[Calculation of mortality tables and trends longevity figures for the Saxony population 1980 to 1994].
Basing on the population figures and deaths between 1980 to 1994, we calculated mortality tables for the Grman province (or "Free State", as 1st is called) of Saxony. The method for calculating the period mortality tables according to Becker, Zeuner based on the year of dying, was modified for small parent populations (correction of baby mortality according to Rahts, smoothing algorithm). The influence exercised by baby mortality and migration on life expectancy is shown. Estimated errors of the model are calculated for the first time (maximum absolute deviation for eo scatter, 95% confidence interval for eo). Presentation of different lifespan data proves that the positive trend of the life prolongation process is continuing. For example, the life expectancy of male newborn increased during the observation period by 1.94 years (from 69.38 to 71.31 years), that of female newborn by 3.50 years (from 75.2 to 78.62). Women increased their lead in life expectancy against men by 1.56 years (from 5.75 to 7.31 years). The reduction in baby morality and in the standardised mortality rate are other favourable factors. These figures dropped during the observation period from M: 12.0 on 7.0 and from F: 8.9 on 4.8, respectively from M: 14.4 on 1.0 and F: 13.3 on 12.7 per 1000 of the population.


[Tuberculous spondylitis in adults: a case series from a reference hospital in Lima, Peru].
We describe the demographic and clinical characteristics of adult patients with tuberculous spondylitis as well as an exploratory analysis that seeked to establish patient characteristics that contributed to the development of this disorder at a reference hospital in Lima. This is a case-series descriptive study where data collection from 33 medical records of patients from 1999 to 2009 was done. Eighteen (55%) were male. Median age was 31 years (IQR 23 to 51 years). Median time of symptoms was 3 months (IQR 1 to 8 months). The most frequent symptom was back pain in 28 (85%). The most frequently affected areas were the thoracic spine involved in 28 (60%) cases and lumbar spine in 13 (28%). Pulmonary tuberculosis was present in fourteen (42%) cases. Twenty four (73%) patients received first line treatment. Treatment duration was 10.5 ± 4.2 months. Clinical and diagnostic characteristics were similar to previous Peruvian case reports and current literature.


Reading the complex skipper butterfly fauna of one tropical place.
An intense, 30-year, ongoing biodiversity inventory of Lepidoptera, together with their food plants and parasitoids, is centered on the rearing of wild-caught caterpillars in the 120,000 terrestrial hectares of dry, rain, and cloud forest of Area de Conservacion Guanacaste (ACG) in northwestern Costa Rica. Since 2003, DNA barcoding of all species has aided their identification and discovery. We summarize the process and results for a large set of the species of two speciose subfamilies of ACG skipper butterflies (Hesperiidae) and emphasize the effectiveness of barcoding these species (which are often difficult and time-consuming to identify). Adults are DNA barcoded by the Biodiversity Institute of Ontario, Guelph, Canada; and they are identified by correlating the resulting COI barcode information with more traditional information such as food plant, facies, genitalia, microlocation within ACG, caterpillar traits, etc. This process has found about 303 morphologically defined species of eudamine and pyrgine Hesperiidae breeding in ACG (about 25% of the ACG butterfly fauna) and another 44 units indicated by distinct barcodes (n = 9,094), which may be additional species and therefore may represent as much as a 13% increase. All but the members of one complex can be identified by their DNA barcodes. Addition of DNA barcoding to the methodology greatly improved the inventory, both through faster (hence cheaper) accurate identification of the species that are distinguishable without barcoding, as well as those that require it, and through the revelation of species "hidden" within what have long been viewed as single species. Barcoding increased the recognition of species-level specialization. It would be no more appropriate to ignore barcode data in a species inventory than it would be to ignore adult genitalia variation or caterpillar ecology.


Neuroprotective Effects of Sinomenine on Experimental Autoimmune Encephalomyelitis via Anti-Inflammatory and Nrf2-Dependent Anti-Oxidative Stress Activity.
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). Sinomenine (SIN), a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, has powerful anti-inflammatory and immunosuppressive therapeutic benefits. In our previous research, we found that SIN increased resistance to oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in PC12 neuronal cells. However, whether SIN can improve the symptoms and pathological features of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, via the Nrf2 signaling pathway remains unclear. EAE was immunized followed by SIN treatment. Then we evaluated the effects of SIN in EAE. Subsequently, primary microglia were cultured to explore the effect of SIN on microglia activation. Further, the levels of Nrf2 and its downstream molecules were detected to assess the molecular mechanisms of SIN. We demonstrated that SIN effectively ameliorated the severity of EAE, accompanied by a reduction in the demyelination, axonal damage and inhibition of inflammatory cell infiltration. Mechanistically, SIN decreased the inflammatory cytokines expression, and suppressed microglia and astrocytes activation in EAE mice. Furthermore, SIN suppressed lipopolysaccharide (LPS)-induced microglial activation and the production of pro-inflammatory factors in vitro. Moreover, SIN inhibited oxidative stress via the activation of the Nrf2 signaling pathway. Our work proves that SIN exerts its neuroprotective effects by the Nrf2-dependent anti-oxidative stress and diminishing neuroinflammation, suggesting that the "antioxiflammation" effect of SIN is expected to be an ideal treatment strategy for MS/EAE.


Preparing for the crewed Mars journey: microbiota dynamics in the confined Mars500 habitat during simulated Mars flight and landing.
The Mars500 project was conceived as the first full duration simulation of a crewed return flight to Mars. For 520 days, six crew members lived confined in a specifically designed spacecraft mock-up. The herein described "MIcrobial ecology of Confined Habitats and humAn health" (MICHA) experiment was implemented to acquire comprehensive microbiota data from this unique, confined manned habitat, to retrieve important information on the occurring microbiota dynamics, the microbial load and diversity in the air and on various surfaces. In total, 360 samples from 20 (9 air, 11 surface) locations were taken at 18 time-points and processed by extensive cultivation, PhyloChip and next generation sequencing (NGS) of 16S rRNA gene amplicons. Cultivation assays revealed a Staphylococcus and Bacillus-dominated microbial community on various surfaces, with an average microbial load that did not exceed the allowed limits for ISS in-flight requirements indicating adequate maintenance of the facility. Areas with high human activity were identified as hotspots for microbial accumulation. Despite substantial fluctuation with respect to microbial diversity and abundance throughout the experiment, the location within the facility and the confinement duration were identified as factors significantly shaping the microbial diversity and composition, with the crew representing the main source for microbial dispersal. Opportunistic pathogens, stress-tolerant or potentially mobile element-bearing microorganisms were predicted to be prevalent throughout the confinement, while the overall microbial diversity dropped significantly over time. Our findings clearly indicate that under confined conditions, the community structure remains a highly dynamic system which adapts to the prevailing habitat and micro-conditions. Since a sterile environment is not achievable, these dynamics need to be monitored to avoid spreading of highly resistant or potentially pathogenic microorganisms and a potentially harmful decrease of microbial diversity. If necessary, countermeasures are required, to maintain a healthy, diverse balance of beneficial, neutral and opportunistic pathogenic microorganisms. Our results serve as an important data collection for (i) future risk estimations of crewed space flight, (ii) an optimized design and planning of a spacecraft mission and (iii) for the selection of appropriate microbial monitoring approaches and potential countermeasures, to ensure a microbiologically safe space-flight environment.


Drug use for the pregnant or lactating patient.
The dental patient who is pregnant or lactating may require management involving the administration or prescription of drugs. The approach of completely avoiding all drugs may not permit appropriate treatment of the patient and most often is not warranted. This article reviews the current considerations in the use of drugs in the dental patient who is either pregnant or lactating. The safety of the local anesthetics, vasoconstrictors, analgesics, antimicrobials, and sedatives used in dentistry is discussed.


Sexual victimization in female and male college students: examining the roles of alcohol use, alcohol expectancies, and sexual sensation seeking.
Alcohol and alcohol expectancies relate to sexual victimization. The present study examined these links in a sample of 407 predominantly Hispanic male and female college students, along the Mexico-US border. The study also examined the independent contribution of sexual sensation seeking to the prediction of victimization. Results showed that victimization was associated with alcohol risk, alcohol consumption-related problems, and positive alcohol expectancies. Importantly, sexual sensation seeking independently predicted victimization and did so after controlling for alcohol risk and expectancies. Our results suggest that associations among victimization, alcohol risk, and expectancies generalize to Hispanic women and men. The study's limitations are noted.


Sulforaphane-Enriched Broccoli Sprouts Pretreated by Pulsed Electric Fields Reduces Neuroinflammation and Ameliorates Scopolamine-Induced Amnesia in Mouse Brain through Its Antioxidant Ability via Nrf2-HO-1 Activation.
Activated microglia-mediated neuroinflammation plays a key pathogenic role in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ischemia. Sulforaphane is an active compound produced after conversion of glucoraphanin by the myrosinase enzyme in broccoli (Brassica oleracea var) sprouts. Dietary broccoli extract as well as sulforaphane has previously known to mitigate inflammatory conditions in aged models involving microglial activation. Here, we produced sulforaphane-enriched broccoli sprouts through the pretreatment of pulsed electric fields in order to trigger the biological role of normal broccoli against lipopolysaccharide-activated microglia. The sulforaphane-enriched broccoli sprouts showed excellent potency against neuroinflammation conditions, as evidenced by its protective effects in both 6 and 24 h of microglial activation in vitro. We further postulated the underlying mechanism of action of sulforaphane in broccoli sprouts, which was the inhibition of an inflammatory cascade via the downregulation of mitogen-activated protein kinase (MAPK) signaling. Simultaneously, sulforaphane-enriched broccoli sprouts inhibited the LPS-induced activation of the NF-κB signaling pathway and the secretions of inflammatory proteins (iNOS, COX-2, TNF-α, IL-6, IL-1β, PGE2, etc.), which are responsible for the inflammatory cascades in both acute and chronic inflammation. It also upregulated the expression of Nrf2 and HO-1 in normal and activated microglia followed by the lowered neuronal apoptosis induced by activated microglia. Based on these results, it may exhibit anti-inflammatory effects via the NF-κB and Nrf2 pathways. Interestingly, sulforaphane-enriched broccoli sprouts improved the scopolamine-induced memory impairment in mice through Nrf2 activation, inhibiting neuronal apoptosis particularly through inhibition of caspase-3 activation which could lead to the neuroprotection against neurodegenerative disorders. The present study suggests that sulforaphane-enriched broccoli sprouts might be a potential nutraceutical with antineuroinflammatory and neuroprotective activities.


Unilateral leg oedema due to spontaneous Achilles tendon rupture.
This is a case of severe unilateral lower leg oedema in a 77-year-old man, due to a spontaneous, complete Achilles tendon rupture. What makes this case unusual is the absence of trauma in the patient's history. The correct diagnosis was made only after magnetic resonance imaging. However, a thorough clinical re-examination of the patient revealed an inability to stand and walk on toes and a palpable defect of the Achilles tendon, which was difficult to detect due to the marked oedema. This case reminds physicians that an Achilles tendon rupture can also occur without clear history of trauma and should be considered as a cause of unilateral lower leg oedema, especially in presence of pain. Moreover, it illustrates the crucial role of a thorough clinical examination (including standing and walking on toes) for the correct diagnosis, even when restricting factors such as oedema and pain are present.


Evaluation of Premature Infants Hospitalized in Neonatal Intensive Care Unit between 2010-2012.
With continuing developments in the field of neonatology, survival rates of low birth weight and small for gestational age infants have increased, which in turn has brought important prematurity-related problems. The aim of this study was to evaluate retrospectively the prematurity problems that are the significant causes of morbidity and mortality. 613 premature infants hospitalized in the neonatal intensive care unit of Ataturk University Medical Faculty Hospital between January 2010 and January 2012 were included in this study. Infants were divided into groups according to their birth weight and gestational age. 323 infants were male (52.6%) and 290 were female (47.4%). 63.9% of infants weighed ≥1500 grams, and 58.5% had a gestational age of ≥33 weeks. Respiratory distress syndrome (RDS) was detected in 249 (40.6%), bronchopulmonary dysplasia (BPD) in 124 (20.2%), necrotizing enterocolitis (NEC) in 41 (6.6%), retinopathy of prematurity (ROP) in 202 (32.9%), and intracranial hemorrhage (ICH) in 15 (2.4%). RDS, BPD, NEC, ROP, and ICH rates were inversely proportional to decreases in gestational age and birth weight, and were found to be statistically significant. Mortality and morbidity rates were similar to the other data published from our country, but the rates were above those reported in developed countries. We believe that our morbidity and mortality rates can reach levels comparable to those of developed countries with improved antenatal care, regular follow-up of pregnancy and increased numbers of physicians and health care personnel per patient.


Motivational determinants of physical activity in disadvantaged populations with (pre)diabetes: a cross-cultural comparison.
Understanding motivational determinants of physical activity (PA) is essential to guide the implementation of PA at individual and population level. Knowledge about the cross-cultural generalizability of these determinants is lacking and they have mostly been studied as separate factors. This study compares a motivational process model across samples from diverse populations with, or at risk of diabetes. Measurement invariance of barrier identified regulation, barrier self-efficacy and social support was assessed in a rural Ugandan sample (n = 712) and disadvantaged samples with high proportions of immigrants in urban South Africa (n = 566) and Sweden (n = 147). These motivational determinants were then compared through multigroup structural equation modeling. The studied motivational constructs showed scalar invariance. Latent mean levels of perceived social support and barrier self-efficacy were lower in South Africa and Sweden. Structural models (for different PA outcomes) were not consistent across settings except for the association between perceived social support and identified regulation. Identified regulation was only associated with vigorous PA in Uganda and with moderate PA in South Africa. The association between social support and PA outcomes ranged from weak to not significant and the association between self-efficacy and PA was not significant. Self-reported PA was highest in Uganda and lowest in Sweden. Self-reported vigorous PA was significantly related to lower hemoglobin A1c levels, while moderate PA was not. Findings suggest that: 1) it is feasible to compare a motivational process model across diverse settings; 2) there is lower perceived social support and self-efficacy in the urban, migrant samples; 3) identified regulation is a more promising determinant of PA than self-efficacy or social support in these populations; 4) associations between motivational determinants and PA depend on the perceived type and/or intensity of PA; 5) perceived relatedness functions as a basic psychological need across diverse settings; and 6) people's perception of the PA they perform depends on their perceived level of intensity of PA which would have major implications for health promotion.


Sequence effects on local DNA topology.
Nuclear Overhauser effect-derived distances between adenine H2 protons and anomeric H1' protons on the same strand or on the complementary strand are presented for several different DNA duplexes. The cross-strand (n)AH2 to (m + 1)H1' distances [designated as x, where (n) and (m) are complementary residues] vary by up to 1 A depending on the sequence. In all possible A-containing pyrimidine-purine steps (CA, TG, and TA), x is greater than 4.5 A. In GA steps, x varies within rather wide limits in the range 3.8-4.5 A, whereas in AA steps the lower limit is 3.7 A and the upper limit is approximately 4.2 A. In purine-purine steps, x is affected by at least three factors: (i) adjacent pyrimidine-purine steps at the 5' end [e.g., YRA sequences (where Y = T or C and R = G or A)], or a pyrimidine-purine step at the 3' end of the pyrimidine-pyrimidine step on the complementary strand, cause x to increase, (ii) an AT step at the 3' end of a purine-purine step (e.g., RAT) causes x to decrease, and (iii) substitution of bases at the next-nearest neighbor position leads to changes in x at GA and AA steps. The latter factor seems to be due to a cooperative effect arising from formation of the "anomalous" B' structure when the substitution produces an AnTm tract (which always produces a decrease in x). The data indicate that (n)AH2-(n + 1)H1' distances on the same strand (designated as s) are also sequence dependent. Thus on AA steps, neighboring substitutions produce the same effect on s as on the cross-strand x distances. The results lead to the ability to predict changes in AH2-H1' distances depending on the DNA sequence. By using high-resolution x-ray B-type structures as a set of allowable B conformations, a very good correlation was found between x and the minor groove width parameters P-P or H1'-H1'. Thus, the x distances are a direct probe of the minor groove width in B-type DNA, and changes in this distance therefore reflect changes in the minor groove width. Since many of the sequences studied are sites of protein recognition, the observed sequence-structure dependence in DNA probably plays an important role in the process of recognition by proteins and minor groove ligands such as drugs.


Chlorine doping of MoSe2 flakes by ion implantation.
The efficient integration of transition metal dichalcogenides (TMDs) into the current electronic device technology requires mastering the techniques of effective tuning of their optoelectronic properties. Specifically, controllable doping is essential. For conventional bulk semiconductors, ion implantation is the most developed method offering stable and tunable doping. In this work, we demonstrate n-type doping in MoSe2 flakes realized by low-energy ion implantation of Cl+ ions followed by millisecond-range flash lamp annealing (FLA). We further show that FLA for 3 ms with a peak temperature of about 1000 °C is enough to recrystallize implanted MoSe2. The Cl distribution in few-layer-thick MoSe2 is measured by secondary ion mass spectrometry. An increase in the electron concentration with increasing Cl fluence is determined from the softening and red shift of the Raman-active A1g phonon mode due to the Fano effect. The electrical measurements confirm the n-type doping of Cl-implanted MoSe2. A comparison of the results of our density functional theory calculations and experimental temperature-dependent micro-Raman spectroscopy data indicates that Cl atoms are incorporated into the atomic network of MoSe2 as substitutional donor impurities.


Assessment of genetic diversity of landraces of Dendrocalamus hamiltonii using AFLP markers and association with biochemical traits.
Fermented bamboo shoots are popular traditional food items of various ethnic groups of the northeastern India, especially in Manipur State. Dendrocalamus hamiltonii is an economically important bamboo species used to produce fermented bamboo shoots. We studied genetic variability of this bamboo species in Chandel and Imphal-East (commercial production districts), using AFLP molecular markers. Each of the selected primers detected polymorphisms and 1614 (95.8%) were found to be polymorphic. Cluster analysis based on Dice similarity coefficients using UPGMA differentiated the populations into two major groups. Principal coordinate analysis based on the AFLP data clearly separated the populations according to their genetic diversity and antioxidant activity. Four primers were tested through multiple regression analysis to identify marker-trait association between AFLP data and biochemical attributes, i.e., antioxidant activity and total cyanide content. The 273 bp generated by EcoRI-AAG(Joe)/MseI-CTC showed high positive correlation with antioxidant activity (r = 0.729, P < 0.01). The 396 bp generated by EcoRI-AAC(Ned)/MseI-CTG were negatively correlated with cyanide content (r = -0.694, P < 0.01). Thus, we found association of DNA markers with antioxidant activities and total cyanide content. These results could be of use for the identification of superior genotypes with desirable traits.


Photodynamic therapy for acne vulgaris: a critical review from basics to clinical practice: part II. Understanding parameters for acne treatment with photodynamic therapy.
Photodynamic therapy requires a photosensitizer, oxygen, and activating light. For acne, pilosebaceous units are "target" structures. Porphyrins are synthesized in vivo from 5-aminolevulinic acid (ALA), particularly in pilosebaceous units. Different photosensitizers and drug delivery methods have been reported for acne treatment. There are a variety of porphyrin precursors with different pharmacokinetic properties. Among them, ALA and methyl-ester of ALA (MAL) are available for possible off-label treatment of acne vulgaris. In addition, various light sources, light dosimetry, drug incubation time, and pre- and posttreatment care also change efficacy and side effects. None of these variables has been optimized for acne treatment, but a number of clinical trials provide helpful guidance. In this paper, we critically analyze clinical trials, case reports, and series of cases published through 2009. After completing this learning activity, participants should be able to analyze photodynamic therapy using 5-aminolevulinic acid and its derivates for acne treatment, predict the effectiveness and outcomes of photodynamic therapy using different parameters and/or different porphyrin-related photosensitizers, and assess and manage the side effects of porphyrin-based photodynamic therapy for acne.


Aspergillosis of the central nervous system: clinicopathological analysis of 17 patients.
The clinical, laboratory, and pathological features of aspergillosis of the central nervous system (CNS) were studied in a series of 17 autopsied patients. Two groups were defined. Group A consisted of 8 patients with diseases commonly associated with CNS aspergillosis: leukemia, lymphoma, aplastic anemia, and renal transplantation. Group B contained 9 patients with various illnesses not generally known to be associated with CNS aspergillosis. CNS aspergillosis was diagnosed and treated before death in only 1 patient. Patients in Group A received cytotoxic drugs, often had granulocytopenia, less commonly had focal neurological deficits, and seldom had seizures. Group B patients were not granulocytopenic, received no cytotoxic agents, underwent nontransplant surgery, and more frequently had focal neurological deficits. Eleven of the 17 patients (65%) had focal deficits, most of them hemiparesis. Meningeal signs were rare, but the cerebrospinal fluid was usually abnormal. The principal neuropathological process was Aspergillus invasion of blood vessels causing hemorrhagic infarction. Focal clinical deficits correlated neuroanatomically with Aspergillus lesions. In 2 patients, such lesions were detected by 99mTc-DTPA or cerebral angiography before computed tomographic scanning. The lungs were the usual portal of entry, but isolated CNS lesions occurred in 2 patients. CNS aspergillosis should be considered as a cause of new onset of focal neurological deficits in patients with illnesses that are more diverse than has generally been appreciated.


[Large-scale fragmentation of dna and the death of tumor cells by the action of the binary system ascorbic acid-metallocomplexes of cobalt in vitro].
High-molecular-weight DNA fragments are the markers of the early stage of apoptosis induced in eukaryotic cells by cytotoxins of different nature. The dynamics of the development of large-scale DNA fragmentation in K-562 leukemia cells by the action of the antitumor drug, the binary system ascorbic acid--cobalt phthalocyanine within 48 h of incubation, which correspond to two periods of the doubling of cell number in growing control cultures, have been studied. It was shown that, within the first hours of incubation, hydrogen peroxide generated by the system induces the formation of DNA fragments from 2200 to 50 kbp long. Later on the cell death accompanied by a decrease in the content of fragmented DNA is observed. Within 24 h of incubation, part of fragmented DNA remains unrepaired; after 48 h of incubation, a delay or a slowed down proliferation of K-562 cells, which differ from control cells also by a high level of death and a higher content of high-molecular-weight DNA fragments, is observed.


Two-dimensional systolic speckle tracking echocardiography provides a noninvasive aid in the identification of acute pediatric heart transplant rejection.
Acute rejection is an important cause of morbidity and mortality in the pediatric heart transplant (HT) population. A reliable noninvasive method for diagnosis of clinical rejection could substantially reduce these negative outcomes. Evaluate left ventricular (LV) global longitudinal strain (GLS), and global circumferential strain (GCS) as early noninvasive indicators of acute pediatric HT rejection. An 18-month prospective cohort study involving 61 patients evaluated absolute change in peak global systolic strain (GLS and GCS) from enrollment (baseline) to next planned clinical encounter (follow-up) or rejection. Acute rejection defined as a biopsy of grade ≥ 2R or treatment with enhanced immunosuppression by the transplant team, blinded to strain analysis. Two patient cohorts three months post HT without evidence of rejection at enrollment were identified. The study cohort experienced rejection. The control cohort remained free from rejection on follow-up. Two-way analysis of variance (ANOVA) models evaluated change in GLS and GCS by cohort group and time. Applying exclusion criteria, 51 patients enrolled in the control cohort and 10 in the study cohort. The study cohort's mean GLS declined 33% from baseline to rejection (P < .001) and mean GCS declined 16.6% (P = .021). No significant change from baseline to follow-up was seen in the control cohort. A threshold absolute GLS value of 16.1% identified acute rejection with 100% sensitivity and 98% specificity (Likelihood Ratio, [LR] 51). Noninvasive global longitudinal strain was sensitive and specific in the identification of acute clinical rejection in pediatric HT recipients.


Reduced solar activity favors twin maternities.
Mechanisms underlying effects of physical factors on twin births are unclear. The present work studied an association between monthly and yearly multiple birth rates (MBRs) in the Novosibirsk region, south-west Siberia, in relation to solar activity (sunspot numbers) and geomagnetic activity (Ap index) from 1957 to 2008. The difference was verified by comparing the yearly MBR observed in 3-year peaks (M = 7.36, SD = 0.33 per 1,000 births) and 3-year troughs (M = 8.10, SD = 0.31 per 1,000 births, p < .001) of an 11-year solar cycle. An inverse correlation (r = -.60, p < .001) was found between sunspot numbers and MBR for a lag of 1 year. Cross-spectral analysis of a 52-year time series established a common signal with the period of 10.5 years, as well as high coherence (K(2) = 0.87). The multiple regression analysis revealed a significant interaction of solar and geomagnetic effects upon the frequency of twin maternities. The results show that elevated solar activity within the 11-year cycle coinciding with the time of conception inhibits multiple births in a manner depending on geomagnetic activity. It is hypothesized that the likely mechanism underlying the association is early fetal loss induced by solar radiation/flux and its terrestrial mediators.


3,3'-Diindolylmethane Suppresses Adipogenesis Using AMPKα-Dependent Mechanism in 3T3-L1 Adipocytes and Caenorhabditis elegans.
3,3'-diindolylmethane is a major in vivo metabolite of indole-3-carbinol, a bioactive compound found in cruciferous vegetables. Although 3,3'-diindolylmethane has been implicated to possess antitumorigenic and anti-inflammatory properties, the effect of 3,3'-diindolylmethane on adipogenesis has not been explored previously. Thus, the present study was conducted to determine if 3,3'-diindolylmethane affects adipogenesis using 3T3-L1 adipocytes and Caenorhabditis elegans. Treatment of 3,3'-diindolylmethane significantly reduced fat accumulation without affecting viability in 3T3-L1 adipocytes. 3,3'-diindolylmethane suppressed expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), fatty acid binding protein 4 (FABP4), and perilipin. In addition, 3,3'-diindolylmethane activated AMP-activated protein kinase α (AMPKα), which subsequently inactivated acetyl CoA carboxylase (ACC), resulting in reduced fat accumulation. These observations were further confirmed in C. elegans as treatment with 3,3'-diindolylmethane significantly reduced body fat accumulation, which was partly associated with aak-1, but not aak-2, orthologs of AMPKα catalytic subunits α1 and α2, respectively. The current results demonstrate that 3,3'-diindolylmethane, a biologically active metabolite of indole-3-carbinol, may prevent adipogenesis through the AMPKα-dependent pathway.


Mps1 phosphorylation of Dam1 couples kinetochores to microtubule plus ends at metaphase.
Duplicated chromosomes are equally segregated to daughter cells by a bipolar mitotic spindle during cell division. By metaphase, sister chromatids are coupled to microtubule (MT) plus ends from opposite poles of the bipolar spindle via kinetochores. Here we describe a phosphorylation event that promotes the coupling of kinetochores to microtubule plus ends. Dam1 is a kinetochore component that directly binds to microtubules. We identified DAM1-765, a dominant allele of DAM1, in a genetic screen for mutations that increase stress on the spindle pole body (SPB) in Saccharomyces cerevisiae. DAM1-765 contains the single mutation S221F. We show that S221 is one of six Dam1 serines (S13, S49, S217, S218, S221, and S232) phosphorylated by Mps1 in vitro. In cells with single mutations S221F, S218A, or S221A, kinetochores in the metaphase spindle form tight clusters that are closer to the SPBs than in a wild-type cell. Five lines of experimental evidence, including localization of spindle components by fluorescence microscopy, measurement of microtubule dynamics by fluorescence redistribution after photobleaching, and reconstructions of three-dimensional structure by electron tomography, combined with computational modeling of microtubule behavior strongly indicate that, unlike wild-type kinetochores, Dam1-765 kinetochores do not colocalize with an equal number of plus ends. Despite the uncoupling of the kinetochores from the plus ends of MTs, the DAM1-765 cells are viable, complete the cell cycle with the same kinetics as wild-type cells, and biorient their chromosomes as efficiently as wild-type cells. We conclude that phosphorylation of Dam1 residues S218 and S221 by Mps1 is required for efficient coupling of kinetochores to MT plus ends. We find that efficient plus-end coupling is not required for (1) maintenance of chromosome biorientation, (2) maintenance of tension between sister kinetochores, or (3) chromosome segregation.


Patients' recollection of day case knee arthroscopy procedure.
A prospective study of 103 consecutive patients who underwent day case knee arthroscopy was performed. The purpose was to evaluate the information delivery system, patient comprehension, and issues of informed consent pertaining to day case arthroscopy procedures. There were 34 females and 69 males in the study group and their mean age was 38.6 years (range: 14.4 to 74.9 years). The diagnosis, procedure, and aftercare were explained to the patients in the outpatients clinic by a trained nurse and by the operating surgeon just prior to the operation. The nurse before the operation gave the patients an information booklet. Postoperatively the patients were informed about the findings and diagnosis prior to their discharge from the day care facility. Patients were requested to complete a questionnaire. Three weeks later they were given the same questionnaire, prior to consultation, in the outpatient clinic. These two forms were compared with the operative findings and diagnosis documented in the copy, of the questionnaire completed by the surgeon as well as the case notes. Most patients (38.8%; 40 patients) had no recollection; 3.9% (4 patients) had partial recollection at their consultation three weeks later; 19.4% (20 patients) found that the arthroscopic photograph was not helpful in making them understand the procedure; and 9.7% (10 patients) found the information booklet to be unhelpful. Further, 23.3% (24 patients) said that it would not help if the booklet were sent to them prior to the operation. The recollection rate was also correlated to their position on the operating list, to ascertain the effect of the anesthetic. There was a 65.9% (58 patients) recollection rate in those patients who were on the first half of the list and there was only a 33.33% recollection rate in those patients who were last or second to the last [p = 0.0225]. We recommend regular evaluation and improvement in the communication and information delivery system provided to patients.


Modulation by betaine of cellular responses to osmotic stress.
Various solutes were tested to see if they could modify the responses of SV-3T3 cells to hyperosmotic (0.5 osM) conditions, which cause an inhibition of general cell protein synthesis and of the rate of cell proliferation, coupled with an induction of amino acid transport activity. The added solutes were glycerol, proline, taurine, betaine, dimethylglycine and sarcosine. Of these, betaine produced the most dramatic and consistent effects. Addition of 10-25 mM-betaine to the hyperosmotic medium largely prevented the 90% inhibition of cell proliferation that occurred in its absence. Whether it was added initially or after the cells were exposed to hyperosmotic medium, 25 mM-betaine also converted a 50% recovery of the rate of protein synthesis into 100%. Similarly, the same concentrations of betaine prevented a 30% decrease in cell volume and decreased the induction of amino acid transport via system A by 73%. Lower concentrations of betaine produced smaller but still significant changes in these functional responses. With chick-embryo fibroblasts, under identical hyperosmotic conditions, 25 mM-betaine completely counteracted a 75% inhibition of the rate of protein synthesis. At present it is not clear how betaine modulates these effects of hyperosmolarity on cell functions.


On the formation of cyclobutane pyrimidine dimers in UV-irradiated DNA: why are thymines more reactive?
The reaction pathways for thermal and photochemical formation of cyclobutane pyrimidine dimers in DNA are explored using density functional theory techniques. Although it is found that the thermal [2 + 2] cycloadditions of thymine + thymine (T + T --> T x T), cytosine + cytosine (C + C --> C x C) and cytosine + thymine (C + T --> C x T) all are similarly unfavorable in terms of energy barriers and reaction energies, the excited-state energy curves associated with the corresponding photochemical cycloadditions display differences that--in line with experimental findings--unanimously point to the predominance of T x T in UV-irradiated DNA. It is shown that the photocycloaddition of thymines is facilitated by the fact that the S1 state of the corresponding reactant complex lies comparatively high in energy. Moreover, at a nuclear configuration coinciding with the ground-state transition structure, the excited-state energy curve displays an absolute minimum only for the T + T system. Finally, the T + T system is also associated with the most favorable excited-state energy barriers and has the smallest S2-S0 energy gap at the ground-state transition structure.


Heterotopic pancreatic tissue located in the gallbladder wall. A case report.
Heterotopia of the pancreas can be defined as the presence of pancreatic tissue in an abnormal location without any continuity with the main body of the pancreas. Heterotopic pancreatic tissue located in the gallbladder is a rare entity. Despite being a congenital condition, it takes years for heterotopic pancreas to become symptomatic. An 80-year-old male patient presented to our hospital with a two-week history of abdominal pain, nausea and vomiting aggravated after meals. Abdominal ultrasonography revealed minimal wall edema and small grain-sized gallstones in the gallbladder. The patient was hospitalized and laparoscopic cholecystectomy was performed for acute cholecystitis. Pathologic examination showed a 6 mm nodular mass of pancreatic tissue in the gallbladder wall, comprised mainly of ductal and acinic structures and a few endocrine cells. We found this case of pancreatic heterotopia worth reporting because of its rare incidence.


Differential behavioral effects of partial bilateral lesions of ventral tegmental area or substantia nigra pars compacta in rats.
Akinesia (or absence of movement) is a prominent feature of Parkinson's disease. Akinetic symptoms, however, are also observed in depression and schizophrenia, which support the hypothesis that akinesia involves more than only motor behavior. A common feature of these disorders is the disruption of dopamine homeostasis in the CNS. Here we aimed at relating the respective involvement of the nigrostriatal and mesocortical dopaminergic pathways to akinesia. We investigated in the rat the relative effects of selective bilateral partial lesions of substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) which did not affect locomotion, on fine motor, motivational and cognitive behaviors. Motor impairments were measured by the evaluation of fine motor control in the stepping test and in the paw reaching test. Cognitive functions were assessed by various paradigms: spontaneous alternation in the Y maze and object exploration task. Motivational behavior was evaluated by the 100-pellets test. The results suggested that specific behavioral impairments are obtained following selective lesions of either SNc or VTA. SNc-lesioned rats exhibited deficits in fine motor functions as previously described in animal models of Parkinson's disease, whereas VTA-lesioned rats demonstrated traits of perseveration without significant motor impairments.


Transmission loss of plates with embedded acoustic black holes.
In recent years acoustic black holes (ABHs) have been developed and demonstrated as an effective method for developing lightweight, high loss structures for noise and vibration control. ABHs employ a local thickness change to tailor the speed and amplitude of flexural bending waves and create concentrated regions of high strain energy which can be effectively dissipated through conventional damping treatments. These regions act as energy sinks which allow for effective broadband vibration absorption with minimal use of applied damping material. This, combined with the reduced mass from the thickness tailoring, results in a treated structure with higher loss and less mass than the original. In this work, the transmission loss (TL) of plates with embedded ABHs was investigated using experimental and numerical methods in order to assess the usefulness of ABH systems for TL applications. The results demonstrated that damped ABH plates offer improved performance compared to a uniform plate despite having less mass. The result will be useful for applying ABHs and ABH systems to practical noise and vibration control problems.


Prognostic factors after treatment for iterative thymoma recurrences: A multicentric experience.
Thymomas are rare neoplasms with a low recurrence rate, which are preferably surgically treated. Iterative thymoma surgery has not been well investigated yet. Study aim is to analyse prognostic factors after iterative recurrence treatment. Clinical, pathological and surgical findings of 155 patients, treated for thymoma recurrence in three high-volume centres from 01/01/1990 to 1/07/2017, were retrospectively reviewed. Recurrence patterns/treatment types (surgery or chemotherapy, radiotherapy or combined) were correlated to overall (OS) and disease free survival (DFS). Myasthenia Gravis was present in 135 (87%) patients. Surgery was performed in 135/155 (87%) patients with 109 (80.7%) complete resections. Sixty (55%)patients experienced a second recurrence surgically treated in 31/60 (52%) cases with 18 (58%) complete resections. Eleven (61%) patients experienced a third recurrence and nine underwent complete resection. Myastenia Gravis (HR: 0.45; 95% CI: 0.20-0.98, p = 0.046), DFS after the initial thymectomy >36 months (HR: 0.9; 95% CI: 0.96-0.99, p = 0.006) and complete second recurrence resection (HR: 1.45; 95% CI 2.07-10.01, p = 0.010) resulted as independent favorable prognostic survival factor. Despite patient selection bias, rewarding long-term survivals was predictable after iterative thymoma surgery (5 and 10 years survival of 79.6% and 64.6%) while a poor prognosis was observed after CT/RT (5 and 10 years OS of 56.7% and 21.5%), Masaoka stage and DFS > 36 months were risk factor for iterative recurrences. Myasthenia Gravis and long DFS after thymectomy are favorable survival factors for multiple thymoma recurrences. Iterative surgical treatment is a viable therapeutic option associated to long-term survival if technically and clinically feasible.


Nerve function impairment in leprosy: design, methodology, and intake status of a prospective cohort study of 2664 new leprosy cases in Bangladesh (The Bangladesh Acute Nerve Damage Study).
The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study designed to investigate epidemiological, diagnostic, therapeutic and operational aspects of acute nerve function impairment in leprosy. The study is based at a single centre in Bangladesh, in an area with a high prevalence of leprosy. The centre, Danish Bangladesh Leprosy Mission, has a well-established vertical leprosy control programme. In this paper, the study design and methodology are described, together with definitions of nerve function impairment (NFI) used in this and subsequent papers. The study recruited 2664 new leprosy cases in a 12-month period. The male:female ratio is 1.25:1, and 17.61% of the cohort are under 15 years of age. In all, 83.33% of the cohort are paucibacillary (PB), and 16.67% multibacillary (MB). However, the MB rate amongst males is 19.72%, and amongst females is 12.85%, despite an equal period of delay to diagnosis. 55% of patients presented for treatment within 12 months of developing symptoms 6.12% of the total number of cases were smear positive, and 36.71% of the MB cases were smear positive. 9.61% of the total number of cases were graded as having World Health Organisation (WHO) disability grade 1, and 5.97% had grade 2. Amongst MB cases, 27.48% had WHO grade 1 disability present, and 18.24% had grade 2 present, compared with 6.04% and 3.51%, respectively, amongst PB cases. A total of 11.90% of the cohort had sensory NFI of any kind, and 7.39% had motor NFI. Ninety patients presented with NFI needing treatment (3.38%), and of these, 61 (67.78%) had silent NFI. MB patients had a prevalence of reaction/NFI needing treatment nearly 7 times higher than PB cases (15.32% amongst MB; 2.30% amongst PB), and males nearly double that of females (5.67% amongst males, 2.96% amongst females). The most commonly affected nerve by function impairment was the posterior tibial (sensory) with 6.46% of nerves affected (9.38% of patients), followed by the ulnar nerve with 3.23% of nerves impaired (5.56% of patients). Future research and publications, building on this foundation, will focus on the following areas: the incidence of NFI and reactive events, the risk factors for developing NFI, and the response to treatment of patients developing acute NFI.


Adolescent condom use consistency over time: global versus partner-specific measures.
The conundrum of measuring condom use consistency, particularly with adolescents, has left researchers with a cacophony of strategies, thereby limiting comparability and interpretation. The aim of this analysis was to compare and contrast two measures of condom use consistency, global versus partner specific, and their relationships with key covariates, using trajectory groups differentiated by stability of condom use consistency over three time points. Using self-report data from sexually active girls (aged 13-17 years) in a clinic-based intervention study aimed at lowering risk for early pregnancy, this analysis compared two measures of self-reported condom use consistency: (a) a global measure: overall condom use consistency in the past 6 months and (b) a partner-specific measure: condom use consistency with the most recent sex partner in the last 6 months. Using a subjective rule-based approach, the adolescent girls in the study (n = 151) were classified into trajectory groups representing their condom use consistency at three time points (baseline and 6 and 12 months). Then, using bivariate methods, trajectory groups were compared on four baseline covariates (age, treatment condition, hormonal use in the last 6 months, and number of sex partners in the last 6 months) and three time-varying covariates measured at baseline and at 6 and 12 months (hormonal use stability, stability of primary sex partner, and stability of number of sex partners). For the trajectory groups formed using the global measure of condom use consistency, stability of the primary sex partner differed significantly between trajectory groups. For the partner-specific trajectory groups, two baseline and one time-varying covariate relationships were significant: hormonal use in the 6 months prior to baseline, number of sex partners in the past 6 months (baseline), and stability of the primary sex partner (time varying), with hormonal use stability (time varying) trending toward significance. The larger number of significant covariate relationships with the partner-specific trajectory groups suggests greater utility in assessing partner-linked behavior rather than a global measure. Despite limitations of the analytic strategy, this study sheds light on a measurement conundrum that has been an obstacle to comparing and contrasting indicators of condom use consistency during adolescence.


Microbial Safety of Wood in Contact with Food: A Review.
Food packaging is multifunctional: it protects from harvest to table. Four main groups of materials for direct food contact are mentioned in the literature: wood, glass, plastic, and metal. In this review, the focus is on wooden packaging for direct contact with food. In Europe, wood as a food contact material is subject to European Regulation (EC) No 1935/2004 states that materials must not transfer their constituents to food. Today, wooden packaging, like other packaging materials, does not have a Europe-wide harmonized specific regulation, so member countries legislate at different levels. Wood has been safely used for centuries in contact with food but is usually questioned because of its microbiological behavior compared with smooth surfaces. Based on a review of published conclusions from scientific studies over the last 20 y and after a description of the general properties of wooden packaging, we focus on the microbiological status of natural wood. Then, we discuss the parameters influencing the survival of microorganisms on wood. Finally, we report on the transfer of microorganisms from wood to food and the factors influencing this phenomenon. This review demonstrates that the porous nature of wood, especially when compared with smooth surfaces, is not responsible for the limited hygiene of the material used in the food industry and that it may even be an advantage for its microbiological status. In fact, its rough or porous surface often generates unfavorable conditions for microorganisms. In addition, wood has the particular characteristic of producing antimicrobial components able to inhibit or limit the growth of pathogenic microorganisms.


Renal elasticity quantification by acoustic radiation force impulse applied to the evaluation of kidney diseases: a review.
For centuries, clinicians have used palpation to evaluate abdominal organs. After exploring almost all the different methods of interaction between x-rays, ultrasound, and magnetic fields on tissues, recent interest has focused on the evaluation of their mechanical properties.Acoustic radiation force impulse (ARFI) is a recent, established ultrasound-based diagnostic technique that allows physicians to obtain a measure of the elastic properties of an organ. Shear wave velocity, obtained by the ARFI technique, depends on the elasticity of tissues.To date, there are studies on the ARFI technique applied to normal kidneys, chronic kidney diseases, and kidney transplants. Mechanical properties of the kidney, such as stiffness and deformity, depend on various conditions that alter its histology, in particular the amount of fibrosis in the renal parenchyma; urinary pressure and renal blood perfusion may be other important contributing factors. Unfortunately, the ARFI technique applied to native renal pathologies is still limited, and not all studies are comparable because they used different methods. Therefore, the results reported in recent literature encourage further improvement of this method and the drawing up of standardized guidelines of investigation.


Application of in vivo and in vitro pharmacokinetics for physiologically relevant drug exposure in a human tumor clonogenic cell assay.
The biological half-lives and decay rate constants under the conditions of a human brain tumor clonogenic cell assay were determined for six clinically used anticancer agents. The agents studied were: 1,3-bis(2-chloroethyl)-1-nitrosourea; 3-(2-chloroethyl-3-nitrosoureido-2-deoxy-D-glucopyranose; cis-diaminedichloroplatinum(II); 2,5-diaziridinyl-3,6-bis-(carboethoxyamino)-1,4-benzoquinone; 4-demethylepipodophylotoxin-D-thylidene glucoside; and 9-hydroxy-2-N-methylellipticine. In vitro decay of all six drugs was found to be according to first order kinetics. The half-lives of two drugs, namely, 1,3-bis(2-chloroethyl-1-nitrosourea and 3-(2-chloroethyl-3-nitrosoureido-2-deoxy-D-glucopyranose under the human tumor clonogenic cell assay (HTCA) conditions were found to be similar to their terminal in vivo half-lives in humans. For the other drugs, however, there was a very large difference between their in vitro and in vivo pharmacokinetics. In the case of 2,5-diaziridinyl-3,6-bis(carboethoxyamine)-1,4-benzoquinone, we observed about an 80-fold difference between its in vitro half-life of 40.76 h and its in vivo terminal half-life of 0.52 h. We describe the principles upon which these data can be used to design clinically more relevant in vitro drug exposure protocols in HTCAs. Since, generally, tumor cells are exposed to drugs in the HTCA either continuously or for a specified duration, e.g., 1 or 2 h, we computed the initial in vitro drug concentrations to which tumor cells should be exposed such that the resulting in vitro (c X t) after a 2-h or a continuous exposure will be within clinically achievable levels. The application of these in vivo and in vitro pharmacokinetic principles will provide for more physiological testing of patient tumor cell sensitivity to anticancer drugs in the HTCA, and is likely to result in lower rates of false positive responses in clinical trials using clonogenic cell assays.


Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.
The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA interactions with RBM7 are known, it remains unclear how NEXT subunits collaborate to recognize and prepare substrates for degradation. Here, we show that MTR4 helicase activity is enhanced when associated with RBM7 and ZCCHC8. While uridine-rich substrates interact with RBM7 and are preferred, optimal activity is observed when substrates include a polyadenylated 3' end. We identify a bipartite interaction of ZCCHC8 with MTR4 and uncover a role for the conserved C-terminal domain of ZCCHC8 in stimulating MTR4 helicase and ATPase activities. A crystal structure reveals that the ZCCHC8 C-terminal domain binds the helicase core in a manner that is distinct from that observed for Saccharomyces cerevisiae exosome cofactors Trf4p and Air2p. Our results are consistent with a model whereby effective targeting of substrates by NEXT entails recognition of elements within the substrate and activation of MTR4 helicase activity.


Genomic Characterization of a B Chromosome in Lake Malawi Cichlid Fishes.
B chromosomes (Bs) were discovered a century ago, and since then, most studies have focused on describing their distribution and abundance using traditional cytogenetics. Only recently have attempts been made to understand their structure and evolution at the level of DNA sequence. Many questions regarding the origin, structure, function, and evolution of B chromosomes remain unanswered. Here, we identify B chromosome sequences from several species of cichlid fish from Lake Malawi by examining the ratios of DNA sequence coverage in individuals with or without B chromosomes. We examined the efficiency of this method, and compared results using both Illumina and PacBio sequence data. The B chromosome sequences detected in 13 individuals from 7 species were compared to assess the rates of sequence replacement. B-specific sequence common to at least 12 of the 13 datasets were identified as the "Core" B chromosome. The location of B sequence homologs throughout the genome provides further support for theories of B chromosome evolution. Finally, we identified genes and gene fragments located on the B chromosome, some of which may regulate the segregation and maintenance of the B chromosome.


Nursing intervention/activity mapping at a Chemotherapy Center: an instrument for workload assessment.
identify the interventions/activities nurses develop at a Chemotherapy Center (CTC) using standardized language and validate their contents. data triangulation was used through the combination of three information sources: semistructured interview, document analysis and questionnaire. The instrument, constructed in accordance with the Nursing Interventions Classification (NIC) taxonomy, was submitted to content validation through meetings with the participants. Thirty-five interventions and 48 activities were mapped and validated, organized in five domains (physiological: basic and physiological: complex, behavioral, safety and health system) and 11 classes. The identification of nurses' interventions/activities at CTC supports the determination of the time consumed and permits measuring the workload. It also helps to define these professionals' role, which permits the redesign of the work process and optimizes productivity.


Effects of individual risk factors on the residual risk of cardiovascular events in a population of treated Chinese patients with hypertension: data from the Felodipine Event Reduction (FEVER) study.
The added cardiovascular risk conferred by risk factors or diseases accompanying hypertension has been investigated in Caucasian patients, and much less is known in Chinese patients. Furthermore, the residual risk persisting in hypertensive patients, despite blood pressure (BP) reduction, due to accompanying conditions has never been explored in Chinese, and whether they differ from Caucasians under this respect is unknown. Felodipine Event Reduction (FEVER) study randomized 9711 Chinese hypertensive patients to more or less intense antihypertensive treatment for 40 months, with outcome monitoring. The present analyses provide information on the role that baseline presence of individual risk factors has in increasing outcome probability despite BP control. Risk ratios were calculated using Cox proportional hazard models, adjusted for a large number of baseline variables, except the one under examination, and also adjusted for on-treatment systolic and diastolic BP. Male sex, older age, diabetes and cardiovascular disease were accompanied by a significantly higher incidence of cardiovascular events (risk ratios 1.41-1.86 according to risk factor), stroke (risk ratios 1.42-1.72), cardiac events (risk ratios 1.40-2.70), all-cause death (risk ratios 1.51-2.16) and cardiovascular death (risk ratios 1.61-2.02). Higher baseline systolic BP and smoking conferred a significantly increased risk of cardiovascular events and strokes. Higher cholesterol was not found to increase any cardiovascular outcome. The same was the case for electrocardiographic left-ventricular hypertrophy and isolated systolic hypertension. A number of additional risk factors increased the residual risk of Chinese hypertensive patients despite effective antihypertensive treatment as much as described in Caucasians. High serum cholesterol was an exception: whether this is a Chinese characteristic or a more general phenomenon remains to be investigated.


Idiopathic REM sleep behavior disorder: toward a better nosologic definition.
REM sleep behavior disorder (RBD) is a parasomnia characterized by a lack of motor inhibition during REM sleep leading to potentially harmful dream-enacting behaviors. RBD affects mainly older men and its prevalence in the general population is estimated to be around 0.5%. RBD may be idiopathic or associated with other neurologic disorders. A strong association between RBD and alpha-synucleinopathies has been recently observed, with the parasomnia often heralding the clinical onset of the neurodegenerative disease. The idiopathic form accounts for up to 60% of the cases reported in the three largest series of patients with RBD. Small clinical follow-up studies revealed that a proportion of these patients will eventually develop a parkinsonian syndrome or a dementia of Lewy bodies type in the years following the RBD diagnosis, while some patients will never show other neurologic signs within several decades from the RBD onset. Recent studies have looked at neurophysiologic and neuropsychological functions in idiopathic RBD and have found evidences of CNS dysfunction during both wakefulness and sleep. An impairment of the cortical activity, specific neuropsychological deficits, and signs of autonomic dysfunction have been observed in a variable proportion of these patients, challenging the concept of idiopathic RBD. Identifying subjects with a high risk of developing a neurodegenerative process may be crucial in order to develop early intervention strategies.


Long-term safety of benoxaprofen.
Adverse experiences were monitored in 1,681 patients with rheumatoid arthritis (RA) or osteoarthritis to evaluate the safety of benoxaprofen at daily doses up to 1,000 mg during long-term therapy. Gastrointestinal side effects with benoxaprofen compared favorably to those reported during aspirin and ibuprofen therapy, with peptic ulcers reported in 0.4% of the patients or 1 ulcer for 200 patient years. The incidence of photosensitivity or onycholysis was 9%. Laboratory examinations revealed no significant changes in BUN, hematocrit, hemoglobin, SGOT, and SGPT values. The only trend toward abnormal values was seen in the LDH in patients with RA.


Sonographic criteria predictive of benign thyroid nodules useful in avoiding unnecessary ultrasound-guided fine needle aspiration.
There has been no individual ultrasound feature of having high accuracy for diagnosis of thyroid malignancy. In this study, we aimed to establish feature-oriented criteria to characterize benign thyroid nodules that do not require ultrasound (US)-guided fine needle aspiration (FNA). We reviewed 374 patients with thyroid nodules who had undergone US-guided FNA at our institution (2005-2008). Thyroid nodules were classified into two groups: Category 1 (benign nodules that required follow-up 6-12 months later but not US-guided FNA); and Category 2 (indeterminate nodules or suspected carcinoma that required US-guided FNA). To test the validity, we reviewed 315 consecutive patients who had histologically proven thyroid carcinoma (n = 39) and randomly selected 40 of the 276 patients with benign nodules (2009-2010). Of 374 nodules, 354 (95%) were benign and 20 (5%) malignant. On US, 260 nodules had no calcification, no increase in vascularity, well-defined margin, and no lymphadenopathy (Category 1). Using a combination of these four features, we were able to discriminate benign from indeterminate nodules or suspected malignant nodules with a sensitivity of 73%, and specificity and positive predictive value of 100%. Validity testing revealed that none of the 39 malignant thyroid nodules had all four US features. All Category 1 nodules (2005-2008) remained benign at the 3-years follow up. The combination of four US features of Category 1 nodules is highly predictive of benign disease, and we could avoid unnecessary US-guided FNA in 69.5% of our patients using this combined features.


Evolutionary novelty is concentrated at the edge of coral species distributions.
Conservation priorities are calculated on the basis of species richness, endemism, and threats. However, areas ranked highly for these factors may not represent regions of maximal evolutionary potential. The relationship between geography and evolutionary innovation was analyzed in a dominant complex of Caribbean reef corals, in which morphological and genetic data concur on species differences. Based on geometric morphometrics of Pleistocene corals and genetically characterized modern colonies, we found that morphological disparity varies from the center to the edge of the Caribbean, and we show that lineages are static at well-connected central locations but split or fuse in edge zones where gene flow is limited. Thus, conservation efforts in corals should focus not only on the centers of diversity but also on peripheral areas of species ranges and population connectivity.


Drivers of land use change and household determinants of sustainability in smallholder farming systems of Eastern Uganda.
Smallholder farming systems in sub-Saharan Africa have undergone changes in land use, productivity and sustainability. Understanding of the drivers that have led to changes in land use in these systems and factors that influence the systems' sustainability is useful to guide appropriate targeting of intervention strategies for improvement. We studied low input Teso farming systems in eastern Uganda from 1960 to 2001 in a place-based analysis combined with a comparative analysis of similar low input systems in southern Mali. This study showed that policy-institutional factors next to population growth have driven land use changes in the Teso systems, and that nutrient balances of farm households are useful indicators to identify their sustainability. During the period of analysis, the fraction of land under cultivation increased from 46 to 78%, and communal grazing lands nearly completely disappeared. Cropping diversified over time; cassava overtook cotton and millet in importance, and rice emerged as an alternative cash crop. Impacts of political instability, such as the collapse of cotton marketing and land management institutions, of communal labour arrangements and aggravation of cattle rustling were linked to the changes. Crop productivity in the farming systems is poor and nutrient balances differed between farm types. Balances of N, P and K were all positive for larger farms (LF) that had more cattle and derived a larger proportion of their income from off-farm activities, whereas on the medium farms (MF), small farms with cattle (SF1) and without cattle (SF2) balances were mostly negative. Sustainability of the farming system is driven by livestock, crop production, labour and access to off-farm income. Building private public partnerships around market-oriented crops can be an entry point for encouraging investment in use of external nutrient inputs to boost productivity in such African farming systems. However, intervention strategies should recognise the diversity and heterogeneity between farms to ensure efficient use of these external inputs.


The involvement of hydrogen-producing and ATP-dependent NADPH-consuming pathways in setting the redox poise in the chloroplast of Chlamydomonas reinhardtii in anoxia.
Photosynthetic microalgae are exposed to changing environmental conditions. In particular, microbes found in ponds or soils often face hypoxia or even anoxia, and this severely impacts their physiology. Chlamydomonas reinhardtii is one among such photosynthetic microorganisms recognized for its unusual wealth of fermentative pathways and the extensive remodeling of its metabolism upon the switch to anaerobic conditions. As regards the photosynthetic electron transfer, this remodeling encompasses a strong limitation of the electron flow downstream of photosystem I. Here, we further characterize the origin of this limitation. We show that it stems from the strong reducing pressure that builds up upon the onset of anoxia, and this pressure can be relieved either by the light-induced synthesis of ATP, which promotes the consumption of reducing equivalents, or by the progressive activation of the hydrogenase pathway, which provides an electron transfer pathway alternative to the CO2 fixation cycle.


Four major dietary patterns identified for a target-population of adults residing in Newfoundland and Labrador, Canada.
Very limited nutritional epidemiological studies conducted to explore the unique dietary exposure in Newfoundland and Labrador (NL). This study aims to identify and characterize major dietary patterns in the target-population from general adult NL residents and assess the associations with selected demographic factors. A total of 192 participants, aged 35-70 years, completed and returned a food-frequency questionnaire (FFQ) and participated in a telephone interview to collect demographic information. Dietary patterns were identified by common factor analysis. Univariate and multivariate linear regression analyses were used to assess determinants of the different food consumption patterns. Pearson's correlation coefficients were calculated for food scores of each pattern, total energy, and energy-adjusted nutrient intakes. Factor analyses identified four dietary patterns, which were labeled as "Meat", "Vegetable/fruit", "Fish", and "Grain" patterns. In combination, the four dietary patterns explained 63% of the variance in dietary habits of the study population. Multivariate linear regression analysis indicated an increasing trend of factor scores for Meat and Grain pattern with age. Male participants were found to be more likely to choose the Meat and Fish patterns. Current smokers and those married/living together tend to choose the Grain pattern. Pearson's correlation coefficients showed positive correlations between fat and cholesterol and the Meat pattern, fiber and the Vegetable/fruits pattern, protein and the Fish pattern, and carbohydrates and the Grain pattern. This study derived four dietary patterns and obtained their significant associations with specific demographic characteristics in this population. It identified one dietary consumption pattern (Fish) not yet seen in other studied populations. These findings will update the current dietary-health information published in this province, and contribute to further research into the association between dietary practices and health.


Incidence, clearance, and factors associated with anal human papilloma virus infection among men with HIV.
This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China. A prospective cohort study. Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping. A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association. Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence.


CCL21/CCR7 prevents apoptosis via the ERK pathway in human non-small cell lung cancer cells.
Previously, we confirmed that C-C chemokine receptor 7 (CCR7) promotes cell proliferation via the extracellular signal-regulated kinase (ERK) pathway, but its role in apoptosis of non-small cell lung cancer (NSCLC) cell lines remains unknown. A549 and H460 cells of NSCLC were used to examine the effect of CCL21/CCR7 on apoptosis using flow cytometry. The results showed that activation of CCR7 by its specific ligand, exogenous chemokine ligand 21 (CCL21), was associated with a significant decline in the percent of apoptosis. Western blot and real-time PCR assays indicated that activation of CCR7 significantly caused upregulation of anti-apoptotic bcl-2 and downregulation of pro-apoptotic bax and caspase-3, but not p53, at both protein and mRNA levels. CCR7 small interfering RNA significantly attenuated these effects of exogenous CCL21. Besides, PD98059, a selective inhibitor of MEK that disrupts the activation of downstream ERK, significantly abolished these effects of CCL21/CCR7. Coimmunoprecipitation further confirmed that there was an interaction between p-ERK and bcl-2, bax, or caspase-3, particularly in the presence of CCL21. These results strongly suggest that CCL21/CCR7 prevents apoptosis by upregulating the expression of bcl-2 and by downregulating the expression of bax and caspase-3 potentially via the ERK pathway in A549 and H460 cells of NSCLC.


Mathematical representation of the velocity curve of sprint running.
Some remarks are tendered on the commonly accepted equations of motion for sprint running. All these involve combinations of one or more exponentials. An alternate form, not discussed in the sports literature, is investigated but though sound, is considered to be mathematically unsuitable. The re-examination of some available data on sprinting suggests that a reformulation of the original differential equation leads to a new solution which is a simple hyperbolic function. This equation may prove a better mathematical model than that commonly accepted as the velocity curve of sprint running. Parameters of the curves are discussed for trainability.


Accretion of a large LL parent planetesimal from a recently formed chondrule population.
Chondritic meteorites, derived from asteroidal parent bodies and composed of millimeter-sized chondrules, record the early stages of planetary assembly. Yet, the initial planetesimal size distribution and the duration of delay, if any, between chondrule formation and chondrite parent body accretion remain disputed. We use Pb-phosphate thermochronology with planetesimal-scale thermal models to constrain the minimum size of the LL ordinary chondrite parent body and its initial allotment of heat-producing 26Al. Bulk phosphate 207Pb/206Pb dates of LL chondrites record a total duration of cooling ≥75 Ma, with an isothermal interior that cools over ≥30 Ma. Since the duration of conductive cooling scales with parent body size, these data require a ≥150-km radius parent body and a range of bulk initial 26Al/27Al consistent with the initial 26Al/27Al ratios of constituent LL chondrules. The concordance suggests that rapid accretion of a large LL parent asteroid occurred shortly after a major chondrule-forming episode.


[Serological markers of viral infections in patients with rheumatoid arthritis].
The authors carried out serologic examination of 202 patients with rheumatoid arthritis (RA) and 200 healthy persons for detecting of specific markers of infections caused with herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C viruses (HBV and HCV) and human T-cell lymphotropic retroviruses 1 and 2 (HTLV-1/2). It was demonstrated that detecting frequencies of HBsAg and total antibodies to HTLV-1/2, HSV and CMV among RA patients and healthy persons were practical equal--only anti-EBV were detected more often among RA patients than among healthy persons. But in the same time IgM-antibodies to HSV, CMV and EBV were detected more often among RA patients than among healthy persons. Authors concluded that most probable RA etiologically can be connected with chronic reproductive infections caused with HSV and EBV, which at least are able to participate in forming of predisposition to this disease by means of autoimmune reactions promotion.


Site-Specific Recombination with Inverted Target Sites: A Cautionary Tale of Dicentric and Acentric Chromosomes.
Site-specific recombinases are widely used tools for analysis of genetics, development, and cell biology, and many schemes have been devised to alter gene expression by recombinase-mediated DNA rearrangements. Because the FRT and lox target sites for the commonly used FLP and Cre recombinases are asymmetrical, and must pair in the same direction to recombine, construct design must take into account orientation of the target sites. Both direct and inverted configurations have been used. However, the outcome of recombination between target sites on sister chromatids is frequently overlooked. This is especially consequential with inverted target sites, where exchange between oppositely oriented target sites on sisters will produce dicentric and acentric chromosomes. By using constructs that have inverted target sites in Drosophila melanogaster and in mice, we show here that dicentric chromosomes are produced in the presence of recombinase, and that the frequency of this event is quite high. The negative effects on cell viability and behavior can be significant, and should be considered when using such constructs.


Certain predictors of coping with stress in adolescents.
The purpose of the study was to search for variables that show a relationship with coping with stress as well as to search for the possibility of predicting a stress coping mechanism in the studied adolescents. Two questions were formulated in the study: Are mental resilience and communication with peers significant predictors of coping with stress in the studied group? To what extent will the analysed predictors explain individual strategies to cope with stress? The study involved three tools: the Resilience Measurement Scale (RMS-18), the Coping Inventory for Stressful Situations Questionnaire (CISS), and the Scale of Communication of Adolescents with Peers (SCAP). The study was carried out on a randomly selected group of 546 adolescents. Due to the pandemic conditions prevailing at that time, the online form of data collection was used. Study tools along with the record were placed on the LimeSurvey platform, and then posted via Facebook on groups for adolescents, not only in secondary schools. Each subject could withdraw at any time without any negative consequences. The collected questionnaires are part of a larger empirical project. The study results showed that open communication with peers as well as general resilience and the resilience factor optimistic attitude and energy had a positive relationship. The general conclusion from the study is that mental resilience and openness in peer relationships are conducive to undertaking strategies of coping with stress in the studied adolescents.


Extent of surgery in the management of phyllodes tumor of the breast: a retrospective multicenter study from India.
Phyllodes tumor (PT) is a rare tumor of the breast. Usually, difficulty in making preoperative diagnoses and unpredictable clinical outcome of this disease leads to inappropriate management. Till date, no definite conclusion regarding the appropriate surgical procedure can be drawn. The objective of this retrospective study is to study the clinicopathological correlation of phyllodes tumors in North-Central part of the India and also to evaluate efficacy of the various surgical options available for the management of phyllodes tumors of the breast. A retrospective study of 24 cases from the archives of department of surgery of three tertiary institutes of North-Central part of India. We reviewed the clinical, pathological features of this disease entity with a view to highlight relevant features. We also analyzed various surgical options done for primary as well as recurrent PT. The breast masses in our study were particularly large. The mean size of the lump was 9.5 +/- 5.5 cm (range was 4.0-23 cm). Histopathological report was benign, borderline, and malignant PT in 62.4%, 20.8%, and 16.8% of the cases, respectively. Overall, 31 surgical procedures (24 in primary and 7 in recurrent) were performed. Simple lumpectomy, wide local excision and simple mastectomy were done in 25%, 27.4% and 27.4% of primary (non-recurrent) cases of PT, respectively. Modified radical mastectomy and simple mastectomy with LD flap reconstruction was done in 7.2% and 2.4% in primary cases, respectively in recurrent cases, simple mastectomy was done in four cases and modified radical mastectomy was done in one case. Overall, recurrence was seen in 29.2% of the cases. The median time for recurrence was 6 months (range 5.0-36 months). 90% (6/7) of recurrence occurred in lumpectomy patients. The unpredictable behavior of histological types and the disputable results of particular surgical procedures have contributed to the controversies. The therapeutic issue is further compounded by an imprecise preoperative diagnosis. This study shows that wide local excision for benign and borderline and simple mastectomy with or without reconstruction for the malignant PT of the breast are acceptable best surgical options.


Trends and Characteristics of Young Non-Small Cell Lung Cancer Patients in the United States.
Although the median age at diagnosis of non-small cell lung cancer (NSCLC) is 70 years, a subset of patients with NSCLC present at a younger age (<40 years). Little is known about the time-trends in incidence of NSCLC in the young, their characteristics and outcomes. The surveillance, epidemiology, and end results database was used to extract NSCLC cases from 1978 to 2010. Yearly incidence rates in various age groups, race, site of disease, histology, treatment patterns, and outcomes were assessed. We modeled Kaplan-Meyer survival curves stratified by age of presentation. Young patients represented 0.6% of incident NSCLC from 1978 to 2010. The incidence of young NSCLC declined significantly during this time-period. Young NSCLCs had a higher proportion of women (51%), Asians or Pacific Islanders (14%), adenocarcinoma histology (59%) and were more likely to present with distant metastases (68%). The young had better all cause and lung cancer-specific survival than the older patients (median survival for localized, regional, and distant disease: not reached, 28, 9 vs. 46, 17, 5 months; p < 0.001 for all groups). Male sex, non-adenocarcinoma histology, and main bronchial primary were independent negative prognostic factors among the young. In contrast to the overall population, black race was a poor prognostic factor among the young. The incidence of NSCLC in the young decreased from 1978 to 2010. The clinical characteristics of NSCLC in the young, including demographic distribution, treatment, and outcomes are different from those observed in the older patients.


Resected colorectal cancer among Medicare beneficiaries:adoption of FDG PET.
To investigate early adoption and potential predictors of postoperative utilization of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients who underwent colorectal cancer resection between July 2001 and December 2002 (the first 18 months of Centers for Medicare and Medicaid Services [CMS] coverage for FDG PET) and who were observed for 2 years from the date of surgery. This HIPAA-compliant study was exempt from institutional review board approval. Informed consent was waived. This was a retrospective cohort study of FDG PET utilization in patients with colorectal cancer following resection between July 1, 2001 and December 31, 2002. Utilization data were drawn from the Surveillance, Epidemiology and End Results-Medicare files during the first 2 years following colorectal surgery. The primary outcome measure was FDG PET utilization. Covariates included disease-, patient-, and hospital-level characteristics, as well as computed tomography (CT) utilization. Univariate and multiple regression analysis were performed. Of 10630 patients (mean age, 77.5 years) who underwent resection for colorectal cancer during the study period, 1056 (10%) patients underwent at least one FDG PET examination in the 2-year period following surgery. A 41% relative increase in utilization of FDG PET was found among patients who underwent resection early in the study period compared with those who underwent resection late in the study period; this was a significant difference (P < .001). There was no change in CT utilization between these two groups (P = .302). The highest utilization of FDG PET was during the first 6 months following surgery. Significant predictors of higher FDG PET utilization included rectal cancer, later date of initial surgery, higher disease stage, older age, marital status, and lower comorbidity. Substantial growth in utilization of FDG PET within 2 years of surgery was found among patients who underwent surgery during the first 18 months of approved CMS coverage, with the highest rates of utilization occurring within 6 months of surgery and lower rates occurring subsequently over the 2-year period following resection.


How pharmacy and medicine students experience the power differential between professions: "Even if the pharmacist knows better, the doctor's decision goes".
Interprofessional Education (IPE) is one approach to improving communication and collaborative practice between professions, which are essential for the optimal delivery of healthcare. Common barriers include negative attitudes, professional stereotypes, professional cultures and power differentials between professional groups. The aim of this qualitative study was to explore how professional hierarchies and power differentials shape interprofessional interactions between preregistration pharmacy and medicine students. Data were gathered via semi-structured interviews and subject to thematic analysis. Four main themes were identified: Reproducing traditional hierarchies; Social norms around respect; Hierarchies in care values and goals; and Challenging the narrative is possible. Students' interactions with and views of the other profession largely reflected traditional stereotypes and power differentials. Hierarchy was evident in how respect was accorded and in how care values and goals were managed. Despite this, students overwhelmingly perceived and reported a sense of agency in changing the status quo. Emerging professional identity and conceptualisation of future roles is heavily influenced by the hierarchical relationship between the professions and can pose a significant barrier to collaborative practice. Greater support for collaborative interprofessional practice is needed at the level of policy and accreditation in health education and healthcare to ensure greater commitment to change.


Application of periodontal ligament cell sheet for periodontal regeneration: a pilot study in beagle dogs.
The ultimate goal of periodontal treatment is to regenerate the damaged periodontal support. Although periodontal ligament (PDL) cells are essential for periodontal regeneration, few studies have reported the transplantation of periodontal ligament cells to periodontal defects. We developed a new method to apply periodontal ligament cells as a sheet to the defect. The aim of this study was to investigate the periodontal healing after application of the periodontal ligament cell sheet in beagle dogs. Autologous periodontal ligament cells were obtained from extracted premolars of each beagle dog. Periodontal ligament cell sheets were fabricated using a temperature-responsive cell culture dish. Dehiscence defects were surgically created on the buccal surface of the mesial roots of bilateral mandibular first molars of each dog. In the experimental group (five defects), periodontal ligament cell sheet with reinforced hyaluronic acid carrier was applied to the defect. Only the hyaluronic acid carrier was applied to the contralateral side as a control (five defects). Eight weeks after surgery, the animals were sacrificed and decalcified specimens were prepared. Healing of the periodontal defects was evaluated histologically and histometrically. No clinical signs of inflammation or recession of gingiva were observed in both experimental and control groups. In the experimental group, periodontal tissue healing with bone, periodontal ligament and cementum formation was observed in three out of five defects. In the control group, such periodontal tissue formation was not observed except in one defect. Histometric analysis revealed that the formation of new cementum in the experimental group was significantly higher than that in the control group. The periodontal ligament cell sheet has a potential to regenerate periodontal tissue and may become a novel regenerative therapy.


Potential of M-Wave Elicited by Double Pulse for Muscle Fatigue Evaluation in Intermittent Muscle Activation by Functional Electrical Stimulation for Motor Rehabilitation.
Clinical studies on application of functional electrical stimulation (FES) to motor rehabilitation have been increasing. However, muscle fatigue appears early in the course of repetitive movement production training by FES. Although M-wave variables were suggested to be reliable indices of muscle fatigue in long lasting constant electrical stimulation under the isometric condition, the ability of M-wave needs more studies under intermittent stimulation condition, because the intervals between electrical stimulations help recovery of muscle activation level. In this paper, M-waves elicited by double pulses were examined in muscle fatigue evaluation during repetitive movements considering rehabilitation training with surface electrical stimulation. M-waves were measured under the two conditions of repetitive stimulation: knee extension force production under the isometric condition and the dynamic movement condition by knee joint angle control. Amplitude of M-wave elicited by the 2nd pulse of a double pulse decreased during muscle fatigue in both measurement conditions, while the change in M-waves elicited by single pulses in a stimulation burst was not relevant to muscle fatigue in repeated activation with stimulation interval of 1 s. Fatigue index obtained from M-waves elicited by 2nd pulses was suggested to provide good estimation of muscle fatigue during repetitive movements with FES.


Value of quantitative and qualitative analyses of serum and urine cell-free DNA as diagnostic tools for bladder cancer: a meta-analysis.
Background: Qualitative and quantitative analysis of circulating cell-free DNA (cfDNA) is a potential detection method for bladder cancer. Many studies have focused on the reliability of these results, but the conclusions have not been consistent. Methods: We performed a diagnostic meta-analysis to investigate the diagnostic significance of serum and urine cfDNAs with tumor tissues as the standard control. We searched the MEDLINE, EMABASE, and Cochrane Central Controlled Trials Register (CCTR) databases until January 2019. Results: A total of 11 studies involving early and/or advanced bladder cancer were finally included. The overall diagnostic accuracy was measured as follows: pooled sensitivity and specifcity were 0.69 (95%CI: 0.67, 0.71) and 0.72 (95%CI: 0.70, 0.74). Pooled positive likelihood ratio and negative likelihood ratio were 3.10 (95%CI: 2.35, 4.07) and 0.41 (95%CI: 0.34, 0.49). Combined diagnostic odds ratio was 8.26 (95%CI: 5.64, 12.11). A high diagnostic accuracy was demonstrated by the summary receiver operating characteristic curve, with area under the curve of 0.80 (95%CI: 0.77, 0.83). Conclusions: CfDNA assay has high diagnostic value for the detection of bladder cancer. Larger sample studies are needed to further confirm our conclusions and to make this approach more sensitive and specific.


Words describing feelings about death: A comparison of sentiment for self and others and changes over time.
Understanding public attitudes towards death is needed to inform health policies to foster community death awareness and preparedness. Linguistic sentiment analysis of how people describe their feelings about death can add to knowledge gained from traditional self-reports. This study provided the first description of emotive attitudes expressed towards death utilising textual sentiment analysis for the dimensions of valence, arousal and dominance. A linguistic lexicon of sentiment norms was applied to activities conducted in an online course for the general-public designed to generate discussion about death. We analysed the sentiment of words people chose to describe feelings about death, for themselves, for perceptions of the feelings of 'others', and for longitudinal changes over the time-period of exposure to a course about death (n = 1491). The results demonstrated that sadness pervades affective responses to death, and that inevitability, peace, and fear were also frequent reactions. However, words chosen to represent perceptions of others' feelings towards death suggested that participants perceived others as feeling more negative about death than they do themselves. Analysis of valence, arousal and dominance dimensions of sentiment pre-to-post course participation demonstrated that participants chose significantly happier (more positive) valence words, less arousing (calmer) words, and more dominant (in-control) words to express their feelings about death by the course end. This suggests that the course may have been helpful in participants becoming more emotionally accepting in their feelings and attitude towards death. Furthermore, the change over time appeared greater for younger participants, who showed more increase in the dominance (power/control) and pleasantness (valence) in words chosen at course completion. Sentiment analysis of words to describe death usefully extended our understanding of community death attitudes and emotions. Future application of sentiment analysis to other related areas of health policy interest such as attitudes towards Advance Care Planning and palliative care may prove fruitful.


Divide and conquer: real-time maximum likelihood fitting of multiple emitters for super-resolution localization microscopy.
Multi-emitter localization has great potential for maximizing the imaging speed of super-resolution localization microscopy. However, the slow image analysis speed of reported multi-emitter localization algorithms limits their usage in mostly off-line image processing with small image size. Here we adopt the well-known divide and conquer strategy in computer science and present a fitting-based method called QC-STORM for fast multi-emitter localization. Using simulated and experimental data, we verify that QC-STORM is capable of providing real-time full image processing on raw images with 100 µm × 100 µm field of view and 10 ms exposure time, with comparable spatial resolution as the popular fitting-based ThunderSTORM and the up-to-date non-iterative WindSTORM. This study pushes the development and practical use of super-resolution localization microscopy in high-throughput or high-content imaging of cell-to-cell differences or discovering rare events in a large cell population.


Hippocampus and neocortex send and receive predictive information.
A recent paper published in Nature by Yadav and colleagues (Nature 608 (7921): 153-160, 2022) illustrates a fundamental aspect on how different brain areas participate in memory storage and retrieval. After identifying neuron activity in the hippocampus CA1 region specific to multi-modal stimuli that predicted appetitive and aversive unconditioned stimuli (conjunctive stimulus encoding), the authors showed that neurons located in the anterior cingulate cortex dynamically encode the discrete sensory features of the outcome-predictive stimuli during training, and these highly specific feature-based projections can excite or inhibit conjunctive-coding neurons in the hippocampus during retrieval.


Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.
Many subjects with cryptogenic cirrhosis have underlying nonalcoholic steatohepatitis (NASH). The natural history of NASH-related cryptogenic cirrhosis after orthotopic liver transplantation (OLT) is not well defined. A primarily retrospective study of patients with the clinical histological phenotype of NASH-related cirrhosis undergoing OLT was performed. Data were compared with 2 sets of age- and weight-matched controls with (1) primary biliary cirrhosis or primary sclerosing cholangitis or (2) alcoholic liver disease. After OLT, all patients were managed by a standard immunosuppressive protocol. Liver biopsies were performed at 6 and 12 months after OLT and at 1- to 2-year intervals thereafter, as well as when liver enzyme levels were elevated enough to warrant diagnostic biopsy. Twenty-seven subjects with cryptogenic cirrhosis and a clinical histological phenotype of NASH and 3 patients with a long-standing diagnosis of NASH before OLT were included. The 30-day perioperative mortality was 1 in 30 patients. During a median follow-up of 3.5 +/- 2.7 years, 2 additional patients died of sepsis. There was a time-dependent increase in the risk for allograft steatosis that approached 100% by 5 years compared with only an approximately 25% incidence of steatosis in the control groups (P <.009, log-rank test). On multivariate analysis, only the cumulative steroid dose correlated with time to development of allograft steatosis. Three patients developed histological progression from hepatic steatosis to steatohepatitis. Of these, 1 patient developed progressive fibrosis. Four patients experienced at least 1 episode of acute cellular rejection; however, no patient developed chronic rejection or graft failure. In conclusion, nonalcoholic fatty liver disease occurs frequently after OLT in patients with the phenotype of NASH-related cirrhosis. Despite the frequent histological recurrence of disease, clinical outcomes are similar to those of other groups of patients undergoing OLT.