"Object vision" and "spatial vision": the neuropsychological evidence for the distinction.
The distinction between "object vision" and "spatial vision" was made by Ungerleider and Mishkin (1982) on the evidence of behavioural and neuroanatomical studies, largely with monkeys. It holds that separate cortical systems are involved, the occipito-temporal in object vision, the occipito-parietal in spatial vision. This distinction has been unquestioned; it appears as though fact in influential textbooks; but has never been subjected to critical scrutiny. Theoretically, there are substantial difficulties, for instance because during perception objects do not form a special category, apart from their features; and because shape, pattern and size are spatial features of objects. Empirically, for the monkey the behavioural distinction does not hold (because parietal cortex is not the sole cortical area involved in "spatial vision"); and in man because parietal lesions have long been known to lead to impaired perception of incomplete pictures. Moreover, although Ungerleider and Mishkin do not generalise their distinction to touch, this sense deserves consideration, given that Mishkin had earlier argued that vision and touch have a similar organisation. In touch there are direct anatomical connections between the areas serving "object touch" and "spatial touch", and both in man and in the monkey it seems established that the same region processes spatial performance in vision and in touch. Further work is needed particularly on the spatial disorder after parietal lesions: in the monkey, research has frequently been confined to one non-specific test; in man, important differences related to the laterality of the lesion, have only recently emerged. Then "spatial performance" may be found to be more closely linked to motor output than to sensory input.


"Political blue sky" in fog and haze governance: evidence from the local major international events in China.
The trade-off between economic development and environmental protection has always been a significant and tough issue for local governments. Studies found that some local governments took temporary measures to control air pollution and created "political blue sky" in certain periods. We collected daily air quality index (AQI) data and individual pollutant concentration data of four cities in China which have hosted major international events in 2019. The air quality of the cities taken temporary measures to control air pollution had an obvious improvement during the events. Furthermore, the improvement mainly occurred in pollution indicators, such as PM2.5 and PM10, which are more valued and sensitive to the public. The sustainability analysis demonstrates that the air quality deteriorated again after the event, indicating that "political blue sky" comes at the cost of retaliatory pollution.


Recruiting, Supporting and Retaining Diversity in Hand Surgery.
All surgical fields that lead to a career in Hand Surgery have a stark lack of diversity of sex/gender and race, at every level of the workforce, from trainees to practicing physicians. Despite consistent statistics in publications on lack of diversity in surgical fields, a guide to effective recruitment and retention is lacking. Although we recognize that a strategy cannot be applied in all practices, this article provides actionable items to consider in the commitment and work toward a more just and equitable practice of Hand Surgery.


Immunogenic variation among the so-called LC strains of Mycoplasma mycoides subspecies mycoides.
Much evidence of immunogenic heterogeneity among the LC strains of Mycoplasma mycoides ssp. mycoides emerged from cross-immunization and -hyper-immunization experiments in mice in which three LC strains (Vom/Plum Island, 74/2488, and Mankefår 2833) were used for challenge purposes. All heterologous LC-strain vaccines cross-immunized against the three challenge strains, but protection was usually only 'partial', i.e. significantly less than that given by homologous vaccine. Cross-hyperimmunization with all heterologous LC but not SC strains produced protection against challenge with Vom/Plum Island that was virtually 'complete', i.e. similar to that produced by homologous vaccine. Challenge with 74/2488 gave generally similar results; but against Mankefår 2833 six heterologous LC vaccines gave complete protection and six did not. Vaccines prepared from the Smith (1423) strain of M. mycoides ssp. capri gave some protection against Vom/Plum Island but none against 74/2488 or Mankefår 2833. The cross-immunizing ability of three further M. mycoides ssp. capri strains appeared to resemble that of Smith (1423). In a cross-hyperimmunization experiment, vaccines prepared from SC strains of M. mycoides ssp. mycoides varied greatly in their ability to protect against challenge with strains 74/2488 and Mankefår 2833.


Hemoglobin degradation in Plasmodium-infected red blood cells.
Intraerythrocytic malaria parasites (Plasmodia) degrade enormous amounts of hemoglobin during a short period of their life cycle. The process involves ingestion of red blood cell cytoplasm through the cytostome, delivery to acidic digestive vacuoles and sequential, efficient proteolysis by a set of specific hydrolases. Amino acids are generated for the growth and maturation of the organism; the heme byproduct is sequestered into a crystalline lattice called hemozoin. These specialized functions makes the digestive vacuole a prime target for antimalarial chemotherapy.


Purification and some characteristics of a beta-galactoside binding soluble lectin from amphibian ovary.
Soluble extracts of Bufo ovaries agglutinate sialidase-treated rabbit erythrocytes. Unlike other amphibian lectins this agglutination activity does not require the presence of calcium ions. It is specifically inhibited by D-galactose and its derivatives. Thiodi-D-galactoside is the most potent saccharide inhibitor followed by lactose and methyl-beta-D-galactoside, respectively. D-Fucose, D-glucose and D-mannose do not inhibit the activity at concentrations at or above 100 mM. The lectin has been purified 500-fold to apparent homogeneity from the ovaries by salt extraction and affinity chromatography on lactose-aminophenyl-agarose, with a yield of about 0.2%. The molecular mass determined by gel filtration under native conditions was 30 kDa; polyacrylamide gel electrophoresis in SDS gave a molecular mass of 15 kDa, suggesting that the lectin is a dimer. The lectin has an isoelectric point of 40 and contains a high proportion of acidic amino acids.


Seaweed-herbivore-predator interactions: host-plant specialization reduces predation on small herbivores.
Because feeding specialization among marine herbivores is rare, marine communities provide a simplified system for identifying factors selecting for specialization. On Australia's Great Barrier Reef, we investigated interactions among the chemically-defended seaweed Chlorodesmis fastigiata, herbivores specialized on this alga, and potential predators of these herbivores. Chlorodesmis is a low preference food for reef fishes but appears to be the only food of the crab Caphyra rotundifrons and the ascoglossan gastropods Elysia sp. and Cyerce nigricans. The crab is found only in patches of Chlorodesmis, feeds solely on the alga, and selectively shelters in it in laboratory choice experiments. Crab grazing on the red seaweed Acanthophora spicifera was stimulated when this alga was coated with increasing concentrations of the cytotoxic diterpenoid chlorodesmin, the major secondary metabolite of Chlorodesmis. Crabs did not sequester Chlorodesmis metabolites but avoided predators by sheltering in the unpalatable alga. All crabs tethered on the reef without access to Chlorodesmis patches were rapidly eaten; those with access to Chlorodesmis patches were much less susceptible to predation. The cryptic ascoglossan Elysia sp. was found exclusively in patches of Chlorodesmis and sequestered metabolites from the alga. Living Elysia were unpalatable to the common wrasse Thalassoma lunare in laboratory assays, but the crude organic extract of Elysia did not significantly deter feeding by Thalassoma. Elysia sequestered chlorodesmin, which deterred feeding by reef fishes in field assays but was ineffective against Thalassoma in laboratory assays at 5% food dry mass. Unlike Elysia, the aposematically colored ascoglossan Cyerce nigricans sequestered Chlorodesmis metabolites in relatively small amounts, but produced larger amounts of unrelated polypropionate compounds. Cyerce were never attacked by fishes and the crude organic extract of this slug strongly deterred feeding by wrasses in laboratory assays. The dorid nudibranch Gymnodoris sp. was found only in Chlorodesmis patches and appeared to be a specialized predator on Elysia; it would not prey on Cyerce. Data from this and other recent investigations demonstrate that some small marine herbivores feed selectively or exclusively on seaweeds that are chemically defended from fishes. This association reduces predation on the herbivores and suggests that escape from and deterrence of predation may be a dominant factor selecting for specialization among these herbivores.


The expression of a private idiotope requires pretreatment with noncomplementary anti-idiotypic antibodies.
The levan-binding ABPC48 myeloma protein is characterized by 3 idiotopes, (Ids), defined by 3 syngeneic monoclonal anti-idiotypic antibodies (IDA 10, IDA 16 and IDA 17). When BALB/c mice are immunized with levan, they produce anti-levan antibodies, some of which carry the Id 10 and Id 16 but not the Id 17 determinants. In the present study, we attempted to induce the synthesis of Id 17 positive anti-levan molecules. We found that immunization with IDA 17 antibodies alone was ineffective in inducing an Id 17 positive anti-levan response. By contrast, successive immunizations with IDA 10, IDA 16 and IDA 17 antibodies resulted in the synthesis of Id 17 positive anti-levan immunoglobulins. The synthesis of these molecules was concommitant with the induction of Id 10 and Id 16 positive anti-levan antibodies. Thus our data suggest that the Id 17 determinant on anti-levan antibodies is coexpressed with Id 10 and Id 16, and that successive anti-idiotypic treatment may result in the selective expansion of rare ABPC48 cross-reactive idiotype B-cell clone precursors.


Association of insomnia disorder with sociodemographic factors and poor mental health in COVID-19 inpatients in China.
To examine insomnia disorder and its association with sociodemographic factors and poor mental health in 2019 novel coronavirus (COVID-19) inpatients in Wuhan, China. and Methods: A total of 484 COVID-19 inpatients in Wuhan Tongji Hospital were selected and interviewed with standardized assessment tools. Insomnia disorder was measured by the Chinese version of the Insomnia Severity Index (ISI-7), a total score of 8 or more was accepted as the threshold for diagnosing insomnia disorder. The prevalence of insomnia disorder in the whole sample was 42.8%. Binary logistic regression analysis revealed that female gender, younger age, and higher fatigue and anxiety severity were more likely to experience insomnia disorder. Given the high rate of insomnia disorder status among COVID-19 inpatients in Wuhan, China, and its negative effects, follow-up assessments and appropriate psychological interventions for insomnia disorder are needed in this population.


Can a gastrointestinal pathologist identify microsatellite instability in colorectal cancer with reproducibility and a high degree of specificity?
Clinical features usually initiate evaluation for Lynch Syndrome (LS) but some colorectal cancer (CRC) histopathology findings are compatible with high microsatellite instability (MSI-H) that also occurs in LS. This led to the suggestion that pathologists request MSI analysis, which is an expensive addition to routine histology. We aimed to see if a Gastrointestinal Pathologist could identify MSI-H features with reproducibility and high (95%) specificity (MSI-H 95%). Histopathology of all CRCs received during 2005 and 4 MSI-H controls were scored using 2 published methods, "MsScore" and "PathScore". MSI analysis was performed on CRCs scored by either method as probable MSI-H 95% and results compared. To examine reproducibility of histopathology, 100 coded slides, including 25 scored MSI-H 95% and 75 scored low, were re-examined to now identify those needing MSI analysis. Costs were evaluated for identifying MSI-H with or without scoring. All 227 CRCs were scored for possible MSI-H 95%; 24 had high scores and MSI analysis. DNA analysis proved 14 MSI-H, PathScore identified 13 (95%), MsPath identified 9 (64%), histopathology alone identified 7 (50%). Reproducibility for identifying histopathology characteristics of MSI-H at re-examination, without scoring, was "moderate agreement" (Kappa statistic = 0.4615). Costs for identifying MSI-H by PathScore were the lowest, $436/identification. Conclusions; PathScore identified the most proven MSI-H CRCs at lowest cost and even an experienced gastrointestinal pathologist has difficulties identify MSI-H without scoring. So, scoring can be facilitated by a computerized evaluation form for routine CRC histology, prompting score computation and recommendation for MSI analysis with high specificity.


In vivo and in vitro EPR oximetry with fusinite: a new coal-derived, particulate EPR probe.
The peak-to-peak line width (LW) of the first derivative electron spin resonance (EPR) spectrum of the coal maceral fusinite is reversibly broadened by O2. The extent of broadening per unit of partial pressure of oxygen (pO2) is unusually large, exceeding that of nitroxides by almost two orders of magnitude. This paramagnetic property of fusinite, combined with its very stable physicochemical properties and low toxicity, is shown to be of utility in the measurement of pO2 in vitro and in vivo. Fusinite particles are endocytosed by chinese hamster ovary (CHO) cells in vitro; this is useful for intracellular O2 measurements with commercially available EPR spectrometers operating at 9.1-9.3 GHz. For measurement of oxygen in vivo using low frequency EPR (1.1-1.3 GHz), fusinite provides a sensitive and persistent means to measure pO2 in tissues. Particles implanted into the gastrocnemius muscle of A/J mice remained interstitially in the same position for months with undiminished sensitivity to pO2 and no specific toxic effects.


Postanesthetic shivering in primates: inhibition by peripheral heating and by taurine.
There has been little research on the cause(s) of postanesthetic shivering (PAS) and on specific interventions. Therefore, the authors investigated PAS in eight unoperated squirrel monkeys anesthetized with halothane-nitrous oxide mixture. Shivering developed in all monkeys in which body temperature was allowed to decrease (mean +/- SEM, 2.8 +/- 0.6 degrees C) during anesthesia. Shivering occurred in 25% of animals in which body temperature was actively maintained at preanesthetic levels during anesthesia. No shivering occurred in animals warmed both during and after anesthesia. Application of radiant heat to the skin stopped PAS immediately, even though deep body temperature remained low; shivering resumed within seconds after this heating was discontinued. Intracerebroventricular (0.1-2 mg) and intravenous (100 mg/kg) administration of the putative inhibitory neurotransmitter taurine also stopped the shivering in preliminary experiments, but central injection of alpha-melanocyte stimulating hormone (100-300 micrograms), an endogenous antipyretic, did not. The results implicate reduced body temperature and activation of central heat production pathways as major factors in PAS and suggest that halothane-nitrous oxide anesthesia per se, elevation of the thermal set-point, and surgical procedures are not essential to the shivering phenomenon. The results suggest for future study two methods to control PAS: application of radiant heat or administration of taurine.


Insights into the genetic diversity, antibiotic resistance and pathogenic potential of Klebsiella pneumoniae from the Norwegian marine environment using whole-genome analysis.
Klebsiella pneumoniae (Kp) can cause hospital- and community acquired infections. Although, Kp is widespread in the environment, very little is known about the genetic diversity and pathogenicity of Kp from the marine environment. The aim of our study was to understand the genetic diversity, resistome and pathogenic potential of 87 Kp isolates from the Norwegian marine environment, using whole-genome sequencing. We identified 50 sequence types, including globally disseminated sequence types associated with multidrug resistance or hypervirulence. Ten isolates carried the yersiniabactin loci. Acquired antibiotic resistance genes were identified in six Kp isolates. Heavy metal resistance genes were widespread among the isolates, with 71% carrying genes encoding resistance to copper, silver, arsenic, nickel and/or mercury. Co-occurrence of antibiotic resistance genes and heavy metal resistance genes was seen in five Kp isolates. Phylogenetic analysis revealed a close genetic relationship between Kp 2016-1200 ST25 isolated from blue mussels (Mytilus edulis) and a clinical isolate reported in Germany. To the best of our knowledge, this study provides the first comprehensive account of genetic diversity among Kp from the marine environment. Our study reveals high diversity of Kp in the Norwegian marine environment and seafood, including globally disseminated pathogenic sequence types carrying clinically relevant antibiotic resistance genes and virulence factors, as well as several heavy metal resistance genes.


Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking.
Single-particle cryo-EM is widely used to determine enzyme-nucleosome complex structures. However, cryo-EM sample preparation remains challenging and inconsistent due to complex denaturation at the air-water interface (AWI). To address this issue, we developed graphene-oxide-coated EM grids functionalized with either single-stranded DNA (ssDNA) or thiol-poly(acrylic acid-co-styrene) (TAASTY) co-polymer. These grids protect complexes between the chromatin remodeler SNF2h and nucleosomes from the AWI and facilitated collection of high-quality micrographs of intact SNF2h-nucleosome complexes in the absence of crosslinking. The data yields maps ranging from 2.3 to 3 Å in resolution. 3D variability analysis reveals nucleotide-state linked conformational changes in SNF2h bound to a nucleosome. In addition, the analysis provides structural evidence for asymmetric coordination between two SNF2h protomers acting on the same nucleosome. We envision these grids will enable similar detailed structural analyses for other enzyme-nucleosome complexes and possibly other protein-nucleic acid complexes in general.


Pharmacokinetics of rhuMAb CD18, a recombinant humanised monoclonal antibody fragment to CD18, in normal healthy human volunteers.
Leucocyte 2 integrin adhesion receptors are hypothesised as a therapeutic target to modify immune responses to ischaemia-reperfusion injury that may be detrimental to recovery in a variety of disease states. Two phase I studies were designed to evaluate the pharmacokinetics, immunogenicity and safety of rhuMAb CD18, a humanised monoclonal antibody F(ab')(2) fragment to the CD18 receptor, in normal healthy human volunteers. The first study evaluated six escalating doses of rhuMAb CD18 (0.06, 0.12, 0.25, 0.5, 1.0, 2.0 mg/kg) in 36 subjects given two intravenous (IV) bolus injections 12 hours apart. In the second study, 16 subjects received IV doses of 1.0 and 2.0 mg/kg as a single dose or as two doses given 12 hours apart. Study endpoints were rhuMAb CD18 serum pharmacokinetics, change in white blood cell (WBC) count, and safety and tolerability. The two studies enrolled a total of 53 subjects. Serum concentration-time profiles demonstrated a monophasic decline and were best characterised by a one-compartment pharmacokinetic model. At the doses administered, the volume of distribution approximated the serum volume (range of means: 42 to 58 ml/kg). The serum clearance decreased with increasing dose until becoming consistent at doses of 0.5 to 2.0 mg/kg (range of means: 3.1 to 5.0 ml/h/kg). At doses of 0.5 to 2.0 mg/kg, the mean elimination half-life ranged from 7.0 to 9.6 hours. WBC counts increased at doses of above 0.06 mg/kg, returning to within 20% of predose values by day 7. Antibodies to rhuMAb CD18 were not detected at day 28. Mild-to-moderate adverse events were observed in both the placebo and treated groups, and were limited to flu-like symptoms. One subject experienced a serious adverse event (febrile reaction) and recovered with minimal intervention. There was no evidence of an increase in infection in subjects who received rhuMAb CD18. Upon IV bolus administration, rhuMAb CD18 serum concentration-time data fit a one-compartment pharmacokinetic model. At doses of 0.5 to 2.0 mg/kg, the pharmacokinetics were linear and the half-life ranged from 7.0 to 9.6 hours with a volume of distribution that approximated the serum volume. No antibodies to rhuMAb CD18 were detected. A transient, dose-dependent increase in the WBC count was observed, consistent with the expected effect of rhuMAb CD18 on leucocyte demargination. No increase in infection was observed. rhuMAb CD18 administered by IV bolus was well tolerated, with the exception of one febrile reaction.


Production of a novel red pigment, rubrolone, by Streptomyces echinoruber Sp. Nov. II. Chemistry and structure elucidation.
Streptomyces echinoruber sp. nov. produces several red pigments. The major component, rubrolone, has been identified as 8(R),9(R),10(S),10a(R)-tetrahydro-9,10,10a,11-tetrahydroxy-3,8-dimethyl-1-propyl-6aH(S)-pyrano[2",3":5',4]furo[2',3':5,6]azuleno[2,3-c]pyridine-5,13-dione (1) by single crystal X-ray analysis of a suitable derivative. A second pigment, B, is probably structurally closely related.


Stochastic ontogenetic allometry: the statistical dynamics of relative growth.
In the absence of stochasticity, allometric growth throughout ontogeny is axiomatically described by the logarithm-transformed power-law model, θt = log(a) b + kφ(t), where θt ≡ θ(t) and φt ≡ φ(t) are the logarithmic sizes of two traits at any given time t. Realistically, however, stochasticity is an inherent property of ontogenetic allometry. Due to the inherent stochasticity in both θt and φt, the ontogenetic allometry coefficients, log(a) b and k, can vary with t and have intricate temporal distributions that are governed by the central and mixed moments of the random ontogenetic growth functions, θt and φt. Unfortunately, there is no probabilistic model for analyzing these informative ontogenetic statistical moments. This study treats θt and φt as correlated stochastic processes to formulate the exact probabilistic version of each of the ontogenetic allometry coefficients. In particular, the statistical dynamics of relative growth is addressed by analyzing the allometric growth factors that affect the temporal distribution of the probabilistic version of the relative growth rate, k ≡ Dt(u<Ωt>)/Dt(v<Ωt>), where <Ωt> is the expected value of the ratio of stochastic θt to stochastic φt, and u<Ωt> and v<Ωt> are the numerator and the denominator of <Ωt>, respectively. These allometric growth factors, which provide important insight into ontogenetic allometry but appear only when stochasticity is introduced, describe the central and mixed moments of θt and φt as differentiable real-valued functions of t. Failure to account for the inherent stochasticity in both θt and φt leads not only to the miscalculation of k, but also to the omission of all of the informative ontogenetic statistical moments that affect the size of traits and the timing and rate of development of traits. Furthermore, even though the stochastic process θt and the stochastic process φt are linearly related, k can vary with t.


"Drug-resistant granuloma faciale": treatment with carbon dioxide-GaAs laser.
Granuloma faciale (GF), also known as "eosinophilic granuloma," is a rare benign leukocytoclastic vasculitis which most commonly occurs on the face of middle-aged Caucasian males. Clinically, GF appears as single or multiple, slowly growing, reddish-brown papules, nodules or plaques which may be cosmetically unpleasant. Its pathogenesis is unknown and GF is notoriously resistant to treatments. Both medical (dapsone, colchicine, gold injections, isoniazid, clofazimine, corticosteroids, psoralen ultraviolet radiation, and topical tacrolimus) and surgical therapies (excision, graft, dermabrasion, argon laser, carbon dioxide laser, pulsed dye laser, cryotherapy, and electrosurgery) have been used for GF but no effective treatment has yet been found. Furthermore, the typical facial location of GF requires an acceptable cosmetic result. We report two cases of drug-resistant GF which were successfully treated with laser vaporization combining two different wavelengths: carbon dioxide (CO2 ) 10,600 nm and GaAs 1540 nm.


The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment.
The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤ .037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤ .046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10-12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUCtraining: 0.82 and AUCvalidation: 0.77). The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS.


Formation of germ-line chimeras from embryonic stem cells maintained with recombinant leukemia inhibitory factor.
Murine embryonic stem (ES) cells can be maintained as stem cells in vitro only in the presence of feeder cells or a soluble factor produced by a number of cell lines. We have previously demonstrated that leukemia inhibitory factor (LIF) is the molecule which prevents ES cell differentiation in culture. In this report we demonstrate that recombinant LIF can substitute for feeder cells in maintaining the full developmental potential of ES cells. The totipotent D3 ES cell line, previously isolated and maintained on growth-arrested primary embryo fibroblasts, was transferred to media supplemented with 1000 U/ml (10 ng/ml) recombinant LIF. In the presence of LIF the ES cells were maintained for over 2 months as undifferentiated cells in the absence of any feeder cells. When injected into blastocysts the ES cells which had been maintained in LIF-supplemented media efficiently formed germ-line chimeras.


Contemporary Topics in Radiation Medicine: Skin Cancer.
Radiation plays an important role in the management of a variety of skin cancers. This article discusses the role of radiation in the treatment of cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, and B-cell lymphomas.


ERCP, endoscopic papillotomy and gallstone removal by JFB2 Olympus and PFSB 1200 Machida.
ERCP is now used as routine technique and has provided a useful tool for both diagnostic and therapeutic purposes in diseases of the biliary tract. Until now this examination has been performed throughout the world including Italy, using preferably an Olympus JF and JF B2 sideviewing duodenoscope. In addition to 727 ERCP and 55 papillotomies performed using this instrument we have also employed a convertible endoscope Machida PFSB 1200; this fiberscope, with which front and side views are possible, can be used in the study of the oesophagus, stomach, duodenum, cannulation of the papilla of Vater and papillotomy. They results obtained and advantages offered by this instrument will be discussed. Since this endoscope is not usually employed, at least in Europe, for these purposes, we considered it of interest to report on the 251 ERCP and 9 papillotomies including stone removal performed in our department with the Machida PFSB 1200.


Induction of micronuclei by ochratoxin A is a sensitive parameter of its genotoxicity in cultured cells.
In order to better characterize the ochratoxin A (OTA)-induced DNA damage and to further investigate factors which may modulate dose-effect relationships in cells, the induction of micronuclei was studied in V79 Chinese hamster fibroblast cells and in primary cultures of porcine urothelial bladder epithelial cells (PUBEC). OTA was able to induce micronuclei in PUBEC and V79 cells at concentrations below those which were overtly cytotoxic. OTA concentrations between 0.03 and 1 μM caused a dose-dependent increase of micronuclei in V79 cells (up to 3-fold compared to controls); but the lowest tested concentration of 0.01 μM OTA did not induce a higher frequency of micronuclei than in the solvent control, indicative of an apparent threshold. Clear evidence for genotoxic effects was also found in PUBEC cultures treated with OTA concentrations of 1 μM and more, although the dose-effect relationship in PUBEC was more variable for several freshly isolated cell batches, pointing to differences in susceptibility to OTA between bladder cells from different donor animals. The chromosomal genotoxicity of OTA demonstrated in this study is in general accord with previous findings on the induction of clastogenic effects and oxidative DNA damage by OTA. In both cases, the shape of the dose-response curve at very low OTA concentrations supports the existence of a threshold for its genotoxicity.


[Individualized management of patients with exudative AMD, IOI protocol: Injection-observational-individualization].
Wet macular degeneration remains a major cause of visual impairment in people over 55years. Through a group of experts belonging to the Federation France Macula, we review the treatment of wet AMD and provide recommendation with a 3 phases protocol called IOI.


Measuring women's preferences for breast cancer treatments and BRCA1/BRCA2 testing.
In establishing decision models in the treatment and prevention of breast cancer, it is important to evaluate patients' preferences for such interventions. The objectives of the present study were: (i) to characterize women's preferences for breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and standard gamble techniques; and (ii) to identify factors associated with these quality of life indices. Data were collected from women with breast cancer (n = 60), high-risk relatives of women with breast cancer (n = 58), and women in the general population (n = 51). Regardless of group membership, participants favoured treatment and prevention options that involved minimal physical invasiveness. Women with breast cancer rated lumpectomy and radiation treatment more highly than high-risk relatives and women in the general population. Preferences did not differ according to participants' intentions to undergo BRCA testing. Age was the only demographic variable associated with health state preferences. These findings hold implications for the application of patient preferences to clinical decision making.


Clinical and morphological characteristics in Streptococcus bovis endocarditis: a comparison with other causative microorganisms in 177 cases.
To compare the clinical and morphological characteristics of patients with Streptococcus bovis endocarditis with those of patients with endocarditis caused by other microorganisms. 177 consecutive patients (Streptococcus bovis, 22; other streptococci, 94; staphylococci, 44; other, 17) with definite infective endocarditis according to the Duke criteria were included. All patients underwent transthoracic and transoesophageal echocardiography. In 88 patients, findings from surgery/necropsy were obtained. S bovis endocarditis was associated with older patients, with a higher mortality (p = 0.04), and with a higher rate of cardiac surgery (p < 0.001) than other microorganisms, although embolic events were observed less often (p = 0.02). Pathological gastrointestinal lesions were detected in 45% of the patients. Multiple valves were affected in 68% of the patients with S bovis endocarditis and in 20% of those with other organisms (p < 0.001). Moderate or severe regurgitation occurred more often in S bovis endocarditis than with other microorganisms (p = 0.05). When surgery or necropsy was performed, infectious myocardial infiltration of the left ventricle was confirmed histopathologically in 36% of the patients with S bovis endocarditis and in 10% of those with other organisms (p = 0.002). S bovis endocarditis is a severe illness because of the more common involvement of multiple valves, and of the frequent occurrence of haemodynamically relevant valvar regurgitation and infectious myocardial infiltration.


Efficacy and safety of selamectin against fleas on dogs and cats presented as veterinary patients in Europe.
Two controlled and masked multi-centre studies were conducted to examine the efficacy of a novel topical avermectin, selamectin, against natural flea infestations on 418 dogs and 345 cats. Veterinary patients with viable flea infestations were enrolled in the studies, which were conducted in United Kingdom, France, Germany, and Italy. Animals were allocated randomly in a 2:1 ratio to one of two treatments: either selamectin alone at a minimum dosage of 6mgkg(-1) or fenthion at recommended dose rates. Concurrent use of an environmental spray (containing methoprene and either pyrethrins or permethrin) was permitted only for fenthion-treated animals. In-contact cats and dogs (animals living in the same home) received the same treatment as the first animal enrolled from the household, if recommended by the veterinarian. Study day 0 was defined as the day of first treatment. Animals were treated on days 0, 30, and 60, and flea comb counts and clinical evaluations were conducted on days 0, 14, 30, 60, and 90. Analysis of variance of ln(flea count+1) showed that values were significantly lower for selamectin alone compared with fenthion (with or without the concurrent use of an environmental spray) in dogs on days 30, 60, and 90 (P<0.05) and in cats on days 14, 30, 60, and 90 (P<0.01). For selamectin, the reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day 0, were 92.5, 90.7, 98.1, and 99.1%, respectively, for dogs and 92.8, 92.7, 97.7, and 98.4%, respectively, for cats. Selamectin was shown to be safe and highly effective in the control of naturally acquired flea infestations on dogs and cats presented as veterinary patients in Europe.


Is Cognitive Status Related to Oral Hygiene Level and Appropriate for Determining Need for Oral Hygiene Assistance?
With declining general health, the maintenance of oral health becomes increasingly difficult. Unfortunately, health care resources are limited. An assessment tool for detecting a patient's need for oral health care assistance would promote its adequate distribution. The aim of this study is to evaluate if the Shulman clock-drawing test score is a suitable assessment tool for determining the need for oral hygiene assistance. Data collected from recent dental checkups of 126 inhabitants of five Austrian residential care facilities were analyzed. The Shulman clock-drawing test score was used as a measure for cognitive abilities and related to tooth and denture hygiene indices, which were assessed using the approximal space plaque index (API) and the denture plaque index (DPI). Shulman score values were distributed almost evenly in the study population. The mean API was 83.6% (SD 20.2%) for the maxilla and 94.9% (SD 15.6%) for the mandible. The mean DPI was 43.9% (SD 31.4%). Cognitive impairment was not statistically related to the dental or denture hygiene index. A high Shulman clock-drawing test score indicates the need for oral hygiene assistance, but it is not suitable as a single tool to assess this need. Patients with other disabilities might equally qualify for assistance. Dentures, however, can be cleaned quickly and efficiently independently of patient compliance; therefore, cleaning the patients' dentures should be part of nursing personnel's daily care routine for every patient.


Detection and Prevention of Mild Cognitive Impairment and Dementia.
Mild cognitive impairment (MCI) is characterized by cognitive deficits alongside essentially preserved competence in activities of daily living [...].


Cholesterol and melatonin regulated membrane fluidity does not affect the membrane breakage triggered by amyloid-beta peptide.
We have studied by means of small angle neutron scattering and diffraction, and molecular dynamics simulations the effect of lipid membrane fluidity on the amyloid-beta peptide interactions with the membrane. These interactions have been discovered previously to trigger the reorganization of model membranes between unilamellar vesicles and planar membranes (bicelle-like structures) during the lipid phase transition. The morphology changes were taking place in rigid membranes prepared of fully saturated lipids and were proposed to play a role in the onset of amyloid related disorders. We show in this study that the replacement of fully saturated lipids by more fluid mono-unsaturated lipids eliminates the mentioned morphology changes, most likely due to the absence of phase transition within the temperature range investigated. We have therefore controlled the membrane rigidity also while ensuring the presence of membrane phase transition within the biologically relevant temperatures. It was done by the addition of melatonin and/or cholesterol to the initial membranes made of saturated lipids. Small angle neutron scattering experiments performed over a range of cholesterol and melatonin concentrations show their distinctive effects on the local membrane structure only. The cholesterol for example affects the membrane curvature such that spontaneously formed unilamellar vesicles are of much larger sizes than those formed by the neat lipid membranes or membranes with melatonin added. The temperature dependent experiments, however, reveal no influence on the previously discovered membrane breakage whether cholesterol or melatonin have been added.


Assays for alloreactive responses by PCR.
In organ transplantation, major efforts are currently developed to minimize or even to withdraw immunosuppressive drugs. Different protocols have therefore been proposed to induce graft tolerance, that is, the survival of an allograft in the absence of continuing immunosuppression. They generally involve pre-transplant conditioning followed by hematopoietic stem cell infusion. Follow-up of immune status is mandatory in this kind of protocol, in order to investigate tolerance and consequently to reduce or withdraw immunosuppression without graft rejection. However, assessment of the alloreactive response using currently available techniques is labor-intensive and requires significant volume of patient's blood. The implementation of such tolerance protocols is thus difficult in routine practice. In this chapter, we describe a novel real-time polymerase chain reaction method based on interferon-gamma and interleukin-2 mRNAs quantification that requires only 10 ml of blood. Moreover, results can be obtained within 48 h. A modified mixed lymphocyte reaction (MLR) using whole blood T lymphocytes as responsive cells and CD3-depleted peripheral blood mononuclear cells (PBMCs) as stimulators is described. An alternative, that is, the use of PBMC as responding cells instead of whole blood, is also depicted. We successfully applied the technique in the monitoring of anti-donor reactivity in living donor liver graft recipients. We suggest that this rapid MLR assay could be valuable for the monitoring of patients undergoing solid organ or hematopoietic stem cell transplantation.


Performance of Regular and Modified Canola and Soybean Oils in Rotational Frying.
Canola and soybean oils both regular and with modified fatty acid compositions by genetic modifications and hydrogenation were compared for frying performance. The frying was conducted at 185 ± 5 °C for up to 12 days where French fries, battered chicken and fish sticks were fried in succession. Modified canola oils, with reduced levels of linolenic acid, accumulated significantly lower amounts of polar components compared to the other tested oils. Canola oils generally displayed lower amounts of oligomers in their polar fraction. Higher rates of free fatty acids formation were observed for the hydrogenated oils compared to the other oils, with canola frying shortening showing the highest amount at the end of the frying period. The half-life of tocopherols for both regular and modified soybean oils was 1-2 days compared to 6 days observed for high-oleic low-linolenic canola oil. The highest anisidine values were observed for soybean oil with the maximum reached on the 10th day of frying. Canola and soybean frying shortenings exhibited a faster rate of color formation at any of the frying times. The high-oleic low-linolenic canola oil exhibited the greatest frying stability as assessed by polar components, oligomers and non-volatile carbonyl components formation. Moreover, food fried in the high-oleic low-linolenic canola oil obtained the best scores in the sensory acceptance assessment.


Concentration measurement of yeast suspensions using high frequency ultrasound backscattering.
This work proposes the use of an ultrasound based technique to measure the concentration of yeasts in liquid suspension. This measurement was achieved by the detection and quantification of ultrasonic echoes backscattered by the cells. More specifically, the technique was applied to the detection and quantification of Saccharomyces cerevisiae. A theoretical approach was proposed to get the average density and sound speed of the yeasts, which were found to be 1116 kg/m(3) and 1679 m/s, respectively. These parameters were needed to model the waves backscattered by each single cell. A pulse-echo arrangement working around 50 MHz, being able to detect echoes from single yeasts was used to characterize experimentally yeast solutions from 10(2) to 10(7)cells/ml. The Non-negative Matrix Factorization denoising technique was applied for data analysis. This technique required a previous learning of the spectral patterns of the echoes reflected from yeasts in solution and the base noise from the liquid medium. Comparison between pulse correlation (without denoising) and theoretical and experimental pattern learning was made to select the best signal processing. A linear relation between ultrasound output and concentration was obtained with correlation coefficient R(2)=0.996 for the experimental learning. Concentrations from 10(4) to 10(7)cells/ml were detected above the base noise. These results show the viability of using the ultrasound backscattering technique to detect yeasts and measure their concentration in liquid cultures, improving the sensitivity obtained using spectrophotometric methods by one order of magnitude.


Bromodeoxyuridine inhibition of Friend leukemia cell induction. Mechanism of reversal by deoxycytidine.
Deoxycytidine (dC) reverses bromodeoxyuridine (brdUrd) inhibition of induction in Friend leukemia cells only if added within the first 6 h after the addition of brdUrd. dC is shown to reduce the uptake of [3H]brdUrd into both soluble nucleotide pools and DNA, substantially expand the dTTP pool, and result in a lower level of brdUrd substitution in DNA. When the conversion of dC to thymidine nucleotides is prevented in BATH medium (containing brdUrd, aminopterin, thymidine, and hypoxanthine), dC no longer reverses brdUrd inhibition. These results show that dC exerts its primary effect via alterations in thymidine pools and probably through the resultant lower substitution of brdUrd in DNA.


Use of Victoria blue in the detection of intrahepatocyte HBs Ag: comparison with other methods.
The authors tested Victoria blue staining in intrahepatocytic HBs Ag detection and compared the results with those obtained by the following methods: direct immunofluorescence, orcein and peroxidase-antiperoxidase (PAP). Although PAP appears to be the best technique for diagnostic research, Victoria blue is a sound method for routine diagnosis in hepatology.


Central effect of 5,8,11,14-eicosatetraenoic acid (arachidonic acid) on the temperature in the conscious rabbit.
Hyperthermia induced by arachidonic acid in rabbit was attenuated by phenoxybenzamine, cyproheptadine and indomethacin. The reduction in arachidonic acid hyperthermia, after 6-OH-DA and the failure of PCPA to reduce this rise, indicates the involvement of noradrenaline in arachidonic acid hyperthermia.


Differential and selective inhibition of cellular and herpes simplex virus DNA synthesis by arabinofuranosyladenine.
The influence of 9-beta-D-arabinofuranosyladenine (beta araAdo) and of its anomer 9-alpha-D-arabinofuranosyladenine (alpha araAdo) was studied in non-infected cells and cells infected with herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). alpha AraAdo is a strong inhibitor of proliferation of non-infected cells. Multiplication of HSV-1 and HSV-2 is not affected at all by alpha araAdo, while their growth is strongly inhibited by beta araAdo. alpha AraAdo exerts no effect on the incorporation of dThd into HSV DNA, but blocks the incorporation into host cell DNA. Its anomer, beta araAdo, affects the incorporation rate of both the viral DNA system and the host cell DNA system (the latter one to a lesser extent). alpha AraAMP is incorporated into newly synthesized cellular DNA but not into HSV DNA. Enzymic studies relevant that alpha araATP has no effect on the HSV DNA polymerase system but a high inhibitory potency in the host cell DNA polymerase alpha system. The anomeric form, beta araATP, is a sensitive inhibitor of HSV DNA polymerase while the cellular DNA polymerases alpha and beta are more refractory.


Extension of the shoulder is essential for functional internal rotation after reverse total shoulder arthroplasty.
Disabling loss of functional internal rotation (fIR) after reverse total shoulder arthroplasty (RTSA) is frequent but not well understood. This study tested the hypothesis that limitation of fIR after RTSA is not primarily related to a deficit in internal rotation. Fifty patients (mean age at RTSA, 74 ± 11.7 years) who were consecutively seen at a yearly follow-up visit at 1-10 years (median, 4 years) after RTSA were prospectively examined with special attention to fIR. Patients with axillary nerve or deltoid dysfunction were excluded. Relative (age- and sex-adjusted) Constant-Murley scores (CSs) and Subjective Shoulder Values were assessed preoperatively and at final follow-up. In addition, active extension and 4 postoperative activities of daily living (ADLs) requiring fIR were tested at follow-up. Rotator cuff fatty infiltration and notching were evaluated radiographically. For analysis, patients were divided into a group with poor fIR (fIR-, n = 19), defined as ≤2 internal-rotation points in the CS, and a group with good fIR (fIR+, n = 31), defined as ≥4 internal-rotation points in the CS. Active extension of the contralateral shoulders was comparable in the fIR- group (mean, 60.3° [standard deviation (SD), 11.2°]) and fIR+ group (66.1° [SD, 14.2°]). Postoperatively, a difference in active extension between the unaffected and operated sides was present in both groups and averaged 16° (55° [SD, 14.3°] in fIR+ group and 39.1° [SD, 10.8°] in fIR- group; P < .001). No patient in the fIR+ group had active extension < 40° (range, 40°-85°). Shoulders with extension ≥ 40° but unsatisfactory fIR had restricted passive internal rotation in extension. The ability to perform ADLs behind the back correlated better with shoulder extension than with so-called fIR measurements in the CS. Functional internal rotation after RTSA requires at least 40° of shoulder extension. If fIR is unsatisfactory despite 40° of extension, passive restriction of internal rotation in full extension is the limiting factor. It is crucial to preserve or restore active shoulder extension to allow ADLs involving internal rotation.


Reduction of renal lipid content and proteinuria by a PPAR-γ agonist in a rat model of angiotensin II-induced hypertension.
An excess of lipids may accumulate in the kidney in conditions such as diabetes and hypertension, and can potentially cause renal injury. We previously reported that an infusion of angiotensin II into a rat induced deposition of lipids in the renal tubular epithelial cells. Here we have examined the effect of pioglitazone, an agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ), on renal lipid accumulation and renal injury induced by angiotensin II infusion. Pioglitazone treatment (2.5mg/kg/day) reduced the amount of triglycerides in the kidney of the angiotensin II-induced hypertensive rat without significantly altering either blood pressure levels or mRNA expression of lipogenic genes in the kidney. In addition, pioglitazone, either alone or in conjunction with angiotensin II, increased the expression of phosphorylated, but not total, AMP-activated protein kinase (AMPK). Proteinuria and kidney weight in the angiotensin II-infused rat were significantly decreased by pioglitazone treatment. In addition, pioglitazone suppressed iron deposition and ferritin protein induction, but did not alter upregulated expression of the antioxidative molecule, heme oxygenase-1, in the kidney of the angiotensin II-infused rat. These findings suggested that pioglitazone suppressed the angiotensin II-induced increase in renal lipid content by inhibiting its proteinuric action, but not by direct alteration of the expression or activity of lipid metabolism-related genes. Reduction of lipotoxic renal damage may represent one of the renoprotective effects provided by pioglitazone in hypertension with activation of the renin-angiotensin system.


Measurement of renal blood flow in human subjects using the ultrasound velocity profiling technique.
To (1) assess the accuracy of the ultrasound velocity profiling (USVP) technique of renal blood flow (RBF) measurement in normal subjects and (2) compare renal blood flow measurements obtained using USVP and renal clearance rate in patients with renal diseases. First, we calculated unilateral renal blood flow (unil-RBF) using USVP and the clearance rate of para-aminohippuric acid (CPAH) simultaneously in six healthy male subjects. We then compared unil-RBFUSVP and unil-RBFPAH in nine patients with chronic glomerulonephritis (CGN). In the first study, the limits of agreement in a Bland-Altman plot ranged from -325.3 to 32.0 ml/min per 1.48 m(2). The mean bias was -146.7 ml/min per 1.48 m(2). Subdivision for values of unil-RBFUSVP by flow showed small discrepancies in values above 280 ml/min per 1.48 m(2): mean bias, -98.2 ml/min per 1.48 m(2); limits of agreement, -223.3 to 26.8 ml/min per 1.48 m(2). The three patients in the second study had immunoglobulin A (IgA) nephropathy, in whom unil-RBFPAH was estimated as being markedly lower than unil-RBFUSVP, contrary to the primary result. Despite its consistent negative bias, USVP may be a reliable method of quantifying renal blood flow noninvasively when measured values exceed 280 ml/min per 1.48 m(2). We assumed that the p-aminohippurate extraction rate (EPAH) was profoundly impaired in the three patients with IgA nephropathy.


Behavioral management of oral medication administration difficulties among children: a review of literature with case illustrations.
Nonacceptance of prescribed oral medications among young children hinders medical treatment. The literature pertaining to teaching children how to swallow pills or capsules is reviewed. In addition, a multiple case study demonstrating the efficacy of a brief, easy-to-implement procedure designed to promote capsule acceptance is presented. In this study, two four-year-old children diagnosed to have chronic illnesses participated. In Case 1, use of verbal instruction, modeling, shaping, and contingent reinforcement resulted in the rapid acquisition of capsule swallowing skills. In Case 2, these training procedures, in combination with physical guidance contingent upon noncompliance, successfully produced repeated acceptance of medication by a child who had refused to swallow capsules. In both cases, compliance has been maintained for at least six months.


Cutaneous vasculitis: its relationship to systemic disease.
Necrotizing vasculitis may be localized to the skin or may involve multiple organs. Although the etiology of cutaneous necrotizing vasculitis is unknown, evidence suggests that circulating immune complexes play an important role. The most common clinical lesion seen is palpable purpura, which histologically demonstrates leukocytoclastic vasculitis. The majority of patients affected with cutaneous necrotizing vasculitis have a benign course.


Effects of methoxychlor and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane on 11β-hydroxysteroid dehydrogenase activities in vitro.
Methoxychlor (MXC) is primarily used as a pesticide and widely present in the environment. The objective of the present study is to investigate the direct effects of MXC and its metabolite 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on two isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2) in vitro. Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11β-HSD1 activity. Human placental and rat kidney microsomes were used for 11β-HSD2 activity. The IC(50) values on human 11β-HSD1 by MXC and HPTE were 1.91±0.07 and 8.88 ± 0.08 μM, respectively. HPTE inhibited rat 11β-HSD1 with IC(50) of 9.15±0.05μM, while MXC did not inhibit the enzyme. MXC and HPTE were competitive inhibitors of 11β-HSD1. HPTE also inhibited human and rat 11β-HSD2 with IC(50) values of 55.57 ± 0.08 and 12.96 ± 0.11 μM, respectively, while MXC did not inhibit 11β-HSD2. In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11β-HSD in a species- and chemical structure-dependent manner.


Inflammation-Responsive Hydrogel Spray for Synergistic Prevention of Traumatic Heterotopic Ossification via Dual-Homeostatic Modulation Strategy.
Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post-traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual-homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate-hyaluronic acid-based hydrogel spray device encapsulating a curcumin-loaded zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo-crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA-seq results demonstrated that CZCH achieved dual-homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations.


Improvement in Parkinson Disease Symptoms After Treatment for COVID-19 with Monoclonal Antibodies.
Parkinson disease (PD) is a neurodegenerative disease characterized by motor symptoms, such as bradykinesia, and non-motor symptoms, such as fatigue, which can be a particularly disabling feature of the disease. We conducted a retrospective chart review on a patient who reported improvement in baseline PD symptoms after COVID-19 treatment. The patient is a 76-year-old male with a six-year history of PD who developed a COVID-19 infection, underwent treatment with COVID-19 monoclonal antibodies, and experienced a remarkable improvement in his pre-COVID PD symptoms, most notably his gait and fatigue. Prior to COVID, he rated his fatigue as '9 out of 10,' which worsened to 10 out of 10 during his COVID infection, and post-COVID treatment, his fatigue improved to '3 out of 10'. We described an unexpected improvement in baseline PD symptoms for a patient treated with COVID-19 monoclonal antibodies. Further investigation will be essential to understand the mechanisms underlying this phenomenon.


[Factors affecting the participation of bacteria of the genus Bdellovibrio in the self-purification processes in the Syr Darya River].
The effect of season, temperature and abundance of microflora on the interrelations between bdellovibrions and host-bacteria in the syr Daryo river compared with the Oka has been studied. These factors and composition of allochthonic gram-negative bacteria in the river influence on the abundance of Bdellovibrio and extent its participation in the self-purification of basins.


BCL-2 promotes migration and invasiveness of human glioma cells.
Malignant progression in gliomas is correlated with increased migratory capacity which involves metalloproteolytic activity. Here, we report that ectopic expression of BCL-2 in two malignant glioma sublines markedly promoted glioma cell migration from spheroids and invasion into Matrigel-coated membranes. Invasion of fetal rat-brain aggregates was enhanced by BCL-2. Zymography revealed activation of matrix metalloproteinase-2 (MMP-2) in BCL-2-expressing cells. BCL-2 expressing cells showed an increase in MMP-2/-3/-12 (LN-18), and MMP-9/-12 and cell surface urokinase-type plasminogen activator (u-PA) (LN-229) mRNA and a reduction in tissue inhibitors of metalloproteinases (TIMP)-2 mRNA (LN-229). Taken together, we propose a novel function for BCL-2 in the malignant phenotype of glioma cells, that is, to enhance migration and invasion by altering the expression of a set of metalloproteinases and their inhibitors.


Quality of life of MS patients in Trinidad and Tobago: Anomaly or adaptation?
There has been growing interest in quality of life associated with multiple sclerosis but the research has been overwhelmingly carried out in developed countries. This study aimed to assess quality of life of multiple sclerosis patients in Trinidad and Tobago. All multiple sclerosis patients were asked to complete demographic, EQ-5D-5L and MSQOL-54 questionnaires. EQ-5D data were compared with population norms for Trinidad and Tobago. MSQOL-54 data were compared with results from a matching cohort of non-MS respondents. Regression analyses were used to explore the association between MSQOL-54 scales and EQ-5D utility. The 97 patients were mainly urban, highly educated and 75% female. EQ-5D-5L data showed more frequent and more severe problems and lower index values than the population and patients of other chronic illness clinics in Trinidad and Tobago. MSQOL-54 results showed that patients were more affected by physical items, but had high scores on mental and emotional items when compared with the matching cohort and patients in other countries. The low prevalence and demographics of patients suggest the possibility of undetected cases in rural areas and/or among less educated groups. Further investigation into the high levels of mental and emotional health among patients may lead to the design of interventions to help patients of multiple sclerosis and other illnesses.


[Age-related characteristics of the effect of periodic low-calorie nutrition on lipid composition of the liver cells, small intestine, adipose tissue and blood serum in albino rats].
It is studied how long-term periodical calorie-insufficient and growth-restraining nutrition promoting appreciable life prolongation in the Wistar-line albino rats influences the lipid metabolism. It is shown that diet has an essential influence on the levels of phospholipids, cholesterol, neutral lipids, fatty acids in different tissue cells. The age specificity is observed in all the studied tissue cells. The lipid composition of cells in aged rats with prolonged life is similar to that of young animals of control group.


Renal cell carcinoma in a solitary kidney: late nephrectomy after 35 years and analysis of tumor deoxyribonucleic acid content.
We report a case of renal cell carcinoma in a solitary kidney, which was palpable for 35 years and verified histopathologically 31 years before nephrectomy. Deoxyribonucleic acid analysis of paraffin embedded and new surgical samples showed a similar aneuploid deoxyribonucleic acid content with an index of 1.3. The unusually long survival of this patient is discussed.


Polypyrrole⁻Nickel Hydroxide Hybrid Nanowires as Future Materials for Energy Storage.
Hybrid materials play an essential role in the development of the energy storage technologies since a multi-constituent system merges the properties of the individual components. Apart from new features and enhanced performance, such an approach quite often allows the drawbacks of single components to be diminished or reduced entirely. The goal of this paper was to prepare and characterize polymer-metal hydroxide (polypyrrole-nickel hydroxide, PPy-Ni(OH)₂) nanowire arrays demonstrating good electrochemical performance. Nanowires were fabricated by potential pulse electrodeposition of pyrrole and nickel hydroxide into nanoporous anodic alumina oxide (AAO) template. The structural features of as-obtained PPy-Ni(OH)₂ hybrid nanowires were characterized using FE-SEM and TEM analysis. Their chemical composition was confirmed by energy-dispersive x-ray spectroscopy (EDS). The presence of nickel hydroxide in the synthesized PPy-Ni(OH)₂ nanowire array was investigated by X-ray photoelectron spectroscopy (XPS). Both FE-SEM and TEM analyses confirmed that the obtained nanowires were composed of a polymer matrix with nanoparticles dispersed within. EDS and XPS techniques confirmed the presence of PPy-Ni(OH)₂ in the nanowire array obtained. Optimal working potential range (i.e., available potential window), charge propagation, and cyclic stability of the electrodes were determined with cyclic voltammetry (CV) at various scan rates. Interestingly, the electrochemical stability window for the aqueous electrolyte at PPy-Ni(OH)₂ nanowire array electrode was remarkably wider (ca. 2 times) in comparison with the non-modified PPy electrode. The capacitance values, calculated from cyclic voltammetry performed at 20 mV s-1, were 25 F cm-2 for PPy and 75 F cm-2 for PPy-Ni(OH)₂ array electrodes. The cyclic stability of the PPy nanowire array electrode up to 100 cycles showed a capacitance fade of about 13%.


Audit of stool analysis results to ensure the prevalence of common types of intestinal parasites in Riyadh region, Saudi Arabia.
The objective of the current study was to determine the incidence of common types of parasites encountered in the Central Region of Saudi Arabia. The current study is a retrospective study which includes the results of 10427 stool sample and occult blood sample. The results obtained during last two years (2005-2007), were compared to the earlier reports on parasites in the Central as well as other regions of Saudi Arabia. Attempts were made to find out the cases of increasing and/or decreasing trend of parasite incidence and to locate any differences between the current study results and the earlier reports.


Pharmacologic enhancement of atrial electrical defibrillation efficacy: role of ibutilide.
The study was designed to identify the influence of ibutilide on activation during atrial fibrillation (AF) and determine its role in enhancing the efficacy of electrical conversion of AF. Vagally-mediated acute AF was induced in 12 anesthetized dogs. In 5 dogs, a cross-shaped epicardial patch containing 16 recording electrodes was placed on the right atrium. In 7 dogs, defibrillation patch electrodes overlying both atria were used to deliver biphasic shocks (50% tilt; 90 microF). Measurements were made at baseline and following ibutilide (0.075 mg/kg bolus followed by 0.075 mg/kg infusion over 10 minutes). Right atrial multisite electrogram recordings revealed significant prolongation in AF cycle length at all sites following ibutilide. In all dogs, AF cycle length increased with ibutilide from 90 +/- 23 to 130 +/- 49 ms (p < 0.005). Whereas, atrial defibrillation threshold decreased from 0.83 +/- 0.5 to 0.53 +/- 0.29 J (p = 0.020). In conclusion, ibutilide prolongs cycle length of canine vagally-mediated acute AF. Furthermore, ibutilide facilitates electrical conversion of AF by lowering energy requirement. Thus, controlled drug infusion in conjunction with electrical defibrillation may be useful for managing AF.


Factors Associated With Latent Tuberculosis Infection Treatment Failure Among Patients With Commercial Health Insurance-United States, 2005-2016.
Approximately 80% of US tuberculosis (TB) cases verified during 2015-2016 were attributed to untreated latent TB infection (LTBI). Identifying factors associated with LTBI treatment failure might improve treatment effectiveness. To identify patients with indicators of isoniazid (INH) LTBI treatment initiation, completion, and failure. We searched inpatient and outpatient claims for International Classification of Diseases (Ninth and Tenth Revisions), National Drug, and Current Procedural Terminology codes. We defined treatment completion as 180 days or more of INH therapy during a 9-month period. We defined LTBI treatment failure as an active TB disease diagnosis more than 1 year after starting LTBI treatment among completers and used exact logistic regression to model possible differences between groups. Among treatment completers, we matched 1 patient who failed treatment with 2 control subjects and fit regression models with covariates documented on medical claims paid 6 months or less before INH treatment initiation. Commercially insured US patients in a large commercial database with insurance claims paid during 2005-2016. (1) Trends in treatment completion; (2) odds ratios (ORs) for factors associated with treatment completion and treatment failure. Of 21 510 persons who began LTBI therapy during 2005-2016, 10 725 (49.9%) completed therapy. Treatment noncompletion is associated with those younger than 45 years, living in the Northeast or South Census regions, and women. Among persons who completed treatment, 30 (0.3%) progressed to TB disease. Diagnoses of rheumatoid arthritis during the 6 months before treatment initiation and being aged 65 years or older (reference: ages 0-24 years) were significantly associated with INH LTBI treatment failure (adjusted exact OR = 5.1; 95% CI, 1.2-28.2; and adjusted exact OR = 5.1; 95% CI, 1.2-25.3, respectively). Approximately 50% of persons completed INH LTBI therapy, and of those, treatment failure was associated with rheumatoid arthritis and persons 65 years or older among a cohort of US LTBI patients with commercial health insurance.


Continuous-flow solar UVB disinfection reactor for drinking water.
Access to safe, reliable sources of drinking water is a long-standing problem among people in developing countries. Sustainable solutions to these problems often involve point-of-use or community-scale water treatment systems that rely on locally-available resources and expertise. This philosophy was used in the development of a continuous-flow, solar UVB disinfection system. Numerical modeling of solar UVB spectral irradiance was used to define temporal variations in spectral irradiance at several geographically-distinct locations. The results of these simulations indicated that a solar UVB system would benefit from incorporation of a device to amplify ambient UVB fluence rate. A compound parabolic collector (CPC) was selected for this purpose. Design of the CPC was based on numerical simulations that accounted for the shape of the collector and reflectance. Based on these simulations, a prototype CPC was constructed using materials that would be available and inexpensive in many developing countries. A UVB-transparent pipe was positioned in the focal area of the CPC; water was pumped through the pipe to allow exposure of waterborne microbes to germicidal solar UVB radiation. The system was demonstrated to be effective for inactivation of Escherichia coli, and DNA-weighted UV dose was shown to govern reactor performance. The design of the reactor is expected to scale linearly, and improvements in process performance (relative to results from the prototype) can be expected by use of larger CPC geometry, inclusion of better reflective materials, and application in areas with greater ambient solar UV spectral irradiance than the location of the prototype tests. The system is expected to have application for water treatment among communities in (developing) countries in near-equatorial and tropical locations. It may also have application for disaster relief or military field operations, as well as in water treatment in areas of developed countries that receive relatively intense solar UVB radiation.


Simultaneous interactions of pyrimidine ring with BeF2 and BF3 in BeF2⋅⋅⋅X-Pyr⋅⋅⋅BF3 complexes: non-cooperativity.
We investigated the mutual interplay between beryllium and boron bonds in the BeF2⋅⋅⋅X-Pyr⋅⋅⋅BF3 complexes (X = CN, F, Cl, Br, H, CH3, OH and NH2, where Pyr and ⋅⋅⋅ denote pyrimidine ring and beryllium and boron bonds, respectively) at the M06-2X/aug-cc-pVDZ level of theory. The results indicate that non-cooperative effects are observed when the two kinds of noncovalent interactions beryllium and boron bonds coexist in the complexes. These effects were studied in terms of the energetic and geometric features of the complexes. Atoms in molecules (AIM) and natural bond orbital (NBO) analyses were also performed to unveil the mechanism of these interactions in the title complexes. The electron-withdrawing/donating substituents decrease/increase the magnitude of the binding energies compared to the unsubstituted BeF2⋅⋅⋅X-Pyr⋅⋅⋅BF3 (X = H) complex. The Esynvalues are in agreement with the geometric features of the complexes. The results stress the importance of the mutual effects between noncovalent interactions involving aromatic systems.


Socio-cultural implications for women's menstrual health in the Pacific Island Countries and Territories (PICTs): a scoping review.
Globally, experiences of menarche and subsequent menstruation are embedded in social and cultural beliefs, norms and practices. Menarche is an important developmental milestone in sexual and reproductive health (SRH) for females. Menarche is intertwined with socio-cultural norms, beliefs and practices, which can impact on women's ability to manage menstruation with dignity. This paper reviews the social and cultural factors that affect women's ability to effectively manage their menstrual health and hygiene (MHH) in Pacific Island Countries and Territories (PICTs). A scoping review was conducted following PRISMA scoping review guidelines and inclusion/exclusion criteria. An online search was conducted for peer-reviewed publications in Medline/OVID; Medline/PubMED; PsycINFO; CINAHL; Scopus and JSTOR, and Google Scholar. A search for grey literature was conducted in Google Scholar and websites of international and local organizations. Experts in the field also contributed additional references. Extracted data were summarised in an Excel spreadsheet. Searches were conducted between May and June, 2019, and then repeated in July, 2020. A total of 11 studies were included; 10 qualitative and one mixed methods study. Studies were conducted in Melanesian (n = 9), Polynesian (n = 1) and Micronesian (n = 1) PICTs. All 11 studies reported elements of societal and personal factors; ten studies reported evidence relating to interpersonal factors; nine studies reported elements relating to environmental factors; and two studies presented evidence linked to biological factors. Managing menstrual health with dignity is challenging for many women and girls because menstruation is associated with menstrual taboos and shame. This review found that the MHH experiences of women in PICTs are affected by social and cultural beliefs, norms and practices. Beliefs, norms and practices about menarche need to be incorporated in SRH planning, programs and education in order to be relevant to diverse village and urban settings.


Cellular and molecular processes leading to embryo formation in sponges: evidences for high conservation of processes throughout animal evolution.
The emergence of multicellularity is regarded as one of the major evolutionary events of life. This transition unicellularity/pluricellularity was acquired independently several times (King 2004). The acquisition of multicellularity implies the emergence of cellular cohesion and means of communication, as well as molecular mechanisms enabling the control of morphogenesis and body plan patterning. Some of these molecular tools seem to have predated the acquisition of multicellularity while others are regarded as the acquisition of specific lineages. Morphogenesis consists in the spatial migration of cells or cell layers during embryonic development, metamorphosis, asexual reproduction, growth, and regeneration, resulting in the formation and patterning of a body. In this paper, our aim is to review what is currently known concerning basal metazoans--sponges' morphogenesis from the tissular, cellular, and molecular points of view--and what remains to elucidate. Our review attempts to show that morphogenetic processes found in sponges are as diverse and complex as those found in other animals. In true epithelial sponges (Homoscleromorpha), as well as in others, we find similar cell/layer movements, cellular shape changes involved in major morphogenetic processes such as embryogenesis or larval metamorphosis. Thus, sponges can provide information enabling us to better understand early animal evolution at the molecular level but also at the cell/cell layer level. Indeed, comparison of molecular tools will only be of value if accompanied by functional data and expression studies during morphogenetic processes.


Relation between gravitational and arm-movement direction in the mechanism of perception in bimanual steering.
This paper presents the effects of the opposing directions of gravity relative to right- and left-arm movement in bimanual steering. We developed a simulated steering system that permits independent left- and right-hand steering and torque presentations on a single axis, and independent measurements of the steering force exerted by each hand. In a steering force measurement experiment, left and right system units were mechanically combined to function as a single steering unit. Measurements of the force exerted by the participants with their left and right hands revealed that in human bimanual steering, the arm moving with gravity exerts a larger steering force than the one moving against gravity. In a steering force discrimination experiment, the system was mechanically configured to provide independence in both the function of the left and right steering units and the presentation of different left- and right-side steering torques. Each participant was then asked whether the steering force was felt to be larger on the left or the right during bimanual steering. The results of this experiment showed no difference between the left and the right arm in the discrimination threshold, but did reveal a perceptual bias in which the forces exerted in arm movements with gravity were perceived as being smaller than the forces exerted against gravity. Furthermore, there was no significant difference between the measured force and the force that would be predicted from the obtained perceptual bias.


Characteristics of memory impairment following lesioning of the basal forebrain and medial septal nucleus in rats.
Memory impairment in rats with lesions of the basal forebrain (BF) and medial septal nucleus (MS) including cell bodies of the cortical and septohippocampal cholinergic systems, respectively, were compared in order to evaluate the functional contribution of the two cholinergic systems to memory. Biochemical assay revealed that lesioning of the BF and MS resulted in marked and selective decreases in both choline acetyltransferase and acetylcholinesterase activities in the cerebral cortex and hippocampus, respectively. Rats with BF lesions exhibited a severe deficit in a passive avoidance task; acquisition of passive avoidance by repeated training was sluggish, and the acquired response was rapidly eliminated in a subsequent extinction test. However, only slight impairment of passive avoidance was observed in rats with MS lesions. Memory impairment in rats with BF or MS lesions was also investigated using two spatial localization tasks, the Morris water task and the 8-arm radial maze task. Both BF and MS lesions elicited a significant impairment in the Morris water task that required reference memory, as demonstrated by an apparent increase in the latency to escape onto a hidden platform in a large water tank. The impairment was much more obvious in the BF-lesioned rats. In contrast, in the radial maze task primarily requiring working memory, rats with lesions of the MS showed severe disruption, exhibiting a marked increase in total errors, a decrease in the number of initial correct responses, and an apparent change in the strategy pattern. However, corresponding changes in the rats with BF lesions were slight. These results suggest that BF lesions may lead to substantial long-term memory impairment while MS lesions may primarily produce short-term or working memory impairment, indicating a qualitatively different contribution of the two cholinergic systems to memory. It is also suggested that these two experimental animal models may be useful for evaluation of therapeutic drugs for senile dementia of the Alzheimer type.


Laser light routing in an elongated micromachined vapor cell with diffraction gratings for atomic clock applications.
This paper reports on an original architecture of microfabricated alkali vapor cell designed for miniature atomic clocks. The cell combines diffraction gratings with anisotropically etched single-crystalline silicon sidewalls to route a normally-incident beam in a cavity oriented along the substrate plane. Gratings have been specifically designed to diffract circularly polarized light in the first order, the latter having an angle of diffraction matching the (111) sidewalls orientation. Then, the length of the cavity where light interacts with alkali atoms can be extended. We demonstrate that a longer cell allows to reduce the beam diameter, while preserving the clock performances. As the cavity depth and the beam diameter are reduced, collimation can be performed in a tighter space. This solution relaxes the constraints on the device packaging and is suitable for wafer-level assembly. Several cells have been fabricated and characterized in a clock setup using coherent population trapping spectroscopy. The measured signals exhibit null power linewidths down to 2.23 kHz and high transmission contrasts up to 17%. A high contrast-to-linewidth ratio is found at a linewidth of 4.17 kHz and a contrast of 5.2% in a 7-mm-long cell despite a beam diameter reduced to 600 μm.


Efficacy analysis of endoscopic treatment of giant gastric gastrointestinal stromal tumors (≥5 cm).
To investigate the safety, feasibility and prognosis of endoscopic treatment of giant (≥5 cm) gastric gastrointestinal stromal tumors (gastric GISTs). Data from patients who underwent surgical resection of nonmetastatic gastric GISTs in our hospital from January 2016 to February 2022 were collected. The patients were divided into an endoscopic group and a laparoscopic group according to the surgical method. The clinical data and tumor recurrence information were compared between the two groups. Eighteen cases were collected in the endoscopic group and sixty-three cases in the laparoscopic group. There were no significant differences in age, gender, tumor diameter, tumor growth site, tumor growth mode, clinical manifestations, risk classification or complication rate between the two groups (P > 0.05). The hospitalization cost, length of postoperative hospital stay and postoperative fasting time of the endoscopic group were less than those of the laparoscopic group, while the operation time was greater than that of the laparoscopic group (P < 0.05). In the endoscopic group, the follow-up was 33.50 ± 19.410 months, and no patients were lost to follow-up. The laparoscopic group was followed up for 59.07 ± 12.964 months, and eleven patients were lost to follow-up. There was no recurrence or metastasis in the two groups during the follow-up. Endoscopic resection of gastric GIST with a diameter ≥5 cm is technically feasible. And it not only achieves a short-term prognosis similar to laparoscopic resection but also has the advantages of rapid postoperative recovery and low cost.


Neurochemical and immunocytochemical studies of serotonin in the Hermissenda central nervous system.
In the preceding paper we showed that serotonin mimics the effects of associative conditioning on Type B photoreceptors of Hermissenda. Here we show that serotonin is present in the Hermissenda central nervous system, and that it is released in a calcium-dependent manner. A large number of serotonergic cell bodies are present in the cerebropleural ganglia (CPG). Cell bodies in the CPG are located in three small, symmetrical clusters. One cluster (2-3 cells) located at the anterior end of the CPG contains a large cell that projects to the buccal ganglion. A second cluster (2-3 cells) is located posterior to the first and near the midline of the nervous system. A third cluster (1-2 cells) was located slightly more posteriorly than the second. Type B photoreceptors and the S/E optic ganglion cell project to a region of the CPG neuropil which is heavily innervated by serotonin immunoreactive fine processes. Since serotonin mimicked the effects of associative conditioning on Type B cells, and is present in an appropriate region of the CPG neuropil, serotonin may mediate some effects of associative conditioning on Type B cells. Results supporting this hypothesis are presented in an accompanying paper.


No adrenergic sensitization of afferent neurons in painful sensory polyneuropathy.
The aim of the present study was to determine (1) if an adrenergic sensitivity of afferent neurons is present in patients with painful polyneuropathy as compared with non-painful polyneuropathy and (2) if there is a correlation between adrenergic sensitisation and the severity of afferent and sympathetic small fiber damage. 10 patients with painful and non painful polyneuropathy and 10 healthy controls were included. The function of small afferent and efferent sympathetic neurons was evaluated. Adrenergic sensitivity of afferent neurons was assessed by cutaneous iontophoresis of norepinephrine. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured. Iontophoresis of norepinephrine did not induce or enhance spontaneous pain or mechanical allodynia, either in painless or painful polyneuropathies. There was no difference in norepinephrine-induced heat hyperalgesia between both neuropathy groups and healthy controls. The response of afferent neurons to norepinephrine was not correlated with the severity of damage to afferent small fibers or efferent sympathetic vasoconstrictor neurons. The results do not support the assumption that in painful polyneuropathies afferent neurons acquire an adrenergic sensitivity after nerve injury and that adrenergic stimulation leads to an exacerbation of spontaneous pain and thermal and mechanical hyperalgesia.


Diagnosis of rotator cuff tears using 3-Tesla MRI versus 3-Tesla MRA: a systematic review and meta-analysis.
To compare the diagnostic accuracy of magnetic resonance imaging (MRI), 2-dimensional magnetic resonance arthrogram (MRA) and 3-dimensional isotropic MRA in the diagnosis of rotator cuff tears when performed exclusively at 3-T. A systematic review was undertaken of the Cochrane, MEDLINE and PubMed databases in accordance with the PRISMA guidelines. Studies comparing 3-T MRI or 3-T MRA (index tests) to arthroscopic surgical findings (reference test) were included. Methodological appraisal was performed using QUADAS 2. Pooled sensitivity and specificity were calculated and summary receiver-operating curves generated. Kappa coefficients quantified inter-observer reliability. Fourteen studies comprising 1332 patients were identified for inclusion. Twelve studies were retrospective and there were concerns regarding index test bias and applicability in nine and six studies respectively. Reference test bias was a concern in all studies. Both 3-T MRI and 3-T MRA showed similar excellent diagnostic accuracy for full-thickness supraspinatus tears. Concerning partial-thickness supraspinatus tears, 3-T 2D MRA was significantly more sensitive (86.6 vs. 80.5 %, p = 0.014) but significantly less specific (95.2 vs. 100 %, p < 0.001). There was a trend towards greater accuracy in the diagnosis of subscapularis tears with 3-T MRA. Three-Tesla 3D isotropic MRA showed similar accuracy to 3-T conventional 2D MRA. Three-Tesla MRI appeared equivalent to 3-T MRA in the diagnosis of full- and partial-thickness tears, although there was a trend towards greater accuracy in the diagnosis of subscapularis tears with 3-T MRA. Three-Tesla 3D isotropic MRA appears equivalent to 3-T 2D MRA for all types of tears.


Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: a randomized, double-blind comparison with atorvastatin alone among Indian patients with dyslipidemia.
To evaluate the efficacy and safety of atorvastatin + hydroxychloroquine fixed-dose combination tablets in comparison with atorvastatin alone in treatment of dyslipidemia. This double-blind, randomized, out-patient study was conducted in 328 patients with primary dyslipidemia having low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL (3.37 mmol/L) to ≤ 250 mg/dL (6.48 mmol/L) and triglycerides ≤ 400 mg/dL (4.52 mmol/L). Eligible patients were randomized to receive either atorvastatin 10 mg (n = 167) or atorvastatin 10 mg + hydroxychloroquine 200 mg (n = 161) for 24 weeks. CTRI/2010/091/006138. To compare percentage change in LDL-C, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to Week 12 and Week 24 between groups. To compare mean change in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), high-sensitivity C-reactive protein (Hs-CRP), and percentage of patients achieving lipid goals at Week 12 and Week 24. At Week 24, percentage reduction in LDL-C (-32.52 [-36.13 to -28.91] vs -39.54 [-43.25 to -35.83]; p = 0.008), TC (-24.41 [-27.10 to -21.72] vs -29.30 [-32.07 to -26.54]; p = 0.013), and non-HDL-C (-30.37 [-33.71 to -27.04] vs -36.76 [-40.18 to -33.33]; p = 0.009) was significantly greater in combination treated patients. Both the treatments showed a significant reduction in triglycerides at Week 24 from baseline, however, this reduction was not statistically significantly different between treatment groups. No significant change in HDL-C was observed in patients from both the treatment groups. At Week 24, change in HbA1c (0.22 [0.07 to 0.37] vs -0.13 [-0.28 to 0.03]; p = 0.002) and FBG was also statistically significant in favor of combination therapy (0.37 [0.07 to 0.67] vs -0.29 [-0.59 to 0.03]; p = 0.003), whereas no statistically significant difference was observed in change in Hs-CRP (p = 0.310). Significantly more patients from the combination group achieved LDL-C and TC goals. Exploratory analysis in patients with pre-diabetes showed development of diabetes in 8 patients (15.09%) from the monotherapy group and 1 patient (1.96%) from the combination group (p = 0.034). Study medications were generally safe and well tolerated. Based on study results and widely reported pleiotropic benefits, hydroxychloroquine could emerge as a potential drug for combination with statins for treatment of dyslipidemia. Long duration studies with larger sample sizes are required to further explore the role of hydroxychloroquine as adjunct to statins in reducing risk of cardiovascular events and prevention of statin-induced diabetes.


Detection of Early Murine Colorectal Cancer by MMP-2/-9-Guided Fluorescence Endoscopy.
Patients with ulcerative colitis are at increased risk for colorectal cancer and endoscopic surveillance is mandatory. Matrix metalloproteinases (MMPs)-2 and -9 activities are increased in malignant colonic mucosa. The aim of the study was to evaluate molecular imaging of MMP-2/-9 by fluorescence endoscopy (FE) for early tumor detection. Colorectal cancer in mice (n = 28) was induced by azoxymethane and dextran sodium sulfate. Twenty-four hours after intravenous injection of a nonpeptidic, Cy5.5-labeled MMP-selective tracer, tumor development was assessed in vivo by white light endoscopy and FE. Topical administration of the tracer was also investigated (after 5 minutes and 24 hours). Colonic tumors were evaluated ex vivo by fluorescence reflectance imaging, immunohistochemistry, Western blot analysis, and zymography. Imaging of MMP-2/-9 expression by FE achieved a significantly higher contrast of the fluorescence signal in colonic adenomas compared with the adjacent nonmalignant mucosa (P < 0.001). Fluorescence reflectance imaging detected a significantly higher tracer uptake in adenoma compared with healthy mucosa (P < 0.001) and revealed a tumor size-dependent increase of tracer uptake (P < 0.01). Topical tracer administration did not facilitate tumor detection. Immunohistochemistry, Western blot analysis, and zymography indicated higher levels of MMP-2 and -9 in high-grade dysplasia and pT1 tumors ex vivo. MMP-2/-9 expression was significantly increased in colorectal neoplasia. FE allows direct visualization of a prognostic parameter (here MMP-2/-9) on a molecular level and may improve the characterization of colorectal lesions and the adenoma detection rate in the future.


How fast can a naturopathic medicine cause skin burn? a case report of garlic burn.
This paper presents a case in which a chemical burn resulted from the use of garlic as a naturopathic medicine for knee pain.


[Twenty-four hour blood pressure monitoring and condition of microcirculation in geriatric patients with hypertension].
Features of a daily structure of blood pressure elderly patients with isolated systolic or systolo-diastolic essential hypertension are shown, features of microcirculation in conjunctivae vessels are revealed depending on essential hypertension from, attempt to estimate daily average parameters of blood pressure elderly patients with isolated systolic or systolo-diastolic essential hypertension is made.


Transient non-coeliac gluten sensitivity (NCGS) with markedly reduced villous height/crypt depth ratio.
There is no confident evidence in the current literature to show or demonstrate that non-coeliac gluten sensitivity (NCGS) exclusively presents with mild or nearly normal duodenal mucosal abnormality. Gluten sensitive patients with negative serology and severe mucosal changes are labelled with the term seronegative coeliac disease (SNCS). There might be at least some overlap between NCGS and SNCD. Transient gluten sensitivity with severe mucosal changes without CD have been previously reported like in our case.


The application of the convective diffusion model and the film equilibrium model to surfactant-facilitated dissolution of gliclazide.
Gliclazide is practically insoluble in water, and has low dissolution rate. Therefore, it was of interest to improve its dissolution rate using anionic and cationic surfactants. The intrinsic dissolution rates of gliclazide in solutions of sodium dodecyl sulfate (SDS) and in solutions of tetradecyltrimethyl ammonium bromide (TDTMAB) were measured using the rotating disk method to study the convective diffusion transport of drug-loaded micelles. Two different approaches were applied to the experimental data; the convective diffusion model and the film equilibrium model. The two approaches are based on the same fundamental assumptions differing only in their interpretation of the diffusional boundary layer. The results obtained from the film equilibrium model were less satisfactory, and in case of TDTMAB the model was inapplicable (negative diffusion coefficient). While excellent results were obtained from the convective diffusion model. The free solute diffusion coefficient (D(s)) obtained experimentally was 2.47 x 10(-5) cm(2)/s, and the diffusion coefficient of the drug-loaded SDS micelle (D(sm)) estimated was 1.74 x 10(-6) cm(2)/s. The drug-loaded SDS micelle radius was 14 A. The thickness of the diffusional boundary layer was 54 and 22 microm for the free solute and the drug-loaded SDS micelle, respectively. TDTMAB showed lower effect in improving the dissolution rate of gliclazide than SDS. The drug-loaded TDTMAB micelle diffusion coefficient was 1.03 x 10(-6) cm(2)/s. The radius of the drug-loaded TDTMAB micelle and the boundary layer thickness were 24 A and 19 microm, respectively.


A robust method for detection of linear and nonlinear interactions: application to renal blood flow dynamics.
We have developed a method that can identify switching dynamics in time series, termed the improved annealed competition of experts (IACE) algorithm. In this paper, we extend the approach and use it for detection of linear and nonlinear interactions, by employing histograms showing the frequency of switching modes obtained from the IACE, then examining time-frequency spectra. This extended approach is termed Histogram of improved annealed competition of experts-time frequency (HIACE-TF). The hypothesis is that frequent switching dynamics in HIACE-TF results are due to interactions between different dynamic components. To validate this assertion, we used both simulation examples as well as application to renal blood flow data. We compared simulation results to a time-phase bispectrum (TPB) approach, which can also be used to detect time-varying quadratic phase coupling between various components. We found that the HIACE-TF approach is more accurate than the TPB in detecting interactions, and remains accurate for signal-to-noise ratios as low as 15 dB. With all 10 data sets, comprised of volumetric renal blood flow data, we also validated the feasibility of the HIACE-TF approach in detecting nonlinear interactions between the two mechanisms responsible for renal autoregulation. Further validation of the HIACE-TF approach was achieved by comparing it to a realistic mathematical model that has the capability to generate either the presence or the absence of nonlinear interactions between two renal autoregulatory mechanisms.


Long-Term Outcomes of StopLoss Jones Tubes for Epiphora in Patients With Early or Multiple Loss of Lester Jones Tubes.
Extrusion is the most common cause of failure in conventional Lester Jones tubes (LJTs). StopLoss Jones tubes (SLJTs) with distal flange are designed to reduce this complication. This study compared the survival of SLJTs with their prior LJTs and control patients with LJTs-only. Retrospective review of consecutive LJT or SLJT insertion between January 2014 and December 2016. Twenty-eight eyes of 23 patients had 31 SLJTs. Before their SLJTs, these patients had 116 cumulative failed LJTs. Forty-seven eyes of 34 patients had 59 LJTs only. Fifty-two percent of SLJT group and 18% of LJT-only group had complex medial canthal conditions (p = 0.003). Compared to their previous LJTs, the SLJTs were less likely to extrude (3% SLJT vs. 64% prior LJT, p < 0.0001); there was no statistical difference in rates of sinking in (26% SLJT vs. 13% prior LJT, p = 0.0964). The median survival of LJTs in those who went on to have a SLJT was 3.5 months. SLJT insertion significantly lengthened the median survival to 26 months (p < 0.0001), comparable to the LJT-only group (25.5 months, p = 0.45). While extrusion was also the most common complication in the LJT-only group, this occurred only in 20% of eyes; tube failure from sink-in occurred in 14% of eyes. SLJTs, in patients prone to multiple or early prior LJT losses, can be used to rescue this group and allow them to regain a similar survival curve to the less complicated LJT-only group. Rates of tube extrusion are significantly reduced with the use of SLJT.


A "smart needle" to facilitate difficult vascular access in pediatric patients.
A new Doppler probe inside a needle was evaluated in a group of infants and children to assess its suitability for subclavian venous access. While the efficient use of this device required learning a new technique, we found the device useful to accurately locate the subclavian vein and differentiate it from the artery in all patients weighing more than 3 kg. This device will be most helpful in cases of difficult access, eg, scar from previous access, obesity, or edema.