Long-term treatment of indomethacin reduces vertebral bone mass and strength in ovariectomized rats.
We investigated the effect of the long-term treatment of indomethacin, on lumbar spinal bone mineral density (LSBMD), cancellous bone mass, structure, and strength of vertebral body in old ovariectomized (OVX) rats. Ten-month-old female Wistar rats were divided into five groups: the sham operated + vehicle (sham + VEH) group, the OVX + vehicle (OVX + VEH) group, the OVX + indomethacin (IN) 1.5 mg/kg/week (OVX + IN1.5) group, the OVX + IN 6.0 mg/kg/week (OVX + IN6.0) group, and the OVX + IN 15.0 mg/kg/week (OVX + IN15.0) group. IN or vehicle were given by subcutaneous injection (s.c.) three times per week. The treatments were started at 1 week after operation and continued for 24 weeks. LSBMD (L2-L5) was measured at 0, 12, and 24 weeks after the beginning of treatment. At the end of the experimental period, the animals were sacrificed, and bone histomorphometrical and biomechanical analysis of lumbar vertebral body were done. LSBMD, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) decreased significantly in a dose-related manner with IN. In the OVX + IN15.0 group, LSBMD decreased by 12.7%, BV/TV decreased by 65.5%, and Tb.Th decreased by 32.8%, compared with the OVX + VEH group. In addition, the maximum stress in a compressive mechanical test of L4 vertebral body in OVX groups was also decreased in a dose-related manner with IN, and this value in the OVX + IN15.0 group was 31.3% lower than in the OVX + VEH group. We conclude that long-term treatment with IN accentuated the OVX-related decrease in trabecular bone mass and the compressive strength of lumbar vertebrae.


Galactose uncovers face recognition and mental images in congenital prosopagnosia: the first case report.
A woman in her early 40s with congenital prosopagnosia and attention deficit hyperactivity disorder observed for the first time sudden and extensive improvement of her face recognition abilities, mental imagery, and sense of navigation after galactose intake. This effect of galactose on prosopagnosia has never been reported before. Even if this effect is restricted to a subform of congenital prosopagnosia, galactose might improve the condition of other prosopagnosics. Congenital prosopagnosia, the inability to recognize other people by their face, has extensive negative impact on everyday life. It has a high prevalence of about 2.5%. Monosaccharides are known to have a positive impact on cognitive performance. Here, we report the case of a prosopagnosic woman for whom the daily intake of 5 g of galactose resulted in a remarkable improvement of her lifelong face blindness, along with improved sense of orientation and more vivid mental imagery. All these improvements vanished after discontinuing galactose intake. The self-reported effects of galactose were wide-ranging and remarkably strong but could not be reproduced for 16 other prosopagnosics tested. Indications about heterogeneity within prosopagnosia have been reported; this could explain the difficulty to find similar effects in other prosopagnosics. Detailed analyses of the effects of galactose in prosopagnosia might give more insight into the effects of galactose on human cognition in general. Galactose is cheap and easy to obtain, therefore, a systematic test of its positive effects on other cases of congenital prosopagnosia may be warranted.


Protein flexibility predictions using graph theory.
Techniques from graph theory are applied to analyze the bond networks in proteins and identify the flexible and rigid regions. The bond network consists of distance constraints defined by the covalent and hydrogen bonds and salt bridges in the protein, identified by geometric and energetic criteria. We use an algorithm that counts the degrees of freedom within this constraint network and that identifies all the rigid and flexible substructures in the protein, including overconstrained regions (with more crosslinking bonds than are needed to rigidify the region) and underconstrained or flexible regions, in which dihedral bond rotations can occur. The number of extra constraints or remaining degrees of bond-rotational freedom within a substructure quantifies its relative rigidity/flexibility and provides a flexibility index for each bond in the structure. This novel computational procedure, first used in the analysis of glassy materials, is approximately a million times faster than molecular dynamics simulations and captures the essential conformational flexibility of the protein main and side-chains from analysis of a single, static three-dimensional structure. This approach is demonstrated by comparison with experimental measures of flexibility for three proteins in which hinge and loop motion are essential for biological function: HIV protease, adenylate kinase, and dihydrofolate reductase.


Discovery of metabolomics biomarkers for early detection of nephrotoxicity.
Drug-induced nephrotoxicity is a major concern, since many pharmacological compounds are filtered through the kidneys for excretion into urine. To discover biochemical biomarkers useful for early identification of nephrotoxicity, metabolomic experiments were performed on Sprague-Dawley Crl:CD (SD) rats treated with the nephrotoxins gentamicin, cisplatin, or tobramycin. Using a combination of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), a global, nontargeted metabolomics analysis was performed on urine and kidney samples collected after one, five, and twenty-eight dosing days. Increases in polyamines and amino acids were observed in urine from drug-treated rats after a single dose, and prior to observable histological kidney damage and conventional clinical chemistry indications of nephrotoxicity. Thus, these metabolites are potential biomarkers for the early detection of drug-induced nephrotoxicity. Upon prolonged dosing, nephrotoxin-induced changes included a progressive loss of amino acids in urine, concomitant with a decrease in amino acids and nucleosides in kidney tissue. A nephrotoxicity prediction model, based on the levels of branched-chain amino acids in urine, distinguished nephrotoxin-treated samples from vehicle-control samples, with 100%, 93%, and 70% accuracy at day 28, day 5, and day 1, respectively. Thus, this panel of biomarkers may provide a noninvasive method to detect kidney injury long before the onset of histopathological kidney damage.


Subcutaneous immunoglobulins in chronic lymphocytic leukemia with secondary antibody deficiency. A monocentric experience during Covid-19 pandemics.
Secondary antibody deficiency (SAD) is a frequent manifestation of chronic lymphocytic leukemia (CLL) that increases the risk of infections. However, no formal guideline are available regarding the eligibility for prophylaxis or the delivery method, dosage, frequency of administration and duration of immunoglobulin replacement therapy (IgRT). The aim of this study was to assess the efficacy and safety of subcutaneous IgRT (SCIg) and its impact on quality of life (QoL) of CLL pts in the Covid-19 era. Ten CLL pts with SAD were treated with subcutaneous IgRT (SCIg) at our institution between October 2019 and December 2020. Median age was 66 years and five patients had comorbidities. Seven patients were receiving therapy for CLL when treatment with SCIg was initiated. All pts received 10 g total dose hyaluronidase-free SCIg independently from body weight. The IgG level and CD4/CD8, CD19 and CD16/56 lymphocytes subset were recorded at baseline and every 3 months. No patient experienced infectious events nor Covid-19 mediated interstitial pneumonia while on SCIg therapy. All patients tolerated well the therapy and experienced an increase of IgG levels, which was then stable in time. We conclude that SCIg administration in CLL pts with SAD is efficacious and safe as infectious prophylaxis. This route of administration appears particularly advantageous in the Covid-19 era, because of the self-administration at home which results in improvement in the QoL and reduced treatment expenditures.


[Anatomo-clinical findings on the ascending pharyngeal artery].
Origin, width, course and twigs of the ascending pharyngeal artery are investigated on 63 head-helves. In about 80% this vessel is a twig from the external carotid artery or from a common trunc from this vessel. In 20% there is a twig from an other artery (In 4,8% the ascending pharyngeal artery is a twig of the internal carotid artery). The ascending pharyngeal artery is 1.57 (0.9-2.3) mm in width and its course is in the most cases straight, medial, mediorostral or laterorostral from the internal carotid artery in the parapharyngeal spaces. Number, course and width of the pharyngeal rami, the rami to the lymphatic nodes, to the superior sympathetic ganglion, the prevertebral tissues in the neighbourhood of the carotic canal, to the external cranial base, to the nasal part of the pharynx and to the hypoglossal canal are prepared and studied. The clinical value is discussed.


Generic method for the absolute quantification of glutathione S-conjugates: Application to the conjugates of acetaminophen, clozapine and diclofenac.
Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione (GSH). Although sensitivity of modern mass spectrometrical methods is extremely high, absolute quantification of GSH-conjugates is critically dependent on the availability of authentic references. Although 1H NMR is currently the method of choice for quantification of metabolites formed biosynthetically, its intrinsically low sensitivity can be a limiting factor in quantification of GSH-conjugates which generally are formed at low levels. In the present study, a simple but sensitive and generic method for absolute quantification of GSH-conjugates is presented. The method is based on quantitative alkaline hydrolysis of GSH-conjugates and subsequent quantification of glutamic acid and glycine by HPLC after precolumn derivatization with o-phthaldialdehyde/N-acetylcysteine (OPA/NAC). Because of the lower stability of the glycine OPA/NAC-derivate, quantification of the glutamic acid OPA/NAC-derivate appeared most suitable for quantification of GSH-conjugates. The novel method was used to quantify the concentrations of GSH-conjugates of diclofenac, clozapine and acetaminophen and quantification was consistent with 1H NMR, but with a more than 100-fold lower detection limit for absolute quantification.


Pathogenesis of encephalomyocarditis experimental infection in young piglets: a potential animal model to study viral myocarditis.
The pathogenesis of encephalomyocarditis (EMC) due to the EMC virus (EMCV) was studied in 24 piglets oro-nasally infected with the field isolate B279/95. Two pigs were kept as negative controls and were euthanised at hour 0. The remaining 24 were euthanised every 6 h up to 78-h post infection (hpi). Virus isolation, histological examination and EMCV immunodetection were performed on the spleen, intestine, pancreas, liver, kidneys, heart, lungs, lymph nodes, tonsils and brain. EMCV was isolated at 6-hpi from the intestine and lymph nodes and at 12-hpi from the heart. From 6 to 12-hpi, scattered degenerate myocardiocytes were immunolabelled. Subsequently, myocarditis developed and progressively worsened. Immunopositive reaction in tonsil macrophages, observed in the early stage of infection (6-hpi), suggests that tonsils are the portal of entry, and by mean of wandering macrophages the EMC virus is then distributed through the body. Afterwards, EMCV-B279/95 replicates intensively in the cytoplasm of myocardiocytes and the acute myocarditis is strictly related to the tropism of these cells. Four pigs died spontaneously. In three animals no post mortem lesions or virus were isolated/detected, although all of them showed mild myocarditis. The experimental infection with EMCV B279/95 indicates: (i) the experimental protocol mimics the individual variability observed in natural disease, (ii) tonsils are the portal of entry of infection and the heart is the target organ, (iii) EMCV provides a valuable animal model for comparative studies on progressive viral myocarditis.


Differential effects of muscle contraction from various body parts on neuromagnetic somatosensory responses.
We studied eight healthy subjects with a whole-scalp 306-channel neuromagnetometer to explore the effect of motor activity from different body parts on somatosensory responses to left median nerve stimulation. The stimuli produced clear tactile sensation without any motor movement. In the rest condition, the subject had no task. During contraction conditions, the subject had to maintain submaximal isometric contraction in masseter, left deltoid, left thenar, or left tibialis muscles. Short-latency responses from the primary somatosensory cortex did not change during contraction. Responses from both the right (contralateral) and left second somatosensory cortices (SII) were significantly enhanced during contraction of the left thenar muscles. Responses from the left SII were significantly enhanced also during contraction of the left deltoid muscles, but they were decreased during contraction of the masseter and left tibialis anterior muscles. This study implies that SII activation is modulated by motor activity and that the effect depends on the topographical proximity of the stimulated and contracted body parts.


[Mechanisms of multi-organ failure in severe influenza].
Severe influenza is characterized by cytokine storm and multi-organ failure with edema. We found that the "influenza virus-cytokine-trypsin/MMP-9 cycle" in the endothelial cells is one of the key mechanisms of vascular hyperpermeability, the major pathogen of multi-organ failure. Upregulated TNF-alpha, IL-6 and IL-beta induce ectopic pancreatic trypsin and pro-MMP-9 in the endothelial cells and in various organs. Trypsin mediates the viral hemagglutinin processing, which is crucial for viral entry and multicycles of replication. In addition, trypsin is the most potent pro-MMP-9 convertase to form active MMP-9 and both proteases synergistically destruct matrix around blood vessels. In addition upregulated trypsin triggers through its receptor, PAR-2, the modification of cellular functions, such as increase in calcium mobilization and mitochondrial membrane permeability, suppression of ATP generation and loss of tight junction constituent, zonula occludens-1. High risk patients who have impaired mitochondrial fuel utilization will easy get into energy crisis, resulting in vascular hyperpermeability in severe influenza.


Efficacy of Timolol 0.1% Gel and a Prostaglandin Analog in an Unfixed Combination Compared to the Corresponding Fixed Combinations.
To investigate the intraocular pressure (IOP) reduction with prostaglandin analogs (PGAs)-timolol fixed combinations versus the unfixed combination of the same PGAs and timolol 0.1% in gel-forming carbomer. Patients with primary open-angle glaucoma (POAG) receiving for at least 4 weeks the fixed combinations of PGA-timolol, administered once a day in the evening (0.005% latanoprost with 0.5% timolol, 0.004% travoprost with 0.5% timolol, 0.03% bimatoprost with 0.5% timolol) were switched to an unfixed combination of the same PGA (once a day in the evening) with timolol 0.1% in gel-forming carbomer (once a day in the morning) for at least 4 weeks. The primary endpoint was to compare efficacy of fixed vs unfixed combinations in lowering IOP. The effects of both regimens on short-term IOP fluctuations were also assessed. A total of 32 patients (64 eyes) fulfilled inclusion criteria: 17 patients received latanoprost-timolol fixed combination, 9 travoprost-timolol fixed combination, 6 bimatoprost-timolol fixed combination. For all considered time periods each unfixed combination induced an IOP reduction significantly higher than the corresponding fixed combination (paired t test: p<0.05 in all measurements). The diurnal IOP reduction was significantly higher during the unfixed combinations (p<0.001). Unfixed combinations significantly decreased IOP diurnal fluctuations and increased the percentage of patients with daily IOP fluctuation ≤2 mm Hg. In this pilot study, PGA and timolol seems to be more effective in POAG treatment when administered as unfixed combinations, reducing both IOP and daily fluctuations. The once a day timolol 0.1% gel-forming carbomer may be a valuable option in PGA-timolol unfixed combination regimen.


Variation of HLA class I (-A and -C) genes in individuals infected with hepatitis B or hepatitis C virus in Cameroon.
The Human Leucocyte Antigens (HLA) work in concert with other immune factors to modulate immunity to viral infections. Extensive variation has been reported in the genetic sequences and functions of classical HLA class I genes in many (mostly Western) populations, and several HLA associations with infectious disease outcomes have been reported. Little is known about their role in the susceptibility or resistance to hepatitis viruses in Central African populations. The aim of this study was to determine variants of two HLA class I genes (HLA-A and -C) in adults infected with hepatitis B (HBV)- or -C (HCV) virus in Cameroon. In this case-control study, a total of 169 unrelated adults comprising 68 HCV-infected, 38 HBV-infected and 63 uninfected (controls) individuals participated. Each consented participant was screened for HBV, HCV, and HIV infections and willingly donated a single blood sample for genomic DNA isolation and some clinical laboratory tests. HLA-A and HLA-C were genotyped using previously described sequence-based techniques (SBT). A total of 54 HLA alleles were identified in the study population (27 HLA-A and 27 HLA-C). HLA-A∗23:01 and HLA-C∗07:01 were the most common alleles with genotype frequencies of 31.4% and 29.3%, respectively. Hepatitis individuals were six times more likely to be HLA-A∗30:01 carriers than uninfected controls (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV), respectively). Similarly, carriers of HLA-C∗17:01 were over-represented in the HBV-infected compared to the uninfected control group (21.9% vs. 6.4%, respectively) suggesting that this allele could play a role in the susceptibility to HBV infection. These findings demonstrate that carriers of HLA-A∗30:01 were over-represented in the hepatitis group compared to uninfected controls while HLA-C∗17:01 was completely absent in the HCV + group.


Rapid internal acyl migration and protein binding of synthetic probenecid glucuronides.
Internal acyl migration reactions of drug 1-O-acyl-beta-D-glucopyranuronates (1beta-acyl glucuronides) are of interest because of their possible role in covalent binding to proteins and consequent adverse effects. The reactivity of the synthetic probenecid 1beta-acyl glucuronide (PRG), the principal metabolite of probenecid (PR) in humans, has been investigated in terms of acyl migration, hydrolysis, and covalent binding to proteins in phosphate buffer (pH 7.4) and human plasma at 37 degrees C. PRG primarily degraded by acyl migration according to apparent first-order kinetics and the 2-, 3-, and 4-acyl isomers sequentially appeared as both alpha- and beta-anomeric forms. In addition, small amounts of PRG and extremely labile 1alpha-acyl isomer existed in the equilibrated mixture favoring the 2alpha/beta-acyl isomer, that provided significant information regarding the mechanism of acyl migration. All of the positional isomers and anomers were characterized using preparative HPLC and NMR spectroscopy. Acyl migration was observed to predominate over hydrolysis in both media although the extent of hydrolysis in plasma was larger than that in the buffer. The overall degradation half-lives (h) in the buffer and plasma were 0.27 +/- 0.003 and 0.17 +/- 0.007, respectively. The covalent binding rapidly proceeded mainly via the Schiff's base mechanism and reached a plateau after 2 h of incubation. The maximal binding was 146 +/- 4.8 pmol/mg of protein, and ca. 10% of the initial concentration of PRG. These results indicated that PRG is most labile and susceptible to acyl migration of all the drug acyl glucuronides reported to date in the physiological conditions, and highly reactive to plasma proteins, that could provide a possible explanation for the immunologically based adverse effects of PR.


Thorn: a new approach to mental health training.
The Thorn Initiative started life as an educational programme focusing on community psychiatric nurses. From the beginning its teaching has been multidisciplinary and at present its students come from a variety of backgrounds. This article describes the rationale for the initiative and describes its progress and impact on those who experience severe mental health problems and their families.


[Value of pulsed Doppler tissue imaging for early detection of myocardial dysfunction with anthracyclines].
The cumulative and definitive nature of chronic cardiotoxicity of anthracyclines requires a preventive strategy of early diagnosis. The authors undertook a prospective study of the association of echocardiography, mitral Doppler and pulsed Doppler tissue imaging of the left ventricular lateral and posterior walls in the context of this problem in 20 patients without cardiac disease undergoing cancer chemotherapy including anthracyclines. Doppler echocardiography was performed before the first session of chemotherapy and at the end of treatment, 6 +/- 4 months later. After a total cumulative dose of 227 +/- 91 mg/m2 of doxorubicine, there were no changes in left ventricular ejection fraction but a significant decrease in mitral E wave velocity (p = 0.04) and in E/A ratio (p = 0.01), suggesting early changes in left ventricular relaxation. The Doppler tissue examination confirmed the presence of radial and longitudinal abnormalities in myocardial relaxation (decreases in myocardial E wave velocities of the posterior and lateral walls of the left ventricle, p = 0.02 and p = 0.01, respectively). The peak velocity of the myocardial systolic wave (Sm) was significantly decreased in the lateral wall (p = 0.02) and approached statistical significance in the posterior wall (p = 0.07). These results suggest concomitant changes in myocardial systolic and diastolic function with moderate doses of anthracyclines. Therefore, pulsed Doppler tissue examination enables earlier detection of left ventricular cardiotoxicity with anthracyclines than classical echocardiographic parameters.


UK recommendations for SDHA germline genetic testing and surveillance in clinical practice.
SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of SDHA PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for SDHA PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more SDHA PGV carriers will be identified in patients with tumours not strongly associated with SDHA, or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert SDHA working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of SDHA PGV carriers in clinical practice.


Pedigree analysis of constitutional delay of growth and maturation: determination of familial aggregation and inheritance patterns.
To investigate the genetic basis of constitutional delay of growth and maturation (CD), 41 families of CD probands underwent interviews regarding pubertal timing, and 12 additional families had history data analyzed from medical records. The family histories of the 53 probands (40 boys and 13 girls) were assessed for pubertal delay using both strict criteria (pubertal delay >or=2 SD beyond the mean) and relaxed criteria (pubertal delay >or=1 SD beyond the mean). These pedigrees were compared with 25 control pedigrees. Mean age of menarche was 14.3 +/- 1.4 yr for mothers of CD probands vs. 12.7 +/- 1.4 yr for mothers of controls (P < 0.0001). Thirty-eight percent of CD mothers met the strict 2 SD criteria, and an additional 29% met the relaxed 1 SD criteria for pubertal delay. By contrast, among the control mothers, 12% met the strict and an additional 8% met the relaxed criteria (P < 0.0001 for comparison with CD mothers). CD fathers were also more likely than the control fathers to have a history of pubertal delay. For first-degree relatives, the estimated relative risk of meeting the 2 SD and 1 SD criteria for delay in CD vs. control pedigrees were 4.8 and 4.9, respectively; estimated relative risk for second-degree relatives were 3.2 and 4.4, respectively. Inheritance patterns varied, but many families showed an apparent autosomal dominant pattern, with or without incomplete penetrance. Although many genes may underlie CD, the inheritance patterns suggest that there are also single genes with major effects whose penetrance is likely affected by genetic or environmental modifiers. The future identification of these major and modifying genes is an exciting prospect that would improve our understanding of the factors that regulate human pubertal timing and modulate the human reproductive endocrine axis.


Topologically Unique Molecular Nanocarbons.
As new forms of carbon are unearthed, they invariably transform the scientific landscape. Numerous researchers have been inspired to discover the unique characteristics of these fascinating materials, consistently leading to the development of important technological innovations in materials science. Recently, studies on the preparation of molecular nanocarbons (small molecule analogues of larger carbon nanostructures) by precision organic synthesis have attracted much attention. Cycloparaphenylene (CPP), the substructure of carbon nanotubes (CNTs), is the oldest of such organic molecules, and since 2008 the successful synthesis of CPP dramatically advanced the synthetic chemistry of molecular nanocarbons. In fact, as pioneering research, we succeeded in producing carbon nanotubes using seed CPP molecules in 2013. This method represented an important landmark in the quest for controlling the diameter of CNTs via utilization of a well-defined small molecule as a template. Other avenues of research on graphene nanoribbons and partial structures of fullerenes such as corannulene and sumanene are also highly active at the current time. On the other hand, carbon forms with nontrivial topologies, i.e., topological nanocarbons, are virtually unexplored. In addition to the 3D network structures represented by the Mackay crystal, many topologically complex structures have been envisioned. To date, there is no rational approach toward the bottom-up synthesis of these carbon structures. As with the case of fullerenes and CNTs, access to these unique carbon structures should undoubtedly revolutionize a wide range of sciences. This Account highlights our efforts toward the synthesis of topologically unique molecular nanocarbons. Starting from CPP as the topologically simple subunit, we have successfully created novel molecular nanocarbons that have more complexed topologies. The first topic is carbon nanobelts, fully fused cylinder-shaped molecular nanocarbons representing the segment structure of armchair-type CNTs. The second topic is carbon nanocages, molecular nanocarbons having a "three-holed" topology representing the joint unit of branched CNTs. The third and fourth topics are all-benzene catenanes consisting of two CPP rings and an all-benzene trefoil knot topologically related to a carbon nanotorus. The world of nanocarbon molecules is only limited by our imagination and creativity. As history has proved, the synthesis of new forms of carbon and topologically complex molecules has always subsequently led to new fields and applications associated with their unforeseen properties and functions.


Colloidal Suspensions of Rodlike Nanocrystals and Magnetic Spheres under an External Magnetic Stimulus: Experiment and Molecular Dynamics Simulation.
Using experiments and molecular dynamics simulations, we explore magnetic field-induced phase transformations in suspensions of nonmagnetic rodlike and magnetic sphere-shaped particles. We experimentally demonstrate that an external uniform magnetic field causes the formation of small, stable clusters of magnetic particles that, in turn, induce and control the orientational order of the nonmagnetic subphase. Optical birefringence was studied as a function of the magnetic field and the volume fractions of each particle type. Steric transfer of the orientational order was investigated by molecular dynamics (MD) simulations; the results are in qualitative agreement with the experimental observations. By reproducing the general experimental trends, the MD simulation offers a cohesive bottom-up interpretation of the physical behavior of such systems, and it can also be regarded as a guide for further experimental research.


Athetosis II: the syndrome of mild athetoid cerebral palsy.
We describe 8 patients who presented with continuous, irregular movements occurring independently in individual fingers and, in some cases, toes, in the setting of mild dystonia present since early childhood and not associated with major disability. The finger movements varied from low-amplitude quivering or wriggling to larger amplitude movements in the plane of abduction-adduction as well as flexion-extension; they were asymmetrical but not unilateral. Quivering or working of the facial muscles was seen in 5 patients. Most patients reported worsening of the movements over the years, but there was no other evidence of a progressive neurological disease. We classify the movement disorder as athetosis as described by Hammond and Shaw and the syndrome as mild athetoid cerebral palsy.


The features and clinical outcomes of inflammatory bowel disease associated with autoimmune pancreatitis: A greater awareness is needed.
The prevalence of inflammatory bowel disease (IBD) has been described in 5% to 40% of autoimmune pancreatitis (AIP) patients. The aim of our study was to evaluate the prevalence, endoscopic features, and outcome of IBD in association with AIP.A retrospective analysis including all consecutive patients with AIP and a histological diagnosis of IBD from 2010 to 2020 was performed. Demographical data, AIP, and IBD features, as well as clinical course, were recorded.Among 267 AIP patients, 45 were diagnosed with ulcerative colitis (UC) (27 men, mean age 31.6), all with a diagnosis of type 2 AIP. The most frequent presentation of AIP was acute pancreatitis (55.5%). Both diffuse (51.1%) and focal (48.9%) pancreatic involvement were observed. The AIP relapse rate was 11.1% over a mean follow-up of 55 months. In 69% of patients, the interval time between the diagnosis of AIP and UC was <1 year. When UC was present at AIP onset, UC was in clinical remission in 50% of patients. Fecal calprotectin levels, when available, were elevated in 86.6% of these patients. Mostly, mild-moderate pancolitis was initially diagnosed (55.5%). During follow-up, escalation therapy for UC was required in 40% of patients after a mean time of 45 months. Two patients (4.4%) underwent colectomy.The prevalence of UC in AIP patients was 17%. Mild pancolitis with a low rate of colectomy was found. Greater awareness is needed to avoid a delayed diagnosis of UC, and the dosage of fecal calprotectin levels could have a role in this setting.


Analysis of trimodal pattern of mortality among hospitalized COVID-19 patients- Lessons from tertiary care hospital.
Many patients with COVID-19 become critically ill and requireICU admission. Risk factors associated with mortality have been studied, but this study provides insight regarding disease progression and hence help to plan rescue strategies to improve patient outcome. This retrospective, observational study included all patients with diagnosis of COVID-19 from March1 to June30,2021 who died in hospital. During the study period, 1600 patients were admitted, with 1138 (71%) needing ICU care. There were 346 (21.6%) deaths, distributed as 15.8%(n = 55) within 48h of admission, 46.2%(n = 160) in next 10 days, and 37.8%(n = 131) thereafter. This trimodal mortality pattern of distribution was similar to polytrauma patients. Patients were divided into categories according to time duration from admission to death. In our cohort, 235 (14.7%) patients required mechanical ventilation, with a mortality of 85.4%(n = 201). Tachypnea was significantly (P < 0.001) associated with death at all times; however, hypotension was associated with early death and low oxygen saturation with poor outcome upto 10 days (P < 0.001). Refractory hypoxia was cause of death in all three groups, while other causes in group II were AKI (28%), sepsis (18%), and MODS (10%). Group III patients had different causes of mortality, including barotrauma (9%), pulmonary thromboembolism (8%), refractory hypercarbia (12%), MODS (13%), AKI (10%), sepsis (7%), and cardiac events (6%). While physiological dearrangements are associated with rapid progression and early death, complications related to hyper-coagulable state, lung injury, and organ failure lead to death later. Providing quality care to a high volume of patients is a challenge for all, but posthoc analysis such as air crash investigation can help find out potential areas of improvement and contribute to better outcomes and mortality reduction.


Predictors of damage and survival in patients with Wegener's granulomatosis: analysis of 50 patients.
To evaluate damage features and impact on survival by Vasculitis Damage Index (VDI) in a cohort of Turkish patients with Wegener's granulomatosis (WG). We enrolled 50 (25 female) patients with WG according to ACR criteria. Birmingham Vasculitis Activity Score (BVAS) and VDI were used to analyze disease activity and damage. Patients had kidney (82%), upper airway (72%), lung (70%), and nervous system (15%) involvement. Median age at diagnosis was 45 years, time to diagnosis was 3.5 months, and total followup time was 35.5 months. All but one patient was positive for antineutrophil cytoplasmic antibodies (ANCA). Mean final dose and duration of corticosteroid and cyclophosphamide was 15 +/- 14 g, 39 +/- 33 months and 36 +/- 34 g, 21 +/- 2 months, respectively. Mean early (e) BVAS were 20.2 +/- 7.1 (4-38) (median 21). Mean e-BVAS and e-VDI scores at presentation and final (f)-VDI scores at last visit were 20.2 +/- 7.1 (4-38), 3.1 +/- 1.7 (median 3) (0-7) and 4.4 +/- 2.6 (0-12), consecutively. Disease related damage was prominent in kidneys (50%) and upper airways (27%). Amenorrhea (90%), cataract (28%), and diabetes (24%) were the most frequent treatment related damages. Rapidly progressive glomerulonephritis at presentation (42%) progressed to endstage renal failure in 20%. Relapses occurred in 25% with mean BVAS of 6.5 +/- 2.3 (4-11). Survival rate was 77% at 37 months. Deaths occurred early (90% in the first year). f-VDI was high in patients who relapsed (6 +/- 3 vs 3.8 +/- 2.1, p = 0.03). Logistic regression analysis demonstrated that age at time of diagnosis and e-VDI were lower in survivors with OR = 0.9 (p = 0.06, 95% CI: 0.78-1) and OR = 0.5 (p = 0.04, 95%CI: 0.25-0.98), respectively. In this cohort, e-VDI score of 5 or more was related to death with 98% sensitivity and 56% specificity (p = 0.004) (CI: 0.66-0.95). Disease related damage outweighed treatment related damage in our cohort of predominantly generalized disease activity. Early damage and older age were found to be predictors of final damage and death.


HLA B*44: protective effects in MS susceptibility and MRI outcome measures.
In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05. Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's effect. We used linear regression and an additive model to test for correlation between an allele and MRI and clinical measures of disease course. After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated as susceptibility alleles (p(A*02) 0.00039 and p(B*44) 0.00092) and remain significantly associated with MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome). The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but only HLA B*44 appears to influence disease course, preserving brain volume and reducing the burden of T2 hyperintense lesions in subjects with MS.


Lower gastrointestinal bleeding and ischemic colitis.
To compare the incidence and clinical characteristics of lower gastrointestinal (LGI) bleeding due to ischemic colitis with those with LGI bleeding of other causes. A chart review was performed of patients admitted with LGI bleeding to Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, between July 1, 1997 and January 31, 2000. Of 124 patients with LGI bleeding, 24 cases were due to ischemic colitis, 62 to diverticulosis, 11 to inflammatory bowel disease (IBD) and 27 to all other causes ('others'). The average ages of patients in each group were 66.5, 76.5, 40.5 and 77.5 years, respectively. Patients with ischemic colitis were statistically younger than those with diverticular bleeding and 'others'. Patients with IBD were younger than those in the other three groups. The only statistical difference for vascular disease risks was hypertension, because of its absence from the IBD group. Three patients with ischemic colitis underwent blood transfusions, while 23 with diverticulosis, 15 'others' and none with IBD received blood. Three patients with ischemic colitis and one patient from the 'others' group died. More women (75) than men (49) had LGI bleeding - in total and within each subgroup. Of women with LGI bleeding, many more with ischemic colitis (44.4%) than with diverticulosis (3.0%), IBD (0%) or 'others' (5.6%) were taking estrogen. Ischemic colitis was the second most common cause of LGI bleeding. LGI bleeding from all causes was more common in women than in men. Many more women in the ischemic colitis group than in the other groups were using estrogen therapy.


STIM and Orai proteins and the non-capacitative ARC channels.
The ARC channel is a small conductance, highly Ca²⁺-selective ion channel whose activation is specifically dependent on low concentrations of arachidonic acid acting at an intracellular site. They are widely distributed in diverse cell types where they provide an alternative, store-independent pathway for agonist-activated Ca²⁺ entry. Although biophysically similar to the store-operated CRAC channels, these two conductances function under distinct conditions of agonist stimulation, with the ARC channels providing the predominant route of Ca²⁺ entry during the oscillatory signals generated at low agonist concentrations. Despite these differences in function, like the CRAC channel, activation of the ARC channels is dependent on STIM1, but it is the pool of STIM1 that constitutively resides in the plasma membrane that is responsible. Similarly, both channels are formed by Orai proteins but, whilst the CRAC channel pore is a tetrameric assembly of Orai1 subunits, the ARC channel pore is formed by a heteropentameric assembly of three Orai1 subunits and two Orai3 subunits. There is increasing evidence that the activity of these channels plays a critical role in a variety of different cellular activities.


The end of the golden age of doctoring.
Eight interrelated reasons for the decline of the golden age of doctoring are discussed in this article. Major extrinsicfactors (generally outside the control of the profession) include (1) the changing nature of the state and loss of its partisan support for doctoring, (2) the bureaucratization (corporatization) of doctoring; (3) the emerging competitive threat from other health care workers; (4) the consequences of globalization and the information revolution; (5) the epidemiologic transition and changes in the public conception of the body; and (6) changes in the doctor-patient relationship and the erosion of patient trust. Major intrinsic factors are (7) the weakening of physicians' labor market position through oversupply; and (8) the fragmentation or weakening of the physicians, union (AMA). Despite the recent sociopolitical transformation of modern U.S. medicine, our thinking remains wedded to a now inadequate theoretical approach. A future sociology of the professions can no longer overlook now pervasive macrostructural influences on provider behavior (corporate dominance). Until these influences are appropriately recognized and incorporated in social analyses, most policies designed to restore the professional ideal have little chance of success.


[The use of selective cytopheresis following cardioplegia during open heart surgery].
The analysis of 20 operations on the open heart performed with selective cytopheresis (apparatus PK-0.5) or without it has demonstrated that in pharmacological and ice-chip cardioplegia the technique to a great extent prevents the loss of the patient's own blood removed with cardioplegic solution and makes it possible to reduce donor blood consumption by 27%. The course of the postoperative period improves considerably: blood loss is reduced, the recovery of blood cellular composition becomes more intensive. Cardioplegia performed in combination with selective cytopheresis does not exclude certain protein loss (up to 15 g/l during one session), which confirms the necessity of adequate homeostasis correction with protein blood preparations.


Determination of the cultivar and aging of Sicilian olive oils using HPLC-MS and linear discriminant analysis.
A large number of certified samples (84) of Sicilian olive oils arising from the eight cultivars most represented in Sicily (Biancolilla, Cerasuola, Moresca, Nocellara del Belice, Nocellara Etnea, Oglialora Messinese, Brandofino and Tonda Iblea) have been collected and analyzed by HPLC/MS using an atmospheric pressure chemical ionization (APCI) source. The sample preparation is very simple; in fact, the oil samples are diluted without any chemical derivatization. A following statistical data treatment by general discriminant analysis (GDA) allows the determination of the olive oil cultivar. Furthermore, changes in the composition of glyceridic components of the olive oils lead to easy discrimination between fresh oils and 1-year-old samples.


Desensitization of mutant acetylcholine receptors in transgenic mice reduces the amplitude of neuromuscular synaptic currents.
While the slow onset of desensitization of nicotinic acetylcholine receptors (AChRs), relative to the rate of acetylcholine removal, excludes this kinetic state from shaping synaptic responses in normal neuromuscular transmission, its role in neuromuscular disorders has not been examined. The slow-channel congenital myasthenic syndrome (SCCMS) is a disorder caused by point mutations in the AChR subunit-encoding genes leading to kinetically abnormal (slow) channels, reduced miniature endplate current amplitudes (MEPCs), and degeneration of the postsynaptic membrane. Because of this complicated picture of kinetic and structural change in the neuromuscular junction, it is difficult to assess the importance of the multiple factors that may be responsible for the reduced endplate current amplitudes, and ultimately the clinical syndrome. In order to address this we have used a transgenic mouse model for the SCCMS that has slow AChR ion channels and reduced endplate responsiveness in the absence of any of the degenerative changes. We found that the reduction in MEPC amplitudes in these mice could not be explained by either reduced AChR number or by reduced AChR channel conductance. Rather, we found that the mutant AChRs in situ manifested an activity-dependent reduction in sensitivity that caused diminished MEPC and endplate current amplitude with nerve stimulation. This observation demonstrates that the basis for the reduction in MEPC amplitudes in the SCCMS may be multifactorial. Moreover, these findings demonstrate that, under conditions that alter their rate of desensitization, the kinetic properties of nicotinic AChRs can control the strength of synaptic responses.


The effect of broad-band noise on the binaural interaction components of human auditory brainstem-evoked potentials.
Three-channel Lissajous trajectories (3-CLTs) of binaural interaction components (BI) of auditory brainstem potentials (ABEPs) were derived from 13 normally hearing adults by subtracting the response to binaural clicks from the algebraic sum of monaurally evoked responses to clicks. ABEPs were recorded in response to 65 dB nHL, alternating-polarity clicks, presented at a rate of 11/s. The procedure was repeated with clicks alone as well as with clicks with broad-band masking noise. Noise was presented at 25 and 45 dB nHL, producing a signal-to-noise ratio of +40 and +20 dB, respectively. All BI 3-CLTs included 6 planar segments (labeled BdI, BdII, BdIII, BeI, BeII and Bf) whose apex latencies, except Bf, increased with increasing noise level above 25 dB nHL, and whose durations, sizes, shapes and orientations did not change across noise levels. There were also significant increases in peak latencies of the BI from single channels vertex-mastoid and vertex-neck with increasing noise level. No significant change was found in the trajectory amplitude of apices, with the exception of apices BdIII and Bf whose amplitudes increased with increasing noise level. We suggest that the paradoxical increase in BI amplitude with masking noise may reflect a binaural enhancement of the effect of noise. The effects observed indicate that, whereas the response to clicks displays occlusion, the response to noise displays spatial facilitation at the brainstem level.


[Effect of nitroprusside on gap junctions of single tracheal smooth muscle cells excised from rats].
To investigate the effect of nitroprusside on gap junctions of tracheal smooth muscle cells, we ionophoretically injected sodium nitroprusside into single tracheal smooth muscle cells excised from rats. The input resistance of the tracheal smooth muscle cells increased after the injection of nitroprusside. This results suggests that nitroprusside blocks gap junctions of tracheal smooth muscle cells.


Automatic quiet sleep detection based on multifractality in preterm neonates: Effects of maturation.
This study investigates the multifractal formalism framework for quiet sleep detection in preterm babies. EEG recordings from 25 healthy preterm infants were used in order to evaluate the performance of multifractal measures for the detection of quiet sleep. Results indicate that multifractal analysis based on wavelet leaders is able to identify quiet sleep epochs, but the classifier performances seem to be highly affected by the infant's age. In particular, from the developed classifiers, the lowest area under the curve (AUC) has been obtained for EEG recordings at very young age (≤ 31 weeks post-menstrual age), and the maximum at full-term age (≥ 37 weeks post-menstrual age). The improvement in classification performances can be due to a change in the multifractality properties of neonatal EEG during the maturation of the infant, which makes the EEG sleep stages more distinguishable.


Serologic demonstration of the albuminoid nature of the B700 murine melanoma antigen.
Limited available evidence indicates that the B700 murine melanoma antigen is related to serum albumin, but potential relationships to other members of the serum albumin protein family have not yet been established. Using specific antibodies raised against each of the members of the albumin family, we have studied cross-reactivity by solid phase enzyme-linked immunosorbent assay and Western immunoblotting. We demonstrate that B700 is serologically cross-reactive to members of the serum albumin family, which includes alpha-fetoprotein and vitamin D binding protein. Therefore, B700 is part of the serum albumin family of proteins, although the mechanism underlying its specific expression by transformed melanocytes remains unknown.


Minimal clinically important difference for change in 6-minute walk test distance of adults with pathology: a systematic review.
The 6-minute walk test (6MWT) is widely used as a test of functional exercise capacity. Several studies have reported the minimal clinically important difference (MCID) for the 6MWT; however, the findings of the studies have not been examined in the context of one another. In this review, we aimed to summarize available information on the MCID for the 6MWT performed by patients with pathology. Relevant literature was identified by searches of 3 electronic databases (PubMed, Scopus, and Cumulative Index of Nursing and Allied Health), examination of article reference lists, and consultation with an expert. Inclusion necessitated that articles (1) be original, full length, and peer reviewed, (2) report an MCID for the 6MWT, and (3) focus on adults with medical issues. Articles were excluded if the MCID was determined by a procedure other than receiver operating characteristic curve analysis. Articles were abstracted for information on participants, interventions, 6MWT distance, and the determination of MCID. Quality was assessed using a hybrid 9-item (0- to 18-point) instrument. Six articles were selected based on the inclusion and exclusion criteria. The populations studied included people with chronic obstructive pulmonary disease, lung cancer, coronary artery disease, diffuse parenchymal lung disease, and non-cystic fibrosis bronchiectasis and adults with fear of falling. Mean baseline 6MWT distances ranged from 295 to 551 m. The MCIDs for which the area under the receiver operating characteristic curve was at least 0.70 ranged from 14.0 to 30.5 m. Based on our findings, a change of 14.0 to 30.5 m may be clinically important across multiple patient groups.


Congruence between mothers' and fathers' differential treatment of siblings: links with family relations and children's well-being.
We studied patterns of mothers' and fathers' differential treatment of firstborn (average age 10.5 years) and secondborn (average age 8 years) school-age siblings, and we examined the links between parents' differential treatment and children's well-being and dyadic family relationships. Mothers, fathers, and both siblings in 110 families were interviewed in their homes. For each dimension of parental behavior that we assessed (i.e., differential affection and discipline) we created groups of families that reflected mothers' and fathers' levels of differential treatment (e.g., discipline the firstborn more, equal treatment, discipline the secondborn more). Although we detected substantial correspondence between the 2 parents' differential treatment, we found a sizable group of families in which parents' reports were incongruent (i.e., 1 parent reported equal and the other differential treatment). Parental patterns were linked to differences between the siblings' well-being and both sibling and parent-child relationships, with younger siblings exhibiting greater vulnerability to differential treatment. Incongruence in differential warmth was associated with marital distress.


Electronic structure of the muonium center as a shallow donor in ZnO.
The electronic structure and the location of muonium centers (Mu) in single-crystalline ZnO were determined for the first time. Two species of Mu centers with extremely small hyperfine parameters have been observed below 40 K. Both Mu centers have an axial-symmetric hyperfine structure along with a <0001> axis, indicating that they are located at the antibonding (AB(O, parallel )) and bond-center (BC( parallel )) sites. It is inferred from their small ionization energy ( approximately 6 and 50 meV) and hyperfine parameters ( approximately 10(-4) times the vacuum value) that these centers behave as shallow donors, strongly suggesting that hydrogen is one of the primary origins of n type conductivity in as-grown ZnO.


Relativistic theory for localized electrostatic excitations in degenerate electron-ion plasmas.
A self-consistent relativistic two-fluid model is proposed for electron-ion plasma dynamics. A one-dimensional geometry is adopted. Electrons are treated as a relativistically degenerate fluid, governed by an appropriate equation of state. The ion fluid is also allowed to be relativistic, but is cold, nondegenerate, and subject only to an electrostatic potential. Exact stationary-profile solutions are sought, at the ionic scale, via the Sagdeev pseudopotential method. The analysis provides the pulse existence region, in terms of characteristic relativistic parameters, associated with the (ultrahigh) particle density.


The effect of plasma exchange on the in vitro monocyte function of patients with immune complex diseases.
In vitro function tests were performed on peripheral blood monocytes isolated from patients with putative immune complex diseases undergoing therapeutic plasma exchange. Bacterial killing by monocytes improved significantly after plasma exchange (pre: 29 +/- 5%; post: 39 +/- 3%). The intracellular content of the acid hydrolase N-acetylglucosaminidase (NAG) after in vitro culture rose significantly following plasma exchange (pre: 48.3 +/- 21 nmol mg protein-1 hr-1; post: 76.6 +/- 30.6), although the amount of NAG released into the supernatant was unchanged. Plasma exchange also resulted in reduced levels of immune complexes (IC) and clinical improvement in most patients. The beneficial effect of plasma exchange in patients with IC diseases may be partly due to removal of IC which are known to influence the functional activity of cells of the mononuclear macrophage series.


Diversity and structure of bacterial chemolithotrophic communities in pine forest and agroecosystem soils.
Obligate lithotrophs (e.g., ammonia oxidizers) and facultative lithotrophs (e.g., CO and hydrogen oxidizers) collectively comprise a phylogenetically diverse functional group that contributes significantly to carbon and nitrogen cycles in soils and plays important roles in trace gas dynamics (e.g., carbon monoxide and nitrous and nitric oxides) that affect tropospheric chemistry and radiative forcing. In spite of their diverse physiologies, facultative and obligate lithotrophs typically possess the Calvin-Benson-Bassham cycle enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisCO). In an effort designed to understand the structure of lithotrophic communities in soil, genomic DNA extracts from surface (0 to 2 cm) and subsurface (5 to 7 cm) soils have been obtained from two sites in a Georgia agroecosystem (peanut and cotton plots) and an unmanaged pine stand (>50 years old). The extracts have been used in PCR amplifications of the cbbL gene for the rubisCO large subunit protein. cbbL PCR products were cloned, sequenced, and subjected to phylogenetic and statistical analyses. Numerous novel lineages affiliated with the form IC clade (one of four form I rubisCO clades), which is typified by facultative lithotrophs, comprised lithotrophic communities from all soils. One of the form IC clone sequences clustered with a form IC clade of ammonia-oxidizing Nitrosospira. Distinct assemblages were obtained from each of the sites and from surface and subsurface soils. The results suggest that lithotrophic populations respond differentially to plant type and land use, perhaps forming characteristic associations. The paucity of clone sequences attributed to ammonia-oxidizing bacteria indicates that even though ammonia oxidation occurs in the various soils, the relevant populations are small compared to those of facultative lithotrophs.


[Proteomics and its application in the research of prostatic carcinoma].
With the development of the proteomics technology, more and more tumorous labeled substrates have been discovered and applied to clinical practice. This can provide the forepart diagnosis of tumor and prognosis monitoring with the reliable evidence. A summary is given of the study strategy of proteomics and its application in the prostatic carcinoma research.


Jacobian-Based Iterative Method for Magnetic Localization in Robotic Capsule Endoscopy.
The purpose of this study is to validate a Jacobian-based iterative method for real-time localization of magnetically controlled endoscopic capsules. The proposed approach applies finite-element solutions to the magnetic field problem and least-squares interpolations to obtain closed-form and fast estimates of the magnetic field. By defining a closed-form expression for the Jacobian of the magnetic field relative to changes in the capsule pose, we are able to obtain an iterative localization at a faster computational time when compared with prior works, without suffering from the inaccuracies stemming from dipole assumptions. This new algorithm can be used in conjunction with an absolute localization technique that provides initialization values at a slower refresh rate. The proposed approach was assessed via simulation and experimental trials, adopting a wireless capsule equipped with a permanent magnet, six magnetic field sensors, and an inertial measurement unit. The overall refresh rate, including sensor data acquisition and wireless communication was 7 ms, thus enabling closed-loop control strategies for magnetic manipulation running faster than 100 Hz. The average localization error, expressed in cylindrical coordinates was below 7 mm in both the radial and axial components and 5° in the azimuthal component. The average error for the capsule orientation angles, obtained by fusing gyroscope and inclinometer measurements, was below 5°.


Association between the polymorphisms in intercellular adhesion molecule-1 and the risk of coronary atherosclerosis: a case-controlled study.
Intercellular adhesion molecule-1 (ICAM-1), an important immune adhesion molecule, is related to the atherosclerosis. We explored the association between the polymorphisms of the ICAM-1 gene and coronary atherosclerotic stenosis to determine whether any risk factors correlate with genetic polymorphisms in Chinese patients with coronary atherosclerosis. Using the SNaPshot assay, we examined six SNPs of rs5491, rs281428, rs281432, rs5496, rs5498 and rs281437 in 604 patients diagnosed with coronary atherosclerotic stenosis by angiography and in 468 controls. We found that AG genotype of rs5498 had higher frequency in the coronary atherosclerotic stenosis patients (41.56% to 34.19%, P = 0.017, OR = 1.368,95%CI 1.057-1.770) and that the haplotype Ars5491Crs281428Grs281432 had higher frequency in patients (13.8% to 12.1%, P = 0.048). When analyzing the clinical risk factors for coronary atherosclerosis, we found that the rs5498 locus was associated with the levels of apolipoprotein A (APOA) (P = 0.0002) and triglycerides (TG) (P = 0.002). Furthermore, the levels of triglycerides (TG) were also associated with rs281432 (P = 0.040). Additionally, the TT genotype of rs281437 was associated with a higher level of apolipoprotein A (APOA) (P = 0.039) and apolipoprotein B (APOB) (P = 0.003). Finally, among those with coronary atherosclerosis, we found no differences in the haplotype analysis of polymorphisms of the ICAM-1 gene from individuals with hypertension or those who smoked. According to our results, the ICAM-1 polymorphisms were associated with risk of coronary atherosclerotic stenosis in Chinese individuals.


Site- and enantioselective formation of allene-bearing tertiary or quaternary carbon stereogenic centers through NHC-Cu-catalyzed allylic substitution.
Catalytic enantioselective allylic substitutions that result in addition of an allenyl group (<2% propargyl addition) and formation of tertiary or quaternary C-C bonds are described. Commercially available allenylboronic acid pinacol ester is used. Reactions are promoted by a 5.0-10 mol % loading of sulfonate-bearing chiral bidentate N-heterocyclic carbene (NHC) complexes of copper, which exhibit the unique ability to furnish chiral products arising from the S(N)2' mode of addition. Allenyl-containing products are generated in up to 95% yield, >98% S(N)2' selectivity, and 99:1 enantiomeric ratio (er). Site-selective NHC-Cu-catalyzed hydroboration of enantiomerically enriched allenes and conversion to the corresponding β-vinyl ketones demonstrates the method's utility.


Methylation and acetylation of 15-hydroxyanandamide modulate its interaction with the endocannabinoid system.
The biological activity of endocannabinoids like anandamide (AEA) and 2-arachidonoylglycerol (2-AG) is subjected in vivo to a "metabolic control", exerted mainly by catabolic enzymes. AEA is inactivated by fatty acid amide hydrolase (FAAH), that is inhibited competitively by hydroxyanandamides (HAEAs) generated from AEA by lipoxygenase activity. Among these derivatives, 15-HAEA has been shown to be an effective (K(i) approximately 0.6 muM) FAAH inhibitor, that blocks also type-1 cannabinoid receptor (CB1R) but not other components of the "endocannabinoid system (ECS)", like the AEA transporter (AMT) or CB2R. Here, we extended the study of the effect of 15-HAEA on the AEA synthetase (NAPE-PLD) and the AEA-binding vanilloid receptor (TRPV1), showing that 15-HAEA activates the former (up to approximately 140% of controls) and inhibits the latter protein (down to approximately 70%). We also show that 15-HAEA halves the synthesis of 2-AG and almost doubles the transport of this compound across the membrane. In addition, we synthesized methyl and acetyl derivatives of 15-HAEA (15-MeOAEA and 15-AcOAEA, respectively), in order to check their ability to modulate FAAH and the other ECS elements. In fact, methylation and acetylation are common biochemical reactions in the cellular environment. We show that 15-MeOAEA, unlike 15-AcOAEA, is still a powerful competitive inhibitor of FAAH (K(i) approximately 0.7 muM), and that both derivatives have negligible interactions with the other proteins of ECS. Therefore, 15-MeOAEA is a FAAH inhibitor more selective than 15-HAEA. Further molecular dynamics analysis gave clues to the molecular requirements for the interaction of 15-HAEA and 15-MeOAEA with FAAH.


Transverse carpal ligament disruption associated with simultaneous fractures of the trapezium, trapezial ridge, and hook of hamate: a case report.
Traumatic disruption of the transverse carpal ligament associated with fractures of the trapezial ridge and hook of hamate is a known entity. Only one report of a coronal fracture of the trapezium has been mentioned in the literature. We report a combination of these two injury patterns. Diagnosis was aided by computed tomography. Treatment involved excision of the trapezial ridge and hook of hamate fragments with lag screw fixation of the trapezial body fracture.


Comparison of peri-implant clinical outcomes of digitally customized and prefabricated abutments: A systematic review and meta-analysis.
Digitally customized abutments are increasingly used in contemporary implant prosthodontics. This systematic review and meta-analysis aimed at comparing the peri-implant clinical outcomes of digitally customized and prefabricated abutments. The search strategies included electronic databases (PubMed, Embase, Scopus, and Cochrane clinical trials database) and related journals up to September, 2020. A qualitative and quantitative synthesis was performed on data extracted from the included studies. Three RCTs (number of patients = 120; number of dental implants = 120) and two prospective cohort studies (number of patients = 144; number of dental implants = 144) with one to three-year follow-up periods were included. The quantitative analyses did not demonstrate a significant difference between digitally customized and prefabricated abutments for peri-implant pocket depth (P = 0.62), plaque index (P = 0.67), bleeding on probing (P = 0.43), keratinized mucosa width (P = 0.75), and pink aesthetic score (P = 0.30) at one-year follow-up visit. The qualitative analyses for marginal bone level change, calculus accumulation, implant survival rate, implant success rate, white aesthetic score, and patient-reported outcomes did not demonstrate a significant difference between two groups during 1 to 3-year follow-up visits. The current data do not provide evidence of significant differences between two abutment fabrication methods in terms of peri-implant clinical outcomes within short-term period (CRD42020170807).


Oncogene or tumor suppressor gene: An integrated pan-cancer analysis of NBPF1.
Neuroblastoma breakpoint family, member 1 (NBPF1), appears to be a double-edged sword with regard to its role in carcinogenesis. On the one hand, the tumor-suppressing functions of NBPF1 have been definitively observed in neuroblastoma, prostate cancer, cutaneous squamous cell carcinoma, and cervical cancer. On the other hand, there is evidence that NBPF1 regulates the colony formation, invasion, and maintenance of liver cancer cells and hence functions as an oncogene. The roles of NBPF1 are strictly dependent on the biological context and type of organization. However, a systematic pan-cancer analysis has thus far not been undertaken, and the significance of NBPF1 in the occurrence and progression of many malignancies is uncertain. In this paper, bioinformatics techniques were employed to analyze NBPF1 expression across different cancers and investigate the relationship between NBPF1 and clinical features, prognosis, genetic alteration, and tumor immune microenvironment, respectively. Our results show that NBPF1 is variably expressed in distinct tumor tissues and is also closely linked to clinical outcomes. In particular, compared to other tumor types, there was a strong negative correlation between NBPF1 expression and various components of the tumor microenvironment in adrenocortical carcinoma (ACC). We thus developed an NBPF1-derived immune risk model based on NBPF1-related immune genes; ACC patients with a high-risk score tended to have a poorer prognosis, accompanied by immune hyporesponsiveness. NBPF1 can be used as a prognostic biomarker for multiple cancers. Moreover, anti-NBPF1 immunotherapy may be suitable for treating ACC patients.


[Localization of alpha 1-adrenoceptors in hypertrophic prostate].
In order to determine the localization of alpha 1-adrenoceptors in human hypertrophied prostates, in vitro autoradiography was performed on the frozen specimens from 13 enucleated hypertrophied prostates with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl] tetralone) and [3H]-prazosin. In vitro autoradiograms showed macroscopically the specific binding site on the areas seemed to the nodular area for [125I]-HEAT, but not so clear specific binding sites for [3H]-prazosin. Microscopic autoradiograms seemed to show binding sites located mainly on the interstitial beneath the gland, and partly on the basement membrane and epithelium of the prostatic gland. Further studies are needed to show clearer specific binding sites of alpha 1-adrenoceptors.


Bayesian Inference on Malignant Breast Cancer in Nigeria: A Diagnosis of MCMC Convergence
Background: There has been no previous study to classify malignant breast tumor in details based on Markov Chain Monte Carlo (MCMC) convergence in Western, Nigeria. This study therefore aims to profile patients living with benign and malignant breast tumor in two different hospitals among women of Western Nigeria, with a focus on prognostic factors and MCMC convergence. Materials and Methods: A hospital-based record was used to identify prognostic factors for malignant breast cancer among women of Western Nigeria. This paper describes Bayesian inference and demonstrates its usage to estimation of parameters of the logistic regression via Markov Chain Monte Carlo (MCMC) algorithm. The result of the Bayesian approach is compared with the classical statistics. Results: The mean age of the respondents was 42.2 ±16.6 years with 52% of the women aged between 35-49 years. The results of both techniques suggest that age and women with at least high school education have a significantly higher risk of being diagnosed with malignant breast tumors than benign breast tumors. The results also indicate a reduction of standard errors is associated with the coefficients obtained from the Bayesian approach. In addition, simulation result reveal that women with at least high school are 1.3 times more at risk of having malignant breast lesion in western Nigeria compared to benign breast lesion. Conclusion: We concluded that more efforts are required towards creating awareness and advocacy campaigns on how the prevalence of malignant breast lesions can be reduced, especially among women. The application of Bayesian produces precise estimates for modeling malignant breast cancer.


Chernobyl experience: biological indicators of exposure to ionizing radiation.
Using the Chernobyl accident as an example, an attempt is made to consider the possibility of using the biological markers of exposure and effects of exposure to ionizing radiation in relation to biology dosimetry, and to predict early and late nonstochastic and stochastic radiation consequences. The biological dosimetry was based on the three markers: chromosome aberrations of peripheral blood lymphocytes, dynamics of blood cell (lymphocytes, neutrophils) counts and electron spin resonance (ESR) of tooth enamel. The first two methods can be applied in a short period of time (days or weeks) after exposure and only after high doses (> 0.5-1 Gy) of acute total body irradiation (TBI). The ESR tooth enamel method possesses dosimetric value at all conditions of uniform gamma TBI (acute, prolonged, chronic and high as well as low level of doses) and at any time after exposure. The low limit of sensitivity of the ESR test is about 0.1 Gy. The use of biological markers of effects of radiation exposure as early diagnostic signs was limited to clinical significant disorders of hemopoietic, immune systems and skin in conditions of acute high-dose irradiation. In cases of acute or prolonged irradiation in low doses, many changes on the cellular as well as organism level were discovered. However, there were not enough data on radiation specificity or dose dependence of these changes. Hence they cannot be considered as the indicators of clinically significant early and late nonstochastic effects. The role of biological markers of stochastic effects in clinical practice is discussed herein.


Endovascular revascularization for aortoiliac atherosclerotic disease.
Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis.


A welfare trap? The duration and dynamics of social assistance use among lone mothers in Canada.
In the late 1990s, the Canadian social assistance policy changed to focus on reducing "dependency" or long-term receipt. Using data from the Survey of Labour and Income Dynamics (1996-2001) and event history models, we investigate the duration of social assistance receipt for lone mothers and other household heads. We find that lone mothers' education and labor force experience were less important predictors for their duration on social assistance than their previous marital history. Although receipt was generally short term, we find evidence of negative duration dependence, or a "welfare trap," after controlling for unobserved heterogeneity. This indicates one way in which a welfare receipt is not only the result of particular life course trajectories but also shapes lives.


Pharmacological management of pain and anxiety during emergency procedures in children.
Painful procedures are frequently required during treatment of children in the emergency department and are very stressful for the children, their parents and healthcare providers. Pharmacological methods to safely provide almost painless local anaesthesia, analgesia and anxiolysis have been increasingly studied in children. With knowledge of these methods, and patience, the emergency care provider can greatly reduce the distress often associated with emergency care of children. Topical local anaesthetics such as LET [lidocaine (lignocaine), epinephrine (adrenaline), tetracaine] or buffered lidocaine injected through the wound with fine needles can almost painlessly anaesthetise lacerations for suturing. Topical creams such as lidocaine/ prilocaine (EMLA) or tetracaine, iontophoresed lidocaine, or buffered lidocaine subcutaneously injected with fine needles can make intravenous catheter placement virtually 'painless'. When anxiety is significant, and mild to moderate analgesia/ anxiolysis/amnesia is needed, nitrous oxide can be administered if the proper delivery devices are available. Alternatively, when intensely painful fracture reduction, burn debridement, or abscess drainage is necessary, well tolerated and effective deep sedation can be achieved with careful use of midazolam and either ketamine or fentanyl.


Expression and purification of recombinant human coagulation factor VII fused to a histidine tag using Gateway technology.
Factor VII (FVII) is a plasma glycoprotein that participates in the coagulation process leading to the generation of fibrin. The aim of this study was to construct, express and purify recombinant FVII fused to a polyhistidine (his) tag using Gateway technology. To construct the entry clone, blunt-end FVII cDNA and subsequent polymerase chain reaction (PCR) product isolated from a HepG2 cell line was TOPO-cloned into a pENTR TOPO vector. To construct the expression clone, a LR recombination reaction was carried out between the entry clone and destination vector, pDEST26. Chinese hamster ovary (CHO) cells were transfected with 1 microg of DNA of PDEST26-FVII using the FuGENE HD transfection reagent. Two cell lines that permanently expressed recombinant FVII were established. The expression of recombinant FVII was confirmed by reverse transcriptase PCR and enzyme-linked immunosorbent assay. Culture medium containing his-tagged FVII was added to the nickel-nitrilotriacetic acid resin column and bound protein was eluted. The purified protein was detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analysis. The biological activity of the recombinant FVII was determined by a prothrombin time assay using FVII-depleted plasma. The results showed that human recombinant FVII was successfully cloned and the accuracy of the nucleotide sequence of the gene and its frame in the vector were confirmed by DNA sequencing. Stable clones transfected with the construct expressed FVII mRNA and related protein but no expression was detected in the CHO cells containing an empty vector. A protein of about 52 KDa was detected in SDS-PAGE and was further confirmed by western blot analysis. A three-fold decrease in clotting time was observed using this recombinant FVII. As far as we are aware, this is the first report of expression of recombinant FVII fused with a his-tag through Gateway technology. The next steps, including large scale expression, purification, activation and stabilisation, are underway.


Citrate and succinate uptake by potato mitochondria.
The uptake of [(14)C]citrate and [(14)C]succinate was studied in potato mitochondria (Solanum tuberosum var. Russet Burbank) using cellulose pore filtration and was found to occur by the same mechanisms as described for mammalian mitochondria. Potato mitochondria, in the absence of respiration, have a very low capacity for uptake by exchange with endogenous anions, taking up only 2.4 nanomoles citrate and 2.0 nanomoles succinate per milligram protein. Maximum citrate uptake of over 17 nanomoles per milligram protein occurs in the presence of inorganic phosphate, a dicarboxylic acid, and an external energy source (NADH), conditions where net anion accumulation proceeds, mediated by the interlinking of the inorganic phosphate, dicarboxylate, and tricarboxylate carriers. Maximum succinate uptake in the absence of respiratory inhibitors requires only added inorganic phosphate.Compounds which inhibit respiration (antimycin), the exchange carriers (mersalyl and benzylmalonate), or the establishment of the membrane proton motive force (uncouplers) reduce substrate accumulation. A potent inhibitor of the citrate carrier in animal mitochondria, 1,2,3-benzenetricarboxylic acid, does not inhibit citrate uptake in potato mitochondria. Citrate uptake is reduced by concurrent ADP phosphorylation and this reduction is sensitive to oligomycin. The initiation of state 3 after a 3-minute substrate state results in a reduction of the steady-state of citrate uptake by approximately 50%. Accumulation of succinate initially is inhibited by increasing sucrose concentration in the reaction medium from 50 to 400 millimolar.Limited substrate uptake is one of the factors responsible for the often observed depressed initial state 3 respiration rates in many mitochondrial preparations. Since nonlimiting levels of substrate in the matrix cannot be attained by energy-independent exchange, a dependence on respiration for adequate uptake results. Substrate limitation therefore occurs in the matrix for the period of time needed for energy-dependent accumulation of nonlimiting levels.


Results of prifinium bromide therapy in irritable bowel syndrome.
An open clinical trial with prifinium bromide, an anticholinergic agent, was carried out in 21 patients with irritable bowel syndrome showing clear psychosomatic characteristics. The clinical efficacy was evaluated by comparing the symptomatic severity before, during, and after treatment with prifinium bromide, 90 mg/day for four weeks. Of these 21 patients, 18 patients were allowed to take antacids or lactobacillus preparations concomitantly only when necessary. As a result, marked or moderate improvement in symptoms such as diarrhea and constipation was seen in 43% after two weeks and 86% after four weeks. Prifinium bromide's efficacy in the treatment of abnormal bowel movements was most evident in patients with diarrhea and slightly less evident in patients with alternation of diarrhea and constipation, and in constipated patients. Side effects attributable to the drug were encountered in four (19%) of the patients. None were serious enough to require that use of the drug be discontinued. All laboratory test values were within normal ranges before and after therapy. Overall, prifinium bromide was judged to be useful in 14 (67%) of the 21 patients studied.


Hepatoprotective activity of hydroalcoholic extract of leaves of Alocasia indica (Linn.).
Oral administration of hydroalcoholic extract of A. indica (250 and 500 mg/kg) effectively inhibited CCl4 and paracetamol induced changes in the serum marker enzymes, cholesterol, serum protein and albumin in a dose-dependent manner as compared to the normal and the standard drug silymarin-treated groups. Hepatic steatosis, fatty infiltration, hydropic degeneration and necrosis observed in CCl4 and paracetamol-treated groups were completely absent in histology of the liver sections of the animals treated with the extracts. The results suggests that the hydroalcoholic extract of leaves of A. indica possess significant potential as hepatoprotective agent.


Acute Limb Ischemia in the Young: A Rare Case of Essential Thrombocytosis.
Acute limb ischemia (ALI) is rarely observed in young populations. The hypercoagulable state is a notable cause of ALI other than artery disease progression and cardiac embolization. A hypercoagulable state occurs in essential thrombocytosis because of the overproduction of hematopoietic cells secondary to the mutation of the JAK2, CALR, or MPL genes. We report a rare case of a 37-year-old woman presenting with Rutherford IIA ALI in the left lower extremity. Laboratory data revealed she had a platelet count reaching up to 1.38 mil/μL, with other blood profiles being normal. A JAK2 mutation examination was later performed and proved positive. After careful management with catheter-directed thrombolysis, surgical thrombectomy, and cytoreductive therapy using hydroxyurea, the symptoms subsided and eventually restored the patient to physical activity in less than one month.


Mechanisms for the generation of gas-exchange surface area in rat lung.
During development, rat lung seems to make use of the mechanisms of 1) expansion, 2) replication, and 3) subdivision to increase its gas-exchange surface area. To quantitate the contribution of each one of these mechanisms from birth to adulthood, four models of lung development have been mathematically evaluated: 1) existing saccules at birth septate (subdivide) during the first 2 postnatal weeks, creating smaller alveoli that undergo a continuous expansion up to adulthood; 2) same as the previous model except that new alveoli are also formed by means other than septation after the second postnatal week; 3) same as the previous model except that the alveoli formed by means other than septation start forming immediately after birth; and 4) saccules continue to be formed up to adulthood and subsequently septate, forming alveoli. In an evaluation of these models mathematically, it was found that expansion followed by replication is the most important mechanism for the generation of gas-exchange surface area in all four models in the maturing lung. Although the contribution of septation is important during early postnatal life, its importance decreases with age.


The effects of heparin and dietary fish oil on embolic events and the microcirculation downstream from a small-artery repair.
In recent studies we demonstrated that platelet emboli induced by arterial injury impair the microcirculation. The present study was performed to determine if heparin or dietary cod liver oil reduces the incidence of emboli following the same arterial injury and, in turn, whether these agents prevent the associated decrease in microcirculatory blood flow. The cremaster muscle of 29 male Sprague-Dawley rats was isolated on a single neurovascular bundle consisting of the iliac artery and vein and the genitofemoral nerve. Emboli were generated by a thrombogenic injury of the iliac artery, and their number and their subsequent effect on capillary perfusion in the downstream microcirculation were measured. Nine animals received heparin (10-unit IV bolus plus 10 units/hour IV infusion), 10 were fed cod liver oil (10 percent by weight of food) for 3 weeks prior to the experiment, and 9 animals receiving no treatment served as controls. The number of emboli was significantly reduced in the heparin group, but there was no accompanying improvement in capillary perfusion. In contrast, in the cod liver oil group, the number of emboli was not reduced, but there was significant improvement in capillary perfusion. These findings suggest that the harmful effect that platelet emboli have on the microcirculation is probably biochemical in nature (vasoconstriction) rather than related to simple mechanical obstruction to flow.


User Experience in Remote Surgical Consultation: Survey Study of User Acceptance and Satisfaction in Real-Time Use of a Telemedicine Service.
Teleguidance, a promising telemedicine service for intraoperative surgical consultation, was planned to scale up at a major academic hospital in partnership with 5 other hospitals. If the service was adopted and used over time, it was expected to provide educational benefits and improve clinical outcomes during endoscopic retrograde cholangiopancreatography (ERCP), which is a technically advanced procedure for biliary and pancreatic disease. However, it is known that seemingly successful innovations can play out differently in new settings, which might cause variability in clinical outcomes. In addition, few telemedicine services survive long enough to deliver system-level outcomes, the causes of which are not well understood. We were interested in factors related to usability and user experience of the telemedicine service, which might affect adoption. Therefore, we investigated perceptions and responses to the use and anticipated use of a system. Technology acceptance, a construct referring to how users perceive a technology's usefulness, is commonly considered to indicate whether a new technology will actually be used in a real-life setting. Satisfaction measures were used to investigate whether user expectations and needs have been met through the use of technology. In this study, we asked surgeons to rate the perceived usefulness of teleguidance, and their satisfaction with the telemedicine service in direct conjunction with real-time use during clinical procedures. We designed domain-specific measures for perceived usefulness and satisfaction, based on performance and outcome measures for the clinical procedure. Surgeons were asked to rate their user experience with the telemedicine service in direct conjunction with real-time use during clinical procedures. In total, 142 remote intraoperative consultations were conducted during ERCP procedures at 5 hospitals. The demand for teleguidance was more pronounced in cases with higher complexity. Operating surgeons rated teleguidance to have contributed to performance and outcomes to a moderate or large extent in 111 of 140 (79.3%) cases. Specific examples were that teleguidance was rated as having contributed to intervention success and avoiding a repeated ERCP in 23 cases, avoiding 3 PTC, and 11 referrals, and in 11 cases, combinations of these outcomes. Preprocedure beliefs about the usefulness of teleguidance were generally lower than postprocedure satisfaction ratings. The usefulness of teleguidance was mainly experienced through practical advice from the consulting specialist (119/140, 85%) and support with assessment and decision-making (122/140, 87%). Users' satisfaction with teleguidance surpassed their initial expectations, mainly through contribution to nontechnical aspects of performance, and through help with general assessment. Teleguidance shows the potential to improve performance and outcomes during ERCP. However, it takes hands-on experience for practitioners to understand how the new telemedicine service contributes to performance and outcomes.


Assessing competence in cognitive-behavioural therapy.
Postgraduate courses on cognitive-behavioural therapy (CBT) assess various competencies using essays, case studies and audiotapes or videotapes of clinical work. To evaluate how reliably a well-established postgraduate course assesses CBT competencies. Data were collected on two cohorts of trainees (n=52). Two examiners marked trainees on: (a) two videotapes of clinical practice; (b) two case studies; and (c) three essays. Essay examinations were more reliable than case studies, which in turn were more reliable than videotaped assessments. The reliability of the latter two assessments was considerably lower than that commonly expected of high-stakes examinations. To assess reliably standard CBT competencies, postgraduate courses would need to examine about 5 essays, 12 case studies and 19 videotapes. Reliable assessment of standard competencies is complex and resource intensive. There would need to be a marked increase in the number of samples of clinical work assessed to be able to make reliable judgements about proficiency.


Sub-Regional Differences of the Human Amniotic Membrane and Their Potential Impact on Tissue Regeneration Application.
For more than 100 years, the human amniotic membrane (hAM) has been used in multiple tissue regeneration applications. The hAM consists of cells with stem cell characteristics and a rich layer of extracellular matrix. Undoubtedly, the hAM with viable cells has remarkable properties such as the differentiation potential into all three germ layers, immuno-modulatory, and anti-fibrotic properties. At first sight, the hAM seems to be one structural entity. However, by integrating its anatomical location, the hAM can be divided into placental, reflected, and umbilical amniotic membrane. Recent studies show that cells of these amniotic sub-regions differ considerably in their properties such as morphology, structure, and content/release of certain bioactive factors. The aim of this review is to summarize these findings and discuss the relevance of these different properties for tissue regeneration. In summary, reflected amnion seems to be more immuno-modulatory and could have a higher reprogramming efficiency, whereas placental amnion seems to be pro-inflammatory, pro-angiogenic, with higher proliferation and differentiation capacity (e.g., chondrogenic and osteogenic), and could be more suitable for certain graft constructions. Therefore, we suggest that the respective hAM sub-region should be selected in consideration of its desired outcome. This will help to optimize and fine-tune the clinical application of the hAM.


CT findings in hepatic involvement by Echinococcus granulosus.
The CT findings in hepatic involvement by Echinococcus granulosus are described. Pathognomonic signs of the hydatid nature of a cystic lesion are visualization of the cystic wall on plain CT, calcification of the cyst wall, daughter cysts, and membrane detachment.


[Identification of Legionella spp. by means of cultural and molecular methods in a public hospital].
An epidemiologic study on the isolation of Legionella spp from the sanitary water of a public Hospital in Cagliari (Italy) has been performed. The aim of the study was the comparison between the isolation of various Legionella spp from different hospital sources and the real hazard of Legionella infection of the inpatients. Two test methods were used for Legionella detection: a) the culture on selective media, that has the disadvantage of being quite time-consuming and of isolating also other bacterial species. Furthermore, the culture method often fails the isolation of vital but not culturable bacteria (VBNC); b) the PCR molecular method, which is rapid and precise and recognizes also VBNC cells. The most relevant result of this work was that, in spite of the isolation of a considerable number of Legionella spp (even Legionella pneumophila), no case of infection was detected in the Hospital during the period of the study.


High Uric Acid-Induced Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via the TLR4/NF-kB Signaling Pathway.
Hyperuricemia is an independent risk factor for causing chronic kidney disease and contributes to kidney fibrosis. After urate crystals get deposited in the kidney, they can cause hyperuricemia nephropathy, leading to glomerular hypertrophy and renal tubular interstitial fibrosis. Recent data showed that uric acid (UA) could induce epithelial mesenchymal transition (EMT) of renal tubular cells, in which NRLP3 inflammatory pathway was involved. However, whether TLR4/NF-κB signaling pathway is also involved in EMT of renal tubular cells induced by UA is not clear. Human renal tubular epithelial cells (HK-2) were directly treated with UA and the phenotypic transition was detected by morphological changes and the molecular markers of EMT. The activation of the TLR4/NF-κB signaling pathway induced by UA was measured by Western blot and its involvement was further confirmed by the inhibition of NF-κB activation or knockdown of toll like receptor 4 (TLR4) expression. UA induced obvious morphological changes of HK-2 cell, accompanied with altered molecular markers of EMT including fibronectin, α-SMA and E-cadherin. In addition, UA significantly upregulated the gene expression of interleukin-1β and tumor necrosis factor-α in a time- and dose-dependent manner. Furthermore, UA significantly activated the TLR4/NF-κB signaling pathway in HK-2 cells, while the inhibition of the TLR4 expression by siRNA and NF-κB activation by PDTC significantly attenuated EMT induced by UA in HK-2 cells. UA can induce EMT in renal tubular epithelial cells by the activation of the TLR4/NF-κB signaling pathway, and the targeted intervention of the TLR4/NF-κB signaling pathway might effectively inhibit UA-induced renal interstitial fibrosis mediated by EMT.


Developmental Roles of the Hog1 Protein Phosphatases of the Maize Pathogen Cochliobolus heterostrophus.
Protein phosphorylation cascades are universal in cell signaling. While kinome diversity allows specific phosphorylation events, relatively few phosphatases dephosphorylate key signaling proteins. Fungal mitogen activated protein kinases (MAPK), in contrast to their mammalian counterparts, often show detectable basal phosphorylation levels. Dephosphorylation, therefore, could act as a signal. In Cochliobolus heterostrophus, the Dothideomycete causing Southern corn leaf blight, ferulic acid (FA)-an abundant phenolic found in plant host cell walls-acts as a signal to rapidly dephosphorylate the stress-activated MAP kinase Hog1 (High Osmolarity Glycerol 1). In order to identify the protein phosphatases responsible, we constructed mutants in Hog1 phosphatases predicted from the genome by homology to yeast and other species. We found that Cochliobolus heterostrophus mutants lacking PtcB, a member of the PP2C family, exhibited altered growth, sporulation, and attenuated dephosphorylation in response to FA. The loss of the dual-specificity phosphatase CDC14 led to slow growth, decreased virulence, and attenuated dephosphorylation. Mutants in two predicted tyrosine phosphatase genes PTP1 and PTP2 showed normal development and virulence. Our results suggest that a network of phosphatases modulate Hog1's dual phosphorylation levels. The mutants we constructed in this work provide a starting point to further unravel the signaling hierarchy by which exposure to FA leads to stress responses in the pathogen.


Acute management of thermal and electrical burns of the upper extremity.
Acute management of upper extremity thermal and electrical injuries requires an aggressive treatment protocol which combines meticulous wound care, intensive hand therapy, and early stable wound coverage to salvage upper extremity function. Electrical injuries inflict severe deep-tissue destruction that frequently results in major limb amputation.


Commentary: evidence-based practice and forensic psychiatry.
A diverse sampling of articles was considered as a landscape against which evidence-based practice has been and should be a part of forensic psychiatry. Caveats were identified, limitations suggested, and recommendations made as to how such a marriage might work.


"Nobody came to help": interviews with women convicted of filicide in Malaysia.
Although filicide is of serious concern, it is poorly understood in Malaysia. Our interviews with health and policy professionals revealed that they attribute responsibility for filicide to women's failure to comply with social norms and religious teachings. This research sought to understand the meaning of and background to filicide from the perspectives of women who have been convicted of filicide in Malaysia. In-depth interviews were conducted in person with all eligible and consenting women convicted of filicide and incarcerated in prisons or forensic psychiatric institutions. Women's accounts were translated into English and analysed using interpretative phenomenological analysis and interpreted using narrative theory. Interviews with nine women convicted of filicide yielded evidence that others were implicated in the crime but punished less severely, if at all, and that the women had experienced lifelong gender-based violence and marginalisation with minimal access to health and social care. These findings illuminate an inadequately understood phenomenon in Malaysia and reveal why existing strategies to reduce filicide, which reflect key stakeholders' views, have had little impact. They reveal the pervasive harm of violence against women and children and its link to filicide.