Redefining early cervical neoplasia: recent progress.
The classification of cervical precancers has evolved over the past 40 years as knowledge concerning the pathogenesis of these human papillomavirus-related lesions has expanded. This commentary reviews the current classification scheme in light of (1) the historical classification systems and (2) the ability of the target epithelium, that is the transformation zone to exhibit varied morphology depending on the cell type that is infected with human papillomavirus. The evolution in our understanding of preinvasive glandular neoplasia is also summarized, with particular attention to so-called superficial (or early) adenocarcinoma in situ. In addition, practical issues in the diagnosis and management of squamous epithelial lesions, particularly the recognition of nonconventional variants and the application of biomarkers, are discussed.


Increased Drug Resistance and Biofilm Formation Ability in ST34-Type Salmonella Typhimurium Exhibiting Multicellular Behavior in China.
Salmonella Typhimurium is an important food-borne pathogen. In this paper, multicellular behavior and associated characteristics of S. Typhimurium isolated from human and animal source food were studied. All the S. Typhimurium strains exhibiting multicellular behavior (100%) belonged to the ST34 type. In addition, most of the ST34-type multicellular behavior S. Typhimurium strains had a human origin (69.11%) and 98% of the ST34-type multicellular behavior strains exhibited strong biofilm formation capacity, which was much higher than that of non-multicellular behavior strains (7%, P < 0.01). Antibiotic resistance in ST34-type multicellular behavior strains was significantly higher than in strains with non-multicellular behavior for most conventional drugs (P < 0.05); notably, Polymyxin B (8%) and Imipenem (1%) resistances were also observed in the ST34-type strains. Furthermore, all the ST34-type multicellular behavior strains (100%) exhibited Multiple Drug Resistance (resistance to ≥3antibiotics), which was much higher than that of the non-multicellular behavior strains (P < 0.05). Consistent with the drug-resistant phenotype, the carrying rates of most drug-resistant genes in ST34-type multicellular behavior strains were higher than that those in non-multicellular behavior strains (P < 0.05). Therefore, this study revealed the emergence of a prevalent ST34-type multicellular behavior S. Typhimurium strains with increased biofilm formation ability and drug resistance rate, which poses a threat to public health safety, and highlights the need for comprehensive monitoring of the strains.


Systemic atrioventricular valve regurgitation in corrected transpositon of the great vessels. Angiographic differentiation of operable and nonoperable valve deformities.
Abnormalities of the systemic atrioventricular (A-V) valve are frequently present in patients with corrected transposition. Systemic A-V valve regurgitation is usually present and may be amenable to operative correction with valve replacement if the regurgitation is caused by normally positioned but deformed valve leaflets or a dilated valve ring, or both. Systemic A-V valve regurgitation secondary to the more common Ebstein-type malformation of the inverted tricuspid valve is an inoperable conditon at present. Displacement of the valve leaflets below the level of the valve ring may be seen in the angiocardiograms of patients with this finding and is the differentiating feature between the two lesions. Ten cases of systemic A-V valve regurgitation in patients with corrected transposition are reviewed to illustrate these features.


Emerging Treatment Options in Mild to Moderate Ulcerative Colitis.
Ulcerative colitis (UC) is a chronic inflammatory condition associated with rectal bleeding and urgency, tenesmus, and diarrhea. Several medical therapies can be used in the treatment of UC. Aminosalicylates are widely used based on their efficacy in the induction and maintenance of remission. Although corticosteroids are effective in patients with more severe disease, systemic use is associated with significant safety concerns. The newer corticosteroid budesonide has lower systemic bioavailability and, consequently, a more favorable safety profile. A budesonide extended-release formulation allows once-daily dosing and delivers the agent locally throughout the colon. Biologic agents used for the treatment of moderate to severe UC include the tumor necrosis factor inhibitors infliximab, adalimumab, and golimumab, and the integrin inhibitor vedolizumab. Rectally administered therapy can also be useful in the treatment of UC. In October 2014, the US Food and Drug Administration approved a budesonide foam formulation for inducing remission in patients with active mild to moderate distal UC extending up to 40 cm from the anal verge. Budesonide foam rapidly distributes to the sigmoid colon and the rectum and avoids some of the drawbacks of suppositories and enemas.


Engineering of Chimeric Protein Based on E Protein Domain III of Tick- Borne Encephalitis Virus and OmpF Porin of Yersinia pseudotuberculosis.
Tick-borne encephalitis poses a serious public health threat in the endemic regions. The disease treatment is restricted to symptomatic therapy, so great expectations are in the development of the prophylactic and therapeutic vaccines. The domain III of E protein of the tickborne encephalitis virus is the main antigenic domain which includes virus-specific epitopes recognized by neutralizing antibodies. The main objective of this study was to design, express, isolate and characterize the chimeric protein based on the fusion of domain III of E protein of the tick-borne encephalitis virus and bacterial porin OmpF from Yersinia pseudotuberculosis. The chimeric gene was obtained by the PCR based fusion method from two fragments containing overlapping linker sequences. Resulting plasmids were transformed into BL21(DE3) pLysS electrocompetent cells for subsequent heterologous protein expression. All recombinant proteins were purified using immobilized metal affinity chromatography under denaturing conditions. The identity of the chimeric protein was confirmed by MALDI-TOF mass spectrometry and immunoblot analysis. The content of antibodies against the EIII protein was estimated in mice blood serum by ELISA. The bacterial partner protein was used for decreasing toxicity and increasing immunogenicity of antigen. The chimeric protein was successfully expressed by the Escherichia coli cells. The purified protein was recognized with immunoblots by anti-E protein of tick-borne encephalitis virus monoclonal antibodies. Furthermore, the protein was able to elicit antibody response against domain III of E protein in immunized mice. The newly obtained chimeric antigen could be valuable for the development of the preventing tick-borne encephalitis subunit vaccines.


Adherence to Antiepileptic Therapy in Adults.
Epilepsy is a neurological disorder affecting 70 million worldwide. The high incidence of relapse can be attributed to nonadherence, thus increasing the incidence of refractory epilepsy to 10%-20%. This study was planned to determine rate of adherence and factors affecting adherence using Antiepileptic Adherence Questionnaire and Baseline Adherence Questionnaire. A cross-sectional, questionnaire-based study was carried out at a rural hospital from May to September 2015. Patients of either gender aged 18-60 years, diagnosed with epilepsy were interviewed after they consented. Patient details, responses to questionnaires were collected and analyzed using descriptive statistics. Among the participants, 67.8% were males and 32.2% were females with the mean age of 38.3 ± 13.9 years. The response rate was 75% (90/120). The majority were literate (64.4%) and employed (58.9%). The duration of disease was <5 years in most individuals; 50% were highly, 21.1% moderately, and 28.9% nonadherent to treatment. Among the highly adherent, 66.7% never skipped medications because they had knowledge of the disease and treatment. More than 97% were satisfied with the social support, and 89% expressed that their family and friends reminded them to take medications. Patients who were nonadherent to treatment attributed it to the lack of knowledge of the disease (57%) and treatment (96%). Reasons for nonadherence were patients assumed drug was harmful, felt cured of the disease, and wanted to avoid side effects. Nearly, 70% expressed the lack of satisfactory support from the social circle. We observed that nearly seventy percent epileptic patients were moderate-highly adherent. Nonadherence was attributed to patient feeling cured of disease and assuming medications to be harmful. Counseling of patients will help in adherence to treatment.


Comparative proteomic analysis provides insight into a complex regulatory network of taproot formation in radish (Raphanus sativus L.).
The fleshy taproot of radish is an important storage organ determining its yield and quality. Taproot thickening is a complex developmental process in radish. However, the molecular mechanisms governing this process remain unclear at the proteome level. In this study, a comparative proteomic analysis was performed to analyze the proteome changes at three developmental stages of taproot thickening using iTRAQ approach. In total, 1862 differentially expressed proteins (DEPs) were identified from 6342 high-confidence proteins, among which 256 up-regulated proteins displayed overlapped accumulation in S1 (pre-cortex splitting stage) vs. S2 (cortex splitting stage) and S1 vs. S3 (expanding stage) pairs, whereas 122 up-regulated proteins displayed overlapped accumulation in S1 vs. S3 and S2 vs. S3 pairs. Gene Ontology (GO) and pathway enrichment analysis showed that these DEPs were mainly involved in several processes such as "starch and sucrose metabolism", "plant hormone signal transduction", and "biosynthesis of secondary metabolites". A high concordance existed between iTRAQ and RT-qPCR at the mRNA expression levels. Furthermore, association analysis showed that 187, 181, and 96 DEPs were matched with their corresponding differentially expressed genes (DEGs) in S1 vs. S2, S1 vs. S3, and S2 vs. S3 comparison, respectively. Notably, several functional proteins including cell division cycle 5-like protein (CDC5), expansin B1 (EXPB1), and xyloglucan endotransglucosylase/hydrolase protein 24 (XTH24) were responsible for cell division and expansion during radish taproot thickening process. These results could facilitate a better understanding of the molecular mechanism underlying taproot thickening, and provide valuable information for the identification of critical genes/proteins responsible for taproot thickening in root vegetable crops.


Negative effects of the COVID-19 pandemic on the musculoskeletal system and depression in healthcare professionals.
During the COVID-19 pandemic, it is thought that healthcare workers are most exposed to musculoskeletal disorders. However, there are limited studies in the literature examining the musculoskeletal disorders among healthcare workers during the COVID-19 pandemic. The aim of this study was to examine musculoskeletal problems and psychological disorders in healthcare personnel working at Dicle University Faculty of Medicine and Research Hospitals during the COVID-19 pandemic and to come up with solutions for rehabilitation. The Cornell Musculoskeletal Disorder Questionnaire (CMDQ) was used to assess musculoskeletal problems in the past week. Additionally, Beck depression inventory (BDI) was used to evaluate the psychological state of the participants. Questions on demographic characteristics, habits, the presence and localisation of musculoskeletal system (MSS) diseases, severity and duration of pain, chronic diseases, trauma history and working conditions were included in the questionnaire prepared by the researchers. The study included 74 nurses, 42 residents, 26 specialists, 24 technicians, 16 dentists, 12 physiotherapists, and 26 other allied health personnel. Dentists had the highest total CMDQ score (160.73) whereas resident doctors had the lowest total CMDQ score (98.33). Low back, neck and back pain were the most common MSS problems. BDI was highest in nurses and 70.27% of the nurses were women. The total workplace ergonomics score was found to be 25.91%, and the visual analogue scale (VAS) was highest in nurses (6.72). While MSS pain is concentrated on the waist, neck and back regions in all healthcare workers. We concluded that the uncertainty associated with the pandemic, delay in preventive measures such as vaccination and medication, rapid and strong transmission of the disease and increasing number of deaths have led to an increase in stress, depression and burnout among healthcare workers.


AN UNUSUAL PATTERN OF GENE FLOW BETWEEN THE TWO SOCIAL FORMS OF THE FIRE ANT SOLENOPSIS INVICTA.
Uncertainty over the role of shifts in social behavior in the process of speciation in social insects has stimulated interest in determining the extent of gene flow between conspecific populations differing in colony social organization. Allele and genotype frequencies at 12 neutral polymorphic protein markers, as well as the numbers of alleles at the sex-determining locus (loci), are shown here to be consistent with significant ongoing gene flow between two geographically adjacent populations of Solenopsis invicta that differ in colony queen number. Data from a thirteenth protein marker that is under strong differential selection in the two social forms confirm that such gene flow occurs. Data from this selected locus, combined with knowledge of the reproductive biology of the two social forms, further suggest that interform gene flow is largely unidirectional and mediated through males only. This unusual pattern of gene flow results from the influence of the unique social enviroments of the two forms on the behavior of workers and on the reproductive physiology of sexuals.


EXPERIMENTAL STUDIES OF THE EVOLUTIONARY SIGNIFICANCE OF SEXUAL REPRODUCTION. VI. A GREENHOUSE TEST OF THE SIB-COMPETITION HYPOTHESES.
This study tests the hypothesis that competition among groups of sexual and asexual siblings generates an advantage for sexual females. Individual tillers of Anthoxanthum odoratum were planted singly, among other siblings from the same family, and among groups of sexual and asexual siblings from different families in pots in an unheated greenhouse. Unlike previous field experiments, there was little difference between the performance of sexual and clonal tillers after two years, despite strong treatment effects and high mortality. The results demonstrate that sib competition does not generate an advantage for sexual reproduction in biotically simple environments.


Persistent measles virus infection in vero and McCoy cell lines.
Persistent measles virus infection was established in two cell lines: Vero and McCoy. Vero cells were infected with a virus that had been propagated five times from an undiluted inoculum. Measles virus infection of McCoy cells caused no cytopathic lesions but led to the establishment of persistent infection. Haemadsorption (HA) and immunofluorescence (IF) results indicated that the majority of Vero and McCoy cells carried measles virus antigen localized in the cell membranes. Both cell lines released infectious virus into the medium. In Vero cells, the virus yield diminished with the number of cell passages. Our results suggest that the presence of defective interfering particles in Vero cells and an antiviral factor in the supernatant of McCoy cells contributed to the maintenance of persistent infection.


Rheumatic disorders in adults under 50. Guidelines for differential diagnosis.
Rheumatic disorders are not uncommon in patients between 20 and 50 years of age, and the differential diagnosis may be difficult. However, after a careful history and thorough physical examination, the cause usually becomes apparent. Laboratory findings alone should not be relied on for diagnosis. Because the impact on younger adults may be devastating and the potential disability may be present for many years, these patients represent an important challenge for any practicing physician.


Modeling, Instrumentation, Automation, and Optimization of Water Resource Recovery Facilities.
A review of the literature published in 2014 on topics relating to water resource recovery facilities (WRRF) in the areas of modeling, instrumentation, automation and optimization of wastewater treatment is presented. Note that WEF has adopted 'WRRF' replacing such previous terms as publicly owned treatment works, wastewater treatment plant (WWTP), and other terms and officially instituted this change in its publications beginning in 2012. It is anticipated the replaced terms will remain in use by other publications and authors for some time. This review will strive to maintain consistency with this change but also avoid confusion where possible.


[Cutaneous lymphangioma. Value of the scanner. Pathogenic hypothesis and therapeutic implications].
The authors report the case of a 10-year-old child with a cutaneous lesion of the thigh present since birth and made up of small translucid raised areas grouped in clumps. The association with these pseudo-vesicles of erysipelatous exacerbations 3 or 4 times a year and the discharge of clear fluid indicative of lymphorrhoea led to a clinical diagnosis of complicated cutaneous lymphangioma. CT scan of the thigh showed absence of spread to deeper layers. This case serves as a basis for discussion of the pathogenic hypothesis of Whimster suggesting that the superficial vesicles are connected to larger lymphatic chambers in the subcutaneous tissue and that the course depends upon pressure variations within these chambers. If this were the case, surgical excision of these lymphatic chambers would be a logical alternative to symptomatic medical treatment of inflammatory episodes.


Differential diagnosis and treatment of impaired bladder emptying.
Although much attention is paid to urinary incontinence, the condition of incomplete bladder emptying is becoming more common with the aging of the US population and the widespread use of anticholinergic drugs to treat overactive bladder. This disorder can often be silent until end-stage presentation of overflow incontinence. In this article, we review the pathophysiologic conditions of the bladder and urethra that can cause impaired bladder emptying and discuss how to evaluate and screen the patient with a bladder that does not empty. In addition, we provide an overview of treatment options available for impaired bladder emptying and consider the research that is under way to find the best therapies for the failing bladder.


Intraoperative fluid restriction predicts improved outcomes in major vascular surgery.
Traditional fluid resuscitation during general anesthesia has been questioned in recent studies. One study of patients undergoing abdominal surgery showed decreased postoperative weight gain, earlier return of bowel function, and shorter intensive care unit (ICU) and hospital length of stay (LOS) when intraoperative crystalloid infusion was restricted. The authors conducted a retrospective study of major vascular surgery patients (neo-aorto iliac system surgery) to correlate clinical outcomes with intraoperative crystalloid fluid administration. The charts of 41 patients who underwent major vascular surgery at our institution were reviewed. Patients were grouped according to the crystalloid volume infused intraoperatively into <3 L (group 1) and >3 L (group 2). Preoperative and postoperative weights, intraoperative crystalloid administration, intraoperative vasopressor use, preoperative and postoperative creatinine, number of days to clear liquid diet, and the time to discharge from the ICU (ICU LOS) and hospital (hospital LOS) were collected. There were statistically significant differences in duration of mechanical ventilation (0.55 +/- 0.934 vs 2.03 +/- 2.735 days, P = .013) and ICU LOS (3.0 +/- 1.48 vs 5.79 +/- 3.938, P = .029) in favor of the fluid restriction group. Major postoperative complications, such as sepsis, acute myocardial infarction, and graft thrombosis, were less frequent in the fluid restriction group but not statistically significant (5 vs 9, P = .742). Intraoperative crystalloid volume was found to be an independent predictor of ICU LOS after adjusting for estimated blood loss and duration of surgery. There was no statistically significant difference in preoperative serum albumin in both groups. Restricted intraoperative administration of crystalloid fluids (<3 L) may be beneficial in major vascular surgery patients. These benefits are similar to those previously described in patients undergoing abdominal surgery.


Polyommatus ripartii: the biological basis for the conservation and the morphology of the developmental stages of a critically endangered, relict population in central Europe.
Ripart's Anomalous Blue Polyommatus ripartii (Freyer, 1830) is one of the most seriously endangered butterfly species in central Europe, a small, relict population of which has survived in two localities in Poland. This isolated population is undoubtedly the last and northernmost remnant of a once much wider range in central Europe. P. ripartii is associated with highly xerophilous vegetation on gypsum and calcareous soils. Only active conservation measures can ensure its survival. For these to be successful, however, precise information on the butterfly's biology, behavior and also its morphology is crucial. The first to do so, this article describes the butterfly's egg-laying preferences, and specifies the numbers of eggs on a single shoot and their placement on it. A unique behavioral trait of the female--the secretion of oviposition-deterring pheromones--is reported. The preferred plant associations and nectar sources have been investigated, and information on overnight roosts is given. In addition, an exhaustive description of the morphologies of the egg, final instar and pupa, as well as new details of adult behavior are provided. The main conclusion of the this study is that the existence of a stable population in the Nida Region is determined by the presence of large patches of sainfoin, which is both the larval host plant and a source of nectar for the imago. Moreover, stress is laid on the importance of Inula ensifolia L. as the secondary nectaring plant, which may facilitate dispersion among patches of suitable habitat. Finally, the study shows that searching for the easily detected eggs may be the best method for proving the existence of the species in a given locality.


Epidemiological analysis of the distribution of cystic and alveolar echinococcosis in Osh Oblast in the Kyrgyz Republic, 2000-2013.
Alveolar and cystic echinococcosis are highly endemic in the Kyrgyz Republic. This report documents the numbers of recorded cases of these two diseases that have been reported in the past 14 years. The number of cases of echinococcosis has increased from approximately 550 to 1044 cases in 2013. This is an increase in incidence from 11.3 to 18.3 cases per 100,000 annually. In 2000 no cases of alveolar echinococcosis (AE) were reported in the Kyrgyz Republic. During this period the disease has emerged, with 148 cases reported in 2013 (2.6 cases per 100,000). Osh Oblast is a highly endemic focus for AE, with 60 cases reported in 2013 (6.0 per 100,000). The Alay Valley in the south of Osh Oblast reported the majority of AE cases for this region. In this valley, in 2013, 42 cases of AE were reported, which is a local incidence of 58 per 100,000.


Molecular modeling of proteinlike inclusions in lipid bilayers: lipid-mediated interactions.
We investigated the insertion of transmembrane structures in a lipid bilayer and their interactions using self-consistent field theory. The lipids are coarse-grained on a united-atom level and consist of a phosphatidylcholinelike headgroup and two hydrophobic tails. The inclusions, acting as simple models for proteins that span biological membranes, are rigid rods (radius R ) with a hydrophobic surface and hydrophilic end caps. The insertion free energy Omega of an individual rod is strongly regulated by the affinity between its hydrophobic surface and the lipid tails. This affinity also controls the best match of the hydrophobic length of the rod with that of the bilayer. The line tension tau(=Omega/2piR) is practically independent of R . The perturbations in the bilayer as a function of distance from the inclusion, have the shape of a damped oscillation. The wavelength and decay length are related to the elastic properties of the bilayer and do not depend on R . These results are used to analyze how the lipid matrix affects the interaction between transmembrane objects, for computational reasons considering the limit of R-->infinity . Contributions on different length scales can be distinguished: (i) a long-range elastic interaction, which is an exponentially decaying oscillation; (ii) an exponentially decaying repulsion on an intermediate length scale, resulting from the loss of conformational entropy of the lipid tails; and (iii) a short-range interaction due to the finite compressibility of the lipid tails, which manifests either as a depletion attraction if there is no affinity between the tails and the inclusions' surface or, otherwise, as an oscillatory structural force.


Changes in outcome measures for impairment, activity limitation, and participation restriction over two years in osteoarthritis of the lower extremities.
To describe changes in outcome measures in patients with knee and hip osteoarthritis (OA) over 2 years according to the International Classification of Functioning, Disability and Health, and to evaluate the sensitivity to change of available outcome instruments. A total of 115 symptomatic knee or hip OA patients (mean age 60.0 years, 80% women) were followed for 2 years. Standardized knee and hip radiographs were scored for joint space narrowing (JSN) using the Osteoarthritis Research Society International Atlas. Pain intensity in knees and hips was graded during physical examination. Self-reported pain and functioning were assessed with the Western Ontario and McMaster Universities OA Index (WOMAC). Social functioning was assessed with social functioning scores of the RAND 36-item Health Survey. Standardized response means (SRMs) were calculated to evaluate sensitivity to change. Substantial increases in JSN and pain intensity total scores over 2 years were observed (SRMs 0.43 and 0.41, respectively). Twenty-three percent of patients had an increase of at least 1 point in JSN total scores. An increase in pain intensity total scores was present in 46% of patients, whereas a decrease was observed in 19.1.% of patients. WOMAC pain and function scores showed small increases (SRMs 0.15 and 0.18, respectively). No change was seen in social functioning scores (SRM 0.01). Objective instruments measuring impairment in body structures and function are more sensitive to change over 2 years in patients with OA than self-reported measurements of impairment in body function, activity limitation, and participation restriction. These findings encourage development of new instruments to improve measurement of disease outcome in OA.


Non-Abelian Majorana Modes Protected by an Emergent Second Chern Number.
The search for topological superconductors and non-Abelian Majorana modes ranks among the most fascinating topics in condensed matter physics. There now exist several fundamental superconducting phases which host symmetry protected or chiral Majorana modes, of which the chiral modes are protected by Chern numbers in even dimensions. Here we propose to observe novel chiral Majorana modes by realizing a Fulde-Ferrell-Larkin-Ovchinnikov state, i.e., the pair density wave (PDW) phase in a Weyl semimetal which breaks time-reversal symmetry. Without symmetry protection, the 3D gapped PDW phase is topologically trivial. However, a vortex line generated in such a phase can host chiral Majorana modes, which are shown to be protected by an emergent second Chern number of a synthetic 4D space generalized from the PDW phase. We further show that these chiral modes in the vortex rings obey 3D non-Abelian loop-braiding statistics, which can be applied to topological quantum computation.


Cell death and cell proliferation in mouse submandibular gland during early post-irradiation phase.
The effects of irradiation on different cell compartments in the submandibular gland were analyzed in adult C57BL/6 mice exposed to X-ray irradiation and followed up for 10 days. Apoptosis was quantified using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling method (TUNEL). Cell proliferation was detected using immunohistochemistry for proliferating cell nuclear antigen (PCNA). Radiation-induced apoptosis occurred rapidly, reaching a maximum 3 days post-irradiation. The percentage of apoptotic cells increased with the irradiation dose. At day 1 post-irradiation, cell proliferation was significantly reduced in comparison to sham-irradiated controls. After post-irradiation arrest of the cell cycle, proliferation increased in all gland compartments, reaching a maximum at day 6 post-irradiation. The proliferation response corresponded to the dose of irradiation. We suggest that the reason for gland dysfunction could be the coexistence of high apoptotic and proliferative activity in the irradiated gland.


Anti-Inflammatory Activity of a Polymeric Proanthocyanidin from Serjania schiedeana.
The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67-89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin-(4β → 8)-epicatechin-(4β → 8, 2β → O → 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1β, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen.


Rationale for reclassification of a distinctive subdivision of mammalian class Mu glutathione S-transferases that are primarily expressed in testis.
A rat testicular Mu-class glutathione S-transferase (GST) resolved by reversed-phase high performance liquid chromatography cross-reacted with peptide sequence-specific antisera raised against the human hGSTM3 subunit. Electrospray ionization mass spectrometry indicated that this rat GST subunit (designated rGSTM5 in this report) has a significantly greater molecular mass (26,541 Da) than the other rat GST subunits. The mouse homologue (mGSTM5 subunit) was also identified and characterized by high performance liquid chromatography and electrospray ionization mass spectrometry. Sequence analysis of rGSTM5 peptide fragments and the sequence deduced from a cDNA clone showed that the protein is highly homologous to the hGSTM3 and murine mGSTM5 subunits. All three GSTs of this subclass have N- and C-terminal extensions with C-terminal cysteine residues, but the two penultimate amino acids near the C terminus are divergent in the three species. The proteins of this class Mu subfamily have similar catalytic specificities and mechanisms, are all cysteine rich, are found mainly in testis, and share characteristics that distinguish them from other GSTs. Moreover, the rGSTM5 subunit isolated from rat testis was not found in heterodimeric combination with other common Mu-class GST subunits. As the rGSTM5, mGSTM5, and hGSTM3 subunits are structurally more closely related to each other than they are to other Mu GSTs, it is proposed that they be considered a functionally distinct and separate subfamily within class Mu. The identification of this unique mammalian GST subclass could advance strategies for interspecies comparisons of GSTs and provides a rodent model for studies on functions and regulatory mechanisms for human GSTs.


Single primer-triggered isothermal amplification for double-stranded DNA detection.
Here we have devised a new generation of isothermal double-stranded DNA (dsDNA) detection method, termed single primer-triggered isothermal amplification (SAMP). It is very simple only requiring one primer and a few copies of dsDNA in less than an hour are detectable with multiple signal amplification steps.


Control of Integrated Task Sequences Shapes Components of Reaching.
Reaching toward an object usually consists of a sequence of elemental actions. Using a reaching task sequence, the authors investigated how task elements of that sequence affected feedforward and feedback components of the reaching phase of the movement. Nine right-handed adults performed, with their dominant and nondominant hands, 4 tasks of different complexities: a simple reaching task; a reach-to-grasp task; a reach-to-grasp and lift object task; and a reach-to-grasp, lift, and place object task. Results showed that in the reach-to-grasp and lift object task more time was allocated to the feedforward component of the reach phase, while latency between the task elements decreased. We also found between-hand differences, supporting previous findings of increased efficiency of processing planning-related information in the preferred hand. The presence of task-related modifications supports the concept of contextual effects when planning a movement.


Idiopathic laryngotracheal stenosis: radiologic findings.
Acquired nonneoplastic laryngotracheal stenosis can be either focal or diffuse. Diffuse tracheal stenosis is caused by sarcoidosis, tuberculosis, histoplasmosis, relapsing polychondritis, tracheopathia osteoplastica, and Wegener's granulomatosis. Focal tracheal stenosis, on the other hand, usually results from placement of an endotracheal or tracheostomy tube or from previous neck trauma. At our institution, since 1971, we have seen 49 cases of focal laryngotracheal stenosis that could not be attributed clinically or histologically to any one of the aforementioned causes. The purpose of this study was to study the radiologic features of these idiopathic laryngotracheal stenoses. A retrospective review of records showed that radiologic studies were still available in only 15 of the 49 patients with idiopathic laryngotracheal stenoses. All 15 patients had radiographs and plain tomograms, and one patient had a CT scan of the neck. Three radiologists reviewed all the images. The radiologic appearance was variable: the stenoses were from 2 to 4 cm long with a lumen between 3 and 5 mm in diameter at the narrowest portion. The narrowing was concentric and shaped like an hourglass in eight patients (53%) and was eccentric in the other seven (47%). The margins of the stenosis were smooth in nine patients (60%) and irregular and lobulated in six patients (40%). A dominant mass measuring approximately 1 cm in diameter was present in two patients (13%). No evidence of calcification or ossification was seen. Idiopathic laryngotracheal stenosis produces focal stenosis of the cervical part of the trachea, 2 to 4 cm long. The lumen is severely compromised, measuring no more than 5 mm in diameter at its narrowest portion. The stenosis can be concentric or eccentric and can have either smooth or lobulated margins. Special attention should be paid to the airways when chest radiographs of patients with a history of prolonged dyspnea and wheezing are reviewed. The prevalence of focal stenosis of the larynx and the upper part of the trachea due to tracheal intubation has declined since the introduction of low-pressure, high-volume retention cuffs. Therefore, idiopathic laryngotracheal stenosis should be considered in the differential diagnosis in patients with focal narrowing of the airway.


Thrombectomy before hepatic resection for hepatocellular carcinoma with a tumor thrombus extending to the inferior vena cava.
Tumor thrombi of hepatocellular carcinoma occasionally invade into the inferior vena cava (IVC) through the hepatic vein. Once the tumor thrombus is dislodged, severe and lethal complications, such as pulmonary infarction, can develop. We successfully operated on a hepatocellular carcinoma (HCC) patient with a tumor thrombus extending to the IVC through the right hepatic vein. To avoid dislodging the thrombus during surgery, a thrombectomy using selective hepatic vascular exclusion was performed before a hepatic resection, which is the most dangerous procedure to dislodge the thrombus.


Cancer chemopreventive 3-substituted-4-oxoretinoic acids.
The introduction of substituents at position 3 of methyl 4-oxoretinoate can be effected in good yields by alkylating the lithium dienolate. A second substituent can be introduced also, but the resulting 3,3-disubstituted-4-oxoretinoates were isolated in lower yields. Evidence was obtained for a slower rate of alkylation at the alpha-position (carbon 14) of the ester group. Some of these 4-oxoretinoic acid analogues showed high activity in assays in vivo for the inhibition of ornithine decarboxylase activity and carcinogen-induced papillomas in mouse skin.


Ulcerogenic drugs and upper gastrointestinal bleeding.
Aspirin and other NSAIDs are drugs for which the causal association with major gastrointestinal bleeding has not been adequately or conclusively demonstrated, although a certain degree of correlation is very likely. For aspirin ingestion in particular the increased risk is confined to patients taking the drug at heavy and regular dosages (less than 1% of users), and can be reduced further by the use of enteric-coated formulations. For non-aspirin NSAIDs, the relative risk of GI bleeding after repeated and prolonged exposure (in comparison to controls) has been quantified between 1.5 and 2.7, which is a small but significant figure, and it is increased by the age of the patients, by the duration of treatment and by the dose of drug. No consistent causal relationship can be found between major GI bleeding (or other major peptic ulcer complications) and steroids or other 'ulcerogenic' drugs. The therapy of drug-induced (or drug-associated) GI bleeding is probably not different from the usual treatment of upper GI haemorrhage. As far as the treatment of drug-associated gastroduodenal mucosal damage is concerned, it appears that with mucoprotective agents or H2 antagonists the healing rates of peptic ulcers is slower than observed in non-drug-associated disease. Prophylactic treatment with prostaglandins has only been proposed; and prophylactic treatment with H2 antagonists has been disappointing.


Standard electrocardiographic and signal-averaged electrocardiographic changes in congestive heart failure.
A 54-year-old man with congestive heart failure and peripheral edema was monitored during treatment with serial electrocardiograms (ECGs) and two signal-averaged ECGs. Weights and a host of ECG parameters were monitored. ECGs recorded in the 5 years before his index admission were also considered in the quantitative ECG analysis. Amelioration of his peripheral edema was associated with reduction of his weight and increase in the QRS and P-wave amplitudes, and duration in QRS complexes and QT intervals in the ECGs, but unchanged signal-averaged ECGs. This case report provides insight into the mechanism of the change in QRS duration in ECGs during changing edematous states resulting from clinical deterioration or improved compensation in patients with congestive heart failure.


Replication of latent Epstein-Barr virus genomes in Raji cells.
The replication of the 50 to 60 latent, predominantly extrachromosomal, Epstein-Barr virus genomes maintained by the Burkitt-lymphoma-derived Raji cell line was investigated by using a Meselson-Stahl density transfer approach. Samples of DNA isolated from cells cultivated for different periods in bromodeoxyuridine-supplemented medium were fractionated according to density, and the distribution of viral and cellular DNAs among the heavy-, hybrid-, and light-density species was quantitated. The results indicate that the majority of latent Epstein-Barr virus DNA plasmids each replicate once during the cell cycle.


Librarians, crystal structures and drug design.
There are now 355,000 published crystal structures of organic and metal-organic compounds, all of which have been acquired, validated, chemically annotated and organised for searching in the Cambridge Structural Database (CSD). The CSD is used in rational drug design and is beginning to answer important questions relevant to the formulation of pharmaceutical active ingredients. The value and credibility of this research are ultimately dependent on the accuracy and completeness of the underlying crystal-structure data.


Critical systolic blood pressure threshold for endovascular aortic occlusion - A multinational analysis to determine when to place a REBOA.
Systolic blood pressure (SBP) is a potential indicator that could guide when to use a resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma patients with life-threatening injuries. This study aims to determine the optimal SBP threshold for REBOA placement by analyzing the association between SBP pre-REBOA and 24-hour mortality in severely injured hemodynamically unstable trauma patients. We performed a pooled analysis of the Aortic Balloon Occlusion (ABO) trauma and AORTA registries. These databases record the details related to the use of REBOA and include data from 14 countries worldwide. We included patients who had suffered penetrating and/or blunt trauma. Patients who arrived at the hospital with a SBP pre-REBOA of 0 mm Hg and remained at 0 mm Hg after balloon inflation were excluded. We evaluated the impact that SBP pre-REBOA had on the probability of death in the first 24 hours. A total of 1107 patients underwent endovascular aortic occlusion, of these, 848 met inclusion criteria. The median age was 44 years [IQR, 27-59 years] and 643(76%) were male. The median injury severity score was 34 [IQR, 25-45]. The median SBP pre-REBOA was 65 mm Hg [IQR: 49-88 mm Hg]. Mortality at 24-hours was reported in 279 (32%) patients. Math modelling shows that predicted probabilities of the primary outcome increased steadily in SBP pre-REBOA below 100 mm Hg. Multivariable mixed-effects analysis shows that when SBP pre-REBOA was lower than 60 mm Hg, the risk of death was more than 50% (relative risk, 1.5; 95%CI, 1.17-1.92; P = .001). In patients who do not respond to initial resuscitation, the use of REBOA in SBP's between 60- and 80-mm Hg may be a useful tool in resuscitation efforts before further decompensation or complete cardiovascular collapse. The findings from our study are clinically important as a first step in identifying candidates for REBOA. Observational Study. Level IV.


Identification of the rctA gene, which is required for repression of conjugative transfer of rhizobial symbiotic megaplasmids.
An analysis of the conjugative transfer of pRetCFN42d, the symbiotic plasmid (pSym) of Rhizobium etli, has revealed a novel gene, rctA, as an essential element of a regulatory system for silencing the conjugative transfer of R. etli pSym by repressing the transcription of conjugal transfer genes in standard laboratory media. The rctA gene product lacks sequence conservation with other proteins of known function but may belong to the winged-helix DNA-binding subfamily of transcriptional regulators. Similar to that of many transcriptional repressors, rctA transcription seems to be positively autoregulated. rctA expression is greatly reduced upon overexpression of another gene, rctB, previously identified as a putative activator of R. etli pSym conjugal transfer. Thus, rctB seems to counteract the repressive action of rctA. rctA homologs are present in at least three other bacterial genomes within the order Rhizobiales, where they are invariably located adjacent to and divergently transcribed from putative virB-like operons. We show that similar to that of R. etli pSym, conjugative transfer of the 1.35-Mb symbiotic megaplasmid A of Sinorhizobium meliloti is also subjected to the inhibitory action of rctA. Our data provide strong evidence that the R. etli and S. meliloti pSym plasmids are indeed self-conjugative plasmids and that this property would only be expressed under optimal, as yet unknown conditions that entail inactivation of the rctA function. The rctA gene seems to represent novel but probably widespread regulatory systems controlling the transfer of conjugative elements within the order Rhizobiales.


The female athlete.
Anatomic considerations are the female athlete's wider pelvis, shorter extremities and lower center of gravity. There is little qualitative difference in the muscle tissue of men and women; differences in strength stem from the amount of muscle mass. Amenorrhea/oligomenorrhea is common in runners, ballet dancers, cyclists, gymnasts, body builders, figure skaters and, to a lesser extent, swimmers. Pregnancy limits activity, but current evidence indicates that exercise during pregnancy is not harmful to either the mother or the fetus.


Aerosol delivery systems in childhood asthma.
Asthma in younger children appears to be increasing in prevalence, whilst at the same time it is recognized that inhaled corticosteroids and bronchodilators are the mainstay of treatment for this condition. Presently the devices available for aerosol treatment of young children are mostly developed for use in older children and adults. However, an awareness of the need for delivery systems dedicated to use by young children is increasing. The devices available at present for aerosol treatment of young children comprises the nebulizer, metered-dose inhaler with spacer, and dry powder inhaler. The inhaler strategy found most useful at present can be summarized as follows: children younger than 2 years can use MDI+spacer+mask or nebulization, while children above 2 years can use MDI+spacer (without mask). Older children (3-4 years) can be easily taught the use of a Rotahaler.


Chronic high dose captopril decreases total heart rate variability and increases heart rate in C57BL/6J mice.
The effects of high dose captopril, within the therapeutic range, on autonomic activity are unknown in those with normal cardiovascular function. Thus the study aims were to assess the effects of high dose captopril on autonomic function in mice. Autonomic activity was measured using heart rate variability (HRV). ECG recordings were obtained from 18 Male C57BL/6J mice (20-25 g) subdivided into control (N=8) or mice receiving oral captopril (0.688 mg/ml captopril in the drinking water for 6 weeks, N=10). HRV results for linear and non-linear parameters were attenuated following chronic captopril for 6 weeks compared to control. Captopril was associated with a trend for an increase in average heart rate and approximate entropy (ApEn), a non-linear measure of HRV decreased significantly compared to control (p<0.05). In conclusion high dose captopril reduces total HRV and increases heart rate in normotensive mice with normal cardiac function.


An analysis of the development of digital health technologies to fight COVID-19 in Brazil and the world.
The coronavirus pandemic that struck the world in late 2019 continues to break records of new cases and deaths from the disease. Guidelines for clinical management of infected patients and prevention of new cases focus on measures to control symptoms, hygiene habits, social distancing, and decrease in human crowding. This forced a change in the way health services provide care, generating the incorporation of new health technologies. The Essay thus aims to compile and analyze experiences in the use of digital health technologies to minimize the impacts of COVID-19. The authors identified the development of technological solutions for clinical management of patients, imaging diagnosis, use of artificial intelligence for risk analysis, geolocation apps, data analysis and reports, self-diagnosis, and even orientation for decision-making. The great majority of the initiatives listed here prove effective in minimizing the impacts of COVID-19 on health systems and aim to decrease human crowding and thus facilitate access to services, besides contributing to the incorporation of new health practices and modes of care.


Solitary adenocarcinoma metastasis mimicking sarcomatous degeneration in Paget's disease.
A rare case of mucinous adenocarcinoma presented as a solitary, metastatic deposit to a region of Paget's disease within the peripheral skeleton. Historical, physical, radiographic, and scintigraphic findings were indistinguishable from those of sarcomatous degeneration arising from pagetoid bone. This case supports the idea that when a painful, osteolytic lesion is discovered within a region of Paget's disease, bone scintigraphy has greater value of disclosing potential multifocal or multicentric disease than for providing etiologic specificity for the principal lesion.


Dietary behaviours and weight management: A thematic analysis of pregnant women's perceptions.
Maternal obesity is associated with increased risk of gestational diabetes and other complications. Although antenatal interventions to help prevent these complications are ongoing, an understanding of overweight and obese pregnant women's opinions and attitudes is lacking. Therefore, this study aims to explore these women's experiences and perceptions of dietary behaviours and weight management during pregnancy. Secondary analysis of qualitative data originally collected to examine lifestyle behaviours in pregnant women was conducted. The data were from a purposive sample of overweight and obese pregnant women attending a public antenatal clinic in Cork, Ireland. The data were explored using thematic analysis. Interviews with 30 overweight and obese pregnant women were analysed. Three themes were developed relating to overweight and obese women's dietary behaviours and weight management perceptions including 'pregnancy's influence on dietary behaviours', 'external influences on dietary behaviours' and 'perception of and preferences for weight related advice and resources'. Together these themes reveal women's experiences of diet and how pregnancy factors (physiological changes) and external factors (family and friends) can influence dietary behaviours. Furthermore, perceptions of weight management advice and lack thereof were highlighted with women drawing attention to potential resources for future use during pregnancy. This study provides important insights into overweight and obese pregnant women's dietary behaviours and perceptions of weight management. According to these findings, there is a need for clear and unambiguous information about weight management, acceptable weight gain, food safety and how to achieve a balanced diet.


Isolation of photoreceptors from mature, developing, and regenerated zebrafish retinas, and of microglia/macrophages from regenerating zebrafish retinas.
This paper describes experimental procedures for the dissociation of retinal cells of the zebrafish (Danio rerio) for subsequent fluorescence-activated cell sorting (FACS) and gene expression studies. Methods for dissociation of zebrafish retinas followed by FACS and RNA isolation were optimized. This methodology was applied to isolate pure sorted samples of rods, long wavelength-sensitive (LWS) cones, medium wavelength-sensitive (MWS; RH2-2) cones, short wavelength-sensitive (SWS2) cones, and UV-sensitive (SWS1) cones from retinas obtained at selective life-history stages of the zebrafish, and for some of these photoreceptors, following retinal regeneration. We also successfully separated lws1-expressing and lws2-expressing LWS cones from fish of a transgenic line in which lws1 is reported with green fluorescence protein (GFP) and lws2 is reported with red fluorescence protein (RFP). Microglia/macrophages were successfully sorted from regenerating retinas (7 days after a cytotoxic lesion) of a transgenic line in which these immune cells express GFP. Electropherograms verified downstream isolation of high-quality RNA from sorted samples. Examples of post-sorting analysis, as well as results of qRT-PCR studies, validated the purity of sorted populations. For example, qRT-PCR samples derived from isolated Rh2-2 cones contained detectable rh2-2 (opn1mw2) opsin transcripts, but lws opsin transcripts (lws1/opn1lw1, lws2/opn1lw2) were not detected, suggesting that the procedure likely separated double cone pairs. Through this method, pure, sorted cell samples can provide RNA that is reliable for downstream gene expression analyses, such as qRT-PCR and RNA-seq, which may reveal molecular signatures of photoreceptors and microglia for comparative transcriptomics studies.


Structure and mechanical properties of carbon fibres: a review of recent microbeam diffraction studies with synchrotron radiation.
Hard X-ray beams with beam sizes in the sub-micrometre range are frequently available at third-generation synchrotron radiation sources, enabling new insights into the structure of materials at different levels of hierarchy by applying novel techniques such as scanning microbeam diffraction or scanning small-angle scattering. The high brilliance of the radiation from wiggler and undulator sources allows in situ experiments such as mechanical testing of single fibres to be performed, and even the combination of microbeam scanning with in situ testing is feasible. Three different experiments on single carbon fibres are presented: an in situ tensile test using a 10 microm collimated beam, a scanning experiment applying a 3 microm beam from a tapered glass capillary, and a scanning experiment with simultaneous in situ bending with a 0.1 microm beam provided by a waveguide structure.


Crossover of the thermal escape problem in annular spatially distributed systems.
The computer simulations of fluctuational dynamics of an annular system governed by the sine-Gordon model with a white noise source are performed. It is demonstrated that the mean escape time (MET) of a phase string for an annular structure can be much larger than for a linear one and has a strongly pronounced maximum as a function of system's length. The location of the MET maximum roughly equals the size of the kink-antikink pair, which leads to evidence of a spatial crossover between two dynamical regimes: when the phase string escapes over the potential barrier as a whole and when the creation of kink-antikink pairs is the main mechanism of the escape process. For large lengths and in the limit of small noise intensity gamma, for both MET and inverse concentration of kinks, we observe the same dependence versus the kink energy E(k): approximately exp(2E(k)/gamma) for the annular structure and approximately exp(E(k)/gamma) for the linear one.


Leukemia-specific DNA sequences in leukocytes of the leukemic member of identical twins.
The discovery in human leukemic cells of particulate elements encapsulating 70S RNA and RNA-directed DNA polymerase made possible the synthesis of a [(3)H]DNA probe that could detect leukemia-specific sequences in the DNA of normal and leukemic individuals. In an earlier study of a series of unrelated leukemic patients, we established that the nuclear DNA of their leukemic cells contain particle-related sequences that cannot be detected in leukocytes of normal individuals. This result is inconsistent with the virogene concept that demands the inclusion of one complete copy of oncogenic information in the genome of every normal cell. The present study carries this analysis one step further by showing, with two sets of identical twins, that the leukemic member contains particle-related sequences in the DNA of his leukocytes that cannot be detected in the leukocytes of his healthy identical sibling. This finding implies that the additional leukemia-specific information found in the DNA of the leukemic individuals must have been inserted subsequent to fertilization. This outcome argues against the virogene hypothesis or any other etiologic concept that invokes vertical transmission through the germ line of the particle-related information found uniquely in the DNA of leukemic cells.


[Assessment of joint structure in patients with rheumatoid arthritis].
Recent progress in the treatment of rheumatoid arthritis (RA) with TNF-inhibitors has brought a paradigm shift, in which clinical and structural remission is now a target to be approached. However, joint damage already develops in a majority of patients before appropriate treatments are provided. Joint damage results from the destruction of bone and cartilage, which can be visualized via radiography as joint erosion (JE) and joint space narrowing (JSN) , respectively. JSN is a surrogate marker for loss of cartilage and it also reflects damage to tissues causing joint dislocation, a phenomenon that is less prevalent among patients with early RA. JE has been perceived to be the most critical indicator of permanent disability in RA. The combination of TNF-inhibitor and MTX reduces the risk of joint damage, measured by radiographic modified total Sharp score (mTSS) . Biologics targeting cytokines and lymphocytes not only expand the array of treatments for RA but also provide important insights into pathogenesis of this disease.


Correlative study between serum matrix metalloproteinase-9 values and neurologic deficit in acute, primary, supratentorial, intracerebral haemorrhage.
One of the essential characteristics of intracerebral haemorrhages (ICH) is the occurrence of brain oedema (BE). Matrix metalloproteinase-9 (MMP-9) belongs to the family of proteolytic enzymes connected with zinc, which in brain bleeding or a stroke can induce matrix proteolyse into the neurovascular unit, and increase the BE. The aim of the study was to determine the MMP-9 values in serum, and to assess the degree of correlation with neurological deficit in patients with acute, primary and supratentorial ICH. The study was prospective and included 62 patients with ICH. The neurological deficit of the patients was evaluated by the National Institute Health Stroke Scale (NIHSS). Serum MMP-9 level was determined by enzyme-linked immune sorbent assay (ELISA). Patients were evaluated in three phases: 1(st), 3(rd) and 7(th) day following the ICH. The mean age of the patients was 64.5 ± 9.4. Within the follow-up period, there was a significant rise of the NIHSS score in the first three days: 11.48 ± 3.7; 13.21 ± 3.78, and a significant rise of serum MMP-9, with greatest values in the third day: 134.7 ± 26.1 ng/ml (p = 0.000). There was a positive, significant correlation (r = 0.886, p = 0.000) between the serum MMP-9 concentration and the NIHSS score. Our study showed that in the first three days of ICH, serum MMP-9 values were rising as well as the neurological deficit and the BE. Determination and evaluation of the MMP-9 in serum is an easy, non-invasive, routine laboratory procedure for the detection and follow-up of BE, and also determines further therapeutic strategy as well as prognosis in these patients.


[Mucous (M) mutants of enteropathogenic, septicemic and saprophytic E. coli (author's transl)].
Mucoid M mutants of enteropathogenic (for suckling pigs), septicemic (for calves), and saprophytic E. Coli were subject of the study. The characteristics of the M colonies have been listed in Table 1. Both spontaneously occurring M mutants which had been isolated by culturing of E. coli strains (S form) in normal horse serum (undiluted) for several weeks were observed. Enzymatic-biochemical tests revealed the existence of M mutants with full enzmatic activity which are identical with the homologous S and R forms. There were also M mutants exhibiting a considerably reduced enzymatic activity. Antigenic-serological analysis (agglutination) exhibited M mutants which were agglutinated by the homologous sera, at low and high titres. In contrast to this, one group of M mutants was found not to be agglutinable, despite autoclaving at 120 degrees C for 2 hours. Some mutants cultured in broth for several weeks were re-exhibiting S colonies of full biochemical activity and full antigen reactivity against homologous agglutinating sera.


Tuning Surface Wettability through Hot Carrier Initiated Impact Ionization in Cold Plasma.
Advanced surface engineering aims to produce surfaces with well-controlled wettabilities; however, precise control over water imbibition (WI) and liquid spreading on patterned surfaces remains a challenge. Nonthermal atmospheric plasma (NAP) treatment can dramatically change wettability; however, for coated biological objects, such as seeds, plasma interaction is not entirely understood. Herein, we employed atmospheric hybrid cold plasma to elucidate how NAP fundamentally interacts with seed surfaces. We show that NAP can control WI and liquid spreading on seeds. By investigating two distinct seed surface structures and their permeabilities, we show that the modified-surface properties are primarily due to the combined effects of enhanced physical etching and chemical functionalization. We propose the tunable surface functionalization model based on electric field-assisted electron ion-initiated impact ionization enhancing the reactive species generation. Importantly, rice seeds are not damaged by plasma treatment, and 90% of treated seeds germinate upon artificial aging. The ability to control the wettability and liquid spreading of seed surfaces can help achieve seedlings of better quality, especially in difficult-to-grow regions, including those affected by drought. Well-controlled wettability and related attributes open up new avenues for the NAP treatment of a broad range of surfaces.


Modulation of renal apical organic anion transporter 4 function by two PDZ domain-containing proteins.
Human organic anion transporter 4 (OAT4) is an apical organic anion/dicarboxylate exchanger in the renal proximal tubules and mediates high-affinity transport of steroid sulfates such as estrone-3-sulfate (E1S) and dehydroepiandrosterone sulfate. Here, two multivalent PDZ (PSD-95/Discs Large/ZO-1) proteins PDZK1 and NHERF1 were examined as interactors of OAT4 by a yeast two-hybrid assay. These interactions require the extreme C-terminal region of OAT4 and the first and fourth PDZ domains of PDZK1 and the first PDZ domain of NHERF1. These interactions were confirmed by surface plasmon resonance assays (K(D): 36 nM, 1.2 microM, and 41.7 microM, respectively). In vitro binding assays and co-immunoprecipitation studies revealed that the OAT4 wild-type but not a mutant lacking the PDZ motif interacted directly with both PDZK1 and NHERF1. OAT4, PDZK1, and NHERF1 proteins were shown to be localized at the apical membrane of renal proximal tubules. The association with PDZK1 or NHERF1 enhanced OAT4-mediated E1S transport activities in HEK293 cells (1.2- to 1.4-fold), and the deletion of the OAT4 C-terminal PDZ motif abolished this effect. The augmentation of the transport activity was accompanied by alteration in V(max) of E(1)S transport via OAT4 and was associated with the increased surface expression level of OAT4 protein. This study indicates that the functional activity of OAT4 is modulated through the PDZ interaction with the network of PDZK1 and NHERF1 and suggests that OAT4 is involved in the regulated apical organic anion handling in the renal proximal tubules, provided by the PDZ scaffold.


Food allergy to Helix terrestre (snail).
Among the rare foods capable of producing food allergies is the snail (Helix terrestre). The snail is a delicacy eaten in Spain, France and Portugal. This study presents the findings of an allergic study of 10 patients with this infrequent food allergy during the past 10 years. The shock organ in the majority (80%) of these patients was the bronchial tree. Six of them did not have any digestive or skin symptoms which are usually seen in cases of food allergy. All patients manifested the symptomatology after ingestion of Helix terrestre. Two also had reactions after eating Patella vulgata (limpet). The snail and the limpet are within the phylogenetic line of molluscs, i.e. of gastropods. All patients tolerated the ingestion of cephalopods and bivalves which belong to two other phylogenetic lines. Skin tests to seafoods (squids, prawns, lobsters and clams) were negative for all patients. This suggests that the sensitizing antigen is probably a protein found only in gastropod molluscs. Skin tests along with the histamine release test were valid diagnostic methods for this food allergy. The limited bibliography on this subject is probably due to the fact that the consumption of snails as well as limpets is limited to specific geographical areas.


[Treatmentof rhinophyma with laser and surgery].
Rhinophyma is a disfiguring skin condition characterised by progressive hyperplasia of the nasal sebaceous glands and proliferation of blood vessels and connective tissue. It is considered the end stage of rosacea and affects primarily older males of Northern European descent. Several surgical and laser treatment options are available. None of these has been compared in randomised, controlled prospective trials. In this review, we provide an overview of the different treatment modalities and account for their respective strengths and limitations.


Effects of some antibiotics on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro and in vivo study.
The in vitro and in vivo effects of some antibiotics on human erythrocyte 6-phosphogluconate dehydrogenase were investigated. Human erythrocyte 6-phosphogluconate dehydrogenase was purified with ammonium sulphate precipitation, 2',5' ADP-Sepharose 4B affinity and gel filtration chromatography. Some antibiotics (netilmicin sulphate, cefepime, amikacin, isepamycin, chloramphenicol, ceftazidim, teicoplanin, ampicillin, ofloxacin, levofloxacin, cefotaxime, penicillin G, gentamicin sulphate, ciprofloxacin) inhibited enzyme activity in vitro but others (cefozin, decefin, streptomycin, combisid, and meronem) were devoid of inhibitory effects. For the drugs having low IC50 values (netilmicin sulphate and cefepime), in vivo studies were performed in rats. Netilmicin sulphate at 15-mg/kg inhibited enzyme activity significantly (p < 0.001) 1 h, 2 h, and 3 h after dosing and cefepime at 200-mg/kg very significantly (p < 0.001) inhibited the enzyme 1 h and 2 h after dosing. Netilmicin sulphate and cefepime inhibited rat erythrocyte 6-phosphogluconate dehydrogenase both in vivo and in-vitro.


Novel agents in the treatment of Waldenström's macroglobulinemia.
Waldenström's macroglobulinemia is a B-cell disorder characterized by bone marrow infiltration with lymphoplasmacytic cells and demonstration of an immunoglobulin M monoclonal gammopathy. Despite advances in therapy, Waldenström's macroglobulinemia remains incurable. As such, novel therapeutic agents are needed for the treatment of Waldenström's macroglobulinemia. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of Waldenström's macroglobulinemia so as to better target therapeutics for this malignancy. Importantly, as part of these efforts, we have prioritized the development of stem cell-sparing drugs because autologous stem cell transplantation remains a viable salvage option in Waldenström's macroglobulinemia. These efforts have led to the development of several novel agents for treating Waldenström's macroglobulinemia, including bortezomib; monoclonal antibodies and/or blocking protein targeting CD40, CD52, or CD70, a proliferation-inducing ligand and B-lymphocyte stimulator; the immunomodulator thalidomide as an enhancer of rituximab activity, as well as agents interfering with stem cell factor, phosphatidylinositol 3-kinase/Akt, phosphodiesterase, cholesterol, and protein kinase C beta signaling. This report provides an update on biologic studies and clinical efforts for the development of these novel agents in the treatment of Waldenström's macroglobulinemia.


A comparison of ethanolamine and potassium hydroxide as quantitative trapping agents for radiolabeled CO2 in metabolism studies.
The efficiency of ethanolamine and potassium hydroxide (KOH) as trapping agents for CO2 was determined using a flow of 500 mL/min through CO2 absorption towers containing trapping solutions. Radiolabeled 14CO2 was produced by acidification of suspensions containing Ba14CO3. Both 100% ethanolamine and 5M ethanolamine in 2-methoxyethanol were evaluated. With 200 mL of either solution, trapping efficiency of 14CO2 decreased when only 5% or less of the amount of ethanolamine available had reacted (22 mmoles of CO2 trapped). In contrast, use of 200 mL of 1M or 5M KOH was effective in retaining 88 mmoles of CO2. This is equivalent to the amount of CO2 produced by a rat over an 8-hr period. In summary, with flow rates commonly used in in vivo metabolism studies, the trapping efficiency of ethanolamine was far less than the theoretical efficiency. In these types of studies KOH would be a more suitable trapping agent or, if used, ethanolamine solutions must be changed frequently.


Pulmonary host defenses and alcohol.
Alcohol abuse is a major risk factor for the development of many infectious diseases, particularly pulmonary infections. Bacterial pneumonia and other lung infections in alcohol-abusing patients are usually severe and associated with a high morbidity and mortality. Normal host defense mechanisms in the respiratory tract consist of both innate and acquired immunity which operate effectively in preventing the invasion of infectious pathogens. Numerous in vivo and in vitro studies have shown that alcohol is an immunosuppressive agent that compromises the function of various components of the immune defense system. In recent years, human immunodeficiency virus infection has become epidemic, especially in individuals who abuse alcohol and other substances. Treatment of pulmonary infections in these immunocompromised hosts has continued to be a major challenge in our health care system. Immunotherapy to improve or enhance pulmonary host defense function in conjunction with aggressive antimicrobial regimens may provide a new approach in the management of infections in these patients.


Granulocyte/macrophage origin of glomerular mesangial cells.
We previously demonstrated the ability of hematopoietic stem cells (HSCs) to generate glomerular mesangial cells by trans-planting clonal populations of cells derived from a single enhanced green fluorescent protein (EGFP)-positive HSC into lethally irradiated mice. To define more precisely the hematopoietic differentiation pathway through which mesangial cells are derived, we studied the relationship between mesangial cell expression and individual hematopoietic lineages by means of a transplantation strategy. In a series of clonal HSC transplantation experiments, we generated 3 mice engrafted predominantly by granulocytes and macrophages (GMs) and 4 mice engrafted with B-cells or with B-cells and T-cells. When the kidneys of these mice were analyzed, the mice exhibiting high GM lineage engraftment revealed much higher levels of EGFP-positive mesangial cells than those with predominantly lymphocyte engraftment. Fluorescence in situ hybridization analysis of the kidneys from a male recipient of an EGFP-positive female donor excluded cell fusion as the cause for the observed differentiation. These results support the notion that glomerular mesangial cells share their origin with GMs.


Person-specific gesture set selection for optimised movement classification from EMG signals.
Movement classification from electromyography (EMG) signals is a promising vector for improvement of human computer interaction and prosthetic control. Conventional work in this area typically makes use of expert knowledge to select a set of movements a priori and then design classifiers based around these movements. The disadvantage of this approach is that different individuals might have different sets of movements that would lead to high classification accuracy. The novel approach we take here is to instead use a data-driven diagnostic test to select a set of person-specific movements. This new approach leads to an optimised set of movements for a specific person with regards to classification performance.


Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia.
Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network.


Improvement of dose distribution in breast radiotherapy using a reversible transverse magnetic field Linac-MR unit.
To investigate the improvement in dose distribution in tangential breast radiotherapy using a reversible transverse magnetic field that maintains the same direction of Lorentz force between two fields. The investigation has a potential application in future Linac-MR units. Computed tomography images of four patients and magnetic fields of 0.25-1.5 Tesla (T) were used for Monte Carlo simulation. Two patients had intact breast while the other two had mastectomy. Simulations of planning and chest wall irradiation were similar to the actual clinical process. The direction of superior-inferior magnetic field for the medial treatment beam was reversed for the lateral beam. For the ipsilateral lung and heart mean doses were reduced by a mean (range) of 45.8% (27.6%-58.6%) and 26.0% (20.2%-38.9%), respectively, depending on various treatment plan setups. The mean V20 for ipsilateral lung was reduced by 55.0% (43.6%-77.3%). In addition acceptable results were shown after simulation of 0.25 T magnetic field demonstrated in dose-volume reductions of the heart, ipsilateral lung, and noninvolved skin. Applying a reversible magnetic field during breast radiotherapy, not only reduces the dose to the lung and heart but also produces a sharp drop dose volume histogram for planning target volume, because of bending of the path of secondary charged particles toward the chest wall by the Lorentz force. The simulations have shown that use of the magnetic field at 1.5 T is not feasible for clinical applications due to the increase of ipsilateral chest wall skin dose in comparison to the conventional planning while 0.25 T is suitable for all patients due to dose reduction to the chest wall skin.


Calibration of the n-electron valence state perturbation theory approach.
Extensive tests have been performed to benchmark and to compare with second-order perturbation theory based on a complete active space self-consistent field reference function (CASPT2), the recently developed n-electron valence state perturbation theory at second order (NEVPT2). Test calculations included the group fifteen diatomic molecules X(2) (X=N, P, As, and Sb) and the (4)S/(2)D and (4)S/(2)P splittings for the corresponding atoms, the (1)A(1)-(3)B(1) splittings for CH(2) and SiH(2), and the absorption spectra of pyrrole and of Cu(Imidazole)(2)(SH)(SH(2))(+), which is a model for plastocyanin. Comparisons with full configuration-interaction calculations and experimental data show that the accuracy of NEVPT2 is in most cases even better than CASPT2. Where intruder states hamper the CASPT2 calculations, NEVPT2 performs significantly better. Care is needed in the choice of active orbitals, for example in the calculation of the (4)S/(2)D and (4)S/(2)P splittings for the group fifteen atoms. This is due to the different treatment of orbitals belonging to the inactive or active spaces, making the NEVPT2 not invariant for the choice of active space, even in cases where the multiconfiguration self-consistent field energy is invariant.


First total synthesis of cyrmenin B1.
A short and efficient synthesis of cyrmenin B(1), an antifungal metabolite of myxobacteria Cystobacter armeniaca and Archangium gephyra, is described. The crucial steps of the synthesis included the formation of the dehydroalanine moiety from the corresponding serine acetate and the formation of the beta-methoxyacrylate system via trimethylsilyldiazomethane methylation of the corresponding beta-hydroxy enamide.


A theory of circular organization and negative feedback: defining life in a cybernetic context.
All life today incorporates a variety of systems controlled by negative feedback loops and sometimes amplified by positive feedback loops. The first forms of life necessarily also required primitive versions of feedback, yet surprisingly little emphasis has been given to the question of how feedback emerged out of primarily chemical systems. One chemical system has been established that spontaneously develops autocatalytic feedback, the Belousov-Zhabotinsky (BZ) reaction. In this essay, I discuss the BZ reaction as a possible model for similar reactions that could have occurred under prebiotic Earth conditions. The main point is that the metabolism of contemporary life evolved from primitive homeostatic networks regulated by negative feedback. Because life could not exist in their absence, feedback loops should be included in definitions of life.


Muscle Attenuation Is Associated With Newly Developed Hypertension in Men of African Ancestry.
Increased ectopic adipose tissue infiltration in skeletal muscle is associated with insulin resistance and diabetes mellitus. We evaluated whether change in skeletal muscle adiposity predicts subsequent development of hypertension in men of African ancestry, a population sample understudied in previous studies. In the Tobago Health Study, a prospective longitudinal study among men of African ancestry (age range 40-91 years), calf intermuscular adipose tissue, and skeletal muscle attenuation were measured with computed tomography. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg, or receiving antihypertensive medications. Logistic regression was performed with adjustment for age, insulin resistance, baseline and 6-year change in body mass index, baseline and 6-year change in waist circumference, and other potential confounding factors. Among 746 normotensive men at baseline, 321 (43%) developed hypertension during the mean 6.2 years of follow-up. Decreased skeletal muscle attenuation was associated with newly developed hypertension after adjustment for baseline and 6-year change of body mass index (odds ratio [95% confidence interval] per SD, 1.3 [1.0-1.6]) or baseline and 6-year change of waist circumference (odds ratio [95% confidence interval] per SD, 1.3 [1.0-1.6]). No association was observed between increased intermuscular adipose tissue and hypertension. Our novel findings show that decreased muscle attenuation is associated with newly developed hypertension among men of African ancestry, independent of general and central adiposity and insulin resistance. Further studies are needed to adjust for inflammation, visceral and other ectopic adipose tissue depots, and to confirm our findings in other population samples.


Cell-specific expression of betaC-activin in the rat reproductive tract, adrenal and liver.
betaC-activin expression was assessed in rat tissues, using reverse transcription and real-time polymerase chain reaction, Western blotting and immunohistochemistry with a specific monoclonal antibody. betaC-activin mRNA was predominantly expressed in liver, but significant amounts were found in rat whole pituitary extracts (n = 5), and in three of five extracts of ovary, testis, and adrenal gland. Specific betaC-activin immunoreactivity was demonstrated in the cytoplasm of hepatocytes, neurosecretory cell terminals in posterior pituitary, ovarian primordial follicles, theca interna, large luteal cells and rete ovarii, spermatogonia, pachytene spermatocytes and Leydig cells of the testis, uterine endometrium, oviduct epithelium and zona glomerulosa of the adrenal. The observation of stage-specific expression in gonadal cells suggests this activin subunit has specific roles, different from those of other activin/inhibin subunits. Small amounts of mRNA in the presence of significant betaC-activin protein highlights the importance of examining betaC-activin expression at both the mRNA and protein level.


Trichoderma Biodiversity of Agricultural Fields in East China Reveals a Gradient Distribution of Species.
We surveyed the Trichoderma (Hypocreales, Ascomycota) biodiversity in agricultural fields in four major agricultural provinces of East China. Trichoderma strains were identified based on molecular approaches and morphological characteristics. In three sampled seasons (spring, summer and autumn), 2078 strains were isolated and identified to 17 known species: T. harzianum (429 isolates), T. asperellum (425), T. hamatum (397), T. virens (340), T. koningiopsis (248), T. brevicompactum (73), T. atroviride (73), T. fertile (26), T. longibrachiatum (22), T. pleuroticola (16), T. erinaceum (16), T. oblongisporum (2), T. polysporum (2), T. spirale (2), T. capillare (2), T. velutinum (2), and T. saturnisporum (1). T. harzianum, T. asperellum, T. hamatum, and T. virens were identified as the dominant species with dominance (Y) values of 0.057, 0.052, 0.048, and 0.039, respectively. The species amount, isolate numbers and the dominant species of Trichoderma varied between provinces. Zhejiang Province has shown the highest diversity, which was reflected in the highest species amount (14) and the highest Shannon-Wiener diversity index of Trichoderma haplotypes (1.46). We observed that relative frequencies of T. hamatum and T. koningiopsis under rice soil were higher than those under wheat and maize soil, indicating the preference of Trichoderma to different crops. Remarkable seasonal variation was shown, with summer exhibiting the highest biodiversity of the studied seasons. These results show that Trichoderma biodiversity in agricultural fields varies by region, crop, and season. Zhejiang Province (the southernmost province in the investigated area) had more T. hamatum than Shandong Province (the northernmost province), not only in isolate amounts but also in haplotype amounts. Furthermore, at haplotype level, only T. hamatum showed a gradient distribution from south to north in correspondence analysis among the four dominant species. The above results would contribute to the application of Trichoderma biocontrol strains.


Biological characterization of Chlamydia trachomatis plasticity zone MACPF domain family protein CT153.
Chlamydia trachomatis strains are obligate intracellular human pathogens that share near genomic synteny but have distinct infection and disease organotropisms. The genetic basis for differences in the pathogen-host relationship among chlamydial strains is linked to a variable region of chlamydial genomes, termed the plasticity zone (PZ). Two groups of PZ-encoded proteins, the membrane attack complex/perforin (MACPF) domain protein (CT153) and members of the phospholipase D-like (PLD) family, are related to proteins that modify membranes and lipids, but the functions of CT153 and the PZ PLDs (pzPLDs) are unknown. Here, we show that full-length CT153 (p91) was present in the elementary bodies (EBs) of 15 C. trachomatis reference strains. CT153 underwent a rapid infection-dependent proteolytic cleavage into polypeptides of 57 and 41 kDa that was independent of de novo chlamydial protein synthesis. Following productive infection, p91 was expressed during the mid-developmental cycle and was similarly processed into p57 and p41 fragments. Infected-cell fractionation studies showed that insoluble fractions contained p91, p57, and p41, whereas only p91 was found in the soluble fraction, indicating that unprocessed CT153 may be secreted. Finally, CT153 localized to a distinct population of reticulate bodies, some of which were in contact with the inclusion membrane.


A retrospective analysis of the risk factors for surgical site infections and long-term follow-up after transpalpebral enucleation in horses.
Implants are often used to improve the cosmetic appearance of horses after enucleation of the eye. When surgical site infection (SSI) occurs, the implant will almost always be lost. The aim of this study is to collect data on the risk factors for SSIs and report long-term follow-up (cosmetic results and return to work) after transpalpebral enucleations. In this retrospective study, records of horses undergoing transpalpebral enucleation were reviewed (2007-2014) and telephone interviews were used to obtain long term follow-up. The potential risk factors for SSIs (indication for enucleation, use of an implant, standing procedures, duration of surgery, opening of the conjunctival sac and prolonged use of antimicrobials) were analysed for their association with the outcome measure 'SSI' vs 'no SSI' by multivariable binary logistic regression testing. Indications for enucleation were grouped as follows: Group 1 (clean) included equine recurrent uveitis, too small or too large globes, and intraocular tumours, Group 2 (non-clean) included corneal perforation/rupture and infected ulcers and Group 3 (tumour) included extraocular tumours. One hundred and seven cases of enucleation were evaluated. An implant was used in 49 horses. The overall number of SSIs was 8 (7.5%). Multivariable logistic regression testing showed implants (OR 7.5, P = 0.04) and standing procedures (OR 12.1; P = 0.03) were significantly associated with the percentage of SSIs and increased the risk of SSI. The eyes of horses in Groups 2 and 3 trended towards a larger risk for developing SSIs (OR 4.9; P = 0.09 and OR 5.9; P = 0.1, respectively). Prolonged use of antimicrobials, long surgery times and the opening of the conjunctival sac during dissection did not show significant associations with SSI risk. The risk of SSI after enucleation is low in clean eyes and when no implant is used. Placing an implant or performing a standing enucleation significantly increases the risk of SSIs. Although implants can be used for eyes that fall into Groups 2 and 3, 17% of the horses in these two groups developed an SSI leading to loss of the implant.


Simple growth models of rigid multifilament biopolymers.
The growth dynamics of rigid biopolymers, consisting of N parallel protofilaments, is investigated theoretically using simple approximate models. In our approach, the structure of a polymer's growing end and lateral interactions between protofilaments are explicitly taken into account, and it is argued that only few configurations are important for a biopolymer's growth. As a result, exact analytic expressions for growth velocity and dispersion are obtained for any number of protofilaments and arbitrary geometry of the growing end of the biopolymer. Our theoretical predictions are compared with a full description of biopolymer growth dynamics for the simplest N=2 model. It is found that the results from the approximate theory are approaching the exact ones for large lateral interactions between the protofilaments. Our theory is also applied to analyze the experimental data on the growth of microtubules.


Comparison of escitalopram and paroxetine in the treatment of major depressive disorder.
This is a single-blind, parallel, flexible-dose study to compare the efficacy and tolerability of escitalopram and paroxetine in the treatment of patients with major depressive disorder. We recruited 399 patients from the outpatient clinics of five hospitals in northern Taiwan. Patients were administered either escitalopram (10-30 mg) or paroxetine (20-40 mg) according to the judgment of clinicians. These patients were assessed using the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety at weeks 0, 1, 2, 4, 6, and 8. A total of 302 patients fulfilled the evaluation criteria and were included in a statistical analysis. We found that escitalopram induced more significant symptom reduction and response rate in terms of the mean HAM-D scores at week 6 (P<0.05) and week 8 (P<0.05) than paroxetine, but that there were no significant differences between the two groups in the remission rate. Escitalopram induced significantly less frequency of adverse effects of weakness (P<0.01), nausea and vomiting (P<0.001), drowsiness (P<0.01) as well as somnolence (P<0.01) than paroxetine, although all these side effects were mild and tolerable. However for a more definitive result, future prospective trials with the inclusion of a placebo group and a double-blind design are needed. In patients who did not have severe depression (HAM-D score at baseline<21), but not in severely depressed patients, escitalopram was statistically superior to paroxetine, as shown by the mean change in the HAM-D score.


Observation of Energy-Dependent Carrier Scattering in Conducting Polymer Nanowire Blends for Enhanced Thermoelectric Performance.
Without sacrificing the intrinsic softness and flexibility of conducting polymers, their blends have been demonstrated to be promising to improve thermoelectric properties of conducting polymers. However, the underlying mechanism for the thermoelectric enhancement is hitherto far from clear and is worthy of being explored deeply. In this work, we report novel conducting polymer nanowire blends by physically mixing poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires and polypyrrole (PPy) nanowires. By carefully tuning the energetic structure of PPy nanowires (nanofillers), the Seebeck coefficients and power factors of nanowire blends are surprisingly increased by ∼20 and ∼32% (compared to PEDOT nanowires), respectively. By means of first-principles calculations and experimental characterizations, we qualitatively confirm that the improved thermoelectric property is a consequence of a built-in energy barrier at nanowire interfaces rather than the commonly used doping/de-doping effect. Subsequently, we further employ the Kang-Snyder transport model and quantitatively demonstrate that the energy barrier involves energy-dependent carrier scattering (thus, a change of total relaxation time) at nanowire heterojunctions, which contributes to the enhanced Seebeck coefficients and power factors. Our work sheds light on the mechanism that can be adopted to design soft but high-performance thermoelectric materials with conducting polymer blends.


Update in cancer chemotherapy: genitourinary tract cancer, Part 5: Ovarian cancer.
An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 5 is a review of treatments for cancer of the ovary.Ovarian cancer is the leading cause of gynecologic cancer deaths and the fourth most frequent cause of death from cancer in women in the United States. Ovarian carcinoma is a classical "hidden" neoplasm of the abdomen and, as such, is insidious in its onset. Combination chemotherapy and cytoreductive surgery, however, have provided improved survival for patients with ovarian cancer. As dosage schedules and other refinements are made, the overall outlook for patients with ovarian cancer is promising.


Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A.
A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC50 of 1.0 μM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (97), a highly potent inhibitor of KAT6A (IC50 = 0.008 μM). WM-8014 competes with acetyl-CoA (Ac-CoA), and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool.


Extremely chaotolerant and kosmotolerant Aspergillus atacamensis - a metabolically versatile fungus suitable for recalcitrant biosolid treatment.
Obligate halophily is extremely rare in fungi. Nevertheless, Aspergillus atacamensis (strain EXF-6660), isolated from a salt water-exposed cave in the Coastal Range hills of the hyperarid Atacama Desert in Chile, is an obligate halophile, with a broad optimum range from 1.5 to 3.4 M of NaCl. When we tested its ability to grow at varied concentrations of both kosmotropic (NaCl, KCl, and sorbitol) and chaotropic (MgCl2, LiCl, CaCl2, and glycerol) solutes, stereoscopy and laser scanning microscopy revealed the formation of phialides and conidia. A. atacamensis EXF-6660 grew up to saturating levels of NaCl and at 2.0 M concentration of the chaotropic salt MgCl2. Our findings confirmed that A. atacamensis is an obligate halophile that can grow at substantially higher MgCl2 concentrations than 1.26 M, previously considered as the maximum limit supporting prokaryotic life. To assess the fungus' metabolic versatility, we used the phenotype microarray technology Biolog FF MicroPlates. In the presence of 2.0 M NaCl concentration, strain EXF-6660 metabolism was highly versatile. A vast repertoire of organic molecules (~95% of the substrates present in Biolog FF MicroPlates) was metabolized when supplied as sole carbon sources, including numerous polycyclic aromatic hydrocarbons, benzene derivatives, dyes, and several carbohydrates. Finally, the biotechnological potential of A. atacamensis for xenobiotic degradation and biosolid treatment was investigated. Interestingly, it could remove biphenyls, diphenyl ethers, different pharmaceuticals, phenols, and polyaromatic hydrocarbons. Our combined findings show that A. atacamensis EXF-6660 is a highly chaotolerant, kosmotolerant, and xerotolerant fungus, potentially useful for xenobiotic and biosolid treatments.


Influence of a meal-replacement diet on quality of life in women with obesity and knee osteoarthritis before orthopedic surgery.
Knee osteoarthritis is a disease with a high prevalence in our environment, especially in women. Weight loss can improve the quality of life of these patients before surgery. To evaluate the effect of a meal-replacement diet on weight loss, body composition, and the improvement of the quality of life in obese women with knee osteoarthritis pending surgery. One branch intervention study was performed over three months on 81 women with a body mass index greater than 30 kg/m2 with knee osteoarthritis before surgery. Patients received a hyperproteic meal-replacement diet with two bottles of an oral nutrition supplement in lunch and dinner (1,035 kcal). Anthropometric parameters, and body composition were measured. The quality of life was assessed by WOMAC and SF-36 test. The mean age of the patients was 62.23 (8.50) years. The percentage of weight loss was 8.23% (4.04). An improvement in the SF-36 total score was observed (basal: 49.35 [20.41], three months: 58.71 [17.07], p < 0.01). There was an improvement in WOMAC test (basal: 49.24% [25.53], three months: 40.59% [21.76], p < 0.01). It was observed that a 10% improvement in the SF-36 test was independently related to weight loss (OR: 1.2 [1.03-1.36], p < 0.02) adjusted by age and changes in body composition. In women with osteoarthritis of the knee treated with a meal-replacement diet, there is a significant decrease in weight and fat mass with a relative increase of the latter. There is an improvement in the quality of life according to SF-36 and WOMAC. There is an independent relationship between weight loss and SF-36 improvement.


Dynamics of the tumor-immune-virus interactions: Convergence conditions to tumor-only or tumor-free equilibrium points.
In the present paper convergence dynamics of one tumor-immune-virus model is examined with help of the localization method of compact invariant sets and the LaSalle theorem. This model was elaborated by Eftimie et al. in 2016. It is shown that this model possesses the Lagrange stability property of positive half-trajectories and ultimate upper bounds for compact invariant sets are obtained. Conditions of convergence dynamics are found. It is explored the case when any trajectory is attracted to one of tumor-only equilibrium points or tumor-free equilibrium points. Further, it is studied ultimate dynamics of one modification of Eftimie et al. model in which the immune cells injection is included. This modified system possesses the global tumor cells eradication property if the influx rate of immune cells exceeds some value which is estimated. Main results are expressed in terms simple algebraic inequalities imposed on model and treatment parameters.