The utility of intramuscular ziprasidone in the management of acute psychotic agitation.
Many psychiatric illnesses, including chronic schizophrenia, bipolar disorder, and dementia, are characterized by episodes of acute agitation, making administration of oral agents difficult or impossible. Ziprasidone, the first atypical antipsychotic available in both intramuscular (IM) and oral formulations, has demonstrated significant control of acute agitation within 15 minutes, as seen in two 24-hour studies in patients with schizophrenia. Improvement was maintained for > or = 4 hours, and a low incidence of extrapyramidal symptoms, akathisia, and dystonia as well as no excessive sedation were observed Also, two 7-day studies (n = 132 and n = 306) and one 6-week study (n = 567) of sequential IM/oral ziprasidone versus IM/oral haloperidol in patients with psychotic disorders found IM ziprasidone more effective than IM haloperidol within 3 days of IM treatment; both drugs produced further comparable improvements in efficacy parameters after transition to oral therapy. IM ziprasidone was associated with a lower incidence of movement disorders than was haloperidol in all of these studies. Overall, discontinuations were similar for IM ziprasidone and haloperidol in the comparative trials, including the sequential IM/oral studies. However, in the 6-week sequential IM/oral trial, the rate of discontinuation due to adverse events was twice as high among haloperidol vs ziprasidone patients. This report focuses on the pharmacology, clinical efficacy, and tolerability of IM ziprasidone, and provides an overview of the utility of other commonly used antipsychotics in the management of acute psychotic agitation.


Synthetic Biology and Computer-Based Frameworks for Antimicrobial Peptide Discovery.
Antibiotic resistance is one of the greatest challenges of our time. This global health problem originated from a paucity of truly effective antibiotic classes and an increased incidence of multi-drug-resistant bacterial isolates in hospitals worldwide. Indeed, it has been recently estimated that 10 million people will die annually from drug-resistant infections by the year 2050. Therefore, the need to develop out-of-the-box strategies to combat antibiotic resistance is urgent. The biological world has provided natural templates, called antimicrobial peptides (AMPs), which exhibit multiple intrinsic medical properties including the targeting of bacteria. AMPs can be used as scaffolds and, via engineering, can be reconfigured for optimized potency and targetability toward drug-resistant pathogens. Here, we review the recent development of tools for the discovery, design, and production of AMPs and propose that the future of peptide drug discovery will involve the convergence of computational and synthetic biology principles.


Early onset sebaceous carcinoma.
Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided.A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.


Compact snapshot multiwavelength interferometer.
We propose a snapshot and compact multiwavelength interferometer for real-time testing of optical surfaces with large slopes. A color camera with a micropolarizer array simultaneously captures the phase-shifted interferograms of multiple wavelengths, from which four interferograms with π/2 phase shift at each wavelength are extracted for multiwavelength phase-shifting interferometric measurement. The accuracy of the proposed system is validated experimentally, and the testing of freeform surface with large slopes is also demonstrated. The proposed system provides a feasible way to obtain the instantaneous online measurement of freeform surfaces while minimizing environmental disturbance.


[LIU Zhi-shun's experience in treatment of infertility with decreasing ovarian reserve with electroacupuncture].
To summarize LIU Zhi-shun's clinical experience in treatment of infertility with decreasing ovarian reserve (DOR) with electroacupuncture. LIU Zhi-shun believes that the location of infertility with DOR is the uterus, mainly involving the kidney, thoroughfare and conception vessels. He advocates to select acupoints by combining "disease-symptom-position" with prescription, and selects acupoint prescription of Bushen Tiaochong Zhuyun included Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25), Sanyinjiao (SP 6), Ciliao (BL 32) and Zhongliao (BL 33) for electroacupuncture treatment. The key points of operation are accurate positioning and deep acupuncture, focusing on regulating mind and getting qi, adopting electroacupuncture treatment and low frequency stimulation and treating slowly for long-term disease.


The use of a contact cooling device to reduce pain and ecchymosis associated with dermal filler injections.
Objectives. Consensus guidelines developed for the use of hyaluronic acid dermal fillers describe the use of cooling the skin to reduce patient discomfort during injection. The vasoconstrictive effects of cold may provide reduced ecchymosis and swelling at the site. However, the effect of applying ice or cooled air is unpredictable because these modalities do not deliver precise temperature, which may result in cold burn or insufficient effect to targeted areas. This open-label, randomized, single-blinded, split-face trial was conducted to measure the extent to which applying a spot cooling device reduces patient discomfort and ecchymoses in the clinical setting in patients undergoing a dermal filler procedure. Subjects. Twenty male and female subjects of any race, ages 35 to 65 years, with moderate and severe nasolabial folds were included in this study. Seven (35%) subjects had received previous small gel particle hyaluronic acid injections. Methods. Prior to injection, the topical cooling system was set at 35 degrees F and a cooled applicator was applied for 20 seconds on one nasolabial fold. A control using a noncooled applicator was applied for 20 seconds on the other nasolabial fold. Postprocedure ice packs were prohibited so as not to confound the subject's perception of procedure-related pain. Subjects (using visual analog pain scales) and blinded investigators rated pain and ecchymosis using predetermined scales and satisfaction surveys. Results. Use of the cooling system was associated with mean pain reduction of 61, 70, and 42 percent compared to control, as measured by visual analog pain scales, immediately following and one hour and three hours post small gel particle hyaluronic acid injection. Additionally, use of the cooling system was associated with mean ecchymosis reduction of 88, 89, 80, and 66 percent compared to control immediately following injection, one hour, three hours, and next-day postinjection. Conclusion. The cooling system provided adequate pain management (both subjectively and objectively through blinded evaluations) during and after small gel particle hyaluronic acid dermal filler injections for the correction of moderate nasolabial folds. Furthermore, results demonstrate that the cooling system is associated with decreased ecchymosis. Future studies are needed comparing the use of topical anesthetics to a cooling system for the reduction of pain and ecchymosis associated with the use of dermal filler injections.


Identification and validation of novel gene markers of osteoporosis by weighted co expression analysis.
Osteoporosis is a serious global public health concern. The present study identified specific osteoporosis biomarkers which were used to generate a predictive prognostic model for patients with osteoporosis. Datasets from the Gene Expression Omnibus (GEO) database were analyzed. Differentially expressed genes (DEGs) between osteoporosis and normal controls were identified by integrated microarray analysis of the GEO database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed gene function were performed. The best diagnostic gene biomarkers for Osteoporosis were identified using Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPIs) networks. Classification models including support vector machines (SVM) was developed to test the diagnostic value of the identified gene biomarkers for osteoporosis. Integrated microarray analysis of the GEO database (GSE62402, GSE7158 and GSE13850) was used for validation. A total of 1,589 DEGs related to osteoporosis were identified in the GSE35959 dataset. These DEGs were enriched in various pathways including the negative regulation of the calcium ion transmembrane transport pathway. WGCNA identified 16 models, with the blue module showing a strong positive association with osteoporosis, and the turquoise module showing a considerable negative association with osteoporosis. Six hub genes were identified and used as features to build a predictive prognostic model for osteoporosis using the GSE35959 dataset. The model was verified using the GSE62402, GSE7158, and GSE13850 datasets. These findings provide crucial insights into the mechanisms of the occurrence and progression of osteoporosis. Furthermore, the identification of novel potential biomarkers may contribute to the early diagnosis, prevention, and treatment of osteoporosis.


Associations between self-reported diet during treatment and chemotherapy-induced peripheral neuropathy in a cooperative group trial (S0221).
The pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) is not well understood. Currently, dose reduction is the only recommendation for alleviating symptoms, often leading to premature treatment cessation. The primary aim of this analysis was to determine the association between components of diet during taxane treatment for breast cancer and change in CIPN symptoms over treatment. Women with stage II or III invasive breast cancer were enrolled into an ancillary study to the North American Breast Cancer Intergroup phase III trial (S0221) led by the Southwest Oncology Group (SWOG). Questionnaires including a food frequency questionnaire and the Functional Assessment of Cancer Treatment Gynecologic Oncology Group-Neurotoxicity were administered to assess diet and neuropathic conditions at baseline and during chemotherapy. Ordinal regression was used to estimate odds ratios (ORs) for associations between various food groups and change in neuropathy score (< 10%, 10-30%, > 30%) (n = 900). The odds of worse neuropathy decreased by 21% for each increase in tertile of grain consumption (OR = 0.79, 95% CI 0.66-0.94, p = 0.009). We also observed a nominal 19% increase with higher consumption of citrus fruits (OR = 1.19, 95% CI 1.01-1.40, p = 0.05). Distinguishing between those who experienced a moderate and a severe change in neuropathy, we found that citrus fruit and grain consumption may play a role in the severity of symptoms. Since there are no existing dietary recommendations for the management of CIPN, further research is needed to investigate whether there may be certain foods that could worsen or alleviate neuropathy symptoms associated with treatment for breast cancer. ClinicalTrials.gov, NCT03413761 . Registered retrospectively on 29 January 2018.


On Staying Grounded and Avoiding Quixotic Dead Ends.
The 15 articles in this special issue on The Representation of Concepts illustrate the rich variety of theoretical positions and supporting research that characterize the area. Although much agreement exists among contributors, much disagreement exists as well, especially about the roles of grounding and abstraction in conceptual processing. I first review theoretical approaches raised in these articles that I believe are Quixotic dead ends, namely, approaches that are principled and inspired but likely to fail. In the process, I review various theories of amodal symbols, their distortions of grounded theories, and fallacies in the evidence used to support them. Incorporating further contributions across articles, I then sketch a theoretical approach that I believe is likely to be successful, which includes grounding, abstraction, flexibility, explaining classic conceptual phenomena, and making contact with real-world situations. This account further proposes that (1) a key element of grounding is neural reuse, (2) abstraction takes the forms of multimodal compression, distilled abstraction, and distributed linguistic representation (but not amodal symbols), and (3) flexible context-dependent representations are a hallmark of conceptual processing.


Lower limbs function and pain relationships after unilateral total knee arthroplasty.
The aim of the study was to evaluate gait characteristics, lower limbs joint function, and pain relationships associated with knee osteoarthritis of female patients before and 3 months after total knee arthroplasty at an outpatient clinic rehabilitation department. Gait parameters were registered, the active range of lower extremity joints was measured, and pain was evaluated. Gait characteristics, walking velocity, and knee joint's extension improved and pain diminished considerably 3 months after arthroplasty, nevertheless did not reach control group level. In conclusion, single support phase and gait velocity change reflect the recovery of gait function after total knee arthroplasty. Beside the affected knee joint's range of motion, attention should be paid to the restoration of the functional reserve of the adjacent joints and joints of contralateral lower extremity after total knee arthroplasty. Affected knee joint pain perceived during level walking influenced the gait velocity of patients before total knee arthroplasty but not 3 months after arthroplasty.


Sudden hearing loss due to AIDS-related cryptococcal meningitis--a temporal bone study.
We have presented the clinical history and temporal bone findings in a patient who manifested sudden hearing loss, and who subsequently was found to have cryptococcal meningitis associated with AIDS. The histopathologic findings are similar to earlier reports in patients without AIDS. Because cryptococcal infection is so much more common in AIDS patients than in the general population, it must be considered a causative factor when presented with an AIDS patient with progressive or sudden hearing loss. This offers the patient a chance for timely and effective treatment.


The impact of ferritin fluctuations on stable hemoglobin levels in hemodialysis patients.
Hemoglobin (Hb) cycling in patients with renal anemia might be associated with a higher mortality rate. We investigated the association of factors relating serum ferritin and dose of erythropoiesis-stimulating agents (ESAs) with Hb levels. We measured Hb and ferritin levels every month in 266 hemodialysis (HD) patients for 12 months. The standard deviation (SD) and residual SD (RSD) (liner regression of Hb or ferritin SD values) values of Hb were significantly correlated with ferritin SD or RSD values, respectively. The percentage achievement of target Hb in the target-ferritin group was significantly higher than in the high-amplitude fluctuation ferritin group. Ferritin SD and RSD values in patients with oral or no iron supplementation were significantly lower than those who received intravenous iron. Iron storage varies over a relatively wide range in HD patients, and this variation is closely associated with Hb cycling. The stability of iron storage and ESA dosage is important for maintaining stable Hb levels.


Pulling rabbits to reveal the secrets of the prion protein.
The Prion protein (PrP) is a membrane-tethered glycoprotein that plays a central role in a unique class of neurodegenerative diseases that affect humans and other mammals. Prion diseases have genetic and sporadic origins, but their infectious nature sets them apart from other neurodegenerative disorders. According to the "protein-only" hypothesis, misfolded PrP conformers (prions) are responsible for both spongiform degeneration of the brain and disease transmissibility. Thus, understanding PrP conformational dynamics is key to developing effective therapies. Classic studies showing the different susceptibility to prion disease in mammals have recently found support in structural and transgenic studies with PrP from susceptible (mouse, hamster) and resistant (rabbit, horse, dog) animals. These studies identify key residues in PrP that determine both PrP structure and its propensity to acquire a β-structure conformation proposed to be neurotoxic.


The emerging role of dipeptidyl peptidase 3 in pathophysiology.
Dipeptidyl peptidase 3 (DPP3), a zinc-dependent aminopeptidase, is a highly conserved enzyme among higher animals. The enzyme cleaves dipeptides from the N-terminus of tetra- to decapeptides, thereby taking part in activation as well as degradation of signalling peptides critical in physiological and pathological processes such as blood pressure regulation, nociception, inflammation and cancer. Besides its catalytic activity, DPP3 moonlights as a regulator of the cellular oxidative stress response pathway, e.g., the Keap1-Nrf2 mediated antioxidative response. The enzyme is also recognized as a key modulator of the renin-angiotensin system. Recently, DPP3 has been attracting growing attention within the scientific community, which has significantly augmented our knowledge of its physiological relevance. Herein, we review recent advances in our understanding of the structure and catalytic activity of DPP3, with a focus on attributing its molecular architecture and catalytic mechanism to its wide-ranging biological functions. We further highlight recent intriguing reports that implicate a broader role for DPP3 as a valuable biomarker in cardiovascular and renal pathologies and furthermore discuss its potential as a promising drug target.


Soybean seed growth in response to long-term exposures to differing oxygen partial pressures.
Short-term studies have indicated that alterations in the oxygen partial pressure (pO(2)) around developing soybean (Glycine max [L.] Merr.) seeds may alter seed growth characteristics. A 2-year field study was undertaken to determine the effects on seed development of long-term exposures of individual pods to either sub-ambient or supra-ambient pO(2). Pod chambers were used through which fixed pO(2) were continuously flowed throughout seed development. No effects on maturity date were observed from exposures to either sub-ambient or supra-ambient pO(2). On the other hand, seed weight was reduced by 0.10 pO(2) in both years of the study implicating an O(2) limitation on seed growth rate at this fairly high pO(2). In 1 of the 2 years, supra-ambient pO(2) resulted in increased seed weight.


Starch digestion and absorption in nonruminants.
Starch digestion and absorption is augmented appreciably by physical processing of grain or legume and by heating to 100 degrees C for several minutes before its ingestion. Starch, a polysaccharide composed of alpha 1,4-linked glucose units (amylose) and alpha 1,4-1,6-linked branched structure (amylopectin), is cleaved in the duodenal cavity by secreted pancreatic alpha-amylase to a disaccharide (maltose), trisaccharide (maltotriose), and branched alpha-dextrins. These final oligosaccharides are hydrolyzed efficiently by complimentary action of three integral brush border enzymes at the intestinal surface: glucoamylase (maltase-glucoamylase, amyloglucosidase), sucrase (maltase-sucrase) and alpha-dextrinase (isomaltase). The final monosaccharide glucose product is then cotransported into the enterocyte along with Na+ by a specific brush border 75-kDa transport protein in the rate-limiting step for overall starch assimilation. By virtue of this sequential luminal and membrane digestion followed by glucose transport, starch is assimilated in a very efficient manner in nonruminants.


The care information system PIK--the fit between user and system.
The presented laboratory study explores the relationship between the care information system PIK and its users, focusing on intuitive program usage, occurring errors, the usefulness of the evaluation method, and the role of person related variables. Three studies were conducted. While thinking aloud, a sample of 26 participants performed certain tasks, which were recorded in protocols. In addition, the occurring errors were rated in an error taxonomy. While the actual use of the program proved quite easy, conceptual structuring caused the participants difficulties. These difficulties stemmed mainly from problems encountered in generating a clear mental picture of the system, and the consequences of the actions. Over time, the program showed a positive development. Discussion of the results focuses on implementation processes in the context of usability research. The need to train users in the conceptual structure of the program and to build realistic expectations are the focus of our outline.


Charge mobility in molecules: charge fluxes from second derivatives of the molecular dipole.
On the basis of the analytical model previously suggested by Dinur, we discuss here a method for the calculation of vibrational charge fluxes in planar molecules, obtained as numerical second derivatives of the molecular dipole moment. This model is consistent with the partitioning of the atomic polar tensors into atomic charge and charge fluxes according to the Equilibrium Charges-Charge Fluxes model and it is directly related to experimentally measurable quantities such as IR intensities. On the basis of density functional theory calculations carried out for several small benchmark molecules, the complete set of charge fluxes is calculated for each molecule and compared with the approximated flux parameters previously derived and reported in the past literature. The degree of localization of charge fluxes is investigated and discussed; in addition, some approximations are analyzed in order to verify the applicability of the method to large and∕or non-planar molecules, aimed at obtaining a description of the electron charge mobility in different molecular environments.


Characterization of D-glucose transport in Trypanosoma rangeli.
Like in other trypanosomatids D-glucose is a crucial source of energy to Trypanosoma rangeli, a non-pathogenic parasite that in Central and South America infects triatomine vectors and different mammalian species, including humans. In several trypanosome species, D-glucose transporters were already described and cloned. In this study, we characterized the D-glucose transport activity present in 2 life-stage forms of T. rangeli (epimastigotes and trypomastigotes) using D-[U-14C]glucose as substrate. Our results indicate that T. rangeli transports D-glucose with high affinity in both epimastigote (Km 30 microM) and trypomastigotes (Km 80 microM) life-forms. Both transport activities were inhibited by Cytochalasin B and Phloretin, indicating that probably D-glucose uptake in T. rangeli is mediated by facilitated diffusion of the sugar. Significant differences were observed between epimastigotes and trypomastigotes in relation to their affinity for D-glucose analogues, and the predicted amino acid sequence of a putative D-glucose transporter from T. rangeli (TrHT1) showed a larger identity with the T. cruzi D-glucose transporter encoded by the TcrHT1 gene than with other transporters already characterized in trypanosomatids.


Fucoidans Stimulate Immune Reaction and Suppress Cancer Growth.
Fucoidans are gaining popularity as natural immunomodulators. The aim of this study was to compare the immunological activities or both purified samples and commercially available mixtures containing fucoidan. We evaluated the effects of various samples on phagocytosis, mitogenic response, natural killer (NK) activity, antibody formation and inhibition of breast cancer growth. We found significant immunostimulating activity, but the strength of these effects was different among individual samples. Fucoidans have strong immunostimulating potential, including inhibition of cancer, with isolated samples offering better activity than commercial mixtures.


Chronic peripheral neuropathy in childhood: an overview.
One hundred and twenty-five cases of biopsy-proven subacute or chronic peripheral polyneuropathy occurring in children under 17 years of age are reviewed. Ninety-three (74%) of the cases have been examined by the authors. At least 71% of cases were considered to be of genetic origin. Hereditary motor and sensory neuropathies were confirmed in over 40% of the cases. From among these a previously poorly defined entity (hereditary motor and sensory neuropathy of neuronal type with onset in early childhood) was delineated. It constituted 7.2% of the cases. When clinical and neurophysiological investigations of the family are combined with histopathological investigation of the affected child, a correct aetiological diagnosis can be reached in over 80% of cases of chronic polyneuropathy in childhood.


Methods of amorphization and investigation of the amorphous state.
The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid- -state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectroscopy) and calorimetry methods.


In vitro study of contact-mediated killing of Candida albicans hyphae by activated murine peritoneal macrophages in a serum-free medium.
Activated peritoneal macrophages obtained from Listeria-immune mice were demonstrated to kill nonphagocytosable Candida albicans hyphae by contact-mediated mechanisms in a serum-free synthetic medium. The actual killing of hyphae was confirmed by a microculture technique utilizing the dimorphic nature of the fungus. The most efficient candidacidal activity was demonstrated by the macrophages obtained from mice first immunized with live Listeria monocytogenes and then elicited with heat-killed L. monocytogenes cells. Resident macrophages from control mice showed only low candidacidal activity against C. albicans hyphae and yeast cells. Direct physical contact appeared to be required for macrophages to efficiently kill oversized C. albicans hyphae. Efficient in vitro killing of hyphae also required relatively high effector/target cell ratios (50 or higher). The contact-mediated candidacidal activity of activated macrophages was not significantly abrogated by oxygen-radical scavengers, suggesting the involvement of oxygen-independent mechanisms. These results suggest that the enhanced nonspecific immunity to candidiasis seen in Listeria-immune hosts can be attributed, at least in part, to activated fungicidal macrophages. The ability of macrophages to detect and destroy both yeast and hyphal C. albicans cells is clearly an important element of the host defense against candidiasis.


A simple preparation of very high methanol tolerant cathode electrocatalyst for direct methanol fuel cell based on polymer-coated carbon nanotube/platinum.
The development of a durable and methanol tolerant electrocatalyst with a high oxygen reduction reaction activity is highly important for the cathode side of direct methanol fuel cells. Here, we describe a simple and novel methodology to fabricate a practically applicable electrocatalyst with a high methanol tolerance based on poly[2,2'-(2,6-pyridine)-5,5'-bibenzimidazole]-wrapped multi-walled carbon nanotubes, on which Pt nanoparticles have been deposited, then coated with poly(vinylphosphonic acid) (PVPA). The polymer coated electrocatalyst showed an ~3.3 times higher oxygen reduction reaction activity compared to that of the commercial CB/Pt and methanol tolerance in the presence of methanol to the electrolyte due to a 50% decreased methanol adsorption on the Pt after coating with the PVPA. Meanwhile, the peroxide generation of the PVPA coated electrocatalyst was as low as 0.8% with 2 M methanol added to the electrolyte, which was much lower than those of the non-PVPA-coated electrocatalyst (7.5%) and conventional CB/Pt (20.5%). Such a high methanol tolerance is very important for the design of a direct methanol fuel cell cathode electrocatalyst with a high performance.


Autocrine activation of PDGFRalpha promotes the progression of ovarian cancer.
Platelet-derived growth factor receptor (PDGFR)alpha expression was found in ovarian cancer cells and tumors by microarray hybridization. This led us to test whether ovarian cancers also produce ligands for this receptor, as this would demonstrate that such malignancies support their own growth and spread through autocrine activation. We assayed the expression of ligands for the PDGFR in ovarian tumors, cell lines and peritoneal fluid using RT-PCR, immunohistochemistry (IHC) and ELISA. We detected strong mRNA expression for the PDGFRalpha ligands in most ovarian tumors. Receptor and ligand expressions (PDGFRalpha and PDGF AB) were also detected by IHC in, respectively, 34 and 32 of 47 ovarian tumors. The stainings for PDGFRalpha and PDGF AB were strongly correlated (P-value=0.014), suggesting that an autocrine loop is functional in ovarian cancer. PDGF AA and BB were quantified in peritoneal fluid by ELISA. Both ligands are secreted at higher levels in ovarian cancer ascites specimens (n=54) than in fluid from nonmalignant disorders (n=8). PDGF was detected in media conditioned by ovarian cancer cells. Such conditioned media induced activation of the PDGFR, Akt and MAPK and stimulated cell proliferation. A neutralizing PDGF antibody blocked these effects. Specific PDGFR inhibition by siRNA or a neutralizing antibody to the receptor inhibited PDGF-stimulated receptor activation and cell proliferation, suggesting that receptor targeting has a role in ovarian cancer treatment.


[Surgical treatment of traumatic epilepsy].
Fifteen patients with traumatic epilepsy were treated surgically. Cortico-electroencephalography was used during the operation. Meningo-encephalo cicatrix was found in 8 patients, scar formation in brain parenchyma in 4, meningoencephalocele in 2, and porencephalia in 1. Seven of the 15 patients were examined by CT, showing more accurate localization of pathological changes. Seizure subsided in 8 patients. Anti-epileptic drugs were still used in 4 patients, but the frequency and severity of epileptic attack were obviously decreased. There was no operative mortality. The indications, techniques of the operation and the postoperative management were discussed.


Human leukocyte elastase gene expression is regulated by PU.1 in conjunction with closely associated cytidine-rich and Myb binding sites.
Leukocyte elastase (LE) degrades connective tissue, is involved in the inflammatory process and implicated in cyclic and congenital neutropenia. The human LE gene is within a serine proteinase locus on chromosome 19 pter13.3. Our observations demonstrate that LE gene expression is regulated by PU.1, a cytidine-rich and a Myb binding site. The LE promoter has two cytidine-rich sites at -158 and -185. The -158 is the active site and it is closest to the PU.1 site. Proximity is essential to activity since separation of the -158 and PU.1 sites by a 20-base pair oligonucleotide reduced promoter activity by 50%. This suggests physical interaction between the transcription proteins binding to the PU.1 and -158 sites. The nuclear protein that binds the -158 site is present in B and T lymphocytes and an erythroleukemia cell line in addition to being abundant in the promyelocytic stage of neutrophil maturation when the LE gene is expressed. The protein binding to the -158 site is absent or expressed at low levels in non-hematopoietic cell lines. We have identified the transcription factors essential for human LE gene expression. Comparison with the mouse LE gene shows similarities and differences.


Formation and pharmacokinetics of the active drug candoxatrilat in mouse, rat, rabbit, dog and man following administration of the prodrug candoxatril.
1. Candoxatrilat, an active neutral endopeptidase inhibitor, was released rapidly from the inactive prodrug candoxatril in vivo in mouse, rat, rabbit, dog and man. 2. Oral doses of [14C]-candoxatril were cleared rapidly, mostly by ester hydrolysis to candoxatrilat, in mouse, dog and man. A complementary intravenous study in man with [14C]-candoxatrilat showed that the active drug was virtually completely renally cleared. Neither candoxatril nor candoxatrilat underwent chiral inversion in man. 3. Systemic availability of candoxatrilat from the oral prodrug was estimated to be 88, 53, 42, 17 and 32% in mouse, rat, rabbit, dog and man respectively. Plasma clearance of candoxatril was too rapid to enable pharmacokinetic parameter calculation in mouse and rabbit; for man, the apparent oral clearance was 57.9 ml/min/kg and the elimination half-life was 0.46 h. 4. For intravenous candoxatrilat, total plasma clearance values were 32, 15, 5.5, 5.8 and 1.9 ml/min/kg for mouse, rat, rabbit, dog and man respectively. Renal clearance values were 8.7, 7.2, 2.9 and 1.7 ml/min/kg for mouse, rat, dog and man and these approximate to the respective glomerular filtration rates. Allometric scaling with respect to bodyweight across the species allowed reasonable prediction of the above two clearance parameters in man.


Tracing sexual identities in "old age": gender and seniority in advice literature of the early-modern and modern periods.
Thus far, historians have interpreted representations of elderly women with reference to women's roles or to women's positions in society. This article proposes a different approach toward gender: to relate representations of the aged to the sexual identities of both men and women. This article analyzes representations of old age in conduct books of the early-modern period and the nineteenth century. By drawing a comparison, the eighteenth-century change of "identity regime" in European culture is brought to the fore. The article points to the influence of sexual identities on the representations of senior persons in advice literature both in Dutch and translated into Dutch.


Development of Novel Epoxyketone-Based Proteasome Inhibitors as a Strategy To Overcome Cancer Resistance to Carfilzomib and Bortezomib.
Over the past 15 years, proteasome inhibitors (PIs), namely bortezomib, carfilzomib (Cfz) and ixazomib, have significantly improved the overall survival and quality-of-life for multiple myeloma (MM) patients. However, a significant portion of MM patients do not respond to PI therapies. Drug resistance is present either de novo or acquired after prolonged therapy through mechanisms that remain poorly defined. The lack of a clear understanding of clinical PI resistance has hampered the development of next-generation PI drugs to treat MM patients who no longer respond to currently available therapies. Here, we designed and synthesized novel epoxyketone-based PIs by structural modifications at the P1' site. We show that a Cfz analog, 9, harboring a hydroxyl substituent at its P1' position was highly cytotoxic against cancer cell lines displaying de novo or acquired resistance to Cfz. These results suggest that peptide epoxyketones incorporating P1'-targeting moieties may have the potential to bypass resistance mechanisms associated with Cfz and to provide additional clinical options for patients resistant to Cfz.


Predictive Values of the New Sarcopenia Index by the Foundation for the National Institutes of Health Sarcopenia Project for Mortality among Older Korean Adults.
We evaluated the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project's recommended criteria for sarcopenia's association with mortality among older Korean adults. We conducted a community-based prospective cohort study which included 560 (285 men and 275 women) older Korean adults aged ≥65 years. Muscle mass (appendicular skeletal muscle mass-to-body mass index ratio (ASM/BMI)), handgrip strength, and walking velocity were evaluated in association with all-cause mortality during 6-year follow-up. Both the lowest quintile for each parameter (ethnic-specific cutoff) and FNIH-recommended values were used as cutoffs. Forty men (14.0%) and 21 women (7.6%) died during 6-year follow-up. The deceased subjects were older and had lower ASM, handgrip strength, and walking velocity. Sarcopenia defined by both low lean mass and weakness had a 4.13 (95% CI, 1.69-10.11) times higher risk of death, and sarcopenia defined by a combination of low lean mass, weakness, and slowness had a 9.56 (3.16-28.90) times higher risk of death after adjusting for covariates in men. However, these significant associations were not observed in women. In terms of cutoffs of each parameter, using the lowest quintile showed better predictive values in mortality than using the FNIH-recommended values. Moreover, new muscle mass index, ASM/BMI, provided better prognostic values than ASM/height2 in all associations. New sarcopenia definition by FNIH was better able to predict 6-year mortality among Korean men. Moreover, ethnic-specific cutoffs, the lowest quintile for each parameter, predicted the higher risk of mortality than the FNIH-recommended values.


Contralateral prophylactic mastectomy and implications for breast reconstruction.
Contralateral prophylactic mastectomy (CPM) rates have continued to rise in the United States, impacting all stakeholders including plastic and reconstructive surgeons. Multiple factors may be influencing this trend, including patient decision-making characteristics, knowledge about breast cancer disease and prognosis, advances in genetic testing and enhanced imaging capabilities, sociodemographic factors, and access to specialty surgical services such as breast reconstruction. In this review, the authors shed light on the current state of CPM and summarize the literature analyzing its increasing prevalence in the United States, as well as outline future directions for study and dissemination of knowledge from providers to patients surrounding this important and complex treatment decision.


Depression in primary care: assessing suicide risk.
Major depression is a common condition seen in the primary care setting. This article describes the suicide risk assessment of a depressed patient, including practical aspects of history-taking, consideration of factors in deciding if a patient requires immediate transfer for inpatient care and measures to be taken if the patient is not hospitalised. It follows on our earlier article about the approach to management of depression in primary care.


Psychoanalysis and cognitive-evolutionary psychology: an attempt at integration.
The authors argue that the abandonment of the theory of trauma in 1897 was a trauma for Freud himself, who was led to 'despair', and possibly reacted with an overemphasis on inner fantasies and drive discharge. They suggest that today we are facing a second trauma in the history of psychoanalysis that we might call the 'abandonment of drive theory', i.e. the notion that human beings strive not primarily to reduce sexual and aggressive drives but rather seek objects, assign meanings, test previous beliefs and assimilate new schemes. Our task is to recover as Freud was able to do, giving a new impetus to psychoanalysis. The current challenge is, on the one hand, a revision of the psychoanalytic conception of inherited information, and, on the other, a theory of motivation based on converging evidence from cognitive science, ethology, infant research and psychotherapy research. Many clinical models are current in contemporary psychoanalysis. Only as one example among these models, some concepts used in Weiss & Sampson's 'Control-Mastery Theory' will be discussed in light of cognitive science and evolutionary epistemology within the framework of (a) the 1960 classic, 'Plans and Structure of Behavior' by Miller, Galanter and Pribram (b) Edelman's neurobiological theory and (c) Bowlby's attachment theory.


Resection and reconstruction of giant cervical metastatic cancer using a pectoralis major muscular flap transfer: A prospective study of 16 patients.
If not promptly or properly treated, certain cervical metastatic cancers that develop from unknown primary tumors may rapidly grow into giant tumors that can invade the blood vessels, muscle and skin. The present study examined the feasibility and efficacy of radical neck dissection combined with reconstruction using the pectoralis major myocutaneous flap for the treatment of giant cervical metastatic cancers that have developed from unknown primary tumors and have invaded the skin. A total of 16 patients who met the inclusion criteria were subjected to radical neck dissection to adequately resect invaded skin, and the pectoralis major myocutaneous flap was used to repair the large skin defect created in the cervical region. Following the surgery, the patients received concurrent chemoradiotherapy. The pectoralis major myocutaneous flap survived in all 16 patients, with no cases of flap necrosis. In addition, no post-operative lymphedema, paresthesia or dysfunction of an upper extremity occurred due to the cutting of a pectoralis major muscle. In 9 cases, patients were satisfied with their post-operative shoulder movement at the donor site; in the remaining 7 cases, patients felt greater weakness in this region following surgery relative to prior to surgery. The 14 male patients were generally satisfied with the post-operative appearance of the donor region, whereas the 2 female patients were dissatisfied with the appearance of this region. Follow-up for 6-53 months after the patients were discharged following surgery and chemotherapy revealed that the recurrence of cervical tumors in 6 cases. Overall, radical neck dissection combined with the use of the pectoralis major myocutaneous flap for reconstruction is a feasible approach for the treatment of giant cervical metastatic cancers that have developed from unknown primary tumors and have invaded the skin. Post-operative concurrent chemoradiotherapy should be administered to improve the local control rate and patient quality of life, allowing a satisfactory therapeutic efficacy to be achieved.


Maternal and child health: is making 'healthy choices' an oxymoron?
The right to exercise choice is fundamental to the Universal Declaration of Human Rights, and it is assumed that all individuals generally enjoy freedom of choice in managing their health. Yet closer examination of this assumption calls into question its credibility and validity, especially with regard to maternal and child health around the globe. We argue that the concept of individual 'healthy choice,' particularly as applied to those with inadequate support and who are relatively disempowered, is flawed and unhelpful when considering the wider social, economic, and political forces underlying poor health. We instead propose that the realistic promotion of healthy choices requires acknowledging that agency lies beyond just the individual, and that individuals need to be supported through education and other structural and policy changes that facilitate a genuine ability to make healthy choices.


Outer retinal transduction by AAV2-7m8 following intravitreal injection in a sheep model of CNGA3 achromatopsia.
Sheep carrying a mutated CNGA3 gene exhibit diminished cone function and provide a naturally occurring large animal model of achromatopsia. Subretinal injection of a vector carrying the CNGA3 transgene resulted in long-term recovery of cone function and photopic vision in these sheep. Research is underway to develop efficacious vectors that would enable safer transgene delivery, while avoiding potential drawbacks of subretinal injections. The current study evaluated two modified vectors, adeno-associated virus 2-7m8 (AAV2-7m8) and AAV9-7m8. Intravitreal injection of AAV2-7m8 carrying enhanced green fluorescent protein under a cone-specific promoter resulted in moderate photoreceptor transduction in wild-type sheep, whereas peripheral subretinal delivery of AAV9-7m8 resulted in the radial spread of the vector beyond the point of deposition. Intravitreal injection of AAV2-7m8 carrying human CNGA3 in mutant sheep resulted in mild photoreceptor transduction, but did not lead to the clinical rescue of photopic vision, while day-blind sheep treated with a subretinal injection exhibited functional recovery of photopic vision. Transgene messenger RNA levels in retinas of intravitreally treated eyes amounted to 4-23% of the endogenous CNGA3 levels, indicating that expression levels >23% are needed to achieve clinical rescue. Overall, our results indicate intravitreal injections of AAV2.7m8 transduce ovine photoreceptors, but not with sufficient efficacy to achieve clinical rescue in CNGA3 mutant sheep.


Transoral laser microsurgery (TLM) +/- adjuvant therapy for advanced stage oropharyngeal cancer: outcomes and prognostic factors.
Document survival, prognostic variables, and functional outcomes of patients with AJCC stage III or IV oropharyngeal cancer, treated with transoral laser microsurgery (TLM) +/- adjuvant therapy. Analysis of prospectively assembled data pertaining to the above-described patient cohort. Patients treated with TLM for AJCC stage III or IV oropharyngeal cancer at Washington University School of Medicine from 1996 to 2006 were followed for a minimum of 2 years. Recurrence, survival, functional, and human papilloma virus data were analyzed. Eighty-four patients met inclusion criteria. Mean follow-up was 52.6 months. Overall AJCC stages were: III 15% and IV 85%. T stages were T1-2, 74%; T3-4, 26%. Eighty-three patients underwent neck dissection, 50 received adjuvant radiotherapy, and 28 received adjuvant chemoradiotherapy. Overall survival at 2 and 5 years was 94% and 88%, respectively. Disease-specific survival at 2 and 5 years was 96% and 92%, respectively. Six patients recurred (7%): locally (one), regionally (four), and distant (five). T stage, positive margins, and p16 status significantly impacted survival. The addition of adjuvant chemotherapy in high-risk patients did not significantly impact survival. Five patients (6%) had major surgical complications, but without mortality. Eighty-one percent of patients had acceptable swallowing function at last follow-up. Immediately postoperatively, 17% required G-tubes, which dropped to 3.4% of living patients at 3 years. In this population, our findings validate TLM +/- adjuvant therapy as a highly effective strategy for survival, locoregional control, and swallowing recovery in AJCC stage III and IV oropharyngeal cancer. Our finding also show that p16 positivity improves survival.


Individual Alpha Peak Frequency, an Important Biomarker for Live Z-Score Training Neurofeedback in Adolescents with Learning Disabilities.
Learning disabilities (LDs) have an estimated prevalence between 5% and 9% in the pediatric population and are associated with difficulties in reading, arithmetic, and writing. Previous electroencephalography (EEG) research has reported a lag in alpha-band development in specific LD phenotypes, which seems to offer a possible explanation for differences in EEG maturation. In this study, 40 adolescents aged 10-15 years with LDs underwent 10 sessions of Live Z-Score Training Neurofeedback (LZT-NF) Training to improve their cognition and behavior. Based on the individual alpha peak frequency (i-APF) values from the spectrogram, a group with normal i-APF (ni-APF) and a group with low i-APF (li-APF) were compared in a pre-and-post-LZT-NF intervention. There were no statistical differences in age, gender, or the distribution of LDs between the groups. The li-APF group showed a higher theta absolute power in P4 (p = 0.016) at baseline and higher Hi-Beta absolute power in F3 (p = 0.007) post-treatment compared with the ni-APF group. In both groups, extreme waves (absolute Z-score of ≥1.5) were more likely to move toward the normative values, with better results in the ni-APF group. Conversely, the waves within the normal range at baseline were more likely to move out of the range after treatment in the li-APF group. Our results provide evidence of a viable biomarker for identifying optimal responders for the LZT-NF technique based on the i-APF metric reflecting the patient's neurophysiological individuality.


Influence of body composition on bone mass in postmenopausal osteoporotic women.
We aimed at evaluating the relationship of lean and fat mass to bone mass in osteoporotic postmenopausal women. We invited 65 women who were being treated at the São Paulo Hospital osteoporosis outpatients' clinic to participate. Body composition and bone mineral density (BMD) measurements were performed using Dual-energy X-ray absorptiometry methodology (DXA). The mean age and weight were 69.7±6.4 years and 56.3±7.6 kg, respectively. Accordingly to the body mass index (BMI), 52.8% were of normal weight and 47.1% of the patients were overweight. Overweight women had significantly higher bone mass. Similarly, skeletal muscle index (SMI) showed a positive effect on BMD measurements and women with sarcopenia had significantly lower BMD measurements in total femur and femoral neck. In multiple regression analysis only lean mass and age, after adjustments to fat mass and BMI, were able to predict total body bone mineral content (BMC) (R(2)=28%). Also lean mass adjusted to age and BMI were able to predict femoral neck BMD (R(2)=14%). On the other hand, none of the components of the body composition (lean mass or fat mass) contributed significantly to explaining total femur BMD and neither body composition measurements were associated with spine BMD. These findings suggest that lean mass has a relevant role in BMC and BMD measurements. In addition, lower BMI and lean mass loss (sarcopenia) is associated to lower BMC and BMD of femoral neck and total femur and possible higher risk of osteoporotic fracture.


Effect of emotional regulation training on depression, anxiety and stress among the patients with alcohol dependence admitted in selected de-addiction centers at south India.
Background The purpose of the study was to assess the effect of emotional regulation training on depression, anxiety, and stress among patients with alcohol dependence. Depression, anxiety, and stress are very common negative emotions seen in the patients with alcohol dependence which leads to relapse of the condition. The emotional regulation could help the individuals to overcome the negative emotions. Methods The present study adopted a one-group pretest and posttest in a preexperimental design. A total of 30 patients with alcohol dependence in two de-addiction centers were recruited using a convenience sampling technique. In this study, the participant received the intervention of emotional regulation training for 13 days to overcome negative emotions. On the 14th-day posttest was conducted. Results There was a statistically significant difference found in the mean scores of depression, anxiety, and stress at p<0.001 level between the pre and posttest. There was no significant association found between the scores of depression, anxiety, stress, and any of the background variables of the patients with alcohol dependence throughout the pretest and posttest. Conclusions The study proved that emotional regulation training is an effective intervention in reducing negative emotions like depression, anxiety, and stress among patients with alcohol dependence.


Comparative Aspects of Canine Melanoma.
Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.


A red-dot-blot protein assay technique in the low nanogram range.
A simple, sensitive, rapid (3 min), and highly reproducible solid-phase assay for the detection of proteins in the low nanogram range (4 ng) is described. The assay is based on differential Ponceau S staining of the protein spots on nitrocellulose and quantification of the protein-dye complexes on lubricated membranes using a densitometer. The dye solution used for protein staining contained 0.1% Ponceau S in 15% phosphoric acid and 10% ethanol. Proteins were directly spotted onto pre-Ponceau S-stained nitrocellulose membranes, cross-linked with glutaraldehyde, rinsed in NaOH, restained with Ponceau S, and finished by rinsing in acid water at pH 3. Dry membranes were lubricated with mineral oil to achieve brightness of the colored spots before scanning with a densitometer at 560 nm. The assay shows tolerance to extreme acidic and basic buffer conditions and no significant protein-to-protein variations were observed. The effects of detergent contaminants and various other reagents such as polyethylene glycol, mercaptoethanol, and urea were also tested in the assay. The nonionic detergent, digitonin, and the anionic detergent, sodium dodecyl sulfate, up to 1%, and Triton X-100 up to 0.25% do not interfere with the assay. Efficacy of the assay was tested for five different proteins and the sensitivity was compared with the most widely used method of Bradford's.


Recombinant mumps viruses expressing the batMuV fusion glycoprotein are highly fusion active and neurovirulent.
A recent study reported the detection of a bat-derived virus (BatPV/Epo_spe/AR1/DCR/2009, batMuV) with phylogenetic relatedness to human mumps virus (hMuV). Since all efforts to isolate infectious batMuV have reportedly failed, we generated recombinant mumps viruses (rMuVs) in which the open reading frames (ORFs) of the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins of an hMuV strain were replaced by the corresponding ORFs of batMuV. The batMuV F and HN proteins were successfully incorporated into viral particles and the resultant chimeric virus was able to mediate infection of Vero cells. Distinct differences were observed between the fusogenicity of rMuVs expressing one or both batMuV glycoproteins: viruses expressing batMuV F were highly fusogenic, regardless of the origin of HN. In contrast, rMuVs expressing human F and bat-derived HN proteins were less fusogenic compared to hMuV. The growth kinetics of chimeric MuVs expressing batMuV HN in combination with either hMuV or batMuV F were similar to that of the backbone virus, whereas a delay in virus replication was obtained for rMuVs harbouring batMuV F and hMuV HN. Replacement of the hMuV F and HN genes or the HN gene alone by the corresponding batMuV genes led to a slight reduction in neurovirulence of the highly neurovirulent backbone strain. Neutralizing antibodies inhibited infection mediated by all recombinant viruses generated. Furthermore, group IV anti-MuV antibodies inhibited the neuraminidase activity of bat-derived HN. Our study reports the successful generation of chimeric MuVs expressing the F and HN proteins of batMuV, providing a means for further examination of this novel batMuV.


Evolution of a new bacterial pathway for 4-nitrotoluene degradation.
Bacteria that assimilate synthetic nitroarene compounds represent unique evolutionary models, as their metabolic pathways are in the process of adaptation and optimization for the consumption of these toxic chemicals. We used Acidovorax sp. strain JS42, which is capable of growth on nitrobenzene and 2-nitrotoluene, in experiments to examine how a nitroarene degradation pathway evolves when its host strain is challenged with direct selective pressure to assimilate non-native substrates. Although the same enzyme that initiates the degradation of nitrobenzene and 2-nitrotoluene also oxidizes 4-nitrotoluene to 4-methylcatechol, which is a growth substrate for JS42, the strain is incapable of growth on 4-nitrotoluene. Using long-term laboratory evolution experiments, we obtained JS42 mutants that gained the ability to grow on 4-nitrotoluene via a new degradation pathway. The underlying basis for this new activity resulted from the accumulation of specific mutations in the gene encoding the dioxygenase that catalyses the initial oxidation of nitroarene substrates, but at positions distal to the active site and previously unknown to affect activity in this or related enzymes. We constructed additional mutant dioxygenases to identify the order of mutations that led to the improved enzymes. Biochemical analyses revealed a defined, step-wise pathway for the evolution of the improved dioxygenases.


Large-size linear and star-shaped dihydropyrazine fused pyrazinacenes.
Linear and star-shaped pyrazinacenes 1a-b and 2 were synthesized via condensation between a new building block 11 and pyrene tetraones or cyclohexaone. Compound 2 represents the largest star-shaped dihydropyrazine fused pyrazinacene reported so far. These largely expanded pyrazinacenes show good solubility and have a strong tendency to aggregate in both solution and thin films, indicating their potential applications for organic electronic devices.


Microemulsions with timolol as potential eye drops.
Stable microemulsions oil-in-water (o/w) and water-in-oil (w/o) with timolol were obtained. These formulations were sterilized using two methods: by autoclaving and by sterile filtering according to the Polish Pharmacopeia V. Microemulsions were kept in the temperatures of 25 degrees C and 5 degrees C during three months. The following physical parameters were investigated: density, dynamic viscosity, refractive index, surface tension, pH and osmotic tension. All the microemulsions met the requirements for eye drops.


[Procalcitonin as monocytic marker for early diagnosis in septic abortion].
In search of sensitive and specific markers of systemic infection procalcitonin (PCT) recently was promoted to the focus of clinical research. Little is known about the biology of PCT and until now no data have been presented about clinical importance of PCT in obstetric patients. Daily PCT values in a 17 year old patient with septic abortion were compared with established markers of systemic inflammation. Cultivated monocytes were analyzed by the means of indirect immunofluorescence for intracellular distribution of PCT. Additionally, PCT release into culture medium was examined. PCT values in comparison with established inflammation markers was demonstrated in the patient with septic abortion. Indirect immunofluorescence studies revealed the presence of PCT within monocytes. In the supernatants of monocyte cultures PCT was detectable under control conditions. Stimulation with lipopolysaccharide resulted in the increased PCT concentrations both in the supernatants of healthy and patient monocyte cultures. In the given patient PCT was superior to other inflammation markers with regard to early and progression diagnosis. Peripheral blood monocytes appear to be a potential site of inflammation-induced PCT production. For the first time intracellular distribution pattern and release of PCT from human monocytes was described. Based on the presented data broad clinical studies devoted to PCT evaluation in obstetric patients seem to be promising. As till now the interpretation of increased PCT values depended on empirical knowledge, extensive studies of the potential production site as well as its biological significance should be performed, too.


lncRedibly versatile: biochemical and biological functions of long noncoding RNAs.
Long noncoding RNAs (lncRNAs) are transcripts that do not code for proteins, but nevertheless exert regulatory effects on various biochemical pathways, in part via interactions with proteins, DNA, and other RNAs. LncRNAs are thought to regulate transcription and other biological processes by acting, for example, as guides that target proteins to chromatin, scaffolds that facilitate protein-protein interactions and complex formation, and orchestrators of phase-separated compartments. The study of lncRNAs has reached an exciting time, as recent advances in experimental and computational methods allow for genome-wide interrogation of biochemical and biological mechanisms of these enigmatic transcripts. A better appreciation for the biochemical versatility of lncRNAs has allowed us to begin closing gaps in our knowledge of how they act in diverse cellular and organismal contexts, including development and disease.


Sterilising embryos for transgenic chimaeras.
1. Experiments were undertaken to attempt to sterilise fowl embryos with ultraviolet light. Such sterilised embryos would be useful as recipients of genetically manipulated germ cells. 2. The germinal crescents of embryos were exposed to a calibrated UV source at stages 4 and 8 to 10 of incubation for 30 s, 3 min and 10 min. Teratological and sterility effects were studied at periods up to 6 d of incubation. 3. Simply exposing embryos by opening the shell produced a number of abnormalities and mortalities. These decreased with the age of the embryo but increased with the dosage of irradiation. 4. Although there was abundant evidence for UV-induced cell damage, the sterility of the embryos was usually less than 75%.


Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia.
Histologic evaluation of low-grade or high-grade intraepithelial neoplasia (LG-IN or HG-IN) of the esophagus is important for estimating the risk of progression to invasive carcinoma. Discrimination between LG-IN and HG-IN, or neoplasia and non-neoplastic lesion (NNL), however, is occasionally difficult. This study was designed to evaluate whether cytokeratin expression can be used for discrimination of these lesions. Esophageal Iodine-unstained lesions (n=154), less than 10 mm, were classified into HG-IN, LG-IN, and NNL. These lesions together with 154 foci of normal esophageal epithelium (NEE) were examined by immunohistochemistry for cytokeratins (CK4 and CK13), p53 overexpression, and the MIB-1 labeling index. The ratios of CK4- and CK13-positive staining were scored from 1 to 3. The CK4- and CK13-positive staining ratios were decreased in NNL (73% and 78%), LG-IN (55% and 69%), and HG-IN (33% and 48%), compared to NEE (91% and 95%). The differences between LG-IN and HG-IN, neoplasia and NNL, and among these three lesions and NEE were statistically significant (p < 0.005). The cytokeratin scores correlated with the MIB-1 labeling index (both: p < 0.0001), but not with p53 overexpression. CK4 and CK13 immunohistochemistry could be an objective method for evaluating the risk for progression to invasive carcinoma.


[Eight cases of neuroendcrine carcinoma of the head and neck].
Small cell neuroendocrine carcinoma of the head and neck is rare, and diagnosis may be difficult. Malignancy is high, as is the incidence of distant metastasis. We reported eight cases of stage IV small cell neuroendocrine carcinoma of the head and neck, all in men with a mean onset age of 62 years (range: 45 to 80 years). Three cases arose from the maxillary sinus, two from the ethmoid sinus, one from the parotid gland, one from the tonsil, and one from the larynx. Histological analysis by hematoxylin-eosin staining tentatively revealed malignant lymphoma and undifferentiated carcinoma in two cases each, while immunohistological and/or electron microscopy analysis confirmed histological diagnosis. All were treated by chemotherapy (VP-16, CDDP) and seven cases with radiotherapy based on the schedule of small cell carcinoma of the lung and two cases with lesional resection. Chemotherapy and radiotherapy were effective locally. Five patients died of distant metastasis to the brain, bone, lung, liver, or skin within 12 months. One is alive with liver metastasis. Two have no evidence of disease--one for eight years and the other for one year. Long-term survival thus requires the effective treatment of distant metastasis.


Controlled decoration of nanoceria on the surface of MoS2nanoflowers to improve the biodegradability and biocompatibility inDrosophila melanogastermodel.
In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100μg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.


[Alveolar bone regeneration stimulated by a combination of platelet-rich plasma and Cerasorb graft in Beagle dogs. Histological and histomorphometric studies].
Healing of extraction wounds was examined in an animal experiment model on Beagle dogs. After bilateral extraction of the premolars of 12 dogs the alveoli were filled up with a combination of beta-tricalcium phosphate (Cerasorb) graft and platelet rich plasma (PRP) on the experimental side, and with Cerasorb alone on the control side. Biopsy specimens were taken from the regenerating bone at 6, 12 and 24 weeks after surgery for histological study. Results of the histologic and histomorphometric examinations revealed that after 6 weeks the newly formed bone was significantly denser on the experimental side. After 12 weeks this difference became moderate, and after 24 weeks the bone forming activity was nearly equal on the two sides. These results suggest that local administration of Cerasorb and PRP results in more intense bone regeneration, especially in the early phase.


Expression profile of maize (Zea mays L.) embryonic axes during germination: translational regulation of ribosomal protein mRNAs.
Seed germination is a critical developmental period for plant propagation. Information regarding gene expression within this important period is relevant for understanding the main biochemical processes required for successful germination, particularly in maize, one of the most important cereals in the world. The present research focuses on the global microarray analysis of differential gene expression between quiescent and germinated maize embryo stages. This analysis revealed that a large number of mRNAs stored in the quiescent embryonic axes (QEAs) were differentially regulated during germination in the 24 h germinated embryonic axes (GEAs). These genes belong to 14 different functional categories and most of them correspond to metabolic processes, followed by transport, transcription and translation. Interestingly, the expression of mRNAs encoding ribosomal proteins [(r)-proteins], required for new ribosome formation during this fast-growing period, remains mostly unchanged throughout the germination process, suggesting that these genes are not regulated at the transcriptional level during this developmental period. To investigate this issue further, comparative microarray analyses on polysomal mRNAs from growth-stimulated and non-stimulated GEAs were performed. The results revealed that (r)-protein mRNAs accumulate to high levels in polysomes of the growth-stimulated tissues, indicating a translational control mechanism to account for the rapid (r)-protein synthesis observed within this period. Bioinformatic analysis of (r)-protein mRNAs showed that 5' TOP (tract of pyrimidines)-like sequences are present only in the 5'-untranslated region set of up-regulated (r)-protein mRNAs. This overall approach to the germination process allows an in-depth view of molecular changes, enabling a broader understanding of the regulatory mechanisms that occur during this process.


In ovo green light photostimulation during the late incubation stage affects somatotropic axis activity.
Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.


Perceived barriers by university students in the practice of physical activities.
The main goal of this research is to study in detail the main characteristics of university students in order to find out the reasons why they have adopted an inactive lifestyle. In order to do so, a questionnaire on the analysis of sports habits and lifestyle was given to 323 students. They were taken from a representative sample of 1834 students. These 323 students had pointed out at the moment of the fieldwork, not having practiced any sport in their spare time. Our findings point out that there are diverse reasons for this. On one hand, reasons referred to as external barriers such as lack of time, on the other hand, internal barriers such as not liking the physical activity, not seeing its practicality or usefulness, feeling lazy or with apathy, or thinking that they are not competent in this type of activities. Other reasons such as the lack of social support are grouped within the external barriers. Finally, it is important to stress that there are also differences based on gender with respect to motivation. Key pointsExternal barriers prevail in university students. The lack of time is among the most highlighted ones.Statistically significant results have been found regarding the gender variable.The results are very important since they are considered to be valuable information for university institutions when guiding and diversifying their offer of physical and sport activities. Also as a guide in the design of support policies and national sport management guidelines.


High-Throughput Assessment of Kinome-wide Activation States.
Aberrant kinase activity has been linked to a variety of disorders; however, methods to probe kinase activation states in cells have been lacking. Until now, kinase activity has mainly been deduced from either protein expression or substrate phosphorylation levels. Here, we describe a strategy to directly infer kinase activation through targeted quantification of T-loop phosphorylation, which serves as a critical activation switch in a majority of protein kinases. Combining selective phosphopeptide enrichment with robust targeted mass spectrometry, we provide highly specific assays for 248 peptides, covering 221 phosphosites in the T-loop region of 178 human kinases. Using these assays, we monitored the activation of 63 kinases through 73 T-loop phosphosites across different cell types, primary cells, and patient-derived tissue material. The sensitivity of our assays is highlighted by the reproducible detection of TNF-α-induced RIPK1 activation and the detection of 46 T-loop phosphorylation sites from a breast tumor needle biopsy.


Aetiology of severe community acquired pneumonia in adults identified by combined detection methods: a multi-centre prospective study in China.
Severe Community Acquired Pneumonia (SCAP) challenges public health globally. Considerable improvements in molecular pathogen testing emerged in the last few years. Our prospective study combinedly used traditional culture, antigen tests, PCR and mNGS in SCAP pathogen identification with clinical outcomes. From June 2018 to December 2019, we conducted a multi-centre prospective study in 17 hospitals of SCAP patients within 48 hours of emergency room stay or hospitalization in China. All clinical data were uploaded into an online database. Blood, urine and respiratory specimens were collected for routine culture, antigen detection, PCR and mNGS as designed appropriately. Aetiology confirmation was made by the local attending physician group and scientific committee according to microbiological results, clinical features, and response to the treatment. Two hundred seventy-five patients were included for final analysis. Combined detection methods made identification rate up to 74.2% (222/299), while 14.4% (43/299) when only using routine cultures and 40.8% (122/299) when not using mNGS. Influenza virus (23.2%, 46/198), S. pneumoniae (19.6%, 39/198), Enterobacteriaceae (14.6%, 29/198), Legionella pneumophila (12.6%, 25/198), Mycoplasma pneumoniae (11.1%, 22/198) were the top five common pathogens. The in-hospital mortality of patients with pathogen identified and unidentified was 21.7% (43/198) and 25.9% (20/77), respectively. In conclusion, early combined detection increased the pathogen identification rate and possibly benefitted survival. Influenza virus, S. pneumoniae, Enterobacteriaceae was the leading cause of SCAP in China, and there was a clear seasonal distribution pattern of influenza viruses. Physicians should be aware of the emergence of uncommon pathogens, including Chlamydia Psittaci and Leptospira.


Changes of blood pressure, serum inflammatory factors and endothelin levels in patients with hypertension under rehabilitative aerobic exercise.
The aim of this study was to evaluate the effects of rehabilitative aerobic exercise on blood pressure, serum inflammatory factors, endothelin and quality of life in patients with hypertension. Ninety patients with mild hypertension visiting West China Hospital of Sichuan University from June 2017 to December 2017 were enrolled and randomly divided into an experimental group and a control group. Patients in both groups were given a low-salt diet, and the experimental group was given an extra three-month treadmill training. Systolic blood pressure (SBP), diastolic blood pressure (DBP), serum tumor necrosis factor α (TNF-α), serum interleukin-6 and endothelin-1, body mass index (BMI), triglyceride (TG) and other indicators were examined in both groups before and after exercise, SF-36 scale was used to evaluate the quality of life. The results showed that after 3 months of exercise, SBP and DBP in the experimental group were significantly lower than those in the control group (P less than 0.05). Compared with the control group, the concentrations of TNF-α, interleukin-6 and endothelin-1 in the experimental group were significantly decreased (P less than 0.05). Correlation analysis showed that IL-6 was positively correlated with SBP (P less than 0.05), and TNF-α and ET-1 were positively correlated with diastolic blood pressure (P less than 0.05). The general health status, energy, mental health, social function, emotional function and health changes of the experimental group were significantly improved compared with before exercise (P less than 0.05). In conclusion, rehabilitative aerobic exercise can lower blood pressure and improve the overall quality of life in mild hypertension patients by inhibiting vascular inflammation and lowering plasma endothelin-1.


Immunosuppressive treatment affects cardiac and skeletal muscle mitochondria by the toxic effect of vehicle.
In order to examine whether immunosuppressive treatment could be responsible for the reduced exercise capacity of heart transplant recipients (HTR), we studied the effects of long-term immunosuppressive treatment with cyclosporin A (CsA) and its vehicle (2/3 cremophor and 1/3 alcohol diluted in olive oil) on in situ mitochondrial respiration of different muscles. Rats were fed for 3 weeks with 10 or 25 mg/kg/day CsA in its vehicle (CsA10 and CsA25 groups), or vehicle or H(2)O. Oxygen consumption rate was measured in saponin skinned fibers without (V(0)) and with ADP until maximal respiration (V(max)) was reached and K(M)for ADP as well as V(max)were calculated using non-linear fit of the Michaelis-Menten equation. In the cardiac muscle of the CsA25 group, V(0)and V(max)were decreased by immunosuppressive treatment respectively from 6.33+/-0.51 to 3.18+/-0.3micromol O(2)/min/g dw (P<0.001) and from 29.0+/-1.5 to 18.1+/-1.6micromol O(2)/min/g dw (P<0.001), an effect which could be entirely attributed to the vehicle itself, with no difference between CsA10 and CsA25. Regulation of cardiac mitochondrial respiration by ADP was altered by vehicle with the K(M)for ADP decreasing from 371+/-37 to 180+/-21microm(P<0.001). A similar trend was observed in the diaphragm or soleus, although to a lesser extent. In contrast, V(0)and V(max)decreased in glycolytic gastrocnemius muscle respectively from 1.7+/-0.2 to 0.94+/-0.14 (P<0. 01) and from 6.8+/-0.3 to 5.1+/-0.4micromol O(2)/min/g dw (P<0.001) in the CsA25 group, but the main effects could be attributed to CsA itself. It was concluded that immunosuppressive treatment induces a deleterious effect on cardiac and skeletal muscle oxidative capacities, mainly due to cremophor, the main component of vehicle.


Inverse Renormalization Group in Quantum Field Theory.
We propose inverse renormalization group transformations within the context of quantum field theory that produce the appropriate critical fixed point structure, give rise to inverse flows in parameter space, and evade the critical slowing down effect in calculations pertinent to criticality. Given configurations of the two-dimensional ϕ^{4} scalar field theory on sizes as small as V=8^{2}, we apply the inverse transformations to produce rescaled systems of size up to V^{'}=512^{2} which we utilize to extract two critical exponents. We conclude by discussing how the approach is generally applicable to any method that successfully produces configurations from a statistical ensemble and how it can give novel insights into the structure of the renormalization group.


Identification and characterization of a gene cluster for synthesis of the polyketide antibiotic 2,4-diacetylphloroglucinol from Pseudomonas fluorescens Q2-87.
The polyketide metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) is produced by many strains of fluorescent Pseudomonas spp. with biocontrol activity against soilborne fungal plant pathogens. Genes required for 2,4-DAPG synthesis by P. fluorescens Q2-87 are encoded by a 6.5-kb fragment of genomic DNA that can transfer production of 2,4-DAPG to 2,4-DAPG-nonproducing recipient Pseudomonas strains. In this study the nucleotide sequence was determined for the 6.5-kb fragment and flanking regions of genomic DNA from strain Q2-87. Six open reading frames were identified, four of which (phlACBD) comprise an operon that includes a set of three genes (phlACB) conserved between eubacteria and archaebacteria and a gene (phlD) encoding a polyketide synthase with homology to chalcone and stilbene synthases from plants. The biosynthetic operon is flanked on either side by phlE and phlF, which code respectively for putative efflux and regulatory (repressor) proteins. Expression in Escherichia coli of phlA, phlC, phlB, and phlD, individually or in combination, identified a novel polyketide biosynthetic pathway in which PhlD is responsible for the production of monoacetylphloroglucinol (MAPG). PhlA, PhlC, and PhlB are necessary to convert MAPG to 2,4-DAPG, and they also may function in the synthesis of MAPG.


Thermal radiation in metabolic chambers.
Emissivities and ratios of surface areas of metabolic chambers and their contents have been usually ignored in studies of the metabolic rates of animals. Failure to take these factors into account can lead to errors in the interpretation of results.


Metabolism of arachidonic acid by human epidermal cells depends upon maturational stage.
Synthesis of 12- and/or 15-HETE by human epidermal cells was investigated after separating basal cells from suprabasal epidermal cell layers. We found that the main metabolite of 3H-arachidonic acid (3H-AA), formed by freshly prepared upper epidermal layers (stratum granulosum and spinosum), upon RP-HPLC co-eluted with authentic 3H-12-HETE. A 3H-15-HETE co-eluting peak selectively occurred in chromatograms obtained from supernatants of fractions containing basal cells. Supernatants of freshly prepared suspensions rich in basal keratinocytes appeared to contain 3H-15-HETE as their main 3H-AA metabolite, by far exceeding the recovered amounts of 3H-12-HETE. Moreover, keratinocytes cultured for 1 week or longer were found to produce predominantly a 3H-AA metabolite co-eluting with 3H-15-HETE. In supernatants of cultured cells, little if any 3H-12-HETE was detectable. Cultured human skin fibroblasts were not found to produce relevant amounts of HETE. Genuine tissue rich in basal cells, i.e., cells of hair follicles, were found to form twice as much 3H-15-HETE as 3H-12-HETE (3H-15-HETE/3H-12-HETE-ratio = 1.9 +/- 0.8; n = 7). Apparently, different epidermal layers are able to produce a characteristic pattern of 3H-AA metabolites. 3H-15-HETE generation seems to be a marker for proliferating keratinocytes, whereas 3H-12-HETE formation appears to be typical for differentiating suprabasal epidermal cells. Our results may explain the heretofore varying patterns of AA-metabolites by keratinocytes reported in the literature.


Direct integration of the inverse Radon equation for X-ray computed tomography.
A new mathematical appoach using the inverse Radon equation for restoration of images in problems of linear two-dimensional x-ray tomography is formulated. In this approach, Fourier transformation is not used, and it gives the chance to create the practical computing algorithms having more reliable mathematical substantiation. Results of software implementation show that for especially for low number of projections, the described approach performs better than standard X-ray tomographic reconstruction algorithms.


[Erythermalgia and type 1 diabetes: diagnosis and management issues. A case report].
Erythermalgia is a very rare acrosyndrome mainly characterized by lower limbs pain. It is either primitive or secondary. Concomittence of erythermalgia and diabetes is a coincidence and since the latter induces neuropathic and vascular lesions, erythermalgia is then considered as a consequence. We report the case of a young type 1 diabetic patient who presents with severe form of erythermalgia. Through this case report and a review of the literature, we shall explain the etiopathogenic mecanisms involved in erythermalgia in a diabetic patient and highlight the diagnosis and management challenges.


Receptive and expressive language function of children with symptomatic HIV infection and relationship with disease parameters: a longitudinal 24-month follow-up study.
To longitudinally assess the receptive and expressive language functioning of children with symptomatic HIV disease and to explore the relationship between immune status, computed tomography (CT) brain scan abnormalities, and language dysfunction over time. Children with symptomatic HIV infection were administered an age-appropriate standardized comprehensive language test and general cognitive measure prior to starting antiretroviral therapy (n = 44) and again after 6 months (n = 29) and 24 months (n = 17). CD4 percentage and CT brain scans were also obtained at each evaluation. Expressive language was significantly more impaired than receptive language at the baseline, 6- and 24-month evaluations. No significant changes over time were found in receptive or expressive language from baseline to after 6 months of antiretroviral therapy, but despite treatment, language scores declined significantly between 6 and 24 months. Overall cognitive function, however, remained stable from baseline to 24 months. Age-adjusted CD4 percentage increased significantly over the initial 6 months, then remained stable. Overall CT brain scan severity ratings did not change significantly over 24 months. Expressive language was consistently more impaired than receptive language over 24 months, further supporting an earlier finding that expressive language was differentially affected by HIV in children with symptomatic disease. Both receptive and expressive language declined significantly after 24 months despite antiretroviral therapy, although overall cognitive function remained stable. Thus, functioning in some domains may be more vulnerable to the effects of HIV and global measures of cognitive ability may mask such differential changes in specific brain functions.


Gas chromatographic determination of glutaraldehyde in the workplace atmosphere after derivatization with 0-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine on a solid-phase microextraction fibre.
Glutaraldehyde is used primarily in hospital environments for the disinfection of various instruments (e.g., endoscopes). We describe in this paper the measurement of glutaraldehyde in a hospital environment using solid-phase microextraction. The method includes, prior to sampling, the adsorption of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine on to the fibre (with polydimethylsiloxane-divinylbenzene). The fibre is then exposed to air, after which desorption is performed in the GC injection port. This process results in the formation of a stable derivative of the glutaraldehyde that is suitable for chromatographic purposes and detectable with classical detection methods, such as flame ionisation and electron-capture detection. We demonstrate that the procedure of adsorption, thermal desorption and derivatization is robust and reproducible. We were able to detect concentrations of 60 microg/m3 (10 s sampling) or 6 microg/m3 (120 s sampling) by electron-capture detection, and 80 microg/m3 (120 s sampling) by flame ionisation detection. We compared our method to currently existing methods of glutaraldehyde measurement and highlighted several important advantages of the method.


Increasing the Therapeutic Potential of Stem Cell Therapies for Critical Limb Ischemia.
Peripheral Arterial Disease (PAD) is a progressive, atherosclerotic disease that at its end stage, Critical Limb Ischemia (CLI), results in severely diminished limb perfusion and causes leg pain at rest, non-healing ulcers, and tissue gangrene. Many patients with CLI fail current medical and surgical therapies and thus are deemed "no option" and require limb amputation. Novel therapies to attempt limb salvage in these "no option" patients are needed. Stem cell therapy is one therapeutic angiogenic avenue that has been tested over the last 20 years. To date, clinical trials have shown promise but with only modest improvement and none demonstrated a significant decrease in amputation rates in those treated with stem cell therapy. Thus, recent investigations into improving stem cell therapy have been the focus of our laboratory and many others. This review aims to describe recent advances in increasing the therapeutic potential of stem cell therapies for CLI.


[A preliminary study of biochemistry of patients with crystalline retinopathy].
To investigate the pathogenesis and biochemical changes of crystalline retinopathy by detecting and analyzing the levels of trace elements (Cu++ and Zn++), blood-lipids and free amino acids in the serum of patients. Blood samples of 10 patients with crystalline retinopathy and 30 normal subjects were collected. The levels of serum Cu++ and Zn++ were detected by using flame atomic absorption spectrometry, while cholesterol and triglyceride were detected by direct colordeveloping process and acetyl-acetone developing process respectively and serum amino acids by the Beckman amino acid analyzer. In comparison with the normal control group, the level of Zinc in serum was much decreased in the crystalline retinopathy group, while Cu++/Zn++ ratio and total cholesterol level in serum were significantly increased. In 3 out of 4 patients the level of taurine is lower than that of control group. The decrease of serum trace elements and taurine and the increase of cholesterol may be one of the important factors for the pathological changes of crystalline retinopathy. The administration of trace elements e. g. Zn++ and taurine might be a new therapy for the patients.


Rapid identification of Staphylococcus aureus directly from Bactec blood culture broth by the BinaxNOW S. aureus test.
The BinaxNOW Staphylococcus aureus testing showed sensitivity, specificity, and positive and negative predicative values of 97.6%, 100%, 100%, and 98.4%, respectively, for identification of S. aureus from Bactec blood culture broth. Importantly, the test performed equally well on aerobic and anaerobic culture broth.


Procedural pain management for children receiving physiotherapy.
This article provides an overview of literature relevant to the prevention and relief of pain and distress during physiotherapy procedures, with guidance for physiotherapists treating children. Physiotherapists are generally well trained in assessing and managing pain as a symptom of injury or disease, but there is a need to improve the identification and management of pain produced by physiotherapy procedures such as stretching and splinting. In contrast to physiotherapy, other health care disciplines, such as dentistry, nursing, paediatrics, emergency medicine, and paediatric psychology, produce extensive literature on painful procedures. Procedural pain in children is particularly important because it can lead to later fear and avoidance of necessary medical care. We emphasize the need for physiotherapists to recognize procedural pain and fear in the course of treatment using verbal, nonverbal, and contextual cues. We present many methods that physiotherapists can use to prevent or relieve procedural pain and fear in paediatric patients and provide an example of a simple, integrated plan for prevention and relief of distress induced by painful procedures.


Switchable regioselection of C-H thiolation of indoles using different TMS counterions.
A switchable regioselectivity in C-H thiolation reaction by simply swapping the counteranions of TMS is reported here for the first time. An exclusive C3-H thiolation of indoles with sodium arylsulfinates was achieved in the presence of TMSCl as a promoter. In contrast, with the use of TMSOTf instead of TMSCl under otherwise identical conditions, a regiospecific C2-H thiolation of indoles was realized with the same set of substrates.


High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women.
Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4-4.5 μIU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima-media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 μIU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 μIU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 μIU/ml were the only significant predictors of PWV (TSH, β-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature.


Prediction of adenocarcinoma development using game theory.
Recent research shows that gene expression changes appear to correlate well with the progression of many types of cancers. Using changes in gene expression as a basis, this paper proposes a data-driven 2-player game-theoretic model to predict the risk of adenocarcinoma based on Nash equilibrium. A key innovation in this work is the pay-off function which is a weighted composite of the expression of a cohort of tumor-suppressor genes (as one player) and an analogous cohort of oncogenes (as the other player). Another novelty of the model is its ability to predict the risk that a healthy sample will develop adenocarcinoma, if its associated gene expression is comparable to that of early-stage tumor samples. The model is validated using two of the largest publicly available adenocarcinoma datasets. The results show that i) the model is able to distinguish between healthy and cancerous samples with an accuracy of 93%, and ii) 95% of the healthy samples said to be at risk had gene expressions comparable to those of samples with stage I or stage II tumors, thereby predicting the imminent onset of adenocarcinoma.