytometry verified three clones that specifically recognized MKN-45 cells. Liquid chromatography-mass spectrometry analysis of the scFv-immunoprecipitated proteins has led to identification of c-Met, HSP90 α and HSP90 β as candidate biomarkers associated with diffuse GC. Immunohistochemistry revealed the capability of purified scFvs to differentiate diffuse and intestinal gastric adenocarcinoma. Taken together, the isolated MKN-45-specific scFv fragments and their cognate antigens would be beneficial in screening and management as well as targeting and therapy of the diffuse gastric adenocarcinoma.


Positive Association between Basal Total Testosterone Circulating Levels and Tumor Grade Groups at the Time of Diagnosis of Prostate Cancer.
To test the hypothesis that basal total testosterone (TT) levels are associated with International Society of Urologic Pathology (ISUP) tumor grade groups at the time of diagnosis of prostate cancer (PCA). From November 2014 to March 2018, preoperative TT and PSA were measured in 601 consecutive patients who were not under androgen deprivation and undergoing surgery for PCA. Patients were classified into low (ISUP 1; reference group), intermediate (ISUP 2/3), and high (ISUP 4/5) tumor grade groups. The association of TT and other clinical factors with tumor groups was evaluated by multinomial multivariate regression analysis. 218 patients (36.3%) were biopsy low grade (ISUP 1), 297 (49.4%) intermediate grade (ISUP 2/3), and 86 (14.3) high grade (ISUP 4/5). Median basal circulating TT levels progressively increased as tumor grade groups increased. On multivariate models, TT, among other clinical factors, was positively associated with the risk of intermediate (OR 1.001; p = 0.023) and high tumor grades (OR 1.002, p = 0.022) compared to low-grade cancers. Increased endogenous circulating basal TT levels were positively associated with ISUP tumor grade groups at the time of diagnosis indicating a close association with tumor biology. Basal TT levels may reflect the heterogeneity of the cancer population.


Patterns of Anterior Inferior Tibiofibular Ligament Avulsion Fracture Accompanied by Ankle Fracture.
The anterior inferior tibiofibular ligament (AITFL) avulsion fracture accompanying an ankle fracture can compromise ankle stability, necessitating accurate evaluation and a clear understanding of its pathophysiology.. The aim of this study was to investigate the association between AITFL avulsion fracture and Lauge-Hansen, Wagstaffe classification. A retro-prospective study was conducted at a university-affiliated tertiary care medical center. We selected 128 patients who underwent surgery at our institution between January 2013 and July 2017 and analyzed the association between AITFL avulsion fracture and the foot position. According to the modified Wagstaffe classification system, there were 39 cases of type II, followed by 9 cases of type III and 8 cases of type IV. Of the7 pronation-abduction fractures, 3 were AITFL avulsion fracture (43%), while of the 21 pronation-external rotation fractures, 9 were AITFL avulsion fracture (43%). Of the 95 supination-external rotation fractures, there were 56 cases (59%) of AITFL avulsion fractures. Of the pronation fractures, 0% were fibular avulsion fractures and 43% were tibial avulsion fractures. Of the supination fractures, 44% were fibular avulsion fractures and 16% were tibial avulsion fracture. The difference in the ratio of fibular to tibial avulsion fractures between pronation and supination fractures was significant (p < 0.001). These results suggest that tibial avulsion fractures of type IV in the modified Wagstaffe classification and pronation fractures occur due to collision with the anterolateral corners of the distal bone when the talus externally rotates. Moreover, In cases of pronation fractures, a new type of AITFL avulsion fracture has been observed.


A novel technique for vas deferens transection repairs.
The purpose of this study is to describe a technique, that is as successful as microsurgery in terms of patency rates and histopathologic assessments, and can be performed even by untrained hands in microsurgery, for repairing vas deferens injuries that can be perceived during inguinal herniorrhaphy. Thirty male Wistar-Albino rats were randomly allocated to five groups. In control group, the vas deferens was harvested without any surgical intervention (Group 1) and in sham group the vas was harvested after a limited dissection (Group 2). Three suture approximation technique was carried out in Group 3, and a novel vasovasostomy technique was carried out by using a hypodermal needle in Groups 4 and 5, with polypropylene and polyglactin 910 (rapid vicryl), respectively. Results were evaluated in terms of operative time, patency and flow rates, inflammation and sperm granuloma. The mean operative times for hypodermal needle assisted approximation of Groups 4 and 5 were found significantly less than Group 3. The compared results of the groups in terms of patency, flow rate, inflammation and spermatic granuloma indicated Group 4 to be superior to the other groups. We have found the hypodermal needle assisted approximation technique to be easier, less time consuming and cost effective. With these promising results, this modus operandi can be described as an appropriate technique for vas deferens transection repairs.


Active Center Size-Dependent Fenton-Like Chemistry for Sustainable Water Decontamination.
Accurately controlling catalytic activity and mechanism as well as identifying structure-activity-selectivity correlations in Fenton-like chemistry is essential for designing high-performance catalysts for sustainable water decontamination. Herein, active center size-dependent catalysts with single cobalt atoms (CoSA), atomic clusters (CoAC), and nanoparticles (CoNP) were fabricated to realize the changeover of catalytic activity and mechanism in peroxymonosulfate (PMS)-based Fenton-like chemistry. Catalytic activity and durability vary with the change in metal active center sizes. Besides, reducing the metal size from nanoparticles to single atoms significantly modulates contributions of radical and nonradical mechanisms, thus achieving selective/nonselective degradation. Density functional theory calculations reveal evolutions in catalytic mechanisms of size-dependent catalytic systems over different Gibbs free energies for reactive oxygen species generation. Single-atom site contact with PMS is preferred to induce nonradical mechanisms, while PMS dissociates and generates radicals on clusters and nanoparticles. Differences originating from reaction mechanisms endow developed systems with size-dependent selectivity and mineralization for treating actual hospital wastewater in column reactors. This work brings an in-depth understanding of metal size effects in Fenton-like chemistry and guides the design of intelligent catalysts to fulfill the demand of specific scenes for water purification.


Experiments on the mechanism of Ménière attacks.
The pattern of response decline following semicircular canal stimulation corresponds to a mechanical process. This process is the elastic recoil of the hairs of the sensory cells. The response decline is the same, whether the endolymph-cupula system is patent or mechanically maintained in a displaced position. The role of the bending of the entire cupula as the principle factor is excluded for the response and its decline. Repeated endolymph displacements immediately after each decline of response always result in an equal response and its decline. This rules out the depletion of a chemical mediator as a cause for the response decline. Indentations of the sidewalks of the ampulla result in reactions suggesting that the ampulla is filled with a loose gel secreted by the planum semilunatum cells.


Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b.
The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.


Control of ACAT2 liver expression by HNF1.
ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this report, we elucidate the mechanisms that control the liver-specific expression of the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2. Targeted deletion of the HNF1 binding site in the DNA sequence abolished not only the basal promoter function in HepG2 and HuH7 cells but also the induction of the ACAT2 promoter by HNF1. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the transcription factors HNF1alpha and HNF1beta interact with this region in the human ACAT2 gene in vitro and in vivo. These data indicate that a) the identified HNF1 binding site serves as a positive regulator sequence, b) the binding site is functionally active both in vivo and in vitro, and c) the transcription factors HNF1alpha and HNF1beta, which bind to this site, play an important part in the regulation of the human ACAT2 promoter.


Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient.
Molecular typing of syphilis-causing strains provides important epidemiologic data. We tested whether identified molecular subtypes were identical in PCR-positive parallel samples taken from the same patient at a same time. We also tested whether subtype prevalence differs in skin and blood samples. Eighteen syphilis positive patients (showing both positive serology and PCR), with two PCR-typeable parallel samples taken at the same time, were tested with both CDC (Centers for Disease Control and Prevention) and sequence-based typing. Samples taken from 9 of 18 patients were completely typed for TP0136, TP0548, 23S rDNA, arp, and tpr loci. The CDC typing revealed 11 distinct genotypes while the sequence-based typing identified 6 genotypes. When results from molecular typing of TP0136, TP0548, and 23S rDNA were analyzed in samples taken from the same patient, no discrepancies in the identified genotypes were found; however, there were discrepancies in 11 of 18 patients (61.1%) samples relative to the arp and tpr loci. In addition to the above described typing, 127 PCR-positive swabs and whole blood samples were tested for individual genotype frequencies. The repetition number for the arp gene was lower in whole blood (WB) samples compared to swab samples. Similarly, the most common tpr RFLP type "d" was found to have lower occurrence rates in WB samples while type "e" had an increased occurrence in these samples. Differences in the CDC subtypes identified in parallel samples indicated genetic instability of the arp and tpr loci and suggested limited applicability of the CDC typing system in epidemiological studies. Differences in treponemal genotypes detected in whole blood and swab samples suggested important differences between both compartments and/or differences in adherence of treponeme variants to human cells.


Comparison of one-dimensional and two-dimensional least-squares strain estimators for phased array displacement data.
In this study, the performances of one-dimensional and two-dimensional least-squares strain estimators (LSQSE) are compared. Furthermore, the effects of kernel size are examined using simulated raw frequency data of a widely-adapted hard lesion/soft tissue model. The performances of both methods are assessed in terms of root-mean-squared errors (RMSE), elastographic signal-to-noise ratio (SNRe) and contrast-to-noise ratio (CNRe). RMSE analysis revealed that the 2D LSQSE yields better results for phased array data, especially for larger insonification angles. Using a 2D LSQSE enabled the processing of unfiltered displacement data, in particular for the lateral/horizontal strain components. The SNRe and CNRe analysis showed an improvement in precision and almost no loss in contrast using 2D LSQSE. However, the RMSE images for different kernel sizes revealed that the optimal 2D kernel size depends on the region-of-interest and showed that the LSQ kernel size should be limited to avoid loss in resolution.


Prevalence and management of behavioural and psychiatric symptoms on a continuing care unit for patients with dementia.
With the increasing concerns over the safety of some pharmacological interventions or lack of sufficient evidence of effectiveness in managing neuropsychiatric symptoms in dementia, there is a constant need to review how such patients are managed. This study looks at the prevalence and management of behavioural and psychiatric symptoms amongst patients with dementia in a National Health Service (NHS) continuing care unit. In this study, a survey of all 50 patients admitted to a longstay NHS-funded dementia care unit was carried out. The socio-demographic details along with severity of dementia, neuropsychiatric symptoms, and medication were obtained on all the patients. All 50 patients were prescribed some form of medication for either physical and/or mental health reasons. Only five (10%) patients were not prescribed any form of psychotropic medication. A lack of non-pharmacological treatment options for the treatment of neuropsychiatric symptoms was evident in the unit with only one occupational therapist available. Effective management of severe behavioural and psychiatric symptoms in dementia is challenging even in a NHS continuing care dementia unit due to the absence of clear benefit from pharmacological interventions and lack of resources for optimum non-pharmacological interventions.


Infection of macrophages by a lymphotropic herpesvirus: a new tropism for Marek's disease virus.
Marek's disease virus (MDV) is classified as an oncogenic lymphotropic herpesvirus of chickens. MDV productively and cytolytically infects B, alphabetaT and gammadeltaT lymphocytes and latently infects T-helper lymphocytes. The aims of this study were to identify whether MDV infects macrophages in vivo and, if so, whether quantitative differences in macrophage infection are associated with MDV strain virulence. Chickens were infected with either virulent MDV (HPRS-16) or 'hypervirulent' MDV (C12/130). Flow cytometry with monoclonal antibodies recognizing MDV pp38 antigen and leukocyte antigens was used to identify MDV lytically infected cells. Macrophages from HPRS-16- and C12/130-infected chickens were pp38(+). It is demonstrated that macrophages are pp38(+) because they are infected and not because they have phagocytosed MDV antigens, as assessed by confocal microscopy using antibodies recognizing MDV antigens of the three herpesvirus kinetic classes: infected cell protein 4 (ICP4, immediate early), pp38 (early) and glycoprotein B (gB, late). Spleen macrophages from MDV-infected chickens were ICP4(+), pp38(+) and gB(+), and ICP4 had nuclear localization denoting infection. Finally, MDV pp38(+) macrophages had high inherent death rates, confirming cytolytic MDV infection, although production of virus particles has not been detected yet. These results have two fundamental implications for understanding MDV pathogenesis: (i) MDV evolved to perturb innate, in addition to acquired, immunity and (ii) macrophages are excellent candidates for transporting MDV to primary lymphoid organs during the earliest stages of pathogenesis.


Strong-field Photoionization of Sputtered Neutral Molecules for Molecular Depth Profiling.
Molecular depth profiles of an organic thin film of guanine vapor deposited onto a Ag substrate are obtained using a 40 keV C(60) cluster ion beam in conjunction with time-of-flight secondary ion mass spectrometric (ToF-SIMS) detection. Strong-field, femtosecond photoionization of intact guanine molecules is used to probe the neutral component of the profile for direct comparison with the secondary ion component. The ability to simultaneously acquire secondary ions and photoionized neutral molecules reveals new fundamental information about the factors that influence the properties of the depth profile. Results show that there is an increased ionization probability for protonated molecular ions within the first 10 nm due to the generation of free protons within the sample. Moreover, there is a 50% increase in fragment ion signal relative to steady state values 25 nm before reaching the guanine/Ag interface as a result of interfacial chemical damage accumulation. An altered layer thickness of 20 nm is observed as a consequence of ion beam induced chemical mixing. In general, we show that the neutral component of a molecular depth profile using the strong-field photoionization technique can be used to elucidate the effects of variations in ionization probability on the yield of molecular ions as well as to aid in obtaining accurate information about depth dependent chemical composition that cannot be extracted from TOF-SIMS data alone.


[The ventilatory response to isocapnic hypoxia during head-down tilt].
The ventilatory response to isocapnic hypoxia was studied using rebreathing techniques in anesthetized and tracheostomized rats both in supine and in head-down tilt position (HDT-30 degrees). Hypoxic responses were calculated by the slope of ventilation against end tidal P(A)O2. The end-tidal P(A)CO2 was kept constant by varying expired gas flow through a CO2-absorbing bypass. The rebreathing was continued until P(A)O2 had fallen to between 70 +/- 3 and 50 +/- 2 mm Hg. The obtained results demonstrated that the maximal minute lung ventilation was 269 +/- 30 % during rebreathing test in supine position and 117 +/- 21% in the head-down tilt. It was also shown that the slopes of the relationship between minute ventilation and the decrease of end tidal P(A)O2 was 3-fold greater in supine than in HDT. The body position seems to affect the ventilatory response to isocapnic progressive hypoxia. In general, it may be a result of hemodynamic conditions alteration which increased respiratory resistive loads, changed the functional condition of carotid hemoreceptors and baroreceptor activity that modulate ventilatory response to chemoreceptor stimulation.


Analysis of the pediatric surgery match: factors predicting outcome.
Applicants in the NRMP for pediatric surgery have little objective data available regarding factors predicting successful matching. We analyzed data from applicants at our institution to attempt to identify parameters correlated with three outcomes: successfully matching, or attaining either a top ten or top three ranking in our final submitted match list. After IRB approval, we reviewed ERAS documents for all applicants (n = 146) over 3 years (candidates for the 2007, 2008, and 2009 fellowship years). An interview was offered to 75% of the applicants (Table 1). We analyzed over 20 factors; including demographics, number of publications and first author publications, number of book chapters, national presentations, prior match attempts, advanced degrees, quality of recommendation letters, and ABSITE scores. Significant variables were evaluated with multiple logistic regression analysis to identify independent predictors. Variables correlated with successful outcome for each of the three endpoints are shown in Table 2. The number of peer-reviewed publications and first author publications, and AOA membership were highly correlated with a favorable outcome for all three endpoints. High ABSITE scores were significantly correlated with top ten rank. Research experience and outstanding letters of recommendation were significantly associated with a top ten ranking and overall match success. Variables associated only with overall match success included number of book chapters, graduation from a US medical school, quality of recommendation letters, and being granted an interview at our institution. Logistic regression analysis demonstrated no independent factors for overall match success; number of publications was significant for both top ten and top three ranking (P = 0.006 for each); number of first author publications (P = 0.002) and AOA membership (P = 0.03) were independent predictors for top three ranking. Applicant variables associated with success in the match included quality of letters, number and type of publications, research experience, graduation from a US medical school, and AOA membership. Factors not correlated with outcome included advanced degrees (PhD, Masters), other fellowship training, and community-based versus university-based residency training. Logistic regression analysis demonstrated no independent factors for overall match success.


Computational Methods for MicroRNA Target Prediction.
MicroRNAs (miRNAs) have been identified as one of the most important molecules that regulate gene expression in various organisms. miRNAs are short, 21-23 nucleotide-long, single stranded RNA molecules that bind to 3' untranslated regions (3' UTRs) of their target mRNAs. In general, they silence the expression of their target genes via degradation of the mRNA or by translational repression. The expression of miRNAs, on the other hand, also varies in different tissues based on their functions. It is significantly important to predict the targets of miRNAs by computational approaches to understand their effects on the regulation of gene expression. Various computational methods have been generated for miRNA target prediction but the resulting lists of candidate target genes from different algorithms often do not overlap. It is crucial to adjust the bioinformatics tools for more accurate predictions as it is equally important to validate the predicted target genes experimentally.


Role of the two-component leader sequence and mature amino acid sequences in extracellular export of endoglucanase EGL from Pseudomonas solanacearum.
The egl gene of Pseudomonas solanacearum encodes a 43-kDa extracellular endoglucanase (mEGL) involved in wilt disease caused by this phytopathogen. Egl is initially translated with a 45-residue, two-part leader sequence. The first 19 residues are apparently removed by signal peptidase II during export of Egl across the inner membrane (IM); the remaining residues of the leader sequence (modified with palmitate) are removed during export across the outer membrane (OM). Localization of Egl-PhoA fusion proteins showed that the first 26 residues of the Egl leader sequence are required and sufficient to direct lipid modification, processing, and export of Egl or PhoA across the IM but not the OM. Fusions of the complete 45-residue leader sequence or of the leader and increasing portions of mEgl sequences to PhoA did not cause its export across the OM. In-frame deletion of portions of mEGL-coding sequences blocked export of the truncated polypeptides across the OM without affecting export across the IM. These results indicate that the first part of the leader sequence functions independently to direct export of Egl across the IM while the second part and sequences and structures in mEGL are involved in export across the OM. Computer analysis of the mEgl amino acid sequence obtained from its nucleotide sequence identified a region of mEGL similar in amino acid sequence to regions in other prokaryotic endoglucanases.


Comprehensive sexuality education in Hong Kong: study protocol for process and outcome evaluation.
Hong Kong lacks comprehensive school-based sexuality education. Recent public health concerns have brought the inadequacies of sex education in Hong Kong to the forefront. The aim of the proposed study is to develop and evaluate the effectiveness of a comprehensive school-based sexuality education program in Hong Kong. The proposed study is a prospective longitudinal study implemented in six secondary schools in Hong Kong over two academic years. The study adopts an ecological approach providing informational workshops for students, teachers and school management, social workers and guidance counsellors and parents. Study outcomes will be evaluated through pre- and post-tests. Key outcomes of interest among students include sexual health knowledge, awareness of values motivating healthy sexual decisions, understanding and efficacy of sexual communication and intention to use contraception. Among school employees and parents key outcomes include self-efficacy to engage in sexual health discussions with students/children, sexual health knowledge and awareness of Hong Kong community sexual health resources. The proposed study will result in the development of a tested school-based culturally relevant comprehensive sexual health education program. Ultimately, this program aims to not only empower adolescents and their trusted adults in building a supportive environment for sexual health promotion but also construct a learning network to generate longitudinal evidence for the effectiveness of comprehensive sexuality education in improving sexual health outcomes. The program has the potential for expansion through widespread adoption in Hong Kong schools to benefit more adolescents and reduce the medical and societal burdens related to crisis pregnancy, sexually transmitted infections and sexual abuse.


Placenta-like structure of the aphid endoparasitic wasp Aphidius ervi: a strategy of optimal resources acquisition.
Aphidius ervi (Hymenoptera: Braconidae) is an entomophagous parasitoid known to be an effective parasitoid of several aphid species of economic importance. A reduction of its production cost during mass rearing for inundative release is needed to improve its use in biological control of pests. In these contexts, a careful analysis of its entire development phases within its host is needed. This paper shows that this parasitoid has some characteristics in its embryological development rather complex and different from most other reported insects, which can be phylogenetically very close. First, its yolkless egg allows a high fecundity of the female but force them to hatch from the egg shell rapidly to the host hemocoel. An early cellularisation allowing a rapid differentiation of a serosa membrane seems to confirm this hypothesis. The serosa wraps the developing embryo until the first instar larva stage and invades the host tissues by microvilli projections and form a placenta like structure able to divert host resources and allowing nutrition and respiration of embryo. Such interspecific invasion, at the cellular level, recalls mammal's trophoblasts that anchors maternal uterine wall and underlines the high adaptation of A. ervi to develop in the host body.


Benign prostatic hyperplasia. Patient evaluation and relief of obstructive symptoms.
Benign prostatic hyperplasia (BPH) is a common and highly manageable disorder that affects most men at some point after age 50. Although classic BPH symptoms mimic those of other genitourinary conditions, several straightforward tools are available to aid accurate diagnosis. For patients in whom the condition is identified early in its progression, prudent management includes periodic assessment of disease progression, pharmacotherapy, and phytotherapy. Some patients presenting with BPH may require or request surgical intervention and several minimally invasive procedures are available, although outcomes and complication rates vary for each.


Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a 'safety belt' binding mechanism for the spindle checkpoint.
The spindle checkpoint protein Mad1 recruits Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. The crystal structure of the Mad1-Mad2 complex reveals an asymmetric tetramer, with elongated Mad1 monomers parting from a coiled-coil to form two connected sub-complexes with Mad2. The Mad2 C-terminal tails are hinged mobile elements wrapping around the elongated ligands like molecular 'safety belts'. We show that Mad1 is a competitive inhibitor of the Mad2-Cdc20 complex, and propose that the Mad1-Mad2 complex acts as a regulated gate to control Mad2 release for Cdc20 binding. Mad1-Mad2 is strongly stabilized in the tetramer, but a 1:1 Mad1-Mad2 complex slowly releases Mad2 for Cdc20 binding, driven by favourable binding energies. Thus, the rate of Mad2 binding to Cdc20 during checkpoint activation may be regulated by conformational changes that destabilize the tetrameric Mad1-Mad2 assembly to promote Mad2 release. We also show that unlocking the Mad2 C-terminal tail is required for ligand release from Mad2, and that the 'safety belt' mechanism may prolong the lifetime of Mad2-ligand complexes.


Methodological challenges in using the Finnish Hospital Discharge Register for studying fire-related injuries leading to inpatient care.
The objective was to examine feasibility of using hospital discharge register data for studying fire-related injuries. The Finnish National Hospital Discharge Register (FHDR) was the database used to select relevant hospital discharge data to study usability and data quality issues. Patterns of E-coding were assessed, as well as prominent challenges in defining the incidence of injuries. Additionally, the issue of defining the relevant amount of hospital days accounted for in injury care was considered. Directly after the introduction of the ICD-10 classification system, in 1996, the completeness of E-coding was found to be poor, but to have improved dramatically around 2000 and thereafter. The scale of the challenges to defining the incidence of injuries was found to be manageable. In counting the relevant hospital days, psychiatric and long-term care were found to be the obvious and possible sources of overestimation. The FHDR was found to be a feasible data source for studying fire-related injuries so long as potential challenges are acknowledged and taken into account. Hospital discharge data can be a unique and powerful means for injury research as issues of representativeness and coverage of traditional probability samples can frequently be completely avoided.


Blood pressure in the Caribbean.
A review of original and published data yields the consistent finding that chronic hypertension is endemic and prevalent throughout the Caribbean area. The prominent involvement of genetics is suggested in several lines of evidence, including significant ethnic differences in blood pressure values, higher incidence in smaller isolated island populations, the discovery of polymorphic blood proteins that appear to be linked to hypertension susceptibility, and the slavery hypothesis of natural selection favoring a salt-conserving physiology in ancestral populations. Environmental factors--climatic, demographic, and cultural--exert strong influences on blood pressure levels and hypertension etiology in the Caribbean. Salt intake and other dietary behaviors, degree of community awareness of the disease, and differential treatment modalities are related to hypertension epidemiology in indigenous and migrant Caribbean populations. The traditional use of medicinal plants, historically successful in part because of the beneficial bioactivity of many antihypertensive phytochemical components, has been recently supplemented with the widespread introduction of synthetic biomedical drugs. Prospective research strategies are recommended that might further elucidate the complex gene-environment interactions contributing to blood pressure variation and hypertension patterns in the Caribbean region.


Effects of fatty acid activation on photosynthetic production of fatty acid-based biofuels in Synechocystis sp. PCC6803.
Direct conversion of solar energy and carbon dioxide to drop in fuel molecules in a single biological system can be achieved from fatty acid-based biofuels such as fatty alcohols and alkanes. These molecules have similar properties to fossil fuels but can be produced by photosynthetic cyanobacteria. Synechocystis sp. PCC6803 mutant strains containing either overexpression or deletion of the slr1609 gene, which encodes an acyl-ACP synthetase (AAS), have been constructed. The complete segregation and deletion in all mutant strains was confirmed by PCR analysis. Blocking fatty acid activation by deleting slr1609 gene in wild-type Synechocystis sp. PCC6803 led to a doubling of the amount of free fatty acids and a decrease of alkane production by up to 90 percent. Overexpression of slr1609 gene in the wild-type Synechocystis sp. PCC6803 had no effect on the production of either free fatty acids or alkanes. Overexpression or deletion of slr1609 gene in the Synechocystis sp. PCC6803 mutant strain with the capability of making fatty alcohols by genetically introducing fatty acyl-CoA reductase respectively enhanced or reduced fatty alcohol production by 60 percent. Fatty acid activation functionalized by the slr1609 gene is metabolically crucial for biosynthesis of fatty acid derivatives in Synechocystis sp. PCC6803. It is necessary but not sufficient for efficient production of alkanes. Fatty alcohol production can be significantly improved by the overexpression of slr1609 gene.


D-dimer and residual vein obstruction as risk factors for recurrence during and after anticoagulation withdrawal in patients with a first episode of provoked deep-vein thrombosis.
D-dimer and residual venous obstruction (RVO) have been separately shown to be risk factors for recurrent venous thromboembolism (VTE) after a first episode of unprovoked proximal deep-vein thrombosis (DVT). It was the objective of this study to assess the predictive value of D-dimer and residual vein obstruction (RVO), alone and in combination, for recurrence after provoked DVT of the lower limbs. A total of 296 consecutive patients with a first episode of symptomatic provoked proximal DVT were evaluated at a university hospital in Bologna, Italy. On the day of anticoagulation withdrawal (T0), RVO was determined by compression ultrasonography. D-dimer levels (cut-off: 500 ng/ml) were measured at T0 and after 30 ±10 days (T1). The main outcome was recurrent VTE during a two-year follow-up. D-dimer was abnormal in 11.6% (32/276) and 31% (85/276) of subjects at T0 and at T1, respectively. RVO was present in 44.8% (132/294) of patients. Recurrence rate was 5.1% (15/296; 95% confidence interval [CI]: 3-8%; 3% patient-years; 95% CI: 2-5 %). An abnormal D-dimer either at T0 or at T1 was associated with an adjusted hazard ratio (HR) for recurrence of 4.2 (95% CI:1.2-14.2; p=0.02) and 3.8 (95%CI: 1.2-12.1; p=0.02), respectively, when compared with normal D-dimer. The HR for recurrence associated with RVO was not significant, and RVO did not increase the recurrence risk associated with an abnormal D-dimer either at T0 or T1. In conclusion, an abnormal D-dimer during vitamin K antagonist (VKA) treatment or at one month after VKA withdrawal is a risk factor for recurrence in patients with provoked DVT, while RVO at the time of anticoagulation withdrawal is not.


[Therapy of gustatory sweating following parotidectomy. Frey's syndrome].
A new suggestion for treating marked sweating with Frey's syndrome namely, sweat suppression by aluminium chloride, is presented, together with a survey of the different attempts to suppress the hyperhidrosis. The mechanism of sweat suppression, the form of application and the results in 28 patients suffering from marked gustatory sweating, are outlined. After a single application, an interval of several weeks free of symptoms can be expected.


Hydrochemistry of urban groundwater, Seoul, Korea: the impact of subway tunnels on groundwater quality.
Hydrogeologic and hydrochemical data for subway tunnel seepage waters in Seoul (Republic of Korea) were examined to understand the effect of underground tunnels on the degradation of urban groundwater. A very large quantity of groundwater (up to 63 million m3 year(-1)) is discharged into subway tunnels with a total length of 287 km, resulting in a significant drop of the local groundwater table and the abandonment of groundwater wells. For the tunnel seepage water samples (n = 72) collected from 43 subway stations, at least one parameter among pathogenic microbes (total coliform, heterotrophic bacteria), dissolved Mn and Fe, NH4+, NO3(-), turbidity, and color exceeded the Korean Drinking Water Standards. Locally, tunnel seepage water was enriched in dissolved Mn (avg. 0.70 mg L(-1), max. 5.58 mg L(-1)), in addition to dissolved Fe, NH4+, and pathogenic microbes, likely due to significant inflow of sewage water from broken or leaking sewer pipes. Geochemical modeling of redox reactions was conducted to simulate the characteristic hydrochemistry of subway tunnel seepage. The results show that variations in the reducing conditions occur in urban groundwater, dependent upon the amount of organic matter-rich municipal sewage contaminating the aquifer. The organic matter facilitates the reduction and dissolution of Mn- and Fe-bearing solids in aquifers and/or tunnel construction materials, resulting in the successive increase of dissolved Mn and Fe. The present study clearly demonstrates that locally significant deterioration of urban groundwater is caused by a series of interlinked hydrogeologic and hydrochemical changes induced by underground tunnels.


Factors associated with patients' decision on colorectal cancer screening.
Cancer prevention and control are critical public health concerns. However, the screening uptake and referral rate for colorectal cancer (CRC) in Taiwan remain low. This study focused on the factors influencing whether a patient with a CRC diagnosis chooses to undergo referral follow-up.A cross-sectional research and used the Health Belief Model was method applied in this study. Variables such as demographic factors, CRC diagnosis-related knowledge factors, and health belief factors were employed to investigate the decisive factors that affect the health behavior of patients diagnosed with CRC who test positive on the fecal occult blood test. Study identified prospective participants in Daliao District, Kaohsiung City, Taiwan aged 50 to 75 years. A structured questionnaire was administered to the individuals, and 200 responded. The questionnaires of 100 who went for a referral group and 80 who did not a nonreferral group were analyzed. The questionnaire was reliable and valid, as determined through an expert evaluation and pretest, respectively.Among the 200 participants, T test indicated that those who underwent a referral were significantly more likely to be younger (Age [Mean ± SD] n: 62.7, 7.1%; Unreferred group: n: 65.1, 7.0%; Referred group: n:60.7, 6.6%; P ≤ .001), be more educated (P = .002), exercise more (P < .05), and have more family members with cancer (P = .001) or CRC (P < .05). Participants who underwent a referral also had significantly more knowledge (P < .001). Furthermore, those who underwent a referral had significantly perceived greater susceptibility (P < .05), greater benefits (P = .002), and lower barriers (P < .001) of screening; they also received greater encouragement to do so from sources (e.g., clinicians or the media) around them (P = .009).Age, education level, number of family members with cancer or CRC, exercise habits, knowledge of CRC, perceived susceptibility, perceived benefits, perceived barriers, and encouragement from others influence referral behavior. Government policy should focus on older patients and health education, especially in the mass media. Hospitals should also ensure the ease of referrals to lower perceived barriers.


A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1.
Phosphorylation of the human p53 protein at Ser-392 has been shown to be responsive to UV but not gamma irradiation. Here we describe identification and purification of a mammalian UV-activated protein kinase complex that phosphorylates Ser-392 of p53 in vitro. This kinase complex contains casein kinase 2 (CK2) and the chromatin transcriptional elongation factor FACT (a heterodimer of hSpt16 and SSRP1). In vitro studies show that FACT alters the specificity of CK2 in the complex such that it selectively phosphorylates p53 over other substrates including casein. In addition, phosphorylation by the kinase complex enhances p53 activity. These results thus provide a potential mechanism for p53 activation by UV irradiation.


Selective formation of a Z-trisubstituted double bond using a 1-(tert-butyl)tetrazolyl sulfone.
In our effort to gain further insight into the enantioselective synthesis of the structural core of phormidolides B and C, we have discovered the formation of a Z-trisubstituted double bond. Here, we describe a highly selective process that can be applied to our target following a strategy that is based on Julia-Kocienski olefination. The use of 1-(tert-butyl)tetrazolyl sulfone affords the construction of the Z-trisubstituted alkene with high efficiency and stereoselectivity.


PI3K mediated activation of GSK-3β reduces at-level primary afferent growth responses associated with excitotoxic spinal cord injury dysesthesias.
Neuropathic pain and sensory abnormalities are a debilitating secondary consequence of spinal cord injury (SCI). Maladaptive structural plasticity is gaining recognition for its role in contributing to the development of post SCI pain syndromes. We previously demonstrated that excitotoxic induced SCI dysesthesias are associated with enhanced dorsal root ganglia (DRG) neuronal outgrowth. Although glycogen synthase kinase-3β (GSK-3β) is a known intracellular regulator neuronal growth, the potential contribution to primary afferent growth responses following SCI are undefined. We hypothesized that SCI triggers inhibition of GSK-3β signaling resulting in enhanced DRG growth responses, and that PI3K mediated activation of GSK-3β can prevent this growth and the development of at-level pain syndromes. Excitotoxic SCI using intraspinal quisqualic acid (QUIS) resulted in inhibition of GSK-3β in the superficial spinal cord dorsal horn and adjacent DRG. Double immunofluorescent staining showed that GSK-3β(P) was expressed in DRG neurons, especially small nociceptive, CGRP and IB4-positive neurons. Intrathecal administration of a potent PI3-kinase inhibitor (LY294002), a known GSK-3β activator, significantly decreased GSK-3β(P) expression levels in the dorsal horn. QUIS injection resulted in early (3 days) and sustained (14 days) DRG neurite outgrowth of small and subsequently large fibers that was reduced with short term (3 days) administration of LY294002. Furthermore, LY294002 treatment initiated on the date of injury, prevented the development of overgrooming, a spontaneous at-level pain related dysesthesia. QUIS induced SCI resulted in inhibition of GSK-3β in primary afferents and enhanced at-level DRG intrinsic growth (neurite elongation and initiation). Early PI3K mediated activation of GSK-3β attenuated QUIS-induced DRG neurite outgrowth and prevented the development of at-level dysesthesias.


Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-specific Factors in Patient-centered Care.
Health equity considerations have not been incorporated into prior Canadian Rheumatology Association guidelines. Our objective was to identify the challenges and possible solutions to mitigate threats to health equity in rheumatoid arthritis (RA) care in Canada. A consultation process informed selection of priority populations, determined to be rural and remote, Indigenous, elderly with frailty, first-generation immigrant and refugee, low income and vulnerably housed, and diverse gender and sex populations. Semistructured interviews were completed with patients with lived experience, healthcare providers, and equity-oriented researchers. These interviews probed on population factors, initial and ongoing healthcare access issues, and therapeutic considerations influencing RA care. Known or proposed solutions to mitigate inequities during implementation of service models for the population group were requested. The research team used a phenomenological thematic analysis model and mapped the data into a logic model. Solutions applicable to several population groups were proposed. Thirty-five interviews were completed to identify realities for each population in accessing RA care. Five themes emerged as primary solutions to population-based inequities, including actively improving the patient-practitioner relationship, increasing accessibility and coordination of care through alternative models of care, upholding autonomy in treatment selection while actively addressing logistical barriers and individualized therapy needs, collaborating with health supports valued by the patient, and being advocates for policy change and health system restructuring to ensure appropriate resource redistribution. The challenges for populations facing inequities in rheumatology care and promising solutions should inform guideline development and implementation, policy change, and health system restructuring.


Physique, body composition and maximum oxygen consumption of selected soccer players of Kunimi High School, Nagasaki, Japan.
This study evaluates the physical and physiological ability of selected soccer players of Kunimi High School in Nagasaki Prefecture, Japan. The Kunimi team is famous for its intensive training, and had won the championship of the All Japan High School Soccer Tournament six times by 2003. We measured physique, body composition, and maximal oxygen uptake of 72 members aged between 16 and 18 years old between 1986 and 1994. They consisted of 66 outfield players (12 forward players, 23 midfielders, 31 defenders) and 6 goalkeepers. Body density was measured by the under-water weighing method, and Brozek's equation was applied to calculate percentage body fat (%Fat, %), fat-free mass (FFM, kg), FFM/height (FFM/Ht, kg.m(-1)), and FFM index (FFM/Ht(3), kg.m(-3)). The following results were obtained: 1. The average of 66 outfield players was 172.7 cm of height, 64.6 kg of weight, 54.0 cm of girth of thigh, and 90.0 cm of girth of hip, 9.3% of %Fat, 58.6 kg of FFM, 33.9 kg.m(-1) of FFM/Ht and 113.8 kg.m(-3) of FFM index. The mean vital capacity was 4.25 L and total lung capacity was 5.58 L. The mean maximal ventilation was 138.7 L.min(-1), VO(2)max was 3.95 L.min(-1), and VO(2)max/Wt was 61.4 ml.kg(-1).min(-1). 2. Goalkeepers were taller and heavier than outfielders, and had a smaller mean value of VO(2)max/Wt than outfielders (p<0.01). 3. For 23 out of the 72 players measured twice with an interval of about one year, FFM increased and %Fat reduced significantly, while V(E)max, VO(2)max and VO(2)max/Wt did not change. Kunimi players of the present study had as large a VO(2)max/Wt as local players, and a similar or slightly smaller VO(2)max/Wt than national-level players. They had similar %Fat and a similar VO(2)max/Wt with professional soccer players in England (Davis et al., 1992) while they had much smaller physiques.


Treading on the unknown-the feasibility of a novel approach to investigating the motor control of walking.
Walking is a complex human behavior, usually performed in a dynamic environment. Gait parameters are thought to reflect this complexity. Re-Step™ is a therapy system in the form of a computerized shoe, originally developed for the training and rehabilitation of individuals with brain damage. This system may be used as model for studying the complexity that underlies gait. As the first step, we present here the feasibility of the model, after establishing the validity and reliability of stride time and stride-time variability, observed in healthy adults. Fifteen healthy adults participated in this study. To establish concurrent validity, we had five participants walk with the Re-Step on a treadmill equipped with a force plate. To establish inter-rater reliability, we used data from ten participants who walked approximately 300 m with the system. Finally, the stride-time variability of perturbed and unperturbed walks was compared to establish the feasibility of the model. The correlation between the stride times observed with the treadmill and those observed with the Re-Step system was r = 0.971. The interclass correlation coefficient between left and right legs was 1.000 for stride time and 0.827 for its variability. A significant increase (mean difference 0.68%) in stride time variability was observed between unperturbed and perturbed walks. The results of this study suggest that stride-time measurements and variability observed in the Re-Step system are valid and reliable and that the model increases the challenge to the control system, thereby making Re-Step useful in the investigation of gait.


Prevalence and treatment of HIV/AIDS in Pakistani population: A retrospective study.
HIV/AIDS epidemic poses an emerging threat around the world. An estimated 0.1% of people aged 15 to 49 years have been infected with HIV/AIDS in Pakistan during the last few years. This research study aims to analyse the prevalence and treatment/management of HIV/AIDS among the Pakistani population aged 15 to 45 years from 1990 to 2020 and this research data was collected during the year 2021. The analysis was done by using E-views software. Descriptive statistical analysis, correlation coefficient, unit root analysis, and linear regression analysis were used. Results indicated that there is low awareness regarding AIDS in the population and there is a significant link between prevalence and population increase, i.e. with the increase in population the prevalence of AIDS also increases. Findings are discussed in terms of implications for prevention and education of HIV/AIDS in Pakistan's population.


[Abundance and seasonality of Diptera (Insecta) in a poultry house in the northeast region of the state of São Paulo, Brazil].
Modern production systems accommodate broody hens in high densities, leading to the accumulation of excrement under the cages. This substrate is excellent for the development of sinantropic flies. Thus, the accomplishment of surveys in these places becomes essential, in order to plan better strategies of control. The present work aimed at studying the entomofauna and the seasonality of the species of dipterous present in the Crisdan poultry house located in the Municipality of São João da Boa Vista, the State of São Paulo, Brazil. In the period of January of 2001 to December of 2002, 1,012,595 flies were captured using the "jug-trap". The species were identified: Drosophila repleta (Wollaston, 1858), Musca domestica (Linnaeus, 1758), Ophyra spp., Hermetria illucens (Linnaeus, 1758), Fannia canicularis (Linnaeus, 1761), Chrysomya megacephala (Fabricius, 1794), and Sepsidae. More frequently D. repleta and M. domestica had added 99.47% of the dipterous. Increased rainfall and the collection months influenced the sampling of dipterous (P<0.05). Drosophila repleta was the most abundant species, representing 91% of all captured flies. However, this diptera did not develop at the surveyed site since immatures were not captured therein.


Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain.
Diadenosine tetraphosphate (AP4A), an endogenous diadenosine polyphosphate, reduces ischemic injury in the heart. In this study, we report the potent and protective effects of AP4A in rodent models of stroke and Parkinson's disease. AP4A, given intracerebroventricularly before middle cerebral artery (MCA) ligation, reduced cerebral infarction size and enhanced locomotor activity in adult rats. The intravenous administration of AP4A also induced protection when given early after MCA ligation. AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochrome c and the increase in cytoplasmic caspase-3 activity in vivo. The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle injection of 6-hydroxydopamine (6-OHDA). One month after lesioning, vehicle-treated rats exhibited amphetamine-induced rotation. Minimal tyrosine hydroxylase immunoreactivity was detected in the lesioned nigra or striatum. No KCl-induced dopamine release was found in the lesioned striatum. All of these indices of dopaminergic degeneration were attenuated by pretreatment with AP4A. In addition, AP4A reduced TUNEL in the lesioned nigra 2 d after 6-OHDA administration. Collectively, our data suggest that AP4A is protective against neuronal injuries induced by ischemia or 6-OHDA through the inhibition of apoptosis. We propose that AP4A may be a potentially useful target molecule in the therapy of stroke and Parkinson's disease.


Clinical and procedural outcome of patients implanted with a quadripolar left ventricular lead: early results of a prospective multicenter study.
Recent studies suggest that cardiac resynchronization therapy (CRT) with a quadripolar left ventricular (LV) lead results in low rates of dislocation and phrenic nerve stimulation (PNS) acutely and at short-term follow-up. Confirmation of these results by long-term observational studies is needed. To evaluate the long-term procedural and clinical outcomes of CRT patients implanted with a quadripolar LV lead. A total of 154 consecutive heart failure patients (79% men, age 68 ± 10 years) having CRT implantation attempts with a quadripolar LV lead were included in this observational registry. Demographic and clinical data were preoperatively collected, and patients were followed up for at least 6 months. The overall implant success rate after coronary sinus cannulation was 97.4%. Mean overall duration and fluoroscopy time of successful procedures was 112 ± 22 and 16 ± 8 minutes, respectively, while 17 ± 13 minutes were necessary for the LV lead placement. After implant, the conventional bipolar configuration was used as the final pacing configuration in 33.3% of the patients. Four lead dislodgments (requiring reoperation) and 9 clinical PNS were reported during follow-up; reprogramming of the device was sufficient to prevent PNS in all patients. Once placed, the LV lead remained stable with excellent pacing thresholds during follow-up (15 ± 5 months). Overall, there were 71.3% CRT responders as assessed by 6-month echocardiography, and 66% improved at least 1 New York Heart Association class. Over the longer term, CRT with the quadripolar LV lead is associated with excellent pacing thresholds, low rates of dislocations, and PNS.


The oligosaccharide of human thrombin: investigations of functional significance.
Functional properties of the carbohydrate chain of human thrombin were examined by quantitating the activity of the enzyme before and after partial removal of its oligosaccharide by exoglycosidases. The following activities were studied: fibrinogen clotting, factor VIII coagulant (VIII:C) activation, inhibition by defibrinated plasma (anti-thrombin-III and alpha 2-macroglobulin), binding to polymerized fibrin, and stimulation of platelet release and aggregation. In general, the published information about the activity of native thrombin in these interactions was confirmed, though differences were observed in the association constants describing thrombin binding to fibrin. Partial deglycosylation had no apparent effect on any of these activities. It is concluded, therefore, that the oligosaccharide of human thrombin is located outside the major protein and platelet-binding regions of the molecule.


Changing perspectives on aging and energy requirements: aging and energy intakes in humans, dogs and cats.
A series of cross-sectional and longitudinal studies conducted in humans has shown that aging is associated with a gradual decline in the maintenance energy requirement. Generally, this is equivalent to a total decrement of 20% of young adult maintenance energy requirements and is a result of a decrease in both physical activity and basal metabolic rate. Relatively few such studies have been conducted in dogs, but the results have been consistent. It appears that maintenance energy requirements decline by approximately 20%, and it is assumed that the causal factors are the same as those for humans. The situation appears to be somewhat different in cats, with evidence to date indicating that maintenance energy requirements remain constant throughout adult life. Why cats should be different from other species is not clear, but it is hypothesized that relative inactivity is typical of most cats' behavior, such that there is no obvious age-related change. In terms of feeding regimens for senior cats and dogs, it is appropriate to decrease energy provision for senior dogs by approximately 20%, whereas the energy provision for senior cats should not be decreased.


A bioinformatics approach to investigating developmental pathways in the kidney and other tissues.
Over the past few years, large amounts of data linking gene-expression (GE) patterns and other genetic data with the development of the mouse kidney have been published, and the next task will be to integrate these data with the molecular networks responsible for the emergence of the kidney phenotype. This paper discusses how a start to this task can be made by using the kidney database and its associated search tools, and shows how the data generated by such an approach can be used as a guide to future experimentation. Many of the events taking place as the kidney develops do, of course, also take place in other tissues and organisms and it will soon be possible to incorporate relevant information from these systems into analyses of kidney data as well as the new information from microarray technology. The key to success here will be the ability to access over the internet data from the textual and graphical databases for the mouse and other organisms now being established. In order to do this, informatic tools will be needed that will allow a user working with one database to query another. This paper also considers both the types of tools that will be necessary and the databases on which they will operate.


Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo.
The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.


[Overview and update on treatment in ulcerative colitis].
Ulcerative colitis is characterized by a chronic intestinal inflammation limited to the mucosa of the colon, of variable proximal extent. Main symptoms are diarrhea, possibly bloody, and abdominal pain. It evolves with phases of relapse and remission. The diagnosis of ulcerative colitis is made based on clinical, endoscopic, and histologic findings. Currently, the various drug treatment options act by, among other things, reducing the activity of the immune system locally or systemically. In mild to moderate forms, 5-ASA remains the mainstay of both induction and maintenance treatment. In more severe flares, cortisone is the treatment of choice. To limit the prolonged/repeated intake of corticosteroids, there are several options of biologics with distinct ranges of action and safety profiles for inducing and/or maintaining remission. Therapeutic goals are evolving and go beyond achieving clinical remission. Endoscopic and histological remission are new targets to further improve quality of life and limit long-term complications, such as colorectal cancer.


Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma.
The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.


A microtubule-activated ATPase from sea urchin eggs, distinct from cytoplasmic dynein and kinesin.
We report an ATPase activity, present in sea urchin egg cytosol, that is activated by microtubules. The activity sediments at 10 S in sucrose gradients and is clearly distinct from activities at 12 S and 20 S due to cytoplasmic dynein. Potent activation of the ATPase is observed when endogenous egg tubulin is induced to assemble with taxol or when exogenous taxol-stabilized pure brain tubulin microtubules or flagellar outer-doublet microtubules are added. No activation by tubulin subunits or taxol alone is detectable. In contrast to flagellar or cytoplasmic dynein, the microtubule-activated enzyme is unaffected by vanadate or by nonionic detergents and hydrolyzes GTP in addition to ATP. In contrast to kinesin, it cosediments with microtubules in the presence or absence of ATP. The microtubule-activated enzyme may have a role in microtubule-based motility.


Transfer, elimination and accumulation of antibiotic resistance genes in decentralized household wastewater treatment facility treating total wastewater from residential complex.
The fate and behavior of antibiotic resistance genes (ARGs) in decentralized household wastewater treatment facilities (DHWWTFs) are unclear. In this study, targeting on a representative DHWWTF that receive all wastewater from a residential complex having 150 households, the transfer, elimination and accumulation of tetG, tetM, sul1, sul2 and intl1 were quantitively studied through real-time PCR-based quantification, mass balance evaluation and the existing state analysis based on size fractionation. Significant abundance changes of the genes were observed in involved biological reactions and the sedimentation process due to microbial growth and decomposition as well as the accumulation of the genes to sludge. tetG and sul1 increased in their fluxes against respective input in the influent. Although substantial portions of the increased genes were found in excess sludge compared to the flux of genes in the influent, those remaining in the discharge were still high, with an average about 3.4 × 1014 copies/d. The abundance of all four genes (tetG, tetM, sul1and sul2) in both water and sludge phases showed a general trend of reduction as sludge accumulated gradually in its storage tank within two months after desludging. Classification of ARGs based on particle sizes (>250 μm 125-250 μm, 75-125 μm, 25-75 μm, 3-25 μm, <3 μm) indicated that while the major part of ARGs were distributed in particles with larger sizes (125-250 μm), ARGs in smaller particles (3-25 μm) and free ARGs (<3 μm) still existed, which may pose a greater threat to water environment due to their poor settleability. The results of this study can benefit the optimization of on-site maintenance and operation of decentralized wastewater treatment facility for elimination of the transfer of ARGs.


Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells.
Recent studies have shown that high insulin-like growth factor I (IGF-I) blood level is a risk factor in breast and prostate cancer. The aim of this study was to determine whether the mitogenic activity of IGF-I in mammary cancer cells can be reduced by the dietary carotenoid lycopene. The anticancer activity of lycopene, the major tomato carotenoid, has been suggested by in vitro, in vivo, and epidemiological studies. Growth stimulation of MCF7 mammary cancer cells by IGF-I was markedly reduced by physiological concentrations of lycopene. The inhibitory effects of lycopene on MCF7 cell growth were not accompanied by apoptotic or necrotic cell death, as determined by annexin V binding to plasma membrane and propidium iodide staining of nuclei in unfixed cells. Lycopene treatment markedly reduced the IGF-I stimulation of tyrosine phosphorylation of insulin receptor substrate 1 and binding capacity of the AP-1 transcription complex. These effects were not associated with changes in the number or affinity of IGF-I receptors, but with an increase in membrane-associated IGF-binding proteins, which were previously shown in different cancer cells to negatively regulate IGF-I receptor activation. The inhibitory effect of lycopene on IGF signaling was associated with suppression of IGF-stimulated cell cycle progression of serum-starved, synchronized cells. Moreover, in cells synchronized by mimosine treatment, lycopene delayed cell cycle progression after release from the mimosine block. Collectively, the above data suggest that the inhibitory effects of lycopene on MCF7 cell growth are not due to the toxicity of the carotenoid but, rather, to interference in IGF-I receptor signaling and cell cycle progression.


Obsessive-Compulsive Disorder: Advances in Diagnosis and Treatment.
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with significant impairment and a lifetime prevalence of 1% to 3%; however, it is often missed in primary care settings and frequently undertreated. To review the most current data regarding screening, diagnosis, and treatment options for OCD. We searched PubMed, EMBASE, and PsycINFO to identify randomized controlled trials (RCTs), meta-analyses, and systematic reviews that addressed screening and diagnostic and treatment approaches for OCD among adults (≥18 years), published between January 1, 2011, and September 30, 2016. We subsequently searched references of retrieved articles for additional reports. Meta-analyses and systematic reviews were prioritized; case series and reports were included only for interventions for which RCTs were not available. Among 792 unique articles identified, 27 (11 RCTs, 11 systematic reviews or meta-analyses, and 5 reviews/guidelines) were selected for this review. The diagnosis of OCD was revised for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, which addresses OCD separately from anxiety disorders and contains specifiers to delineate the presence of tics and degree of insight. Treatment advances include increasing evidence to support the efficacy of online-based dissemination of cognitive behavioral therapies, which have demonstrated clinically significant decreases in OCD symptoms when conducted by trained therapists. Current evidence continues to support the use of selective serotonin reuptake inhibitors as first-line pharmacologic interventions for OCD; however, more recent data support the adjunctive use of neuroleptics, deep-brain stimulation, and neurosurgical ablation for treatment-resistant OCD. Preliminary data suggest safety of other agents (eg, riluzole, ketamine, memantine, N-acetylcysteine, lamotrigine, celecoxib, ondansetron) either in combination with selective serotonin reuptake inhibitors or as monotherapy in the treatment of OCD, although their efficacy has not yet been established. The dissemination of computer-based cognitive behavioral therapy and improved evidence supporting it represent a major advancement in treatment of OCD. Although cognitive behavioral therapy with or without selective serotonin reuptake inhibitors remains a preferred initial treatment strategy, increasing evidence that supports the safety and efficacy of neuroleptics and neuromodulatory approaches in treatment-resistant cases provides alternatives for patients whose condition does not respond to first-line interventions.


Illumination estimation via thin-plate spline interpolation.
Thin-plate spline interpolation is used to interpolate the chromaticity of the color of the incident scene illumination across a training set of images. Given the image of a scene under unknown illumination, the chromaticity of the scene illumination can be found from the interpolated function. The resulting illumination-estimation method can be used to provide color constancy under changing illumination conditions and automatic white balancing for digital cameras. A thin-plate spline interpolates over a nonuniformly sampled input space, which in this case is a training set of image thumbnails and associated illumination chromaticities. To reduce the size of the training set, incremental k medians are applied. Tests on real images demonstrate that the thin-plate spline method can estimate the color of the incident illumination quite accurately, and the proposed training set pruning significantly decreases the computation.