Statin therapy is associated with improved outcomes in vascular surgery patients with renal impairment.
Little is known about the association between baseline kidney function, statin therapy, and outcome after vascular surgery in patients with and without chronic kidney disease. A total of 2126 patients underwent elective major vascular surgery and were divided into 2 categories based on baseline creatinine clearance (CrCl), calculated using the Cockcroft-Gault equation: CrCl > or = 60 mL/min (n = 1358, reference) and CrCl < 60 mL/min (n = 768). Outcome measures were 30-day and long-term all-cause, cardiac, and cerebrocardiovascular mortality. Mean follow-up was 6.0 +/- 3.7 years. Multivariate Cox regression analysis, including potential confounders and propensity score for statin use, was applied. Data are presented as hazard ratios (HRs) with 95% CI. Thirty-day all-cause, cardiac, and cerebrocardiovascular mortality rates were 3.8% versus 10.2%, 1.3% versus 4.2%, and 2.7% versus 7.8%, respectively, according to the 2 categories of kidney function. In addition, long-term all-cause, cardiac, and cerebrocardiovascular mortality rates were 46.6% versus 72.5%, 14.6% versus 26.4%, and 23.0% versus 40.6%, respectively. Statin therapy was associated with an overall significant improved 30-day and long-term all-cause mortality, independent of other important confounders. However, in patients with a CrCl > or = 60 mL/min, the long-term cardiac and cerebrocardiovascular beneficial effects did not reach statistical significance (HR 0.93, 95% CI 0.61-1.41 and HR 0.89, 95% CI 0.63-1.24, respectively) when compared with patients with a CrCl of < 60 mL/min (HR 0.63, 95% CI 0.41-0.96 and HR 0.67, 95% CI 0.48-0.94, respectively). The level of kidney function is an independent predictor of short- and long-term outcome after major noncardiac surgery. In addition, perioperative statin use in patients with kidney disease is associated with a reduction in the short- and long-term all-cause, cardiac, and cerebrocardiovascular mortality.


Altered absorption and regulation of iron in chicks with acute Salmonella gallinarum infection.
Chicks aged 15 days were infected orally with Salmonella gallinarum. During the six-day period immediately following infection the absorption of 59Fe from the gut fell progressively to be eventually about half that in noninfected chicks. This reduced uptake was accompanied by a shift in the distribution of the 59Fe absorbed, more occurring in the spleen and less in the liver and blood. During the eight-day period that immediately followed infection in another experiment, serum iron concentration on day 4 and 6 in infected chicks was significantly lower than that in noninfected birds. In the infected chicks also the transferrin saturation was significantly lower and the unsaturated ironbinding capacity higher, on days 4, 6, and 8 after infection. These findings show that there is a major disturbance in iron regulation in acute systemic bacterial infection in the immature fowl and suggest that the mild anaemia which occurs in chicks during acute S gallinarum infection a shortage of iron in the body.


Arginine cluster introduction on framework region in anti-lysozyme antibody improved association rate constant by changing conformational diversity of CDR loops.
Antibodies are used for many therapeutic and biotechnological purposes. Because the affinity of an antibody to the antigen is critical for clinical efficacy of pharmaceuticals, many affinity maturation strategies have been developed. Although we previously reported an affinity maturation strategy in which the association rate of the antibody toward its antigen is improved by introducing a cluster of arginine residues into the framework region of the antibody, the detailed molecular mechanism responsible for this improvement has been unknown. In this study, we introduced five arginine residues into an anti-hen egg white lysozyme antibody (HyHEL10) Fab fragment to create the R5-mutant and comprehensively characterized the interaction between antibody and antigen using thermodynamic analysis, X-ray crystallography, and molecular dynamics (MD) simulations. Our results indicate that introduction of charged residues strongly enhanced the association rate, as previously reported, and the antibody-antigen complex structure was almost the same for the R5-mutant and wild-type Fabs. The MD simulations indicate that the mutation increased conformational diversity in complementarity-determining region loops and thereby enhanced the association rate. These observations provide the molecular basis of affinity maturation by R5 mutation.


An attempt to independently verify the utility of the Van Nuys Prognostic Index for ductal carcinoma in situ.
The Van Nuys Prognostic Index (VNPI) purports to predict the risk of ipsilateral breast tumor recurrence (IBTR) after excision of ductal carcinoma in situ (DCIS). It is a simple scoring scheme based on a retrospective evaluation of data from a single group of investigators. Various versions of VNPI have been proposed using clinical and pathologic features including tumor size, tumor grade, margin width, and patient age. Despite common use of VNPI in the clinical management of patients with DCIS, independent validation is lacking. A total of 222 patients were retrospectively analyzed with mammographically detected DCIS who were treated with surgical excision alone. Wire-localized excisional biopsy was performed and surgical specimens were measured and inked to assist in margin assessment. Multiple sections of each specimen were evaluated for histopathologic subtype, histologic and nuclear grade, presence of necrosis, maximum dimension of the lesion, and margin width. Each patient was prospectively evaluated by a multidisciplinary management team and presented with adjuvant treatment options including whole breast radiotherapy and/or tamoxifen. All patients in this cohort declined radiotherapy. Thirty-one percent of patients received tamoxifen. Patients were followed clinically every 3 to 6 months, and mammographically every 6 to 12 months. IBTR was confirmed by biopsy. Wilcoxon regression analysis was used to evaluate risk groups according to 3 proposed VNPI classification schemes: VNPI Group 1 (margin, grade, and size), VNPI Group 2 (margin, grade, size, and patient age), and VNPI Group 3 (margin only). With a median follow-up of 4.6 years, the crude rate of IBTR was 8.6% for the entire cohort. Of the patients who developed an IBTR, 73.7% had a lesion with a maximum dimension of < or =15 mm, 47.4% had a margin > or =10 mm, and 36.8% had grade 1 histology. At 5 years, IBTR was statistically indistinguishable for the 3 VNPI models. The 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups according to VNPI Group 1 was 96%, 84%, and 100%, respectively (P = .20). Similarly, the 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups according to VNPI Group 2 was 95%, 83%, and 100%, respectively (P = .19). Taking into account margin status only (VNPI Group 3) the 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups was 92%, 91%, and 91%, respectively (P = .98). Tamoxifen use did not appear to affect the 5-year rate of IBTR (95% vs 94%; P = 1.0). The results of the current study suggest that VNPI or margin width alone is not a valid tool with which to assist in the stratification of patients after excision alone for their risk of IBTR at 5 years. Further follow-up may strengthen the predictive utility of the various VNPI classification schemes.


Families' Knowledge Change in Paediatric Drug Resistant Epilepsy: A Novel Clinic Model.
Epilepsy is a chronic condition that affects approximately 95,000 Ontarians, of whom approximately 15,000 are children under the age of 18. Drug resistant epilepsy (DRE) will affect around 30% of these children who will require more advanced care due to their medical complexities. The purpose of this study is to determine if receiving care in a paediatric Comprehensive Epilepsy Clinic (CEC) is associated with positive outcomes for children living with DRE and their families by looking at three health outcomes: 1) families' knowledge of their child's diagnosis and treatment plan, 2) navigational access to both the hospital and community epilepsy services, and 3) health behaviours. This was a prospective cohort study in which families of children diagnosed with DRE would be exposed to a CEC care model for the first time and followed for 6-months after enrollment. This was analyzed by utilizing surveys from new families at baseline and 6 months post receiving care within a CEC. Results revealed a statistical significance in change of knowledge in families' knowing the type of epilepsy their child has and what epilepsy co-morbidities are. Families' also had a significant change in utilizing hospital epilepsy resources and knowing who to contact in the community and hospital for their epilepsy related questions. A CEC model improves families' knowledge about epilepsy diagnosis and treatment plan, navigational access to both the hospital and community epilepsy services, and health behaviours.


A randomized, double-blind, placebo-controlled study of the efficacy of tetracaine gel (Ametop) for pain relief during topical photodynamic therapy.
Many patients find topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) painful. Local anaesthetics are not routinely used and their effect on PDT pain has not been examined. To evaluate the efficacy of tetracaine gel (Ametop) for pain relief during and after PDT. A prospective, double-blind, placebo-controlled study of 42 patients with lesions (< or =2 cm diameter) of superficial nonmelanoma skin cancer or dysplasia. Patients were randomized to either tetracaine (4% w/w) (n=22) or vehicle (n=20) gel under occlusion for 1 h pre-irradiation. Pain was assessed during and after irradiation using a visual analogue scale (VAS) and faces pain scale. Patients who received tetracaine gel experienced only slightly less pain during PDT (median VAS 4) compared with those who received placebo (median VAS 4.5) (95% confidence interval for difference 0-3, P=0.08). No significant difference in pain was experienced between the treatment groups immediately after irradiation or later. When compared with placebo, tetracaine gel did not significantly reduce pain during or after PDT for small lesions of superficial basal cell carcinoma, Bowen's disease or actinic keratosis.


Dissociating prefrontal contributions during a recency memory task.
Neuroimaging studies of normal young adults have consistently found right prefrontal cortex (RPFC) activity during the performance of recency memory tasks. However, it is unclear whether the involvement of RPFC during these tasks reflects retrieval processes or executive processes such as: strategic ordering or monitoring. In the current study, we distinguish between those PFC regions that are more related to retrieval processes, versus strategic ordering processes. An event-related fMRI study was conducted in which eight young subjects were scanned while performing verbal episodic retrieval tasks (recognition and recency memory tasks), and verbal non-memory strategic organizing control tasks (reverse alphabetizing of words). The fMRI results show that young subjects engaged right dorsolateral PFC during recency and reverse alphabetizing control tasks. Left ventral PFC was engaged across all tasks; however, a subset of voxels within this region was more active during retrieval tasks. Left dorsolateral and right ventral PFC activity was more related to the performance of reverse alphabetizing tasks, respectively. We conclude that right dorsolateral PFC activity during recency memory reflects more general strategic organizational or monitoring processes, and is not EM-specific.


Endothelial protection: avoiding air bubble formation at the phacoemulsification tip.
To investigate the conditions under which bubbles form during phacoemulsification. Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. In the first part of the study, the partial pressure of oxygen (pO(2)) was used as a surrogate measure for the partial pressure of air. Irrigation solutions packaged in glass and plastic containers were studied. A directly vented glass bottle was also tested. The pO(2) of the various irrigation solutions was measured as the containers were emptied. In the second part, phacoemulsification procedures were performed in rabbit eyes with different power settings and different irrigation solutions. Intracameral bubble formation during the procedure was recorded. Following the phacoemulsification procedures, the corneas were stained for F-actin and examined for endothelial injury. The initial pO(2) in irrigation solutions packaged in glass bottles was about half that at atmospheric levels; in solutions packaged in plastic, it was at atmospheric levels. As irrigation solutions were drained from the container, the pO(2) of the solution tended to rise toward atmospheric levels. The rate of pO(2) increase was markedly reduced by using a directly vented glass bottle. In the phacoemulsification procedures, bubble formation was most likely to occur with higher pO(2) and higher power settings. Observation of bubbles by the surgeon was highly correlated with endothelial damage. Keeping the pO(2) low reduced the risk of endothelial damage, especially at higher phacoemulsification powers. The packaging of irrigation solutions was the most important factor in controlling the initial pO(2) of the solution. The pO(2) can be minimized throughout a phacoemulsification procedure by using a directly vented glass bottle.


Sex steroids in serum of prepubertal male and female horses and correlation with bone characteristics.
We used radioimmunoassay (RIA) to measure monthly serum levels of unconjugated and conjugated sex steroids (testosterone T, androstenedione A, estradiol E(2), and estrone E(1)) in 4 male and 4 female foals during their first year of life. Maximal production of sex steroids was detected from April to August with hormonal peaks, corresponding to the natural breeding season in adults. In males, only A levels were more steady. Total estrogens (unconjugated plus conjugated E(2) and E(1)) were the major steroids in immature males in contrast to adults. Estrogens generally peaked in young females before males; the major estrogen was E(1), and total estrogens overtook total androgens (unconjugated and conjugated T and unconjugated A). We also sampled 3 male and 3 female foals with bone alterations in adulthood. For all animals, serum levels of four bone formation markers were obtained: osteocalcin (O), hydroxyproline (HP), and alkaline phosphatase (AP), and a radiographic score was determined. Only male foals with normal skeletal frame (good radiographic score GRS) in adulthood showed a correlation (P < 0.01) between the distribution frequency of each bone formation marker and unconjugated E(2) or E(1) levels; this finding highlighted the role of unconjugated estrogens in bone maturation in horses, since this was not found in the groups with bone alterations. In females, the threshold of estrogen synthesis and sensitivity was probably sufficient to be a nonlimiting factor at this stage of development. Our results strongly suggest a differential regulation of the estrogen/androgen balance in horses according to sex, sexual maturation, and photoperiod. Moreover, estrogens appear to be crucial for skeletal development in male colts, and these steroids are good modulators of skeletal frame characteristics in adulthood.


Lack of an effect of Madopar on the disposition of tolcapone and its 3-O-methylated metabolite in rats.
The effect of Madopar (benserazide and L-dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-L-methionine by Madopar would change the disposition of tolcapone. There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.


Genotypic influences on lead-induced hyperactivity in mice.
Male mice, genetically selected for differences in brain weight or from a heterogeneous (HET) stock, were used to explore potential interactions between genotype and exposure to lead as manifested in activity. At the time of birth dams and their pups were given either water or a 0.5% lead acetate solution as the sole source of fluid. Fluid conditions remained constant throughout the experiment. The effects of chronic lead on activity in young adult mice depended on the genotype of the individual. Specifically, in an open field, HET mice exposed to lead tended to be more active than their control counterparts. Low- and high-brain weight lead-exposed mice at times were hypoactive but this effect depended on the specific nature of the measure.


Neonatal hypertension from a unilateral multicystic dysplastic kidney.
Multicystic renal dysplasia is an extremely uncommon cause of hypertension in children and the few reported cases have not been of newborns. We report on a neonate in whom severe hypertension associated with elevated peripheral plasma renin resulted from a unilateral multicystic dysplastic kidney. Hypertension and plasma renin activity normalized after unilateral nephrectomy. No evidence of perfusion or excretory renal function in the dysplastic kidney was present on a radionuclide renal scan. This child demonstrates a relationship between hypertension and unilateral multicystic renal dysplasia.


Maternal dietary patterns during pregnancy and the risk of infantile eczema during the first year of life: a cohort study in northeast China.
There are few studies on the relationship between diet during pregnancy and infantile eczema and the conclusions are inconsistent. The aim of the present study was to explore the impact of dietary patterns during pregnancy on infantile eczema. A total of 495 mother-child pairs from a prospective cohort in Shenyang, China was recruited. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered food frequency questionnaire. The data of infantile eczema was assessed using a structured questionnaire. Factor analysis to derive dietary patterns. The relationship between the dietary pattern and infantile eczema was examined by the logistic regression analysis. The cumulative incidence of eczema in 6 months and 12 months in northeast China was 45.7% and 57.8%, respectively. Three dietary patterns were identified. There was a tendency for an expose-response relationship between the maternal high-protein dietary pattern during pregnancy and the risk of infantile eczema within 12 months (P for trend = 0.023): the adjusted odds ratio (95% confidence interval) in the Q1, Q2, Q3, Q4 were 1.00 (reference), 1.63 (0.96-2.76), 1.81 (1.06-3.06), and 1.87 (1.09-3.20), respectively. No association between Western and plant-based patterns during pregnancy and infantile eczema within 12 months was found. Infantile eczema within 6 months was not associated with any of the three dietary patterns. The maternal high-protein pattern during pregnancy may be a risk factor for infantile eczema during the first year of life.


Beta-adrenoceptor antagonists affect amyloid nanostructure; amyloid hydrogels as drug delivery vehicles.
Beta-adrenocepetor antagonists (beta-blockers) alter the nanostructure of lysozyme amyloids, resulting in different drug release profiles.


The comparative toxicity of vitamin D metabolites in the weanling mouse.
The potential toxicity of vitamin D, alpha-calcidol [1 alpha(OH)D3], and calcitriol [1,25(OH)2D3] was studied by administration of these compounds at three different doses to weanling C57BL/6J mice over a 4-week period. Drug effects on calcium were monitored by serum calcium and urine calcium/creatinine ratio determinations. Tests of renal function included serum creatinine, 24-h urine volume, urinary protein, and glucose excretion, and histological evaluation of renal tissue. At 2 weeks, serum calcium was significantly elevated in animals receiving the higher doses of alpha-calcidol (2.78 +/- 0.25 at 50 ng/kg and 3.45 +/- 0.13 at 250 ng/kg body wt vs 2.14 +/- 0.06 mmol/l in controls, respectively). A similar effect was seen in the urinary calcium/creatinine ratio but serum creatinine remained unchanged. By 4 weeks, all animals receiving alpha-calcidol had significantly higher serum calcium and urinary calcium/creatinine ratios than other groups. Severe nephrocalcinosis was observed in the high-dose alpha-calcidol group only. We conclude that alpha-calcidol is more toxic than calcitriol in the mouse and suggest that the degree of toxicity is correlated to the degree of hypercalcemia and to the vitamin D metabolite used.


Staphylococcus aureus mutants lacking cell wall-bound protein A found in isolates from bacteraemia, MRSA infection and a healthy nasal carrier.
Staphylococcus aureus is a major human pathogen and a multitude of virulence factors enables it to cause infections, from superficial lesions to life-threatening systemic conditions. Staphylococcal protein A (SpA) is a surface protein contributing to S. aureus pathogenesis by interfering with immune responses and activating inflammation. Seven isolates with frameshift mutations in the spa repeat region were investigated to determine whether these mutations lead to truncation and secretion of SpA into the extracellular environment. Five isolates originated from blood cultures, one from an MRSA infection and one from a persistent nasal carrier. Full-length spa genes from the seven isolates were sequenced, and Western blot experiments were performed to localize SpA. Three isolates had identical deviating 25-bp spa repeats, but all isolates displayed different repeat successions. The DNA sequence revealed that the frameshift mutations created premature stop codons in all seven isolates, resulting in truncated SpA of different lengths, however, all lacking the XC region with the C-terminal sorting signal. SpA was detected by Western blot in six of the seven isolates, mainly extracellularly. Our findings demonstrate that S. aureus isolates with truncated SpA, not anchored to the cell wall, can still be found in bacteraemia, infection and among carriers.


Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice.
Cytochrome P450IIE1 (P450IIE1) is responsible for the metabolic activation of N-nitrosodimethylamine (NDMA), a potent environmental carcinogen. This P450 enzyme displays a high-affinity NDMA demethylase (NDMAd) activity and is known to be induced by fasting and acetone administration. In the present work, the effects of pituitary hormones on the regulation of P450IIE1 in the liver were investigated and compared in rats and mice. There was no difference in liver microsomal NDMAd activity (nmol/min/mg protein) in rats in the intact (0.38 +/- 0.12), sham-operated (0.44 +/- 0.06), and hypophysectomized (0.52 +/- 0.04) groups. However, hypophysectomy caused a 2-fold increase in hepatic P450IIE1 protein levels as determined by immunoblot analysis. The P450IIE1 mRNA level in hypophysectomized rat was also significantly increased. The levels of blood ketone bodies (acetone, acetoacetate, and beta-hydroxybutyrate) were not different in the intact, sham-operated, and hypophysectomized groups, suggesting that ketone bodies are not involved in the induction of P450IIE1 protein and its mRNA by hypophysectomy. The discrepancy between the NDMAd activity and the increased P450IIE1 protein in rat liver by hypophysectomy can be partially explained by the lower hepatic NADPH-P450 reductase activity (50% that of the control) in the hypophysectomized rats. Upon the induction of liver NDMAd activity by fasting and acetone, hypophysectomy attenuated the effect of acetone but abolished the effect of fasting completely. Nevertheless, fasting still caused a 3-fold increase in the liver P450IIE1 mRNA level. An involvement of pituitary hormones in the regulation of liver microsomal P450IIE1 in mouse, however, was not observed. There was no difference in constitutive NDMAd activity between genetically growth hormone-deficient (lit/lit) mice and their phenotypically normal heterozygotes (lit/+). Fasting for 48 h caused 1.5- to 2-fold induction and acetone caused 2- to 3-fold induction, in both groups. The above changes in enzyme activity were due to the changes of P450IIE1 levels as verified by the immunoblot analysis. In male BALB/c mice, neither the hepatic NDMAd activity nor the P450IIE1 protein level was altered by hypophysectomy. The effects of acetone on the liver NDMAd activity were also similar in hypophysectomized and sham-operated mice. The results suggest that pituitary hormones are important in the regulation of the expression and activity of hepatic P450IIE1 in rats but not in the mouse strains investigated.


Preoperative prealbumin and transferring: Relation to 30-day risk of complication in elective spine surgical patients.
There is growing interest in identifying nutritional biomarkers associated with poor outcomes of elective spine surgery. Prealbumin and transferrin are both biomarkers of nutritional status that can be obtained from clinical laboratories. However, associations of preoperative measures of these nutritional biomarkers across their range with risk of complications from spine surgery have not been fully investigated. Determine associations of preoperative prealbumin and transferrin levels with 30-day risk of complication among elective spine surgery patients. Cohort study with preoperative prealbumin and transferrin collected as standard of care. 30-day risk of medical complication. Data were obtained from medical records of 274 consecutive adult patients ages ≥50 years who underwent elective spine surgery from June 2013 to June 2014. Prealbumin (mg/dL), serum transferrin (mg/dL), and preoperative factors were abstracted from medical records. Prealbumin and transferrin levels were categorized into quartiles and as below versus median or higher. The primary outcome measure was 30-day risk of medical complication, such as renal failure or infections. Associations of the biomarkers with outcome risk were assessed with chi-square tests and with risk ratios (RR) and 95% confidence intervals (CI) estimated with multivariable log-binomial regression. The 274 adults studied had a median prealbumin level of 27.4 mg/dL and a median transferrin level of 265.0 mg/dL. The 30-day risk of complication was 12.8% (95% CI: 8.8%-16.7%). Risk of complication did not vary by quartile for either prealbumin (P = .26) or transferrin (P = .49) and was not associated either with prealbumin (below median, RR = 1.1, 95% CI: 0.8, 1.5) or transferrin (below median, RR = 1.1, 95% CI: 0.8, 1.6). Among adults undergoing elective spine surgery, the 30-day risk of complication was not associated with prealbumin or transferrin. Nutrition status, as measured by prealbumin and transferrin, does not appear to be associated with complication risk. Level III.


Cross-section profile of the nonlinear refractive index of Gorilla Glass obtained by nonlinear ellipse rotation measurements.
In this work we determined the influence of potassium-to-sodium ion exchange in the nonlinear refractive value (n2) of Corning's Gorilla Glass (GG). Due to the production process, GG has a rich potassium surface in comparison to the original sodium matrix glass. In order to determine the nonlinear cross-section profile, we have used a highly sensitive nonlinear elliptical rotation spatial measurement. Using a simple model, where the nonlinearity varies exponentially with depth, we observed that the value of the nonlinear refraction at the surface is about 22% greater than that of the matrix interior with a penetration depth constant of ∼50 μm.


New targets for pyrimidine antimetabolites for the treatment of solid tumours. 2: Deoxycytidine kinase.
Deoxycytidine kinase is an enzyme required for the activation of, for example, cytarabine, the most widely used agent for the chemotherapy of haematological malignancies. However, deoxycytidine kinase also plays an important role in the activation of several new agents used in the treatment of leukaemia, such as cladribine. Recently, a new cytidine analogue, gemcitabine, has shown impressive activity as a single agent against several solid malignancies (ovarian cancer, non-small cell lung cancer), demonstrating that in solid tumours deoxycytidine kinase can be an important target for the activation of antimetabolites. Studies on the regulation of deoxycytidine kinase have shown that the enzyme has a complicated regulation (feedback inhibition by the product and regulation by ribonucleotides). Modulation of deoxycytidine kinase activity has already been shown to be an effective way to improve the effect of cytarabine and will probably be a target for new therapies.


Integrating full-length transcriptomics and metabolomics reveals the regulatory mechanisms underlying yellow pigmentation in tree peony (Paeonia suffruticosa Andr.) flowers.
Tree peony (Paeonia suffruticosa Andr.) is a popular ornamental plant in China due to its showy and colorful flowers. However, yellow-colored flowers are rare in both wild species and domesticated cultivars. The molecular mechanisms underlying yellow pigmentation remain poorly understood. Here, petal tissues of two tree peony cultivars, "High Noon" (yellow flowers) and "Roufurong" (purple-red flowers), were sampled at five developmental stages (S1-S5) from early flower buds to full blooms. Five petal color indices (brightness, redness, yellowness, chroma, and hue angle) and the contents of ten different flavonoids were determined. Compared to "Roufurong," which accumulated abundant anthocyanins at S3-S5, the yellow-colored "High Noon" displayed relatively higher contents of tetrahydroxychalcone (THC), flavones, and flavonols but no anthocyanin production. The contents of THC, flavones, and flavonols in "High Noon" peaked at S3 and dropped gradually as the flower bloomed, consistent with the color index patterns. Furthermore, RNA-seq analyses at S3 showed that structural genes such as PsC4Hs, PsDFRs, and PsUFGTs in the flavonoid biosynthesis pathway were downregulated in "High Noon," whereas most PsFLSs, PsF3Hs, and PsF3'Hs were upregulated. Five transcription factor (TF) genes related to flavonoid biosynthesis were also upregulated in "High Noon." One of these TFs, PsMYB111, was overexpressed in tobacco, which led to increased flavonols but decreased anthocyanins. Dual-luciferase assays further confirmed that PsMYB111 upregulated PsFLS. These results improve our understanding of yellow pigmentation in tree peony and provide a guide for future molecular-assisted breeding experiments in tree peony with novel flower colors.


Thyroid cancer in childhood.
A rare case of a papillary thyroid cancer in a young boy is reported. At the age of 8 years a rapidly growing tumour of the right antero-lateral neck region was detected. Biopsy revealed a cervical lymph node metastasis of a papillary thyroid carcinoma. Any adequate therapy was rejected by the patient's father. After two years of delay, at the age of ten, a severe dyspnoea urged to an emergency tracheotomy. The further investigations revealed a bilateral partly papillary, partly follicular and partly anaplastic thyroid carcinoma with infiltration and compression of the cervical trachea and the cricoid and with right recurrent nerve paralysis. The thyroid cancer was classified as T3N2bM0. To save the boy's life an extensive operation was performed with total extirpation of the thyroid gland and the adjacent tissues, total laryngectomy and resection of the cervical trachea, combined with bilateral neck dissection. The patient has been given no other treatment than hormone substitution during 16 years after surgery. The patient grew up normally and stayed recurrence-free. As far as we could find in world literature, this is the youngest patient with total laryngectomy, partial resection of the trachea, total thyroidectomy and bilateral neck dissection.


Eight-year follow-up of excimer laser trabeculostomy alone and combined with phacoemulsification in patients with open-angle glaucoma.
To describe the 8-year results of excimer laser trabeculostomy (ELT) alone and ELT in conjunction with phacoemulsification (phaco). University hospital. Retrospective review. 308 nm excimer laser energy delivered through an intraocular fiber-optic probe created channels through the inner wall of Schlemm canal. 2 groups were studied: ELT alone and ELT + phaco. Inclusion criteria were adult patients with open-angle glaucoma or ocular hypertension on 1 or more intraocular pressure (IOP)-lowering medications and, in the ELT + phaco group, presence of visually significant cataract. Primary outcome measures were change of IOP from baseline and number of IOP-lowering medications. 164 eyes in 2 groups, ELT alone (n = 90) and ELT + phaco (n = 74), were followed up for 8 years. Baseline IOP was 22.17 ± 7.0 mm Hg and 21.9 ± 6.44 mm Hg in the ELT alone and the ELT + phaco groups, respectively. IOP in the ELT alone group decreased to 16.84 ± 5.2 mm Hg at 1 year (n = 69) and remained at 15.9 ± 3.5 (n = 19) at 8 years. IOP in the ELT + phaco group was 14.04 ± 4.1 mm Hg at 1 year (n = 63) and 13.7 ± 2.8 mm Hg at 8 years (n = 13). The number of IOP-lowering medications at baseline in the ELT alone group was 1.85 ± 0.8 and decreased to 1.19 ± 1.10 at 1 year and 1.4 ± 1.4 at 8 years. In the ELT + phaco group, it was 1.58 ± 0.8 at baseline and decreased to 0.97 ± 0.95 at 1 year and 1.85 ± 0.7 at 8 years. ELT demonstrated long-term IOP lowering and decrease in the number of IOP-lowering medications. Benefits of this laser-based implant-free microinvasive glaucoma surgery procedure included a high safety profile and long-term efficacy.


Synthesis and numerical simulation of formamidinium-based perovskite solar cells: a predictable device performance at NIS-Egypt.
Formamidinium lead triiodide (δ-FAPbI3)-based perovskite solar cells showed remarkable potential as light harvesters for thin-film photovoltaics. Herein, the mechanochemical synthesis of δ-FAPbI3, MAPbI3, and mixed-cation FA1-xMAxPbI3 with (x = 0.3, 0.5, and 0.7) perovskite materials were prepared as a novel green chemistry method for scaling up production. Crystallinity, phase identification, thermal stability, optoelectronic properties, and nanoscale composition are discussed. The results demonstrated that the prepared mixed-cation samples are enhanced in the visible absorption region and are consistent with previous works. The crystal structure of δ-FAPbI3 was altered to a cubic structure due to the change in FA-cation. Moreover, the performance of [Formula: see text]-FA-based perovskites was investigated using the Solar Cell Capacitance Simulator (SCAPS-1D) software. The validity of the device simulation was confirmed by comparing it to real-world devices. The photovoltaic characteristics and impact of absorber thickness on device performance were explained. The [Formula: see text]-FA-based solar cell with a 50% MA-doped molar ratio shows a better performance with an efficiency of 26.22% compared to 8.43% for δ-FAPbI3. The outcome results of this work confirm the beneficial effect of mixed cations on device operation and advance our knowledge of the numerical optimization of perovskite-based solar cells.


Botany, traditional uses, phytochemistry and pharmacology of Waltheria indica L. (syn. Waltheria americana): a review.
Waltheria indica L. (syn. Waltheria americana) is commonly used in traditional medicine in Africa, South America and Hawaii, mainly against pain, inflammation, conditions of inflammation, diarrhea, dysentery, conjunctivitis, wounds, abscess, epilepsy, convulsions, anemia, erectile dysfunctions, bladder ailments and asthma. Aim of the review to provide an up-to-date overview of the botany, phytochemistry, traditional uses, pharmacological activities and toxicity data of Waltheria indica. Additionally, studies providing an evidence for local and traditional uses of Waltheria indica are discussed. Further phytochemical and pharmacological potential of this species are suggested for future investigations. The information was collected from scientific journals, books, theses and reports via academic libraries and electronic search. These sources include Pubmed, Web of Science, Portal de Portales-Latindex, Science Research.com and Google scholar. These studies about the medical botanical, traditional uses, chemical, pharmacological and toxicological data on Waltheria indica were published in English, Portuguese, Spanish, German and French. Crude extracts and isolated compounds from Waltheria indica were investigated and showed analgesic, anti-inflammatory, antibacterial, antifungal, antimalarial, anti-anemic, anti-oxidant, sedative and anticonvulsant activities. The phytochemical investigations showed the presence of cyclopeptid alkaloids, flavonoids (e.g., (-)-epicatechin, quercetin, kaempferol, kaempferol-3-O-β-d-(6″-E-p-coumaryl)-glucopyranoside), tannins, sterols, terpenes, saponins, anthraquinones. Studies of acute toxicity in animal indicated that Waltheria indica can be toxic. Waltheria indica possess therapeutic potential in the treatment of inflammation, malaria, infectious diseases (e.g., lungs infection due to Klebsiella pneumoniae, diarrhea due to Candida albicans or Escherichia coli) and prevention of oxidative stress. Further studies are necessary to explore pure compounds responsible for the pharmacological effects and the mechanisms of action. Further investigations are also needed to provide an evidence base for traditional uses of this species against pain, anemia, convulsions and epilepsy. In addition, there is a pressing need to investigate the other traditional uses such as dysentery, syphilis, erectile dysfunctions and asthma.


Adsorption of thrombin from buffer and modified plasma to polystyrene resins containing sulphonate and sulphamide arginyl methyl ester groups.
The adsorption of albumin and thrombin to insoluble modified polystyrene resins bearing sulphonate (PSSO3) and L-arginyl methyl ester groups (PAOM) was investigated in both purified and plasma systems. Radioiodinated proteins were used to follow adsorption in a 'minicolumn' experiment. Albumin adsorption was found to follow the Langmuir model and specific surface areas of the various resins were evaluated from plateau albumin adsorption data. The adsorption isotherms of thrombin both in buffer and in antithrombin III/fibrinogen-free plasma were also found to be Langmuir-like, and the quantities adsorbed at the isotherm plateaux are in the monolayer range. Analysis of the isotherms at 4 degrees and 37 degrees C for the purified system shows that adsorption is endothermic. Adsorption capacities in plasma remain high (30-50% of those in the purified system) despite competition from the other plasma proteins. These data confirm the strong affinity and selectivity of these resins for thrombin.


Risk of readmission for infection after surgical intervention for intracerebral hemorrhage.
Several operative interventions are performed to reduce the mortality and morbidity of Intracerebral hemorrhage (ICH) in the acute setting, including: craniotomy or craniectomy, placement of an external ventricular drain (EVD), placement of a ventriculo-peritoneal shunt (VPS) and stereotactic craniotomy. Infections are a major source of readmissions following ICH. We explored the association between operative interventions for ICH and 30-day readmissions for infection-related causes. The Nationwide Readmissions Database contains >14 million discharges for all payers and uninsured in 2013. International Classification of Disease, Ninth Revision, Clinical Modification codes were used to identify index cases of ICH, intracranial procedures, and comorbidities. We summarized demographics and comorbidities during index admission, stratified by receipt of operative interventions. We calculated differences in means (using t-tests) and frequencies (using chi-square) by group (any intervention versus none). Top 5 causes of 30-day readmission and top 5 causes for infectious readmissions were identified. Cox regression analysis was performed for time to readmission for infectious causes. There were 27,739 index admissions with ICH, 13% had operative interventions. In the operative group, 45.5% underwent craniotomy, 65.4% had EVD placement and 7.6% had VPS placement. Acute cerebrovascular disease was the top cause of readmission followed by infection in the entire cohort and those with interventions. Among infectious causes of readmissions, septicemia was the largest in the intervention group (65%). In both adjusted and unadjusted models, there was significant association between ICH intervention and risk of readmission for infectious causes. Among those with operative interventions for ICH, risk of readmission with infection is double the risk in the non-intervention group. Cumulative risk of readmission was higher for infection following ICH, starting after approximately 50 days, in the intervention group (log-rank p-value <.0001). Infections and cerebrovascular complications contribute to most readmissions after ICH. There is a dose-response relationship between number of interventions and risk of infectious readmission, and this risk significantly increases after approximately 50-days.


Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders.
Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 μg/μl) or N-methyl-d-aspartic acid (NMDA; 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder.


Evolution of pyruvate kinase-deficient Escherichia coli mutants enables glycerol-based cell growth and succinate production.
The aim of this study was to engineer Escherichia coli strains that efficiently produce succinate from glycerol under anaerobic conditions after an aerobic growth phase. We constructed E. coli strain ss195 with deletions of pykA and pykF, which resulted in slow growth on glycerol as sole carbon source. This growth defect was overcome by the selection of fast-growing mutants. Whole-genome resequencing of the evolved mutant ss251 identified the mutation A595S in PEP carboxylase (Ppc). Reverse metabolic engineering by introducing the wild-type allele revealed that this mutation is crucial for the described phenotype. Strain ss251 and derivatives thereof produced succinate with high yields above 80% mol mol(-1) from glycerol under nongrowth conditions. The results show that during the aerobic growth of ss251, the formation of pyruvate proceeds via the proposed POMP pathway, starting with the carboxylation of PEP by Ppc. The resulting oxaloacetate is reduced by malate dehydrogenase (Mdh) to malate, which is then decarboxylated back to pyruvate by a malic enzyme (MaeA or MaeB). Mutation of ppc is crucial for fast growth of pykAF mutants on glycerol. An E. coli mutant that is capable of achieving high yields of succinate (a top valued-added chemical) from glycerol (an abundant carbon source) was constructed. The identified ppc mutation could be applied to other production strains that require strong PEP carboxylation fluxes.


Comparison of Directigen Flu A+B with Real Time PCR in the Diagnosis of Influenza.
Early diagnosis and treatment of patients with influenza is the reason why physicians need rapid high-sensitivity influenza diagnostic tests that require no complex lab equipment and can be performed and interpreted within 15 min. The Aim of this study was to compare the rapid Directigen Flu A+B test with real time PCR for detection of influenza viruses in the Republic of Macedonia. One-hundred-eight respiratory samples (combined nose and throat swabs) were routinely collected for detection of influenza virus during influenza seasons. Forty-one patients were pediatric cases and 59 were adult. Their mean age was 23 years. The patients were allocated into 6 age groups: 0-4 yrs, 5-9 yrs, 10-14 yrs, 15-19 yrs, 20-64 yrs and > 65 yrs. Each sample was tested with Directigen Flu A+B and CDC real time PCR kit for detection and typisation/subtypisation of influenza according to the lab diagnostic protocol. Directigen Flu A+B identified influenza A virus in 20 (18.5%) samples and influenza B virus in two 2 (1.9%) samples. The high specificity (100%) and PPV of Directigen Flu A+B we found in our study shows that the positive results do not need to be confirmed. The overall sensitivity of Directigen Flu A+B is 35.1% for influenza A virus and 33.0% for influenza B virus. The sensitivity for influenza A is higher among children hospitalized (45.0%) and outpatients (40.0%) versus adults. Directigen Flu A+B has relatively low sensitivity for detection of influenza viruses in combined nose and throat swabs. Negative results must be confirmed.


Retraction Note: Living annulative π-extension polymerization for graphene nanoribbon synthesis.
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41586-020-2950-0 .


Balanced reciprocal translocations: risk factors for aneuploid segregant viability.
Reciprocal translocations were studied in two groups of balanced carrier couples: 202 had 210 translocation aneuploid between (LB) infants, and 95 couples had repetitive abortions (AB) without liveborn aneuploids. The observed translocation aneuploidies in the LB group were compared to predicted potential aneuploidies in AB by frequency of chromosome involvement, meiotic segregation mode, and mean trisomic, monosomic and combined genomic imbalances. Qualitative and quantitative differences identified genomic regions and chromosomes possibly vital for in utero survivability. LB aneuploidies indicate non-random chromosome involvement, selection of least detrimental segregants and segments, and predominant transmission from maternal balanced carriers (especially in 3:1 tertiary segregation, 93.5%). For an individual with a balanced reciprocal translocation and untested reproductive capability, an approach is given for predicting whether a translocation aneuploid conceptus will be liveborn or aborted.


Microorganism viability influences internal phase droplet size changes during storage in water-in-oil emulsions.
Water-in-oil emulsions provide an alternative for long-term stabilization of microorganisms. Maintaining physical stability of the emulsion and cell viability is critical for large-scale application. Water-in-oil (W/O) emulsions were prepared with the biolarvacide Lagenidium giganteum and the green alga Chlorella vulgaris. Physical stability was measured via light scattering measurements of the internal phase droplets and cell viability was measured by plating and enumerating colony forming units. Emulsions were demonstrated to stabilize L. giganteum and C. vulgaris for more than 4 months without refrigeration. Introducing nutrients into the internal phase of W/O emulsions without cells had no significant effect on changes in aqueous phase droplet size dynamics. Internal phase droplet size changes that occurred over time were greater in the presence of cells. Increases in droplet size were correlated with cell death indicating measurement of internal phase droplet size changes may be an approach for monitoring declines in cell viability during storage.


Resource limitation, habitat segregation, and species interactions of british tree-hole mosquitoes in nature.
The insect fauna of water-filled tree holes in southern Britain consists primarily of the mosquitoes Aedes geniculatus, Anopheles plumbeus, Culex torrentium, and a benthic detritivorous fauna that includes primarily the scirtid beetle Prionocyphon serricornis and the chironomid midge Metriocnemus martinii. Culex torrentium has been documented only relatively recently in tree holes but all three species of mosquitoes partition the resource in space and time. When mosquito larvae were forced to coexist in natural tree holes at limiting densities and at higher than natural levels of interspecific encounter, there was no evidence that Aedes geniculatus or Anopheles plumbeus affected pupation success, pupal weight, or development time of the other or that either Aedes geniculatus or C. torrentium affected the survivorship, pupation success, pupal weight, and biomass yield of the other. When A. geniculatus at limiting densities were forced in natural tree holes to live without or to coexist with natural or twice natural densities of P. serricornis and M. martinii, the presence, absence, or superabundance of the benthic insects did not affect pupation success or pupal weight of A. geniculatus; development time of A. geniculatus was faster when a superabundance of the benthic fauna was present. Effects of the benthic fauna on A. geniculatus are slight and the only significant interaction is facilitative, not competitive. The pattern of habitat segregation among treehole mosquitoes in southern Britain is characteristic of their respective genera and we propose that this pattern is more likely (but not certain) to have arisen through a process of independent evolution than through competitively driven niche shifts among already coexisting species.


Considerations of Methodological Approaches in the Recruitment and Retention of Immigrant Participants.
This study aims to identify effective strategies related to recruitment and retention of immigrant survey participants. The study used a multi-mode approach in, first, conducting a literature review of recent articles on surveys that either targeted immigrants or included large numbers of immigrants in their samples. Next, six surveys were reviewed that either targeted or included large numbers of immigrants. Finally, expert opinions on immigration were gathered regarding recruitment and retention of immigrant survey participants. Although immigrants may be difficult to recruit due to limited English proficiency, mistrust of strangers, and/or high mobility, many of these challenges can be overcome by adopting the same strategies used when surveying ethnically diverse populations (e.g., snowballing versus advertisement, establishing a personal connection with data collectors). Nonetheless, a few practices were identified as most relevant for recruitment and retention of immigrant populations, including involving local community organizations relevant to immigrants, translation of materials tailored to the vernacular language of the various ethnicities, and customizing non-monetary incentives to the specific ethnicity. Based on the reviews and expert interviews, multiple strategies have been shown to be effective in recruiting and retaining immigrant participants.


Smad3 and Snail show circadian expression in human gingival fibroblasts, human mesenchymal stem cell, and in mouse liver.
Smads are intracellular signaling mediators. Complexes of Smad2 and Smad3 with Smad4 transmit transforming growth factor-beta (TGF-β) receptor-induced signaling. Snail plays important roles in mesoderm formation, gastrulation, neural crest development, and epithelial mesenchymal transition. However, it remains unknown whether Smad3 and Snail expression is circadian rhythm-dependent. Here, we showed for the first time that Smad3 and Snail show circadian expression in human gingival fibroblasts (HGF-1) and human mesenchymal stem cells (MSC) after serum shock. They also showed circadian expression in the mouse liver. We confirmed that BMAL1/2, DEC1/2, VEGF, and PER1/2/3 also show circadian expression in both HGF-1 and MSC. The mRNA peaks and phases in circadian expression of these genes differed between HGF-1 and MSC. In a luciferase assay, Smad3 promoter activity was upregulated by CLOCK/BMAL1. These findings suggest that Smad3 and Snail have circadian rhythm in vitro and vivo, and that circadian expression of Smad3 depends on CLOCK/BMAL1.


[The frequency of hearing impairment in patients with diabetes mellitus type 2].
To determine the prevalence of hardness of hearing in patients with diabetes mellitus type 2 and to compare the diabetes characteristics between diabetic patients with and without hardness of hearing. Computerized general practitioners office in Nijverdal, the Netherlands. Descriptive, cross-sectional study. In all patients aged 55 years and over, registered at the general practitioners (n = 1184), diabetes mellitus type 2 and hardness of hearing were determined. Hardness of hearing was defined as use of a hearing aid or an audiometrically determined hearing loss of at least 40db. A hearing aid was three to four times more prevalent in patients with diabetes mellitus type 2 (n = 86) than in subjects without diabetes of the same age (p < 0.001). Of the diabetic patients 48% had impaired hearing. Patients with hardness of hearing had a longer duration of diabetes than diabetic patients with a normal hearing (10.5 years (SD: 6.9) versus 6.9 years (6.8); p = 0.06, adjusted for age). They suffered less hypertension and had a lower level of glycated haemoglobin. Hardness of hearing is frequent in elderly patients with diabetes mellitus type 2. It may be due to diabetic neuropathy.


A new QEXAFS system on the general XAFS beamline at the Shanghai Synchrotron Radiation Facility.
A new quick-scanning extended X-ray absorption fine-structure (QEXAFS) system for in situ studies has been developed and tested on the general XAFS beamline at the Shanghai Synchrotron Radiation Facility. In the new system, an analog-to-digital converter (ADC) with 1 MHz sampling rate is used to acquire the detector data while one scaler is used to precisely calculate the scanning energy. Two external hardware trigger signals were adopted to synchronize the data collection of the ADC and the scaler. The software development platforms of the double-crystal monochromator control system and the new QEXAFS system have been unified with the Experimental Physics and Industrial Control System. By comparing the spectra acquired by the conventional step-by-step XAFS system with an energy range of 1200 eV at the 7.5um Cu foil K-edge, the new system demonstrates satisfactory signal-to-noise ratio and energy resolution. The previous shortcomings, including distortion of the spectrum and energy shift, have been overcome. The tests with different integration times indicated that appropriate parameters not only ensure good experimental results but also enhance the smoothness of the XAFS spectrum at high energy zones. The reliability of the new system has also been verified.


Has CT scanning a role to play in the radiotherapy planning of palliative treatment?
Radiotherapy is useful in the palliative treatment of many large incurable tumours. This study evaluates the effectiveness of computed tomography (CT) as an adjunct in the radiotherapy planning of these patients. Forty-five patients had their treatment fields simulated using findings from physical examination, x-rays etc. The patients were then scanned under conditions simulating the radiotherapy and the dosimetry was recalculated. CT scanning was found to be valuable in the radiotherapy planning in 56% of the treatment series (field geometry: 27% dosimetry: 46%).


Digital cardiac radiology.
The purpose of this article is to provide the general diagnostic radiologist with an overview of digital radiographic techniques. The development of digital cardiac radiology is discussed first, followed by discussions of intravenous and intra-arterial digital left ventriculography. There is a discussion of the use of digital techniques in the diagnosis of congenital heart disease, and some comments on the use of digital techniques to study myocardial perfusion.


Patient education and engagement in postoperative pain management decreases opioid use following knee replacement surgery.
Effects of patient education on perioperative analgesic utilization are not well defined. We designed a simple pain management educational card for total knee arthroplasty (TKA) patients and retrospectively reviewed clinical data before and after implementation to test the hypothesis that more informed patients will use less opioid. With IRB approval, we analyzed clinical data collected perioperatively on all TKA patients one month before (PRE) and one month after (POST) card implementation. The card was designed using a modified Delphi method; the front explained all analgesic medications and the Defense and Veterans Pain Rating Scale was on the back. The primary outcome was total opioid dosage in morphine milligram equivalents (MME) for the first two postoperative days. Secondary outcomes included daily opioid usage, pain scores, ambulation distance, hospital length of stay and use of antiemetics. There were 20 patients in each group with no differences in baseline characteristics. Total two-day MME [median (10th-90th percentiles)] was 71 (32-285) for PRE and 38 (1-117) for POST (p = 0.001). There were no other differences. Educating TKA patients in multimodal pain management using a simple tool decreases opioid usage. Empowering TKA patients with education can reduce opioid use perioperatively.


Whole-Liver Apparent Diffusion Coefficient Histogram Analysis for the Diagnosis and Staging of Liver Fibrosis.
Conventional diffusion-weighted imaging is limited in the quantitative evaluation of liver fibrosis, and whole-liver apparent diffusion coefficient (ADC) histogram analysis might contribute to the diagnosis and staging of liver fibrosis. To explore the value of whole-liver ADC histogram parameters in the diagnosis and staging of liver fibrosis. Retrospective. Twenty individuals with no liver disease and 86 patients with liver fibrosis, including 30 with chronic viral hepatitis, 29 with autoimmune hepatitis, and 27 with unexplained liver fibrosis patients. 3.0T/T1 -weighted, T2 -weighted, and diffusion-weighted images. A region of interest (ROI) was drawn in each slice of the diffusion-weighted images. Whole-liver histogram parameters were obtained with dedicated software by accumulating all ROIs. The effectiveness of the parameters in differentiating stage 1 or greater (≥F1), stage 2 or greater (≥F2), and stage 3 or greater (≥F3) liver fibrosis was assessed. Mann-Whitney U-test and receiver operating characteristic curve analysis. Kurtosis, entropy, skewness, mode, and 90th and 75th percentiles exhibited significant differences among the pathological fibrosis stages (P < 0.05). Kurtosis was found to be the most meaningful parameter in differentiating fibrosis stages of the viral hepatitis, autoimmune hepatitis, and unexplained liver fibrosis group (area under the curve) (AUC = 0.793, 0.771, 0.798, respectively). In the combined liver fibrosis group, kurtosis achieved the highest AUC (0.801; 95% confidence interval [CI]: 0.702-0.900; sensitivity: 0.750; specificity: 0.850; positive likelihood ratio: 4.953; negative likelihood ratio: 0.302; positive predictive value: 0.946; negative predictive value: 0.486), with a cutoff value of 1.817, in differentiating fibrosis stage ≥F1. Kurtosis, entropy, skewness, mode, and 90th and 75th percentiles may contribute to the diagnosis and staging of liver fibrosis, especially kurtosis. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1745-1754.


Propranolol-induced changes in the catecholamine-containing cells and vesicles of SHR sympathetic ganglia.
The ultrastructural effects of long-term propranolol administration on the catecholamine-containing (CC) cells of cervical sympathetic ganglia were studied in spontaneously hypertensive rats. After 2 months of propranolol administration, there were hydrops of mitochondria, together with swelling and vesiculation of Golgi complex and rough endoplasmic reticulum. Such swollen organelles seemed to coalesce with each other, resulting in transformation of major parts of the cytoplasm into large membrane bound saccules. In that group of animals, the number of CC vesicles showed a significant decrease (P less than 0.025) compared to the control. Moreover, such vesicles looked more electron dense, with decreased electron-lucent haloes compared to the control. Blood pressure recording via rat tail cuff showed a significant drop (P less than 0.0001) of the mean systolic blood pressure in the treated animals. One month after stopping propranolol administration, resorption of the cytoplasmic saccules occurred, but the cytoplasm looked lighter and lost its granular appearance. The mitochondria regained their normal shape, though they appeared fewer in number. The CC vesicles were significantly reduced in number (P less than 0.001) and were less electron dense compared to the control. The possible implications of these findings on the mechanism of action of propranolol as an antihypertensive agent are discussed.


Subcutaneous granuloma annulare of the penis in 2 adolescents.
Granuloma annulare (GA) is a benign inflammatory disorder of unknown etiology characterized histologically by dermal palisading granulomas with central degeneration of collagen (necrobiosis). There is a rare subcutaneous clinical variant, this occurring more frequently in children than in adults and very rarely involves the penis. We describe 2 cases of penile subcutaneous GA developing in adolescent boys who to our knowledge has not previously been described in literature. Both were initially treated with surgical excision. Circumcision was performed on one of the boys, with subsequent improvement with the resolution of most of the nodules. Granuloma annulare of the penis is very rare, with only 7 cases reported to date [Narouz N, Allan PS, Wade AH. Penile granuloma annulare. Sex Transm Infect 1999;75(3):186-7; Trap R, Wiebe B. Granuloma annulare localised to the shaft of the penis. Scand J Urol Nephrol 1993;27(4):549-51; Laird SM. Granuloma annulare of the penis. Genitourin Med 1992;68(4):277; Hillman RJ, Waldron S, Walker MM, et al. Granuloma annulare of the penis. Genitourin Med 1992;68(1):47-9; Kossard S, Collins AG, Wegman A, et al. Necrobiotic granulomas localised to the penis: a possible variant of subcutaneous granuloma annulare. J Cutan Pathol 1990;17(2):101-4] and no previous reports in children or adolescents to our knowledge. All except one of the cases reported so far were of the subcutaneous (nodular) form of GA.


Effect of Coracoid Drilling for Acromioclavicular Joint Reconstruction Techniques on Coracoid Fracture Risk: A Biomechanical Study.
To biomechanically compare the stability of the coracoid process after an anatomic double-tunnel technique using two 4-mm drill holes or a single-tunnel technique using one 4-mm or one 2.4-mm drill hole. For biomechanical testing, 18 fresh-frozen cadaveric scapulae were used and randomly assigned to one of the following groups: two 4-mm drill holes (group 1), one 4-mm drill hole (group 2), or one 2.4-mm drill hole (group 3). After standardized coracoid drilling, load was applied to the conjoined tendons at a rate of 120 mm/min and ultimate failure load, along with the failure mode, was recorded. There was no significant difference between groups regarding load to failure. Mean load to failure in group 1 was 392 N; group 2, 459 N; and group 3, 506 N. The corresponding P values were .55, .74, and .20 for group 1 versus group 2, group 2 versus group 3, and group 1 versus group 3, respectively. However, the failure mode for the group with one 4-mm drill hole and the group with two 4-mm drill holes was coracoid fracture, whereas the group with one 2.4-mm drill hole showed 5 tears of the conjoined tendons and only 1 coracoid fracture (P = .015). Although there was no significant difference regarding load-to-failure testing between groups, the failure mechanism analysis showed that one 2.4-mm drill hole led to less destabilization of the coracoid than one or two 4-mm drill holes. Techniques with small, 2.4-mm drill holes might decrease the risk of severe iatrogenic fracture complications.


Nevirapine induces apoptosis in liver (HepG2) cells.
To generate insights into the mechanism of NVP induced hepatotoxicity. Liver (HepG2) cells were cultured with various concentrations of NVP. This cell line was chosen because it has low expression of cytochrome P450, allowing evaluation of the effects of NVP rather than specific metabolites. Cytotoxicity was determined using a proliferation assay and cell numbers were monitored using trypan blue exclusion assay for long term culture experiments and apoptosis induction was determined by morphological and biochemical investigation. HepG2 cells treated with the highest concentration of NVP tested (819 μM) initially showed a rounded morphology and all cells had died by week three of exposure. Nuclear condensation and fragmentation, increased Annexin V/propidium iodide staining and caspase 9 activation all supported the induction of apoptosis in HepG2 cells in response to NVP treatment. There is a clear induction of apoptosis in response to NVP which suggests that NVP has significant cytotoxicity, over and above any cytotoxicity of metabolites and may contribute directly to patient hepatotoxicity.


High-contrast en bloc staining of mouse whole-brain and human brain samples for EM-based connectomics.
Connectomes of human cortical gray matter require high-contrast homogeneously stained samples sized at least 2 mm on a side, and a mouse whole-brain connectome requires samples sized at least 5-10 mm on a side. Here we report en bloc staining and embedding protocols for these and other applications, removing a key obstacle for connectomic analyses at the mammalian whole-brain level.


Hypertonic saline mimics the effects of vasopressin on inhibitory avoidance in the rat.
Rats tested in a step-through inhibitory avoidance task were administered hypertonic saline (2 ml of 0.25. 0.5, and 1.0 M intraperitoneally) or arginine vasopressin (1.0, 2.0, and 4.0 micrograms) injected subcutaneously (sc) after the training trial where the rats received a mild footshock (0.2 mA, 3 s). Both hypertonic saline and vasopressin produced significant increases in latency to reenter 24 h later. These treatments failed to increase reentry latencies in animals that received the same procedure but no shock. The facilitation of inhibitory avoidance produced by hypertonic saline was reversed by sc administration of 25 micrograms of the vasopressor (V-1) vasopressin antagonist, dPtyr(Me)AVP. The results suggest that the endogenous release of vasopressin can be behaviorally significant in situations of acute homeostatic challenge.


Robustness meets accuracy in adversarial training for graph autoencoder.
Graph autoencoder (GAE) is an effective deep method for graph embedding, while it is vulnerable to the graph adversarial attacks. Adversarial training, which generates adversarial examples in the adversarial scope(neighborhood of natural examples), is effective to improve the robustness of GAE. However, it may lead to degradation of natural accuracy (accuracy on natural examples) due to the extra training examples generated in the adversarial scope (the reasonable scope of adversarial examples). Therefore, considering robustness and natural accuracy is crucial to GAE. In this paper, an improved GAE model is formulated by combining the Structure and Feature encoders, and a novel Adversarial Training strategy (GAE-SFAT) is proposed based on improved GAE. GAE-SFAT has a smaller but more reasonable adversarial scope for adversarial training, which keeps the robustness and reduces the degradation of natural accuracy compared with ordinary adversarial training. In addition, a novel algorithm considering the robustness and accuracy is designed to optimize the GAE-SFAT. We conduct experiments both on the natural graphs as well as perturbed graphs for three datasets. The results show that GAE-SFAT can perform better than state of arts adversarial training model under different kinds of perturbations.


Design of prospective study of acute coronary syndrome hospitalization after smoking ban in public places in Hyogo prefecture: comparison with Gifu, a prefecture without a public smoking ban.
Hyogo is the second prefecture, after Kanagawa, to enact a smoking ban in public places in Japan. The effect of this smoking ban on acute coronary syndrome (ACS) has not been evaluated. Changes in the annual number of ACS hospital cases in Hyogo Prefecture, before and after the enactment of the prefectural legislative ban on smoking in public places, are to be compared with those in Gifu Prefecture, where there is no smoking-ban legislation. Consecutive Hyogo residents with ACS, admitted to 33 major hospitals in the Hanshin-Awaji-Kobe district, which covers 56% of the population, during the 12 months before implementation of the legislation (April 2012 through March 2013) and during the same 24 months thereafter (April 2013 through March 2015) will be enrolled. Consecutive patients with ACS, who are Gifu residents, treated at the 20 major hospitals in Gifu Prefecture will be enrolled as geographical controls. The primary endpoint is the change in number of ACS admissions from April 2012 through March 2015, considering the periods before and after the smoking-ban legislation in Hyogo prefecture. Our study has certain strengths: (1) This is the first large Japanese study of ACS registry with smoking-ban legislation. (2) Major hospitals in the Hanshin-Awaji-Kobe district are included. (3) The data will cover 3 years including 1 year before legislation enactment. (4) The data will be compared with those of Gifu Prefecture, where smoking-ban legislation will not be enacted. (5) The very large database makes possible analysis of subgroups based on age and gender.


A potentially general method for the in vivo selection of inhibitory peptides targeted at a specific protein using yeast.
Although invaluable for biology and medicine, general methods for the selection of inhibitors directed against any protein activity are still missing. To test whether the fitness-based interferential genetics (FIG) approach performed in yeast might contribute to changing this situation, we used this method for the selection of artificial-gene-encoded peptides targeted at firefly luciferase, a foreign protein which was expressed in yeast. Some of these peptides were shown to inhibit the light-producing activity of luciferase in vitro. These results obtained within a totally artificial setting provide a direct demonstration of FIG selection for antagonistic components. Moreover, they open the way for FIG as a simple and general approach for selecting peptides against any specific protein activity expressed in a cellular environment, thus yielding compounds of potential scientific, medical and therapeutic value. Conditions for the development of such valuable compounds in the future using FIG are discussed.


Combined injuries of the cranium and face.
The neurosurgeon and plastic surgeon are increasingly called upon to manage the care of patients with combined injuries of the cranium and face. The authors briefly review the pathogenesis and classification of craniofacial fractures and outline historical approaches to them. Current principles of management are then discussed. Experience with 167 patients is presented with emphasis on surgical technique, the sequence of repair and early primary reconstruction. The controversial issue of fontal sinus fracture repair is addressed. The authors favour preservation of the frontal sinus cavity, where possible, and do not obliterate the nasofrontal duct. With injuries to the floor of the sinus, the base of the sinus and frontonasal duct are sealed with bone graft and a vascularised soft tissue flap and the sinus is cranialised. Immediate bone grafts, using split skull or rib, are used to reconstruct areas of bony destruction or loss. Ninety-eight patients required 402 grafts. Immediate bone grafting resulted in few complications and low incidence of secondary deformities needing correction.


Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-gamma and tumor necrosis factor-alpha.
Astrocytes can function as antigen-presenting cells (APC) upon expression of class II major histocompatibility complex (MHC) antigens, which are induced by interferon-gamma (IFN-gamma). Previous data from this laboratory had shown that the cytokine tumor necrosis factor-alpha (TNF-alpha) enhances IFN-gamma-mediated class II antigen expression on astrocytes. We have now investigated the effect of IFN-gamma and TNF-alpha on class II MHC mRNA expression in astrocytes using Northern blot analysis. Astrocytes do not constitutively express mRNA for class II MHC. Kinetic analysis of class II MHC mRNA expression in IFN-gamma-treated cells demonstrated an 8 h time lag, which was followed by an increase over the next 16 h. Optimal expression of class II mRNA was detected after a 24 h incubation with IFN-gamma. This level of expression was further enhanced by the simultaneous addition of IFN-gamma and TNF-alpha to the astrocytes, while TNF-alpha alone had no effect on class II mRNA expression. TNF-alpha does not act by increasing the stability of IFN-gamma-induced class II mRNA, indicating its action is not at that specific level of post-transcriptional control. Furthermore, astrocyte class II mRNA expression was inhibited when cycloheximide (CHX) was added together with IFN-gamma or IFN-gamma/TNF-alpha, and when CHX was added up to 4 h after treatment with IFN-gamma or IFN-gamma/TNF-alpha. These results indicate that astrocyte class II mRNA expression is mediated by newly synthesized proteins induced by IFN-gamma and/or IFN-gamma/TNF-alpha. The expression of class II antigens on astrocytes, and cytokine modulation of their expression, may be important in the initiation and perpetuation of intracerebral immune responses.


Campylobacter jejuni isolated from poultry meat in Brazil: in silico analysis and genomic features of two strains with different phenotypes of antimicrobial susceptibility.
Campylobacter jejuni is the most common bacterial cause of foodborne diarrheal disease worldwide and is among the antimicrobial resistant "priority pathogens" that pose greatest threat to public health. The genomes of two C. jejuni isolated from poultry meat sold on the retail market in Southern Brazil phenotypically characterized as multidrug-resistant (CJ100) and susceptible (CJ104) were sequenced and analyzed by bioinformatic tools. The isolates CJ100 and CJ104 showed distinct multilocus sequence types (MLST). Comparative genomic analysis revealed a large number of single nucleotide polymorphisms, rearrangements, and inversions in both genomes, in addition to virulence factors, genomic islands, prophage sequences, and insertion sequences. A circular 103-kilobase megaplasmid carrying virulence factors was identified in the genome of CJ100, in addition to resistance mechanisms to aminoglycosides, beta-lactams, macrolides, quinolones, and tetracyclines. The molecular characterization of distinct phenotypes of foodborne C. jejuni and the discovery of a novel virulence megaplasmid provide useful data for pan-genome and large-scale studies to monitor the virulent C. jejuni in poultry meat is warranted.


Microbiota in promoting liver regeneration.
Extensive work has revealed well-coordinated mechanisms that underlie liver regeneration, albeit with a focus on intrinsic interactions within hepatic cells. Here, Hess et al.1 demonstrate that Mycobacterium leprae infection can induce liver growth of nine-banded armadillo without obvious side effects.


Exercise-associated hyponatremia: role of cytokines.
Exercise-associated hyponatremia (EAH) has emerged in recent years as a life-threatening complication of endurance sports that may lead to fatal cerebral and pulmonary edema. Defined as a serum sodium concentration <135 mEq/L (1 mEq/L = 1 mmol/L), symptomatic EAH is a dilutional hyponatremia with abnormal fluid retention mediated by decreased urine production, which is a variant of the syndrome of inappropriate antidiuretic hormone secretion. Strategies for prevention and treatment must take into account the pathophysiology underlying this dominant clinical paradigm. Beyond educating runners to drink moderately, monitoring changes in body weight during endurance sports may facilitate the early detection of positive fluid balance characteristic of symptomatic cases. Rapid diagnosis by point-of-care testing indicates the need for fluid restriction in mild cases and emergent treatment with hypertonic (3%) NaCl to reverse acute hypotonic encephalopathy. The efficacy of arginine vasopressin V(2) receptor antagonists warrants study as an alternative treatment to loop diuretics for volume overload in these patients. Nonosmotic stimulation of arginine vasopressin secretion may be mediated in part by enhanced release of muscle-derived interleukin-6 during glycogen depletion, linking exertional rhabdomyolysis to the pathogenesis of EAH.


Association between biphasic reactions and the systems of symptoms and treatment in patients with anaphylaxis hospitalized from the emergency department.
Anaphylaxis is a severe, life-threatening, generated or systemic reaction, and biphasic reaction could occur in some cases. We investigated the clinical course of anaphylaxis in our hospital and studied the relationship between biphasic reactions and the symptoms and treatments for predicting the onset of biphasic reactions. We retrospectively reviewed the medical records of 120 patients with anaphylaxis who were admitted to our hospital from the emergency department during April 2008-October 2015. The incidence of biphasic reactions of anaphylaxis in our hospital was 10.8% (13 patients) without significant difference when compared with that in previous reports. Regarding the development of biphasic reactions, symptoms, the number of systems of symptoms and severity of the initial reaction, and treatment with adrenaline and corticosteroid were not clearly related with biphasic reaction. Use of adrenaline in the initial treatment was approximately 60%. Of the 13 biphasic reactions, 11 (84.5%) were as equal/mild as the original symptoms. This study could not show the factors predicting the onset of biphasic reactions. Further prospective and nationwide studies are required to research biphasic reactions.


Influence of feeding and earthworm density on compound bioaccumulation in earthworms Eisenia andrei.
Earthworm density and feeding during exposure to contaminated soil have been used inconsistently in bioaccumulation studies, which may lead to possible errors in risk assessment and modeling. Hydrophobic organic pollutants with a wide range of environmental properties (phenanthrene, pyrene, lindane, p,p'-DDT, and PCB 153) were used to study the effect of different earthworm densities in combination with the presence or absence of feeding on bioaccumulation factors (BAFs). Similar BAFs were found at various soil-to-worm ratios, with the exception of phenanthrene. We recommend using at least 15 gsoil dw per earthworm. The absence of feeding doubled the BAFs and, thus, using no food ration can be considered as "the worst case scenario". Whenever food is to be applied (i.e. to ensure the validity of the test in earthworm mass loss), we suggest feeding depending on the organic carbon content of the studied soil.


The effect of triacylglycerol chain length on food intake in domestic fowl.
Triacylglycerols of varying chain lengths were tested for their effects on food intake in fasted Single-Comb White Leghorn cockerels 9-12 weeks of age. Tributyrin, tricaprylin, triolein, or saline were intubated intragastrically or infused intrahepatically. All triacylglycerol administrations were in 10 ml volumes with 10 kcal being infused intrahepatically and 10 or 20 kcal being infused intragastrically. When administered intragastrically, the short-chained triacylglycerol tributyrin decreased food intake at most times tested; the medium chain-length tricaprylin and the long chain-length triolein affected food intake sporadically. When infused into the liver, tributyrin and tricaprylin decreased food intake at most times tested, whereas triolein decreased food intake at 60 and 180 minutes only. Satiating effectiveness was related to triacylglycerol chain length when intubated, which may reflect rate of absorption from the gut; however, hepatic satiety receptors were also differentially sensitive to triacylglycerol chain length indicating that more than rate of assimilation from the gut must be considered.


Optimality in the variation of average branching angle with generation in the human bronchial tree.
In the human bronchial tree the branching angle becomes larger with generation or for the smaller branches. Previous theories based on single parameter optimization have not been successful at all in predicting the consistent increasing trend of branching angle with continued bifurcation. In this study a new theory for the optimality of the branching angle is proposed, which is based on the optimization between dual competing performances, the maximum space-filling capability at the expense of minimum energy loss. A large-angle branching gives an effect of delivering air into a new direction away from the preceding airways. It then has an effect of utilizing the lung volume with better uniformity, but at the same time inevitably requires a high pressure loss. It is shown in this paper that the ever increasing branching angle with generation can be well explained as the optimum branching structure where the dual opposing performance of space filling and pressure loss is optimized. In estimating the pressure loss, branching loss is considered in addition to the Poiseuille loss. Change of predicted optimum branching angle with generation shows an excellent agreement with the observed data found in the human conducting airways.


The spatial distribution of polyribosomes in 3T3 cells and the associated assembly of proteins into the skeletal framework.
Acridine fluorescence reveals polyribosomes in fibroblasts and Triton-extracted skeletal frameworks; simultaneous phase-contrast images show cellular structure. Polyribosomes appear near nuclei of both intact fibroblasts and skeletal frameworks. Simultaneous autoradiography of cells so examined locates radioactive proteins. After synthesis, most proteins diffuse rapidly through the cytoplasm; intact cells autoradiographed afer a 35S pulse show grains throughout. In sharp contrast, extraction with Triton leaves only radioactive skeletal proteins, which, although released from ribosomes, are near polyribosomes after a pulse. After a chase, skeletal-associated radioactivity is found throughout the framework structure. However, skeletal proteins migrate only if protein synthesis continues. Emetine administered following a pulse block protein migration; skeletal framework radioactivity remains near polyribosomes. This also indicates limited exchange between skeletal framework and soluble cytoplasmic proteins. The fact that proteins insert themselves into the skeletal framework at or near their synthesis site, with limited subsequent exchange, appears to contradict current view of protein self-assembly.


Use of graphitised carbon negative ion LC-MS to analyse enzymatically digested glycosaminoglycans.
Capillary liquid chromatography-mass spectrometry using graphitised carbon stationary phase and ion trap mass spectrometry was shown to be a powerful technique for analysing glycosaminoglycans digested with endoglycosidases. Commonly found disaccharides from heparin/heparan sulphate digests at sub nanomole levels were found to be separated by mass and/or retention time and detected by negative ion electrospray mass spectrometry predominantly as [M-H]- ions using a standard electrospray interface and flow rate between 6-10 microL/min. Graphitised carbon liquid chromatography-fragmentation mass spectrometry provided sequence data of disaccharides and oligosaccharides. Sequence information was obtained from either collision of the [M-H]- ions (low sulphated disaccharides) or of the [M+Na-2H]- ions (highly sulphated disaccharides). This separation and identification method of endoglycosidase digestion and sample preparation using a combination of cation exchange and graphitised carbon, was used to successfully analyse digests of keratan sulphate (keratanase) and heparin (heparinase) standards, and hyaluronic acid (hyaluronidase) from synovial fluid samples.


Orientation to nutrition care process standards improves nutrition care documentation by nutrition practitioners.
To compare documentation of two groups of clinical nutrition practitioners for evidence of the nutrition care process. This study used a comparative descriptive design. A retrospective chart review was conducted on all nutrition documentation in closed patient records. Documentation of two groups of nutrition practitioners (institution A=practitioners who received initial orientation and routine reinforcement in use of nutrition care process standards; institution B=practitioners who received orientation in use of a further assessment and medical nutrition therapy intervention procedure) was compared for evidence of a six-step nutrition care process. The sample consisted of randomly selected patient records (N=60). A total of 15 oncology and 15 chronic renal failure patient records from each of two Midwestern tertiary-care hospitals were reviewed. Outcome measures were number of nutrition care process steps documented, appropriate relationships among documented steps in the nutrition care process, and the number of complete, incomplete, and interrupted chains. Two-sample t tests and chi(2) analyses were used. Nutrition practitioners at institution A documented approximately three times as many nutrition care process steps per patient per chain that demonstrated appropriate relationships as did nutrition practitioners at institution B (2.69+/-1.15 and 0.80+/-0.62, respectively [mean+/-standard deviation]) (P<.001). There were no outcome judgments related to goals documented in chains at either institution and because of this there were no completed nutrition care process chains at either institution. Nutrition practitioners with orientation to nutrition care process standards documented more related nutrition care process steps than practitioners without this orientation. Providing nutrition practitioners with ongoing education and clinical experiences in use and documentation of the nutrition care process and a standardized language may be indicated to increase the number of completed nutrition care process chains and improve documentation of nutrition care and patient outcomes.


Effects of COVID-19 vaccination and previous infection on Omicron SARS-CoV-2 infection and relation with serology.
An increasing proportion of the population has acquired immunity through COVID-19 vaccination and previous SARS-CoV-2 infection, i.e., hybrid immunity, possibly affecting the risk of new infection. We aim to estimate the protective effect of previous infections and vaccinations on SARS-CoV-2 Omicron infection, using data from 43,257 adult participants in a prospective community-based cohort study in the Netherlands, collected between 10 January 2022 and 1 September 2022. Our results show that, for participants with 2, 3 or 4 prior immunizing events (vaccination or previous infection), hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Differences in risk of infection are partly explained by differences in anti-Spike RBD (S) antibody concentration, which is associated with risk of infection in a dose-response manner. Among participants with hybrid immunity, with one previous pre-Omicron infection, we do not observe a relevant difference in risk of Omicron infection by sequence of vaccination(s) and infection. Additional immunizing events increase the protection against infection, but not above the level of the first weeks after the previous event.


Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial.
Observational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant women in populations considered to be iodine sufficient may negatively impact child neurodevelopment. We aim to determine the effect of reducing iodine intake from supplements for women who have adequate iodine intake from food on the cognitive development of children at 24 months of age. A multicentre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. Using a hybrid decentralised clinical trial model, 754 women (377 per group) less than 13 weeks' gestation with an iodine intake of ≥165 µg/day from food will be randomised to receive either a low iodine (20 µg/day) multivitamin and mineral supplement or an identical supplement containing 200) µg/day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age assessed with the Cognitive Scale of the Bayley Scales of Infant Development, fourth edition. Secondary outcomes include infant language and motor development; behavioural and emotional development; maternal and infant clinical outcomes and health service utilisation of children. Cognitive scores will be compared between groups using linear regression, with adjustment for location of enrolment and the treatment effect described as a mean difference with 95% CI. Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/17/WCHN/187). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. NCT04586348.


Polluted at the faucet: Exaggeration and hype of research results in the media often originate earlier at the press office.
The mass media are frequently accused of overhyping science and health stories. But often, the press releases by universities and research institutes are the source of hype and exaggeration.


Whack induced psychosis: A case series.
'Whack' is a new psychoactive substance available until recently in 'head shops'. It contains two active constituents, 4-fluorotropacocaine and desoxypipradrol. We present two case reports of subjects who developed acute psychotic states after using Whack. Both individuals displayed similar affective and anxiety symptoms in the presence of significant psychotic symptoms. Both required inpatient treatment but displayed a good treatment response to atypical antipsychotic agents. To our knowledge, this is the first published case series relating to this psychoactive substance.


Antagonism by indomethacin of neurogenic hyperthermia produced by unilateral puncture of the anterior hypothalamic/preoptic region.
1. In unanaesthetized rats, restrained at an ambient temperature of 24 degrees C, the anterior hypothalamic/preoptic (AH/PO) region was lesioned unilaterally by acute mechanical puncture.2. In control (no pre-treatment) rats, unilateral AH/PO puncture produced a neurogenic hyperthermia which began immediately, reached its peak magnitude (mean peak magnitude = +2.3 degrees C) within 60-90 min and persisted usually for 8-16 hr. At defervescence, core temperature fell to a level near that of the pre-lesioning base line.3. The prostaglandin synthesis inhibitor, indomethacin, administered I.P. at doses of 5 and 15 mg/kg 1 hr before puncture of the AH/PO region, attenuated the lesion-induced hyperthermia in a dose dependent fashion. The higher dose reduced peak magnitude by 80% and the 6 hr Fever Index by 88%. The vehicle used to dissolve the indomethacin (60% DMSO/40% saline) did not significantly attenuate the hyperthermia.4. In rats that were hyperthermic after AH/PO damage, indomethacin (10-15 mg/kg I.P.) caused core temperature to fall promptly to near the prelesion base line. Reversal occurred whether the indomethacin was injected while core temperature was still rising or late in the plateau phase of the hyperthermia.5. It is suggested that the neurogenic hyperthermia elicited by unilateral lesioning of the AH/PO region was mediated by prostaglandins released from injured tissue and possibly from extravasated blood. Evidence is cited indicating that the most likely sites of action of the released prostaglandins are the surviving portion of the AH/PO region on the punctured side and the intact contralateral AH/PO region.


Accelerated MRI of the fetal heart using compressed sensing and metric optimized gating.
To develop and validate a method for accelerated time-resolved imaging of the fetal heart using a combination of compressed sensing (CS) and metric optimized gating (MOG). Joint optimization of CS and MOG reconstructions was used to suppress competing artifact from random undersampling and ungated cardiac motion. Retrospectively and prospectively undersampled adult and fetal data were used to validate the proposed reconstruction algorithm qualitatively based on visual assessment, and quantitatively based on reconstruction error, blur, and MOG timing error. Excellent agreement was observed between the fully sampled and retrospectively undersampled reconstructions, up to an undersampling factor of four. Visually, differences between ECG and MOG reconstructions of adult data were negligible. This was consistent with quantitative comparisons of reconstruction error (RMSEECG = 0.07-0.13; RMSEMOG = 0.08-0.13), and image blur (BECG = 1.03-1.20; BMOG = 1.03-1.20). The calculated MOG timing error (2-42 ms) was comparable to the acquired temporal resolution (∼60 ms). Quantitative evaluation of retrospectively undersampled (R = 2-8) fetal data (RMSEMOG = 0.06-0.12; BMOG = 1.04-1.27) was comparable to the adult volunteer results. CS-MOG for dynamic imaging of the fetal heart was developed and validated. Using CS-MOG, images were obtained up to four times faster than conventional acquisitions. Magn Reson Med 77:2125-2135, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


End-of-life care and intensive care unit clinician involvement in a private acute care hospital: A retrospective descriptive medical record audit.
More Australians die in the hospital than in any other setting. This study aimed to (i) evaluate the quality of end-of-life (EOL) care in the hospital against an Australian National Standard, (ii) describe the characteristics of intensive care unit (ICU) clinician involvement in EOL care, and (iii) explore the demographic and clinical factors associated with quality of EOL care. A retrospective descriptive medical record audit was conducted on 297 adult inpatients who died in 2017 in a private acute care hospital in Melbourne, Australia. Data collected related to 20 'Processes of Care', considered to contribute to the quality of EOL care. The decedent sample was separated into three cohorts as per ICU clinician involvement. The median age of the sample was 81 (25th-75th percentile = 72-88) years. The median tally for EOL care quality was 16 (25th-75th percentile = 13-17) of 20 care processes. ICU clinicians were involved in 65.7% (n = 195) of cases; however, contact with the ICU outreach team or an ICU admission during the final inpatient stay was negatively associated with quality of EOL care (coefficient = -1.51 and -2.07, respectively). Longer length of stay was positively associated with EOL care (coefficient = .05). Specialist palliative care was involved in 53% of cases, but this was less likely for those admitted to the ICU (p < .001). Evidence of social support, bereavement follow-up, and religious support were low across all cohorts. Statistically significant differences in the quality of EOL care and a negative association between ICU involvement and EOL care quality suggest opportunities for ICU outreach clinicians to facilitate discussion of care goals and the appropriateness of ICU admission. Advocating for inclusion of specialist palliative care and nonclinical support personnel in EOL care has merit. Future research is necessary to investigate the relationship between ICU intervention and EOL care quality.