Performance of children on symptom validity tests: TOMM, MSVT, and FIT.
Symptom validity testing is a major topic in the field of neuropsychological research, but until now, few studies focus on effort testing in children. Three symptom validity tests (SVTs), the Medical Symptom Validity Test, the Test of Memory Malingering, and the Fifteen Item Test plus several standard neuropsychological tests were administered to 73 German-language school children from 6 to 11 years. Participants were either instructed to give full effort or to follow a malingering scenario. It could be demonstrated that, except for one child, all participants with a basic reading level of grade 2 were able to pass all administered SVTs according to established cutoffs for poor effort (i.e., earned a score higher than the cutoff). For the experimental malingerers, however, it was fairly difficult to act according to the scenario throughout the session. While they scored worse in the neuropsychological tests, all but one of them failed at least one SVT. The results support the use of SVTs in childhood age. More elaborate experimental designs and studies with bona-fide patients and suspected malingerers are needed in order to evaluate both the appropriateness of available effort tests and the capabilities of children to fake poor performance.


Characterization of labeled oligonucleotides using enzymatic digestion and tandem mass spectrometry.
A simple and powerful method for the determination of labeling sites on oligodeoxynucleotides (ODN) has been developed. The method is based on the finding that nuclease P1 (NP1) digestions of label-containing ODNs produce site-specific products: 5'-labeled ODNs produce label-nucleotide (L-N); 3'-labeled ODN produces phosphorylated label (pL); and a label in between the ODN termini produces pL-N. Mass spectrometry spectra of these products from the digestion mixture can be easily utilized for structural verification of labeled ODNs such as DNA probes. We also developed a method for the determination of the labeling sites of ODNs with unknown label structures. In this method, NP1 digestion products generate site-specific fragmentation patterns upon collision-induced dissociation. These patterns can be easily recognized and used for the identification of labeling sites of ODNs with unknown label structures. When an ODN is internally labeled, phosphodiesterase digestion may be used to determine the exact labeling site (sequence location). It was demonstrated that these methods can be applied for ODNs with single or multiple labels, and for ODNs with the same or different labels within an ODN.


Retraction: Application of piezoelectric nanogenerator in medicine: bio-experiment and theoretical exploration.
[This retracts the article on p. 1300 in vol. 6, PMID: 25276373.].


A water-dependent reversible photoacidity strategy for cancer treatment.
In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which contained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) has been found, in which the proton is not dissociated from TQs-Th-PEG5 itself but from a water locked by TQs-Th-PEG5 under the irradiation of a 660 nm laser. After turning off the laser, the produced acid will disappear quickly. This process is repeatable with no consumption of TQs-Th-PEG5. More importantly, water is indispensable. Furthermore, it is confirmed that there is no other element involved in the process except TQs-Th-PEG5, light and water. Excitingly, W-RPA therapy mediated by TQs-Th-PEG5 nanoparticle exhibits remarkable antitumor effect both in vitro and in vivo, especially in hypoxic tumors with diameter larger than 10 mm owing to its oxygen-independent feature. This study not only discovers a W-RPA mechanism but also provides a novel phototherapy strategy for cancer treatment.


Predicting enzyme behavior in nonconventional media: correlating nitrilase function with solvent properties.
The insolubility of nitrile substrates in aqueous reaction mixture decreases the enzymatic reaction rate. We studied the interaction of fourteen water miscible organic solvents with immobilized nitrile hydrolyzing biocatalyst. Correlation of nitrilase function with physico-chemical properties of the solvents has allowed us to predict the enzyme behavior in such non-conventional media. Addition of organic solvent up to a critical concentration leads to an enhancement in reaction rate, however, any further increase beyond the critical concentration in the latter leads to the decrease in catalytic efficiency of the enzyme, probably due to protein denaturation. The solvent dielectric constant (epsilon) showed a linear correlation with the critical concentration of the solvent used and the extent of nitrile hydrolysis. Unlike alcohols, the reaction rate in case of aprotic solvents could be linearly correlated to solvent log P. Further, kinetic analysis confirmed that the affinity of the enzyme for its substrate (K (m)) was highly dependent upon the aprotic solvent used. Finally, the prospect of solvent engineering also permitted the control of enzyme enantioselectivity by regulating enantiomer traffic at the active site.


Thermospray mass spectrometer as a quantitative specific, sensitive, detector for liquid chromatography. Its application to the analysis of pyridostigmine in human plasma.
A thermospray interface between a HPLC system and a mass spectrometer has been used to develop an assay for pyridostigmine bromide measuring plasma concentrations down to 1 ng ml-1 on a routine basis. Plasma is loaded onto an AASP reversed-phase cartridge, injected onto a HPLC system connected to a Finnigan 4500 mass spectrometer via a thermospray interface and the molecular ion monitored. A deuterated internal standard is used, but calculations with and without the internal standard show its use does not materially improve the quantitation. The precision and accuracy at the limit of quantitation is less than +/- 5% and 95-105%, respectively. The method is used to analyse samples from a bioavailability study by fully automated unattended overnight sample analysis.


Aminotransferase changes in burned patients.
The time course of serum transaminases (alanine aminotransferase and aspartate aminotransferase) has been followed in 30 selected consecutive patients presenting burn sizes ranging from 10% to 95% of the total body surface (mean 43.13) and a survival index from 0.99 to 0.00 (mean 0.59). The results show that in all the patients both transaminases change in parallel, increasing in 18 patients (60%). In nearly all patients both enzymes increase during the second week after injury and aspartate aminotransferase increases later than alanine aminotransferase. The higher transaminase levels are noted in moderately ill patients. No clear correlation between the overall increase of transaminases and the extent of burned surface area has been found. We conclude that functional liver alterations mostly contribute to the increase of serum transaminases in burns.


The management of primary rhegmatogenous retinal detachment not involving the fovea.
To establish the likelihood of, and risk factors associated with, progression of 'macula-on' retinal detachment. A multi-centre prospective observational study of patients with acute retinal detachment, not involving the fovea, was conducted over a 6-month period. Data collected included duration of symptoms, visual acuity, presence of posterior vitreous detachment, retinal drawings and subretinal fluid (SRF) distance from the fovea at a minimum of two time points. A total of 82 data sets from 15 institutions were analysed. Of 82 cases 11 (13%) demonstrated progression of fluid. Mean progression in those cases which progressed was 2.3 disc diameters (dd) and the average rate of progression was 1.80 dd/day. Binary regression analysis failed to reveal any statistically significant risk factors for progression. Multiple regression analyses were made to identify risk factors. With distance of SRF from fovea at operation as a function, distance of SRF at presentation was the only statistically significant risk factor. In all, 26% of patients underwent surgery out-of-hours. A total of 83% patients achieved a 6-week best-corrected vision of 6/9 or better. Most retinal detachments in this study did not progress within the first few days. The distance of SRF from the fovea at presentation was the only statistically significant risk factor for progression to foveal detachment.


Effects of Health Coaching on Cardiometabolic Health in Middle-Aged Adults: A Systematic Review and Meta-analysis.
To appraise and synthesize evidence on the effects of health coaching as the primary intervention on cardiometabolic health among middle-aged adults. Six electronic databases (MEDLINE, Embase, PsycINFO, CINAHL, PubMed, and the Cochrane library) were searched from inception until July 2021. Randomized controlled trials and controlled clinical trials published in English, reporting health coaching aimed to promote behavioral changes for improving cardiometabolic health among middle-aged adults were included. Studies on health coaching as secondary intervention were excluded. Two reviewers selected the articles, appraised the study quality, and extracted data independently. All kinds of outcomes related to cardiometabolic health, including health behaviors, psychological and physiological outcomes, were included. Meta-analysis was performed if three or more studies reported the same outcomes. Narrative synthesis was performed if pooling of data for meta-analysis was not feasible. Eight studies were reviewed. Most studies involved substantial risk of bias. The majority of the participants were women (99.1%). Meta-analysis showed a small but significant effect of health coaching on increasing physical activity (SMD = .34, 95% CI = .08-.60, p = .01, I2 = 0%); however, its effect on perceived barriers to physical activity and depressive symptoms was nonsignificant. Narrative synthesis yielded inconsistent results on diet, smoking, anxiety, goal achievement and self-efficacy for behavioral change, physiological outcomes, and metabolic syndrome severity, and nonsignificant effects on alcohol consumption, sleep quality, perceived benefits of physical activities, and cardiovascular symptoms. Health coaching has significant effects on increasing physical activity among middle-aged adults; however, its effects on health behaviors and risk factors related to cardiometabolic health are inconclusive. Further efforts are warranted to examine how health coaching can improve cardiometabolic health among middle-aged adults.


Benzimidazole modified silica as a novel reversed-phase and anion-exchange mixed-mode stationary phase for HPLC.
A novel stationary phase based on benzimidazole modified silica was prepared and evaluated as reversed-phase and anion-exchange mixed-mode stationary phase for high performance liquid chromatography (HPLC). Using the phase, polycyclic aromatic hydrocarbons, phthalates, anilines and phenols were respectively separated depending on formation of different types of chemical bonds like hydrogen bonding, π-π stacking, electrostatic forces and hydrophobic interactions by reversed-phase chromatography; inorganic and organic anions were also separated mainly through anion-exchange and π-π interactions by anion-exchange chromatography with high resolution and column efficiency. The proposed benzimidazole modified silica is a promising mixed-mode stationary phase for the separation of complex samples in HPLC.


The translational potential of cholesterol-based therapies for neurological disease.
Cholesterol is an important metabolite and membrane component and is enriched in the brain owing to its role in neuronal maturation and function. In the adult brain, cholesterol is produced locally, predominantly by astrocytes. When cholesterol has been used, recycled and catabolized, the derivatives are excreted across the blood-brain barrier. Abnormalities in any of these steps can lead to neurological dysfunction. Here, we examine how precise interactions between cholesterol production and its use and catabolism in neurons ensures cholesterol homeostasis to support brain function. As an example of a neurological disease associated with cholesterol dyshomeostasis, we summarize evidence from animal models of Huntington disease (HD), which demonstrate a marked reduction in cholesterol biosynthesis with clinically relevant consequences for synaptic activity and cognition. In addition, we examine the relationship between cholesterol loss in the brain and cognitive decline in ageing. We then present emerging therapeutic strategies to restore cholesterol homeostasis, focusing on evidence from HD mouse models.


Effects of extracorporeal shock wave lithotripsy on the structure and function of rabbit kidney.
An animal model was developed to investigate the effect of extracorporeal shock wave lithotripsy (ESWL) on a normal kidney. Rabbits were treated with 3,000 shock waves at 18 kV to each kidney. Blood and urine samples were collected daily before and after shock wave treatment. Serum levels of hemoglobin, creatinine, lactic dehydrogenase (LDH), creatinine phosphokinase (CPK), and total protein were determined. Urine determination of volume, total protein, hemoglobin, and creatinine were also made. All kidneys, after sacrifice, were subjected to histologic analysis. The average pre-treatment creatinine clearance of our rabbits was 8.3 ml./min. After the treatment, a significant (p less than 0.01) reduction in creatinine clearance was noted for four days. The reduction was to 0.61 ml./min. on day one, 0.87 on day two, 1.04 on day three, and so forth. Urine hemoglobin rose significantly (p less than 0.01) for the first three days from 0.0 to 1.5 gm./dl. Histologic examination at seven days showed focal subcapsular hemorrhage, tubular dilation, and interstitial hemorrhage. Histologic evaluation at two months revealed focal interstitial fibrosis. In conclusion, this study reveals that shock waves to the kidney have short term physiologic effects on renal function and permanent focal histologic effects, which do not effect long term physiologic function. Further research on the effects of ESWL on renal function and structure could be facilitated with the use of this model.


Brief antecedent assessment and treatment of tics in the general education classroom: a preliminary investigation.
The purpose of this study was to determine if specific classroom antecedents were associated with motor and vocal tics in two males diagnosed with Tourette's syndrome. A functional assessment consisting of teacher and student interviews, direct observations, brief functional analysis, and confirmatory naturalistic observations indicated that specific antecedents could be identified for each participant. Simplified habit reversal was then implemented only under the antecedent condition that resulted in the highest rate of tics. The rate of tics decreased under the specific antecedent condition as well as at other times as validated by behavioral observations conducted at random times. The discussion focuses on the utility of conducting such assessments, the methodological and applied limitations of the current study, and avenues for further research.


Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors.
Bisphosphonic acids (or bisphosphonates) have been successfully used in the clinic treatment of bone diseases for over decades. Additionally, the antiinflammatory activity of these compounds has been gaining attention. In our previous work, we synthesized and in vivo evaluated the bisphosphonic esters 1 and 2, finding a moderate edema inhibition upon oral and topical administration on BALB/c mice. Thus, in this work, the bioisosteric replacement of an amide functional group for an ester afforded the new bisphosphonates 3-6, which had a moderate oral edema inhibition (25 mg/kg dose) and a significant topical antiinflammatory activity (2 mg/ear) on BALB/c mice, with 6 being the most active hit (55.9% edema inhibition), comparable to the positive control (55.5% edema inhibition) on a TPA topical model. Next, to assess the acute toxicity of the synthesized derivatives, test animals were administered with 50-100 mg/kg of 3-6, respectively, by an oral route, and after 14 days, neither lethality nor a significative weight loss were observed. Finally, a structure-activity relationship (SAR) and a molecular docking analysis of 3-6 helped us to explain the trend observed in biological tests. Considering all these aspects, we propose the inhibition of MMP-8 and MMP-9 as a possible action mechanism of the synthesized derivatives.


Peritoneal Metastases in Colorectal Cancer: Biology and Barriers.
Advances in the molecular biology of tumor metastasis have paralleled the evolution in the management of metastatic disease from colorectal cancer. In this review, we summarize the current understanding of the mechanism of colorectal cancer metastases, in particular that of peritoneal metastases, as well as clinical data on the treatment of this disease. A review of relevant English literature using MEDLINE/PubMed on the biology of colorectal cancer metastases, determinants of oligometastasis, and use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of metastatic colorectal cancer is presented. Recognition of oligometastasis in the evolution of colorectal peritoneal metastases provides the theoretical framework for which cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy is considered. Clearly, a subset of patients benefit from peritoneal metastasectomy. Advances in cancer biology and clinical imaging promise to expand the role of cytoreductive surgery with or without intraperitoneal chemotherapy in the management of peritoneal metastases from colorectal cancer.


Accessibility and effects of binder types on the physical and energetic properties of ecological coal.
The objective of this paper was to determine the effects of binders on the physical and energetic properties of briquettes as well as their accessibility. Proximate analysis and investigation on binder cost on local market were conducted. The results show that the addition of binder increases the durability and density, but decreases the LHV of briquettes. However, when the LHV of the binder is higher than that of the biomass used for briquette making, the LHV will increase. Among the binders used, cassava starch contains more LHV (19.082 ± 0.381 MJ/kg), followed by cow dung (17.088 ± 0.274 MJ/kg), arabic gum (16.015 ± 0.631 MJ/kg), bark of Grewia bicolor comes last with 14.020 ± 0.272 MJ/kg, and black clay does not contain energy. For a piece of briquette which weighs 20 g, bark of G. bicolor gives a better hardness with a crushing limit load of 22 kg, followed by arabic gum with 19.5 kg, and cow dung with 14 kg. Similarly, bark of G. bicolor gives the higher density, followed by arabic gum. A kg of gum arabic, G. bicolor and starch costs between US$ 1.60 and 3.17. It is important to afforest the plant species that produce binders.


The cause of cancer: biochemical defects in the cancer cell demonstrated by the effects of electromagnetic radiation, glucose and oxygen.
The responses of a person carrying a cancer to 434 MHz electromagnetic radiation are such that they demonstrate that each human cell contains at least two separate respiratory pathways which can convert glucose to energy. The first pathway produces energy by an anaerobic mechanism and it can be demonstrated that this energy is used for the purpose of cell replication. The second pathway(s) produces energy from glucose by aerobic oxidative processes which can be shown to energise other cellular functions. One of these functions is that of controlling its own cell division. Other demonstrable functions of this aerobic energy producing mechanism are concerned with individual cellular repair processes, multicellular organisation and repair and the preservation of gross anatomical perfection. Release of the first or anaerobic system from supervisory control by the second or aerobic sytem(s) permits the unlimited cell division which is the phenomenon known as cancer. The available circumstantial evidence suggests that this is not the result of nuclear or chromosomal defects or mutations but is due to direct irreversible sublethal damage to the cellular aerobic glucose metabolic system whilst the anaerobic system remains intact.


Sequences on the N-terminus of ACh receptor subunits regulate their assembly.
Mutant alpha subunits of Torpedo acetylcholine receptors (AChR) were constructed and expressed in Xenopus oocytes together with other normal subunits to investigate regions in the subunit that are required for subunit assembly. I have found that chimeric alpha subunits, consisting of the N-terminal extracellular domain of the AChR alpha subunit, followed either by the hydrophobic transmembrane segments of GABAA receptor or glutamate receptor subunits, were still recognized as the AChR subunit and associated with co-expressed other normal AChR subunits, suggesting that this part of the N-terminal extracellular domain contains 'assembly signals'.


Chromatin movement in the maintenance of genome stability.
Mechanistic analyses based on improved imaging techniques have begun to explore the biological implications of chromatin movement within the nucleus. Studies in both prokaryotes and eukaryotes have shed light on what regulates the mobility of DNA over long distances. Interestingly, in eukaryotes, genomic loci increase their movement in response to double-strand break induction. Break mobility, in turn, correlates with the efficiency of repair by homologous recombination. We review here the source and regulation of DNA mobility and discuss how it can both contribute to and jeopardize genome stability.


Long-term follow-up after recurrent otitis media and ventilation tube insertion: Hearing outcomes and middle-ear health at six years of age.
To investigate the long-term impact of recurrent otitis media (rOM) and ventilation tube insertion (VTI) in early childhood on hearing outcomes and middle-ear health three to five years later, in a prospective pregnancy cohort study. Children were classified into rOM (n = 314), VTI (n = 94), and reference (n = 1735) groups, according to their otitis media (OM) history in their first three years of life. Audiometry at frequencies 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz, and tympanometry were performed when children were approximately six years of age. A binary logistic regression incorporating a range of potential confounding variables showed that hearing outcomes and middle-ear health status in children who had early childhood rOM with or without undergoing VTI were not significantly different to those in the reference group. The only significant difference was found in the VTI group for both tympanometry (OR = 2.190; 95% CI = 1.123, 4.270) and audiometry outcomes at 4000 Hz (OR = 3.202; 95% CI 1.341, 6.717), in the left ear only. The median score of the better ear 4FA was 20 dB in children in all groups. Children with rOM with or without undergoing VTI in the first three years of childhood had comparable hearing outcomes and middle-ear health status to those with no history of the disease, at around the age of six years. Although children who underwent VTI had an increased risk of abnormal middle-ear status and some elevation in hearing levels in their left ear only, their audiometry results were still within normal limits, indicating that the impact of VTI in early childhood is unlikely to have clinically significant adverse impact on later hearing outcomes.


The Finnish version of The National Institutes Of Health Chronic Prostatitis Symptom Index correlates well with the visual pain scale: translation and results of a modified linguistic validation study.
Authors from Finland have assessed a version in their language of the National Institutes of Health-Chronic Prostatitis Symptom Index; they found that their translated version was valid and easily understandable in the management of the symptoms of chronic pelvic pain syndrome. They felt it should be used as a primary outcome measure in studies with these patients. There are three papers in this issue relating to the effect of drugs on LUTS; the first of these is a pooled analysis of three double-blind placebo-controlled studies into the safety and efficacy of the 10 mg dose of alfuzosin. The second evaluates the effect on quality-of-life issues of treatment with dutasteride. Finally, authors from Australia compare the effect of a Serenoa repens extract with placebo for LUTS. To provide a fluent and easily comprehensible Finnish version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and to study its linguistic validity and correlation with a visual pain scale (VAS). The double-back translation method with two interim modifications was used to produce the Finnish version of the NIH-CPSI. The validity was tested by presenting the questionnaire to 155 men with clinically confirmed chronic pelvic pain syndrome (CPPS) and 12 controls with no previous urological symptoms. Convergent validity of the NIH-CPSI was tested by determining the correlation between the Finnish NIH-CPSI and VAS. Patients' and urologists' opinions about the utility of the Finnish NIH-CPSI were also reviewed. The total Finnish NIH-CPSI scores and the pain domain and voiding symptom domain scores differed significantly (P < 0.001) between the groups, suggesting good discriminant validity of the symptom index. The NIH-CPSI scores correlated well with the VAS (Pearson's correlation 0.76). The preciseness and comprehensibility of the questionnaire were consistently evaluated to be 'good' or 'excellent' both by patients and urologists. The Finnish version of the NIH-CPSI is valid and easily comprehensible for measuring CPPS symptoms. In addition, it provides good discriminant and convergent validity in distinguishing CPPS symptoms and should be used as primary outcome measure in CPPS studies.


Electrophoresis: the march of pennies, the march of dimes.
The present review encompasses ca. 65 years of history of developments in electrokinetic separations, taking as a starting point the year 1937, i.e. the official launching of Tiselius' moving boundary electrophoresis (MBE). The 1950s have been particularly rich in introducing novel methodologies in zone electrophoresis (ZE), thus bringing about the decline of MBE. Among them of extraordinary importance was the development of electrophoresis on agar gels coupled to immuno-diffusion at right angles, which brought a big revolution not only in biochemistry but also in clinical chemistry. Also the by now forgotten paper electrophoresis was a landmark in separation science, in that it implemented, in its "fingerprinting" version, the first genuine two-dimensional (2D) map, coupling orthogonally a charge to a hydrophobic scale separation, while permitting for the first time the detection of spot mutations, i.e. single amino acid replacements in a polypeptide chain, that paved the way to modern genetic analysis. Equally important was the introduction of starch-block electrophoresis, that brought about the notion of sieving and the first discontinuous buffers, refined, in the 1960s, by Ornstein and Davies with their classical papers combining multiphasic buffer systems to polyacrylamide gels, that went down to history as disc-electrophoresis. The 1960s also contributed with two fundamental techniques, isoelectric focusing (IEF) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) that permitted to discriminate proteins solely on the basis of surface charge and molecular mass, respectively. The 1970s gave other fundamental contributions, such as isotachophoresis, the first example of a fully instrumental approach to electrophoresis, both in its analytical and preparative version (Tachophor and Tachofrac), 2D maps combining IEF to SDS-PAGE at right angles and silver staining techniques, that incremented sensitivity by 3 orders of magnitude. The 1980s generated immobilized pH gradients and capillary zone electrophoresis (CZE), two big players that dominated the electrokinetic horizon for all the 1990s and still in vigorous use in present days. The review terminates with a glimpse, in the third millennium, onto microchip technology and hyphenated techniques, notably direct interfacing of various electrophoretic separation methods with mass spectrometry (MS).


The 1A protein gene of human respiratory syncytial virus: nucleotide sequence of the mRNA and a related polycistronic transcript.
The 1A mRNA is the smallest mRNA of human respiratory syncytial (RS) virus and encodes a single protein of approximate molecular weight 9500 as estimated previously by gel electrophoresis. The nucleotide sequence of the 1A mRNA, determined from several full-length cDNA clones, is reported. The 1A mRNA consists of 405 nucleotides, exclusive of poly(A), with relatively long nontranslated regions at the 5' and 3' ends (84 and 126 nucleotides, respectively). The sequences at the 5' and 3' termini of the 1A mRNA conform to the previously described conserved consensus sequences for RS virus mRNAs. The major open reading frame of the 1A mRNA codes for a hydrophobic polypeptide of 64 amino acids with a calculated molecular weight of 7536. The 5' terminus of the 1A mRNA was mapped and sequenced by primer extension under conditions for sequencing by partial chain termination. These experiments also identified a population of polycistronic RNA having the general structure: 5' M protein mRNA-1A mRNA 3'. This polytranscript was sequenced in order to determine the intergenic sequence. In the polytranscript, the nucleotide sequence of the M gene is followed by, in mRNA sense, six A residues and the intergenic sequence 5' ... UAUACACNN (N represents unidentified nucleotide).


Calicophoron microbothrioides (Price and McIntosh, 1944) (Paramphistomidae: Paramphistominae) in Malaysian sambar deer (Cervus unicolor).
Amphistomes of Calicophoron microbothrioides were recovered from the rumen of a Malaysian sambar deer (Cervus unicolor). Some measurements and illustrations of C. microbothrioides are given. This is a new host record for the species C. microbothrioides.


Atomic force microscopy and laser confocal scanning microscopy analysis of callose fibers developed from protoplasts of embryogenic cells of a conifer.
Efficiency of novel fiber formation was much improved in protoplast culture of embryogenic cells (ECs) of a conifer, Larix leptolepis (Sieb. et Zucc.) Gord., by pre-culturing ECs in a medium containing a high concentration of glutamine (13.7 mM). The fibrillar substructures of large and elongated fibers of protoplasts isolated from Larix ECs were investigated by laser confocal scanning microscopy (LCSM) after Aniline Blue staining and atomic force microscopy (AFM) using a micromanipulator without any pre-treatment. Fibers were composed of bundles of fibrils and subfibrils, whose diameters were defined as 0.7 and 0.17 mum, respectively, by image analysis after LCSM and AFM. These fibers were proven to be composed of callose by using specific degrading enzymes for beta-1,4-glucan and beta-1,3-glucan.


Chromatin structure: mapping proteins associated with genomic DNA using crosslinking.
The structure and structural dynamics of chromatin and nucleosomes in transcription and replication were studied by DNA-protein crosslinking. A general strategy has been designed and a number of methods have been developed to map proteins bound to the genomic DNA, to sequence the arrangement of such proteins along DNA in multi-protein complexes, and to identify interacting nucleotides and amino acid residues. Perspectives for large-scale mapping of proteins associated with genomic DNA are discussed.


Spontaneous vertebral arteriovenous fistula causing cervical myelopathy and acute ischemic strokes treated by endovascular balloon-assisted coiling and Onyx embolization.
Vertebral arteriovenous fistulas (VAVF) are infrequent lesions characterized by abnormal communication of the extracranial vertebral artery or one of its branches to the surrounding venous plexuses, without the presence of any intervening vessels. We describe a rare occurrence of a patient with VAVF presenting with acute ischemic stroke, encephalomalacia from multiple prior embolic events, and cervical myelopathy, which was successfully treated by coil-assisted Onyx embolization (ev3 Endovascular, Plymouth, MN, USA) with balloon for flow arrest. Our patient demonstrates that point occlusion with embolization for VAVF can be a feasible, safe, and effective treatment option for complete obliteration of the fistula, with subsequent reduction in the volume of the intra-spinal canal venous plexus. Although it is postulated that thromboembolism is less common because of redirection of flow to the venous side of the fistula, our patient also illustrates the potential for to-fro flow in such a fistula to result in embolic injury to the distal circulation.


[The effect of laser irradiation on arthritis in rats].
Based on the analgesic effect of laser therapy in clinic, the effect of laser irradiation at acupoints on the experimental arthritis in rats was further observed. The experiments were carried out on Wistar rats, which were divided into three groups: The normal group (n = 6): without any treatment. The laser group (n = 8): 24 hours after an injection of Freund's adjuvant, the typical symptoms of acute arthritis (red, swelling, pain and hyperalgesia) occurred. Then transcutaneous irradiation with a low power Helium-neon laser (3 mw, 6328 A) at ipsilateral Kun-Lun point was applied ten minutes every day for five days. The control group (n = 8): with the same treatment as the laser group except laser irradiation. All the indexes, such as foot volume, pain score and pain threshold (Heat-leg-withdrawal latency, HWL and electric-shock vocalization, VOC) were measured every day. Comparing with the symptoms in the control group, the intensity of pain as measured on pain score and the swelling of the ankles (foot volume) were significantly reduced by laser irradiation (P less than 0.01), but the pain threshold (HWL and VOC) did not show any improvement in laser group. However, immediately after laser irradiation, the average pain threshold (VOC) was significantly raised (P less than 0.01). It is concluded that low power laser irradiation at local points can produce the relief from arthralgia and reduction in the swelling of ankles, and it can also produce instant analgesic effect in test of pain threshold (VOC).


Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor.
Genetic strategies for perturbing activity of selected neurons hold great promise for understanding circuitry and behavior. Several such strategies exist, but there has been no direct demonstration of reversible inactivation of mammalian neurons in vivo. We previously reported quickly reversible inactivation of neurons in vitro using expression of the Drosophila allatostatin receptor (AlstR). Here, adeno-associated viral vectors are used to express AlstR in vivo in cortical and thalamic neurons of rats, ferrets, and monkeys. Application of the receptor's ligand, allatostatin (AL), leads to a dramatic reduction in neural activity, including responses of visual neurons to optimized visual stimuli. Additionally, AL eliminates activity in spinal cords of transgenic mice conditionally expressing AlstR. This reduction occurs selectively in AlstR-expressing neurons. Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective for selective, quick, and reversible silencing of mammalian neurons in vivo.


Antihypertensive Efficacy of the Direct Renin Inhibitor Aliskiren as Add-on Therapy in Patients with Poorly Controlled Hypertension.
A direct renin inhibitor, aliskiren, has a longer stable antihypertensive effect compared with other renin-angiotensin-aldosterone system (RAAS) inhibitors. This study was a 6-month, single-center, open trial conducted between December 2010 and November 2011 to assess the antihypertensive effect of adding aliskiren (300 mg) to the treatment of essential hypertension patients whose target blood pressure (BP) had not been achieved and to assess whether it was possible to reduce the amount of antihypertensive drugs used. The results showed an overall improvement in the target BP achievement rate of 60% for clinic BP and 52% for home BP measurements (75 cases total). The mean number of drugs before treatment with aliskiren was 3.28±1.52, whereas at the end of the six months the mean number of drugs prescribed other than aliskiren was 2.85±1.72 (p<0.0001). Moreover, no worsening of the renal function was observed in patients with diabetes or chronic kidney disease (CKD) who were being treated with other RAAS inhibitors in combination to aliskiren. These results showed that when aliskiren was added to the treatment of poorly controlled hypertension, the BP achievement rate increased, and it was possible to reduce the amount of antihypertensive drugs used in combination with aliskiren. Moreover, as a result of careful monitoring of the renal function or decreasing the amounts of drugs used in combination, no worsening of the renal function was observed even in the cases complicated by diabetes or CKD being treated with other RAAS inhibitors.


Structure of the Staphylococcus aureus AgrA LytTR domain bound to DNA reveals a beta fold with an unusual mode of binding.
The LytTR domain is a DNA-binding motif found within the AlgR/AgrA/LytR family of transcription factors that regulate virulence factor and toxin gene expression in pathogenic bacteria. This previously uncharacterized domain lacks sequence similarity with proteins of known structure. The crystal structure of the DNA-binding domain of Staphylococcus aureus AgrA complexed with a DNA pentadecamer duplex has been determined at 1.6 A resolution. The structure establishes a 10-stranded beta fold for the LytTR domain and reveals its mode of interaction with DNA. Residues within loop regions of AgrA contact two successive major grooves and the intervening minor groove on one face of the oligonucleotide duplex, inducing a substantial bend in the DNA. Loss of DNA binding upon substitution of key interacting residues in AgrA supports the observed binding mode. This mode of protein-DNA interaction provides a potential target for future antimicrobial drug design.


Apelin-potential therapy for COVID-19?
We believe that, in parallel to the attempts for direct blockade of the SARS-CoV-2 penetration into host cell and repurposing drugs, finding new therapeutic strategies for patients with lung injury or cardiovascular complications/coagulopathies associated with COVID-19 should be paid particular attention. Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation. These drugs have potential to improve acute lung injury and cardiovascular/coagulopathy complications in COVID-19 which are associated with elevated Ang-II/Ang(1-7) ratio.


Annual rescreening for alcohol misuse: diminishing returns for some patient subgroups.
Routine alcohol screening is widely recommended, and Medicare now reimburses for annual alcohol screening. Although up to 18% of patients will screen positive for alcohol misuse, the value of annual rescreening for patients who repeatedly screen negative is unknown. To evaluate the probability of converting to a positive alcohol screen at annual rescreening among VA outpatients who previously screened negative 2-4 times. Retrospective cohort study. A total of 179,035 VA outpatients (10,588 women) who previously screened negative on 2 and up to 4 consecutive annual alcohol screens and were rescreened the next year. AUDIT-C alcohol screening scores (range, 0-12) were obtained from electronic medical record data. The probability of converting to a positive screen (scores: men ≥4; women, ≥3) at rescreening after 2-4 prior negative screens was evaluated overall and across subgroups based on age, sex, and prior negative screen scores (scores: men, 0-3; women, 0-2). The overall probability of converting to a positive subsequent screen decreased modestly from 3.5% to 1.9% as the number of prior consecutive negative screens increased from 2 to 4, yet varied widely across subgroups based on age, sex, and prior negative screen scores (0.6%-38.7%). The likelihood of converting to a positive screen at annual rescreening is strongly influenced by age, sex, and scaled screening scores on prior negative alcohol screens. Algorithms for the frequency of repeat alcohol screening for patients who repeatedly screen negative should be based on these factors. These results may have implications for other routine behavioral health screenings.


Camelus dromedarius putative cytochrome P450 enzyme CYP2E1: complete coding sequence and phylogenetic tree.
This study determined the full-length sequence of CYP2E1, one of six cytochrome P450 genes previously examined in camel tissues by western blotting and semi-quantitative PCR. The Camelus dromedarius CYP2E1 has an open reading frame of 1,473 bp, and the cDNA encodes a protein of 490 amino acid residues with a molecular weight of 54.8 kDa. The deduced amino acid sequence showed the highest identity with Bos taurus (88%), Sus scrofa (87%), and Homo sapiens (83%). In a phylogenetic analysis, the C. dromedarius CYP2E1 isoform was located beside cattle and pigs. The deduced amino acid sequence of camel CYP2E1 showed the conserved proline-rich amino terminus and the heme-binding signature localized near the carboxy terminus of the protein.


Prediction of common labels for universal domain adaptation.
Universal domain adaptation (UniDA) is an unsupervised domain adaptation that selectively transfers the knowledge between different domains containing different label sets. However, the existing methods do not predict the common labels of different domains and manually set a threshold to discriminate private samples, so they rely on the target domain to finely select the threshold and ignore the problem of negative transfer. In this paper, to address the above problems, we propose a novel classification model named Prediction of Common Labels (PCL) for UniDA, in which the common labels are predicted by Category Separation via Clustering (CSC). It is noted that we devise a new evaluation metric called category separation accuracy to measure the performance of category separation. To weaken negative transfer, we select source samples by the predicted common labels to fine-tune model for better domain alignment. In the test process, the target samples are discriminated by the predicted common labels and the results of clustering. Experimental results on three widely used benchmark datasets indicate the effectiveness of the proposed method.


Effects of destruxins on free calcium and hydrogen ions in insect hemocytes.
Destruxins, cyclohexadepsipeptidic mycotoxins isolated from the entomopathogenic fungus Metarhizium anisopliae, inhibit innate insect immunity. However, their mechanism of action remains unclear. In this study, the effects of destruxins on changes in free calcium and hydrogen ions in the hemocytes of Exolontha serrulata, Bombyx mori and the Spodoptera litura SL-1 cell line were detected using laser scanning confocal microscopy (LSCM). An instant Ca(2+) influx of hemocytes induced by destruxins A and B (DA and DB) was recorded. The DA/DB-dependent Ca(2+) influx was not influenced by the Ca(2+) channel inhibitors 2-aminoethoxydiphenyl borane (2-APB) and U73122. It also had an apparently different LSCM profile from that of the ionomycin-dependent Ca(2+) influx. However, the instant Ca(2+) influx was not seen in the SL-1 cells; on the contrary, a slow, moderate enhancement of intracellular Ca(2+) was observed. Meanwhile, an instant intracellular free H(+) decrease aroused by DA and DB was found. DB at 20 μmol/L and DA at 690 μmol/L significantly reduced intracellular free H(+) levels. Furthermore, the vacuolar H(+)-ATPase (V-ATPase) inhibitor bafilomycin A1 had obvious effects on the decreases of intracellular free H(+) in hemocytes. These results suggest that the mechanism of DA/DB-dependent Ca(2+) influx is perhaps not related to Ca(2+) channels and ionophores; rather, the intracellular free H(+) decrease might be due to V-ATPase inhibition.


Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain.
To compare the pattern of activation of motor cortex produced by transcranial magnetic stimulation and epidural electrical stimulation. The spinal volleys evoked by transcranial magnetic stimulation and epidural electrical stimulation over the cerebral motor cortex were recorded from an electrode inserted into the cervical epidural space of one conscious subject who also had a cortical epidural electrode over the motor area. The volleys were termed D- and I-waves according to their latency. Magnetic stimulation was performed with a figure-of-eight coil and the induced current flowed either in a postero-anterior (PA) or in latero-medial (LM) direction. At active motor threshold intensity LM magnetic stimulation evoked a D wave whereas PA stimulation evoked an I(1) wave with later I waves being recruited at increasing stimulus intensities. Electrical epidural stimulation evoked both a D wave and I waves. However, the D wave evoked by electrical epidural stimulation had a longer latency than the LM D wave, suggesting either a more proximal site of activation of the pyramidal axon or activation of slightly faster conducting set of corticospinal fibres by LM stimulation. The I3 wave evoked by electrical epidural stimulation also had a longer latency than the PA I3-wave Epidural stimulation of the motor cortex can produce repetitive excitation of corticospinal neurones. The order of recruitment of the volleys, and the latency of the D and I3 waves may be slightly different to that seen after transcranial magnetic stimulation. Our findings suggest that there may be subtle differences in the populations of neurones activated by the two forms of stimulation.


QTc interval prolongation due to spinal anesthesia in patients with and without diabetes: an observational study.
Spinal anesthesia and autonomic neuropathy (caused by diabetes) prolong the QTc interval. Changes in the duration of the QTc interval following subarachnoid blockade in patients with diabetes have not been evaluated. We hypothesized that after subarachnoid blockade, QTc interval prolongation would be greater in patients with diabetes than in those without. Accordingly, we compared the QTc interval, T wave peak-to-end interval (Tp-e interval), blood pressure, heart rate, and heart rate variability before and after spinal anesthesia in patients with and without diabetes. This prospective observational study (Clinical Research Information Service identifier: KCT0004897) was conducted in a tertiary university hospital and included 24 patients with diabetes mellitus (DM group) and 24 patients without it (control group) who were scheduled for spinal anesthesia. The QTc interval, Tp-e interval, heart rate variability, blood pressure, and heart rate were measured before (T1) and 1 (T2), 5 (T3), and 10 min (T4) following subarachnoid blockade. Ten minutes following subarachnoid blockade, the QTc intervals of patients in the DM group were significantly longer than the baseline values, whereas the change in the QTc interval in the control group was not significant (p < 0.0001 vs. p = 0.06). Spinal anesthesia caused a more significant prolongation of the QTc interval in patients with diabetes than in those without.


Peptides based on the conserved predomain sequence of matrix metalloproteinases inhibit human stromelysin and collagenase.
Prostromelysin, a member of the family of matrix metalloproteinases, is secreted as a zymogen which is activated after cleavage of the His81-Phe82 bond. The 82 amino acid propeptide that is removed during activation contains 12 amino acids, MRKPRC75GVPDVG, that are highly conserved in all MMPs. We evaluated a series of peptides that span this region for their ability to inhibit stromelysin. The hexapeptide, Ac-RCGVPD, and the pentapeptide, Ac-RCGVP had IC50 values of approx. 10 microM. The tetrapeptide, Ac-RCGV, was somewhat less potent with an IC50 of 60 microM. Smaller peptides, e.g. Ac-RCG, were significantly less potent as inhibitors. Substitutions of Cys75 with Ser resulted in a complete loss of inhibitory activity. The peptides in this series also inhibited human fibroblast collagenase.


Probiotic - An emerging therapy in recolonizing periodontal pocket.
One of the etiological factors in the pathogenesis of periodontitis is reduction or the absence of the so-called "beneficial bacteria". Most of the globally applied treatment approach is based on subgingival bacterial elimination but recolonization with less pathogenic bacteria is seen within weeks. Therefore, researchers have started focusing on shifting the current treatment approach from specific bacterial elimination to restoring periodontal pocket with beneficial bacteria. This alteration in the ecology of niches from the one with the pathological plaque to the one with the biofilm of commensals can be achieved via subgingival application of probiotics. This article suggests the important prospects of subgingival delivery of probiotics in guiding periodontal recolonization with beneficial bacteria and emphasizes research in this study field.


The Prognostic Value of Micropapillary Pattern in Colon Cancer and Its Role as a High-Risk Feature in Patients With Stage II Disease.
The association of a micropapillary pattern with oncologic outcomes has not been fully studied in patients with colon cancer. We evaluated the prognostic value of a micropapillary pattern, especially for patients with stage II colon cancer. A retrospective comparative cohort study using propensity score matching. This study was conducted at a single tertiary center. Patients with primary colon cancer undergoing curative resection from October 2013 to December 2017 were enrolled. Patients were grouped into micropapillary pattern positive or micropapillary pattern negative. Disease-free survival and overall survival. Of the eligible 2192 patients, 334 (15.2%) were with micropapillary pattern (+). After 1:2 propensity score matching, 668 patients with micropapillary pattern-negative status were selected. The micropapillary pattern-positive group showed significantly worse 3-year disease-free survival (77.6% vs 85.1%, p = 0.007). Three-year overall survival of micropapillary pattern-positive and micropapillary pattern-negative patients did not show a statistically significant difference (88.9% vs 90.4%, p = 0.480). In multivariable analysis, micropapillary pattern-positive was an independent risk factor for poor disease-free survival (HR 1.547, p = 0.008). In the subgroup analysis for 828 patients with stage II disease, 3-year disease-free survival deteriorated significantly in micropapillary pattern-positive patients (82.6% vs 93.0, p < 0.001). Three-year overall survival was 90.1% and 93.9% in patients positive and negative for micropapillary pattern, respectively ( p = 0.082). In the multivariable analysis for patients with stage II disease, micropapillary pattern-positive status was an independent risk factor for poor disease-free survival (HR 2.003, p = 0.031). Selection bias due to the retrospective nature of the study. Micropapillary pattern-positive status may serve as an independent prognostic factor for colon cancer, especially for patients with stage II disease. ANTECEDENTES:La asociación del patrón micropapilar con los resultados oncológicos no ha sido completamente estudiada en pacientes con cáncer de colon.OBJETIVO:Evaluamos el valor pronóstico del patrón micropapilar, especialmente en pacientes con cáncer de colon en estadio II.DISEÑO:Estudio de cohortes comparativo y retrospectivo que utilize el emparejamiento por puntuación de propensiones.AJUSTE:Estudio realizado en un solo centro terciario.PACIENTES:Se incluyeron los pacientes con cáncer de colon primario sometidos a resección curativa desde octubre de 2013 hasta diciembre de 2017. Los pacientes se agruparon en patrón micropapilar positivo ( + ) o patrón micropapilar negativo ( - ).PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida libre de enfermedad y la sobrevida global.RESULTADOS:De los 2192 pacientes elegibles, 334 (15,2%) tenían patrón micropapilar (+). Después de emparejar el puntaje de propensión 1:2, se seleccionaron 668 pacientes con patrón micropapilar (-). El grupo con patrón micropapilar (+) mostró una sobrevida libre de enfermedad significativamente inferior a los tres años (77,6% frente a 85,1%, p = 0,007). La sobrevida global a los tres años del patrón micropapilar (+) y del patrón micropapilar (-) no mostró una diferencia estadísticamente significativa (88,9 % frente a 90,4%, p = 0,480). En el análisis multivariable, el patrón micropapilar (+) fue un factor de riesgo independiente para una deficiente sobrevida libre de enfermedad (índice de riesgo 1,547, p = 0,008). En el análisis de subgrupos de 828 pacientes con enfermedad en estadio II, la sobrevida libre de enfermedad a los tres años se deterioró significativamente en los pacientes con patrón micropapilar (+) (82,6% frente a 93,0, p < 0,001). La sobrevida global a los tres años fué del 90,1% y del 93,9% en el patrón micropapilar (+) y el patrón micropapilar (-), respectivamente ( p = 0,082). En el análisis multivariable de los pacientes con enfermedad en estadio II, el patrón micropapilar (+) fue un factor de riesgo independiente para una sobrevida libre de enfermedad deficiente (índice de riesgo 2,003, p = 0,031).LIMITACIONES:Sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:El patrón micropapilar (+) sirve como factor pronóstico independiente para el cáncer de colon, especialmente para pacientes con enfermedad en estadio II. (Traducción-Dr. Xavier Delgadillo ).


Cross-site collaboration on infection prevention and control research-room for improvement? A 7-year comparative study in five European countries.
The spread of SARS-CoV-2, multidrug-resistant organisms and other healthcare-associated pathogens represents supra-regional challenges for infection prevention and control (IPC) specialists in every European country. To tackle these problems, cross-site research collaboration of IPC specialists is very important. This study assesses the extent and quality of national research collaborations of IPC departments of university hospitals located in Austria, England, France, Germany, and the Netherlands, identifies network gaps, and provides potential solutions. Joint publications of IPC heads of all university hospitals of the included countries between 1st of June 2013 until 31st of May 2020 were collected by Pubmed/Medline search. Further, two factors, the journal impact factor and the type/position of authorship, were used to calculate the Scientific Collaboration Impact (SCI) for all included sites; nationwide network analysis was performed. In five European countries, 95 sites and 125 responsible leaders for IPC who had been in charge during the study period were identified. Some countries such as Austria have only limited national research cooperations, while the Netherlands has established a gapless network. Most effective collaborating university site of each country were Lille with an SCI of 1146, Rotterdam (408), Berlin (268), Sussex (204), and Vienna/Innsbruck (18). The present study indicates major differences and room for improvement in IPC research collaborations within each country and underlines the potential and importance of collaborating in IPC.


Variation in primary sequence and tandem repeat copy number among i-antigens of Ichthyophthirius multifiliis.
The immobilization antigens (i-antigens) of Ichthyophthirius multifiliis are potential vaccine candidates for the prevention of 'white spot' disease in freshwater fish. These antigens vary with respect to antigenicity and molecular mass, and at least five i-antigen serotypes have been identified among parasite isolates thus far. In previous studies, the gene and corresponding cDNA encoding a approximately 48 kDa i-antigen from parasite isolate G1 (serotype A), had been cloned and sequenced. We now report on the isolation of two new genes, designated IAG52A[G5] and IAG52B[G5], encoding approximately 52/55 kDa i-antigens from a parasite isolate representing a different serotype, namely, D. Based on their deduced sequences, the approximately 52/55 kDa gene products have the same structural features as the 48 kDa protein including hydrophobic N- and C-termini, periodic cysteine residues with the potential for metal binding, and tandemly repetitive amino acid sequence domains that span their length. Nevertheless, the products of these genes vary in their tandem repeat copy number, and share only approximately 50% homology overall. When expressed in heterologous systems, the products of the newly described genes react strongly with monospecific polyclonal antisera against the i-antigens of serotype D and are clearly i-antigens. It would nevertheless appear that mRNA transcripts from the two genes are present at widely different levels within parasites themselves. Analysis at the protein level using 2-D SDS-PAGE would further suggest that multiple i-antigens are expressed within the same serotype at any given time.


Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain.
Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.


Scaffolding proteins in G-protein signaling.
Heterotrimeric G proteins are ubiquitous signaling partners of seven transmembrane-domain G-protein-coupled receptors (GPCRs), the largest (and most important pharmacologically) receptor family in mammals. A number of scaffolding proteins have been identified that regulate various facets of GPCR signaling. In this review, we summarize current knowledge concerning those scaffolding proteins that are known to directly bind heterotrimeric G proteins, and discuss the composition of the protein complexes they assemble and their effects on signal transduction. Emerging evidence about possible ways of regulation of activity of these scaffolding proteins is also discussed.


The role of calcium ion as a mediator of the effects of angiotensin II, catecholamines, and vasopressin on the phosphorylation and activity of enzymes in isolated hepatocytes.
Angiotensin II, catecholamines, and vasopressin are thought to stimulate hepatic glycogenolysis and gluconeogenesis via a cyclic AMP-independent mechanism that requires calcium ion. The present study explores the possibility that angiotensin II and vasopressin control the activity of regulatory enzymes in carbohydrate metabolism through Ca2+-dependent changes in their state of phosphorylation. Intact hepatocytes labeled with [32P]PO43- were stimulated with angiotensin II, glucagon, or vasopressin and 30 to 33 phosphorylated proteins resolved from the cytoplasmic fraction of the cell by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. Treatment of the cells with angiotensin II or vasopressin increased the phosphorylation of 10 to 12 of these cytosolic proteins without causing measurable changes in cyclic AMP-dependent protein kinase activity. Glucagon stimulated the phosphorylation of the same set of 11 to 12 proteins through a marked increase in cyclic AMP-dependent protein kinase activity. The molecular weights of three of the protein bands whose phosphorylation was increased by these hormones correspond to the subunit molecular weights of phosphorylase (Mr = 93,000), glycogen synthase (Mr = 85,000), and pyruvate kinase (Mr = 61,000). Two of these phosphoprotein bands were positively identified as phosphorylase and pyruvate kinase by affinity chromatography and immunoprecipitation, respectively. Incubation of hepatocytes in a Ca2+-free medium completely abolished the effects of angiotensin II and vasopressin on protein phosphorylation but did not alter those of glucagon. Treatment of hepatocytes with angiotensin II, glucagon, or vasopressin stimulated phosphorylase activity by 250 to 260%, inhibited glycogen synthase activity by 50%, and inhibited pyruvate kinase activity by 30 to 35% (peptides) to 70% (glucagon). The effects of angiotensin II and vasopressin on the activity of all three enzymes were completely abolished if the cells were incubated in a Ca2+-free medium while those of glucagon were not altered. The results imply that angiotensin II, catecholamines, and vasopressin control hepatic carbohydrate metabolism through a Ca2+-requiring, cyclic AMP-independent pathway that leads to the phosphorylation of important regulatory enzymes.


Seroepidemiology of rinderpest in bovids in Sri Lanka using the enzyme linked immunosorbent assay (ELISA) technique.
Approximately 0.2% (n = 4397) of the bovids (cattle and buffalo) in Sri Lanka were sampled, from June 1992 using a multi-stage sampling procedure. Serum antibodies for the rinderpest virus were detected using the competitive enzyme-linked immunosorbent assay. The age, the agroclimatic zone, the management system practiced in the farms, and the vaccination history of the sampled bovids were studied as potential risk factors for being seropositive. The prevalence of rinderpest antibodies in non-vaccinated bovids was 3.5% (n = 4101). The prevalence was higher in the dry zone (9%; where the outbreak emerged in 1987), compared to bovids in the other zones (1%). Seropositive bovids over three years of age were approximately at fourfold higher chances of being seropositive compared to those that were < or = 3 years old. The higher prevalence in older animals is probably due to exposure to the virus during the 1987 epidemic. Bovids from the dry zone (annual rainfall 20 to 35 inches) were at higher odds of being seropositive even after controlling for the possible effects of age, agroclimatic zone, management system and vaccination. The fact that 62% of bovids from the dry zone in this study were reared under extensive management system (free grazing) which allow unrestricted contact between animals, may be the reason for the above finding. A relatively poor response to vaccination observed in vaccinated bovids (seroprevalence = 12%; n = 296) could be attributed to difficulties in maintaining the vaccine at recommended temperatures in the field. This is the first island-wide study on seroprevalence of rinderpest in Sri Lanka.


Transposition of the great arteries and hypocalcemia in a patient with fetal hydantoin syndrome.
We report a patient with fetal hydantoin syndrome (FHS) with associated d-transposition of the great arteries (d-TGA) and persistent hypocalcemia. d-TGA and hypocalcemia have each been individually reported once in association with FHS, but these patients were also prenatally exposed to phenobarbital. To our knowledge, this is the first report of these problems occurring after prenatal exposure to hydantoin alone. The combination of congenital heart disease and hypocalcemia in our patient raises the possibility of a hydantoin effect on neural crest migration.


Generation and nonlinear self-trapping of optical propelling beams.
We generate optical beams with rotating intensity blades by employing the moiré technique. We show that the number of the blades and the speed and direction of rotation can be controlled at ease with a spatial light modulator, while no mechanical movement or phase-sensitive interference is involved. By applying a noninstantaneous self-focusing nonlinearity, we demonstrate both theoretically and experimentally self-trapping of such optical propelling beams.


TP53 copy number and protein expression inform mutation status across risk categories in acute myeloid leukemia.
Mutant TP53 is an adverse risk factor in acute myeloid leukemia (AML), but large-scale integrated genomic-proteomic analyses of TP53 alterations in patients with AML remain limited. We analyzed TP53 mutational status, copy number (CN), and protein expression data in AML (N = 528) and provide a compilation of mutation sites and types across disease subgroups among treated and untreated patients. Our analysis shows differential hotspots in subsets of AML and uncovers novel pathogenic variants involving TP53 splice sites. In addition, we identified TP53 CN loss in 70.2% of TP53-mutated AML cases, which have more deleterious TP53 mutations, as well as copy neutral loss of heterozygosity in 5/32 (15.6%) AML patients who had intact TP53 CN. Importantly, we demonstrate that mutant p53 protein expression patterns by immunohistochemistry evaluated using digital image-assisted analysis provide a robust readout that integrates TP53 mutation and allelic states in patients with AML. Expression of p53 by immunohistochemistry informed mutation status irrespective of TP53 CN status. Genomic analysis of comutations in TP53-mutant AML shows a muted landscape encompassing primarily mutations in genes involved in epigenetic regulation (DNMT3A and TET2), RAS/MAPK signaling (NF1, KRAS/NRAS, PTPN11), and RNA splicing (SRSF2). In summary, our data provide a rationale to refine risk stratification of patients with AML on the basis of integrated molecular and protein-level TP53 analyses.


Microhardness of dentine underlying ART restorations in primary molars: an in vivo pilot study.
To evaluate the microhardness of dentine underlying glass ionomer restorations made with Atraumatic Restorative Treatment. An experimental single-centre study. University Department, Brazil, 2001. Sixteen children were selected showing primary molars containing carious cavities (n = 29), which were restored using Fugi IX. Subsequently, some teeth were extracted respecting Nolla stage 7 or 8 of the permanent successor, and categorised according to the post-restoration time in the mouth: G1 (baseline, immediate extraction), G2 (30 days), G3 (90 days) and G4 (180 days). Four teeth were excluded because they were not in time of normal exfoliation. The 25 extracted teeth were resin embedded, sectioned mesiodistally and prepared metallographically. Knoop microhardness analysis (Micromet 2003; 10g for 1.5 sec.) produced identations in three areas of dentine: Zone 1 (just below the restoration), Zone 3 (as close as possible to the pulp) and Zone 2 (intermediate region between 1 and 3). Non-parametric statistical tests were done--at a significance level of 5%. Four teeth were excluded. No significant difference was noted among the zones, inside the groups. Zones 1 and 2 showed a considerable increase of microhardness according to the time, except for Group 3 (p > 0.05). Although microhardness had increased, it was not sufficiently equal to the microhardness of the healthy dentine, regardless of the depth evaluated.


Phenotypic and comparative transcriptomics analysis of RDS1 overexpression reveal tolerance of Saccharomyces cerevisiae to furfural.
The yeast Saccharomyces cerevisiae able to tolerate lignocellulose-derived inhibitors like furfural. Yeast strain performance tolerance has been measured by the length of the lag phase for cell growth in response to the furfural inhibitor challenge. The aims of this work were to obtain RDS1 yeast tolerant strain against furfural through overexpression using a method of in vivo homologous recombination. Here, we report that the overexpressing RDS1 recovered more rapidly and displayed a lag phase at about 12 h than its parental strain. Overexpressing RDS1 strain encodes a novel aldehyde reductase with catalytic function for reduction of furfural with NAD(P)H as the co-factor. It displayed the highest specific activity (24.8 U/mg) for furfural reduction using NADH as a cofactor. Fluorescence microscopy revealed improved accumulation of reactive oxygen species resistance to the damaging effects of inhibitor in contrast to the parental. Comparative transcriptomics revealed key genes potentially associated with stress responses to the furfural inhibitor, including specific and multiple functions involving defensive reduction-oxidation reaction process and cell wall response. A significant change in expression level of log2 (fold change >1) was displayed for RDS1 gene in the recombinant strain, which demonstrated that the introduction of RDS1 overexpression promoted the expression level. Such signature expressions differentiated tolerance phenotypes of RDS1 from the innate stress response of its parental strain. Overexpression of the RDS1 gene involving diversified functional categories is accountable for stress tolerance in yeast S. cerevisiae to survive and adapt the furfural during the lag phase.


The Impact of Self-Efficacy on Activity Limitations in Patients With Hip Osteoarthritis: Results From a Cross-Sectional Study.
Pain and activity limitations are the main health complaints in osteoarthritis. We explored pathways between pain and activity limitations in a chain mediation model that involved self-efficacy, physical activity behavior, and muscle function in patients with hip osteoarthritis not awaiting hip replacement. We used cross-sectional, baseline data from a randomized controlled trial on 152 patients with clinical hip osteoarthritis according to the American College of Rheumatology not awaiting hip replacement. The associations between pain, self-efficacy, self-reported physical activity, muscle function (leg extensor power), and activity limitations (performance-based and self-reported activity limitation outcomes) were modeled using structural equation models. The effect of pain on performance-based activity limitation was fully mediated by self-efficacy, physical activity, and muscle function. Of the total effect of self-efficacy on performance-based activity limitation, the direct effect accounted for 63% (95% CI: 45%-82%), whereas the indirect effect via physical activity constituted 16% (95% CI: 1%-30%) and the indirect effect via muscle function constituted 21% (95% CI: 9%-32%). In contrast, physical activity and muscle function had no effect on self-reported activity limitations, whereas pain had a direct effect and an indirect effect mediated by self-efficacy. Our results suggest that self-efficacy should be taken into consideration in prevention and treatment of activity limitations in patients with hip osteoarthritis not awaiting hip replacement. Coupling exercise with programs of self-efficacy enhancement could potentially increase the positive effects of exercise.


The sustained second phase of hormone-stimulated diacylglycerol accumulation does not activate protein kinase C in GH3 cells.
Numerous hormones activate cells through receptor-regulated hydrolysis of phosphoinositides resulting in elevated cellular diacylglycerol (DAG), an activator of protein kinase C (PKC). Our previous studies showed that thyrotropin-releasing hormone (TRH) treatment of GH3 cells stimulated a rapid (less than 10 s) but transient (less than 60 s) association of cytosolic PKC with the membrane. In this study, we investigated the roles of hormone-stimulated Ca2+ and DAG levels in initiating and terminating the membrane association of PKC. The initial effects of TRH were not mimicked by elevating CA2+ levels, however, inhibiting TRH-stimulated Ca2+ increases blocked hormone-stimulated PKC translocation. Hence, the TRH stimulation of both Ca2+ and DAG levels were essential for the initial PKC translocation. The termination of PKC membrane association could not be attributed to proteolysis of PKC nor to limiting Ca2+ levels. Treatment of cells with phorbol diesters potentiated and prolonged the effects of TRH on PKC translocation, suggesting that DAG levels limited the membrane association of PKC. Since TRH stimulated a sustained increase in DAG levels, DAG composition was analyzed. There was a marked shift in DAG from tetraenoic (at 15 s) to more saturated DAGs at longer times. In addition, increases in plasma membrane DAG in response to TRH were transient rather than sustained. We propose that the TRH stimulation of PKC translocation is short-lived due to the metabolism of plasma membrane DAGs which are effective in promoting PKC activation. In contrast, DAGs which accumulate in intracellular membranes during the sustained phase of TRH treatment appear to be ineffective as activators of PKC.


Comparison of three malnutrition risk screening tools in identifying malnutrition according to Global Leadership Initiative on Malnutrition criteria in gastrointestinal cancer.
Malnutrition is common in patients with gastrointestinal cancer. The first step in the diagnosis of malnutrition is to evaluate the malnutrition risk by validated screening tools according to the Global Leadership Initiative on Malnutrition (GLIM). This study aimed to determine the best nutritional screening tool for identifying GLIM malnutrition and validate the performance of these tools in different age subgroups. We did a prospective cohort study of patients who were diagnosed with gastrointestinal cancer from February 2016 to November 2019. The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and area under the receiver operating characteristic (ROC) curve (AUC) of three screening tools (Nutritional risk screening 2002 (NRS 2002), Geriatric Nutritional Risk Index (GNRI), MNA-SF) were calculated. A total of 488 patients were enrolled, and 138 patients (28.27%) were malnutrition according to the GLIM criteria. The consistency of NRS 2002, GNRI, and MNA-SF with GLIM-defined malnutrition was 74.8, 72.1, and 71.1%, respectively. In the subgroup analysis of young patients (<65 years), NRS 2002 exhibited the best discrimination with the AUC of 0.724 (95% CI, 0.567-0.882), the sensitivity of 64.3% (95% CI, 35.6-86.0), and the specificity of 80.6% (95% CI, 69.2-88.6). In patients older than 65 years, MNA-SF exhibited the best discrimination with the AUC of 0.764 (95% CI, 0.714-0.814), the sensitivity of 82.3% (95% CI, 74.1-88.3), and the specificity of 70.5% (95% CI, 64.7-75.7). Nutritional risk screening 2002 (NRS 2002) is the best malnutrition screening tool in gastrointestinal cancer patients younger than 65 years, and MNA-SF is the best malnutrition screening tool in patients older than 65 years. It is necessary to select targeted nutritional screening tools according to the difference in age.


Insights into the role of tooling characteristics on compressibility evolution in non-flat faced tablets.
The robustness of tablet manufacturability largely depends on compressibility behavior of a powder. The compressibility assessment is traditionally conducted on cylindrical flat-faced compacts in contrast to the fact that marketed tablets are majorly produced using non-flat faced or shaped toolings. The present work demonstrates the feasibility of quantifying average compressibility on shaped toolings through a proof-of-concept study by investigating the central band portion and the entire volume of the tablet, which led to several notable findings. Firstly, the yield stress (deformability) was found independent of type of tooling for a given powder in the in-die condition, but for the same tooling it conversely spanned over a wide range in the out-die condition due to characteristic elastic recovery. Secondly, the yield stress parameter correlated with the change in band volume of the shaped tablet with applied compaction pressure, thereby establishing an orthogonal approach to assess compressibility on non-flat faced toolings. The study emphasizes that tooling characteristics may affect compressibility and tablet robustness of a same powder, which should be practiced cautiously in drug product manufacturing.


Systemic trafficking of plant virus nanoparticles in mice via the oral route.
The plant virus, cowpea mosaic virus (CPMV), is increasingly being used as a nanoparticle platform for multivalent display of peptides. A growing variety of applications have employed the CPMV display technology including vaccines, antiviral therapeutics, nanoblock chemistry, and materials science. CPMV chimeras can be inexpensively produced from experimentally infected cowpea plants and are completely stable at 37 degrees C and low pH, suggesting that they could be used as edible or mucosally-delivered vaccines or therapeutics. However, the fate of CPMV particles in vivo, or following delivery via the oral route, is unknown. To address this question, we examined CPMV in vitro and in vivo. CPMV was shown to be stable under simulated gastric conditions in vitro. The pattern of localization of CPMV particles to mouse tissues following oral or intravenous dosing was then determined. For several days following oral or intravenous inoculation, CPMV was found in a wide variety of tissues throughout the body, including the spleen, kidney, liver, lung, stomach, small intestine, lymph nodes, brain, and bone marrow. CPMV particles were detected after cardiac perfusion, suggesting that the particles entered the tissues. This pattern was confirmed using methods to specifically detect the viral capsid proteins and the internal viral RNA. The stability of CPMV virions in the gastrointestinal tract followed by their systemic dissemination supports their use as orally bioavailable nanoparticles.


Distribution of leukotriene B4 receptors in human hematopoietic cells.
Leukotriene B4 (LTB4), a product of arachidonic acid metabolism, plays an important role in inflammatory responses. We have cloned from human erythroleukemia cells, a G protein-coupled receptor, designated P2Y(7), which was later identified as the receptor for LTB4 (B-LTR). We have investigated the distribution of LTB4 receptors in various hematopoietic cells. Northern blotting and reverse transcription-coupled polymerase chain reaction (RT-PCR) analyses using radiolabeled LTB4 receptor cDNA as a probe indicated the presence of LTB4 receptor mRNA in peripheral blood leukocytes but not in platelets. Flow cytometry analysis of peripheral blood cells using specific LTB4 receptor antibodies revealed that monocytes, granulocytes, and lymphocytes, but not platelets, express LTB4 receptors. RT-PCR-Southern hybridization analysis revealed that peripheral blood leukocytes and human umbilical vein endothelial cells express the LTB4 receptor. Of the hematopoietic cell lines tested, promonocytic U937 cells, promyelocytic HL-60 cells, K562 cells, and human erythroleukemia cells express the LTB4 receptor. These results suggest a physiological role for the LTB4 receptor in the stimulation of monocytes, neutrophils, and endothelial cells.


Malignant potential of chronic ulcerative colitis. Preliminary report.
Prior studies confirm the increased incidence of carcinoma of the colon in chronic ulcerative colitis. The authors reviewed clinical and histologic data retrospectively in 23 patients with colon carcinoma and chronic ulcerative colitis. Twenty-two of these patients had dysplasia of colonic epithelium remote from the cancer. The authors prospectively reviewed clinical data and rectal and colonoscopic biopsy specimens on 36 patients with chronic ulcerative colitis, 12 with Crohn's colitis, and 12 with miscellaneous disorders. Eight patients with chronic ulcerative colitis had dysplasia; 6 have had colectomy, and 2 of these had carcinoma. No patient without chronic ulcerative colitis had dysplasia. Patients with chronic ulcerative colitis should have periodic rectal and colonoscopic biopsies, and those with moderate to marked dysplasia require colectomy because of the increased risk of colon carcinoma.


Comparison of quiet breathing and controlled ventilation in the high-resolution CT assessment of airway disease in infants with cystic fibrosis.
Respiratory motion and low lung volumes limit the quality of HRCT examinations in infants and young children. To assess the effects of respiratory motion and lung inflation on the ability to diagnose airway abnormalities and air trapping (AT) using HRCT in infants with cystic fibrosis (CF). HRCT images of the lungs were obtained at four anatomical levels in 16 sedated children (age 2.4+/-1.1 years, mean+/-SD) with CF using controlled ventilation at full lung inflation (CVCT-I), at resting end exhalation (CVCT-E), and during quiet breathing (CT-B). Two blinded reviewers independently and then by consensus scored all images for the presence or absence of bronchiectasis (BE), bronchial wall thickening (BWT), and AT. Of the 64 images evaluated, BE was identified in 19 (30%) of the CVCT-I images compared to 6 (9%) of the CVCT-E images (P=0.006) and 4 (6%) of the CT-B images (P=0.044). AT was seen in 29 (45%) of the CVCT-E images compared to 14 (22%) of the CVCT-I images (P=0.012) and 12 (19%) of the CT-B images (P=0.012). There were no significant differences in the detection of BWT among the three methods. In infants with CF, fully inflating the lung improved the ability to diagnose early BE, and obtaining motion-free images at end exhalation enhanced the detection of AT.


Psychophysical evaluation of toxic effects on sensory systems.
Toxic effects on sensory systems have rarely been evaluated by psychophysical methods. As examples of possible applications four studies are described. Sodium salicylate and kanamycin, both reported to produce hearing deficits in man, have also been demonstrated to affect auditory thresholds in monkeys. With the latter drug the deficits measured were found to be correlated with specific loss of receptor cells in the cochlea. Pheniprazine, known to induce red-green color blindness, was found to disrupt a wavelength discrimination in pigeons. Trans 11-amino-10,11-dihydro-5-(3-dimethylaminopropyl)-5,10-expoxy-5H-dibenzo[a,d]-cycloheptene dihydrochloride, which was found to bleach the tapidum lucidum in dogs when given subacutely, was found to decrease sensitivity to light. The loss in sensitivity measured by behavioral techniques was correlated with the loss of coloration of the tapidum. Monkeys, not having a tapidum, did not show a similar effect.


A selective electrochemical sensor for caffeic acid and photocatalyst for metronidazole drug pollutant - A dual role by rod-like SrV2O6.
In the present study, well-defined one-dimensional (1D) rod-like strontium vanadate (SrV2O6) was prepared by simple hydrothermal method without using any other surfactants/templates. The successful formation of rod-like SrV2O6 was confirmed by various analytical and spectroscopic techniques. Interestingly, for the first time the dual role of as-prepared rod-like SrV2O6 were employed as an electrochemical sensor for the detection of caffeic acid (CA) as well as visible light active photocatalyst for the degradation of metronidazole (MNZ) antibiotic drug. As an electrochemical sensor, the SrV2O6 modified glassy carbon electrode (GCE) demonstrated a superior electrocatalytic activity for the detection of CA by chronoamperometry and cyclic voltammetry (CVs). In addition, the electrochemical sensor exhibited a good current response for CA with excellent selectivity, wide linear response range, lower detection limit and sensitivity of 0.01-207 µM, 4 nM and 2.064 μA μM-1cm-2, respectively. On the other hand, as-synthesized rod-like SrV2O6 showed highly efficient and versatile photocatalytic performances for the degradation of MNZ, which degrades above 98% of MNZ solution under visible light irradiation within 60 min. The obtained results evidenced that the improvement of rod-like SrV2O6 might be a resourceful electrocatalyst and photocatalyst material in the probable applications of environmental and biomedical applications.


Identification of multilevel right-to-left shunting in a dog using nuclear scintigraphy imaging.
A 27-month-old male neutered French bulldog that was originally diagnosed with tricuspid valve dysplasia and a bidirectional shunting patent foramen ovale was evaluated for progressive polycythemia and exertional cyanosis. There was a high clinical suspicion for a right-to-left shunting patent ductus arteriosus, but given the presence of agitated saline within the left atrium, left ventricle, ascending aorta, and abdominal aorta from the previously diagnosed bidirectional shunting patent foramen ovale, a definitive diagnosis could not be made. The use of dynamic and static nuclear scintigraphy imaging using technetium-labeled macroaggregated albumin (99mTc-MAA) allowed a definitive diagnosis to be made in this animal with multilevel right-to-left shunting as well as quantifying the severity of the right-to-left shunt in a minimally invasive and cost-effective manner.


Detection of basic drugs (methamphetamine, antidepressants, and nicotine) from human hair.
Human hair contains methamphetamine, amitriptyline, imipramine, nicotine, and their metabolites in some amount, which can be detected by routine toxicological methods. Sometimes, the level of drugs reaches over 100 micrograms/g. Animal experiments indicate that these drugs are found solely in sections of hair grown after administration of the drugs. The negative stage after the administration of drugs means that the hair section containing drugs has not come out of the hair follicle. Toxicological examination of the hairs may give some clue helping to identify the chronology of the intoxication.


The role of affective touch in modulating emotion processing among preschool children.
Recognizing emotional expressions is a prerequisite for understanding others' feelings and intentions, a key component of social interactions that develops throughout childhood. In multisensory social environments, touch may be crucial for emotion processing, linking external sensory information with internal affective states. The current study investigated whether affective touch facilitates recognition of emotional expressions throughout childhood. Preschool children (N = 121 3- to 6-year-olds) were presented with different tactile stimulations followed by an emotion-matching task. Results revealed that affective touch fosters the recognition of negative emotions and increases the speed of association of positive emotions, highlighting the centrality of tactile experiences for socioemotional understanding. The current research opens new perspectives on how to support emotional recognition with potential consequences for the development of social functioning.


[Initiating insulin therapy in patients with diabetes mellitus type 2: in a transmural setting is at least as effective as in an outpatient setting; a retrospective study with a 4-year follow-up].
Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. Retrospective comparative cohort study. In 1997 data were collected from 52 patients with diabetes mellitus type 2 all of whom were above 40 years of age and transferred to insulin therapy in 1993: 25 in a transmural care setting and 27 in an outpatients setting, both in Amsterdam, the Netherlands. Both groups were treated according to one protocol concerning the initiation and monitoring of insulin therapy, treatment goals and follow-up. Outcome measures were: percentage of glycated haemoglobin (HbA1c), health status, self-care behaviour and patient satisfaction. In 1993 the mean age was (transmural/outpatients setting): 67.5/65.3 years; percentage of men: 32%/48%; mean duration of diabetes: 7.3/10.6 years; HbA1c: 9.1%/9.3%; mean body mass index: 27.4/29.1 kg/m2. In the period 1993-1997 the mean HbA1c decreased from 9.1% to 7.2% in the transmural care group and from 9.3% to 7.6% in the outpatients care group (both: p = 0.000). The percentage of patients with poor glycaemic control (HbA1c > 8%) decreased from 60 to 8 in the transmural care group and from 59 to 15 in the outpatients care group. The percentage of patients with good glycaemic control (HbA1c < 7%) increased from 4 to 52 in the transmural care group and from 11 to 30 in the outpatients care group. No statistically significant differences were found between the patient groups with respect to health status, self-care behaviour and patient satisfaction. The transfer of patients with diabetes mellitus type 2 insulin therapy in a shared care setting was at least as effective as in an outpatients setting.


The in vivo formation of nonbilayer lipid phase in E. coli membranes during the development of Ca2-dependent competence.
31P-NMR studies on E. coli cells reveal the in vivo formation of nonbilayer lipid structures, presumably of H11 phase, during Ca2-dependent competence induction. The data suggest the involvement of these structures in the exogenous DNA transfer into the cells during genetic transformation and transfection. The suggestion is supported by in vitro experiments in which the liposomes composed of different phospholipid species bind 14C-DNA in DNase and wash resistant form in conditions promoting the hexagonal phase formation.


Possible demographic consequences of AIDS in developing countries.
Simple mathematical models of the transmission dynamics of HIV that incorporate demographic and epidemiological processes to assess the potential impact of AIDS on human population growth and structure in developing countries suggest that AIDS is capable of changing population growth rates from positive to negative values over timescales of a few decades. The disease is predicted to have little if any impact on the dependency ratio of a population, defined as the number of children below age 15 years and elderly people over 64 years, divided by the number of adults between 15 to 64 years.


MiR-126 suppresses colon cancer cell proliferation and invasion via inhibiting RhoA/ROCK signaling pathway.
Recent data strongly suggests the profound role of miRNAs in cancer progression. Here, we showed miR-126 expression was much lower in HCT116, SW620 and HT-29 colon cancer cells with highly metastatic potential and miR-126 downregulation was more frequent in colorectal cancers with metastasis. Restored miR-126 expression inhibited HT-29 cell growth, cell-cycle progression and invasion. Mechanically, microarray results combined with bioinformatic and experimental analysis demonstrated miR-126 exerted cancer suppressor role via inhibiting RhoA/ROCK signaling pathway. These results suggest miR-126 function as a potential tumor suppressor in colon cancer progression and miR-126/RhoA/ROCK may be a novel candidate for developing rational therapeutic strategies.


Closed percutaneous catheter drainage of a cervical abscess.
The advantages offered by a percutaneous catheter system are: The procedure is done using only local anesthesia. Computed tomography is used for exquisite anatomical detail and pinpoint guidance. If required, aspiration, irrigation, and dependent or suction drainage can all be done. Isolation of purulent material from the skin and site of drainage is accomplished. A true anaerobic culture specimen is obtainable with the initial aspiration. The esthetic results, are superior to surgical management. Percutaneous abscess drainage should thus be seriously considered as an alternative to surgery in the treatment of head and neck abscesses.


The feasibility of 18F-FDG gated positron emission tomography (PET) for left ventricular dyssynchrony assessment in comparison with 99mTc-MIBI gated single-photon emission computed tomography (SPECT) among patients with prior myocardial infarction.
Phase analysis by 99mTc-MIBI gated single-photon emission computed tomography (GSPECT) has been considered to be an adequate method in the validation of left ventricular (LV) dyssynchrony. Compared with GSPECT, prior myocardial infarction patients with myocardial perfusion defects but myocardial viability usually show preserved uptake of 18F-FDG, and extensive myocardium is detected by 18F-FDG gated positron emission tomography (GPET). Thus, theoretically, it should be more accurate. The aim of this study was to investigate the feasibility of GPET for LV dyssynchrony assessment in comparison with GSPECT among infarction patients. A total of 146 patients with infarction underwent 2 consecutive days of GSPECT and GPET examinations. Quantitative gated SPECT-derived LV phase analysis was applied to GPET and GSPECT data to assess the presence of LV dyssynchrony via histogram bandwidth (BW) and phase standard deviation (SD). The correlation and agreement of BW and SD between GSPECT and GPET were examined. Factors (i.e., total perfusion defect, scar and mismatch) related to the discrepancies of LV dyssynchrony (i.e., BW and SD) in GPET and GSPECT were assessed by univariate and multivariate regression analysis. A moderate correlation between GPET and GSPECT was found in the measurements of BW (r=0.554) and SD (r=0.537). Bland-Altman analysis revealed that GPET overestimated both BW and SD (20.5° and 9.5°, respectively). In addition, the BW and SD measured by GPET were still overestimated after subgroup analysis. Between GPET and GSPECT, multivariate regression analysis revealed that total perfusion defects were related to the difference in BW measurement (P<0.001), and mismatch was associated with the difference in SD measurement (P<0.01). In patients with infarction, GPET moderately correlated with GSPECT in assessing LV dyssynchrony. GPET overestimated both BW and SD, so these analyses should not be interchangeable in individual patients.


Preliminary studies on the prevalences of natural fasciolosis in cattle, sheep, and the host snail (Galba truncatula) in north-eastern Algeria.
Three series of investigations on natural infections with Fasciola hepatica were carried out in north-eastern Algeria): (1) on different samples from cattle and sheep slaughtered at Constantine and Jijel from 1994 to 1996, (2) from 31 cattle- and sheep-breeding farms from 1999 to 2001, using serology on blood samples, and (3) on overwintering Galba truncatula from four populations, in 2002 and 2003. Significantly higher prevalences of fasciolosis were found in the cattle and sheep from Jijel (27.0% in slaughtered cattle and 27.3% in cattle from farms, compared to 9.1% and 6.3%, respectively, in cattle from Constantine). No significant differences in the prevalences were recorded between 1994 and 1996 and 1999 and 2001 for each species of ruminant, whatever the department considered. The infection rates for overwintering snails were also higher in the two populations from Jijel compared with those from the department of Constantine (a mean of 4.6-5.9% instead of 2.6-3.1%)). These results may be explained by the climatic conditions in the department of Jijel (an annual rainfall of 750-900 mm instead of 350 mm at Constantine), and the mode of anthelminthic treatment (the periods of treatment would be inappropriate in the case of Jijel).


Osteogenic sarcomas mimicking left atrial myxomas: clinical and two-dimensional echocardiographic features.
Two patients presenting with acute pulmonary edema were found to have a left atrial cardiac osteogenic sarcoma (primary and secondary). The two-dimensional echocardiographic appearance in both cases mimicked that of atrial myxoma. However, two echocardiographic features (that is, tumor extension into pulmonary veins and origin from nonseptal atrial walls) suggested the presence of a nonmyxomatous cardiac tumor.


Predictive evaluation in animals of the contact allergenic potential of medically important substances. I. Comparison of different methods of inducing and measuring cutaneous sensitization.
Groups of guinea pigs were sensitized with a 0.1% solution of dinitrochlorobenzene (DNCB) by the Draize intracutaneous method. The course of the induction process, the influence of the vehicles used and the extent to which the reactions are amenable to assessment according to objective criteria were examined. The sensitivity of the standardized Draize test was then compared with that of various other sensitization techniques, including: The intracutaneous test with adjuvant (optimization test) The maximization test according to Magnusson & Kligman (1969) The epidermal sensitization test The epidermal sensitization test with prior irritation of the contact site (by croton oil or sodium lauryl sulphate). Comparison of these methods revealed that either the additional application of adjuvant or prior irritation of the contact site augmented the degree of sensitization of DNCB just as greatly as the simultaneous use of adjuvant and prior irritation of the skin, (maximization test). The improved sensitization methods, and in particular the standardized optimization test, may prove to be of particular value for the study of so-called weak allergens.


Heteronuclear Dirhodium-Gold Anionic Complexes: Polymeric Chains and Discrete Units.
In this article, we report on the synthesis and characterization of the tetracarboxylatodirhodium(II) complexes [Rh2(μ-O2CCH2OMe)4(THF)2] (1) and [Rh2(μ-O2CC6H4-p-CMe3)4(OH2)2] (2) by metathesis reaction of [Rh2(μ-O2CMe)4] with the corresponding ligand acting also as the reaction solvent. The reaction of the corresponding tetracarboxylato precursor, [Rh2(μ-O2CR)4], with PPh4[Au(CN)2] at room temperature, yielded the one-dimensional polymers (PPh4)n[Rh2(μ-O2CR)4Au(CN)2]n (R = Me (3), CH2OMe (4), CH2OEt (5)) and the non-polymeric compounds (PPh4)2{Rh2(μ-O2CR)4[Au(CN)2]2} (R = CMe3 (6), C6H4-p-CMe3 (7)). The structural characterization of 1, 3·2CH2Cl2, 4·3CH2Cl2, 5, 6, and 7·2OCMe2 is also provided with a detailed description of their crystal structures and intermolecular interactions. The polymeric compounds 3·2CH2Cl2, 4·3CH2Cl2, and 5 show wavy chains with Rh-Au-Rh and Rh-N-C angles in the ranges 177.18°-178.69° and 163.0°-170.4°, respectively. A comparative study with related rhodium-silver complexes previously reported indicates no significant influence of the gold or silver atoms in the solid-state arrangement of these kinds of complexes.