Bile Acid-Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs.
Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC50, Ki values, and bile acid−drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.


Confusion and compensation in visual perception: effects of spatiotemporal proximity and selective attention.
The authors investigated spatial, temporal, and attentional manipulations in a short-term repetition priming paradigm. Brief primes produced a strong preference to choose the primed alternative, whereas long primes had the opposite effect. However, a 2nd brief presentation of a long prime produced a preference for the primed word despite the long total prime duration. These surprising results are explained by a computational model that posits the offsetting components of source confusion (prime features are confused with target features) and discounting (evidence from primed features is discounted). The authors obtained compelling evidence for these components by showing how they can cooperate or compete through different manipulations of prime salience. The model allows for dissociations between prime salience and the magnitude of priming, thereby providing a unified account of "subliminal" and "supraliminal" priming.


An integrated methods study of the experiences of youth with severe disabilities in leisure activity settings: the importance of belonging, fun, and control and choice.
The aim was to examine the leisure activity setting experiences of two groups of youth with severe disabilities - those with complex continuing care (CCC) needs and those who have little functional speech and communicate using augmentative and alternative communication (AAC). Twelve youth took part in a mixed methods study, in which their experiences were ascertained using qualitative methods (observations, photo elicitation and interviews) and the measure of Self-Reported Experiences of Activity Settings (SEAS). Data integration occurred using a "following a thread" technique and case-by-case analysis. The analysis revealed several highly valued aspects of leisure activity setting experiences for youth, including engagement with others, enjoying the moment, and control and choice in selection and participation in activity settings. The findings provide preliminary insights into the nature of optimal activity settings for youth with severe disabilities, and the mediators of these experiences. Compared to other youth, the data illustrate both the commonalities of experiences and differences in the ways in which these experiences are attained. Implications for research concern the utility of mixed methods approaches in understanding the complex nature of participation experiences. Implications for clinical practice concern the importance of not assuming the nature of youths' experiences.


Transition Metal Substitution Effects on Metal-to-Polyoxometalate Charge Transfer.
A series of hetero-bimetallic transition metal-substituted polyoxometalates (TMSPs) were synthesized based on the Co(II)-centered ligand [Co(II)W11O39](10-). The eight complex series, [Co(II)(M(x)OHy)W11O39]((12-x-y)-) (M(x)OHy = V(IV)O, Cr(III)(OH2), Mn(II)(OH2), Fe(III)(OH2), Co(II)(OH2), Ni(II)(OH2), Cu(II)(OH2), Zn(II)(OH2)), of which six are reported for the first time, was synthesized starting from [Co(III)W11O39](9-) and studied using spectroscopic, electrochemical, and computational techniques to evaluate the influence of substituted transition metals on the photodynamics of the metal-to-polyoxometalate charge transfer (MPCT) transition. The bimetallic complexes all show higher visible light absorption than the plenary [Co(II)W12O40](6-) and demonstrate the same MPCT transition as the plenary complex, but they have shorter excited-state lifetimes (sub-300 ps in aqueous media). The decreased lifetimes are rationalized on the basis of nonradiative relaxation due to coordinating aqua ligands, increased interaction with cations due to increased negative charge, and the energy gap law, with the strongest single factor appearing to be the charge on the anion. The most promising results are from the Cr- and Fe-substituted systems, which retain excited-state lifetimes at least 50% of that of [Co(II)W12O40](6-) while more than tripling the absorbance at 400 nm.


Association of urinary macromolecules with calcium oxalate crystals induced in vitro in normal human and rat urine.
This study was undertaken to identify proteins which are found associated with calcium oxalate crystals induced in vitro in normal human and rat urine. Crystallization was initiated by adding sodium oxalate individually to each urine sample without centrifugation and filtration. Crystals were collected and analyzed by scanning electron microscopy and X-ray diffraction. Crystal matrix proteins (CMPs) were obtained by demineralization of the crystals with ethylenediaminetetra-acetic acid (EDTA) and analyzed by western blotting technique for immunological identification. Crystals produced in human urine were found to be a mixture of calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) while those produced in rat urine were exclusively COD. CMPs extracted from crystals in human urine comprised, in addition to prothrombin-related proteins, osteopontin and albumin. However, CMPs extracted from crystals in rat urine contained only osteopontin and albumin. Prothrombin-related proteins were found only in trace amounts. In a separate experiment, rat urine samples were supplemented with COM before inducing crystallization. Similar results were observed showing that CMP contained osteopontin, albumin and trace amounts of prothrombin-related proteins. We conclude that several urinary macromolecules including not only prothrombin-related proteins, but also osteopontin and albumin, become associated with CaOx crystals. The incorporation of these proteins in growing stones is not only due to the presence of gamma-carboxyglutamic acid as it was suggested for prothrombin-related proteins, but may be due to other factors such as urinary chemistry, presence of glutamic and aspartic acid residues, and calcium-binding sites.


Myofascial Release for Vulvar Pain and Pubic Shear After a Straddle Injury in a 3-Year-Old Girl.
Pelvic malalignment is a somatic dysfunction that can lead to pelvic discomfort, despite normal genital examination findings. A 3-year-old girl presented with vulvar discomfort after a straddle injury sustained while riding a tricycle. The symptoms persisted despite standard medical treatment for vulvovaginitis and chronic vulvar irritation. An osteopathic structural examination revealed distortions of the bony pelvis, often associated with genitourinary complaints. After 5 osteopathic manipulative treatment sessions, the patient experienced significant relief. With persistent vulvar pain, somatic dysfunction should be considered in the differential diagnosis. A brief musculoskeletal examination of the pubic tubercles, iliac crest, and iliac spines can help to identify somatic dysfunction in a gynecologic patient with symptoms that are unresponsive to standard treatments.


Probiotics in Celiac Disease.
Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.


Loss of elongation factor P disrupts bacterial outer membrane integrity.
Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.


Recovery Goals and Long-term Treatment Preference in Persons Who Engage in Nonmedical Opioid Use.
While most opioid use disorder (OUD) treatment providers consider opioid abstinence to be the preferred outcome, little is known about the treatment preferences of the larger population of individuals who engage in nonmedical opioid use and have not yet sought treatment. This study sought to descriptively quantify the proportion of out-of-treatment individuals with nonmedical opioid use that have abstinent and nonabstinent recovery goals. Participants (N = 235) who engage in nonmedical opioid use and met self-reported criteria for OUD were recruited online and participated in a cross-sectional survey on recovery goals and treatment perceptions. Participants were dichotomized as having either abstinent (70.6%) or nonabstinent (29.4%) recovery goals. Participants were presented with 13 treatment options and asked which treatment they would "try first" and which treatment they thought would be the best option for long-term recovery. Persons in the nonabstinent group were more likely to want to continue use of prescription opioids as prescribed by a physician compared with the abstinent group (χ[1] = 9.71, P = 0.002). There were no group differences regarding preference for individual OUD treatments. The most frequently endorsed treatments that participants would "try first" were physician visits (23.4%), one-on-one counseling (18.7%), and 12-step groups (13.2%), whereas the most frequently endorsed treatments for long-term recovery were one-on-one counseling (17.4%), residential treatment (16.7%), and buprenorphine (15.3%). Public health initiatives to engage out-of-treatment individuals should take into account recovery goals and treatment preferences to maximize treatment initiation and retention.


HLA genes associated with autoimmunity and progression to disease in type 1 diabetes.
Insulin dependent diabetes mellitus (type I DM) is caused by an autoimmune process which culminates in destruction of pancreatic beta cells with resultant loss of insulin production. Preceding the clinical diagnosis of type I DM is a preclinical stage characterized by autoantibodies to insulin, glutamic acid decarboxylase (GAD) and a tyrosine phosphatase-like molecule (IA-2). We have studied both HLA class I and class 2 allele distributions in diabetic probands and autoantibody positive individuals in members of 452 families recruited for the Australian type I diabetes DNA repository. The results demonstrate that progression to autoimmunity as measured by the appearance of autoantibodies is strongly associated with the class 2 alleles DRB1*03 and DRB*04 and with DRB1*03/04 heterozygosity. In contrast, the progression to clinical disease appears associated with class I alleles A24, A30 and B18 while A1, A28, B14 and B56 appear negatively associated. The class 2 alleles appear to have a minimal role in the progression from autoantibody positivity to clinical disease. These results are consistent with the view that CD4+ T cells responding to peptides in the context of class 2 molecules are responsible for initiating autoantibody production, while the destruction of islet cells leading to clinical expression of the disease is the function of CD8+ T cells recognizing relevant peptides in the context of class I molecules.


Distinct Populations of Motor Thalamic Neurons Encode Action Initiation, Action Selection, and Movement Vigor.
Motor thalamus (Mthal) comprises the ventral anterior, ventral lateral, and ventral medial thalamic nuclei in rodents. This subcortical hub receives input from the basal ganglia (BG), cerebellum, and reticular thalamus in addition to connecting reciprocally with motor cortical regions. Despite the central location of Mthal, the mechanisms by which it influences movement remain unclear. To determine its role in generating ballistic, goal-directed movement, we recorded single-unit Mthal activity as male rats performed a two-alternative forced-choice task. A large population of Mthal neurons increased their firing briefly near movement initiation and could be segregated into functional groups based on their behavioral correlates. The activity of "initiation" units was more tightly locked to instructional cues than movement onset, did not predict which direction the rat would move, and was anticorrelated with reaction time (RT). Conversely, the activity of "execution" units was more tightly locked to movement onset than instructional cues, predicted which direction the rat would move, and was anticorrelated with both RT and movement time. These results suggest that Mthal influences choice RT performance in two stages: short latency, nonspecific action initiation followed by action selection/invigoration. We discuss the implications of these results for models of motor control incorporating BG and cerebellar circuits.SIGNIFICANCE STATEMENT Motor thalamus (Mthal) is a central node linking subcortical and cortical motor circuits, though its precise role in motor control is unclear. Here, we define distinct populations of Mthal neurons that either encode movement initiation, or both action selection and movement vigor. These results have important implications for understanding how basal ganglia, cerebellar, and motor cortical signals are integrated. Such an understanding is critical to defining the pathophysiology of a range of BG- and cerebellum-linked movement disorders, as well as refining pharmacologic and neuromodulatory approaches to their treatment.


Layer-by-layer assembly of versatile nanoarchitectures with diverse dimensionality: a new perspective for rational construction of multilayer assemblies.
Over the past few decades, layer-by-layer (LbL) assembly of multilayer thin films has garnered considerable interest on account of its ability to modulate nanometer control over film thickness and its extensive choice of usable materials for coating planar and particulate substrates, thus allowing for the fabrication of responsive and functional thin films for their potential applications in a myriad of fields. Herein, we provide elaborate information on the current developments of LbL assembly techniques including different properties, molecular interactions, and assembly methods associated with this promising bottom-up strategy. In particular, we highlight the principle for rational design and fabrication of a large variety of multilayer thin film systems including multi-dimensional capsules or spatially hierarchical nanostructures based on the LbL assembly technique. Moreover, we discuss how to judiciously choose the building block pairs when exerting the LbL assembly buildup which enables the engineering of multilayer thin films with tailor-made physicochemical properties. Furthermore, versatile applications of the diverse LbL-assembled nanomaterials are itemized and elucidated in light of specific technological fields. Finally, we provide a brief perspective and potential future challenges of the LbL assembly technology. It is anticipated that our current review could provide a wealth of guided information on the LbL assembly technique and furnish firm grounds for rational design of LbL assembled multilayer assemblies toward tangible applications.


Atrial arrhythmogenic properties in wild-type and Scn5a+/- murine hearts.
Loss- and gain-of-function cardiac Na(+) channel (SCN5A) mutations are associated with the Brugada and long QT type 3 syndromes (LQT3), respectively. Both result in ventricular arrhythmias, but have differing atrial effects. We have recently reported decreased incidences of atrial arrhythmias in a murine Scn5a+/Delta cardiac system used to model LQT3. We now explore for atrial arrhythmias in a murine Brugada syndrome model. Programmed electrical stimulation and burst pacing were applied to 10 wild-type (WT) and 10 Scn5a+/- Langendorff-perfused murine hearts. These induced arrhythmias in similar proportions of the Scn5a+/- and WT hearts, in contrast to their decreased incidences previously reported for Scn5a+/Delta. Almost half of the Scn5a+/- hearts displayed spontaneous atrial arrhythmias never observed in WT. Both these WT and Scn5a+/- hearts showed positive critical intervals, given by the difference between action potential durations at 90% recovery (APD(90)) and atrial effective refractory periods, before pharmacological intervention. Both flecainide and quinidine then prevented both induced and spontaneous atrial arrhythmias in all the arrhythmic WT and Scn5a+/- hearts, in contrast to their differing ventricular effects. However, flecainide prolonged APD(90) in WT but not Scn5a+/-, whereas quinidine prolonged APD(90) in both WT and Scn5a+/-. Nevertheless, addition of both agents markedly increased atrial effective refractory periods to values exceeding the corresponding values of APD(90). This resulted in negative critical intervals in both WT and Scn5a+/-. These findings demonstrate a clear-cut relationship between critical interval and atrial arrhythmic tendency for the first time and extend previous reports that had related critical interval to ventricular arrhythmia.


Variance reduction in the inverse probability weighted estimators for the average treatment effect using the propensity score.
The propensity methodology is widely used in medical research to compare different treatments in designs with a nonrandomized treatment allocation. The inverse probability weighted (IPW) estimators are a primary tool for estimating the average treatment effect but the large variance of these estimators is often a significant concern for their reliable use in practice. Inspired by Rao-Blackwellization, this paper proposes a method to smooth an IPW estimator by replacing the weights in the original estimator by their mean over a distribution of the potential treatment assignment. In our simulation study, the smoothed IPW estimator achieves a substantial variance reduction over its original version with only a small increased bias, for example two-to-sevenfold variance reduction for the three IPW estimators in Lunceford and Davidian [Statistics in Medicine, 23(19), 2937-2960]. In addition, our proposed smoothing can also be applied to the locally efficient and doubly robust estimator for added protection against model misspecification. An implementation in R is provided.


United States Department of Justice findings letters in psychiatric hospital CRIPA cases: an aid or a distraction?
The Civil Rights of Institutionalized Persons Act (CRIPA) of 1980 allows the United States Department of Justice (DOJ) to investigate and file lawsuits against certain institutions, including state and county psychiatric hospitals, where individuals within may face unconstitutional conditions. Subsequent to an investigation and before negotiations or litigation, the state is provided a Findings Letter generated by the DOJ that generally contains recommended remedial measures. It has never been determined to what extent a Findings Letter provides a state with a recommendation specific to the institution for corrective action before the state enters into negotiations with the DOJ. Three study groups were derived from a sample of 15 Findings Letters written to states concerning their psychiatric hospitals between 2003 and 2009. The individual recommended remedial measures, labeled texts of interest (TOI), were identified, and the degree of overlap among the Findings Letters was determined. To a surprising degree, TOIs overlapped to various extents, from exact copies of text to paraphrased versions, in Findings Letters written between 2003 and 2009 to different states and for multiple state hospitals in the same state. The recommended remedial measures provided in the DOJ's Findings Letters are not specific to each state hospital's deficiencies. The Findings Letters offer limited guidance to the state on how to remedy the deficiencies before negotiating with the DOJ. This lack of specificity causes inefficient and delayed remediation of unconstitutional conditions and other deficiencies in care and treatment in psychiatric hospitals. While the current process most often leads to improvements in state hospitals, it is a costly, inefficient remedy, despite the possibility of alternative remedial processes of less expensive and equal or greater effectiveness.


[Activity of antioxidant enzymes in liver and brain is decreased in the early stage of diabetes, and this decrease depends on the function of NMDA-receptors].
Antioxidant enzyme activities in rat liver and forebrain and the effect of the MK-801 administration on these activities were estimated on 6th day of alloxan-induced diabetes. The catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase activities of cytosolic fractions from both liver and forebrain were shown to decrease significantly in prediabetic rats, and these alterations were virtually prevented by the course of MK-801 administration. The results suggest that the suppression of antioxidant enzymes can be the primary biochemical disturbance in diabetes progression and that glutamate NMDA receptors can be involved in the molecular mechanism underlying this condition.


Association of discoid lupus erythematosus with clinical manifestations and damage accrual in a multiethnic lupus cohort.
To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort. SLE patients (per American College of Rheumatology [ACR] criteria) ages ≥16 years with a disease duration of ≤10 years at enrollment and defined ethnicity (African American, Hispanic, or white) from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations, and disease damage (per the Systemic Lupus International Collaborating Clinics/ACR Damage Index) were determined. The association of discoid lupus erythematosus (DLE) with clinical manifestations and disease damage was examined using multivariable logistic regression. A total of 2,228 SLE patients were studied. The mean ± SD age at diagnosis was 34.3 ± 12.8 years and the mean ± SD disease duration was 7.9 ± 6.0 years; 91.8% were women. DLE was observed in 393 patients with SLE (17.6%). In the multivariable analysis, patients with DLE were more likely to be smokers and of African American ethnicity and to have malar rash, photosensitivity, oral ulcers, leukopenia, and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity and to have arthritis, end-stage renal disease, and antinuclear, anti-double-stranded DNA, and antiphospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers. In this cohort of SLE patients, DLE was associated with several clinical features, including serious manifestations such as vasculitis and chronic seizures.


Au-Mesoporous silica nanoparticles gated with disulfide-linked oligo(ethylene glycol) chains for tunable cargo delivery mediated by an integrated enzymatic control unit.
We report a delivery system based on Au-mesoporous silica (MS) nanoparticles functionalized with acetylcholinesterase on the Au face as a control unit and with disulfide-containing oligo(ethylene glycol) chains on the MS face as caps. The control unit handles the chemical information in the environment (the presence of acetylthiocholine or enzyme inhibitors) that results in a tuned cargo delivery from the nanocarrier. The nanodevice displayed an enhanced cargo delivery in cancer cells (safranin O and doxorubicin) in the presence of acetylthiocholine.


[Evaluation test and masking therapy of subjective tinnitus].
To undergo tinnitus evaluation test and masking therapy of subject tinnitus associated with sensorineural hearing loss as a reference for diagnosis and guiding masking therapy. The 66 patients with subject tinnitus were diagnosed as sensorineural hearing loss. Sixty-six patients divide into three groups according to the results of pure tone audiometry, including steep drop type in 28 patients, slow drop type in 20 patients, and flat type in 18 patients. All the patients underwent tinnitus evaluation tests (pitch matching, intensity matching, tinnitus masking curves, residual inhibition) and masking therapy. Tinnitus with steep drop type manifest was as low intensity [average intensity (5.7 +/- 2.9) dB (x(-) +/- s)] and high frequency (median with 4750 Hz). Residual inhibition was almost positive, but was usually consistent with convergence and congruence tinnitus masking curves. Masking therapy had better effect in the treatment of this type of tinnitus (effective rate 89.3%). Tinnitus with slow drop type manifest was as low intensity [average intensity: (6.2 +/- 4.8) dB] and high frequency (median: 4050 Hz). The distribution of residual inhibition and tinnitus masking curves had no obviously characteristics. The effective rate of masking therapy of this type of tinnitus (55.0%) was higher than tinnitus with flat type but low than that of tinnitus with steep drop type. The intensity of tinnitus with flat type [average intensity: (9.2 +/- 5.0) dB] was higher than that of the previous groups. The distribution of frequency of this type had no obviously characteristics. The residual inhibition was almost negative, and was usually consistent with divergence and persistence tinnitus masking curves. Masking therapy had unsatisfactory curative effect in the treatment of this type of tinnitus (effective rate 11.1%). The effective rate of masking therapy was significant differences among the three groups (chi(2) = 9.127, P < 0.05). For the tinnitus patients with steep drop type audiometric curve, they are recommended masking therapy. For the tinnitus patients with slow drop type audiometric curve, masking therapy may be attempted to perform. For the tinnitus patients with flat type audiometric curve, they do not recommend the masking therapy.


The effects of three different types of orthoses on the range of motion of the lumbar spine during 15 activities of daily living.
Prospective cohort study. To quantify which 3 common lumbar orthoses of varying rigidity restrict both full, active range of motion (ROM) and functional ROM required for activities of daily living (ADL). Spinal orthoses are implemented to restrict lumbar motion. Despite widespread prevalence of lumbar bracing, the efficacy of these appliances for immobilizing the spine has not been definitively established. The full, active ROM of 10 asymptomatic individuals was quantified using an electrogoniometer that registered maximum rotation in all planes. Subjects subsequently completed 15 simulated ADLs during which time their functional ROM was measured; performed without a brace and while wearing a corset, semirigid lumbosacral orthosis (LSO), and rigid custom-molded LSO. For flexion/extension, the mean percentage decreases (with SDs) in full, active ROM that were recorded with corset, semirigid, and a custom orthosis were 24.1 ± 7.9%, 46.8 ± 7.1%, and 64.7 ± 8%, respectively (P < 0.001 relative to no brace). In the coronal plane, motion was restricted by 33.9 ± 8.8%, 51.9 ± 9.4%, and 49.1 ± 11.8%, respectively (P < 0.001). Finally, rotation was limited by 39.6 ± 8.8%, 59.2 ± 10.2%, and 70.6 ± 5.4%, respectively (P < 0.001). There were no significant discrepancies between the ROM recorded in the semirigid and custom LSOs for the ADLs. Likewise, functional ROM associated with corset and semirigid LSOs were only different for 2 ADLs whereas significant disparities between values with corset and custom LSOs were observed for 4 simulations. The full, active ROM allowed by lumbar braces evaluated was greater than employed during ADLs in absence of any brace. The motion decrease beyond actual restriction of the braces suggests they will act primarily as proprioceptive guides to regulate movement.


Inferring gene regulatory networks using differential evolution with local search heuristics.
We present a memetic algorithm for evolving the structure of biomolecular interactions and inferring the effective kinetic parameters from the time series data of gene expression using the decoupled Ssystem formalism. We propose an Information Criteria based fitness evaluation for gene network model selection instead of the conventional Mean Squared Error (MSE) based fitness evaluation. A hill-climbing local-search method has been incorporated in our evolutionary algorithm for efficiently attaining the skeletal architecture which is most frequently observed in biological networks. The suitability of the method is tested in gene circuit reconstruction experiments, varying the network dimension and/or characteristics, the amount of gene expression data used for inference and the noise level present in expression profiles. The reconstruction method inferred the network topology and the regulatory parameters with high accuracy. Nevertheless, the performance is limited to the amount of expression data used and the noise level present in the data. The proposed fitness function has been found more suitable for identifying correct network topology and for estimating the accurate parameter values compared to the existing ones. Finally, we applied the methodology for analyzing the cell-cycle gene expression data of budding yeast and reconstructed the network of some key regulators.


Difunctionalisation of arenes and heteroarenes by directed metallation and sulfoxide-magnesium exchange.
The aryl sulfoxide moiety allows an expedient two-step difunctionalisation of readily available diaryl sulfoxides. Highly functionalised 1,2,4-trisubstituted arenes and difunctionalised heteroarenes (furans, thiophenes, benzofurans and pyridines) were prepared in a two-step sequence, triggered by an aryl sulfoxide group. In the first step, the sulfoxide moiety acts as a metallation-directing group, allowing smooth ortho-magnesiation with TMPMgCl⋅LiCl (TMP=tetramethylpiperidine). After a quenching reaction with an electrophile, the resulting sulfoxide is converted into a second magnesium reagent with iPrMgCl⋅LiCl (sulfoxide-magnesium exchange), which can be trapped with various electrophiles. Highly chemoselective TMPMgCl⋅LiCl and iPrMgCl⋅LiCl are compatible with a broad range of functional groups (e.g., F, Cl, CF(3) , CN, CO(2) tBu, alkynyl, ethers, thioethers). Large-scale reactions (25-40 mmol) and the preparation of fully functionalised furans and thiophenes are also reported.


Heat inactivation of monkeypox virus.
Different kinds of media spiked with monkeypox virus (MPXV) were subjected to heat inactivation at different temperatures for various periods of time. The results showed that MPXV was inactivated in less than 5 min at 70 °C and less than 15 min at 60 °C, with no difference between viruses from the West African and Central African clades. The present findings could help laboratory workers to manipulate MPXV in optimal biosafety conditions and improve their protocols.


Developing a matrix to identify and prioritise research recommendations in HIV prevention.
HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research. Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention. 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention. This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.


Using a sequence of estrogen response elements as a DNA aptamer for estrogen receptors in vitro.
Estrogen receptors (ERs) are overexpressed in approximately 70% of breast cancer cases, and they play an important role in tumorigenesis. ERs are strong predictive factors for measuring responses to hormonal therapies. Aptamers are short and single stranded oligonucleotides that are able to recognize target molecules with high affinity. In the present study, we selected and synthesized an oligonucleotide, which has a similar sequence to estrogen response element in the Xenopus Vitellogenin A2 gene. The synthesized oligonucleotide was evaluated by using immunostaining of paraffin-embedded breast cancer tissues and treating MCF-7 human mammary carcinoma cell line in vitro. We found that the synthesized oligonucleotide had a high binding affinity to ER similar to estradiol. Using a specific anti-ER antibody as a standard control, we showed that the synthesized oligonucleotide specifically recognized and immunostained tumor cells of breast cancer without cross-reaction with normal tissues. The overall agreement of ER detection between the anti-ER antibody and the ER aptamer was 97.1% (kappa value=0.943; 95% CI=0.879-1.006; p<0.002). Similar to tamoxifen or fulvestrant, the oligonucleotide also had an inhibitory effect on cell proliferation of MCF-7 cell line in a dose- and time-dependent fashion but had no cytotoxic effect on human normal mammary epithelial cells. Therefore, the synthesized oligonucleotide may be used as an aptamer for immunostaining of paraffin-embedded tissue sections for breast cancer diagnosis, as well as a potential ER antagonist in the treatment of breast cancer.


Vibrotactile perception assessment for a haptic interface on an antigravity suit.
Haptic technology is used in various fields to transmit information to the user with or without visual and auditory cues. This study aimed to provide preliminary data for use in developing a haptic interface for an antigravity (anti-G) suit. With the structural characteristics of the anti-G suit in mind, we determined five areas on the body (lower back, outer thighs, inner thighs, outer calves, and inner calves) on which to install ten bar-type eccentric rotating mass (ERM) motors as vibration actuators. To determine the design factors of the haptic anti-G suit, we conducted three experiments to find the absolute threshold, moderate intensity, and subjective assessments of vibrotactile stimuli. Twenty-six fighter pilots participated in the experiments, which were conducted in a fixed-based flight simulator. From the results of our study, we recommend 1) absolute thresholds of ∼11.98-15.84 Hz and 102.01-104.06 dB, 2) moderate intensities of 74.36 Hz and 126.98 dB for the lower back and 58.65 Hz and 122.37 dB for either side of the thighs and calves, and 3) subjective assessments of vibrotactile stimuli (displeasure, easy to perceive, and level of comfort). The results of this study will be useful for the design of a haptic anti-G suit.


Implementation of a wireless sensor network for heart rate monitoring in a senior center.
Wearable sensor systems are widely used to monitor vital sign in hospitals and in recent years have also been used at home. In this article we present a system that includes a ring probe, sensor, radio, and receiver, designed for use as a long-term heart rate monitoring system in a senior center. The primary contribution of this article is successfully implementing a cheap, large-scale wireless heart rate monitoring system that is stable and comfortable to use 24 h a day. We developed new finger ring sensors for comfortable continuous wearing experience and used dynamic power adjustment on the ring so the sensor can detect pulses at different strength levels. Our system has been deployed in a senior center since May 2012, and 63 seniors have used this system in this period. During the 54-h system observation period, 10 alarms were set off. Eight of them were due to abnormal heart rate, and two of them were due to loose probes. The monitoring system runs stably with the senior center's existing WiFi network, and achieves 99.48% system availability. The managers and caregivers use our system as a reliable warning system for clinical deterioration. The results of the year-long deployment show that the wireless group heart rate monitoring system developed in this work is viable for use within a designated area.


Sarcoma of the breast: an update on a rare entity.
Breast sarcoma is a rare condition. It consists of a heterogeneous group of non-epithelial tumours arising from the mesenchymal tissue of the breast. It has a distinctly different natural history, treatment response and prognosis as compared with carcinoma of the breast. A different diagnostic approach and treatment strategy have to be defined for this group of tumours. Due to its rarity, the current understanding on breast sarcoma is limited and is mostly based on small retrospective case series or case reports. Hence, the management generally follows the algorithms derived from randomised control trials of soft tissue sarcomas in the extremities and chest wall. Through this review, we discuss the results of major retrospective studies on breast sarcomas including data on epidemiology, aetiology, diagnostic approach, treatment strategies and outcomes of this challenging and potentially aggressive condition.


A High Serum-Ascites Albumin Gradient and Mediastinal Fibrosarcoma: A Case Report.
Accumulation of free fluid in the peritoneal cavity is called ascites. The first step in identifying its etiology is to determine the serum-ascites albumin gradient (SAAG). According to this parameter, a high SAAG is regarded as a gradient greater than 1.1 g/dL. This condition has some differential diagnoses such as liver cirrhosis, Budd-Chiari syndrome, heart failure, and idiopathic portal fibrosis. In the present article, we present a young man with abdominal distention due to a high SAAG. Further evaluation of the abdominal and thoracic cavity revealed a mass in the posterior mediastinum, which had compressed the inferior vena cava and left atrium and led to Budd-Chiari syndrome. Evaluation of the biopsy sample showed fibrosarcoma. Mediastinal fibrosarcomas, though rare, should be considered in the differential diagnosis of mediastinal masses.


Prospective and Retrospective Evaluation of the Performance of the FDA-Approved Cepheid Xpert Flu/RSV XC Assay.
Rapid and accurate detection of respiratory viruses is important in patient care and in guiding therapy and infection prevention policy. Rapid viral antigen assays are simple to perform and provide results within 15 to 30 minutes but are limited by their modest-to-moderate sensitivity. Molecular assays are more sensitive and specific but require more technical time and expertise and are more expensive. We verified the performance of the Xpert Flu/RSV XC assay prospectively, using patient respiratory samples from the 2014-2015 respiratory season, and, retrospectively, with frozen patient samples from the previous respiratory season. A total of 60 specimens were assayed on the Xpert Flu/RSV XC assay and by the GenMark Diagnostics eSensor Respiratory Viral Panel. The sensitivity of the Xpert Flu/RSV XC for Flu A was 100% (23/23), for Flu B, 80% (8/10), and for respiratory syncytial virus (RSV), 94.1% (16/17), compared to the reference assay (GenMark). The specificity was 100%. Eight specimens were positive for viruses other than Flu A/B or RSV, and this did not interfere with detection of targets in the Xpert assay. We demonstrated that the performance of the Xpert Flu/RSV XC was comparable to the more comprehensive molecular respiratory assay.


Improved Efficiency of Polymer Solar Cells by Modifying the Side Chain of Wide-Band Gap Conjugated Polymers Containing Pyrrolo[3,4- f]benzotriazole-5,7(6 H)-dione Moiety.
Two novel wide-band gap donor-acceptor-type conjugated copolymers, PTzBI-S and PTzBI-Ph, are designed and synthesized, based on alkylthio-thienyl- or alkylphenyl-substituted benzodithiophene (BDT) derivatives as the electron-donating unit and pyrrolo[3,4- f]benzotriazole-5,7(6 H)-dione as the electron-withdrawing unit. The as-generated copolymers show the comparable optical and electrochemical properties. The alkylthio-thienyl-substituted BDT unit facilities a benign decrease of the highest occupied molecular orbital (HOMO) levels. This consequently enhances open-circuit voltages ( VOC) over 0.9 V in relevant solar cells with the fullerene acceptor ([6, 6]-phenyl-C71-butyric acid methyl ester, PC71BM) or the nonfullerene acceptor (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3- d:2',3'- d']- s-indaceno[1,2- b:5,6- b']dithiophene, ITIC). The combination studies of Fourier transform photocurrent spectroscopy and electroluminescence further rationalize the VOC difference between solar cells with fullerene and nonfullerene acceptors. An impressively high power conversion efficiency of 10.19% is obtained for the device based on PTzBI-Ph:ITIC, outperforming the 8.84% achieved by the PC71BM-based device. Our results demonstrate that the modification of substituents of BDT units can effectively decrease the HOMO level and consequently improve VOC, ultimately allowing the attainment of high-efficiency polymer solar cells.


Penta-zirconium copper tribismuth.
Penta-zirconium copper tribismuth, Zr5CuBi3, crystallizes in the hexa-gonal Hf5CuSn3 structure type. The asymmetric unit contains two Zr sites (site symmetries 3.2 and m2m), one Cu site (site symmetry 3.m) and one Bi site (site symmetry m2m). The environment of the Bi atoms is a tetra-gonal anti-prism with one added atom and a coordination number (CN) of 9. The polyhedron around the Zr1 atom is a defective cubo-octa-hedron with CN = 11. The bicapped hexa-gonal anti-prism (CN = 14) is typical for Zr2 atoms. The Cu atom is enclosed in a eight-vertex polyhedron (octa-hedron with two centered faces). The metallic type of bonding was indicated by an analysis of the inter-atomic distances and electronic structure calculation data.


Development of stage-dependent glycans on the Fc domains of IgG antibodies of ALS animals.
We recently revealed a unique glycan on the Fc domain of IgG antibodies in ALS patients that mediates antibody-dependent cell cytotoxicity (ADCC). This glycan has a bi-antennary structure that lacks the core fucose and sialic acid residues but contains a bisecting GlcNAc (A2BG2). Little is known, however, about the incidence of A2BG2 expression and IgG cytotoxicity under ALS conditions within well-defined clinical stages. Here, we characterize the IgG antibodies produced in ALS Tg mice by detecting intra- and extra-cellular antigens of motor neurons that express different glycan patterns during the disease. The increased number of innate immune cells found at the disease onset was insufficient to induce an optimal systemic T-cell response. Nevertheless, IgG antibodies were produced against intracellular antigens at the pre-symptomatic stage in the secondary lymphoid organs under the conditions of a poor systemic immune response. Moreover, while the glycosyltransferases of plasma B-cells that synthesize the Fc-glycans were regulated by IL-2 or IL-4, the observed glycosyltransferase pattern did not match that found in ALS Tg mice. We further found that A2BG2 glycan is specific for ALS, its quantity increased with disease progression and that the IgG antibodies identifying extracellular motor neuron antigens were developed at the final stage of the disease. Therefore, the most effective ADCC of motor neurons was observed at the end stage of the disease. We conclude that in ALS, IgG antibodies are produced despite the poor systemic immune response and that the frequency and quantity of A2BG2 glycan expression on the Fc domain depends on the clinical stage. Therefore, A2BG2 is a potential prognostic biomarker for ALS.


The effectiveness of routine dental checks: a systematic review of the evidence base.
To systematically review the effectiveness of routine dental checks of different recall frequencies in adults and children. Search methods included electronic bibliographic databases up to March 2001, relevant internet sites, citation checking and contact with experts and professional dental bodies. (1) STUDY DESIGN: any; (2) POPULATION: deciduous, mixed and permanent dentition; (3) INTERVENTION: 'Routine dental check': 'clinical examination, advice, charting (including monitoring of periodontal status) and report' as defined in the NHS Executive General Dental Service Statement of Dental Remuneration; (4) Comparator: no routine dental check or routine dental check(s) of different recall frequency; (5) PRIMARY OUTCOMES: caries, periodontal disease, quality of life, oral cancer. Twenty eight studies were identified for the review. Studies were poorly reported and clinically heterogenous which restricted comparison between studies and limited generalisability to the UK situation. There was no consistency across multiple studies in the direction of effect of different dental check frequencies on measures of caries in deciduous mixed or permanent dentition, periodontal disease or oral cancer in permanent dentition. No studies were identified linking empirical measures of quality of life associated with oral health and dental check frequency. There is no existing high quality evidence to support or refute the practice of encouraging six-monthly dental checks in adults and children.


[Pathogenesis of spinal osteochondrosis and its neurologic manifestations at different ages].
The paper deals with the modern pathogenetic concepts of vertebral osteochondrosis in the age aspect. It was demonstrated that most frequently vertebrogenic lesions of the peripheral nervous system appear in patients aged 30 to 50 years. The role of different pathogenetic mechanisms in the development of the disease (biochemical, autoimmune changes in the intravertebral discs, the state of the higher nervous acitivity, the vestibular apparatus, etc.) was investigated. Pathomorphological studies permitted to establish certain correlations between the intensity of the generative-dystrophic changes in the lumbar part of the vertebral column and the level of the blood supply. Vertebral osteochondrosis can be considered as a polyetiologic but monopathogenetic disease, the clinical signs of which depend upon different endogenous and exogenous factors. The clinical traits of vertebrogenic diseases of the peripheral nervous system in children and adolescents, as well as in patients of old age are described.


Effect of interpregnancy interval on outcomes of pregnancy after recurrent pregnancy loss.
To examine the effect of interpregnancy interval (IPI) on outcomes of pregnancy after recurrent pregnancy loss (RPL). A retrospective cohort study including 325 patients treated at a RPL clinic, with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy, of whom 163 had IPI ≤ 6 months, and 212 had IPI > 6 months. Pregnancy loss rate in the index pregnancy was positively associated with increased IPI (18.6% in women with IPI ≤ 6 months, and 29.7% in women with IPI > 6 months; p = 0.029). In a multivariable logistic analysis, excluding women with fertility problems, and adjusting for maternal age and ethnicity, the OR for pregnancy loss rate for IPI longer than 6 months compared to shorter IPI was 1.76 (95%CI: 0.96-3.22, p = 0.067). Our results suggest that IPI shorter than 6 months, in women with no fertility problems, is associated with lower rate of subsequent miscarriage. Further studies are needed to substantiate this finding.


Large leg of superficial venous stasis, excluding disorders of the deep venous circulation.
Any abnormal increase in the volume of a lower member may be defined as "swollen leg", whether it is general and segmentary, or partial and local. This work concentrates on swollen legs caused by primary varicose disorders and does not deal with obstructions in the deep venous trunks. Swollen leg due to varicose disorder is marked by huge varices in clusters with total avalvulation. This constitutes a "phantom" swollen leg, for the evidence disappears when the patient lies down. It usually involves the long saphenous vein. It can be treated efficiently by surgery or sclerotherapy. Swollen leg of chronic venous stasis is due to vesperal oedema of complex character. Saphena insufficiency is to be observed, sometimes of the long saphenous vein, but usually of the saphena parva. Eventually large leg becomes permanent. Diagnosis is often difficult in swollen legs of deep venous stasis, and required venous functional investigations. Acute and painful forms may closely resemble ambulatory phlebitis. In all cases, lymphoedema ought to be considered, and the bruise test is conclusive. Sclerotherapy of the dilated saphenous trunks is often enough. Elastic stocking compression is sometimes necessary in order to obtain the best results, in conjunction with phlebotonics and crenotherapy. Swollen, inflammed legs are of two types: --Superficial thromboses, whether varicose or not, may be revelatory of underlying thromboembolic, cancerous, or hemopathic disease. This is the case for ascending phlebitis of the great saphenous vein which carries the risk of embolus, hyperuricemia, and, in the most localized forms, a risk of focal infection. --Phlebitis of the small saphenous vein, while rare, may be mistakenly taken to be deep lep phlebitis. The swollen legs seen in varicose trophic disorders are characterized by infectious or inflammatory edema, hypodermitis, and often, an ulcer. They may take on all of the clinical aspects of post-phlebitic disease, but functional vein studies will demonstrate patency of deep vein trunks. Active treatment and careful follow-up of venous and tissular lesions as well as suppression of aggravating factors should result in healing.


Spatial resolution of a hard x-ray CCD detector.
The spatial resolution of an x-ray CCD detector was determined from the widths of the tungsten x-ray lines in the spectrum formed by a crystal spectrometer in the 58 to 70 keV energy range. The detector had 20 microm pixel, 1700 by 1200 pixel format, and a CsI x-ray conversion scintillator. The spectral lines from a megavolt x-ray generator were focused on the spectrometer's Rowland circle by a curved transmission crystal. The line shapes were Lorentzian with an average width after removal of the natural and instrumental line widths of 95 microm (4.75 pixels). A high spatial frequency background, primarily resulting from scattered gamma rays, was removed from the spectral image by Fourier analysis. The spectral lines, having low spatial frequency in the direction perpendicular to the dispersion, were enhanced by partially removing the Lorentzian line shape and by fitting Lorentzian curves to broad unresolved spectral features. This demonstrates the ability to improve the spectral resolution of hard x-ray spectra that are recorded by a CCD detector with well-characterized intrinsic spatial resolution.


Executive functions and their relationship with intellectual capacity and age in schoolchildren with intellectual disability.
There is certain empirical evidence of, on the one hand, a positive correlation between executive functions (EFs) and intelligence in people with intellectual disability (ID) and, on the other hand, a slower rate of development of EFs in these people relative to people without ID. This evidence is not, however, unequivocal, and further studies are required. We analysed the relationship between development of EFs and both age and intellectual capacity, in a sample of 106 students with either ID or borderline intellectual functioning (BIF) at a special education centre [63 boys and 43 girls, 11-18 years old, mean total intelligence quotient (TIQ) of 59.6]. We applied nine instruments to evaluate both neuropsychological development (working memory, inhibitory control, cognitive flexibility, planning, processing speed and verbal fluency) and behavioural development [teachers' perceptions of the EFs of their students by Behavior Rating Inventory of Executive Function - Second Edition (BRIEF-2) School]. ID and BIF groups were statistically compared in terms of mean performance measures in EF tests. We looked at the correlation between EFs and age, and correlations between EFs and intelligence: TIQ, fluid intelligence [measured by the perceptual reasoning (PR) sub-index of Wechsler Intelligence Scale for Children-IV (WISC-IV)] and crystallised intelligence (measured by the verbal comprehension (VC) sub-index of WISC-IV). Regression models were built for variables with strong correlation. In most of the tests used to evaluate EFs, the ID subgroup performed significantly worse than the subgroup with BIF. In general, teachers' thought that participants had 'medium-low' levels of EFs. TIQ, by WISC-IV scale, correlated significantly with scores in all tests for all EFs. The PR sub-index correlated significantly with 14 of the tests for EFs; 35% of the variation in PR can be explained by variation in performance in Picture Span (working memory) and Mazes (planning). The VC sub-index correlated weakly with seven of the EF tests. We found significant correlations in the ID group between age and scores in all tests of working memory and inhibitory control. Age - considering all participants - did not correlate with any of the variables of teachers' perception except for working memory, and this correlation was not strong. The results of our study are consistent with descriptions of the typical population: (1) fluid intelligence is more related to EFs than crystallised intelligence is; and (2) working memory capacity is the EF most strongly related with general, fluid and crystallised forms of intelligence. The results suggest that as children and adolescents with ID/BIF get older, their capacities for working memory and inhibitory control increase; development of the other EFs studied was less evident. Teachers' perceptions of the EFs of children with ID or BIF were independent of intellectual capacity and age. More research is needed to delve further into the development of EFs in people with ID/BIF.


Role of the 11beta-hydroxysteroid dehydrogenase type 2 in blood pressure regulation.
The renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor (MR) from occupation by glucocorticoids. The gene is highly expressed in all sodium-transporting epithelia, but also in human placenta, pancreas, and thyroid. Mutations in the HSD11B2 gene cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, compromised 11betaHSD2 enzyme activity results in overstimulation of the MR by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Recent evidence suggests a role of the 11betaHSD2 in essential hypertension. We found hypertension with no other characteristic signs of AME in the heterozygous father of a child with AME and in a girl with a homozygous gene mutation resulting in a mild deficiency of 11betaHSD2. Moreover, some studies in patients with essential hypertension showed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites, suggesting a deficient 11betaHSD2 activity. These abnormalities may be genetically determined. A genetic association of a microsatellite flanking the HSD11B2 gene and hypertension in black patients with end-stage renal disease has been reported. We recently analyzed a CA-repeat allele polymorphism in unselected patients with essential hypertension, but did not find any correlation between this marker and blood pressure. However, we did find an association between this polymorphic CA microsatellite marker and salt sensitivity. Moreover, the activity of the 11betaHSD2, as shown by elevated mean ratios of urinary cortisol to cortisone metabolites, was decreased in salt-sensitive compared with salt-resistant subjects. These findings indicate that variants of the HSD11B2 gene contribute to the enhanced blood pressure response to salt in humans.


Suspected adverse methylphenidate-imipramine interactions in children.
Two cases are presented which illustrate the dangers inherent in utilizing a polypharmacy approach in treating children with psychotropic medication. In each case, severe adverse effects, including cognitive and mood deterioration, were experienced by the child when treated with a combination of methylphenidate and imipramine. Possible mechanisms at the neurotransmitter level are described as postulated determinants for this pharmacological interaction.


[Auxiliary motor innervation of the laryngeal muscles via the internal branch of the superior laryngeal nerve].
According to our present knowledge of the neuromuscular innervation of the intrinsic laryngeal muscles, the cricothyroid muscle is innervated by the external branch of the superior laryngeal nerve (NLS), whereas all other remaining muscles get their supply from the inferior laryngeal (recurrent) nerve. Mainly in the phoniatric literature, however, opinions differ concerning an additional motoric laryngeal innervation. In human larynges, excised for large unilateral carcinoma, horseradish peroxidase (HRP) was injected into the internal branch of the NLS. Anterograde labelling of axons was demonstrated histochemically. In adjacent sections of the different muscles, end plates and axons were stained histochemically with silver impregnation and acetylcholinesterase. Evidence is presented of motor innervation of the internal branch of the NLS in some laryngeal muscles. With retrograde HRP-tracing in sheep, motoneurons were detected in the nucleus ambiguus, although the recurrent nerve and the external branch had been divided and excised. Thus, histologically an additional neuromuscular supply via the internal branch of the NLS is demonstrated.


Biases in the Explore-Exploit Tradeoff in Addictions: The Role of Avoidance of Uncertainty.
We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore-exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.


Evaluation of BMI as a Risk Factor for Complications following Gender-affirming Penile Inversion Vaginoplasty.
Gender affirmation surgery (GAS) has a positive impact on the health of transgender patients; however, some centers employ body mass index (BMI) as a strict selection criterion for surgical candidacy. Several single-center studies have found no clear correlation between BMI and complication rates. We conducted a retrospective multicenter study at 2 university-based centers to test the null hypothesis: obesity is not a significant determinant of the risk of acute surgical complications in patients undergoing penile inversion vaginoplasty (PIV). This is a retrospective chart review of all adult patients at the University of Michigan and the University of Miami undergoing gender-affirming PIV with minimum follow-up time of 3 months between 1999 and 2017. A logistic regression model of analysis is used to examine the predictive factors for surgical complications and delayed revision urethroplasty in our patient sample. One hundred and one patients met inclusion criteria for this study. The mean BMI at the time of procedure was 26.9kg/m2 (range 17.8-48.2). Seventeen patients (16.8%) had major complications and 36 patients (35.6%) had minor complications. On logistic regression analysis, none of the recorded covariates were significant predictors of delayed revision urethroplasty or major, minor, or any complications. We found that obese patients can safely undergo GAS and that BMI alone should not preclude appropriately selected patients from undergoing GAS. We acknowledge that selection based on overall health and other medical comorbidities is certainly warranted for gender-affirming PIV and all other surgical procedures.


Trait Mindfulness and Functional Connectivity in Cognitive and Attentional Resting State Networks.
Mindfulness has been described as an orienting of attention to the present moment, with openness and compassion. Individuals displaying high trait mindfulness exhibit this tendency as a more permanent personality attribute. Given the numerous physical and mental health benefits associated with mindfulness, there is a great interest in understanding the neural substrates of this trait. The purpose of the current research was to examine how individual differences in trait mindfulness associated with functional connectivity in five resting-state networks related to cognition and attention: the default mode network (DMN), the salience network (SN), the central executive network (CEN), and the dorsal and ventral attention networks (DAN and VAN). Twenty-eight undergraduate participants completed the Five-Facet Mindfulness Questionnaire (FFMQ), a self-report measure of trait mindfulness which also provides scores on five of its sub-categories (Observing, Describing, Acting with Awareness, Non-judging of Inner Experience, and Non-reactivity to Inner Experience). Participants then underwent a structural MRI scan and a 7-min resting state functional MRI scan. Resting-state data were analyzed using independent-component analyses. An analysis of covariance (ANCOVA) was performed to determine the relationship between each resting state network and each FFMQ score. These analyses indicated that: (1) trait mindfulness and its facets showed increased functional connectivity with neural regions related to attentional control, interoception, and executive function; and (2) trait mindfulness and its facets showed decreased functional connectivity with neural regions related to self-referential processing and mind wandering. These patterns of functional connectivity are consistent with some of the benefits of mindfulness-enhanced attention, self-regulation, and focus on present experience. This study provides support for the notion that non-judgmental attention to the present moment facilitates the integration of regions in neural networks that are related to cognition, attention, and sensation.


Reduction in ribosomal protein synthesis is sufficient to explain major effects on ribosome production after short-term TOR inactivation in Saccharomyces cerevisiae.
Ribosome synthesis depends on nutrient availability, sensed by the target of rapamycin (TOR) signaling pathway in eukaryotes. TOR inactivation affects ribosome biogenesis at the level of rRNA gene transcription, expression of ribosomal proteins (r-proteins) and biogenesis factors, preribosome processing, and transport. Here, we demonstrate that upon TOR inactivation, levels of newly synthesized ribosomal subunits drop drastically before the integrity of the RNA polymerase I apparatus is severely impaired but in good correlation with a sharp decrease in r-protein production. Inhibition of translation by cycloheximide mimics the rRNA maturation defect observed immediately after TOR inactivation. Both cycloheximide addition and the depletion of individual r-proteins also reproduce TOR-dependent nucleolar entrapment of specific ribosomal precursor complexes. We suggest that shortage of newly synthesized r-proteins after short-term TOR inactivation is sufficient to explain most of the observed effects on ribosome production.


Valley precession and valley polarization in graphene with inter-valley coupling.
We theoretically investigate the valley precession and valley polarization in graphene under inter-valley coupling. Our results show that the inter-valley coupling can induce valley polarization in graphene and also precess valleys in real space in a manner similar to the Rashba spin-orbit interaction rotating spins. Moreover, using strain modulation, we can achieve high valley polarization with large valley-polarized currents. These findings provide a new way to create and manipulate valley polarization in graphene.


Full Counting Statistics of Charge in Chaotic Many-Body Quantum Systems.
We investigate the full counting statistics of charge transport in U(1)-symmetric random unitary circuits. We consider an initial mixed state prepared with a chemical potential imbalance between the left and right halves of the system and study the fluctuations of the charge transferred across the central bond in typical circuits. Using an effective replica statistical mechanics model and a mapping onto an emergent classical stochastic process valid at large on-site Hilbert space dimension, we show that charge transfer fluctuations approach those of the symmetric exclusion process at long times, with subleading t^{-1/2} quantum corrections. We discuss our results in the context of fluctuating hydrodynamics and macroscopic fluctuation theory of classical nonequilibrium systems and check our predictions against direct matrix-product state calculations.


Predicted class-I aminoacyl tRNA synthetase-like proteins in non-ribosomal peptide synthesis.
Recent studies point to a great diversity of non-ribosomal peptide synthesis systems with major roles in amino acid and co-factor biosynthesis, secondary metabolism, and post-translational modifications of proteins by peptide tags. The least studied of these systems are those utilizing tRNAs or aminoacyl-tRNA synthetases (AAtRS) in non-ribosomal peptide ligation. Here we describe novel examples of AAtRS related proteins that are likely to be involved in the synthesis of widely distributed peptide-derived metabolites. Using sensitive sequence profile methods we show that the cyclodipeptide synthases (CDPSs) are members of the HUP class of Rossmannoid domains and are likely to be highly derived versions of the class-I AAtRS catalytic domains. We also identify the first eukaryotic CDPSs in fungi and in animals; they might be involved in immune response in the latter organisms. We also identify a paralogous version of the methionyl-tRNA synthetase, which is widespread in bacteria, and present evidence using contextual information that it might function independently of protein synthesis as a peptide ligase in the formation of a peptide- derived secondary metabolite. This metabolite is likely to be heavily modified through multiple reactions catalyzed by a metal-binding cupin domain and a lysine N6 monooxygenase that are strictly associated with this paralogous methionyl-tRNA synthetase (MtRS). We further identify an analogous system wherein the MtRS has been replaced by more typical peptide ligases with the ATP-grasp or modular condensation-domains. The prevalence of these predicted biosynthetic pathways in phylogenetically distant, pathogenic or symbiotic bacteria suggests that metabolites synthesized by them might participate in interactions with the host. More generally, these findings point to a complete spectrum of recruitment of AAtRS to various non-ribosomal biosynthetic pathways, ranging from the conventional AAtRS, through closely related paralogous AAtRS dedicated to certain pathways, to highly derived versions of the class-I AAtRS catalytic domain like the CDPSs. Both the conventional AAtRS and their closely related paralogs often provide aminoacylated tRNAs for peptide ligations by MprF/Fem/MurM-type acetyltransferase fold ligases in the synthesis of peptidoglycan, N-end rule modifications of proteins, lipid aminoacylation or biosynthesis of antibiotics, such as valinamycin. Alternatively they might supply aminoacylated tRNAs for other biosynthetic pathways like that for tetrapyrrole or directly function as peptide ligases as in the case of mycothiol and those identified here.


Comparison of player-dependent and independent high-speed running thresholds to model injury risk in football.
High-speed running (HSR) loads have been linked with non-contact injury risks in team-sports. This study investigated whether player-specific speed zones, reflecting individual fitness characteristics, impact the associations between non-contact injury and acute and chronic HSR loads. Semi-professional soccer players from two clubs (n = 47) were tracked over two seasons using 10 Hz GPS (5552 observations). HSR distances were calculated arbitrarily (≥5.5 m·s-1), and in an individualised fashion based on the final speed of the 30-15 intermittent fitness test. Cumulative running loads were represented by exponentially weighted moving averages with 7-(acute) and 28-day (chronic) decay parameters. Physiotherapists collected non-contact, lower-limb, time-loss injury data (n = 101). Injury models using session type (training vs matches), coach, as well as arbitrary or individualised running loads were constructed via mixed-effect logistic regression. Session type had the largest effect on injury (training vs match OR = 0.28; 95%CI:0.17-0.44). Variations in individualised or arbitrary acute and chronic HSR loads within the mid-range of the observed data had negligible effects on predicted injury risk. However, the uncertainty of estimated effects at extreme values of acute and chronic HSR loads prevented any conclusive findings. Therefore, the efficacy of using customised speed thresholds in quantifying load for injury risk mitigation purposes remains unclear.


Manual acupuncture for myofascial pain syndrome: a systematic review and meta-analysis.
To assess the efficacy of manual acupuncture (MA) in the treatment of myofascial pain syndrome (MPS). We searched for randomised controlled trials (RCTs) comparing MA versus sham/placebo or no intervention in patients with MPS in the following databases from inception to January 2016: PubMed; Cochrane Library; Embase; Web of Science; and China Biology Medicine. Two reviewers independently screened the literature extracted data and assessed the quality of the included studies according to the risk of bias tool recommended by the Cochrane Handbook (V.5.1.0). Then, a meta-analysis was performed using RevMan 5.3 software. Ten RCTs were combined in a meta-analysis of MA versus sham, which showed a favourable effect of MA on pain intensity after stimulation of myofascial trigger points (MTrPs; standardised mean difference (SMD) -0.90, 95% CI -1.48 to -0.32; p=0.002) but not traditional acupuncture points (p>0.05). Benefit was seen both after a single treatment (SMD -1.05, 95% CI -1.84 to -0.27; p=0.009) and course of eight sessions (weighted mean difference (WMD) -1.96, 95% CI -2.72 to -1.20; p<0.001). We also found a significant increase in pressure pain threshold following MA stimulation of MTrPs (WMD 1.00, 95% CI 0.32 to 1.67; p=0.004). Two of the included studies reported mild adverse events (soreness/haemorrhage) secondary to MA. Through stimulation of MTrPs, MA might be efficacious in terms of pain relief and reduction of muscle irritability in MPS patients. Additional well-designed/reported studies are required to determine the optimal number of sessions for the treatment of MPS.


Diabetes and gender.
It is often assumed that there is little or no sex bias within either Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. This review considers evidence that sex effects of interest and importance are present in both forms of the disease. Type I diabetes is the only major organ-specific autoimmune disorder not to show a strong female bias. The overall sex ratio is roughly equal in children diagnosed under the age of 15 but while populations with the highest incidence all show male excess, the lowest risk populations studied, mostly of non-European origin, characteristically show a female bias. In contrast, male excess is a consistent finding in populations of European origin aged 15-40 years, with an approximate 3:2 male:female ratio. This ratio has remained constant in young adults over two or three generations in some populations. Further, fathers with Type I diabetes are more likely than affected mothers to transmit the condition to their offspring. Women of childbearing age are therefore less likely to develop Type I diabetes, and--should this occur--are less likely to transmit it to their offspring. Type II diabetes showed a pronounced female excess in the first half of the last century but is now equally prevalent among men and women in most populations, with some evidence of male preponderance in early middle age. Men seem more susceptible than women to the consequences of indolence and obesity, possibly due to differences in insulin sensitivity and regional fat deposition. Women are, however, more likely to transmit Type II diabetes to their offspring. Understanding these experiments of nature might suggest ways of influencing the early course of both forms of the disease.


Glucuronidation in cultures of human skin epithelial cells.
Glucuronidation of p-aminophenol, p-nitrophenol and bilirubin has been investigated in cultures of human skin epithelial cells (HE cells) and human skin fibroblasts (FB) and in homogenates from the same cells. HE cells in culture glucoronidated p-aminophenol and p-nitrophenol at rates of about 5 and 10 nmol/mg cell protein per h respectively. Bilirubin was not conjugated by HE cells. In homogenates from HE cells supplemented with UDP glucuronic acid (UDPGA) both p-aminophenol and p-nitrophenol were glucuronidated at about the same rate as by living cells in culture. Assuming that the transferase activity is the same in the whole cells compared to the homogenates, transferase activity and not UDPGA production may be the limiting factor in glucuronidation of p-aminophenol and p-nitrophenol in these cells. The glucuronidation rate of HE cells was not increased by benzpyrene or benzanthrazene. FB did not glucuronidate p-aminophenol, p-nitrophenol or bilirubin.


[Surgical therapy of gastrinoma with associated Zollinger-Ellison syndrome].
During a period of 13.5 years 17 patients with a gastrinoma and an associated Zollinger-Ellison syndrome were treated. In three patients (18%) the gastrinoma was part of a multiple endocrine neoplasia type I (MEN I). The median interval from the initial symptoms to the definite diagnosis was 5.0 years. During this interval seven patients (41%) underwent gastric surgery up to four times. The preoperative imaging studies localized the primary tumor in only seven patients (41%). In five of six diagnostic laparotomies the primary site of the tumor was identified and proved by pathologic work-up. The surgical procedures (n = 13) included five resections of the pancreas (3 x pancreatic head, 2 x left pancreatic resection), two duodenal resections, three enucleations of the tumor and three palliative operations (hospital mortality: 0%). Following laparotomy the gastrinoma could be histologically proved in eleven of 17 patients (6 x pancreas, 4 x duodenum, 1 x in the hepatoduodenal ligament). The rate of metastatic spread as characteristic feature of malignancy was 59%. After complete resection of the primary tumor (n = 8) none of these patients died because of the gastrinoma during the follow-up (median: 7.3 years). In the remaining patients three deaths were caused by the metastatic spread of the gastrinoma. Considering the high rate of preceding operations, the high malignancy rate and the excellent prognosis after RO-resection the diagnostic interval in patients with ZES is too long. Despite the modern radiographic imaging the exploratory laparotomy is of high value in patients with ZES.


[New infant formula based on soy milk and corn flour].
In recent years the use of infant feeding formulas based on soy bean has been increasing. We report a trial of a new, soy bean-based formula to which starch was added. A control group was given a cow milk-based formula widely used in this country ("Materna" with cornflour, Ma'abaroth Products Ltd.). Healthy infants, between 3-6 months of age and of normal length and weight were enrolled at random at Infant Welfare Centers in Jerusalem. 25 received the soy formula, and 21 the cow milk-based formula. During the 2-month trial the infants did not receive any other foods. They were examined by the senior author every 2 weeks and weight, length and head circumference were measured at their Infant Welfare Clinic visits. The mothers filled questionnaires concerning the amount of formula ingested, the nature and number of stools, and complaints, such as crying. Both groups gained weight at the normal rate during the trial. In each group, the mothers were satisfied with the product and wanted to continue with it after the trial. We conclude that a soy-based formula containing starch is comparable to a cow milk formula containing star.


Flow diversion in anterior cerebral artery aneurysms.
Anterior cerebral artery (ACA) aneurysms are commonly encountered in clinical practice but can be challenging to treat. Flow diversion is a viable treatment in this population. We retrospectively evaluated patients treated at our center from May 2017 to December 2020 who underwent flow diversion for an ACA aneurysm at or distal to the anterior communicating artery (ACOM). We defined ACA aneurysms as any aneurysm involving the ACOM itself, at the junction of the ACA with the ACOM (A1/A2), or in distal A2/A3 branches; both ruptured and unruptured aneurysms were included. Baseline and follow-up clinical and angiographic data were collected; the primary measure was elimination of the aneurysm on follow-up angiogram. Patients underwent flow diversion with a Pipeline stent. A single flow diverting stent was placed in the dominant ACA spanning from the A2 segment extending into the A1 segment; two patients required H-pipe technique. Distal aneurysms were treated with a single Pipeline device deployed across the parent vessel, covering the aneurysm. Two-seven patients underwent a total of 28 flow diversion procedures; median age was 57 and 16 (59.3%) were male. Thirteen (48.2%) patients presented with subarachnoid hemorrhage; of these, four were treated within 6 weeks of the index hemorrhage. Most patients (22; 81.5%) had significant ACA asymmetry. There was one postoperative intracerebral hemorrhage and one groin complication. Follow-up data were available for 19 patients, 15 (78.9%) of which showed no residual aneurysm and 17 (89.5%) had protection of the dome. Flow diversion of ACA aneurysms can be a primary treatment modality in an unruptured aneurysm or a complement to initial coil protection of a ruptured aneurysm. Further studies are needed to confirm these results.


Therapy after injury to the hand.
Surgical and nonsurgical management of upper extremity disorders benefits from the collaboration of a therapist, the treating physician, and the patient. Hand therapy plays a role in many aspects of treatment, and patients with upper extremity injuries may spend considerably more time with a therapist than with a surgeon. Hand therapists coordinate edema control; pain management; minimization of joint contractures; maximization of tendon gliding, strengthening, and work hardening; counseling; and ongoing diagnostic evaluation. Modalities used to manage hand injuries include ultrasound, splinting, Fluidotherapy (Chattanooga Group, Chattanooga, TN), cryotherapy, various electrical modalities, phonophoresis, and iontophoresis.


A quantitative evaluation of the distal displacement of the gingival zenith in the maxillary anterior teeth.
The aim of this study was to quantify the specific distal displacement of the gingival zenith in the maxillary anterior dentition. Bilateral measurements, taken with a digital caliper in maxillary stone casts were recorded in six maxillary anterior teeth to evaluate distal displacement of the gingival zenith in relation to the long axis of the crowns. The gingival zenith was distally displaced between 0.45 and 1.01 mm in 90%, 85% and 60% of the central incisors, lateral incisors and canines, respectively. Contralateral comparisons between the tooth groups revealed significantly larger distal displacement of the zenith in left canine (p < 0.05). Ipsilateral comparisons revealed that the lateral displacement of the zenith was significantly larger in central than in lateral incisors (p < 0.05). Similarly, the zenith of lateral incisors was displaced significantly more distal than that of canine teeth (p < 0.05). Comparisons of the frequency of coincidence of the position of the gingival zenith with the long axis of the tooth revealed that it was significantly greater in canines than in lateral and central incisors (p < 0.05). The frequency and magnitude of distal displacement is tooth-dependent and larger in central than in lateral incisors, which in turn, is larger than in canines. These data could be used as reference points during esthetic anterior oral rehabilitation, especially in case of porcelain laminate veneers.


Natural Time Analysis: The Area under the Receiver Operating Characteristic Curve of the Order Parameter Fluctuations Minima Preceding Major Earthquakes.
It has been reported that major earthquakes are preceded by Seismic Electric Signals (SES). Observations show that in the natural time analysis of an earthquake (EQ) catalog, an SES activity starts when the fluctuations of the order parameter of seismicity exhibit a minimum. Fifteen distinct minima-observed simultaneously at two different natural time scales and deeper than a certain threshold-are found on analyzing the seismicity of Japan from 1 January 1984 to 11 March 2011 (the time of the M9 Tohoku EQ occurrence) 1 to 3 months before large EQs. Six (out of 15) of these minima preceded all shallow EQs of magnitude 7.6 or larger, while nine are followed by smaller EQs. The latter false positives can be excluded by a proper procedure (J. Geophys. Res. Space Physics 2014, 119, 9192-9206) that considers aspects of EQ networks based on similar activity patterns. These results are studied here by means of the receiver operating characteristics (ROC) technique by focusing on the area under the ROC curve (AUC). If this area, which is currently considered an effective way to summarize the overall diagnostic accuracy of a test, has the value 1, it corresponds to a perfectly accurate test. Here, we find that the AUC is around 0.95 which is evaluated as outstanding.


Electrochemotherapy as First Line Cancer Treatment: Experiences from Veterinary Medicine in Developing Novel Protocols.
Tumor microenvironment is one of the major obstacles to the efficacy of chemotherapy in cancer patients. The abnormal blood flow within the tumor results in uneven drug distribution. Electrochemotherapy (ECT) is a tumor treatment that adopts the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This allows the use of lipophobic drugs that frequently have a narrow therapeutic index maintaining at the same time a reduced patient morbidity and preserving appropriate anticancer efficacy. Its use in humans is addressed to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, and a standard operating procedure has been devised. On the other hand, in veterinary oncology this approach is gaining popularity, thus becoming a first line treatment for different cancer histotypes, in a variety of clinical conditions due to its high efficacy and low toxicity. This review summarizes the state of the art in veterinary oncology as a preclinical model and reports the new protocols in terms of drugs and therapy combination that have been developed.


Von Willebrand factor-cleaving protease activity remains at the intermediate level in thrombotic thrombocytopenic purpura.
A 59-year-old woman, diagnosed with chronic myelogenous leukemia (chronic phase) and treated with interferon-alpha for 13 years, developed renal failure. Renal biopsy showed thrombotic thrombocytopenic purpura, but intensive therapy including plasma exchange and steroid administration was not effective. The activity of von Willebrand factor-cleaving protease was detectable at the intermediate level (15-46%) during the clinical course, suggesting that this case was not compatible with the previously reported pattern of idiopathic or drug-induced thrombotic thrombocytopenic purpura, but with the pattern associated with malignant disease or immunological disorders. Further studies to determine the effects of interferon-alpha on endothelial cells in chronic myelogenous leukemia patients are needed.


Power spectral density of unevenly sampled data by least-square analysis: performance and application to heart rate signals.
This work studies the frequency behavior of a least-square method to estimate the power spectral density of unevenly sampled signals. When the uneven sampling can be modeled as uniform sampling plus a stationary random deviation, this spectrum results in a periodic repetition of the original continuous time spectrum at the mean Nyquist frequency, with a low-pass effect affecting upper frequency bands that depends on the sampling dispersion. If the dispersion is small compared with the mean sampling period, the estimation at the base band is unbiased with practically no dispersion. When uneven sampling is modeled by a deterministic sinusoidal variation respect to the uniform sampling the obtained results are in agreement with those obtained for small random deviation. This approximation is usually well satisfied in signals like heart rate (HR) series. The theoretically predicted performance has been tested and corroborated with simulated and real HR signals. The Lomb method has been compared with the classical power spectral density (PSD) estimators that include resampling to get uniform sampling. We have found that the Lomb method avoids the major problem of classical methods: the low-pass effect of the resampling. Also only frequencies up to the mean Nyquist frequency should be considered (lower than 0.5 Hz if the HR is lower than 60 bpm). We conclude that for PSD estimation of unevenly sampled signals the Lomb method is more suitable than fast Fourier transform or autoregressive estimate with linear or cubic interpolation. In extreme situations (low-HR or high-frequency components) the Lomb estimate still introduces high-frequency contamination that suggest further studies of superior performance interpolators. In the case of HR signals we have also marked the convenience of selecting a stationary heart rate period to carry out a heart rate variability analysis.


Metabolic changes observed in astronauts.
Study of metabolic alterations that occur during space flight can provide insight into mechanisms of physiologic regulation. Results of medical experiments with astronauts reveal rapid loss of volume (2 L) from the legs and a transient early increase in left ventricular volume index. These findings indicate that, during space flight, fluid is redistributed from the legs toward the head. In about 2 days, total body water decreases 2 to 3%. Increased levels of plasma renin activity and antidiuretic hormone while blood sodium and plasma volume are reduced suggest that space flight-associated factors are influencing the regulatory systems. In addition to fluid and electrolyte loss. Skylab astronauts lost an estimated 0.3 kg of protein. Endocrine factors, including increased cortisol and thyroxine and decreased insulin, are favorable for protein catabolism. The body appears to adapt to weightlessness at some physiologic cost. Readaptation to Earth's gravity at landing becomes another physiologic challenge.


Effect of ventriculectomy versus ventriculocordectomy on upper airway noise in draught horses with recurrent laryngeal neuropathy.
Little is known about the efficacy of bilateral ventriculectomy (VE) or bilateral ventriculocordectomy (VCE) in draught horses. To compare the effect of VE and VCE on upper airway noise in draught horses with recurrent laryngeal neuropathy (RLN) by use of quantitative sound analysis techniques. In competitive draught horses with grade 4 RLN, VE and VCE reduce upper airway noise during exercise, but VCE is more effective. Thirty competitive hitch or pulling draught horses with grade 4 RLN were evaluated for upper airway sound during exercise. Respiratory rate (RR), inspiratory (Ti) and expiratory time (Te), the ratio between Ti and Te (Ti/Te), inspiratory (Sli) and expiratory sound levels (Sle), the ratio between Sli and Sle (Sli/Sle), and peak sound intensity of the second formant (F2) were calculated. Eleven horses were treated with VE and 19 with VCE. After 90 days of voice and physical rest and 30 days of work, the horses returned for post operative upper airway sound evaluation and resting videoendoscopy. VE significantly reduced Ti/Te, Sli, Sli/Sle and the sound intensity of F2. Respiratory rate, Ti, Te and Sle were unaffected by VE. VCE significantly reduced Ti/Te, Ti, Te, Sli, Sli/Sle and the sound intensity of F2, while RR and Sle were unaffected. The reduction in sound intensity of F2 following VCE was significantly greater than following VE. After VE and VCE, 7/11 (64%) and 15/18 (83%) owners, respectively, concluded that the surgery improved upper airway sound in their horses sufficiently for successful competition. VE and VCE significantly reduce upper airway noise and indices of airway obstruction in draught horses with RLN, but VCE is more effective than VE. The procedures have few post operative complications. VCE is recommended as the preferred treatment for RLN in draught horses. Further studies are required to evaluate the longevity of the procedure's results.


Prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria.
It is well known that factors like high blood pressure, hyperglycemia, dyslipidemia, obesity and hyperuricemia tend to cluster together giving rise to what is called metabolic syndrome. In spite of the high prevalence of hypertension in Nigeria, there is a dearth of data describing the prevalence of metabolic syndrome in Nigerian hypertensive patients. We therefore set out to look at the prevalence of metabolic syndrome in hypertensive patients presenting to the cardiology clinic of a tertiary institution in Abuja, Nigeria. Metabolic syndrome was defined in patients according to the World Health Organisation's definition. Of the 362 patients studied, 56.9% were male and 43.1% were female. The mean age was 51.80 +/- 11.63 years, mean duration of hypertension was 8.90 +/- 3.95 years, mean body mass index was 29.36 +/- 6.12 kg/m2 and mean arterial blood pressure was 110.28 +/- 18.17 mm Hg. Overall, 13.0% of the study population had metabolic syndrome; 16.7% of females and 10.2% of males. The prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria is comparable to rates observed in some general populations in Europe. This might imply the epidemiological transition in disease pattern already being experienced in many parts of sub-Saharan Africa.


Perception of unmet basic needs as a predictor of depressive symptoms among community-dwelling older adults.
In previous studies we found that, among older adults (>64 years), perception that basic needs were not being met increased mortality risk and risk for functional decline. In this study, we determined, controlling for reported income and functional status, if perceived inadequate basic needs predicted depressive symptoms. Repeated-measures analysis was used to determine, during three intervals in a 10-year longitudinal study (the Duke Established Populations for Epidemiologic Studies of the Elderly, n = 4162 at baseline), if perceived inadequate basic needs at the beginning of each interval predicted more depressive symptoms at the end of the interval. We included time invariant covariates known to be associated with depressive symptoms--age, sex, race, and education. We also included time-varying covariates at the beginning of the three intervals--income, cognitive status, functional status, depressive symptoms, and interval. In the repeated-measures controlled analyses, the perception of inadequate basic needs was a highly significant predictor of future depressive symptoms (p <.0001). Race, education, baseline depression, baseline function, interval, and income were also significant predictors of depression. The interaction between interval and depression was not significant. The perception that one's basic needs are not being met predicted future depressive symptoms in a highly controlled analysis. These results suggest that perception of inadequate basic needs, even when income and other known correlates of depression are controlled, is a strong predictor of future depressive symptoms.