Extraction of nanocellulose and in-situ casting of ZnO/cellulose nanocomposite with enhanced photocatalytic and antibacterial activity.
Polymer hosted metallic nanostructures with diverse applications have become a prominent area of materials science, engineering and technology. In this study nanocellulose (NC) was synthesized from oil palm empty fruit bunches biomass via alkaline treatment and acid hydrolysis and characterized. The obtained NC was used as a host polymer for the synthesis of zinc oxide (ZnO) nanostructures through in-situ solution casting method. Alkaline treatment and acid hydrolysis increased the percentage crystalline index from 35.7% to 43.3% and 53.3% respectively. X-ray diffraction studies pointed to cellulose I, with a monoclinic structure. Zinc oxide/cellulose nanocomposite displayed more photocatalytic activity than pure ZnO nanostructures upon degradation of methylene blue, and also improved antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli.


Redefining Boundaries: Ruth Myrtle Patrick's Ecological Program at the Academy of Natural Sciences of Philadelphia, 1947-1975.
Ruth Myrtle Patrick (1907-2013) was a pioneering ecologist and taxonomist whose extraordinary career at the Academy of Natural Sciences of Philadelphia spanned over six decades. In 1947, an opportunity arose for Patrick to lead a new kind of river survey for the Pennsylvania Sanitary Water Board to study the effects of pollution on aquatic organisms. Patrick leveraged her already extensive scientific network, which included ecologist G. Evelyn Hutchinson, to overcome resistance within the Academy, establish a new Department of Limnology, and carry out the survey, which was a resounding success and brought much needed money to the Academy. As demand for her expertise grew among industrial companies, such as the chemical company DuPont, Patrick became more active in the world of applied science. She repurposed data and instruments from her river surveys to run new experiments, test ecological theories, and conduct long-term ecological studies. Through these studies, she advanced an argument that biologist Thomas Lovejoy dubbed the "Patrick principle," the idea that the ecological health of a body of water could be measured by the relative abundance and diversity of species living there. Patrick was elected to the National Academy of Sciences in 1970, became a board member of DuPont in 1975, and received two of the most prestigious awards in ecology: the Eminent Ecologist Award from the Ecological Society of America in 1972 and the Tyler Ecology Award in 1975. This article analyzes Patrick's unusual success in bridging the worlds of science and industry and her unusual ability to cross, and redefine, the perceived boundary between basic and applied fields in biology. It argues that Patrick's position at the Academy, an institution of natural history that was both willing and able to accept money from industrial corporations, is key to understanding her success in, and influence on, the field of river ecology.


Financial Hardship Among Pregnant and Postpartum Women in the United States, 2013 to 2018.
Financial hardship affects health care access and health outcomes among peripartum women. To evaluate the prevalence of financial hardship among peripartum women over time and by insurance type and income. This cross-sectional study included peripartum women, defined as women aged 18 to 45 years who reported being currently pregnant or pregnant in the past 12 months, who participated in the National Health Interview Survey from 2013 to 2018. Data were analyzed from January to May 2021. Current pregnancy or recent pregnancy as well as insurance type and income. Three measures of financial hardship within the last year were evaluated: (1) unmet health care need due to cost (unmet need for medical care or delayed or deferred medical care due to cost); (2) health care unaffordability (worry about paying for potential medical bills or existing medical debt); and (3) general financial stress (worry about subsistence spending [eg, monthly bills, housing]). The study cohort included 3509 peripartum women, weighted to represent 1 050 789 women (2018: an estimated 36 045 of 184 018 [19.6%] Hispanic, 39 017 [21.2%] Black, and 97 366 [52.9%] White), with a mean (SD) age of 29 (6) years. Overall, from 2013 to 2018, 24.2% (95% CI, 22.6%-26.0%) of peripartum women reported unmet health care need, 60.0% (95% CI, 58.0%-61.9%) reported health care unaffordability, and 54.0% (95% CI, 51.5%-56.5%) reported general financial stress. The prevalence of financial hardship outcomes did not substantially change between 2013 and 2018 (unmet health care need in 2013: 27.9% [95% CI, 24.4%-31.7%]; in 2018: 23.7% [95% CI, 19.5%-28.6%]; health care unaffordability in 2013: 65.7% [95% CI, 61.1%-70.0%]; in 2018: 58.8% [95% CI, 53.4%-64.0%]; general financial stress in 2013: 60.6% [95% CI, 55.2%-65.8%]; in 2018: 53.8% [95% CI, 47.8%-59.8%]). Women with private insurance had lower odds of unmet need (adjusted odds ratio [aOR], 0.67; 95% CI, 0.52-0.87) but higher odds of health care unaffordability (aOR, 1.88; 95% CI, 1.49-2.36) compared with women with public insurance. Peripartum women with household incomes less than 400% of the federal poverty level had higher odds of unmet need (aOR, 1.50; 95% CI, 1.08-2.08) and unaffordable care (aOR, 1.98; 95% CI, 1.54-2.55) compared with those with household incomes 400% or more of federal poverty level. These findings suggest that financial hardship among peripartum women in the United States was common from 2013 to 2018, including 24% of pregnant and postpartum women reporting unmet health care need and 60% reporting health care unaffordability. Women with private insurance and those living on lower incomes were more likely to experience unaffordable health care than women with pubic insurance and those with higher incomes, respectively. Targeted policy interventions are needed to improve health care affordability and promote overall economic security among peripartum women.


Structure, Process, and Culture Differences of Pediatric Trauma Centers Participating in an International Comparative Effectiveness Study of Children with Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is an important worldwide cause of death and disability for children. The Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial is an observational, cohort study to compare the effectiveness of six aspects of TBI care. Understanding the differences between clinical sites-including their structure, clinical processes, and culture differences-will be necessary to assess differences in outcome from the study and can inform the overall community regarding differences across academic centers. We developed a survey and queried ADAPT site principal investigators with a focus on six domains: (i) hospital, (ii) pediatric intensive care unit (PICU), (iii) medical staff characteristics, (iv) quality of care, (v) medication safety, and (vi) safety culture. Summary statistics were used to describe differences between centers. ADAPT clinical sites that enrolled a subject within the first year (32 US-based, 11 international) were studied. A wide variation in site characteristics was observed in hospital and ICU characteristics, including an almost sevenfold range in ICU size (8-55 beds) and more than fivefold range of overall ICU admissions (537-2623). Nursing staffing (predominantly 1:1 or 1:2) and the presence of pharmacists within the ICU (79 %) were less variable, and most sites "strongly agreed" or "agreed" that Neurosurgery and Critical Care teams worked well together (81.4 %). However, a minority of sites (46 %) used an explicit protocol for treatment of children with severe TBI care. We found a variety of inter-center structure, process, and culture differences. These intrinsic differences between sites may begin to explain why interventional studies have failed to prove efficacy of experimental therapies. Understanding these differences may be an important factor in analyzing future ADAPT trial results and in determining best practices for pediatric severe TBI.


SARS-Cov-2 ORF3a: Mutability and function.
In this study, analysis of changes of SARS-CoV-2 ORF3a protein during pandemic is reported. ORF3a, a conserved coronavirus protein, is involved in virus replication and release. A set of 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020 have been scanned. All ORF3a mutations in the virus genomes were grouped according to the collection date interval and over the entire data set. The considered intervals were: start of collection-February, March, April, May, June, July and August 2020. The top five most frequent variants were examined within each collection interval. Overall, seventeen variants have been isolated. Ten of the seventeen mutant sites occur within the transmembrane (TM) domain of ORF3a and are in contact with the central pore or side tunnels. The other variant sites are in different places of the ORF3a structure. Within the entire sample, the five most frequent mutations are V13L, Q57H, Q57H + A99V, G196V and G252V. The same analysis identified 28 sites identically conserved in all the genome isolates. These sites are possibly involved in stabilization of monomer, dimer, tetramerization and interaction with other cellular components. The results here reported can be helpful to understand virus biology and to design new therapeutic strategies.


Sarcopenia and Treatment Toxicity in Older Adults Undergoing Chemoradiation for Head and Neck Cancer: Identifying Factors to Predict Frailty.
This study was performed to identify treatment related toxicities in older adults undergoing concurrent chemoradiotherapy for head and neck cancer and nutritional and skeletal muscle measures that might identify frailty. Imaging analysis was done with the following skeletal muscle measurements: skeletal muscle index (SMI), skeletal muscle density (SMD), and skeletal muscle gauge (SMG). Patients were dichotomized by age into younger (<70 years old, 221 patients) and older age groups (≥70 years old, 51 patients). Low SMI was more common in older patients (86.7%) compared to younger patients (51.7%, p < 0.01), as were low SMD (57.8% vs. 37.3%, p = 0.012) and low SMG (76.1% vs. 44.2%, p < 0.01), despite having similar BMIs (27.3 kg/m2 versus 27.7 kg/m2, p = 0.71). Older patients were significantly more likely to experience chemotherapy toxicity than younger patients (54.9% versus 32.3%, p < 0.01). On multivariate analysis age (p < 0.01), current smoking status (p < 0.01), and low SMI (p < 0.01) remained as significant predictors for missed chemotherapy cycles or discontinuation. Older patients were more likely to require ≥5-day radiation breaks than younger patients (27.5% versus 8.6%, p < 0.01). On multivariate analysis, age (p < 0.01), low albumin status (p = 0.03), and low SMI (p = 0.04) were identified as predictors of prolonged radiation treatment breaks. Based on the results of our study, sarcopenia may be used as an additional marker for frailty alongside traditional performance status scales.


Does mild mean minor? Recovery after closed head injury.
The sequelae of severe closed head injury has received much attention in the literature, but the effects of mild closed head injury are less well established. The course of an 18-year-old female who sustained a mild closed head injury is presented. Substantial gains in intellectual function were observed over the year postinjury, with the most dramatic improvement coming in the first 6 months after the accident. Psychologic adjustment did not mirror the cognitive recovery. The implications of these findings are discussed.


Identification of a consensus site for TRAF6/p62 polyubiquitination.
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an ubiquitin ligase that regulates a diverse array of physiological processes via forming Lys-63 linked polyubiquitin chains. In this study, the lysine selection process for TRAF6/p62 ubiquitination was examined. The protein sequence of two characterized TRAF6/p62 substrates, NRIF and TrkA, revealed a conserved consensus pattern for the ubiquitination site of these two TRAF6 substrates. The consensus pattern established in the verified substrates was common to the other Trk receptor family members, TrkB and TrkC. Interestingly, Lysine 811 in TrkB was selected for ubiquination, and mutation of Lysine 811 diminished the formation of TRAF6/p62 complex that is necessary for effective ubiquination. Moreover, downstream signaling was affected upon binding of BDNF to the mutant TrkB receptor. These findings reveal a possible selection process for targeting a specific lysine residue by a single E3 ligase and underscore the role of the scaffold, p62, in this process.


Riluzole has no acute effect on motor unit parameters in ALS.
Riluzole is the only drug to have been approved for the treatment of amyotrophic lateral sclerosis (ALS/MND). Its mechanism of action is complex and includes actions on NMDA and kainate receptors and modulation of voltage gated Na channels. In ALS, its effects on measurable parameters of the motor units utilising current neurophysiological techniques are unknown. In an acute randomized, double-blind, placebo-controlled, cross-over experiment, we serially assessed the effects of riluzole on motor units in muscles affected by ALS/MND using EMG. We discuss the results of our observations in the light of previous clinical trials, and their implications.


Prostate-specific antigen and prostate cancer mortality: a systematic review.
Although findings from recently published clinical trials and a review from the U.S. Preventive Services Task Force suggest that there is limited to no prostate cancer mortality benefit associated with prostate-specific antigen (PSA) screening, confusion remains as to whether the use of PSA as a screening tool for prostate cancer is warranted. A systematic literature review was done in 2012 to identify case-control studies from the past 20 years that focused on evaluating the association between screening for prostate cancer and prostate cancer mortality. Emphasis was put on synthesizing the results of these studies, evaluating their limitations, and identifying remaining questions and issues that should be addressed in future studies. A total of seven studies were identified in this time period, with the majority suggesting that a reduction in prostate cancer mortality is associated with PSA screening. However, the findings may be limited by various biases inherent to case-control studies of screening tests, such as selection biases resulting from both case and control subject selection, exposure measurement issues, lead and length biases, and issues specific to prostate cancer screening such as the influence of digital rectal examinations. Findings from existing case-control studies of PSA and prostate cancer mortality suggest that there is a mortality benefit from PSA screening. However, these studies may be limited by bias and must therefore be interpreted with caution. As uncertainty regarding PSA screening remains, future studies to evaluate the association between PSA and prostate cancer mortality should address these potential biases directly.


Pyrenocines J-M: four new pyrenocines from the endophytic fungus, Phomopsis sp.
Four new pyrenocines, named pyrenocines J-M (1-4), were isolated from an endophytic fungus, Phomopsis sp, by a bioassay-guided method. The structures of the new compound have been assigned from ¹H and ¹³C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. Preliminary studied showed that compounds 1, 2 and 4 showed good antifungal, antibacterial, and algicidal properties, while compound 3 had good antibacterial and algicidal properties.


Evaluation of Tellurium as a Fuel Additive in Neodymium-Containing U-Zr Metallic Fuel.
Phase-stability in a U-Zr-Te-Nd multi-component metallic fuel for advanced nuclear reactors is systematically investigated by taking into account binary, ternary and quaternary interactions between elements involved. Historically, the onset of fuel-cladding chemical interactions (FCCI) greatly limits the burnup potential of U-Zr fuels primarily due to interactions between lanthanide fission products and cladding constituents. Tellurium (Te) is evaluated as a potential additive for U-Zr fuels to bind with lanthanide fission products, e.g. neodymium (Nd), negating or mitigating the FCCI effect. Potential fresh fuel alloy compositions with the Te additive, U-Zr-Te, are characterized. Te is found to completely bind with Zr within the U-Zr matrix. Alloys simulating the formation of the lanthanide element Nd within U-Zr-Te are also evaluated, where the Te-Nd binary interaction dominates and NdTe is found to form as a high temperature stable compound. The experimental observations agree well with the trends obtained from density functional theory calculations. According to the calculated enthalpy of mixing, Zr-Te compound formation is favored in the U-Zr-Te alloy whereas NdTe compound formation is favored in the U-Zr-Te-Nd alloy. Further, the calculated charge density distribution and density of states provide sound understanding of the mutual chemical interactions between elements and phase-stability within the multi-component fuel.


Human B-lymphocyte colony responses: suboptimal colony responsiveness in aged humans associated with defective function of B cells and monocytes.
The abilities of human B cells from young and aged subjects to form colonies in semisolid cultures stimulated with Staphylococcus protein A were investigated. Approximately three-fourths of aged adults had significantly diminished colony responses compared to young adults. In 55% of these aged adults, the in vitro blocking of monocyte prostaglandin synthesis lead to a 1.5-fold or greater augmentation of the depressed colony responses. Other experiments showed that the improvement with indomethacin could not be explained by the greater sensitivity of aged versus young B-cell colony precursors to prostaglandin suppression. However, indomethacin failed to improve the depressed colony responses of the remaining aged adults. This failure could not be attributed to deficient interleukin 1 production, detectable alterations in accessory cell subsets of monocytes, or the lack of potential colony precursors bearing sIgD/M. Instead, the B cells from these aged subjects demonstrated a substantial decrease in the capping of sIgD/M compared to the B cells of aged subjects which displayed improved colony responses with indomethacin and compared to the B cells from young adults. Thus, these data indicate that the diminished B-cell colony responses of aged humans represent aberrancies within both the B-cell and monocyte lineages which might coexist.


Craniometaphyseal dysplasia associated with hydrocephalus: case report.
Craniometaphyseal dysplasia is a rare bone disorder that may cause a variety of neurological abnormalities; hydrocephalus has not been observed with this disorder, however. A case of craniometaphyseal dysplasia associated with hydrocephalus is reported, and possible causes are discussed.


Dietary calcium modulates Mycobacterium paratuberculosis infection in beige mice.
A 6-month study was conducted to evaluate the effects of feeding different levels of dietary calcium (Ca) on the persistence of Mycobacterium paratuberculosis infection using a mouse model. Beige mice, averaging 8 weeks of age, were randomly assigned to one of the following dietary treatments: 1) 0.02% Ca, 2) 0.15% Ca, 3) 0.45% Ca, and 4) 1.0% Ca. Mice were infected intraperitoneally with 10(8) CFU viable M. paratuberculosis for 1, 3, and 6 month periods. Plasma Ca levels was unaffected by dietary Ca (x = 7.3 mg/dl). Plasma levels of 1,25(OH)2D3 was elevated significantly in 0.02% and 0.15% Ca groups compared to other treatments at the end of each period, with the highest levels observed for 0.02% Ca mice and intermediate values for 0.15% Ca mice. One month after infection, numbers of viable M. paratuberculosis cultured from the spleen were significantly reduced for 0.15% Ca mice, whereas the number of bacteria isolated from the liver and mesenteric lymph node (MLN) were higher for the 0.02% Ca group. There were no differences in bacterial numbers in the ileum although they tended to be higher for the 0.02% Ca group. Three months after infection, bacterial numbers in the spleen, ileum, and MLN did not differ across treatments, however, significantly lower numbers were found in the liver of 1.0% Ca mice. Reduced bacterial counts were also observed in the liver of 0.15%. 0.45%, and 1.0% Ca mice after a 6-month infection period compared to the 0.02% Ca group, with the lowest numbers isolated from the 1.0% Ca mice. Numbers of viable bacteria cultured from the ileum and MLN after 6 months of infection were also significantly reduced in 1.0% Ca mice. These results suggest that Ca metabolism is an important modulator of M. paratuberculosis infection.


From ACE to ACENO: How America's Munson added Harley's British mixture to nitrous oxide.
An Ohio dentist, Corydon Munson, patented a gasometer with an attachment for vaporizing trace amounts of volatile general anesthetics or their mixtures into unoxygenated nitrous oxide. After vaporizing a variant of George Harley's ACE mixture into nitrous oxide, Munson branded his own novel anesthetic combination as ACENO.


Common culprits in childhood poisoning: epidemiology, treatment and parental advice for prevention.
Unintentional poisoning in children less than 6 years of age is a common occurrence. The majority of cases involve 1- and 2-year-old children who ingest nonpharmaceutical products. Although the clinical outcomes of these exposures is usually favourable, deaths do occur. In the US, the causes of death most commonly reported by the American Association of Poison Control Centers Toxic Exposure Surveillance System (AAPCC TESS) are carbon monoxide and adult formulations of iron. The exposures most commonly reported by the AAPCC TESS are cosmetic/personal care products (e.g. perfume, cologne and aftershave), household cleaning substances (e.g. bleach and alkaline corrosives) and analgesics [e.g. paracetamol (acetaminophen)]. Prevention is important and exposure to poisons should be considered a preventable childhood injury. The use of child-resistant packaging and the secure storage of household substances are the basis of preventing unintentional exposures. Parents and healthcare professionals need to be aware of what constitutes high risk exposure, as well as those exposures which are common but not serious. Poison prevention efforts should also address the appropriate role of the poison information centre.


Failure to induce neoplasia in nude mice by injection of disrupted cells from continuous cell lines.
Nude mice were injected subcutaneously with disrupted cells from three continuous cell lines (HeLa, NCTC clone 2472 and Morris hepatoma). No tumours were observed at either the inoculation site or in other organs taken at 35 or 90 days after injection. Live cells from one line (HeLa) produced tumours at the inoculation site after eight to 12 days.


Negative inotropic effect of selective AT2 receptor stimulation and its modulation by the endocardial endothelium.
Angiotensin II is an octapeptide whose effects are mediated by two types of receptors. AT(1) receptors are responsible for the vasoconstrictor, positive inotropic and growth promoting properties, while AT(2) receptors have been linked to vasodilator and anti-mitogenic properties. In this study we investigated the effects of selective AT(2) receptor stimulation on myocardial contractility and lusitropy. Effects of selective AT(2) receptor activation were evaluated in rabbit right papillary muscles (n=96) by adding increasing concentrations of H-9395, an AT(2) receptor agonist, alone or in presence of a selective AT(1) receptor antagonist (ZD-7155), or alternatively, by adding increasing concentrations of angiotensin II in presence of ZD-7155. In the latter conditions, selective AT(2) receptor activation was also performed in presence of NG-nitro-L-Arginine, indomethacin, proadifen, hydroxocobalamin, apamin plus charybdotoxin, Hoe-140 or PD-123,319, as well as, after endocardial endothelium removal. Selective AT(2) stimulation induced a negative inotropic and lusitropic effect in the first three protocols. This effect was completely abolished after selective removal of the endocardial endothelium and blunted in presence of Hoe-140, hydroxocobalamin, apamin plus charybdotoxin and PD-123,319, but maintained in presence of NG-nitro-L-Arginine, indomethacin or proadifen. Selective AT(2) receptor stimulation induces a negative inotropic and lusitropic effect, which is modulated by endocardial endothelium and mediated by bradykinin B(2) receptors through NO release and calcium dependent potassium channels activation. Such findings may help to better understand the therapeutic effects of selective AT(1) antagonists, which are increasingly used for treating cardiovascular diseases.


Determination of the emission probabilities of the principal gamma-rays for 134Cs to a high precision.
While multi-gamma-ray emitting nuclides such as 75Se, 134Cs and 152Eu have reasonably well-defined decay scheme, some inconsistencies still remain. Detailed evaluations and weighted-mean analyses result in the recommendation of gamma-ray emission probabilities with small uncertainties, although significant deviations exist in the measured values. Therefore, the gamma-ray emission probabilities of 134Cs have been measured to a high precision after an extremely accurate calibration of detection efficiency. The resulting data agree extremely well with the evaluated values in IAEA-TECDOC-619 (IAEA, X-ray and gamma-ray standards for detector calibration, IAEA-TECDOC-619, IAEA, Vienna, 1991).


Image quality in CT: From physical measurements to model observers.
Evaluation of image quality (IQ) in Computed Tomography (CT) is important to ensure that diagnostic questions are correctly answered, whilst keeping radiation dose to the patient as low as is reasonably possible. The assessment of individual aspects of IQ is already a key component of routine quality control of medical x-ray devices. These values together with standard dose indicators can be used to give rise to 'figures of merit' (FOM) to characterise the dose efficiency of the CT scanners operating in certain modes. The demand for clinically relevant IQ characterisation has naturally increased with the development of CT technology (detectors efficiency, image reconstruction and processing), resulting in the adaptation and evolution of assessment methods. The purpose of this review is to present the spectrum of various methods that have been used to characterise image quality in CT: from objective measurements of physical parameters to clinically task-based approaches (i.e. model observer (MO) approach) including pure human observer approach. When combined together with a dose indicator, a generalised dose efficiency index can be explored in a framework of system and patient dose optimisation. We will focus on the IQ methodologies that are required for dealing with standard reconstruction, but also for iterative reconstruction algorithms. With this concept the previously used FOM will be presented with a proposal to update them in order to make them relevant and up to date with technological progress. The MO that objectively assesses IQ for clinically relevant tasks represents the most promising method in terms of radiologist sensitivity performance and therefore of most relevance in the clinical environment.


Sleep as a Therapeutic Target for Pain Management.
The purpose of this review is to provide a summary of the utilization of sleep as a therapeutic target for chronic pain and to evaluate the recent literature on current and proposed pharmacologic and non-pharmacologic sleep interventions used in the management of pain disorders. Sleep is a promising therapeutic target in the treatment of pain disorders with both non-pharmacologic and pharmacologic therapies. Non-pharmacologic therapies include cognitive behavioral therapy and sensory-based therapies such as pink noise, audio-visual stimulation, and morning bright light therapy. Pharmacologic therapies include melatonin, z-drugs, gabapentinoids, and the novel orexin antagonists. However, more research is needed to clarify if these therapies can improve pain specifically by improving sleep. There is a vast array of investigational opportunities in sleep-targeted therapies for pathologic pain, and larger controlled, prospective trials are needed to fully elucidate their efficacy.


Association between delta anion gap and hospital mortality for patients in cardiothoracic surgery recovery unit: a retrospective cohort study.
High level of anion gap (AG) was associated with organic acidosis. This study aimed to explore the relationship between delta AG (ΔAG = AGmax - AGmin) during first 3 days after intensive care unit (ICU) admission and hospital mortality for patients admitted in the cardiothoracic surgery recovery unit (CSRU). In this retrospective cohort study, we identified patients from the open access database called Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). A logistic regression model was established to predict hospital mortality by adjusting confounding factors using a stepwise backward elimination method. We conducted receiver operating characteristic (ROC) curves to compare the diagnostic performance of acid-base variables. Cox regression model and Kaplan Meier curve were applied to predict patients' 90-day overall survival (OS). A total of 2,860 patients were identified. ΔAG was an independent predictive factor of hospital mortality (OR = 1.24 per 1 mEq/L increase, 95% CI: 1.11-1.39, p < 0.001). The area under curve (AUC) values of ΔAG suggested a good diagnostic accuracy (AUC = 0.769). We established the following formula to estimate patients' hospital mortality: Logit(P) = - 15.69 + 0.21ΔAG + 0.13age-0.21BE + 2.69AKF. After calculating Youden index, patients with ΔAG ≥ 7 was considered at high risk (OR = 4.23, 95% CI: 1.22-14.63, p = 0.023). Kaplan Meier curve demonstrated that patients with ΔAG ≥ 7 had a poorer 90-day OS (Adjusted HR = 3.20, 95% CI: 1.81-5.65, p < 0.001). ΔAG is a prognostic factor of hospital mortality and 90-day OS. More prospective studies are needed to verify and update our findings.


Liver development during Xenopus tropicalis metamorphosis is controlled by T3-activation of WNT signaling.
Thyroid hormone (T3) regulates vertebrate organ development, growth, and metabolism through the T3 receptor (TR). Due to maternal influence in mammals, it has been difficult to study if and how T3 regulates liver development. Liver remodeling during anuran metamorphosis resembles liver maturation in mammals and is controlled by T3. We generated Xenopus tropicalis animals with both TRα and TRβ genes knocked out and found that TR double knockout liver had developmental defects such as reduced cell proliferation and failure to undergo hepatocyte hypertrophy or activate urea cycle gene expression. RNA-seq analysis showed that T3 activated canonical Wnt pathway in the liver. Particularly, Wnt11 was activated in both fibroblasts and hepatic cells, and in turn, likely promoted the proliferation and maturation of hepatocytes. Our study offers new insights into not only how T3 regulates liver development but also on potential means to improve liver regeneration.


[Clinical and genetic analysis of an infant with combined pituitary hormone deficiency due to POU1F1 gene variants].
To explore the clinical characteristics and genetic basis for an infant featuring combined pituitary hormone deficiency. Clinical data and results of DNA sequencing of the child were analyzed. The 10-month-old male infant presented with recurrent hypoglycemia, extremely poor appetite and constipation, and severe growth retardation from 2 months on, in addition with pituitary hormone deficiency involving growth hormone, thyroid stimulating hormone, and prolactin. Next generation sequencing revealed a novel heterozygous c.767-769del (p.Glu256del) variant of the POU1F1 gene in the patient. The patient was diagnosed with combined pituitary hormone deficiency due to the POU1F1 gene variant, for which replacement therapy including thyroxine and growth hormone was provided. Hypoglycemia is unusual in patients carrying POU1F1 gene variants and requires close attention in clinical practice. For children with multiple pituitary hormone deficiency, genetic testing should be recommended to determine the cause.


Polyphosphoinositide synthesis and protein phosphorylation in the plasma membrane from full-grown Bufo arenarum oocytes.
1. Polyphosphoinositide content and phosphorylation of lipids and proteins were analyzed in oocytes of the toad Bufo arenarum Hensel. 2. Plasma membrane-enriched fractions obtained from full-grown, prophase-arrested oocytes incorporated 32P into both phospholipids and proteins after incubation with [gamma-32P]ATP in an Mg(2+)-containing medium. Phosphatidylinositol 4-phosphate (PIP), phosphatidate (PA) and phosphatidylinositol-4,5-bisphosphate (PIP2) were the only labelled lipids. The 32P incorporation depended on incubation time, the amount of protein, and the ATP concentration. 3. Autoradiography of polyacrylamide gel electropherograms and scintillation counting showed that the radioactivity was mainly associated with a group of membrane proteins having an M(r) of 87,000. 4. This paper provides evidence for the capacity of prophase-arrested oocytes from Bufo arenarum to synthesize polyphosphoinositides and to phosphorylate distinct membrane proteins.


Nucleotide and nucleoside-based drugs: past, present, and future.
Nucleotide and nucleoside-based analogue drugs are widely used for the treatment of both acute and chronic viral infections. These drugs inhibit viral replication due to one or more distinct mechanisms. It modifies the virus's genetic structure by reducing viral capacity in every replication cycle. Their clinical success has shown strong effectiveness against several viruses, including ebolavirus, hepatitis C virus, HIV, MERS, SARS-Cov, and the most recent emergent SARS-Cov2. In this review, seven different types of inhibitors have been selected that show broad-spectrum activity against RNA viruses. A detailed overview and mechanism of actionof both analogues are given, and the clinical perspectives are discussed. These inhibitors incorporated the novel SARS-CoV-2 RdRp, further terminating the polymerase activity with variable efficacy. The recent study provides a molecular basis for the inhibitory activity of virus RdRp using nucleotide and nucleoside analogues inhibitors. Furthermore, to identify those drugs that need more research and development to combat novel infections. Consequently, there is a pressing need to focus on present drugs by establishing their cell cultures. If their potencies were evidenced, then they would be explored in the future as potential therapeutics for novel outbreaks.


Particulate enhanced membrane uptake of 1,2-benzanthracene observed by fluorescence spectroscopy: a possible role in co-carcinogenesis.
In recognition of the co-carcinogenic effects of particulate matter and chemical carcinogens, we investigated the effect of particulate silica on the rates of membrane uptake of 1,2-benzanthracene. The fluorescence emission spectra and the apparent quantum yields of benzanthracene and dependent upon adsorption to silica and upon the surface density of benzanthracene on the silica. The fluorescence spectral shifts which occur upon transfer of benzanthracene from the silica surface to phospholipid vesicles provided a convenient means to quantitate the membrane uptake of benzanthracene from particulates. The rate of benzanthracene uptake by dipalmitoyl-L-alpha-phosphatidylcholine vesicles was independent of the concentration of lipid, indicating that the rate-limiting step may involve its solubilization in the aqueous phase. These uptake rates were also independent of the surface density of benzanthracene on the silica, indicating that the benzathracene molecules are dispersed uniformly on the silica surface. Rates of membrane uptake of benzanthracene from the crystalline, microcrystalline, and the silica-absorbed states were compared, and are greatly enhanced by a reduction in crystal size. Silica-adsorbed benzanthracene had the most rapid rate of membrane uptake. Silica did not cause disruption of the lipid vesicles. These results indicate that particulates can enhance the cellular availability of the chemical carcinogens.


Seawater intrusion mapping using electrical resistivity tomography and hydrochemical data. An application in the coastal area of eastern Thermaikos Gulf, Greece.
The aim of this study was to determine the extent and geometrical characteristics of seawater intrusion in the coastal aquifer of the eastern Thermaikos Gulf, Greece. Hydrochemical data and geoelectrical measurements were combined and supplemented to determine the hydrochemical regime of the study site in regard to seawater phenomena. Chemical analysis of groundwater was performed in 126 boreholes and fifteen electrical resistivity tomographies (ERT) were measured, whereas in two sites the ERT measurements were repeated following the wet season. The Cl(-) concentrations recorded reached 2240 mg/L indicating seawater intrusion which was also verified by ionic ratios. The ionic ratios were overlapped and a seawater intrusion map (SWIM) was produced. A significant part of the coastal aquifer (up to 150 km(2)) is influenced by seawater intrusion. The areas with the most intensive salinization are located between Nea Kallikratia-Epanomi and Aggelochori-Peraia. According to the ERTs, in the influenced areas the salinization of the aquifer exceeds 1 km toward the mainland and its depth reaches 200 m. In the area surrounding Thessaloniki airport, the ERTs revealed salinization of the upper aquifer to depths of up to 40 m, whereas the lower aquifer is uninfluenced. This abnormal distribution of seawater intrusion demonstrates the value of geoelectrical methods in the study of seawater intrusion especially in areas with limited available hydrochemical data.


Pitfalls of prenatal diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia.
Hormonal measurements and HLA genotyping of amniotic fluid at midgestation correctly predicted the postnatal diagnosis of congenital adrenal hyperplasia (CAH) in 29 of 32 fetuses at risk. Of these 29, 7 were predicted to have prenatal-onset classical 21-hydroxylase deficiency (21-OH def) based on elevated amniotic fluid 17-hydroxyprogesterone (17-OHP) and delta 4-androstenedione (delta 4-A) levels. These 7 fetuses and their index cases were ultimately proven to have salt-wasting classical 21-OH def. Of 5 who were HLA typed, the genotype was identical to the index case in 4; in one, HLA prediction was not possible, because the parents shared identical HLA antigens. Normal amniotic fluid 17-OHP and delta 4-A levels in the remaining 22 fetuses predicted that they were not affected with classical CAH. These children have been clinically asymptomatic to date or proven biochemically not to have classical or nonclassical CAH. Of the 22 fetuses, 11 were predicted by HLA genotyping to be homozygous normal or heterozygous for 21-OH def. In 3 of the 32 fetuses, prenatal diagnosis was incorrect. In one, the fetus was predicted to have CAH based on HLA identity to the index case. However, amniotic fluid 17-OHP and delta 4-A were normal, and the fetus was normal. The index case of this family did not have CAH, but was a normal child. Thus, amniotic fluid hormone levels accurately predicted a normal fetus, while HLA genotyping was not relevant in prenatal diagnosis because the index case was unaffected. The second fetus was predicted to be affected on the basis of HLA genotyping and to be unaffected based on normal amniotic fluid 17-OHP and delta 4-A. During infancy, this female infant had postnatal-onset nonclassical CAH. The index case in this family, presumed to have classical simple virilizing CAH, was later diagnosed to have nonclassical CAH. Thus, in nonclassical CAH, hormonal measurement of 17-OHP and delta 4-A is not useful in prenatal diagnosis; only HLA genotyping of the fetus is valuable. In the third case, the fetus was predicted to be a heterozygote by HLA genotyping and to be unaffected by hormonal measurement. Postnatally, at age 2 7/12 yr, the male child was found to have classical simple virilizing CAH and to be HLA-B-DR identical to his brother (index case) who also has classical simple virilizing CAH.(ABSTRACT TRUNCATED AT 400 WORDS)


Micromotion at the head-stem taper junction of total hip prostheses is influenced by prosthesis design-, patient- and surgeon-related factors.
Taper junctions of modular hip prostheses are susceptible to fretting and crevice corrosion. Prevalence and significance increase for cobalt-chromium heads assembled on titanium-alloy stems. Retrieval and in-vitro studies have identified micromotion between the taper components to accelerate the corrosion process. The aim of this study was to identify the most critical factors contributing to increased micromotion, which is most likely influenced by design-, patient- and surgeon-related aspects. Micromotion between head and stem taper surfaces was measured for different taper surface topographies and load orientations. Consecutive visual images were recorded through windows in the head component. By image matching analysis the local micromotions at the taper junction between head and stem tapers were determined. To extend the findings to taper regions not visible through the windows, finite element models were generated. The models were further utilized to investigate the influence of head length, taper angle difference and assembly force on micromotion. Significantly higher micromotion (+20%) was found under varus loading (7.1 µm) in comparison to valgus loading (5.9 µm). Smooth and microgrooved stem tapers exhibited equal amounts of micromotion. The numerical model revealed head tilting and recurring taper contact changes in terms of cyclic engagement/disengagement during the loading sequences. Especially long heads (+240%) and low assembly forces (+53%) were found to substantially increase micromotion (from 2.7 µm to 9.3 µm and from 4.1 µm to 8.8 µm, respectively). This study accentuates the susceptibility of taper junctions to a variety of factors, which need to be appreciated in preoperative planning and surgical procedure to reduce the amount of micromotion and such minimize the risk of critical corrosion.


Analysis of fatalities in road accidents.
This paper is based on the analysis of 524 autopsies carried out on the victims of road accidents at the Office of the Judicial Medical Officer, Colombo for a 2-year period ending December 1985. 51.4% of the fatalities were among pedestrians. The highest number of fatalities were in the age group 20-29 years. Cranio-cerebral injury was the commonest cause of death in all groups of victims.


Analysis of the relationship between health status and mortality in hypercapnic patients with noninvasive ventilation.
Health status and mortality are important outcomes in patients with advanced pulmonary diseases receiving noninvasive ventilation (NIV). However, their relationship has not been thoroughly investigated. The present study prospectively recruited 56 stable outpatients treated with NIV for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease and/or pulmonary tuberculosis sequelae. At baseline, health status was measured by the Medical Outcomes Study 36-item short form, a generic questionnaire; the St. George's Respiratory Questionnaire (SGRQ), a respiratory-specific questionnaire; and two respiratory failure-specific questionnaires, the Maugeri Respiratory Failure questionnaire and the Severe Respiratory Insufficiency (SRI) questionnaire. Arterial blood gas, pulmonary function, dyspnea and psychological status were also measured. In cross-sectional comparisons of the four health status questionnaires, the SGRQ and SRI questionnaire had lower floor and ceiling effects. During the 3-year follow-up, 16 patients (29%) died. Health status shown by the SGRQ and SRI was significantly predictive of mortality, independently of the physiological measures of low body mass index (BMI), hypercapnia, and low pulmonary function. Stepwise multivariate analyses indicated that the SRI summary score was the most significant predictor of mortality (P = 0.0006) followed by BMI (P = 0.012). There was a significant relationship between health status and 3-year mortality in patients with NIV, independently of under-nutrition, hypercapnia and low pulmonary function. Health status measurement is important not only to comprehensively evaluate disease severity in relation to its close association with mortality, but also to elucidate factors that improve the survival of patients with advanced respiratory diseases.


[The role of monoclonal antibodies to Venezuelan equine encephalomyelitis virus in specific activation of immunocompetent cells].
Effects of rabbit monoclonal antiviral antibodies on the function of splenic cells at passive immunization of animals was studied. A reliable increase of stimulation index was observed at in vitro activation of BALB/c murine splenocytes with Venezuelan equine encephalomyelitis virus, the mice being passively immunized with rat monoclonal antibodies 8D2, 3G1, and 5E7.


Human immune reconstitution with spleen cells in SCID/Beige mice.
We developed an original experimental model to study chronic vascular rejection (CVR) consisting of a graft of human mesenteric artery followed by human immune reconstitution into CB.17 SCID/Beige mice. Human immune reconstitution achieved after human PBMC injection has often been variable and incomplete. The aim of this work was to develop an alternative method to achieve a complete, functional human immune reconstitution. After institutional authorizations, spleen cells were recovered from cadaveric organ donors. Single intraperitoneal injections of various doses of spleen cells were made into 70 CB.17 SCID/Beige mice. Reconstitution of the human immune system was monitored by flow cytometry (circulating human cells) and ELISA (human IgG). Colonization of murine lymphoid organs by human cells was studied by immunohistochemistry and flow cytometry. Evaluation of the immune function consisted of examination of CVR lesions in human arterial grafts. The animals were humanely killed at day 28. After injection of 30 to 40 x 10(6) spleen cells, the mice showed significant human CD3(+), CD19(+), and CD56(+) populations in peripheral blood. The mean human cells levels were, respectively, 8.2% +/- 5.4%, 2.9% +/- 1.2%, and 5.3% +/- 5.1%. Murine spleen and mesenteric lymph nodes were colonized by human T and B cells, while the murine thymus was only colonized by human T cells. Human IgG was detected in murine serum (65.9 +/- 63.3 mg/L) and typical CVR lesions were observed within the allogeneic grafts. Intraperitoneal injection of 30 to 40 x 10(6) human spleen cells into CB.17 SCID/Beige mice induces complete and functional human immune reconstitution allowing the study of CVR under human allogeneic conditions.


Cloning and functional characterization of the ovine malic enzyme promoter.
While in human and rodents lipogenesis occurs predominantly in the liver, adipose tissue is the major site in ruminants. Here we report the nucleotide sequence of the 5'-flanking region of the ovine malic enzyme gene (ME1). The ME1 promoter is located within a GC-rich region fulfilling the criteria of CpG islands and lacks a TATA-box. Deletion analysis identified a region (-231/-170) that suppressed promoter activity in luciferase assays in HepG2 hepatoma cells but not in 3T3-L1 adipocytes. This region contains a putative triiodothyronine response element (T3RE) that differs from the human ME1 T3RE by two nucleotides. When the human ME1 T3RE was introduced into the ovine ME1 promoter context, transcriptional activity was increased in the hepatic cell lines HepG2 and H4IIE but not in differentiated 3T3-L1 cells. Our results suggest that the sequence of the T3RE in the ME1 promoter determines differences in the tissue/species activity of malic enzyme in ruminants and human.


Myelin expression is altered in the brains of neonatal rats reared in a fluctuating oxygen atmosphere.
Preterm infants receiving supplemental oxygen therapy experience frequent fluctuations in their blood oxygen levels, the magnitude of which has been associated with the incidence and severity of retinopathy of prematurity in such infants. Our objective was to investigate in a relevant animal model whether the immature brain with its poorly vascularised white matter might also be susceptible to injury when exposed to such fluctuations in blood oxygen. Newborn rats were reared in an atmosphere in which a computer reproduced the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24-week preterm infant who had developed severe retinopathy. Following 14 days of exposure, we measured the expression of active caspase-3, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat pups raised in room air. Compared to room air controls, at day 14, the expression of active caspase-3 was increased by up to 162% (significant increase in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21, following 7 days of reparative recovery, GFAP levels in most areas of oxygen-exposed brains had returned to near control levels. There were no longer significant differences in caspase-3 levels apart from the cerebral cortex, cerebellum and striatum. In contrast, MBP expression was now much higher in most regions of the treated brains compared to controls. We conclude that fluctuations in blood oxygen, observed in preterm survivors, may constitute a source of injury to the white matter and corpus striatum of the developing brain and contribute to the neurological sequelae in extremely premature infants.


Uneven paths: Soft Policy's benefits to recovery in Louisiana Parishes after Hurricanes Katrina and Rita.
Factors driving community recovery trajectories after disaster are not well understood. We assess why some communities show stronger recoveries from disaster than others, examining the role of four policy toolkits that U.S. county governments frequently adopt to recover from disaster. Using mixed methods, we examine the cases of Hurricanes Katrina and Rita with a novel dataset of recovery policies adopted within each Louisiana parish following the disasters. We typologize recovery strategies and analyze policy adoption patterns after crises. To compare which policy toolkit leads to the best recovery outcomes, we use synthetic control experiments on the 20 parishes hit by Hurricanes Katrina and Rita between August and September 2005, tracking net income inflow and net in-migration measures from 1997 to 2018 over 1408 parish-year observations, paired with qualitative case studies of parish policies and recovery outcomes. On average, soft and local recovery policies focused on community policies and feedback helped parishes stem the flow of finances away from the disaster-zone, as did infrastructural 'hard' policies, to a degree. in comparison, state policies focused on top-down planning experienced weaker recovery. Evidence shows that soft and local policy toolkits can accelerate recovery and that governments seeking to rebuild infrastructure should invest in locally-engaged community development in order to attain better overall recovery.


Kinematics of shoulder, trunk, pelvis, and hip while reaching forward to progressively distant targets.
Information on the normal contribution of various body regions to forward reaching provides a basis for assessing the maneuver. The purpose of this study was to describe the kinematics of the shoulder, trunk, pelvis, and hip of healthy young males while they stood and reached toward a target at arm's length and 5%, 10%, 15%, and 20% of body height beyond. Twelve healthy adult males were marked with 22 spherical reflective markers. Two trials of unilateral forward reaching were performed towards a target placed at five target distances. Motion was captured via reflective markers and an infrared camera system. Sagittal and transverse plane motions demonstrated high reliability between trials at each target distance (ICC = 0.716 trunk flexion to 0.977 shoulder flexion). Shoulder flexion and horizontal abduction were major contributors to forward reaching with components of trunk flexion and left trunk rotation at all target distances. Hip flexion, pelvic tilt, left pelvis rotation, and hip external rotation made notable contributions at the furthest targets. All motions became more pronounced as target distance increased (P ≤ .001). Kinematic analysis demonstrated that right forward reaching requires composite movements at the shoulder, trunk, pelvis, and hip. The contribution of each body region to forward reaching became more pronounced as the target became more distant. These findings may be helpful when identifying localized movement impairments contributing to limited forward reach in a clinical population, although clinical validation is needed.


Feasibility of Surfgrass Phyllospadix iwatensis Transplantation Along the Rocky Coasts of Shandong Peninsula, China.
Surfgrass Phyllospadix iwatensis is a dominant seagrass species along the east coast of Shandong Peninsula, China. Like other seagrasses in the world, surfgrass has been declining in the past decades. To assess the possibility of transplanting P. iwatensis in the coastal area, a new surfgrass transplant system was designed and applied to conduct a surfgrass transplantation experiment in a tide pool and a subtidal area, and its survival, morphological and physiological parameters were examined from May 2019 to June 2020. The results showed that after a year since transplantation, more than 65% of the transplants survived and the survival rate was higher in the subtidal site than in the tide pool. The morphological measurements including shoot height, leaf width, number of leaves per shoot, rhizome diameter and elongation rate, and number of roots per shoot were all higher in the subtidal area than in the tide pool, showing that the P. iwatensis transplants grew better in the subtidal area than in the tide pool in the study area. These results indicated that surfgrass can be transplanted in the two areas, and it is probably more suitable in subtidal area than in tide pool in the study area.


The major 36 kDa Neospora caninum tachyzoite surface protein is closely related to the major Toxoplasma gondii surface antigen.
The tachyzoites and the tissue cysts containing bradyzoites of Neospora caninum and Toxoplasma gondii, respectively, are difficult to distinguish morphologically. Specific antigens have been identified in T. gondii tachyzoites and bradyzoites, some of which are stage-specifically expressed, and different functions have been attributed to some of them. A tachyzoite stage-specifically expressed surface protein is the major surface antigen 1 (SAG1) which has been shown to be involved in host cell attachment and invasion. Previously we have identified a cell surface-associated glycoprotein (p36) in N. caninum tachyzoites. The full length coding sequence of the cDNA coding for p36 was determined, and analysis of the deduced amino acid sequence demonstrated that p36 is closely related to SAG1. p36 is encoded by a single copy gene which produces a transcript of 1.4 kb. Immunogold labeling of resin-embedded parasites using polyclonal antibodies affinity-purified on a recombinant p36 fusion protein expressed in Escherichia coli showed that this protein is located exclusively on the tachyzoite cell surface. As SAG1 in T. gondii, p36 is expressed in the tachyzoite stage, but is absent from bradyzoites. p36 is recognized by antibodies present in sera of cows experimentally infected with N. caninum tachyzoites.


The Impact of Medicaid Expansion on Head and Neck Malignancies Presentation and Survival.
Under the Affordable Care Act (ACA), Medicaid expansion became effective in states that have adopted it. We aim to examine its impact on head and neck cancers. A retrospective study that utilizes the Surveillance, Epidemiology, and End Results database, 2010-2016. Study population included patients with head and neck squamous cell carcinoma (HNSCC), differentiated thyroid carcinoma, and head and neck cutaneous melanoma. The objective is to examine disease-specific survival before and after Medicaid expansion. In states that adopted Medicaid expansion, the ratio of Medicaid: uninsured patients increased from 3:1 to 9:1 (p < 0.001). In states that did not adopt Medicaid expansion, the ratio increased from 1:1 to 2:1 (p < 0.001), making the increase in Medicaid coverage in states that adopted the expansion significantly higher (p < 0.001). Patients diagnosed with HNSCC before the expansion had worse survival (hazard ratio [HR]: 1.24, 95% confidence interval: 1.11, 1.39, p < 0.001) in states that adopted Medicaid expansion. Early data indicate that implementation of ACA improved disease-specific survival of patients with HNSCC. 3 Laryngoscope, 133:1409-1414, 2023.


Adiponectin promotes myogenic differentiation via a Mef2C-AdipoR1 positive feedback loop.
Adiponectin is an important hormone that regulates systemic metabolism, and it has been reported that globular adiponectin promotes myogenic differentiation. However, the mechanisms by which adiponectin promotes myogenic differentiation is not fully understood. In the present study, we show that adiponectin and its receptor 1 are significantly up-regulated during myogenic differentiation and that adiponectin increased the expression level of a core myogenic regulator, Mef2C, which is required for the effects of adiponectin on promoting myogenic differentiation. A transcriptional inhibitor of Mef2C, HDAC9, was down-regulated by adiponectin. In turn, Mef2C overexpression up-regulates adiponectin and its receptor, AdipoR1, to increase myogenic differentiation. We showed that mechanistically, Mef2C directly binds to AdipoR1 promoter to transcriptionally up-regulate AdipoR1 expression, which is required for the effects of Mef2C overexpression on myogenic differentiation. Thus, adiponectin/AdipoR1 and Mef2c form a positive feedback loop to promote myogenic differentiation.


Normative data and control studies of flash VEP's for comparison to a clinical population.
The effects of aging, interocular comparisons, pupil dilation, iris pigmentation, and simulated cataracts on bright flash visual evoked potentials (VEP's) of normal observers were studied to assess the flash VEP as a potential predictor of postsurgical visual function in cataract patients. Seventy-six observers (from 20 to 80 years old) were tested for age differences in flash VEP's. Implicit time measures for transient responses increased significantly as a function of age, but neither transient nor steady-state response amplitudes were altered significantly. Moreover, no significant changes in VEP's occurred as a function of interocular comparisons, pupil dilation, or differences in iris pigmentation of normal observers. Simulation of cataracts with 14 observers did not affect implicit time measures, but did change response amplitudes significantly. Therefore, implicit time measures of cataract patients should be compared either to those of normal age-matched controls or, in the case of a unilateral problem, to the normal fellow eye. Delayed implicit time measures, after the appropriate comparison, suggest optic nerve/pathway dysfunction. However, comparisons of amplitude measures require compensation for opacity density.


Evaluation of endoscopic visible light spectroscopy: comparison with microvascular oxygen tension measurements in a porcine model.
Visible light spectroscopy (VLS) is a technique used to measure the mucosal oxygen saturation during upper gastrointestinal endoscopy to evaluate mucosal ischemia, however in vivo validation is lacking. We aimed to compare VLS measurements with a validated quantitative microvascular oxygen tension (μPO2) measurement technique. Simultaneous VLS measurements and μPO2 measurements were performed on the small intestine of five pigs. First, simultaneous measurements were performed at different FiO2 values (18%-100%). Thereafter, the influence of bile was assessed by comparing VLS measurements in the presence of bile and without bile. Finally, simultaneous VLS and μPO2 measurements were performed from the moment a lethal dose potassium chloride intravenously was injected. In contrast to μPO2 values that increased with increasing FiO2, VLS values decreased. Both measurements correlated poorly with R2 = 0.39, intercept 18.5, slope 0.41 and a bias of - 16%. Furthermore, the presence of bile influenced VLS values significantly (median (IQR)) before bile application 57.5% (54.8-59.0%) versus median with bile mixture of the stomach 73.5% (66.8-85.8), p = < 2.2 * 10-16; median with bile mixture of small bowel 47.6% (41.8-50.8) versus median after bile removal 57.0% (54.7-58.6%), p = < 2.2 * 10-16). Finally, the VLS mucosal oxygen saturation values did not decrease towards a value of 0 in the first 25 min of asystole in contrast to the μPO2 values. These results suggest that VLS measures the mixed venous oxygen saturation rather than mucosal capillary hemoglobin oxygen saturation. Further research is needed to establish if the mixed venous compartment is optimal to assess gastrointestinal ischemia.


Depletion of brainstem epinephrine stores by alpha-methyldopa: possible relation to attenuated sympathetic outflow.
The antihypertensive effect of alpha-methyldopa (MD) is believed to be critically dependent on its ability to deplete endogenous catecholamines or cause the synthesis of false neurotransmitters. We used liquid chromatography with electrochemical detection (LCEC) and negative chemical ionization gas chromatography-mass spectrometry (GC-MS) for quantitation of catecholamines and MD metabolites in rat. MD intraperitoneally (100 mg/kg q12 hr X 12 days), significantly increased alpha-methylnorepinephrine (MNE) in brain (1.02 +/- 0.33 micrograms/g), heart (1.67 +/- 0.57 micrograms/g) and adrenal glands (114.93 +/- 50.47 micrograms/g) Endogenous norepinephrine (NE), epinephrine (E) and dopamine (DA) were reduced. ME levels were 2.19 +/- 0.44 micrograms/g (n = 6) in the adrenal gland but only 99 +/- 26 pg/g (n = 3) in the brainstem. MD-induced endogenous brainstem NE depletion was more than compensated by MNE production, but brainstem E depletion was not compensated for by a stoichiometric production of brainstem ME. We conclude (1) although ME is a metabolite of MD, it is present in extremely low concentrations in brainstem and (2) central epinephrine-containing neurons are depleted of neurotransmitter by MD therapy. If this selective epinephrine depletion occurs in the bulbospinal tract neurons responsible for maintaining sympathetic tone, then this effect could contribute to the antihypertensive effect of MD.


Synthesis, antidiabetic activity and molecular docking studies of novel aryl benzylidenethiazolidine-2,4-dione based 1,2,3-triazoles.
A series of novel aryl benzylidenethiazolidine-2,4-dione based 1,2,3-triazoles synthesized in a straightforward route consisting of benzylidenethiazolidine-2,4-dione and 1,2,3-triazole pharmacophores. The new scaffolds tested for in vitro antidiabetic activity by inhibition of aldose reductase enzyme and its inhibition measured in half of Inhibition Concentration (IC50). The activity results correlated with standard reference Sorbinil (IC50: 3.45 ± 0.25 µM). Among all the titled compounds 8f (1.42 ± 0.21 µM), 8d (1.85 ± 0.39 µM), 13a (1.94 ± 0.27 µM) and 8b (1.98 ± 0.58 µM) shown potent activity. In addition, molecular docking results against the crystal structure of aldose reductase (PDB ID: 1PWM) revealed that the binding affinities shown by all synthesized compounds are higher than the reference compound Sorbinil. The docking scores, H-bond interactions, and hydrophobic interactions well defined inhibition strength of all compounds.


Prognostic Impact of Preoperative Anemia on Urothelial and Extraurothelial Recurrence in Patients With Upper Tract Urothelial Carcinoma.
To investigate the prognostic impact of preoperative anemia on urothelial and extraurothelial recurrence after radical nephroureterectomy. A single-center series of 238 consecutive patients who were treated with radical nephroureterectomy for upper tract urothelial carcinoma was evaluated. We categorized patients on the basis of hemoglobin level into 2 groups, including normal or anemia. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to evaluate the association of preoperative anemia with outcome, controlling for clinicopathologic variables. Ninety-seven patients (40.8%) had anemia (median hemoglobin level, 143 vs. 107 g/L). Preoperative anemia was associated with history of bladder cancer (P = .01), tumor multifocality (P = .03), lymphovascular invasion (P = .05), and adjuvant chemotherapy (P = .01). Higher tumor stage and grade, and lymph node metastasis were significantly associated with preoperative anemia. Preoperative anemia was independently associated with extraurothelial recurrence (hazard ratio, 1.95; 95% confidence interval, 1.14-3.34; P = .01) in multivariate Cox regression analyses. Only a history of bladder tumor (hazard ratio, 2.07; P = .009) and tumor multifocality (hazard ratio, 3.97; 95% confidence interval, 2.37-6.67; P < .001) were independently associated with urothelial recurrence. The 5-year cancer-specific survival for patients with normal hemoglobin level was 82.1% and for patients with preoperative anemia was 54.2%. Patients with preoperative anemia had a greater probability of having upper tract urothelial carcinoma with higher tumor stages, higher tumor grades, and lymph node metastasis (pN+). Preoperative anemia was statistically significantly associated with worse cancer-specific survival and extraurothelial recurrence in patients who underwent radical nephroureterectomy.


Angiosarcoma associated with a Kasabach-Merritt syndrome: report of two cases treated with paclitaxel.
Angiosarcomas are rare, aggressive vascular malignancies of endothelial cell differentiation. Kasabach-Merritt syndrome is a rare condition defined by the association of thrombocytopenia and consumption coagulopathy with specific vascular tumors, such as tufted angioma or kaposiform hemangioendothelioma. We report here two cases of angiosarcomas complicated by a Kasabach-Merritt syndrome and their outcome after treatment with paclitaxel.


Encephalitogenic and tolerogenic potential of altered peptide ligands of MOG and PLP in Biozzi ABH mice.
Altered peptide ligands (APL) are highly effective in inhibiting experimental autoimmune encephalomyelitis (EAE) in rodents although clinical trials in multiple sclerosis reveal severe limitations probably due to the diverse and differential effects of APL in vivo compared to in vitro. Myelin oligodendrocyte glycoprotein (MOG 8-21) induces relapsing EAE in ABH (A(g7)) mice associated with broadening of the autoimmune repertoire thus providing a dynamic system to examine the efficacy of peptide analogues. Subtle changes in MOG 8-21 dramatically influenced disease susceptibility and T cell responses in vitro. Non-encephalitogenic APL that induce production of the 'regulatory' cytokines IL-10 and/or TGFbeta and concomitant low levels of the 'proinflammatory' cytokines IFNgamma and TNFalpha modulated relapsing EAE but were far less effective than the 'proinflammatory' wild-type MOG 8-21 peptide. These data reveal that APL differ greatly in their ability to activate encephalitogenic T cells. The extensive heterogeneity of responses of APL in vitro suggests that selection of APL on this criteria is highly unpredictable and probably less effective for therapy than selecting the dominant wild-type epitope and delivering it using a tolerogenic route.


Genome-wide association analysis identifies loci governing mercury accumulation in maize.
Owing to the rapid development of urbanisation and industrialisation, heavy metal pollution has become a widespread environmental problem. Maize planted on mercury (Hg)-polluted soil can absorb and accumulate Hg in its edible parts, posing a potential threat to human health. To understand the genetic mechanism of Hg accumulation in maize, we performed a genome-wide association study using a mixed linear model on an association population consisting of 230 maize inbred lines with abundant genetic variation. The order of relative Hg concentrations in different maize tissues was as follows: leaves > bracts > stems > axes > kernels. Combined two locations, a total of 37 significant single-nucleotide polymorphisms (SNPs) associated with kernels, 12 with axes, 13 with stems, 27 with bracts and 23 with leaves were detected with p < 0.0001. Each significant SNP was calculated and the SNPs significant associated with kernels, axes, stems, bracts and leaves explained 6.96%-10.56%, 7.19%-15.87%, 7.11%-10.19%, 7.16%-8.71% and 6.91%-9.17% of the phenotypic variation, respectively. Among the significant SNPs, nine co-localised with previously detected quantitative trait loci. This study will aid in the selection of Hg-accumulation inbred lines that satisfy the needs for pollution-safe cultivars and maintaining maize production.


Zeta potential changing phosphorylated nanocomplexes for pDNA delivery.
The objective of this study was to evaluate the suitability of a zeta potential changing system as gene delivery system. The phosphate ester bearing ligand 6-phosphogluconic acid (6-PGA) was attached to linear and branched polyethyleneimine (PEI) via a carbodiimide-mediated reaction whereby 287 μmol and 413 μmol 6-PGA could be coupled per gram polymer. Nanocomplexes of these modified polymers with pDNA showed a zeta potential of +12 mV for nanocomplexes with the linear PEI-6PGA and +16 mV in case of the branched derivative. By the addition of carboxymethylcellulose (CMC), zeta potentials of the complexes were reduced to +2.86 and +3.25, respectively. Phosphate release studies on Caco 2 cells and HEK-293 cells demonstrated the ability to cleave the phosphate ester. Compared to HEK-293 cells, enzymatic degradation of the phosphate ester in Caco 2 cells was 2.3-fold higher from nanocomplexes comprising linear PEI and 4.3-fold higher from those with branched PEI. Furthermore, incubation with alkaline phosphatase led to an increase in the zeta potential of nanocomplexes based on linear PEI-6PGA to +6.96mV and +8.26 mV in nanocomplexes comprising branched PEI-6PGA. Studying transfection efficiency in Caco 2 cells and HEK-293 cells, a higher expression of the green fluorescent protein (GFP) could be detected in HEK-293 cells. In presence of a phosphate inhibitor, transfection efficiencies were decreased in both cells lines, due to a lacking shift of the zeta potential of the tested pDNA complexes. According to these results, zeta potential changing systems seem to be a promising strategy for future gene delivery systems, as this concept allows the in situ generation of positive charges in close proximity to the cellular surface.


Feasible outcome of blinatumomab followed by allogeneic hematopoietic cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first salvage.
In adult patients with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-negative) B-cell presursor acute lymphoblastic leukemia (BCP-ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph-negative BCP-ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo-HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1 <12 months. After the first blinatumomab cycle, 22 (68.8%) achieved CR. At the end of the second cycle, 20 of the 22 patients remained in persistent CR, and 1 patient achieved new CR. The overall minimal residual disease negativity rate was 75% among evaluable patients with persistent CR. Patients with CRD1 <12 months were associated with poorer response to blinatumomab. Twenty (62.5%) of 32 patients underwent allo-HCT in blinatumomab-induced CR. After a median follow-up of 15.2 months, the 1-year OS rates for all patients and patients receiving allo-HCT in CR were 55.5% (median OS, 18.2 months) and 70.7%, respectively. Patients with CRD1 <12 months, extramedullary disease (EMD), and high peripheral blood blasts were associated with poorer OS. Blinatumomab is effective for achieving good quality CR and bridging to allo-HCT for adult patients with R/R Ph-negative BCP-ALL in first salvage. The role of blinatumomab in patients with CRD1 <12 months, EMD, or high tumor burden should be evaluated in future trials.


The bi-scapular flap.
The free transfer of two transverse scapular flaps in continuity is described. This provides a donor site capable of yielding a skin flap 50 x 10 cm. Some observations on the vascularity of adjacent axial territories are made.


Studies on the charge transfer band in high spin state of ferric myoglobin and hemoglobin by low temperature optical and magnetic circular dichroism spectroscopy.
The behavior of charge transfer band, appearing at 600-650 nm in ferric high spin derivatives of myoglobin and hemoglobin, was studied under various conditions by low temperature optical and magnetic circular dichroism spectroscopy. Optical absorption spectra have demonstrated that: (1) The charge transfer band at 630 nm of myoglobin (Fe3+)-H2O (pH 7.0) at room temperature split into three bands, 627 nm, 645 nm and 664 nm (shoulder) at 77 degrees K, whereas that of hemoglobin (Fe3+)-H2O showed no splitting. (2) By lowering the pH value from 7.5 to 4.3 this splitting in myoglobin was observed to disappear only in the presence of a small amount of phosphate ion, accompanying a midpoint at pH 6.7 +/- 0.1. This does not originate from the released hemin. (3) Hemin (pH 7.55) showed no splitting of the charge transfer band at 77 degrees K. (4) This splitting depended on the species of 6th ligand. For myoglobin-F- the splitting could scarcely be observed, whereas the proton-donating ligands such as HCOOH and CH3OH exhibit the splitting as well as H2O. Magnetic circular dichroism spectra have demonstrated that: (5) The charge transfer band at 600-500 nm indicated Faraday A term and B term. (6) A negative B term band was observed at 650 nm for myoglobin-H2O in the glassic solvent of potassium glycerophosphate-glycerol, whereas it was not observed for hemoglobin-H2O. Several discussions were performed on the origin of splitting of the charge transfer band in myoglobin-H2O. It is now concluded that the hydrogen bond between the 6th ligand and the distal histidine contributes to the splitting of the charge transfer band around 630 nm for myoglobin Fe3+)-H2O at low temperature and that disappearance of the splitting at low pH is originated from the presence of phosphate ion.


Patient time and out-of-pocket costs for long-term prostate cancer survivors in Ontario, Canada.
Time and out-of-pocket (OOP) costs can represent a substantial burden for cancer patients but have not been described for long-term cancer survivors. We estimated these costs, their predictors, and their relationship to financial income, among a cohort of long-term prostate cancer (PC) survivors. A population-based, community-dwelling, geographically diverse sample of long-term (2-13 years) PC survivors in Ontario, Canada, was identified from the Ontario Cancer Registry and contacted through their referring physicians. We obtained data on demographics, health care resource use, and OOP costs through mailed questionnaires and conducted chart reviews to obtain clinical data. We compared mean annual time and OOP costs (2006 Canadian dollars) across clinical and sociodemographic characteristics and examined the association between costs and four groups of predictors (patient, disease, system, symptom) using two-part regression models. Patients' (N = 585) mean age was 73 years; 77 % were retired, and 42 % reported total annual incomes less than $40,000. Overall, mean time costs were $838/year and mean OOP costs were $200/year. Although generally low, total costs represented approximately 10 % of income for lower income patients. No demographic variables were associated with costs. Radical prostatectomy, younger age, poor urinary function, current androgen deprivation therapy, and recent diagnosis were significantly associated with increased likelihood of incurring any costs, but only urinary function significantly affected total amount. Time and OOP costs are modest for most long-term PC survivors but can represent a substantial burden for lower income patients. Even several years after diagnosis, PC-specific treatments and treatment-related dysfunction are associated with increased costs. Time and out-of-pocket costs are generally manageable for long-term PC survivors but can be a significant burden mainly for lower income patients. The effects of PC-specific, treatment-related dysfunctions on quality of life can also represent sources of expense for patients.


Vasoactive intestinal polypeptide-like immunoreactivity in the bovine heart: high degree of coexistence with neuropeptide Y-like immunoreactivity.
It is not known whether VIP coexists with other neuropeptides or neurotransmitters in the heart. In the present study, the distribution of nerve fibers showing VIP-like immunoreactivity (VIP-LI) in various parts of the bovine heart was compared with that of fibers possessing neuropeptide Y (NPY)- and dopamine-beta-hydroxylase (DBH)-LI. It was found that fibers showing VIP-LI most regularly occurred in the regions of sinuatrial and atrioventricular nodes and intracardiac ganglia, the nerve fibers being associated with nodal and ganglionic cells and arterial walls. Furthermore, it was observed that almost all fibers showing VIP-LI also exhibited NPY-LI. The fibers displaying VIP-LI occurred close to fibers endowed with DBH-LI, and on some occasions it appeared that varicosities showing immunolabeling for VIP also displayed DBH-LI. VIP- and NPY-LI, but not DBH-LI, was detected in some of the intracardiac ganglionic cells. The observations are discussed in relation to the previously known distribution and function of VIP in the heart and other organs. Further studies examining the effects of VIP and NPY in the heart should take into account possible interactions between these two peptides.


Methicillin-Resistant Staphylococcus aureus (MRSA).
Occupational and environmental health nurses can prevent the spread of MRSA when evaluating and treating workers' injuries.


Prognostic factors in limited rectal cancer treated with intracavitary irradiation.
At the Centre Georges-François Leclerc of Dijon, 91 limited rectal tumors received a complete intracavitary 50 kV contact radiotherapy alone or associated with interstitial brachytherapy according to the guidelines of J. Papillon. Nineteen had a villous adenoma and 72 a well or moderately differentiated rectal adenocarcinoma. The majority of patients had contra-indications for major surgical procedures. The median age was 70 years. Seventy-six percent (69/91) of the rectal tumors remained free from local recurrence. After salvage therapy, the local control was 91% (83/91). Sphincter preservation was obtained in 85% (77/91). "De novo" adenocarcinomas developed on pre-existing benign pathology and villous adenomas were not significantly different with regard to local control (76% resp. 75% versus 59.5%; p = 0.22). According to the Dijon clinical staging system, the local relapse-free survival at 5 years was 97% for CS T1A, 77% for CS T1B, 65% for CS T2A, and 60% for CS T2B. Tumors of the anterior rectal wall had a better local control rate than lateral and posterior primaries (100% versus 63% versus 67%). For the middle rectum, the local relapse-free survival was 94% compared to 54% of the upper and 77% of the lower rectum. Four additional patients had a preoperative intracavitary therapy and salvage surgery for incomplete tumor regression; the complete remission rate is 96% (91/95). Intracavitary radiotherapy alone is an effective treatment for limited rectal cancers. Contact X ray therapy can be used alone in CS T1A whereas a combination of contact X ray therapy and interstitial brachytherapy is often the optimal approach in CS T1B and CS T2A. In CS T2B, our data do not support the use of intracavitary techniques alone. In these cases, the sequence external irradiation followed by an interstitial implant seems of interest and deserves further evaluation with more patients and follow-up.


Breast cancer in Brazil: present status and future goals.
Breast cancer is the most common cancer in women worldwide and 70% of breast cancer deaths occur in women from low-income and middle-income countries. Latin America has about 115,000 new cases of disease every year, with about 50,000 arising in Brazil. We examined the present status of breast cancer in Brazil as an example of the health effects of geographical, ethnic, and socioeconomic diversities on delivery of care. Our goal was to identify deficiencies that could be responsible for disparities in survival from breast cancer. We searched the English and Portuguese published work and reviewed national databases and Brazilian publications. Although the availability of publications specific to Brazil is low in general, we identified several factors that could account for disparities: delays in diagnosis due to low cancer awareness and implementation of mammography screening, unknown quality of surgery, and restricted access to radiotherapy and modern systemic therapies.


Determining Severity Strata for Three Atopic Dermatitis Patient-Reported Outcome Questionnaires: Defining Severity Score Ranges for the Worst Pruritus Numerical Rating Scale and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS).
Three patient-reported outcome (PRO) questionnaires-Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)-were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation. Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate-severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups. The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1-2 with minimal, 3 with mild, 4-7 with moderate, and 8-10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3-6 with moderate, and 7-10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0-1 was associated with absent, 2-11 with minimal, 12-22 with mild, 23-47 with moderate, and 48-70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1-3 with minimal, 4-6 with mild, 7-20 with moderate, and 21-30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1-2 with minimal, 3-7 with mild, 8-25 with moderate, and 26-40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1-2 with minimal, 3-8 with mild, 9-22 with moderate, and 23-30 with severe. These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice. NCT03568318.


The role of mesopelagic fishes as microplastics vectors across the deep-sea layers from the Southwestern Tropical Atlantic.
Microplastics (MPs; <5 mm) are a macro issue recognised worldwide as a threat to biodiversity and ecosystems. Widely distributed in marine ecosystems, MPs have already been found in the deep-sea environment. However, there is little information on ecological mechanisms driving MP uptake by deep-sea species. For the first time, this study generates data on MP contamination in mesopelagic fishes from the Southwestern Tropical Atlantic (SWTA) to help understand the deep-sea contamination patterns. An alkaline digestion protocol was applied to extract MPs from the digestive tract of four mesopelagic fish species: Argyropelecus sladeni, Sternoptyx diaphana (Sternoptychidae), Diaphus brachycephalus, and Hygophum taaningi (Myctophidae). A total of 213 particles were recovered from 170 specimens, and MPs were found in 67% of the specimens. Fibres were the most common shape found in all species, whereas polyamide, polyethylene, and polyethylene terephthalate were the most frequent polymers. The most contaminated species was A. sladeni (93%), and the least contaminated was S. diaphana (45%). Interestingly, individuals caught in the lower mesopelagic zone (500-1000 m depth) were less contaminated with MPs than those captured in the upper mesopelagic layer (200-500 m). Our results highlight significant contamination levels and reveal the influence of mesopelagic fishes on MPs transport in the deep waters of the SWTA.


Rate of Hospitalizations and Underlying Reasons Among People with Parkinson's Disease: Population-Based Cohort Study in UK Primary Care.
Hospitalization in Parkinson's disease (PD) is associated with reduced quality of life, caregiver burden and high costs. However, no large-scale studies of rate and causes of hospitalizations in patients with PD have been published. To investigate the rate and reasons for hospitalization and factors associated with hospitalization among people with PD compared to the general population. We examined rate and causes of admission in PD patients and matched controls in The Health Improvement Network from 2006 to 2016. Multivariable Poisson regression was used to explore the effects of age, gender, social deprivation, urbanicity and practice geographic location on hospitalization. In the longitudinal data from 9,998 newly diagnosed individuals with PD and 55,554 controls without PD aged ≥50 years, 39% of PD patients and 28% of controls were hospitalised over a median follow-up of 5.1 years. The adjusted incidence rate ratio (IRR) of hospitalization in PD compared to controls was 1.33 (95% CI:1.29-1.37) and rose with increased follow-up duration. Hospitalization rate was overall higher in the older age groups, but the adjusted IRR of hospitalization compared to controls was highest in the youngest age group. PD patients were more often admitted with falls/fractures, infections, gastrointestinal complications, PD, dementia, psychosis/hallucinations, postural hypotension, electrolyte disturbances, stroke and surgical procedures and slightly less often due to hypertension. People with PD have an increased hospitalization rate compared to controls, particularly in the younger age groups, and it increases with longer disease duration. The complications of motor and non-motor features of PD are amongst the main reasons for admission, some of which could be managed preventatively to avoid admissions.


Twenty-five types of T-cell receptor Vbeta family repertoire in patients with Kawasaki syndrome.
Recently, a possible relationship between Kawasaki syndrome (KS) and superantigen has been discussed since the report of selective expansion of specific Vbeta family in the acute phase of KS. To further investigate the relationship between KS and superantigens, we examined 25 types of T-cell receptor Vbeta family repertoire in patients with KS using the reverse transcription polymerase chain reaction. This is the first attempt to examine all of 25 Vbeta families in KS. A non radioisotope method was used to quantify mRNA so that the experiment was safer, simpler, and faster. An expression index (EI) for each Vbeta was defined as: (the amount of each Vbeta mRNA)/(the sum of all Vbeta mRNA) x 100. Ten patients with KS and ten normal children were studied. The Vbeta9 and Vbeta15 of acute phase of KS showed both significantly lower mean EI and significantly higher frequency of a decreased EI value as compared with control children. Selective expansion of the Vbeta family in the patients with KS was not observed. Although highly increased EIs were observed in various Vbetas, their frequency was not statistically significant. The pattern of increased Vbetas did not show the specific pattern that indicates a particular superantigen. In Kawasaki syndrome non-radioisotope method for analysing Vbeta mRNA is useful in cases where many samples have to be handled. The depletion of Vbeta9 and Vbeta15 or highly increased expression index in the acute phase of Kawasaki syndrome might suggest a relationship to superantigens.


[Do the patients medicate themselves correctly?].
To find the main pathologies which give rise to self-medication, the most commonly used pharmacological groups, how these drugs are obtained and the correctness of their instructions. Observation study of a crossover type. An urban Health Centre. 396 patients, who attended during the months of February and March 1993 with requests for medication or who were already taking something, were selected at random--95% Confidence Interval with 0.049 exactness. 76% attended when they were already taking medication, a percentage which was significantly lower among elderly people (p < 0.001). The most common pharmacological groups were analgesics (32.6%), antibiotics (19.9%) and antiflu drugs (17.6%); and the most common pathologies were respiratory conditions with or without temperature (26.2% and 32.3% respectively). Self-medication was correct in 75.5% of cases. It was least correct for antibiotics and vitamins and in descriptions of asthenia, where, in turn, demand was more frequent than self-consumption (p < 0.001). The main reason for taking medication was its previous medical prescription (38.64%). Patients correctly use the commonest medicines used in primary care, especially if they have been prescribed before. This suggests the importance of daily health education for each prescription, especially for the most common pathologies.


A novel population of B7-1+ T cells producing intracellular IL-4 is decreased in patients with multiple sclerosis.
We identified a novel population of human T cells, studied directly ex vivo, that co-express surface B7-1 and intracellular IL-4. These peripheral blood B7-1+/CD4+ T cells expressed cell surface molecules associated with differentiation including CD45RO and MHC class II, yet were CD69(-) and CD25(-). In short-term cultures, T cell receptor (TCR) cross-linking induced further IL-4 production with little IFN-gamma or TNF-alpha. In marked contrast, CD4+ T cells negative for B7-1 expressed intracellular IFN-gamma and high amounts of TNF-alpha but little IL-4 upon TCR cross-linking. The CD4+/B7-1+/IL-4-expressing T cells were of polyclonal origin based on their diverse TCR repertoire. To explore the biological significance of this B7-1+/IL-4+ T cell population and to assess its potential regulatory role in autoimmune disease, we examined whether these T cells isolated ex vivo were altered in subjects with multiple sclerosis (MS). While the frequency of B7-1+ T cells was enhanced in patients with MS as compared to normal subjects, there was a significant diminution of B7-1+/IL-4+ T cells in the patients. The decrease in these IL-4-producing T cells in patients with autoimmune disease is consistent with a possible role as immunoregulatory T cells.


Modelling ligand depletion for simultaneous affinity and binding site quantification on cells and tissue.
The quantification of the number of targets in biological systems is an important parameter to assess the suitability of surface markers as targets for drugs, drug delivery and medical imaging. Likewise, quantifying the interaction with the target in terms of affinity and binding kinetics is essential during drug development. Commonly used approaches to quantify membrane antigens on live cells are based on manual saturation techniques that are labour-intensive, require careful calibration of the generated signal and do not quantify the binding rates. Here, we present how measuring interactions in real-time on live cells and tissue under ligand depletion conditions can be used to simultaneously quantify the kinetic binding parameters as well as the number of available binding sites in a biological system. Suitable assay design was explored with simulated data and feasibility of the method verified with experimental data for exemplary low molecular weight peptide and antibody radiotracers as well as fluorescent antibodies. In addition to revealing the number of accessible target sites and improving the accuracy of binding kinetics and affinities, the presented method does not require knowledge about the absolute signal generated per ligand molecule. This enables a simplified workflow for use with both radioligands and fluorescent binders.


Polydimethylsiloxane/metal-organic frameworks coated stir bar sorptive extraction coupled to gas chromatography-flame photometric detection for the determination of organophosphorus pesticides in environmental water samples.
In this work, the metal-organic frameworks (MOFs), MIL-101-Cr-NH2 was synthesized via a direct hydrothermal method, and a polydimethylsiloxane (PDMS)/MIL-101-Cr-NH2 coated stir bar was prepared by sol-gel technique. Good reproducibility was obtained for the preparation of PDMS/MIL-101-Cr-NH2 coated stir bar with the relative standard deviations (RSDs) ranging from 3.7 to 5.2% (n=7) in one batch, and from 5.4 to 9.2% (n=7) among different batches. With the high surface area and rich benzene ring structure of MIL-101-Cr-NH2, the prepared PDMS/MIL-101-Cr-NH2 coated stir bar presented higher extraction efficiency for target organophosphorus pesticides (OPPs, including phorate, diazinon, malathion, fenthion, quinalphos and ethion) over PDMS coated stir bar. Based on it, a new method of PDMS/MIL-101-Cr-NH2 coated stir bar sorptive extraction (SBSE) coupled to gas chromatography-flame photometric detection (GC-FPD) was proposed for the determination of six OPPs in environmental water samples. The operation parameters affecting the extraction efficiency of SBSE, including extraction time, stirring rate, desorption time and ionic strength, were investigated. Under the optimal conditions, the limits of detection (S/N=3) were found to be in the range of 0.043-0.085μgL(-1) for the six target OPPs, and the linear range was 0.5-100μgL(-1) for malathion and 0.2-100μgL(-1) for other five OPPs. The RSDs of the proposed method evaluated at 1µgL(-1) for each OPP were in the range of 5.9-8.7% (intra-day, n=7) and 6.1-10.7% (inter-day, n=5), respectively. The enrichment factors were varied from 110 to 151-fold (theoretical enrichment factor was 200-fold). The proposed method was applied to the analysis of OPPs in East Lake and pond water samples with recoveries in the range of 89.3-115% and 80.0-113% for the spiked East Lake and pond water samples, respectively.


A study of correlations between metabolic syndrome factors and osteosarcopenic adiposity.
Aging reduces the quality and strength of bones and muscles and increases body fat, which can lead to the simultaneous occurrence of sarcopenia, osteopenia, and adiposity, a condition referred to as OsteoSarcopenic Adiposity (OSA). While previous studies have demonstrated that metabolic syndrome is associated with sarcopenia, osteopenia, and adiposity, the relationship between metabolic syndrome and OSA remains largely unknown. We analyzed data for a sample of middle-aged individuals from a Health Management Center database, which was collected in 2016-2018. There are 2991 cases of people over 50 years from a physical examination center in a hospital in Taiwan during 2016-2018. In addition to descriptive statistics, chi-squared test, analysis of variance, and multinomial logistic regression analysis were conducted to examine OSA risk and associated factors. Based on multinomial logistic regression analysis, in different OSA severity level (1-3 more serious), those who are with metabolic syndrome has increased the 2.49-2.57 times risk of OSA (p < 0.001) in OSA = 2 and 3 groups while there is no significant difference in OSA =1 group. The prevalence of OSA may impair the health and quality of life in the elderly group, especially those diagnosed with metabolic syndrome, increasing the risk of OSA. These results can help promote early diagnosis and treatment of OSA in clinical settings, particularly among aging individuals with abnormal physical function, the group with the highest OSA incidence.


Hamartoma of the tongue.
Hamartomas of the tongue are rare. A case of a 6-year-old girl with hamartoma at the base of the tongue is reported. The diagnosis was confirmed by a histopathologic examination of the mass after removal in a wedge fashion by the CO2 laser under general anesthesia. The literature is reviewed and discussed.