Which frailty tool best predicts morbidity and mortality in ambulatory patients with heart failure? A prospective study.
Frailty is common in patients with heart failure (HF) and is associated with adverse outcome, but it is uncertain how frailty should best be measured. To compare the prognostic value of commonly-used frailty tools in ambulatory patients with HF. We assessed, simultaneously, three screening tools [clinical frailty scale (CFS); Derby frailty index (DFI); acute frailty network (AFN) frailty criteria), three assessment tools (Fried criteria; Edmonton frailty score (EFS); deficit index (DI)) and three physical tests (handgrip strength, timed get-up-and-go test (TUGT), 5-metre walk test (5MWT)] in consecutive patients with HF attending a routine follow-up visit. 467 patients (67% male, median age = 76 years, median NT-proBNP = 1156 ng/L) were enrolled. During a median follow-up of 554 days, 82 (18%) patients died and 201 (43%) patients were either hospitalised or died. In models corrected for age, Charlson score, haemoglobin, renal function, sodium, NYHA, atrial fibrillation (AF), and body mass index, only log[NT-proBNP] and frailty were independently associated with all-cause death. A base model for predicting mortality at 1 year including NYHA, log[NT-proBNP], sodium and AF, had a C-statistic = 0.75. Amongst screening tools: CFS (C-statistic = 0.84); amongst assessment tools: DI (C-statistic = 0.83) and amongst physical test: 5MWT (C-statistic = 0.80), increased model performance most compared with base model (P <0.05 for all). Frailty is strongly associated with adverse outcomes in ambulatory patients with HF. When added to a base model for predicting mortality at 1 year including NYHA, NT-proBNP, sodium, and AF, CFS provides comparable prognostic information with assessment tools taking longer to perform.


Hippocampal metabolic proteins are modulated in voluntary and treadmill exercise rats.
Systematic protein expression studies in the brain of exercising and sedentary animals have not been carried out so far and it was therefore decided to determine differences in metabolic protein levels in rat hippocampus of sedentary, voluntary and involuntary exercising rats by a proteomic approach. Aged, male Sprague-Dawley rats, 23 months old, were used for the study: the first group consisted of sedentary rats, the second of rats with voluntary exercise from five to 23 months and the third group was performing involuntary exercise on a treadmill from five to 23 months. Two-dimensional gel electrophoresis with subsequent mass spectrometrical identification of spots followed by quantification of spots was carried out. Identification of significantly differential proteins was validated by the determination of the corresponding enzyme activity. Five individual metabolic proteins showed differential protein levels in the three groups: mitochondrial precursors of ornithine aminotransferase, isocitrate dehydrogenase [NAD] subunit alpha, malate dehydrogenase, ubiquinol-cytochrome-c reductase complex core protein 1, and ubiquitin carboxyl-terminal hydrolase isozyme L1. The unambiguously identified metabolic proteins were mainly of mitochondrial localization and fit the expectations of altered mitochondrial activity in exercise. Reduced ubiquitin carboxyl-terminal hydrolase isoenzyme L1 levels in treadmill (forced) exercise show the involvement of the proteasomal pathway as a novel finding. These results not only form the basis for functional studies elucidating mechanisms and differences between voluntary and forced exercise in hippocampal metabolism but also highlight the most intriguing aspect that exercise is affecting the brain at the protein level.


Stable carbon isotopic ratio measurement of polycyclic aromatic hydrocarbons as a tool for source identification and apportionment--a review of analytical methodologies.
The measurement of the ratio of stable isotopes of carbon ((13)C/(12)C expressed as a δ(13)C) in the individual components of a sample may be used as a means to identify the origin of these components. This article reviews the approaches and reports on the successes and failures of source identification and apportionment of Polycyclic Aromatic Hydrocarbons (PAHs) with the use of compound-specific isotope analysis (CSIA). One of the conditions for a precise and accurate analysis of isotope ratios with the use of GC-C-IRMS is the need for well separated peaks, with no co-elutions, and reduced unresolved complex mixture (UCM). Additionally, special care needs to be taken for an investigation of possible isotope fractionation effects introduced during the analytical treatment of samples. With the above-mentioned problems in mind, this review discusses in detail and compares current laboratory methodologies, mainly in the extraction and subsequent clean-up techniques used for environmental samples (air particulate matter, soil and sediments). Sampling strategies, the use of isotopic internal standards and the ranges for precision and accuracy are also reported and discussed.


Small metacentric marker chromosomes, particularly isochromosomes, in cancer.
At least two types of small metacentrics, which are isochromosomes for 12p and either 4p or 5p, respectively, are significantly associated with certain types of cancer and their formation may represent important stages in the development of these tumours. The specificity of the i(12p) for testicular cancer is now well established (it may also be present, however, in dysgerminomas and mixed Müllerian tumours of the ovary). This review is therefore mainly concerned with another marker, probably an i(5p) although an i(4p) should also be considered. Recent data suggest that this marker represents a significant chromosomal change occurring with a fairly high frequency in a variety of cancers, including carcinomas of the cervix, ovary, breast, bladder and bronchus (excluding small-cell carcinomas). These isochromosomes may contribute to tumour development through gene amplification; consistent with this is the frequent presence of these markers in two or more copies.


Di(2-ethylhexyl) phthalate induces reproductive toxicity and transgenerational reproductive aging in Caenorhabditis elegans.
With the large-scale production and use of plastic products, the global plastic pollution problem is becoming more and more serious. The plasticizer di (2-ethylhexyl) phthalate (DEHP), which is widely used in the production of plastics, has caused great concern for the health of the population. Exposure of organisms to DEHP can cause a variety of health damage, of which reproductive system damage is an important part. At present, there are still few studies on DEHP in reproductive aging, and it is of great significance to explore the role of DEHP in promoting reproductive aging and its underlying mechanism. In this study, the model organism Caenorhabditis elegans (C. elegans) was used to preliminarily explore the mechanism of DEHP-induced female reproductive senescence. The results showed that DEHP reduced the number of offspring and gonad area of C. elegans, resulting in shortened reproductive and life span, abnormal phenotypes in somatic gonad structure including the Emo phenotype, the BOW phenotype, a twisted gonad arm, and atrophied oocytes. Biochemical studies showed that DEHP promoted oxidative stress and autophagy in C. elegans. Further, we found the decreased number of offspring, malformed somatic gonad structure, oxidative damage and autophagy induced by DEHP in parental worms can be inheritance to the not directly exposed offspring.


Effects of water hardness on toxicological responses to chronic waterborne silver exposure in early life stages of rainbow trout (Oncorhynchus mykiss).
Rainbow trout embryos and larvae were exposed to 0, 0.1, and 1 microg/L total silver (as AgNO3) in water of three different hardnesses (soft water [2 mg/L as CaCO3], moderately hard water [150 mg/L], and hard water [400 mg/L]) in a flow-through system from fertilization to swim-up (64 d). The objective of the study was to investigate the effects of water hardness on chronic silver toxicity. In the absence of silver, elevating hardness had a positive effect on early life stage survival and development, significantly decreasing mortality and accelerating time to 50% swim-up. Following hatch, exposure to 1 microg/L Ag significantly increased mortality relative to exposure to 0 microg/L Ag. No significant effects of silver on time to 50% hatch were observed; however, time to 50% swim-up was delayed, and 50% swim-up was not achieved over the course of the experiment during some exposures to 1 microg/L Ag. These results suggest that the current Canadian Water Quality Guideline (http://www.ccme.ca/assets/pdf/e1_062.pdf) of 0.1 microg/L Ag is sufficient in preventing mortality and altered development in early life stages of rainbow trout. Increasing water hardness from 2 to 150 or 400 mg/L was modestly protective against the mortality and delays in time to 50% swim-up associated with exposure to 1 microg/L Ag. The 150- and 400-mg/L hardnesses were equally protective against mortality, but 150-mg/L was more protective than 400-mg/L hardness against the delays in time to 50% swim-up. Overall, the protective effects of hardness on chronic silver toxicity in early life stages of rainbow trout are modest but similar to the protection afforded to acute silver toxicity in juvenile and adult rainbow trout.


Ethyl acetate extract of Elephantopus mollis Kunth induces apoptosis in human gastric cancer cells.
Gastric cancer is one of the most leading causes of cancer death worldwide. Therefore, treatment studies have been being conducted, one of which is screening of novel agents from medicinal herbs. Elephantopus mollis Kunth (EM) belonging to Asteraceae family is a perennial herb with several therapeutic properties including anticancer activity. However, the effect of this species on gastric cancer has not been reported yet. In this study, cytotoxicity of different EM crude extracts was investigated on AGS gastric cancer cell line. Besides, the effects of extract on nuclear morphology, caspase-3 activation, and gene expression were also explored. The results showed that ethyl acetate extract exhibited a remarkably inhibitory ability (IC50 = 27.5 μg/ml) on the growth of AGS cells, while causing less toxicity to normal human fibroblasts. The extract also induced apoptotic deaths in AGS cells as evidenced by cell shrinkage, formation of apoptotic bodies, nuclear fragmentation, caspase-3 activation, and the upregulation of BAK and APAF-1 pro-apoptotic genes related to mitochondrial signaling pathway. Specifically, BAK and APAF-1 mRNA expression levels showed 2.57 and 2.71-fold increases respectively. The current study not only proved the anti-gastric cancer activity of EM ethyl acetate extract but also proposed its molecular mechanism. The extract could be a potential candidate for further investigation.


Screening and selection process for studies of menstrually-related changes.
The screening process of women who volunteered to participate in "studies of the menstrual cycle" is described. It is demonstrated that in order to arrive at a desired number of subjects who meet criteria for premenstrual changes and are in a good physical and mental status, one should recruit an extremely large number of candidates to start with. The yield of each screening procedure is presented. It is clear that fulfillment of inclusion and exclusion criteria can be obtained by a phone interview while important criteria can be clarified only by prospective monitoring of symptoms and personal structured interviews. Methods and procedures that can improve yield and decrease effort in recruitment are suggested.


Nursing and midwifery students' perspectives of using digital systems on placement: A qualitative study.
To explore undergraduate nursing and midwifery student perspectives of using digital patient systems on clinical placements. This was an interpretative qualitative design study. Undergraduate nursing and midwifery students in a large Australian metropolitan university were invited to participate in two focus groups from April to June 2019. Twenty (20) students participated and data on their perspective of using digital systems on placement were collected. Thematic analysis using NVivo 12 software was undertaken. Students identified benefits and challenges when moving between paper records and digital systems. Whilst paper reporting was more efficient for some processes, the students recognised the advantages of digital technology, such as enabling greater confidentiality and consolidation of patient data in one place. However, they also reported difficulty with student access and the size of the portal digital workstation at the bedside. Generally, the lack of preparation and access was considered frustrating and mitigated some of the benefits described when using digital systems. Nursing and midwifery students prefer to be prepared for both paper and digital record keeping. Whilst students identify the benefits of digital platforms, not having direct access mitigates the benefits of these systems. Students identified the use of simulation and interactive modules prior to commencement of clinical practice to enable them to feel more confident with using the systems in patient care. Health care students require direct access to digital health platforms whilst on clinical placement to facilitate their learning. Higher Education Institutions (HEIs) are in a unique position to work with health care providers to better prepare health care professionals, including nurses and midwives, to work with digital health care systems. Further research is needed to develop the educational preparation for nurses, midwives, and other health care professionals to work with digital systems in practice.


Long-term effectiveness of computer-generated tailored patient education on benzodiazepines: a randomized controlled trial.
Chronic benzodiazepine use is highly prevalent and is associated with a variety of negative health consequences. The present study examined the long-term effectiveness of a tailored patient education intervention on benzodiazepine use. A randomized controlled trial was conducted comprising three arms, comparing (i) a single tailored intervention; (ii) a multiple tailored intervention and (iii) a general practitioner letter. The post-test took place after 12 months. Five hundred and eight patients using benzodiazepines were recruited by their general practitioners and assigned randomly to one of the three groups. Two tailored interventions, the single tailored intervention (patients received one tailored letter) and the multiple tailored intervention (patients received three sequential tailored letters at intervals of 1 month), were compared to a short general practitioner letter that modelled usual care. The tailored interventions not only provided different and more information than the general practitioner letter; they were also personalized and adapted to individual baseline characteristics. The information in both tailored interventions was the same, but in the multiple tailored intervention the information was provided to the participants spread over three occasions. In the multiple tailored intervention, the second and the third tailored letters were based on short and standardized telephone interviews. Benzodiazepine cessation at post-test was the outcome measure. The results showed that participants receiving the tailored interventions were twice as likely to have quit benzodiazepine use compared to the general practitioner letter. Particularly among participants with the intention to discontinue usage at baseline, both tailored interventions led to high percentages of those who actually discontinued usage (single tailored intervention 51.7%; multiple tailored intervention 35.6%; general practitioner letter 14.5%). It was concluded that tailored patient education can be an effective tool for reducing benzodiazepine use, and can be implemented easily.


Alteration of the mechanical properties of sickle cells by repetitive deoxygenation: role of calcium and the effects of calcium blockers.
The formation of dense, poorly deformable sickle cells was studied by subjecting pre-separated, less dense cells to repeated deoxygenation and reoxygenation for 15 h. In the presence of Ca (2 mmol/l), this process caused the number of irreversible sickled cells to increase five-fold, mean cell haemoglobin concentration to increase by 13% and cellular potassium to decrease by 22%. Also, red cell filterability through 5 microns filter pores was greatly worsened. These effects decreased but were not totally abolished when the extracellular Ca concentration was lowered to zero or 0.01 mmol/l. If a high K medium was used (135 mmol/l), cell swelling rather than shrinkage occurred. Swelling also occurred if ouabain was added to the incubation. The Ca-channel blockers nitrendipine and nisoldipine had different effects. Nitrendipine, in the range 10(-7) - 10(-5) mol/l, was partially protective against all the induced changes, but nisoldipine was not protective at 10(-8) or 10(-6) mol/l. Thus, deterioration in the properties of sickle cells appears to be linked to Ca-dependent potassium loss during repeated sickling and is inhibited by nitrendipine.


[PET/MRI for cardiac imaging. Possibilities and limits].
The positron emission tomography/magnetic resonance imaging (PET/MRI) technique represents a new hybrid imaging modality in nuclear cardiology. The standard radiological method in this field is PET/computed tomography (CT). For morphological correlation MRI is used instead of CT. Furthermore, the creation of attenuation maps (μ-maps) has to be accomplished using MRI data. For this new hybrid imaging modality only limited data are so far available, especially in the field of nuclear cardiology; however, the available data show a relatively good agreement between both modalities with the PET/CT as the modality of reference. In comparison to PET/CT a major advantage of PET/MRI is the lower radiation dose to the patient; however, the more complex workflow using this new imaging modality also has to be taken into account. Furthermore, some indications are still at an experimental stage using the PET/MRI. In daily practice, PET/MRI should be considered especially in younger patients due to the lower exposure to radiation. Furthermore, there are some advantages for this modality in the field of nuclear cardiology, such as imaging of inflammatory myocardial processes (e.g. cardiac sarcoidosis) or myocardial viability imaging.


Development, Implementation, and Evaluation of an Open Access, Level-Specific, Core Content Curriculum for Emergency Medicine Residents.
Leaders in graduate medical education must provide robust clinical and didactic experiences to prepare residents for independent practice. Programs traditionally create didactic experiences individually, requiring tremendous resources with variable content exposure and quality. We sought to create and implement a free, open access, learner-centric, level-specific, emergency medicine (EM) residency curriculum. We developed Foundations of Emergency Medicine (FoEM) Foundations I and II courses using Kern's model of curriculum development. Fundamental topics were identified through content guidelines from the American Board of Emergency Medicine. We incorporated learner-centric strategies into 2 flipped classroom, case-based courses targeting postgraduate year (PGY) 1 and PGY-2 residents. The curriculum was made freely available online in 2016. Faculty and resident users were surveyed annually for feedback, which informed iterative refinement of the curriculum. Between 2016 and 2020, registration for FoEM expanded from 2 sites with 36 learners to 154 sites and 4453 learners. In 2019, 98 of 102 (96%) site leaders and 1618 of 2996 (54%) learners completed the evaluative survey. One hundred percent of responding leaders and 93% of learners were "satisfied" or "very satisfied" with FoEM content. Faculty and residents valued FoEM's usability, large volume of content, quality, adaptability, organization, resident-faculty interaction, and resident-as-teacher opportunities. Challenges to implementation included resident attendance, conference structure, technology limitations, and faculty engagement. We developed and implemented a learner-centric, level-specific, national EM curriculum that has been widely adopted in the United States.


Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, Papio papio.
The effects of intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine.


Exploring the association between loot boxes and problem gambling: Are video gamers referring to loot boxes when they complete gambling screening tools?
Concerns regarding the similarities between video game 'loot boxes' and gambling have been supported by correlations in survey studies between loot box engagement and problem gambling scores. It is generally noted that this correlation could reflect loot box users migrating to conventional gambling, and/or people with gambling problems being attracted to loot boxes when they play video games. We describe a third possibility, that when gamers complete problem gambling screens they may be referring to harms incurred from their loot box use. Using three secondary datasets from cross-sectional online surveys, we explore this account in two ways. First, in participants who do not endorse any participation in conventional forms of gambling, we compare rates of positive (i.e. non-zero) scores on the Problem Gambling Severity Index (PGSI) in participants with and without loot box use. Second, noting that some PGSI items have less relevance to loot box use versus gambling, we compare endorsement rates of individual PGSI items, in gamers versus gamblers, and loot box users vs non-loot box users (focusing on item 3 "going back another day to win back the money you lost"). In analysis 1, positive PGSI scorers among non-gamblers were significantly elevated in loot box users vs non-loot box users, although absolute numbers were low overall. In analysis 2, there were no reliable differences (gamers vs gamblers, loot box users vs non-loot box users) in PGSI item 3 endorsement rates. We conclude that these results provide partial support for this third option, and highlight a need for future studies to consider this possibility more directly.


[Pharmacologic influencing of fetal phospholipid synthesis. Part IV: influencing the DPL(dipalmitoyl-lecithin) content of fetal lung by betamethasone (author's transl)].
Dipalmitoyllecithinic (DPL) is the quantitatively largest and most active portion of the surfactant system. Hence only a quantitative DPL determination allows a relevant statement of fetal lung maturity. The antenatal prophylaxis of RDS should result in an increase of the DPL-level in a fetal lung. A new gaschromatographical method for determination of DPL was developed. The results were secured by gaschromatography-mass-spectrometry-couplings. After treatment with betamethasone an increase of the relative DPL-amount in fetal rat lung lecithin species was found, but not an increase of the lecithin-level in the lung-tissue. Corticosteroids probably induce transesterification of the lecithins.


Expression, Folding, and Activation of Halophilic Alkaline Phosphatase in Non-Halophilic Brevibacillus choshinensis.
Halophilic enzymes contain a large number of acidic amino acids and marginal large hydrophobic amino acids, which make them highly soluble even under strongly hydrophobic conditions. This characteristic of halophilic enzymes provides potential for their industrial application. However, halophilic enzymes easily degrade when used for industrial applications compared with enzymes from other extremophiles because of their instability in low-salt environments. We aimed to clarify the stabilization mechanism of halophilic enzymes. We previously attempted to express halophilic alkaline phosphatase from Halomonas (HaALP) in non-halophilic E. coli. However, the expressed HaALP showed little activity. Therefore, we overexpressed HaALP in Gram-positive non-halophilic Brevibacillus choshinensis in this study, which was successfully expressed and purified in its active form. HaALP was denatured in 6 M urea, refolded using various salts and the non-ionic osmolyte trimethylamine N-oxide (TMAO), and assessed by native polyacrylamide gel electrophoresis. HaALP refolded in 3 M NaCl or 3 M TMAO containing Na+ ions. Hydrophobic interactions due to a high salt concentration or TMAO enhanced the formation of the folding intermediate (the monomer precursor), and only Na+ ions activated the dimer form. This insight into the stabilization mechanism of HaALP may lead to the development of industrial applications of halophilic enzymes under low-salt conditions.


Handedness and the mental rotation of perceived patterns.
The present experiment investigated the effect of hemispheric dominance, as indicated by handedness, and perceptual processing. Displays containing two visual patterns were presented to right- and left-handed subjects who classified the two patterns as being the same or different. Also the two patterns in a display were in either an identical orientation or nonidentical orientations. Overall, left handers were faster than right handers at the "same-different" judgement. Additionally, latency increased with the angular discrepancy in orientation between patterns for both handedness groups but this increase was smaller for left handers than for right handers. Apparently, left handers evaluate overall perceptual similarity faster than right handers and they also mentally rotate perceived patterns of discrepant orientations faster than right handers. These findings contradict previous generalizations that left handers are deficient perceptually. Moreover, the present results support the position that left handers should be faster at global perceptual tasks because left handers have less neural distance than right handers mediating the transmission of information between the locus of perception and the locus of dominance.


Left Ventricular Hypertrophy Increases Susceptibility to Bupivacaine-induced Cardiotoxicity through Overexpression of Transient Receptor Potential Canonical Channels in Rats.
Local anesthetics, particularly potent long acting ones such as bupivacaine, can cause cardiotoxicity by inhibiting sodium ion channels; however, the impact of left ventricular hypertrophy on the cardiotoxicity and the underlying mechanisms remain undetermined. Transient receptor potential canonical (TRPC) channels are upregulated in left ventricular hypertrophy. Some transient receptor potential channel subtypes have been reported to pass relatively large cations, including protonated local anesthetics; this is known as the "pore phenomenon." The authors hypothesized that bupivacaine-induced cardiotoxicity is more severe in left ventricular hypertrophy due to upregulated TRPC channels. The authors used a modified transverse aortic constriction model as a left ventricular hypertrophy. Cardiotoxicity caused by bupivacaine was compared between sham and aortic constriction male rats, and the underlying mechanisms were investigated by recording sodium ion channel currents and immunocytochemistry of TRPC protein in cardiomyocytes. The time to cardiac arrest by bupivacaine was shorter in aortic constriction rats (n =11) than in sham rats (n = 12) (mean ± SD, 1,302 ± 324 s vs. 1,034 ± 211 s; P = 0.030), regardless of its lower plasma concentration. The half-maximal inhibitory concentrations of bupivacaine toward sodium ion currents were 4.5 and 4.3 μM, which decreased to 3.9 and 2.6 μM in sham and aortic constriction rats, respectively, upon coapplication of 1-oleoyl-2-acetyl-sn-glycerol, a TRPC3 channel activator. In both groups, sodium ion currents were unaffected by QX-314, a positively charged lidocaine derivative, that hardly permeates the cell membrane, but was significantly decreased with QX-314 and 1-oleoyl-2-acetyl-sn-glycerol coapplication (sham: 79 ± 10% of control; P = 0.004; aortic constriction: 47± 27% of control; P = 0.020; n = 5 cells per group). Effects of 1-oleoyl-2-acetyl-sn-glycerol were antagonized by a specific TRPC3 channel inhibitor. Left ventricular hypertrophy exacerbated bupivacaine-induced cardiotoxicity, which could be a consequence of the "pore phenomenon" of TRPC3 channels upregulated in left ventricular hypertrophy.


Alteration in lymphocyte recognition repertoire during aging. II. Changes in the expressed T-cell receptor repertoire in aged mice and the persistence of that change after transplantation to a new differentiative environment.
Changes in the T-lymphocyte alloreceptor repertoire associated with aging by exploring the frequency of cytotoxic T-lymphocyte precursors (CTLp) available for activation by various major histocompatibility complex (MHC) haplotypes in mice of different ages have been investigated. There was no consistent pattern of change in CTLp frequencies. Thus, for instance, while the frequency of responder C57B1/6 CTLp for ATH alloantigen decreased with age, the frequency for C3H alloantigen increased. There was no significant change in the overall frequency of splenic CTLp (assessed irrespective of antigen specificity). No evidence was found that CTL produced by activated CTLp of aged mice were less specific in their lytic capacity that CTL produced by CTLp of young mice. However, by assaying responder CTLp cultures at limiting dilution we obtained evidence that the "burst size" (mean lytic capacity per responder well assayed at limiting dilution) was diminished with age of the donor of the CTLp pool. Furthermore, we obtained evidence that the apparent affinity of CTL for their target antigen was consistently decreased when those effector cells were derived from a pool of CTLp of aged mice. All of these changes reflected in mature T cells derived from aged mice were already apparent in the bone marrow stem cell pool of aged individuals and were not due to environmental influences alone, as assessed by the phenotype of T cells derived from young or old bone marrow stem cells transplanted to young or aged recipient mice. A final study has examined evidence for more subtle changes in the T-cell alloreceptor repertoire, reflecting heterogeneity in young or aged mice in the recognition repertoire associated with a given antigenic specificity. By preparing F1 anti (parent anti-F1)-suppressor cells directed against CTL from young parental mice (a, b, c), or aged parental mice (x, y, z), we have explored the heterogeneity in the anti-C3H alloreceptor repertoire in individual young or aged C57B1/6 mice. Suppression by immunized F1 animals was assessed in tissue culture (inhibition of mixed lymphocyte culture (MLC) responses) or in vivo (inhibition of lethal GvHD induced by inoculation of parental lymphocytes into sublethally irradiated F1 hybrid mice). Irrespective of the assay system used, the data suggests that the receptor repertoire of aged T lymphocytes uses recognition structures different from those of young individuals, and that there is less individual-to-individual variation in the receptor repertoire of aged mice than in young mice.


Consuming intracellular glucose and regulating the levels of O2/H2O2 via the closed cascade catalysis system of Cu-CeO2 nanozyme and glucose oxidase.
Imbalances in the intracellular environment caused by high levels of glucose, H2O2, and hypoxia can greatly impact cancer development and treatment. However, there is limited research on regulating the levels of these species simultaneously in tumor cells. Here, a pH-responsive nanozyme-enzyme hybrid system was developed to regulate intracellular glucose, H2O2 and O2. The system, named DMSN@Cu-CeO2@GOx, consists of Cu-CeO2 nanoparticles and glucose oxidase (GOx) immobilized in dendritic mesoporous silica (DMSN) spheres. GOx efficiently consumes glucose in tumor cells, causing a drop in pH and producing a significant amount of H2O2. Cu-CeO2 then catalyzes the conversion of H2O2 to O2 due to its high catalase-like (CAT) activity in weakly acidic conditions. The process was monitored by fluorescence probes, and the mechanism was investigated through fluorescence spectroscopy and confocal laser scanning microscopy. The cascade catalytic system with excellent biocompatibility continuously consumes glucose and elevates the level of O2 in cells. This hybrid nanomaterial offers a means to regulate the glucose/H2O2/O2 levels in cells and may provide insights into starvation therapy by modulating reactive species within cells.


Chemical strategies and tandem mass spectrometry for the detection and identification of protein modifications by electrophilic lipoxidation products.
The post-translational modification of proteins by electrophilic oxylipids is emerging as an important mechanism that contributes to the complexity of proteomes. Originally considered solely as markers of oxidative insult, more recently the modifications of proteins by lipid peroxidation products are being recognized as having roles in cell signaling with relevance to redox homeostasis, adaptive response and inflammatory resolution. We report on mass spectrometry-based methods in conjunction with chemoselective strategies that are capable of detecting, identifying and characterizing protein adducts of lipoxidation products in biological samples with high complexity.


Bupivacaine/ketamine is superior to intra-articular ketamine analgesia following arthroscopic knee surgery.
Centroneuraxial and parenteral administration of ketamine has been shown to produce analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to determine whether ketamine alone or in combination with bupivacaine provides superior pain relief after surgery in patients undergoing knee arthroscopy. Sixty patients (classified as ASA status I or II) under-going arthroscopic meniscus repair during general anesthesia were randomized to receive 1.0 mg x kg(-1) ketamine (Group K), 0.25% bupivacaine (Group B) or a combination of 1.0 mg x kg(-1) ketamine and 0.25% bupivacaine (Group BK) to a total volume of 20 mL by intra-articular route following surgery. Visual analogue score in the postanesthesia care unit at 0.5, 1, 2, 4, 6, 8, 12 and 24 hr after surgery, duration of analgesia and subsequent 24 hr consumption of rescue analgesic (dextroproxyphene/acetaminophen) were evaluated. The results showed significantly higher pain scores in Group K as compared to Group B and Group BK. The duration of analgesia was significantly shorter in Group K as compared to the other two groups (Group B = 5.7 +/- 0.8; Group BK = 5.1 +/- 1.1 vs Group K = 1.7 +/- 0.9 hr; P < 0.05). However, 24 hr consumption of analgesic was similar in the three groups. We conclude that intra-articular bupivacaine-ketamine combination provides better pain relief than intra-articular ketamine after day care arthroscopic knee surgery.


Prostaglandin PGE2: a possible mechanism for bone destruction in calcinosis circumscripta.
A patient showed evident osteolysis in phalanges and heavy periarticular calcium deposits of the fingers, wrists and toes which avidly took up 47Ca. The dense, white, tooth-paste like fluid contained in the periarticular calcium deposits has been studied by two different X-ray diffraction methods, by Ubatuba's bioassay for prostaglandin, by thin layer chromatography and by mass spectrometry. The calcium deposits were hydroxyapatite and prostaglandin PGE2 was detected in them. The bone resorption stimulating activity of PGE2 would be expected to result in increased bone destruction with release of calcium salts and this could be a working hypothesis of the pathogenesis of calcinosis circumscripta.


Percutaneous transvenous mitral commissurotomy: immediate and long-term follow-up results.
Percutaneous transvenous mitral commissurotomy has emerged as an effective nonsurgical technique for the treatment of patients with symptomatic mitral stenosis. This report highlights the immediate and long-term follow-up results of this procedure in an unselected cohort of patients with rheumatic mitral stenosis from a single center. It was performed in a total of 4,850 patients using double balloon in 320 (6.6%), flow-guided Inoue balloon technique in 4,374 (90.2%), and metallic valvulotome in 156 (3.2%) patients. Their age range was 6.5-72 years (mean, 27.2 +/- 11.2 years) and 1,552 (32%) patients were under 20 years of age. Atrial fibrillation was present in 702 (14.5%) patients. No patient was rejected on the basis of echocardiographic score using the Wilkins criteria. Echocardiographic score of > or = 8 was present in 1,632 (33.6%) patients, of which 103 (2.1%) had densely calcified (Wilkins score 4+) valve. A detailed clinical and echocardiographic (two-dimensional, continuous-wave Doppler and color-flow imaging) assessment was done at every 3 months for the first year and at 6-month interval thereafter. The procedure was technically successful in 4,838 (99.8%) patients but optimal result was achieved in 4,408 (90.9%) patients with an increase in mitral valve area (MVA) from 0.7 +/- 0.2 to 1.9 +/- 0.3 cm(2) (P < 0.001) and a reduction in mean transmitral gradient from 29.5 +/- 7.0 to 5.9 +/- 2.1 mm Hg (P < 0.001). The mean left atrial pressure decreased from 32.1 +/- 9.8 to 13.1 +/- 6.2 mm Hg (P < 0.001). Although there was no statistically significant difference in the MVA achieved between de novo and restenosed valves (1.9 +/- 0.3 and 1.8 +/- 0.2 cm(2), respectively; P > 0.05), or between noncalcific and calcific valves (2.0 +/- 0.3 and 1.8 +/- 0.2 cm(2), respectively; P > 0.05), on the whole MVA obtained after percutaneous transvenous mitral commissurotomy was less in restenosed and calcific valves. Ten (0.20%) patients had cardiac tamponade during the procedure. Mitral regurgitation appeared or worsened in 2,038 (42%) patients, of which 68 (1.4%) developed severe mitral regurgitation. Urgent mitral valve replacement was carried out in 52 (1.1%) of these patients. Data of 3,500 patients followed over a period of 94 +/- 41 months (range, 12-166 months) revealed MVA of 1.7 +/- 0.3 cm(2). Elective mitral valve replacement was done in 34 (0.97%) patients. Mitral restenosis was seen in 168 (4.8%) patients, of which 133 (3.8%) were having recurrence of class III or more symptoms. Thus, percutaneous transvenous mitral commissurotomy is an effective and safe procedure with gratifying results in high percentage of patients. The benefits are sustained in a majority of these patients on long-term follow-up. It should be considered as the treatment of choice in patients with rheumatic mitral stenosis of all age groups.


Prognostic values of systemic inflammation and nutrition-based prognostic indices in oropharyngeal carcinoma.
Pretreatment systemic inflammation and nutrition-based prognostic indices (SINBPI) have demonstrated significance. This study investigated the prognostic value of pretreatment SINBPI for patients with oropharyngeal cancer and identified unfavorable prognostic markers. We retrospectively reviewed the data of 124 patients with oropharyngeal squamous cell carcinoma (OPSCC) who received definitive treatment between January 2010 and December 2018. The prognostic utility of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index, and high-sensitivity modified Glasgow prognostic score (HS-mGPS) was assessed for disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) using univariate and multivariate analyses. Multivariate analyses revealed that human papillomavirus (HPV) status and HS-mGPS were significantly associated with DFS, DSS, and OS. Patients with a HS-mGPS of 2 had a significantly higher rate of treatment-related deaths than those with a HS-mGPS of 0 or 1. The combination of the HS-mGPS and PLR had more accurate predictive ability in DFS and OS compared with the HS-mGPS alone, and the combination of the HS-mGPS and LMR had more accurate predictive ability in DSS and OS. Our results indicated that the HS-mGPS was a useful prognostic marker for patients with OPSCC, and combined markers consisting of the HS-mGPS and PLR or LMR may provide more accurate prognostic predictions.Level of Evidence: 3.


Abnormal Degree Centrality as a Potential Imaging Biomarker for Right Temporal Lobe Epilepsy: A Resting-state Functional Magnetic Resonance Imaging Study and Support Vector Machine Analysis.
Previous studies have reported altered neuroimaging features in right temporal lobe epilepsy (rTLE). However, the alterations in degree centrality (DC) as a diagnostic method for rTLE have not been reported. Therefore, we aimed to explore abnormalities in the DC of the rTLE and whether such alterations could be applied to the diagnosis of rTLE. Resting-state functional magnetic resonance imaging (fMRI) was used to scan 82 patients with rTLE and 69 healthy controls. The DC and support vector machine (SVM) methods were used for an analysis of the imaging data. Compared to the control group, the rTLE patients exhibited lower DC values in the right hippocampus, right superior temporal gyrus, and right caudate. Compared to the control group, the rTLE patients showed higher DC values in the right medial superior frontal gyrus (SFGmed), left dorsolateral superior frontal gyrus (SFGdor), right inferior parietal lobule (IPL), and the left postcentral. The highest diagnostic accuracy of 99.34% (150/151), based on SVM analysis, was demonstrated for the combination of abnormal DC in the right IPL and the left SFGdor, along with a sensitivity of 100% (82/82), and a specificity of 98.55% (68/69) for the differentiation of rTLE patients from healthy controls. The study demonstrated abnormal functional connectivity in rTLE patients. Thus, a distinctive DC pattern may serve as an imaging marker for the diagnosis of rTLE patients.


Phenotypic impact of genomic structural variation: insights from and for human disease.
Genomic structural variants have long been implicated in phenotypic diversity and human disease, but dissecting the mechanisms by which they exert their functional impact has proven elusive. Recently however, developments in high-throughput DNA sequencing and chromosomal engineering technology have facilitated the analysis of structural variants in human populations and model systems in unprecedented detail. In this Review, we describe how structural variants can affect molecular and cellular processes, leading to complex organismal phenotypes, including human disease. We further present advances in delineating disease-causing elements that are affected by structural variants, and we discuss future directions for research on the functional consequences of structural variants.


Reuse of reactive dyes for dyeing of jute fabric.
The aim of the work was to find out suitable method of dyeing so that costly reactive dye can be reused without draining them. The bleached jute fabric was dyed with four different class of reactive dyes namely, cold brand, hot brand, vinyl sulphone and high exhaustion (HE) brand. It is found that the two-step two-bath method of reactive dyeing, where exhaustion and fixation step is separated, is most ideal for reuse of dye bath. Separate original samples produced K/S value same as that of original sample and the K/S value of separate reuse sample varied from 50% to 80% of the original sample depending on the class of dye. In case of same bath method, colour yield of original reuse samples varies from only 10% to maximum 30% of the original samples depending on the class of dyes. Reuse of reactive dyes following separate bath method is particularly suitable for higher depth of shade (4% and above). This process not only utilises costly reactive dyes to the maximum extent but it also produces low water pollution as the effluent contain minimum amount of dye. So the process is economic and eco-friendly as well.


Medication based machine learning to identify subpopulations of pediatric hemodialysis patients in an electronic health record database.
Electronic health records (EHRs) have given rise to large and complex databases of medical information that have the potential to become powerful tools for clinical research. However, differences in coding systems and the detail and accuracy of the information within EHRs can vary across institutions. This makes it challenging to identify subpopulations of patients and limits the widespread use of multi-institutional databases. In this study, we leveraged machine learning to identify patterns in medication usage among hospitalized pediatric patients receiving renal replacement therapy and created a predictive model that successfully differentiated between intermittent (iHD) and continuous renal replacement therapy (CRRT) hemodialysis patients. We trained six machine learning algorithms (logistical regression, Naïve Bayes, k-nearest neighbor, support vector machine, random forest, and gradient boosted trees) using patient records from a multi-center database (n = 533) and prescribed medication ingredients (n = 228) as features to discriminate between the two hemodialysis types. Predictive skill was assessed using a 5-fold cross-validation, and the algorithms showed a range of performance from 0.7 balanced accuracy (logistical regression) to 0.86 (random forest). The two best performing models were further tested using an independent single-center dataset and achieved 84-87% balanced accuracy. This model overcomes issues inherent within large databases and will allow us to utilize and combine historical records, significantly increasing population size and diversity within both iHD and CRRT populations for future clinical studies. Our work demonstrates the utility of using medications alone to accurately differentiate subpopulations of patients in large datasets, allowing codes to be transferred between different coding systems. This framework has the potential to be used to distinguish other subpopulations of patients where discriminatory ICD codes are not available, permitting more detailed insights and new lines of research.


Characterization of a newly discovered putative DNA replication initiator from Paenibacillus polymyxa phage phiBP.
The bacteriophage phiBP contains a newly discovered putative replisome organizer, a helicase loader, and a beta clamp, which together may serve to replicate its DNA. Bioinformatics analysis of the phiBP replisome organizer sequence showed that it belongs to a recently identified family of putative initiator proteins. We prepared and isolated a wild type-like recombinant protein, gpRO-HC, and a mutant protein gpRO-HCK8A, containing a lysine to alanine substitution at position 8. gpRO-HC had low ATPase activity regardless of the presence of DNA, while the ATPase activity of the mutant was significantly higher. gpRO-HC bound to both single- and double-stranded DNA substrates. Different methods showed that gpRO-HC forms higher oligomers containing about 12 subunits. This work provides the first information about another group of phage initiator proteins, which trigger DNA replication in phages infecting low GC Gram-positive bacteria.


[Effect of dexamethasone at the level of cerebral metastases. Evaluation by CT and nuclear medicine].
Thirty five patients with brain metastases and edema were treated with dexamethasone. The results were evaluated by cranial computed tomography and nuclear medicine. Edema was alleviated in 32 out of the 35 patients after a two weeks treatment.


Effect of dentin roughness on the adhesive performance in non-carious cervical lesions: A double-blind randomized clinical trial.
This double-blind randomized clinical trial evaluates the influence of dentin roughening (RO) on the clinical behavior of a new universal multi-mode adhesive (Tetric N-Bond Universal; Ivoclar-Vivadent) applied as self-etch and as etch-and-rinse in non-carious cervical lesions (NCCLs). A total of 192 restorations were randomly placed in 48 patients according to the following groups: ER - Etch-and-rinse (no preparation); SE - self-etch (no preparation); ER+RO and; SE+RO. The resin composite Empress Direct (Ivoclar-Vivadent) was placed incrementally. The restorations were evaluated after one week (baseline), 6 and 18 months, using the FDI and USPHS criteria. Statistical analyses were performed using appropriate tests (α=0.05). Fifteen restorations were lost at 18 months (3 for SE, 2 for ER, 5 for SE+RO and 5 for ER+RO) (p >0.05 between groups). Post-operative sensitivity wasn't observed in any of the recall periods. Eighty-four restorations were considered to have minor discrepancies in marginal adaptation at the 18-month recall using the FDI criteria (24 for SE, 18 for ER, 22 for SE+RO and 20 for ER+RO; p >0.05 between groups). Nineteen restorations were considered to have minor discrepancies in marginal discoloration at the 18-month recall (10 for SE, 03 for ER, 05 for SE+RO and 01 for ER+RO; p >0.05 between groups). The dentin roughening before application of Tetric N-Bond Universal as self-etch and etch-and-rinse didn't affect the clinical behavior of composite restorations placed in NCCLs.


Both antiplatelet and anticoagulant therapy may favorably affect outcome in patients with advanced heart failure. A retrospective analysis of the PRIME-II trial.
Current guidelines of chronic heart failure (CHF) do not recommend the use of oral anticoagulants (OAC) or antiplatelet therapy (APT). We performed a post-hoc analysis to evaluate the effect of the use of anti-thrombotic therapy with APT and OAC. We examined 427 patients with advanced CHF, and assessed the effects of the use of APT or OAC at baseline on mortality. We employed a Cox-proportional hazard model to value the effects of APT or OAC use. After a mean follow-up of 3.4 years (range 2.0-5.4), 214 patients died (51%). Forty-one (41) percent (95%CI: 29-53%) of the patients on APT died, and 52% (47-57%) of the patients not on APT (P=0.07). Forty-eight (48) percent (42-54%) of the patients on OAC died, and 55% (46-63%) of the patients not on OAC (P=0.20). This effect of OAC was seen both in patients in sinus rhythm and in atrial fibrillation. After adjusting for important prognostic variables, such as age, LVEF, renal function, and NYHA class, both the use of APT (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.40-0.97; P=0.04) and the use of OAC (HR 0.60, 95%-CI 0.43-0.83; P<0.01) were related to an improved prognosis. This post-hoc analysis suggests that in CHF patients the use of APT or OAC is associated with a higher survival.


Detection of motor imagery based on short-term entropy of time-frequency representations.
Motor imagery is a cognitive process of imagining a performance of a motor task without employing the actual movement of muscles. It is often used in rehabilitation and utilized in assistive technologies to control a brain-computer interface (BCI). This paper provides a comparison of different time-frequency representations (TFR) and their Rényi and Shannon entropies for sensorimotor rhythm (SMR) based motor imagery control signals in electroencephalographic (EEG) data. The motor imagery task was guided by visual guidance, visual and vibrotactile (somatosensory) guidance or visual cue only. When using TFR-based entropy features as an input for classification of different interaction intentions, higher accuracies were achieved (up to 99.87%) in comparison to regular time-series amplitude features (for which accuracy was up to 85.91%), which is an increase when compared to existing methods. In particular, the highest accuracy was achieved for the classification of the motor imagery versus the baseline (rest state) when using Shannon entropy with Reassigned Pseudo Wigner-Ville time-frequency representation. Our findings suggest that the quantity of useful classifiable motor imagery information (entropy output) changes during the period of motor imagery in comparison to baseline period; as a result, there is an increase in the accuracy and F1 score of classification when using entropy features in comparison to the accuracy and the F1 of classification when using amplitude features, hence, it is manifested as an improvement of the ability to detect motor imagery.


Time course of lesion-induced atrophy in multiple sclerosis.
White matter (WM) tract disruption impacts volume loss in connected deep gray matter (DGM) over 5 years in people with multiple sclerosis (PwMS). However, the timeline of this phenomenon remains poorly characterized. Annual serial MRI for 181 PwMS was retrospectively analyzed from a 10-year clinical trial database. Annualized thalamic atrophy, DGM atrophy, and disruption of connected WM tracts were measured. For time series analysis, ~700 epochs were collated using a sliding 5-year window, and regression models predicting 1-year atrophy were applied to characterize the influence of new tract disruption from preceding years, while controlling for whole brain atrophy and other relevant factors. Disruptions of WM tracts connected to the thalamus were significantly associated with thalamic atrophy 1 year later (β: 0.048-0.103). This effect was not observed for thalamic tract disruption concurrent with the time of atrophy nor for thalamic tract disruption preceding the atrophy by 2-4 years. Similarly, disruptions of white matter tracts connected to the DGM were significantly associated with DGM atrophy 1 year later (β: 0.078-0.111), but not for tract disruption concurrent with, nor preceding the atrophy by 2-4 years. Increased rates of thalamic and DGM atrophy were restricted to 1 year following newly developed disruption in connected WM tracts. In research and clinical settings, additional gray matter atrophy may be expected 1 year following new lesion growth in connected white matter.


Elective Management of the Neck in Parotid Tumours.
Management of the clinically node-negative (cN0) neck for parotid tumours remains controversial. Options include observation, elective neck dissection (END) or elective nodal irradiation (ENI). We reviewed the evidence for ENI on a background of current practice among UK clinical oncologists. We carried out a systematic search of PubMed between 1 January 1980 and 31 December 2016. Articles on patients treated with parotidectomy and either END or ENI, and studies on nodal patterns of disease, were included. UK clinical oncologists were asked to complete an online questionnaire regarding their use of neck radiotherapy in this setting. From 96 references, 20 studies met the inclusion criteria: 11 reported on END, five on ENI and two on both. Eight studies reported on nodal patterns of disease. The prevalence of occult nodal metastases after END ranged from 0 to 45%. Five year locoregional control was variable (range 64-100%). For ENI, 5 year locoregional control varied from 74 to 100%. High-grade and T3/T4 tumours were factors for nodal relapse after END or ENI, which most commonly occurred in levels I-III. For the survey, 33/50 (66%) of cancer centres responded. Fourteen (42%) centres had guidelines for ENI. Most centres considered high-grade tumours (96%), T3/T4 disease (80%) and lymphovascular invasion (88%) as indications for ENI. Twelve centres (36%) irradiated levels Ib-IV electively; the remaining centres treated other various combinations of nodal levels. There is heterogeneity in the use and indications for ENI in the UK. ENI is a reasonable alternative to END as elective management for the cN0 neck in patients with high-grade tumours or T3/T4 disease. The elective clinical target volume should at least encompass nodal levels I-III.


Testing of instantaneity hypothesis for blind source separation of extensor indicis and extensor digiti minimi surface electromyograms.
Human muscle activity can be assessed with surface electromyography (SEMG). Depending on electrode location and size, the recording volume under the sensor is likely to measure electrical potentials emanating from muscles other than the muscle of interest. This crosstalk issue makes interpretation of SEMG data difficult. The purpose of this paper was to study a crosstalk reduction technique called blind source separation (BSS). Most straightforward separation techniques rely on linearity and instantaneity (LI) of signal mixtures on the sensors. Literature on BSS for SEMG often makes hypothesis of linearity and instantaneity of the mixing model. Using simulation of SEMG mixtures and real SEMG recordings on the human extensor indicis (EI) and extensor digiti minimi (EDM) muscles during a task consisting of selective successive activations of EI and EDM muscles, cross-correlation between the sensors was proven to be directly dependent on instantaneity of the sources. Instantaneity hypothesis testing on real SEMG recordings showed that source instantaneity hypothesis is very sensitive to electrode location along the fibers direction. Source separation gains using JADE BSS algorithm depend strongly on instantaneity hypothesis. Using LI BSS on SEMG requires great attention to electrode positioning; we provide a tool to test these on EI/EDM muscles.


Ischemic stroke recurrence during pregnancy: a case series and a review of the literature.
Aims of the study were to determine the risk of stroke recurrence in a case series of women with a history of ischemic stroke and to review current available literature on this issue. Charts from patients referring to the obstetrical service of our Institute were reviewed to identify pregnant women with a history of ischemic stroke. Demographic, historical and clinical data were collected from outpatient and inpatient charts. Women were contacted at least 6 months after delivery to assess maternal and neonatal health. A review of the literature regarding pregnancy in women with a history of ischemic stroke was also performed. Twenty-four pregnant women with a history of ischemic stroke referred to our Institution. All women received prophylaxis to prevent stroke recurrence during pregnancy. No recurrent episode was recorded in our series (0.0 %, 95% CI 0.0-11.3 %). One woman had a TIA. Considering collective data from the literature and from the present study, five cases of stroke recurrence out of 184 pregnancies were identified, corresponding to a rate of 2.7 % (95% CI 1.0-5.8 %). All of them were under prophylactic treatment at the time of stroke. Thrombophilia and preeclampsia may represent predisposing conditions for recurrence during pregnancy. Stroke recurrence in pregnant women with a history of ischemic stroke is uncommon, but not rare and prophylactic treatment does not fully protect against it. Further evidence is required to better clarify clinical factors predisposing to recurrence.


Long-term effectiveness of extracorporeal shockwave therapy in the treatment of previously untreated lateral epicondylitis.
To describe the outcomes of a cohort of individuals involved in a randomized control trial of extracorporeal shockwave therapy (ESWT) in the treatment of lateral epicondylitis (LE) not previously treated. Prospective cohort. General population. Sixty subjects (23 female, 37 male) who participated in a double-blind randomized control trial on the effectiveness of ESWT in the treatment of LE. All subjects had previously not received therapy for their LE. At the 8-week follow-up of a randomized control trial comparing ESWT with a stretching protocol for treatment of LE, all subjects were unblinded to their treatment allocation, and subjects initially allocated to sham therapy were offered active therapy. Overall elbow pain (10-cm visual analogue scale [VAS]) and maximum pain-free grip strength were evaluated at 0, 4, and 8 weeks and 3, 6, and 9 to 12 months postinitiation of therapy. Time to pain-free status (less than 1 cm on the VAS) was calculated from time of onset of symptoms, time of inclusion into the trial, and time from initiation of active therapy. A statistically significant difference in time to pain-free status was not detected between groups. Duration of symptoms was identified to be an effect modifier of early response to therapy (at least 50% improvement on the VAS at 8-week postinitiation of therapy). A higher proportion of subjects treated within 16 weeks of onset of LE symptoms showed a response to ESWT than subjects treated after 16 weeks of onset of their LE symptoms. The use of ESWT with a stretching program is not supported by this study, with the possible exception of the possible interaction effect of time of ESWT initiation from the time of onset of symptoms, which requires further investigation.


Why do breast cancer patients decline entry into randomised trials and how do they feel about their decision later: a prospective, longitudinal, in-depth interview study.
This paper presents an exploration of the reasons why breast cancer patients decline entry into randomised clinical trials of adjuvant cancer therapy. The study employed a qualitative, longitudinal design based on in-depth interview post diagnosis, with follow-up interviews at 6 and 12 months later. Twenty-two consecutive patients, newly diagnosed with breast cancer, who had declined entry into a clinical trial were prospectively recruited from five outpatient breast cancer clinics in the North Trent Cancer Network. Analysis of patients' narratives indicated that fear of the illness and limited understanding of medical research in general, compounded by unhelpful explanations of the trial purpose and process by health professionals, resulted in patients opting for the 'tried and tested' treatment. Some patients had persisting guilt about their decision not to take part. Many of the reasons why breast cancer patients decline entry to clinical trials could be addressed, as they tend to be a product of situational and process factors, rather than being rooted in deep-seated antipathy towards research.


Decoupling the role of stress and corrosion in the intergranular cracking of noble-metal alloys.
Intergranular stress-corrosion cracking (IGSCC) is a form of environmentally induced crack propagation causing premature failure of elemental metals and alloys. It is believed to require the simultaneous presence of tensile stress and corrosion; however, the exact nature of this synergy has eluded experimental identification. For noble metal alloys such as Ag-Au, IGSCC is a consequence of dealloying corrosion, forming a nanoporous gold layer that is believed to have the ability to transmit cracks into grain boundaries in un-dealloyed parent phase via a pure mechanical process. Here using atomic-scale techniques and statistical characterizations for this alloy system, we show that the separate roles of stress and anodic dissolution can be decoupled and that the apparent synergy exists owing to rapid time-dependent morphology changes at the dealloyed layer/parent phase interface. We discuss the applicability of our findings to the IGSCC of important engineering Fe- and Ni-based alloys in critical applications.


Evaluation of Ingestive Behavior, Ruminal and Blood Parameters, Performance, and Thermography as a Phenotypic Divergence Markers of Residual Feed Intake in Rearing Dairy Heifers.
The objectives of this study were: (1) to identify and rank phenotypically divergent animals for residual feed intake (RFI) regarding their efficiency (high: HE or low: LE); (2) to evaluate their relationships with ingestive behavior, ruminal and blood parameters, performance, and infrared thermography; and (3) to determine if such measurements can be used as feed efficiency markers in rearing dairy heifers. Thirty-eight heifers, 143 d ± 4 (Mean ± SD) of age and 108.7 kg ± 17.9 of body weight were used. The animals were fed with a total mixed ration during the 91 d of the trial. A phenotypic divergence of DMI for RFI was observed between -0.358 and 0.337 kg/d for HE and LE, respectively. Dry matter intake (DMI) was lower in the HE (2.5 kg DMI/d vs. 3.1 kg DMI/d), as was the number of visits to the feed bin with consumption (59 vs. 71). Feed intake was the best predictor of said divergence. Water intake and number of visits to the feed bin were presented moderate correlations with RFI. The ruminal fermentation variables, blood metabolites, blood hormones (such as the other ingestive behavior variables), and infrared thermography were not able to accurately predict HE or LE animals.


Fungal growth and biomass development is boosted by plants in snow-covered soil.
Soil microbial communities follow distinct seasonal cycles which result in drastic changes in processes involving soil nutrient availability. The biomass of fungi has been reported to be highest during winter, but is fungal growth really occurring in frozen soil? And what is the effect of plant cover on biomass formation and on the composition of fungal communities? To answer these questions, we monitored microbial biomass N, ergosterol, and the amount of fungal hyphae during summer and winter in vegetated and unvegetated soils of an alpine primary successional habitat. The winter fungal communities were identified by rDNA ITS clone libraries. Winter soil temperatures ranged between -0.6°C and -0.1°C in snow-covered soil. We found distinct seasonal patterns for all biomass parameters, with highest biomass concentrations during winter in snow-covered soil. The presence of plant cover had a significant positive effect on the amount of biomass in the soil, but the type of plant cover (plant species) was not a significant factor. A mean hyphal ingrowth of 5.6 m g(-1) soil was detected in snow-covered soil during winter, thus clearly proving fungal growth during winter in snow-covered soil. Winter fungal communities had a typical species composition: saprobial fungi were dominating, among them many basidiomycete yeasts. Plant cover had no influence on the composition of winter fungal communities.


Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction.
The effects of coffee on myocardial infarction are uncertain. We hypothesize that coffee in the presence of predisposing factors can induce a cascade of events that, through sympathetic nervous activation, can induce the onset of myocardial infarction. We recruited 503 incident cases of nonfatal myocardial infarction between 1994 and 1998 in Costa Rica. We used a case-crossover design to calculate relative risks (RRs) and 95% confidence intervals (95% CIs). The RR of myocardial infarction in the hour after coffee intake was 1.49 (95% CI = 1.17-1.89). Occasional coffee drinkers (< or =1 cup/day, n = 103) had a RR of myocardial infarction of 4.14 (2.03-8.42), moderate coffee drinkers (2-3 cups/day, n = 280) had a RR of 1.60 (1.16-2.21), and heavy coffee drinkers (> or =4 cups/d, n = 120) had a RR of 1.06 (0.69-1.63; P = 0.006, test of homogeneity). Patients with 3 or more risk factors (n = 101) had a RR of myocardial infarction of 2.10 (1.30-3.39), whereas patients with fewer than 3 risk factors (n = 396) had a RR of 1.39 (1.04-1.82; P = 0.15, test of homogeneity); and RR was 1.72 (1.30-2.30) among sedentary patients compared with 1.07 (0.66-1.72) among nonsedentary (P = 0.10, test of homogeneity). The findings indicate that coffee intake may trigger myocardial infarction. The association is particularly strong among people with light/occasional intake of coffee (< or =1 cup/day), with sedentary lifestyle, or with 3 or more risk factors for coronary heart disease.


A controlled prospective study of early mobilization of minimally displaced fractures of the distal radial metaphysis.
A controlled prospective trial of early exercise of slightly displaced fractures of the distal radial metaphysis has been performed. Twenty-eight fractures were enclosed in a tubigrip support 7-13 days after injury and 28 fractures were splinted in below-elbow plaster for 4 weeks. It was found that early movement of the wrist produced a superior functional result at 5 and 7 weeks (P less than 0.05) and allowed an earlier recovery of domestic skills (P less than 0.05). Early exercise did not improve recovery of strength of grip and did not produce a higher incidence of malunion. Patients treated in tubigrip experienced no more pain in weeks 4 and 6 and apart from one failure, no patient actively disliked this form of treatment and 22 were totally satisfied.


Management of Overactive Bladder in Older Women.
This review will highlight our current understanding of age-related changes in bladder function and propose important clinical considerations in the management of overactive bladder (OAB) specific to older women. Frailty, functional and cognitive impairment, multimorbidity, polypharmacy, estrogen deficiency, and remaining life expectancy are important clinical factors to consider and may impact OAB symptom management in older women. Third-line therapies, particularly PTNS, may be preferable over second-line therapy in some cases. Due to the complexity within this population, the standard treatment algorithms may not be applicable, thus a broader, more holistic focus is recommended when managing OAB in older women.


Infrared stretching frequencies of CO in carbomonoxyhemoglobin from trout.
The infrared spectra of the carbomonoxy derivatives of the hemoglobin components I and IV from trout have been measured in the CO stretching frequency region using a high resolution infrared spectrometer. The CO stretching frequency of Hb I CO is very close to that of carbomonoxy human hemoglobin and is pH-independent. In contrast, the CO stretching frequency of Hb IV CO is higher and shows a small but significant pH dependence in the range 6.2-7.8. These results point to a decreased strength of the iron-CO bond in Hb IV CO at low pH, in agreement with the conclusions drawn from the reported difference spectra of Hb IV CO as a function of pH.


Micro RNA responses to chronic or acute exposures to low dose ionizing radiation.
Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose γ-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of (137)Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate γ-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation.


Ultrasound as an aid in intrauterine transfusion.
Although the number of patients with Rh isoimmunization in pregnancy has been decreasing in recent years, intrauterine transfusion is still an important form of therapy for those patients whose infants have erythroblastosis. We have used both gray-scale and real-time ultrasonography for the last ten cases in which intrauterine transfusion was necessary. These techniques were used in preference to fluoroscopy and x-ray control to identify the placental site and fetal abdomen and to direct the insertion and placement of the transfusion needle. We were able to visualize the needle when it entered the amniotic cavity and the fetal abdomen. The technique afforded continuous visualization and a cross-sectional image of the fetus, steps which increase the efficiency and safety of the procedure and decrease radiation to the fetus.


Diminished embryonic movements of developing embryo by direct exposure of sidestream whole smoke solutions.
Embryonic movements (EM) are considered to be the first sign of life and cigarette smoking during pregnancy has been linked to affect EM. Exposure to sidestream smoke, produced from the emissions of a smoldering cigarette, may result in poor pregnancy outcome and increased risk of serious perinatal morbidity and mortality. In this study, the chicken embryo bioassay was used to systematically assess the effects of short-term exposure to sidestream whole smoke solutions (SSWSS) on EM, recorded in real time by a video camera for 60 min and each EM was counted for every 3-min interval. Application of different types of SSWSS to the embryos caused significant changes in all types of EM from 15 to 18 min of recording time. Extensive reduction (P<0.001) and some time complete stoppage of swing-like movements and whole-body movements were observed in almost all treated embryos. Our data clearly link between exposure of SSWSS and substantial decrease in EM. It is unclear whether nicotine and/or other ingredients present in sidestream smoke are responsible for these alterations in EM. This article provides an outline of the relevance of SSWSS on EM for evolutionary developmental biology and this assay can be used to investigate the complex mixtures with regard to their effects on EM.


Chemotherapy for advanced non-small-cell lung cancer: role of paclitaxel and gemcitabine.
OBJECTIVE: To review the role of chemotherapy in advanced non-small-cell lung cancer, focusing on cisplatin-based regimens and two new drugs: paclitaxel and gemcitabine. DATA SOURCES: Medline search of the relevant English literature. STUDY SELECTION: Open and randomised comparative (phases II and III2) studies, and meta-analyses of cytotoxic drugs/regimens used to treat advanced non-small-cell lung cancer. DATA EXTRACTION: The following factors were studied and compared: symptomatic response rates; tumour response rates: median survival time and 1-year survival rates; and side effects of cisplatin-, paclitaxel-, and gemcitabine-based regimens. DATA SYNTHESIS: Using cisplatin-based chemotherapy achieves significant relief of disease-related symptoms of advanced non-small-cell lung cancer and a slight improvement in the median survival time (by approximately 1.5 months). New cytotoxic drugs that are effective and have good safety profiles include paclitaxel and gemcitabine. When used as single agents, these two drugs give response rates of approximately 25%. When used with cisplatin/carboplatin, response rates increase to 45% to 62% and 1-year survival rates increase to 40% to 60%. CONCLUSION: Paclitaxel, gemcitabine, and other drugs such as decetaxel and vinorelbine are promising new chemotherapeutic agents in the treatment of advanced non-small-cell lung cancer. These drugs can palliate disease symptoms and improve the median survival time. The optimal dose and treatment schedules, however, are yet to be defined.


Relation between myocardial thallium-201 kinetics during exercise and quantitative coronary angiography in patients with one vessel coronary artery disease.
This study examined the relation between the kinetics of thallium-201 and coronary stenosis in 30 patients with one vessel coronary artery disease; 25 patients had no visible collateral vessels. The myocardial thallium concentration in the postexercise images and percent washout were determined in the distribution of the diseased vessel and a normal vessel, and each was expressed as a ratio. Coronary stenosis was assessed as minimal diameter stenosis, minimal area stenosis and percent diameter stenosis. The correlations between the myocardial concentration ratio or washout ratio and the descriptors of coronary stenosis improved when the patients with collateral vessels were excluded. There were significant correlations between the myocardial thallium concentration ratio and minimal diameter stenosis (r = 0.73, p less than 0.001), minimal area stenosis (r = 0.72, p less than 0.001) and, to a lesser degree, percent diameter stenosis (r = -0.51, p less than 0.01). Similarly, there were significant correlations between washout ratio and minimal diameter stenosis (r = 0.50, p less than 0.01) and minimal area stenosis (r = 0.45, p less than 0.02) but not percent diameter stenosis (r = 0.37, p = 0.06). Thus, variation in thallium kinetics in relation to the severity of coronary stenosis can be demonstrated with conventional imaging in patients with one vessel disease. The myocardial thallium concentration and washout are physiologic expressions of the severity of perfusion deficit and are dependent on collateral flow. The myocardial thallium concentration ratio and washout ratio correlate better with minimal diameter and area stenosis than with percent diameter stenosis.


The mRNA expression of the human 1,25-dihydroxyvitamin D3 receptor and the c-myc protooncogene in cultured human keratinocytes.
The human vitamin D receptor mRNA expression in preconfluent human cultured keratinocytes was upregulated by treatment of these cells with 10(-8) M 1,25(OH)2D3 for 24 hours. Additionally, human c-myc mRNA expression was decreased in a dose dependent manner by 1,25(OH)2D3 in both preconfluent and confluent cultured human keratinocytes.


Attitudes of Saudi parents toward separation from their children during dental treatment.
The purpose of this study was to investigate the attitudes of Saudi parents to being separated or not separated from their children in the dental office and to assess the factors affecting such attitudes. Five hundred and five parents participated in the study by completing a questionnaire which included questions related to their sex, marital status, job, family income and reasons for seeking dental treatment for the child. Questions were also designed to determine the responses and attitudes of the parents regarding their presence in the dental clinic. Ninety-seven percent of the respondents preferred to stay with their children during dental treatment of their children. The main reason given by 83% of the parents was that the child would feel safe. More than 72% of the parents reported that they would reduce their child's fear and comfort him/her during the dental treatment. From the parent's point of view, the most threatening dental procedure undergone by their children was dental anesthesia (87.7%) followed by the use of dental drills (55.4%). It can be concluded from the results that majority of Saudi parents studied preferred to stay with their children during treatment. Dentists should consider this when treating children.


Concise synthesis and preliminary biological evaluation of new triazolylthioacetone derivatives bearing pyridine, pyrazine, and 3,4,5-trimethoxybenzyl fragment.
Based on our previous work, a series of novel triazolylthioacetones incorporating pyridine, pyrazine, and 3,4,5-trimethoxybenzyl fragment were synthesized, and evaluated for antiproliferative activities and interactions with tubulin. Some analogues exhibited moderate to excellent potency, with the most promising compound IIc possessing IC50 values of 0.62, 1.46, and 3.65 μM against HT-29, HCT116, and HepG2 tumor cells, respectively, which were comparable with the positive control CA-4. Mechanistical studies revealed that IIc concentration-dependently caused cell cycle arrest at the G2/M phase in HCT116 tumor cells, and displayed a significant inhibition of tubulin polymerization with an IC50 value of 12.7 μM. Moreover, molecular docking analysis suggested that IIc could occupy the colchicine-binding site in a similar way with typical tubulinpolymerizationinhibitors. These results highlighted the 4-amino-triazolylthioacetone scaffold as potential tubulin polymerization inhibitors for development of highly efficient anticancer agents.


Evolutionarily conserved structure of the 3' non-translated region of a Chinese hamster polyubiquitin gene.
From a V79 Chinese hamster genomic library, we isolated a clone containing a polyubiquitin gene (designated as CHUB1), and determined its nucleotide sequence. The coding region of the CHUB1 gene consisted of five direct repeats of the ubiquitin unit with no spacer, followed by a single tyrosine residue. Northern hybridization analysis with a synthesized probe specific to the 3' non-translated region of the CHUB1 gene revealed that it codes for a 1.8 kb mRNA. An evident homology to the human polyubiquitin gene UbB and the chicken UbI gene was observed in the region corresponding to the full extent of the mature mRNA sequence, suggesting that these three genes belong to a common polyubiquitin gene subfamily, and that the sequence in the 3' non-translated region of the CHUB1 gene is unique to this subfamily.


Effect of a comprehensive nutrition education program on nutritional behavior and food security of female-headed households who receive welfare support in Zanjan Province, Iran.
In recent years, the food security and dietary quality of many Iranian families have deteriorated due to unprecedented inflation. Nutrition education programs can be an effective and inexpensive method to improve food quality and security. The present study aimed to investigate the effect of a comprehensive nutrition education program for low-income women who are heads of households and are covered by the Zanjan province's welfare. The food security of 2600 female-headed households covered by the Welfare of Zanjan province was evaluated using a standard 6-item questionnaire. A total of 600 women with the highest food insecurity scores were selected for the comprehensive nutrition education program. The participants received six sessions of 1.5 h of courses about how to improve the quality of their diets and manage their budgets and be physically active. At the beginning of the study and one month after the completion of the intervention, the participants were asked to complete a questionnaire designed and validated by the investigators. The scores of each section before and after the intervention were compared using paired t-test method and p values of < 0.05 were considered statistically significant. The prevalence of severe food insecurity among female-headed households who receive welfare support in Abhar, Khodabandeh, and Zanjan cities was 59.5%, 75%, and 62%, respectively. A total of 505 participants successfully completed the courses. After completion of the educational intervention, diet quality, physical activity, budgeting, and food safety scores of the participants increased by 6%, 4%, 4%, and 5%, respectively, which were statistically significant (p < 0.001). However, no significant difference was observed in the food insecurity scores. The comprehensive nutrition education program without financial or nutritional support can have a small but significant impact on the improvement of the nutritional behaviors and dietary quality of low-income people.


Synthesis of 3-substituted quinolines via transition-metal-catalyzed reductive cyclization of o-nitro Baylis-Hillman acetates.
Reductive cyclization of o-nitro-substituted Baylis-Hillman acetates by carbon monoxide, catalyzed by [CpFe(CO)(2)](2), gives moderate to good yields of 3-substituted quinolines.


UK dentists' attitudes and behaviour towards Atraumatic Restorative Treatment for primary teeth.
Atraumatic Restorative Treatment (ART) was introduced a decade ago as a minimal intervention treatment for caries in unindustrialised countries, but UK general dental practitioners (GDPs) may also be using this technique. This study aimed to determine the materials and techniques used by a group of UK GDPs to treat caries in primary teeth. A questionnaire, designed to determine GDPs' use of materials and techniques in the restoration of caries in primary teeth, was distributed to 600 GDPs in Scotland and England, with an explanatory letter and reply-paid envelope. The questionnaire included colour illustrations of two carious cavities in primary molar teeth and a request that respondents draw the cavity outline that they would use on the illustrations. The cavity outlines were assessed independently by two examiners. All other data were collated and analysed. 390 usable replies were received, a response rate of 65%. Of the respondents, 99% treated child patients and 42% of respondents were aware of ART. For treatment of a small Class II cavity, 37% drew a cavity outline without extension beyond removal of caries and a majority suggested use of an adhesive material (51% glass ionomer, 13% compomer). For cavity preparation, 47% of respondents used a drill, 10% an excavator and 41% used both. For treatment of a large occluso-lingual cavity, again most used an adhesive technique (44% glass ionomer, 12% compomer) for its restoration, while 50% used a drill, 7% an excavator and 42% used both for cavity preparation. Most respondents used adhesive materials for restoration of caries in primary molars, but, despite 42% of respondents stating that they were aware of the treatment, "true" ART was adopted by fewer than 10% of respondents.


Cervical spine trauma in diffuse idiopathic skeletal hyperostosis: injury characteristics and outcome with surgical treatment.
Retrospective study of a consecutive series of operatively managed patients with cervical fractures with diffuse idiopathic skeletal hyperostosis (DISH) presenting to 3 institutions over an 8 year period. Assess demographics, fracture characteristics, outcome and complications in patients managed surgically. Cervical spine injuries related to DISH represent a difficult subgroup of trauma patients to treat. This subset is fraught with potential complications related to the injury of the ankylosed spine, high rate of co-morbidities, and older demographics. The data in the literature on treatment, outcomes and complications is largely comprised of case reports and small case series. All patients with cervical fractures in the setting of DISH between January 2001 and December 2008 were reviewed retrospectively. Charts and radiographs were reviewed assessing demographics, injury characteristics and short-term outcomes. Statistical analysis was performed analyzing the impact of distinct parameters on the incidence of medical and surgical complications. Thirty-three patients with age 73.8 ± 11 years were identified. DISH-affected segments numbered 5.5 ± 2.1. Injury severity as assessed by the Subaxial-Injury-Classification scoring-system (SLIC) averaged 7.2 ± 1.4 points. 7 patients (20.6%) were ASIA-A on admission, 4 (11.8%) ASIA-B, 4 (11.8%) ASIA-C, 10 (29.4%) ASIA-D, and 7 (20.6%) ASIA-E. All but 2 patients (6%) had medical co-morbidities. Inpatient stay was 26.6 ± 23.4 days. 16 patients (47%) had anterior, 12 patients (35.3%) had posterior, and 5 patients (14.7%) had combined anterior-posterior instrumented fusion. 25 patients (73.5%) had medical/surgical complications. 20 patients (58.8%) suffered serious pulmonary complications not related to the neurologic injury (p < 0.05). Nine patients (26.5%) had died. Seven patients (20.6%) showed improved ASIA-scores, 18 patients (52.9%) had no improvement and 2 patients (5.9%) deteriorated. The current findings pinpoint the potential for medical and surgical complications in this high risk subgroup. Surgeons should be aware of the unique aspects associated with treatment of these injuries.


Stieltjes constants of L-functions in the extended Selberg class.
Let f be an arithmetic function and let S # denote the extended Selberg class. We denote by L ( s ) = ∑ n = 1 ∞ f ( n ) n s the Dirichlet series attached to f. The Laurent-Stieltjes constants of L ( s ) , which belongs to S # , are the coefficients of the Laurent expansion of L at its pole s = 1 . In this paper, we give an upper bound of these constants, which is a generalization of many known results.


[Relationships between the macroscopic placentary condition and postnatal state of underweight neonates. A contribution to the correlational pathology of the placenta (author's transl)].
Results of macroscopic examinations of placentae, which were obtained under routine clinical conditions for a total of 615 underweight neonates, were checked for their capability of a respiratory distress syndrome, and perinatal mortality. Evidence was obtained for a (partially statistically significant) trend showing that, within individual gestatory age groups and for equal weights of babies, premature infants born in the period up to and including the thirty-fifth week of gestation and having relatively low placental weights premature babies born during the thirty-sixth week of pregnancy, and hypotrophic babies born at term and showing a relatively heigh weight of the placenta are particularly exposed to a number of dangers in the further postnatal course of life. The clinical importance of these results to attending neonatologists is pointed out. Other conditions. such as the form of attachment of the umbilical cord of the nature of allantochorial vasculature, were not found to be closely related to the parameters studied in this investigation.


Botulinum Toxin Treatment of Objective Tinnitus Because of Essential Palatal Tremor: A Systematic Review.
In contrast to subjective tinnitus, objective tinnitus can be heard by the examiner as well as by the patient. It can be triggered by, among many other etiologies, idiopathic muscular tremor in the soft palate, the essential palatal tremor (EPT). Many treatment modalities have been investigated, of which only Botulinum toxin (BT) injections have shown promising results. The aim of this study was to evaluate the effect of BT treatment on objective tinnitus due to EPT by a systematic review of the literature. In accordance with PRISMA guideline a systematic literature search in three databases was performed. Twenty-two studies fulfilled the inclusion criteria, mainly case reports and case series. A total of 51 BT treated patients diagnosed with EPT were identified in the literature. The studies were evaluated with focus on diagnostics, injection technique and BT dose, follow-up, effect on objective tinnitus, complications, and adverse effects. The included studies suffer from an extremely low evidence level with several sources of bias. When optimally injected, BT seems to be an effective treatment of objective tinnitus due to EPT, with few adverse effects and complications. We suggest BT injections as first choice in case of EPT and present a guideline regarding diagnostics, treatment, and follow-up.


Identification and validation of potential prognostic lncRNA biomarkers for predicting survival in patients with multiple myeloma.
Dysregulated long non-coding RNAs (lncRNAs) have been found to have oncogenic and/or tumor suppressive roles in the development and progression of cancer, implying their potentials as novel independent biomarkers for cancer diagnosis and prognosis. However, the prognostic significance of expression profile-based lncRNA signature for outcome prediction in patients with multiple myeloma (MM) has not yet been investigated. LncRNA expression profiles of a large cohort of patients with MM were obtained and analyzed by repurposing the publically available microarray data. An lncRNA-focus risk score model was developed from the training dataset, and then validated in the testing and another two independent external datasets. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the prognostic performance for survival prediction. The biological function of prognostic lncRNAs was predicted using bioinformatics analysis. Four lncRNAs were identified to be significantly associated with overall survival (OS) of patients with MM in the training dataset, and were combined to develop a four-lncRNA prognostic signature to stratify patients into high-risk and low-risk groups. Patients of training dataset in the high-risk group exhibited shorter OS than those in the low-risk group (HR = 2.718, 95 % CI = 1.937-3.815, p <0.001). The similar prognostic values of four-lncRNA signature were observed in the testing dataset, entire GSE24080 dataset and another two independent external datasets. Multivariate Cox regression and stratified analysis showed that the prognostic power of four-lncRNA signature was independent of clinical features, including serum beta 2-microglobulin (Sβ2M), serum albumin (ALB) and lactate dehydrogenase (LDH). ROC analysis also demonstrated the better performance for predicting 3-year OS. Functional enrichment analysis suggested that these four lncRNAs may be involved in known genetic and epigenetic events linked to MM. Our results demonstrated potential application of lncRNAs as novel independent biomarkers for diagnosis and prognosis in MM. These lncRNA biomarkers may contribute to the understanding of underlying molecular basis of MM.


Primary hyperparathyroidism is associated with subclinical peripheral neural alterations.
Some case reports have suggested primary hyperparathyroidism (PHPT) and peripheral polyneuropathy (PPN) are associated; however, there are no reports of studies examining this possible relationship. The aim of this study was to evaluate peripheral nerve conduction in subjects with PHPT. The study involved 17 patients with PHPT. Mean patient age was 60.5 ± 12.9 years, serum calcium concentration was 11.5 ± 1.0 mg/dL, and the serum parathyroid hormone (PTH) level was 315 ± 569 pg/dL. The control group comprised 17 individuals without PHPT. The mean age of controls was 60.8 ± 12.5 years and the serum calcium concentration was 9.8 ± 0.3 mg/dL. Motor and sensory nerve conduction was assessed by electroneurography (ENG). The following ENG parameters differed significantly between the PHPT and control groups: right (R) sural sensory nerve action potential conduction velocity (52.7 ± 6.3 m/s versus 58.0 ± 8.0 m/s; P = .041); R median compound muscle action potential (CMAP) amplitude (7.4 ± 1.6 mV versus 8.9 ± 1.7 mV; P = .002); R median CMAP latency (4.3 ± 1.2 ms versus 3.6 ± 0.6 ms; P = .032); R tibial CMAP latency (4.2 ± 1.1 ms versus 3.3 ± 0.4 ms; P = .001). The neurological examination was normal in all patients. Our data demonstrate an association between PHPT and peripheral neurological alterations, consistent with subclinical sensory-motor PPN.


Risk factors for ovarian cancer: lesbian and heterosexual women.
To compare the distribution of risk factors for developing ovarian cancer in lesbian and heterosexual women. Secondary analysis of a retrospective medical record review. Urban health clinic with special outreach to lesbians. Typical participant (N = 1,019) was 42.9 years old and white (70%). Most were without health insurance, and 99% were poor (< $15,780 annual income). The majority (58%, n = 586) described themselves as heterosexual; 42% (n = 433) said they were lesbian. Data were collected from medical records and analyzed using analysis of covariance and logistic regression techniques. Ovarian cancer risk factors (parity, exogenous hormone use, smoking, body mass index [BMI], and tubal ligation/hysterectomy). Lesbians had a higher BMI; heterosexual women had higher rates of current smoking and a higher incidence of the protective factors of pregnancy, children, miscarriages, abortions, and use of birth control pills. The results of this study indicate that lesbians may have an increased risk for developing ovarian cancer. A study designed specifically to explore the risk factors of lesbian and heterosexual women for developing ovarian cancer must be undertaken to confirm these findings. Differences in risk levels may exist for lesbians; therefore, healthcare providers must become comfortable asking questions about sexual orientation and behavior.


Species and strain specificity of Lactobacillus probiotics effect on weight regulation.
Certain strains of Lactobacillus appear to have a reproducible effect on weight as a weight-gain effect in lean humans and animals or a weight-loss effect in overweight/obese humans and animals. These results are completely sufficient to capture the attention of the scientific community to assess the effect on the weight of Lactobacillus-containing probiotics sold for human consumption.