Hospital-wide first-responder automated external defibrillator programme: 1 year experience.
The first year experience with a hospital-wide first-responder automated external defibrillator (AED) programme implemented in a 683-bed University Hospital is reported. Throughout the hospital, 14 "AED access spots" were identified which could be easily reached from all wards and diagnostic rooms within 30s. AEDs were installed (Lifepak 500; Medtronik PhysioControl Corp., Redmond, USA, equipped with a Biolog 3000i portable ECG monitor; Micromedical Industries Ltd., Labrador, Australia). Within 3 months, 120 medical officers, 750 nurses, and 50 administrative or technical staff underwent a 2h training programme. An AED was applied and activated by nurses/medical staff before the cardiac arrest team arrived in 27 of 33 cases (81.8%) of witnessed cardiac arrest. The median time from onset of the emergency call to the activation of the AED (record of ECG) was on average 2.1 min (range 1.0--4.5 min). In 18 of 27 cases in which the AED was installed promptly, the primary arrest rhythm was either VT or VF, and the AED delivered a shock. For this subgroup, the rate of return of spontaneous circulation and the rate of discharge at home were 88.9 and 55.6%, respectively. This encourages us to extend the concept of first-responder AED-defibrillation throughout our hospital.


[The pulmonary aspiration-washing: new treatment of severe bacterial pneumopathies (author's transl)].
Over the last few years, the apparition of severe broncho-pulmonary suppurations in relation with an often poly-immune bacterial flora presents intricate therapeutic problems. The use of broncho-fibroscopy to enable several focussed cycles of broncho-pulmonary aspiration-washing perfusion, gave us interesting results.


Expired-air carbon monoxide as a predictor of 16-year risk of all-cause, cardiovascular and cancer mortality.
Measurement of expired-air carbon monoxide (EACO) is commonly used to ascertain non-smoking status, although it can also reflect exposures not related to smoking. Our aim was to assess 16-year mortality according to EACO measured at baseline, in a general population. Our analysis was based on the Third French MONICA population survey (1994-1997). Causes of death were obtained 16 years after inclusion, and assessment of determinants of mortality was based on Cox modeling. EACO was measured in 2232 apparently healthy participants aged 35-64. During follow-up, 195 deaths occurred (19% were due to cardio-vascular (CV) causes and 49% to cancer). At baseline, the mean EACO was 11.8 (±7.4)ppm, 4.6 (±2.5)ppm, 4.3 (±2.2)ppm for current, former and never smokers, respectively (P<0.001). After adjustment for main mortality risk factors and smoking, the hazard ratio (HR) for total mortality was 1.03[95% confidence interval: 1.01-1.06] per 1-unit increase in EACO, and it was 1.04[1.01-1.07] for cancer mortality. Adjusted HR for CV mortality was 1.05[1.01-1.10] but did not remain significant after additional adjustment for smoking (0.98[0.91-1.04]). Interactions between EACO and smoking were not significant. In a general population, baseline EACO is an independent predictor of 16-year all-cause and cancer mortality, after adjustment for confounders including smoking. Given that the effect of EACO is similar among smokers and non-smokers, EACO is probably not solely related to smoking but could also be a marker of inhaled ambient carbon monoxide and/or endogenous production. Besides, smoking better predicts CV mortality than EACO.


Apolipoprotein(a) gene polymorphisms (TTTTA)n and G/A-914 affect Lp(a) levels in ischemic heart disease patients from Serbia.
Lipoprotein(a) (Lp(a)) concentration is determined primarily by the apolipoprotein(a) (apo(a)) gene. The pentanucleotide (TTTTA)n repeat and G/A-914 polymorphisms are in the 5' promoter region of the apo(a) gene. To elucidate whether these polymorphisms affect Lp(a) levels, a total of 211 Serbian adults were investigated. One hundred and eleven patients with ischemic heart disease and 100 healthy controls were genotyped and Lp(a) levels determined. Lp(a) concentrations differed according to the (TTTTA)n genotypes: among those having at least one allele 8, patients had significantly higher Lp(a) values than controls. A decreasing trend of Lp(a) values was associated with the -914A allele in controls but the opposite was true in patients. Patients with genotype TTTTA allele 8/AA-914 had significantly higher Lp(a) values than those without allele 8/AA (p < 0.05). The >8>8/GG genotype was not detected. Significant linkage disequilibrium between (TTTTA)n and G/A-914 polymorphism (p < 0.001) was found. In multivariate regression analysis, the G/A-914 polymorphism significantly (p < 0.05) affected Lp(a) levels in patients, after taking into account the (TTTTA)n polymorphism. These results indicate that (TTTTA)n and G/A-914 polymorphisms affect Lp(a) levels in ischemic heart disease as a consequence of the linkage disequlibrium.


[Basicervical ectopic goiter associated with a eutopic thyroid gland: a case report].
Thyroid gland is an endocrine gland playing a major role in energy and phosphocalcic metabolism, among others. It commonly occurs in the anterior cervical and pretracheal region. Ectopic thyroid is quite rare. It is dominated by ectopic basilingual thyroid. We here report the case of a patient with goiter in normal cervical position (eutopic) and ectopic thyroid tissue in basicervical position. Cervicotomy revealed the ectopic nodule and the diagnosis was confirmed by histology. This clinical case illustrates a differential diagnosis of cervical masses.


Ligamentum teres hepatis wrapping of the gastroduodenal artery stump for protection in total laparoscopic pancreaticoduodenectomy: a single-center experience.
Hemorrhage from the stump of the gastroduodenal artery (GDA) is a significant postoperative risk with pancreaticoduodenectomy (PD). Studies have shown that wrapping the GDA stump using the omentum or the falciform ligament can help prevent bleeding. We aimed to determine whether wrapping the GDA stump with the ligamentum teres hepatis (LTH) would reduce postoperative PD hemorrhage. We retrospectively reviewed data for 148 patients who underwent laparoscopic pancreatoduodenectomy (LPD) at our hospital from November 2015 to September 2021. We compared perioperative data from 63 LPD patients without wrapping of the GDA (unwrapped group) and 85 whose GDA stumps were wrapped (wrapped group). There were no significant differences in the groups' baseline characteristics. The postoperative GDA stump bleeding incidence was significantly lower in the wrapped group than that in the unwrapped group (7.9% vs. 0, respectively). There was also no significant difference in the incidence of other complications (intra-abdominal infection, postoperative pancreatic fistula (POPF), biliary fistula, and gastrointestinal bleeding). Using the LTH to wrap the GDA stump during LPD can reduce bleeding from the GDA stump but not the incidence of other complications.


Quality Hospice Care in Adult Family Homes: Barriers and Facilitators.
Older adults in need of residential services are increasingly spending their final days in small, domestic-style care settings such as adult family homes. In this study, we sought to identify processes that facilitated the provision of quality hospice care to seriously ill residents of adult family homes and their family members. We conducted a secondary analysis of qualitative data collected as part of a randomized clinical trial of a problem-solving intervention for family members of hospice patients. The original trial was conducted in partnership with 2 large, community-based hospice agencies in the state of Washington. Data from 73 family members of residents of adult family homes receiving hospice services were included in the analysis. Data were collected via semi-structured individual interviews, which were audio-recorded and transcribed prior to analysis. Family members described quality hospice care in the adult family home as care that is consistent with residents and families' values and that results in comfort and social connectedness for residents while promoting peace of mind and decreasing burden for residents' families. They identified numerous processes that facilitated the provision of quality care including personalizing care, sharing information and expertise, working together to resolve conflicts, and prioritizing residents and families' values over existing or competing philosophies of care. The adult family home setting can amplify both the benefits and challenges associated with receipt of hospice. When choosing an adult family home, older adults and their families should strongly consider selecting a home with a track record of positive collaborations with hospice agencies if the need for end-of-life care is anticipated.


The relationship between health and housing in low-income older adults: A secondary analysis of survey data.
To examine the health-housing relationship in low-income older adults, and differences by income and receipt of housing assistance. Secondary analysis of longitudinal survey data. About 10,858 adults aged 62+ who completed at least one wave of the 2014 Survey of Income and Program Participation (SIPP) (n = 37,333 observations). SIPP variables representing demographics and housing quality, affordability, stability, and neighborhood were analyzed. Low-income and higher-income participants were differentiated by the household income-to-poverty ratio. Low-income participants were significantly more likely to be in poor health and report problems with housing quality, affordability, and neighborhood safety compared to higher-income participants (p < .001). Increased household size and problems with housing quality and neighborhood safety were associated with poor health in both groups (p < .05). Low-income participants who received housing assistance were significantly poorer, less healthy, and food insecure than participants not receiving assistance (p < .001); however, the health-housing relationship was not different in the two groups. Results provide additional support for housing as a social determinant of older adult health. Though housing assistance programs reached a subset of low-income older adults, the results suggest a housing assistance shortfall. Implications for public health nurses and researchers are explored.


Neuronal diversity can improve machine learning for physics and beyond.
Diversity conveys advantages in nature, yet homogeneous neurons typically comprise the layers of artificial neural networks. Here we construct neural networks from neurons that learn their own activation functions, quickly diversify, and subsequently outperform their homogeneous counterparts on image classification and nonlinear regression tasks. Sub-networks instantiate the neurons, which meta-learn especially efficient sets of nonlinear responses. Examples include conventional neural networks classifying digits and forecasting a van der Pol oscillator and physics-informed Hamiltonian neural networks learning Hénon-Heiles stellar orbits and the swing of a video recorded pendulum clock. Such learned diversity provides examples of dynamical systems selecting diversity over uniformity and elucidates the role of diversity in natural and artificial systems.


Generation and characterization of epiblast stem cells from blastocyst-stage mouse embryos.
Mouse epiblast stem cells (EpiSCs) are pluripotent embryonic cells that can be used to interrogate developmental transitions that occur during gastrulation. EpiSCs can also be robustly differentiated into functional somatic and germ cell derivatives making them a useful tool for studying development and regenerative medicine. Typically, mouse EpiSCs are isolated from the early postimplantation epiblast around 5.5 days post coitum (dpc). This chapter describes the methods for isolation of mouse EpiSCs from preimplantation blastocyst-stage mouse embryos (3.5 dpc). This technique enables the routine ability to derive EpiSC lines as it is much less labor intensive than isolation of EpiSCs from the postimplantation epiblast. We also detail relevant assays used to characterize new EpiSC lines and distinguish them from mouse embryonic stem cells.


Growth and development of transcutaneous monitoring in the U.S.A.--1978-1986.
Surface blood gas monitoring is an invaluable clinical technique. It is, unfortunately, subject to many errors unless carefully carried out. This can be done by clinicians. Clinicians, however, cannot be responsible for the cumulative effects of changes in the electrodes made by manufacturers. Before a modified electrode is approved for use its accuracy under clinical conditions and at high arterial PO2 tensions has to be established. In America this has not and is not being done. The F.D.A. met in December, 1986, to consider this problem. Recommendations are expected to be published in 1987. In any new regulations similar but not identical requirements for accuracy should be demanded from pulse oximeters, as these devices have their own unique limitations under hyperoxic and hypoxic conditions.


NAD(P)H quinone oxidoreductase 1 (NQO1) genetic C609T polymorphism is associated with the risk of digestive tract cancer: a meta-analysis based on 21 case-control studies.
The relationships between the NAD(P)H quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of digestive tract (DT) cancer are controversial. Therefore, we performed a meta-analysis to assess the relationships. The databases of Medline, Embase, and WanFang (updated to 15 May 2011) were reviewed. Odds ratios and 95% confidence intervals were calculated to assess the strength of the associations. Overall, 21 individual case-control studies in 20 papers with 5340 cases and 5911 controls were included in this meta-analysis. The results of combined analyses indicated that the T allele of NQO1 C609T was significantly associated with increased risk of DT cancer [odds ratio (95% CI): 1.58 (1.22-2.07) for TT vs. CC and 1.13 (1.06-1.22) for T carriers vs. C carriers]. Subgroup analyses for different types of cancers indicated that the T allele was significantly associated with an increased risk of gastric cancer [1.19 (1.13-1.47) for T carriers vs. C carriers], but not with esophageal cancer [1.05 (0.86-1.27) for T carriers vs. C carriers] and colorectal cancer [1.09 (0.98-1.21) for T carriers vs. CC]. Subgroup analyses for ethnicities and countries indicated that the T allele was associated with risk of DT cancer among Europeans [1.52 (1.05-2.19) for TT vs. CC] and Asians [1.52 (1.05-2.19) for TT vs. CC], and German, Indian, and Chinese populations but not among English and Japanese populations. In addition, subgroup analyses also indicated that the T allele was significantly associated with risk of DT cancer in studies with large and small sample sizes and in population-based studies, but not in hospital-based studies. This meta-analysis suggests that NQO1 C609T is significantly associated with risk of DT cancer among both Europeans and Asians, especially gastric cancer. Because of the limited number of cases and controls in the subgroup analyses, more well-designed studies with a large sample of participants are needed to verify our findings.


Substrate level optimization for better yield of oyster mushroom (Pleurotus ostreatus) production, using different ratio of rice straw and sugarcane bagasse.
Mushroom cultivation has been identified as a cost-effective technique for converting lignocellulosic wastes. This study utilized a combination of two distinct agro-wastes as a substrate for better Pleurotus ostreatus cultivation. Oyster mushroom has been cultivated on substrates made up of rice straw and sugarcane bagasse with different ratios. This technique gives a significant difference between mycelium running, fruit body formation, yield, biological efficiency, and better-quality taste of Pleurotus ostreatus mushroom. A minimum of 19 days were required for 1st harvesting from bag number T4 where substrate ratio was used at 3:2. The maximum yield was found as T4 (886 g/kg) in bag number on the dry substrate from the first flushing. According to proximate analyses, protein contents were increased in treatment bags compared with the control. Anyhow, the enrichment of L-glutamine content in the fruit body was found at 11.8 mg/g from 1st flushing in T4 bag, among the other bags and the flavour was changed due to the substrate level composition. According to the study, 3:2 is an ideal substrate ratio for the development of oyster mushrooms cultivation. According to this ratio, it helps the farmer for minimum time to grow the mushroom fruit body and reduce the lignocellulosic waste materials from the environmental pollution along with increasing the flavour in the fruitbody compared with commonly produced mushroom substrate (T6). Therefore, more research should be conducted to assess the consequences of combining different substrates and decreasing the lignocellulosic biomass by converting a protein-rich edible product through the oyster mushroom.


An alternative model.
In present Western societies, we witness the growing power of the state over the citizens, with an ever-growing flow of freedom-encroaching regulations, legitimated by the wish to keep full employment for all, for all of life. It is suggested here that a major political challenge for the rest of this millenium is to find a limit for the state's material responsibility for, and claims on, its citizens. This can only be done if we divide society into one highly regulated basic needs sector and other free sectors, in which state influence is minimized. This is like dividing trains into smoking and non-smoking compartments.


The use of droperidol before and after the Food and Drug Administration black box warning: a survey of the members of the Society of Ambulatory Anesthesia.
To determine the practice of members of the Society of Ambulatory Anesthesia (SAMBA) in the management of postoperative nausea and vomiting (PONV) before and after the Food and Drug Administration (FDA) black box warning on droperidol. Survey questionnaire. The Society of Ambulatory Anesthesia. After institutional review board approval, a survey was posted on the SAMBA Web site from June 1, 2005, until October 30, 2005. Visitors of the Web site were invited to participate in the survey. The survey was designed to elicit information about the management of PONV, particularly the use of droperidol, before and after the FDA black box warning. Participants were also asked about reasons for not using droperidol in their current practice and whether they believed that the black box warning was justified. Two hundred ninety-five physicians of 1,179 eligible SAMBA members completed the survey for a 25% response rate. For PONV prophylaxis, the choice of droperidol as a first-line agent decreased from 47% to 5% after the black box warning appeared (P < 0.0001). Similarly, for treatment of established PONV, the choice of droperidol decreased from 38% to 8% during this same period (P < 0.0001). A total of 261 (92%) of responders did not believe that the black box warning was justified. Although most surveyed practitioners believed that the FDA black box warning on droperidol is not justified, the use of this cost-effective agent has significantly declined.


Is the caregivers' oral health related to dental caries in children or adolescents? A systematic review.
This systematic review aimed to evaluate evidence on the relation between the caregivers' oral health condition and dental caries prevalence in their offspring. Scientific literature was searched in PubMed, Scopus, LILACS, Web of Science, the Cochrane Library databases, and Grey Literature. Observational studies were included if mentioning oral health conditions in caregivers and dental caries in offsprings. The internal validity of the selected articles was judged by two evaluators according to a previously published guideline based on eight questions (1 point each). Studies included were divided into low methodological quality (1-3 points), moderate (4-6 points), or high (7-8 points) according to the quality assessment. The GRADE approach was used to assess the quality of evidence provided by the selected studies. Initially, 12.458 records were recovered, of which 54 full-text articles were evaluated. Hand search added 5 records, but after application of the exclusion criteria, only 16 articles which met the adopted eligibility criteria remained. Critical assessment scored one study as low, 10 moderate, and 5 with high validity. Most of the studies plotted correlations between the variables (12) while 4 studies compared DMFT (3) or ICDAS (1) scores between caries-active/caries-free children with caries experience in caregivers. Regarding the main study question, 15 studies (93.7%), containing 5704 caregivers and 5467 children/adolescents, found a significant relationship between mothers/caregivers and children's/adolescents' caries prevalence; one study found this relationship only for individuals showing active caries and one study did not disclose any relationship between caries prevalence in caregivers-children's/adolescents' pairs. The overall evidence was, however, qualified as low due to problems in the imprecision of the included studies. Caregivers' oral health may be considered as an important risk marker in children's and adolescent's caries prevalence. Assuming the contribution of caregivers' oral health conditions on dental caries in their offspring may help to establish control measures for such prevalent disease in the family environment.


Hysteroscopy and the treatment of uterine fibroids.
Fibroids or (leio)myomas are benign tumours that very commonly derive from smooth muscle cells of the myometrium. They are the most common indication for a hysterectomy. However, in women desirous of preservation of their uterus or of their fertility, a myomectomy may be a more appropriate form of surgical therapy. The submucous variant is often associated with heavy menstrual bleeding or subfertility. It can be removed with hysteroscopic surgery. Refinements of hysteroscopic surgical techniques have resulted in a better ability to remove submucous myomas. The state of the art of such hysteroscopical techniques and instrumentation to treat submucous myomas and what has been proven is discussed.


Insights into zinc and cadmium biology in the nematode Caenorhabditis elegans.
Zinc is an essential metal that is involved in a wide range of biological processes, and aberrant zinc homeostasis is implicated in multiple human diseases. Cadmium is chemically similar to zinc, but it is a nonessential environmental pollutant. Because zinc deficiency and excess are deleterious, animals require homeostatic mechanisms to maintain zinc levels in response to dietary fluctuations. The nematode Caenorhabditis elegans is emerging as a powerful model system to investigate zinc trafficking and homeostasis as well as cadmium toxicity. Here we review genetic and molecular studies that have combined to generate a picture of zinc homeostasis based on the transcriptional control of zinc transporters in intestinal cells. Furthermore, we summarize studies of cadmium toxicity that reveal intriguing parallels with zinc biology.


Efficacy and tolerability of duloxetine in elderly patients with generalized anxiety disorder: a pooled analysis of four randomized, double-blind, placebo-controlled studies.
To assess the efficacy and tolerability of duloxetine in elderly patients with generalized anxiety disorder (GAD). Acute-phase data from a subset of patients (>or=65 years) with GAD were pooled from four randomized, double-blind, placebo-controlled trials of duloxetine (3 flexible, 1 fixed dosing). Patients were treated with duloxetine 60-120 mg once daily or placebo for 9-10 weeks. The primary outcome measure was the mean baseline-to-endpoint change in Hamilton anxiety scale (HAMA) total score. Secondary measures included the HAMA psychic and somatic anxiety subscales and the Hospital Anxiety Depression Scale (HADS). Of 1491 patients randomly assigned to treatment, 4.9% (duloxetine, n = 45; placebo, n = 28) were >or= 65 years old. Compared with placebo-treated patients, duloxetine-treated patients experienced significantly greater improvements on the HAMA-total (p = 0.029), the HAMA-psychic anxiety factor (p = 0.034), HADS-anxiety (p = 0.049) and -depression scales (p = 0.026), but not the HAMA somatic anxiety factor (p = 0.074). Nausea was reported significantly more often in duloxetine-treated patients (30.0% vs. 7.1%, p = 0.023); duloxetine-treated patients experienced greater weight loss (p = 0.018). More duloxetine-treated patients discontinued treatment due to an adverse event (22.2% vs. 0%; p = 0.006). Duloxetine was effective in an elderly patient subset with GAD, although there was a high rate of discontinuations due to adverse events.


Abdominal aortic aneurysm disease in New Zealand: epidemiology and burden between 2002 and 2006.
Abdominal aortic aneurysm (AAA) rupture has a high mortality. Four randomised controlled trials indicate significant mortality benefit from population screening for AAA. There is a lack of information on the epidemiology and burden of AAA disease in New Zealand, necessary to support policy in this area. A retrospective analysis was conducted on a dataset consisting of all AAA deaths and all hospital discharges with a AAA diagnosis between 2002 and 2006. Analysis by age, sex, ethnicity, and operative status was performed. On average, there were 267 elective repairs and 87 emergency repairs annually between 2002 and 2006. The operative mortality rate was 35.2% for emergency repair, and 6.7% for elective repair. There were about 236 known AAA-related deaths annually. Ninety-four percent of AAA deaths between 2002-2006 occurred in individuals >65 years. The case fatality for females was higher than males across every age group. The standardised mortality rate in Maori was twice as high as New Zealand Europeans. This study provides essential information to evaluate the appropriateness and feasibility of AAA screening here. A population-based prevalence study is recommended, along with further investigation of high case fatality in females and high mortality in Maori.


Induction of A549 Nonsmall-Cell Lung Cancer Cells Proliferation by Photoreleased Nicotine.
Caged compounds comprise the group of artificially synthesized, light-sensitive molecules that enable in situ derivation of biologically active constituents capable of affecting cells, tissues and/or biological processes upon exposure to light. Ruthenium-bispyridine (RuBi) complexes are photolyzed by biologically harmless visible light. In the present study, we show that RuBi-caged nicotine can be used as a source of free nicotine to induce proliferation of A549 nonsmall-cell lung cancer (NSCLC) cells by acting on nicotinic acetylcholine receptors expressed in these cells. RuBi-nicotine was photolyzed using LED light source with the spectrum matching RuBi-absorption. Photorelease of free nicotine ([Nic]p/r ) was quantified by high-performance liquid chromatography (HPLC). 5-s-long light exposure of 10 μm of RuBi-nicotine generated 2 μm [Nic]p/r which enhanced A549 cell proliferation similarly to the 2 μm of plain nicotine during 72 h of cell culturing. Both RuBi-nicotine per se and its photolysis byproduct exerted no effect on A549 cells. We conclude that RuBi-nicotine can be a good source of free nicotine for inducing short- and long-term biological effects. Photolysis of RuBi-nicotine is quite effective, and can produce biologically relevant concentrations of nicotine at acceptable concentrations of the source material with the use of simple, inexpensive, and easily accessible light sources.


Perimetry, visual evoked potentials and visual evoked spectrum array in homonymous hemianopsia.
Confrontation field examination, perimetry, visual evoked potentials (VEPs) to pattern hemi-field stimulation and visual evoked spectrum array to flash stimulation were compared in 50 patients with homonymous hemianopsia. Visual field could be examined by confrontation in all patients and demonstrated the field defect in 96% of cases. Goldmann perimetry could only be performed in 60% of patients, but always quantitatively defined the margins of the defect. VEPs could only be tested in 77% of patients and demonstrated an abnormality in 79% of cases. VEPs were absent to stimulation of the affected hemifield in every case of homonymous field defects with macular splitting. Visual evoked spectrum array could be tested in 95% of patients and revealed abnormalities in 67% of cases. The relative value of each test is discussed.


Zeolite encapsulated Ni(II)-Schiff-base complex: a novel size-selective electro-catalyst for the determination of the purity of stevioside.
Ship-in-a-bottle complex of nickel(II) containing the ligand N,N'-bis(2,4-dihydroxyacetophenone)-2,2-dimethylpropandiimine (H2{salnptn(4-OH)2}) has been synthesized in zeolite Y. The characteristics of the encapsulated complex are identified by the methods of EDX, SEM, XRD, FT-IR and cyclic voltammetry. A catalytic effect in the electrochemical oxidation of glucose, fructose and sucrose, and a blocking effect in stevioside oxidation are demonstrated on the Ni(II){salnptn(4-OH)2}-Y/CPE. The effects of some parameters, such as potential scan rate and concentration of carbohydrates are investigated. The rate constants for the catalytic reaction (k') of carbohydrates are also obtained. The size-selective electro-catalyst shows a good linear dependency on carbohydrates' concentration in the range of 0.01-0.06 M with the detection limit of 6.4mM at the signal-to-noise ratio of 3. Furthermore, the modified electrode exhibits no interference with the simultaneous presence of stevioside. In brief, these results demonstrate that Ni(II){salnptn(4-OH)2}-Y composites have a great potential for synthesizing size-selective electrocatalysts for determining the purity of stevioside.


Vertebral osteomyelitis and epidural abcess due to mucormycosis, a case report.
A patient is described, with a history of pain in the neck, followed by a slowly progressive loss of muscle strength in both arms, followed by tetraplegia. Medical history included laryngectomy with partial hypopharyngectomy preceded by radiotherapy, because of carcinoma. X-ray of the cervical spine was suggestive for metastases. The patient died as a consequence of massive pulmonary embolism and at autopsy the cause of the neurological deficit turned out to be vertebral osteomyelitis and epidural abscess due to mucormycosis.


Mechanistic insights of removing pollutant in adsorption and advanced oxidation processes by sludge biochar.
With the accelerated industrialization, more and more sewage sludge (SS) needs to be treated properly. The conversion of sludge into harmless biochar material with dual utilization value of adsorption and catalysis by pyrolysis is in line with the concept of sustainable development. However, the reaction mechanisms of pristine sludge biochar (SDBC) and its composites (SDBCs) in adsorption, persulfate (PS), and Fenton-like advanced oxidation processes (AOPs) are very closely related to its adsorption performance and catalytic efficiency. In this paper, from the application mechanisms of SDBC in adsorption and AOPs, we review in detail the common methods for synthesizing SDBC and their characteristics. We discuss the synthesis techniques that affect the structural, chemical, and catalytic properties of SDBC, including gasification, pyrolysis, and hydrothermal carbonation (HTC). The pyrolysis temperature, environmental factors, and sludge characteristics have important effects on the properties of SDBC, leading to different mechanisms in adsorption and catalytic processes. Furthermore, this paper systematically generalizes the mechanisms of SDBCs in adsorption, where π-π interactions and electrostatic attractions are the main adsorption mechanisms. Then, activation mechanisms of SDBCs in PS and Fenton-like AOPs systems are discussed, including free radical pathways and non-free radical pathways. Finally, we present several challenges and perspectives for the application of SDBC and SDBCs in the field of adsorption, PS, and Fenton-like AOPs from the mechanistic point of views.


Glomerella cingulata endophthalmitis.
To report a case of an exogenous endophthalmitis caused by the fungal species Glomerella cingulata. A 71-year-old male presented with an infectious keratitis that evolved into endophthalmitis. Combined cataract extraction and pars plana vitrectomy was performed and the vitreous specimen cultured Glomerella cingulata, a variant of the Colletotrichum gloeosporioides fungal species. Despite early treatment with topical, systemic and intravitreal doses of both voriconazole and amphotericin B, the patient had a poor visual and anatomical outcome. Glomerella cingulata may rarely cause endophthalmitis with devastating visual outcomes.


Distribution of plasma copeptin levels and influence of obesity in children and adolescents.
In recent years, a more stable AVP surrogate, called copeptin, has been used as an adjuvant diagnostic tool for dysnatremia in adults and appears to be promising even in the pediatric age. The aim of this study is to present the distribution of plasma copeptin in a large pediatric cohort and to observe the influence of fluid consumption and obesity on its values. A cohort of 128 children and adolescents was divided into two groups on the basis of nocturnal deprivation (group A) or free access to oral fluids in the 6-8 h before blood collection (group B). At all distribution percentiles, copeptin levels were higher (p < 0.0001) in group A, as were plasma sodium levels and osmolality (p = 0.02 and p = 0.008, respectively). The influence of BMI on copeptin levels was investigated by dividing the cohort into nonobese (group C) and obese children and adolescents (group D). Copeptin levels were higher in group D (p = 0.04).Conclusion: The measurement of copeptin could represent a useful tool for the diagnostic pathway of dysnatremic conditions, but its interpretation should take into consideration the state of hydration. Furthermore, it could also be a promising marker for obesity and metabolic syndrome, although this hypothesis needs further studies to be confirmed. What is Known: • Copeptin use as a diagnostic tool in AVP-related disorders, such as diabetes insipidus or syndrome of inappropriate secretion of antidiuretic hormone, is well established in adults • In pediatric age, few studies are available, but the preliminary data, including our previous study, seems to be promising. What is New: • In this study, we represent the distribution of copeptin levels in a pediatric cohort and show the significant influence of fluid ingestion on its plasma levels. • Also BMI seems to be a significant variable on copeptin levels and may be used as an obesity marker in pediatric age.


The correlation of WDR76 expression with survival outcomes and immune infiltrates in lung adenocarcinoma.
WD repeat domain 76 (WDR76) is a predicted member of the WD40-repeat-containing domain superfamily and possibly involves in various biological processes, but its function in cancers is poorly characterized. This study aimed to evaluate the role of WDR76 in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD). WDR76 expressions in LUAD tissues and normal tissues were primarily compared by The Cancer Genome Atlas (TCGA) database, and were validated in cohorts from Gene Expression Omnibus (GEO) database. The associations between WDR76 expression and clinicopathologic characteristics were analyzed. Kaplan-Meier and Cox regression analyses were performed to determine the impact of WDR76 expression on survival outcomes. The protein interaction network of WDR76 was built using STRING website. TIMER and GEPIA databases were used to investigate the correlation between WDR76 expression and immune infiltrates. WDR76 expression was elevated in LUAD (P < 0.001) and high WDR76 expression was associated with advanced N stage, M stage and pathologic stage. Expectedly, high WDR76 expression significantly correlated with poor survival outcomes and was the independent risk factor for overall survival (OS) (HR 1.468, 95% CI [1.031-2.089], P = 0.033) and disease specific survival (DSS) (HR 1.764, 95% CI [1.095-2.842], P = 0.020). DDB1 and LSH were the important proteins interacting with WDR76. WDR76 expression correlated with CD8+ T cells presence and was also positively associated with levels of inhibitory receptors. WDR76 expression was involved in the regulation of immune infiltrates and had predictive value for prognosis in LUAD.


Interaction between heparin and human pregnancy-associated plasma protein A (PAPP-A): a simple purification procedure.
Human pregnancy-associated plasma protein A (PAPP-A) binds to heparin-Sepharose. This affinity chromatography preceded by molecular sieve chromatography provides a simple two-step purification procedure of PAPP-A from late pregnancy plasma. One hundred percent of the applied PAPP-A was recovered, with more than 40% being electrophoretically homogeneous after the two procedures. The remaining PAPP-A could be purified by negative affinity chromatography on anti-total human serum immobilized on agarose.


Quantitative proteomic dataset of mouse caput epididymal epithelial cells exposed to acrylamide in vivo.
This article reports the proteomic legacy of in vivo exposure to the xenobiotic, acrylamide, on the epithelial cell population of the proximal segments of the mouse epididymis. Specifically, adult male mice were administered acrylamide (25 mg/kg bw/day) or vehicle control for five consecutive days before dissection of the epididymis. Epididymal epithelial cells were isolated from the proximal (caput) epididymal segment and subjected to quantitative proteomic analysis using multiplexed tandem mass tag (TMT) labeling coupled to mass spectrometry. Here, we report the data generated by this strategy, including the identification of 4405 caput epididymal epithelial cell proteins, approximately 6.8% of which displayed altered expression in response to acrylamide challenge. Our interpretation and discussion of these data features in the article "Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development".


Reduced tumorigenicity of cultured neuroblastoma cells after treatment in vitro with dexamethasone.
The effect of dexamethasone on tumorigenicity of cultured neuroblastoma and on de novo synthesis of DNA and protein was determined. Within 12 hr dexamethasone caused a dose-dependent inhibition of [3H]-thymidine incorporation into DNA. Incorporation of [3H]-leucine into protein was not affected by dexamethasone. Neurite formation was interrupted by actinomycin D or cycloheximide. Cells treated with dexamethasone before inoculation into A/J mice produced fewer tumors with longer latent periods than controls. About 2.6 times as many neuroblastoma cells treated with 50 micrograms/ml dexamethasone for 4 days were required for tumor development in 50% of recipient animals as compared to controls. Reduced tumorigenicity was dependent upon the length of treatment and the concentration of dexamethasone used. Cortexolone did not mimic the effects of dexamethasone. If, instead of inoculation, cells were replated and grown without dexamethasone, cellular aggregations appeared among the cells cultured in the absence of dexamethasone. By autoradiography, replated cells previously treated with ethanol displayed uniform incorporation of [3H]-thymidine, whereas replated cells from dexamethasone-treated cultures exhibited no incorporation in differentiated cells. However, incorporation was noted among the clusters. We hypothesize that tumors arising after dexamethasone treatment may be due to the presence of an unresponsive subpopulation of cells.


Rapid evolution in a fraction of the Drosophila nuclear genome.
Previous observations have indicated that Drosophila DNA contains a component that evolves so rapidly that it fails to hybridize between the DNAs of sibling species. To establish the reality of this component and study its properties, the fraction (about 20%) of Drosophila simulans (Dsim) DNA that fails to hybridize to Drosophila melanogaster (Dmel) DNA has been isolated. The majority of the hybridizable part of this isolated fraction (based on control tests on Dsim DNA) fails to hybridize with Dmel DNA under the conditions used for the initial fractionation. Clones of this fraction do hybridize with Dmel DNA at open criterion producing duplexes with greatly reduced thermal stability, indicating that the underlying process is rapid sequence divergence rather than loss of the homologous sequences by relatively large deletions. Cloned fragments from the nonhybridizing fraction from Dsim are more than 15% divergent from the Dmel homologues, whereas the fraction that does hybridize is only 3-5% divergent. In comparison, synonymous substitutions in the coding regions of five genes show a 9% average divergence between Dsim and Dmel. They appear to be intermediate in their degree of divergence between the hybridizing and nonhybridizing components.


Comparative analysis of mitochondrial genome data for Necator americanus from two endemic regions reveals substantial genetic variation.
Necator americanus is a blood-sucking, intestinal nematode of major human health importance in many tropical and subtropical regions of the world. The aim of the present study was to compare the complete mitochondrial genome sequence from one N. americanus individual from Togo with another from China, in order to estimate the magnitude of genetic variability for different mitochondrial genes and non-coding regions. For the 12 protein genes, this comparison revealed sequence differences at both the nucleotide (3-7%) and amino acid (1-7%) levels. The most conserved of these was the nad4L gene, whereas the nad1 gene was least conserved at both the nucleotide and amino acid levels. Nucleotide differences were also detected in 14 of the 22 transfer RNAs (trns) (1-13%), the AT-rich region ( approximately 8%), non-coding regions (8-25%) and in the small (rrnS) and large (rrnL) subunits of mitochondrial ribosomal RNA (rrn) ( approximately 1%). Comparison of the rrnL sequences among multiple individual worms revealed nine unequivocal nucleotide differences between N. americanus from the two countries. Consistent with previous studies, these findings provide evidence for substantial genetic variation within N. americanus, which may have implications for the transmission and control of hookworm disease.


Long-term prognosis of patients with infantile spasms following ACTH therapy.
The influence of ACTH on the prognosis of patients with infantile spasms remains controversial. We have examined retrospectively the long-term benefits of initially successful ACTH therapy in patients treated at this institution between 1961 and 1974. Individuals with equivocal or minimal improvement during ACTH therapy were excluded from this study. Eighteen affected infants showed a favorable early response consisting of cessation of seizures for at least 3 weeks during ACTH therapy and concurrent disappearance of the hypsarhythmic EEG pattern. Modal age at last follow-up was 5 years (range, 15 months to 16 years). Infantile spasms recurred in 7 patients (39%), and 8 patients subsequently had other seizure types. All epileptiform (spike) activity disappeared from the EEGs of 8 patients during ACTH therapy, but in 4 of these cases epileptiform activity was present in later tracings. In the remaining 10 patients the hypsarhythmic pattern disappeared in association with ACTH therapy, but the EEG remained epileptiform (often only in sleep). Later EEGs were free of epileptiform activity in 5 of the 10 patients whose tracings contained spike discharges in the early follow-up period. Four patients (22%) were seizure free and without intellectual impairment when last evaluated.


Deciphering serous ovarian carcinoma histopathology and platinum response by convolutional neural networks.
Ovarian cancer causes 151,900 deaths per year worldwide. Treatment and prognosis are primarily determined by the histopathologic interpretation in combination with molecular diagnosis. However, the relationship between histopathology patterns and molecular alterations is not fully understood, and it is difficult to predict patients' chemotherapy response using the known clinical and histological variables. We analyzed the whole-slide histopathology images, RNA-Seq, and proteomics data from 587 primary serous ovarian adenocarcinoma patients and developed a systematic algorithm to integrate histopathology and functional omics findings and to predict patients' response to platinum-based chemotherapy. Our convolutional neural networks identified the cancerous regions with areas under the receiver operating characteristic curve (AUCs) > 0.95 and classified tumor grade with AUCs > 0.80. Functional omics analysis revealed that expression levels of proteins participated in innate immune responses and catabolic pathways are associated with tumor grade. Quantitative histopathology analysis successfully stratified patients with different response to platinum-based chemotherapy (P = 0.003). These results indicated the potential clinical utility of quantitative histopathology evaluation in tumor cell detection and chemotherapy response prediction. The developed algorithm is easily extensible to other tumor types and treatment modalities.


Teledermatology: how to start a new teaching and diagnostic era in medicine.
"Telemedicine" is defined as the use of telecommunication technologies for the exchange of medical information across distances. Applications include patient management as well as research and education. Teledermatology is a steadily growing category of telemedicine. This article presents general aspects of telemedicine, such as modes of data transmission, and practical applications with a special emphasis on their significance for teledermatology.


Higher G2 sensitivity to the induction of chromosomal damage in the CHO mutant EM9 than in its parental line AA8 by camptothecin, an inhibitor of DNA topoisomerase I.
The induction of chromosomal alterations by camptothecin (CPT), an inhibitor of DNA topoisomerase I, in the G2 stage was studied in a CHO mutant cell line EM9, which has an elevated baseline frequency of SCEs, and in its parental cell line AA8. EM9 cells were found to be more sensitive to CPT than the parental cell line. It is proposed that the effect of camptothecin in this phase of the cell cycle is caused by a 'residual' DNA synthesis which is higher in EM9 than in AA8 cells.


Spatial association network of PM2.5 and its influencing factors in the Beijing-Tianjin-Hebei urban agglomeration.
In this paper, we empirically study the spatial association network of PM2.5 and the factors influencing those correlations using the gravity model, social network analysis (SNA), and the quadratic assignment procedure (QAP) based on data from the Beijing-Tianjin-Hebei urban agglomeration (BTHUA) in China from 2005 to 2018. We draw the following conclusions. First, the spatial association network of PM2.5 exhibits relatively typical network structure characteristics: the network density and network correlations are highly sensitive to efforts to control air pollution, and there are obvious spatial correlations within the network. Second, cities in the center of the BTHUA have large network centrality values, while cities in the peripheral region have small centrality values. Tianjin is a core city in the network, and the spillover effect of PM2.5 pollution in Shijiazhuang and Hengshui is the most noticeable. Third, the 14 cities can be divided into four plates, with each plate having obvious geographical location characteristics and linkage effects. The cities in the association network are divided into three tiers. Beijing, Tianjin, and Shijiazhuang are located in the first tier, and a considerable number of PM2.5 connections are completed through these cities. Fourth, differences in geographical distance and urbanization are the main drivers of the spatial correlations of PM2.5. The greater the urbanization differences, the more likely the generation of PM2.5 links is, while the opposite is true for differences in geographical distance.


Adolescent clinic visits for contraception: support from mothers, male partners and friends.
To increase effective contraceptive use among adolescents at high risk of pregnancy, it is important to understand what factors influence them to visit a clinic for contraception, including support from their mothers, male partners and friends. Data from a prospective cohort study of 399 teenage clinic attendees using the pill, the implant or condoms were collected through a questionnaire at baseline and at a one-year follow-up interview. Data were analyzed using multivariate regression analysis to show differences in social support for adolescents' clinic visit at baseline and method continuation at one year. Almost all teenagers (96%) reported that their mother, a male partner or a friend was aware of their clinic visit for contraception; of these, 92-96% also said that their mother or a male partner was supportive. Teenagers who chose the pill or implant were more likely than condom users to report that their mother and male partner were aware and that their mother was supportive of their contraceptive clinic visit. Implant users were significantly more likely than those who chose the pill or condom to continue using their chosen method for one year. Teenagers who took part in high-risk behaviors were more likely than others to involve a friend but not their mother or a male partner in their contraceptive decision-making. Pregnancy prevention programs and counseling protocols that integrate supportive networks for teenagers into contraceptive services may help adolescents to use effective methods.


Multiple roles for O-glycans in Notch signalling.
Notch signalling regulates a plethora of developmental processes and is also essential for the maintenance of tissue homeostasis in adults. Therefore, fine-tuning of Notch signalling strength needs to be tightly regulated. Of key importance for the regulation of Notch signalling are O-fucose, O-GlcNAc and O-glucose glycans attached to the extracellular domain of Notch receptors. The EGF repeats of the Notch receptor extracellular domain harbour consensus sites for addition of the different types of O-glycan to Ser or Thr, which takes place in the endoplasmic reticulum. Studies from Drosophila to mammals have demonstrated the multifaceted roles of O-glycosylation in regulating Notch signalling. O-glycosylation modulates different aspects of Notch signalling including recognition by Notch ligands, the strength of ligand binding, Notch receptor trafficking, stability and activation at the cell surface. Defects in O-glycosylation of Notch receptors give rise to pathologies in humans. This Review summarizes the nature of the O-glycans on Notch receptors and their differential effects on Notch signalling.


Retention of carboxypropeptides in type-II collagen fibrils in chick embryo chondrocyte cultures.
An antibody reacting with the C-propeptide of chick type-II procollagen was used in an attempt to localize this terminal extension of the procollagen molecule (by immunogold labelling) during early collagen fibrillogenesis in chondrocyte cultures. After 2 days in culture the chondrocytes were surrounded by pericellular type-II collagen, as demonstrated by an indirect immunofluorescence labelling technique. An electron microscopy study of these cultures showed that the collagen fibrils were thin (approximately 15 nm diameter), with a poorly visible cross striation, sometimes enhanced by slight thickenings. The antibody against the C-propeptide of type-II procollagen labelled most of the collagen fibrils, according to a very regular pattern constituting a 60 nm periodicity. After 3 days the label was still present on the pericellular collagen fibrils but disappeared from the collagen fibrils of the extracellular matrix. Our results indicate that the C-propeptide of type-II procollagen is retained in the newly formed fibrils.


In vivo MRI discrimination between live and lysed iron-labelled cells using balanced steady state free precession.
The goal of this study was to evaluate the ability of balanced steady state free precession (b-SSFP) magnetic resonance imaging sequence to distinguish between live and lysed iron-labelled cells. Human breast cancer cells were labelled with iron oxide nanoparticles. Cells were lysed using sonication. Imaging was performed at 3 T. The timing parameters for b-SSFP and the number of iron-labelled cells in samples were varied to optimise the b-SSFP signal difference between live and lysed iron-labelled cell samples. For in vivo experiments, cells were mixed with Matrigel and implanted into nude mice. Three mice implanted with live labelled cancer cells were irradiated to validate this method. Lysed iron-labelled cells have a significantly higher signal compared with live, intact iron-labelled cells in bSSFP images. The contrast between live and dead cells can be maximised by careful optimisation of timing parameters. A change in the b-SSFP signal was measured 6 days after irradiation, reflecting cell death in vivo. Histology confirmed the presence of dead cells in the implant. Our results show that the b-SSFP sequence can be optimised to allow for the discrimination of live iron-labelled cells and lysed iron-labelled cells in vitro and in vivo.


Simulation of the interaction between muscle fiber conduction velocity and instantaneous firing rate.
In this study, the relationships between the early and late afterpotentials and velocity and amplitude recovery functions (VRF and ARF) in skeletal muscle were examined using model simulation. A mathematical model of the muscle fiber action potential, that incorporated a tubular slow potassium conductance, was developed and used to simulate muscle fiber action potentials at a range of interpulse intervals. The slow potassium conductance produced an afterhyperpolarization which resulted in supernormal action potential conduction velocity and amplitude for interpulse intervals>7 ms. Increasing the number of conditioning stimuli caused a further increase in conduction velocity and amplitude, and an additional phase of supernormality, with a peak at approximately 100 ms. Positive correlations between instantaneous firing rate and both conduction velocity and amplitude were also observed during simulation of repetitive stimulation of the muscle fiber. The relationships were eliminated when the slow potassium conductance channel was removed from the model. The results suggest that an afterhyperpolarization, possibly due to a slow tubular potassium conductance, could cause the VRF and ARF observed in muscle. They additionally suggest that the positive correlations between instantaneous firing rate, conduction velocity, and amplitude are directly related to the VRF and ARF.


Association of Paget's disease of bone with calcific aortic valve disease.
To test the hypothesis that Paget's disease of bone is associated with a greater incidence of calcific aortic valve disease, a computer-generated list was obtained of all autopsy subjects from the Johns Hopkins Hospital in whom Paget's disease was diagnosed (n = 92). The severity of Paget's disease and cardiac valvular lesions was graded on a scale of 0 to 3, with 3 as the most severe. Two control cases were obtained for each case of Paget's disease. Each was the case either immediately before or after the Paget's case, and was matched for age, race, sex, and extent of autopsy. The incidences of moderate (10.9 percent) and severe (5.4 percent) calcific aortic valve disease were both fourfold greater than in the control group (chi-square analysis, p less than 0.01 and p less than 0.05, respectively). Additionally, the frequency of advancing grades of calcific aortic valve disease was greater in more advanced stages of Paget's disease. In fact, there was a dose-response effect of Paget's disease upon calcific aortic valve disease (trend analysis for proportion, p less than 0.01). These data therefore support the hypothesis that Paget's disease is associated with calcific aortic valve disease in a dose-response manner.


Plain water consumption is associated with lower intake of caloric beverage: cross-sectional study in Mexican adults with low socioeconomic status.
Plain water (PW) should be the main beverage consumed by the population. However, consumption of caloric beverages (CB) has increased considerably worldwide. The purpose of this paper is to analyze the association between CB and PW intake in Mexican adults with a low socioeconomic status (SES). In a cross-sectional design, beverage consumption was evaluated with a 24-h beverages recall using the five-step multiple-pass method recommended by the U.S. Department of Agriculture. Physical activity, anthropometric and sociodemographic information were obtained. CB was defined as those beverages that provide energy, with the exception of low-fat milk and beverages with noncaloric sweeteners. Participants were classified into five groups according to their PW consumption (nondrinkers and four quartiles). Differences between groups were evaluated with ANOVA and Bonferroni tests for multiple comparisons among quartiles. A two-stage Heckman regression model was designed with robust standard errors, adjusting for potential confounders. A total of 1108 adults between 21 and 59 years of age were evaluated. A negative association was noted between PW intake and CB consumption (p <0.001) with the exception of natural juice, which was positive (p <0.01) and sodas that no differences were found between quartiles. Specifically, for every milliliter of PW, the intake of CB was 3.4, 1.3, 0.68 and 0.38 mL in each quartile, respectively (p <0.001). In Heckman's model, PW consumers were 0.5 times less likely to consume CB (p = 0.029). This probability increased to 0.9 for low-fat milk, skim milk and beverages without added sugar (LFM-BWAS) consumers (p <0.001). Also, for every 100 mL of PW consumption, CB intake diminished by 20 mL (p <0.001). In turn, for every 100 mL of LFM-BWAS consumption, a reduction of 47 mL in CB was observed (p <0.001). Higher PW consumption was associated with lower CB consumption. This association suggests that future studies are warranted to determine if increasing PW intake in a low SES Mexican population can reduce intake of CB.


Effect of shock and mixed loading on the performance of SND based sequencing batch reactors (SBR) degrading nitrophenols.
The effect of nitrophenolic shock loads on the performance of three lab scale SBRs was studied using a synthetic feed. Nitrophenols were biotransformed by Simultaneous heterotrophic Nitrification and aerobic Denitrification (SND) using a specially designed single sludge biomass containing Thiosphaera pantotropha. Reactors R1, R2 and R3 were fed with 200mg/L concentration of 4-nitrophenol (4-NP), 2,4-dinitrophenol (2,4-DNP), and 2,4,6-trinitrophenol (2,4,6-TNP) whereas reactor R was used as a background control. Three nitrophenolic shock loadings of 400, 600 and 800 mg/Ld were administrated by increasing the influent nitrophenolic concentration while keeping the hydraulic retention time as 48 h. The shocks were given continuously for a period of 4 days before switching back to normal nitrophenolic loading (200mg/Ld). The reactors were allowed to recover to normal performance level before administrating the next nitrophenolic shock load. The study showed that a nitrophenolic shock load, as high as 600 mg/Ld was completely degraded by the 4-NP & 2,4-DNP bioreactors while almost half degraded by the 2,4,6-TNP bioreactor without affecting the reactor's performance irreversibly. After resuming the normal nitrophenolic loading, it took almost 8-10 days for the reactors to recover from the shock effect. The study was further extended to evaluate the maximum possible mixed nitrophenolic loading (4-NP:2,4-DNP:2,4,6-TNP 1:1:1) to which a reactor (R3) containing 2,4,6-TNP acclimated single sludge biomass can be exposed without hampering the reactor performance irreversibly. The reactor was able to achieve pseudo-steady-state at a mixed nitrophenolic loading of 300 mg/Ld with more than 90% removal of all the three nitrophenols, but could remove half of the mixed nitrophenolic loading of 600 mg/Ld.


Single-Nucleus and In Situ RNA-Sequencing Reveal Cell Topographies in the Human Pancreas.
Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been yet established because of the local concentration and cascade of hydrolytic enzymes that can rapidly degrade cells and RNA upon pancreatic resection. We sought to better understand the heterogeneity and cellular composition of the pancreas in neonates and adults in healthy and diseased conditions using single-cell sequencing approaches. We innovated single-nucleus RNA-sequencing protocols and profiled more than 120,000 cells from pancreata of adult and neonatal human donors. We validated the single-nucleus findings using RNA fluorescence in situ hybridization, in situ sequencing, and computational approaches. We created the first comprehensive atlas of human pancreas cells including epithelial and nonepithelial constituents, and uncovered 3 distinct acinar cell types, with possible implications for homeostatic and inflammatory processes of the pancreas. The comparison with neonatal single-nucleus sequencing data showed a different cellular composition of the endocrine tissue, highlighting the tissue dynamics occurring during development. By applying spatial cartography, involving cell proximity mapping through in situ sequencing, we found evidence of specific cell type neighborhoods, dynamic topographies in the endocrine and exocrine pancreas, and principles of morphologic organization of the organ. Furthermore, similar analyses in chronic pancreatitis biopsy samples showed the presence of acinar-REG+ cells, a reciprocal association between macrophages and activated stellate cells, and a new potential role of tuft cells in this disease. Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology and provides a crucial reference set for comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.


Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women.
The aim of this study was to examine the association between brachial artery flow-mediated dilation (FMD) and cardiovascular events in a cohort of initially asymptomatic post-menopausal women, with adjustment for the presence of the major cardiovascular risk factors. Conventional major cardiovascular risk factors (cigarette smoking, hypercholesterolemia, hypertension, and diabetes) fail to explain nearly 50% of cardiovascular events. Defining the magnitude of future risk for the development of clinical events is a major focus of effective primary prevention. Evaluation of endothelial function, utilizing the noninvasive measurement of the brachial artery FMD, may serve as a screening tool to individualize high-risk patients. We conducted a prospective study on 2,264 post-menopausal women, age 54 +/- 6 years. The length of the follow-up was 45 +/- 13 months (range 6 to 65 months). During observation, 90 major events were recorded. Risk-adjusted relative risk values resulted 1.0, 1.33 (95% confidence interval [CI] 1.09 to 4.09), and 4.42 (95% CI 2.97 to 8.01) for women in the higher, intermediate, and lower tertile of FMD, respectively (p < 0.0001 for trend). The event rate for women in the lower tertile (FMD <or=4.5%) was greater than the combined event rate noted in the other 2 tertiles (women in the lower tertile accounted for 51 events [56.6% of total events]). When added to age and other conventional cardiovascular risk factors (smoking habits, presence of hypercholesterolemia, history of diabetes, hypertension), FMD contributed significantly to the model predicting cardiovascular events (likelihood ratio chi-square change: 10.22; p < 0.0001). In post-menopausal women, the knowledge of FMD provided incremental prognostic information regarding the risk of developing cardiovascular events.


Spontaneous sinus conversion of permanent atrial fibrillation during treatment of hyperkalemia.
Hyperkalemia is a common adverse effect of treatment for heart failure and is associated with high mortality and morbidity. The cardiac manifestations of hyperkalemia include various electrocardiogram changes. We describe a case of a 74-year-old woman with heart failure and permanent atrial fibrillation who reverted to normal sinus rhythm during recovery from hyperkalemia.


The fate of fusion Cry1Ab/1Ac proteins from Bt-transgenic rice in soil and water.
Toxin proteins form transgenic crops entering into the environment are likely affect non-target organisms. To investigate the entry route and fate of fusion Cry1Ab/1Ac proteins from transgenic rice expressing insecticide toxins from Bacillus thuringiensis (Bt) in soil and water, we conducted greenhouse and field experiments in 2013 and 2014. Cry1Ab/1Ac proteins from Bt-transgenic rice in soil was found within a horizontal range of 25cm, where most of plant roots distributed. Concentration of Cry1Ab/1Ac proteins was lower in water than in soil in the greenhouse experiment, and no Cry1Ab/1Ac protein was detected in field water. Cry1Ab/1Ac concentration from rice straws was higher in ditch water than in distilled water due to the existence of aquatic organisms in ditch water. Bt proteins from transgenic crops enter into soil ecosystems mainly through root exudates and into aquatic ecosystems through plant residues, which determines Bt fate in the environment.


Phosphinothricin resistance in Aspergillus niger and its utility as a selectable transformation marker.
Aspergillus niger is moderately susceptible to inhibition by phosphinothricin (PPT)-a potent inhibitor of glutamine synthetase. This growth inhibition was relieved by L-glutamine. PPT inhibited A. niger glutamine synthetase in vitro (K(I), 54 microM) and the inhibition was competitive with L-glutamate. The bar gene, imparting resistance to PPT, was successfully exploited as a dominant marker to transform this fungus. Very high PPT concentrations were required in the overlay for selection. Apart from bar transformants, colonies spontaneously resistant to PPT were frequently encountered on selection media. Reasons for such spontaneous resistance, albeit of moderate growth phenotype, were sought using one such isolate (SRPPT). The SRPPT isolate showed a 2-3-fold decrease in its glutamate uptake rate. Elevated external glutamate levels further suppressed the PPT-induced growth inhibition. Cellular entry of PPT could be through the L-glutamate uptake system thereby accounting for the observed spontaneous resistant phenotype. These results were useful in the fine-tuning of bar-selection in A. niger.


Ophiopogonin D suppresses TGF-β1-mediated metastatic behavior of MDA-MB-231 breast carcinoma cells via regulating ITGB1/FAK/Src/AKT/β-catenin/MMP-9 signaling axis.
Ophiopogonin D, a steroidal glycoside extracted from the Traditional Chinese Medicine Ophiopogon japonicus, shows anti-tumor property in several lines of cancers; however, its effect on triple-negative breast cancer (TNBC) has not been investigated. In this study, the anti-metastatic effect of Ophiopogonin D in TNBC cells as well as the underlying mechanism in such process was explored. Ophiopogonin D dose-dependently decreased cell proliferation of MDA-MB-231 cells. Meanwhile, Ophiopogonin D significantly inhibited TGF-β1-induced metastatic behavior of MDA-MB-231 cells, including EMT, anoikis resistance as well as migration and invasion, via suppressing MMP-9 activity. Mechanically, Ophiopogonin D achieved its effect through efficiently abolishing ITGB1 expression, thus reducing the phosphorylation of FAK, Src and AKT, as well as upregulating nuclear β-catenin. ITGB1 overexpression partly recovered Ophiopogonin D's inhibitory effect on metastatic behavior via activating MMP-9. These results demonstrated that Ophiopogonin D could suppress TGF-β1-mediated metastatic behavior of MDA-MB-231 cells by regulating ITGB1/FAK/Src/AKT/β-catenin/MMP-9 signaling axis, which might provide new insight for the control of TNBC metastasis.


The metabolism and kinetics of 125I-labeled intravenous human IgG preparation (C-425) in rats and rabbits. II. Excretion into bile, tissue distribution and placental permeability.
The metabolism and kinetics of unmodified human IgG (125I-C-425) was studied in rats and rabbits after intravenous injection with regard to changes as a function of time of radioactivity in the blood and other tissues, excretion into the bile and placental permeability. A microautoradiographic study on the cellular interaction between 125I-C-425 and rat tissues was also performed using 125I-Polyglobin as the control drug. Results showed plasma radioactivity to be the highest followed by blood, lung, heart, kidney, bone marrow etc. in decreasing order. Tissues considered to contain larger amounts of blood, gave higher radioactivity values with some exceptions, such as the thyroid and skin. Biliary excretion within 72 hours was 7.57% for 125I-C-425 and 10.74% for 125I-Polyglobin. In pregnant rats, relatively high radioactivity was counted in the ovarium, uterus and placenta, and radioactivity in the fetus and amniotic fluid approached that of uterus and placenta up to 72 hours, indicating that placental permeability was gradual. Microautoradiographic findings revealed no cellular interaction such as aggregate formation, between human IgG and rat tissues. Further study is needed to elucidate immunological interaction under pathological conditions.


Cryogenic signal amplification combined with helium-temperature MAS DNP toward ultimate NMR sensitivity at high field conditions.
The low sensitivity of NMR spectroscopy is of historical concern in the field, and various approaches have been developed to mitigate this limitation. On the shoulder of giants, today one can routinely implement, for example, the pulse/Fourier transform NMR with the cross polarization together with the ultra-low temperature MAS DNP under high-field conditions. We show in this work this current opportunity should further be augmented by combining them with the cryogenic signal amplification. Our presented MAS DNP probe operates with the closed-cycle helium MAS system, and cools the internal preamplifier-duplexer module with the "return" helium gas on its way back to the compressor in the loop. The signal-to-noise (S/N) gain relative to the room-temperature measurements of a factor of 4.6 and 2.4 was found for the measurement using the cold- and room-temperature preamplifier, respectively, at the sample temperature of T = 20 K at B0 = 16.4 T. The ratio of these factors reveals ∼ two-fold sensitivity improvement that results purely from the introduction of the cold signal amplification, i.e., noise reduction. Together with the increase of the thermal Boltzmann polarization at low temperatures, the combined S/N gain of max. ∼70-fold is possible without DNP. The DNP enhancement factor of ∼40 as we found in this work for a microcrystalline MLF sample may be multiplied to this gain. We also demonstrated the sensitivity improvement with a 13C-detected 2D NCaCx spectrum, illustrating the generality of the S/N gain from combining DNP with the cold signal amplification.


FUS Mutant Human Motoneurons Display Altered Transcriptome and microRNA Pathways with Implications for ALS Pathogenesis.
The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases. Several microRNAs (miRNAs) were also deregulated in FUS mutant motoneurons, including miR-375, involved in motoneuron survival. We report that relevant targets of miR-375, including the neural RNA-binding protein ELAVL4 and apoptotic factors, are aberrantly increased in FUS mutant motoneurons. Characterization of transcriptome changes in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS.


Construction of solid-liquid fluorine transport channel to enable highly reversible conversion cathodes.
Conversion-type iron fluoride is a promising alternative cathode to intercalation oxides because of its higher energy density. However, its intrinsic solid-solid conversion is sluggish during repeated splitting and rebonding of metal-fluorine moieties. Here, we propose a solid-liquid conversion mechanism to activate the fluorine transport kinetics of iron oxyfluorides enabled by fluoride anion receptor of tris(pentafluorophenyl)borane (TPFPB). TPFPB promotes the dissociation of inert lithium fluoride and provides a facile fluorine transport channel at multiphase interfaces via the formation of solvated F− intermediate therein. The construction of solid-liquid channel with fluorinated cathode electrolyte interface is the key for the achievement of FeO0.3F1.7 and FeO0.7F1.3 in terms of sustaining conversion reaction (with an energy efficiency approaching 80%) and high-rate performance (with reversible capacity of 320 mAh/g at 2 A/g). The cathode energy densities can reach 1100 Wh/kg for FeO0.3F1.7 and 700 Wh/kg for FeO0.7F1.3 under the power densities of 220 and 4300 W/kg, respectively.


The enhancement of haemopoietic stem cell recovery in irradiated mice by prior treatment with cyclophosphamide.
Studies are reported of the enhancement of stem cell recovery following whole body irradiation as a result of prior administration of cyclophosphamide. It is shown that the much larger enhancement of regeneration observed for the hosts own surviving stem cells, compared to the regeneration of injected bone marrow stem cells, is due to the different numbers of stem cells initiating the regeneration in conjunction with the time course of stem cell regeneration. The results show that the environmental changes produced by cyclophosphmide greatly enhance haemopoietic recovery even though at the dose used this agent is relatively toxic to stem cells. Furthermore it has been shown that the level of stem cell regeneration is nearly independent of the gamma-ray dose in the range 3-8 gray (300-800 rad). If human bone marrow should respond similarly it follows that regeneration produced by cytotoxic drugs administered prior to radiation embodies a considerable safety factor as far as recovery of the haemopoietic system is concerned.


A single vomeronasal receptor promotes intermale aggression through dedicated hypothalamic neurons.
The pheromonal information received by the vomeronasal system plays a crucial role in regulating social behaviors such as aggression in mice. Despite accumulating knowledge of the brain regions involved in aggression, the specific vomeronasal receptors and the exact neural circuits responsible for pheromone-mediated aggression remain unknown. Here, we identified one murine vomeronasal receptor, Vmn2r53, that is activated by urine from males of various strains and is responsible for evoking intermale aggression. We prepared a purified pheromonal fraction and Vmn2r53 knockout mice and applied genetic tools for neuronal activity recording, manipulation, and circuit tracing to decipher the neural mechanisms underlying Vmn2r53-mediated aggression. We found that Vmn2r53-mediated aggression is regulated by specific neuronal populations in the ventral premammillary nucleus and the ventromedial hypothalamic nucleus. Together, our results shed light on the hypothalamic regulation of male aggression mediated by a single vomeronasal receptor.


Dynamic changes in fibrinogen and D-dimer levels in COVID-19 patients on nafamostat mesylate.
Critical illnesses associated with coronavirus disease 2019 (COVID-19) are attributable to a hypercoagulable status. There is limited knowledge regarding the dynamic changes in coagulation factors among COVID-19 patients on nafamostat mesylate, a potential therapeutic anticoagulant for COVID-19. First, we retrospectively conducted a cluster analysis based on clinical characteristics on admission to identify latent subgroups among fifteen patients with COVID-19 on nafamostat mesylate at the University of Tokyo Hospital, Japan, between April 6 and May 31, 2020. Next, we delineated the characteristics of all patients as well as COVID-19-patient subgroups and compared dynamic changes in coagulation factors among each subgroup. The subsequent dynamic changes in fibrinogen and D-dimer levels were presented graphically. All COVID-19 patients were classified into three subgroups: clusters A, B, and C, representing low, intermediate, and high risk of poor outcomes, respectively. All patients were alive 30 days from symptom onset. No patient in cluster A required mechanical ventilation; however, all patients in cluster C required mechanical ventilation, and half of them were treated with venovenous extracorporeal membrane oxygenation. All patients in cluster A maintained low D-dimer levels, but some critical patients in clusters B and C showed dynamic changes in fibrinogen and D-dimer levels. Although the potential of nafamostat mesylate needs to be evaluated in randomized clinical trials, admission characteristics of patients with COVID-19 could predict subsequent coagulopathy.


New insights into molecular and cellular mechanisms of zoledronate in human osteosarcoma.
Osteosarcoma is the most common primary malignant tumor of the skeleton in teenagers and young adults and continues to confer a generally poor prognosis in patients who do not respond to chemotherapy or who present with metastatic diseases at diagnosis. The nitrogen-containing zoledronate, the third generation bisphosphonate (BP), effectively inhibits osteoclastic bone resorption and is widely utilized in the treatment of metabolic and metastatic bone diseases nowadays. Owing to an acceptable safety profile and tolerability, zoledronate is the only BP currently approved for the prevention and treatment of skeletal relevant events in patients with metastatic bone lesions, especially bone metastases from advanced renal cell carcinoma and prostate cancer, and breast cancer, due to all solid malignancy. Moreover, zoledronate possesses diverse anti-osteosarcoma properties and may have potential to become an adjunctive treatment for high-grade osteosarcoma to enhance survival rates and to obliterate complications of the chemotherapy. Herein we highlighted the pharmacology of BPs and its underlying molecular mechanisms in osteoclasts and various cancer cells. We further provided the available literature on in vitro studies to illustrate the new insights into the intracellular molecular mechanisms of zoledronate in human osteosarcoma cell lines and in vivo animal models that led to the development and regulatory approval of zoledronate in patients with human osteosarcoma. This review also addresses clinical trials to focus on the efficacy of zoledronate on human osteosarcoma.


Development and properties of a brief scale to assess intimate partner relationship in the postnatal period.
Poor quality intimate partner relationship is associated with postnatal depression and anxiety among women. Existing scales assessing the quality of this relationship are long and measure stable aspects of the relationship rather than specific behaviours which may respond to targeted interventions. The aim was to develop and investigate the properties of a brief, life stage-specific scale to assess potentially modifiable partner behaviours in the postpartum period. Participants were primiparous women from diverse geographical and socio-economic backgrounds in Victoria, Australia. Seven study-specific items were developed to assess potentially modifiable aspects of the intimate partner relationship at 6 months postpartum. Women's mental health was assessed using the Composite International Diagnostic Interview and the Patient Health Questionnaire depression and generalised anxiety modules. Factor analysis was conducted on the 7 items, and associations calculated between factor scores. Factor scores were compared for women with and without mental health problems. Mean inter-item correlations were computed to assess internal consistency. Factor analysis on data from 355 women revealed two factors with good internal consistency: Caring Partner Behaviours and Emotionally Abusive Partner Behaviours. Having mental health problems was associated with lower Caring Partner Behaviours and higher Emotionally Abusive Partner Behaviours scores. Interaction between partners was not observed; thus external criterion validity was not assessed. This brief scale is a promising means of assessing potentially modifiable aspects of the intimate partner relationship in the postnatal period.


Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ.
The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS). Women with DCIS who were treated with BCS and RT from 1980 through 2010 were identified from a prospectively maintained database. IBTR rates, measured from the time of RT completion, were compared between those who initiated RT ≤8 weeks, >8 to 12 weeks, and >12 weeks after the completion of surgery. The association between RT timing and IBTR was evaluated by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis. A total of 1323 women met the inclusion criteria. The median follow-up was 6.6 years, with 311 patients followed for ≥10 years. A total of 126 IBTR events occurred. Patients were categorized by RT timing: 806 patients (61%) with timing of ≤8 weeks, 386 patients (29%) with timing of >8 to 12 weeks, and 131 patients (10%) with timing >12 weeks. The 5-year and 10-year IBTR rates were 5.8% and 13.0%, respectively, for RT starting ≤8 weeks after surgery; 3.8% and 7.6%, respectively, for RT starting >8 to 12 weeks after surgery; and 8.8% and 23.0%, respectively, for an RT delay >12 weeks after surgery (P = .004). On multivariable analysis, menopause (hazard ratio [HR], 0.54; P = .0009) and endocrine therapy (HR, 0.45; P = .002) were found to be protective against IBTR, whereas a delay in RT >12 weeks compared with ≤8 weeks was associated with a higher risk of IBTR (HR, 1.92; P = .014). There was no difference in IBTR noted between RT initiation at ≤8 weeks and initiation at >8 to 12 weeks after BCS (P = .3). A delay in RT >12 weeks is associated with a significantly higher risk of IBTR in women undergoing BCS for DCIS. Efforts should be made to avoid delays in starting RT to minimize the risk of disease recurrence. Cancer 2018;124:46-54. © 2017 American Cancer Society.


Extracorporeal photopheresis in cutaneous T-cell lymphoma and graft-versus-host disease induces both immediate and progressive apoptotic processes.
Extracorporeal photopheresis (ECP) therapy is used in the treatment of many T-cell-mediated conditions including cutaneous T-cell lymphoma and graft-versus-host disease and involves the reinfusion of a patient's own white cells following exposure to 8-methoxypsoralen and ultraviolet A. ECP has been demonstrated to induce significant levels of apoptosis in treated lymphocytes. Previous work has highlighted the importance of mitochondria and the caspase cascade in the regulation and execution of apoptosis and, more recently, a functional role for CD10 has been proposed for apoptotic lymphoid cells in vivo. To determine the effect of ECP on phosphatidylserine (PS) exposure, mitochondrial function, caspase activation and CD10 expression of treated lymphocytes. Lymphocytes were tested pre-ECP and at several stages post-ECP for changes to PS, mitochondrial transmembrane potential (DeltaPsim), activated caspases and CD10 expression. Early apoptosis induced a disruption in DeltaPsim, while caspase activation was not observed until 24 h post-ECP. CD10 expression was very weak and "late" in the apoptotic process. The early induction of apoptosis by ECP involves mitochondrial dysfunction, while later apoptosis is associated with the activation of caspases. CD10 expression was very weak and "late", preceded by a strong PS exposure. These apoptotic processes, in vivo, would induce the immediate and progressive phagocytosis of the majority of ECP-treated lymphocytes within 48 h.


Intervening with practitioners to improve the quality of prevention: one-year findings from a randomized trial of assets-getting to outcomes.
There continues to be a gap in prevention outcomes achieved in research trials versus those achieved in "real-world" practice. This article reports interim findings from a randomized controlled trial evaluating Assets-Getting To Outcomes (AGTO), a two-year intervention designed to build prevention practitioners' capacity to implement positive youth development-oriented practices in 12 community coalitions in Maine. A survey of coalition members was used to assess change on individual practitioners' prevention capacity between baseline and one year later. Structured interviews with 32 program directors (16 in the intervention group and 16 in the control group) were used to assess changes in programs' prevention practices during the same time period. Change in prevention capacity over time did not differ significantly between the intervention and control groups. However, in secondary analyses of only those assigned to the AGTO intervention, users showed greater improvement in their self-efficacy to conduct Assets-based programming and increases in the frequency with which they engaged in AGTO behaviors, whereas among non-users, self-efficacy to conduct Assets-based programming declined. Interview ratings showed improvement in several key areas of performance among intervention programs. Improvement was associated with the number of technical assistance hours received. These results suggest that, after one year, AGTO is beginning to improve the capacity of community practitioners who make use of it.


Zinc oxide nanostructures enhanced photoluminescence by carbon-black nanoparticles in Moiré heterostructures.
ZnO/carbon-black heterostructures were synthesized using a sol-gel method and crystallized by annealing at 500 °C under 2 × 10-2 Torr for 10 min. The crystal structures and binding vibration modes were determined by XRD, HRTEM, and Raman spectrometry. Their surface morphologies were observed by FESEM. The Moiré pattern that is observed in the HRTEM images confirms that the carbon-black nanoparticles were covered by the ZnO crystals. Measurements of optical absorptance revealed that the optical band gap of the ZnO/carbon-black heterostructures increased from 2.33 to 2.98 eV as the carbon-black nanoparticle content increases from 0 to 8.33 × 10-3 mol owing to the Burstein-Moss effect. The photoluminescence intensities at the near-band edge and of the violet, and blue light were increased by factors about 68.3, 62.8, and 56.8, respectively, when the carbon-black contents is of the 2.03 × 10-3 mol. This work reveals that the proper carbon-black nanoparticle content involved increases the PL intensities of the ZnO crystals in the short wavelength regime, supporting their potential application in the light-emitting devices.


Role of autophagy in di-2-ethylhexyl phthalate (DEHP)-induced apoptosis in mouse Leydig cells.
Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry. DEHP can cause testicular atrophy, yet the exact mechanism remains unclear. In this study, male mice were intragastrically (i.g.) administered with 0, 100, 200 or 400 mg DEHP/kg/day for 21 days. We found that DEHP caused disintegration of the germinal epithelium and decreased sperm density in the epididymis. Furthermore, there was a significant increase in the levels of cleaved Caspase-8, cleaved Caspase-3 and Bax proteins and a decrease in Bcl2 protein. The results indicated that DEHP could induce apoptosis of the testis tissue. Meanwhile, DEHP significantly induced autophagy in the testis tissues with increases in LC3-II, Atg5 and Beclin-1 proteins. The serum testosterone concentration decreased in the DEHP-treated group, implying that DEHP might lead to Leydig cell damage. Furthermore, oxidative stress was induced by DEHP in the testis. To further investigate the potential mechanism, mouse TM3 Leydig cells were treated with 0-80 μM DEHP for 48 h. DEHP significantly inhibited cell viability and induced cell apoptosis. Oxidative stress was involved in DEHP-induced apoptosis as N-Acetyl-L-cysteine (NAC), an inhibitor of oxidative stress, could rescue the inhibition of cell viability and induction of apoptosis by DEHP. Similar to the in vivo findings, DEHP could also induce cell autophagy. However, inhibition of autophagy by 3-Methyladenine (3-MA) significantly increased cell viability and inhibited apoptosis. Taken together, oxidative stress was involved in DEHP-induced apoptosis and autophagy of mouse TM3 Leydig cells, and autophagy might play a cytotoxic role in DEHP-induced cell apoptosis.


Trends of cancer mortality in Xi'an City, China: 2005-2020.
Describe and predict the malignant tumor deaths in Xi'an so as to provide evidence for the government to formulate the prevention and treatment plans. Overall malignant tumor death in Xi'an in the past 16 years was described. The multi-decrease life table was used to calculate cumulative mortality risk by cause and life expectancy reduction years by cause of malignant tumors in 2020. The join point regression models were used to analyze the change trend of standard mortality of malignant tumors in Xi'an from 2005 to 2020. The appropriate gray models were selected to predict the death of malignant tumors in Xi'an in the next decade. The mortality of total malignant tumors in Xi'an showed that men are higher than women and the elderly are higher than other groups. As for 2020, lung cancer had the highest risk of death for both men and women, while leukemia had the highest life expectancy reduction years by cause. From 2005 to 2020, standardized mortality of majority malignant tumors showed downward trends, which were particularly obvious in recent years. The prediction results of several major malignant tumors showed that in the next decade, the mortality of most malignant tumors had downward trends, but combined with the increase of population in the future, the number of malignant tumor deaths in Xi'an will continue to increase. Malignant tumors in Xi'an have decreasing mortality trends in recent years, and effective measures to prevent and treat tumors should be strengthened in the future.


Monostable multivibrators as novel artificial neurons.
Retriggerable and non-retriggerable monostable multivibrators are simple timers with a single characteristic, their period. Motivated by the fact that monostable multivibrators are implementable in large quantities as counters in digital programmable hardware, we set out to investigate their applicability as building blocks of artificial neural networks. We derive the nonlinear input-output firing rate relations for single multivibrator neurons as well as the equilibrium firing rate of large recurrent networks. We show that in rate-encoded monostable multivibrators networks the synaptic weights are tunable as the period ratio of connected units, and thus reconfigurable at run time in a counter-based digital implementation. This is illustrated with the task of handwritten digit recognition. Furthermore, we show in a task-independent manner that networks of monostable multivibrators are capable of nonlinear separation, when operating directly on pulse streams. Our research implies that pulse-coupled neural networks with excitable neurons showing a delayed response can perform computations even when working solely with suprathreshold pulses.


Leukoencephalopathy associated with intra-arterial ACNU in patients with gliomas.
Thirty cases of gliomas treated by surgery, radiotherapy and intra-arterial (IA) ACNU were reviewed with a focus on the late side-effect known as leukoencephalopathy. All cases were classified into three groups; remission (10 cases), regrowth (15 cases) and leukoencephalopathy (5 cases) from their outcome. The average total doses of IA ACNU were 49.8 mg/sqm body surface area in the remission group, 157.3 mg/sqm in the regrowth group and 203.1 mg/sqm in the leukoencephalopathy group. There were significant differences in the total IA ACNU doses between the remission group and both regrowth and leukoencephalopathy groups, while no significant differences were noticed in the dose of radiation given. There was a correlation between the total dose of IA ACNU and the occurrence of leukoencephalopathy. An autopsy of a typical case of leukoencephalopathy revealed various degrees of myelin breakdown and thickening of arterial walls, which probably manifested progressive dementia accompanied by urinary incontinence and gait disturbance.


Surgical manifestations of eosinophilic gastroenteritis in the pediatric patient.
Eosinophilic gastroenteritis, an inflammatory bowel disease of unknown etiology, occurs in one of 10,000 admissions to this Children's Hospital. We had added 4 cases to the 11 retrieved from a literature review. The inflammation is characterized by mature eosinophils predominating a transmural process which may produce pain, obstruction, perforation, bleeding, or fistulae. All levels of the gastrointestinal tract are involved, but stomach (25.9%) and small bowel (66.7%) lesions are most common. Eosinophilia occurs in 61% of children and allergy in 13%. X-rays may demonstrate a diffuse or localized process. Operative intervention may be necessary to exclude tumors or regional enteritis, and at times to extirpate complications of local disease, but conservative therapy is the treatment of choice for this exacerbating-remitting disease.


[Effects of orthodontic force on tumor necrosis factor alpha protein expression in the inflammatory periodontal tissues].
To explore the combined effects of orthodontic force and inflammation on the remodelling of periodontal tissues. The upper first molars underwent mesial orthodontic force on 48 rats suffering experimental periodontitis and 48 rats injected lipopolysaccharide, respectively. The TNF-alpha protein expression in the compressed periodontal tissues fluctuated during 0, 2, 12 hours and 2, 7, 14 days stages, the OD value got to the peak in the compressed periodontal tissues in 2 days. The mechanical remodelling effects were hindered due to the circumstance of acute or chronic inflammation. The research suggests that the orthodontic treatment to adult patients with periodontal inflammation should be taken carefully.


What can be revealed by extending the sensitivity of HBsAg detection to below the present limit?
We investigated what can be revealed by extending the sensitivity of HBsAg detection to below the present limit. We examined the sensitivity of this immunoassay in comparison with real-time PCR detection of HBV DNA using serially diluted sera from HBV carriers. Low HBsAg was measured in 210 healthy volunteers and 368 patients with non-B chronic liver diseases who were negative for HBsAg by a standard EIA method. The radical immunoassay was able to detect HBsAg at a concentration of 0.025 ng/ml. Low HBsAg was positive in 6 of 210 normal volunteers (2.86%), 5 of 65 non-B, non-C cirrhosis patients (7.69%), 6 of 62 non-B, non-C hepatocellular carcinoma patients (9.68%: p=0.04 vs. volunteers), 12 of 134 chronic hepatitis C patients (8.96%: p<0.02 vs. volunteers), and 11 of 107 hepatocellular carcinoma patients complicated by chronic hepatitis C (10.28%: p<0.008 vs. volunteers). Although no HBV DNA was positive in healthy volunteers, 9 patients with non-B chronic liver diseases were positive for HBV DNA by real-time PCR analysis. Increasing the sensitivity of HBsAg detection to below the present limit has revealed that infection with HBV, including occult HBV, is far more endemic than suspected previously.


A State-of-the-Art Review: Personalization of Tinnitus Sound Therapy.
Background: There are several established, and an increasing number of putative, therapies using sound to treat tinnitus. There appear to be few guidelines for sound therapy selection and application. Aim: To review current approaches to personalizing sound therapy for tinnitus. Methods: A "state-of-the-art" review (Grant and Booth, 2009) was undertaken to answer the question: how do current sound-based therapies for tinnitus adjust for tinnitus heterogeneity? Scopus, Google Scholar, Embase and PubMed were searched for the 10-year period 2006-2016. The search strategy used the following key words: "tinnitus" AND "sound" AND "therapy" AND "guidelines" OR "personalized" OR "customized" OR "individual" OR "questionnaire" OR "selection." The results of the review were cataloged and organized into themes. Results: In total 165 articles were reviewed in full, 83 contained sufficient details to contribute to answering the study question. The key themes identified were hearing compensation, pitched-match therapy, maskability, reaction to sound and psychosocial factors. Although many therapies mentioned customization, few could be classified as being personalized. Several psychoacoustic and questionnaire-based methods for assisting treatment selection were identified. Conclusions: Assessment methods are available to assist clinicians to personalize sound-therapy and empower patients to be active in therapy decision-making. Most current therapies are modified using only one characteristic of the individual and/or their tinnitus.