Enhancing p-Type Thermoelectric Performances of Polycrystalline SnSe via Tuning Phase Transition Temperature.
SnSe emerges as a new class of thermoelectric materials since the recent discovery of an ultrahigh thermoelectric figure of merit in its single crystals. Achieving such performance in the polycrystalline counterpart is still challenging and requires fundamental understandings of its electrical and thermal transport properties as well as structural chemistry. Here we demonstrate a new strategy of improving conversion efficiency of bulk polycrystalline SnSe thermoelectrics. We show that PbSe alloying decreases the transition temperature between Pnma and Cmcm phases and thereby can serve as a means of controlling its onset temperature. Along with 1% Na doping, delicate control of the alloying fraction markedly enhances electrical conductivity by earlier initiation of bipolar conduction while reducing lattice thermal conductivity by alloy and point defect scattering simultaneously. As a result, a remarkably high peak ZT of ∼1.2 at 773 K as well as average ZT of ∼0.5 from RT to 773 K is achieved for Na0.01(Sn1-xPbx)0.99Se. Surprisingly, spherical-aberration corrected scanning transmission electron microscopic studies reveal that NaySn1-xPbxSe (0 < x ≤ 0.2; y = 0, 0.01) alloys spontaneously form nanoscale particles with a typical size of ∼5-10 nm embedded inside the bulk matrix, rather than solid solutions as previously believed. This unexpected feature results in further reduction in their lattice thermal conductivity.


Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience.
Migraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption. Patients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13-16 of the drug holiday; 4) in weeks 9-12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period. This study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 ± 6.3 at the end of the drug holiday to 7.8 ± 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 ± 6.3 MMD vs. 7.5 ± 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life. Reinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.


Efficient enhancement of the visible-light absorption of cyclometalated Ir(III) complexes triplet photosensitizers with Bodipy and applications in photooxidation and triplet-triplet annihilation upconversion.
We report molecular designing strategies to enhance the effective visible-light absorption of cyclometalated Ir(III) complexes. Cationic cyclometalated Ir(III) complexes were prepared in which boron-dipyrromethene (Bodipy) units were attached to the 2,2'-bipyridine (bpy) ligand via -C≡C- bonds at either the meso-phenyl (Ir-2) or 2 position of the π core of Bodipy (Ir-3). For the first time the effect of π conjugating (Ir-3) or tethering (Ir-2) of a light-harvesting chromophore to the coordination center on the photophysical properties was compared in detail. Ir(ppy)2(bpy) (Ir-1; ppy = 2-phenylpyridine) was used as model complex, which gives the typical weak absorption in visible range (ε < 4790 M(-1) cm(-1) in region > 400 nm). Ir-2 and Ir-3 showed much stronger absorption in the visible range (ε = 71,400 M(-1) cm(-1) at 499 nm and 83,000 M(-1) cm(-1) at 527 nm, respectively). Room-temperature phosphorescence was only observed for Ir-1 (λ(em) = 590 nm) and Ir-3 (λ(em) = 742 nm). Ir-3 gives RT phosphorescence of the Bodipy unit. On the basis of the 77 K emission spectra, nanosecond transient absorption spectra, and spin density analysis, we proposed that Bodipy-localized long-lived triplet excited states were populated for Ir-2 (τT = 23.7 μs) and Ir-3 (87.2 μs). Ir-1 gives a much shorter triplet-state lifetime (0.35 μs). Complexes were used as singlet oxygen ((1)O2) photosensitizers in photooxidation. The (1)O2 quantum yield of Ir-3 (ΦΔ = 0.97) is ca. 2-fold of Ir-2 (ΦΔ = 0.52). Complexes were also used as triplet photosensitizer for TTA upconversion; upconversion quantum yields of 1.2% and 2.8% were observed for Ir-2 and Ir-3, respectively. Our results proved that the strong absorption of visible light of Ir-2 failed to enhance production of a triplet excited state. These results are useful for designing transition metal complexes that show effective strong visible-light absorption and long-lived triplet excited states, which can be used as ideal triplet photosensitizers in photocatalysis and TTA upconversion.


Pattern of Visual-Motor Integration, Visual Perception, and Fine Motor Coordination Abilities in Children Being Assessed for Fetal Alcohol Spectrum Disorder.
Motor skill assessment is part of the fetal alcohol spectrum disorder (FASD) multidisciplinary assessment. Some clinicians opt to exclude assessment of the subcomponents of visual-motor integration (visual perception and motor coordination), on the assumption that challenges will be revealed based on the assessment of visual-motor integration. The objective is to describe the visual-motor integration, visual perception, and fine motor coordination pattern of abilities in children with confirmed prenatal alcohol exposure being assessed for fetal alcohol spectrum disorder. This cross-sectional study included 91 children (65 males; mean age: 10 years, 6 months SD = 2 years, 10 months) undergoing assessment for FASD. Friedman and Wilcoxon statistics were used to compare mean visual-motor integration, visual perception, and fine motor coordination percentiles from the Beery-Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition (Beery-6). Children being assessed for FASD (n = 91) had the highest normative scores in visual perception, followed by visual-motor integration and fine motor coordination (mean percentiles (SD): 35.9 (24.9), 20.6 (18.3), and 13.8 (15.5), respectively) (χ 2 distribution = 46.909, p ≤ 0.001). Children being assessed for FASD experience more challenges with fine motor coordination compared with visual-motor integration and visual perception tasks. This pattern differs from the pattern established for the general population in which tasks that require visual-motor integration are more challenging than tasks that isolate visual perception and fine motor coordination. These results suggest that fine motor coordination should be included in FASD diagnostic assessments and considered as an area for intervention.


Involvement of gut microbiota in the association between gastrointestinal motility and 5‑HT expression/M2 macrophage abundance in the gastrointestinal tract.
Serotonin (5‑hydroxytryptamine; 5‑HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5‑HT expression and macrophage abundance in the GI tract was examined. Germ‑free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen‑free mice and their GI tissues were evaluated 4 weeks later. The expression of 5‑HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution. The numbers of 5‑HT‑positive endocrine cells and muscularis MR‑positive macrophages were significantly increased in the upper GI and colon of GF mice subjected to fecal transplantation (FT) compared with control GF mice without FT. GITT was significantly decreased in GF mice subjected to FT compared with GF mice without FT, and negatively correlated with the numbers of 5‑HT‑positive cells in the upper GI and muscularis MR‑positive macrophages throughout the GI tract. The numbers of 5‑HT‑positive endocrine cells and muscularis MR‑positive macrophages were significantly correlated throughout the GI tract. The present results suggest that the gut microbiota is involved in the association between accelerated GI motility and induction of the 5‑HT/muscularis MR‑positive macrophage axis in the GI tract.


First Report of Colletotrichum fioriniae Causing Anthracnose on Rhododendron delavayi in China.
Rhododendron delavayi Franch, a member of Ericaceae family, is globally famous for its garden flowers with significant ornamental value (Liu et al., 2020). In July 2020 and 2021, a disease survey of R. delavayi groves was conducted in Baili Azalea Forest Area (N27°10'-27°20', E 105°04'-106°04'). We arbitrarily selected an area with around 280 R. delavayi trees covering 2.5 hectares in R. delavayi grove where 20-35% of leaves showed symptoms of anthracnose. Typical symptoms included elliptical to irregularly shaped brown lesions on leaves and masses of black dots clustered on it. About 30 pieces of leaves with anthracnose lesions were collected. A few black dots were picked from the lesions with a sterilized needle, plated on water agar and incubated at 25℃ for 12 h to observe spore germination (Fang, 2007). Then the germinated spores were transferred onto PDA medium for further purification and morphological observation. Fourteen single-spore isolates with similar morphology were obtained. The surface of the colony was white or gray and spongy; the edge was smooth; and the back side was pinkish brown after 7 days of growth on PDA. Conidia were spindle-shaped, transparent, 11.1-16.6×3.6-4.9 μm (n=50). Appressorium from conidia was nearly ovate or proximate, brown or dark brown in color, 4.3-10.3 ×3.2-7.6 μm (n=50). These characteristics are consistent with Colletotrichum fioriniae reported by Shivas and Tan (2009). DNA was extracted from a representative isolate MYDJ12. The internal transcribed spacer region (ITS), the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-tubulin (TUB), actin (ACT), and chitin synthase 1 (CHS-1) genes were amplified using primer pairs described by Damm et al. (2012). The sequences were deposited in GenBank with accession number MW692854 (ITS), MW727518 (GAPDH), MW727519 (TUB2), MW727520 (ACT), and MW727521 (CHS-1). BLASTN searches of the ITS, GADPH, TUB2, ACT and CHS-1 genes revealed 100% (540/540 nucleotides), 100% (254/254 nucleotides), 99.38% (4488/491 nucleotides), 98.77% (242/245 nucleotides) and 100% (282/282 nucleotides) homology with those of C. fioriniae CBS:128517T in GenBank (NR_111747, JQ948622, JQ949943, JQ949613 and JQ948953 respectively). The phylogenetic tree showed the isolate MYDJ12 to cluster with C. fioriniae CBS:128517T. Finally, two-year old R. delavayi plants (n=5) were inoculated by wounding with a syringe needle and placing 10 μL of spore suspension (106 spores per mL) of the isolate MYDJ12 on three leaves per plant. Control leaves were inoculated with sterile water. The experiment was conducted twice. Inoculated leaves were wrapped in parafilm tape and then the plants were placed in a greenhouse at 25°C with high relative humidity (90 to 95%). Seven days after incubation, brown lesions appeared, similar to those observed in the grove. Black dots clustered on the lesions after 15 days. Re-isolation was conducted 20 days after inoculation. From all the five inoculated plants, similar symptoms were observed, and the same pathogen was re-isolated. One of the isolates was selected for morphological observation and multi-gene (ITS, GAPDH, ACT, TUB2 and CHS-1) analysis indicated the reisolated fungus to be C. fioriniae. No fungal pathogens were isolated from mock inoculated plants. This study can provide effective management and useful information for the control of this disease on R. delavayi in Baili Azalea Forest Area. References: Damm, U., et al. 2012. Stud Mycol 73: 37. Fang, Z. D. 2007. Research Methods of Plant Diseases (Third edition). China Agriculture Press. Liu, J., et al. 2020. Mitochondrial DNA B 5:37. Shivas, R, G; Tan, Y, P. 2009. Fungal Divers 39:111.


[Reliability of digital subtraction angiocardiography for the evaluation of left ventricular function and physical stress].
The reliability of determinations of left ventricular dimensions from digital subtraction angiocardiographies during exercise using intravenous injection of contrast material was proved in 20 patients. All angiocardiograms could be analyzed qualitatively and quantitatively only by means of the time-interval-difference (TID-) mode. Compared with other mask modes the superiority of the TID-mode results from the close temporal relationship between mask and contrasted frame. Thus, changes in position and brightness of the background structures are small, and left ventricular contours can be determined accurately despite intense respiratory movements. The intra-observer variability of determinations of end-diastolic and end-systolic volumes was +/- 12 ml (i.e. 7.5% of the mean value), corresponding inter-observer variability was +/- 24 ml (i.e. 17% of the mean value), respectively. Intra-observer deviation in determining ejection fraction was 2.8% (i.e. 4.5% of the mean value). The intra-observer variability in determining left ventricular axes was basal +/- 0.40 cm (i.e. 7% of the mean value), equatorial +/- 0.73 cm (i.e. 13% of the mean value) and apical +/- 0.34 cm (i.e. 8% of the mean value). Deviations of corresponding circumferential fiber shortening rates were basal +/- 0.22 s-1 (i.e. 14% of the mean value), equatorial +/- 0.32 s-1 (i.e. 22% of the mean value), and apical +/- 0.18 s-1 (i.e. 13% of the mean value). The results show that left ventricular dimensions can be determined accurately from intravenous angiocardiograms during exercise using digital subtraction angiocardiography.


Rho GTPases in A549 and Caco-2 cells dominating the endocytic pathways of nanocarbons with different morphologies.
Endocytosis of nanomaterials is the first step of nano-bio interaction and current regulation is mostly by nanomaterials but seldom by intracellular signaling proteins. Herein, we synthesized tubular nanocarbon (oxMWCNT) and lamellar-like nanocarbon (oxGRAPHENE) and formulated their aqueous dispersion. A549 and Caco-2 cells were selected as the models of tumor and intestinal epithelial cells, respectively. After knocking down three members of Rho GTPases (Cdc42, Rac1, RhoA) in these two cell lines, their silencing effects on the uptake pathways of nanomaterials with different morphologies were investigated. An unexpected finding was that the knock-down led to opposite uptake trends in different types of cells. The endocytosis of carbon nanomaterials increased in Caco-2 cells when Rho GTPases were inactivated, while that in A549 cells decreased. For nanomaterials with different shapes, the involved GTPase member of Rho family, or regulating protein molecule, was different. Concretely, Cdc42 and Rac1 were involved in oxMWCNT endocytosis, while all three GTPases participated in oxGRAPHENE internalization. More interestingly, such difference induced different uptake pathways, namely, the cellular uptake of oxMWCNT was clathrin-mediated and oxGRAPHENE was caveolin-modulated, both with the involvement of dynamin. In conclusion, this study provides new insights for the potential intervention in nano-bio interplay.


[The problem of viral hepatitis C in the Russian Federation].
The incidence of chronic viral hepatitides (CVH) has increased 2.2-fold in the Russian Federation over the past decade. This increase is mainly determined by an almost threefold rise in the incidence of chronic hepatitis C (CHC): from 12.9 in 1999 to 39.1 per 100,000 population in 2012. The calculated data of hepatitis C burden in the Russian Federation show that in 2010 the total medical and social losses and expenses associated with hepatitis C and its implications were 48.47 billion rubles or 0.108% of the gross domestic product, the direct medical costs were 17.1 billion (35.28%) rubles, GDP losses were 26.05 billion (53.75%) rubles, and the disability payments were 5.32 billion (10.97%) rubles. The patients (mean age 45 years) with liver cirrhosis (LC) were 15.2% in the structure of the CHC patients (mean age 37 years) admitted to Moscow infectious diseases hospitals in 2010. Analysis of the regional registers of the Russian Federation, the proportion of patients with LC among those with CHC was 18%. The existing forms for recording morbidity and mortality from poor CHC outcomes cannot significantly estimate the true disease stage distribution of patients and hepatitis C-associated disability and mortality rates. In this connection, it is necessary to introduce a federal register and to change recording forms for patients with viral hepatitides. Standard interferon, pegylated interferon alpha 2a and pegylated alpha 2b, and the HCV protease inhibitors telaprevir, boceprevir, and simeprevir have been registered for the treatment of hepatitis C in the Russian Federation.


Deformation and collapse of microtubules on the nanometer scale.
We probe the local mechanical properties of microtubules at the nanometer scale by radial indentation with a scanning force microscope tip. We find a linear elastic regime that can be described by both thin-shell theory and finite element methods, in which microtubules are modeled as hollow tubes. We also find a nonlinear regime and catastrophic collapse of the microtubules under large loads. The main physics of protein shells at the nanometer scale shows simultaneously aspects of continuum elasticity in their linear response, as well as molecular graininess in their nonlinear behavior.


The yin and yang of VEGF and PEDF: multifaceted neurotrophic factors and their potential in the treatment of Parkinson's Disease.
Over the last few decades, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) have emerged as multifaceted players in not only the pathogenesis, but potential treatment, of numerous diseases. They activate diverse intracellular signaling cascades known to have extensive crosstalk, and have been best studied for their effects in cardiology and cancer biology. Recent work with the two factors indicates that the activity of one growth factor is often directly related to the action of the other. Their respective neuroprotective effects, in particular, raise important questions regarding the treatment of neurodegenerative disorders, including Parkinson's disease.


Catalytic Asymmetric Construction of Axially Chiral Indole-Based Frameworks: An Emerging Area.
Axially chiral indole-based frameworks have been recognized as a class of important five-membered heterobiaryls and developing catalytic asymmetric approaches for constructing these frameworks in an enantioselective manner is highly desirable. In recent years, synthetic chemists have paid much attention to this research field, and rapid developments have occurred. At this point, a range of axially chiral indole-based scaffolds have been constructed via various catalytic asymmetric reactions based on different strategies. Thus, the catalytic asymmetric construction of axially chiral indole-based frameworks has become an emerging area. This minireview summarizes the rapid advances in this field and gives some insights into future developments, which will help this research field to thrive.


Pregnancy and Waldmann disease.
We present a case of a woman with intestinal lymphangiectasia and pregnancy. She had been treated with albumin transfusions beginning from the age of 2 years. No major complications were caused to the pregnancy. During pregnancy she was given albumin transfusions at regular intervals, while measuring total proteins, albumin and calcium concentrations in the serum. Due to the increasing needs in proteins as the pregnancy went on, the interval between each transfusion went decreasing. Finally, at 39 weeks of gestation she gave birth by cesarean section due to placenta previa to a healthy female fetus. A worsening of hypoproteinemia and edema was noted during puerperium and lactation. Weaning improved her clinical status. The baby was followed by pediatricians and found her in good health. Summing up, normal pregnancy is compatible with the condition. A strict maternal and fetal care during pregnancy and puerperium is recommended.


Pulmonary clearance of intratracheally administered 63Ni3S2 in strain A/J mice.
The pulmonary clearance of particulate 63Ni3S2 was evaluated in strain A/J mice following the intratracheal instillation of 3 microCi of 63Ni3S2 (1.66 micron, mass median diameter). Lung and tissue burdens were determined from serially sacrificed animals using scintillation counting techniques. Lung clearance over the 35-day observation period could be separated into two distinct components with initial and final phase biological half-times corresponding to 1.2 and 12.4 days, respectively. Radioactivity was detected in the blood, liver, kidney, and femur within 4 hr, and was eliminated at rates comparable to that in the lung. Excretion involved primarily urinary (60% of dose eliminated) but also fecal (40% of dose eliminated) pathways. The data are consistent with the relatively rapid translocation, solubilization, and elimination of particulate 63Ni3S2 from the body.


Predictors of upper gastrointestinal bleeding in patients with schistosomal periportal fibrosis.
A case-control study was conducted between 1985 and 1987 in the Gezira-Managil area of central Sudan to assess the major predictors of haematemesis. Eighty-four patients who had suffered at least one attack of oesophageal bleeding and had schistosomal periportal fibrosis demonstrated by ultrasonography were compared with 173 subjects without bleeding but with ultrasonographic evidence of periportal fibrosis. A splenic longitudinal dimension of more than 11 cm, periportal fibrosis worse than grade I and varices more than grade I were independently associated with a significant risk of variceal bleeding. Age, sex, presence of a palpable liver and portal vein diameter were not associated with a significant risk of bleeding after adjustment for potential confounding variables. Factors identified in this study could be helpful in the prophylactic management of patients with complicated schistosomiasis.


Exploring the evolution of nonverbal synchrony in psychotherapy: The idiographic perspective provides a different picture.
Objectives: A methodological obstacle for the assessment of psychotherapy process concerns the compatibility between nomothetic versus idiographic approaches. Using quantitative methodology at an idiographic level, we seek to narrow this gap for the special case of nonverbal synchrony in psychotherapy dyads.Methods: Using quantitative idiographic process analysis (QUIPA), we combined the assessments of nonverbal synchrony-the coordination of patient's and therapist's body-movement-quantified with motion energy analysis (MEA), patient- and therapist session-reports, and patient's self-reports of symptomatology into multivariate time-series of psychotherapy process across the course of N = 12 dyadic psychotherapies with a total of N = 150 sessions. Adopting both mixed models as well as vector auto regressive models (VAR) to time-series, we aimed to extend previous results assessed in a randomized sample by exploring the evolution of nonverbal synchrony in psychotherapy dyads across time.Results: Aggregated idiographic data revealed that nonverbal synchrony was different from findings based on a previously reported nomothetic account: Associations with session-level outcome were weaker and did not replicate cross-sectional analyses.Conclusions: The application of idiographic assessments may help broadening our conception of synchrony in psychotherapy and also reminds us that ergodicity is not necessarily the usual case, but one of many possibilities.


Familial HDL deficiency characterized by hypercatabolism of mature apoA-I but not proapoA-I.
We have previously described patients with familial high density lipoprotein (HDL) deficiency (FHD) having a marked reduction in the plasma concentration of HDL cholesterol and apolipoprotein (apo) A-I but lacking clinical manifestations of Tangier disease or evidence of other known causes of HDL deficiency. To determine whether FHD in these individuals was associated with impaired HDL production or increased HDL catabolism, we investigated the kinetics of plasma apoA-I and apoA-II in two related FHD patients (plasma apoA-I, 17 and 37 mg/dL) and four control subjects (apoA-I, 126+/-18 mg/dL, mean+/-SD) by using a primed constant infusion of deuterated leucine. Kinetic analysis of plasma apolipoprotein enrichment curves demonstrated that mature plasma apoA-I production rates (PRs) were similar in patients and control subjects (7.9 and 9.1 versus 10.5+/-1.7 mg x kg[-1] x d[-1]). Residence times (RTs) of mature apoA-I were, however, significantly less in FHD patients (0.79 and 1.66 days) compared with controls (5.32+/-1.05 days). Essentially normal levels of plasma proapoA-I (the precursor protein of apoA-I) in FHD patients were associated with normal plasma proapoA-I PRs (7.8 and 10.4 versus 10.9+/-2.6 mg x kg[-1] x d[-1]) and proapoA-I RTs (0.18 and 0.15 versus 0.16+/-0.03 day). The RTs of apoA-II were, however, less in patients (3.17 and 2.92 days) than control subjects (7.24+/-0.71 days), whereas the PRs of apoA-II were similar (1.8 and 1.9 versus 1.7+/-0.2 mg x kg[-1] x d[-1]). Increased plasma catabolism of apoA-II in FHD patients was associated with the presence in plasma of abnormal apoA-II-HDL (without apoA-I). These results demonstrate that FHD in our patients is characterized, like Tangier disease, by hypercatabolism of mature apoA-I and apoA-II, but unlike Tangier disease, by essentially normal plasma catabolism and concentration of proapoA-I.


The ontogeny of blood cells, complement, and immunoglobulins in 3- to 12-week-old 15I5-B congenic white Leghorn chickens.
Six partially developed line 15I5-B congenic White Leghorn chicken strains were used to investigate age and B haplotype effects on hematocrit, total and differential leukocyte counts, hemolytic complement, immunoglobulins, and body weights. The .C-12 line had the lowest hematocrit values throughout the study. The .15I-5 line always had the highest mean hematocrit value and differed from the .C-12 and .P-13 lines at 3, 8, and 12 weeks, as well as lines .N-15 and .6-2 at 12 weeks. Ontogenically, the total leukocyte, hemolytic complement, immunoglobulins, and body weight values increased after 3 weeks in all lines. Lymphocytes were the predominant leukocyte after 3 weeks in all lines studied. At 12 weeks, the .C-12 line had the highest total leukocytes, heterophils, lymphocytes, and monocytes among the lines studied. The .6-2 line had a significantly higher hemolytic complement level than the .P-13 or the .C-12 line at all 3 ages, and at 12 weeks it also differed from the .7-2 line. The lines were found to be comparable for immunoglobulin classes M and G. In this study the line 15I5-B congenic lines differ for the traits of hematocrit and hemolytic complement level, and the results suggest the difference may be determined by genes in the B complex.


Angiotensin II receptor blocker telmisartan: effect on blood pressure profile and left ventricular hypertrophy in patients with arterial hypertension.
In this open-label, non-comparative study, the anti-hypertensive efficacy and effect on left ventricular hypertrophy (LVH) of 24 weeks' treatment with once-daily telmisartan 40-80 mg was evaluated in 24 patients with mild-to-moderate hypertension and LVH. Patients were titrated to the higher dose of study drug at week 4 if they did not achieve blood pressure normalization (i.e. systolic blood pressure [SBP]/diastolic blood pressure [DBP] remained > or = 140/90 mmHg). The anti-hypertensive action of telmisartan was assessed using clinic cuff measurements and 24-h ambulatory blood pressure monitoring, and left ventricular mass index (LVMI) was determined by two-dimensional echocardiography at baseline and after 24 weeks of therapy. Telmisartan significantly reduced mean 24-h, daytime and night-time SBP and DBP compared with baseline after 12 and 24 weeks of therapy. Target blood pressure levels, defined as SBP/DBP < 140/90 mm Hg, were achieved in 16 (69.6%) patients at the end of the treatment period. After 24 weeks of telmisartan treatment, LVMI decreased from 151.6 +/- 5.4 to 135.1 +/- 5.9 g/m2. In conclusion, anti-hypertensive treatment with telmisartan for 24 weeks produced significant reductions in blood pressure and regression of LVH, as assessed by LVMI, in patients with hypertension and LVH.


Emergency appendectomy in a patient with Eisenmenger's syndrome.
For the successful management of an emergency appendectomy and abscess drainage in an Eisenmenger's patient with diffuse peritonitis, it may be preferable to use general anesthesia with awake intubation. Epidural anesthesia is commonly combined with this anesthetic management for emergency abdominal surgery. However, the combination of topical anesthesia with epidural anesthesia should be avoided for fear of toxicity of local anesthetics in a patient with complications due to Eisenmenger's syndrome.


C-terminal extension of calmodulin-like 3 protein from Oryza sativa L.: interaction with a high mobility group target protein.
A large number of calmodulin-like (CML) proteins are present in plants, but there is little detailed information on the functions of these proteins in rice (Oryza sativa L.). Here, the CML3 protein from rice (OsCML3) and its truncated form lacking the C-terminal extension (OsCML3m) were found to exhibit a Ca2+-binding property and subsequent conformational change, but the ability to bind the CaM kinase II peptide was only observed for OsCML3m. Changes in their secondary structure upon Ca2+-binding measured by circular dichroism revealed that OsCML3m had a higher helical content than OsCML3. Moreover, OsCML3 was mainly localized in the plasma membrane, whereas OsCML3m was found in the nucleus. The rice high mobility group B1 (OsHMGB1) protein was identified as one of the putative OsCML3 target proteins. Bimolecular fluorescence complementation analysis revealed that OsHMGB1 bound OsCML3, OsCML3m or OsCML3s (cysteine to serine mutation at the prenylation site) in the nucleus presumably through the methionine and phenylalanine-rich hydrophobic patches, confirming that OsHMGB1 is a target protein in planta. The effect of OsCML3 or OsCML3m on the DNA-binding ability of OsHMGB1 was measured using an electrophoretic mobility shift assay. OsCML3m decreased the level of OsHMGB1 binding to pUC19 double-stranded DNA whereas OsCML3 did not. Taken together, OsCML3 probably provides a mechanism for manipulating the DNA-binding ability of OsHMGB1 in the nucleus and its C-terminal extension provides an intracellular Ca2+ regulatory switch.


Inertial range statistics of the entropic lattice Boltzmann method in three-dimensional turbulence.
We present a quantitative analysis of the inertial range statistics produced by entropic lattice Boltzmann method (ELBM) in the context of three-dimensional homogeneous and isotropic turbulence. ELBM is a promising mesoscopic model particularly interesting for the study of fully developed turbulent flows because of its intrinsic scalability and its unconditional stability. In the hydrodynamic limit, the ELBM is equivalent to the Navier-Stokes equations with an extra eddy viscosity term. From this macroscopic formulation, we have derived a new hydrodynamical model that can be implemented as a large-eddy simulation closure. This model is not positive definite, hence, able to reproduce backscatter events of energy transferred from the subgrid to the resolved scales. A statistical comparison of both mesoscopic and macroscopic entropic models based on the ELBM approach is presented and validated against fully resolved direct numerical simulations. Besides, we provide a second comparison of the ELBM with respect to the well-known Smagorinsky closure. We found that ELBM is able to extend the energy spectrum scaling range preserving at the same time the simulation stability. Concerning the statistics of higher order, inertial range observables, ELBM accuracy is shown to be comparable with other approaches such as Smagorinsky model.


Early Elevation of Thioredoxin-1 Serum Levels Predicts 28-Day Mortality in Patients with Sepsis.
Sepsis is the leading cause of death in critically ill patients, and the prevention of which requires precise outcome prediction and early intervention. We evaluated the prognostic prediction value of serum thioredoxin-1 (Trx-1) as an anti-inflammatory factor in patients with sepsis. As a prospective study, patients with sepsis admitted to the intensive care unit (ICU) of our hospital during 2020 were recruited. Medical history collection, sequential organ failure assessment (ΔSOFA), and laboratory tests were performed within 24 h of admission. Serum levels of Trx-1 and other inflammatory biomarkers were detected with samples dynamically collected before, during, and after septic shock. Patients were categorized as survivors and non-survivors according to survival status on day 28. Correlation between Trx-1 and other sepsis-associated parameters as well as the correlation of Trx-1 and other sepsis-associated parameters with 28-day mortality were evaluated. Prognostic factors were identified by Cox regression analyses. A total of 187 patients were recruited. Serum Trx-1 level was positively correlated with inflammatory factors (interleukin-6, C-reactive protein, procalcitonin) and index of sepsis severity (ΔSOFA score, partial pressure of oxygen/fraction of inspired oxygen), all of which were significantly higher in non-survivors than survivors. While Trx-1 level at different timepoints and its evolution over time significantly differed between survivors and non-survivors, the initial Trx-1 level outperformed the other parameters in predicting 28-day survival. With 38.27 ng/mL as the cutoff value, serum Trx-1 predicted 28-day survival with optimal sensitivity and specificity. Early increases in serum levels of Trx-1 can predict 28-day mortality in sepsis patients in the ICU.


Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice.
We recently developed a mouse model of appetitive operant aggression and reported that adult male outbred CD-1 mice lever-press for the opportunity to attack subordinate male mice and relapse to aggression seeking during abstinence. Here we studied the role of nucleus accumbens (NAc) dopamine receptor (Drd)1- and Drd2-expressing neurons in aggression self-administration and aggression seeking. We trained CD-1 mice to self-administer intruders (9 d, 12 trials/d) and tested them for aggression self-administration and aggression seeking on abstinence Day 1. We used immunohistochemistry and in situ hybridization to measure the neuronal activity marker Fos in the NAc, and cell-type-specific colocalization of Fos with Drd1- and Drd2-expressing neurons. To test the causal role of Drd1- and Drd2-expressing neurons, we validated a transgenic hybrid breeding strategy crossing inbred Drd1-Cre and Drd2-Cre transgenic mice with outbred CD-1 mice and used cell-type-specific Cre-DREADD (hM4Di) to inhibit NAc Drd1- and Drd2-expressing neuron activity. We found that aggression self-administration and aggression seeking induced higher Fos expression in NAc shell than in core, that Fos colocalized with Drd1 and Drd2 in both subregions, and that chemogenetic inhibition of Drd1-, but not Drd2-, expressing neurons decreased aggression self-administration and aggression seeking. Results indicate a cell-type-specific role of Drd1-expressing neurons that is critical for both aggression self-administration and aggression seeking. Our study also validates a simple breeding strategy between outbred CD-1 mice and inbred C57-based Cre lines that can be used to study cell-type and circuit mechanisms of aggression reward and relapse.SIGNIFICANCE STATEMENT Aggression is often comorbid with neuropsychiatric diseases, including drug addiction. One form, appetitive aggression, exhibits symptomatology that mimics that of drug addiction and is hypothesized to be due to dysregulation of addiction-related reward circuits. However, our mechanistic understanding of the circuitry modulating appetitive operant aggression is limited. Here we used a novel mouse model of aggression self-administration and relapse, in combination with immunohistochemistry, in situ hybridization, and chemogenetic manipulations to examine how cell types in the nucleus accumbens are recruited for, and control, operant aggression self-administration and aggression seeking on abstinence Day 1. We found that one population, dopamine receptor 1-expressing neurons, act as a critical modulator of operant aggression reward and aggression seeking.


Important issues in planning a proteomics experiment: statistical considerations of quantitative proteomic data.
Mass spectrometry is frequently used in quantitative proteomics to detect differentially regulated proteins. A very important but unfortunately oftentimes neglected part in detecting differential proteins is the statistical analysis. Data from proteomics experiments are usually high-dimensional and hence require profound statistical methods. It is especially important to already correctly design a proteomic experiment before it is conducted in the laboratory. Only this can ensure that the statistical analysis is capable of detecting truly differential proteins afterwards. This chapter thus covers aspects of both statistical planning and the actual analysis of quantitative proteomic experiments.


THE LIMITS OF AMINO ACID SEQUENCE DATA IN ANGIOSPERM PHYLOGENETIC RECONSTRUCTION.
Amino acid sequence data are available for ribulose biphosphate carboxylase, plastocyanin, cytochrome c, and ferredoxin for a number of angiosperm families. Cladistic analysis of the data, including evaluation of all equally or almost equally parsimonious cladograms, shows that much homoplasy (parallelisms and reversals) is present and that few or no well supported monophyletic groups of families can be demonstrated. In one analysis of nine angiosperm families and 40 variable amino acid positions from three proteins, the most parsimonious cladograms were 151 steps long and contained 63 parallelisms and reversals (consistency index = 0.583). In another analysis of six families and 53 variable amino acid positions from four proteins, the most parsimonious cladogram was 161 steps long and contained 50 parallelisms and reversals (consistency index = 0.689). Single changes in both data matrices could yield most parsimonious cladograms with quite different topologies and without common monophyletic groups. Presently, amino acid sequence data are not comprehensive enough for phylogenetic reconstruction among angiosperms. More informative positions are needed, either from sequencing longer parts of the proteins or from sequencing more proteins from the same taxa.


Oral Lichen Planus in a 7-year-old Child: A Rare Case Report.
Lichen planus is a chronic inflammatory mucocutaneous disease reported most frequently in adults and relatively rare in children with the prevalence being 0.03%. This article reports a case of oral lichen planus (OLP) in a 7-year-old girl without any attendant skin lesions, diagnostic workup, and management protocol for the same. This article also emphasizes the need to consider OLP as a differential diagnosis for white lesions of oral mucosa in children. How to cite this article: Chinnasamy NK, Venugopal DC, Sankarapandian S, et al. Oral Lichen Planus in a 7-year-old Child: A Rare Case Report. Int J Clin Pediatr Dent 2020;13(1):91-93.


The conservative management of chronic renal failure.
The management of patients with chronic renal failure is complicated and demanding for both physician and patient, but is frequently rewarding. When specific treatment of the underlying cause is not possible, therapy is aimed at making the maximum use of existing nephrons and preventing further loss of nephrons through hypertension and infection. Careful attention to salt and water balance is necessary, and all patients and all drugs prescribed must be considered with care. Special problems exist with regard to anaemia, bone disease, pericarditis and hyperkalaemia. An important aspect of care at this time is the education of patients about the next major phase of management, dialysis and transplantation.


Differential to Terminal Ileitis: Terminal Ileum Neuroendocrine Tumor Identified on Screening Colonoscopy.
Background: Asymptomatic patients at average risk of developing colorectal cancer are encouraged to undergo screening colonoscopy beginning at age 45 years. While ileal intubation is often considered the gold standard for a complete colonoscopy, the relatively low diagnostic yield has prevented widespread adoption. Small bowel cancers, including neuroendocrine tumors, may present incidentally as terminal ileitis on routine colonoscopy with terminal ileum intubation. Neuroendocrine tumors, the most common primary neoplasm of the small intestine, are often asymptomatic or present as nonspecific abdominal pain in the sixth or seventh decade of life. Case Report: A 51-year-old asymptomatic male with unremarkable physical examination underwent screening colonoscopy that revealed scattered ulcerations of the terminal ileum. Immunohistochemistry of the lesion was consistent with well-differentiated neuroendocrine tumor, World Health Organization Grade I. DOTATATE positron emission tomography/computed tomography demonstrated avid adjacent right mesenteric lymph node and avid focal pancreatic body lesion. Fine-needle biopsy and immunohistochemistry of the pancreatic lesion confirmed neuroendocrine tumor, while the mesenteric lymph node was found to be benign. The patient underwent robotic-assisted ileocolic resection and has ongoing surveillance of the pancreatic lesion. Conclusion: Terminal ileitis encompasses a host of pathologic processes, including inflammatory states, infectious disease, malignancy, and vasculitis. Importantly, small bowel cancer is an increasing cause of terminal ileitis. Screening colonoscopy with ileal intubation can be a valuable tool for early detection of these lesions.


Quantification of energy transfer in bimetallic Pt(ii)-Ln(iii) complexes featuring an N^C^N-cyclometallating ligand.
Cyclometallated Pt(ii) complexes with arylpolypyridyl ligands have impressive photophysical properties (high quantum yields, long lifetimes and tuneable emission) which can be readily tuned by modification of the organic ligand. Despite this, few examples of cyclometallated Pt(ii) complexes as sensitisers for Ln(iii) emission have been reported. Herein, we report the photophysical properties for a series of bimetallic complexes incorporating an N^C^N-coordinated Pt(ii) bearing an alkynyl terpyridine as a metalloligand for a Ln(iii) ion (where Ln = Nd, Gd, Er, Yb and Lu). Using a combination of steady state, time-resolved, and transient absorption experiments, the influence on the photophysical properties of the metalloligand exerted by the different Ln(iii) cations has been investigated, together with the energy transfer efficiency from the metalloligand to the Ln(iii) 4f* excited state.


Subfractionation and characterization of soluble c-type cytochromes from Paracoccus denitrificans cultured under various limiting conditions in the chemostat.
Soluble c-type cytochromes were partially purified from Paracoccus denitrificans cells grown in succinate- and methanol-limited aerobic, nitrate-limited anaerobic and oxygen-limited chemostat cultures. Five c types could be distinguished with the following apparent molecular masses, absorption maxima and midpoint potentials. (a) 9.2 kDa, 549 nm and +190 mV; (b) 14 kDa, 549 nm and +227 mV; (c) 22 kDa, 552 nm and +190 mV; (d) 30 kDa, 552.7 nm and +160 mV; (e) 45 kDa, a dihaem: 555 nm, +128 mV and 551 nm, -163 mV. The 14-kDa polypeptide was present under all growth conditions examined and most probably is the already well characterized cytochrome c550. In methanol-limited grown cells three additional cytochromes were found, the 9.2-kDa, 22-kDa and 30-kDa ones. Under oxygen-limited conditions the 45-kDa and under anaerobic growth conditions small quantities of the 30-kDa and 45-kDa cytochromes c were present. Based on the apparent molecular masses the 14-kDa, 22-kDa, 30-kDa and 45-kDa cytochromes may also be present in membrane-fractions.


The role of Toll-like receptors in the regulation of neutrophil migration, activation, and apoptosis.
Toll-like receptors (TLRs) play an essential role in the detection of invading pathogens and in the induction of host antimicrobial defenses. TLR4, the major endotoxin receptor, and TLR2, with agonists derived principally from gram-positive organisms, are likely to be important in the pathogenesis of sepsis. Both TLR2 and TLR4 agonists regulate important neutrophil functions, including adhesion, generation of reactive oxygen species, and release of chemokines, and activate major proinflammatory signaling pathways, including the nuclear factor- kappa B pathway. TLR stimulation produces only a modest direct inhibition of neutrophil apoptosis, although this signal is greatly amplified by the presence of monocytes, suggesting that regulation of the life span of neutrophils by TLR agonists may be principally mediated by responses of other endotoxin-responsive cells. We suggest that activation of neutrophils by TLRs is highly regulated, permitting acute neutrophil antimicrobial responses to TLR activation while providing a "brake" on inflammation by requiring the presence of mononuclear cells to significantly extend neutrophil survival.


Simple goniometric search for electron microscopy.
We developed a special software to memorize specific points on a grid for later fine analysis. This program is based on a goniometry search, and implemented on the PC coupled microscope. This allows automatic shifting of the grid, but it can also be programmed on a simple pocket calculator.


Human hydatid disease in Peru is basically restricted to Echinococcus granulosus genotype G1.
A molecular PCR study using DNA from 21 hydatid cysts was performed to determine which strain type is responsible for human infection in Peru. The mitochondrial cytochrome c oxidase subunit 1 (CO1) gene was amplified in 20 out of 21 samples, revealing that all but 1 sample (19/20, 95%) belonged to the common sheep strain (G1). The remaining samples belonged to the camel strain (G6). The G1 genotype was most frequently found in human cases of cystic hydatid disease (CHD) in Peru. Local control measures should focus primarily on decreasing dog and sheep infection rather than intermediate reservoirs.


Incidence and management of myelosuppression in patients with chronic- and accelerated-phase chronic myeloid leukemia treated with omacetaxine mepesuccinate.
Omacetaxine mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.


MicroRNA profiling in the serums of SCA3/MJD patients.
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is the most common type of spinocerebellar ataxia in China. However, the pathogenesis of SCA3/MJD is still unknown. MicroRNAs (miRNAs) have been repeatedly demonstrated to exist in human peripheral serum in a bio-stable form and have been shown to be useful biomarkers for other neurodegenerative disorders. However, no study of SCA3/MJD patients has assessed specific changes in regulatory miRNAs. Therefore, we systematically used the miRCURYTM LNA Array, followed by quantitative real-time polymerase chain reaction validation, to access miRNA expression levels in the serums from SCA3/MJD patients. Our results show that miR-25, miR-125b, miR-29a, and miR-34b could be potential biomarkers for SCA3/MJD and could be used to further investigate the pathogenesis of SCA3/MJD and drug development.


Diagnosis of neonatal transient tachypnea and its differentiation from respiratory distress syndrome using lung ultrasound.
Transient tachypnea of the newborn (TTN) is one of the most common causes of perinatal dyspnea and is traditionally diagnosed by chest x-ray. This study aimed to explore the diagnostic value of lung ultrasonography (LUS) for TTN as well as differentiate it from respiratory distress syndrome (RDS) by using LUS. From January 2013 to February 2014, 60 infants who were diagnosed with TTN based on medical history, clinical manifestations, arterial blood gas analysis, and chest radiography were recruited to the study group. During the same period, 40 hospitalized neonates with nonlung diseases and 20 patients with RDS were recruited to the control group. In a quiet state, infants were placed in the supine, lateral, or prone position for the examination. Each lung of every infant was divided into 3 regions: the anterior, lateral, and posterior regions as bordered by the anterior axillary and posterior axillary lines. The probe was placed perpendicular to the ribs. Each region of both the lungs was carefully scanned.The common ultrasonographic manifestations of TTN were double-lung point (DLP), interstitial syndromes or white lungs, pleural line abnormalities, and A-line disappearance. A small number of infants (20%) with TTN exhibited pleural effusions, whereas the main ultrasonographic manifestation of RDS was lung consolidation with air bronchograms, which does not occur in TTN. The sensitivity and specificity of DLP for the diagnosis of TTN were 76.7% and 100%, respectively. LUS can accurately and reliably diagnose TTN. The DLP and lung consolidation possess great value in the diagnosis and differential diagnosis of TTN with RDS. Thus, we believe that LUS can be widely used in neonatal intensive care units.


[Salvage external beam radiation therapy for prostate cancer recurrence after high-intensity focused ultrasound ablation].
The article outlines oncological and functional outcomes of salvage external beam radiation therapy after HIFU-ablation in 49 patients. The study determined overall and relapse-free survival, compared the rates of adverse events stratified by CTCAE, erectile function and continence scores assessed by questionnaire survey. Univariate and multivariate analysis of risk factors for failure of salvage radiation therapy after prostate HIFU-ablation were conducted. In univariate analysis the level of prostate-specific antigen (PSA) prior to radiotherapy, the risk group, PSA nadir after radiotherapy, PSA nadir greater than 0.2 ng/mL and the time to nadir after salvage therapy were predictors of failure. There were no serious gastrointestinal side effects. The most frequent urinary adverse event was urgency. The difference in the rates of urinary incontinence before and 1 year after radiotherapy was not statistically significant. The study confirmed the appropriateness of radiotherapy after HIFU-ablation. Radiation therapy can be considered as a treatment option for prostate cancer recurrence after HIFU-ablation.


Influence of placental malaria infection on foetal outcome in the Gambia: twenty years after Ian Mcgregor.
Malaria infection in pregnancy has serious health consequences among mothers and offspring. The influence of placental malaria infection on foetal outcome was studied in a Gambian rural setting where few pregnant women take antimalarial chemoprophylaxis. During July-December 1997, three hundred thirteen mother-newborn pairs (singletons only) were consecutively recruited into a study of the effects of placental malaria infection on the outcome of pregnancy. Placental blood and tissue were collected at delivery. Babies were clinically assessed until discharge. The overall prevalence of placental malaria infection was 51.1% by placental histology and 37.1% by blood smear. The primigravid women were more susceptible to placental malaria than the multigravidae (65.3% vs 44.7%, p=0.01). Placental malaria was significantly associated with pre-term deliveryand intrauterine growth retardation (p<0.01), and there was a four-fold risk of delivering low-birth-weight babies if mothers had parasitized placentae [OR=4.42, 95% confidence interval (CI) 2.10-9.27]. A reduction of mean birth-weight of babies by 320 g was associated with placental malaria infection (p<0.001). Similarly, a two-fold risk of stillbirth delivery (OR=2.22, 95% CI 1.04-4.72) was observed among the infected mothers. The findings showed that there was still an overall poor foetal outcome associated with placental malaria infection. The findings of this study confirm the findings of an earlier study by McGregor in the Gambia that the low birth-weight rate is significantly higher if the placenta is parasitized. In addition, this study observed that the high stillbirth and prematurity rates were associated with placental malaria infection. The findings of the present study suggest undertaking of effective malaria-control strategies during pregnancy, such as use of insecticide-impregnated bednets, intermittent and early treatment for malaria, and antimalarial chemoprophylaxis, in the Gambia.


Test-retest reliability of measurements of abdominal and multifidus muscles using ultrasound imaging in adults aged 50-79 years.
Test-retest reliability of the combined process of ultrasound imaging (USI) and image measurement of thickness of abdominal and upper lumbar multifidus (MF) muscles and MF cross sectional area (CSA) of older adults has not been established. Imaging muscles of older adults can be challenging due to age-related changes in the spine and skeletal muscle so establishing test-retest reliability in this population is important. This study aimed to evaluate test-retest reliability of USI of abdominal and MF muscle thickness and MF CSA for adults aged 50-79 years. One operator took single sets of ultrasound images of abdominal and MF muscles of 23 adults aged 50-79 years participating in a clinical trial of vitamin D supplementation for knee osteoarthritis, on two occasions, one week apart. Images were subsequently measured by a single examiner. Test-retest reliability for abdominal muscle thickness and MF CSA was substantial (intraclass correlation coefficients (ICC) > 0.81) and for MF thickness ranged from fair to substantial (ICC 0.55-0.86). The standard error of measurement (SEM) was low (0.02-0.21) in every case. ICCs were low and SEM values were high for percentage thickness change. The substantial test-retest reliability of abdominal and MF (L4-L5) muscle thickness and of MF CSA supports the use of USI as a clinical and research tool to assess abdominal and MF muscle thickness and MF CSA of older adults.


Dysmyelination of shiverer mutant mice in vivo and in vitro.
Demyelination in the CNS of shiverer mutant mice was studied in vivo and in vitro. By immunohistochemical reaction with glial fibrillary acidic protein antibody, hypertrophy of the fibrous astrocytes was observed in the white matter of shiverer cerebella. The cerebella of shiverer mice in primary culture from the day of birth showed very poor myelination under optical microscopy. Axons of Purkinje cells are thought to be the main myelinated axons in the primary culture of the cerebellum. Purkinje cells from shiverer appeared normal with regard to Bodian silver impregnation, hematoxylin and eosin staining, and P400 protein characterization of Purkinje cells. Addition of the conditioned culture medium of shiverer to the control culture did not interfere with myelination. We concluded that the demyelination in the CNS of shiverer could be caused by an intrinsic defect of the oligodendrocyte rather than by hypertrophy of the astrocytes or by diffusible factors.


[Cervical spondylosis misdiagnosed as cerebral infarction: a case report].
Here we report a case of cervical spondylosis misdiagnosed as cerebral infarction. The patient was a 55-year-old man with a one-day history of weakness in his right extremities. Brain magnetic resonance imaging (MRI) showed no acute abnormality, cerevical MRI showed that cervical spondylisis, C4/5, C5/6 disc herniation, spinal canal stenosis and compression of the spinal cord. Then the patient was transferred to the Department of Orthopaedics and underwent surgical treatment of cervical spondylosis. Followed-up for six months, the weakness of his right extremities returned to normal.


Milolides G-N, new Briarane diterpenoids from the Western Pacific octocoral Briareum stechei.
Twelve new briarane diterpenes, designated milolides (1-12), and one known diterpene, 9-deacetylstylatulide lactone (13), were isolated from the Micronesian octocoral Briareum stechei collected at Yap, Federated States of Micronesia. Their structures were determined from spectral data.


Red wine consumption prevents vascular oxidative stress induced by a high-fat meal in healthy volunteers.
In order to investigate the effect of red wine on plasma lipid and oxidative stress parameters after a high-fat meal, fifteen healthy volunteers were studied: three days after a high-fat meal with 250 mL of water, they received the same meal with 250 mL of red wine. During both periods, serial blood samples were drawn before and 2, 4, and 8 hours after the meal to evaluate plasma lipids (cholesterol and triglycerides; retinyl palmitate), oxidative stress (D-ROM, and malondialdehyde) and antioxidant (total plasma antioxidant levels and uric acid) parameters. During the meal without wine, plasma lipid parameters increased significantly, whereas plasma total plasma antioxidant levels decreased, and a trend toward reduction of uric acid levels was seen). A similar trend in lipid parameters was observed after the meal with wine; no significant difference in individual lipid parameter trends after a meal with and without wine was observed. Wine ingestion induced higher total plasma antioxidant levels and uric acid; malondialdehyde levels remained constant after wine ingestion. Plasma D-ROM showed a significant postprandial increase in both experiments, but it was significantly lowered after wine ingestion. Our results give evidence of oxidative stress following a fat-rich meal in healthy subjects, suggesting that ingestion of red wine during a high-fat meal significantly reduces oxidative stress without inducing any significant modification in postprandial lipemia.


9-(1,3-Dihydroxy-2-propoxymethyl)guanine (ganciclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome.
9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) was used to treat 41 patients (median age, 37 years) with the acquired immunodeficiency syndrome and cytomegalovirus gastrointestinal infection. Sites of infection were the colon in 31, the esophagus in 5, the rectum in 4, and the small bowel in 1. Patients received ganciclovir, 5 mg/kg body weight, intravenously every 12 hours for 14 days. Clinical improvement was seen in 30 patients and virologic response in 32. Mainly hematologic toxicity occurred: moderate leukopenia (1000 to 1900/mm3) was seen in 7 patients and severe (less than 1000/mm3) in 1, and moderate neutropenia (500 to 1000/mm3) in 5 and severe (less than 500/mm3) in 1. A cutaneous rash developed in 2 patients. Median overall survival was 16 weeks (range, 2 to 56). Cytomegalovirus recurred in 13 patients; median time to recurrence was 9 weeks from the start of treatment. Ganciclovir may be effective in treating cytomegalovirus gastrointestinal disease in patients with the acquired immunodeficiency syndrome.


Pulsed field ionization electron spectroscopy and molecular structure of aluminum uracil.
Al-uracil (Al-C4H4N2O2) was synthesized in a laser-vaporization supersonic molecular beam source and studied with pulsed field ionization-zero electron kinetic energy (ZEKE) photoelectron spectroscopy and density functional theory (DFT). The DFT calculations predicted several low-energy Al-uracil isomers with Al binding to the diketo, keto-enol, and dienol tautomers of uracil. The ZEKE spectroscopic measurements of Al-uracil determined the ionization energy of 43 064(5) cm-1 [or 5.340(6) eV] and a vibrational mode of 51 cm-1 for the neutral complex and several vibrational modes of 51, 303, 614, and 739 cm-1 for the ionized species. Combination of the ZEEK spectrum with the DFT and Franck-Condon factor calculations determined the preferred isomeric structure and electronic states of the Al-uracil complex. This isomer is formed by Al binding to the O4 atom of the diketo tautomer of uracil and has a planar Cs symmetry. The ground electronic states of the neutral and ionized species are 2A' ' and 1A', respectively. The 2A' ' neutral state has a slightly shorter Al-O4 distance than the 1A' ion state. However, the 1A' ion state has stronger metal-ligand binding compared to the 2A' ' state. The increased Al-O4 distance from the 2A' ' state to the 1A' state is attributed to the loss of the pi binding interaction between Al and O4 in the singlet ion state, whereas the increased metal-ligand binding strength is due to the additional charge-dipole interaction in the ion that surpasses the loss of the pi orbital interaction.


[Esophageal melanoma: report of two cases].
Esophageal melanomas correspond to 0.1 to 0.2% of esophageal tumors. We report two patients with the disease. The first patient is a 51 year-old woman pre-sentingwith dysphagia and weight loss. An upper gastrointestinal endoscopy showed a polypoid ulcerated lesion in the middle third of the esophagus. The pathological study ofthe biopsy disclosed a malignant melanoma. The patient was subjected to an esophagectomy with a satisfactory postoperative evolution. Four months later, liver metastases were detected and the patient died eleven months after the operation. The second patient is a 59 year-old mole that consulted by dysphagia. An endoscopy showed a pigmented esophageal lesion whose pathological diagnosis was a malignant melanoma. The patient was subjected to an esophagectomy and sixteen months after surgery there was no evidence of relapse.


Interleukin-3 and interleukin-17 do not play a dynamic role in the immunopathogenesis of osteoarticular tuberculosis.
Osteoarticular tuberculosis accounts for one to three per cent of all cases of active TB. IL-3 stimulates the proliferation, differentiation and survival of pluripotent stem cells. IL-17 has shown to promote inflammatory cell recruitment and granuloma organization throughout infection with Mycobacterium tuberculosis. During the chronic phase of the infection, a balance between Th1 and Th17 responses needs to be achieved to limit immunopathology. To correlate the serum levels of IL-3 and IL-17 at presentation and after completion of treatment in clinicoradiologically proven cases of osteoarticular tuberculosis. 32 clinicoradiologically confirmed cases of osteoarticular tuberculosis were included. Archived serum samples of eight patients of osteoarticular tuberculosis of an earlier study, confirmed by PCR, AFB smear or by histopathology with previously determined IL-12 and TGF-beta levels were available. A detailed history was noted and their general physical, local and relevant systemic examination was performed. Various laboratory parameters including TL-3 and IL-17 levels in serum were estimated at presentation and at six months of DOTS CAT-1 treatment. There was a significant improvement in the clinical and radiological parameters after treatment. No correlation was found between IL-3 and IL-17 levels before and after treatment. A significant correlation (p value= 0.022) was shown between levels of IL-3 and IL-12 after six months of treatment. Qualitative and quantitative fluctuations in IL-3 and IL-17 levels were not able to serve as useful indices of disease activity.


[Transfer and transport of newborn babies in vital distress in Yaoundé, Cameroon: situational analysis conducted in a reference hospital].
This study aims to describe transfer modalities of newborn babies in vital distress to the ESSOS Hospital Center in Yaoundé, Cameroon. We conducted a prospective cross-sectional study from October 2014 to January 2015. Data were collected using a short questionnaire from the transfer operator. Main parameters: means of transport, reason for transfer, transfer delay, number of detours (itinerary before admission) prevalence for hypothermia, neonatal mortality rate. We recorded 73 transfers during the study period. Nearly 1/5 (22%) of infants were born within the health district of the reference structure. 24/73 newborns were referred for tertiary care centers (33%). The main reason for transfer was prematurity (40%) followed by neonatal asphyxia (26%). Medical transfer was performed in 5/73 (7%) cases, inter-hospital transfer effected through a nurse was performed in 10/73 (13.6%) cases. The average transfer time was 17 hours, 60% of babies were transferred within the first 6 hours of life, 22% (16/73) within the first two hours of life. For more than half of newborns, a transfer to another hospital was done before admission. Hypothermia (central temperature less than 36° C) on arrival was found in 20% of cases. 15/73 (20.5%) of transferred newborns died. The mean temperature in the dead infants upon their arrival to the hospital was 35.5° C versus 37° C in the non-deceased (p = 0.006). The percentage of newborns who underwent =2 tranfers was 57% in the deceased infants versus 30% in the non-deceased ones (p=0,02). In Yaoundé, transfers conditions of newborns in precarious conditions of life hinder early neonatal prognosis because of an erratic itinerary, which increases the risk of hypothermia and death. This reinforces the need for a perinatal network.


Effects of cis-diamminedichloroplatinum(II) on Escherichia coli and bacteriophage systems.
The effects of cis-diamminedichloroplatinum(II) (cisplatin) on Escherichia coli cells and bacteriophages were investigated. The bacteriocidal effect of cisplatin was stronger on uvrA or recA mutants than on wild type cells. The drug, like UV, induced prophage development in lysogenic bacteria. Host cell reactivation of alpha3 replicative form (RF) I DNA treated with cisplatin in vitro was more efficient in wild type or recA cells than in uvrA host. When wild type cells were exposed to cisplatin, decay of the host's capacity to sustain the viral multiplication proceeded nearly in parallel with the loss of colony-forming ability, whereas the capacity of uvrA mutant was much more resistant to the drug, as compared with the viability. In the DNA preparation from cisplatin-treated alpha3-infected wild type cells, RF II was deficient, but the RF I molecules extracted from the cells were moderately infective. The microvirid gene A protein, required for RF I-->RF II conversion, was hardly detectable in wild type cells exposed to cisplatin. The possible relationship between uvr+-dependent repair and synthesis of the viral protein is discussed.


AIDS and the new medical gaze: bio-politics, AIDS, and homosexuality.
The essay argues that the contemporary resurgence of homophobia and the remedicalization of homosexuals in the wake of AIDS is, in part, an unintended but predictable effect of a quarter century of fractious identity-politics. Prominent gay and lesbian political strategies of the 1970s and 1980s borrowed heavily from increasingly discredited, if once politically correct, discourses that valorized individuals on the basis of membership in governmentally constructed bio-bureaucratic categories. Drawing on the work of prominent gay intellectuals, such as Foucault, Watney, and Richard Rodriguez, and locating their insights within the context of contemporary cultural and political conflicts, the essay argues that gay advocates who essentialize homosexual identity, however benignly, unwittingly participate in constituting the ground for an emergence of a neoeugenic movement at millennium's end. The essay concludes with the observation that escaping the conceptual prison of bio-bureaucratic categories is not a uniquely gay or lesbian task. It is a human task.


Projective filtering of time-aligned ECG beats.
A method of electrocardiographic (ECG) signal processing developed by introduction of time synchronization into the method of nonlinear state-space projections is presented. It can be regarded as an extension of time averaging but contrary to usual averaging it preserves variability of ECG beats morphology. For this purpose, after the respective beats time alignment, the synchronized intervals of the signal undergo processing according to the rules of principal component analysis (PCA). PCA allows for determination of orthogonal basis functions which can be employed for approximation of the respective intervals. The operation is aimed to retain the deviations from the mean which result from the desired component changes and to reject the deviations caused by noise. The method's capabilities are investigated and some of its applications are presented.


Cytokines impact natural killer cell phenotype and functionality against glioblastoma in vitro.
Natural killer (NK) cells are a part of the innate immune system and first-line defense against cancer. Since they possess natural mechanisms to recognize and kill tumor cells, NK cells are considered as a potential option for an off-the-shelf allogeneic cell-based immunotherapy. Here, our objective was to identify the optimal cytokine-based, feeder-free, activation and expansion protocol for cytotoxic NK cells against glioblastoma in vitro. NK cells were enriched from human peripheral blood and expanded for 16 days with different activation and cytokine combinations. The expansion conditions were evaluated based on NK cell viability, functionality, expansion rate and purity. The cytotoxicity and degranulation of the expanded NK cells were measured in vitro from co‑cultures with the glioma cell lines U‑87 MG, U‑87 MG EGFR vIII, LN-229, U-118 and DK-MG. The best expansion protocols were selected from ultimately 39 different conditions: three magnetic cell‑selection steps (Depletion of CD3+ cells, enrichment of CD56+ cells, and depletion of CD3+ cells followed by enrichment of CD56+ cells); four activation protocols (continuous, pre-activation, re-activation, and boost); and four cytokine combinations (IL-2/15, IL‑21/15, IL‑27/18/15 and IL-12/18/15). The expansion rates varied between 2-50-fold, depending on the donor and the expansion conditions. The best expansion rate and purity were gained with sequential selection (Depletion of CD3+ cells and enrichment of CD56+ cells) from the starting material and pre-activation with IL‑12/18/15 cytokines, which are known to produce cytokine-induced memory-like NK cells. The cytotoxicity of these memory-like NK cells was enhanced with re-activation, diminishing the donor variation. The most cytotoxic NK cells were produced when cells were boosted at the end of the expansion with IL-12/18/15 or IL-21/15. According to our findings the ex vivo proliferation capacity and functionality of NK cells is affected by multiple factors, such as the donor, composition of starting material, cytokine combination and the activation protocol. The cytokines modified the NK cells' phenotype and functionality, which was evident in their reactivity against the glioma cell lines. To our knowledge, this is the first comprehensive comparative study performed to this extent, and these findings could be used for upscaling clinical NK cell manufacturing.


H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of noradrenaline release in the guinea-pig brain.
The effect of histamine and related drugs on the tritium overflow evoked electrically (0.3 Hz) or by introduction of Ca2+ ions into Ca2+-free K+-rich (25 mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex slices preincubated with 3H-noradrenaline. The electrically evoked tritium overflow in guinea-pig cortex slices was inhibited by histamine; the H3 receptor antagonist clobenpropit reversed the effect of histamine to a slight facilitation. The facilitatory effect of histamine (obtained in the presence of clobenpropit) was not affected by the H1 receptor antagonist mepyramine but abolished by the H2 receptor antagonist ranitidine. In the absence of clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices superfused in the presence of ranitidine, the evoked overflow was inhibited by histamine and, more potently, by the H3 receptor agonist R-alpha-methylhistamine in a concentration-dependent manner (maximum inhibitory effect obtained for both agonists 30-35%). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonist thioperamide. R-alpha-methylhistamine inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar, hippocampal and hypothalamic slices. In cortex slices superfused in the presence of clobenpropit, the H2 receptor agonists impromidine and, less potently, R-sopromidine facilitated the evoked overflow in a concentration-dependent manner. S-Sopromidine only tended to increase the evoked overflow. The effect of impromidine was counteracted by the H2 receptor antagonists ranitidine and cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15-20%) was about the same when (i) the Ca2+ concentration in the medium was reduced from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced from 28 to 8 min or (iii) cerebellar, hippocampal or hypothalamic slices were used instead of cortical slices. The Ca2+-induced tritium overflow in guinea-pig cortex slices was inhibited by histamine (in the presence of ranitidine); this effect was abolished by clobenpropit. In slices superfused in the presence of clobenpropit, impromidine failed to facilitate the Ca2+-evoked tritium overflow. The electrically evoked tritium overflow in mouse brain cortex slices was inhibited by histamine by about 60% (both in the absence or presence of ranitidine). The inhibitory effect of histamine was abolished (but not reversed) by clobenpropit. In conclusion, noradrenaline release in the guinea-pig brain cortex is inhibited via presynaptic H3 receptors and facilitated via H2 receptors not located presynaptically. In the mouse brain cortex, only inhibitory H3 receptors occur. The extent of the H3 receptor-mediated effect is more marked in the mouse than in the guinea-pig brain cortex.


Effects of intravenous Injections Paederiae and Stauntonia on spontaneous pain, hyperalgesia and inflammation induced by cutaneous chemical tissue injury in the rat.
To study whether commercial traditional Chinese medicinal preparations Injection Paederiae (IP) or Injection Stauntonia (IS) has anti-nociceptive and/or anti-inflammatory effects, we used two persistent pain models (bee venom and formalin test) to evaluate the systemic effects of IP or IS on the chemical tissue injury-induced persistent spontaneous pain-related responses (PSPR), primary thermal/mechanical hyperalgesia and inflammation in conscious rats. Injection of bee venom (BV, 0.1 mg, 50 microl) into the plantar surface of one hind paw resulted in not only a 1-h monophasic PSPR such as flinching reflex in the injected paw and a subsequent period of 3-4 days primary heat and mechanical hyperalgesia, but also a marked sign of inflammation, including redness and swelling of the plantar surface in the injected paw. Intraplantar injection of formalin produced two phases of PSPR as reported previously. Systemic pre-treatment with three doses of IP (0.32, 1.6 and 9.0 ml/kg, 500%) or IS (0.32, 1.6 and 9.0 ml/kg, 250%) produced a dose-dependent suppression of the BV- or formalin-induced flinching reflex of 1 h time course as compared with the saline control group. Post-treatment with IP or IS 5 min after BV injection also produced a significant suppression of the flinching reflex in both BV test and formalin test respectively, as compared with the control group. However, neither pre- nor post-treatment with IP or IS produced any significantly suppressive effect on the BV-induced primary heat and mechanical hyperalgesia and inflammation. The analgesia produced by IP or IS was not mediated by the endogenous opioid receptors since naloxone, a non-selective opioid receptor antagonist, had no reversal effect on the IP and IS-produced analgesia in the BV-induced PSPR. Our present results suggest that IP or IS might prevent and relieve clinical persistent spontaneous pain, but without any anti-nociceptive and anti-inflammatory effects on the primary heat hyperalgesia, mechanical hyperalgesia, as well as inflammatory responses. The BV test might be a useful model of pain to evaluate and screen anti-nociceptive and anti-inflammatory effects of certain compounds of the Chinese medicinal herbs on the pathological origins of pain.


[The many faces of endocarditis].
Over the past years we have had a relatively large number of patients in our hospital with endocarditis. There has been a variety of clinical presentations, as illustrated by the following case presentations. We have conducted a search in our data-based archives of the period from 1.1.1994 to 31.12.2001 and found 25 patients discharged with a diagnosis of endocarditis. We have chosen five case histories that we discuss in the context of published literature. The signs and symptoms presented include a stroke, severe back pain, a swollen knee, pneumonia and cardiac failure. We especially discuss intravenous drug users and endocarditis of the heart's right side.


Epidemiology of subacute sclerosing panencephalitis (SSPE) in Germany from 2003 to 2009: a risk estimation.
Subacute sclerosing panencephalitis (SSPE) is a fatal long-term complication of measles infection. We performed an estimation of the total number of SSPE cases in Germany for the period 2003 to 2009 and calculated the risk of SSPE after an acute measles infection. SSPE cases were collected from the Surveillance Unit for Rare Paediatric Diseases in Germany and the Institute of Virology and Immunobiology at the University of Würzburg. The total number of SSPE cases was estimated by capture-recapture analysis. For the period 2003 to 2009, 31 children with SSPE who were treated at German hospitals were identified. The capture-recapture estimate was 39 cases (95% confidence interval: 29.2-48.0). The risk of developing SSPE for children contracting measles infection below 5 years of age was calculated as 1∶1700 to 1∶3300. This risk is in the same order of magnitude as the risk of a fatal acute measles infection.


Direct Ras Inhibitors Identified from a Structurally Rigidified Bicyclic Peptide Library.
A one-bead-two-compound (OBTC) library of structurally rigidified bicyclic peptides was chemically synthesized on TentaGel microbeads (90 μm), with each bead displaying a unique bicyclic peptide on its surface and a linear encoding peptide of the same sequence in its interior. Screening of the library against oncogenic K-Ras G12V mutant identified two classes of Ras ligands. The class I ligands apparently bind to the effector-binding site and inhibit the Ras-Raf interaction, whereas the class II ligand appears to bind to a yet unidentified site different from the effector-binding site. These Ras ligands provide useful research tools and may be further developed into therapeutic agents.


Pravastatin reduces radiation-induced damage in normal tissues.
Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.


Parents of homosexuals--not guilty? Interpretation of childhood psychological data.
Data obtained in a study of 200 Dutch male homosexuals in treatment contradict the idea that parents are not causing homosexuality in their sons. Notably, the combination of overconcernedness of the mother and detachment and hypercriticism of the father push the boy into avoidance of "masculine" behavior, which in turn is leading to a feeling of inferiority because the boy considers himself as lacking in manliness. The homosexual urge is an expression of an infantile longing for acceptance to counteract the loneliness and self-pity of not belonging and must be seen as a specific neurotic manifestation.


Barriers to hospice care and referrals: survey of physicians' knowledge, attitudes, and perceptions in a health maintenance organization.
Many proponents of hospice care believe that this service is underutilized. To determine physicians' perceptions of hospice utilization and of their own hospice referral pattern; their perceived and actual knowledge of appropriate hospice referral diagnoses; and perceived barriers to hospice referral. Surveys for anonymous response were distributed to 125 physicians in 2 internal medicine departments of a large not-for-profit health maintenance organization (HMO). Of these 125 physicians, 89% responded, including 91 staff physicians and 20 residents. Of the 111 physician-respondents, 78% reported their belief that hospice care was underutilized; 84% were unable to identify appropriate hospice diagnoses; and 12% were aware of the "National Hospice Organization Medical Guidelines for Determining Prognosis in Selected Non-Cancer Diseases." Difficulty of predicting death to within 6 months was cited by 37% as the foremost barrier to hospice referral. In addition, 28% expressed concern that patients or families would interpret hospice referral as a cost saving measure; 11% of respondents had been accused of using hospice referral for this purpose. Our study-the first major survey of physician attitudes and practices regarding hospice utilization in an HMO setting-showed that barriers to hospice referral are similar to those in non-HMO settings; physicians have difficulty predicting life expectancy and lack knowledge of patient eligibility guidelines. Physician concern that patients or their family members would construe hospice referral as a cost-saving technique may be a barrier particularly troublesome in an HMO setting.


Comparative genomic analysis of primary versus metastatic colorectal carcinomas.
To compare the mutational and copy number profiles of primary and metastatic colorectal carcinomas (CRCs) using both unpaired and paired samples derived from primary and metastatic disease sites. We performed a multiplatform genomic analysis of 736 fresh frozen CRC tumors from 613 patients. The cohort included 84 patients in whom tumor tissue from both primary and metastatic sites was available and 31 patients with pairs of metastases. Tumors were analyzed for mutations in the KRAS, NRAS, BRAF, PIK3CA, and TP53 genes, with discordant results between paired samples further investigated by analyzing formalin-fixed, paraffin-embedded tissue and/or by 454 sequencing. Copy number aberrations in primary tumors and matched metastases were analyzed by comparative genomic hybridization (CGH). TP53 mutations were more frequent in metastatic versus primary tumors (53.1% v 30.3%, respectively; P < .001), whereas BRAF mutations were significantly less frequent (1.9% v 7.7%, respectively; P = .01). The mutational status of the matched pairs was highly concordant (> 90% concordance for all five genes). Clonality analysis of array CGH data suggested that multiple CRC primary tumors or treatment-associated effects were likely etiologies for mutational and/or copy number profile differences between primary tumors and metastases. For determining RAS, BRAF, and PIK3CA mutational status, genotyping of the primary CRC is sufficient for most patients. Biopsy of a metastatic site should be considered in patients with a history of multiple primary carcinomas and in the case of TP53 for patients who have undergone interval treatment with radiation or cytotoxic chemotherapies.


Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious diseases ward.
A study of 240 consecutive admissions to a single hospital ward over a 6-month period was conducted to determine the prevalence of and risk factors for Clostridium difficile colonization at admission. The prevalence rate of C. difficile colonization at admission was 13.3%. Seventy-four percent of the patients admitted to the ward were infected with human immunodeficiency virus (HIV). Multivariate analysis identified three risk factors for C. difficile colonization: clindamycin use (adjusted odds ratio [OR], 9.4; P < .001), penicillin use (adjusted OR, 3.9; P = .018), and a history of cytomegalovirus infection (adjusted OR, 4.2; P = .02). C. difficile colonization at admission to our infectious diseases ward was common. Antibiotic treatments received before admission were the main risk factors for C. difficile colonization. HIV infection per se was not associated with C. difficile colonization. It is interesting that there was an association between C. difficile colonization and a history of cytomegalovirus infection.


Victims' voices and victims' choices in three IPV courts.
Critics of mandatory interventions for intimate partner violence (IPV) propose that the justice system disempowers victims by denying them voice and choice in legal proceedings. This exploratory study examines this claim through observations of three criminal courts. Findings show that victims are offered voice and a degree of choice in only one of the three courts. Court procedures that enhance victim voice and choice include a specialized IPV court, victim advocates trained in victims' rights issues, and a lead judge who models respectful treatment of victims. The author proposes that voice and choice are distinct aspects of victim empowerment and that the provision of voice may have benefits to IPV victims that are distinct from the benefits of choice.


A case of hereditary pancreatitis and pancreas divisum.
Hereditary pancreatitis is a rare form of chronic pancreatitis inherited as an autosomal dominant. Pancreas divisum results from a developmental failure of fusion of the dorsal and ventral parts of the pancreas and is associated with an increased incidence of pancreatitis. Co-existence of the two conditions in one patient is very rare. We report a case.


Evaluating the learning curve for robot-assisted laparoscopic radical cystectomy.
We seek to describe the learning curve of robot-assisted laparoscopic radical cystectomy by evaluating some of the surgical, oncologic, and clinical outcomes in our initial experience with 50 consecutive patients undergoing this novel procedure. Fifty consecutive patients (representing our initial experience with robot-assisted cystectomy) underwent radical cystectomy and urinary diversion from January 2006 to December 2007. Several different metrics were used to evaluate the learning curve of this procedure, including estimated blood loss (EBL), operative (OR) time, pathologic outcomes, and complication rate. We evaluated patients as a continuous variable, divided into five distinct time periods (quintiles), and stratified by first half and second half of robotic experience. EBL was not significantly lower until the third quintile (patients 21-30), after which further significant reductions were not observed. Mean OR time declined between each quintile for the first 30 patients (1-10 v 11-20 v 21-30). No significant declines occurred after the third quintile (21-30). When evaluated as a continuous variable, the statistical cut point at which no further significant reductions were observed was after patient 20 for OR time. No differences were observed with regard to time to flatus, bowel movement, or hospital discharge. Furthermore, complications were not different between the initial 25 patients and the most recent patients. There has been no case of a positive margin, and there was only one inadvertent bladder entry. Lymph node yield has also not significantly changed over time. This report helps to define the learning curve associated with robot-assisted laparoscopic radical cystectomy for bladder cancer. Despite the higher OR times and blood loss that is observed early in the learning curve, no such compromises are observed with regard to these oncologic parameters even early in the experience.


Is There a Relationship Between First-Trimester Aneuploidy Screening Serum Biomarker Values and Nuchal Translucency Measurements and the Development of Retinopathy of Prematurity (ROP) in Premature Infants?
Purpose The purpose of this study is the evaluation of serum biomarker and nuchal translucency (NT) values measured during first-trimester aneuploidy screening in terms of the development of retinopathy of prematurity (ROP) in premature infants and investigation of whether the development of ROP is associated with these parameters. Methods In this retrospective cohort study, 3,750 premature infants who underwent ROP screening from 2016 to 2021 were identified from the hospital medical record system. Among 2,130 premature babies screened for first-trimester aneuploidy, 166 babies whose mothers had single pregnancies were screened by the same method and showed the same clinical course in both eyes were included in the study. The infants were divided into two groups according to the presence of ROP, and those with ROP were further evaluated in two groups according to the presence of proliferation. The groups were compared in terms of the serum values of human chorionic gonadotropin and pregnancy-associated plasma protein A, among aneuploidy screening biomarkers, and NT measurements. Results There was no significant difference in the evaluated serum biomarker values and NT measurements between the ROP and non-ROP groups or between the proliferative ROP, non-proliferative ROP, and non-ROP groups. Conclusion Our results showed that first-trimester aneuploidy screening serum biomarker values and NT measurements were not associated with the development of ROP in premature infants.


The devastating consequence of iodine deficiency.
Endemic cretinism is the most striking consequence of iodine deficiency. Although cretinism is a serious condition, it usually involves only about 5% of the population even in serious endemic areas. There is a spectrum between cretinism and normality, many are able to perform simple work and look apparently normal, but it is difficult for them to perform skilled labor. Studies in China using the IQ distribution curve revealed that every person in an endemic area lost about 10-15 IQ points, so that the socio-economic development of the community was severely affected.


CCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects.
Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Delta32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5?32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Delta32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5?32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.


[Inverted papilloma of the nasal cavity - a case report].
Inverted papilloma is a rare, benign sinonasal tumor. Its etiology is the most likely related to HPV infection. Inverted papilloma originates from the ciliated respiratory epithelium, typically from the lateral nasal wall. The tumor is characterized by endophytic growth inwards the stroma with adjacent tissues destruction. The clinical symptoms are non-specific, such as: unilateral obstruction of the nasal duct, rhinorrhoea, epistaxis and anosmia. The treatment consists in a complete surgical excision of the tumor. Inverted papilloma has a tendency to recurrence with incomplete resection and a potential to malignant transformation to squamous cell carcinoma. This manuscript presents a case of a young woman who suffered from recurrent epistaxis from ulceration of the mucous of the anterior part of the nasal septum. The patient in the interview had indicated the symptoms since six months and unsuccessful treatment with cetirizine. The woman was qualified to a surgical removal of the lesion with a transnasal approach. The histopahtological examination of the sample revealed Papilloma inversum. One-year follow up did not disclose the recurrence of the tumor.


Cyclopentenones, scaffolds for organic syntheses produced by the endophytic fungus mitosporic dothideomycete sp. LRUB20.
Two new natural products, 2-hydroxymethyl-3-methylcyclopent-2-enone (1) (synthetically known) and cis-2-hydroxymethyl-3-methylcyclopentanone (2), and a known compound, asterric acid (3), were isolated from the endophytic fungus mitosporic Dothideomycete sp. LRUB20, which was isolated from the stem of the Thai medicinal plant Leea rubra. Compound 2 was separated and identified in the form of its 2,4-dinitrophenylhydrazone derivative (5). Compounds 1, 3, and hydrazone 5 exhibited mild antimycobacterial activity, both with MIC values of 200 microg/mL. Compounds 1, 3, and 4 were inactive (at 50 microg/mL) toward Vero, KB, NCI-H187, and BC cell lines. Hydrazone 5 showed only mild cytotoxicity against the Vero cell line with an IC(50) value of 21.7 microg/mL; however, it was inactive toward KB, NCI-H187, and BC cell lines. Endophytic fungi may be a source for the production of building blocks for organic syntheses.


Roles of cellular polyamines in mucosal healing in the gastrointestinal tract.
The mammalian gastrointestinal (GI) mucosa is a rapidly self-renewing tissue in the body, and its integrity is preserved through the strict regulation of epithelial cell proliferation, growth arrest, and apoptosis. Polyamines are shown to play an important role in the regulation of gastrointestinal mucosal growth and healing after injury under physiological and various pathological conditions. In this review, we highlight the importance of cellular polyamines in the control GI mucosal proliferation, migration, apoptosis, angiogenesis and GI barrier function during mucosal repair after injury.