[Post-stroke depression: an experience in using cipramil].
Fifteen patients, 12 males, 3 females, aged 59.6 +/- 9.6 years, with depression after stroke, occurred 9 months--1 year and 3 months before, were treated with cipramil in dose 20 mg/day during 2.5 months. Control group comprised 10 patients matched for demographic and clinical characteristics and been not assigned to cipramil. All patients were fully examined by clinical methods, including computer tomography. Besides, for patient's state evaluation, Hamilton rating scale for depression and Lindmark scale for focal neurologic deficit measuring have been administered. The initial scores on these scales were 22.8 +/- 4.5 and 381.4 +/- 33.4 in the basic group and--22.2 +/- 6.3 and 390.6 +/- 29.8 in the controls, respectively. While cipramil using, an improvement was observed rather quickly--after 2-3 weeks, being stable during the whole treatment course. After treatment finishing, depression scores on Hamilton scale decreased to 15.8 +/- 5.2 (p < 0.001) in the basic group and did not change in the control one. The neurological deficit expression has not been changed. Side effects were mildly expressed in 20% of the patients. In one-third of the patients, antidepressant effect diminished in 1.5 months after treatment finishing. A need for longer antidepressant treatment of post stroke patients is discussed.


Foster family care review by judicial-citizen panels: an evaluation.
The findings of this study are mixed. In general, after one year of judicial-citizen review, there is no clear indication that this alternative to internal case review has led to more positive outcomes for children in foster care. This finding should be heartening to public child welfare agency personnel whose motivation for accountability has been called into question by proponents of external foster care review. At least when compared with a new citizen review system, the already existing internal review system measured up quite well. Although the study did not indicate a clear pattern of more positive outcomes for the study group, there is evidence of some favorable characteristics of CRPs that may show promise for the future. With additional training in developing behaviorally measurable and time-limited parental objectives, citizen panels may be able to maintain some of their initial strength in this area. Increased involvement of juvenile court judges in cases where little or no progress is made could motivate some parents to meet specified objectives and speed up the process of terminating parental rights when no progress has been demonstrated within specified time periods. The data also indicate a need for some adjustment to the process used to involve parents in case reviews. Another potentially positive outcome was highlighted during interviews with the juvenile court judges and the DFCS staff in the three study counties. Many of these respondents believed that the process had the potential for moving children out of foster care more quickly than does the internal review process. In addition to this primary goal, however, respondents were excited about the potential for heightened community awareness and education as citizens come to understand more about the plight of foster children and family conditions that can lead to placement. Interviews with panel members themselves indicated a definite belief that the community needed to accept more responsibility for children in foster care. One panel member's comment reflects the general sentiment expressed by other respondents: "These are kids we used to call 'those kids,' but now they are 'our kids'." It is hoped that the judicial-citizen review process will help to create a community environment in which needed resources can be developed both to prevent placement and to provide more support for families and children when placement occurs. This is the sentiment of the three juvenile court judges and almost all DFCS staff members who were interviewed, when they asserted that they felt the CRP process should be continued and expanded statewide.(ABSTRACT TRUNCATED AT 400 WORDS)


Predicting the host of influenza viruses based on the word vector.
Newly emerging influenza viruses continue to threaten public health. A rapid determination of the host range of newly discovered influenza viruses would assist in early assessment of their risk. Here, we attempted to predict the host of influenza viruses using the Support Vector Machine (SVM) classifier based on the word vector, a new representation and feature extraction method for biological sequences. The results show that the length of the word within the word vector, the sequence type (DNA or protein) and the species from which the sequences were derived for generating the word vector all influence the performance of models in predicting the host of influenza viruses. In nearly all cases, the models built on the surface proteins hemagglutinin (HA) and neuraminidase (NA) (or their genes) produced better results than internal influenza proteins (or their genes). The best performance was achieved when the model was built on the HA gene based on word vectors (words of three-letters long) generated from DNA sequences of the influenza virus. This results in accuracies of 99.7% for avian, 96.9% for human and 90.6% for swine influenza viruses. Compared to the method of sequence homology best-hit searches using the Basic Local Alignment Search Tool (BLAST), the word vector-based models still need further improvements in predicting the host of influenza A viruses.


Blended-ALMAMAR app for inpatient mental health care for refugees: study protocol for a multicenter implementation study within the I-REACH consortium (Internet based REfugee mentAl healtH Care).
Refugees are at high risk for developing mental illnesses. Due to language and cultural barriers, there is need for specifically adapted therapeutic procedures for refugees in inpatient mental health care settings. Internet-based applications in refugee mother tongues have the potential to improve the outcomes of mental health care for this vulnerable population. The key research question of the present implementation study is whether the newly developed "blended ALMAMAR" app for Arabic and Farsi speaking refugees in Germany is used and accepted by patients and professionals in routine inpatient mental health care (blended care). We present the design of an observational, prospective multicenter implementation study in eight psychiatric hospitals. We plan to recruit 100 Farsi or Arabic speaking refugees receiving in-patient treatment due to depression, anxiety disorder, posttraumatic stress disorder or substance use disorders. These patients will get access to the "blended ALMAMAR" app during their inpatient stay in a blended-care approach. We will assess the usage (e.g., duration and frequency of use of the app) as well as subjective acceptability and usability of the intervention. To identify sociodemographic and clinical factors associated with "blended ALMAMAR" usage, we will also perform clinical and questionnaire assessments. The newly developed "blended ALMAMAR" app may help to close communication gaps for the hard-to reach and vulnerable group of refugees in inpatient mental health care. It is the first blended-care intervention that addresses severely mentally ill refugees in an inpatient psychiatric setting in Germany. The trial was registered in the German Clinical Trials Register on November 11, 2021 (DRKS00025972) and adapted on November 14, 2023.


HORMONOMETER: a tool for discerning transcript signatures of hormone action in the Arabidopsis transcriptome.
Plant hormones regulate growth and responses to environmental change. Hormone action ultimately modifies cellular physiological processes and gene activity. To facilitate transcriptome evaluation of novel mutants and environmental responses, there is a need to rapidly assess the possible contribution of hormone action to changes in the levels of gene transcripts. We developed a vector-based algorithm that rapidly compares lists of transcripts yielding correlation values. The application as described here, called HORMONOMETER, was used to analyze hormone-related activity in a transcriptome of Arabidopsis (Arabidopsis thaliana). The veracity of the resultant analysis was established by comparison with cognate and noncognate hormone transcriptomes as well as with mutants and selected plant-environment interactions. The HORMONOMETER accurately predicted correlations between hormone action and biosynthetic mutants for which transcriptome data are available. A high degree of correlation was detected between many hormones, particularly at early time points of hormone action. Unforeseen complexity was detected in the analysis of mutants and in plant-herbivore interactions. The HORMONOMETER provides a diagnostic tool for evaluating the physiological state of being of the plant from the point of view of transcripts regulated by hormones and yields biological insight into the multiple response components that enable plant adaptation to the environment. A Web-based interface has been developed to facilitate external interfacing with this platform.


Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats.
We investigated the effects of a selective beta(2)-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (ZL) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to ZL spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.


HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes.
HOXA10 is necessary for embryonic patterning of skeletal elements, but its function in bone formation beyond this early developmental stage is unknown. Here we show that HOXA10 contributes to osteogenic lineage determination through activation of Runx2 and directly regulates osteoblastic phenotypic genes. In response to bone morphogenic protein BMP2, Hoxa10 is rapidly induced and functions to activate the Runx2 transcription factor essential for bone formation. A functional element with the Hox core motif was characterized for the bone-related Runx2 P1 promoter. HOXA10 also activates other osteogenic genes, including the alkaline phosphatase, osteocalcin, and bone sialoprotein genes, and temporally associates with these target gene promoters during stages of osteoblast differentiation prior to the recruitment of RUNX2. Exogenous expression and small interfering RNA knockdown studies establish that HOXA10 mediates chromatin hyperacetylation and trimethyl histone K4 (H3K4) methylation of these genes, correlating to active transcription. HOXA10 therefore contributes to early expression of osteogenic genes through chromatin remodeling. Importantly, HOXA10 can induce osteoblast genes in Runx2 null cells, providing evidence for a direct role in mediating osteoblast differentiation independent of RUNX2. We propose that HOXA10 activates RUNX2 in mesenchymal cells, contributing to the onset of osteogenesis, and that HOXA10 subsequently supports bone formation by direct regulation of osteoblast phenotypic genes.


Synchronous Endometrial Cancer Detected on 68 Ga-DOTATATE PET/CT.
A 50-year-old woman with history of metastatic neuroendocrine tumor underwent a follow-up PET/CT with 68 Ga-DOTATATE. An enlarged uterus with diffuse increased uptake warranted further investigation with an MRI that showed mass-like thickening of the endometrium, T2 hyperintensity, lobulated contour, and invasion of more than 50% of the myometrium. Biopsy revealed endometrial carcinoma with mucinous features. Mild to moderate uptake of the 68 Ga-DOTATATE by the uterus can be a normal physiological finding; however, it should prompt further investigation, particularly in a postmenopausal woman with concerning imaging or clinical findings.


Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats.
Heat shock proteins (Hsps), induced by cell stress, are known to protect against cellular injury. Recent studies have indicated that Hsp60 expression, induced by exposure to water immersion stress, protects against pancreatitis induced by administration of supramaximal doses of cerulein in rats. However, the mechanisms responsible for this protection are not known. Rats were water-immersed for 3-12 hours. Pancreatitis was induced by cerulein administration. The results confirm that prior induction of Hsp60 expression by water-immersion stress significantly ameliorates the severity of cerulein-induced pancreatitis as judged by the markedly reduced degree of hyperamylasemia, pancreatic edema, and acinar cell necrosis. Water immersion also prevents the subcellular redistribution of cathepsin B from a lysosome-enriched fraction to a heavier, zymogen granule-enriched fraction that is known to occur in this model of pancreatitis. Intra-acinar cell activation of trypsinogen that occurs shortly after exposure to a supramaximally stimulating dose of cerulein both in vivo and in vitro is prevented by prior water-immersion stress and Hsp60 expression. The protection against pancreatitis that follows water-immersion stress is not caused by alterations of cholecystokinin receptors, because water immersion does not alter the typical biphasic amylase secretory response to stimulation with cerulein. Water-immersion stress induces Hsp60 expression, ameliorates cerulein-induced pancreatitis, and prevents intra-acinar cell activation of trypsinogen. We suggest that Hsp60 protects against cerulein-induced pancreatitis by preventing trypsinogen activation within acinar cells.


Maize dependence or market integration? Caries prevalence among indigenous Maya communities with maize-based versus globalized economies.
The relationship between diet and oral health is widely known, yet data on dental caries prevalence is lacking for many indigenous groups with traditional or rapidly modernizing diets. This research documents caries prevalence in two Maya communities from northern Yucatán (Mexico) with significantly different levels of market integration, subsistence, and diet: Yalsihón, with a traditional, maize-based subsistence economy, and Dzilam, with access to globalized food markets. Each sample was subdivided by sex into 15-19, 20-24, and 25-30 years-of-age classes. Caries prevalence was considered separately both when the lesion affected the enamel superficially (grade 1+) and when it reached the dentin (grade 2+). In both villages, females of all age classes manifest more caries than males. Results show higher prevalence of caries at Dzilam than at Yalsihón, except for grade 1+ caries among 15-19-year-old males and grade 2+ caries among 15-19-year-old females. Though differences are not significant, earlier pregnancies among 15-19-year-old females at Yalsihón could be a causative factor. A survey indicated a more balanced diet at Yalsihón despite a heavier intake of maize than at Dzilam. Striking differences were documented in the ingestion of soda and globalized foods; sodas were virtually absent at Yalsihón, while at Dzilam they were ingested daily in great quantities. The decline in oral health at Dzilam is inferred to result from consumption of industrially processed foods and drinks, while a traditional diet leads to less caries despite daily heavy consumption of maize, which must be considered when interpreting caries rates in archaeological samples.


Technology evaluation: Valspodar, Novartis AG.
Valspodar (PSC-833) is a derivative of cyclosporin but devoid of the immunosuppressive and nephrotoxic properties seen in cyclosporin A. It exhibited high affinity binding to Mdr1 P-glycoprotein (P-gp) and demonstrated multidrug resistance-reversing activity superior to cyclosporin A and verapamil both in vitro and in vivo. Preclinical and phase I/II clinical data have indicated that plasma levels of PSC-833 with multidrug resistance-reversing activities are achievable. Potent inhibition of intestinal, hepatobiliary and blood-brain barrier P-gp function has been demonstrated. Since valspodar is also a substrate of cytochrome P450 3A (CYP3A), dual interactions of this compound with P-gp and CYP3A are the basis for the pharmacokinetic interactions seen in preclinical and clinical studies. A new formulation of the drug has recently been developed with better oral bioavailability (60%) and less interindividual variability. The toxicity profiles of valspodar are acceptable and dose-limited by transient and reversible cerebellar ataxia. It has shown multidrug resistance-modulating activities towards acute myeloid leukemia, multiple myeloma and ovarian cancer in phase I/II clinical trials. Phase III studies with respect to these three diseases are ongoing.


Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis.
RNA interference (RNAi) can achieve sequence-selective inactivation of gene expression in a wide variety of eukaryotes by introducing double-stranded RNA corresponding to the target gene. Here we explore the potential of RNAi as a therapy for amyotrophic lateral sclerosis (ALS) caused by mutations in the Cu, Zn superoxide dismutase (SOD1) gene. Although the mutant SOD1 is toxic, the wild-type SOD1 performs important functions. Therefore, the ideal therapeutic strategy should be to selectively inhibit the mutant, but not the wild-type SOD1 expression. Because most SOD1 mutations are single nucleotide changes, to selectively silence the mutant requires single-nucleotide specificity. By coupling rational design of small interfering RNAs (siRNAs) with their validation in RNAi reactions in vitro and in vivo, we have identified siRNA sequences with this specificity. A similarly designed sequence, when expressed as small hairpin RNA (shRNA) under the control of an RNA polymerase III (pol III) promoter, retains the single-nucleotide specificity. Thus, RNAi is a promising therapy for ALS and other disorders caused by dominant, gain-of-function gene mutations.


Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice.
Clara cell secretory protein (CCSP) is an abundant component of the extracellular lining fluid of airways. Even though the in vivo function of CCSP is unknown, in vitro studies support a potential role of CCSP in the control of inflammatory responses. CCSP-deficient mice (CCSP -/-) were generated to investigate the in vivo function of this protein (13). In this study, we used hyperoxia exposure as a model to investigate phenotypic consequences of CCSP deficiency following acute lung injury. The pathologic response of the mouse lung to hyperoxia, and recovery of the lung, include inflammatory cell infiltrate and edema. Continuous exposure to > 95% O2 was associated with significantly reduced survival time among CCSP -/- mice as compared with strain-, age-, and sex-matched wild-type control mice. Differences in survival were associated with early onset of lung edema in CCSP -/- mice as compared with wild-type controls. To further investigate these differences in response, mice were exposed to > 95% O2 for either 48 h or 68 h with one group receiving 68 h of hyperoxia followed by room-air recovery. Lung RNA was characterized for changes in the abundance of cytokine messenger RNA (mRNA) using a ribonuclease (RNase) protection assay. After 68 h of hyperoxia, interleukin-6 (IL-6), IL-1beta, and IL-3 mRNAs were 14-, 3-, and 2.5-fold higher, respectively, in CCSP -/- mice than in similarly exposed wild-type control mice. Increased expression of IL-1beta mRNA in hyperoxia-exposed CCSP -/- mice was localized principally within the lung parenchyma, suggesting that the effects of CCSP deficiency were not confined to the airway epithelium. We conclude that CCSP deficiency results in increased sensitivity to hyperoxia-induced lung injury as measured by increased mortality, early onset of lung edema, and induction of proinflammatory cytokine mRNAs.


Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation.
Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.


The urban wage premium is disappearing in U.S. micropolitan areas.
A key driver of urbanization is the pursuit of economic opportunities in cities. One such opportunity is the promise of higher wages in larger cities, a phenomenon known as the urban wage premium. While an urban wage premium has been well-documented among U.S. metropolitan areas, little is known about its existence in micropolitan areas, which represent an important link between rural and dense urban areas. Here we measure the power law scaling coefficient of annual wages versus employment for both U.S. metropolitan and micropolitan areas over a 37-year period. We take this coefficient to be a quantification of the urban wage premium for each type of urban area and find the relationship is superlinear in all years for both area types. Though both area types once had wage premiums of similar magnitude, the wage premium in micropolitan areas has steadily declined since the late 1980s while in metropolitan areas it has generally increased. This growing gap between micropolitan and metropolitan wage premiums is ongoing in parallel to other diverging characteristics, such as inequality and voting behavior, suggesting that our result is part of a broader social, cultural, and political divergence between small and large cities. Finally, we speculate that if urban residents respond to the COVID-19 crisis by migrating, the trends we describe may change significantly.


Advances in molecular genetics of alpha-2- and alpha-3/4-fucosyltransferases.
Fucosyltransferases are involved in the last steps of the biosynthesis of ABH and Lewis oligosaccharide antigens. Seven human genes (FUT1 to FUT7) and one pseudogene (Sec 1) have been cloned and localized on different chromosomes (9q34.3; 11q21; 19p13.3 and 19q13.3). Their locations and their high degree of primary sequence identity, suggest that they have appeared by successive duplications followed by translocation and divergent evolution. Their expression is tissue specific and they present a switch during human embryo-foetal development similar to that of hemoglobins. Polymorphic genes FUT1-FUT2 and FUT3-FUT5-FUT6 are organized in two clusters and each gene is partially or totally inactivated by different types of point mutations (nonsense, missense and frame shift), complete gene deletion or a fusion gene. The products of the monomorphic genes FUT4 and FUT7 seem implicated in cell-cell interactions during embryo-foetal development and in the leukocyte adhesion phenomena to endothelial cells in the adult. A phylogenetic tree of the 28 available nucleotide coding sequences of fucosyltransferases has allowed us to situate the duplication events with respect to the separation of species from the main evolutionary path (nematods, birds, mammals, primates and humans). Recently, using a computer approach a general structure of fucosyltransferases has been proposed, inspired from the crystalline structure of the beta-glucosyltransferase of bacteriophage T4. This folding contains two domains with an alternate succession alpha and beta chains. In this model the GDP-fucose binding site would be located between the two domains.


Preparation of cell blocks for lung cancer diagnosis and prediction: protocol and experience of a high-volume center.
Minimally invasive diagnostic techniques are increasingly being used to obtain specimens for pathological diagnosis and prediction. Referring to lung cancer, both endobronchial and endoesophageal ultrasound are used worldwide as diagnostic routine methods. Consequently, an increasing number of pathological samples are cytological and fewer are histological. On the other hand, the requirements for specific and sensitive tumor subtyping complemented by predictive analyses are steadily increasing and are an essential basis for evidence-based treatment decisions. In this article we focus on the cell block method as a helpful tool for diagnostic and predictive analyses in lung cancer and point out its advantages and disadvantages in comparison to conventional cytological and biopsy specimens. Furthermore, we retrospectively analyze the diagnostic results of the cell block method in a high-volume center over 5 years. The main advantages of cell blocks are the availability of established and validated protocols, archiving and the opportunity to have serial sections from the same specimens to provide or repeat molecular analyses. Actually, in case of tumor progression, even additional biomarkers can be tested using the original cell block when re-biopsies are not feasible. The cell block method should be considered as a reliable, complimentary approach to conventional cytological or biopsy procedures, which is helpful to fulfill the increasing requirements of high-quality diagnostics and prediction.


Distinct microRNAs expression profile in primary biliary cirrhosis and evaluation of miR 505-3p and miR197-3p as novel biomarkers.
MicroRNAs are small endogenous RNA molecules with specific expression patterns that can serve as biomarkers for numerous diseases. However, little is known about the expression profile of serum miRNAs in PBC. First, we employed Illumina deep sequencing for the initial screening to indicate the read numbers of miRNA expression in 10 PBC, 5 CH-C, 5 CH-B patients and 5 healthy controls. Comparing the differentially expressed miRNAs in the 4 groups, analysis of variance was performed on the number of sequence reads to evaluate the statistical significance. Hierarchical clustering was performed using an R platform and we have found candidates for specific miRNAs in the PBC patients. Second, a quantitative reverse transcription PCR validation study was conducted in 10 samples in each group. The expression levels of the selected miRNAs were presented as fold-changes (2(-ΔΔCt)). Finally, computer analysis was conducted to predict target genes and biological functions with MiRror 2.0 and DAVID v6.7. We obtained about 12 million 32-mer short RNA reads on average per sample and the mapping rates to miRBase were 16.60% and 81.66% to hg19. In the statistical significance testing, the expression levels of 81 miRNAs were found to be differentially expressed in the 4 groups. The heat map and hierarchical clustering demonstrated that the miRNA profiles from PBC clustered with those of CH-B, CH-C and healthy controls. Additionally, the circulating levels of hsa-miR-505-3p, 197-3p, and 500a-3p were significantly decreased in PBC compared with healthy controls and the expression levels of hsa-miR-505-3p, 139-5p and 197-3p were significantly reduced compared with the viral hepatitis group. Our results indicate that sera from patients with PBC have a unique miRNA expression profile and that the down-regulated expression of hsa-miR-505-3p and miR-197-3p can serve as clinical biomarkers of PBC.


Impact of robotic dispensing machines in german pharmacies on business performance indicators.
To assess the impact of robotic dispensing machines in community pharmacies on staff efficiency and sales of over-the-counter drugs. The study was done on 253 community pharmacies in Germany that use a robotic dispensing machine manufactured by ROWA during 2008. Data concerning the financial and economic impact of using a robotic dispensing machine in community pharmacies was gathered using a structured questionnaire and analysed in terms of its financial implications. The response rate was 29%. In most pharmacies (79%) the robotic dispensing machine was retrofitted. In 59% of the pharmacies additional space was gained for self-service and behind-the-counter display. As a result of using a robotic dispensing machine, personnel costs were reduced by an average of 4.6% during the first 12 months after start-up. Over-the-counter sales increased in the same period by an average of 6.8%. Despite average initial costs of 118,000 euros, total costs within the first 12 months fell in 50% of cases and at least remained the same in 44%. On average, robotic dispensing machines lead to modest savings in personnel costs and slight increases in sales of over-the-counter drugs. Substantial savings can be achieved only if the staffing level is adapted to the changed personnel requirements.


Key Topics in Molecular Docking for Drug Design.
Molecular docking has been widely employed as a fast and inexpensive technique in the past decades, both in academic and industrial settings. Although this discipline has now had enough time to consolidate, many aspects remain challenging and there is still not a straightforward and accurate route to readily pinpoint true ligands among a set of molecules, nor to identify with precision the correct ligand conformation within the binding pocket of a given target molecule. Nevertheless, new approaches continue to be developed and the volume of published works grows at a rapid pace. In this review, we present an overview of the method and attempt to summarise recent developments regarding four main aspects of molecular docking approaches: (i) the available benchmarking sets, highlighting their advantages and caveats, (ii) the advances in consensus methods, (iii) recent algorithms and applications using fragment-based approaches, and (iv) the use of machine learning algorithms in molecular docking. These recent developments incrementally contribute to an increase in accuracy and are expected, given time, and together with advances in computing power and hardware capability, to eventually accomplish the full potential of this area.


Brain tumor surgery with 3-dimensional surface navigation.
Precise lesion localization is necessary for neurosurgical procedures not only during the operative approach, but also during the preoperative planning phase. To evaluate the advantages of 3-dimensional (3-D) brain surface visualization over conventional 2-dimensional (2-D) magnetic resonance images for surgical planning and intraoperative guidance in brain tumor surgery. Preoperative 3-D brain surface visualization was performed with neurosurgical planning software in 77 cases (58 gliomas, 7 cavernomas, 6 meningiomas, and 6 metastasis). Direct intraoperative navigation on the 3-D brain surface was additionally performed in the last 20 cases with a neurosurgical navigation system. For brain surface reconstruction, patient-specific anatomy was obtained from MR imaging and brain volume was extracted with skull stripping or watershed algorithms, respectively. Three-dimensional visualization was performed by direct volume rendering in both systems. To assess the value of 3-D brain surface visualization for topographic lesion localization, a multiple-choice test was developed. To assess accuracy and reliability of 3-D brain surface visualization for intraoperative orientation, we topographically correlated superficial vessels and gyral anatomy on 3-D brain models with intraoperative images. The rate of correct lesion localization with 3-D was significantly higher (P = .001, χ), while being significantly less time consuming (P < .001, χ) compared with 2-D images. Intraoperatively, visual correlation was found between the 3-D images, superficial vessels, and gyral anatomy. The proposed method of 3-D brain surface visualization is fast, clinically reliable for preoperative anatomic lesion localization and patient-specific planning, and, together with navigation, improves intraoperative orientation in brain tumor surgery and is relatively independent of brain shift.


p53 Promotes cell survival due to the reversibility of its cell-cycle checkpoints.
The tumor suppressor p53 (TP53) has a well-studied role in triggering cell-cycle checkpoint in response to DNA damage. Previous studies have suggested that functional p53 enhances chemosensitivity. In contrast, data are presented to show that p53 can be required for cell survival following DNA damage due to activation of reversible cell-cycle checkpoints. The cellular outcome to DNA damage is determined by the duration and extent of the stimulus in a p53-dependent manner. In response to transient or low levels of DNA damage, p53 triggers a reversible G2 arrest, whereas a sustained p53-dependent cell-cycle arrest and senescence follows prolonged or high levels of DNA damage. Regardless of the length of treatment, p53-null cells arrest in G2, but ultimately adapt and proceed into mitosis. Interestingly, they fail to undergo cytokinesis, become multinucleated, and then die from apoptosis. Upon transient treatment with DNA-damaging agents, wild-type p53 cells reversibly arrest and repair the damage, whereas p53-null cells fail to do so and die. These data indicate that p53 can promote cell survival by inducing reversible cell-cycle arrest, thereby allowing for DNA repair. Thus, transient treatments may exploit differences between wild-type p53 and p53-null cells. Although p53 status has been suggested as a clinical predictor of chemotherapeutic efficacy, studies to date have not always supported this. This study demonstrates that p53 is still an important determinant of cell fate in response to chemotherapy, under the appropriate treatment conditions.


Dynamics of water in conical solvation shells around a benzene solute under different thermodynamic conditions.
Water molecules in different parts of the anisotropic hydration shell of an aromatic molecule experience different interactions. In the present study, we investigate the anisotropic dynamics of water molecules in different non-overlapping conical shells around a benzene solute at sub- and supercritical conditions by means of molecular dynamics simulations using both non-polarizable and polarizable models. In addition to the dynamical properties, the effects of polarizability on the hydration structure of benzene at varying thermodynamic conditions are also investigated in the current study. The presence of πH-bonding in the solvation shell is found to be an important factor that influences the anisotropic dynamics of the benzene hydration shell. The water molecules located axial to the benzene plane are found to be maximally influenced by the πH-bonding. The extent of πH-bonding is found to be somewhat reduced on inclusion of polarizability. The πH-bonded water molecules are found to reorient through large-amplitude angular jumps where the jump-angle amplitude increases at higher temperatures and lower densities. For both non-polarizable and polarizable models, it is found that the water molecules in the axial conical shells possess faster orientational and hydrogen bond dynamics compared to those in the equatorial plane. Water molecules in the axial conical shells are also found to diffuse at a faster rate than bulk molecules due to the relatively weaker benzene-water πH-bonding interactions in the axial region of the hydration shell. The residence dynamics of water molecules in different conical solvation shells around the solute is also investigated in the current study.


Interventions Within the Scope of Occupational Therapy to Improve Activities of Daily Living, Rest, and Sleep in People With Parkinson's Disease: A Systematic Review.
People with Parkinson's disease (PD) commonly experience difficulty in performing activities of daily living (ADLs), which affects their perceived quality of life. To examine the evidence for the effectiveness of interventions within the scope of occupational therapy to improve performance and participation in ADLs, rest, and sleep in adults with PD. Databases searched were MEDLINE, PsycINFO, CINAHL, OTseeker, and Cochrane Collection. Included articles were published between January 2011 and December 2018. Study Selection and Data Collection: Articles describing Level 1b, 2b, and 3b studies that examined outcomes related to ADLs, rest, and sleep in people with PD were included following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Forty-five articles (10 Level 1b, 27 Level 2b, and 8 Level 3b) met the inclusion criteria. Strong strength of evidence was found to support inpatient multidisciplinary intensive rehabilitation treatment (MIRT) to improve ADLs, and moderate strength of evidence that MIRT improves sleep performance. Low strength of evidence was present for outpatient occupational therapy to improve ADL and sleep outcomes. Low strength of evidence was found for resistance exercise programs to improve ADLs, but moderate strength of evidence indicates that multimodal exercise programs and targeted exercise programs can improve ADLs. Low to moderate strength of evidence suggested that alternative therapies and cognitive-behavioral therapy have a positive impact on ADLs and sleep. These results can be used to inform evidence-based occupational therapy practice. What This Article Adds: This article provides information for practitioners on the effectiveness of interventions within the scope of occupational therapy practice to improve ADLs and sleep.


[Incidence of endogenous uveitis at Kyushu University Hospital].
We performed a clinical statistical study on recent patients with endogenous uveitis at the clinic of the Department of Ophthalmology, Kyushu University Hospital. We studied 616 patients with endogenous uveitis who first visited the clinic of the Department of Ophthalmology, Kyushu University Hospital, between January 1996 and December 2001. The most frequent clinical entity was sarcoidosis (8.6%), followed by Behçet's disease (8.4%), Vogt-Koyanagi-Harada syndrome (6.5%), human T-lymphotropic virus type I (HTLV-1) uveitis (3.9%), and toxoplasmosis (2.6%). Unclassified uveitis comprised 58.1% in our study. Next we classified the subjects into four age groups; adolescent (0-19 years old), young (20-39 years old), middle-aged (40-59 years old), and elderly (60-years old). We also classified the disease into four groups: uveitis pan, anterior, intermediate, and posterior uveitis, according to the site of inflammation. The most frequent clinical entity was Behçet's disease in the young group, and sarcoidosis in the elderly group. The frequency of unclassified uveitis was high in the adolescent and the elderly groups. As to the anatomic diagnosis of uveitis, panuveitis was most frequent, followed by anterior, posterior, and intermediate uveitis. Finally we investigated the frequency of secondary glaucoma. The frequency in all 616 patients was 19.7%. Secondary glaucoma was more frequent in male patients and more frequent in the middle-aged and the elderly groups.


The association between lower limb biomechanics and ball release speed in cricket fast bowlers: a comparison of high-performance and amateur competitors.
The aim of this study was to compare the associations between lower limb biomechanics and ball release speed in 15 high-performance (HP) and 15 amateur fast bowlers. Kinematic and kinetic variables of the lower limbs collected in the laboratory environment with a 3D Vicon motion analysis system were compared between groups, as well as their associations with ball release speed. HP bowlers had a significantly higher run-up velocity at back foot impact but this difference became non-significant at ball release. Front knee kinematics were not statistically different, however effect sizes revealed medium-large differences with the HP group displaying a more extended knee joint at maximum flexion (d = 0.72) and ball release (d = 0.76). Only front hip positive power was significantly higher in the HP group and it was suggested that the probable cause was the HP bowlers having less knee flexion after front foot impact. From a joint power analysis, the extensor muscle groups of the hip and knee were shown to be important in developing ball release speed. This highlights the need for lower limb/core strength programmes to be multifaceted and focus on the muscles associated with both power and stability.


Familiarity or conceptual priming: event-related potentials in name recognition.
Recent interest has been drawn to the separate components of recognition memory, as studied by event-related potentials (ERPs). In ERPs, recollection is usually accompanied by a late, parietal positive deflection. An earlier, frontal component has been suggested to be a counterpart, accompanying recognition by familiarity. However, this component, the FN400, has alternatively been suggested to reflect a form of implicit memory, conceptual priming. The present study examined the ERP components of recognition memory using an episodic memory task with a stimulus material consisting of names, half of which were famous. Along a different dimension, the names varied in how rare or common they were. These dimensions, frequency and fame, exerted powerful effects on memory accuracy, and dissociated the two recognition processes, such that frequency gave rise to familiarity and fame fostered recollection, when the receiver operating characteristics data were analyzed with Yonelinas' dual-process signal detection model. The ERPs corresponded fully to the behavioral data because frequency affected the frontal component exclusively, and fame affected the parietal component exclusively. Moreover, a separate behavioral experiment showed that conceptual priming was sensitive to fame, but not to frequency. Our data therefore indicate that the FN400 varies jointly with familiarity, but independently of conceptual priming.


Aberrometry Repeatability and Agreement with Autorefraction.
Commercially available aberrometers are essential to clinical studies evaluating refractive error and image quality. The Discovery System (Innovative Visual Systems, Elmhurst, IL) is a promising clinical instrument that allows investigators to export aberration data for research and analysis purposes. An assessment of the Discovery System's performance is essential to the interpretation of the data obtained. The aims of this study were to determine the between-visit repeatability of refractive error and higher-order aberration measurements with the Discovery System and to examine between-instrument agreement of refractive error measurements with the Discovery System and Grand Seiko WAM-5500 open-field autorefractor (Grand Seiko Co., Hiroshima, Japan). Cycloplegic refractive error values from the Discovery System (over a 3-mm pupil) and the Grand Seiko autorefractor were converted to power vectors (M, J0, and J45), and averaged. Zernike coefficients were also calculated by the Discovery System over a 6-mm pupil through the sixth radial order. Between-visit repeatability and agreement were evaluated using Bland-Altman difference-versus-mean plots. A t-test compared each mean difference (bias) to zero, and the 95% limits of agreement were calculated. Twenty-five young adults with a mean (±SD) cycloplegic spherical-equivalent refractive error of -2.91 ± 1.85 diopters (D) (range, -6.96 to +0.74 D) were enrolled. There were no significant between-visit differences with the Discovery System for M, J0, J45, third- through sixth-order root mean square (RMS), higher-order RMS, or spherical aberration (all P > .30), and the repeatability for defocus and higher-order RMS were ±0.31 D and ±0.095 μm, respectively, for a 6-mm pupil. At a 3-mm pupil, the Discovery System, on average, measured slightly more positive values than the Grand Seiko for M (0.28 D), J0 (0.11 D), and J45 (0.12 D; all P < .005). The Discovery System was very repeatable and would be an appropriate instrument to measure cycloplegic refractive error and higher-order aberration changes in adults. Small differences in refractive error were found between the Discovery System and Grand Seiko.


Prevalence of plasmid-mediated quinolone resistance genes among ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from blood cultures in Korea.
To analyze the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants in ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from patients at a tertiary care hospital in Korea. A total of 102 nonduplicate isolates of ciprofloxacin-intermediate or ciprofloxacin-resistant E coli (n=80) and K pneumoniae (n=22) from blood cultures were obtained. The qnr (qnrA, qnrB, qnrS), aac(6')-Ib-cr, qepA and oqxAB genes were detected using polymerase chain reaction (PCR) and confirmed using direct sequencing. To determine whether the PMQR-positive plasmid was horizontally transferable, conjugation experiments were performed. Of the 102 isolates, 81 (79.4%) had one or more PMQR genes; these consisted of 59 (73.8%) E coli and 22 (100%) K pneumoniae isolates. The qnr genes were present in 15 isolates (14.7%): qnrB4 was detected in 10.8% and qnrS1 was detected in 3.9%. The aac(6')-Ib-cr, qepA and oqxAB genes were detected in 77.5%, 3.9% and 10.8%, respectively. In conjugation experiments, PMQR genes were successfully transferred from seven (8.6%) isolates. The range of minimum inhibitory concentrations of ciprofloxacin for these seven transconjugants increased to 0.5 mg/L to 1 mg/L, which was 16- to 33-fold that of the recipient E coli J53 bacteria. PMQR genes were highly prevalent among ciprofloxacin-nonsusceptible E coli and K pneumoniae from blood cultures in the authors' hospital. Therefore, it is necessary to monitor for the spread of PMQR genes of clinical isolates and to ensure careful antibiotic use in a hospital setting.


Arsenic removal from groundwater by a newly developed adsorbent.
A novel adsorbent, which had been developed for phosphate adsorption, was adopted for arsenic removal from groundwater. Adsorption isotherm, pH dependence of the isotherm and adsorption rate were studied by batch method. Furthermore, by using a granular adsorbent of 1.8 mm diameter which is commercially available, lab-scale experiments of continuous adsorption treatment of actual groundwater containing arsenic at 50 mg m(-3) were conducted to examine the performance of the adsorbent. A large amount of arsenic, i.e., 10 g As kg(-1), was adsorbed at pH 7.0 and 10 mg As m(-3) in equilibrium concentration. It was only a 5% higher amount compared to conventional activated alumina. However, twice the bed volume, i.e., total volume of effluent divided by empty column volume, was achieved till breakthrough by using this novel adsorbent. This may be because the pH decrease, which enlarges apparent adsorption capacity of the adsorbent, is caused by a self-pH decrease function of the adsorbent. The self-pH decrease function must be delivered by dissociation of Al (III) aquoion. The proton release was clearly observed in batch experiments.


Desmopressin Acetate in Percutaneous Ultrasound-Guided Native Kidney Biopsy in Patients with Reduced Kidney Function: A Double-Blind Randomized Controlled Trial.
Bleeding events are the most common complications after kidney biopsy. This study aims to evaluate the effect of desmopressin administration on bleeding complication, in native kidney biopsy candidates with reduced kidney function. This double-blind randomized clinical trial enrolled 18 to 80 years old patients with 15 < eGFR < 90 mL/min/ 1.73m² from July 2017 to August 2020. Patients were randomly assigned to receive either 3 µg/kg of intranasal desmopressin acetate or 1 mL/kg of intranasal sodium chloride 0.65%, one hour before ultrasound-guided, percutaneous native kidney biopsy. The primary outcome was the post-biopsy bleeding complications, and secondary outcomes were the volume of perirenal hematoma, and changes of post-biopsy hemoglobin and hematocrit level, plasma sodium and blood pressure (Clinical Trial Registration ID: IRCT20090701002112N3). A total of 120 patients (58 men and 62 women), 60 patients in each group, were analyzed. The mean age and eGFR of the patients were 45.29 ± 15.95 years and 51.77 ± 18.02 ml/min/ 1.73m², respectively. Desmopressin administration significantly decreased post-biopsy perirenal hematoma compared to placebo (7/60 [11.6%]) vs. 33/60 [40%]; P < .05), and the hematoma volume was significantly smaller in the desmopressin group, in case of hematoma formation (2.31 ± 1.17 vs. 7.72 ± 5.45 mm³, P < .05). Desmopressin administration before kidney biopsy is a safe and effective strategy to prevent bleeding complications. Considering absolute risk reduction of about 28%, the number needed to treat is about 4 procedures. We recommend considering desmopressin administration before percutaneous native kidney biopsy. DOI: 10.52547/ijkd.6966.


Women's awareness of the human papilloma virus and related health problems.
This paper is a report of a study of women's awareness of the human papilloma virus and related health problems. Cervical cancer is an important cause of mortality, making up approximately 12% of all cancers in women. Awareness on the part of carriers of human papilloma virus is crucial in preventing transmission of the infection and protecting against cervical cancer. The study was performed as a cross-sectional descriptive study. The study consists of 79 human papilloma virus-positive women who had not been diagnosed with cervical cancer and 150 women who had not been diagnosed with human papilloma virus. Data were collected via questionnaires between November 2007 and April 2008. Percentages and chi-square test were used. A significantly higher percentage of women with positive human papilloma virus knew the definition of human papilloma virus, the fact that it is transmitted via sexual contact and that it can lead to cervical cancer than did women with negative human papilloma virus. It was established that approximately half the women with positive human papilloma virus presented at the hospital with a genital wart. None of the women knew that a Pap smear test was a necessary tool in the prevention of cervical cancer. Women with positive human papilloma virus have insufficient knowledge of human papilloma virus, sexually transmitted diseases, the health risks associated with human papilloma virus and the means of preventing these risks. It is therefore necessary to evaluate the education of health workers, and especially of nurses, on human papilloma virus and its prevention.


Conflict tasks and the diffusion framework: Insight in model constraints based on psychological laws.
Formal models of decision-making have traditionally focused on simple, two-choice perceptual decisions. To date, one of the most influential account of this process is Ratcliff's drift diffusion model (DDM). However, the extension of the model to more complex decisions is not straightforward. In particular, conflicting situations, such as the Eriksen, Stroop, or Simon tasks, require control mechanisms that shield the cognitive system against distracting information. We adopted a novel strategy to constrain response time (RT) models by concurrently investigating two well-known empirical laws in conflict tasks, both at experimental and modeling levels. The two laws, predicted by the DDM, describe the relationship between mean RT and (i) target intensity (Piéron's law), (ii) standard deviation of RT (Wagenmakers-Brown's law). Pioneering work has shown that Piéron's law holds in the Stroop task, and has highlighted an additive relationship between target intensity and compatibility. We found similar results in both Eriksen and Simon tasks. Compatibility also violated Wagenmakers-Brown's law in a very similar and particular fashion in the two tasks, suggesting a common model framework. To investigate the nature of this commonality, predictions of two recent extensions of the DDM that incorporate selective attention mechanisms were simulated and compared to the experimental results. Both models predict Piéron's law and the violation of Wagenmakers-Brown's law by compatibility. Fits of the models to the RT distributions and accuracy data allowed us to further reveal their relative strengths and deficiencies. Combining experimental and computational results, this study sets the groundwork for a unified model of decision-making in conflicting environments.


Surface morphology and microstructure of Bauhinia variegata L. flowers and leaves.
The main purpose of this research is to characterize the wettability and microstructure of Bauhinia variegata L. flowers and leaves, aiming to provide a biological template for the preparation of hydrophobic surfaces. The contact angle test results show that the surfaces of flowers and leaves are hydrophobic, and the contact angle of the adaxial side and abaxial side of the leaves is highly significant difference, which is mainly affected by the topological morphology of the surface microstructure. The topological structure of flower and leaf surface morphology was revealed by scanning electron microscopy (SEM) and super-depth of field three-dimensional microscope. The results showed that the cell structure of flower surface array was the main factor leading to the hydrophobicity of flowers. The snowflake-like structure on the leaf surface is the main factor leading to hydrophobicity of leaves, and the burr structure of the micro-nano dual-level structure unique to the abaxial side of the leaf further enhances the hydrophobicity of the abaxial side, and the contact angle increases, resulting in a highly significant difference in wettability between the adaxial side and abaxial side. This provides an important biological template and reference value for the preparation of biomimetic materials.


Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas.
Pirfenidone, an oral anti-inflammatory, antifibrotic agent with activity in idiopathic pulmonary fibrosis, may mediate anti-tumor activity in neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) by inhibition of fibroblast proliferation and collagen synthesis. The primary objective of this open label, single arm phase II trial was to evaluate the activity of pirfenidone in children and young adults with inoperable PN. Patients (3-21 years) with NF1-related progressive PN received pirfenidone at the previously determined optimal dose (500 mg/m(2) orally, q8h) on a continuous dosing schedule (one cycle = 28 days). Volumetric MRI analysis was used to assess response. Progression was defined as ≥ 20% PN volume increase compared to baseline. Pirfenidone would be considered active if it doubled the median time to progression (TTP) compared to the TTP on the placebo arm of a phase II trial with the farnesyltransferase inhibitor tipifarnib, which used near identical eligibility criteria. Toxicities, objective response rate, and quality of life (QOL) also were evaluated. Thirty-six patients were enrolled and tolerated pirfenidone well with intermittent nausea and vomiting as the most frequent toxicities. A dose reduction was required in only three patients. The median TTP for pirfenidone was 13.2 months compared to 10.6 months for the placebo control group from the tipifarnib trial (two-tailed P = 0.92; one-tailed P = 0.46). No objective responses were observed. Pirfenidone was well tolerated, but did not demonstrate activity as defined in this trial and does not warrant further evaluation in children with NF1 and progressive PN.


[Pulmonary diffusion of carbon monoxide in patients with mitral stenosis].
The aim of our work has been the study of CO diffusion capacity in mitral valve stenosis patients. We have studied 15 control subjects and 15 patients with mitral valve stenosis. We performed spirometry study and CO pulmonary diffusion tests (DLCO) by single breath method to determine two components: pulmonary capillary blood volume (Vc) and membrane diffusion factor (Dm). In addition, in mitral valve stenosis patients we performed a ecocardiography-doppler study. The mitral valve stenosis group had higher values of DLCO and Vc and a lower ratio of Dm/Vc than the control group. There is a negative correlation between Vc and the mitral valve area (r = -0.63; p = 0.037). We do not find any another correlation between the rest of ecocardiography doppler parameters and lung function test variables that we have measured. We have not found any differences between both groups in Dm. Mitral valve stenosis patients present a increase of CO pulmonary diffusion capacity and pulmonary capillary blood volume without changes in membrane diffusion factor.


Purification of resveratrol, arachidin-1, and arachidin-3 from hairy root cultures of peanut (Arachis hypogaea) and determination of their antioxidant activity and cytotoxicity.
Antioxidant stilbenoids, such as resveratrol, arachidin-1, and arachidin-3, have demonstrated beneficial effects on human health. Although resveratrol is commercially available, arachidin-1 and arachidin-3 are not, resulting in an opportunity to explore purification methods and to confirm biological activity. Recently, Arachis hypogaea hairy root cultures (produced via Agrobacterium rhizogenes-mediated transformation) were reported to secrete stilbenoids into liquid growth media upon elicitation in quantities sufficient for commercial production. The purpose of this study was to purify substantial quantities of resveratrol, arachidin-1, and arachidin-3 from A. hypogaea hairy root cultures using centrifugal partition chromatography (CPC), determine the antioxidant activity of these compounds using the thiobarbituric acid reactive substances (TBARS) assay, and determine the cytotoxicity of the compounds using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In a single run of CPC, resveratrol, arachidin-1, and arachidin-3 were separated to a purity of 97.1%, 97.0%, and 91.8%, respectively. Lipid oxidation was inhibited by a 27 and 7 μM dose for reference standards of resveratrol and arachidin-1, respectively, while oxidation was not inhibited up to a 27 μM dose for reference standard of arachidin-3. Oxidation was inhibited at a 14, 7, and 14 μM doses for CPC-purified resveratrol, arachidin-1, and arachidin-3, respectively. Arachidin-1 and arachidin-3 demonstrated cytotoxicity at 27 and 55 μM in RAW 264.7 and HeLa cell lines, respectively; while resveratrol exhibited no cytotoxicity to either cell line. These results demonstrate the integration of a production and purification system for the manufacturing of A. hypogaea-derived stilbenoids.


Identification of two common variants contributing to serum apolipoprotein B levels in Mexicans.
Although the Mexican population has a high predisposition to dyslipidemias and premature coronary artery disease, this population is underinvestigated for the genetic factors conferring the high susceptibility. This study attempted to determine these genetic factors. First, we investigated apolipoprotein B (apoB) levels in Mexican extended families with familial combined hyperlipidemia using a two-step testing strategy. In the screening step, we screened 5721 single-nucleotide polymorphisms (SNPs) for linkage signals with apoB. In the test step, we analyzed the 130 SNPs residing in regions of suggestive linkage signals for association with apoB. We identified significant associations with two SNPs (ie, rs1424032 [P=6.07x10(-6)] and rs1349411 [P=2.72x10(-4)]) that surpassed the significance level for the number of tests performed in the test step (P<3.84x10(-4)). Second, these SNPs were tested for replication in Mexican hyperlipidemic case-control samples. The same risk alleles as in the families with familial combined hyperlipidemia were significantly associated (P<0.05) with apoB in the case-control samples. The rs1349411 resides near the apoB messenger RNA editing enzyme (APOBEC1) involved in the processing of APOB messenger RNA in the small intestine. The rs1424032 resides in a highly conserved noncoding region predicted to function as a regulatory element. We identified two novel variants, rs1349411 and rs1424032, for serum apoB levels in Mexicans.


[Contribution of intravenous immunoglobulins to the treatment of myasthenia].
Myasthenia Gravis (MG) is an autoimmune disease characterized by the production of auto antibodies directed against the acetylcholine receptor of the neuro-muscular synapse. The signs and symptoms are a muscular deficit involving the spinal or cranial muscles. The degree of weakness changes spontaneously over shorter or longer periods. Some exacerbations, called myasthenia crisis, involve the respiratory muscle and are life-threatening. The prognosis of these crisis has been transformed by the use of mechanical ventilation. Treatments directed on immune-regulation such as thymectomy, corticosteroids or immunossupressive drugs contribute to the improvement in functional status and reduce the risk of exacerbation. Plasma exchanges lead to a rapid improvement of weakness during exacerbations. They are, despite the lack of controlled study, the reference treatment for acute exacerbations. More recently, high doses of immunoglobulins have been proposed and a controlled study has shown that they could be an alternative for the treatment of acute exacerbations of MG. Indication of immunoglobulin in the long term management of MG is not established.


Pharmacy Educators' Knowledge of Medication Safety and Their Perception Toward Its Integration into the Doctor of Pharmacy Curriculum in Saudi Arabia.
Objective. To assess pharmacy educators' knowledge of medication safety and their perception toward its integration into the PharmD curriculum in Saudi Arabia. Methods. A survey was administered to pharmacy educators at a college of pharmacy and its affiliate hospital. Knowledge, training, and perception toward integrating medication safety into the PharmD curriculum were evaluated. Results. More than 50% of respondents indicated that medication safety should be covered within selected courses, and 65% indicated that such courses should be mandatory. Pharmacy practice educators had significantly higher levels of knowledge about medication safety than their nonpractice counterparts. Perceptions toward medication safety integration into the curriculum varied significantly by general discipline, academic degree, years of experience, and gender. Conclusion. Pharmacy educators in Saudi Arabia understand the importance of medication safety and its integration into the curriculum. Further studies are needed to guide curricular change to achieve this integration.


Investigation of hematological and biochemical parameters in small ruminants naturally infected with Babesia ovis.
Babesia ovis plays an important role in causing anemia and kidney dysfunction in affected animals. There are few extensive studies about hematological and biochemical findings of small ruminants' babesiosis caused by B. ovis. The aim of this study was to evaluate the effect of babesiosis on some hematological and biochemical parameters in infected small ruminants with B. ovis. A total of 280 sheep and 122 goats from 40 herds were randomly examined for the presence of B. ovis in blood samples. Of 402 samples, 67 animals (16.7%) were positive for B. ovis of which 52 (18.5%) were sheep and 15 (12.2%) goats, respectively. The infected animals were divided into four subgroups according to parasitemia rates (<1%, 1%, 2%, and 3%). As a control group, 67 uninfected animals were also selected from the same farms. With increase in parasitemia rates, hemoglobin concentration (Hb), packed cell volume (PCV), red blood cells (RBCs), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) significantly decreased (P < 0.05), while, total leukocyte count, number of lymphocyte, monocyte, neutrophil and eosinophil showed a significant increase (P < 0.05). Infected animals presented a significant elevation (P < 0.05) of total proteins and significantly lower level (P < 0.05) of albumin compared to non-infected animals. Significant elevation (P < 0.05) of BUN, creatinine, cholestrol, triglyceride, HDL and LDL level were found with parasitemia progression.


Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1.
Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a -3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.


Migration of human intestinal lamina propria lymphocytes, macrophages and eosinophils following the loss of surface epithelial cells.
Lymphocytes and macrophages are present in the normal intestinal lamina propria, separated from the epithelial monolayer by the basement membrane. There is evidence for movement of mononuclear cells through the lamina propria, entering from the systemic circulation and exiting via lymphatic channels. The goal of our studies was to investigate the capacity of cells to migrate out from the lamina propria into the lumen following the loss of surface epithelial cells. An in vitro model was therefore established in which normal human intestinal mucosal samples, denuded of the surface epithelium, were maintained in culture. Electron microscopy showed that during culture, large numbers (>2 x 10(6)/g tissue per 24 h) of cells migrated out of the lamina propria via discrete 'tunnels' which were in continuity with pores (diameter <4 microm) in the basement membrane. The emigrating cells were T cells (68.5 +/- 5.1%), macrophages (10.5 +/- 1.3%) and eosinophils (7.1 +/- 1.3%). Our studies have therefore demonstrated, for the first time, the capacity for large numbers of lymphocytes, macrophages and eosinophils to migrate out of the lamina propria, via basement membrane pores. We postulate that such emigration of cells occurs in vivo following the loss of surface epithelial cells due to injury, and could represent an important form of host defence against luminal microorganisms and also facilitate wound repair by enhancing restitution by neighbouring epithelial cells, via peptide factors.


Integrating home HIV counselling and testing into household TB contact investigation: a mixed-methods study.
Setting: Community health workers (CHWs) increasingly deliver community-based human immunodeficiency virus (HIV) counselling and testing (HCT) services. Less is known about how this strategy performs when integrated with household tuberculosis (TB) contact investigations. Objective: We conducted a prospective mixed-methods study to evaluate the feasibility and quality of CHW-facilitated, home-based HCT among household TB contacts. Design: CHWs visited households of consenting TB patients to screen household contacts for TB and HIV. They performed HIV testing using a serial enzyme-linked immunosorbent assay rapid-antibody testing algorithm. Laboratory technicians at health facilities re-tested the samples and coordinated quarterly HIV panel testing for CHWs. We conducted focus group discussions (FGDs) with CHWs on their experiences in carrying out home-based HCT. Results: Of 114 household contacts who consented to and underwent HIV testing by CHWs, 5 (4%) tested positive, 108 (95%) tested negative, and 1 (1%) had indeterminate results; 110 (96%) samples had adequate volume for re-testing. Overall agreement between CHWs and laboratory technicians was 99.1% (κ = 0.90, 95%CI 0.71-1.00, P < 0.0001). In FGDs, CHWs described context-specific social challenges to performing HCT in a household setting, but said that their confidence grew with experience. Conclusion: Home-based HCT by CHWs was feasible among household TB contacts and produced high-quality results. Strategies to address social challenges are required to optimize yield.


National malaria control and scaling up for impact: the Zambia experience through 2006.
With its 2006-2011 National Malaria Strategic Plan, Zambia committed to control malaria at a national scale. This scale-up for impact approach was facilitated by sound business planning and financing in 2006 of approximately US$35 million. Compared with surveys in 2001 and 2004, a 2006 national survey of 14,681 persons in 2,999 households at the end of the transmission season showed substantial coverage increases for preventive interventions. Ownership and use rates of insecticide-treated mosquito nets (ITNs) among vulnerable groups doubled, with 44% of households owning ITNs and 23% of children less than five years of age and 24% of pregnant women using them. Roll Back Malaria Abuja targets for intermittent preventive treatment in pregnancy (IPTp) were exceeded, with 62% of pregnant women receiving at least two doses of IPTp. As of 2006, Zambia is demonstrating substantial progress toward the national targets (80% population coverage rates for the interventions) and aspires to show that malaria need not be its leading health problem, and that malaria control is a sound national investment.


The role of antioxidants in the mediterranean diets: focus on cancer.
The incidence of certain cancers in the Mediterranean area is lower than in other areas of the world (e.g. in northern Europe and the USA). As nutrition and dietary factors comprise one of the three major factors for human carcinogenesis, the hypothesis was formulated that the dietary profile of the Mediterranean diet, rich in antioxidants, might exert preventive actions. Alas, the vast majority of experiments to prove this hypothesis have been obtained in vitro, and most of the necessary information on the absorption, distribution and metabolism of oligonutrients is currently lacking. Yet, even though the exact role of antioxidants in the Mediterranean diet is yet to be fully established, data from observational studies are strong enough to reinforce the notion that a diet low in saturated fat and alcohol and rich in plant food and whole grain, such as the traditional Mediterranean diet, is associated with lower risk of cancer and should be actively promoted.


On IEEE 802.15.6 IR-UWB receivers - simulations for DBPSK modulation.
In 2002, Federal Communications Commission (FCC) was the first in defining regulations for ultra wideband (UWB) communications followed by Europe and Japan some years later. Focusing on impulse radio (IR) UWB, in 2007 was the time for the first published standard targeting in personal area networks, released by the IEEE. The second IEEE released standard including UWB definitions is targeted for wireless body area networks (WBAN) and was published in 2012. As the wireless communications has been and will be passing through almost any levels in society, the natural step with WBAN is using it in different medical, healthcare and wellbeing applications. The arguments for these are related to the modern lifestyle, in which people have increasingly more free time and are more interested in taking care of their health and wellbeing. Another challenge is the population composition, i.e., aging in developed countries which call for new solutions and procedures, particularly from cost wise. In this paper, we are evaluating UWB receivers based on the IEEE 802.15.6 physical layer definitions and capable of detecting differentially encoded modulation. The evaluation is performed using two different WBAN channel models.


Automatic Segmentation of the Paediatric Femoral Head.
Developmental dysplasia of the hip (DDH) is a developmental deformity occurring in 0.1-3.4% of infants. Timely surgical intervention can ameliorate the condition in stable hips and reduce future cases of osteoarthritis and total hip replacement. However, current definitions of DDH are subjective, and thus would benefit from a more objective and reliable assessment metric. Since the shape of the femoral head and its congruence with the acetabulum are disrupted by DDH, analysis of the femoral head could potentially play a role in the development of novel objective morphological metric for stable DDH. Therefore, this paper aimed to segment the paediatric femoral head in stable hips from radiographs, which has not been attempted before in the chosen focus age group (1-16 years) where the pelvis and hip joint undergo significant development. Two techniques were compared against a baseline U-Net: data augmentation and region-of-interest (ROI) networks. Four models were developed either without, with just one, or with both techniques. Evaluated using tenfold cross-validation, the U-Net trained with both techniques achieved the best results, with a Dice Similarity Coefficient (DSC) of 0.951±0.037 (mean ± standard deviation, calculated with 720 images). Future work will use this segmentation algorithm to accurately characterise hip joint morphology and estimate the benefit of early surgical intervention in DDH.


Ancient Polyploidy and Genome Evolution in Palms.
Mechanisms of genome evolution are fundamental to our understanding of adaptation and the generation and maintenance of biodiversity, yet genome dynamics are still poorly characterized in many clades. Strong correlations between variation in genomic attributes and species diversity across the plant tree of life suggest that polyploidy or other mechanisms of genome size change confer selective advantages due to the introduction of genomic novelty. Palms (order Arecales, family Arecaceae) are diverse, widespread, and dominant in tropical ecosystems, yet little is known about genome evolution in this ecologically and economically important clade. Here, we take a phylogenetic comparative approach to investigate palm genome dynamics using genomic and transcriptomic data in combination with a recent, densely sampled, phylogenetic tree. We find conclusive evidence of a paleopolyploid event shared by the ancestor of palms but not with the sister clade, Dasypogonales. We find evidence of incremental chromosome number change in the palms as opposed to one of recurrent polyploidy. We find strong phylogenetic signal in chromosome number, but no signal in genome size, and further no correlation between the two when correcting for phylogenetic relationships. Palms thus add to a growing number of diverse, ecologically successful clades with evidence of whole-genome duplication, sister to a species-poor clade with no evidence of such an event. Disentangling the causes of genome size variation in palms moves us closer to understanding the genomic conditions facilitating adaptive radiation and ecological dominance in an evolutionarily successful, emblematic tropical clade.


Evaluating the Effectiveness of Ozone Management Efforts in the Presence of Meteorological Variability.
It is difficult to assess the effectiveness of regulatory programs in improving ozone air quality in the presence of meteorological fluctuations. In this paper, techniques are presented that improve upon previous methods for moderating the effects of meteorology on ozone concentrations. This approach entails the use of the relations between ozone and meteorological variables to construct meteorologically adjusted ozone time series. To this end, the effectiveness and usefulness of various methods for separating time series of ozone and meteorological data into long-term (climate- and policy-related), seasonal (solar-induced), and short-term (weather-related) components are examined. Correlations between baseline components (sum of long-term and seasonal variations) of ozone and meteorological variables are then investigated independently of correlations between short-term components (weather effects) of ozone and meteorological variables. This allows us to account for the effects of the dominant meteorological variables on each time scale embedded in time series of ozone data. Ozone time series that are devoid of seasonal and climatic variations as well as weather-related fluctuations can then be constructed to detect and track changes in ozone due to the emission control policies implemented. The results of this study reveal that the combination of solar radiation and specific humidity performs best in filtering the seasonal and climatic variations from the baseline component of the ozone data. The combination of temperature and dew point depression performs best in moderating the weather-related effects on the short-term component of ozone data. This method is able to explain about 65% of the variance in ozone data through meteorological variables at several locations examined here.


Sarcoidosis in an Australian aborigine and a Torres Strait Islander.
This is the second case report of sarcoidosis in an Australian Aborigine and the first in a Torres Strait Islander. The Australian Aborigine had atypical superior mediastinal lymphadenopathy and uveitis while the Torres Strait Islander had persistent pulmonary disease requiring oral corticosteroids. Indigenous Australians appear to be rarely affected by sarcoidosis. However, it is common in people of Celtic origin. The presence of a European (Celtic) ancestor in the family tree of both individuals suggests that yet unknown genetic factors may be important in the pathogenesis of their disease.


Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.
In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die.


Nonsomatostatin secretory peptide(s) derived from prosomatostatin's amino terminus in a rat medullary thyroid carcinoma cell line.
We have established a system, the CA77 rat medullary thyroid carcinoma cell line, for studying the products of somatostatin (SS) gene expression. Based on the amino acid sequence of proSS, we developed a RIA for the amino terminus of proSS (proSS-NTP) and demonstrated in acidic cell extracts two major proSS-NTP-containing species of 8000 and 4000 daltons. Studies were then performed on species secreted into culture medium. Serial dilutions of culture medium showed tracer displacement curves parallel to serial dilutions of synthetic proSS-NTP standard. Analysis by gel filtration chromatography of 24-h culture medium showed the major proSS-NTP-containing species to have an estimated mol wt of 8000 daltons. No 4000-dalton species was observed. The acute effects of calcium and glucagon, known secretagogues of SS, on secretion of immunoreactive (i) proSS-NTP were investigated in 3-h experiments. Basal (0.5 mM calcium) secretory rates (mean +/- SE) of iproSS-NTP and iSS were 1.29 +/- 0.36 and 7.38 +/- 1.51 ng/mg acid-extractable protein, respectively. High calcium (3 mM) stimulated iproSS-NTP and iSS secretion 302 +/- 100% and 363 +/- 105%, respectively. High calcium plus 10(-6) M glucagon also stimulated secretion of iproSS-NTP and iSS in a coordinate fashion. Analyses by gel filtration chromatography of 3-h culture medium revealed that high calcium markedly increased the 8000-dalton proSS-NTP-containing species. No 4000-dalton species was observed. The absence of 4000-dalton proSS-NTP species in 24-h culture medium, the lack of degradation of 4000-dalton proSS-NTP (recovered from CA77 cell extracts) added to tissue culture medium, and the selective secretion of the 8000-dalton proSS-NTP species under both basal and stimulated conditions coordinate with the secretion of SS indicate that the 4000-dalton proSS-NTP-containing species is not secreted.


[Tuberculosis mortality in Argentina during the twentieth century].
The aim of this article is to provide an analysis of the mortality curve for tuberculosis in Argentina throughout the twentieth century, from 1911 to 2007. Using data from various official sources, the mortality rate is divided into historical phases and sub-periods, in order to show how the behavior of tuberculosis mortality depended on the historical moment. Thus, the progress of the disease is linked to the methods that were developed to combat it. The fluctuations in mortality are analyzed by regions of the country, on the assumption that mortality varied according to economic and social conditions and the development of healthcare.


Genetic ablation of calcium-independent phospholipase A2gamma prevents obesity and insulin resistance during high fat feeding by mitochondrial uncoupling and increased adipocyte fatty acid oxidation.
Phospholipases are critical enzyme mediators participating in many aspects of cellular function through modulating the generation of lipid 2nd messengers, membrane physical properties, and cellular bioenergetics. Here, we demonstrate that mice null for calcium-independent phospholipase A(2)γ (iPLA(2)γ(-/-)) are completely resistant to high fat diet-induced weight gain, adipocyte hypertrophy, hyperinsulinemia, and insulin resistance, which occur in iPLA(2)γ(+/+) mice after high fat feeding. Notably, iPLA(2)γ(-/-) mice were lean, demonstrated abdominal lipodystrophy, and remained insulin-sensitive despite having a marked impairment in glucose-stimulated insulin secretion after high fat feeding. Respirometry of adipocyte explants from iPLA(2)γ(-/-) mice identified increased rates of oxidation of multiple different substrates in comparison with adipocyte explants from wild-type littermates. Shotgun lipidomics of adipose tissue from wild-type mice demonstrated the anticipated 2-fold increase in triglyceride content after high fat feeding. In sharp contrast, the adipocyte triglyceride content was identical in iPLA(2)γ(-/-) mice fed either a standard diet or a high fat diet. Respirometry of skeletal muscle mitochondria from iPLA(2)γ(-/-) mice demonstrated marked decreases in state 3 respiration using multiple substrates whose metabolism was uncoupled from ATP production. Shotgun lipidomics of skeletal muscle revealed a decreased content of cardiolipin with an altered molecular species composition thereby identifying the mechanism underlying mitochondrial uncoupling in the iPLA(2)γ(-/-) mouse. Collectively, these results identify iPLA(2)γ as an obligatory upstream enzyme that is necessary for efficient electron transport chain coupling and energy production through its participation in the alterations of cellular bioenergetics that promote the development of the metabolic syndrome.


Systematic review of pharmacoeconomic models for schizophrenia.
Background: Economic models are broadly used in the economic evaluation of antipsychotics in schizophrenia. Our objective was to summarize the structure of these models. Methods: Model-based economic evaluations of antipsychotics in schizophrenia were identified through Medline and Embase. General information was extracted including analysis type, model type, perspective, population, comparator, outcome, and timeframe. Model-specific structures for decision tree (DT), cohort- and patient-level Markov model (CLMM, PLMM), and discrete-event simulation (DES) models were extracted. Results: A screen of 1870 records identified 79 studies. These were mostly cost-utility analyses (n = 48) with CLMM (n = 32) or DT models (n = 29). They mostly applied payer perspective (n = 68), focused on general schizophrenia for relapse prevention (n = 73), compared pharmacotherapies as first-line (n = 71), and evaluated incremental cost per quality-adjusted life year (QALY) gained (n = 40) with a 1-year (n = 32) or 5-year (n = 26) projection. DT models progressed with the branching points of response, relapse, discontinuation, and adherence. CLMM models transitioned between disease states, whereas PLMM models transitioned between adverse event states with/without disease state. DES models moved forward with times to remission, relapse, psychiatrist visit, and death. Conclusions: A pattern of pharmacoeconomic models for schizophrenia was identified. More subtle structures and patient-level models are suggested for a future modelling exercise.


Chronic exposure to polystyrene microplastics increased the chemosensitivity of normal human liver cells via ABC transporter inhibition.
Microplastics (MPs) are ubiquitous in environmental compartments and consumer products. Although liver is frequently reported to be a target organ of MP accumulation in mammals, few studies have focused on MP hepatoxicity in humans. In this study, we used normal human liver cells, THLE-2, to assess the acute and chronic toxicity of polystyrene (PS) MPs with sizes of 0.1 and 1 μm. The results showed that after 48 h of exposure, both kinds of PS MPs could enter THLE-2 cells and cause no obviously acute cytotoxicity at <20 μg/mL. In contrast, metabolomic analysis revealed that 90 days of PS MPs exposure at environmentally relevant dose (0.2 μg/mL) could significantly alter the metabolic profiles of the cells, especially the nanosized MPs. KEGG pathway analysis showed that the ATP-binding cassette (ABC) transporter pathway was the most significantly changed pathway. Cell functional tests confirmed that chronic PS MP treatment could inhibit the activity of the ABC efflux transporter and further increase the cytotoxicity of arsenic, indicating that the PS MPs had a chemosensitizing effect. These findings underline the chronic risk of MPs to human liver.


Clinical reliability of the "furcation arrow" as a diagnostic marker.
The radiographic entity known as the "furcation arrow" has long been used in practice even though little is known about its usefulness as a clinical indicator. The definitive study of the furcation arrow suggests that its presence on a radiograph reliably predicts furcation invasion, but this has not been confirmed in an in vivo investigation. The purpose of this study was to evaluate the furcation arrow in a clinical setting, testing the assertion that the furcation arrow image is an accurate predictor of furcation invasion. Specifically, we sought to determine the following. First, what is the prevalence of furcation arrow images in the radiographs of maxillary molars with periodontitis? Second, what is the interexaminer agreement on what constitutes a furcation arrow? Third, how does the presence or absence of a furcation arrow correlate with the true clinical status of the furcation? Fourth, what is the sensitivity and specificity of the furcation arrow as a diagnostic indicator? Eighty-nine patients requiring surgical treatment of periodontitis in the maxillary molar regions were included in this study. Before surgery, one of five calibrated examiners viewed periapical and bitewing radiographs of the surgical site and recorded the presence or absence of a furcation arrow at each proximal furcation. Before administering anesthesia, the same examiner recorded a Hamp index value of each proximal furcation, with a second Hamp index taken after flap reflection and debridement. After surgery, each of the four remaining examiners independently reviewed the radiographs for furcation arrows. Descriptive statistical analysis was performed to correlate the appearance of the furcation arrow image to the actual degree of furcation invasion as determined by the intrasurgical Hamp index. A total of 164 maxillary molars were examined, providing 328 interproximal furcations; 111 (33.8%) furcations were determined at surgical debridement to have a furcation invasion of Hamp degree 1 or greater. Of the 111 furcation invasions, 43 (38.7%) were predicted by a furcation arrow image seen by at least three of the five examiners. When comparing the appearance of the radiographic image to the extent of furcation invasion, 20 of 64 (31.3%) Hamp 1 furcation invasions and 23 of 47 (48.9%) Hamp 2 and 3 furcation invasions were predicted by furcation arrows observed by at least three of five examiners. The multirater kappa statistic for interexaminer agreement on the presence or absence of the image was 0.489. The sensitivity of the furcation arrow image as a diagnostic marker was 38.7%, and the specificity was 92.2%; the positive predictive value of the image was 71.7%, and the negative predictive value was 74.6%. Of the 324 furcations used to compare clinical indices, the agreement of preanesthesia and postdebridement Hamp indices was 0% for degree 3, 83.7% for degree 2, and 98.4% for degree 1 furcation lesions. These data suggest that the furcation arrow has limited usefulness as a diagnostic marker of furcation invasion. The image is difficult to interpret and highly subjective and can correctly predict furcation invasions only approximately 70% of the time when present on the radiograph. In addition, when furcation invasions are truly present, the furcation arrow is seen in <40% of sites.


The anti-inflammatory effects of 1,1 dimethyl-4-phenylpiperazinium (DMPP) compared to dexamethasone in a guinea pig model of ovalbumin induced asthma.
Inflammatory cells involved in the pathophysiology of asthma express nicotinic receptor. Therefore 1,1 dimethyl(-4-)phenylpiperazinium (DMPP) in two doses were compared to dexamethasone in asthmatic guinea pigs. Six groups were included; Normal control and five asthmatic (OVA-sensitized and challenged) groups; which were treated for 10 days as follows: two vehicles, dexamethasone (DEXA, 1 mg/kg) and DMPP (0.4 and 0.8 mg/kg) groups. Pulmonary functions and airway hyper-responsiveness were assessed. Leukocytic count, tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6) and immunoglobulin E (IgE) were measured in both blood and bronchoalveolar lavage fluid (BALF). Histopathological examination of the lung tissues was conducted. Asthmatic untreated animals exhibited significant increase in early and late airway resistance (RxV) and airway hyper-responsiveness, with reduction in tidal volume. Both blood and BALF showed significant increase in total leukocytic count (TLC), eosinophils, lymphocytes, monocytes, TNF-α, IL-6 and IgE with significant decrease in neutrophils. Airway inflammatory cell infiltration and smooth muscle thickness significantly increased. DMPP 0.4 mg/kg significantly decreased late phase RXV, TLC, BALF lymphocytes, TNF-α, smooth muscle thickness and increased neutrophils in BALF over both DEXA and DMPP 0.8 mg/kg. Moreover, DMPP 0.4 mg/kg significantly decreased IL-6 and BALF eosinophils than DMPP 0.8 mg/kg and decreased serum IgE and parenchymal inflammatory infiltration than DEXA. Low dose DMPP has more anti-inflammatory effect than a high dose in most parameters and sometimes than dexamethasone. Cholinergic anti-inflammatory pathway may therefore represent a potential drug target for allergic asthma. The dose related effect of DMPP and the mechanism underlying this effect require further evaluation.


Self-expanding metal stent procedure for afferent loop syndrome with ascending cholangitis caused by remnant gastric cancer: A case report.
Self-expanding metal stent placement is a useful procedure for intestinal obstruction. Afferent loop syndrome after gastrectomy is an uncommon complication of gastroenterostomy reconstruction. Ascending cholangitis caused by afferent loop syndrome is a potential, but rare, complication. A 73-year-old man with abdominal pain and vomiting was admitted to the emergency room. His medical history was significant for subtotal gastrectomy with Billroth II anastomosis for benign gastric ulcer perforation 40 years prior. He had notable tenderness to palpation, particularly on the epigastric area, and a temperature of 39.0°C. Abdominal computed tomography revealed afferent loop syndrome with ascending cholangitis caused by remnant gastric cancer. Percutaneous catheter drainage for management of ascending cholangitis was performed on the day of admission. He was subsequently treated with self-expandable metal stent insertion into the stenotic lesion. After treatment with percutaneous transhepatic insertion of a self-expanding stent, the patient achieved complete resolution of symptoms. The patient died of disease progression 2 months later, without further recurrence of afferent loop syndrome. Our case shows that insertion of a metal stent via percutaneous transhepatic biliary drainage (PTBD) can effectively treat ascending cholangitis and resolve afferent loop syndrome in inoperable patients.


The Risk of Primary Open-Angle Glaucoma Following Vitreoretinal Surgery-A Population-based Study.
To determine the risk of primary open-angle glaucoma (POAG) following vitreoretinal surgery. Retrospective, population-based cohort study. All residents of Olmsted County, Minnesota, undergoing scleral buckle and/or vitrectomy between 2004 and 2015 were included in the operative cohort. The fellow nonoperative eyes were included in the comparison cohort. The study and comparison cohorts consisted of 344 and 277 eyes, respectively. The main outcome measure was the development of POAG. Secondary glaucomas were excluded. The probability of glaucoma in operative eyes and nonoperative fellow eyes was compared. The observed rate of POAG in the operative eyes was also compared to the rate of POAG in the population of Olmsted County. The mean age was 64.7 years and the median follow-up period was 4.9 years. There were 58, 57, and 229 study eyes in the scleral buckle, scleral buckle with vitrectomy, and vitrectomy only cohorts, respectively. The 10-year cumulative probability of developing glaucoma was significantly greater in the operative group (8.9%, 95% confidence interval [CI] 3.8%-14%) compared to the nonoperative group (1.0%, 95% CI 0-2.4%; P = .02). None of the eyes in the scleral buckle group developed glaucoma. The 10-year probability of POAG was 17.5% (95% CI 0-34.9%) and 10.0% (95% CI 3.0%-17.0%) in the scleral buckle with vitrectomy and vitrectomy alone cohorts, respectively. The rates of POAG in operative eyes undergoing scleral buckle with vitrectomy and vitrectomy alone were significantly greater than the rate of POAG for the Olmsted County general population (1.0%, P < .001). The risk of POAG is increased after vitrectomy.