Resuming anticoagulation in patients with atrial fibrillation experiencing intracranial hemorrhage.
Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were <20 years old, who were not using OACs 6 months prior to ICH, or who had a CHA2DS2-VASc score of ≤1. We also excluded patients who died during admission for ICH, with follow-up for <6 weeks after discharge, or who started OAC >6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20-0.76) and IS/SE (HR = 0.12, 95% CI = 0.03-0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34-0.93) and IS/SE (HR = 0.26, 95% CI = 0.09-0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.


The healthy diabetes plate.
Diabetes education presents two major challenges to the U.S. Cooperative Extension System. The first is that the majority of diabetes education services are provided in more populated areas, resulting in large nonurban areas being underserved. The second is that many individuals with diabetes find the meal-planning component of diabetes education confusing. The University of Idaho, a land-grant institution, includes teaching, research, and extension as part of its mission. Extension means "reaching out," and in Idaho, the Extension Service provides research-based programs on agricultural, natural resources, youth, family, community, and environmental issues in 42 of Idaho's 44 counties, making it accessible to most Idahoans. The University of Idaho Extension Service collaborated with dietitians and certified diabetes educators to develop and test materials that simplify the meal-planning component of diabetes education. The result was a four-lesson curriculum, The Healthy Diabetes Plate, which used the plate format to teach individuals about the type and amount of foods they should consume at each meal. In 2004, the four-lesson curriculum was taught in three urban and five rural counties. Surveys, hands-on activities, and note-taking of participants' comments were used to collect data on participants' characteristics, their ability to plan meals, and changes in eating habits. Participants were able to correctly plan breakfast, lunch, and dinner meals and improved their intake of fruit and vegetables. Quantitative and qualitative evaluation information gathered from class participants helped identify which components of The Healthy Diabetes Plate curriculum were effective.


Herpes simplex virus eliminates host mitochondrial DNA.
Mitochondria have crucial roles in the life and death of mammalian cells, and help to orchestrate host antiviral defences. Here, we show that the ubiquitous human pathogen herpes simplex virus (HSV) induces rapid and complete degradation of host mitochondrial DNA during productive infection of cultured mammalian cells. The depletion of mitochondrial DNA requires the viral UL12 gene, which encodes a conserved nuclease with orthologues in all herpesviruses. We show that an amino-terminally truncated UL12 isoform-UL12.5-localizes to mitochondria and triggers mitochondrial DNA depletion in the absence of other HSV gene products. By contrast, full-length UL12, a nuclear protein, has little or no effect on mitochondrial DNA levels. Our data document that HSV inflicts massive genetic damage to a crucial host organelle and show a novel mechanism of virus-induced shutoff of host functions, which is likely to contribute to the cell death and tissue damage caused by this widespread human pathogen.


Pure red cell aplasia induced by epoetin zeta.
Pure red cell aplasia (PRCA) may develop in patients with chronic kidney disease receiving erythropoiesis-stimulating agents (ESA). We report on a 72-year-old patient who developed hypo-proliferative anaemia unresponsive to ESA following the administration of epoetin zeta subcutaneously for 7 months. On the basis of severe isolated hypoplasia of the erythroid line in the bone marrow and high-titre neutralizing anti-erythropoietin antibodies (Ab), a diagnosis of Ab-mediated PRCA was made. Epoetin zeta was discontinued and the patient was given steroids. This was associated with anaemia recovery. To our knowledge this is the first PRCA case related to epoetin zeta.


Early life stress induces submissive behavior in adult rats.
Maternal-deprivation of rodent pups is a relevant model of extreme early-life stress that can be relevant to the understanding of long-term effects of war, migration, parental loss and displacement. Although even mild stress during infancy affects brain development and behavior, the current study focused on the effects of six hour daily maternal-separation, a model that reflects the severe distress often experienced in those circumstances. This study emphasizes the effect of maternal separation on social behavior in the context of a variety of factors that measure cognitive and emotional behavior which were subject to principle component analysis. Sprague-Dawley pups were separated from the dam for 6 h each day during the first 3-weeks of life and underwent a battery of behavioral tests at 3-months of age. We found that rodents exposed to postnatal maternal deprivation displayed submissive behavior in resident-intruder and dominant-submissive tests, as well as significantly more anxiety and anhedonia than control rats. The results of multivariate statistical analysis show that the dominant-submissive behavior correlates with depressive, anxiety and social behavior and can be predicted with an accuracy of 86.2%. The increased submissive behavior in male rats that had been subjected to severe postnatal stress suggests that exposure to stress during infancy and childhood could have long-term effects on social relationships. The mechanism of the long-term effects on depression, anxiety and submissive behavior requires further investigation.


Triphosphine-supported bimetallic Au(I)-M(I) (M = Ag, Cu) alkynyl clusters.
The reactions of gold acetylides (AuC2R)n with triphosphine ligands PPh2-(CH2)n-PPh-(CH2)2-PPh2 (n = 1, dpmp; 2, dpep) in the presence of M(+) ions (M = Cu, Ag) lead to an assembly of the heterometallic clusters, the composition of which is determined by the steric bulkiness of the alkynyl groups and the flexibility of the phosphine motifs. For R = Ph, an unprecedented hexanuclear complex [Au5Cu(C2R)4(dpmp)2](2+) (1) was isolated, while for the aliphatic alkynes (R = 1-cyclohexanolyl, 2-borneolyl, 2,6-dimethyl-4-heptanolyl) a family of compounds based on a tetrametallic framework was prepared, [Au3Cu(C2R)3(dpmp)](+) (2, R = 1-cyclohexanolyl), [Au3M(C2R)3(dpep)]2(+2) (3, M = Cu, R = 1-cyclohexanolyl; 4, M = Cu, R = 2-borneolyl; 5, M = Ag, R = 2-borneolyl), and [Au3Ag(C2R)3(dpep)](+) (6, R = 2,6-dimethyl-4-heptanolyl). Clusters 1, 2, and 4-6 were studied by X-ray crystallography. The NMR spectroscopic investigations showed that 1 and 3-5 are stereochemically non-rigid in solution and reversibly undergo possible dissociation (3) or isomerization (4, 5) processes. All the title complexes exhibit room temperature luminescence in the solid state in the spectral region from 414 to 566 nm, showing a dependence of emission energy on the structure and composition of the metal core. Computational studies with density functional methods were carried out to rationalize the dynamic and photophysical behavior of these compounds.


Vinblastine, intermittent bleomycin, and single-dose cis-dichlorodiammineplatinum(II) in the management of stge III testicular cancer.
A program for treating advanced testicular cancer with vinblastine, bleomycin, and a single dose of cis-dichlorodiammineplatinum(II) was used in an attempt to reduce the toxicity of a 5-day regimen while maintaining a high response rate. In ten previously untreated and six previously treated patients, the complete remission rate was 25%. Toxic reactions were frequent, and there was one drug-related death. This single-dose cis-dichlorodiammineplatinum(II) program is ineffective in the treatment of testicular cancer. Other means for reducing toxicity will have to be considered.


The effect of OH(.) radicals generated by Fenton reaction on the growth and cartilage differentiation in limb bud cell culture.
A consistent chondrogenesis takes place in micro high-density cultures of chick limb bud mesenchyme cells stage 22-24. The effect of an increased generation of OH(.) free radicals by Fenton reaction was tested in these cultures. Components of Fenton reaction (i.e., ferrous iron in form of ADP-Fe2+ complex in 0.1 mM concentration, or 0.2 mM H2O2, or the combination of these components with each other, as well as with 0.2 mM ascorbate) were supplemented to the culture medium after the first 24 h. ADP-Fe2+ complex resulted in a drastic decrease of the frequency and confluence of the cartilage nodules seen in light microscope, accompanied electron microscopically by a strikingly increased frequency of occurrence of lipofuscin-like, residual bodies in the cells. Biochemical methods revealed a significant decrease of both the DNA and glycosaminoglycan contents (to 48.6 and 20.7% of the controls, respectively), in day 6 cultures. H2O2 alone caused similar alterations of the cultures, whereas the combination of it with ADP-Fe2+ complex proved to be lethal for the cells. Ascorbate when added to the ADP-Fe2+-treated cultures displayed a slight protective effect for the glycosaminoglycan content but not for DNA. The results are interpreted in terms of free radical theory of aging.


The solution structure of REF2-I reveals interdomain interactions and regions involved in binding mRNA export factors and RNA.
The RNA binding and export factor (REF) family of mRNA export adaptors are found in several nuclear protein complexes including the spliceosome, TREX, and exon junction complexes. They bind RNA, interact with the helicase UAP56/DDX39, and are thought to bridge the interaction between the export factor TAP/NXF1 and mRNA. REF2-I consists of three domains, with the RNA recognition motif (RRM) domain positioned in the middle. Here we dissect the interdomain interactions of REF2-I and present the solution structure of a functionally competent double domain (NM; residues 1-155). The N-terminal domain comprises a transient helix (N-helix) linked to the RRM by a flexible arm that includes an Arg-rich region. The N-helix, which is required for REF2-I function in vivo, overlaps the highly conserved REF-N motif and, together with the adjacent Arg-rich region, interacts transiently with the RRM. RNA interacts with REF2-I through arginine-rich regions in its N- and C-terminal domains, but we show that it also interacts weakly with the RRM. The mode of interaction is unusual for an RRM since it involves loops L1 and L5. NMR signal mapping and biochemical analysis with NM indicate that DDX39 and TAP interact with both the N and RRM domains of REF2-I and show that binding of these proteins and RNA will favor an open conformation for the two domains. The proximity of the RNA, TAP, and DDX39 binding sites on REF2-I suggests their binding may be mutually exclusive, which would lead to successive ligand binding events in the course of mRNA export.


Identifying and managing inhibitor patients requiring orthopaedic surgery - the multidisciplinary team approach.
Until recently, surgery in haemophilia patients with inhibitors was strongly contraindicated and was therefore often not even contemplated. Inhibitor patients entering the surgical arena face unique challenges; the most frequently encountered problem during surgical intervention is bleeding, and thrombosis is occasionally observed. The activated prothrombin complex concentrate, FEIBA(TM), and recombinant activated factor VII (rFVIIa) are available as haemostatic cover during surgery. The use of rFVIIa enables inhibitor patients to undergo orthopaedic surgery with an expectation of success, and results are generally good. An organized team approach is critical to this success. However, further information is required to enable different procedures to be optimized in terms of both outcome and safety.


Analysis of prognostic factors for borderline resectable pancreatic cancer after neoadjuvant chemotherapy: the importance of CA19-9 decrease in patients with elevated pre-chemotherapy CA19-9 levels.
Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel. From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors. Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)]. In patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.


European guidelines for vascular access: clinical algorithms on vascular access for haemodialysis.
Vascular access remains the Achilles heel of end-stage renal disease patients, receiving haemodialysis. The increase in the number of elderly dialysis patients with additional cardiovascular co-morbidities and diabetes mellitus makes the creation and maintenance of functioning vascular access, more difficult and cumbersome. Therefore, the development of guidelines for vascular access management seems logical. A team of multidisciplinary vascular access experts created a set of algorithms covering the whole spectrum from pre-operative vessel assessment, peri-operative access management and post-operative follow up and surveillance. Additionally, a range of various access complications with their diagnosis and treatment options were included in these algorithms. The new European guidelines for vascular access augment the knowledge of vascular access problems and their management. Additionally, the use of algorithms facilitates the decision-making when treating complications by all physicians dedicated to this field of healthcare.


A comparative study of transdermal nitroglycerine patch and oral nifedipine in preterm labor.
Currently, the main goal for the use of tocolytic therapy is to delay the birth so as to allow the use of corticosteroids for accelerating fetal lung maturity and maternal transfer to a tertiary care center and thereby reducing neonatal morbidity and mortality. The aims amd objectives were to compare the safety and efficacy of transdermal nitroglycerine patch with oral nifedipine as a tocolytic agent to arrest preterm labor and prevent preterm birth. Based on the selection criteria, 50 patients were selected randomly in Group A and Group B. Group A women were given transdermal nitroglycerin patch, which delivered 10 mg Nitroglycerin (NTG) over 24 h and it was applied to the woman's abdomen followed by another patch of 10 mg after 1 h if contractions persisted. After 24 h, it was replaced by a fresh patch. Group B women were given an oral loading dose of nifedipine 20 mg followed by a similar dose if contractions persisted after 1 h. A maintenance dose of 10 mg thrice daily was given if contractions were suppressed. Patients were monitored from the time of admission to the time of discharge. The mean duration of prolongation of pregnancy in Group B (3.68 ± 1.91 days) was significantly more than Group A (2.78 ± 1.39 days). Headache was seen significantly more in Group A (42%) than group B (6%). Tachycardia, hypotension, and palpitation showed no statistically significant difference between them. There was no statistically significant difference in the birth weight of the babies in both the groups. Nifedipine is a safe and effective drug in prolonging preterm labor and has minimal maternal and neonatal side effects.


Benign pleomorphic adenomas in children.
Benign pleomorphic adenomas of the salivary glands in children are rare. Reported are 30 patients under the age of 21 years presenting with this neoplasm. Twelve patients were first seen with recurrent or persistent tumor following previous attempts at removal. Retreatment resulted in control of the neoplasm in eight patients with follow-up from 5 to 24 years. Two additional patients have developed malignant degeneration of their neoplasms. All 18 previously untreated patients have remained free of recurrence. As with adults, the treatment of choice for benign pleomorphic adenomas of the parotid gland developing in children is parotidectomy with preservation of the facial nerve. Tumors arising in the submandibular gland are best treated by complete excision of the gland as well as the tumor.


Assessment of the oxidant tolerance of Methanosarcina acetivorans.
All methane-producing Archaea (methanogens) are strict anaerobes, but the majority of species are tolerant to oxidants. Methanosarcina species are important environmental and industrial methanogens as they are one of only two genera capable of producing methane with acetate. Importantly, Methanosarcina species appear to be the most oxidant-tolerant; however, the mechanisms underlying this tolerance are poorly understood. We report herein two similar methods (spot-plating and microtiter plate) developed to examine the oxidant tolerance of Methanosarcina acetivorans by viability assessment. Both methods revealed that M. acetivorans can tolerate exposure to millimolar levels of hydrogen peroxide (H2O2 ) without a complete loss of viability. The exogenous addition of catalase was also shown to protect M. acetivorans from H2O2 toxicity, indicating catalase can serve as an antioxidant enzyme in methanogens even though oxygen is a byproduct. Of the two methods, the microtiter plate method provided a simple, reliable, and inexpensive method to assess viability of M. acetivorans. Combined with recent advances in the genetic manipulation of methanogens, methods in assessment of methanogen oxidant tolerance will aid in the identification of components of the antioxidant defense systems.


Association between the Matrix Metalloproteinase-9 rs3918242 Polymorphism and Ischemic Stroke Susceptibility: A Meta-Analysis.
In recent years, dozens of case-control studies showed that matrix metalloproteinase (MMP)-9 rs3918242 variants were associated with ischemic stroke (IS) susceptibility. However, the conclusions of case-control studies that evaluated the relationship between MMP-9 rs3918242 variants and the risk of IS were still equivocal. Herein, we conducted a comprehensive meta-analysis to investigate the association between MMP-9 rs3918242 variants and the risk of IS. We searched 5 databases (PubMed, EMBASE, Google Scholar, Web of Science, and Chinese Biomedical Literature Database) to identify the eligible studies up to October of 2016. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association of MMP-9 rs3918242 variants with IS susceptibility under the allelic model (T versus C) and the dominant model (TT + CT versus CC). A total of 14 studies with 3233 cases and 3123 controls were included in this meta-analysis. Our meta-analysis indicated that MMP-9 rs3918242 variants were associated with significantly increased risk of IS in overall populations (T versus C: OR = 1.43, 95% CI = 1.20-1.71, P < .001; TT + CT versus CC: OR = 1.39, 95% CI = 1.16-1.67, P < .001). Subgroup analysis based on ethnicity (Chinese and Caucasian) suggested that MMP-9 rs3918242 variants contributed to increase the risk of IS in Chinese population; However, no association was detected between MMP-9 rs3918242 variants and the risk of IS in Caucasian population. Therefore, our meta-analysis suggested that MMP-9 rs3918242 variants (T allele, TT and CT genotypes) contributed to significantly increase the risk of IS in the Chinese population.


Antigenic modification, rosette-forming cells, and Salmonella typhimurium resistance in outbred and inbred mice.
To assess the separate contributions of host T cells and the physical state of the antigen in the development of effective. Salmonella resistance, glutaraldehyde-treated and untreated protein- and ribonucleic acid-rich extracts (E-RNA extracts) of virulent Salmonella typhimurium SR-11 or attenuated S. typhimurium RIA were used to immunize Salmonella-resistant Salmonella-susceptible strains of mice for the purpose of determining whether antigen-specific T-cell or B-cell responses were formed and, if so, which responses predominated. The resistance imparted to each mouse strain after vaccination with S. typhimurium RIA was used as the standard for comparison. The inbred mouse strains C57BL/6 and DBA/2 and their F(1) hybrid (strain BDF(1)), outbred ICR Swiss mice, and endotoxin-resistant C3H/HeJ mice were examined for the capacity to develop resistance to lethal Salmonella infections, as well as the ability to generate antigen-reactive T cells. Only the BDF(1), C3H/HeJ, and ICR Swiss mice were able to develop resistance to challenge infections mediated by the virulent SR-11 strain of S. typhimurium after vaccination with the living, attenuated RIA strain of S. typhimurium or immunization with E-RNA extracts. We developed an assay to identify the antigen-reactive rosette-forming lymphocytes present in lymph nodes and spleens of immunized mice. Levels of 0.2% or higher of theta antigen-bearing, antigen-reactive rosette-forming cells were found in the lymph nodes or spleens or both of only the BDF(1), C3H/HeJ, and ICR Swiss mice (i.e., in the "Salmonella responder" strains). Mouse strains C57BL/6 and DBA/2, which failed to develop resistance to lethal infections after immunization with the S. typhimurium RIA vaccine or with the E-RNA extracts, lacked effective numbers of antitheta antigen-sensitive rosette-forming cells. Modification of the effective E-RNA extracts by polymerization with glutaraldehyde resulted in a marked diminution in their abilities to induce resistance to salmonellosis in the two responder mouse strains tested (BDF(1) and ICR Swiss), even though detectable levels of antibody were induced.


An Adaptive SSVEP-Based Brain-Computer Interface to Compensate Fatigue-Induced Decline of Performance in Practical Application.
Brain-computer interfaces based on steady-state visual evoked potentials are promising communication systems for people with speech and motor disabilities. However, reliable SSVEP response requires user's attention, which degrades over time due to significant eye-fatigue when low-frequency visual stimuli (5-15 Hz) are used. Previous studies have shown that eye-fatigue can be reduced using high-frequency flickering stimuli (>25 Hz). Here, it is quantitatively demonstrated that the performance of a high-frequency SSVEP BCI decreases over time, but this amount of decrease can be compensated effectively by using two proposed adaptive algorithms. This leaded to a robust alternative communication system for practical applications. The asynchronous spelling system implemented in this study uses a threshold-based version of LASSO algorithm for frequency recognition. In long online experiments, when participants typed a sentence with the BCI system for 16 times, accuracy of the system was close to its maximum along the experiment. However, regression analysis on typing speed of each sentence demonstrated a significant decrease in all 7 subjects ( ) when thresholds obtained from a calibration test were kept fixed over the experiment. In comparison, no significant change in typing speed was observed when the proposed adaptive algorithms were used. The analysis of variances revealed that the average typing speed of the last four sentences when using adaptive relational algorithm (8.7 char/min) was significantly higher than the tolerance-based algorithm (8.1 char/min) and significantly above 6 char/min when the fixed thresholds were used. Therefore, the relational algorithm proposed in this paper could successfully compensate for the effect of fatigue on performance of the SSVEP BCI system.


Gaze detection and gaze cuing in Alzheimer's disease.
People with Alzheimer's disease (AD) show problems with social processing in tasks which require the understanding of others' mental states. However traditional social processing tasks are cognitively complex, which may influence the effects of AD. Less is known about how AD influences more basic aspects of social perception, such as the ability to decode eye gaze direction or follow the gaze of another. The current research assessed whether those with AD showed difficulty in both explicitly decoding subtle manipulations of gaze direction (Study 1), and reflexively following another's eye gaze (Study 2). Those with AD were more impaired than a matched control group when making explicit discrimination distinctions between direct and averted gaze. In contrast people with Alzheimer's disease performed comparably to a control group when following gaze. This pattern indicates that more automatic aspects of social perception such as gaze following are unaffected by AD. In contrast, more controlled processes such as deciding whether someone is looking towards you are impaired in AD. This has implications for socially engaging with other people and interpreting their focus of interest.


A contribution to the knowledge of the centipedes of Saint Barthélemy Island (French Antilles), with re-descriptions of Newportia heteropoda Chamberlin, 1918 and Cormocephalus impressus Porat, 1876 (Chilopoda: Scolopendromorpha).
The paper provides descriptions of three scolopendromorph centipede species collected in Saint Barthélemy Island. Two of them, Newportia heteropoda Chamberlin, 1918 and Cormocephalus impressus Porat, 1876 are redescribed and their systematic position is discussed. The taxonomic status of Newportia cubana Chamberlin, 1915 is revised, this nominal taxon being treated as the subspecies N. longitarsis cubana stat. nov. C. guildingii Newport, 1845 is confirmed as a valid species of which C. bonaerius Attems, 1928 is considered as a junior synonym. An identification key to the Scolopendromorpha of the island is presented.


A carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET probe targeting PI3K/mTOR in cancer.
The PI3K/Akt/mTOR pathway is frequently dysregulated in cancer due to its central role in cell growth, survival, and proliferation. Overactivation of the PI3K/Akt/mTOR pathway may occur through varying mechanisms including mutations, gene amplification, and upstream signaling events, ultimately resulting in cancer. Therefore, PI3K/Akt/mTOR pathway has emerged as an attractive target for cancer therapy and imaging. A promising approach to inhibit this pathway involves a simultaneous inhibition of both PI3K and mTOR using a dual inhibitor. Recently, a potent dual PI3K/mTOR inhibitor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (7), was discovered and demonstrated excellent kinase selectivity IC50 (PI3K/mTOR) = 0.20/21 nM; good cellular growth inhibition IC50 (HCT-116 cell) = 10 nM, modest plasma clearance, and acceptable oral bioavailability. Expanding on this discovery, here we present the synthesis of the carbon-11 labeled imidazo[1,2-a]pyridine derivative 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-[11C]methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (N-[11C]7) as a new potential radiotracer for the biomedical imaging technique positron emission tomography (PET) imaging of PI3K/mTOR in cancer. The reference standard 7 and its N-demethylated precursor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(piperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (11), were synthesized in 7 and 8 steps with 10% and 7% overall chemical yield, respectively. N-[11C]7 was prepared from 11 using [11C]methyl triflate ([11C]CH3OTf) through N-11C-methylation and isolated by high-performance liquid chromatography (HPLC) and solid-phase extraction (SPE) formulation in 40-50% radiochemical yield decay corrected to end of bombardment (EOB) based on [11C]CO2. The radiochemical purity was > 99% and the molar activity (Am) at EOB was in the range of 296-555 GBq/µmol (n = 5).


Frequent discordance between morphology and mitochondrial DNA in a species group of European water beetles (Coleoptera: Dytiscidae).
The Hydroporus memnonius species group includes both widespread and range restricted diving beetle taxa in the western Palaearctic, some of which have been divided into a number of geographical subspecies. Of these, Hydroporus necopinatus is distributed in the far west of Europe, from central Spain to southern Britain, and has been split into three subspecies, occurring in Iberia (necopinatus sst.), France (robertorum) and England (roni) respectively-the last of these being a rare example of an insect taxon apparently endemic to northern Europe. Here we explore inter-relationships between populations and subspecies of H. necopinatus and related members of the Hydroporus melanarius subgroup, using mitochondrial COI sequence data. We reveal widespread discordance between mitochondrial DNA sequence variation and morphology in areas where H. necopinatus and H. melanarius come into contact, consistent with historical introgressive hybridization between these taxa. In light of this discordance, the lack of clear genetic divergence between H. necopinatus subspecies, and the fact that both robertorum and roni are morphologically intermediate between H. necopinatus sstr. and H. melanarius, we suggest that these taxa may be of hybridogenic origin, rather than representing discrete evolutionary lineages.


Application of the Still-Face Paradigm in Early Screening for High-Risk Autism Spectrum Disorder in Infants and Toddlers.
Background: Although autism spectrum disorder (ASD) can currently be diagnosed at the age of 2 years, age at ASD diagnosis is still 40 months or even later. In order to early screening for ASD with more objective method, behavioral videos were used in a number of studies in recent years. Method: The still-face paradigm (SFP) was adopted to measure the frequency and duration of non-social smiling, protest behavior, eye contact, social smiling, and active social engagement in high-risk ASD group (HR) and typical development group (TD) (HR: n = 45; TD: n = 43). The HR group was follow-up until they were 2 years old to confirm final diagnosis. Machine learning methods were used to establish models for early screening of ASD. Results: During the face-to-face interaction (FF) episode of the SFP, there were statistically significant differences in the duration and frequency of eye contact, social smiling, and active social engagement between the two groups. During the still-face (SF) episode, there were statistically significant differences in the duration and frequency of eye contact and active social engagement between the two groups. The 45 children in the HR group were reclassified into two groups after follow-up: five children in the N-ASD group who were not meet the criterion of ASD and 40 children in the ASD group. The results showed that the accuracy of Support Vector Machine (SVM) classification was 83.35% for the SF episode. Conclusion: The use of the social behavior indicator of the SFP for a child with HR before 2 years old can effectively predict the clinical diagnosis of the child at the age of 2 years. The screening model constructed using SVM based on the SF episode of the SFP was the best. This also proves that the SFP has certain value in high-risk autism spectrum disorder screening. In addition, because of its convenient, it can provide a self-screening mode for use at home. Trial registration: Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.


Thyrotoxicosis in patients with hypothyroidism is not just overtreatment.
A 62-year-old Caucasian woman presented with hypothyroid symptoms and biochemical thyrotoxic picture. Previously, she underwent right-sided subtotal thyroidectomy and left partial thyroid lobectomy for thyroid lumps, and treated with thyroxine replacement for hypothyroidism. Although there were no significant findings on clinical examination, investigations confirmed thyrotoxicosis with positive autoimmunity against thyroid glandâ€"all in line with a diagnosis of Graves' hyperthyroidism. We would like to highlight atypical presentations of thyroid dysfunction and conversion of underactive to overactive thyroid status with this case. Early recognition, diagnosis and intervention are essential to prevent and/or reduce associated morbidity and mortality. When encountered with such clinical conundrums, we recommend seeking opinion from an experienced endocrinologist while interpreting such situation.


Dermis-fat orbital implantation: 118 cases.
During the previous six years the authors have performed 118 dermis-fat orbital implants. Fifty-one were primary implantations performed at the time of enucleation. Nineteen grafts were implanted after migrated implants were removed, and 19 grafts were used to correct superior sulcus deformities. Nine dermis-fat grafts expanded contracted sockets. It is becoming increasingly clear that these autogenous implants are effective in maintaining orbital volume while preserving the fornicies and conserving the conjunctiva. Although significant atrophy of primary grafts does not occur very frequently, it is more common in cases of secondary implantation, particularly in cases of chemically injured severely contracted sockets (3 of 9 cases). We have noted only one case of significant atrophy following a primary procedure. This occurred two and a half years following an apparently successful primary graft.


Equine synovial sepsis laboratory submissions yield a low rate of positive bacterial culture and a high prevalence of antimicrobial resistance.
To investigate (1) variables associated with the likelihood of obtaining a positive culture, (2) commonly isolated microorganisms, and (3) antimicrobial resistance patterns of isolates from horses with presumptive synovial sepsis. Synovial fluid, synovium, and bone samples from equine cases with presumptive synovial sepsis submitted to the Cornell University Animal Health Diagnostic Center from 2000 to 2020 for microbial culture and antimicrobial sensitivity testing. Univariable and multivariable analyses were performed to determine the effect of variables on the likelihood of positive culture. Frequency distributions for isolated organisms and antimicrobial resistance were generated. Multidrug resistance patterns and associations were assessed with association rule mining. The positive culture rate for all samples was 37.4%, while the positive culture rate among samples confirmed to be septic by a combination of clinical pathological variables and case details was 43%. Blood culture vial submissions were 1.7 times more likely to yield a positive culture compared to samples submitted in a serum tube. Structure sampled, tissue submitted, and horse age were associated with a positive culture. Staphylococcus spp (23.7%), Streptococcus spp (22.4%), and Enterococcus spp (9.67%) were commonly isolated. Multidrug resistance prevalence decreased from 92% (2000 to 2009) to 76% (2010 to 2020) of gram-negative isolates and 60% (2000 to 2009) to 52% (2010 to 2020) of gram-positive isolates. The positive culture rate from synovial fluid submissions with traditional sampling and culture methods remains low and may be optimized by submitting samples in blood culture vials. Overall, antimicrobial resistance was frequently observed but did not increase from the first to second decade for most genera.


Discrimination among protein variants using an unfoldase-coupled nanopore.
Previously we showed that the protein unfoldase ClpX could facilitate translocation of individual proteins through the α-hemolysin nanopore. This results in ionic current fluctuations that correlate with unfolding and passage of intact protein strands through the pore lumen. It is plausible that this technology could be used to identify protein domains and structural modifications at the single-molecule level that arise from subtle changes in primary amino acid sequence (e.g., point mutations). As a test, we engineered proteins bearing well-characterized domains connected in series along an ∼700 amino acid strand. Point mutations in a titin immunoglobulin domain (titin I27) and point mutations, proteolytic cleavage, and rearrangement of beta-strands in green fluorescent protein (GFP), caused ionic current pattern changes for single strands predicted by bulk phase and force spectroscopy experiments. Among these variants, individual proteins could be classified at 86-99% accuracy using standard machine learning tools. We conclude that a ClpXP-nanopore device can discriminate among distinct protein domains, and that sequence-dependent variations within those domains are detectable.


Minimally Invasive Single-Implant Treatment in the Esthetic Zone.
Clinicians face significant challenges when placing single-tooth, implant-supported restorations in the esthetic zone. Understanding myriad factors, such as smile design, patient expectations, and hard- and soft-tissue responses, plays a vital role in achieving a predicable outcome. This article presents a case report demonstrating a minimally invasive approach, which combined immediate implant placement, hard- and softtissue augmentation, and immediate provisionalization in 1 visit.


NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices.
Endogenous reactive oxygen species (ROS) can act as modulators of neuronal activity, including synaptic transmission. Inherent in this process, however, is the potential for oxidative damage if the balance between ROS production and regulation becomes disrupted. Here we report that inhibition of synaptic transmission in rat hippocampal slices by H2O2 can be followed by electrical hyperexcitability when transmission returns during H2O2 washout. As in previous studies, H2O2 exposure (15 min) reversibly depressed the extracellular population spike (PS) evoked by Schaffer collateral stimulation. Recovery of PS amplitude, however, was typically accompanied by mild epileptiform activity. Inclusion of ascorbate (400 microM) during H2O2 washout prevented this pathophysiology. No protection was seen with isoascorbate, which is a poor substrate for the stereoselective ascorbate transporter and thus remains primarily extracellular. Epileptiform activity was also prevented by the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5) during H2O2 washout. Once hyperexcitability was induced, however, AP5 did not reverse it. When present during H2O2 exposure, AP5 did not alter PS depression by H2O2 but did inhibit the recovery of PS amplitude seen during pulse-train stimulation (10 Hz, 5 s) in H2O2. Inhibition of glutamate uptake by l-trans-2,4-pyrrolidine dicarboxylate (PDC; 50 microM) during H2O2 washout markedly enhanced epileptiform activity; coapplication of ascorbate with PDC prevented this. These data indicate that H2O2 exposure can cause activation of normally silent NMDA receptors, possibly via inhibition of redox-sensitive glutamate uptake. When synaptic transmission returns during H2O2 washout, enhanced NMDA receptor activity leads to ROS generation and consequent oxidative damage. These data reveal a pathological cycle that could contribute to progressive degeneration in neurological disorders that involve oxidative stress, including cerebral ischemia.


The use of levonorgestrel implants (Norplant) for contraception in adolescent mothers.
Although levonorgestrel implants (Norplant) would appear to be a good contraceptive option for adolescent mothers, there is little information about the use of Norplant in this population. We studied 100 postpartum adolescents who chose a contraceptive method at an urban teaching hospital between September 1991 and July 1992. Structured interviews were conducted and medical records were reviewed soon after delivery and at a mean (+/- SD) of 15.5 +/- 2.9 months post partum. Forty-eight of the adolescent mothers chose Norplant, 50 chose oral contraceptives, and 2 (not further studied) chose barrier methods of contraception. The factors significantly associated with the choice of Norplant were older age (16.7 years among those who chose Norplant, vs. 16.2 years among those who chose oral contraceptives), multiparity (24 subjects vs. 6 subjects), and previous use of oral contraceptives (34 subjects vs. 21 subjects). During follow-up, there were no differences between the Norplant group and the oral-contraceptive group in the frequency of clinic visits (an average of 2.3 visits per subject in each group), failure to return after the postpartum visit (9 subjects vs. 11 subjects), or the incidence of sexually transmitted diseases (42 percent vs. 36 percent). At follow-up, 95 percent of the subjects in the Norplant group and 33 percent of those in the oral-contraceptive group were still using the method they had chosen (P < 0.001). During the first postpartum year 1 subject in the Norplant group and 19 in the oral-contraceptive group became pregnant (P < 0.001). Norplant users did not differ from all other adolescents studied with regard to sexual activity or condom use. The selection of Norplant by adolescent mothers as a method of contraception is associated with higher rates of continued use and lower rates of new pregnancy than the selection of oral contraceptives and does not affect the use of health care services, sexual activity, condom use, or the rate of sexually transmitted diseases.


In Silico Analysis Identifies Differently Expressed lncRNAs as Novel Biomarkers for the Prognosis of Thyroid Cancer.
Thyroid cancer (TC) is one of the most common type of endocrine tumors. Long noncoding RNAs had been demonstrated to play key roles in TC. Material and Methods. The lncRNA expression data were downloaded from Co-lncRNA database. The raw data was normalized using the limma package in R software version 3.3.0. The differentially expressed mRNA and lncRNAs were identified by the linear models for the microarray analysis (Limma) method. The DEGs were obtained with thresholds of ∣logFC∣ > 1.5 and P < 0.001. The hierarchical cluster analysis of differentially expressed mRNAs and lncRNAs was performed using CLUSTER 3.0, and the hierarchical clustering heat map was visualized by Tree View. In the present study, we identified 6 upregulated and 85 downregulated lncRNAs in TC samples. Moreover, we for the first time identified 16 downregulated lncRNAs was correlated to longer disease-free survival time in patients with TC, including ATP1A1-AS1, CATIP-AS1, FAM13A-AS1, LINC00641, LINC00924, MIR22HG, NDUFA6-AS1, RP11-175K6.1, RP11-727A23.5, RP11-774O3.3, RP13-895J2.2, SDCBP2-AS1, SLC26A4-AS1, SNHG15, SRP14-AS1, and ZNF674-AS1. Bioinformatics analysis revealed these lncRNAs were involved in regulating the RNA metabolic process, cell migration, organelle assembly, tRNA modification, and hormone levels. This study will provide useful information to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets for TC.


The effect of mixing on the extrusion-spheronisation of a micro-crystalline cellulose paste.
The effect of mixer shear strain rate on the performance of a model micro-crystalline cellulose pharmaceutical paste undergoing extrusion-spheronisation was studied using a laboratory scale planetary mixer and a screw-based mixer. The maximum shear strain rate in each mixer was estimated. Five pastes were prepared, one each at 97 and 265 s(-1) in the planetary mixer, and one each at 304, 988 and 2220 s(-1) in the screw mixer. The rheology of the pastes was quantified by Benbow-Bridgwater characterisation based on ram extrusion. Each paste was spheronised and pellet size and shape distributions obtained by automated size analysis. Mixer type (rather than shear strain rate) was found to have the strongest influence on the paste properties, with the screw-mixed material having a higher yield strength and forming smaller pellets with a narrower size distribution when spheronised under identical conditions.


Maternal-newborn nurses' experiences of inconsistent professional breastfeeding support.
This paper is a report of a study to describe the meaning and significance of common, essential elements of inconsistent professional breastfeeding support as revealed through the experiences of maternal-newborn nurses in a hospital. Professional breastfeeding support has been found to have a beneficial effect on breastfeeding, although mothers also report that inconsistent professional breastfeeding support has a negative influence on their breastfeeding efforts. An existential-phenomenological approach was used, and interviews were conducted with 12 maternal-newborn nurses between October 2005 and January 2006. Interview transcripts were subjected to thematic analysis. Inconsistency in professional breastfeeding support was directly related to the fact that 'supporting' breastfeeding is a dynamic, multidimensional process with relational, contextual and situational components. Eight themes were identified: Inconsistencies still exist but things are changing; A need for 'buy in'; There is no escaping personal experience; What works for one does not work for all; Time impacts recommendations; We have a privileged vantage point; 'My job': what it is and what it is not and After all, breastfeeding is a maternal 'choice'. Addressing inconsistent professional breastfeeding support involves understanding the multiple institutional and personal factors that influence this phenomenon. Because multiple practitioners assist each mother-infant dyad in learning to breastfeed, fostering strong collaborative relationships within this support team is essential. Regular opportunities for all team members to dialogue and actively participate in the updating of breastfeeding policies may increase 'buy in', promote greater collaboration and decrease both conflict and inconsistencies.


Assessment of Cryptococcus albidus for biopulping of eucalyptus.
Cryptococcus albidus shows delignification activity in nature. It was used for the biopulping of eucalyptus wood (Eucalyptus grandis) to access its potential for industrial application in the pulp and paper industry. Enzyme analysis on days 15, 30, and 60 showed the presence of laccase and xylanase as key enzymes. The production of endo-glucanase (CMCase) and exo-glucanase (FPase) was very low. Scanning electron microscopy (SEM) showed the surface colonization of wood and loosening of wood fibers in C. albidus-treated samples. Fourier-transformation infrared spectroscopy (FT-IR) indicated the chemical modification of eucalyptus wood. Denaturing gradient gel electrophoresis (DGGE) analysis on days 15, 30, and 60 confirmed the presence of C. albidus throughout the experiments. Cryptococcu albidus was able to suppress the growth of a native population. Further, after 60 days both the control and treated eucalyptus wood chips were given kraft pulping treatment. The kappa number of pulp of control wood was 21 and for treated wood was 17. Kappa number is considered a measure of lignin content in wood; hence the treatment of eucalyptus by C. albidus (biopulping) was effective in reducing its lignin content and can be used for biopulping in the pulp and paper industry.


ODaCCI: Ontology-guided Data Curation for Multisite Clinical Research Data Integration in the NINDS Center for SUDEP Research.
Sudden Unexpected Death in Epilepsy (SUDEP) is the leading mode of epilepsy-related death. The Center for SUDEP Research (CSR) is an NINDS-funded Center Without Wall's initiative aimed at prospectively creating a comprehensive clinical research resource for SUDEP. This resource consists of a growing set of data and biological samples of a statistically significant cohort of patients at an elevated risk, best represented by the Epilepsy Monitoring Unit (EMU) patient population. The Informatics and Data Analytics Core (IDAC) of CSR has developed a state-of-the- art informatics infrastructure, to integrate patient data captured in multiple EMU's at a greatly accelerated pace. Data quality assurance is a priority of IDAC. This paper reports our approach, Ontology-guided Data Curation for Multisite Clinical Research Data Integration (ODaCCI), to address the challenging task of centralized data curation while new data is continuously generated and integrated from distributed sites. ODaCCI leverages the Epilepsy and Seizure Ontology not only for upstream data capture, but also for supporting a range of quality assurance tasks such as data quality monitoring, data update, and data reports. Between October 2014 and February 2016, ODaCCI has integrated phenotypic and electroencephalogram signal data of 629 patients from 7 clinical sites, while supporting continuous and asynchronous data quality enhancement overtime.


Implications of free breathing motion assessed by 4D-computed tomography on the delivered dose in radiotherapy for esophageal cancer.
The aim of this study was to assess the effect of breathing motion on the delivered dose in esophageal cancer 3-dimensional (3D)-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). We assessed 16 patients with esophageal cancer. All patients underwent 4D-computed tomography (4D-CT) for treatment planning. For each of the analyzed patients, 1 3D-CRT, 1 IMRT, and 1 VMAT (RapidArc-RA) plan were calculated. Each of the 3 initial plans was recalculated on the 4D-CT (for the maximum free inspiration and maximum free expiration) to assess the effect of breathing motion. We assessed the minimum dose (Dmin) and mean dose (Dmean) to the esophagus within the planning target volume, the volume changes of the lungs, the Dmean and the total lung volume receiving at least 40Gy (V40), and the V30, V20, V10, and V5. For the heart we assessed the Dmean and the V25. Over all techniques and all patients the change in Dmean as compared with the planned Dmean (planning CT [PCT]) to the esophagus was 0.48% in maximum free inspiration (CT_insp) and 0.55% in maximum free expiration (CT_exp). The Dmin CT_insp change was 0.86% and CT_exp change was 0.89%. The Dmean change of the lungs (heart) was in CT_insp 1.95% (2.89%) and 3.88% (2.38%) in CT_exp. In all, 4 patients had a clinically relevant change of the dose (≥ 5% Dmean to the heart and the lungs) between inspiration and expiration. These patients had a very cranially or caudally situated tumor. There are no relevant differences in the delivered dose to the regions of interest among the 3 techniques. Breathing motion management could be considered to achieve a better sparing of the lungs or heart in patients with cranially or caudally situated tumors.


Corn starch/polyvinyl alcohol based films incorporated with curcumin-loaded Pickering emulsion for application in intelligent packaging.
The intelligent pH indicator films were prepared by incorporating curcumin-loaded Pickering emulsion with corn starch (CS) and polyvinyl alcohol (PVA) matrix. The mechanical properties, barrier properties and functional characteristics of the films were studied and the films were applied to monitor fish freshness. Fourier transform infrared (FTIR) spectroscopy and Scanning electron microscopy (SEM) showed that Pickering emulsion can form hydrogen bonds with CS and PVA. The antioxidant activity of the films was detected, which showed that Pickering emulsion could reduce the decomposition of curcumin during the process of preparation and storage. Bactericidal tests showed that the films can inhibit the growth of S. aureus, B. subtilis, and E. coli, and the effect of the films on Gram-positive (G+) bacteria is stronger than Gram-negative (G-) bacteria. Application of the films presented here is supported by an activation test of Pangasius bocouti. With time changed, the color of films changed from yellow to red, and the color change of films prepared with curcumin-loaded Pickering emulsion was more evident than the films prepared with curcumin solution. Therefore, the films prepared with curcumin-loaded Pickering emulsion had better performance and can be used to indicate the quality of food.


Glucose metabolism and antidepressant medication.
Impaired glucose tolerance is observed in depressed patients, and patients suffering from depression have an increased risk to develop diabetes mellitus. In depressed and diabetic patients, studies have shown both a beneficial effect of antidepressants on glucose homeostasis and the opposite. This review aims to structure the conflicting data and focuses on the question, which effect specific antidepressants have on glucose homeostasis. We therefore performed a systematic review of all available studies referenced in Medline from 1960 to 2011. We included antidepressant agents indexed in the Anatomical Therapeutic Chemical (ATC) classification system of the WHO in 2011 and searched for studies investigating their effects on glucose metabolism in clinical samples as well as in healthy subjects. Of 876 studies screened we included 66. Most studies had small sample sizes and lacked a placebo group limiting conclusions about antidepressant effects on glucose tolerance. However, some evidence points to beneficial effects on glucose homeostasis of hydrazine-type monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). In case of SSRIs, the effect is more pronounced in diabetic patients or patients with comorbid depression and diabetes mellitus. Noradrenegic substances (and possibly also dualacting antidepressants), in contrast, may deteriorate glucose tolerance. They can be used in depressed patients when favorable effects on mood outweigh adverse metabolic effects, but in depressed diabetics this can be at the expense of worsening of glycemic control. The effects of other antidepressants, like bupropione, mirtazapine or newer agents, require further investigation before reliable conclusions can be made. The synthesis of the findings is discussed in light of the specific pharmacodynamic properties of the antidepressants as well as the pathophysiological changes in depression and impaired glucose homeostasis, including animal studies.


Development of orally dissolving films for pediatric-centric administration of anti-epileptic drug topiramate - A design of experiments (DoE) study.
Children have often been treated as small adults in relation to drug formulation, but research has now shown this not to be the case. Therefore, there is a push from regulatory bodies to provide drug formulations specifically tailored towards the needs of this fragmented population. Orally dissolving films (ODFs) have been identified as an emerging opportunity, to bridge this gap. Therefore, the aim of this study was to prepare ODFs containing topiramate, an antiepileptic drug, using solvent casting method as a potential alternative to oral tablets/powders for paediatrics. For this purpose, a Design of Experiment (DoE) was employed to optimise formulation parameters. 24 formulations were prepared by changing the polymer type (HPMC, Guar-Gum or PEO), concentration (0.4%-1.2%w/v); plasticizer type (glycerol\sorbitol) and concentration (0.1-0.3%w/v). Disintegration time, content-uniformity, film quality and thickness uniformity were the responses. Surface and molecular profiling were conducted on the optimal formulation (N4). TGA and XRD results demonstrated the stability of materials upon production into films, while the SEM images showed smooth films that proved to be resilient due to good mechanical properties. HPMC-glycerine based ODFs are presented as an effective dosage form to enhance the ease of administration and patient compliance of topiramate, specifically for paediatric patients.


Aeroacoustic source term computation based on radial basis functions.
In low Mach number aeroacoustics, the known disparity of length scales makes it possible to apply well-suited simulation models using different meshes for flow and acoustics. The workflow of these hybrid methodologies include performing an unsteady flow simulation, computing the acoustic sources, and simulating the acoustic field. Therefore, hybrid methods seek for robust and flexible procedures, providing a conservative mesh to mesh interpolation of the sources while ensuring high computational efficiency. We propose a highly specialized radial basis function interpolation for the challenges during hybrid simulations. First, the computationally efficient local radial basis function interpolation in conjunction with a connectivity-based neighbor search technique is presented. Second, we discuss the computation of spatial derivatives based on radial basis functions. These derivatives are computed in a local-global approach, using a Gaussian kernel on local point stencils. Third, radial basis function interpolation and derivatives are used to compute complex aeroacoustic source terms. These ingredients are necessary to provide flexible source term calculations that robustly connect flow and acoustics. Finally, the capabilities of the presented approach are shown in a numerical experiment with a co-rotating vortex pair.


Idiopathic left bundle-branch block-shaped ventricular tachycardia may originate above the pulmonary valve.
Idiopathic left bundle-branch block (LBBB)-like ventricular tachycardia (VT) is considered to originate in the right ventricular outflow tract (RVOT) or from the aortic root. Both regions are derived from the embryonic outflow tract. We now report that also the pulmonary trunk can give rise to VT, suggesting a common etiology of these tachycardias. We studied 6 patients with symptomatic idiopathic LBBB-VT using electrophysiological mapping techniques. The VT origin was determined by analyzing the electrograms and the angiographic location of the catheter tip at the successful ablation site or the earliest activation site. Eight VTs were induced. Two VTs, with a mean earliest endocardial activation time of -5 and -20 ms and optimal pace mapping, were successfully ablated in the RVOT. In the remaining 6 VTs, the earliest activation site was found in the pulmonary artery, and, at this site, a sharp potential was present -38+/-12 ms before the QRS in 5 VTs. The mean earliest endocardial activation time in the RVOT was -1+/-2 ms. Ablation was attempted in 5 of 6 VTs and resulted in an acutely successful procedure. After a mean follow-up of 10+/-4 months, 1 of 5 patients had a recurrence. The site of origin of idiopathic LBBB-VT can be in the root of the pulmonary artery, suggesting a myocardial connection from this site to the RVOT. If no good criteria for ablation in the RVOT are found, detailed mapping of the pulmonary artery should be performed.


Assessing Intimate Partner Abuse: Associated Factors and Health Consequences among Jordanian Women.
In this cross-sectional study, we assessed levels and types of psychological and physical intimate partner abuse (IPA), and the association of IPA with socio-demographic factors and health consequences. The Abusive Behavior Inventory was completed by 471 Jordanian women. IPA was higher among older women who were: of older age, of younger age at marriage, married to unemployed spouses, living in urban residence, and of lower educational level. IPA was associated with most of the health problems except dental injuries and burns. We recommend educational programs that raise women's awareness to their rights to education, free choices in marital age, and policies that mitigate IPA in Jordan and similar patriarchal societies.


[Detection and clinical significance of circulating tumor cells in osteosarcoma using immunofluorescence combined with in situ hybridization].
Objective: To investigate the clinical significance of detection of circulating tumor cells (CTCs) in peripheral blood from patients with osteosarcoma (OS) using the iFISH (immunofluorescence and fluorescence in situ hybridization) method. Methods: The live cells recovery rate of immune-magnetic beads was evaluated by live-cell fluorescent tracer technology. The expression of CD45 and CK18 on the cell surface of HOS and HepG2 cells was measured by flow cytometry. And the chromosome aneuploidy was detected by centromeric FISH probe CEP8. Subsequently, 23 OS patients were enrolled and divided into two groups, relapse or metastasis group and primary group. And the prognostic significance of CTCs numbers was analyzed. Results: The live cells recovery rate of immune-magnetic beads was higher than 90%. The flow cytometry results showed that HOS cells were double negative for the surface biomarkers of CD45 and CK18. In addition, the FISH-CEP8 signal abnormality rate were 96.5% in HOS cells. Thus, CTC was identified using the criteria as follows: the cells with CEP8-positive signal >2 accounted for more than 96.5% of the total cells, of which the cells with >3 positive signal were more than 65.0%. Among the enrolled patients, 19 patients had detectable CTCs in the peripheral blood. The CTCs numbers in the relapse or metastasis group and primary group were 2.846±1.281 and 1.400±1.506, respectively. The results showed that the CTCs in patients with recurrence or metastasis were significantly higher than those in primary patients (P=0.021). Conclusions: To our knowledge, this is the first evidence of existence of CTCs in OS patients. The CTCs numbers were positively associated with disease progression and poor prognosis. These results may provide a potential prognostic tool for monitoring metastasis and recurrence in OS patients. Trial registration: Chinese Clinical Trial Registry, ChiCTR-OOC-15005925.


The roles of oxytocin and CD38 in social or parental behaviors.
The nine amino acid peptide oxytocin (OXT) has been directly associated with different types of behavioral reactions. The formation and maintenance of social relationships in youth and middle age are important components of human mental health. A deficit in healthy behavioral formation leads to social isolation and limitation of well-being. Mice are social animals and are therefore useful for investigating the neurobiological mechanisms of cognitive process control, including the development of social relationships and social skills. Studies in mice may broaden our understanding of the human condition. The multifunctional protein CD38/ADP-ribosyl cyclase is highly expressed in the brain, plays an important role in central OXT release, and regulates social memory. In this review article, we discuss the mechanisms of social behavior affected by the dysregulation of brain OXT function as a consequence of a lack of CD38. OXT bound to OXT receptors initiates autoregulatory positive feedback of OXT release in the hypothalamus and posterior pituitary. OXT bio-behavioral positive feedback is usually implicated in female reproductive systems, but can also be observed in social behavior. Exogenous stimuli (OXT treatment in vitro, OXT intravenous or intraventricular administration, and nasal OXT delivery) initiate activation of OXT neurons via PKC-CD38/ADP-ribosyl cyclase cascades and result in the modulation of social behavior in humans and mice. Based on these findings, we reviewed the functions of OXT and its properties with respect to the development of therapies for human social behavior impairments in psychological diseases. In addition, preliminary studies of continuous nasal OXT administration on subjects with autism spectrum disorders are described.


Asymptomatic Left Ventricle Systolic Dysfunction.
Heart failure is a common debilitating illness, associated with significant morbidity and mortality, rehospitalisation and societal costs. Current guidelines and position statements emphasise the management of patients with overt symptomatic disease, but the increasing prevalence of congestive heart failure underscores the need to identify and manage patients with early left ventricular dysfunction prior to symptom onset. Asymptomatic left ventricular systolic dysfunction (ALVSD), classified as stage B heart failure, is defined as depressed left ventricular systolic function in the absence of clinical heart failure. Early initiation of therapies in patients with presumed ALVSD has been shown to lead to better outcomes. In this article, the authors clarify issues surrounding the definition and natural history of ALVSD, outline clinical tools that may be of value in identifying patients with ALVSD and highlight potential opportunities for future investigations to better address aspects of our understanding of this complex syndrome.


Occipital headaches stemming from the lateral atlanto-axial (C1-2) joint.
Studies in normal volunteers have demonstrated that the lateral atlanto-axial joints (C1-2) are capable of causing pain in the occiput, but few clinical studies have validated this source of occipital headache. The present study tested the null hypothesis that the lateral atlanto-axial joints are not a common source of occipital headache. Patients presenting with occipital pain underwent diagnostic blocks of their lateral atlanto-axial joints if they demonstrated clinical features presumptively suggestive of a C1-2 origin for their pain. Of 34 patients investigated, 21 obtained complete relief of their headache following diagnostic blocks, indicating that a C1-2 source of occipital pain is not rare. The clinical features used to select patients for blocks, however, had a positive predictive value of only 60%. Further study of headaches from C1-2 seems justified in order to establish more definitively the prevalence of this condition and how it might become better recognized in practice.


LncNetP, a systematical lncRNA prioritization approach based on ceRNA and disease phenotype association assumptions.
Our knowledge of lncRNA is very limited and discovering novel disease-related long non-coding RNA (lncRNA) has been a major research challenge in cancer studies. In this work, we developed an LncRNA Network-based Prioritization approach, named "LncNetP" based on the competing endogenous RNA (ceRNA) and disease phenotype association assumptions. Through application to 11 cancer types with 3089 common lncRNA and miRNA samples from the Cancer Genome Atlas (TCGA), our approach yielded an average area under the ROC curve (AUC) of 83.87%, with the highest AUC (95.22%) for renal cell carcinoma, by the leave-one-out cross validation strategy. Moreover, we demonstrated the excellent performance of our approach by evaluating the influencing factors including disease phenotype associations, known disease lncRNAs and the numbers of cancer types. Comparisons with previous methods further suggested the integrative importance of our approach. Taking hepatocellular carcinoma (LIHC) as a case study, we predicted four candidate lncRNA genes, RHPN1-AS1, AC007389.1, LINC01116 and BMS1P20 that may serve as novel disease risk factors for disease diagnosis and prognosis. In summary, our lncRNA prioritization strategy can efficiently identify disease-related lncRNAs and help researchers better understand the important roles of lncRNAs in human cancers.


An in vitro study with various vehicles of diffusion of formocresol and its components.
Pulpotomy in primary teeth using the formocresol method results in varying degrees of devitalization of the root pulp. The extent of this devitalization depends on, among other things, the ability of the components of formocresol to leave the dressing. The purpose of this study was to evaluate the rate and duration of diffusion of the components of formocresol when incorporated in different vehicles. The antimicrobial effect of the drugs was used to assess the diffusion of the components of formocresol in blood agar, with a sensitive microorganism as an indicator. Evaluation of the MICs assessed in broth medium for formalin, formocresol and cresol, respectively, and the zone size of growth inhibition on blood agar from these components when incorporated in ZnO or ZnO-eugenol cement, suggested that the initial zone of inhibition from formocresol was due mainly to the diffusion of formaldehyde. Cresol diffused more slowly from the dressing. The presence of eugenol in the dressing, as in ZnO-eugenol cement, gave smaller initial release of formaldehyde, formocresol and cresol compared with the release from ZnO, but more prolonged diffusion. A higher initial release of formaldehyde was obtained when the formocresol was incorporated in ZnO alone compared with ZnO-eugenol cement or Pharmatec.


Safety and Cost-Effectiveness in Thyroidectomy Using the HARMONIC Scalpel Compared to Traditional Hemostasis: A Controlled Clinical Assay.
The aim of this clinical control trial is to analyze the cost-effectiveness and to understand the efficacy of the HARMONIC FOCUS®+ (Ethicon Inc., Somerville, New Jersey) scalpel as the only system to cut and coagulate in thyroidectomy. One hundered patients of the thyroid clinic of the Mexico City General Hospital were included. All patients underwent surgery and were divided into two randomized groups. In Group 1, the HARMONIC scalpel was the only device used for cut and coagulate (50 patients), and in Group 2 clamp, tie, and electrocautery (50 patients) were used. Surgical bleeding, operative time, complications, diagnosis, thyroid size, and hospital stay were evaluated in both groups. The statistical analysis was done using central trend measurements, Student's t-, chi-squared, and Fisher's exact test, with a significance level of p < 0.05. The cost-effectiveness analysis was completed by determining the total cost of the surgical procedure per hour in US dollars, and the evolution to compare efficacy will be the number of re-interventions due to postoperative bleeding. The use of the HARMONIC scalpel in thyroid surgery had the same results as the traditional method when comparing complications, reoperation, hospital stay, and hypoparathyroidism. In total thyroidectomy patients, the bleeding in Group 1 was 55.16ml ( ± 32.97) and 85.4ml ( ± 69.41) in Group 2 , p=0.034. Operative time in Group 1 was 74.6 minutes (± 23.39) and 104.09 minutes (± 34.66) in Group 2, p= 0.0001. In both groups, there were no statistical differences in lobectomy. Cost-effectiveness analysis implies an adequate hemostasis if we are using a hemostatic device, and above all, the avoidance of a re-intervention due to hematoma, and the cost-effectiveness with regard to the re-intervention as a result of a hematoma implies that $161 US more is spent for each re-intervention. The utilization of the HARMONIC scalpel device is similar to the traditional technique of ligature and knots as far as cost-effectiveness is concerned, due to the fact that the greater expense of the device is compensated by the lower expense in time and surgical re-intervention.


Fatal pulmonary cysticercosis caused by Cysticercus longicollis in a captive ring-tailed lemur (Lemur catta).
Here we describe fatal pulmonary cysticercosis caused by Cysticercus longicollis, the larval stage of Taenia crassiceps in a 15-year-old female ring-tailed lemur (Lemur catta) from Sarajevo Zoo. After sudden death, the lemur was subjected to necropsy and large multicystic structure, subdivided with fibrous septa and filled with numerous translucent, oval to ellipsoid bladder-like cysts (cysticerci), almost completely replacing right lung lobe was observed. In addition, numerous free and encysted cysticerci were found in the thoracic cavity. Histopathology revealed connective tissue outlined cavities that compress lung parenchyma. Each cavity contained several thin walled cysticerci with single inverted protoscolex, one or more suckers and rostelum with two rows of hooks. In many of the cysticerci one or several exogenous buds of daughter cysticerci were observed. Based on morphology and microscopic appearance the parasite was identified as C. longicollis. Subsequent molecular analysis and sequencing confirmed presumptive diagnosis. To our knowledge, this case represents the first report of T. crassiceps and cysticercosis caused by C. longicollis in Bosnia and Herzegovina.


Can the use of urgent care clinics improve access to care without undermining continuity in primary care?
There is a niche for urgent care clinics as an alternate source of health care in the United States. This systematic review examines whether the use of urgent care clinics can improve access to care or if these facilities undermine continuity of primary care. Databases used were Cumulative Index for Nursing and Allied Health (CINAHL) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Articles from 2004 to 2014 were searched using keywords-access, barriers, continuity of care, nurse practitioner (NP), urgent care, retail clinic, emergency, and primary care. Urgent care clinics can improve access to care, but may also negatively impact continuity of care, preventative services, and ongoing management of chronic conditions. Barriers to primary care and benefits of urgent care are inversely related. Insufficient knowledge regarding navigation of the healthcare system, perceived urgency of medical need, and deflection of care contribute to use of urgent care over primary care. NPs are frontline healthcare providers essential to developing and maintaining successful communication and collaboration among providers across healthcare settings. In both primary care and urgent care facilities, NPs can ensure continuity of care, decreased healthcare costs, and optimized health outcomes for patients.


Crystallization and preliminary crystallographic analysis of acylamino-acid releasing enzyme from the hyperthermophilic archaeon Aeropyrum pernix.
Crystals of acylamino-acid releasing enzyme from the hyperthermophilic archaeon Aeropyrum pernix strain K1 have been grown at 291 K using ammonium phosphate as a precipitant. The diffraction pattern of the crystal extends to 2.4 A resolution at 100 K using Cu Kalpha radiation. The crystal belongs to space group P1, with unit-cell parameters a = 107.5, b = 109.9, c = 119.4 A, alpha = 108.1, beta = 109.8, gamma = 91.9 degrees. The presence of eight molecules per asymmetric unit gives a crystal volume per protein mass (V(M)) of 2.4 A(3) Da(-1) and a solvent content of 48% by volume. A full set of X-ray diffraction data was collected to 2.9 A from the native crystal.


Impact of commercial marketing on patient demand.
This pilot study attempts to determine the impact of commercial direct-to-consumer advertising on the incidence of patients requesting medication for urinary incontinence by brand name. Of 310 patients interviewed prior to urodynamics, 237 (76%) sought treatment after seeing related commercials. After testing, 119 (50.2%) were prescribed the advertised drug for detrusor instability. Fifty-nine (24.8%) were diagnosed with intrinsic sphincter deficiency and were recommended anticholinergics, collagen injections, or surgery. Forty-one (17.2%) men were found to have bladder outlet obstruction, but only four were prescribed the advertised drug. Three (1.2%) were recommended intermittent catheterization along with the advertised drug and 15 (6.6%) had various other treatments. The results suggest that 50% of those seeking treatment were not candidates for the medication advertised.


Can low-dose CT perfusion imaging accurately assess response of advanced gastric cancer with neoadjuvant chemotherapy?
To explore the value of low-dose CT perfusion imaging (LDCTPI) technology and its perfusion parameters in assessing response of neoadjuvant chemotherapy (NAC) in patients with advanced gastric cancer (AGC). Thirty patients with AGC were studied prospectively by LDCTPI to measure two parameters including blood flow (BF) and blood volume (BV) of tumor area before and after chemotherapy, respectively. All of the patients received two courses of NAC and surgical resection of gastric tumor within one week after chemotherapy, and then obtained the result of postoperative pathology response for chemotherapy. The comparisons of BF and BV values of AGC before and after chemotherapy were analyzed by paired-samples t-test, respectively; and the correlations between BF as well as BV decrease rates after NAC and the pathology response grade were analyzed by Spearman statistical test. Thirty patients were divided into effective and ineffective groups according to different pathology response grade. Comparisons of BF as well as BV decrease rates between effective and ineffective groups were analyzed by independent-samples t-test, respectively. Receiver operating characteristic (ROC) curves were used to determine the cutoff values of BF and BV decrease rates as evaluation indicators of AGC after NAC and calculate area under the curve (AUC). There were significant differences in BF and BV values of AGC between before and after NAC (p < 0.001), respectively, and there were obvious correlations between BF as well as BV decrease rates and pathology response grade (r = 0.660, p < 0.001; r = 0.706, p < 0.001), respectively. There were also significant differences in BF and BV decrease rates of AGC between effective and ineffective groups (P = 0.001), respectively. If BF decrease rate of 12.1% (AUC was 0.816, P = 0.005) was used as the cutoff value for chemotherapy effectiveness of AGC, the sensitivity of 82% and specificity of 84% were achieved, and if BV decrease rate of 32.8% (AUC was 0.844, P = 0.002) was used as the cutoff value for chemotherapy effectiveness of AGC, the sensitivity of 82% and specificity of 89% were achieved. BF and BV decrease rates have potential to be used as effective indicators to assess chemotherapy efficacy of AGC from the hemodynamics.


A Mixed Comparisons of Different Intensities and Types of Physical Exercise in Patients With Diseases Related to Oxidative Stress: A Systematic Review and Network Meta-Analysis.
The balance of oxidative and antioxidant systems is of great importance to the human body. Physical exercise, as one of the ways to improve physical health, seems to modulate this balance. However, different intensities and types of physical exercise have other effects on the treatment of unhealthy people. To understand the impact of exercise training on the oxidative and antioxidant systems of adults with oxidative stress-related disorders, a network meta-analysis was used to compare the mixed effects of different intensities and types of exercise training. This systematic review included all eligible RCTs from PubMed, Medline, Cochrane Library, and CINAHL. Eleven of the studies met the inclusion criteria (at study completion, n = 666 participants). Seven studies reported that the level of MDA decreased significantly after exercise (p < 0.05), and 3 studies reported that the level of SOD increased significantly after exercise (p < 0.05). In conclusion, long-term high-intensity aerobic training and Tai Chi or Yoga can effectively improve oxidative stress in unhealthy people. In addition, different types of diseases on the effect of exercise intervention seems to be other, diabetes and chronic kidney patients using moderate-intensity aerobic training or Tai chi and Yoga effect are better; Moderate-intensity aerobic training had a better impact on OS improvement in patients with irritable bowel syndrome and severe depression. However, more research is needed to determine the effects of different levels and types of physical activity on oxidative stress in unhealthy populations. Systematic Review Registration: PROSPERO identifier: CRD42021242025. https://www.crd.york.ac.uk/prospero/.


Unprecedented transformation of tetrathienoanthracene into pentacene on Ni(111).
The imaging and characterization of single-molecule reaction events is essential to both extending our basic understanding of chemistry and applying this understanding to challenges at the frontiers of technology, for example, in nanoelectronics. Specifically, understanding the behavior of individual molecules can elucidate processes critical to the controlled synthesis of materials for applications in multiple nanoscale technologies. Here, we report the synthesis of an important semiconducting organic molecule through an unprecedented reaction observed with submolecular resolution by scanning tunneling microscopy (STM) under ultrahigh vacuum (UHV) conditions. Our images reveal a sulfur abstraction and cyclization reaction that converts tetrathienoanthracene precursors into pentacene on the Ni(111) surface. The identity of the final reaction product was confirmed by time-of-flight secondary ion mass spectrometry (TOF-SIMS). This reaction has no known literature analogue, and highlights the power of local-probe techniques for exploring new chemical pathways.


Key informants' perspectives of implementing chromosomal microarrays into clinical practice in Australia.
High-resolution genomic tests have the potential to revolutionize healthcare by vastly improving mutation detection. The use of chromosomal microarray (CMA) represents one of the earliest examples of these new genomic tests being introduced and disseminated in the clinic. While CMA has clear advantages over traditional karyotyping in terms of mutation detection, little research has investigated the process by which CMA was implemented in clinical settings. Fifteen key informants, six clinicians, and nine laboratory scientists from four Australian states were interviewed about their experiences during and in the time since CMA was adopted for clinical use. Participants discussed challenges such as result interpretation and communication. Strengths were also highlighted, including the collaborative approaches of some centers. Clinical experiences and opinions can inform larger studies with a range of stakeholders, including patients. The historical perspectives from this retrospective study can be helpful in guiding the implementation of future genomic technologies such as whole exome/genome sequencing.


Rapid Ethical Assessment on Informed Consent Content and Procedure in Hintalo-Wajirat, Northern Ethiopia: A Qualitative Study.
Informed consent is a key component of bio-medical research involving human participants. However, obtaining informed consent is challenging in low literacy and resource limited settings. Rapid Ethical Assessment (REA) can be used to contextualize and simplify consent information within a given study community. The current study aimed to explore the effects of social, cultural, and religious factors during informed consent process on a proposed HPV-serotype prevalence study. A qualitative community-based REA was conducted in Adigudom and Mynebri Kebeles, Northern Ethiopia, from July to August 2013. Data were collected by a multi-disciplinary team using open ended questions concerning informed consent components in relation to the parent study. The team conducted one-to-one In-Depth Interviews (IDI) and Focus Group Discussions (FGDs) with key informants and community members to collect data based on the themes of the study. Tape recorded data were transcribed in Tigrigna and then translated into English. Data were categorized and thematically analyzed using open coding and content analysis based on pre-defined themes. The REA study revealed a number of socio-cultural issues relevant to the proposed study. Low community awareness about health research, participant rights and cervical cancer were documented. Giving a vaginal sample for testing was considered to be highly embarrassing, whereas giving a blood sample made participants worry that they might be given a result without the possibility of treatment. Verbal consent was preferred to written consent for the proposed study. This rapid ethical assessment disclosed important socio-cultural issues which might act as barriers to informed decision making. The findings were important for contextual modification of the Information Sheet, and to guide the best consent process for the proposed study. Both are likely to have enabled participants to understand the informed consent better and consequently to comply with the study.


Isolated Medial Malleolus Fractures: Conventional Techniques Versus Headless Compression Screw Fixation.
The aim of the present study was to evaluate the clinical and radiologic results of surgically treated isolated medial malleolar fractures and compare the clinical and radiologic results of the fixation methods of headless cannulated fully threaded compression screws and cancellous lag screws and tension band wiring. We included 32 patients who attended the final follow-up examination. Group 1 consisted of 11 patients (34.4%) treated with headless cannulated fully threaded compression screws. Group 2 consisted of 10 patients (31.2%) treated with cancellous lag screws. Group 3 consisted of 11 patients (34.4%) treated with Kirschner wires and intraosseous tension wiring. Standard ankle radiographs, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and visual analog scale for pain were assessed. No statistically significant differences were found among the groups in regard to age, gender, preoperative fracture type, follow-up time, radiologic bone union time, and baseline AOFAS scale scores. The interval to fracture healing was 2.2 ± 0.42 months in group 1, 2.5 ± 0.71 months in group 2, and 2.45 ± 0.52 months in group 3. The AOFAS ankle-hindfoot scale score was 96.73 ± 5.55 in group 1, 93.1 ± 5.43 in group 2, and 93.73 ± 5.52 in group 3. Hardware removal was not required in any patient in group 1 but was required in 2 patients (20%) in group 2 and 3 patients (27.3%) in group 3. The visual analog scale score for pain on palpation at the medial malleolus was significantly lower statistically in the headless compression screw group (group 1; p = .003).


Epidemiology of cryptosporidiosis among persons with acquired immunodeficiency syndrome in Los Angeles County.
To determine the occurrence and factors associated with Cryptosporidium among persons with acquired immunodeficiency syndrome (AIDS) in Los Angeles County, data were analyzed from the AIDS surveillance registry for the 10-year period 1983-1992. Among 16,953 persons with AIDS, a total of 638 (3.8%) cryptosporidiosis cases were reported during the study period. The prevalence of cryptosporidiosis was higher in persons whose suspected human immunodeficiency virus (HIV) exposure category was through sexual contact (3.9%) than among persons in other HIV exposure categories (2.6%; P < 0.01) and in immigrants from Mexico (5.2%) than in American born patients (3.8%; P < 0.01). Blacks (2.7%) were less likely than whites (4.1%) and Latinos (4.2%) to be reported with cryptosporidiosis (P < 0.001). A temporal trend was observed from 1983 to 1986 when the prevalence decreased from 6.7% to 3.6% (P < 0.001, by chi-square test for trend). After controlling for confounding variables by stratified analysis, persons whose HIV exposure was sexual (adjusted odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.3, 2.4, P < 0.01) and immigrants from Mexico (adjusted OR = 1.6, 95% CI 1.2, 2.1, P < 0.01) were more likely to have cryptosporidiosis. The negative association with black race remained significant (adjusted OR = 0.7, 95% CI 0.57, 0.96, P = 0.02). The prevalence of cryptosporidiosis decreased with age in gay and bisexual males (Mantel-Haenszel test for trend, P < 0.01) but not among female and heterosexual male cases.(ABSTRACT TRUNCATED AT 250 WORDS)


When patients and surgeons disagree about surgical outcome: investigating patient factors and chart note communication.
Effective physician-patient communication is a critical component of a clinical practice and in order to achieve optimal patient outcomes. We aimed to investigate indirect effects of physician-patient communication by examining the relationship between a physician-patient mismatch in perceived outcomes and content in the medical record's clinical note. We compared patient records whose perceived subjective assessment of surgery outcomes agreed or disagreed with the surgeon's perception of that outcome (Subjective Disagreement). This study included 172 spine surgery patients at a teaching hospital. Patient-reported outcomes included the Oswestry Disability Index; the Short-Form 36; and a Visual Analogue Scale items for leg and back pain. We content-analyzed the clinical note in the medical record, and used logistic regression to evaluate predictors of Subjective Disagreement (n = 41 disagreed vs. 131 agreed). Patient and surgeon agreed in 76% of cases and disagreed in 24% of cases. Patients who assessed their outcome worse than their surgeons tended to be less educated and involved in litigation. They also tended to report worsened mental health and leg pain. Content analysis revealed group differences in surgeon communication patterns in the chart notes related to how symptom change was emphasized, how follow-up was described, and a specific word reference. Specifically, disagreement was predicted by using "much" to emphasize the findings and noting long-term prognosis. Agreement was predicted by use of positive emphasis terms, having an "as-needed" follow-up plan, and using "happy" in the chart note. The nature of measuring outcomes of surgery is based on patient perception. In surgeon-patient perspective mismatches, patient factors may serve as barriers to improvement. Worsened change on patient-reported mental health may be an independent factor which colors the patient's general perceptions. This aspect of treatment may be missed by the spine surgeon. Chart note communication styles reflect the subjective disagreement. Investigating and/ or treating mental health deterioration may be valuable in resolving this mismatch and for overall outcome.


A case report of the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion.
Cardiometabolic health significantly impacts on the mortality of people with severe mental illness. Clozapine has the greatest efficacy for Treatment Resistant Schizophrenia (TRS) but the greatest negative impact on cardiometabolic health. Balancing the risks and benefits of treatment, dignity, autonomy, liberty, mental and physical health can be challenging, particularly when imposing interventions with potentially life threatening adverse events, such as clozapine. We describe the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion for a gentleman with TRS in high secure psychiatric services. The impact of clozapine on a 44-year-old gentleman with TRS, extreme violence requiring physical restraint and long-term segregation, and numerous other significant physical health complications is described. He had metabolic syndrome; a poor diet, sedentary lifestyle, Body Mass Index (BMI) of 31.5, poorly controlled lipids and had smoked heavily since childhood. During preparations to initiate clozapine, he suffered a myocardial infarction and pulmonary embolism. His compliance with secondary prevention medications was poor due to paranoid persecutory and somatic delusions. Despite these concerns, nasogastric administration of clozapine was approved and prescribed within nine months of his myocardial infarction and a month from his pulmonary embolism but was ultimately not required. Accepting oral medication, his mental state made a rapid and dramatic improvement. After spending 1046 days in seclusion, this was terminated 94 days after clozapine initiation. He has been compliant with all medications for 24 months, had no incidents of violence or seclusion, and has been transferred to medium secure services. His physical health stabilised despite continuing to lead a sedentary lifestyle and remaining obese (BMI of 35). He developed hypertension, Type II Diabetes Mellitus and his triglycerides rose to 22.2 mmol/L in the same month after clozapine initiation. However, with pharmacological intervention, 24 months later these are controlled, and he has had no further thromboembolic events. We highlight that despite significant physical health concerns, clozapine can be successfully initiated and safely prescribed with a significantly positive effect on both the psychiatric and holistic care of patients with treatment resistant schizophrenia.


The clinicopathological and prognostic role of thrombocytosis in patients with cancer: A meta-analysis.
Previous studies have linked the presence of thrombocytosis with the progression and development of cancer; however, this trend requires further investigation. The present study aimed to derive an estimation of the degree of association between thrombocytosis and the 5-year overall survival rate of patients with cancer, as well as common clinicopathological features, by performing a meta-analysis of 20 (n=12,778) published studies. The PubMed and Embase databases were searched systematically for all relevant articles published in English. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using a fixed effects or random effects model to evaluate the degree of the observed associations. The results suggested that thrombocytosis (platelet count, >400×109/l) correlated with a decreased 5-year overall survival rate (OR=2.70, 95% CI=2.03-3.61) and an advanced tumor-node-metastasis stage (III + IV; OR=2.14, 95% CI=1.58-2.90). Furthermore, these associations remained robust following stratification of the data by cancer type and ethnicity. In addition, thrombocytosis (platelet count, >300×109/l) correlated with a decreased 5-year overall survival rate in patients with colorectal cancer (OR=3.49, 95% CI=1.44-8.46). Although certain biases were not able to be eliminated, the present meta-analysis suggested that thrombocytosis is a valuable indicator for the evaluation of pathological diagnosis and prognosis for patients with cancer. Further studies are required to investigate the effect of thrombocytosis on the prognosis of patients with cancer.


Paecilomyces Rot: A New Apple Disease.
Paecilomyces niveus is an important food spoilage fungus that survives thermal processing in fruit products, where it produces the mycotoxin patulin. Spoilage of products has been attributed to soil contamination; however, little is known about the ecology of this organism. In this study, orchard soils and culled apple fruit were surveyed and the ability of P. niveus to infect apple was tested on two popular apple varieties. P. niveus was found in 34% of sampled orchard soils from across New York. Completing Koch's postulates, P. niveus was demonstrated to cause postharvest disease in Gala and Golden Delicious apple. Symptoms of this disease, named Paecilomyces rot, resemble several other apple diseases, including black rot, bitter rot, and bull's-eye rot. External symptoms of Paecilomyces rot include brown, circular, concentrically ringed lesions, with an internal rot that is firm and cone-shaped. Both Gala and Golden Delicious apple fruit inoculated with P. niveus developed lesions ≥43 mm in size at 22 days after inoculation. There is some evidence that the size of lesions and rate of infection differ between Gala and Golden Delicious, which may indicate differing resistance to P. niveus. This work shows that P. niveus is common in New York orchard soil and can cause a novel postharvest fruit disease. Whether infected fruit can serve as an overlooked source of inoculum in heat-processed apple products requires further study.


Facilitating post traumatic growth.
Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth.