TaylorActive--Examining the effectiveness of web-based personally-tailored videos to increase physical activity: a randomised controlled trial protocol.
Physical inactivity levels are unacceptably high and effective interventions that can increase physical activity in large populations at low cost are urgently needed. Web-based interventions that use computer-tailoring have shown to be effective, though people tend to 'skim' and 'scan' text on the Internet rather than thoroughly read it. The use of online videos is, however, popular and engaging. Therefore, the aim of this 3-group randomised controlled trial is to examine whether a web-based physical activity intervention that provides personally-tailored videos is more effective when compared with traditional personally-tailored text-based intervention and a control group. In total 510 Australians will be recruited through social media advertisements, e-mail and third party databases. Participants will be randomised to one of three groups: text-tailored, video-tailored, or control. All groups will gain access to the same web-based platform and a library containing brief physical activity articles. The text-tailored group will additionally have access to 8 sessions of personalised physical activity advice that is instantaneously generated based on responses to brief online surveys. The theory-based advice will be provided over a period of 3 months and address constructs such as self-efficacy, motivation, goal setting, intentions, social support, attitudes, barriers, outcome expectancies, relapse prevention and feedback on performance. Text-tailored participants will also be able to complete 7 action plans to help them plan what, when, where, who with, and how they will become more active. Participants in the video-tailored group will gain access to the same intervention content as those in the text-tailored group, however all sessions will be provided as personalised videos rather than text on a webpage. The control group will only gain access to the library with generic physical activity articles. The primary outcome is objectively measured physical activity. Secondary outcomes include website engagement and retention, quality of life, depression, anxiety, stress, sitting time, sleep and psychosocial correlates of physical activity. Outcomes will be measured at baseline, 3, and 9 months. This study presents an ideal opportunity to study the effectiveness of an isolated feature within a web-based physical activity intervention and the knowledge generated from this study will help to increase intervention effectiveness. Australian New-Zealand Clinical Trial Registry: ACTRN12615000057583 . Registered 22 January 2015. CQUniversity Ethics Project Number: H14/07-163.


Detection of nonexudative choroidal neovascularization secondary to angioid streaks using optical coherence tomography angiography.
To present a case of nonexudative choroidal neovascularization secondary to angioid streaks in a patient with pseudoxanthoma elasticum. The lesion was monitored over an 8-month period with the use of optical coherence tomography angiography. Case report. The neovascular tissue area increased by 0.160 mm2 over a period of 8 months without any sign of exudation seen on optical coherence tomography or fluorescein angiography. To our knowledge, this is the first report of a nonexudative choroidal neovascularization secondary to angioid streaks. Given that once a patient with angioid streaks develops choroidal neovascularization in one eye there is a high risk of bilateral involvement within a short amount of time, optical coherence tomography angiography can prove a useful tool for monitoring such lesions over time.


Acute varicella infection mimics recurrent Hodgkin's disease on F-18 FDG PET/CT.
We report a case where acute varicella infection, chickenpox, mimics the findings of recurrent Hodgkin disease on F-18 FDG PET/CT. A 28-year-old man with a history of Hodgkin disease in remission had fatigue, pyrexia, and a raised ESR. His F-18 FDG PET/CT, performed to exclude lymphoma recurrence, demonstrated FDG-avid lymphadenopathy and increased FDG uptake in his spleen. A day later he developed the generalized rash of acute varicella infection. This was managed with valacyclovir. Repeat F-18 FDG PET/CT done 1 month later showed no evidence of FDG-avid disease. In this patient the stimulation of an immune response by the acute viral infection mimics recurrent lymphoma.


Comparative analysis of the stress distribution in five anatomical types of maxillary central incisor.
The maxillary central incisor is one of the most important anatomical indicators in esthetics, and stress distribution may vary among its five anatomical views (labial, palatal, mesial, distal, and incisal). To compare stress distribution among the five anatomical views of the maxillary central incisor under loading force at five angles and to observe and analyze the stress distribution in the dentin and periodontal ligament. We established three-dimensional finite element models of the five different views, which simulated the bite force with a static load force at 0∘, 30∘, 45∘, 60∘, and 90∘. The stress and displacement values for the cementoenamel junction (CEJ)-apical labial, palatal, mesial, and distal and the equivalent stress values on the periodontal ligament of the maxillary central incisor were calculated. As the angle increased, the equivalent stress on the periodontal ligament, overall tooth displacement, equivalent stress, and displacement over the four views increased. The peaks of equivalent stress over the four views appeared within 0.8-17 mm below the CEJ, although all equivalent stress values decreased while approaching the peak. Within 1-19 mm below the CEJ, the equivalent stress over the M1 and P1 views of the maxillary central incisor decreased substantially. The peaks of the equivalent stress over the M1 and P1 views of the maxillary central incisor and their stress distribution were lower than those of the other three types. Our findings provided theoretical data on the biomechanics of this esthetically important tooth, which may be useful during implantation of missing maxillary central incisors.


Diurnal transcriptome dynamics reveal the photoperiod response of Pyrus.
Photoperiod provides a key environmental signal that controls plant growth. Plants have evolved an integrated mechanism for sensing photoperiods with internal clocks to orchestrate physiological events. This mechanism has been identified to enable timely plant growth and improve fitness. Although the components and pathways underlying photoperiod regulation have been described in many species, diurnal patterns of gene expression at the genome-wide level under different photoperiods are rarely reported in perennial fruit trees. To explore the global gene expression in response to photoperiod, pear plants were cultured under long-day (LD) and short-day (SD) conditions. A time-series transcriptomic study was implemented using LD and SD samples collected at 4 h intervals over 2 days. We identified 13,677 rhythmic genes, of which 7639 were identified under LD and 10,557 under SD conditions. Additionally, 4674 genes were differentially expressed in response to photoperiod change. We also characterized the candidate homologs of clock-associated genes in pear. Clock genes were involved in the regulation of many processes throughout the day, including photosynthesis, stress response, hormone dynamics, and secondary metabolism. Strikingly, genes within photosynthesis-related pathways were enriched in both the rhythmic and differential expression analyses. Several key candidate genes were identified to be associated with regulating photosynthesis and improving productivity under different photoperiods. The results suggest that temporal variation in gene expression should not be ignored in pear gene function research. Overall, our work expands the understanding of photoperiod regulation of plant growth, particularly by extending the research to non-model trees.


Fluoropolymer-Containing Opals and Inverse Opals by Melt-Shear Organization.
The preparation of highly ordered colloidal architectures has attracted significant attention and is a rapidly growing field for various applications, e.g., sensors, absorbers, and membranes. A promising technique for the preparation of elastomeric inverse opal films relies on tailored core/shell particle architectures and application of the so-called melt-shear organization technique. Within the present work, a convenient route for the preparation of core/shell particles featuring highly fluorinated shell materials as building blocks is described. As particle core materials, both organic or inorganic (SiO₂) particles can be used as a template, followed by a semi-continuous stepwise emulsion polymerization for the synthesis of the soft fluoropolymer shell material. The use of functional monomers as shell-material offers the possibility to create opal and inverse opal films with striking optical properties according to Bragg's law of diffraction. Due to the presence of fluorinated moieties, the chemical resistance of the final opals and inverse opals is increased. The herein developed fluorine-containing particle-based films feature a low surface energy for the matrix material leading to good hydrophobic properties. Moreover, the low refractive index of the fluoropolymer shell compared to the core (or voids) led to excellent optical properties based on structural colors. The herein described fluoropolymer opals and inverse opals are expected to pave the way toward novel functional materials for application in fields of coatings and optical sensors.


Essential Thrombocythemia Due to Janus Kinase 2 Mutation Unmasked After Splenectomy.
Reactive thrombocytosis after splenectomy is common and often self-limiting. However, thrombocytosis can be multifactorial, especially extreme thrombocytosis (platelet count > 100 x 104/cubic mm). It can lead to thrombotic or hemorrhagic complications. Hence, in patients with rising platelet count after splenectomy, detailed evaluation may be required to rule out other causes of thrombocytosis, such as infection, iron deficiency, and myeloproliferative disorders. Timely treatment of patients with thrombocytosis can prevent the development of life-threatening complications. The index case highlights the importance of regular follow-up of the patients after splenectomy to detect thrombocytosis and suspect other causes if the spleen was diseased or the platelet count fails to resolve spontaneously.


ISSR-Derived Species-Specific SCAR Marker for Rapid and Accurate Authentication of Ocimum tenuiflorum L.
Ocimum tenuiflorum has been widely used in traditional medicine and has high medicinal value. High volume trade of this potential medicinal plant species led to unscrupulous adulteration of both crude drugs as well as formulations. Morphology-based authentication is difficult in cases of incomplete or damaged samples and in dried herbal materials. In such cases, PCR-based molecular methods may aid in accurate identification. The present study aimed at developing species-specific DNA marker(s) for the authentication of O. tenuiflorum. A species-specific amplicon (279 bp) generated through an inter-simple sequence repeat marker (UBC 835) in all individuals of O. tenuiflorum was cloned, sequenced, and a primer pair was developed (designated as CIM-OT-835F/CIM-OT-835R). The newly developed sequence characterized amplified region marker was validated through PCR amplification in all available seven species of Ocimum, and its specificity for O. tenuiflorum was confirmed with the consistent generation of an amplicon of 177 bp. The developed marker can be used for accurate and rapid identification of the species for certification purposes and will be useful in quality control of medicinal preparations containing this important medicinal species.


Clinical and Radiographic Outcomes After Submuscular Plating (SMP) of Pediatric Femoral Shaft Fractures.
To evaluate lower extremity strength and alignment among children who underwent submuscular plating (SMP). Subjects who underwent SMP for a length unstable femoral fracture returned for isokinetic strength testing ≥2 years after surgery. Extensor and flexor strength deficits (percent difference) between the operative and nonoperative limbs were evaluated. Radiographic measurements of mechanical alignment [anatomic lateral distal femoral angle (aLDFA)] and qualitative measurements (The Pediatric Outcomes Data Collection Instrument, PODCI) were obtained from all subjects. The upper 97.5% confidence interval approach to establishing clinical equivalency was utilized to compare differences in strength and alignment between the operative and nonoperative limbs. An extensor strength deficit of >19% and an aLDFA discrepancy of >5 degrees were considered to be clinically significant. The average age at surgery of the 10 subjects included in the study was 8.7 years. The hardware was placed an average of 27.9 mm from the distal femoral physis and was removed 6.4 months postsurgery. Among all subjects, the median PODCI scores were ≥97 according to all subscales. There was no significant difference in extension torque between the operative versus nonoperative limbs at 60 degrees/s (P=0.5400), 120 degrees/s (P=0.4214), or 180 degrees/s (P=0.8166). More importantly, extension strength deficits between the operative and nonoperative limbs were not clinically significant at 60 degrees/s [upper 97.5% confidence interval (CI), 10.9%], 120 degrees/s (upper 97.5% CI, 11.0%), or 180 degrees/s (upper 97.5% CI, 10.7%). The difference in aLDFA between the operative and nonoperative limb was less than the predefined clinically significant threshold of 5 degrees for all subjects. SMP achieves satisfactory clinical and functional results. In this series, extensor strength deficits and/or lower extremity malalignment were not clinically meaningful. High patient satisfaction can be expected after implant removal. Level IV-case series.


Activation of distinct protein kinase C isozymes by phorbol esters: correlation with induction of interleukin 1 beta gene expression.
Treatment of human promyelocytic leukemia cells U937 with phorbol 12-myristate 13-acetate (TPA) induces them to differentiate into monocytic cells [Harris, P., & Ralph, P. (1985) J. Leukocyte Biol. 37, 407-422]. Here we investigated the effects of TPA on interleukin 1 gene expression and the possible role of protein kinase C (PKC) in this process. Addition of TPA to serum-starved U937 cells induced the expression of the interleukin 1 beta (IL-1 beta) gene. This effect was apparent as early as 2 h and peaked at 24 h in the presence of 5 X 10(-8) M TPA. Higher concentrations of TPA, which partially or totally depleted protein kinase C levels in the cells (10(-9)-2 X 10(-5) M), had an inhibitory effect on IL-1 beta mRNA expression. Cell-permeable 1,2-dioctanoyl-sn-glycerol (diC8), a diacylglycerol that activates PKC in intact cells and cell-free systems, did not mimic the effect of TPA on the IL-1 beta mRNA induction. To determine the protein kinase C isozymes present in the control and TPA- (5 X 10(-8) M) treated U937 cells, we prepared antipeptide antibodies that specifically recognize the alpha, beta, and gamma isoforms of protein kinase C in rat brain cytosol and U937 cell extracts. In "control" U937 cells, 30% of PKC alpha was particulate, and PKC beta was cytosolic, while there was no detectable PKC gamma.(ABSTRACT TRUNCATED AT 250 WORDS)


Hard x-ray phase contrast imaging using a tabletop Talbot-Lau interferometer with multiline embedded x-ray targets.
We demonstrate hard x-ray phase contrast imaging (XPCI) using a tabletop Talbot-Lau interferometer in which the x-ray source and source grating are replaced with an x-ray source with multiline metal targets embedded in a diamond substrate. This source realizes an array of linear x-ray sources of a few micrometers width without fabrication difficulty because of the shallow penetration depth of electrons irradiated to the metal targets. This enhances the coherence of x rays from each linear source and allows XPCI within 45 cm source-detector distance under 1.2 W input power for 8 keV x rays.


On the mode of action of lomofungin, an inhibitor of RNA synthesis in yeast.
Lomofungin is a potent inhibitor of RNA synthesis in yeast. Studies on the mode of action of the inhibitor were carried out using yeast RNA polymerases A and B and bacterial RNA polymerase. In vitro inhibition of RNA synthesis is independent of the nature and concentration of the template used and of the nucleoside triphosphate concentration. The extent of inhibition is strongly dependent upon the nature and concentration of divalent cations used to simulate transcription. The three RNA polymerases were inhibited to the same extent in the presence of Mn2+ ions whereas little inhibition was observed with Mg2+ ions. Spectrophotometric studies reveal the formation of different complexes between lomofungin and divalent cations (Mn2+, Mg2+, or Zn2+) with the respective stoichiometries of 0.5, 1, and 2 divalent cations per molecule of lomofungin. The complexes formed depend upon the nature of the divalent cation involved. No direct interaction between lomofungin and DNA could be observed in the presence of divalent cations but evidence is presented that lomofungin interacts with yeast RNA polymerase A. Inhibition of RNA synthesis occurs at the level of both chain initiation and elongation.


Prevalence of Polycystic Ovarian Syndrome and Its Link to Obesity in Adolescent Girls.
Polycystic ovarian syndrome (PCOS), also referred to as Stein-Leventhal syndrome, happens to be one of most common hormonal disorders found in females, causing large-sized ovaries with small cysts of non-ovulated oocytes in the outer medulla part of the ovary. Women suffering from PCOS often exhibit symptoms like oligomenorrhoea, elevated testosterone levels, acne, alopecia, hirsutism, sudden weight gain and many more. It can predispose a woman to developing infertility in future, and thus, difficulties in conceiving; due to the cystic changes in the ovaries, it results in anovulation and amenorrhea. The early symptoms of PCOS are being commonly observed nowadays in young women who are in their early 20s and those who are overweight or obese. The metabolic expression of PCOS increases with obesity. Obesity is a factor that is considered to contribute the most in the occurrence of various long-standing and non-transmissible illnesses apart from PCOS such as atherosclerosis, hypertension, diabetes, high blood cholesterol and even certain types of cancers. In obesity, there is an increase in the size and number of fat cells in the body. Obese and overweight young girls have a heightened likelihood of developing PCOS and its corresponding metabolic and reproductive health complications.


ACR Appropriateness Criteria® Head Trauma-Child.
Head trauma is a frequent indication for cranial imaging in children. The majority of accidental pediatric head trauma is minor and sustained without intracranial injury. Well-validated pediatric-specific clinical decision guidelines should be used to identify very low-risk children who can safely forgo imaging. In those who require acute imaging, CT is considered the first-line imaging modality for suspected intracranial injury because of the short duration of the examination and its high sensitivity for acute hemorrhage. MRI can accurately detect traumatic complications, but often necessitates sedation in children, owing to the examination length and motion sensitivity, which limits rapid assessment. There is a paucity of literature regarding vascular injuries in pediatric blunt head trauma and imaging is typically guided by clinical suspicion. Advanced imaging techniques have the potential to identify changes that are not seen by standard imaging, but data are currently insufficient to support routine clinical use. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Materno-fetal cholesterol transport during pregnancy.
Cholesterol is a major nutrient required for fetal growth. It is also a precursor for the synthesis of steroid hormones and essential for the development and maturation of fetal organs. During pregnancy, the placenta controls the transport of cholesterol from the mother to the fetus and vice versa. Cholesterol originating from the maternal circulation has to cross two main membrane barriers to reach the fetal circulation: Firstly, cholesterol is acquired by the apical side of the syncytiotrophoblast (STB) from the maternal circulation as high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)- or very-low-density lipoprotein (VLDL)-cholesterol and secreted at the basal side facing the villous stroma. Secondly, from the villous stroma cholesterol is taken up by the endothelium of the fetal vasculature and transported to the fetal vessels. The proteins involved in the uptake of HDL-, LDL-, VLDL- or unesterified-cholesterol are scavenger receptor type B class 1 (SR-B1), cubulin, megalin, LDL receptor (LDLR) or Niemann-Pick-C1 (NPC1) which are localized at the apical and/or basal side of the STB or at the fetal endothelium. Through interaction with apolipoproteins (e.g. apoA1) cholesterol is effluxed either to the maternal or fetal circulation via the ATP-binding-cassette (ABC)-transporter A1 and ABCG1 localized at the apical/basal side of the STB or the endothelium. In this mini-review, we summarize the transport mechanisms of cholesterol across the human placenta, the expression and localization of proteins involved in the uptake and efflux of cholesterol, and the expression pattern of cholesterol transport proteins in pregnancy pathologies such as pre-eclampsia, gestational diabetes mellitus and intrauterine growth retardation.


Histopathological Spectrum and Immunophenotypic Characterization of Symmetrical Drug-Related Intertriginous and Flexural Exanthema.
Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a clinically very well-defined drug eruption, but the histopathological findings are still considered to be nonspecific. To characterize the histopathological and immunophenotypical features of SDRIFE. We performed a retrospective study that identified 11 biopsies from 9 patients with SDRIFE. The histopathological features were analyzed in conjunction with the immunohistochemical findings. The most common histopathological feature was basal cell vacuolization, which was often associated with necrotic keratinocytes and focal spongiosis. TIA1+ T cells and neutrophils were frequently detected in the epidermis and at the dermoepidermal junction. The dermal inflammatory infiltrate was mixed, consisting of CD3+ T cells, macrophages, granulocytes, low numbers of CD20+ B cells, and plasma cells. A combination of histopathological patterns was observed in 5 cases. The most frequent combined histopathological patterns were interface dermatitis, spongiotic dermatitis, and psoriasiform dermatitis. Other histopathological patterns found in different combinations were pustular dermatitis, perivascular and interstitial neutrophilic dermatitis, and interstitial granulomatous dermatitis. In the other 4 cases, a single histopathological pattern predominated, such as psoriasiform dermatitis, vacuolar interface dermatitis of erythema multiforme-like type, or superficial and deep perivascular and interstitial dermatitis with eosinophils and neutrophils. SDRIFE is characterized histologically by a vacuolar interface dermatitis induced by cytotoxic T lymphocytes and neutrophilic granulocytes. This pattern may be obscured by accompanying spongiotic, psoriasiform, or pustular features combined with a mixed superficial and sometimes deep dermal infiltrate.


Effect of cyclic pneumatic soft tissue compression on simulated distal radius fractures.
We investigated the effect of pneumatic pressure applied to the proximal musculature of the sheep foreleg on load at the site of a transverse osteotomy of the distal radius. The distal radii of 10 fresh sheep foreleg specimens were osteotomized and a pressure sensor was inserted between the two bone fragments. An inflatable cuff, connected to a second pressure sensor, was positioned around the proximal forelimb musculature and the leg then was immobilized in a plaster cast. The inflatable cuff was inflated and deflated repeatedly to various pressures. Measurements of the cuff pressure and corresponding change in pressure at the osteotomy site were recorded. The results indicated that application of pneumatic pressure to the proximal foreleg musculature produced a corresponding increase in load at the osteotomy site. For the cuff pressures tested (109.8-238.4 mm Hg), there was a linear correlation with the load at the osteotomy site with a gradient of 12 mm Hg/N. It is conceivable, based on the results of this study, that a technique could be developed to provide dynamic loading to accelerate fracture healing in the upper limb of humans.


Antipsychotic-Induced Laryngeal Dystonia.
We present the case of a young gentleman with diagnoses of bipolar affective disorder, high body mass index, and obstructive sleep apnoea. He was commenced on zuclopenthixol due to an inadequate response to quetiapine, but this swiftly led to marked physical health deterioration including shortness of breath, back pain, tachycardia, tachypnoea, and hypoxia. He was urgently transferred to hospital where he required intubation and intensive care admission. AFTER excluding other causes, it was felt that commencing zuclopenthixol had induced laryngo-pharyngeal dystonia leading to upper airway compromise and severely impaired respiratory function. He progressively recovered after zuclopenthixol was stopped, and he was transferred back to the psychiatric hospital after eight days. THIS case highlights the potential challenges in diagnosing this rare but potentially fatal reaction to antipsychotics. We review the available literature on other cases including a potential interaction between typical antipsychotics and serotonin-specific reuptake inhibitors. Psychiatrists and emergency physicians should be aware of this condition and be alert in considering the administration of anticholinergics, which could be a simple yet life-saving intervention.


Cytokine inhibition in chronic fatigue syndrome patients: study protocol for a randomized controlled trial.
Chronic fatigue syndrome (CFS) is a medically unexplained syndrome for which no somatic or pharmacological treatment has been proven effective. Dysfunction of the cytokine network has been suspected to play a role in the pathophysiology of CFS. The disturbances of the cytokine network detected in CFS patients are highly variable, in part due to the lack of adequate controls in many studies. Furthermore, all studies have been performed on peripheral venous blood of patients. As cytokines mainly act in tissues, for example, the brain, the information that can be derived from peripheral blood cells is limited. The information regarding the possible role of cytokines in the pathophysiology could come from intervention studies in which the activities of relevant cytokines are reduced, for example, reducing interleukin-1, interleukin-6 or tumor necrosis factor. In this study, the clinical usefulness of anakinra, an IL-1 antagonist, will be assessed in patients with CFS. A randomized placebo-controlled, double-blind trial will be conducted. Fifty adult female patients meeting the Centers for Disease Control (CDC) criteria for CFS and without psychiatric co-morbidity will be included. After inclusion, patients will be randomized between treatment with anakinra (recombinant human interleukin-1 receptor antagonist) or placebo. Each group will be treated for 4 weeks. Outcome measures will be assessed at baseline, after 4 weeks of intervention, and 6 months after baseline assessment. The primary outcome measure will be fatigue severity at 4 weeks, measured with the validated Checklist of Individual Strength (CIS). Secondary outcome measures are functional impairment, physical and social functioning, psychological distress, pain severity, presence of accompanying symptoms, and cytokine and cortisol concentrations. This is the first randomized placebo-controlled trial that will evaluate the effect of interference with IL-1 on the experience of fatigue in patients with CFS. The results of this study may expand treatment options for patients with CFS, for whom graded exercise therapy and cognitive behavioral therapy are the only evidence-based interventions that exist at this moment. Clinicaltrials.gov: NCT02108210 . Clinicaltrials.gov registration date: 8 April 2014. EudraCT: 2013-005466-19.


Cross-species complementation reveals conserved functions for EARLY FLOWERING 3 between monocots and dicots.
Plant responses to the environment are shaped by external stimuli and internal signaling pathways. In both the model plant Arabidopsis thaliana (Arabidopsis) and crop species, circadian clock factors are critical for growth, flowering, and circadian rhythms. Outside of Arabidopsis, however, little is known about the molecular function of clock gene products. Therefore, we sought to compare the function of Brachypodium distachyon (Brachypodium) and Setaria viridis (Setaria) orthologs of EARLY FLOWERING 3, a key clock gene in Arabidopsis. To identify both cycling genes and putative ELF3 functional orthologs in Setaria, a circadian RNA-seq dataset and online query tool (Diel Explorer) were generated to explore expression profiles of Setaria genes under circadian conditions. The function of ELF3 orthologs from Arabidopsis, Brachypodium, and Setaria was tested for complementation of an elf3 mutation in Arabidopsis. We find that both monocot orthologs were capable of rescuing hypocotyl elongation, flowering time, and arrhythmic clock phenotypes. Using affinity purification and mass spectrometry, our data indicate that BdELF3 and SvELF3 could be integrated into similar complexes in vivo as AtELF3. Thus, we find that, despite 180 million years of separation, BdELF3 and SvELF3 can functionally complement loss of ELF3 at the molecular and physiological level.


Development of human calcitonin gene-related peptide (CGRP) receptor antagonists. 1. Potent and selective small molecule CGRP antagonists. 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-l-lysyl]-4-(4-pyridinyl)piperazine: the first CGRP antagonist for clinical trials in acute migraine.
Although the triptans have greatly improved the acute treatment of migraine headache, there are yet many shortcomings. Therefore, new strategies for the treatment of migraine are needed which offer advantages over current therapy, e.g. triptans. Our novel approach was based on the hypothesis that the release of calcitonin gene-related peptide (CGRP) could play a causative role in migraine headache. Thus we initiated a program aimed at the design and synthesis of small molecule CGRP receptor antagonists. High throughput screening led to the identification of (R)-Tyr-(S)-Lys dipeptide-like compounds that showed weak but unequivocal binding to the human CGRP receptor. Lead optimization afforded highly potent CGRP antagonists, the prototype being compound 19 (BIBN4096). This compound exhibiting a favorable biological profile was selected for initial clinical trials. A proof of concept study indicated that intravenous application of 19 was effective in the treatment of acute migraine headache. This finding strongly supports our initial working hypothesis that CGRP plays an important role in the pathophysiology of migraine.


Inadvertent ligation of the left pulmonary artery during intended ductal ligation.
Inadvertent ligation of the left pulmonary artery during attempted surgical closure of a Patent Ductus Arteriosus has long been recognized as one of the less common complications of this procedure. Surgical reconstruction of the left pulmonary artery was then often attempted but was difficult or impossible in some of the patients with hypoplasia of the left pulmonary artery and the left lung. A 10-year-old girl presented with marked exercise intolerance and palpitations and was diagnosed to have large PDA. She had feeding difficulty, diaphoresis, failure to gain weight, recurrent chest infections during infancy and early childhood. Physical examination revealed an underweight child with wide pulse pressure and bounding peripheral pulses. She had active precordium with accentuated P2 and machinery murmur in the left 2nd intercostal space and mid diastolic rumble at the mitral area. Echocardiography showed a 12 mm patent arterial duct. She was taken for an intended surgical ligation of the duct but a control echocardiogram on the 3rd postoperative day revealed that the left pulmonary artery, instead of the duct, was ligated. Surgical reconstruction of the left pulmonary artery was undertaken 3 years later, however, this was complicated by post reconstruction left pulmonary artery stenosis. Successful percutaneous stenting of the left pulmonary artery was performed 18 months after the surgical reconstruction. The incidence of inadvertent LPA ligation may be underestimated where PDA ligation is done by less experienced surgeons and postoperative echocardiography is not routinely performed. Late correction of inadvertent LPA ligation is an important surgical challenge, especially if the duct is still patent. Percutaneous stenting as a primary option may carry significant risk, as the ligated pulmonary artery is fragile. In our case, a good result was achieved with surgical repair followed by percutaneous stenting.


Case study of the comparison of data from conference abstracts and full-text articles in health technology assessment of rapidly evolving technologies: does it make a difference?
The aim of this study was to examine (i) the consistency of reporting research findings presented in conference abstracts and presentations and subsequent full publications, (ii) the ability to judge methodological quality of trials from conference abstracts and presentations, and (iii) the effect of inclusion or exclusion of data from these sources on the pooled effect estimates in a meta-analysis. This report is a case study of a selected health technology assessment review (TAR) of a rapidly evolving technology that had identified and included a meta-analysis of trial data from conference abstracts and presentations. The overall quality of reporting in abstracts and presentations was poor, especially in abstracts. There was incomplete or inconsistent reporting of data in the abstract/presentations. Most often inconsistencies were between conference slide presentations and data reported in published full-text articles. Sensitivity analyses indicated that using data only from published papers would not have altered the direction of any of the results when compared with those using published and abstract data. However, the statistical significance of three of ten results would have changed. If conference abstracts and presentations were excluded from the early analysis, the direction of effect and statistical significance would have changed in one result. The overall conclusions of the original analysis would not have been altered. There are inconsistencies in data presented as conference abstracts/presentations and those reported in subsequent published reports. These inconsistencies could impact the final assessment results. Data discrepancies identified across sources included in TARs should be highlighted and their impact assessed and discussed. Sensitivity analyses should be carried out with and without abstract/presentation data included in the analysis. Incomplete reporting in conference abstracts and presentations limits the ability of reviewers to assess confidently the methodological quality of trials.


"Spontaneous electrolysis" and simultaneously assembly hierarchy nanostructures of copper tetracyanoquinodimethane.
A simple method was developed to generate nanolamellas of CuTCNQ based on the principle of "spontaneous electrolysis". The nanolamellas were identified to belong to phase I of CuTCNQ. Intermediate products before nanolamellas were monitored with this method and beautiful artificial flowers were assembled based on the "spontaneous electrolysis." Moreover, CuTCNQ nanocrystal arrays could be grown on TCNQ single crystal surface homogeneously, which suggested a new method to assembly nanomaterials on crystal surface.


A new criterion including the aspartate aminotransferase-to-platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria.
Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA. In this prospective cross-sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two-dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow-up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia. Twenty-five patients (aged 0-18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut-off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase-to-platelet ratio index (APRI) instead of the platelet count with cut-off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies. A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA.


Hypoglycemic and other related effects of Boswellia glabra in alloxan-induced diabetic rats.
The hypoglycemic effect of the aqueous extract of the leaves and roots of Boswellia glabra was examined using alloxan-induced diabetic rats. A single oral administration of Boswellia glabra leaf and root extract decreased the blood glucose level. The continued use of leaf and root extract for 28 days produced significant hypoglycemic effects; also there was a decrease in serum glucose, cholesterol, triglyceride, urea and creatinine levels and enzyme activities (alkaline phosphatase and glucose-6-phosphatase). Ultra structural studies of beta cell of alloxan-induced diabetic rats treated with root extract showed numerous granulated sacs in comparison to rats treated with leaf extract. Thus, rats treated with root extract showed less degranulated sacs and more number of filled secretory granules in comparison to diabetic rats. Thus the use of aqueous extract of Boswellia glabra increased the synthesis of secretory granules in the beta-cell.


Assessment of antioxidant capacity and phenolic content of selected commercial beverages.
This study was aimed at assessing the antioxidant capacity and phenolic (free, bound, and total) contents in selected commercial beverages. Three different types of beverages commonly available in Malaysian supermarkets namely, cocoa, coffee and tea were selected. Phenolic contents were determined using a Folin-Ciocalteu assay. Antioxidant capacity (ferric reducing power and scavenging activity) was determined using FRAP and TEAC assays. Based on analysis of variance, coffee showed the highest amount of free phenolic compounds and antioxidant capacity compared to cocoa and tea (p < 0.05). The major phenolic compound detected in coffee was chlorogenic acid. Cocoa showed higher phenolic content than tea. However, cocoa and tea have similar catechin content and possessed comparable antioxidant capacity. The free phenolic content in the three beverages was found to be highly correlated with antioxidant capacity. In addition, moderate correlation was observed between total phenolic content and antioxidant capacity. On the other hand, there was no significant contribution of bound phenolic compounds towards antioxidant capacity. The contribution of antioxidant capacity in these beverages could be due to phenolic compounds in the free form. The study indicated that the beverages studied possessed varying degrees of antioxidant capacity and phenolic contents.


Hospitalized patients with community-acquired pneumonia in Hong Kong: a randomized study comparing imipenem/cilastatin and ceftazidime.
The aetiology and outcome of hospitalized patients with moderate to severe community-acquired pneumonia (CAP) were evaluated in 60 adult patients (38 male 22 female, mean age 68.4 years). They were randomized for treatment with either ceftazidime or imipenem/cilastatin intravenously for 7 days. Bacteriological diagnoses were made in 25 cases (41.6%): Streptococcus pneumoniae (5), Haemophilus influenzae (5), Pseudomonas spp. in particular Pseudomonas aeruginosa (8), Staphylococcus aureus (4), Chlamydia spp. (2), Mycobacterium tuberculosis (2) and Moraxella catarrhalis (3); mixed organisms were found in 4 patients. Forty-two patients (70%) responded satisfactorily to the regimens with improvement in sputum purulence cough and dyspnoea scores; there was no difference in response between the two groups. Sixteen patients (26.6%) underwent bronchoscopy on day 4 because of inadequate response to the antibiotics regimens, and 9 of them (15%) required a modification of the initial treatment with addition of erythromycin in 5 patients vancomycin in 1 cloxacillin in 1 and antituberculous drugs in 2. Three out of the 60 patients (5%) died of pulmonary sepsis: the aetiological agents were M. tuberculosis in one, Pseudomonas spp./methicillin-resistant S. aureus in another, but were not identified in the third. We conclude that treatment with either ceftazidime or imipenem/cilastatin was efficacious for moderate to severe CAP in Hong Kong.


Therapeutic effect of magnesium sulphate on carbon monoxide toxicity-mediated brain lipid peroxidation.
Carbon monoxide (CO) toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. Studies show that CO may cause brain lipid peroxidation and leukocyte-mediated inflammatory changes in the brain. The aim of this study was to investigate whether magnesium sulphate could prevent or diminish brain lipid peroxidation caused by carbon monoxide toxicity in rats. Fourty rats were divided into five groups of 8 rats each. Group l was not received any agent during the experiment. Group 2 was inhaled CO gas followed by intraperitoneally normal saline 30 minutes (min) later. Group 3 was inhaled CO gas followed by 100 mg/kg magnesium sulphate intraperitoneally 30 min later. Group 2 and Group 3 rats was undergone laparotomy and craniotomy while still under anesthesia at 6 hour, and tissue sample was obtained from the cerebrum. Group 4 was inhaled CO gas followed by intraperitoneally normal saline 30 min later. Group 5 was inhaled CO gas followed by 100 mg/kg magnesium sulphate intraperitoneally 30 min later. Group 4 and Group 5 rats was undergone laparotomy and craniotomy while still under anesthesia at 24 hour, and tissue sample was obtained from the cerebrum. Nitric oxide levels were no significantly different between all groups. Malonyldialdehyde levels increased in intoxication group (group 2) and decreased in treatment group (group 3). Activities of superoxide dismutase decreased in intoxication group (group 2) and increased in treatment group (group 3). Activities of catalase increased in intoxication group (group 2) and decreased in treatment group (group 3). Activities of glutathione peroxidase (GSH-Px) decreased in intoxication group (group 4) and increased in treatment group (group 5). CO poisoning caused significant damage, detected within the first 6 hours. Due to antioxidant enzymes, especially GSH-Px activity reaching the top level within 24th hours, significant oxidative damage was not observed. The protective effect against oxidative damage of magnesium sulfate has been identified within the first 6 hours.


A multidomain outer membrane protein from Pasteurella multocida: modelling and simulation studies of PmOmpA.
PmOmpA is a two-domain outer membrane protein from Pasteurella multocida. The N-terminal domain of PmOmpA is a homologue of the transmembrane beta-barrel domain of OmpA from Escherichia coli, whilst the C-terminal domain of PmOmpA is a homologue of the extra-membrane Neisseria meningitidis RmpM C-terminal domain. This enables a model of a complete two domain PmOmpA to be constructed and its conformational dynamics explored via MD simulations of the protein embedded within two different phospholipid bilayers (DMPC and DMPE). The conformational stability of the transmembrane beta-barrel is similar to that of a homology model of OprF from Pseudomonas aeruginosa in bilayer simulations. There is a degree of water penetration into the interior of the beta-barrel, suggestive of a possible transmembrane pore. Although the PmOmpA model is stable over 20 ns simulations, retaining its secondary structure and fold integrity throughout, substantial flexibility is observed in a short linker region between the N- and the C-terminal domains. At low ionic strength, the C-terminal domain moves to interact electrostatically with the lipid bilayer headgroups. This study demonstrates that computational approaches may be applied to more complex, multi-domain outer membrane proteins, rather than just to transmembrane beta-barrels, opening the possibility of in silico proteomics approaches to such proteins.


Changes in quadriceps femoris muscle perfusion following different degrees of cold-water immersion.
We examined the influence of graded cold-water immersion (CWI) on global and regional quadriceps muscle perfusion with positron emission tomography (PET) and [15O]H2O. In 30 healthy men [33 ± 8 yr; 81 ± 10 kg; 184 ± 5 cm; percentage body fat: 13 ± 5%; peak oxygen uptake (V̇o2peak): 47 ± 8 mL·kg-1·min-1] quadriceps perfusion, thigh and calf cutaneous vascular conductance (CVC), intestinal, muscle, and local skin temperatures, thermal comfort, mean arterial pressure, and heart rate were assessed before and after 10 min of CWI at 8°C, 15°C, or 22°C. Global quadriceps perfusion did not change beyond a clinically relevant threshold (0.75 mL·100 g·min-1) in any condition and was similar between conditions {range of differences [95% confidence interval (CI)]: 0.1 mL·100 g·min-1 (-0.9 to 1.2 mL·100 g·min-1) to 0.9 mL·100 g·min-1 (-0.2 to 1.9 mL·100 g·min-1)}. Muscle perfusion was greater in vastus intermedius (VI) compared with vastus lateralis (VL) (2.2 mL·100 g·min-1; 95% CI 1.5 to 3.0 mL·100 g·min-1) and rectus femoris (RF) (2.2 mL·100 g·min-1; 1.4 to 2.9 mL·100 g·min-1). A clinically relevant increase in VI muscle perfusion after immersion at 8°C and a decrease in RF muscle perfusion at 15°C were observed. A clinically relevant increase in perfusion was observed in VI in 8°C compared with 22°C water (2.3 mL·100 g·min-1; 1.1 to 3.5 mL·100 g·min-1). There were no clinically relevant between-condition differences in thigh CVC. Our findings suggest that CWI (8-22°C) does not reduce global quadriceps muscle perfusion to a clinically relevant extent; however, colder water increases (8°C) deep muscle perfusion and reduces (15°C) superficial muscle (RF) perfusion in the quadriceps muscle.NEW & NOTEWORTHY Using positron emission tomography, we report for the first time muscle perfusion heterogeneity in the quadriceps femoris in response to different degrees of cold-water immersion (CWI). Noxious CWI temperatures (8°C) increase perfusion in the deep quadriceps muscle, whereas superficial quadriceps muscle perfusion is reduced in cooler (15°C) water. Therefore, these data have important implications for the selection of CWI approaches used in the treatment of soft tissue injury, while also increasing our understanding of the potential mechanisms underpinning CWI.


Axial tomographic confocal fluorescence microscopy.
By physical rotation of the sample, axial tomography enables the acquisition of otherwise inaccessible spatial information from an object. In combination with confocal microscopy, the method can fundamentally improve the effective three-dimensional (3D) resolution. In this report we present a novel method for high resolution reconstruction of confocal axial tomographic data. The method automatically determines the relative angles of rotation, aligns the data from different rotational views and reconstructs a single high resolution 3D dataset. The reconstruction makes use of a known point spread function and is based on an unconstrained maximum likelihood deconvolution performed simultaneously from multiple (in our case three) angular views. It was applied to simulated as well as to experimental confocal datasets. The gain in resolution was quantified and the effect of choice of overrelaxation factors on the speed of convergence was investigated. A clearly improved 3D resolution was obtained by axial tomography together with reconstruction as compared with reconstruction of confocal data from only a single angular view.


Prison needle exchange programs work.
On 27 October 2004 the Canadian HIV/AIDS Legal Network and the Ontario Medical Association (OMA) released reports recommending that needle exchange programs (NEPs) be implemented in prisons, based on evidence that such programs promote and protect the health of both prisoners and prison staff. At the same time, the Scottish Prison Service announced that it was looking at providing such programs, and an Iranian physician reported on a pilot project in his country.


The Place of Atopy in the Aetiology of Acute Appendicitis in Children.
Appendicitis, the most common cause of abdominal pain requiring surgery in children, refers to inflammation of the vermiform appendix. The aetiology of appendicitis is multifactorial, although it is affected by several precursor factors. The purpose of this study was to investigate whether allergic diseases cause a predisposition to appendicitis. One hundred and sixteen patients who underwent surgery for acute appendicitis and who had a diagnosis of acute appendicitis confirmed pathologically, and a control group of 124 individuals of similar ages and genders, were enrolled. The level of inflammation of appendiceal material in cases diagnosed with acute appendicitis was classified pathologically. The skin prick test (SPT) was used to determine allergic sensitization. A significant difference was determined between the patient and control groups in terms of skin prick positivity (p < 0.05). While there are several known factors implicated in the causation of acute appendicitis, the cause cannot be identified in some cases. We think that atopy may also be a risk factor in the development of acute appendicitis.


[Multiple sclerosis in central Hungary: experiences and future possibilities of developing a local database].
Data during routine patient care are created in multiple digital and paper-based hardcopy systems, therefore their retrieval is cumbersome in the follow-up of patients. Multiple sclerosis is the most prevalent neurological disorder in the young age, with major consequences on health and socio-economic status. We set forth to create a user-friendly, detailed local database where it is easy to access, register and analyze data. Based on our experiences during building this registry, we develop the model of a modern type of database. First we established a local registry in Excel, then data were transferred to the worldwide used iMed system. Separate pages were used to register basic data, follow-up visits, relapses, accompanying diseases, results of neuroimaging, cerebrospinal fluid, evoked response and other tests, pharmacological and non-pharmacological treatments. The database currently contains data of 316 patients. MRI was performed in 96%, cerebrospinal fluid examination in 45% of the patients. The rate of primary progressive disease at disease onset is 9%. Disease modifying treatments were applied in 82% of the patients. The traditional manual data entry and data export in PDF format is obsolete and time-consuming. The development of local disease-specific databases appropriate for clinical and research purposes requires continuous and mostly automatic data entry. In future local registries the establishment of uniform documentational language and structure, and automatic transfer of information among different digital systems are required. We present the model of such a registry, which is based on a healthcare data lake. Orv Hetil. 2019; 160(4): 131-137.


Factors affecting the adoption of healthcare information technology.
In order to improve the quality and performance of healthcare services, healthcare information technology is among the most important technology in healthcare supply chain management. This study sets out to apply and test the Unified Theory of Acceptance and Use of Technology (UTAUT), to examine the factors influencing healthcare Information Technology (IT) services. A structured questionnaire was developed and distributed to healthcare representatives in each province surveyed in Thailand. Data collected from 400 employees including physicians, nurses, and hospital staff members were tested the model using structural equation modeling technique. The results found that the factors with a significant effect are performance expectancy, effort expectancy and facilitating conditions. They were also found to have a significant impact on behavioral intention to use the acceptance healthcare technology. In addition, in Thai provincial areas, positive significance was found with two factors: social influence on behavioral intention and facilitating conditions to direct using behavior. Based on research findings, in order for healthcare information technology to be widely adopted and used by healthcare staffs in healthcare supply chain management, the healthcare organizational management should improve healthcare staffs' behavioral intention and facilitating conditions.


CD146 defines commitment of cultured annulus fibrosus cells to express a contractile phenotype.
Characterization of cells is important for facilitating cell-based therapies for degenerative diseases of intervertebral discs. For this purpose, we analyzed mouse annulus fibrosus cells by flowcytometory to detect phenotypic change in their primary cultures. After examination of sixteen cell surface proteins, we focused on CD146 that solely increased during culture expansion. CD146 is known to be a marker for mesenchymal stem cells and for their vascular smooth muscle commitment with expression of contractile phenotype enhanced by SM22α. We sorted CD146+ cells to elucidate their characteristics and the key factors that play a role in this change. Whole cell cultures showed the ability for tripotent differentiation toward mesenchymal lineages, whereas sorted CD146+ cells did not. Expression of CD146 was elevated by addition of transforming growth factor β1, and sorted CD146+ cells expressed higher levels of mRNA for SM22α and Elastin than did CD146- cells. Morphologically, CD146+ cells more broadly deposited extracellular type I collagen than CD146- cells and showed filamentous actin bundles traversing their cytoplasm and cell-cell junctions. Moreover, CD146+ cells demonstrated significantly higher gel contraction properties than CD146- cells when they were embedded in collagen gels. Human annulus fibrosus CD146+ cells also showed higher contractility. Immunohistochemistry determined CD146+ cells localized to the outermost annulus layers of mouse intervertebral disc tissue with co-expression of SM22α. These results suggest that increment of CD146 expression indicates gradual change of cultured annulus fibrosus cells to express a contractile phenotype and that transforming growth factor β1 enhances this cellular commitment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1361-1372, 2016.


TiO2 anatase nanorods with non-equilibrium crystallographic {001} facets and their coatings exhibiting high photo-oxidation of NO gas.
Development of highly active photocatalysts is mandatory for more widespread application of this alternative environmental technology. Synthesis of photocatalysts, such as anatase TiO2, with more reactive, non-equilibrium, crystallographic facets is theoretically justified by a more efficient interfacial charge transfer to reactive adsorbed species, increasing quantum efficiency of photocatalyst. Air and vacuum calcinations of protonated trititanate nanotubes lead to their transformation to anatase nanorods. The nanorods synthesized by air calcination demonstrate photo-oxidation of NO gas more than three times superior to the one presented by the benchmark P-25 photocatalyst. This performance has been explained in terms of 50% higher specific surface area and, more importantly, through the predominance of more reactive, non-equilibrium, {001} crystallographic facets of the anatase nanorods. These facets present a high density of undercoordinated Ti cations, which favors adsorption of reactant species, and strained Ti-O-Ti bonds, leading to more efficient photo-oxidation reactions. Reduced Ti species, such as Ti3+, were not observed in the as-obtained nanorods, while reactive adsorbed molecules are scarce on the nanorods obtained through vacuum calcination. Dip-coating of TiO2 anatase nanorods (air calcined) over soda-lime glass plates was used to prepare visible light transparent, superhydrophilic and highly adherent photocatalytic coatings with homogenously distributed nanopores.


Negotiating indoor air-case report on negotiation of teachers' union, school board on air contaminants.
School districts increasingly understand the need for an indoor air quality plan, but may have difficulty in producing a plan that all necessary parties will accept. This article provides a case study of how one Massachusetts school district, after experiencing environmental problems in an elementary school, worked with parents and unions to develop a comprehensive indoor air quality plan.


A narrative review of treatment interventions to improve cognitive performance in schizophrenia, with an emphasis on at-risk and early course stages.
Cognitive dysfunction is a core feature of schizophrenia (SCZ), which unfavorably affects SCZ patients' daily functioning and overall clinical outcome. An increasing body of evidence has shown that cognitive deficits are present not only at the beginning of the illness but also several years before the onset of psychosis. Nonetheless, the majority of treatment interventions targeting cognitive dysfunction in SCZ, using both pharmacological and nonpharmacological approaches, have focused on chronic patients rather than individuals at high risk or in the early stages of the disease. In this article, we provide a narrative review of cognitive interventions in SCZ patients, with a particular focus on pre-emptive interventions in at-risk/early course individuals when available. Furthermore, we discuss current challenges for these pre-emptive treatment interventions and provide some suggestions on how future work may ameliorate cognitive dysfunction in these individuals.


Reliability, validation and norms of the Chinese version of Anxiety Sensitivity Index 3 in a sample of military personnel.
This study aimed to explore the properties of the Chinese version of the Anxiety Sensitivity Index- 3 (ASI-3) in a sample of military personnel. Using non-probabilistic sampling, the Chinese version of the ASI-3 was administered to 3,077 valid participants aged 16 to 36 years old (M = 22.35, SD = 3.57) from nine military units. The Depression Anxiety Stress Scales-21 (DASS-21) and The State-Trait Anxiety Inventory (STAI) were used to assess the construct validity. A one-way analysis of variance was conducted to compare the differences in the services and positions of the participants. It was found that ①The indices of confirmatory factor analysis met the standard values, which supported the hypothesis of the three-factor model of the original ASI-3; ②ASI-3 was significantly associated with DASS-21 in positive ways, which indicated the high convergent validity; on the other hand, the correlation between ASI-3 and TAI was relatively low, which indicated there was an empirical discrimination between anxiety sensitivity and trait anxiety. ③The Cronbach's α coefficients were 0.926 for the total scale and 0.828-0.841 for the three subscales; ④At a cut-off score of 16, the sensitivity and specificity levels were 71.1% and 76.7%, respectively, where the sum of sensitivity and specificity becomes the maximum, accompanied with improvement of PPV and NPV; ⑤There were significant findings in the ASI and subscales among the five services and four positions. This study provides new evidence that the Chinese version of the Anxiety Sensitivity Index-3 has good validity and reliability and could be applied as an effective tool to assess anxiety sensitivity in military personnel. Our recommendations to researchers and practitioners are that the three factor model should be replicated across some different special forces and the items and constructs could be modified on Chinese culture.


The short term effects of a single limbal relaxing incision combined with clear corneal incision.
To compare the effects of performing a single limbal relaxing incision (LRI) combined with a clear corneal incision on a corneal astigmatism with that of paired LRIs in cataract surgery. Medical records for 25 eyes in 20 patients who had undergone LRIs during cataract operations for with-the-rule astigmatism of 1.5 diopters (D) or more in topography were retrospectively reviewed. Single or paired LRIs were assigned randomly and were performed on the steepest axis; the degrees of arc were determined using the modified Gills nomogram. A clear corneal wound was made on the steepest vertical axis. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest refraction, and corneal astigmatism on topography were evaluated preoperatively and one month postoperatively. Naeser's polar value analysis was used to assess the efficacy of the LRIs. The mean depth of the LRIs and degrees of arc were 620+/-31 microm (87.1% of corneal thickness) and 56.84+/-19.68 degrees , respectively. The mean postoperative UCVA and BCVA (log MAR) were significantly improved (0.51+/-0.37 and 0.09+/-0.12, respectively) (p<0.05). Average refractive and corneal astigmatisms were significantly reduced by 49.4 percent and 32.4 percent, respectively (p<0.05). The single LRI combined with clear corneal incision showed reduced efficacy in refractive astigmatism by 47 percent, which is similar to that of paired LRIs where a 48 percent reduction in efficacy was seen. The short-term effects of a single LRI combined with clear corneal incision on a corneal astigmatism appears to be as effective as performing paired LRIs when combined with cataract incision.


Acute myeloma.
This patient had an acute onset of myeloma, with hypercalcemia, a high M-component in the plasma, Bence Jones proteinuria, and 37% plasma cells in the bone marrow sample. After melphalan treatment (210 mg totally) he seems to have a complete cure, with total disappearance of the M-component, Bence Jones proteinuria, myeloma cells, hypercalcemia and elevated ESR for almost three years.


A phase 1, open label, dose escalation study to investigate the safety, tolerability, and pharmacokinetics of MG1102 (apolipoprotein(a) Kringle V) in patients with solid tumors.
Purpose MG1102 is a potent inhibitor of angiogenesis in both in vitro and in vivo models. The purpose of the study was to investigate the safety and tolerability, pharmacokinetic (PK) profile, and preliminary antitumor efficacy of MG1102. Methods Patients with refractory solid tumors were eligible. Each patient received 1 dose of MG1102 followed by a 6-day rest period, during which they underwent PK assessments and safety monitoring. If the initial dose was tolerated, the patient continued with the 21-day treatment of MG1102 (5 days on, 2 days off for 3 weeks). Dose escalation was planned in 6 cohorts (6, 12, 24, 48, 96, and 192 mg/m2). Primary objectives included safety and maximum tolerated dose (MTD) assessment. Secondary objectives included assessment of PK, pharmacodynamics, and efficacy. Results A total of 16 patients were enrolled and 12 (75%) completed the study. The most common cancer type was colorectal cancer (n = 10). There was no dose limiting toxicity and the MTD was not reached at 192 mg/m2. The most frequent treatment-emergent adverse events were gastrointestinal disorders, including nausea (30.8%), abdominal pain (23.1%), constipation (23.1%), and dyspepsia (23.1%). The PK of MG1102 was slightly less than dose proportional from Cohorts 3 to 6. Among 13 response-evaluable patients, 1 unconfirmed partial response (PR) was seen (in the 48 mg/m2 cohort) and 4 patients had stable disease. Conclusions The safety profile of MG1102 was generally manageable and the toxicities resolved quickly. Potential antitumor activity was observed with 1 unconfirmed PR (60% size reduction).


Disparities in Excess Mortality Associated with COVID-19 - United States, 2020.
The COVID-19 pandemic has disproportionately affected Hispanic or Latino, non-Hispanic Black (Black), non-Hispanic American Indian or Alaska Native (AI/AN), and non-Hispanic Native Hawaiian or Other Pacific Islander (NH/PI) populations in the United States. These populations have experienced higher rates of infection and mortality compared with the non-Hispanic White (White) population (1-5) and greater excess mortality (i.e., the percentage increase in the number of persons who have died relative to the expected number of deaths for a given place and time) (6). A limitation of existing research on excess mortality among racial/ethnic minority groups has been the lack of adjustment for age and population change over time. This study assessed excess mortality incidence rates (IRs) (e.g., the number of excess deaths per 100,000 person-years) in the United States during December 29, 2019-January 2, 2021, by race/ethnicity and age group using data from the National Vital Statistics System. Among all assessed racial/ethnic groups (non-Hispanic Asian [Asian], AI/AN, Black, Hispanic, NH/PI, and White populations), excess mortality IRs were higher among persons aged ≥65 years (426.4 to 1033.5 excess deaths per 100,000 person-years) than among those aged 25-64 years (30.2 to 221.1) and those aged <25 years (-2.9 to 14.1). Among persons aged <65 years, Black and AI/AN populations had the highest excess mortality IRs. Among adults aged ≥65 years, Black and Hispanic persons experienced the highest excess mortality IRs of >1,000 excess deaths per 100,000 person-years. These findings could help guide more tailored public health messaging and mitigation efforts to reduce disparities in mortality associated with the COVID-19 pandemic in the United States,* by identifying the racial/ethnic groups and age groups with the highest excess mortality rates.


Covalent Organic Frameworks as a Platform for Multidimensional Polymerization.
The simultaneous polymerization and crystallization of monomers featuring directional bonding designs provides covalent organic frameworks (COFs), which are periodic polymer networks with robust covalent bonds arranged in two- or three-dimensional topologies. The range of properties characterized in COFs has rapidly expanded to include those of interest for heterogeneous catalysis, energy storage and photovoltaic devices, and proton-conducting membranes. Yet many of these applications will require materials quality, morphological control, and synthetic efficiency exceeding the capabilities of contemporary synthetic methods. This level of control will emerge from an improved fundamental understanding of COF nucleation and growth processes. More powerful characterization of structure and defects, improved syntheses guided by mechanistic understanding, and accessing diverse isolated forms, ranging from single crystals to thin films to colloidal suspensions, remain important frontier problems.


States of water located in the continuous organic phase of 1-butyl-3-methylimidazolium tetrafluoroborate/Triton X-100/triethylamine reverse microemulsions.
We demonstrate a novel ionic liquid (IL) microemulsion, consisting of 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4) and nonionic surfactant Triton X-100 prepared in triethylamine which is used either as an organic solvent or a Lewis base. The effects of small amounts of added water on the microstructure of the IL microemulsion are investigated by various techniques. UV/Vis spectroscopic analysis and FTIR spectra indicate that these water molecules are not solubilized into the IL pools of the microemulsions. 1H NMR spectra further show that the added water binds with triethylamine to form a surrounding OH- base environment. Some of OH- ions enter the palisade layers of the IL microemulsions and a continuous base interface is created. The unique solubilization behavior of water reveals that it is possible to use the triethylamine microemulsions as a template to prepare metal hydroxides as well as metal oxides in the microemulsions, which is not possible when using traditional microemulsions.


Protomer-Specific Photochemistry Investigated Using Ion Mobility Mass Spectrometry.
The utility of tandem ion mobility mass spectrometry coupled with electronic spectroscopy to investigate protomer-specific photochemistry is demonstrated by measuring the photoisomerization response for protomers of protonated 4-dicyanomethylene-2-methyl-6-para-dimethylaminostyryl-4H-pyran (DCM) molecules. The target DCMH+ species has three protomers that are distinguished by their different collision cross sections with He, N2, and CO2 buffer gases, trends in abundance with ion source conditions, and from their photoisomerization responses. The trans-DCMH+ protomers with the proton located either on the tertiary amine N atom or on a cyano group N atom exhibit distinct S1← S0 photoisomerization responses, with the maxima in their photoisomerization action spectra occurring at 420 and 625 nm, respectively, consistent with predictions from accompanying electronic structure calculations. The cis-DCMH+ protomers are not distinguishable from one another through ion mobility separation and give no discernible photoisomerization or photodissociation response, suggesting the dominance of other deactivation pathways such as fluorescence. The study demonstrates that isobaric protomers and isomers generated by an electrospray ion source can possess quite different photochemical behaviors and emphasizes the utility of isomer and protomer selective techniques for exploring the spectroscopic and photochemical properties of protonated molecules in the gas phase.


Rare forms of peripheral arterial embolism: review of 11 cases.
The purpose of this study was to present 11 patients operated on owing to rare forms of peripheral arterial embolism at the Institute for Cardiovascular Diseases of the Serbian Clinical Center over a period of 20 years. Three patients were operated on owing to a foreign body embolism, two owing to a septic embolism, three owing to emboli that originated from malignant tissues, two owing to an embolization from cardiac myxoma, and one owing to an embolism from a myxomatous atrial septal defect. The preoperative evaluation included clinical examination, laboratory findings, and electrocardiography; in the majority of cases, ultrasonography and angiography were performed. Surgical treatment included foreign body extraction in three cases; thromboembolectomy in seven cases, and artery resection and saphenous graft interposition in one patient with septic embolism. In addition, three cardiosurgical procedures were done: aortic valve replacement in the patient with a septic embolism and tumor excision in patients with atrial myxoma. In addition to the usual clinical signs of acute limb ischemia, in the rare forms of arterial embolism, the presence of certain uncommon clinical symptoms was also observed. The early results of vascular surgical treatment were very good in all patients. Further follow-up revealed a poor prognosis in patients with malignant arterial embolism.


Catalytic aerobic photooxidation of triarylphosphines using dibenzo-fused 1,4-azaborines.
Although dibenzo-fused 1,4-heteroaromatics are utilized as strongly reducing photocatalysts in organic synthesis and polymerization, they have rarely been employed in catalytic photooxidation. Moreover, to date, their boron-analogs, dibenzo-fused 1,4-azaborines (DBABs), have not been applied in photocatalysis despite their promising potential as photocatalysts. Accordingly, herein, aerobic photooxidation of triarylphosphines (Ar3P) was performed using DBABs as photocatalysts. The reaction smoothly proceeded in an aprotic solvent, and phosphine oxides were obtained in appropriate yields. Density functional theory calculations suggested that DBAB captured and activated phosphadioxirane intermediates, which were generated by the interaction of Ar3P with 1O2, at the Lewis acidic boron center.


Adult neurogenesis reduction by a cytostatic treatment improves spatial reversal learning in rats.
Adult neurogenesis in the dentate gyrus adds a substantial number of new functional neurons to the hippocampus network in rodents. To date, however, the function of these new granule cells remains unclear. We conducted an experiment to assess the contribution of adult neurogenesis in the dentate gyrus to acquisition and reversal learning in a task that predominantly requires generalization of a rule. Young adult male Long-Evans rats were repeatedly administered either a cytostatic temozolomide or saline for a period of four weeks (3 injections per week). Post treatment, animals were injected with bromodeoxyuridine to quantify adult neurogenesis in the dentate gyrus. For behavioral assessment we used hippocampus-dependent active place avoidance with reversal in a Carousel maze. Animals first learned to avoid a 60° sector on the rotating arena. Afterwards, sector was relocated to the opposite side of the rotating arena (reversal). The administration of temozolomide significantly improved the reversal performance compared to saline-treated rats. Our results suggest a significant, level-dependent, improvement of reversal learning in animals with reduced adult neurogenesis in hippocampus.


Biology and immunology of human strongyloidiasis.
Strongyloidiasis is an important human parasitic infection primarily because of its potential for serious and even lethal disease in immunosuppressed patients. Certain features of the biology of Strongyloides stercoralis, such as the ability to autoinfect the host, help explain why the parasite is dangerous. Characteristics of the parasite can also be exploited in parasitological diagnosis of infection with the Baermann concentration procedure and by culture. Use of filariform larval antigens in ELISA or immunofluorescent-antibody tests now provide reliable serological tests for diagnosis, and, in most patients, antibody levels decline one to two years after successful treatment. Immediate hypersensitivity is a prominent component of the immune response to strongyloides infection and may play a role in the pathogenesis of disease as well as in protection. An IgE-mediated skin test appears to be useful in diagnosis. Animal models used for immunologic studies of other intestinal helminths have lacked relevance to human strongyloidiasis. Features of the human disease, however, including hyperinfection syndrome, can be produced by S. stercoralis in the Patas monkey and in dogs.


Clinical Assessment of the Efficiency of Low Level Laser Therapy in the Treatment of Oral Lichen Planus.
Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa of uncertain etiology. To evaluate the effect of using low level laser therapy (LLLT (970 nm Siro laser Advance) for the treatment of symptomatic (OLP). The present study was conducted on ten patients suffering from persistent oral lichen planus (OLP). Patients were treated with diode laser (970nm) for the symptomatic relief of pain and burning sensation. The patients were assessed before, during and after the completion of the laser treatment which was done twice weekly for two successive months with maximum of ten sessions. The assessment was performed using visual analogue scale (VAS) and clinical investigation for each patient. Detailed significant reduction in lesion size and showed complete remission of burning sensation and pain. No reported complications or therapy side effects were observed in any of the treated patients. Diode laser therapy seems to be an effective adjunctive treatment modality for relieving pain and clinical symptoms of OLP.


SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice: A Review of an Adjunct Clinical Symposium of the American College of Gastroenterology Meeting October 16, 2016 • Las Vegas, Nevada.
Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients.


Mild cognitive impairment, amnestic type: an epidemiologic study.
To estimate the prevalence and examine the course of mild cognitive impairment (MCI), amnestic type, using current criteria, within a representative community sample. Retroactive application of MCI criteria to data collected during a prospective epidemiologic study was performed. The subjects were drawn from voter registration lists, composing a cohort of 1,248 individuals with mean age of 74.6 (5.3) years, who were nondemented at entry and who were assessed biennially over 10 years of follow-up. The Petersen amnestic MCI criteria were operationalized as 1) impaired memory: Word List Delayed Recall score of <1 SD below mean; 2) normal mental status: Mini-Mental State Examination score of 25+; 3) normal daily functioning: no instrumental impairments; 4) memory complaint: subjective response to standardized question; 5) not demented: Clinical Dementia Rating Scale score of <1. At the five assessments, amnestic MCI criteria were met by 2.9 to 4.0% of the cohort. Of 40 persons with MCI at the first assessment, 11 (27%) developed dementia over the next 10 years. Over each 2-year interval, MCI persons showed increased risk of dementing (odds ratio = 3.9, 95% CI = 2.1 to 7.2); 11.1 to 16.7% progressed to Alzheimer disease and 0 to 5.0% progressed to other dementias. Over the same intervals, 11.1 to 21.2% of those with MCI remained MCI; of 33.3 to 55.6% who no longer had MCI, half had reverted to normal. In this community-based sample, 3 to 4% of nondemented persons met MCI operational criteria; despite increased risk of progressing to dementia, a substantial proportion also remained stable or reverted to normal during follow-up. Amnestic MCI as currently defined is a high-risk but unstable and heterogeneous group.


Novel targets for the treatment of atherosclerosis.
Atherosclerosis remains the leading cause of death in developed countries and thus demands the development of safe therapeutic treatments. Novel risk factors, in addition to the traditional targets, are being assessed. The significance of inflammation in atherosclerotic plaque development has become indisputable. A large number of published studies support the fact that investigations of the inflammatory aspects of atherosclerosis will be the target for future development. The C-reactive protein in particular has drawn specific attention due to its role as an inflammatory marker of atherosclerosis. Novel targets for atherosclerotic intervention include inhibitors of cholesterol synthesis and absorption such as acyl-coenzyme A:cholesterol acyltransferase, acyl-coenzyme A:diacylglycerol acyltransferase and cholesteryl ester transfer protein inhibitors, potential novel antioxidants other than anti-inflammatory peroxisome proliferator activated receptor agonists, and apolipoprotein A-I mimetic peptides.


Biosimilars for breast cancer.
Introduction: Cancer treatment has evolved significantly with the introduction of biologic agents, especially in the breast cancer (BC) area. The use of trastuzumab for HER2 amplified BCsignificantly improves survival in both metastatic and early stage disease. Although the efficacy of biologics is undeniable, their high costs increased the expenses of cancer care, becoming a problem to health-care systems, mainly in low and middle-income, but also for high-income countries. In an attempt to lower the costs and allow a greater access of biologics to cancer patients, biosimilars are rapidly being developed as an alternative to the reference biologics. Areas covered: A literature review based on the MEDLINE/PubMed search about biosimilars allied with the FDA and EMA's latest statements of this topic were conducted to summarize the development and the use of currently available biosimilars for BC, with a focus on trastuzumab. Expert opinion: Biosimilars are drugs that have similar efficacy and safety profile to those of the original biological product with equivalent immunogenicity and, as these agents hold the potential to improve patient´s access to monoclonal antibodies because their production costs are estimated to be 20-30% lower compared to the reference product, they are progressively being incorporated into clinical practice.


Maternal and neonatal morbidity and mortality in cesarean section.
Maternal mortality rates after cesarean delivery are low, but cesarean section is more hazardous than vaginal delivery by a factor of two to four. Operative complications can be minimized by careful technique and are more often seen in emergency than elective cases. Prophylactic antibiotics are of some benefit in reducing postoperative endometritis in patients with risk factors. Cesarean birth rarely causes the death of a newborn. Nevertheless, significant newborn pulmonary problems, especially respiratory distress syndrome, may follow an inappropriately timed cesarean delivery. Careful attention to clinical measures and supporting evidence of pulmonary maturity from ultrasound will avoid most instances of iatrogenic prematurity. Amniocentesis, with a higher complication rate than ultrasound, may still be required to prove pulmonary maturity in some circumstances. If concern or doubt precludes elective delivery of patients with previous low transverse uterine incisions, one can wait for the patient to go into spontaneous labor.


Older women with osteoporosis have increased postural sway and weaker quadriceps strength than counterparts with normal bone mass: overlooked determinants of fracture risk?
Fracture risk is determined by both bone health and fall risk. Evidence suggests that older women with osteoporosis may have a greater risk of falling compared with their age-matched counterparts without osteoporosis ( 1). To determine whether fall risk screening should be a routine part of medical assessment in older women with osteoporosis, a comparison of fall risk between those with osteoporosis and healthy age-matched counterparts is needed. The purpose of this study was to compare 3 established fall risk factors between these 2 groups of women. 42 women between the ages of 64 and 75 years old participated in this study. 21 women with osteoporosis were matched by age and current physical activity level to 21 women without osteoporosis. The performance on 3 fall risk factors (quadriceps strength, balance, and functional mobility) was compared between the 2 groups using multivariate analysis of variance. The level of significance was set at p <or=.05. There was an overall difference between the 2 groups on the fall risk factors (Wilk's lambda = 0.769, p =.018). Dominant quadriceps strength and composite balance score were, respectively, 18% significantly less and 11% worse in women with osteoporosis than those without. Functional mobility was not significantly different between the 2 groups. This study highlights older women with osteoporosis as a high fracture risk group due to having both lower bone density, and possibly, higher fall risk compared with their age-matched counterparts without osteoporosis. Both fall risk screening and fall risk reduction may be prudent to prevent fractures in women with osteoporosis.


Limited effects of source population identity and number on seagrass transplant performance.
Global declines in coastal foundation species highlight the importance of effective restoration. In this study, we examined the effects of source population identity and diversity (one vs. three sources per plot) on seagrass (Zostera marina) transplant success. The field experiment was replicated at two locations in Massachusetts with adjacent natural Zostera marina beds to test for local adaptation and source diversity effects on shoot density. We also collected morphological and genetic data to characterize variation within and among source populations, and evaluate whether they were related to performance. Transplants grew and expanded until six months post-transplantation, but then steadily declined at both sites. Prior to declines, we observed variation in performance among source populations at one site that was related to morphological traits: the populations with the longest leaves had the highest shoot densities, whereas the population with the shortest leaves performed the worst at six months post-transplantation. In addition, multiple source plots at this same transplant site consistently had similar or higher shoot densities than single source plots, and shoots from weak-performing populations showed improved performance in multiple source plots. We found no evidence for home site advantage or benefits of population-level genetic variation in early transplant performance at either site. Our results show limited effects of source population on early transplant performance and suggest that factors (e.g., morphology) other than home site advantage and population genetic variation serve a role. Based on our overall findings that transplant success varied among source populations and that population diversity at the plot level had positive but limited effects on individual and plot performance, we support planting shoots from multiple source sites in combination to enhance transplant success, particularly in the absence of detailed information on individual source characteristics.


Medical Oncology Care Plan: a tool for improving the provision of clinical information to patients.
Improving clinical communication between patient and clinician through the provision of written information empowers patients to make informed decisions, underpinning patient-centred care and leading to greater health outcomes. The Townsville Cancer Centre has formulated a holistic care plan template for each patient as a tool to enhance this communication. Using questionnaire-based and qualitative surveys, understanding of the patient's cancer and perspectives of clinicians were examined. The results demonstrate that patients generally have a firm knowledge base of their disease with the predominant finding being that patients wish to be more informed with written information about their diagnosis and alternatives for treatment. While initially time consuming, completion of care plans had many benefits for clinicians; they prompted them to collect holistic information, engage in discussions to capture patient goals and document details about prognosis, treatment options and management of side-effects. Medical oncology care plans provide a sustainable method to provide clinicians a practical template to gather vital information and encourage patients to participate in the decision-making process for healthcare.


The decline of swimming performance with advancing age: a cross-sectional study.
The aim of this cross-sectional study was to measure the swimming parameters-speed (V), stroke frequency (SF), and stroke length (SL)- in 162 male athletes aged 50-90 (divided into 7 age groups, from A to G) participating in the World Master Championships in the 200-m freestyle event, and to analyze the rates and magnitudes of their age-associated declines. The swimmers were video-recorded by 2 digital cameras during the competitions and the swimming parameters related to every 50-m section (lap) and to the entire race (average) subsequently measured or calculated. Lap V and SF decreased in the second and third quarter (11 and 4% on average) and increased (3% on average) in the fourth quarter of the race, whereas lap SL decreased from the first to the last 50-m section. Average V (m.s(-1)) decreased from 1.39 +/- 0.09 (group A) to 0.84 +/- 0.11 (group G); average SL (m) decreased from 2.10 +/- 0.20 (group A) to 1.78 +/- 0.19 (group G); and average SF (cycles.s(-1)) decreased from 0.67 +/- 0.06 (group A) to 0.47 +/- 0.04 (group G). One-way analysis of variance showed significant declines in average V, SL, and SF (p < 0.01) across the 7 groups. The swimming parameters were normalized to the highest values (set equal to 100); thereafter, a linear regression curve was fitted and the regression equations calculated. Decline of SF was about 2.5 times steeper than that of SL. It was highlighted that (a) among the swimming parameters, SL is less affected by the ageing process; (b) SL decreased from group A through group C and thereafter tended to keep steady, whereas the trend for SF was opposite. The results have the potential to give master swimmers and their coaches useful information for training program design.


Emergence of highly designable protein-backbone conformations in an off-lattice model.
Despite the variety of protein sizes, shapes, and backbone configurations found in nature, the design of novel protein folds remains an open problem. Within simple lattice models it has been shown that all structures are not equally suitable for design. Rather, certain structures are distinguished by unusually high designability: the number of amino acid sequences for which they represent the unique lowest energy state; sequences associated with such structures possess both robustness to mutation and thermodynamic stability. Here we report that highly designable backbone conformations also emerge in a realistic off-lattice model. The highly designable conformations of a chain of 23 amino acids are identified and found to be remarkably insensitive to model parameters. Although some of these conformations correspond closely to known natural protein folds, such as the zinc finger and the helix-turn-helix motifs, others do not resemble known folds and may be candidates for novel fold design.


Clinical and laboratory characteristics of type 1 diabetes in children and adolescents: experience from a medical center.
The incidence of type 1 diabetes (T1D) is increasing rapidly worldwide, predominantly in younger individuals. We developed a checklist of all symptoms of T1D reported in the literature and compared the completeness of the recording of symptoms at initial presentation before and after the checklist was adopted. We retrospectively reviewed the records of patients newly diagnosed with T1D from January 1, 1979 through September 30, 2006 to assess the presenting features and test the usefulness of a symptom checklist in evaluating the history on presentation. The checklist was incorporated into the records as of October 1, 1994. Of the 304 patients identified, 130 (43%) had checklists in the charts. There were 146 (48%) boys, 98 (32%) who were diagnosed under the age of 6 years, and 198 (65%) presented with diabetic ketoacidosis (DKA). Records with a checklist noted diabetic symptoms that were subtle and easily ignored more often than records without the checklist. As compared with those diagnosed at an older age, patients diagnosed at < or = 6 years were more likely to be male, have DKA and a shorter symptom duration, and report more episodes of preceding viral infection and dyspnea. Patients with DKA also had a shorter symptom duration. A diabetic symptom checklist was helpful in identifying clinical diabetic symptoms and signs which were otherwise easily ignored. Younger children were more likely to have a shorter symptom duration and a higher incidence of DKA.


Trefoil factor 3 as a marker of intestinal cell damage during sepsis.
Gastrointestinal dysfunction or gut failure frequently occurs in seriously ill patients and can be responsible for multi-organ failure. Trefoil factor 3 (TFF3) was characterized for its role in reconstitution of an epithelial barrier after mucosal injury in the jejunum. The aims of our study was an analysis of TFF3 levels dynamics in patients with sepsis and the correlation of TFF3 with severity of sepsis and mortality. Prospective observational study, a ten days evaluation period in children aged 0-19 years with systemic inflammatory response syndrome or septic state. Blood tests to determine levels of TFF3 were obtained as long as the patient met the criteria for systemic inflammatory response syndrome or sepsis. Analysis of dynamics revealed steady levels of TFF3 during the 10 day period evaluated. TFF3 levels could not differentiate between various septic conditions in patients until a marked organ dysfunction developed. Higher Area Under Curve was noticed between control group and patients with sepsis. We could not make any strong conclusions based on mortality model. Levels of TFF3 are elevated in paediatric patients with sepsis through organ dysfunction.


Pulmonary involvement in patients with HTLV-I-associated myelopathy: increased soluble IL-2 receptors in bronchoalveolar lavage fluid.
A chronic spastic myelopathy associated with HTLV-I infection (HTLV-I-associated myelopathy: HAM) shows subclinical pulmonary involvement with bronchoalveolar T lymphocytosis. In the present study, we investigated 18 patients with HAM: five HTLV-I carriers without myelopathy and 13 normal control subjects seronegative for HTLV-I to determine if soluble IL-2 receptors (IL-2R), a marker of lymphocyte activation, were increased in serum and bronchoalveolar lavage (BAL) fluid from HAM patients. Serum IL-2R levels were significantly increased in patients with HAM as compared to normal control subjects (HAM versus control subjects: 633 +/- 395 versus 278 +/- 53 U/ml, p less than 0.01). There was also an increase of serum IL-2R levels in one of five HTLV-I carriers. BAL levels of soluble IL-2R were low but detectable in four normal control subjects and in one HTLV-I carrier. In HAM patients, however, soluble IL-2R levels in BAL fluid were remarkably elevated (173 +/- 110 U/mg of albumin) and were nearly 13 times higher on average than in serum (BAL fluid/serum ratio: 13 +/- 10). In patients with HAM, lavage IL-2R levels correlated well with the number of T lymphocytes (CD3+ cells) and CD4+ cells in BAL fluid (p less than 0.01). Furthermore, BAL lymphocytes obtained from HAM patients synthesized DNA spontaneously when cultured in vitro. These results suggest that, in HAM, T lymphocytes increased in the lung are activated locally to produce soluble IL-2R. Based on the results of this study, we conclude that immunologic mechanism(s) may play an important role in the development of pulmonary lesions in HAM patients.


Frequency and causes for exclusion from randomization of healthy volunteers screened for a phase 1 study in India.
Only a proportion of screened potential participants were actually randomized while conducting a phase 1 study of a humanized rabies monoclonal antibody. We aimed to assess the challenges in defining who is a normal volunteer and the issues that affect volunteer recruitment and thus accrual. One hundred and fifty-six volunteers were screened and 74 (47.4%) were randomized in a phase 1 study. Data on all participants screened for the study were analysed and reasons for their non-randomization were classified. The reasons for volunteers not being randomized were: (i) deranged laboratory parameters (n=62); (ii) non-laboratory causes (n=4); and (iii) withdrawal of consent (n=16). A large proportion of screen failures were due to low haemoglobin levels, which led to the protocol being amended midway during the study. An informal interview of those who declined consent showed that they had only wanted to get themselves investigated thoroughly or were interested in getting their HIV status evaluated. Our study shows that < 50% participants screened for a phase 1 study in a developing country actually get randomized. The main reason for non-randomization is abnormal laboratory tests. This may help investigators and sponsors to plan protocols better, define normal ranges with acceptable variations based on their own populations a priori and have more pragmatic accrual targets.