Hydrotherapy versus conventional land-based exercise for the management of patients with osteoarthritis of the knee: a randomized clinical trial.
This study was designed to evaluate the effectiveness of hydrotherapy in subjects with osteoarthritis (OA) of the knee compared with subjects with OA of the knee who performed land-based exercises. Sixty-four subjects with OA of the knee were randomly assigned to 1 of 2 groups that performed exercises for 18 weeks: a water-based exercise group and a land-based exercise group. The outcome measures included a visual analog scale (VAS) for pain in the previous week, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain during gait assessed by a VAS at rest and immediately following a 50-foot (15.24-m) walk test (50FWT), walking time measured at fast and comfortable paces during the 50FWT, and the Lequesne Index. Measurements were recorded by a blinded investigator at baseline and at 9 and 18 weeks after initiating the intervention. The 2 groups were homogenous regarding all parameters at baseline. Reductions in pain and improvements in WOMAC and Lequesne index scores were similar between groups. Pain before and after the 50FWT decreased significantly over time in both groups. However, the water-based exercise group experienced a significantly greater decrease in pain than the land-based exercise group before and after the 50FWT at the week-18 follow-up. Both water-based and land-based exercises reduced knee pain and increased knee function in participants with OA of the knee. Hydrotherapy was superior to land-based exercise in relieving pain before and after walking during the last follow-up. Water-based exercises are a suitable and effective alternative for the management of OA of the knee.


Anti-interleukin-5 antibody therapy in eosinophilic diseases.
Eosinophilia in atopic diseases and hypereosinophilic syndrome is often associated with a high expression of interleukin-5 (IL-5). IL-5 plays an important role in regulating the production, differentiation, recruitment, activation, and survival of eosinophils. Therefore, neutralizing IL-5 with an antibody is a promising therapeutic strategy in eosinophilic diseases. In patients with hypereosinophilic syndrome and eosinophilic esophagitis, anti-IL-5 antibody therapy resulted in an improvement of symptoms. In patients with bronchial asthma, no effect on the late phase reaction and on airway hyperresponsiveness has been observed. Moreover, patients with atopic dermatitis demonstrated only a moderate improvement of their skin lesions and pruritus. Anti-IL-5 therapy was followed by a rapid and sustained decrease of peripheral blood eosinophil numbers. The decrease of tissue eosinophils was, however, less dramatic. Investigating the effects of anti-IL-5 therapy will improve our understanding of the pathogenic roles of both IL-5 and eosinophils in eosinophilic inflammatory responses.


A Critical Review of Low Back Pain Guidelines.
Low back pain (LBP) remains one of the most common and challenging musculoskeletal conditions encountered by health care professionals and is a leading cause of absenteeism. Clinical guidelines are often considered best evidence in health care. The aim of this critical review was to assess the quality and recommendations of LBP guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. Electronic databases were used to identify LBP guidelines published between 2000 and 2015. Nine guidelines were selected for review from a total of 17. Only five guidelines effectively addressed the AGREE scoring. On the basis of the appraisal and domain scores, only four guidelines were strongly recommended. Improved translation of research evidence from guidelines to clinical practice is needed.


Thiosulfate-dependent chemolithoautotrophic growth of Bradyrhizobium japonicum.
Thiosulfate-oxidizing sox gene homologues were found at four loci (I, II, III, and IV) on the genome of Bradyrhizobium japonicum USDA110, a symbiotic nitrogen-fixing bacterium in soil. In fact, B. japonicum USDA110 can oxidize thiosulfate and grow under a chemolithotrophic condition. The deletion mutation of the soxY(1) gene at the sox locus I, homologous to the sulfur-oxidizing (Sox) system in Alphaproteobacteria, left B. japonicum unable to oxidize thiosulfate and grow under chemolithotrophic conditions, whereas the deletion mutation of the soxY(2) gene at sox locus II, homologous to the Sox system in green sulfur bacteria, produced phenotypes similar to those of wild-type USDA110. Thiosulfate-dependent O(2) respiration was observed only in USDA110 and the soxY(2) mutant and not in the soxY(1) mutant. In the cells, 1 mol of thiosulfate was stoichiometrically converted to approximately 2 mol of sulfate and consumed approximately 2 mol of O(2). B. japonicum USDA110 showed (14)CO(2) fixation under chemolithotrophic growth conditions. The CO(2) fixation of resting cells was significantly dependent on thiosulfate addition. These results show that USDA110 is able to grow chemolithoautotrophically using thiosulfate as an electron donor, oxygen as an electron acceptor, and carbon dioxide as a carbon source, which likely depends on sox locus I including the soxY(1) gene on USDA110 genome. Thiosulfate oxidation capability is frequently found in members of the Bradyrhizobiaceae, which phylogenetic analysis showed to be associated with the presence of sox locus I homologues, including the soxY(1) gene of B. japonicum USDA110.


Telehealth for patients with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis protocol.
Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic disease characterised by persistent respiratory symptoms. A focus of COPD interventional studies is directed towards prevention of exacerbations leading to hospital readmissions. Telehealth as a method of remote patient monitoring and care delivery may be implemented to reduce hospital readmissions and improve self-management of disease. Prior reviews have not systematically assessed the efficacies of various telehealth functionalities in patients with COPD at different stages of disease severity. We aim to evaluate which COPD telehealth interventions, classified by their functionalities, are most effective in improving patient with COPD management measured by both clinical and resource utilisation outcomes. We will conduct a systematic review which will include randomised controlled trials comparing the efficacy of telehealth interventions versus standard care in patients with COPD with confirmed disease severity based on forced expiratory volume(%) levels. An electronic search strategy will be used to identify trials published since 2000 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINHAL. Telehealth is described as remote monitoring and delivery of care where patient data/clinical information is routinely or continuously collected and/or processed, presented to the patient and transferred to a clinical care institution for feedback, triage and intervention by a clinical specialist. Two authors will independently screen articles for inclusion, assess risk of bias and extract data. We will merge studies into a meta-analysis if the interventions, technologies, participants and underlying clinical questions are homogeneous enough. We will use a random-effects model, as we expect some heterogeneity between interventions. In cases where a meta-analysis is not possible, we will synthesise findings narratively. We will assess the quality of the evidence for the main outcomes using GRADE. Research ethics approval is not required. The findings will be disseminated through publication in a peer-reviewed journal. CRD42018083671.


STAT-dependent upregulation of 12/15-lipoxygenase contributes to neuronal injury after stroke.
Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and -1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke.


Endoscopic endonasal pituitary gland hemi-transposition for resection of a dorsum sellae meningioma.
A 69-year-old female with incidental diagnosis of a dorsum sellae meningioma had shown significant tumor growth after initial conservative management. The procedure started with a microscopic sublabial transsphenoidal approach to the sella and the suprasellar space. Due to limitations to a safe dissection and removal of the retrosellar component, the surgery was converted to a purely endoscopic endonasal approach with left hemi-transposition of the pituitary gland, followed by drilling of the dorsum sellae and removal of the left posterior clinoid process. A complete tumor resection was achieved, and a multilayer skull base reconstruction was performed without complications. The video can be found here: https://youtu.be/BEolyK-To_A .


Developing a positive patient experience with nurses in general practice: An integrated model of patient satisfaction and enablement.
To develop a conceptual model that provides a comprehensive understanding of the structures and processes underpinning patient enablement and satisfaction in general practice nurse consultations. Current evidence regarding patient satisfaction and enablement arising from general practice nursing care is either quantitative or qualitative. To date, no studies have integrated the results of mixed methods research to provide a deeper understanding of processes that facilitate their achievement. A concurrent mixed methods study. Our 2013-2014 concurrent mixed methods study comprised a quantitative study that analysed variables identified in interviews with general practice nurses, patients and practice managers with data from a cross-sectional survey of 678 patients receiving nursing care in 21 general practices; and a qualitative study that used a grounded theory approach to in-depth interviews with nurses and patients from these same practices. Using joint displays, we compared and integrated the results of the multilevel analyses and the grounded theory model derived from these studies. We conceptualized a model-'developing a positive patient experience with nurses in general practice'-in which time, continuity of care, nursing scope of practice and autonomy, and patients' health conditions provide platforms for the processes of triggering healthcare partnerships and tailoring care in nurse consultations. This model builds on previous evidence describing processes and characteristics that optimize the quality of care in general practice nurse consultations. It provides a practical tool to inform education and training for general practice nurses and other clinicians.


Community residential adjustment: the relationship among environment, performance, and satisfaction.
A cohort of 153 persons released from a state school for mentally retarded persons was studied with regard to two outcome measures of community residential adjustment: (a) adaptive behavior as measured by the percentage of mastered skills that a subject performed regularly and independently and (b) subjects' satisfaction with aspects of their residential environments. Five environmental dimensions of six residential program types were examined, and significant differences among the program types on these environmental dimensions were reported. A multiple regression analysis was performed to explain the relationship between the measures of adaptive behavior and individual and environmental characteristics. Benefits of this study's measurement of community adjustment were discussed in terms of their potential use for future research and for use by planners and providers of services.


Deciphering Cryptic Binding Sites on Proteins by Mixed-Solvent Molecular Dynamics.
In recent years, molecular dynamics simulations of proteins in explicit mixed solvents have been applied to various problems in protein biophysics and drug discovery, including protein folding, protein surface characterization, fragment screening, allostery, and druggability assessment. In this study, we perform a systematic study on how mixtures of organic solvent probes in water can reveal cryptic ligand binding pockets that are not evident in crystal structures of apo proteins. We examine a diverse set of eight PDB proteins that show pocket opening induced by ligand binding and investigate whether solvent MD simulations on the apo structures can induce the binding site observed in the holo structures. The cosolvent simulations were found to induce conformational changes on the protein surface, which were characterized and compared with the holo structures. Analyses of the biological systems, choice of probes and concentrations, druggability of the resulting induced pockets, and application to drug discovery are discussed here.


Emotional responses to pleasant and unpleasant olfactory, visual, and auditory stimuli: a positron emission tomography study.
Neural correlates of responses to emotionally valenced olfactory, visual, and auditory stimuli were examined using positron emission tomography. Twelve volunteers were scanned using the water bolus method. For each sensory modality, regional cerebral blood flow (rCBF) during presentation of both pleasant and unpleasant stimuli was compared with that measured during presentation of neutral stimuli. During the emotionally valenced conditions, subjects performed forced-choice pleasant and unpleasant judgments. During the neutral conditions, subjects were asked to select at random one of a two key-press buttons. All stimulations were synchronized with inspiration, using an airflow olfactometer, to present the same number of stimuli for each sensory modality. A no-stimulation control condition was also performed in which no stimulus was presented. For all three sensory modalities, emotionally valenced stimuli led to increased rCBF in the orbitofrontal cortex, the temporal pole, and the superior frontal gyrus, in the left hemisphere. Emotionally valenced olfactory and visual but not auditory stimuli produced additional rCBF increases in the hypothalamus and the subcallosal gyrus. Only emotionally valenced olfactory stimuli induced bilateral rCBF increases in the amygdala. These findings suggest that pleasant and unpleasant emotional judgments recruit the same core network in the left hemisphere, regardless of the sensory modality. This core network is activated in addition to a number of circuits that are specific to individual sensory modalities. Finally, the data suggest a superior potency of emotionally valenced olfactory over visual and auditory stimuli in activating the amygdala.


[The phagetype and detection of drug-resistance of Salmonella typhi-muriun in Fujian province].
Salmonella typhimurium has accounted for 29.43% of total Salmonella according to the surveillance in Fujian province since 1975. Seven common phagetypes of S. typhimurium were found. The principal phagetype was 7774, which accounted for 46.6% of all phagetypes. S. typhimurium was significantly more resistant to antibiotics in early 1990's than in the 1980's. 57%-72% of the S. typhimurium strains were resistant to aminoglycosides (except amikacin), about 70% were strains resistant to first generation penicillins and tetracyclins while a high proportion of S. typhimurium strains have rapidly become resistant to new broad-spectrum penicillins. The strains of S. typhimurium which are resistant to the first and the second generation of cephalothins become sensitive only to the third generation of cephalo thins. There has been 20% of S. typhimurium strains resistant to some types of quinolones. All S. typhimurium were sensitive to norfloxacin, ofloxacin and ciprofloxacin. In the early 1980's resistant strains to 2-3 kinds of antibiotics accounted for 97%, and nostrains was resistant to more then 6 kinds of antibiotics. In the early 1990's, the strain resistant to 2-3 kinds of antibiotics were less than 20%; while strains resistant to more than 10 kinds of antibiotics were 66%. The increasing rate of resistant strains to antibiotics with widening of drug resistant pattern and the extensive appearance of multiresistant strains have become serious problems to be solved.


Transient receptor potential vanilloid 4: The sixth sense of the musculoskeletal system?
The critical discovery in the past two decades of the transient receptor potential (TRP) superfamily of ion channels has revealed the potential mechanisms by which cells sense diverse stimuli beyond the prototypical "five senses," identifying ion channels that are gated by heat, cold, mechanical loading, osmolarity, and other physical and chemical stimuli. TRP vanilloid 4 (TRPV4) is a Ca(2+)-permeable nonselective cation channel that appears to play a mechanosensory or osmosensory role in several musculoskeletal tissues. In articular cartilage, TRPV4 exhibits osmotic sensitivity, controlling cellular volume recovery, and other physiologic responses to osmotic stress. TRPV4 is expressed in both osteoblasts and osteoclasts, and the absence of TRPV4 prevents disuse-induced bone loss. TRPV4 activation promotes chondrogenesis by inducing SOX9 transcription, whereas a TRPV4 gain-of-function mutation leads to a developmental skeletal dysplasia, suggesting a critical role for TRPV4 in skeletal development. These studies provide mounting evidence for a regulatory role for the sensory channel TRPV4 in control of musculoskeletal tissues.


Functional expression of mung bean Ca2+/H+ antiporter in yeast and its intracellular localization in the hypocotyl and tobacco cells.
The Ca2+-transport activity and intracellular localization of the translation product of cDNA for mung bean Ca2+/H+ antiporter (VCAX1) were examined. When the cDNA was expressed in Saccharomyces cerevisiae that lacked its own genes for vacuolar Ca2+-ATPase and the antiporter, VCAX1 complemented the active Ca2+ transporters, and the microsomal membranes from the transformant showed high activity of the Ca2+/H+ antiporter. Treatment of the vacuolar membranes with a cross-linking reagent resulted in a clear band of the dimer detected with antibody specific for VCAX1p. The antibody was also used for immunolocalization of the antiporter in fractions obtained by sucrose-density-gradient centrifugation of the microsomal fraction from mung bean. The immunostained band was detected in the vacuolar membrane fraction and the slightly heavy fractions that exhibited activity of the Golgi marker enzyme. A fusion protein of VCAX1p and green fluorescent protein was expressed in tobacco cells. The green fluorescence was clearly observed on the vacuolar membrane and, in some cases, in the small vesicles. The subcellular fractionation of transformed tobacco cells confirmed the vacuolar membrane localization of the fusion protein. These results confirm that VCAX1p functions in the vacuolar membrane as a Ca2+/H+ antiporter and also suggest that VCAX1p may exist in the Golgi apparatus.


MiR-485-5p promotes the development of osteoarthritis by inhibiting cartilage differentiation in BMSCs.
To investigate whether microRNA-485-5p (miR-485-5p) can participate in osteoarthritis by inhibiting chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promoting the secretion of inflammatory factors. BMSCs were obtained from mouse bone marrow samples and identified by flow cytometry. The expression of specific genes and miR-485-5p in the differentiation of BMSCs was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The influence of miR-485-5p on chondrogenic differentiation was subsequently evaluated by toluidine blue staining, detection of chondrogenic specific gene expression and inflammatory factors. After over-expressing SOX9, it was assessed whether miR-485-5p can affect the chondrogenic differentiation of BMSCs by inhibiting SOX9, so as to promote the secretion of inflammatory factors. The miR-485-5p level was negatively correlated with the degree of differentiation of BMSCs. After overexpression of microRNA-485-5p in BMSCs, the expression of cartilage surface marker genes and toluidine blue staining were reduced, while the expression of cartilage surface inflammation factors, including interleukin and tumor necrosis factor, was significantly enhanced. Meanwhile, opposite results were observed when miR-485-5p was inhibited. In addition, overexpression of SOX9 could restore the secretion of inflammatory cytokines induced by microRNA-485-5p. MiR-485-5p can decrease the level of SOX9, promote the production of inflammatory factors on the cartilage surface, and block the differentiation of mouse BMSCs into chondrocytes.


Behavioral measures of auditory streaming in ferrets (Mustela putorius).
An important aspect of the analysis of auditory "scenes" relates to the perceptual organization of sound sequences into auditory "streams." In this study, we adapted two auditory perception tasks, used in recent human psychophysical studies, to obtain behavioral measures of auditory streaming in ferrets (Mustela putorius). One task involved the detection of shifts in the frequency of tones within an alternating tone sequence. The other task involved the detection of a stream of regularly repeating target tones embedded within a randomly varying multitone background. In both tasks, performance was measured as a function of various stimulus parameters, which previous psychophysical studies in humans have shown to influence auditory streaming. Ferret performance in the two tasks was found to vary as a function of these parameters in a way that is qualitatively consistent with the human data. These results suggest that auditory streaming occurs in ferrets, and that the two tasks described here may provide a valuable tool in future behavioral and neurophysiological studies of the phenomenon.


Green fluorescent protein variants as ratiometric dual emission pH sensors. 3. Temperature dependence of proton transfer.
In parts 1 and 2 of this series [Hanson, G. T., McAnaney, T. B., Park, E. S., Rendell, M. E. P., Yarbrough, D. K., Chu, S. Y., Xi, L. X., Boxer, S. G., Montrose, M. H., and Remington, S. J. (2002) Biochemistry 41, 15477-15488; McAnaney, T. B., Park, E. S., Hanson, G. T., Remington, S. J., and Boxer, S. G. (2002) Biochemistry 41, 15489-15494], we described the structure, excited-state dynamics, and applications of pH-sensitive, ratiometric dual emission green fluorescent protein (deGFP) variants with fluorescence emission that is modulated between blue (lambda(max) approximately equal 465 nm) and green (lambda(max) approximately equal 515 nm) depending on the pH of the bulk solvent. In this paper, we consider the energetic origin of the dual emission properties of these GFP variants by examining the temperature dependence of the steady-state absorption and fluorescence emission. In most cases, the quantum yield of the green emission decreased as the temperature was lowered, indicating that the excited-state proton transfer (ESPT) which produces the green emitting form is an activated process. The activation energies of ESPT, determined by modeling the quantum yields of both blue and green emissions between 260 and 298 K in the context of a simple photocycle, were found to be larger at low pH than at high pH. These results indicate that the ratiometric dual emission properties of deGFP mutants are due to this pH-sensitive ESPT rate, combined with a modulation of the ground-state neutral and anionic chromophore populations with pH. The time-resolved fluorescence of one of the deGFP mutants was studied in detail. The time-resolved emission spectra of this mutant are the first ultrafast spectra obtained for a GFP. These spectra demonstrate that the rising kinetics for green emission, considered a hallmark of ESPT, is the sum of the contribution from both the neutral and intermediate anionic forms of the chromophore at the probe wavelength and may not be observed in all mutants that undergo ESPT, depending on the relative contributions of the two forms.


Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis.
Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment. A systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics. A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus. By excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal-limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.


Implant-Retained Overdentures Using an Attachment with True-Alignment Correction: A Case Series.
Implant parallelism is considered a cardinal criterion for the successful rehabilitation of edentulous jaws with implant-retained overdentures (IODs), especially if freestanding anchorage systems (unsplinted attachments) are employed. This report aimed to demonstrate the successful use of a novel IOD attachment with a true-alignment capability in complex cases with large inter-implant angular discrepancies. The report further aimed to highlight the use of a novel polyetherketoneketone (PEKK) framework as a reinforcement material for fabricating a completely metal-free IOD. Although some freestanding attachments exploit their geometric form and/or use various retentive inserts to compensate for inter-implant angular discrepancies, a true-alignment correction is seldom achieved. The CM LOC FLEX (Cendres+Métaux attachment provides a true alignment correction and produces parallelism between implants in clinical situations where the implants are not parallel to one another. The functionality of the CM LOC FLEX was described in this case report for two different clinical situations: a conventional mandibular IOD retained by two implants, and a maxillary IOD retained by four implants. Both cases involved a complex clinical situation with compromised implant parallelism. The CM LOC FLEX abutment has a true-alignment correction mechanism that can be advantageous in clinical situations where the inter-implant axial alignments are not parallel. PEKK frameworks are lightweight, strong, and can be esthetic substitutes for conventional metal frameworks. However, well-designed clinical studies are further needed to assess the clinical performance as well as the maintenance requirements of the illustrated novel attachment and the PEKK framework before advocating them as validated and standard protocols.


Sand flies (Diptera: Phlebotominae) in Sanliurfa, Turkey: relationship of Phlebotomus sergenti with the epidemic of anthroponotic cutaneous leishmaniasis.
Sand fly (Diptera: Phlebotominae) fauna were surveyed in various districts of Sanliurfa in southeast Turkey for 3 yr immediately after an epidemic of cutaneous leishmaniasis (Leishmania tropica). Sticky papers and CDC light traps collected a total of 10,937 sand flies, of which 10,919 (4,158 females and 6,761 males) were identified as Phlebotomus and 18 (11 females and seven males) as Sergentomyia (S. theodori Parrot; S. adleri Theodor). Eight Phlebotomus spp. were identified: P. sergenti Parrot (72.3%), P. papatasi (Scopoli) (27.2%), P. brevis Theodor & Mesghali (0.20%), P. neglectus Leger & Pesson (0.13%), P. perfiliewi Parrot (0.05%), P. mascitti Grassi, P. halepensisTheodor, and P. alexandri Sinton (0.01%). Phlebotomus mascitti and P. neglectus, along with both Sergentomyia sp., have not been previously described from the study area. Similar results were obtained when both trapping methods were applied in the same houses, indicating that local P. sergenti and P. papatasi populations were equally attracted to the light. P. sergenti was consistently abundant, agreeing with the general view that this species is the vector of leishmaniasis in the region. There was no apparent decrease in the relative abundance of this vector versus the other species, suggesting that factor (s) other than a change in the dynamics of sand fly populations precipitated the decline of the human leishmaniasis epidemic in Sanliurfa.


Substituted aziridines by lithiation-electrophile trapping of terminal aziridines.
[reaction: see text] Regio- and stereoselective deprotonation of N-Bus (Bus = tert-butylsulfonyl)-protected terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide generates a nonstabilized (H-substituted) aziridinyl anion that undergoes in situ or external electrophile trapping under experimentally straightforward conditions to give trans-disubstituted aziridines in good to excellent yields.


Singlet oxygen plays a key role in the toxicity and DNA damage caused by nanometric TiO2 in human keratinocytes.
Nanometric TiO2 has been reported to be cytotoxic and genotoxic in different in vitro models when activated by UV light. However, a clear picture of the species mediating the observed toxic effects is still missing. Here, a nanometric TiO2 powder has been modified at the surface to completely inhibit its photo-catalytic activity and to inhibit the generation of all reactive species except for singlet oxygen. The prepared powders have been tested for their ability to induce strand breaks in plasmid DNA and for their cytotoxicity and genotoxicity toward human keratinocyte (HaCaT) cells (100-500 μg mL(-1), 15 min UVA/B exposure at 216-36 mJ m(-2) respectively). The data reported herein indicate that the photo-toxicity of TiO2 is mainly triggered by particle-derived singlet oxygen. The data presented herein contribute to the knowledge of structure-activity relationships which are needed for the design of safe nanomaterials.


Qianliexin capsule exerts anti-inflammatory activity in chronic non-bacterial prostatitis and benign prostatic hyperplasia via NF-κB and inflammasome.
Qianliexin capsule (QLX) is a standardized traditional Chinese herbal preparation that has long been used to treat chronic non-bacterial prostatitis (CNP) and benign prostatic hyperplasia (BPH). This study investigated the anti-inflammatory activity of QLX in improving lower urinary tract symptoms (LUTS) associated with CNP and BPH. Rat models of CNP and BPH were induced by oestradiol or testosterone (hormonal imbalance) or chemical inflammation (carrageenan). QLX significantly relieved LUTS in CNP and BPH rat model by reducing prostate enlargement, epithelial thickness, pain response time, urine volume and bleeding time, and by improving prostatic blood flow. The expression of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α, the pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inflammasome components (NLRP3, caspase-1 and ASC) in CNP and BPH tissues was reduced by QLX addition. QLX treatment was followed by reduced cellular malondialdehyde and increased superoxide dismutase, catalase and glutathione peroxidase activity, consistent with antioxidant activity. Increases in Beclin-1 expression and the LC3II/I ratio following QLX treatment indicated that autophagy had been induced. QLX relieved LUTS in CNP and BPH rat models by inhibiting inflammation. The underlying mechanisms included inhibition of inflammasome activation, NF-κB activation, oxidant stress and autophagy.


Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults.
To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear. A secondary analysis of a multicentre randomised controlled trial including 121 patients (18-40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years. In total, 82/121 (68%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1%) patients and osteophytes developed in two (2.6%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95% CI) adjusted differences in change in KOOS4 between intervention groups from baseline to 2 years was -1.4 (-9.1, 6.2) points. The mean improvement in KOOS4 was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales. The 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs. NCT02995551.


Total infectome investigation of diphtheritic stomatitis in yellow-eyed penguins (Megadyptes antipodes) reveals a novel and abundant megrivirus.
First identified in 2002, diphtheritic stomatitis (DS) is a devastating disease affecting yellow-eyed penguins (Megadyptes antipodes, or hoiho in te reo Māori). The disease is associated with oral lesions in chicks and has caused significant morbidity and mortality. DS is widespread among yellow-eyed penguin chicks on mainland New Zealand yet appears to be absent from the subantarctic population. Corynebacterium spp. have previously been suspected as causative agents yet, due to inconsistent cultures and inconclusive pathogenicity, their role in DS is unclear. Herein, we used a metatranscriptomic approach to identify potential causative agents of DS by revealing the presence and abundance of all viruses, bacteria, fungi and protozoa - together, the infectome. Oral and cloacal swab samples were collected from presymptomatic, symptomatic and recovered chicks along with a control group of healthy adults. Two novel viruses from the Picornaviridae were identified, one of which - yellow-eyed penguin megrivirus - was highly abundant in chicks irrespective of health status but not detected in healthy adults. Tissue from biopsied oral lesions also tested positive for the novel megrivirus upon PCR. We found no overall clustering among bacteria, protozoa and fungi communities at the genus level across samples, although Paraclostridium bifermentans was significantly more abundant in oral microbiota of symptomatic chicks compared to other groups. The detection of a novel and highly abundant megrivirus has sparked a new line of inquiry to investigate its potential association with DS.


Diagnosis of inborn errors of metabolism.
Systematic detection of inborn errors of metabolism (IEM) has usually encountered difficulties in developing countries. We present our experience in a high-risk population in Mexico between 1973 and 1998 with particular reference to the last 10 years, during which time infrastructure and support were considerably improved. Only disorders of intermediary metabolism were sought. The total number of patients studied is not available, but in the last 10 years, patients numbered 5,186. Routine metabolic screening was performed on all patients, with additional tests according to the clinical picture and screening results. The referral criteria have increasingly diversified, one-third being neurological conditions. Of the referrals, 33.8% were from pediatricians (31.1% of whom were at critical medicine departments) and the remainder from specialists. The number of diagnosed patients has increased to 1 per 43.9 patients studied. Amino acid defects have been the most prevalent, the proportion of organic acid and carbohydrate disorders having increased in the last 10 years, associated with improved diagnostic facilities. The most frequently diagnosed diseases were PKU, type 1a glycogen storage, and maple syrup urine disease (MSUD), their frequency apparently varying among different regions of Mexico. Other results of our program include training of specialists and technicians, development of the Latin American Metabolic Information Network, a procedure to locally prepare a special food product low in phenylalanine for the treatment of PKU patients, and extension of approaches for these disorders to the investigation metabolic derangements of infant malnutrition. This work demonstrates that inherited metabolic diseases constitute a significant load in pediatric pathology and that their study can and should be pursued in developing nations.


The use of texture analysis to delineate suspicious masses in mammography.
In mammography, national breast screening programmes have lead to a large increase in the number of mammograms needing to be studied by radiologists. Lesion indicators can be pointlike as in microcalcifications or extended as in stellate (spiculate) lesions or regular masses. Texture analysis has been proposed as a promising method for studying radiographic images in relation to the quantitation of extended objects. Filters have been designed, which may be used to segment or classify an image using textural features, and these have been reported as being of value in automatic mammographic glandular tissue classification. The work reported here suggests the incorporation of additional steps of image processing in an attempt to improve the performance of these filters in the quantitation of lesions. By deriving approximate outlines, which are used to identify suspicious regions, the investigation illustrates the properties of one of the filters. After applying the method to a small prediagnosed database of stellate lesions and regular masses, the results show that the filter is able to outline the malignant masses in all cases presented. The erroneous areas extracted are small for the initial part of the work, which deals with 256 x 256 pixel image extracts, though slightly larger in some cases when the whole mammogram is considered. Simple methods for the removal of these artefacts are proposed. For each non-suspicious case studied, the sum of any false positive areas is statistically insignificant when compared with the regions correctly outlined in the prediagnosed instances.


Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses.
To test the efficacy of combined high-throughput analyses (HTA) in target gene identification, screening criteria were set using >fivefold difference by microarray and statistically significant changes (p<0.01) in SAGE and EST. Microarray analysis of two normal and seven breast cancer samples found 129 genes with >fivefold changes. Further SAGE and EST analyses of these genes identified four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1 in breast cancer was further confirmed at mRNA level by Human Breast Cancer Tissue Profiling Array and at protein level by immunohistochemical staining. This study demonstrated that combined HTA effectively narrowed the number of genes for further study, while retaining the sensitivity in identifying biologically important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast cancer suggests its involvement in maintaining normal breast biology.


Steady-state models of photosynthesis.
In the challenge to increase photosynthetic rate per leaf area mathematical models of photosynthesis can be used to help interpret gas exchange measurements made under different environmental conditions and predict underlying photosynthetic biochemistry. To do this successfully it is important to improve the modelling of temperature dependencies of CO₂ assimilation and gain better understanding of internal CO₂ diffusion limitations. Despite these shortcomings steady-state models of photosynthesis provide simple easy to use tools for thought experiments to explore photosynthetic pathway changes such as redirecting photorespiratory CO₂, inserting bicarbonate pumps into C₃ chloroplasts or inserting C₄ photosynthesis into rice. Here a number of models derived from the C₃ model by Farquhar, von Caemmerer and Berry are discussed and compared.


Stereochemistry and mechanism of reactions catalyzed by tryptophanase Escherichia coli.
Several beta replacement and alpha,beta elimination reactions catalyzed by tryptophanase from Escherichia coli are shown to proceed stereospecifically with retention of configuration. These conversions include synthesis of tryptophan from (2S,3R)- and (2s,3s)-[3(-3H)]serine in the presence of indole, deamination of these serines in D2O to pyruvate and ammonia, and cleavage of (2S,3R)-and (2S,3S)-[3(-3H)]tryptophan in D2O to indole, pyruvate, and ammonia. A coupled reaction with lactate dehydrogenase was used to trap the stereospecifically labeled [3-H,2H,3H]pryuvates as lactate, which was oxidized to acetate for chirality analysis of the methyl group. During deamination of tryptophan there is significant intramolecular transfer of the alpha proton of the amino acid to C-3 of indole. To determine the exposed face of the cofactor.substrate complex on the enzyme surface and to analyze its conformational orientation, sodium boro[3H]hydride was used to reduce tryptophanase-bound alaninepyridoxal phosphate Schiff's base. Degradation of the resulting pyridoxylalanine to (2S)-[2(-3H)]alanine and (4'S)-[4'(-3H)]pyridoxamine demonstrates that reduction occurs from the exposed si face at C-4' of the complex and that the ketimine double bond is trans.


There is Only One Valid Definition of Clearance: Critical Examination of Clearance Concepts Reveals the Potential for Errors in Clinical Drug Dosing Decisions.
Drug dosing decisions in clinical medicine and in introducing a drug to market for the past 60 years are based on the pharmacokinetic/clinical pharmacology concept of clearance. We used chemical reaction engineering models to demonstrate the limitations of presently employed clearance measurements based upon systemic blood concentration in reflecting organ clearance. The belief for the last 49 years that in vivo clearance is independent of the mechanistic model for organ clearance is incorrect. There is only one valid definition of clearance. Defining organ clearance solely on the basis of systemic blood concentrations can lead to drug dosing errors when drug effect sites reside either in an eliminating organ exhibiting incremental clearance or in a non-eliminating organ where intraorgan concentration is governed by transporter actions. Attempts to predict clearance are presently hampered by the lack of recognition that what we are trying to predict is a well-stirred model clearance.


Efficient quadratic regularization for expression arrays.
Gene expression arrays typically have 50 to 100 samples and 1000 to 20,000 variables (genes). There have been many attempts to adapt statistical models for regression and classification to these data, and in many cases these attempts have challenged the computational resources. In this article we expose a class of techniques based on quadratic regularization of linear models, including regularized (ridge) regression, logistic and multinomial regression, linear and mixture discriminant analysis, the Cox model and neural networks. For all of these models, we show that dramatic computational savings are possible over naive implementations, using standard transformations in numerical linear algebra.


FAM71D is dispensable for spermatogenesis and male fertility in mice.
In mammals, the generation of sperm cells capable of fertilization is a highly complex process including spermatogenesis in the testis and maturation in the epididymis. In our previous study, we have demonstrated that FAM71D (Family with sequence similarity 71, member D), which could interact with calmodulin, was highly expressed in human and mouse testis. To investigate the physiological role of FAM71D in spermatogenesis, we next generate Fam71d loss-of-function mouse model using CRISPR/Cas9 technology. We performed immunofluorescence and RT-qPCR to examine the protein and mRNA expression in testicular cells. We found that FAM71D was predominantly localized in the round and elongated spermatids. And FAM71D KO mice displayed normal development of germ cell and fertility. Furthermore, testicular histology and sperm concentration showed no significant difference between WT and KO mice. These data demonstrate that FAM71D is dispensable for mouse spermatogenesis and male fertility.


[Microvascular decompression intervention in the treatment of trigeminal neuralgia].
The incidence of trigeminal neuralgia is about 5/10. Generally elderly people are affected by the so called "essential" form, although an early onset is not infrequent in secondary forms. The etiopathogenesis as well as the efficacy of different surgical treatments are still unclear because of the lack of animal sperimental models and of randomized controlled clinical studies. Nevertheless the hypothesis of a vascular conflict as the main etiologic factor is generally accepted. According both to our experience and to the literature data, microvascular decompression in the cerebello-pontine-angle appears to be the best clinical option presenting the most advantageous cost-benefit balance. The use of percutaneous lesive techniques, even if effective, should be limited in consideration of the risk of developing neuropathic disturbances, sometimes more difficult to treat than the original pain.


Difference between antegrade and retrograde orbital atherectomy system debulking using an artificial pulsatile heart model.
Debulking devices are necessary to treat severe calcified lesions. OAS has a unique characteristic that the burr moves forward and backward. There are few studies reporting the differences of ablation style between only-antegrade and only-retrograde OAS. The aim of this study was to evaluate the difference of ablation style between only-antegrade and only-retrograde orbital atherectomy system (OAS) using an artificial pulsatile heart model (HEARTROID system®) and optical coherence tomography (OCT). The calcified lesion model was inserted into the mid of left anterior descending in the HEARTROID®. Only-antegrade and only-retrograde ablation of OAS were conducted for each five lesions. Pre-OCT, OCT after low speed debulking and OCT after high speed debulking were conducted. The width and the depth of debulked area, the debulked area and the direction of debulked area were investigated. In all of 210 cross-sections, 91 debulked cross sections were chosen for analysis. Only-antegrade group had 47 debulked cross-sections, and only-retrograde group 44 cross-sections. In the evaluation of OCT after high speed debulking, the debulked area (0.76 mm2 [0.58-0.91] vs. 0.53 mm2 [0.36-0.68], p < 0.001) and the depth of debulked area (0.76 mm [0.58-0.91] vs. 0.53 mm [0.36-0.68], p < 0.001) were significantly higher in only-antegrade group compared to only-retrograde group. The debulked bias and the width of debulked area are not significantly different between the two groups. Compared to only-retrograde debulking, only-antegrade debulking acquired larger debulked area because of larger cutting depth, although the debulked bias and the width of debulked area were comparable between the two groups.


Extensive characterization of Tupaia belangeri neuropeptidome using an integrated mass spectrometric approach.
Neuropeptidomics is used to characterize endogenous peptides in the brain of tree shrews (Tupaia belangeri). Tree shrews are small animals similar to rodents in size but close relatives of primates, and are excellent models for brain research. Currently, tree shrews have no complete proteome information available on which direct database search can be allowed for neuropeptide identification. To increase the capability in the identification of neuropeptides in tree shrews, we developed an integrated mass spectrometry (MS)-based approach that combines methods including data-dependent, directed, and targeted liquid chromatography (LC)-Fourier transform (FT)-tandem MS (MS/MS) analysis, database construction, de novo sequencing, precursor protein search, and homology analysis. Using this integrated approach, we identified 107 endogenous peptides that have sequences identical or similar to those from other mammalian species. High accuracy MS and tandem MS information, with BLAST analysis and chromatographic characteristics were used to confirm the sequences of all the identified peptides. Interestingly, further sequence homology analysis demonstrated that tree shrew peptides have a significantly higher degree of homology to equivalent sequences in humans than those in mice or rats, consistent with the close phylogenetic relationship between tree shrews and primates. Our results provide the first extensive characterization of the peptidome in tree shrews, which now permits characterization of their function in nervous and endocrine system. As the approach developed fully used the conservative properties of neuropeptides in evolution and the advantage of high accuracy MS, it can be portable for identification of neuropeptides in other species for which the fully sequenced genomes or proteomes are not available.


Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers.
Type B Niemann-Pick disease (NPD) is a multiorgan system disorder caused by a genetic deficiency of acid sphingomyelinase (ASM), for which lung is an important and challenging therapeutic target. In this study, we designed and evaluated new delivery vehicles for enzyme replacement therapy of type B NPD, consisting of polystyrene and poly(lactic-coglycolic) acid polymer nanocarriers targeted to intercellular adhesion molecule (ICAM)-1, an endothelial surface protein up-regulated in many pathologies, including type B NPD. Real-time vascular imaging using intravital microscopy and postmortem imaging of mouse organs showed rapid, uniform, and efficient binding of fluorescently labeled ICAM-1-targeted ASM nanocarriers (anti-ICAM/ASM nanocarriers) to endothelium after i.v. injection in mice. Fluorescence microscopy of lung alveoli actin, tissue histology, and 125I-albumin blood-to-lung transport showed that anti-ICAM nanocarriers cause neither detectable lung injury, nor abnormal vascular permeability in animals. Radioisotope tracing showed rapid disappearance from the circulation and enhanced accumulation of anti-ICAM/125I-ASM nanocarriers over the nontargeted naked enzyme in kidney, heart, liver, spleen, and primarily lung, both in wild-type and ASM knockout mice. These data demonstrate that ICAM-1-targeted nanocarriers may enhance enzyme replacement therapy for type B NPD and perhaps other lysosomal storage disorders.


Time and risk preferences and the use of asthma controller medication.
We investigated the role of risk tolerance, time preference, and asthma-specific attitudes in adherence to asthma control medications. Students with persistent asthma completed an online survey on asthma beliefs, risk tolerance, and time preference (n = 47). The time preference questions measure the degree to which the individual discounts future outcomes and essentially prefers immediate gratification to delayed gratification. The risk tolerance questions indicate the individual's dislike of uncertainty about outcomes. We analyzed the relationship between the independent and dependent variables. Feelings of embarrassment and concern about medication, as well as risk tolerance and time preference, were found to be significant predictors of adherence to control medication in the logistic regression. Analysis of probabilities associated with different profiles shows that at high rates of risk tolerance and discounting of future outcomes, the probability of adherence is near 0 regardless of asthma-specific attitudes. Asthma attitudes have a statistically significant effect for individuals with low rates of risk tolerance and time preference. The risk tolerance and time preferences of the target group should be considered when designing an asthma-intervention program. Individuals who strongly prefer immediate gratification over future benefits and are willing to tolerate uncertain outcomes are unlikely to adhere to controller medication, regardless of their asthma attitudes. In contrast, efforts to affect relevant attitudes will be most fruitful for individuals with low rates of risk tolerance and time preference. However, as we cannot extrapolate these results to a larger population, we must view them with caution.


Development of TaqMan real-time polymerase chain reaction for the detection of the newly emerging form of carbapenem resistance gene in clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii.
The newly emerging form of the so-called New Delhi Metallo-beta-lactamases (NDM-1) has been reported recently from patients worldwide and broadly thought as a potential source for the major global health problem. Thus, it is important to study the epidemiology of the so-called NDM-1 harbouring bacteria to prevent its further spread and to place effective control measures. The present study describes the use of the real-time polymerase chain reaction (PCR) assay for the detection of the bla NDM-1 gene using TaqMan probes among clinical isolates. Clinical isolates of Escherichia coli (11 strains), Klebsiella pneumoniae (17 strains) and Acinetobacter baumannii (six strains) that were resistant to either of the carbapenems (meropenem or imipenem) were included in the study. The presence of carbapenemases in such strains was confirmed using the modified Hodge test. A real-time PCR assay was optimized for the detection of NDM-1 using a cloned synthetic gene fragment followed by testing of the clinical isolates. The findings were further confirmed using PCR and gene sequencing. TaqMan probe assay displayed a good detection limit with analytical sensitivity of the assay up to 10 copies of bla NDM-1 gene per reaction. The isolates of E. coli and K. pneumoniae revealed narrow range crossing point values (Cp values) between (12-17) cycles (mean Cp value 14), indicating number of bla NDM-1 gene copies of 106-108. The wider range of Cp values (15-34) cycles with a higher mean Cp value (23.6) was observed in A. baumannii with number of bla NDM-1 gene copies of 103-108. The study demonstrates that real-time PCR assay based on TaqMan chemistry is a useful technique for the detection of bla NDM-1 harbouring clinical isolates of E. coli, K. pneumoniae and A. baumannii. The assay has great precision in measuring the number of bla NDM-1 gene copies per specimen of DNA.


Influence of dietary fiber on xylanolytic and cellulolytic bacteria of adult pigs.
Xylanolytic and cellulolytic bacteria were enumerated over an 86-day period from fecal samples of 10 8-month-old gilts that were fed either a control or a 40% alfalfa meal (high-fiber) diet. Fecal samples were collected from all pigs on days 0, 3, 5, 12, 25, 37, 58, and 86. Overall, the numbers of xylanolytic bacteria producing greater than 5-mm-diameter zones of clearing on 0.24% xylan roll tube medium after 24 to 36 h of incubation were 1.6 X 10(8) and 4.2 X 10(8)/g (dry weight) of feces for the control pigs and those fed the high-fiber diet, respectively. After 1 week of incubation, a large number of smaller zones of clearing (1 to 2 mm) appeared. Besides Bacteroides succinogenes and Ruminococcus flavefaciens, which produced faint zones of clearing in xylan roll tubes, three strains which closely resembled B. ruminicola hydrolyzed and used xylan for growth. The overall numbers of cellulolytic bacteria producing zones of clearing in 0.5% agar roll tube medium were 0.36 X 10(8) and 4.1 X 10(8)/g for the control pigs and those fed the high-fiber diet, respectively. B. succinogenes was the predominant cellulolytic isolate from both groups of pigs, and R. flavefaciens was found in a ratio of approximately 1 to 15 with B. succinogenes. Degradation of xylan and cellulose, measured by in vitro dry matter disappearance after inoculation with fecal samples, was significantly greater for pigs fed the high-fiber diet than that for the controls. These data suggest that the number of fibrolytic microorganisms and their activity in the large intestine of the adult pig can be increased by feeding pigs high-alfalfa-fiber diets and that these organisms are similar to those found in the rumen.


White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study.
We aimed to study if age-related white matter changes (WMC) and vascular risk factors were predictors of cognitive decline in elderly subjects with WMC living independently. The Leukoaraiosis and Disability prospective multinational European study (LADIS) evaluates the impact of WMC on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Additionally, dementia, subtypes of dementia, and cognitive decline without dementia were classified according to usual clinical criteria. MRI was performed at entry and at the end of the study. A total of 639 subjects were included (74.1 +/- 5 years, 55% women, 9.6 +/- 3.8 years of schooling). At end of follow-up, 90 patients had dementia and 147 had cognitive impairment no dementia. Using Cox regression analysis, WMC severity independently predicted cognitive decline (dementia and not dementia), independently of age, education, and medial temporal atrophy (MTA). Diabetes at baseline was the only vascular risk factor that independently predicted cognitive decline during follow-up, controlling for age, education, WMC severity, and temporal atrophy. Considering subtypes of dementia, Alzheimer disease (AD) was predicted only by MTA, while vascular dementia was predicted by previous stroke, WMC severity, and MTA. WMC severity and diabetes are independent predictors of cognitive decline in an initially nondisabled elderly population. Vascular dementia is predicted by previous stroke and WMC, while AD is predicted only by MTA.


Dysfunctional fat cells, lipotoxicity and type 2 diabetes.
Type 2 diabetes is characterized by insulin resistance and impaired insulin secretion. Considerable evidence implicates altered fat topography and defects in adipocyte metabolism in the pathogenesis of type 2 diabetes. In individuals who develop type 2 diabetes, fat cells tend to be enlarged. Enlarged fat cells are resistant to the antilipolytic effects of insulin, leading to day-long elevated plasma free fatty acid (FFA) levels. Chronically increased plasma FFA stimulates gluconeogenesis, induces hepatic and muscle insulin resistance, and impairs insulin secretion in genetically predisposed individuals. These FFA-induced disturbances are referred to as lipotoxicity. Enlarged fat cells also have diminished capacity to store fat. When adipocyte storage capacity is exceeded, lipid 'overflows' into muscle and liver, and possibly the beta-cells of the pancreas, exacerbating insulin resistance and further impairing insulin secretion. In addition, dysfunctional fat cells produce excessive amounts of insulin resistance-inducing, inflammatory and atherosclerosis-provoking cytokines, and fail to secrete normal amounts of insulin-sensitizing cytokines. As more evidence emerges, there is a stronger case for targeting adipose tissue in the treatment of type 2 diabetes. Peroxisome-proliferator activated receptor gamma (PPARgamma) agonists, for example the thiazolidinediones, redistribute fat within the body (decrease visceral and hepatic fat; increase subcutaneous fat) and have been shown to enhance adipocyte insulin sensitivity, inhibit lipolysis, reduce plasma FFA and favourably influence the production of adipocytokines. This article examines in detail the role of adipose tissue in the pathogenesis of type 2 diabetes and highlights the potential of PPAR agonists to improve the management of patients with the condition.


Substrate specificity and copper loading of the manganese-oxidizing multicopper oxidase Mnx from Bacillus sp. PL-12.
Manganese(ii) oxidation in the environment is thought to be driven by bacteria because enzymatic catalysis is many orders of magnitude faster than the abiotic processes. The heterologously purified Mn oxidase (Mnx) from marine Bacillus sp. PL-12 is made up of the multicopper oxidase (MCO) MnxG and two small Cu and heme-binding proteins of unknown function, MnxE and MnxF. Mnx binds Cu and oxidizes both Mn(ii) and Mn(iii), generating Mn(iv) oxide minerals that resemble those found on the Bacillus spore surface. Spectroscopic techniques have illuminated details about the metallo-cofactors of Mnx, but very little is known about their requirement for catalytic activity, and even less is known about the substrate specificity of Mnx. Here we quantify the canonical MCO Cu and persistent peripheral Cu bound to Mnx, and test Mnx oxidizing ability toward different substrates at varying pH. Mn(ii) appears to be the best substrate in terms of kcat, but its oxidation does not follow Michaelis-Menten kinetics, instead showing a sigmoidal cooperative behavior. Mnx also oxidizes Fe(ii) substrate, but in a Michaelis-Menten manner and with a decreased activity, as well as organic substrates. The reduced metals are more rapidly consumed than the larger organic substrates, suggesting the hypothesis that the Mnx substrate site is small and tuned for metal oxidation. Of biological relevance is the result that Mnx has the highest catalytic efficiency for Mn(ii) at the pH of sea water, especially when the protein is loaded with greater than the requisite four MCO copper atoms, suggesting that the protein has evolved specifically for Mn oxidation.


Non-tuberculous mycobacterial infections in the Scottish Borders: identification, management and treatment outcomes--a retrospective review.
Non-tuberculous mycobacteria are opportunist pathogens increasingly recognised as a cause of pulmonary and extrapulmonary disease. Treatment is complicated, prolonged and potentially toxic, and due to a limited evidence base, potentially contentious and idiosyncratic. This is a retrospective review of non-tuberculous mycobacteria cases in the NHS Borders Health Board between 1992 and 2010. We consider incidence, species identified, drug sensitivity testing and treatment outcome with reference to the British and American Thoracic Society guidelines. Thirty-eight cases of non-tuberculous mycobacteria isolates were identified; 84.21% were pulmonary and 42.11% were Mycobacterium avium complex. Incidence rose from 1.92/100,000 in 1993 to 4.43/100,000 in 2010. The British Thoracic Society guidelines were followed in 45.45% of cases. A total of 36.36% were successfully treated with another 36.36% still being treated with antimicrobials. There is a clear need for more research on treatment for this group of 'emerging pathogens' and it remains to be seen if concordance with current guidelines will improve treatment outcomes.


Increasing cultural competence in nursing through international service-learning experiences.
As society becomes increasingly culturally diverse, preparing nursing students to become culturally competent practitioners has become more critical. The authors share one school's experience with the development and implementation of a cross-cultural, international, service-learning experience. Discussion will include the development of an elective nursing course with cross-cultural content and the implementation of an international service-learning trip to Quito, Ecuador.


Increased expression of intestinal P-selectin and pulmonary E-selectin during intravenous total parenteral nutrition.
Intravenous total parenteral nutrition (TPN) induces intestinal polymorphonuclear neutrophil recruitment with increased intestinal intercellular adhesion molecule-1 expression. While intercellular adhesion molecule-1 causes firm adhesion of leukocytes to the endothelial cells, P- and E-selectin mediate leukocyte recruitment via rolling. Therefore, manipulation of nutrition may also affect P- and E-selectin expression in organs. Prospective randomized experimental trials. Laboratory. Male mice. Fifty-three mice were randomized to chow, intravenous TPN, or intragastric TPN. After 5 days of diet, mice were administered iodine 125-labeled anti-P-selectin antibody (or iodine 125-labeled anti-E-selectin antibody) and iodine 131-labeled nonbinding antibody to quantify P-selectin (or E-selectin) expression in organs (lung, liver, kidney, small intestine, colon, stomach, pancreas, mesentery, heart, and skeletal muscle). P-selectin in small intestine, colon, stomach, and pancreas in the intravenous TPN group increased significantly as compared with the chow and the intragastric TPN groups. E-selectin expression was up-regulated after intravenous TPN in the lung but not in other sites. In a time frame (5 days) when intercellular adhesion molecule-1 expression and neutrophil recruitment are increased, intestinal expression of P-selectin remains up-regulated. Early lung inflammatory changes are reflected by increases in E-selectin. This change may reflect early pulmonary dysfunction with intravenous TPN, but its significance requires further study.


The prognostic effect of lymph node dissection in secondary lung tumor metastasectomies.
In this study, we aimed to investigate the prognostic effect of lymph node dissection in secondary lung tumor metastasectomies. Between January 2001 and December 2015, a total of 201 patients (122 males, 79 females; mean age: of 41.4±19.2 years; range, 3 to 79 years) who had pulmonary metastasectomy due to colorectal carcinoma, renal cell carcinoma, and soft tissue - skeletal sarcomas were retrospectively analyzed. The clinicopathological features of the patients, overall survival, and complication rates according to the presence of lymph node dissection were evaluated. The most common histopathological subtype was a sarcoma in 118 (58.7%) patients, followed by colorectal carcinoma in 63 (31.3%) patients, and renal cell carcinoma in 20 (10%) patients. A total of 88 (43.7%) patients underwent systematic lymph node dissection with pulmonary metastasectomy. The mean overall survival of patients with and without lymph node dissection were 49±5.9 (95% confidence interval 37.3-60.6) and 26±4.4 (95% confidence interval 17.2-34.7) months, respectively (p=0.003). The five-year survival rates in colorectal carcinoma, renal cell carcinoma, and sarcoma were 52%, 30%, and 23%, respectively (p=0.002). Locoregional recurrences occurred in 15 (35.7%) patients in the lymph node dissection group and in 23 (60.5%) patients in the non-lymph node dissection group (p=0.026). Lymph node dissection did not show a significant relationship regarding to postoperative complications (p=0.09). Lymph node dissection following pulmonary metastasectomy may improve the overall survival and reduce locoregional recurrence, without any increase in morbidity and mortality.


PlayStation purpura.
A 16-year-old boy presented with a number of asymptomatic pigmented macules on the volar aspect of his index fingers. Dermoscopy of each macule revealed a parallel ridge pattern of homogenous reddish-brown pigment. We propose that these lesions were induced by repetitive trauma from a Sony PlayStation 3 (Sony Corporation, Tokyo, Japan) vibration feedback controller. The lesions completely resolved following abstinence from gaming over a number of weeks. Although the parallel ridge pattern is typically the hallmark for early acral lentiginous melanoma, it may be observed in a limited number of benign entities, including subcorneal haematoma.


A case report of Aspergillus hypersensitivity syndrome with obstructing bronchial aspergillosis.
A 62-year-old Indian male with diabetes mellitus presented with atypical, overlap features of Aspergillus hypersensitivity syndrome and obstructing bronchial aspergillosis. He was febrile and tachypnoeic with diffuse crepitations and wheezing. Chest X-ray was normal but eosinophil count was 2900/mm3 and Ig E > 10,000 IU/ml. He responded initially to high dose steroid therapy but deteriorated subsequently from extensive mucus plugging of the bronchial tree which resulted in respiratory failure and death. He was HIV-negative. Culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs should be performed as early treatment may be life-saving.


Association of Dietary Habits with Severity of Acute Pancreatitis.
The effect of diet on risk of acute pancreatitis (AP) has been suggested by prior studies, but the association of dietary habits with severity of AP has not been previously evaluated. The objective of the study was to assess differences in reported dietary habits in patients with severe AP compared with those with mild or moderate AP. A prospectively maintained cohort of patients with AP was utilized. A brief questionnaire on dietary habits was implemented. Dietary habits were categorized based on the overall type of diet, fruit/vegetable servings, fat content, dairy consumption, dessert/sweets consumption, and fluid intake. Patients were grouped into mild/moderate and severe AP. Multivariate analysis was used to determine whether dietary habits have an independent association with AP severity. 407 patients with AP were studied. Mean patient age was 51 y, and 202 (50%) were men. 29% of patients were smokers and 46% actively consumed alcohol. 225 patients had mild AP, 103 moderate AP, and 79 developed severe AP. The 3 groups were comparable in race, body mass index, etiology of AP, and comorbidities. Dietary factors were overall comparable between the groups except for diet type: subjects with severe AP had a higher percentage of consuming a meat-rich diet (84%) than patients with mild AP (72%) and moderate AP (67%) (P = 0.04). Based on multivariable logistic regression, the OR of developing severe AP was 2.5 (95% CI: 1.24-5.32, P = 0.01) between patients who eat a meat-rich diet and those who consume a vegetable-based diet. A meat-rich diet is independently associated with the development of persistent organ failure (severe disease) in patients with AP. These findings require further evaluation and could be useful for patient counseling, risk stratification, and disease prevention. This study is registered at clinicaltrials.gov as NCT03075605.


Sperm glyceraldehyde 3-phosphate dehydrogenase gene expression in asthenozoospermic spermatozoa.
It has been suggested that the energy required for sperm motility is produced by oxidative phosphorylation while glycolysis seems to be an important source for ATP transmission along the flagellum. Some studies have investigated the chemical and kinetic properties of the enzyme glyceraldehyde 3-phosphate dehydrogenase to identify any changes in the regulation of glycolysis and sperm motility. In contrast, there are few studies analyzing the genetic basis of hypokinesis. For this reason, we investigated the glyceraldehyde 3-phosphate dehydrogenase gene in human sperm to evaluate whether asthenozoospermia was correlated with any changes in its expression. Semen examination and glyceraldehyde 3-phosphate dehydrogenase gene expression studies were carried out on 116 semen samples divided into two groups - Group A consisted of 58 normokinetic samples and Group B of 58 hypokinetic samples. Total RNA was extracted from spermatozoa, and real-time PCR quantification of mRNA was carried out using specific primers and probes. The expression profiles for the Groups A and B were very similar. The mean delta Ct was as follows - Group A, 5.79 ± 1.04; Group B, 5.47 ± 1.27. Our study shows that in human sperm, there is no difference in glyceraldehyde 3-phosphate dehydrogenase gene expression between samples with impaired motility and samples with normal kinetics. We believe that this study could help in the understanding of the molecular mechanisms of sperm kinetics, suggesting that hypomotility may be due to a possible posttranscriptional impairment of the control mechanism, such as mRNA splicing, or to posttranslational changes.


Adult Langerhans cell histiocytosis presenting as metachronous colonic polyps.
Langerhans cell histiocytosis (LCH) is a rare disease characterized by proliferation of Langerhans-type cells that express CD1a, Langerin (CD207) and S100 protein. Birbeck granules are a hallmark by ultrastructural examination. LCH presents with a wide clinical spectrum, ranging from solitary lesions of a single site (usually bone or skin) to multiple or disseminated multisystemic lesions, which can lead to severe organ dysfunction. Most cases occur in children. Gastrointestinal tract involvement is rare and has been associated with systemic illness and poor prognosis especially in children under the age of 2 years. Adult gastrointestinal LCH is very rare. We report a case of a previously healthy, nonsmoking 48-year-old male who was referred for routine screening colonoscopy. Two sessile, smooth, firm and yellowish LCH polyps measuring 0.2 cm and 0.3 cm were detected in the sigmoid colon. Fifteen months later a second colonoscopy found two histologically confirmed hyperplastic polyps at the sigmoid colon. No other LCH lesions were seen. A third colonoscopy after 28 months of follow-up found a submucosal 0.5 cm infiltrated and ulcerated LCH polyp in the cecum, close to the ostium of the appendix. The patient had been asymptomatic for all this period. Imaging investigation for systemic or multiorgan disease did not find any sign of extracolonic involvement. On histology all lesions showed typical LCH features and immunohistochemical analysis showed strong and diffuse staining for CD1a and CD207. This case illustrates two distinct clinicopathologic features not previously reported in this particular clinical setting: metachronous colonic involvement and positivity for CD207.


Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial.
Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted. Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR- tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2-. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P = 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab.


Effect of air pollutant emission reduction policies on hospital visits for asthma in Seoul, Korea; Quasi-experimental study.
To improve air quality and reduce adverse health effects due to air pollutants, Seoul metropolitan government has introduced emission reduction policies in Seoul metropolitan area since 2007. As a result, air quality in Seoul has improved. However, no study has reported whether emission reduction policies have affected respiratory morbidities in Korea. Thus, we aimed to assess an association between air pollutant emissions and ambient concentrations, and the effect of implemented emission reduction policies on asthma. The population of Daejeon, one of the metropolitan cities in Korea other than Seoul was used as a reference population to adjust for possible long-term background trend. Trends of air pollutant emissions, ambient concentrations, and hospital visit rates in Seoul and Daejeon were evaluated using descriptive statistics. To evaluate the possible beneficial effect of air pollutant emission reduction policies implemented since 2007 on hospital visits for asthma in Seoul, we conducted interrupted time-series analysis. As a result, we found evidence for the association between emission reductions and reduced ambient concentrations. Trends in hospital visit rates for asthma, which were previously increasing in Seoul, have decreased since the implementation of the policies. Prevented hospital visits cases for asthma in the total population and younger population (0-18 years) were estimated as 500,000 (11.3% of hospital visit cases if there was no intervention) cases and 320,000 (15.5% of hospital visit cases if there was no intervention) cases, respectively in Seoul. Our study provides evidence for the possible beneficial effect of emission reduction policies on hospital visits for asthma.


Evaluating the Effects of Denmark's New Tobacco Control Act on Young People's Use of Nicotine Products: A Study Protocol of the §SMOKE Study.
(1) Background: In December 2020, a broad majority of political parties in Denmark agreed on a new tobacco control act. In addition, price increases on tobacco in 2020 and 2022 became part of the Danish Finance Act. This study protocol describes the study "§SMOKE-A Study of Tobacco, Behavior, and Regulations" designed to monitor and evaluate the implementation and effect of the new strengthened tobacco control acts. The overall aim is to monitor tobacco use among young people before, during, and after implementation of the new tobacco control legislation, including an increased price on tobacco, a ban on point-of-sale tobacco displays, and plain packaging. Subgoals are to monitor overall use of nicotine products, attitudes, and norms. (2) Methods: This study is designed as a five-year impact evaluation with repeated cross-sectional survey data collections. The baseline survey was conducted before implementing an increased price on tobacco, the first step in the new legislation, initiated 1 April 2020. Study participants (n = 37,500) were a random sample of individuals living in Denmark aged 15 to 29 years. (3) Conclusions: This study examines the impact of the new strengthened tobacco control legislation in Denmark from 2020 to 2025. The findings of this study are relevant to other countries facing implementation of similar measures to explore intended and unintended consequences of the legislation and help to identify how the legislation could be further improved.


Web-Based Behavioral Intervention Utilizing Narrative Persuasion for HIV Prevention Among Chinese Men Who Have Sex With Men (HeHe Talks Project): Intervention Development.
In the era of potent antiretroviral therapy, a high level of condomless anal intercourse continues to drive increases in HIV incidence in recent years among men who have sex with men. Effective behavior change strategies for promoting HIV-preventive behaviors are warranted. Narrative persuasion is a novel health communication approach that has demonstrated its persuasive advantages in overcoming resistance to counterattitudinal messages. The efficacy of narrative persuasion in promoting health behavior changes has been well documented, but critical research gaps exist for its application to HIV prevention. In this study, we aimed to (1) capitalize on narrative persuasion to design a web-based multisession intervention for reducing condomless anal intercourse among men who have sex with men in Hong Kong (the HeHe Talks Project) by following a systematic development process; and (2) describe the main components of the narrative intervention that potentially determine its persuasiveness. Persuasive themes and subtopics related to reducing condomless anal intercourse were initially proposed based on epidemiological evidence. The biographic narrative interview method was used to elicit firsthand experiential stories from a maximum variation sample of local men who have sex with men with diverse backgrounds and experiences related to HIV prevention; different types of role models were established accordingly. Framework analysis was used to aggregate the original quotations from narrators into collective narratives under 6 intervention themes. A dedicated website was finally developed for intervention delivery. A series of video-based intervention messages in biographic narrative format (firsthand experiential stories shared by men who have sex with men) combined with topic-equivalent argumentative messages were produced and programmed into 6 intervention sessions. The 6-week intervention program can be automatically delivered and monitored online. We systematically created a web-based HIV prevention intervention derived from peer-generated stories. Strategies used to enhance the efficacy of the narrative intervention have been discussed within basic communication components. This paper describes the methods and experiences of the rigorous development of a narrative communication intervention for HIV prevention, which enables replication of the intervention in the future.


Magnetic resonance imaging (MRI) evaluation of developmental delay in pediatric patients.
Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child's ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with developmental delay plus. The clinical diagnosis of developmental delay should not be the end point, but rather a springboard for an effective search for causal factors. MRI is the best investigation with a high yield in such patients.


A lightning multiple casualty incident in Sequoia and Kings Canyon National Parks.
Multiple casualty incidents (MCIs) are uncommon in remote wilderness settings. This is a case report of a lightning strike on a Boy Scout troop hiking through Sequoia and Kings Canyon National Parks (SEKI), in which the lightning storm hindered rescue efforts. The purpose of this study was to review the response to a lightning-caused MCI in a wilderness setting, address lightning injury as it relates to field management, and discuss evacuation options in inclement weather incidents occurring in remote locations. An analysis of SEKI search and rescue data and a review of current literature were performed. A lightning strike at 10,600 feet elevation in the Sierra Nevada Mountains affected a party of 5 adults and 7 Boy Scouts (age range 12 to 17 years old). Resources mobilized for the rescue included 5 helicopters, 2 ambulances, 2 hospitals, and 15 field and 14 logistical support personnel. The incident was managed from strike to scene clearance in 4 hours and 20 minutes. There were 2 fatalities, 1 on scene and 1 in the hospital. Storm conditions complicated on-scene communication and evacuation efforts. Exposure to ongoing lightning and a remote wilderness location affected both victims and rescuers in a lightning MCI. Helicopters, the main vehicles of wilderness rescue in SEKI, can be limited by weather, daylight, and terrain. Redundancies in communication systems are vital for episodes of radio failure. Reverse triage should be implemented in lightning injury MCIs. Education of both wilderness travelers and rescuers regarding these issues should be pursued.


MUSCLE VOLUME CHANGES: RELATION TO THE ACTIVE STATE.
The volume of a frog sartorius muscle increases during a single twitch and subsequently decreases. The magnitude of volume change is 10(-5) cm(3) per gram of muscle. The time courses of change in volume and of onset of tension vary with temperature in a similar way, which implies a relation between the volume changes and the contraction mechanism. The character of the change depends upon the initial length of the muscle: the greatest decrease accompanies an isometric twitch at reference length. Treatment of the muscle with an iodide Ringer solution prolongs the active state and the volume change. These results suggest a correlation between the volume changes and the active state.


Computerized tailored physical activity reports. A randomized controlled trial.
Computerized, tailored interventions have the potential to be a cost-effective means to assist a wide variety of individuals with behavior change. This study examined the effect of computerized tailored physical activity reports on primary care patients' physical activity at 6 months. Two-group randomized clinical trial with physicians as the unit of randomization. Patients were placed in the intervention (n=187) or control group (n=207) based on their physician's assignment. Primary care physicians (n=22) and their adult patients (n=394) from Philadelphia PA. The study and analyses were conducted from 2004 to 2010. The intervention group completed physical activity surveys at baseline, 1, 3, and 6 months. Based on their responses, participants received four feedback reports at each time point. The reports aimed to motivate participants to increase physical activity, personalized to participants' needs; they also included an activity prescription. The control group received identical procedures, except that they received general reports on preventive screening based on their responses to preventive screening questions. Minutes of physical activity measured by the 7-Day Physical Activity Recall interview at 6 months. Participants were 69% female, 59% African-American, and had diverse educational and income levels; the retention rate was 89.6%. After adjusting for baseline levels of activity and gender, there were no differences in physical activity at 6 months. The intervention group increased their total physical activity by a mean of 139 minutes; the control group had a mean increase of 109 minutes (p=0.45). Although physical activity increased within both groups, computerized tailored physical activity reports did not significantly increase physical activity between groups at 6 months among ethnically and socioeconomically diverse adults in primary care.


Plant Poisoning among Children in Rural Sri Lanka.
Plant poisoning is a common presentation in paediatric practice and an important cause of preventable mortality and morbidity in Sri Lanka. The burden of plant poisoning is largely underexplored. The current multicenter study based in rural Sri Lanka assessed clinical profiles, poison related factors, clinical management, complications, outcomes, and risk factors associated with plant poisoning in the paediatric age group. Among 325 children, 57% were male with 64% being below five years of age. 99.4% had ingested the poison. Transfer rate was 66.4%. Most had unintentional poisoning. Commonest poison plant was Jatropha circus and poisoning event happened mostly in home garden. 29% of parents practiced harmful first-aid practices. 32% of children had delayed presentations to which the commonest reason was lack of parental concern regarding urgency of seeking medical care. Presence of poisonous plants in home garden was the strongest risk factor for plant poisoning. Mortality rate was 1.2% and all cases had Oleander poisoning. The study revealed the value of community awareness regarding risk factors and awareness among healthcare workers regarding the mostly benign nature of plant poisoning in children in view of limiting incidence of plant poisoning and reducing expenditure on patient management.


The environmental impact of mastitis: a case study of dairy herds.
Mastitis is defined as an inflammatory reaction of udder tissue to bacterial, chemical, thermal or mechanical injury, which causes heavy financial losses and milk wastage throughout the world. Until now, studies have focused on the economic aspects from which perspective mastitis can generally be considered as the most serious disease in dairy cows; however, costs are not the only negative consequence resulting from the infection. The environmental impact is also significant; milk is discarded, which means lower efficiency and hence a greater environmental impact per produced liter of milk. Less milk is produced, which leads to an increased need for calf feed, and meat production is also affected. The main aim of this paper was to quantify the environmental impact of mastitis incidence. A standard scenario (representative of present-day reality in Galicia, Spain) and an improved scenario (in which mastitis incidence rate is reduced by diverse actions) have been defined and compared using Life Cycle Assessment (LCA) methodology. Among the impact categories studied, acidification, eutrophication and global warming were found to be the most significant environmental impacts. In all these categories, it was revealed that a decrease in mastitis incidence has a positive influence as the environmental impact is reduced. Even if the quantitative results cannot show a considerable decrease in the environmental burden, the impact cannot be regarded as negligible when the total consumption or total production of a region is considered. For example, the outcome of the proposed improvement measures for Spain's greenhouse gas emissions can be quantified as 0.06% of total emissions and 0.56% of emissions by the agricultural sector.


Theoretical study of long oligothiophene dications: bipolaron vs polaron pair vs triplet state.
A series of oligothiophene dications (from the sexithiophene dication to the 50-mer oligothiophene dication, nT2+, n = 6-50) were studied. Density functional theory (DFT) at the B3LYP/6-31G(d) level and, in some cases, also at BLYP/6-31Gd, was applied to study the singlet and triplet states of the whole series. We found that the singlet state is the ground state for all oligothiophene dications up to the 20-mer, and that the singlet and triplet states are degenerate for longer oligomers. Thus, the triplet state is never a pure ground state for these dications. We found that, for short oligothiophenes dication (e.g., 6T2+), the bipolaron state is the more important state, with only a small contribution made by the polaron pair state. For medium size oligothiophene dications (e.g., 14T2+), both the bipolaron state and the polaron-pair state contribute to the electronic structure. Finally, in long oligothiophene dications, such as 30T2+ and 50T2+, the contribution from the polaron pair state becomes dominant, and these molecules can be considered as consisting of two independent cation radicals or a polaron pair. Results from isodesmic reactions show that the stability of oligothiophene cation radicals over dications is inversely proportional to chain length. Small oligothiophene dications (n = 6-12) were studied at the CASSCF(m,m)/6-31G(d) (m = 4, 6, and 10) level. The major conclusions of this paper regarding the relative energy of the singlet state versus the triplet state and regarding the relative stability of the bipolaron versus the polaron pair were also supported by CASSCF calculations.


Expression of the gene encoding the matrix gla protein by mature osteoblasts in human fracture non-unions.
Osteoblast phenotypic abnormality, namely the expression of collagen type III, has been shown previously in fracture non-union woven bone. To investigate osteoblasts from fracture non-unions for evidence of gene expression of non-collagenous bone matrix proteins that have been implicated in mineralisation, namely matrix gla protein (MGP), osteonectin, osteopontin, and osteocalcin. MGP is a consistent component of bone matrix, but there are no reports of osteoblasts in the skeleton expressing the gene for MGP, and the site of synthesis of skeletal MGP (perhaps the liver) has yet to be determined. Biopsies from normally healing human fractures and non-unions were examined by means of in situ hybridisation, using 35S labelled probes and autoradiography to disclose levels of gene expression. In normally healing fractures, mature osteoblasts on woven bone were negative for MGP mRNA, but positive for osteonectin, osteopontin, and osteocalcin mRNA molecules. In non-unions, osteoblasts displayed a novel phenotype: they were positive for MGP mRNA, in addition to osteonectin, osteopontin, and osteocalcin mRNA molecules. Mature osteoblasts in slowly healing fractures have an unusual phenotype: they express the gene encoding MGP, which indicates that control of osteoblast gene expression in non-unions is likely to be abnormal. This might be of importance in the pathogenesis of non-uniting human fractures, and is of current interest given the emerging status of MGP as an inhibitor of mineralisation.