Nonlinear dependence between China's carbon market and stock market: new evidence from quantile coherency and causality-in-quantiles.
This study examines the nonlinear dependence between carbon market and stock market in China under normal and extreme market conditions by employing two novel nonlinear approaches, namely, quantile coherency and causality-in-quantiles methods. Given our results on the overall and sector level of stock market, we find that there is a negative dependence between the two markets under bearish and normal market states in the short- and medium-term respectively, while the dependence becomes positive under bearish and bullish market states in the long-term. Furthermore, we also prove that the Granger causality from carbon market to stock market exists. However, no evident impacts from stock market to carbon market have been found. Additionally, at sector stock market, we discover heterogeneity across market conditions. And emission-intensive sector stock indices are more affected by carbon prices.


Mixed scaling deconstruction in vacuum membrane distillation for desulfurization wastewater treatment by a cascade strategy.
Mineral scaling is one key obstacle to membrane distillation in hypersaline wastewater desalination, but the scaling or fouling mechanism is poorly understood. Addressing this challenge required revealing the foulants layer formation process. In this work, the scaling process was deconstructed with a cascade strategy by stepwise changing the composition of the synthetic desulfurization wastewater. The flux decline curves presented a 3-stage mode in vacuum membrane distillation (VMD). Heterogeneous nucleation of CaMg(CO3)2, CaF2, and CaCO3 was the main incipient scaling mechanism. Mg-Si complex was the leading foulant in 2nd-stage, during which the scaling mechanism shifted from surface to bulk crystallization. The flux decreased sharply for the formation of a thick and compacted scaling layer by the bricklaying of CaSO4 and Mg-Si-BSA complexes in the 3rd-stage. Bulk crystallization was identified as the key scaling mechanism in VMD for the high salinity and concentration multiple. The organic matter had an anti-scaling effect by changing the bulk crystallization. Humic acids (HA) and colloidal silica also contributed to incipient scaling for the high affinity to membrane, bovine serum albumin (BSA) acting as the cement of Mg-Si complexes. Mg altered the Si scaling from polymerization to Mg-Si complex formation, which significantly influence the mixed scaling mechanism. This work deconstructed the mixed scaling process and illuminated the role of main foulants, filling in the knowledge gap on the mixed scaling mechanism in VMD for hypersaline wastewater treatment and recovery.


Surgical wound closure by staples or sutures?: Systematic review.
To compare the effects of sutures and staples for skin closure of surgical wounds. We included published and unpublished randomized controlled trials (RCTs) and cluster-randomized trials comparing staples with sutures. Patients were adults (aged 18 years or over) who had undergone any type of surgery. The primary outcomes were risk of overall and severe wound infection. Secondary outcomes included length of hospital stay, readmission rate, adverse events, patient satisfaction with cosmetic results, postoperative pain. Forty-two very low to low quality RCTs with a total of 11,067 patients were included. Sutures resulted in slightly fewer overall wound infections (4.90%) compared to staples (6.75%) but it is uncertain whether there is a difference between the groups (risk ratio [RR] 1.20, 95% confidence intervals [CI] 0.80-1.79; patients = 9864; studies = 34; I = 70%). The evidence was also insufficient to state a difference in terms of severe wound infection (staples 1.4% vs sutures 1.3%; RR 1.08, 95% CI 0.61-1.89; patients = 3036; studies = 17; I = 0%), grade of satisfaction (RR 0.99, 95% CI 0.91-1.07; patients = 3243; studies = 14; I = 67%) and hospital stay. Staples may increase the risk of adverse events (7.3% for staples vs 3.5% for sutures; RR 2.00, 95% CI 1.44-2.79; patients = 6246; studies = 21; I = 33%), readmission rate (RR 1.28, 95% CI 0.18-9.05; patients = 2466; studies = 5; I = 66%) and postoperative pain (standardized mean difference [SMD] 0.41,95%CI -0.35 to 1.16; I = 88%, patients = 390 patients, studies = 5). Due to the lack of high quality evidence, we could not state if sutures are better than staples in terms of wound infection, readmission rate, adverse events, and postoperative pain. With a low quality of evidence, sutures reduce postoperative pain and improve grade of satisfaction with the cosmetic outcome.


Rhodococcus equi pneumonia in 48 foals: response to antimicrobial therapy.
Case records of 48 foals with pneumonia due to Rhodococcus equi were reviewed. Twenty of the 48 foals survived and 28 died or were euthanized. There was no significant difference between the survivors and non-survivors in the age of onset of illness, duration of illness prior to admission, the mean white blood cell (WBC) count, or the mean plasma fibrinogen content. All foals had R. equi isolated from a tracheobronchial aspirate or lung specimens obtained at necropsy. All organisms were susceptible in vitro (Kirby-Bauer) to erythromycin and gentamicin. Susceptibilities to other drugs were: trimethoprim-sulfamethoxazole (88%), tetracycline (87%), chloramphenicol (83%); 97% were resistant to cephalothin and 83% to penicillin. Thirteen of the 20 surviving foals were treated with erythromycin and/or rifampin. A decline in mortality rate was observed with the introduction of the combination of erythromycin and rifampin. None of the 17 foals treated with penicillin and gentamicin survived. Chronic, active, non-septic synovitis was confirmed in 17 foals. These foals had joint distension with mild or no apparent lameness.


Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers.
Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation on the breast cancer lifetime risk, when adjusted for referral bias. A Dutch national cohort including 1,314 proven BRCA1/2 mutation carriers and covering 54,752 person years. Data were collected by family cancer clinics, via questionnaires and from the national Dutch Cancer Registry. The parent-of-origin effect was assessed using Cox regression analyses, both unadjusted and adjusted for referral bias. Referral bias was operationalized by number of relatives with cancer and by personal cancer history. The mutation was of paternal origin in 330 (42%, P < 0.001) BRCA1 and 222 (42%, P < 0.001) BRCA2 carriers. Paternal origin increased the risk of prevalent breast cancer for BRCA1 [HR, 1.54; 95% confidence interval (CI), 1.19-2.00] and BRCA2 carriers (HR, 1.40; 95% CI, 0.95-2.06). Adjusted for referral bias by several family history factors, these HRs ranged from 1.41 to 1.83 in BRCA1 carriers and 1.27 to 1.62 in BRCA2 carriers. Adjusted for referral bias by personal history, these HRs were 0.66 (95% CI, 0.25-1.71) and 1.14 (95% CI, 0.42-3.15), respectively. A parent-of-origin effect is present after correction for referral bias by family history, but correction for the personal cancer history made the effect disappear. There is no conclusive evidence regarding incorporating a BRCA1/2 parent-of-origin effect in breast cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 25(8); 1251-8. ©2016 AACR.


Clinical and microbiological profile of otomycosis in Lagos, Nigeria.
Otomycosis is a global disease, common in the world's tropical and subtropical regions. The diagnosis is clinical, but mycological examination is required for its confirmation. There is a paucity of published data on otomycosis particularly the aetiologic agents in Nigeria. This study aims to fill in this gap by assessing the clinical presentations, risk factors and aetiologic agents of otomycosis in our setting. This was a prospective study of 126 clinically diagnosed patients and 30 controls. Mycological analysis of debris and swab samples from their external auditory canal was carried out. One hundred and twenty-six patients were recruited, with 162 ear samples collected. There was mycological confirmation of otomycosis in 100 (79.4%) patients (subjects) and 127 (78.4%) specimens. The subjects' age range was 1-80 years, 30.89 ± 21.15 mean age, and 29-year median age. The peak prevalent age of 1-10 years was statistically significant, P = 0.022. The common symptoms in the subjects were itching 86 (86%), ear blockage 84 (84%) and otalgia 73 (73%). Regular ear cleaning 67 (67.0%) was the most common risk factor. Noted aetiologic agents were Aspergillus species 81 (63.8%), Candida species 42 (33.1%) and Yeast 4 (3.1%). Aspergillus flavus (40/127; 31.5%) was the most common fungus isolated. Unilateral otomycosis 73 (73%) was more common than bilateral otomycosis 27 (27%). Otomycosis is common in all ages, and is a commonly unilateral disease. Regular ear cleaning is the most common risk factor. A. flavus was the most common aetiologic agent in this study.


Neck mass and tracheostomy in a young lady depicted by Piero di Cosimo.
Among surgical procedures currently in use, tracheostomy has a particularly long history. The first written description of the procedure is due to Brasavola, and dates from 1546. Piero di Cosimo (1462-1522) was an early Renaissance painter who painted a work traditionally known as Cephalus and Procris or The Death of Procris (1495-1500). In this painting, a vertical tracheostomy can be observed in a young woman lying on the ground. A giant mass can be seen in the lower left neck with superficial venous vessels, suggesting a thyroid malignancy. This appears to be the first detailed depiction of a malignant cervical mass and a possibly therapeutic tracheostomy. We discuss the clinical differential diagnosis and also make some comments from an art history perspective.


Endothelial oxidative stress induced by serum from patients with severe trauma hemorrhage.
Shock induces oxidative stress by ischemia-reperfusion phenomenon. Endothelial cells are involved in the inflammatory response and oxidative stress responsible for microcirculation impairment and organ failure. We examined the potential of serum from patients to induce in vitro reactive oxygen species production by cultured human umbilical vein endothelial cells (HUVECs). Three groups were compared: hemorrhagic shock trauma patients, isolated brain injured patients, and healthy volunteers. In the hemorrhagic shock group we sought a correlation between reactive oxygen species production and severity of shock. Serum was separated and perfused in an in vitro model of perfused HUVECs. Ex vivo reactive oxygen species production was assessed by fluorescence microscopy using dichlorodihydrofluorescein, an intracellular dye oxidized by H2O2. Results are expressed in proportional change from baseline and normalized by protidemia to control for variation related to hemodilution. Reactive oxygen species production by endothelial cells exposed to serum from hemorrhagic shock patients (46.2+/-24.9%) was significantly greater than in those with brain injury (3.9+/-35.1%) and in healthy volunteers (-6.8+/-5.8%). In the hemorrhagic shock group dichlorodihydrofluorescein fluorescence was strongly correlated positively to Simplified Acute Physiology Score II and lactatemia and negatively to [HCO3-]. Serum from trauma patients with hemorrhagic shock induces reactive oxygen species formation in naive endothelial cells which is correlated to shock severity.


Evaluation of importance of cystoscopy in staging gynecologic carcinomas.
Of 265 patients with gynecologic carcinoma undergoing initial evaluation during a 5-year period 238 were staged prospectively with procedures that included cystoscopy. Endometrial carcinoma was noted in 98 patients, none of whom had evidence of bladder extension nor did the clinical stage of disease change after cystoscopy. Of 120 patients with carcinoma of the cervix 7 were found to have extension of tumor to the bladder. The clinical stage was elevated in 3 of these cases but remained unchanged in 4 because of the cytoscopic findings. Of all 238 patients with gynecologic carcinoma 3 (1 per cent) also were found to have unsuspected low grade transitional cell carcinoma of the bladder.


Power as a structural phenomenon.
In an effort to inform empowerment theory and research, this paper provides a structural conception of power. First, we examine the essential features present in three dominant conceptions of power in community psychology: social power, psychopolitical power, and relational power. Next, commonalities in the key features of power identified by these conceptions are explored and pared down to yield a more parsimonious conception of power that is grounded only in the structural pattern of relationships through which resources are exchanged. Drawing on social exchange theory, we offer a method for measuring this streamlined, structural conception of power that allows for its more precise examination. Finally, we discuss the implications of a structural conception and measurement of power for targeting and facilitating empowering processes and evaluating empowered outcomes.


Multi-modality deep forest for hand motion recognition via fusing sEMG and acceleration signals.
Bio-signal based hand motion recognition plays a critical role in the tasks of human-machine interaction, such as the natural control of multifunctional prostheses. Although a large number of classification technologies have been taken to improve the motion recognition accuracy, it is still a challenge to achieve acceptable performance for multiple modality input. This study proposes a multi-modality deep forest (MMDF) framework to identify hand motions, in which surface electromyographic signals (sEMG) and acceleration signals (ACC) are fused at the input level. The proposed MMDF framework constitutes of three main stages, sEMG and ACC feature extraction, feature dimension reduction, and a cascade structure deep forest for classification. A public database "Ninapro DB7" is used to evaluate the performance of the proposed framework, and the experimental results show that it can achieve a significantly higher accuracy than that of competitors. Besides, our experimental results also show that MMDF outperforms other traditional classifiers with the input of the single modality of sEMG signals. In sum, this study verifies that ACC signals can be an excellent supplementary for sEMG, and MMDF is a plausible solution to fuse mulit-modality bio-signals for human motion recognition.


The Hispanic Americans Baseline Alcohol Survey (HABLAS): the association between birthplace, acculturation and alcohol abuse and dependence across Hispanic national groups.
Hispanics are heterogeneous in national origin, evidenced by wide ranges of alcohol abuse and dependence rates across different Hispanic national groups. This paper examines associations between 12-month rates of DSM-IV alcohol abuse and dependence with birthplace and acculturation. The 2006 Hispanic Americans Baseline Alcohol Survey, using a multistage cluster sample design, interviewed 5224 adults (18+ years) in five selected U.S. metropolitan areas: Miami, New York, Philadelphia, Houston, and Los Angeles. Comprehensive data on drinking behavior were collected and the analyses include bivariate and multivariate regression techniques. Alcohol abuse and dependence rates were higher among U.S.-born Puerto Ricans and South/Central Americans compared to their foreign-born counterparts, while no such differences were found for Cuban and Mexican Americans. Overall, those with higher acculturation report higher rates of abuse and dependence (statistically significant only for abuse among Puerto Ricans). Risk factors for abuse include being male and being in the high acculturation group. Risk factors for dependence include being male, being Puerto Rican or Mexican American, having less than a college education, and being U.S.-born. Hispanics were found to share several common risk factors with the larger U.S. population for abuse and dependence, such as male gender, lower education, and lower income.


Measles immunity in employees of a multihospital healthcare provider.
To assess the potential for nosocomial measles transmission by measuring seropositivity among healthcare workers in Utah. Blood specimens were collected for measurement of measles IgG antibody by enzyme immunoassay (EIA). Individuals with undetectable or equivocal antibody levels were considered at risk for infection. Employees were grouped according to the decade of their birth, and analyses of serological findings were done by the Mantel-Haenszel chi-square test for trend. The study was performed in a healthcare organization comprised of six urban and 10 rural hospitals. Employees (n = 5825) were tested regardless of age, history of disease, or immunization. There were 599 employees (10.3%) who were nonimmune. A trend showing age-related differences in immunity was not noted among employees born prior to 1957 (4.7% nonimmune). However, for employees born after that time, there was a significant age-associated increase in the percentage of susceptible individuals (P = 0.00001). The rate of susceptibility was 8.1% for individuals born between 1957 and 1959, 16.3% for individuals born during the 1960s, and 33.7% for those born in the 1970s. We concluded that employees born after 1960 represent a material risk for transmission of measles in the hospital setting. Despite the low percentage of susceptibility among those born before 1957, the 144 susceptible individuals in this group also are at risk for measles transmission. Thus, during periods of increased measles prevalence, we would recommend screening all healthcare workers regardless of age and vaccinating those who are susceptible.


MRI contrast media are used to improve visualization of abnormal structures or lesions in various parts of the body. Introduction.
Until recently it was believed that extracellular gadolinium based contrast agents (Gd-CA) were safe for both the kidneys and all other organs within the dose range up to 0.3mmol/kg body weight. However, in 2006, it was demonstrated that some Gd-CA may trig the development of nephrogenic systemic fibrosis, a generalized fibrotic disorder, in renal failure patients. This sub-section of European Journal of Radiology covers the current knowledge about NSF from many aspects. The prevention of NSF must be given high priority, but it should not lead to a denial of a well-justified, enhanced MRI examination with a stable agent.


NOD/Shi-scid IL2rgamma(null) (NOG) mice more appropriate for humanized mouse models.
"Humanized mice," in which various kinds of human cells and tissues can be engrafted and retain the same functions as in humans, are extremely useful because human diseases can be studied directly. Using the newly combined immunodeficient NOD-scid IL2rgamma(null) mice and Rag2(null) IL2rgamma(null) humanized mice, it has became possible to expand applications because various hematopoietic cells can be differentiated by human hematopoietic stem cell transplantation, and the human immune system can be reconstituted to some degree. This work has attracted attention worldwide, but the development and use of immunodeficient mice in Japan are not very well known or understood. This review describes the history and characteristics of the NOD/Shi-scid IL2rgamma(null) (NOG) and BALB/cA-Rag2(null) IL2rgamma(null) mice that were established in Japan, including our unpublished data from researchers who are currently using these mice. In addition, we also describe the potential development of new immunodeficient mice that can be used as humanized mice in the future.


Robust Non-negative Tensor Factorization, Diffeomorphic Motion Correction, and Functional Statistics to Understand Fixation in Fluorescence Microscopy.
Fixation is essential for preserving cellular morphology in biomedical research. However, it may also affect spectra captured in multispectral fluorescence microscopy, impacting molecular interpretations. To investigate fixation effects on tissue, multispectral fluorescence microscopy images of pairs of samples with and without fixation are captured. Each pixel might exhibit overlapping spectra, creating a blind source separation problem approachable with linear unmixing. With multiple excitation wavelengths, unmixing is intuitively extended to tensor factorizations. Yet these approaches are limited by nonlinear effects like attenuation. Further, light exposure during image acquisition introduces subtle Brownian motion between image channels of non-fixed tissue. Finally, hypothesis testing for spectral differences due to fixation is nontrivial as retrieved spectra are paired sequential samples. To these ends, we present three contributions, (1) a novel robust non-negative tensor factorization using the β-divergence and L 2,1-norm, which decomposes the data into a low-rank multilinear and group-sparse non-multilinear tensor without making any explicit nonlinear modeling choices or assumptions on noise statistics; (2) a diffeomorphic atlas-based strategy for motion correction; (3) a non-parametric hypothesis testing framework for paired sequential data using functional principal component analysis.


Early hyperreactive malarial splenomegaly and risk factors for evolution into the full-blown syndrome: a single-centre, retrospective, longitudinal study.
The hyperreactive malarial splenomegaly (HMS) represents a chronic, potentially fatal complication of malaria. Case definition includes: gross splenomegaly, high level of anti-malarial antibody and IgM, response to long-term anti-malarial prophylaxis. In this study, a large series of patients not fully meeting the case definition was tentatively classified as early hyperreactive malarial splenomegaly (e-HMS). The main research questions was: does "e-HMS" tend to evolve to the full-blown syndrome? And if so, what are the main factors influencing this evolution? Retrospective, longitudinal study. The patient database was searched to retrieve all potentially eligible patients. e-HMS was defined by splenomegaly of any size (with or without raised IgM), high anti-malarial antibody titre and exclusion of other causes of splenomegaly. The clinical outcome at following visits was analysed in relation to re-exposure to malaria, and to treatment (only part of the patients with e-HMS were treated with a single anti-malarial treatment and advised to follow an effective anti-malarial prophylaxis, if re-exposed). The association of the outcome with the main independent variables was first assessed with univariate analysis. A stepwise logistic regression model was then performed to study the association of the outcome with the main independent variables. One hundred and twenty-six subjects with e-HMS were retrieved. Eighty-one had at least one follow-up visit. Of 46 re-exposed to malaria for a variable period, 21 (46 %) had progressed, including 10/46 (22 %) evolving to full-blown HMS, while of 29 patients not re-exposed, 24 (93 %) had improved or cured and five (7 %) progressed (p < 0.001). At logistic regression re-exposure was confirmed as a major risk factor of progression (OR 9.458, CI 1.767-50.616) while treatment at initial visit was protective (OR 0.187, CI 0.054-0.650). e-HMS should be regarded as a clinical condition predisposing to HMS. Although the case definition may include false positives, e-HMS should be treated just as the full-blown syndrome. A single anti-malarial treatment is probably adequate, followed by effective prophylaxis for patients exposed again to malaria transmission.


Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene.
Existing animal models of cystic fibrosis (CF) have provided key insights into CF pathogenesis but have been limited by short lifespans, absence of key phenotypes, and/or high maintenance costs. Here, we report the CRISPR/Cas9-mediated generation of CF rabbits, a model with a relatively long lifespan and affordable maintenance and care costs. CF rabbits supplemented solely with oral osmotic laxative had a median survival of approximately 40 days and died of gastrointestinal disease, but therapeutic regimens directed toward restoring gastrointestinal transit extended median survival to approximately 80 days. Surrogate markers of exocrine pancreas disorders were found in CF rabbits with declining health. CFTR expression patterns in WT rabbit airways mimicked humans, with widespread distribution in nasal respiratory and olfactory epithelia, as well as proximal and distal lower airways. CF rabbits exhibited human CF-like abnormalities in the bioelectric properties of the nasal and tracheal epithelia. No spontaneous respiratory disease was detected in young CF rabbits. However, abnormal phenotypes were observed in surviving 1-year-old CF rabbits as compared with WT littermates, and these were especially evident in the nasal respiratory and olfactory epithelium. The CF rabbit model may serve as a useful tool for understanding gut and lung CF pathogenesis and for the practical development of CF therapeutics.


Ethanol effects on female aggression vary with opponent size and time within session.
Female rats displayed different patterns of attack to large and small male intruders into their home cages, as a function of ethanol dose levels. In confrontations with small male intruders, female attack increased significantly at 0.3 g/kg ethanol, declining to saline levels with higher doses (0.6 and 1.2 g/kg). Attack toward large intruders was (nonsignificantly) higher at 0.3 g/kg ethanol, and declined to significantly lower than saline levels with the higher ethanol doses. The attack increases seen with low ethanol doses came in the initial 5-min block of the 30 min test session, and did not persist. These findings suggest that low ethanol doses may especially increase overt aggression in situations in which the tendency to attack is only moderately inhibited by factors such as opponent size or the potential danger of retaliatory attack.


Epidemiology of preeclampsia in Mauritius island.
In Mauritius, the maternal mortality rate (MMR) was 21 per 100000 live births for the year 2001 and this is comparable with figures from developed countries. There has been poor documentation in the area of hypertensive disorders of pregnancy until recently in the island. Consequently, we analysed data from the Ministry of Health. Hypertensive disorders of pregnancy occurred in 6.7% gravidas in 2001. Out of four maternal deaths recorded in 2001, two occurred due to severe eclampsia. In the second part of our study, we scrutinised also the obstetric notes and interviewed 862 hospitalised women from four main hospitals of the island between 1995 and 1997. The majority of women were affected by non-proteinuric hypertension (70%), followed by preeclampsia (24%) and chronic hypertension (6%). Preeclamptic primi and multigravidas developed the condition earlier and also gave birth to growth-retarded babies. Highly significant results supported the relationship between growth retardation and preeclampsia in different parities, irrespective of the length of exposure of the baby in utero. Preeclampsia affects both Indo-Mauritians and Creoles to the same extent, but the latter are much more prone to gestational hypertension. In addition, hypertensive disorders of pregnancy are more a problem of multigravid women in Creoles while they are more classically a condition of primigravidae in Indians.


Modifications in activation of lower limb muscles as a function of initial foot position in cycling.
Cyclic movements, such as walking/cycling, require the activity of spinal-circuits, the central-pattern-generators (CPG). To our knowledge little work has been done to investigate the activation of these circuits, e.g., the muscular and kinematic activity during cycling initiation. This study aims to detail the muscle output properties as a function of the initial lower limb-position using a simple cycling paradigm. Therefore, subjects were required to pedal on a cycle-ergometer in seated position starting at different-crank-angles (0-150°). Surface-electromyography was recorded from the gluteus major (GL), vastus lateralis (VL), and gastrocnemius medialis (GM), while crank position was recorded using a linear-encoder. Gluteus major peak-activity (PA) occurred at 65.0±12.4° when starting with 0° initial crank position (ICP), while occurred maximally at 110.5±2.9 when starting with 70° ICP. Vastus lateralis PA occurred at 40.7±8.8° with 0° ICP, whereas with 70° ICP PA occurred at 103.4±4.0°. Similarly, GM PA occurred at 112.0±10.7° with 0° ICP, whereas with 70° ICP PA occurred at 142.5±4.2° PA. Gluteus major and gastrocnemius medialis showed similar PA phase shifts, which may suggest they are controlled by same local circuitry, in agreement with their common spinal origin, i.e., motoneurons pool in S1-S2.


Three new prenyloxy chromanones from aerial parts of Hypericum aucheri.
Three new prenyloxy chromanone derivatives, aucherine A-C (6, 7 and 9) as well as six known prenylated phloroglucinols (1-5 and 8) were isolated from the aerial parts of Hypericum aucheri Jaub. Et Spach. The structures of the isolated compounds were established by means of spectral techniques (HRESIMS, 1D and 2D NMR). The new compounds were tested on а panel of human tumor cell line using MTT assay. All tested compounds exerted moderate cytotoxicity with IC50 values ranging from 19.6 to 57.8 μM. The influence of the new compounds on some key signaling molecules (procaspase-9 and Bcl-xL), implicated in the regulation of programmed cell death was assessed by Western blot analysis.


Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.
Topical menthol-based analgesics increase skin blood flow (SkBF) through transient receptor potential melastatin 8 (TRPM8) receptor-dependent activation of sensory nerves and endothelium-derived hyperpolarization factors. It is unclear if menthol-induced TRPM8 activation mediates a reflex change in SkBF across the dermatome in an area not directly treated with menthol. The purpose of this study was to determine the effects of localized topical menthol application on SkBF across a common dermatome. We hypothesized that SkBF would be increased with menthol at the site of application and across the dermatome (contralateral limb) through a spinal reflex mechanism. In a double blind, placebo controlled, cross-over design, 15 healthy participants (7 men; age = 22 ± 1 yrs) were treated with direct application (3 ml over 8 × 13 cm) of 5% menthol gel (Biofreeze™) or placebo gel on the L4 dermatome, separated by 48 h. Red blood cell flux was measured using laser Doppler flowmetry over the area of application, on the contralateral leg of the same dermatome, and in a separate dermatome (L5/S1) to serve as control. Cutaneous vascular conductance was calculated for each measurement site (CVC = flux/MAP). At baseline there were no differences in CVC between menthol and placebo gels, or among sites (all p > 0.05). After 30 ± 6 min, CVC increased at the treated site with menthol (0.12 ± 0.02 vs. 1.36 ± 0.19 flux/mm Hg, p < 0.01) but not the placebo (0.10 ± 0.01 vs. 0.18 ± 0.04 flux/mm Hg, p = 0.91). There was a modest increase in CVC at the contralateral L4 dermatome with menthol gel (0.16 ± 0.04 vs. 0.29 ± 0.06 flux/mm Hg, p < 0.01), but not placebo (0.11 ± 0.02 vs. 0.15 ± 0.03 flux/mm Hg, p = 0.41). There was no effect on SkBF from either treatments at the L5/S1 control dermatome (both, p > 0.05), suggesting the lack of a systemic response. In conclusion, menthol containing topical analgesic gels increased SkBF at the treated site, and modestly throughout the dermatome. These data suggest menthol-induced activation of the TRPM8 receptors induces an increase in SkBF across the area of common innervation through a localized spinal reflex mechanism.


Capillary feeding of specific dsRNA induces silencing of the isac gene in nymphal Ixodes scapularis ticks.
Ixodes scapularis transmits several pathogens including Borrelia burgdorferi. Bioactive compounds in tick saliva support tick feeding and influence pathogen transmission to the mammalian host. These studies utilized oral delivery of dsRNA to silence an anticomplement gene (isac) in I. scapularis nymphs. Silencing of isac significantly reduced fed-tick weight compared to delivery of control lacZ dsRNA, and immunoblots specific for FlaB protein indicated a reduction in spirochete load in isac-silenced infected nymphs. SDS-PAGE demonstrated that isac gene silencing affected expression of a number of salivary and non-salivary gland proteins in ticks. Finally, multiple isac cDNA homologues were cloned, and these may represent a new gene family coexpressed during tick feeding. This work presents a novel oral delivery approach for specific gene silencing in I. scapularis nymphs and characterizes the effect of isac on blood-feeding in an attempt to block transmission of B. burgdorferi.


The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation.
In Saccharomyces cerevisiae, several of the proteins involved in the Start decision have been identified; these include the Cdc28 protein kinase and three cyclin-like proteins, Cln1, Cln2 and Cln3. We find that Cln3 is a very unstable, low abundance protein. In contrast, the truncated Cln3-1 protein is stable, suggesting that the PEST-rich C-terminal third of Cln3 is necessary for rapid turnover. Cln3 associates with Cdc28 to form an active kinase complex that phosphorylates Cln3 itself and a co-precipitated substrate of 45 kDa. The cdc34-2 allele, which encodes a defective ubiquitin conjugating enzyme, dramatically increases the kinase activity associated with Cln3, but does not affect the half-life of Cln3. The Cln--Cdc28 complex is inactivated by treatment with non-specific phosphatases; prolonged incubation with ATP restores kinase activity to the dephosphorylated kinase complex. It is thus possible that phosphate residues essential for Cln-Cdc28 kinase activity are added autocatalytically. The multiple post-translational controls on Cln3 activity may help Cln3 tether division to growth.


Avidin traps biotin diffusing out of chicken egg yolk.
1. The unequal distribution of biotin and biotin-binding proteins between the yolk and albumen of freshly laid chicken eggs provides the potential for time-dependent redistribution of biotin that could affect egg quality, biotin availability, and hatchability. 2. Avidin-bound biotin was measured in albumen next to the shell and next to the yolk in eggs stored up to 23 days. 3. Biotin bound to biotin-binding proteins (BBP-I and BBP-II) was measured at the center and periphery of yolk from the same eggs. 4. After 11 days of storage, significant amounts of biotin from the yolk began to accumulate in the albumen adjacent to the yolk. 5. This transfer is attributed to a change in the vitelline membrane that permits diffusion of biotin, not BBP-I or BBP-II, out of the yolk. 6. The dynamics of this phenomenon suggest that in addition to its antimicrobial role, avidin may be involved in the utilization of biotin by the chick embryo.


Prostaglandin production by the progesterone-dominated sheep uterus.
Daily treatment of sheep with progesterone resulted in the accumulation of sterile fluid in the uterus. The fluid contained high concentrations of prostaglandin (PG) F2 alpha but low concentrations of PGE2 and 6-oxo-PGF1 alpha. Uterine venous plasma also contained high concentrations of PGF2 alpha and low concentrations of PGE2. PGF2 alpha was the major PG synthesised by the sheep endometrium, but appreciable quantities of PGE2 and 6-oxo-PGF1 alpha were also formed. The findings of this study suggest that biochemical mechanisms exist in the progesterone-dominated sheep uterus which specifically synthesise and secrete PGF2 alpha.


Soil properties and crop productivity as influenced by flyash incorporation in soil.
Field experiments were carried out during 1996-97 at Gulawathi, Muthiani and Salarpur Villages, IARI Farm, New Delhi and NCPP Campus, Dadri to evaluate changes in soil characteristics and growth of wheat (Triticum aestivum L.), mustard (Brassica juncea L.), lentil (Lence esculenta Moench.), rice (Oryza sativa L.) and maize (Zea mays L.) by varying amounts of flyash addition (up to 50t ha(-1)) in soils at sowing/transplanting time of crops. Flyash addition in areas adjoining NCPP Thermal Power Plant, Dadri, Ghaziabad, U.P. ranged from 5-12 t ha(-1)] yr(-1) in 1995-96. Shoot and root growth and yield of test crops at different locations after flyash incorporation resulted in beneficial effects of flyash addition in most cases. The silt dominant texture of flyash improved loamy sand to sandy loam textures of the surface soils at the farmers' fields. The increased growth in yield of crops with flyash incorporation was possibly due to modifications in soil moisture retention and transmission characteristics, bulk density, physico-chemical characters such as pH and EC and organic carbon content. The response of flyash addition in the soil on soil health and crop productivity needs to be evaluated on long-term sustainable aspects.


Refining the role of preoperative C-reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma.
Elevated inflammatory biomarkers such as C-reactive protein (CRP) and the recently identified neutrophil/lymphocyte ratio (NLR) were demonstrated to be associated with prognosis in human cancers. The aim of our present study is to analyze the relationship of preoperative levels of CRP and NLR with clinicopathological factors and prognosis in oral squamous cell carcinoma (OSCC) patients. Retrospective study. This study was performed on 226 OSCC patients between July 2007 and April 2012. Their serum CRP levels and NLR were measured preoperatively. CRP level ≥ 5.0 mg/L was significantly associated with NLR ≥ 2.44 (linear regression, P < .001). Elevated CRP and NLR were significantly associated with pathological tumor status (P < .001), pathologic nodal metastasis (P < .001), tumor depth (≥10 mm vs. <10 mm, P < .001), disease-free survival (P < .001), and overall survival (P = .001). The influence of CRP level and NLR on disease-free survival (hazard ratio [HR] = 2.259, 95% confidence interval [CI] = 1.170-4.361) and overall survival (HR = 2.176, 95% CI = 1.116-4.245]) still existed after adjusting for tumor status, lymph node metastasis, and tumor cell differentiation. The present study demonstrates that elevated CRP is an independent prognostic factor in OSCC. Elevated NLR in the high CRP group identifies patients at high risks of recurrence and shorter survival. Incorporating NLR into CRP level therefore has significant potential as a biomarker for risk stratification in OSCC.


Degradation performance of biodegradable Fe-Mn-C(-Pd) alloys.
Biodegradable metals offer great potential in circumventing the long-term risks and side effects of medical implants. Austenitic Fe-Mn-C-Pd alloys feature a well-balanced combination of high strength and considerable ductility which make them attractive for use as degradable implant material. The focus of this study is the evaluation of the degradation performance of these alloys by means of immersion testing and electrochemical impedance spectroscopy in simulated body fluid. The Fe-Mn-C-Pd alloys are characterized by an increased degradation rate compared to pure Fe, as revealed by both techniques. Electrochemical measurements turned out to be a sensitive tool for investigating the degradation behavior. They not only show that the polarization resistance is a measure of corrosion tendency, but also provide information on the evolution of the degradation product layers. The mass loss data from immersion tests indicate a decreasing degradation rate for longer times due to the formation of degradation products on the sample surfaces. The results are discussed in detail in terms of the degradation mechanism of Fe-based alloys in physiological media.


A cerebellar projection onto the pontine nuclei in the albino rat.
Following removal of a significant part of the dentate nucleus and most of the interpositus nucleus in the rat cerebellum degenerated cerebellopontine fibres are shown to end in three fairly restricted regions in the contralateral pontine gray: in the paramedian position, in the middle and in the lateral third. The three regions are arranged in rostro-caudal longitudinal columns in the caudal three-quarters of the pons and these columns are continuous with one another by regions of scattered degeneration. The fibres appear to end in relation to distal dendrites of the pontine cells.


Genetic differences between primary larynx and pharynx carcinomas and their matched lymph node metastases by multiplex ligation-dependent probe amplification.
Lymph nodes metastasis is a major risk factor related to poor survival in larynx and pharynx carcinomas. The aim of this study is to search for markers of lymph node involvement analyzing the genetic differences between primary larynx and pharynx squamous cell carcinomas and their corresponding lymph node metastases. Twenty-five primary tumors and their corresponding lymph node metastases were examined. DNA copy number changes of 37 genes were analyzed by multiplex ligation-dependent probe amplification (MLPA). Loss of CDKN2A (9p21) occurred in 14 out of 25 pairs (56%) of primary tumor and lymph node metastases. Loss of LMNA (1q21) was exclusively detected in 8 lymph node samples (32%). Loss of CTNNB1 (3p22) and gain of CDKN2D (19p13) were also significantly more frequent in lymph node metastases. Other aberrations related to lymph node metastases were loss of MFHAS1 (8p23), RECQL4 (8q24) and gain of N33 (8p22) and TP53 (17p13). Primary tumor and corresponding lymph node metastases showed common genetic changes. However, the lymph node metastases presented with a number of additional alterations. Acquisition of these alterations may play a role in lymphatic metastasis development.


PaMADS7, a MADS-box transcription factor, regulates sweet cherry fruit ripening and softening.
E-class MADS-box transcription factors, SEPALLATA (SEP) genes have an important role in floral organ initiation and development and fruit ripening. In this study, four sweet cherry SEP-like genes (PaMADS2, PaMADS4, PaMADS5, and PaMADS7) were cloned and functionally characterized. Gene expression analysis showed that the differential expression levels of PaMADS4 and PaMADS7 coincided with fruit ripening, and expression of PaMADS2 and PaMADS5 did not. Expression of PaMADS7 was affected by ABA and IAA. Subcellular localization assay demonstrated that four sweet cherry SEP-like proteins were all localized inside the nucleus. Silencing PaMADS7 using TRV-mediated virus-induced gene silencing inhibited fruit ripening and influenced major ripening-related physiological processes, such as ABA content, soluble sugar contents, fruit firmness, and anthocyanin content, as well as expression of ripening-related genes. In addition, silencing of PaMADS7 induced phenotype defects that suppressed fruit ripening, which were rescued by exogenous ABA. Furthermore, yeast one-hybrid assay (Y1H) and transient expression analyses revealed that PaMADS7 directly binds to the promoter of PaPG1, which is involved in sweet cherry fruit softening, and positively activated PaPG1expression. These results showed that PaMADS7 is an indispensable positive regulator of sweet cherry fruit ripening and softening.


Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes.
This study determined whether the decrease in pancreatic triacylglycerol during weight loss in type 2 diabetes mellitus (T2DM) is simply reflective of whole-body fat or specific to diabetes and associated with the simultaneous recovery of insulin secretory function. Individuals listed for gastric bypass surgery who had T2DM or normal glucose tolerance (NGT) matched for age, weight, and sex were studied before and 8 weeks after surgery. Pancreas and liver triacylglycerol were quantified using in-phase, out-of-phase MRI. Also measured were the first-phase insulin response to a stepped intravenous glucose infusion, hepatic insulin sensitivity, and glycemic and incretin responses to a semisolid test meal. Weight loss after surgery was similar (NGT: 12.8 ± 0.8% and T2DM: 13.6 ± 0.7%) as was the change in fat mass (56.7 ± 3.3 to 45.4 ± 2.3 vs. 56.6 ± 2.4 to 43.0 ± 2.4 kg). Pancreatic triacylglycerol did not change in NGT (5.1 ± 0.2 to 5.5 ± 0.4%) but decreased in the group with T2DM (6.6 ± 0.5 to 5.4 ± 0.4%; P = 0.007). First-phase insulin response to a stepped intravenous glucose infusion did not change in NGT (0.24 [0.13-0.46] to 0.23 [0.19-0.37] nmol ⋅ min(-1) ⋅ m(-2)) but normalized in T2DM (0.08 [-0.01 to -0.10] to 0.22 [0.07-0.30]) nmol ⋅ min(-1) ⋅ m(-2) at week 8 (P = 0.005). No differential effect of incretin secretion was observed after gastric bypass, with more rapid glucose absorption bringing about equivalently enhanced glucagon-like peptide 1 secretion in the two groups. The fall in intrapancreatic triacylglycerol in T2DM, which occurs during weight loss, is associated with the condition itself rather than decreased total body fat.


Effects of streptozotocin-diabetes on rat intestinal mucin and goblet cells.
Intestinal mucin and goblet cells were examined in streptozotocin-diabetic rats and age-matched controls. Mucin (tissue content and secretion) was measured using a highly specific enzyme-linked immunoassay. In contrast to the increased protein to deoxyribonucleic acid ratio, an absolute decrease was observed in the mucin to deoxyribonucleic acid ratio in mucosal homogenates of the diabetic intestine. This was not due to a loss of goblet cells as their numbers per crypt-villus unit increased in diabetic rats (in proportion to the rise in enterocyte numbers and crypt-villus length). Histochemically, goblet cell mucin was unchanged in diabetes. After a 90-min incubation of everted intestinal segments in Krebs' buffer, pH 7.4, at 37 degrees C, the amount of mucin released into the medium was the same in diabetic and control rats when expressed relative to tissue deoxyribonucleic acid. However, secreted mucin represented a significantly larger proportion of the total tissue mucin content in diabetic animals. Thus, to maintain mucin output at normal levels, the rate of mucin secretion is apparently increased in the diabetic intestine, despite (or perhaps causing) a large decrease in the tissue mucin content.


Effect of chronic rosiglitazone, metformin and glyburide treatment on beta-cell mass, function and insulin sensitivity in mZDF rats.
Here we investigate the effect of rosiglitazone (RSG), metformin (MET) and glyburide (GLIB) on plasma glucose levels, beta-cell mass, function and insulin sensitivity in 10-week-old diabetic male Zucker diabetic fatty (mZDF) rats using quantitative morphometry and a mathematical model beta-cell mass, insulin and glucose kinetics (betaIG). At treatment start, 10-week-old diabetic mZDF rats were severely hyperglycaemic and had very low beta-cell function (insulin secretory capacity). RSG treatment significantly lowered plasma glucose levels in 67% of the mZDF rats. MET was effective at lowering plasma glucose levels in 33% of the mZDF rats, while GLIB was completely ineffective at lowering blood glucose levels in 10-week-old mZDF rats. RSG treatment prevented the fall in beta-cell mass after 6-8 weeks of treatment accompanied by a significant decrease in beta-cell death while MET treatment had no effect on beta-cell mass. RSG treatment increased insulin sensitivity 10-fold, increased beta-cell function fivefold and modestly increased beta-cell mass 1.4-fold. MET treatment increased insulin sensitivity fourfold, with no significant effect on beta-cell function or mass. Although RSG treatment was highly successful in lowering plasma glucose levels, the 33% of mZDF rats that did not respond to the treatment had significantly lower beta-cell function prior to treatment start compared with the responder group. Thus, the low level of beta-cell function at treatment start may explain why none of these agents were completely effective at lowering blood glucose levels in 10-week-old diabetic mZDF rats. Nevertheless, these data suggest that the preservation of beta-cell mass and improvement in beta-cell function play a role in the overall beneficial effect of RSG in 10-week-old diabetic mZDF rats.


Factors affecting optimal antenatal care utilization in Indonesia: implications for policies and practices.
Most maternal deaths are preventable with good antenatal care. The study aimed to examine factors relevant to optimal frequency of Antenatal Care (ANC) visits in Indonesia using the Indonesian Demographic and Health Survey 2017 data. Our study outcome was optimal numbers of ANC visits (≥ 8 visits). Predictors include age, had pregnancy termination, number of children, education level, employment status, awareness of pregnancy problems, wealth index, residence, region, health insurance coverage, and barriers to reach healthcare facilities. Of 3738 participants, about 60.2% had optimal number of ANC visits. There was an association between optimal ANC utilization and: experiencing pregnancy complications, distance to the healthcare facility, health insurance coverage, residence, region, awareness of pregnancy problems, and the number of children. Policymakers should improve healthcare facilities' availability, expand health insurance coverage, and educate women about the importance of ANC. This finding might be relevant in developing countries with similar health infrastructure situation.


[A 52-year-old woman with acute shock and purpura fulminans. Pneumococcal sepsis].
We report a 52-year-old female patient admitted with fever, chills, and myalgias since the previous day. On the day of admission she had a generalized seizure. The patient had no previous illnesses. Laboratory investigations showed consumptive coagulopathy with clinical manifestations of shock and development of multiple organ failure. Pneumococci were detected in blood cultures. Furthermore the skin showed purpura fulminans all over. The patient died within 24 h after admission in the intensive care unit. On autopsy, in addition to adrenal and myocardial hemorrhages, hypoplasia of the spleen was found. Fulminant pneumococcal sepsis is a life-threatening disease that occurs in patients with risk factors like splenic hypoplasia or asplenia. Sometimes a fulminant pneumococcal sepsis may be the first clinical manifestation of a hitherto unknown splenic hypoplasia. In this context the general recommendation of vaccination against pneumococci in patients with risk factors like splenic hypoplasia or asplenia, in patients older than 60, and in children from 2 months onward has to be emphasized.


Effects of olfactory bulbectomy on neuropeptide gene expression in the rat olfactory/limbic system.
Bilateral olfactory bulbectomy in the rat produces a well-characterized syndrome that is independent of anosmia. This syndrome is reversed by chronic antidepressant administration, which provides the basis for the olfactory bulbectomy model of depression. The present experiments focused on neuropeptide plasticity in central olfactory/limbic structures following olfactory bulbectomy in rats. Male Sprague-Dawley rats received bilateral surgical ablation of the olfactory bulbs, sham surgery, or no surgery and were killed either three, seven, 14 or 28 days later. Relative levels of messenger RNA encoding neuropeptide Y, somatostatin, thyrotropin-releasing hormone, and corticotropin-releasing factor precursors in the forebrain were measured by quantitative in situ hybridization histochemistry using oligonucleotide probes. Prepro-neuropeptide Y messenger RNA levels in the piriform cortex and dentate gyrus were significantly elevated in bulbectomized rats 14 and 28 days after surgery compared to sham-operated and surgically naive rats. Prepro-somatostatin messenger RNA levels in the piriform cortex were marginally increased in bulbectomized rats at these time-points. Thyrotropin-releasing hormone and corticotropin-releasing factor precursor messenger RNA levels were not altered in the brain regions studied. The results indicate that olfactory bulbectomy causes long-term increases in the expression of the neuropeptide Y gene. These findings suggest that neuropeptide Y plasticity in the olfactory/limbic system may contribute to the olfactory bulbectomy syndrome in rats, and they provide further evidence of a role for neuropeptide Y in the pathophysiology of depression.


Alterations in components of the ubiquitin-protein ligase system following maturation of reticulocytes to erythrocytes.
Previous studies have shown that the activity of the ubiquitin-mediated proteolytic system declines markedly following reticulocyte maturation, but the specific alterations responsible for this phenomenon have not been defined. We find that the rate of ATP-dependent degradation of 125I-albumin is reduced 20-fold in lysates of rabbit erythrocytes, as compared to reticulocyte lysates. The activity of the proteolytic system in erythrocyte extracts can be restored by supplementation with components of the ubiquitin-protein ligase system purified from reticulocytes by affinity chromatography. These components are the ubiquitin-carrier protein E2, the activity of which is nearly completely absent, and the ligase E3, the activity of which is partially reduced in erythrocytes. Erythrocyte extracts contain other ligases which attach a single, or a few ubiquitin molecules to proteins; these products are different from the multi-ubiquitin derivatives which are formed by the ligase system of protein breakdown. Mature red cells may thus serve to distinguish between different ubiquitin-protein ligase systems with presumably different functions.


Medical Student Perceptions of Cost-Conscious Care in an Internal Medicine Clerkship: A Thematic Analysis.
Although as much as 87 % of all healthcare spending is directed by physicians, studies have demonstrated that they lack knowledge about the costs of medical care. Similarly, learners have not traditionally received instruction on cost-conscious care. To examine medical students' perceptions of healthcare delivery as it relates to cost consciousness Retrospective qualitative analysis of medical student narratives Third-year medical students during their inpatient internal medicine clerkship Students completed a reflective exercise wherein they were asked to describe a scenario in which a patient experienced lack of attention to cost-conscious care, and were asked to identify solutions and barriers. We analyzed these reflections to learn more about students' awareness and perceptions regarding the practice of cost-conscious care within our medical center. Eighty students submitted the assignment between July and December 2012. The most common problems identified included unnecessary tests and treatments (n = 69) and duplicative tests and treatments (n = 20.) With regards to solutions, students described 82 scenarios, with 125 potential solutions identified. Students most commonly used discussion with the team (speak up, ask why) as the process they would use (n = 28) and most often wanted to focus lab testing (n = 38) as the intervention. The most common barriers to high-value care included increased time and effort (n = 19), ingrained practices (n = 17), and defensive medicine or fear of missing something (n = 18.) Even with minimal clinical experience, medical students were able to identify instances of lack of attention to cost-conscious care as well as potential solutions. Although students identified the hierarchy in healthcare teams as a potential barrier to improving high value care, most students stated they would feel comfortable engaging the team in discussion. Future efforts to empower learners at all levels to question value decisions and to develop and implement solutions may result in improved healthcare.


Stage IVS neuroblastoma.
This is a review of the findings in 10 cases of stage IVS neuroblastoma, that have been observed in the First Surgical Department of Hokkaido University Hospital. The patients under the age of 1 yr in stage IVS neuroblastoma have a favorable prognosis; the survival rate was 70%. The regressions were histologically confirmed as maturation of the neuroblastoma cells to ganglioma cells. The lymphocyte counts and T-cell function were well maintained in the surviving patients but both were markedly reduced in the patients who later died. The treatment should be conservative so that immune mechanisms are not inhibited and should be withheld until respiratory failure or progressive signs toward stage IV are identified.


Evaluation of Artificial Tactile Sense in Mass Detection in Silicone Phantom for the Diagnosis of Prostate Tumor.
We analyzed the kinetic and kinematic variables of artificial tactile and artificial vibrotactile sensing test for mass detection in silicon phantom to determine tactile intensity and speed to obtain the best result in detecting the type and location of the mass. This study has utilized Artificial Tactile Sensing Instrument for Mass Detection (ATSIMD) in cylindrical silicone phantoms. The masses embedded in these samples were inserted in axial and environmental, deep and surface positions. The loading velocity, probe location, and the frequency of the applied force were considered as the independent variables in this study. It was found that for superficial mases the accuracy of detection at low speed 5 mm/sec, although dependent on the probe, but was 50% higher than under other conditions. For deep masses, with increasing mass depth, the accuracy of detection at medium speed of 8 mm/sec was 30% higher than at low speed. Mass detection by ATSIMD used in this study showed maximum efficiency at medium loading velocity. At low and high loading velocities, the dependence of mass detection on the probe location is related to the interaction of the testing method, tissue, and viscoelastic properties of the tissue.


Lethal no-differentiation and the development of the imaginal discs during the larval stage inDrosophilia.
1. Lethal no-differentiation, symboll-nd, is characterised by the failure of some or all of the imaginal buds to continue differentiation during the larval third instar. This is due to abnormal proliferation of the imaginal disc mesoderm. 2. There is a well-defined sequence in the sensitivity of the different organs to the lethal effect, the legs being the most commonly affected, and the genital disc the least commonly. 3. The abnormal proliferation of the mesoderm is preceded by degenerative changes in the lymph glands. 4. The mechanism of differentiation of the imaginal buds is discussed and it is argued that the organisation of the imaginal organs is determined primarily by the mesoderm. 5. It is suggested that the proliferation of the imaginal bud mesoderm is normally inhibited by a "bud-differentiation hormone" secreted by the lymph glands. The requirements of the different imaginal discs from this postulated hormone were represented by a histogram, in fig. 14.


[Modeling atrial and ventricular contractility of the heart muscle. I. Modeling single contractions].
A system of differential equations describing myocardium contractions in isometric and isotonic regimes has been obtained. On the basis of these equations functioning of myocardium was modelled on an electronic computer. An effect has been revealed of the coefficients of rheological equations and activation function on isometric and isotonic contraction of the force/rate ratio. A good agreement between the results of modelling and the experimental data has been observed.


Corneal xanthogranuloma in association with multiple endocrine neoplasia 1: A clinicopathologic case report and review of the literature.
Juvenile xanthogranuloma (JXG) is a benign inflammatory condition of uncertain pathogenesis. It is characterized by skin and ocular involvement - typically in the iris - in children. It has been reported in older age groups and has been also observed to involve other ocular structures such as the cornea and conjunctiva. In this case report, we are presenting an extensive right eye corneal lesion in a 43-year old male which showed the typical histopathological feature of JXG and in association with multiple endocrine neoplasia (type 1). Similar cases in the English-language literature have been also reviewed.


The specificity of neuropsychological impairment in predicting antidepressant non-response in the very old depressed.
In an earlier report, response inhibition predict antidepressant non-response in late-life depression (Sneed et al., 2007). The purpose of this study was to ascertain whether this effect is specific to response inhibition or whether impairment in other cognitive domains also predicts non-response. Older depressed patients (n = 84) enrolled in an 8-week trial of citalopram were classified as impaired or non-impaired relative to the sample on mental status, psychomotor speed, reaction time, spatial judgment, and memory, and contrasted with regard to antidepressant response. Patients who were impaired relative to the sample on digit symbol performance did not respond as quickly to citalopram as those who were unimpaired. By the end of the 8-week trial, however, both groups reached the same level of response. Impairment in other domains had no impact on antidepressant response. Non-response was not attributable to impairment on any of the neuropsychological tests suggesting that antidepressant non-response is specific to impaired response inhibition.


The influence of audiometric configuration on pure-tone, warble-tone and narrow-band noise thresholds of adults with sensorineural hearing losses.
Thresholds measurements for pure tones, warble tones, and narrow-band noise were compared for adult sensorineural hearing-impaired subjects with gradual and sharp audiometric configurations. Results demonstrated that audiometric configuration does not significantly affect the relationship between pure tones and warble tones but does affect the relationship between pure tones and narrow-band noise. Differences were most apparent at the higher frequencies. Clinical implications are discussed.


Free educational material on the EULAR school of rheumatology website.
There is lots of educational content including free educational material for all those interested in rheumatic and musculoskeletal diseases (RMDs) on the EULAR School of Rheumatology (ESOR) website. It's easy to access and just three clicks can take you straight to the content you need. Search for ESOR in your web browser (1), click on 'catalog', click on 'free learning material'. Choose what you need, one more click, and you're there. In particular, the EULAR imaging library and EULAR learning material for RA will give you lots of images and slides to help with your presentations. EULAR has a long history of providing education for rheumatologists, health professionals in rheumatology and people with RMDs. This commitment to education is enshrined in the EULAR strategy and will always be a large part of what EULAR does.


Comparison of two immunoassays in the determination of IGF-I levels and its correlation with oral glucose tolerance test (OGTT) and with clinical symptoms in acromegalic patients.
The aim of our study was to evaluate two different methodologies in IGF-I levels determination, its correlation with GH nadir in OGTT <1 and <0.4 ng/ml and with clinical symptoms in acromegalic patients. We analyzed 37 patients. Sixteen patients had not undergone any kind of treatment (Group 1). Twenty-one patients underwent surgery as primary treatment, and after that, some of them another kind of treatment (except pegvisomant) (Group 2). Serum IGF-I levels were measured by Immulite-1000 (IMM) and by an immunoradiometric assay (DSL) and, GH by immunochemiluminometric assay. IGF-I levels by IMM and by DSL showed a significant difference. When we analyzed in both groups the concordance by crosstabs-Kappa coefficients, between different parameters, GH nadir <1 and <0.4 ng/ml with IGF-I by DSL and IMM showed concordance in group 1, but in group 2 only GH nadir <1 and <0.4 ng/ml had a weak concordance with IGF-I by IMM. When we analyzed clinical symptoms in the patients and, GH nadir <1 and <0.4 ng/ml and IGF-I levels by both methodologies, more than 90% of clinically active patients had abnormal GH response or/and elevated IGF-I levels in group 1, but less than 70% in group 2. In the 8 patients under medical treatment, GH nadir was higher than 0.4 ng/ml in all patients, and IGF-I levels were elevated in 8/8 by DSL and in 6/8 by IMM. In conclusion, discrepant GH and IGF-I levels in the diagnosis and follow-up of patients with acromegaly requires consideration of many factors that influence these parameters.


Performance of a multidisciplinary team and the impact of bundles for reducing health care associated infections in adult intensive care unit: 22 years of experience.
A retrospective cohort study was conducted to evaluate the bundle of techniques developed by the multidisciplinary team to minimize infections in an adult intensive care unit over a 22-year span. Two periods were analyzed: 1996-2006 and 2007-2017. Bloodstream infections, urinary tract infections, and ventilator-associated pneumonia declined 58.6%, 56.7%, and 82.6%, respectively (P < .05) from 2007 to 2017 compared with these same infections during 1996-2006.


Protective role of hydrogen peroxide pretreatment on defense systems and BnMP1 gene expression in Cr(VI)-stressed canola seedlings.
To evaluate the ameliorating effects of hydrogen peroxide (H2O2, 200 μM) on hexavalent chromium [Cr(VI)] toxicity in canola (Brassica napus L.), we focused on the plant growth, chlorophyll content, thiol contents, lipid peroxidation, antioxidant enzymes, and the expression of metallothionein protein (BnMP1) mRNA. Cr(VI) at 50 μM significantly decreased the plant growth (fresh and dry weights). The decrease in growth was accompanied by increased lipid peroxidation and decreased chlorophyll content in leaves. Hydrogen peroxide pretreatment, however, enhanced plant growth parameters and led to the reduced levels of lipid peroxidation and higher levels of pigment. In addition, H2O2 pretreatment increased Cr accumulation in aerial parts of seedlings. The tendency of increase in thiol content under Cr(VI) stress was further increased with H2O2 pretreatment. The activities of antioxidant enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (POD) and catalase (CAT) were differentially altered. SOD and POD activities increased under Cr(VI) stress, whereas APX and CAT activities decreased. The SOD and CAT activities remained unaffected in both durations due to H2O2 pretreatment, but activities of APX and POD were promoted in the Cr(VI)-stressed seedlings. Metallothioneins are a family of low-molecular-weight Cys-rich proteins and are thought to play a possible role in metal metabolism or detoxification. In real-time quantitative PCR analysis, the expression level of BnMP1 mRNA was increased at 1 day after treatment (DAT), whereas it was decreased at 7 DAT in Cr(VI)-stressed seedlings. At 1 DAT, pretreatment of H2O2 before Cr(VI) stress reduced the expression of BnMP1 mRNA as compared to Cr(VI) stress alone, but this effect was not significant. At 7 DAT, H2O2 pretreatment alleviated the Cr(VI) stress-mediated decrease in the expression of BnMP1 mRNA. These results suggest that H2O2 may act as a signal that triggers defense mechanisms which in turn protects canola seedlings from Cr(VI)-induced oxidative damage.


Thrombocytopenia (TCP), MELD Score, and Fibrosis Index (FI) Among Hospitalized Patients with Chronic Liver Disease (CLD) in Ma'abar City, Dhamar Governorate, Yemen: A Cross-Sectional Study.
This study sought to assess the prevalence of thrombocytopenia (TCP), underlying aetiologies of chronic liver disease, and the grading and prognostic systems for chronic liver disease (CLD) using non-invasive biomarkers: the Fibrosis index and the Model for End-Stage Liver Disease-Na (MELD-Na) Score, respectively. This was a 15-month multi-centric cross-sectional study of 105 patients with chronic liver disease (CLD). The study was conducted using Sept 2019 to Nov 2020 admission records of CLD patients from Ma'abar City in Dhamar Governorate, Yemen. A total of 63 (60%) and 42 (40%) patients were identified as thrombocytopenic and non-thrombocytopenic, respectively. The means ± SD of the MELD score and FI were 19 ± 7.302 and 4.1 ± 1.06. TCP prevalence among leukopenic and non-leukopenic patients was 89.5% and 53.5%, respectively (P = 0.004). Likewise, the prevalence of traditional-ultrasonography-diagnosed cirrhotic patients needing liver transplantation (LT) was 82.3% versus 61.3% among corresponding non-cirrhotic patients (P = 0.000). The prevalence of TCP among the participants of this study was similar to the global rate. However, the prevalence of decompensation was much higher among CLD patients than that found elsewhere, highlighting a need to improve methods for the early diagnosis of CLD in Yemen. This study also identified problems with the diagnostic work-up for non-infectious aetiologies of CLD. The findings suggest the need to improve clinician awareness about effective diagnostic strategies for these aetiologies.


Noncoding RNAs and cancer.
The study of miRNAs and other noncoding RNAs has revolutionised our understanding of gene expression regulation during cancer development and progression, creating one of the fastest-growing research fields in cancer with realistic therapeutic potential. The 2011 Non-coding RNAs and Cancer Symposium hosted by the University College London Cancer Institute focused on the function and regulation of noncoding RNAs during oncogenesis.


Abnormal gray matter structure in children and adolescents with high-functioning autism spectrum disorder.
The present study aimed to explore the brain structural mechanisms underlying clinical dysfunction in patients with ASD using magnetic resonance imaging (MRI). After screening T1 structural images from the Autism Brain Imaging Data Exchange (ABIDE) database, 111 children and adolescents with high-functioning ASD and 151 typically developing (TD) subjects matched were included in this study. We first compared the differences in gray matter volume (GMV) and gray matter density (GMD) between the two groups. Then, the relationships between GMV/GMD and clinical assessments in ASD patients were evaluated. We found that compared with the TD group, the ASD group showed increased GMV/GMD in the precuneus, thalamus, hippocampus and cingulate gyrus. Moreover, in the ASD group, social interaction was negatively correlated with GMD in the bilateral superior temporal gyrus and limbic system; communication was positively correlated with GMD in the right middle temporal gyrus, inferior frontal gyrus, and anterior cingulate gyrus; and repetitive behavior was positively correlated with GMD in the cerebellum and negatively correlated with GMV in the prefrontal cortex. In conclusion, the gray matter structure in children and adolescents with ASD was abnormal, and different clinical dysfunctions in ASD patients were related to structural abnormalities in specific regions.


Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease.
Numerous investigations point to the importance of oxidative imbalance in mediating AD pathogenesis. Accumulated evidence indicates that lipid peroxidation is an early event during the evolution of the disease and occurs in patients with mild cognitive impairment (MCI). Because MCI represents a condition of increased risk for Alzheimer's disease (AD), early detection of disease markers is under investigation. Previously we showed that HNE-modified proteins, markers of lipid peroxidation, are elevated in MCI hippocampus and inferior parietal lobule compared to controls. Using a redox proteomic approach, we now report the identity of 11 HNE-modified proteins that had significantly elevated HNE levels in MCI patients compared with controls that span both brain regions: Neuropolypeptide h3, carbonyl reductase (NADPH), alpha-enolase, lactate dehydrogenase B, phosphoglycerate kinase, heat shock protein 70, ATP synthase alpha chain, pyruvate kinase, actin, elongation factor Tu, and translation initiation factor alpha. The enzyme activities of lactate dehydrogenase, ATP synthase, and pyruvate kinase were decreased in MCI subjects compared with controls, suggesting a direct correlation between oxidative damage and impaired enzyme activity. We suggest that impairment of target proteins through the production of HNE adducts leads to protein dysfunction and eventually neuronal death, thus contributing to the biological events that may lead MCI patients to progress to AD.


Shining light on the chloroplast protein import machinery of plants.
Sunny days for chloroplast protein import: Srinivasan et al. (2023) report on the isolation and provide the first structural information on the pea TOC complex that mediates protein translocation across the outer chloroplast membrane. While two cryoEM structures for algal import complexes have been published, this is the gateway to long-sought-after structures from land plants.


Microplastic accumulation in commercial fish from the Adriatic Sea.
We assessed the presence and concentration of microplastics in fishes from the Northern Adriatic Sea on sale for human consumption. Microplastics were extracted from the digestive tract of 180 specimens, belonging to 6 different species (2 pelagic, and 4 demersal). Microplastics were identified through Nile red staining, and selected particles were analyzed by μ-Raman spectroscopy. The 47.8% of examined fish were found to contain microplastics (233 fragments). The mean concentration of microplastics in the 6 species ranged between 4.11 ± 2.85 items/individual in Adriatic soles, and 1.75 ± 0.71 items/individual in pilchards. Microplastics ranged in size between 0.054 mm and 0.765 mm. Polyethylene and polypropylene were the polymer types identified through μ-Raman spectroscopy. Despite our estimates are underestimations, these results are of particular concern, as the fish analyzed are consumed without being eviscerated, and the microplastics they contain are transferred directly to humans.


Surgical treatment of sacral chordoma: survival and prognostic factors.
Sacral chordoma is a rare low-to-intermediate grade malignant tumour. The mainstay of treatment is still surgery with en bloc and wide resection margins, which can grant the best chances of a long-term control or cure of this disease. The first aim of this paper is to collect data about survival, time to local recurrence and metastasis among patients affected by sacral chordoma and primarily treated with surgery. The second aim is to analyze the influence of level resection, tumor volume and surgical margins on local recurrence. The study population was composed of 14 patients treated with sacral chordoma resection at the National Tumour Institute of Naples-Pascale (Italy) from January 2000 to June 2013. The median follow-up was 84 months (range 24-132 months). The follow-up was characterized by: standard radiographs, MRI, and a CT scan of the chest annually. Time to recurrence or metastasis was calculated from the date of resection to the date of diagnosis of first recurrence or metastasis. Out of all the patients, six died (42.86 %) during the follow-up; 6 (42.86 %) had local recurrence; 4 (28.57 %) had metastasis. At univariate analysis wide surgical margins (R0) were associated with increased survival up to a local recurrence (OR = 0.0286; 95 % CI = 0.0014-0.5739; P = 0.026); the level of resection (OR = 3.33; 95 % CI = 0.3619-30.7025; P = 0.592) and tumour volume (P = 1) did not show a statistically significant correlation. Based on our experience, we hope all patients to be treated by surgery, the only good standard treatment of this disease. The resection should result in margins as wide as possible. For these reasons, it is essential for this disease to be treated in highly specialized centres because only a complete surgery can offer a chance to care for these patients. Solid survival at long-term follow-up can be achieved by a surgical resection performed with wide margins.


Driving the cell cycle to cancer.
Cell cycle progression requires the co-ordinated activation of several kinases, some of which are activated upon the binding of a cyclin subunit. At least four of these so-called cyclin-dependent kinases, namely Cdk4, Cdk6, Cdk2 and Cdk1, have specific roles at particular stages of the cell cycle, including passage through the various cell cycle transitions and the response to specific checkpoints. Not surprisingly, most human tumors carry mutations that deregulate at least one of these kinases. To analyze their specific role in vivo, we are generating strains of gene-targeted mice carrying either activated or defective alleles of these Cdks. As an example, Cdk4 expression appears to be expendable in most cell types since mice lacking Cdk4 are viable. Yet, Cdk4 mutant mice are smaller in size and infertile (only partial infertility in males). In addition, Cdk4 defective mice develop insulin dependent diabetes early in life. However, the importance of these Cdks in tumor cell cycles is underscored by the phenotype of knock in mice where the normal Cdk4 gene has been replaced by a Cdk4 R24C (insensitive to INK inhibitors) mutant. These animals develop a wide spectrum of spontaneous tumors and are highly susceptible to specific carcinogenic treatments. These models are being used now to understand how deregulation of these Cdks leads to cancer development and will be a valuable tool to design and validate new therapeutic strategies against tumour development.


Elucidation of cellulose accessibility, hydrolysability and reactivity as the major limitations in the enzymatic hydrolysis of cellulose.
The precipitous decline in the rates of enzymatic hydrolysis of cellulose with conversion is one of the major limitations to the commercialization of second-generation biofuel. In this work, various rate-limiting factors (fractal kinetics, changes in crystallinity, accessibility, reactivity and hydrolysable fraction, enzyme clogging, and degree of polymerization) were investigated employing experimental as well as computational studies. Model-guided experiments showed cellulose accessibility and the hydrolysable fraction of accessible substrate (a previously undefined and unreported quantity) to decrease steadily until a conversion level of nearly 70%, while cellulose reactivity, defined in terms of hydrolytic activity per amount of actively adsorbed cellulase, remained constant. Substrate depletion, accessibility and hydrolysability decrease accounted for approximately 90% of rate retardation up to 70% conversion. Faster restart rates were observed on partially converted cellulose as compared to uninterrupted hydrolysis rates, supporting an enzyme clogging phenomenon that could possibly be responsible for the additional rate decrease.


Multiple primary tumors in men with breast cancer diagnoses: a SEER database review.
Male breast cancer (MBC) comprises 1% of all breast cancers and less than 1% of cancer cases in men. After a diagnosis of MBC, men are at risk of developing a second primary cancer, particularly a second primary breast cancer. The objective of this study is to analyze the characteristics of the population of men diagnosed with a second malignancy, specifically a second MBC. Using the Surveillance, Epidemiology, and End Results (SEER) database, 4,873 male patients diagnosed with invasive or in situ breast cancer from 1973 to 2004 were identified and data from patients who developed a second MBC were reviewed. Additional non-breast primary cancer diagnoses were also recorded. A review of 4,966 records corresponding to 4,873 patients revealed 4,462 invasive and 504 in situ breast cancer events. Of the 4,873 patients, 93 (1.9%) were identified with a second MBC. Among the 4,873 patients with MBC, 1,001 (21%) have other non-breast primary cancer diagnoses recorded in the SEER registry. Although MBC is uncommon, these patients are at risk of a contralateral breast cancer and second primary non-breast cancers. Our findings support that men with breast cancer would benefit from continued long-term surveillance for breast cancer and appropriate screening for non-breast cancers.


Midline malignant reticulosis and lymphomatoid granulomatosis. A case report.
A patient had lethal midline granuloma syndrome of the malignant midline reticulosis type. Lymphomatoid granulomatosis of the lung eventually developed that resulted in respiratory failure. There is a histology and biologic behavior associated with these two diseases, and they possibly represent different expressions of the same disease process.


Recognition of novel glycolipid antigens from smooth variants of Mycobacterium tuberculosis.
A major polar and three minor slightly less polar glycolipids were identified in extracts of two smooth (Canetti) strains of Mycobacterium tuberculosis. Immunostaining on thin-layer chromatograms and enzyme-linked immunosorbent assay (ELISA) of purified lipids demonstrated that the major and the two most polar of the minor glycolipids are potent antigens, reacting with homologous antisera and also with that raised against the type strain (H37Rv).


A method for fabricating an occlusal splint for a patient with limited mouth opening.
This article describes the fabrication of an occlusal splint for a patient with limited mouth opening due to temporomandibular disorder. A face-bow fork is used as a tray to obtain an accurate dual-arch impression and occlusal registration.


Effect of ketamine on the minimum infusion rate of propofol needed to prevent motor movement in dogs.
To determine the minimum infusion rate (MIR) of propofol required to prevent movement in response to a noxious stimulus in dogs anesthetized with propofol alone or propofol in combination with a constant rate infusion (CRI) of ketamine. 6 male Beagles. Dogs were anesthetized on 3 occasions, at weekly intervals, with propofol alone (loading dose, 6 mg/kg; initial CRI, 0.45 mg/kg/min), propofol (loading dose, 5 mg/kg; initial CRI, 0.35 mg/kg/min) and a low dose of ketamine (loading dose, 2 mg/kg; CRI, 0.025 mg/kg/min), or propofol (loading dose, 4 mg/kg; initial CRI, 0.3 mg/kg/min) and a high dose of ketamine (loading dose, 3 mg/kg; CRI, 0.05 mg/kg/min). After 60 minutes, the propofol MIR required to prevent movement in response to a noxious electrical stimulus was determined in duplicate. Least squares mean ± SEM propofol MIRs required to prevent movement in response to the noxious stimulus were 0.76 ± 0.1 mg/kg/min, 0.60 ± 0.1 mg/kg/min, and 0.41 ± 0.1 mg/kg/min when dogs were anesthetized with propofol alone, propofol and low-dose ketamine, and propofol and high-dose ketamine, respectively. There were significant decreases in the propofol MIR required to prevent movement in response to the noxious stimulus when dogs were anesthetized with propofol and low-dose ketamine (27 ± 10%) or with propofol and high-dose ketamine (30 ± 10%). Ketamine, at the doses studied, significantly decreased the propofol MIR required to prevent movement in response to a noxious stimulus in dogs.


Mechanisms of opioid-induced tolerance and hyperalgesia.
Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.


Risks of new-onset allergic sensitization and airway inflammation after early age swimming in chlorinated pools.
Irritant chlorination products in swimming pools can cause respiratory problems in swimmers but their possible implication in allergies development is still unclear. To assess prospectively whether early-life attendance at chlorinated pools increases the risks of IgE sensitization and of airways inflammation later during childhood. We conducted a two-year prospective study among 196 kindergarten children (mean age of 5.7 years, 54% of boys). We measured exhaled nitric oxide (eNO) and aeroallergen-specific IgE in nasal mucosa. Parents completed a questionnaire about the child's health, chlorinated pool attendance and potential confounders. Ever swimming at indoor or outdoor chlorinated pools before the age of three years was associated with higher odds for new-onset IgE sensitization to house dust mite (adjusted odds ratio [aOR] 2.93, 95% confidence interval [CI] 1.14-7.55) and for new-onset increased eNO (>15 ppb; aOR, 4.54, 95% CI 1.48-13.9). For both outcomes, aORs increased dose-dependently with time spent in chlorinated pools with values reaching, respectively, 3.60 (95% CI 1.21-10.7) and 5.92 (95% CI 1.72-20.5) when the cumulative pool attendance exceeded 60 h These risks appeared independently of each other, of parental history of allergies and of pre-existing diseases, including eczema, which at baseline was more prevalent in early swimmers (aOR, 2.91; 95% CI 1.23-6.89). Such associations were not seen with IgE sensitization to pollen or cat allergens. Attendance at chlorinated swimming pools in early life is associated with higher risks of new-onset airways inflammation and IgE sensitization to house dust mite, independently of other risk factors.


H2AX haploinsufficiency modifies genomic stability and tumor susceptibility.
Histone H2AX becomes phosphorylated in chromatin domains flanking sites of DNA double-strand breakage associated with gamma-irradiation, meiotic recombination, DNA replication, and antigen receptor rearrangements. Here, we show that loss of a single H2AX allele compromises genomic integrity and enhances the susceptibility to cancer in the absence of p53. In comparison with heterozygotes, tumors arise earlier in the H2AX homozygous null background, and H2AX(-/-) p53(-/-) lymphomas harbor an increased frequency of clonal nonreciprocal translocations and amplifications. These include complex rearrangements that juxtapose the c-myc oncogene to antigen receptor loci. Restoration of the H2AX null allele with wild-type H2AX restores genomic stability and radiation resistance, but this effect is abolished by substitution of the conserved serine phosphorylation sites in H2AX with alanine or glutamic acid residues. Our results establish H2AX as genomic caretaker that requires the function of both gene alleles for optimal protection against tumorigenesis.


The use of hypoxic cultured mesenchymal stem cell for oncolytic virus therapy.
The safety of oncolytic viruses, such as conditionally replicative adenoviruses (CRAds), has been validated in clinical trials for cancer therapy. Their antitumor efficacy is limited by the presence of preexisting neutralizing antibodies (NAbs). Mesenchymal stem cells (MSCs) are attractive as a cellular vehicle to carry antitumor agents, not only because they are easily obtained and expanded to great numbers in vitro, but also because of their ability to migrate and engraft to tumors. MSCs expanded under hypoxic conditions decrease in replicative senescence and increase in proliferation capacity and differentiation potentials. However it remains to be clarified whether these hypoxic MSCs also are good carriers for the delivery of CRAds to tumor cells in the presence of NAbs. This study firstly demonstrated hypoxic MSCs with an increased ability to migrate toward tumors through the upregulation of chemokine receptors, such as CXCR4 and CX3CR1. It is then demonstrated that hypoxic MSCs has the capacity to carry CRAds, without inducing apoptosis, for up to one week. Using an in vitro coculture with human colon cancer cells and with intraperitoneally (i.p.) and subcutaneously (s.c.) developed human colon cancer xenografts, it is demonstrated that hypoxic MSCs are able to protect CRAds from attack by NAbs, thereby successfully delivering them to the target tumor cells. These results show that hypoxic MSCs can serve as cell carriers for CRAds and may help to develop new strategies against cancer.


A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation.
Large pleiomorphic carriers leave the Golgi complex for the plasma membrane by en bloc extrusion of specialized tubular domains, which then undergo fission. Several components of the underlying molecular machinery have been identified, including those involved in the budding/initiation of tubular carrier precursors (for example, the phosphoinositide kinase PI(4)KIIIβ, the GTPase ARF, and FAPP2), and in the fission of these precursors (for example, PKD, CtBP1-S/BARS). However, how these proteins interact to bring about carrier formation is poorly understood. Here, we describe a protein complex that mediates carrier formation and contains budding and fission molecules, as well as other molecules, such as the adaptor protein 14-3-3γ. Specifically, we show that 14-3-3γ dimers bridge CtBP1-S/BARS with PI(4)KIIIβ, and that the resulting complex is stabilized by phosphorylation by PKD and PAK. Disrupting the association of these proteins inhibits the fission of elongating carrier precursors, indicating that this complex couples the carrier budding and fission processes.


Exploring the minimal functional unit of the transporter associated with antigen processing.
TAP, an ABC transporter in the ER membrane, provides antigenic peptides derived from proteasomal degradation to MHC class I molecules for inspection by cytotoxic T lymphocytes at the cell surface so as to trace malignant or infected cells. To investigate the minimal number of transmembrane segments (TMs) required for assembly of the TAP complex based on hydrophobicity algorithms and alignments with other ABC transporters we generated N-terminal truncation variants of human TAP1 and TAP2. As a result, a 6+6 TM core-TAP complex represents the minimal functional unit of the transporter, which is essential and sufficient for heterodimer assembly, peptide binding, and peptide translocation into the ER. The TM1 of both, core-TAP1 and core-TAP2 are critical for heterodimerization of the complex.


Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease.
Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.


Domestic airborne black carbon and exhaled nitric oxide in children in NYC.
Differential exposure to combustion by-products and allergens may partially explain the marked disparity in asthma prevalence (3-18%) among New York City neighborhoods. Subclinical changes in airway inflammation can be measured by fractional exhaled nitric oxide (FeNO). FeNO could be used to test independent effects of these environmental exposures on airway inflammation. Seven- and eight-year-old children from neighborhoods with lower (range 3-9%, n=119) and higher (range 11-18%, n=121) asthma prevalence participated in an asthma case-control study. During home visits, FeNO was measured, and samples of bed dust (allergens) and air (black carbon; BC) were collected. Neighborhood built-environment characteristics were assessed for the 500 m surrounding participants' homes. Airborne BC concentrations in homes correlated with neighborhood asthma prevalence (P<0.001) and neighborhood densities of truck routes (P<0.001) and buildings burning residual oil (P<0.001). FeNO concentrations were higher among asthmatics with than in those without frequent wheeze (≥4 times/year) (P=0.002). FeNO concentrations correlated with domestic BC among children without seroatopy (P=0.012) and with dust mite allergen among children with seroatopy (P=0.020). The association between airborne BC in homes and both neighborhood asthma prevalence and FeNO suggest that further public health interventions on truck emissions standards and residual oil use are warranted.


Impact of access to improved water and sanitation on diarrhea reduction among rural under-five children in low and middle-income countries: a propensity score matched analysis.
Diarrhea, the second leading cause of child morbidity and mortality worldwide, is responsible for more than 90% of deaths in children under 5 years of age in low and middle-income countries (LMICs). The high burden of diarrhea is mainly attributable to the limited access to improved water and sanitation. However, the impacts of improved sanitation and drinking water in preventing diarrheal diseases are not well understood. Therefore, this study estimated both the independent and joint effects of improved sanitation and water on diarrhea occurrence among rural under-five children in LMICs. The current study utilized secondary data from the Demographic and Health Survey (DHS) datasets conducted between 2016 and 2021 in 27 LMICs. A total weighted sample of 330,866 under-five children was included in the study. We employed propensity score matching analysis (PSMA) to examine the effects of accessing improved water and sanitation on childhood diarrheal disease reduction. The prevalence of diarrhea among children under 5 years of age in rural LMICs was 11.02% (95% CI; 10.91%, 11.31%). The probability of developing diarrhea among under-five children from households with improved sanitation and water was 16.6% (Average Treatment Effect on the Treated (ATT) = - 0.166) and 7.4% (ATT = - 0.074) times less likely among those from households with unimproved sanitation and water, respectively. Access to improved water and sanitation is significantly associated with a 24.5% (ATT = - 0.245) reduction of diarrheal disease among under-five children. Improved sanitation and drinking water source reduced the risk of diarrhea among under-five children in LMIC. The effects of both interventions (improved water and sanitation) had a larger impact on the reduction of diarrheal disease than the improvements to water or sanitation alone. Therefore, achieving Sustainable Development Goal 6 (SDG 6) is key to reducing diarrhea among rural under-five children.


Occurrence of PFASs and its effect on soil bacteria at a fire-training area using PFOS-restricted aqueous film-forming foams.
Fire-training areas (FTAs) are an important source of perfluoroalkyl and polyfluoroalkyl substances (PFASs) pollution. However, the effect of PFASs on soil bacterial communities remains limited. Here, we detected the PFASs in soils ranging from 3.4 to 531.7 μg kg-1 dry weight in seven plots at an FTA where PFOS-restricted aqueous film-forming foams (AFFFs) have been used for 6 years. PFOS was still the dominant homologue despite the restriction by Stockholm Convention, but it was almost three orders of magnitude lower than that in previous studies. PFASs played an important role in shaping the bacterial community, and high levels of PFASs (>100 μg kg-1 dw) reduced the biodiversity and connectivity of soil bacteria. The extreme condition-tolerant bacteria were identified as biomarkers at the FTA. Our study provides valuable insights into the effect of PFOS-restricted AFFFs on soil bacterial communities at the FTA.


Influence of diabetes on rat liver mitochondria: decreased unsaturation of phospholipid and D-beta-hydroxybutyrate dehydrogenase activity.
Liver mitochondria and submitochondrial vesicles have been prepared from rats made diabetic by treatment with streptozotocin (diabetic membranes). The membranes were characterized in terms of phospholipid and fatty acid composition, electron transport functions, and D-beta-hydroxybutyrate dehydrogenase activity and compared with mitochondria and submitochondrial vesicles prepared from control animals (control membranes). No change in the phospholipid composition (44% lecithin, 35% phosphatidylethanolamine, and 21% diphosphatidylglycerol) was found, but a marked alteration in fatty acid composition of both the total phospholipid and lecithin occurred within 3 weeks after streptozotozin treatment and persisted thereafter. In lecithin, the 18:1/18:0 ratio decreases approximately 33% and the 20:4/18:2 ratio decreases approximately 55%. D-beta-hydroxybutyrate dehydrogenase is a lipid-requiring enzyme which has a specific requirement of lecithin for function. In diabetic membranes, there is a progressive decrease in D-beta-hydroxybutyrate dehydrogenase activity with time after streptozotocin treatment to about 40% of control value at 15 weeks. In contrast, succinate oxidase and succinate- or NADH-cytochrome c reductase activities remain essentially unaltered. Further, the Arrhenius plot characteristics differ for D-beta-hydroxybutyrate dehydrogenase in diabetic membranes as compared with control membranes, in that the break point of the biphasic plot increases from 20 +/- 1 degree C in controls to 29 +/- 1 degree C in samples from diabetic animals. The change occurs about 3 weeks after streptozotocin treatment and is correlatable with the increased saturation of the fatty acid moiety of the phospholipids. The observed changes in D-beta-hydroxybutyrate dehydrogenase function and phospholipid composition were prevented by administration of insulin to the diabetic animals and are therefore referable to insulin insufficiency.