Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study.
The benefits of nutritional supplementation, with or without psychosocial stimulation, on the growth of stunted children were evaluated. Children aged 9-24 mo with lengths less than -2 SD of the National Center for Health Statistics references (n = 129) were randomly assigned to four groups: control, nutritional supplementation, stimulation, and both interventions. A fifth group with lengths greater than -1 SD was also enrolled. Length, weight, head and arm circumferences, and triceps and subscapular skinfold thicknesses were measured on enrollment and 6 and 12 mo later. Multiple-regression analysis was used to determine the effects of the interventions in which age, sex, initial status, initial dietary intake, and several socioeconomic variables were controlled for. Stimulation had no effect on growth and there was no interaction between the interventions. After 12 mo supplemented children had significantly increased length, weight, and head circumference (all P less than 0.01). The effects of supplementation were not cumulative but occurred in the first 6 mo.


Expression of TIMP-1, TIMP-2 and collagenase mRNA in periodontitis-affected human gingival tissue.
Collagenolysis in periodontitis is thought to be modulated by the expression of three genes, collagenase, tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2). We assessed the possible difference in TIMP-1, TIMP-2 and collagenase mRNA levels between gingival samples from patients with periodontitis and those from healthy subjects by reverse transcription-polymerase chain reaction (RT-PCR). This technique allows detection of transcripts from a very small sample quantity. The experiments showed that levels of TIMP-1 and collagenase transcripts relative to beta-actin are significantly higher in the diseased group than in healthy controls (8.11 +/- 0.83 versus 1.38 +/- 0.28% for TIMP-1 and 0.50 +/- 0.10 versus 0.0075 +/- 0.0024% for collagenase, respectively). The difference in TIMP-2 between the two groups (2.91 +/- 0.46 versus 1.84 +/- 0.87%) did not differ. Therefore, the host would have responded to the increase in collagenase level by preferentially producing TIMP-1 against tissue destruction. The differential gene expression of TIMP-1 and TIMP-2 in our study may account for a distinct genetic regulation of TIMP-1 and -2 in vivo.


Synthesis, Characterization and the Solvent Effects on Interfacial Phenomena of Jatropha Curcas Oil Based Non-Isocyanate Polyurethane.
Non-isocyanate polyurethane (NIPU) was prepared from Jatropha curcas oil (JCO) and its alkyd resin via curing with different diamines. The isocyanate-free approach is a green chemistry route, wherein carbon dioxide conversion plays a major role in NIPU preparation. Catalytic carbon dioxide fixation can be achieved through carbonation of epoxidized derivatives of JCO. In this study, 1,3-diaminopropane (DM) and isophorone diamine (IPDA) were used as curing agents separately. Cyclic carbonate conversion was catalyzed by tetrabutylammonium bromide. After epoxy conversion, carbonated JCO (CJCO) and carbonated alkyd resin (CC-AR) with carbonate contents of 24.9 and 20.2 wt %, respectively, were obtained. The molecular weight of CJCO and CC-AR were determined by gel permeation chromatography. JCO carbonates were cured with different amine contents. CJCO was blended with different weight ratios of CC-AR to improve its characteristics. The cured NIPU film was characterized by spectroscopic techniques, differential scanning calorimetry, and a universal testing machine. Field emission scanning electron microscopy was used to analyze the morphology of the NIPU film before and after solvent treatment. The solvent effects on the NIPU film interfacial surface were investigated with water, 30% ethanol, methyl ethyl ketone, 10% HCl, 10% NaCl, and 5% NaOH. NIPU based on CCJO and CC-AR (ratio of 1:3) with IPDA crosslink exhibits high glass transition temperature (44 °C), better solvent and chemical resistance, and Young's modulus (680 MPa) compared with the blend crosslinked with DM. Thus, this study showed that the presence of CC-AR in CJCO-based NIPU can improve the thermomechanical and chemical resistance performance of the NIPU film via a green technology approach.


The complement of protein phosphatase catalytic subunits encoded in the genome of Arabidopsis.
Reversible protein phosphorylation is critically important in the modulation of a wide variety of cellular functions. Several families of protein phosphatases remove phosphate groups placed on key cellular proteins by protein kinases. The complete genomic sequence of the model plant Arabidopsis permits a comprehensive survey of the phosphatases encoded by this organism. Several errors in the sequencing project gene models were found via analysis of predicted phosphatase coding sequences. Structural sequence probes from aligned and unaligned sequence models, and all-against-all BLAST searches, were used to identify 112 phosphatase catalytic subunit sequences, distributed among the serine (Ser)/threonine (Thr) phosphatases (STs) of the protein phosphatase P (PPP) family, STs of the protein phosphatase M (PPM) family (protein phosphatases 2C [PP2Cs] subfamily), protein tyrosine (Tyr) phosphatases (PTPs), low-M(r) protein Tyr phosphatases, and dual-specificity (Tyr and Ser/Thr) phosphatases (DSPs). The Arabidopsis genome contains an abundance of PP2Cs (69) and a dearth of PTPs (one). Eight sequences were identified as new protein phosphatase candidates: five dual-specificity phosphatases and three PP2Cs. We used phylogenetic analyses to infer clustering patterns reflecting sequence similarity and evolutionary ancestry. These clusters, particularly for the largely unexplored PP2C set, will be a rich source of material for plant biologists, allowing the systematic sampling of protein function by genetic and biochemical means.


[Hearing loss due to mutations in the genes responsible for Usher syndrome].
Usher syndrome is characterized by congenital bilateral sensorineural hearing loss and progressive retinitis pigmentosa, and has an autosomal recessive type of inheritance. The purpose of this work is to summarize the modern data of a clinical picture of Usher syndrome and analyse hearing impairment properties. The frequency of the syndrome among children suffering from hearing loss and deafness is from 3 to 10%. The prevalence of the syndrome in the world is estimated as 4.4 per 100.000 population. The complexity of the diagnosis of the syndrome lies in the significant clinical and genetic heterogeneity. Hearing and vision problems begin at different ages. Primary diagnosis begins with the clinical diagnosis of bilateral hearing loss and visual impairment manifests later. In this case the initial diagnosis of nonsyndromal hearing loss will not be definitive. Molecular genetic studies contribute to the early clinical diagnosis of the syndrome. Understanding the cause of the disease allows to conduct correct medical and genetic counseling and get closer to solving treatment problems.


Lycium Barbarum Polysaccharide-Iron (III) Chelate as Peroxidase Mimics for Total Antioxidant Capacity Assay of Fruit and Vegetable Food.
Quantitative evaluation of the antioxidant capacity of foods is of great significance for estimating food's nutritional value and preventing oxidative changes in food. Herein, we demonstrated an easy and selective colorimetric method for the total antioxidant capacity (TAC) assay based on 3,3',5,5'-tetramethyl-benzidine (TMB), hydrogen peroxide (H2O2) and synthetic Lycium barbarum polysaccharide-iron (III) chelate (LBPIC) with high peroxidase (POD)-like activity. The results of steady-state kinetics study showed that the Km values of LBPIC toward H2O2 and TMB were 5.54 mM and 0.16 mM, respectively. The detection parameters were optimized, and the linear interval and limit of detection (LOD) were determined to be 2-100 μM and 1.51 μM, respectively. Additionally, a subsequent study of the determination of TAC in six commercial fruit and vegetable beverages using the established method was successfully carried out. The results implied an expanded application of polysaccharide-iron (III) chelates with enzymatic activity in food antioxidant analysis and other biosensing fields.


Intercellular communication in cultured human vascular smooth muscle cells.
Intercellular communication through gap junction channels plays a fundamental role in regulating vascular myocyte tone. We investigated gap junction channel expression and activity in myocytes from the physiologically distinct vasculature of the human internal mammary artery (IMA, conduit vessel) and saphenous vein (SV, capacitance vessel). Northern and Western blots documented the presence of connexin43 (Cx43) in frozen tissues and cultured cells from both vessels. Northern blots also confirmed the presence of Cx40 mRNA in cultured IMA and SV myocytes. Dual whole cell patch-clamp experiments revealed that macroscopic junctional conductance was voltage dependent and characteristic of that observed for Cx43. In the majority of records, in both vessels, single-channel activity was dominated by a main-state conductance of 120 pS, with subconducting events comprising less than 10% of the amplitude histograms. However, some records showed "atypical" unitary events that had a conductance similar to Cx40 (approximately 140-160 pS), but gating behavior like that of Cx43. As such, it is conceivable that the presence and coexpression of Cx40 and Cx43 in IMA and SV myocytes may result in heteromeric channel formation. Nonetheless, in terms of gating, Cx43-like behavior clearly dominates.


Dimeric Macrocyclic Antagonists of Inhibitor of Apoptosis Proteins for the Treatment of Cancer.
A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XIAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule.


Streptomyces lividans groES, groEL1 and groEL2 genes.
The Streptomyces lividans groES/EL1 operon and groEL2 gene were cloned and their respective DNA sequences determined. The sequenced DNA comprised the genes and their respective regulatory regions in both cases. Transcription of both groES/EL1 and groEL2 seemed to be subjected to temporal control at 30 degrees C. At 45 degrees C the amount of the groEL2 transcript increased considerably in comparison to that of groES/EL1. Among the proteins synthesized under heat shock by S. lividans, a fraction enriched in GroEL2 showed the presence of a ring-shaped structure that resembles that of other chaperonins and was active in a rhodanase folding assay.


The Highly Reduced Plastome of Mycoheterotrophic Sciaphila (Triuridaceae) Is Colinear with Its Green Relatives and Is under Strong Purifying Selection.
The enigmatic monocot family Triuridaceae provides a potentially useful model system for studying the effects of an ancient loss of photosynthesis on the plant plastid genome, as all of its members are mycoheterotrophic and achlorophyllous. However, few studies have placed the family in a comparative context, and its phylogenetic placement is only partly resolved. It was also unclear whether any taxa in this family have retained a plastid genome. Here, we used genome survey sequencing to retrieve plastid genome data for Sciaphila densiflora (Triuridaceae) and ten autotrophic relatives in the orders Dioscoreales and Pandanales. We recovered a highly reduced plastome for Sciaphila that is nearly colinear with Carludovica palmata, a photosynthetic relative that belongs to its sister group in Pandanales, Cyclanthaceae-Pandanaceae. This phylogenetic placement is well supported and robust to a broad range of analytical assumptions in maximum-likelihood inference, and is congruent with recent findings based on nuclear and mitochondrial evidence. The 28 genes retained in the S. densiflora plastid genome are involved in translation and other nonphotosynthetic functions, and we demonstrate that nearly all of the 18 protein-coding genes are under strong purifying selection. Our study confirms the utility of whole plastid genome data in phylogenetic studies of highly modified heterotrophic plants, even when they have substantially elevated rates of substitution.


Numerical Simulation on the Effect of Burner Bias Angles on the Performance of a Two-Stage Entrained-Flow Gasifier.
A 2000 t/day HNCERI (Huaneng Clean Energy Research Institute) entrained-flow pulverized coal gasifier suffers from the problem of a high ash-slag ratio. An appropriate bias angle of the burners is the key to solve this issue for the gasifier with a specific structure. A random pore model considering bulk and pore diffusion effects was extended by user-defined function to describe the gasification reactions. The simulation of the gas flow and char gasification characteristics under different bias angles (0, 1.5, 2.5, 3.5, and 4.5°) of the four burners in the first stage was conducted. The simulation results showed favorable agreement with the industrial data. The evaporation, devolatilization, and char oxidation mainly occurred in the first-stage jet zone, and the upflow and downflow zones are dominated by the gasification reactions. The bias angles of the burners mainly affect the scale of gasification reaction zones. As the bias angles increased from 0 to 4.5°, the gas temperature at the slag tap hole decreased from 1880 to 1500 K. The carbon conversion efficiency of the first stage decreases and that of the second stage increases with the bias angle increasing. An optimal bias angle of 2.5° is recommended for the HNCERI gasifier with a total carbon conversion efficiency of 98.16%.


Parotid gland tumors: preliminary data for the value of FDG PET/CT diagnostic parameters.
The purpose of this article is to establish (18)F-FDG metabolic imaging parameters to differentiate benign and malignant tumors of the parotid gland. Forty-nine patients with increased FDG uptake in the parotid gland were selected for the study group (29 men and 20 women; mean age, 63.14 ± 12.32 years). Another 49 patients without head and neck malignancies were selected as the control group (24 men and 25 women; mean age, 65.80 ± 11.51 years); they did not have a parotid lesion or increased FDG uptake in the parotid gland. Maximum standardized uptake value (SUV(max)) was obtained for all patients. Metabolic tumor volume and total glycolytic activity were measured in patients with a discrete parotid lesion (n = 24). Nonparameteric Student t test (Mann-Whitney U test) was performed for between-group analysis. The median SUV(max) of the increased diffuse uptake (2.55; interquartile range [IQR], 1.03-4.07) was significantly lower than the median SUV(max) of tumors (8.48; IQR, 1.46-15.5) (p < 0.01). The median SUV(max) of malignant tumors (11.8; IQR, 4.45-19.15) was significantly (p < 0.05) higher than that of benign tumors (6.4; IQR, 3.4-9.0). There was significant difference (p = 0.003) in the median metabolic tumor volume for malignant tumors (8.9; IQR, 5.1-25.5) and benign tumors or lesions (1.4; IQR, 1.00-2.9). Similar results were found for total glycolytic activity for malignant tumors (67.9; IQR, 24.2-137.6) and benign tumors or lesions (8.4; IQR, 3.9-13.6) (p = 0.002). FDG PET/CT SUV(max), metabolic tumor volume, and total glycolytic activity are imaging parameters to differentiate benign and malignant tumors of the parotid gland.


The first vancomycin-intermediate Staphylococcus aureus strains isolated from patients in Thailand.
We screened 533 and 361 methicillin (meticillin)-resistant Staphylococcus aureus strains isolated in a university hospital in 2002 and 2003 and in 2006 and 2007, respectively, and identified 4 (0.8%) of the strains in the first group and 8 (2.2%) of the strains in second group as heterogeneous vancomycin-resistant S. aureus (heterogeneous VISA) strains and 3 (0.8%) of the strains in the second group as VISA strains. This is the first report of VISA strains isolated from patients in Thailand.


[Antimicrobial salicylanilides and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones].
Salicylanilides and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones are strong antimycobacterial substances which can be considered to be potential antituberculotics. In order to be able to verify the prognostics of the relationships between the structure and antimycobacterial activity, the series of previously evaluated substances was extended to include 4'-ethoxycarbonylsalicylanilide, 4'-trifluoromethylsalicylanilide, 4'-cyanidosalicylanilide, 4'-thiocarbamoylsalicylanilide, 3-(4-ethoxycarbonylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dione, 3-(4-trifluoromethylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dione, and 3-(4-cyanidophenyl)-2H-1,3-benzoxazine-2,4-(3H)-dione. The substances were evaluated against Mycobacterium tuberculosis, M. kansasii, and M. avium. In harmony with the previous study (see ref. 1), antimycobacterial activity increased with increasing lipophilicity and electron-acceptor properties of substituents. As the values of regression coefficients were not substantially changed after the complementation of the group, the present authors consider the problem under study to be solved.


Ethylene Production by Attached Leaves or Intact Shoots of Tobacco Cultivars Differing in Their Speed of Yellowing during Curing.
Using an open air flow system, differences in the yellowing rate of leaves during curing were assessed in relation to ethylene production by shoots of intact seedlings or attached mature leaves of 60 day old tobacco (Nicotiana tabacum L.) plants. The rate of ethylene evolution from the leaves of the fast yellowing cultivars was significantly higher than in the slow yellowing ones. The same differences were obtained with shoots of intact seedlings. The findings suggest that it is possible to use ethylene production by seedlings as a selection criterion in screening for genotypic differences in the rate of yellowing. The ability of carbon dioxide (1%) to enhance ethylene production by attached leaves was significant in a slow, but not in a fast yellowing cultivar. However, similar amounts of ethylene were produced on administration of 1-aminocyclopropane-1-carboxylic acid to a slow and a fast yellowing cultivar. Exposure of attached leaves to exogenous ethylene (0.1 microliter per liter) accelerated the loss of chlorophyll and protein. This treatment was effective only for slightly yellow leaves and not for fully expanded green ones. The significance and possible use of ethylene in the flue-curing process are discussed.


Flow cytometric analysis and immunohistochemistry of delayed-type hypersensitivity responses in mice immunized with rat hepatocytes.
Delayed-type hypersensitivity (DTH) responses to rat hepatocytes (HCs) in mice were investigated by flow cytometric analysis and immunohistochemistry with monoclonal antibodies directed against murine class II, CD4, and CD8 antigens. Mice were immunized subcutaneously (s.c.) with 10(6) rat HCs (referred to as s.c.-immunized mice), and control mice were injected s.c. with sterile Hanks' solution (non-immunized mice). Four days later, 10(5) rat HCs were injected into the footpad of s.c.-immunized mice and non-immunized mice. The DTH response in s.c.-immunized mice significantly increased after challenge when compared to that in non-immunized mice. The numbers of class II+, CD4+, and CD8+ cells in the footpad, and CD4+ and CD8+ cells in the inguinal lymph node of s.c.-immunized mice significantly increased during the DTH response. An increase in the number of CD4+ cells in the footpad of s.c.-immunized mice after challenge was more significant than that of non-immunized mice. The number of CD4+ cells increased more markedly in the footpad of s.c.-immunized mice as compared to that of CD8+ cells. Furthermore, immunohistochemical studies of the footpad of s.c.-immunized mice showed more severe infiltration of CD4+ cells rather than CD8+ cells at the injection site of rat HCs. These results suggest that the DTH response in the footpad of mice immunized with rat HCs is associated with severe infiltration of CD4+ cells.


Sutherlandia frutescens may exacerbate HIV-associated neuroinflammation.
Neuroinflammation is central to the aetiology of HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS. Anti-retroviral (ARV) treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is common practice for HIV+ individuals in developing countries to make use of traditional medicines. One such medicine is Sutherlandia frutescens - commonly consumed as a water infusion. Here its efficacy as an anti-inflammatory modality in this context was investigated in an in vitro co-culture model of the blood-brain barrier (BBB). Single cultures of human astrocytes (HA), HUVECs and primary human monocytes, as well as co-cultures (BBB), were stimulated with HIV-1 subtype B & C Tat protein and/or HL2/3 cell secretory proteins after pre-treatment with S.frutescens extract. Effects of this pre-treatment on pro-inflammatory cytokine secretion and monocyte migration across the BBB were assessed. In accordance with others, B Tat was more pro-inflammatory than C Tat, validating our model. S.frutescens decreased IL-1β secretion significantly (P < 0.0001), but exacerbated both monocyte chemoattractant protein-1 (P < 0001) - a major role player in HIV-associated neuroinflammation - and CD14+ monocyte infiltration across the BBB (P < 0.01). Current data illustrates that the combined use of HL2/3 cells and the simulated BBB presents an accurate, physiologically relevant in vitro model with which to study neuroinflammation in the context of HIV/AIDS. In addition, our results caution against the use of S.frutescens as anti-inflammatory modality at any stage post-HIV infection.


Isolation of a DNA plasmid in the fungus Rhizoctonia solani.
A DNA plasmid, designated pRS64, was detected in three isolates of anastomosis group 4 (AG-4) of Rhizoctonia solani Kühn by biophysical methods. The plasmid was a linear double-stranded DNA with a molecular weight of 1.68 +/- 0.06 X 10(6) or 2617 +/- 87 bp. Weakly pathogenic isolates of R. solani, 1668 RI-1, 1271 RI-64 and 1272 RI-1, which showed abnormally slow growth, contained the plasmids, but pathogenic isolates, 1668, 1271 and 1272, showing normal growth, contained no detectable plasmid DNA.


Twenty-six-Week carcinogenicity study of chloroform in CB6F1 rasH2-transgenic mice.
The carcinogenic potential of chloroform was evaluated in a short-term carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg) male and female mice received doses of 140 mg/kg and 240 mg/kg, respectively. N-methyl-N-nitrosourea was administered to rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. In both the rasH2-Tg and non-Tg mice, there was no significant increase in the incidence of neoplastic lesions by chloroform treatment. The incidence of hepatocellular foci in the rasH2- and non-Tg females receiving 240 mg/kg was increased. Forestomach tumors and malignant tumors occurred in most of the rasH2-mice in the positive control group. Swelling or vacuolation of hepatocytes, a toxic change induced by chloroform, occurred in both the rasH2-Tg and non-Tg mice. It is concluded that chloroform, a putative human noncarcinogen, did not show evidence of carcinogenic potential in the present study using rasH2-Tg mice. This study suggests that the rasH2-Tg mouse model may not be appropriate for detecting nongenotoxic carcinogens. However, the sensitivity of rasH2-Tg mice to nongenotoxic carcinogens should be assessed with consideration of the results from the other ILSI-HESI project studies.


Interface chemistry engineering of protein-directed SnO₂ nanocrystal-based anode for lithium-ion batteries with improved performance.
A novel uniform amorphous carbon-coated SnO2 nanocrystal (NCs) for use in lithium-ion batteries is formed by utilizing bovine serum albumin (BSA) as both the ligand and carbon source. The SnO2 -carbon composite is then coated by a controlled thickness of polydopamine (PD) layer through in situ polymerization of dopamine. The PD-coated SnO2 -carbon composite is finally mixed with polyacrylic acid (PAA) which is used as binder to accomplish a whole anode system. A crosslink reaction is built between PAA and PD through formation of amide bonds to produce a robust network in the anode system. As a result, the designed electrode exhibits improved reversible capacity of 648 mAh/g at a current density of 100 mA/g after 100 cycles, and an enhanced rate performance of 875, 745, 639, and 523 mAh/g at current densities of 50, 100, 250, and 500 mA/g, respectively. FTIR spectra confirm the formation of crosslink reaction and the stability of the robust network during long-term cycling. The great improvement of capacity and rate performance achieved in this anode system is attributed to two stable interfaces built between the active material (SnO2 -carbon composite) and the buffer layer (PD) and between the buffer layer and the binder (PAA), which effectively diminish the volume change of SnO2 during charge/discharge process and provide a stable matrix for active materials.


Controlled Morphing of Microbubbles to Beaded Nanofibers via Electrically Forced Thin Film Stretching.
Topography and microstructure engineering are rapidly evolving areas of importance for biomedical and pharmaceutical remits. Here, PVA (Polyvinyl alcohol) microbubbles (diameter range ~126 to 414 μm) were used to fabricate beaded (beads-on) nanofibers using an electrohydrodynamic atomization (EHDA) technique. Mean fiber diameter, inter-bead distance, and aspect ratio (AR) were investigated by regulating EHDA process parameters. PVA fibers (diameter range ~233 to 737 nm) were obtained possessing bead ARs in the range of ~10 to 56%. AR was used to modulate hydrophilicity and active release.


Headache of Wearing PPE; A Survey for Neurological Symptoms with PPE amongst Health Care Workers.
The COVID-19 pandemic has put the entire medical fraternity into a very challenging and demanding situation. Along with always being at the risk of COVID infection, healthcare workers (HCWs) are also facing neurological problems due to long working hours in personal protective equipment (PPE). These symptoms and their characteristics need to be observed and studied in-depth to understand the problems experienced by HCWs and to design new solutions to overcome such problems. This study intends to evaluate the various neurological manifestations among the HCWs wearing PPE for prolonged periods. We conducted a questionnaire-based cross-sectional study at a Covid care center from western India from April 20 to June 01, 2021 by using a self-administered web-based questionnaire. A total of 256 HCWs were surveyed. The de-identified data were analyzed using JMP 15.0.0. Among a total of 256 HCWs surveyed for this study, the majority (58.6%) were aged 24-35 years, with a male preponderance (65.62%, n = 168). Participants included doctors (41%), nurses (35%), paramedical staff (22%), and housekeeping staff (1%). The symptoms encountered among the HCWs wearing the PPE were headache, classified further as donning headache in 112 (44.98%), doffing headache in 56 (26.24%), slowed mentation in 48 (21.05%), and excessive sleepiness in 86 (38.74%), which affected their work performance. The age of the HCWs had a significant correlation with all the symptoms. Headache, slowed mentation, and excessive sleepiness was encountered among the HCWs wearing PPE, which depended upon the duration of PPE usage. The most common symptom was headache, which was of moderate to severe intensity.


Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease.
Diabetic heart disease (DHD) is the leading cause of morbidity and mortality among the people with diabetes, with approximately 80% of the deaths in diabetics are due to cardiovascular complications. Importantly, heart disease in the diabetics develop at a much earlier stage, although remaining asymptomatic till the later stage of the disease, thereby restricting its early detection and active therapeutic management. Thus, a better understanding of the modulators involved in the pathophysiology of DHD is necessary for the early diagnosis and development of novel therapeutic implications for diabetes-associated cardiovascular complications. microRNAs (miRs) have recently been evolved as key players in the various cardiovascular events through the regulation of cardiac gene expression. Besides their credible involvement in controlling the cellular processes, they are also released in to the circulation in disease states where they serve as potential diagnostic biomarkers for cardiovascular disease. However, their potential role in DHD as modulators as well as diagnostic biomarkers is largely unexplored. In this review, we describe the putative mechanisms of the selected cardiovascular miRs in relation to cardiovascular diseases and discuss their possible involvement in the pathophysiology and early diagnosis of DHD.


In vivo relevance of two critical levels for NAD(P)H:quinone oxidoreductase (NQO1)-mediated cellular protection against electrophile toxicity found in vitro.
NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones is suggested to be involved in cancer prevention. In the present study, using transfected CHO cells, it was demonstrated that the relation between NQO1 activity and the resulting protection against the cytotoxicity of menadione shows a steep dose-response curve revealing a 'lower protection threshold' of 0.5mumol DCPIP/min/mg protein and an 'upper protection threshold' at 1mumol DCPIP/min/mg protein. In an additional in vivo experiment it was investigated how both in vitro critical activity levels of NQO1, relate to NQO1 activities in mice and man, either without or upon induction of the enzyme by butylated hydroxyanisol (BHA) or indole-3-carbinol (I(3)C). Data from an experiment with CD1 mice revealed that base-line NQO1 levels in liver, kidney, small intestine, colon and lung are generally below the observed 'lower protection threshold' in vitro, this also holds for most human tissue S-9 samples. To achieve NQO1 levels above this 'lower protection threshold' will require 5-20 fold NQO1 induction. Discussion focuses on the relevance of the in vitro NQO1 activity thresholds for the in vivo situation. We conclude that increased protection against menadione toxicity can probably not be achieved by NQO1 induction but should be achieved by other mechanisms. Whether this conclusion also holds for other electrophiles and the in vivo situation awaits further definition of their NQO1 protection thresholds.


CAR-T Plus Radiotherapy: A Promising Combination for Immunosuppressive Tumors.
Radiotherapy (RT) is the standard-of-care treatment for more than half of cancer patients with localized tumors and is also used as palliative care to facilitate symptom relief in metastatic cancers. In addition, RT can alter the immunosuppressive tumor microenvironment (TME) of solid tumors to augment the anti-tumor immune response of immune checkpoint blockade (ICB). The rationale of this combination therapy can also be extended to other forms of immunotherapy, such as chimeric antigen receptor T cell (CAR-T) therapy. Similar to ICB, the efficacy of CAR-T therapy is also significantly impacted by the immunosuppressive TME, leading to compromised T cell function and/or insufficient T cell infiltration. In this review, we will discuss some of the key barriers to the activity of CAR-T cells in the immunosuppressive TME and focus on how RT can be used to eliminate or bypass these barriers. We will present the challenges to achieving success with this therapeutic partnership. Looking forward, we will also provide strategies currently being investigated to ensure the success of this combination strategy in the clinic.


A High-Robust Automatic Reading Algorithm of Pointer Meters Based on Text Detection.
Automatic reading of pointer meters is of great significance for efficient measurement of industrial meters. However, existing algorithms are defective in the accuracy and robustness to illumination shooting angle when detecting various pointer meters. Hence, a novel algorithm for adaptive detection of different pointer meters was presented. Above all, deep learning was introduced to detect and recognize scale value text in the meter dial. Then, the image was rectified and meter center was determined based on text coordinate. Next, the circular arc scale region was transformed into a linear scale region by polar transform, and the horizontal positions of pointer and scale line were obtained based on secondary search in the expanded graph. Finally, the distance method was used to read the scale region where the pointer is located. Test results showed that the algorithm proposed in this paper has higher accuracy and robustness in detecting different types of meters.


[Age distribution and clinical characteristics in acute appendicitis].
The retrospective analysis comprised 986 of 1050 patients operated on for acute appendicitis in the period 1983-1987. Appendicitis was most common in the age group from 11 to 20 years. The perforation frequency was 12.4%. Seventy four percent of patients came to the first medical examination with already perforated appendix. The necessary period of observation is the first 12 hours after onset of troubles. Probable presence of phlegmonous appendicitis is small if 48 hours have passed after initiation of troubles. The frequency of the studied symptoms (nausea, vomiting, temperature, leukocytosis) ranged from 49.4% to 64.8%. The most common postoperative complication is wound infection. The overall mortality rate was 0.1%.


[Medical importance of GTP-binding proteins].
Small GTP-binding proteins consist of one single, 21 kD polypeptide chain. These regulatory proteins are active in the GTP-bound but inactive in the GDP-bound form. They are involved in the regulation of several important cell functions, such as cell division, cell motility, shape changes, intracellular membrane traffic, transport of macromolecules between cytoplasm and nucleus, assembly of enzyme complexes. Recently several mutations have been described which modify the function of small G-proteins resulting in typical pathological changes. These diseases and the molecular alterations involved in their pathomechanism are summarized in this review.


Structural insights into the conformational selectivity of STI-571 and related kinase inhibitors.
STI-571 (Gleevec) is a highly successful cancer drug due to its activity as an inhibitor of the Abelson cytoplasmic tyrosine kinase (Abl), which is constitutively active in a majority of patients with chronic myelogenous leukemia. STI-571 also inhibits two type III receptor tyrosine kinases, c-Kit and platelet-derived growth factor receptor, and functions by targeting inactive conformations of these kinases. This review focuses on recent developments in X-ray co-crystal structure analyses of STI-571 bound to Abl and the c-Kit receptor tyrosine kinase domain, and also three other relevant kinase inhibitor co-crystal structures. The similar structural features of these inactive kinases suggest they will be useful for the successful drug discovery and development of specific and targeted gene-based cancer drugs.


[Study on relative problems of acupuncture and moxibustion for treatment of simple obesity].
There are many methods of acupuncture and moxibustion for treatment of simple obesity with definite therapeutic effects, so, they are followed with interest. However, their therapeutic effects are very different for different individuals, and there are many factors influencing therapeutic effects. The author consults 31 papers in publication about Chinese medicine, acupuncture and moxibustion at home in recent years, and in combination with own clinical practice and experience of many years on acupuncture and moxibustion for slimming, and ponders over the relative problems of syndrome differentiation treatment, therapeutic course, rebound, diet control, sports, psycho-therapy, etc. in clinical treatment, and raises personal some knowledge, so as to probe to increasing clinical effects of acupuncture and moxibustion on simple obesity and provide reference material for clinical treatment in future.


Homology and errors.
A recent review of the homology concept in cladistics is critiqued in light of the historical literature. Homology as a notion relevant to the recognition of clades remains equivalent to synapomorphy. Some symplesiomorphies are "homologies" inasmuch as they represent synapomorphies of more inclusive taxa; others are complementary character states that do not imply any shared evolutionary history among the taxa that exhibit the state. Undirected character-state change (as characters optimized on an unrooted tree) is a necessary but not sufficient test of homology, because the addition of a root may alter parsimonious reconstructions. Primary and secondary homology are defended as realistic representations of discovery procedures in comparative biology, recognizable even in Direct Optimization. The epistemological relationship between homology as evidence and common ancestry as explanation is again emphasized. An alternative definition of homology is proposed. © The Willi Hennig Society 2012.


Cylindrical inclusions in the cytoplasm of leaf cells infected with tobacco etch virus.
Combined tracings from electron micrographs of serial sections of leaf tissue infected with tobacco etch virus show that one type of cytoplasmic inclusion, when sectioned in different planes, can produce configurations which have been interpreted as being two distinct types of inclusion bodies.


[From urostoma to bladder replacement: current possibilities in urinary diversion].
To analyse 48 urinary diversions in an oncological patient population. Retrospective study. The Dutch cancer institute 'Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis' in Amsterdam, the Netherlands. The medical records of all patients who had a urinary diversion in the period 1989-1993 were analysed for type of diversion, indication for this specific type and postoperative complications. In 48 patients (24 women and 24 men with a mean age of 62.1 years) a urinary diversion was constructed because of cystectomy for bladder cancer (n = 27), cystectomy in total pelvic exenteration (13), total urinary incontinence following radiotherapy (5), urethral cancer (1) or local palliation (2). Twenty-one diversions according to Bricker, 25 continent reservoirs according to Rowland and (or) neo-bladders, I ureterosigmoidostomy and I continent access to the bladder (Mitrofanoff procedure) were done. The standard diversion according to Bricker was preferred in the following circumstances: extensive intestinal resections (also previous ones), older age, fear of incontinence or no need for continent diversion. Specific problems of the new diversion techniques were difficulties of patients with catheterising the reservoir and folic acid deficiency. All other postoperative problems were related to the extensiveness of the primary oncological procedure rather than to the diversion technique. Apart from a few contraindications such as shortage of intestine, tumour growth into the urethra and patients' inability or unwillingness to catheterize themselves, there are no objections to the new diversion techniques (continent reservoir/neo-bladder). Patients being considered for urinary diversion ought to be informed about these new techniques.


Prediction of overall survival in patients with pancreatic ductal adenocarcinoma: histogram analysis of ADC value and correlation with pathological intratumoral necrosis.
To evaluate the utility of histogram analysis (HA) of apparent diffusion coefficient (ADC) values to predict the overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) and to correlate with pathologically evaluated massive intratumoral necrosis (MITN). Thirty-nine patients were included in this retrospective study with surgically resected PDAC who underwent preoperative magnetic resonance imaging. Twelve patients received neoadjuvant chemotherapy. HA on the ADC maps were performed to obtain the tumor HA parameters. Using Cox proportional regression analysis adjusted for age, time-dependent receiver-operating-characteristic (ROC) curve analysis, and Kaplan-Meier estimation, we evaluated the association between HA parameters and OS. The association between prognostic factors and pathologically confirmed MITN was assessed by logistic regression analysis. The median OS was 19.9 months. The kurtosis (P < 0.001), entropy (P = 0.013), and energy (P = 0.04) were significantly associated with OS. The kurtosis had the highest area under the ROC curve (AUC) for predicting 3-year survival (AUC 0.824) among these three parameters. Between the kurtosis and MITN, the logistic regression model revealed a positive correlation (P = 0.045). Lower survival rates occurred in patients with high kurtosis (cutoff value > 2.45) than those with low kurtosis (≤ 2.45) (P < 0.001: 1-year survival rate, 75.2% versus 100%: 3-year survival rate, 14.7% versus 100%). HA derived kurtosis obtained from tumor ADC maps might be a potential imaging biomarker for predicting the presence of MITN and OS in patients with PDAC.


Antidiarrheal Effect of 80% Methanol Extract and Fractions of the Roasted Seed of Coffea arabica Linn (Rubiaceae) in Swiss Albino Mice.
Globally in 2019, diarrhea was the second leading cause of mortality in children, accounting for more than half a million under-five deaths yearly. Several societies use Coffea arabica Linn for the treatment of diarrhea. However, its use is not scientifically validated. The study was conducted to evaluate antidiarrheal activity of 80% methanol extract and solvent fractions of roasted seed of Coffea arabica Linn in mice. Coffea arabica Linn seed was roasted, milled, extracted, and fractionated using hexane, ethyl acetate, and distilled water. Castor oil-induced diarrhea, enteropooling, and motility tests were conducted. Effects on onset, number of feces, weight of feces, fluid content, volume and weight of intestinal content, and motility were evaluated by administering 100 mg/kg, 200 mg/kg, and 400 mg/kg of each extract. Negative controls received 10 ml/kg of the vehicle, and positive controls received either loperamide (3 mg/kg) or atropine (1 mg/kg). Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. Ethyl acetate fraction at all tested doses significantly prolonged (p < 0.05) onset of diarrhea. The number and weight of feces were also reduced significantly by crude extract and ethyl acetate fraction. Reduction in fluid content was observed at 200 mg/kg and 400 mg/kg of the crude extract (p < 0.01) and aqueous fraction (p < 0.001) as well as all tested doses of ethyl acetate fraction (p < 0.001). Similarly, the crude extract, ethyl acetate fraction, and aqueous fraction showed a significant reduction in the volume and weight of intestinal content. At 400 mg/kg, the crude extract, hexane fraction, aqueous fraction, and all doses of ethyl acetate fraction showed significant antimotility activity. The results of this study revealed that the roasted seed of Coffea arabica Linn has antidiarrheal activity.


Complications of epilepsy surgery in children and adolescents.
The Children's Hospital of Eastern Ontario's Epilepsy Surgery Series of 47 medically intractable children and adolescents was reviewed and analyzed to assess complications of surgical treatment. Complications and rates of incidence are discussed, and compared with the existing literature regarding children, adolescents and adults. No deaths or permanent disabling complications were incurred. Minor morbidity was minimal: 2 (4.2%) sustained permanent but nondisabling complications while an additional 3 (6.4%) incurred transient neurologic deficits which resolved rapidly. Epilepsy surgery in children and adolescents is safe, highly effective, and underutilized.


Three-Dimensional Electrochromic Soft Photonic Crystals Based on MXene-Integrated Blue Phase Liquid Crystals for Bioinspired Visible and Infrared Camouflage.
Developing bioinspired camouflage materials that can adaptively change color in the visible and infrared (IR) regions is an intriguing but challenging task. Herein, we report an emerging strategy for fabricating dynamic visible and IR camouflage materials by the controlled in situ growth of novel photopolymerizable blue phase liquid crystals with cubic nanoarchitectures onto highly aligned MXene nanostructured thin films. The resulting MXene-integrated 3D soft photonic crystals exhibit vivid structural colors and reversible switching between a bright colored state and a dark black state under a low DC electric field. As an illustration, proof-of-concept pixelated devices that allow for pixel-controllable electrochromism are demonstrated. Furthermore, a free-standing electrochromic flexible film of such 3D soft photonic crystals is fabricated, where visible electrochromism and thermal camouflage are enabled by leveraging the superior electrothermal conversion and low mid-IR emissivity of MXene nanomaterials.


Quantitative analysis of rough endoplasmic reticulum approaches to the cell membrane in the secretory ameloblast of the rat incisor.
The distribution of approaches of rough endoplasmic reticulum to the cell membrane within the supranuclear region of the secretory ameloblast of the rat incisor was quantitated using a Zeiss MOP-3. In ameloblasts cut in cross section, most of these approaches appear as circular profiles representing cross sections of elongated cisternae, which are aligned parallel to the long axis of the cell. Because of their position, orientation, and distribution of ribosomes, these approaches were consistent with the appearance of subsurface cisternae. Using cross-sectioned ameloblasts, the lengths of apposed plasma membranes either between or within rows of cells were measured from electron micrographs. Along these lengths, matched approaches of rough endoplasmic reticulum from opposite sides of the apposed plasma membranes were counted. Approaches from either side that were unmatched were also counted. Thirteen percent of the approaches were matched between rows of ameloblasts, and 13.5% of the approaches were matched within rows, demonstrating no significant difference between the two sites. Furthermore, mathematical analysis showed that the theoretical probability of two approaches coinciding is 17%. The experimental values are not statistically different from the theoretical probability, and it is concluded that the matching of rough endoplasmic reticulum approaches to the plasma membrane, or subsurface cisternae, occurs at random.


The role of organic phosphate in the spatial control of periodontium complex bio-mineralization: an in vitro study.
The periodontal structure is a particularly exquisite model of hierarchical spatial control of mineralization. Extracellular matrix control in the selective mineralization of the periodontium complex remains elusive since the extracellular matrix is a set of mineralization promoters and inhibitors. The phosphorylated proteins, which are ubiquitous in the extracellular matrix of the periodontium complex, are well-documented as primary factors in the regulation of tissue mineralization. Whether organic phosphates are key regulators in defining the interfaces between dentin, cementum, periodontal ligament and alveolar bone is an issue worthy of research. Here, we investigated the in vitro remineralization process of demineralized and dephosphorylated periodontal tissue sections. When exposed to a metastable mineralization solution, a large number of calcospherulites deposited on the surface of the dephosphorylated sections and the tissue selective mineralization were disrupted. Interestingly, on adding a dentin matrix protein-1 analogue named polyacrylic acid, the surface mineralization rate in the dephosphorylated periodontal complex reduced dramatically. In contrast, hierarchical mineralization was displayed by the demineralized section at the tissue collagen fibrillar levels in both alveolar bone and dentin regions. These results demonstrated that the organic phosphate could prevent surface mineral deposition, and the minerals could penetrate the collagen fibrils to initiate a selective and hierarchal tissue mineralization with the assistance of the dentin matrix protein-1 analogue in the periodontal complex. This study enhances our understanding of the mineralization discrepancy in the periodontal tissues, which will provide some insight into the development of biomaterials for the regeneration of soft-hard tissue interfaces.


Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study.
Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long-term effects on perfusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administered to 14 heroin-dependent patients from a stable heroin-assisted treatment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel-Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM) and a whole-brain Pearson r correlation. We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short-term effects, while placebo-associated perfusion is more related to long-term effects. In order to restrict our analyses to fronto-temporal regions, we used an explicit mask for our analyses. Correlation analyses revealed a significant positive correlation in frontal areas between GM and both perfusion conditions (heroin and placebo). Heroin-associated perfusion was also negatively correlated with GM in the inferior temporal gyrus on both hemispheres. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with low perfusion within frontal regions.


Signaling pathways for antigen receptor-mediated induction of transcription factor CREB in B lymphocytes.
We previously reported that cross-linking surface immunoglobulin (sIg) leads to induction of the transcription factor CREB in B lymphocytes through phosphorylation at Ser133, despite the lack of an increase in cAMP. Further, cAMP-raising agents fail to induce CREB Ser133 phosphorylation and CRE-dependent gene expression in these cells, which differs sharply from the situation in PC12 rat pheochromocytoma cells where CREB responds to elevation of cAMP through the activity of protein kinase A. In this study, we characterized the signal transduction pathways leading from sIg engagement to CREB activation. By using specific inhibitors for protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), and protein kinase A (PKA), we found that anti-Ig-induced CREB Ser133 phosphorylation depends on PKC, but does not require activation of PKA or CaM kinase II. The differential responsiveness of CREB to forskolin in PC12 cells and BAL-17 B cells may relate to the more marked elevation of cAMP in the former as opposed to the latter; however, high concentrations of dbcAMP which should readily enter B cells and artificially increase cAMP levels still failed to induce CREB Ser133 phosphorylation, even in conjunction with a phosphodiesterase inhibitor. Taken together, the cAMP/PKA pathway does not appear to be as active a contributor to CREB phosphorylation in B lymphocytes as in PC12 cells, and does not appear to be involved in sIg-induced, PKC-dependent, CREB activation.


Glucose-induced protein kinase C activity regulates arachidonic acid release and eicosanoid production by cultured glomerular mesangial cells.
Changes in glomerular eicosanoid production have been implicated in the development of diabetes-induced glomerular hyperfiltration and glomerular mesangial cells (GMC) are major eicosanoid-producing cells within the glomerulus. However, the mechanism for the effect of diabetes mellitus on glomerular mesangial eicosanoid production is unknown. The present study therefore examined whether elevated glucose concentrations activate protein kinase C (PKC) in GMC and whether this PKC activation mediates an effect of elevated glucose concentrations to increase the release of arachidonic acid and eicosanoid production by GMC. The percentage of [3H]arachidonic acid release per 30 min by preloaded GMC monolayers was significantly increased after 3-h exposure to high glucose (20 mM) medium (177% vs control medium) and this increase was sustained after 24-h exposure to high glucose concentrations. 3-h and 24-h exposure to high glucose medium also increased PGE2, 6-keto-PGF1 alpha, and thromboxane (TXB2) production by GMC. High glucose medium (20 mM) increased PKC activity in GMC at 3 and 24 h (168% vs control). In contrast, osmotic control media containing either L-glucose or mannitol did not increase arachidonic acid release, eicosanoid production, or PKC activity in GMC. Inhibiting glucose-induced PKC activation with either H-7 (50 microM) or staurosporine (1 microM) prevented glucose-induced increases in arachidonic acid release and eicosanoid production by GMC. These data demonstrate that elevated extracellular glucose concentrations directly increase the release of endogenous arachidonic acid and eicosanoids by GMC via mechanisms dependent on glucose-induced PKC activation.


A mouse model for sleeve gastrectomy: applications for diabetes research.
Discovery of enhanced glucose tolerance following bariatric surgery has sparked renewed interest in the investigation of unchartered underlying pathways of glucose homeostasis. Delineation of this pathway may ultimately be the first step in the creation of a novel therapy for type II diabetes. Nevertheless, the technical complexity and formidable nature of these surgeries coupled with the fragile nature of small rodents has made the creation of a mouse model to study these effects incredibly challenging. We have created a simplified sleeve gastrectomy mouse model to study the effects of bariatric surgery on glucose tolerance and beta cell proliferation. Nineteen mice were randomized to undergo either sleeve gastrectomy (SG) (9) or sham operation (SH) (10). Weight and serum glucose were measured three times weekly and serum insulin measurements and pancreatic harvest were performed at the time of sacrifice. Five mice from each group were sacrificed after one week and the remainder sacrificed after one month. Survival of mice was 100% for both groups. The SG group demonstrated an initial drop in weight and serum glucose as compared to SH, which normalized by one month following surgery. Serum insulin levels and rate of beta cell proliferation were similar in both groups after one week and one month. The simplified sleeve gastrectomy is a technically straightforward, low-mortality technique for creating a bariatric mouse model which most faithfully replicates bariatric surgery performed in humans. This model can be a valuable tool to investigate the glucose tolerance and beta cell effects of bariatric surgery.


White Matter Integrity Deficit Associated with Betel Quid Dependence.
Betel quid (BQ) is a commonly consumed psychoactive substance, which has been regarded as a human carcinogen. Long-term BQ chewing may cause Diagnostic and Statistical Manual of Mental Disorders-IV dependence symptoms, which can lead to decreased cognitive functions, such as attention and inhibition control. Although betel quid dependence (BQD) individuals have been reported with altered brain structure and function, there is little evidence showing white matter microstructure alternation in BQD individuals. The present study aimed to investigate altered white matter microstructure in BQD individuals using diffusion tensor imaging. Tract-based spatial statistics was used to analyze the data. Compared with healthy controls, BQD individuals exhibited higher mean diffusivity (MD) in anterior thalamic radiation (ATR). Further analysis revealed that the ATR in BQD individuals showed less fractional anisotropy (FA) than that in healthy controls. Correlation analysis showed that both the increase of MD and reduction of FA in BQD individuals were associated with severity of BQ dependence. These results suggested that BQD would disrupt the balance between prefrontal cortex and subcortical areas, causing declined inhibition control.


Cell adhesion molecules in the development and progression of malignant melanoma.
Cell adhesion molecules belonging to the integrin, cadherin and immunoglobulin superfamilies have been implicated in tumor progression in cutaneous melanoma. Expression of the alpha v beta 3 integrin first appears with the change from radial to vertical growth, a step which is associated with the development of metastatic potential. VLA-4 expression is characteristic of advanced primary tumors and may mediate interaction of the tumor cells with VCAM-1 on vascular endothelium. Expression of these integrins is a marker of poor prognosis in patients and can confer invasive (alpha v beta 3) and metastatic (VLA-4) properties to human melanoma cells injected into nude mice. Expression of the immunoglobulin superfamily molecules MUC18/MCAM and ICAM-1 are associated with primary tumors and metastases. MUC18/MCAM expression confers metastatic potential and increased tumorigenicity to human melanoma cells. Expression of ICAM-1 has been shown to be a marker of poor prognosis in stage I tumors and interfering with its expression inhibits experimental metastasis by melanomas in nude mice. E-cadherin is used by epidermal melanocytes to interact with neighboring keratinocytes. Changes in E-cadherin expression and cellular localization is first observed in the radial growth phase, the earliest stage in melanoma development. Loss of E-cadherin function is associated with upregulation or induction of MUC18/MCAM and alpha v beta 3 in melanocytic cells in vitro and with alterations in the levels and cellular distribution of the transcriptional regulator beta-catenin in melanomas in vivo. These observations suggest that disturbances in E-cadherin function is not only important in carcinomas but may also be a critical event in melanoma tumor progression.


[Application of augmented reality and mixed reality navigation technology in laparoscopic limited right hepatectomy].
Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.


1,3-Diborata-2,4-diphosphoniocyclobutane-1,3-diyls communicate through a para-phenylene linker.
The presence of a second 1,3-diborata-2,4-diphosphoniocyclobutane-1,3-diyl in the para-position of a phenylene linker favors the diradical form over the 1,3-diborata-2,4-diphosphoniobicyclo[1.1.0]butane bond stretch isomer, as long as the two planar diradical units are coplanar with the linker. This demonstrates that two BPBP diradicals communicate through the phenyl ring.


The ACA's Cost-Sharing Reduction Plans: A Key to Affordable Health Coverage for Millions of U.S. Workers.
Issue: Without the cost-sharing reductions (CSRs) made available by the Affordable Care Act, health plans sold in the marketplaces may be unaffordable for many low-income people. CSRs are available to households earning between 100 percent and 250 percent of the federal poverty level that choose a silver-level marketplace plan. In 2016, about 7 million people received cost-sharing reductions that substantially lowered their deductibles, copayments, coinsurance, and out-of-pocket limits. Goal: To examine variations in consumer cost-sharing reductions between silver-level plans with CSRs to traditional marketplace plans and to employer-based insurance. Methods: Data analysis of 1,209 CSR-eligible plans sold in individual marketplaces in all 50 states and Washington, D.C. Key findings and conclusions: Cost-sharing amounts in silver plans with CSRs are much less than those in non-CSR base silver plans; silver plans with CSRs generally offer far better financial protection than those without. General annual deductibles range from $246 for CSR silver plans with a platinum-level actuarial value (94%) to as much as $3,063 for non-CSR silver plans. Out-of-pocket limits vary from $6,223 in base silver plans to $1,102 in silver plans with CSRs and a platinum-level actuarial level.


Deformities of the forearm in patients who have multiple cartilaginous exostosis.
Thirty-five patients who had multiple cartilaginous exostosis and deformities of the wrist and forearm were evaluated to determine the natural history and prognostic factors for the deformities. Radial and ulnar shortening were correlated linearly (r2 = 0.86), showing that both bones of the forearm were symmetrically involved. The angular growth abnormality of the distal aspect of the radius was correlated with radial shortening (r2 = 0.53) and ulnar shortening (r2 = 0.61), but it had no correlation with negative variance of the ulnar (r2 = 0.30). Carpal slip was an independent factor, with no correlation with any of the factors studied. The ulnar tether theory for deformities of the wrist in patients who have multiple cartilaginous exostosis was not substantiated by this study.


Conformation-specific self-assembly of thermo-responsive poly(ethylene glycol)-b-polypeptide diblock copolymer.
Poly(ethylene glycol)-block-poly(γ-(2-methoxyethoxy)esteryl-L-glutamate) (PEG-b-poly-L-EG2Glu) was synthesized via ring-opening polymerization (ROP) of L-EG2Glu N-carboxyanhydride (NCA) using PEG-NH2 as macroinitiator. This diblock contained a thermo-responsive poly-L-EG2Glu block, which adopted primarily helical conformation in pristine aqueous solution. We found that PEG-b-poly-L-EG2Glu diblock can display two levels of self-assembly behaviors associated with hydrophobic interactions and conformation-specific reassembly, respectively. Upon temperature increase, the PEG-b-poly-L-EG2Glu diblock formed wormlike micelles, in which the poly-L-EG2Glu formed the micelle core and maintained helical conformation. However, extension of thermal annealing time drove the secondary structure transformation of the poly-L-EG2Glu block from helical conformation to β-sheet, which accounted for an assembly structure transition from wormlike micelles to nanoribbons. The critical factor was that poly-L-EG2Glu block can undergo thermo-induced hydrophobicity and conformation transformation, which offered an additional parameter to tune the nature of molecular interactions, i.e., intermolecular versus intramolecular hydrogen bonding interactions. The corresponding conformation and assembly structure changes were characterized using FTIR and electron microscopy, respectively.


QuantPipe: A User-Friendly Pipeline Software Tool for DIA Data Analysis Based on the OpenSWATH-PyProphet-TRIC Workflow.
Targeted analysis of data-independent acquisition (DIA) mass spectrometry data requires elegant software tools and strict statistical control. OpenSWATH-PyProphet-TRIC is a widely used DIA data analysis workflow. The OpenSWATH-PyProphet-TRIC workflow is typically executed by running command lines. Here, we present QuantPipe, which is a graphic interface software tool based on the OpenSWATH-PyProphet-TRIC workflow. In addition to OpenSWATH-PyProphet-TRIC functions, QuantPipe can convert the spectral library to the assay library and output peptides and protein intensities. We demonstrated that QuantPipe can be used to analyze SWATH-MS data from TripleTOF 5600 and TripleTOF 6600, phospho-SWATH-MS data, DIA data from Orbitrap instrument, and diaPASEF data from TimsTOF Pro instrument. The executable files, user manual, and source code of QuantPipe are freely available at https://github.com/tachengxmu/QuantPipe/releases.


[Clinical evaluation of ω-5 gliadin-specific IgE test].
To reveal the clinical utility of an IgE test specific to ω-5 gliadin in the diagnosis of immediate-type wheat allergy. We detected ω-5 gliadin-specific IgE in sera from all patients examined for wheat-specific IgE in our allergy clinic between January and October, 2008. The diagnostic value of the test was analyzed against the true diagnosis of wheat allergy based on oral wheat challenge or convincing clinical history. Subjects comprised 233 patients (median age, 3.6 years), 59 patients were diagnosed with wheat allergy, and 174 were judged to have no wheat allergy. The prevalence of being diagnosed as wheat allergy was 68% in the patients with CAP score 2 to ω-5 gliadin IgE (n=31), and 87% in those with CAP score 3 (n=15). All of the 3 patients with CAP score 4 or more were wheat allergic. However, 24% of patients with wheat allergy showed negative results (<0.35 UA/ml). According to the data, we proposed the probability curve of ω-5 gliadin-specific IgE. IgE testing specific to ω-5 gliadin can offer a useful clinical marker for the diagnosis of immediate-type wheat allergy. But the data should always be evaluated with wheat-specific IgE titers, because of the low clinical sensitivity to detect the patients with wheat allergy.


Aortoventriculoplasty for different types of left ventricular outflow tract obstructions.
Since the first clinical application of aortoventriculoplasty for tunnel subaortic stenosis in 1974 the indication for this method was extended to other types of left ventricular outflow tract stenoses (LVOTO). The operative technique consists of enlarging both the left and right ventricular outflow tracts and inserting an aortic prosthetic valve. 47 operations have been performed in patients with various types of LVOTO: 8 narrow annulus, 23 diffuse subaortic stenosis (multiple level stenosis), 9 complex forms of tunnel subaortic stenosis (Shone complex) 3 outgrown prosthesis, 4 obstructive idiopathic hypertrophic subaortic stenosis. Patients ages ranged from 4 to 35 years. Overall mortality was 13%, there were no late deaths, in the last 34 patients there was no death. In 25 patients there had been 1, and in 13 patients 2 previous procedures. As a result of the operation 9 patients developed complete right bundle branch block or left anterior hemi-block; 2 patients developed total a-v block with the need of a permanent pacemaker 25 patients had catheterization postoperatively. The mean gradient across the left ventricular outflow tract was significantly reduced from 91.5 +/- 21 mm Hg to 13.1 +/- 15 mm Hg. According to our experience aortoventriculoplasty can be used routinely in all forms of diffuse subaortic stenosis, narrow aortic annulus, reoperation in HOCM, multiple level stenosis and outgrown aortic prosthesis.


Early Biomarkers and Hearing Impairments in Patients with Neonatal Hypoxic-Ischemic Encephalopathy.
Identifying biomarkers for hearing impairments (HIs) in patients with neonatal hypoxic-ischemic encephalopathy (HIE), to initialize early hearing habilitation, is crucial. Seventy-eight neonates with HIE were divided into the following two groups: those with HIs and those without HIs. We compared those patients with 11,837 newborns without HIE, and analyzed the risk factors of HIs among neonatal HIE. Of the 78 patients, 11 were confirmed to have an HI, which is a substantially higher percentage than in the 11,837 newborns without HIE (14.1% vs. 0.87%; p < 0.001). More patients with moderate-to-severe HIE had confirmed HIs (p = 0.020; odds ratio, 8.61) than those with mild HIE. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE. The patients who exhibited HIs had significantly higher lactate (104.8 ± 51.0 vs. 71.4 ± 48.4; U = 181, p = 0.032) and serum glucose (159.5 ± 86.1 vs. 112.1 ± 62.3; U = 166, p = 0.036) levels than those without HIs. A higher prevalence of HIs was noted in the patients with stage III HIE than those with stage II HIE (43.8% vs. 10%; p = 0.008). The degree of HI correlated with brain anomalies and neurodevelopmental outcomes at 1 year of age. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE.


Laser beam steering for GRACE Follow-On intersatellite interferometry.
The GRACE Follow-On satellites will use, for the first time, a Laser Ranging Interferometer to measure intersatellite distance changes from which fluctuations in Earth's geoid can be inferred. We have investigated the beam steering method that is required to maintain the laser link between the satellites. Although developed for the specific needs of the GRACE Follow-On mission, the beam steering method could also be applied to other intersatellite laser ranging applications where major difficulties are common: large spacecraft separation and large spacecraft attitude jitter. The beam steering method simultaneously coaligns local oscillator beam and transmitted beam with the laser beam received from the distant spacecraft using Differential Wavefront Sensing. We demonstrate the operation of the beam steering method on breadboard level using GRACE satellite attitude jitter data to command a hexapod, a six-degree-of-freedom rotation and translation stage. We verify coalignment of local oscillator beam/ transmitted beam and received beam of better than 10 μrad with a stability of 10 μrad/ √Hz in the GRACE Follow-On measurement band of 0.002...0.1 Hz. Additionally, important characteristics of the beam steering setup such as Differential Wavefront Sensing signals, heterodyne efficiency, and suppression of rotation-to-pathlength coupling are investigated and compared with analysis results.


Bacteriological profile of intra-abdominal infections in a tertiary care hospital.
Intra-abdominal infections (IAIs) include a wide spectrum of pathological conditions, ranging from uncomplicated appendicitis to fecal peritonitis .The resulting infections should be diagnosed early and treated based on the organism isolated and its susceptibility. In this study the bacteriological profile and antimicrobial resistance pattern of intra-abdominal infections was analyzed. A retrospective analysis of samples received from 119 cases of intra-abdominal infections in our Institute from January 2015 to December 2017 was analyzed. Patients with primary peritonitis from cirrhosis or ascites were not included in the study. The specimens were primarily processed, as per standard methods. Identification and antimicrobial susceptibility testing was done by the Vitek-2 system. Anaerobic culture was performed on 5% sheep blood agar plates and incubated in GEN bag anaerobic pouches. In our study perforative peritonitis 43/119 (36.1%) was predominant IAI followed by acute pancreatitis 14/119 (11.7%) and pancreatic necrosis 12/119 (10%). Microbial growth was observed in 66.3% (79/119) of the cases and combined infections were observed in14/119 (11.7%) of the cases. Escherichia coli was the predominant organism isolated in 58/119 (40.8%), out of which 41/58 (70.6%) were ESBL producers and 16/58 (27.5%) were multi drug resistant isolates. Klebsiella pneumoniae was isolated from 11/119 (9.2%) cases out of which 8/11 (72.7%) were ESBL and 3/11 (27.2%) were multidrug resistant isolates. Post-operative complications was observed in 12/119 (10%) patients with mortality in 15/119 (12.6%) patients. Early diagnosis and appropriate management of the infections will help to prevent the morbidity and mortality associated with these infections.


Fostering research by radiologists: recommendations of the 1991 Summit meeting.
At the annual Radiology Summit Meeting sponsored by the Intersociety Commission of the American College of Radiology, leaders of U.S. and Canadian radiologic organizations met in part to discuss ways to improve radiology research. Support by radiology departments and radiologic organizations is currently not sufficient to improve the research of the specialty. Five issues of central importance to improving research are (a) the need for a definition of radiology research, (b) a lack of financial resources, (c) a lack of mentors, (d) hesitancy to embark on a research career, and (e) conflicts between clinicians and researchers. The adoption of 31 recommendations regarding these five issues was urged.


Downstream of the HOX genes: Explaining conflicting tumour suppressor and oncogenic functions in cancer.
The HOX genes are a highly conserved group of transcription factors that have key roles in early development, but which are also highly expressed in most cancers. Many studies have found strong associative relationships between the expression of individual HOX genes in tumours and clinical parameters including survival. For the majority of HOX genes, high tumour expression levels seem to be associated with a worse outcome for patients, and in some cases, this has been shown to result from the activation of pro-oncogenic genes and pathways. However, there are also many studies that indicate a tumour suppressor role for some HOX genes, sometimes with conclusions that contradict earlier work. In this review, we have attempted to clarify the role of HOX genes in cancer by focusing on their downstream targets as identified in studies that provide experimental evidence for their activation or repression. On this basis, the majority of HOX genes would appear to have a pro-oncogenic function, with the notable exception of HOXD10, which acts exclusively as a tumour suppressor. HOX proteins regulate a wide range of target genes involved in metastasis, cell death, proliferation and angiogenesis, and activate key cell signalling pathways. Furthermore, for some functionally related targets, this regulation is achieved by a relatively small subgroup of HOX genes.


The effects of being habitually barefoot on foot mechanics and motor performance in children and adolescents aged 6-18 years: study protocol for a multicenter cross-sectional study (Barefoot LIFE project).
Barefoot locomotion has evoked an increasing scientific interest with a controversial debate about benefits and limitations of barefoot and simulated barefoot walking and running. While most current knowledge comes from cross sectional laboratory studies, the evolutionary perspective suggests the importance of investigating the long-term effects. Observing habitually barefoot populations could fill the current gap of missing high quality longitudinal studies. Therefore, the study described in this design paper aims to investigate the effects of being habitually barefoot on foot mechanics and motor performance of children and adolescents. This study has a cross-sectional, binational design and is part of the "Barefoot Locomotion for Individual Foot- and health Enhancement (Barefoot LIFE)" project. Two large cohorts (n(total) = 520) of healthy children and adolescents between 6 and 18 years of age will be included respectively in Germany and South Africa. A barefoot questionnaire will be used to determine habitually barefoot individuals. The testing will be school-based and include foot mechanical (static arch height index, dynamic arch index, foot pliability) and motor performance (coordination, speed, leg power) outcomes. Gender, BMI and level of physical activity will be considered for confounding. The strength of this study is the comparison of two large cohorts with different footwear habits to determine long-term effects of being habitually barefoot on foot mechanics and motor performance.


Intensity modulated radiation therapy (IMRT): a new promising technology in radiation oncology.
Intensity modulated radiation therapy (IMRT) is a new technology in radiation oncology that delivers radiation more precisely to the tumor while relatively sparing the surrounding normal tissues. It also introduces new concepts of inverse planning and computer-controlled radiation deposition and normal tissue avoidance in contrast to the conventional trial-and-error approach. IMRT has wide application in most aspects of radiation oncology because of its ability to create multiple targets and multiple avoidance structures, to treat different targets simultaneously to different doses as well as to weight targets and avoidance structures according to their importance. By delivering radiation with greater precision, IMRT has been shown to minimize acute treatment-related morbidity, making dose escalation feasible which may ultimately improve local tumor control. IMRT has also introduced a new accelerated fractionation scheme known as SMART (simultaneous modulated accelerated radiation therapy) boost. By shortening the overall treatment time, SMART boost has the potential of improving tumor control in addition to offering patient convenience and cost savings.


[A new therapy concept for the treatment of dry eye--the usefulness of phospholipid liposomes].
Most of the eye drops currently used replace only the aqueous phase of the tear film. But, due to the fact that, with approximately 80 % of the patients with a dry eye, a disturbance of the lipid phase is present, an approach for new treatment methods needed to be found. We examined a new therapy concept with an eye spray containing liposomes for the therapy of the "dry eye" in a long-term study. An examination of the effectiveness of a liposome eye spray (TEARS AGAIN, Optima Pharmaceutical GmbH, Germany) in patients with "dry eye" compared with a spray containing a balanced salt solution was carried out. Between August 2003 and May 2004 a double-blind study with 382 patients was accomplished. The treatment group (V; n = 191) was compared with the control group (K; n = 191) for a period of 6 months regarding the following examination criteria: eyelid edge parallel conjunctival folds (LIPCOF), BREAK UP time (BUT), Schirmer I test, best corrected visual acuity, as well as slit lamp findings of the cornea and conjunctiva. Follow-up was after 4 weeks and 6 months. The statistical analysis was performed with the statistical program SPSS v.11.5. The examined parameters such as LIPCOF, BUT and Schirmer were significantly better in the treatment group than in the control group. We found likewise significant improvements of the inflammations of the edge of eyelid with a remarkable decrease of around 89.5 %. Questioning of the patients resulted in, among other things, the belief that the liposome eye spray led altogether to a clear subjective improvement of the symptoms in 72 % of the cases, although an initial burning sensation was mentioned after the application. All patients were of the opinion that application with a spray is more favourably and more pleasant than teardrops. The liposome tear substitute shows statistically significant advantages against a balanced salt solution. This new liposome eye spray represents a new, revolutionary and effective procedure in the therapy of the "dry eye". Considering the disturbance of the lipid phase in 80 % of the patients, TEARS AGAIN ought to be a first choice treatment.


Multifunctionality of cerium decoration in enhancing the cycling stability and rate capability of a nickel-rich layered oxide cathode.
The structural collapse and surface chemical degradation of nickel-rich layered oxide cathodes (NCM) of lithium-ion batteries during operation, which result in severe capacity attenuation, are the major challenges that hinder their commercial development. To improve the cycle and rate performances of LiNi0.8Co0.1Mn0.1O2 (NCM811), in this study, we have constructed a double-shell structure protective layer with a surface CeO2-x coating and interfacial spinel-like phase, which mitigate particle microcrack formation and isolate the NCM811 particles from electrolyte erosion. Additionally, during heat-treatment calcination, tetravalent cerium ions with strong oxidation ability can be partially doped into the material, which causes partial oxidation of Ni2+ to Ni3+, thereby reducing the Li+/Ni2+ mixing. The strong Ce-O bonds formed in the lattice help to improve the stability of the structure in the highly de-lithiated state. Thus, the synergy of multifunctional cerium modification effectively improves the structural stability and electrochemical kinetics of the material during cycling. Impressively, the obtained Ce-NCM811 exhibits capacity retention of 80.3% at a high discharge rate of 8 C after 500 cycles, which is much higher than that of the pristine cathode (only 44.3%). This work successfully designed a material with multi-functional Ce modification to provide a basis for Ni-rich cathode materials, which is crucial as it effectively improves the electrochemical performance.


Hypopharyngeal paraganglioma: a case report.
Paragangliomas are neuroendocrine neoplasms that primarily afflict patients during the fourth and fifth decades of life. The majority of extra-adrenal paragangliomas arise in the head and neck region, notably from the carotid and aortic bodies, jugular bulb and tympanic plexus. Although one-fifth of all parapharyngeal neoplasms are paragangliomas, primary hypopharyngeal paraganglioma is relatively uncommon, only one other case having previously been documented by Filippin et al. (1989). We report a second case of hypopharyngeal paraganglioma in an 18-year-old male as seen in our center.


Mercury impairs human primary endometrial stromal cell function†.
Heavy metal exposures could compromise endometrial cells. Although studies assessed mercury toxicity in cell lines, limited data are available on the concentration of mercury that damage human endometrial stromal cells (hEnSCs) and alter endometrial function. This research aims to study the effects of mercury exposure on cell viability and functional features of hEnSCs. Primary hEnSCs were isolated from 23 endometrial biopsies obtained from healthy donors. After in vitro mercury exposure cell viability of hEnSCs was evaluated via tetrazolium salt metabolism and oxidative stress was assessed by 2', 7'-dichlorofluorescin diacetate assay. hEnSCs were decidualized in vitro in the presence of mercury (0, 25, 50, 75, 250, and 350 nM). Decidualization was evaluated based on prolactin and insulin-like growth factor-binding protein (IGFBP1) secretion and cytoskeletal rearrangement (F-actin staining). Cell proliferation and apoptosis were evaluated by Ki67 immunostaining and TUNEL assay. Mercury doses of 250 nM (P = 0.028) and 500 nM (P = 0.026) increased reactive oxygen species production in hEnSCs after 24 h. Cell viability significantly decreased after 48 h and 72 h (P < 0.05) of mercury exposure at 500 nM. After in vitro decidualization and mercury treatment, decidual hEnSCs showed a dose-dependent decrease in prolactin and IGFBP1 secretion, particularly at 350 nM (P = 0.016). Cell proliferation was decreased in hEnSCs treated with 350 nM mercury (P < 0.001); an increase in apoptosis followed a dose-dependent trend in non-decidual and decidual hEnSCs. These findings support that mercury-induced damage could be due to an increase in ROS production.


The synthetic antimicrobial peptide KLKL5KLK enhances the protection and efficacy of the combined DNA vaccine against Mycobacterium tuberculosis.
In this study, we evaluated the potential of the synthetic antimicrobial peptide KLKL(5)KLK to augment the immune response and protective efficacy of the combined DNA vaccine against Mycobacterium tuberculosis. We demonstrated that immunization of mice with a combined DNA vaccine/KLKL(5)KLK mixture resulted in significantly higher protection than that induced by the combined DNA vaccine alone or by the Bacillus Calmette-Guérin (BCG) vaccine after challenge with a virulent M. tuberculosis strain (p < 0.01). Detailed analysis of the immune response revealed that the combined DNA vaccine/KLKL(5)KLK mixture stimulated higher IL-12 secretion, resulted in significantly more CD4(+)/CD44(high) and CD8(+)/CD44(high) T-cell production (p < 0.01), elicited 1.5- to 1.8-fold higher interferon-gamma (IFN-gamma) production, and produced stronger antigen-specific cytotoxic T lymphocyte activity than the combined DNA vaccine alone. Further, 125 days after the final immunization, mice immunized with the combined DNA vaccine/KLKL(5)KLK mixture significantly outpaced their combined DNA vaccine-immunized counterparts regarding antigen-specific IFN-gamma-producing cell numbers (p < 0.05) and antigen-specific IgG titers, indicating that KLKL(5)KLK provides a stronger and longer Th1-associated immune response. Taken together, our results indicate that the synthetic peptide KLKL(5)KLK is a potent adjuvant that can enhance and prolong the immune response of the combined DNA vaccine against M. tuberculosis.


The Ca2+-activated Cl- channel TMEM16B regulates action potential firing and axonal targeting in olfactory sensory neurons.
The Ca(2+)-activated Cl(-) channel TMEM16B is highly expressed in the cilia of olfactory sensory neurons (OSNs). Although a large portion of the odor-evoked transduction current is carried by Ca(2+)-activated Cl(-) channels, their role in olfaction is still controversial. A previous report (Billig et al. 2011. Nat. Neurosci. http://dx.doi.org/10.1038/nn.2821) showed that disruption of the TMEM16b/Ano2 gene in mice abolished Ca(2+)-activated Cl(-) currents in OSNs but did not produce any major change in olfactory behavior. Here we readdress the role of TMEM16B in olfaction and show that TMEM16B knockout (KO) mice have behavioral deficits in odor-guided food-finding ability. Moreover, as the role of TMEM16B in action potential (AP) firing has not yet been studied, we use electrophysiological recording methods to measure the firing activity of OSNs. Suction electrode recordings from isolated olfactory neurons and on-cell loose-patch recordings from dendritic knobs of neurons in the olfactory epithelium show that randomly selected neurons from TMEM16B KO mice respond to stimulation with increased firing activity than those from wild-type (WT) mice. Because OSNs express different odorant receptors (ORs), we restrict variability by using a mouse line that expresses a GFP-tagged I7 OR, which is known to be activated by heptanal. In response to heptanal, we measure dramatic changes in the firing pattern of I7-expressing neurons from TMEM16B KO mice compared with WT: responses are prolonged and display a higher number of APs. Moreover, lack of TMEM16B causes a markedly reduced basal spiking activity in I7-expressing neurons, together with an alteration of axonal targeting to the olfactory bulb, leading to the appearance of supernumerary I7 glomeruli. Thus, TMEM16B controls AP firing and ensures correct glomerular targeting of OSNs expressing I7. Altogether, these results show that TMEM16B does have a relevant role in normal olfaction.


Hormone Therapy and its Effect on the Prognosis in Breast Cancer Patients.
Introduction: Use of hormone therapy (HT) has declined dramatically in recent years. Some studies have reported that HT use before a diagnosis of breast cancer (BC) may be a prognostic factor in postmenopausal patients. This study aimed to examine the prognostic relevance of HT use before BC diagnosis. Methods: Four BC cohort studies in Germany were pooled, and 4492 postmenopausal patients with HT use data were identified. Patient data and tumor characteristics were compared between users and nonusers, along with overall survival (OS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Cox proportional hazards models were stratified by study center and adjusted for age at diagnosis, tumor stage, grading, nodal status, and hormone receptors. Results: Women with HT use before the diagnosis of BC were more likely to have a lower tumor stage, to be estrogen receptor-negative, and to have a lower grading. With regard to prognosis there were effects seen for OS, DMFS and LRFS, specifically in the subgroup of women with a positive hormone receptor. In these subgroups, BC patients had a better prognosis with previous HT use. Conclusions: HT use before a diagnosis of BC is associated with a more favorable prognosis in women with a positive hormone receptor status. It may be recommended that the prognostic factor HT should be documented and analyzed as a confounder for prognosis in studies of postmenopausal hormone-responsive breast cancers.


Alpha2-adrenergic agonist modulation of [35S]GTPgammaS binding to guanine-nucleotide-binding-proteins in human platelet membranes.
Alpha2-adrenoceptor (alpha2-AR)-regulated binding of the labelled GTP analog, guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS), to guanine-nucleotide-binding proteins (G proteins) was studied in human platelet membranes. Under optimal conditions, the potent alpha2-AR agonist, 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), increased the binding of [35S]GTPgammaS up to approximately 1.8 fold, with half-maximal increase at 60 nM and was competitively inhibited by the alpha2-AR antagonist Rauwolscine. The actions of both UK 14304 and Rauwolscine were modulated by monovalent and divalent cation levels, as well as by the concentrations of GDP. [35S]GTPgammaS binding induced by UK 14304 had a Kd value of 4.5 +/- 0.3 nM and a Bmax value of 4.15 +/- 0.40 pmol/mg protein. The rank order of potencies of adrenergic ligands tested in stimulating [3S]GTPgammaS binding and inhibiting forskolin-stimulated c-AMP accumulation was UK 14304> Guanabenz acetate> Oxymetazoline hydrochloride> B-HT 920 dihydrochloride> p-Aminoclonidine hydrochloride> Clonidine hydrochloride. The data presented indicate that enhancement of [35S]GTPgammaS binding by alpha2-AR in human platelet membranes provides a simple functional measure for receptor activation and can be used for determination of potencies and efficacies of ligands at the alpha2-AR.


Use of natural language programming to extract medication from unstructured electronic medical records.
The purpose of this study is to evaluate the feasibility of applying natural language processing in the automated extraction of medications information from unstructured electronic records. Sixty-two documents containing medications were subjected to both manual and automated extraction. Both were able to identify over 90% medications. The automated method identified more medications than manual review, 97% vs 92%. However, the automated extraction included a substantial percentage (17%) of non-medication items but none with manual review.


Hyperammonaemic encephalopathy in an adult patient with citrin deficiency associated with a novel mutation.
We report on an adult patient with citrin deficiency in Hong Kong, in whom a novel mutation was identified. The patient presented with recurrent hyperammonaemic encephalopathy due to impairment of the liver urea cycle enzyme argininosuccinate synthetase. This autosomal recessive condition is also characterised by interesting food preferences, notably aversion to carbohydrates and craving for protein-rich and/or lipid-rich foods, as well as neuropsychiatric symptoms. Plasma amino acid analysis is very useful in revealing urea cycle disorders, and mutational analysis of the SLC25A13 gene can confirm the diagnosis.


Forty years of monensin for the control of coccidiosis in poultry.
In July 1971, the polyether ionophorous antibiotic monensin was introduced in the United States for the control of coccidiosis in poultry. At that time, prospects for new anticoccidial agents were not good. Amprolium had enjoyed several years of use, but many other compounds had been abandoned as resistance to them developed. After the introduction of monensin, most commercial broilers were medicated with the drug and it is still widely used for this purpose today. Apart from in poultry, monensin is also used to control coccidiosis in game birds, sheep, and cattle. Indeed, more animals have been medicated with ionophores, such as monensin, for control of disease than any other medicinal agents in the history of veterinary medicine. In this review, we discuss the discovery, mode of action, and efficacy of monensin, together with matters of importance to the poultry industry such as commercial use, drug resistance, toxicity, pharmacology and residues, host immunity to coccidiosis, and effects in other avian species.


Screening for microalbuminuria by RIA in 131I-treated thyroid cancer patients.
Thyroid cancer patients are treated with up to 9.9 GBq of 131I to ablate remnant thyroid tissue and/or any functioning metastases that may be present. Radioiodine therapy is repeated as often as required. However, only a small fraction of the 131I is taken up by remnant thyroid and metastases, the remainder being eliminated by the kidneys, which are therefore subject to irradiation. External radiation therapy to the kidneys is known to lead to nephritis and albuminuria. The study included 113 patients treated with one to four doses of 131I (1.1-9.9 GBq each dose) and followed up 1 month to more than 8 years later. Spot samples of urine were collected and microalbuminuria measured by in-house radioimmunoassay. Twelve patients had elevated levels (normal range up to 34 micrograms ml-1), but their clinical history revealed such predisposing factors as diabetes and/or hypertension and proteinuria before therapy commenced. The remaining patients had normoalbuminuria. Grouping the patients based on the total dose of 131I administered resulted in a median microalbuminuria of 2.4-12.9 micrograms ml-1. Hence, this study showed that the dose of 131I normally used in treating thyroid cancer does not increase microalbuminuria to any significant extent.


Identification of a point mutation in the human lysosomal alpha-glucosidase gene causing infantile glycogenosis type II.
Two patients in a consanguineous Indian family with infantile glycogenosis type II were found to have a G to A transition in exon 11 of the human lysosomal alpha-glucosidase gene. Both patients were homozygous and both parents were heterozygous for the mutant allele. The mutation causes a Glu to Lys substitution at amino acid position 521, just three amino acids downstream from the catalytic site at Asp-518. The mutation was introduced in wild type lysosomal alpha-glucosidase cDNA and the mutant construct was expressed in vitro and in vivo. The Glu to Lys substitution is proven to account for the abnormal physical properties of the patients lysosomal alpha-glucosidase precursor and to prevent the formation of catalytically active enzyme. In homozygous form it leads to the severe infantile phenotype of glycogenosis type II.