Selective Nonoperative Management of Abdominal Gunshot Wounds from Heresy to Adoption: A Multicenter Study of the Research Consortium of New England Centers for Trauma (ReCoNECT).
Selective nonoperative management (SNOM) of abdominal gunshot wounds is being practiced in certain trauma centers, but its broader acceptance in the surgical community is unknown. We hypothesized that SNOM has been adopted in New England as an acceptable method of abdominal gunshot wound management. We reviewed the medical records of abdominal gunshot wound patients admitted from January 1996 to June 2015, in 10 New England Level I and II trauma centers. Outcomes included the incidence, success, and failure of SNOM, and morbidity and mortality related to SNOM. Of 922 patients, 707 (77%) received immediate laparotomy (IMMLAP) and 215 (23%) were managed by SNOM. Compared with IMMLAP patients, those with SNOM had a lower median Injury Severity Score (16 vs 8; p < 0.001), lower incidence of complications (34.7% vs 8.5%; p < 0.001) and mortality (5.2% vs 0.5%; p = 0.002), and shorter ICU and hospital stays (median days 1 of 8 vs 0 of 2, respectively; p < 0.001). One SNOM patient died after 3 days due to a gunshot wound to the head. The overall incidence of SNOM increased from 18% before 2010 to 27% in the following years (p = 0.001). Eighteen patients (8.4%) had unsuccessful SNOM and underwent delayed laparotomy at an average of 12.5 hours (range 141 minutes to 48 hours) after arrival. Nine of them (4.2%) experienced complications that were not directly related to the delayed laparotomy, and none died. The rate of nontherapeutic laparotomies was 14.7% among IMMLAP and 5.5% among delayed laparotomy patients (p = 0.49). Selective nonoperative management of abdominal gunshot wounds, despite being a heresy only a few years ago, has now been established as an acceptable method of management in Level I and II trauma centers in New England.


A Multivariant Surrogate Neutralization Assay Identifies Variant-Specific Neutralizing Antibody Profiles in Primary SARS-CoV-2 Omicron Infection.
Primary infection with the Omicron variant of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) can be serologically identified with distinct profiles of neutralizing antibodies (nAbs), as indicated by high titers against the Omicron variant and low titers against the ancestral wild-type (WT). Here, we evaluated whether a novel surrogate virus neutralization assay (sVNT) that simultaneously quantifies the binding inhibition of angiotensin-converting enzyme 2 (ACE2) to the proteins of the WT- and Omicron-specific receptor-binding domains (RBDs) can identify nAb profiles after primary Omicron infection with accuracy similar to that of variant-specific live-virus neutralization tests (NTs). Therefore, we comparatively tested 205 samples from individuals after primary infection with the Omicron variant and the WT, and vaccinated subjects with or without Omicron breakthrough infections. Indeed, variant-specific RBD-ACE2 binding inhibition levels significantly correlated with respective NT titers (p < 0.0001, Spearman's r = 0.92 and r = 0.80 for WT and Omicron, respectively). In addition, samples from individuals after primary Omicron infection were securely identified with the sVNT according to their distinctive nAb profiles (area under the curve = 0.99; sensitivity: 97.2%; specificity: 97.84%). Thus, when laborious live-virus NTs are not feasible, the novel sVNT we evaluated in this study may serve as an acceptable substitute for the serological identification of individuals with primary Omicron infection.


Accuracy of visual correction in photorefractive keratectomy.
To investigate the accuracy of preoperative optical assessment and other factors that influenced the final visual outcome after photorefractive keratectomy (PRK). The records of 126 eyes from 54 male and 72 female eyes were studied retrospectively, ranging from 6 months to 3 years post-PRK. Refractive errors ranged from low to high myopia and astigmatism, and proper and careful preoperative selection of patients was made. A single standard ablation zone (AZ) of 6.00 mm and transition zone (TZ) of 7.00 mm was made in all cases. The study population showed a high degree of accuracy in visual outcome. In simple myopia, 92.3% of female eyes and 84.1% of male eyes had a visual acuity of more than 6/9 or better. In myopia with astigmatism, 83.05% of female and 65.9% of male eyes had a visual acuity of 6/9 (20/40) or better. However, despite the residual myopia, whether with or induced astigmatism, post PRK visual acuity seemed to be less influenced by it, than as in the pre-PRK status. This study showed an accuracy in visual outcome of > 90% for females and > 80% for males. The Nidek EC-500 was satisfactory for its purpose.


Early complication of pediatric central venous cannulation.
We describe a case of hemothorax following central venous catheter (CVC) insertion in an infant. Presumably injury occurred as a result of perforation with the dilator. Strategies to reduce the risk of complications and possible factors influencing the unsatisfactory delay in diagnosis, including the role of 'Fixation Error', are discussed.


Complex formation of cytochrome C with a calixarene carboxylic acid derivative: a novel solubilization method for biomolecules in organic media.
A calixarene carboxylic acid derivative has been found to form a complex with the cationic protein cytochrome c. The solubilized cytochrome c was stable and showed peroxidase activity in chloroform. The calix[6]arene and the calix[8]arene achieved quantitative extraction of the protein. The calix[6]arene, whose cavity is well-fitted to a protonated amino group, exhibited a selectivity to lysine-rich proteins due to the recognition of the epsilon-amino groups in lysine residues on the surface of the protein. This is the first report showing protein extraction by calixarenes. The solubilized cytochrome c could catalyze an oxidative reaction in organic solvents. This host compound functions as a novel solubilization tool for biomolecules and a separation tool for lysine-rich proteins.


Anxiety symptoms and felt stigma among young people living with perinatally or behaviourally-acquired HIV in Ukraine: A cross-sectional survey.
Ukraine has the second largest European HIV epidemic. This study aimed to describe stigma, demographic and social factors and their association with anxiety among perinatally and behaviourally-HIV-infected (PHIV; BHIV) young people in Kiev and Odessa. 104 PHIV and 100 BHIV young people aged 13-25 years completed a confidential tablet-based survey. Survey tools included the Hospital Anxiety and Depression Scale (HADS) (anxiety sub-scale scores of 8-10 indicating mild and ≥11 moderate/severe symptoms in last 7 days), Rosenberg Self-Esteem Scale (RSES) and HIV Stigma Scale (HSS) (short version, composite of disclosure, negative self-image and public attitudes sub-scales). Unadjusted Poisson regression models were fitted to explore factors associated with moderate/severe anxiety symptoms. PHIV and BHIV young people were of median age 15.5 [IQR 13.9-17.1] and 23.0 [21.0-24.3] years, having registered for HIV care a median 12.3 [10.3-14.4] and 0.9 [0.2-2.4] years previously; 97% (97/100) and 66% (65/99) respectively were on ART. Overall 43% (95%CI 36-50%) reported any and 13% (95%CI 9-19%) moderate/severe anxiety symptoms, with no difference by HIV acquisition mode (p = 0.405) or gender (p = 0.700). 42% (75/180) reported history of an emotional health problem for which they had not been referred/attended for care. Moderate/severe anxiety symptoms were associated with HIV-related stigma (prevalence ratio (PR) 1.24 95%CI 1.14-1.34 per HSS unit increase), lower self-esteem (PR 0.83 95%CI 0.78-0.90 per RSES point increase), CD4 ≤350 cells/mm3 (PR 2.29 95%CI 1.06-4.97), having no-one at home who knew the respondent's HIV status (PR 9.15 95%CI 3.40-24.66 vs all know) and, among BHIV, less stable living situation (PR 6.83 95%CI 1.99-23.48 for ≥2 vs no home moves in last 3 years) and history of drug use (PR 4.65 95%CI 1.83-11.85). Results indicated unmet need for psychosocial support. Further work is needed to explore strategies for mental health support, particularly around disclosure, self-esteem and stigma.


Perception of Students on Online Assessment: A Descriptive Study among Medical Undergraduates at Basic Sciences.
Background Assessment drives learning. Student assessment cannot be neglected in the long ongoing online learning during COVID-19 pandemic to motivate and assess students' learning. Hence Patan Academy of Health Sciences (PAHS) conducted online assessment to medical undergraduates amidst limitations. Objective To measure the perception of online assessment of students which will provide applicable insights for the further improvement. Method This is a single center, cross-sectional and descriptive study. A Google form containing a semi-structured questionnaire was sent to MBBS students of Basic Science at PAHS who attended online classes and online examination. The responses from close ended questions expressed in percentage and Chi-square test was used to find the association. Open ended questions were analyzed using Braun and Clarke's thematic analysis. Result Of 118 students that responded, 75% passed the online examination. A majority of students (73%) stated that online exam motivated them in learning process and it could be a good alternative during pandemic time. However the most of students (56%) were unsatisfied with the modality of online assessment and reasons that they mentioned were technical problems (89%), inadequate online proctoring (77%), insufficient examination time (58%), lack of orientation to exam, lack of computer skills. Technical problem was worse in rural areas. Conclusion Even though online assessment motivated students' learning during online classes, a large number of students were unsatisfied with assessment modality.


New phenolic principles from Hypericum sampsonii.
Using the anti-hepatitis B virus (HBV)-producing cell line MS-G2 in vitro cultural system-guided screening was performed, and two new benzophenones, 2,6-dihydroxy-4-[(E)-5-hydroxy-3,7-dimethylocta-2,7-dienyloxy]benzophenone (1) and 2,6-dihydroxy-4-[(E)-7-hydroxy-3,7-dimethylocta-2-enyloxy]benzophenone (2), a new xanthone, hyperxanthone (3), a new bisanthraquinone glycoside, R-(-)-skyrin-6-O-beta-D-xylopyranoside (4), and 2-caffeoyloxy-3-hydroxy-3-(3,4-dihydroxyphenyl)propyl alcohol (5), and 16 known compounds were isolated from the anti-HBV active fraction of the whole herbs of Hypericum sampsonii. Their structures were elucidated using spectroscopic methods, mainly 2D NMR and MS spectrometry. Circular dichroism was used to determine the stereochemistry of bisanthraquinone glycosides.


Physicochemical properties of ionic and non-ionic biocompatible hydrogels in water and cell culture conditions: Relation with type of morphologies of bovine fetal fibroblasts in contact with the surfaces.
Cationic, anionic and non-ionic hydrogels having acrylamide polymer backbones were synthesized via free radical polymerization with N,N-methylenebisacrylamide (BIS) as crosslinker. The chemical structures of the hydrogels were characterized by Fourier Transform Infrared Spectroscopy (FTIR). Physicochemical properties such as swelling kinetic, maximum swelling capacity, volume phase transition temperature (VPTT) and wettability (static water contact angle) of hydrogels swollen in aqueous and cell culture medium, at room and cell culture temperatures were studied. In order to correlate the surface properties of the hydrogels and cellular adhesivity of bovine fetal fibroblasts (BFFs), cellular behaviour was analyzed by inverted fluorescence optical microscopy and atomic force microscopy (AFM). MTT assay demonstrated that the number of viable cells in contact with hydrogels does not significantly change in comparison to a control surface. Flattened and spindle-shaped cells and cell spheroids were the adopted morphologies during first days of culture on different hydrogels. Cell spheroids were easily obtained during the first 5days of culture in contact with PNIPAM-co-20%HMA (poly (N-isopropylacrylamide-co-20%N-acryloyl-tris-(hydroxymethyl)aminomethane)) hydrogel surface. After 15days of culture all hydrogels showed high adhesion and visual proliferation. According to obtained results, non-ionic and hydrophilic surfaces with moderated wettability induce the formation of BFFs cell spheroids. These hydrogel surfaces could be used in clinical and biochemical treatments at laboratory level to cell growth and will allow generating the base for future biotechnologic platform.


Five-year study of antimicrobial susceptibility and beta-lactamase production in Haemophilus influenzae.
We evaluated 582 Haemophilus influenzae isolates from patients between January 2000 and December 2004. Overall, 433 isolates were obtained from sputum and bronchial washings, 124 isolates were from pus, 19 isolates were from blood and 6 isolates form cerebrospinal fluid. H. influenzae was sensitive to amoxicillin/clavulanate, ampicillin/sulbactam, gentamicin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin, ofloxacin, imipenem, meropenem (range 97-100%), chloramphenicol (75%), ampicillin/amoxicillin (52%), but resistant to trimethoprim-sulphamethoxazole. As for beta-lactamase production, 48.4% of the isolates tested were positive.


The modified Dunn procedure for slipped capital femoral epiphysis: the Bernese experience.
Based on previous investigations on the vascular blood supply to the femoral head, a technique for anatomical reduction after slipped capital femoral epiphysis was developed. This technique is a modification of the original technique by Dunn using a retinacular soft-tissue flap. This allows the visual control of the epiphyseal vascular blood supply. We report the experience at the inventor's institution with a critical discussion of the available literature. Using a trochanteric osteotomy for surgical dislocation of the hip, a retinacular soft tissue flap is created containing the deep branch of the medial femoral circumflex artery, the external rotators and the capsule. The femoral epiphysis can be mobilised safely and reduced on the femoral neck after resection of the almost constantly present reactive metaphyseal callus. In our institution, the rate of avascular necrosis with 2% is comparably low to Dunn's original results. It is only present in cases where no bleeding was already evident before reduction of the epiphysis. The ten-year long-term results are favorable in these cases with a good functional result and only little progression of osteoarthritis. However, other authors have reported higher rates of avascular necrosis up to 24% in their initial experience. In experienced hands using the correct meticulous surgical technique, the results are favorable regarding the rates of avascular necrosis, the functional outcome and the development of radiographic osteoarthritis - even in acute and severe cases. Avascular necrosis is rare but can be observed if there is no evidence of intra-operative femoral head perfusion before and after reduction of the epiphysis.


Proteomic analysis of Metarhizium anisopliae secretion in the presence of the insect pest Callosobruchus maculatus.
Crop improvement in agriculture generally focuses on yield, seed quality and nutritional characteristics, as opposed to resistance to biotic stresses. Consequently, natural antifeedant toxins are often rare in seed material, with commercial crops being prone to insect pest predation. In the specific case of cowpea (Vigna unguiculata), smallholder cropping is affected by insect pests that reproduce inside the stored seeds. Entomopathogenic organisms can offer an alternative to conventional pesticides for pest control, producing hydrolases that degrade insect exoskeleton. In this study, protein secretions of the ascomycete Metarhizium anisopliae, which conferred bioinsecticidal activity against Callosobruchus maculatus, were characterized via 2D electrophoresis and mass spectrometry. Proteases, reductases and acetyltransferase enzymes were detected. These may be involved in degradation and nutrient uptake from dehydrated C. maculatus. Proteins identified in this work allowed description of metabolic pathways. Their potential applications in biotechnology include both novel compound development and production of genetically modified plants resistant to insect pests.


Promoter Effects of Functional Groups of Hydroxide-Conductive Membranes on Advanced CO2 Electroreduction to Formate.
The electrochemical reduction of CO2 at ambient conditions provides a latent solution of turning waste greenhouse gases into commodity chemicals or fuels; however, a satisfactory ion-conducting membrane for maximizing the performance of a CO2 electrolyzer has not been developed. Here, we report the synthesis of a sequence of hydroxide-conductive polymer membranes, which are based on polymer composites of poly(vinyl alcohol)/Guar hydroxypropyltrimonium chloride, for use in CO2 electrolysis. The effect of different membrane functional groups, including thiophene, hydroxybenzyl, and dimethyloctanal, on the efficiency and selectivity of CO2 electroreduction to formate is thoroughly evaluated. The membrane incorporating thiophene groups exhibits the highest Faradaic efficiency of 71.5% at an applied potential of -1.64 V versus saturated calomel electrode (SCE) for formate. In comparison, membranes containing hydroxybenzyl and dimethyloctanal groups produced lower efficiencies of 67.6 and 68.6%, respectively, whereas the commercial Nafion 212 membrane was only 57.6% efficient. The improved efficiency and selectivity of membranes containing thiophene groups are attributed to a significantly increased hydroxide conductivity (0.105 S cm-1), excellent physicochemical properties, and the simultaneous attenuation of formate product crossover.


Efficacy of venlafaxine XR for the treatment of pain in patients with spinal cord injury and major depression: a randomized, controlled trial.
To (1) determine the efficacy of venlafaxine XR for the treatment of pain (secondary aim) in individuals with spinal cord injury (SCI) enrolled in a randomized controlled trial (RCT) on the efficacy of venlafaxine XR for major depressive disorder (MDD) (primary aim); and (2) test the hypothesis that venlafaxine XR would be effective for both neuropathic and nociceptive pain. Multisite, double-blind, randomized (1:1) controlled trial with subjects block randomized and stratified by site, lifetime history of substance abuse, and prior history of MDD. Six Departments of Physical Medicine and Rehabilitation in university-based medical schools. Individuals (N=123) with SCI and major depression between 18 and 64 years of age, at least 1 month post-SCI who also reported pain. Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule. A 0-to-10 numeric rating scale for pain, pain interference items of the Brief Pain Inventory; 30% and 50% responders. The effect of venlafaxine XR on neuropathic pain was similar to that of placebo. However venlafaxine XR resulted in statistically significant and clinically meaningful reductions in nociceptive pain site intensity and interference even after controlling for anxiety, depression, and multiple pain sites within the same individual. For those who achieved a minimally effective dose of venlafaxine XR, some additional evidence of effectiveness was noted for those with mixed (both neuropathic and nociceptive) pain sites. Venlafaxine XR could complement current medications and procedures for treating pain after SCI and MDD that has nociceptive features. Its usefulness for treating central neuropathic pain is likely to be limited. Research is needed to replicate these findings and determine whether the antinociceptive effect of venlafaxine XR generalizes to persons with SCI pain without MDD.


Time Domain Reflectometry for Water Content Measurement of Municipal Solid Waste.
Water content measurement of municipal solid waste (MSW) is critical to water balance analysis of landfill, leachate collection and recirculation, and acceleration of MSW degradation. Time domain reflectometry (TDR) is commonly applied to soils for the measurement of water content. Application of TDR methods for moisture measurement in MSW is difficult, because MSW is a heterogeneous and highly conductive material. This study investigated the application of TDR surface reflection method for the determination of apparent dielectric constant and water content of MSW. A series of experiments were conducted to study the dielectric properties of MSW and its main components such as paper, plastic, and organics. Results indicate that the effect of waste material type seems to be negligible on the measurement of water content. TDR technique can effectively measure the intrinsic water of organics in the absence of significant bound water effects. Results of dielectric constant by surface reflection method gave similar accuracy as the conventional travel time analysis for waste materials with low electrical conductivities. In addition, surface reflection method provides higher accuracy for waste materials with high electrical conductivities than travel time analysis. This research provides experimental basis for the use of TDR surface reflection method in landfills.


TT virus among blood donors in Alexandria.
TTV is a non enveloped, single-stranded, circular- DNA virus that has been assigned to the Family Circiniviridae. The primary mode of TTV transmission was proposed to be transfusion (and hence its name). Little is known about the clinical significance and the natural history of TTV infection. Hence, responsibility of the virus for specific liver disease is still debated. In our study, we tested ninety five blood donors attending Kom EL-Decka regional blood bank in Alexandria for the presence of TTV DNA in their sera by PCR technique. The same samples were tested for ALT and AST levels by colorimetric technique and for HBsAg and anti-HCV by the ELISA technique. Out of the 95 blood donors, 46 (48.4%) had TTV DNA in their sera. None of the 95 blood donors included in this study was positive for HBsAg, while 22 (23.2%) were anti-HCV positive. Out of the 22 anti-HCV positive blood donors, 13 (59.1%) were TTV DNA positive, while out of the 73 anti-HCV negative blood donors, 33 (45.2%) had TTV DNA in their sera. There was no statistically significant difference between the prevalence of TTV DNA and anti-HCV in blood donors. No biochemical evidence of liver disease potentially linked to the TTV infection was observed in our blood donors who were TTV DNA positive. Furthermore, the occurrence of elevated serum AST and ALT was most often linked to HCV rather than TTV.


[Tracheobronchopathia osteochondroplastica: a case report].
Tracheobronchopathia osteochondroplastica (TO) is a rare disorder with unknown aetiology. In this paper, a case with TO was presented. A 77 year-old-man was admitted with cough for 2 years. Chest X-ray showed interstitial changes. Computed tomography of thorax demonstrated calcific density lesion in the trachea and in the left and right main bronchi. Fiberoptic bronchoscopy revealed numerous white, hard, irregular nodules on the anterior and lateral walls of trachea and on main bronchi. Pathologic diagnosis of bronchoscopic biopsy was TO.


Comparison of variation in frequency for SNPs associated with asthma or liver disease between Estonia, HapMap populations and the 1000 genome project populations.
Allele-specific analyses to understand frequency differences across populations, particularly populations not well studied, are important to help identify variants that may have a functional effect on disease mechanisms and phenotypic predisposition, facilitating new Genome-Wide Association Studies (GWAS). We aimed to compare the allele frequency of 11 asthma-associated and 16 liver disease-associated single nucleotide polymorphisms (SNPs) between the Estonian, HapMap and 1000 genome project populations. When comparing EGCUT with HapMap populations, the largest difference in allele frequencies was observed with the Maasai population in Kinyawa, Kenya, with 12 SNP variants reporting statistical significance. Similarly, when comparing EGCUT with 1000 genomes project populations, the largest difference in allele frequencies was observed with pooled African populations with 22 SNP variants reporting statistical significance. For 11 asthma-associated and 16 liver disease-associated SNPs, Estonians are genetically similar to other European populations but significantly different from African populations. Understanding differences in genetic architecture between ethnic populations is important to facilitate new GWAS targeted at underserved ethnic groups to enable novel genetic findings to aid the development of new therapies to reduce morbidity and mortality.


The role of school desk on the learning of graphic skills in early childhood education in Brazil.
The role of two different layouts of school furniture was investigated in the pattern legibility and spatial-temporal parameters of a graphic skill acquisition. Thirty children from the first grade of elementary school (mean age = 6 years) practiced a graphic task according to a criterion figure. They were assigned to two groups, Group of Fixed School Desk (GF) and Group with Adjustable School Desk (GA). Each child practiced the task on a digital tablet for 25 trials. The software Movalyser 2.3 processed the data from which the following measures were obtained: pattern legibility, linear spatial error and speed of execution. Two expert teachers also judged legibility. Children in the GA showed more number of legible patterns, they were slower to complete the task but they were more accurate in its reproduction. The adjustable school desk facilitates the acquisition of legible graphic patterns. Since stable graphic skills are positively correlated to the production of creative texts, studies unraveling the role of school desks to facilitate handwriting and drawing skills will contribute ultimately children's literacy and overall educational development.


Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups.
To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy, a randomized phase III trial was performed in patients with locally advanced anal cancer. From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks, a boost of 20 or 15 Gy was given in case of partial or complete response, respectively. Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered on day 1. The addition of chemotherapy to radiotherapy resulted in a significant increase in the complete remission rate from 54% for radiotherapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and colostomy-free interval (P = .02 and P = .002, respectively), both in favor of the combined modality treatment. The locoregional control rate improved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. No significant difference was found when severe side effects were considered, although anal ulcers were more frequently observed in the combined-treatment arm. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement, and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis. Event-free survival, defined as free of locoregional progression, no colostomy, and no severe side effects or death, showed significant improvement (P = .03) in favor of the combined-treatment modality. The 5-year survival rate was 56% for the whole patient group. The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects.


Influence of the synthesis method on the catalytic activity of mayenite for the oxidation of gas-phase trichloroethylene.
Catalytic oxidation of trichloroethylene (TCE) in heterogeneous phase (gas-solid) is an effective strategy for the conversion of this pollutant in less harmful compounds, namely CO2, CO and HCl. In this work, we have studied the use of mayenite, a cost-effective material, as an active catalyst for the TCE conversion. In particular, we have assessed the influence of the mayenite synthesis method (hydrothermal, sol-gel and ceramic) on the reaction performance. The materials have been characterized by different techniques, such as XRD, N2-sorption (BET), TPR, Raman spectroscopy, FESEM-EDX and TEM. The analysis of the light-off curves and product distribution, has shown that the use of the hydrothermal method for the mayenite synthesis results in the most active and selective catalyst. This has been related with a higher surface area and with a higher concentration of oxygen anions in the mayenite prepared by this method. It has been found that the presence of water in the stream do not influence the catalytic performance of the material. A mechanism for the reaction and for the partial deactivation of the catalyst has been proposed.


Stimulation of anti-tumor immunity by photodynamic therapy.
Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a 'danger signal' to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy.


Creating a safety net for patients with depression in primary care; a qualitative study of care managers' experiences.
The aim of this study was to explore nurses' experiences and perceptions of working as care managers at primary care centers. Qualitative, focus group study. Systematic text condensation was used to analyze the data. Primary health care in the region of Västra Götaland and region of Dalarna in Sweden. Eight nurses were trained during three days including treatment of depression and how to work as care managers. The training was followed by continuous support. The nurses' experiences and perceptions of working as care managers at primary care centers. The care managers described their role as providing additional support to the already existing care at the primary care center, working in teams with a person-centered focus, where they were given the opportunity to follow, support, and constitute a safety net for patients with depression. Further, they perceived that the care manager increased continuity and accessibility to primary care for patients with depression. The nurses perceived that working as care managers enabled them to follow and support patients with depression and to maintain close contact during the illness. The care manager function helped to provide continuity in care which is a main task of primary health care. Key Points The care managers described their role as an additional support to the already existing care at the primary care center. • They emphasized that as care managers, they had a person-centered focus and constituted a safety net for patients with depression. • Their role as care managers enabled them to follow and support patients with depression over time, which made their work more meaningful. • Care managers helped to achieve continuity and accessibility to primary health care for patients with depression.


[The value of ultrasound-guided multiple systematic biopsies in the early diagnosis of cancer of the prostate].
Endorectal ultrasonography using a 7 mHZ probe was performed in 99 patients with a negative history for surgery of the prostate and either findings on rectal examination suggestive of cancer (T3 stage excluded) or a serum level of prostate-specific antigen of 2.5 mg/ml or more. A biopsy gun was used to harvest 1.5 centimetre long specimens. Ultrasound-guided biopsies were performed in peripheral hypoechogeneic areas; in addition, regardless of the result of the endorectal ultrasonography, routine multiple ultrasound-guided biopsies were performed in both lobes of the prostate (3 per lobe). Morbidity consisted in two cases of prostatitis (2%). Among the 99 patients, ultrasound guided biopsies found 16 carcinomas (16.1%), and routine multiple ultrasound-guided biopsies found 32 (32.3%) carcinomas. Four patients with normal results upon rectal examination and endorectal ultrasonography were found to have carcinoma of the prostate. These findings suggest that the morbidity of routine multiple ultrasound-guided biopsies is low; that routine multiple ultrasound-guided biopsies is more sensitive than ultrasound guided biopsies, with 16/99 (16%) additional carcinomas detected in this study and 56% of carcinomas among those patients with findings upon the rectal examination suggestive of malignant disease; and that routine multiple ultrasound-guided biopsies can allow the detection of carcinomas responsible for isolated elevation of prostate-specific antigen levels without anomalies of the rectal examination or endorectal ultrasonography (8% of the carcinomas in this study).


Treatment of dermatophyte toenail onychomycosis in the United States. A pharmacoeconomic analysis.
This study attempted to determine the cost-effectiveness of therapies for dermatophyte toenail onychomycosis in the United States in 2001. The antimycotic agents evaluated were ciclopirox 8% nail lacquer and the oral agents terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A treatment algorithm for the management of onychomycosis was developed, and a meta-analysis was carried out to determine the average mycologic and clinical response rates for the various agents. The cost of the regimen was figured as the sum of the costs of drug acquisition, medical management, and management of adverse effects. The expected cost of management and disease-free days were determined, and a sensitivity analysis was conducted. It was concluded that ciclopirox 8% nail lacquer, which has recently become available in the larger size of 6.6 mL, is a cost-effective agent for the management of toenail onychomycosis.


Risk factors for postoperative delirium in patients undergoing vascular surgery.
Postoperative delirium (PODE) remains a common complication after vascular surgery procedures although the exact pathogenesis remains unclear, mainly because of its multifactorial character. The aim of this systematic review was to evaluate pooled data on potential risk factors for PODE in patients undergoing vascular surgery procedures. A systematic literature review was conducted conforming to established criteria to identify eligible articles published from 1990 to 2016. Eligible studies evaluated potential risk factors for PODE after vascular surgery procedures, using both univariate and multivariate analysis. PODE was defined as a disturbance of consciousness with reduced ability to focus, sustain, or shift attention after vascular surgery procedures and was diagnosed in all studies using well-established criteria. Only risk factors reported in at least four studies were included in this review. Pooled results were calculated, and further multivariate regression analysis was conducted. Overall, nine studies (published from 2003 to 2015) including 2388 patients in total were evaluated (457 with and 1931 without PODE). Patients with PODE were older (73.27 vs 69.87 years; P < .0001) and showed a higher male sex rate (78.1% vs 73.5%; P = .043). Open aortic surgery was the most frequent procedure in this analysis, followed by lower limb revascularization. Patients with PODE also showed higher rates of diabetes mellitus, hypertension, cardiac disease, and neurologic disease; lower hemoglobin level; larger duration of surgery; longer hospital and intensive care unit stay; and higher blood loss. Mean age (odds ratio [OR], 3.44; 95% confidence interval [CI], 2.933-4.034; P < .0001), hypertension (OR, 1.94; 95% CI, 1.469-2.554; P < .0001), cardiac disease (OR, 3.16; 95% CI, 2.324-4.284; P < .0001), open aortic surgery (OR, 1.74; 95% CI, 1.421-2.143; P < .0001), blood loss (OR, 1.01; 95% CI, 1.007-1.010; P < .0001), hospital stay (OR, 2.26; 95% CI, 1.953-2.614; P <. 0001), and intensive care unit stay (OR, 6.12; 95% CI, 4.699-7.957; P < .0001) were identified as the strongest risk predictors for PODE, followed by male sex, diabetes mellitus, neurologic disease, and history of smoking. However, body mass index, renal failure, preoperative hemoglobin level, and general anesthesia were not found to be risk factors for PODE in such patients. This study has confirmed that PODE after vascular surgery procedures is a multifactorial disease, and several independent risk factors have been identified. However, pooled data regarding the effect of PODE on primary outcomes after vascular surgery procedures are still lacking. The results of this review could contribute to the designation of future prediction models and improve prevention of PODE in these patients.


Antiviral effect of 25-hydroxycholesterol against porcine reproductive and respiratory syndrome virus in vitro.
Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that causes economically huge losses to the pig industry worldwide. Current control of PRRSV infection remains inadequate although various means have been implemented. Thus, investigating novel antiviral therapeutics to combat PRRSV infection is essential. In the present study, the antiviral effect in vitro of 25-hydroxycholesterol (25HC) against PRRSV was investigated. Cell viability assay was performed to examine the impact of 25HC on the cell viability. Indirect immunofluorescence assay and virus titration were utilized to evaluate the levels of PRRSV growth. Viral attachment assay, penetration assay and release assay were conducted to investigate the antiviral mechanism of 25HC against PRRSV. Real-time RT-PCR assay was used to analyse the effect of 25HC on the genome synthesis of PRRSV. We demonstrated that the growth of PRRSV was significantly inhibited in 25HC-pretreated cells and PRRSV-infected cells by 25HC. Moreover, 25HC could impair the attachment and entry of PRRSV in vitro, but not affect viral genome synthesis and virion release. Our findings clearly indicate that 25HC can exert antiviral effect against PRRSV infection in vitro, suggesting that 25HC might be a novel potential agent to control PRRSV infection.


Treatment of saphenous vein graft lesions with drug-eluting stents: immediate and midterm outcome.
The purpose of the present report was to evaluate clinical and angiographic outcomes of drug-eluting stent (DES) implantation in saphenous vein graft (SVG) lesions. The safety and efficacy of DES implantation for the treatment SVG lesions remains uncertain. We evaluated in-hospital and six-month outcomes in 61 consecutive patients treated with DES in SVG lesions from March 2002 to March 2004 (DES group), as compared to 89 consecutive patients treated with bare-metal stents (BMS) in the 24 months immediately before the introduction of DES (BMS group). Major adverse cardiac events (MACE) including death, myocardial infarction, target lesion revascularization (TLR), and target vessel revascularization (TVR) were recorded in-hospital and at six-month follow-up. The rate of in-hospital MACE was similar between the two groups (6.6% vs. 5.6%, p = 1.0). Cumulative MACE at six months was 11.5% in the DES group and 28.1% in the BMS group (p = 0.02). The DES group had a significantly lower incidence of in-segment restenosis (10.0% vs. 26.7%, p = 0.03), TLR (3.3% vs. 19.8%, p = 0.003), and TVR (4.9% vs. 23.1%, p = 0.003). By Cox regression analysis, diabetes (hazard ratio [HR]: 3.03; 95% confidence interval [CI]: 1.33 to 6.90; p = 0.008), usage of BMS (HR: 2.53; 95% CI: 1.07 to 5.97; p = 0.03), and age of SVG (HR: 1.10; 95% CI: 1.02 to 1.19; p = 0.02) were identified as predictors of MACE at six-month follow-up. Compared to BMS implantation, DES implantation in SVG lesions appears safe with favorable and improved mid-term outcomes.


Robotic- vs laparoscopic-assisted proctectomy for locally advanced rectal cancer based on propensity score matching: Short-term outcomes at a colorectal center in China.
Reports in the field of robotic surgery for rectal cancer are increasing year by year. However, most of these studies enroll patients at a relatively early stage and have small sample sizes. In fact, studies only on patients with locally advanced rectal cancer (LARC) and with relatively large sample sizes are lacking. To investigate whether the short-term outcomes differed between robotic-assisted proctectomy (RAP) and laparoscopic-assisted proctectomy (LAP) for LARC. The clinicopathological data of patients with LARC who underwent robotic- or laparoscopic-assisted radical surgery between January 2015 and October 2019 were collected retrospectively. To reduce patient selection bias, we used the clinical baseline characteristics of the two groups of patients as covariates for propensity-score matching (PSM) analysis. Short-term outcomes were compared between the two groups. The clinical features were well matched in the PSM cohort. Compared with the LAP group, the RAP group had less intraoperative blood loss, lower volume of pelvic cavity drainage, less time to remove the pelvic drainage tube and urinary catheter, longer distal resection margin and lower rates of conversion (P < 0.05). However, the time to recover bowel function, the harvested lymph nodes, the postoperative length of hospital stay, and the rate of unplanned readmission within 30 days postoperatively showed no difference between the two groups (P > 0.05). The rates of total complications and all individual complications were similar between the RAP and LAP groups (P > 0.05). This retrospective study indicated that RAP is a safe and feasible method for LARC with better short-term outcomes than LAP, but we have to admit that the clinically significant of part of indicators are relatively small in the practical situation.


The Society of Thoracic Surgeons General Thoracic Surgery Database: 2021 Update on Outcomes and Research.
The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) remains the largest and most robust thoracic surgical database in the world. Participating sites receive risk-adjusted performance reports for benchmarking and quality improvement initiatives. The GTSD also provides several mechanisms for high-quality clinical research using data from 271 participant sites and nearly 720,000 procedures since its inception in 2002. Participant sites are audited at random annually for completeness and accuracy. During the last year and a half, the GTSD Task Force continued to refine the data collection form, ensuring high-quality data while minimizing data entry burden. In addition, the STS Workforce on National Databases has supported robust GTSD-based research program, which led to 10 scholarly publications in 2020. This report provides an update on outcomes, volume trends, and database improvements as well as a summary of research productivity resulting from the GTSD over the preceding year.


Wind energy harvester using piezoelectric materials.
Wireless sensor networks play a very important role in environmental monitoring, structural health monitoring, smart city construction, smart grid, and ecological agriculture. The wireless sensor nodes powered by a battery have a limited service life and need periodic maintenance due to the limitation of battery capacity. Fortunately, the development of environmental energy harvesting technology provides an effective way to eliminate the needs and the replacement of the batteries. Among the environmental stray energy, wind energy is rich, almost endless, widely distributed, and clean. Due to the advantages of simple structure, miniaturization, and high power density, wind energy harvesters using piezoelectric materials (PWEHs) have attracted much attention. By the ways of principal exploration, structure design, and performance optimization, great and steady progress has been made in the research of PWEH. This Review is focused on the review of PWEHs. After introducing the basic principle of PWEHs, the structural performance and research status of PWEHs based on different mechanisms, such as a rotating turbine, vortex-induced vibration, flutter, and galloping, are analyzed and summarized. Finally, the development trend of PWEHs has been prospected.


Patterns of Depression Treatment in Medicare Beneficiaries with Depression after Traumatic Brain Injury.
There are no clinical guidelines addressing the management of depression after traumatic brain injury (TBI). The objectives of this study were to (1) describe depression treatment patterns among Medicare beneficiaries with a diagnosis of depression post-TBI; (2) compare them with depression treatment patterns among beneficiaries with a diagnosis of depression pre-TBI; and (3) quantify the difference in prevalence of use. We conducted a retrospective analysis of Medicare beneficiaries hospitalized with TBI during 2006-2010. We created two cohorts: beneficiaries with a new diagnosis of depression pre-TBI (n=4841) and beneficiaries with a new diagnosis of depression post-TBI (n=4668). We searched for antidepressant medications in Medicare Part D drug event files and created variables indicating antidepressant use in each 30-day period after diagnosis of depression. We used provider specialty and current procedural terminology to identify psychotherapy in any location. We used generalized estimating equations to quantify the effect of TBI on receipt of depression treatment during the year after diagnosis of depression. Average monthly prevalence of antidepressant use was 42% among beneficiaries with a diagnosis of depression pre-TBI and 36% among those with a diagnosis post-TBI (p<0.001). Beneficiaries with a diagnosis of depression post-TBI were less likely to receive antidepressants compared with a depression diagnosis pre-TBI (adjusted odds ratio [OR] 0.87; 95% confidence interval [CI] 0.82, 0.92). There was no difference in receipt of psychotherapy between the two groups (OR 1.08; 95% CI 0.93, 1.26). Depression after TBI is undertreated among older adults. Knowledge about reasons for this disparity and its long-term effects on post-TBI outcomes is limited and should be examined in future work.


Evaluation of antioxidant activity and characterization of phenolic constituents of Phyllanthus amarus root.
The antioxidant property of the 70% aqueous ethanol extract of Phyllanthus amarus roots and its ether-soluble, ethyl acetate-soluble, and aqueous fractions were investigated by various in vitro assays. The root extracts showed higher DPPH, hydroxyl, superoxide, and nitric oxide radical scavenging and reducing power activity. Among all the samples, the ethyl acetate-soluble fraction demonstrated highest radical scavenging activity and total phenolics content. Twenty-eight different phenolic compounds were identified by LCMS/MS analysis of the ethyl acetate-soluble fraction. The majority of the compounds were found to exist as their glycosides, and many of these were gallic acid derivatives. Free epicatechin and gallic acid were also identified in the ethyl acetate-soluble fraction. The present investigation suggested that P. amarus root is a potent antioxidant and can be used for the prevention of diseases related to oxidative stress.


IgG oligoclonal bands in sera of HIV-1 infected patients are mainly directed against HIV-1 determinants.
In a series of 60 HIV-1-infected individuals, serum electrofocusing analysis disclosed clonally restricted IgG patterns in 9 patients (15%), most with limited disease progression (stages WR1-WR3). These oligoclonal bands had a very heterogeneous light chain pattern, and most showed specificity for HIV-1 in affinity-driven transfer studies; virus specificity was more clear-cut following adsorption of sera with the relevant antigen. These findings further stress the profound B-cell function derangement in HIV-1 infection; their possible relevance to AIDS-associated lymphoma development is discussed.


A comparative study of long acting diltiazem (Tildiem LA) with sustained release nifedipine (nifedipine SR) and bendrofluazide in the treatment of mild to moderate hypertension.
The therapeutic efficacy of long acting diltiazem 300 mg od (Tildiem LA) was compared with sustained release nifedipine 20 mg bd and bendrofluazide 5 mg od in a multicentre study with 230 patients diagnosed with mild to moderate essential hypertension, with 77, 77 and 76 randomized to the diltiazem, nifedipine SR and bendrofluazide groups respectively. Patients were entered into this randomised, single (investigator) blind, parallel-group multicentre study if the systolic and diastolic blood pressures were > or = 145 mm Hg and/or 95 mm Hg respectively at the admission visit. Twenty-one general practitioners and two hospital physicians monitored patients at baseline and at four and eight weeks of continuous dosing. After eight weeks of therapy, clinically acceptable control of blood pressure was seen in all groups: reductions were 19.2/13.5 mm Hg, 20.4/14 mm Hg and 18.5/10.8 mm Hg for the Tildiem, nifedipine and bendrofluazide groups respectively. Significant differences were shown between bendrofluazide and the other two groups on diastolic pressures (p = 0.01). The non-significant trend was for systolic pressures to mirror these effects. Significantly higher withdrawals caused by adverse events were seen with nifedipine. These were as follows: 14 patients receiving nifedipine (18%), 5 patients receiving diltiazem (6%) and 4 patients receiving bendrofluazide (5%). The difference in this withdrawal rate between treatments was statistically significant (p = 0.01). Post hoc tests revealed that both diltiazem and bendrofluazide had statistically significant lower withdrawals for adverse events than the nifedipine group (p = 0.047). Nifedipine was associated with a marginal increase in standing apex pulse rate and only diltiazem LA significantly maintained serum potassium levels. These results indicate that diltiazem 300 mg is an effective antihypertensive agent and is equivalent in efficacy to nifedipine SR 20 mg and both are superior to bendrofluazide. Nifedipine SR was however the worst tolerated and had the highest withdrawal rate (p = 0.013).


Improving the efficiency of screening for major depression in people with spinal cord injury.
To investigate the metric properties, relative efficiency, sensitivity and specificity, and positive predictive value of a short form of the Patient Health Questionnaire-9 (PHQ-9) that may be used as a screening test for depression. Data from the National Spinal Cord Injury Statistical Center Database containing 3,652 records with complete data for the PHQ-9 were analyzed using Confirmatory Factor Analysis, Item Response Theory Graded Response Model analysis, and sensitivity and specificity analysis of classification. A scale comprised of items 1, 2, and 6 from the PHQ-9 has a relative efficiency of 0.66 compared to the 9-item scale. Using this 3-item scale and a cutoff score of 3 or more provides specificity of 0.93 and sensitivity of 0.87; a cutoff of 4 provides specificity of 0.95 and sensitivity of 0.82. The shorter version of the scale reduces the effect of response bias caused by gender. The relative efficiency of the 9-item scale is 0.88 for women compared to men; the 3-item scale increases the relative efficiency to 0.93. A 3-item scale provides adequate information for clinical screening purposes. Cutoff scores of either 3 or 4 are acceptable and present options for decision making within a particular clinical setting. Additionally, the 3-item scale reduces the effect of gender of the respondent on the score obtained.


LIF/LIFR oncogenic signaling is a novel therapeutic target in endometrial cancer.
Endometrial cancer (EC) is the fourth most common cancer in women. Advanced-stage EC has limited treatment options with a poor prognosis. There is an unmet need for the identification of actionable drivers for the development of targeted therapies in EC. Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a major role in cancer progression, metastasis, stemness, and therapy resistance. However, little is known about the functional significance of the LIF/LIFR axis in EC progression. In this study using endometrial tumor tissue arrays, we identified that expression of LIF, LIFR is upregulated in EC. Knockout of LIFR using CRISPR/Cas9 in two different EC cells resulted in a significant reduction of their cell viability and cell survival. In vivo studies demonstrated that LIFR-KO significantly reduced EC xenograft tumor growth. Treatment of established and primary patient-derived EC cells with a novel LIFR inhibitor, EC359 resulted in the reduction of cell viability with an IC50 in the range of 20-100 nM and induction of apoptosis. Further, treatment with EC359 reduced the spheroid formation of EC cancer stem cells and reduced the levels of cancer stem cell markers SOX2, OCT4, NANOG, and Axin2. Mechanistic studies demonstrated that EC359 treatment attenuated the activation of LIF-LIFR driven pathways, including STAT3 and AKT/mTOR signaling in EC cells. Importantly, EC359 treatment resulted in a significant reduction of the growth of EC patient-derived explants ex vivo, EC cell line-derived xenografts, and patient-derived xenografts in vivo. Collectively, our work revealed the oncogenic potential of the LIF/LIFR axis in EC and support the utility of LIFR inhibitor, EC359, as a novel targeted therapy for EC via the inhibition of LIF/LIFR oncogenic signaling.


[Diagnosis and therapeutic aspects of epithelial thymomas].
The authors present histopathology, clinical course, and therapy results of seven patients with epithelial thymomas who have been irradiated subsequently to operation between 1971 and 1981. Four patients are alive without tumors two to twelve years after radiotherapy. One patient died ten years after treatment without any sign of recurrence, two patients died from a local recurrence or metastases eight months and four years after diagnosis, respectively. The therapy of choice is a resection of tumorous tissues performed as completely as possible which succeeds mostly in sano in case of encapsulated thymomas. Our experiences show that an irradiation is indicated for inoperable or incompletely resected thymomas in order to decrease the high risk of local recurrences and to obtain favorable long-term results.


In vivo burn imaging using Mueller optical coherence tomography.
We report on the use of a high-speed, fiber-based Mueller-matrix optical coherence tomography system with continuous source-polarization modulation for in vivo burn depth evaluation and healing monitoring. A homemade hand-held probe with integrated optical scanning and beam delivering optics was coupled in the sample arm. In vivo burn imaging was demonstrated on porcine skin at different stages of the wound healing process, where porcine skin was used because of its similarity to the human skin. Thermally damaged region was clearly localized in the depth-resolved phase retardation image extracted from the measured Jones matrix. The burn areas in the OCT images agreed well with the histology. By using a decomposition algorithm developed by our group, we also mapped the local birefringence of the skin. The experimental results demonstrate the system's potential for in vivo burn-depth determination.


Culture instability of auxotrophic amino acid producers.
The long-term dynamic characteristics of the L-lysine producer Corynebcterium glutamicum in continuous culture were studied over a range of specific growth rates. The double-auxotroph parent strain was found to be susceptible to a back mutation, or reversion, which negated the regulatory bypass that allows this strain to accumulate L-lysine in culture but also gives rise to a L-threonine auxotrophic requirement. Consequently, the revertant cells no longer over-produced L-lysine, nor were they limited in their growth by the low levels of L-threonine in the medium. All continuous culture experiments were eventually taken over by these revertants. The instability of the culture was found to be primarily due to the growth rate differential between the two competing populations, the (productive) parent auxotrophs and the (nonproductive) revertants. A deterministic mathematical model of the culture dynamics, incoroporating two limiting-substrate balances, satisfactorily described the takeover profiles. A linear stability analysis of the model equations identified that although long-term culture demise is inevitable, the dimensionless ratio of the two limiting substrates controls the rate of takeover by nonproductive cells. The analysis further demonstrated the importance of proper medium design in delaying the onset of takeover in cultures of this double-auxotroph strain. The theoretical medium design criterion was then confirmed experimentally by the stabilization of a fed-batch culture against revertant takeover for an extended fermentation time.


A trial of oral oxamniquine in the treatment of Schistosoma infection in children.
Oral oxamniquine 800 mg/m2 body surface area/day in divided doses for 2 days, was given to 57 children with schistosomal infections. Haematological and biochemical tests suggest that this drug is safe, even in the presence of significant liver enlargement. Parasitological investigations in 32 children who were followed up for 1 month indicate that oxamniquine is effective in the treatment of S. mansoni infection, but that it has little effect on S. haematobium infection.


Bull Fertility and Its Relation with Density Gradient Selected Sperm.
Sperm selection method is usually used to collect these cells for in vitro-assisted reproduction. Few studies reported the relationship of in vivo fertility and semen parameters after sperm selection; hence, the present study attempted to assess different semen parameters after post-thaw or sperm selection, using density gradient separation BoviPure®, to predict in vivo fertility. In this experimental study, frozen semen quality of four Montbeliarde bulls were assessed after post-thaw (PT) or after sperm selection (SSp), using density gradient separation BoviPure®, to predict the fertility rate in vivo. In addition to PT or SSp, semen was examined for concentration, motility, morphology abnormalities, viability, acrosome and plasma membrane integrities. Fertility was measured as non-return rates within 56 days after the first insemination (NRR) or as corrected NRR, expressed as CNRR, to the factors influencing fertility using linear mixed model. Non-parametric Kruskal-Wallis test was performed to compare semen parameter variables. Fertility rates were compared using Chi-square test. Pearson correlation analysis was used to test the relationship between CNRR and semen parameters. Data was analysed using SPSS package program, version 21.0. Most of the examined bulls exhibited a high fertility rate (3/4 bulls, 62.1- 81.8% for NRR or 67.2-98.5% for CNRR). Fertility rate, expressed as CNRR, was significantly related to semen parameters after SSp, but not after PT. Thus, CNRR was increased with decrease of total motility, progressive spermatozoa and abaxial implantation frequencies after SSp (r=-0.999, P=0.001; r=-0.990, P=0.010; r=-0.988, P= 0.012, respectively); while, CNRR was decreased with decrease of SSp immotile spermatozoa (r=+0.995, P=0.005), underlying that maximal limit of determined immotile spermatozoa is 47%. High frequencies of total and progressive motility spermatozoa, and abaxial implantation in gradient selected sperm appear to be not favorable for fertility in vivo.


Integrated evaluation of lung disease in single animals.
During infectious disease, pathogen load drives inflammation and immune response that together contribute to tissue injury often resulting in organ dysfunction. Pulmonary failure in SARS-CoV2-infected hospitalized COVID-19 patients is one such prominent example. Intervention strategies require characterization of the host-pathogen interaction by accurately assessing all of the above-mentioned disease parameters. To study infection in intact mammals, mice are often used as essential genetic models. Due to humane concerns, there is a constant unmet demand to develop studies that reduce the number of mice utilized while generating objective data. Here, we describe an integrated method of evaluating lung inflammation in mice infected with Pseudomonas aeruginosa or murine gammaherpesvirus (MHV)-68. This method conserves animal resources while permitting evaluation of disease mechanisms in both infection settings. Lungs from a single euthanized mouse were used for two purposes-biological assays to determine inflammation and infection load, as well as histology to evaluate tissue architecture. For this concurrent assessment of multiple parameters from a single euthanized mouse, we limit in-situ formalin fixation to the right lung of the cadaver. The unfixed left lung is collected immediately and divided into several segments for biological assays including determination of pathogen titer, assessment of infection-driven cytokine levels and appearance of cell death markers. In situ fixed right lung was then processed for histological determination of tissue injury and confirmation of infection-driven cell death patterns. This method reduces overall animal use and minimizes inter-animal variability that results from sacrificing different animals for different types of assays. The technique can be applied to any lung disease study in mice or other mammals.


3-Hydroxy-alpha-methyltyrosine progenitors: synthesis and evaluation of some (2-oxo-1,3-dioxol-4-yl)methyl esters.
The (5-methyl-2-oxo-1,3- dioxol -4-yl)methyl and (5-tert-butyl-2-oxo-1, 3- dioxol -4-yl)methyl esters of 3-hydroxy-alpha-methyltyrosine (methyldopa) were prepared and evaluated as progenitors of the amino acid. 1H NMR experiments reveal that the esters are converted cleanly to methyldopa and the corresponding alpha-diketone at pH 7.4, with the 5-methyl derivative undergoing hydrolysis faster than the 5-tert-butyl analogue. Bioavailability studies in dogs show that the esters, particularly the 5-methyl derivative, yield significant plasma levels of methyldopa. Both esters are orally effective antihypertensive agents in spontaneously hypertensive (SH) rats. These studies indicate that (2-oxo-1,3- dioxol -4-yl)methyl esters are viable prodrugs for the latentiation of methyldopa.


Extrahepatic Portal Vein Obstruction in Children: Role of Preoperative Imaging.
Extrahepatic portal vein obstruction (EHPVO) is characterized by features of recent thrombosis or portal hypertension with portal cavernoma as a sequel of portal vein obstruction. Imaging of spleno-portal axis is the mainstay for the diagnosis of EHPVO. The aim of this study is to analyze the role of imaging in the preoperative assessment of the portal venous system in children with EHPVO. A hospital-based cross-sectional study was conducted on twenty children with EHPVO aged between 1 and 18 years over a period of 1 year. The children were evaluated clinically, followed by upper gastrointestinal endoscopy. Radiological assessment included imaging of the main portal vein, its right and left branches, splenic vein, and superior mesenteric vein using color Doppler ultrasonography (CDUSG) and magnetic resonance portovenogram (MRP). Evidence of portal biliopathy, status of collaterals, and possible sites for portosystemic shunt surgery were also examined. All the patients presented in chronic stage with portal cavernoma and only one patient (5%) had bland thrombus associated with cavernoma. The CDUSG and MRPs had a sensitivity of 66.6-90% and 96.7% and specificity of 91.5% and 98.3% respectively with regard to the assessment of the extent of thrombus formation and flow in the portal venous system. Both the modalities were found to be complementary to each other in preoperative assessment of EHPVO. However, the sensitivity of MRP was slightly superior to CDUSG in detecting occlusion and identifying portosystemic collaterals and dilated intrahepatic biliary radicals. Results of the present study indicate that MRP is well suited and superior to CDUSG in the preoperative imaging of patients with EHPVO.


Fermented Rice Bran Supplementation Inhibits LPS-Induced Osteoclast Formation and Bone Resorption in Mice.
Fermented rice bran (FRB) is known to have numerous beneficial bioactivities, amongst which is its anti-inflammatory properties when used as a supplement. To determine its effects, we examined osteoclastogenesis and bone resorption caused by injections of lipopolysaccharide (LPS), using mice with and without FRB supplementation. The results were favorable: those that received FRB showed reduced osteoclast numbers and bone resorption compared to those with the control diet. Notably, receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-α (TNF-α) mRNA levels were shown to be lower in the LPS-treated animals with FRB supplementation. FRB's inhibitory effect on RANKL- and TNF-α-induced osteoclastogenesis was further confirmed in vitro. In culture, macrophages exhibited decreased TNF-α mRNA levels when treated with FRB extract and LPS versus treatment with LPS alone, but there was no significant change in RANKL levels in osteoblasts. We can conclude that FRB supplementation dampens the effect of LPS-induced osteoclastogenesis and bone resorption by controlling TNF-α expression in macrophages and the direct inhibition of osteoclast formation.


Effects of light and autochthonous carbon additions on microbial turnover of allochthonous organic carbon and community composition.
The fate of allochthonous dissolved organic carbon (DOC) in aquatic systems is primarily controlled by the turnover of heterotrophic bacteria. However, the roles that abiotic and biotic factors such as light and DOC release by aquatic primary producers play in the microbial decomposition of allochthonous DOC is not well understood. We therefore tested if light and autochthonous DOC additions would increase allochthonous DOC decomposition rates and change bacterial growth efficiencies and community composition (BCC). We established continuous growth cultures with different inocula of natural bacterial communities and alder leaf leachates (DOCleaf) with and without light exposure before amendment. Furthermore, we incubated DOCleaf together with autochthonous DOC from lysed phytoplankton cultures (DOCphyto). Our results revealed that pretreatments of DOCleaf with light resulted in a doubling of bacterial growth efficiency (BGE), whereas additions of DOCphyto or combined additions of DOCphyto and light had no effect on BGE. The change in BGE was not accompanied by shifts in the phylogenetic structure of the BCC, but BCC was influenced by the DOC source. Our results highlight that a doubling of BGE is not necessarily accompanied by a shift in BCC and that BCC is more strongly affected by resource properties.


Rivaroxaban in heart failure patients with left ventricular thrombus: A retrospective study.
Background: The role of rivaroxaban in patients with heart failure (HF) combined with left ventricular (LV) thrombus remains unknown in current guideline-directed anticoagulant therapy. The aim of this study was to investigate the impact on clinical outcomes of rivaroxaban compared to vitamin K antagonists (VKAs) in patients with HF combined with LV thrombus. Methods: We retrospectively extracted clinical, echocardiographic and follow-up data of HF patients (all classifications) admitted at China-Japan Union Hospital of Jilin University from January 2017 to June 2021. A total of 198 patients with HF were identified with LV thrombus by echocardiography, 78 of them were managed with VKAs, 109 with rivaroxaban. Results: The median follow-up was 17.0 months (interquartile range: 6.0-24.0 months). High rates of major cardiovascular adverse events (MACEs) were observed in both the rivaroxaban and VKAs groups (49.5% vs. 57.7%). However, rivaroxaban versus VKAs observed a decrease in MACEs (adjusted HR:0.636; 95%CI:0.418-0.970; p = 0.035) and systemic embolism (4.6% vs. 12.8%; adjusted HR:0.318; 95%CI:0.108-0.933; p = 0.037; Gray's test p = 0.041) but was not found to have a benefit with regard to LV thrombus resolution (59.6% vs. 70.6%; adjusted HR: 1.303; 95% CI:0.898-1.890; p = 0.163; Gray's test p = 0.073). Additionally, there was no significant between-group difference in the rate of International Society on Thrombosis and Hemostasis (ISTH) bleeding events. Conclusion: Our data found that in populations with HF combined with LV thrombus, the overall prognosis in both the rivaroxaban and VKAs groups was catastrophic. Although rivaroxaban improved the prognosis to some extent, a considerable need remains for new treatments to improve their clinical course.


[Effects of feixin decoction on the contents of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in the rat model of hypoxic pulmonary hypertension].
To explore the effects of Feixin Decoction (FXD) on the hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in the rat model of hypoxic pulmonary hypertension (HPH), and to study its mechanisms for treating HPH. Forty healthy male SD rats were randomly divided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifedipine group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia method. Except the normal control group, rats in the rest groups were fed in a self-made hypoxic plexiglass cabin, with the poor oxygen condition for 8 h daily for 14 successive days. Then the distilled water (at 30 mL/kg) was given by gastrogavage to rats in the normal control group and the HPH model group. FXD (at 28 g/kg) and Nifedipine (at 20 mg/kg) were given by gastrogavage to rats in the FXD group and the Nifedipine group respectively, once daily, for 14 successive days. Besides, hypoxia was continued for 14 days while medicating. The mean pulmonary artery pressure (mPAP) was detected on the second day after the last medication. The morphology of the pulmonary arteriole was detected. The ratio of pulmonary artery wall area and tube area (WA%) was determined. The protein and mRNA expressions of HIF-1alpha and VEGF were detected using immunohistochemistry and in situ hybridization technique. Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly increased in the model group (P < 0.01, P < 0.05). Compared with the HPH model group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly decreased in the FXD group (P < 0.01, P < 0.05). FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1alpha. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular smooth muscle.


The suitability of Ta6Br12(2+) for phasing in protein crystallography.
The title compound Ta6Br12(2+) is of interest for the analysis of biological structures as a heavy metal derivative with great potential for the structure determination of large protein systems. In macromolecular crystallography the phases of the measured structure factor amplitudes have to be determined by compounds that produce measurable changes of the diffraction intensities. Ta6Br12(2+) uniquely meets the demands of a heavy metal derivative and is an important tool for phase determination, especially considering the structure determination of large protein systems.


Effect of a High Estrogen Level in Early Pregnancy on the Development and Behavior of Marmoset Offspring.
The use of assisted reproductive technology (ART) has risen steadily worldwide over the past 3 decades and helps many infertile families. However, ART treatments lead to an abnormal internal environment in the uterus, which may increase the risks of health problems for the offspring. Higher maternal estradiol (E2) is a notable feature in women who use ART treatments, and this has been suggested as a key factor for the risk of diseases in the offspring. In the current study, we have established a marmoset model with a high E2 level in early pregnancy to examine its potential risk to the development and behavior of the offspring. In comparison with the normal group, babies of the high E2 group exhibited lower average survival rates and birth weights. However, those who survived in the high E2 group demonstrated normal vocal production with rich call repertoires, normal speed during locomotion, and normal behaviors in the home cage. In contrast to the normal group, surviving babies of the high E2 group spent more time sleeping during development without signs of sleep disorders. In summary, our study revealed that high estrogen in early pregnancy may cause low survival rates and birth weights of the offspring, though the surviving infants did not show obvious behavioral deficiencies during development. The current study is a valuable and highly important non-human primate study for evaluating the safety of ART treatments. However, it is worth noting that some results did not reach the significant level, which may be due to the small sample size caused by animal shortage stemming from the COVID-19 epidemic.


Reduction in daily milk yield associated with subclinical bovine herpesvirus 1 infection.
The aim of this observational cohort study was to investigate the potential economic impact of subclinical bovine herpesvirus 1 (BoHV-1) infection in a commercial UK dairy herd in terms of milk yield depression. Infection status of cows (infected or not infected) was assigned from serology on a single occasion. A multi-level linear model was used to evaluate the impact of infection status on milk production, using milk records that were routinely collected over two years. BoHV-1 seropositive cows produced 2.6 kg/day less milk over the study period compared with cows that were seronegative. This result highlights the importance of appropriate management of risks associated with subclinical infection with BoHV-1 as part of proactive herd health and production management.


The effect of subsequent immunosuppressant use in organ-transplanted patients on prostate cancer incidence: a retrospective analysis using the Korean National Health Insurance Database.
Prostate cancer (PC) is the most common solid organ cancer. However, there is still no definite consensus before and after organ transplantation (TPL). We aimed to analyze whether PC incidence increased in TPL patients with subsequent use of immunosuppressants using the Korean National Health Insurance Database. TPL patients between 2003 and 2015(N = 12,970) were age- and year-matched to non-TPL patients (N = 38,910) in a 1:3 ratio. Multivariate Cox regression analysis adjusted for significant prognostic clinicopathological parameters, including the duration of immunosuppressant agent use (0-300 or > 300 days), and Kaplan-Meier analysis with log-rank test were used to evaluate the association of TPL with PC incidence between the groups. Median overall survival was 4.86 years; overall mortality rate was 3.4% (n = 1761). Regardless of differences in baseline characteristics between the groups, multivariate analysis for PC incidence showed that age, immunosuppressant use, and TPL organ subtypes were significant factors for the overall population, whereas only age was significant in the TPL group (p < 0.05). After adjusting for age, underlying disease, and prescribed medication (aspirin, statin), multiple subgroup analysis models for PC incidence were evaluated. PC incidence was increased in the TPL group (hazard ratio [HR] 1.965, p < 0.001); however, PC incidence in the TPL group became insignificant after adjusting for immunosuppressant use (p = 0.194). Kaplan-Meier curves also showed that PC incidence was significantly different according to age and TPL with the use of immunosuppressants between the TPL and non-TPL groups. PC incidence was higher in the TPL group using immunosuppressants than in the non-TPL group. The study was retrospectively registered.


Automated recognition of urinary microscopic solid particles.
Urine analysis reveals the presence of many problems and diseases in the human body. Manual microscopic urine analysis is time-consuming, subjective to human observation and causes mistakes. Computer aided automatic microscopic analysis can help to overcome these problems. This paper introduces a comprehensive approach for automating procedures for detecting and recognition of microscopic urine particles. Samples of red blood cells (RBC), white blood cells (WBC), calcium oxalate, triple phosphate and other undefined images were used in experiments. Image processing functions and segmentation were applied, shape and textural features were extracted and five classifiers were tested to get the best results. Repeated experiments were done for adjusting factors to produce the best evaluation results. A good performance was achieved compared with many related works.


Identification and characterization of GSTT3, a third murine Theta class glutathione transferase.
A novel Theta class glutathione transferase (GST) isoenzyme from mouse termed mGSTT3 has been identified by analysis of the expressed sequence tag database. The gene encoding mGSTT3 is clustered with the mGSTT1 and mGSTT2 genes on chromosome 10 and has an exon/intron structure that is similar to that of the other Theta class genes. mGSTT3 is expressed strongly in the liver and to a decreasing extent in the kidney and testis. Recombinant mGSTT3-3 expressed in Escherichia coli had a substrate-specificity profile that differed significantly from that of GSTT1-1 and GSTT2-2 isoenzymes. A molecular model of mGSTT3 suggested that, in comparison with GSTT2, a decrease in volume of the hydrophobic substrate-binding site and the loss of the sulphate-binding pocket prevents its use of the GSTT2 substrate 1-menaphthyl sulphate.


Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice.
Gelsemine is a natural alkaloid extracted from Gelsemium elegans Benth., a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases. In this study, we have found, for the first time, that gelsemine at low concentrations (5-10 μg/kg) significantly alleviated cognitive impairments induced by β-amyloid (Aβ) oligomer, a main neurotoxin of Alzheimer's disease (AD). In addition, gelsemine substantially prevented Aβ oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3β (GSK3β), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aβ oligomer-induced reduction of PSD-95, a representative post-synaptic protein. All these results directly demonstrated the anti-Aβ oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aβ-associated neurodegeneration disorders, including AD in particular.


Mind wandering in sentence reading: decoupling the link between mind and eye.
When people read, their thoughts sometimes drift away from the task at hand: They are "mind wandering." Recent research suggests that this change in task focus is reflected in eye movements and this was tested in an experiment using controlled stimuli. Participants were presented with a series of sentences containing high- and low-frequency words, which they read while being eye-tracked, and they were sometimes probed to indicate whether they were on task or mind wandering. The results showed multiple differences between reading prior to a mind-wandering response and reading when on task: Mind wandering led to slower reading times, longer average fixation duration, and an absence of the word frequency effect on gaze duration. Collectively, these findings confirm that task focus could be inferred from eye movements, and they indicate that the link between word identification and eye scanning is decoupled when the mind wanders.


Immunological study of antisera to to artificial O-antigen of Pseudomonas aeruginosa.
O-sera were obtained by immunizing rabbits with artificial antigens: polysaccharide extracted from the lipopolysaccharide of P. aeruginosa (strain No. 868; 03a, 3d, 3e), or the high-molecular-weight or low-molecular-weight fraction of this polysaccharide, complexed with a natural protein (human IgG or rabbit globulin). The antisera to these antigenic complexes were highly O-specific. Antisera to the complexes of polysaccharide-protein and high-molecular-weight fraction-protein were more active in the passive haemagglutination reaction, slide agglutination test and immunodiffusion test in agar gel than was antiserum to the low-molecular-weight fraction-protein complex. The artificial antigens prepared and employed in the study are apt to be used for the preparation of monospecific immune sera.


The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease.
The glycemic index was proposed in 1981 as an alternative system for classifying carbohydrate-containing food. Since then, several hundred scientific articles and numerous popular diet books have been published on the topic. However, the clinical significance of the glycemic index remains the subject of debate. The purpose of this review is to examine the physiological effects of the glycemic index and the relevance of these effects in preventing and treating obesity, diabetes, and cardiovascular disease.


Hepatocarcinomas, cholangiocarcinomas, and hepatoblastomas produced by chemically transformed cultured rat liver epithelial cells. A light- and electron-microscopic analysis.
The histology and ultrastructure of more than 100 tumors produced by a chemically transformed rat liver epithelial cell line and its single-cell-derived clonal subpopulations were studied. Wide-ranging morphologic presentations were observed, including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors. In addition to epidermoid and adenocarcinomas, several tumors were morphologically indistinguishable from hepatocellular carcinomas. The "mixed epithelial-mesenchymal" tumors reproduced most of the various histologic features of human hepatoblastomas. In many instances, the epithelial component occupied focal areas of tumors, and transmission electron microscopic studies of the "sarcomatous" regions revealed either spindle-shaped epithelial tumor cells or, in most cases, scattered epithelial tumor cells surrounded by numerous fibroblasts or myofibroblasts. Similar findings were observed in several "sarcomas" examined ultrastructurally, which suggests that most of the mixed tumors or sarcomas actually were spindle cell carcinomas and/or carcinomas with marked host fibroblastic reaction. However, in a few mixed tumors produced by clonally derived cell strains, unequivocal carcinosarcomas with neoplastic osteoid or chondroid tissue were demonstrated. The findings of this study are discussed in the context of current insights on the cellular composition of the liver and on the histogenesis of human hepatoblastoma.


Blood pressure variability increases connexin expression in the vascular smooth muscle of rats.
Following sinoaortic denervation (SAD), isolated rat aortas present oscillatory contractions and demonstrate a heightened contraction for alpha-adrenergic agonists. Our aim was to verify the effects of SAD on connexin43 (Cx43) expression and phenylephrine-induced contraction in isolated aortas. Three days after surgery (SAD or sham operation), isolated aortic rings were exposed to phenylephrine and acetylcholine (0.1-10 microM) in the presence or absence of the gap junction blocker 18beta-glycyrrhetinic acid (18beta-GA, 100 microM). Vascular reactivity to potassium chloride (KCl, 4.7-120 mM) was also examined. The incidence of rats presenting oscillatory contractions was measured. Effects of SAD on the vascular smooth muscle expression of the Cx43 mRNA by RT-PCR and western blotting for Cx43 protein were examined. Phenylephrine-induced contraction was higher in SAD rat aortas compared with the control. In the presence of 18beta-GA, the response to phenylephrine was similar in both groups. Oscillatory contractions were observed in 10/10 SAD rat aortas vs. 2/10 controls. Relaxing response to acetylcholine was similar in both groups, but in the presence of 18beta-GA, the response to acetylcholine decreased significantly in the sham-operated group (82.7 +/- 7.6% reduction of relaxation), whereas a half-maximal relaxation (reduction of 46.2 +/- 5.3%) took place in SAD rat aortas. KCl-induced contraction was similar in both groups. Following SAD, RT-PCR revealed significantly increased levels of Cx43 mRNA (9.85 fold, P < 0.01). Western blot analysis revealed greater levels of Cx43 protein (P < 0.05). Blood pressure variability evoked by SAD leads to increased expression of Cx43, which could contribute to enhanced phenylephrine-induced contraction and oscillatory activity in isolated aortas.


A polysaccharide found in Dendrobium nobile Lindl stimulates calcium signaling pathway and enhances tobacco defense against TMV.
A neutral polysaccharide separated from Dendrobium nobile Lindl was designated as DNPE6(4). It was structurally characterized using a combination of spectral and chemical analysis. Its average molecule weight was 99.2 kDa. The monosaccharide composition was Araf, Glcp, Galp, and Manp in a molar ratio of 2.5:0.9:0.3:0.8. Their linkage types were →1)-L-Araf-(3→, →1)-D-Glcp-(4→, →1)-D-Galp-(3→, →1)-D-Galp-(6→, →1)-D-Manp-(3, 6→, and T-D-Manp. The polysaccharide was found to have anti-TMV and anti-CMV activities for the first time in vivo. Notably, DNPE6(4) exhibited excellent protective activity against TMV. Furthermore, several proteins related to calcium signaling pathway and pathogen related proteins were up-regulated, and we also found expression levels of EDS1, ICS1, and PR1 involved in SA pathway up-regulated after DNPE6(4) treatment. In addition, some defense enzymes increased in the same condition. All these findings revealed DNPE6(4) was an elicitor to stimulate calcium signaling pathway to enhance the tobacco defense against TMV. This study therefore revealed that DNPE6(4) was a promising antiviral agent for future study.


A new brain-penetrant glucosylceramide synthase inhibitor as potential Therapeutics for Gaucher disease.
Gaucher disease (GD), the most common lysosomal storage disorders, is caused by GBA gene mutations resulting in glycosphingolipids accumulations in various tissues, such as the brain. While suppressing glycosphingolipid accumulation is the central strategy for treating peripheral symptoms of GD, there is no effective treatment for the central nervous system symptoms. As glycosphingolipid biosynthesis starts from ceramide glycosylation by glucosylceramide synthase (GCS), inhibiting GCS in the brain is a promising strategy for neurological GD. Herein, we discovered T-036, a potent and brain-penetrant GCS inhibitor with a unique chemical structure and binding property. T-036 does not harbor an aliphatic amine moiety and has a noncompetitive inhibition mode to the substrates, unlike other known inhibitors. T-036 exhibited sufficient exposure and a significant reduction of glucosylsphingolipids in the plasma and brain of the GD mouse model. Therefore, T-036 could be a promising lead molecule for treating central nervous system symptoms of GD.


Digital analysis of flap parameter accuracy and objective assessment of opaque bubble layer in femtosecond laser-assisted LASIK: a novel technique.
The purpose of this study was to determine flap parameter accuracy, extent of the opaque bubble layer, and incidence of skip lines in femtosecond laser-assisted stromal in situ keratomileusis (LASIK) using the WaveLight(®) FS200 laser and optoelectronic clinical measurements. Images from 101 flaps were automatically recorded during consecutive routine LASIK procedures performed using the WaveLight FS200 femtosecond laser and the EX500 excimer laser. Digital processing of these images was used to evaluate objectively the diameter of FS200-created flaps, by comparing planned versus achieved procedures and to evaluate the incidence and extent (area) of the opaque bubble layer. The intended flap diameters were between 8.00 mm and 9.50 mm. The achieved flap diameters showed extremely high precision, and were on average -0.16 ± 0.04 mm smaller for a 8.00 mm intended flap diameter, -0.12 ± 0.03 mm smaller for a 8.50 mm flap, and up +0.06 ± 0.06 mm wider for a 9.50 mm flap. With an average flap area of 72.4 mm(2), the mean area of the opaque bubble layer (4.1 ± 4.3 [range 0-14.34] mm(2)) corresponded to a 6% opaque bubble layer-to-flap area. Specifically, 80% of the femtosecond-created flaps had an essentially zero opaque bubble layer (<2.7% of the flap area). In our clinical experience, flaps created using FS200 and this novel highly objective assessment technique demonstrate both precision and reproducibility. The incidence of opaque bubble layer was minimal.


Sublethal Effects of Beauveria bassiana (Ascomycota: Hypocreales) on Life Table Parameters of Frankliniella occidentalis (Thysanoptera: Thripidae).
We assessed effects of parental exposure to Beauveria bassiana on life history traits of subsequent generations of western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). Progeny from individuals that survived fungal exposure as second instars had significantly shorter egg stages, but longer prepupal development times than corresponding untreated controls. However, survivorship to adulthood of these progeny groups did not differ. Although fecundities of the parental types did not differ, the sex ratio of progeny from fungal-treated parents was male-biased, whereas sex ratio of progeny from untreated control parents was even. We calculated life table parameters for the progeny and found that all parameters, except for generation time, were significantly less for the progeny of fungal-treated parents than for progeny of untreated parents. The intrinsic rate of increase, finite rate of increase, net reproductive rate, mean generation time, and gross reproductive rate were 0.199 d(-1), 1.229 d(-1), 21.84, 15.48 d, and 27.273, respectively, for progeny of treated thrips, and 0.266 d(-1), 1.316 d(-1), 52.540, 14.92 d, and 70.64, respectively, for progeny of control thrips. Consequently, population projections demonstrated that offspring of parents exposed to B. bassiana would increase their population more slowly than those from untreated parents. These results demonstrate that B. bassiana has sublethal effects that reduce the reproductive success of F. occidentalis and these effects should be taken into account when evaluating its use in management programs for F. occidentalis.


Autoimmunity and its association with regulatory T cells and B cell subsets in patients with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifests a wide clinical variability such as autoimmunity, as well as T cell and B cell abnormalities. A total of 72 patients with CVID were enrolled in this study. Patients were evaluated for clinical manifestations and classified according to the presence or absence of autoimmune disease. We measured regulatory T cells (Tregs) and B-cell subsets using flow cytometry, as well as specific antibody response (SAR) to pneumococcal vaccine, autoantibodies and anti-IgA in patients. Twenty-nine patients (40.3%) have shown at least one autoimmune manifestation. Autoimmune cytopenias and autoimmune gastrointestinal diseases were the most common. A significant association was detected between autoimmunity and presence of hepatomegaly and splenomegaly. Among CVID patients, 38.5% and 79.3% presented a defect in Tregs and switched memory B-cells, respectively, whereas 69.0% presented CD21low B cell expansion. Among patients with a defect in Treg, switched memory and CD21low B cell, the frequency of autoimmunity was 80.0%, 52.2% and 55.0%, respectively. A negative correlation was observed between the frequency of Tregs and CD21low B cell population. 82.2% of patients had a defective SAR which was associated with the lack of autoantibodies. Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures.


Myocardial uptake of labeled oleic and linoleic acids.
Oleic acid labeled with 14C, (14C-OA) or 131I (131I-OA) and 131I-labeled linoleic acid (131I-LOA) were administered intravenously to rats and tissue distribution studies completed at various time intervals from 5 to 60 min. Tissue distribution of 131-I-labeled oleic acid or linoleic acid was also studied in dogs at 5- and 30-min time intervals after intravenous administration of the tracer dose. There were distinct differences in the patterns of tissue distribution between 14C-OA, 131I-OA, and 131I-LOA. Radioactivity concentration in the myocardium was the highest at all time intervals in the rats given 131I-OA only. In dogs, the myocardial uptake of 131I-OA was significantly higher than the radioactivity in the blood or other tissues at 30 min after injection. The disappearance rates of 131I-OA and 131I-LOA were almost identical but myocardial concentration of 131I-LOA at 30 min after the dose in the dog was half that of 131I-OA whereas 131I-LOA liver concentration was higher than that of 131I-OA. Since the concentrations of our formulated 131I-OA in the blood and in the myocardium are both highest at the earlier intervals, it should be difficult to detect myocardial ischemia or infarction with 131I-OA scanning.


Predictors of health-promoting behavior of African-American and white caregivers of impaired elders.
Several longitudinal studies have examined declines in health of caregivers, but few have explored the health-promoting behavior Because caregivers neglect their health, they are at risk for developing a number of physical and psychological problems. What is not well known are the factors that contribute to increased health-promoting behavior ultimately preventing poor health and premature death. Therefore, the purpose of this study was to explore the predictors and the change in predictors of health-promoting behavior in African-American and White caregivers over a 3-year period. Pender, Murdaugh, and Parsons' (2002) health promotion model guided the study. This present study is a secondary data analysis of a larger study aimed at examining predictors of health-promoting behavior among 66 African-American (n=66) and 110 (n=110) and White caregivers of impaired older adults recruited primarily through random digit dialing. The larger data set consisted of 391 (N=391) subjects (n=136 African-American; n=255 White). The larger prospective study was based on face-to-face interviews. In the original study, trained interviewers collected data on depression, psychological distress, self-perceived health, religiosity, number of chronic conditions, and demographic characteristics using well-established instruments. Data in this present study were collected at three time points over a three-year period with one-year intervals at Time1 (T1), Time2 (T2), and Time3 (T3). Analysis of the data in this present study suggested that, although, the number of health-promoting behaviors significantly differed for African-American and White caregivers at T1, T2, and T3, no predictors were significantly associated with a change in health-promoting behavior over time. Nonetheless, this finding suggests that nurses can develop useful information in helping to focus more attention on the health of caregivers in the future.