Are homografts superior to conventional prosthetic valves in the setting of infective endocarditis involving the aortic valve?
Surgical dogma suggests that homografts should be used preferentially, compared with conventional xenograft or mechanical prostheses, in the setting of infective endocarditis (IE), because they have greater resistance to infection. However, comparative data that support this notion are limited. From the prospective databases of 2 tertiary academic centers, we identified 304 consecutive adult patients (age ≥17 years) who underwent surgery for active IE involving the aortic valve (AV), in the period 2002 to 2014. Short- and long-term outcomes were evaluated using propensity scores and inverse-probability weighting to adjust for selection bias. Homografts, and xenograft and mechanical prostheses, were used in 86 (28.3%), 139 (45.7%), and 79 (26.0%) patients, respectively. Homografts were more often used in the setting of prosthetic valve endocarditis (58.1% vs 28.8%, P = .002) and methicillin-resistant Staphylococcus (25.6% vs 12.1%, P = .002), compared with conventional prostheses. Early mortality occurred in 17 (19.8%) in the homograft group, and 20 (9.2%) in the conventional group (P = .019). During follow-up (median: 29.4 months; interquartile-range: 4.7-72.6 months), 60 (19.7%) patients died, and 23 (7.7%) experienced reinfection, with no significant differences in survival (P = .23) or freedom from reinfection rates (P = .65) according to the types of prostheses implanted. After adjustments for baseline characteristics, using propensity-score analyses, use of a homograft did not significantly affect early death (odds ratio 1.61; 95% confidence interval [CI], 0.73-3.40, P = .23), overall death (hazard ratio 1.10; 95% CI, 0.62-1.94, P = .75), or reinfection (hazard ratio 1.04; 95% CI, 0.49-2.18, P = .93). No significant benefit to use of homografts was demonstrable with regard to resistance to reinfection in the setting of IE. The choice among prosthetic options should be based on technical and patient-specific factors. Lack of availability of homografts should not impede appropriate surgical intervention.


The effect of vitamin K4 supplementation on insulin resistance in individuals with type 2 diabetes: a double-blind randomised placebo-controlled clinical trial.
The purpose of this study was to assess the possible clinical effects of vitamin K4 supplementation in individuals with type 2 diabetes namely insulin resistance, glycaemic control, and lipid profile. This was a prospective randomised double-blind placebo-controlled clinical trial. A total of 106 patients were randomised to receive either 1 mg of vitamin K4 (menadiol diacetate) or placebo for 24 weeks. Ninety patients (n = 45 in each study group) were included in the final analysis. After 24 weeks, homeostatic model assessment of insulin resistance (HOMA-IR) (16.54 ± 7.81 vs. 29.09 ± 36.56, P = 0.027) and fasting serum insulin (FSI) (6.86 ± 3.45 vs. 11.13 ± 12.66 µU/ml, P = 0.032) were significantly lower in the vitamin K group compared to placebo. Additionally, triglycerides (TG) (144.94 ± 50.7 vs. 172.8 ± 101.5 mg/dl, P = 0.031) and very low-density lipoproteins (VLDL) levels (28.9 ± 9.88 vs. 34.6 ± 20.30 mg/dl, P = 0.027) decreased significantly in the vitamin K group after 24 weeks compared to baseline. Moreover, more patients in the vitamin K group (35.6%) had their antidiabetic medication doses reduced after 24 weeks compared to placebo (13.3%, P = 0.029). Vitamin K4 supplementation for 24 weeks is capable of improving insulin resistance and TG levels in individuals with type 2 diabetes. In addition, the improvement in insulin resistance was reflected in the decrease in antidiabetic medication doses. However, it did not affect fasting plasma glucose (FPG) or glycated haemoglobin (HbA1c). The study was registered on clinicaltrials.gov with ID: NCT04285450.


Hurricane-induced modification of nitrogen and phosphorus resorption in an aspen clone: an example of diffuse disturbance.
On 27 September 1985, Hurricane Gloria intersected the Rhode Island land mass and disrupted normal autumnal element resorption in 20 ramets of a trembling aspen clone (Populus tremuloides). No mechanical injury to the plants was observed, but in contrast to undamaged aspens, the wind/salt-damaged aspens did not withdraw nitrogen (N) or phosphorus (P) from senescing leaves. There was actually 17% more N in abscising leaves than in presenescent, pre-hurricane leaves.


Dissociation between parathyroid hormone-stimulated cAMP and calcium increase in UMR-106-01 cells.
We used the osteogenic sarcoma cell line, UMR-106-01, to determine whether the rise in free cytosolic Ca2+ concentration ([Ca2+]i) and cellular cAMP following PTH stimulation are able to be regulated independently. For this purpose, we compared the effect of a PTH antagonist, stimulation of protein kinase C, augmentation by prostaglandins, and the time course of desensitization of the two cellular responses. Two x 10(-7) M of the PTH antagonist 8,18Nle 34Tyr-bPTH(3-34) amide ([Nle,Tyr]bPTH(3-34)A) was required to inhibit 10(-9) M bPTH(1-34)-stimulated cAMP generation by 50%. 10(-7) M bPTH(1-34) completely overcame the inhibition induced by 10(-6) M [Nle,Tyr]bPTH(3-34)A. Only 7 x 10(-8) M and 2.7 x 10(-7) M [Nle,Tyr]bPTH(3-34)A were required to half maximally inhibit the [Ca2+]i increase evoked by 3 x 10(-8) and 10(-7) M bPTH(1-34), respectively. In addition, dissociation between [Ca2+]i and cAMP signals was observed when modulation by protein kinase C and prostaglandins was tested. Preincubation of the cells with 10 nM TPA for 5 minutes markedly inhibited the PTH-evoked [Ca2+]i increase. Short incubation with PGF2 alpha augmented the PTH-evoked [Ca2+]i increase. Similar pretreatments had no effect on the PTH-stimulated cAMP increase. Finally, preincubation with 1.5 x 10(-9) M bPTH(1-34) for 20 minutes almost completely blocked the effect of 10(-7) M bPTH(1-34) on [Ca2+]i, while preincubation with 5 x 10(-9) M bPTH(1-34) for 4 hours was required to inhibit the effect of 10(-8) M bPTH(1-34) on cAMP production by 50%. The differences in the regulation of the two PTH-stimulated cellular signaling systems, in particular, the response to antagonists and the time course of desensitization, could be at the level of the PTH receptor(s) or at a postreceptor domain.


Efficacy of ursodeoxycholic acid combined with Tongdan Decoction () on immunological indices and histopathological changes in primary biliary cirrhosis patients.
To observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage. Sixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years. After 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological <inflammation grading and fibrosis staging declined to a lower rank, and the effect on inflammation was superior in the treatment group to the control group shown by non-parameters Wilcoxon paired symbols test ( Z=2.761,P=0.006). Combined therapy of Tongdan Decoction and UDCA showed a better therapeutic effect: than UDCA monotherapy on PBC, especially in improving immunological indices and histopathological hepatic changes.


Is physician anesthesia cost-effective?
One of the most controversial issues in anesthesia is whether nonmedically directed nurse anesthetists are relatively more cost-effective than anesthesiologists in the provision of anesthesia care. We electronically surveyed anesthesia practices throughout the United States to estimate the range in anesthesia professional costs from the payer perspective. Using this survey data on anesthesia reimbursement and published outcomes studies, we developed an ad hoc model to estimate the cost-effectiveness of physician-directed anesthesia relative to a nonmedically directed nurse anesthetist model of care from the payer perspective. Cost-effectiveness ratios were defined as the ratio of incremental costs associated with physician anesthesia relative to the estimated incremental life expectancy gains with this model of care (i.e., dollars per year of life saved [US dollars /YLS]). Reference case results suggest that physician anesthesia is cost saving with an estimated incremental cost-effectiveness ratio of -US dollars 2601/YLS for a younger privately insured patient and an estimated cost-effectiveness ratio of -US dollars 4410/YLS for an elderly Medicare insured patient. Cost-effectiveness ratios ranged from -US dollars 4410 to US dollars 38778/YLS in univariate and multivariate sensitivity analyses across payer types. Results were most sensitive to assumed differences in reimbursement (commercial conversion factors) and to mortality rate assumptions by provider type. This analysis offers economic evidence in support of the physician anesthesia model of care. Recent outcome studies suggest improved patient outcomes when physicians medically direct nurse anesthetists versus anesthesia care delivered with nonmedically directed nurses. The relative cost-effectiveness of this practice model is, however, unknown. This economic analysis suggests that outcome gains with physician anesthesia may be obtained at cost savings or, under conservative assumptions, at a cost deemed reasonable by society.


Instrumental activities of daily living and neuropsychological functioning among patients with different types of cancer.
The ability to perform instrumental activities of daily living (IADL) is important for maintaining independent living, and optimal health-related quality of life and well-being. Neuropsychological measures are predictors of IADL ratings. The aims of the present study were to measure ability to perform IADL in patients with cancer and to explore the relationship between IADL and neuropsychological functioning. We evaluated IADL in 182 patients with four different types of cancer (thyroid, colorectal, breast and prostate cancer) and examined the relationship between IADL and neuropsychological functioning 6 months after chemotherapy treatment. Our results showed that patients with breast cancer had significantly greater difficulty in performing IADL compared to patients with other types of cancer. There were no differences in IADL performance among the other three study groups. In addition, we found that neuropsychological score was a predictor of IADL; the greater the patients' disability, the lower their performance on neuropsychological measures. This is in accordance with the literature that suggests neuropsychological measures to be predictors of IADL ratings. The present findings are important because, although many researchers have studied the relationship between IADL and neuropsychological functioning in cancer, few studies have investigated IADL in different types of cancer. Optimal neuropsychological functioning is connected with better ability with regard to IADL.


Theta but not beta activity is modulated by freedom of choice during action selection.
Large-scale neurophysiological markers of action competition have been almost exclusively investigated in the context of instructed choices, hence it remains unclear whether these markers also apply to free choices. This study aimed to compare the specific brain dynamics underlying instructed and free decisions. Electroencephalography (EEG) was recorded while 31 participants performed a target selection task; the choice relied either on stimulus-response mappings (instructed) or on participants' preferences (free). Choice difficulty was increased by introducing distractors in the informative stimulus in instructed choices, and by presenting targets with similar motor costs in free choices. Results revealed that increased decision difficulty was associated with higher reaction times (RTs) in instructed choices and greater choice uncertainty in free choices. Midfrontal EEG theta (4-8 Hz) power increased with difficulty in instructed choices, but not in free choices. Although sensorimotor beta (15-30 Hz) power was correlated with RTs, it was not significantly influenced by choice context or difficulty. These results suggest that midfrontal theta power may specifically increase with difficulty in externally-driven choices, whereas sensorimotor beta power may be predictive of RTs in both externally- and internally-driven choices.


[Morphological changes in the neurons of the rat nucleus raphe dorsalis following application of 5,7-dihydroxytryptamine. A golgi-rapid-impregnation study].
The effect of stereotactically applicated 5,7-dihydroxytryptamine on the demonstrability of the different neuron types of the nucleus raphe dorsalis of the rat was investigated by means of the Golgi-rapid-impregnation technique. Degenerative changes could be demonstrated on the polygonal neurons, only. Typical variations of the dendritic structure was shown on the fusiform neurons. The pyriform neuron typ was not affected.


Disseminated blue naevus and malignant blue naevus associated with excessive aromatase syndrome.
We report a case of a 17-year-old boy who had a giant congenital blue naevus with multiple satellite pigmented lesions. Later the patient developed melanoma arising in the pre-existing lesion. He also had gynaecomastia and was diagnosed as having aromatase excess syndrome. To our knowledge, the association of these two rare conditions has not been previously reported. Further studies should be performed to investigate this unusual combination, which may have a genetic, endocrine or local cutaneous link leading to its occurrence.


Indications and outcomes of neonatal intubation: A single-center, prospective study in a middle-income country.
This study assessed the success rate and associated complications of hospital-wide neonatal endotracheal intubations by pediatric residents and neonatal fellows using direct laryngoscopy. Secondary objectives were to identify characteristics and indications for the procedure in a tertiary-care center. A cross-sectional observational study was conducted. We prospectively collected performance and infant outcome data after neonatal intubation between March 1, 2019 and February 29, 2020. 171 intubations were observed in 105 infants. The median infant gestational age was 31.0 weeks (interquartile range [IQR]: 27.5-36.0 weeks). Fifty infants (48%) were very low birth weight (VLBW, <1500 g; median 1640 g [IQR: 870-2420 g]). The most common indication for intubation was respiratory failure (65%). Pediatric residents and neonatal fellows had overall success rates of 66% and 98%, respectively. The success rate for the first intubation attempt was higher with more advanced pediatric residency training (P < 0.001). The median attempts for each intubation were 1 (IQR: 1-2) for both VLBW and non-VLBW infants (P = 0.48). The adverse outcome rates were 5% and 3% for VLBW and non-VLBW infants, respectively (P = 0.53). More than 2 intubation attempts was the only significant independent risk factor for adverse outcomes (adjusted odds ratio 6.7; 95% CI 1.3-33.6; P = 0.02). The success rate of pediatric residents for neonatal intubation was similar for VLBW and non-VLBW infants. The main indication was respiratory failure, and nearly half were infants with VLBW. To minimize adverse sequelae, written guidelines limiting the number of intubation attempts by junior trainees are warranted.


Impact of weather seasonality and sexual transmission on the spread of Zika fever.
We establish a compartmental model to study the transmission of Zika virus disease including spread through sexual contacts and the role of asymptomatic carriers. To incorporate the impact of the seasonality of weather on the spread of Zika, we apply a nonautonomous model with time-dependent mosquito birth rate and biting rate, which allows us to explain the differing outcome of the epidemic in different countries of South America: using Latin Hypercube Sampling for fitting, we were able to reproduce the different outcomes of the disease in various countries. Sensitivity analysis shows that, although the most important factors in Zika transmission are the birth rate of mosquitoes and the transmission rate from mosquitoes to humans, spread through sexual contacts also highly contributes to the transmission of Zika virus: our study suggests that the practice of safe sex among those who have possibly contracted the disease, can significantly reduce the number of Zika cases.


[Carney complex: a syndrome with cardial, cutaneous and neuronal tumours].
A 12 year-old boy presented with neurological symptoms and was found to have a left atrial myxoma. Characteristic facial skin pigmentation raised a suspicion of Carney complex, a rare autosomal dominant disease, which includes cutaneous changes, atrial myxomas and neuroendocrine tumours. The boy's mother had similar skin pigmentation and on subsequent cardiac echocardiography she was found to have left and right atrial myxomas. Both mother and child underwent successful surgical resection of the myxomas.


Addition of Somatostatin After Successful Endoscopic Variceal Ligation Does not Prevent Early Rebleeding in Comparison to Placebo: A Double Blind Randomized Controlled Trial.
Efficacy of endoscopic sclerotherapy in controlling acute variceal bleeding is significantly improved when vasoactive drug is added. Endoscopic variceal ligation (EVL) is superior to sclerotherapy. Whether efficacy of EVL will also improve with addition of somatostatin is not known. We compared EVL plus somatostatin versus EVL plus placebo in control of acute variceal bleeding. Consecutive cirrhotic patients with acute esophageal variceal bleeding were enrolled. After emergency EVL, patients were randomized to receive either somatostatin (250 mcg/hr) or placebo infusion. Primary endpoint was treatment failure within 5 days. Treatment failure was defined as fresh hematemesis ≥2 h after start of therapy, or a 3 gm drop in Hb, or death. 61 patients were enrolled (EVL plus somatostatin group, n = 31 and EVL plus placebo group, n = 30). The baseline characteristics were similar. Within the initial 5-day period, the frequency of treatment failure was similar in both the groups (EVL plus somatostatin group 8/31 [26%] versus EVL plus placebo group 7/30 [23%]; P = 1.000). The mortality was also similar in the two groups (3/31 [10%] vs. 3/30 [10%]; P = 1.000). Baseline HVPG ≥19 mm Hg and active bleeding at index endoscopy were independent predictors of treatment failure. Addition of somatostatin infusion to EVL therapy does not offer any advantage in control of acute variceal bleeding or reducing mortality. The reason for this may be its failure to maintain sustained reduction in portal pressure for five days. Active bleeding at index endoscopy and high baseline HVPG should help choose early alternative treatment options. Trial registered with ClincalTrials.gov vide NCT01267669.


The Yin-Yang of Cytokinin Homeostasis and Drought Acclimation/Adaptation.
Increasing evidence has shown that cytokinins (CKs) regulate plant drought acclimation/adaptation through a multistep phosphorelay pathway. Recent progress has allowed us to suggest a yin-and-yang-type relationship between CK homeostasis and acclimation/adaptation responses that modulates plant fitness and yields stability under drought through a complex network involving crosstalk with abscisic acid (ABA).


Effects of periplocoside X on midgut cells and digestive enzymes activity of the soldiers of red imported fire ant.
The pathological effects of ingested periplocoside X, an insecticidal component isolated from the root of Periploca sepium Bunge, on the midgut epithelial cells of the soldiers of red imported fire ant were studied and the symptom was described. The results showed that periplocoside X could induce a severe, time-dependent cytotoxicity in the midgut epithelial cells. An optical microscopy showed that epithelial cells swelled firstly and then lysed. Transmission electron microscopy (TEM) showed that numerous swollen lysosomes were appeared, microvilli were disrupted and sloughed off, and the numbers of the rough endoplasmic reticulum and the mitochondria decreased sharply in earlier stage. Numerous vacuoles were observed in the later stage. Finally, periplocoside X resulted in cell death by cytolysis. Assay of main three digestive enzymes activity indicated that amylase activity was significantly inhibited, but no significant changes were seen for lipase activity and total protease activity. So it is suggested that periplocoside X induced mainly to organic damage of midgut epithelium cells of insect. In all, insect midgut is one of targets for periplocoside X.


Incidence and seasonality of major ocular trauma: a nationwide population-based study.
We designed this study to identify the epidemiological characteristics and trends of various types of ocular trauma in the population of the Republic of Korea. We conducted a nationwide, population-based, cross-sectional study using the Korean National Health Insurance claims database for January 2010 to December 2018. We compiled the monthly numbers of patients diagnosed with hyphema and those who received open reduction surgery due to orbital blowout fracture (BOF), primary closure of the cornea or sclera (PCCS), or intraocular foreign body (IOFB) removal. We obtained annual and monthly incidence rates, and differences according to age, sex, yearly trends, and seasonal variations. The incidence rate (per 100,000 person-years) was high in the order of hyphema (18.43), BOF (11.58), PCCS (1.99) and IOFB removal (0.39). Male predominance was evident in all types of major ocular trauma, but the age distribution varied with the type: hyphemas were most prevalent at 10-14 years of age, BOFs at 25-29 years of age, and open globe injuries (OGIs) at age 60 and older. Although all types of trauma showed significant seasonality, hyphemas (amplitude: 174.81) and BOFs (23.17) showed higher amplitudes compared to OGIs (PCCS: 11.96; IOFB removal: 6.72). While the incidence of blunt trauma injuries, including hyphemas and orbital BOFs, decreased steadily from 2010 to 2018, that of OGIs showed no remarkable change.


Hippocampal signaling cascades are modulated in voluntary and treadmill exercise rats.
Systematic protein expression studies in the brain of exercising and sedentary animals have not been carried out for far. Signaling proteins are main structures regulating hippocampal function and we decided to determine differences in signaling protein levels in rat hippocampus by a proteomic approach. Aged, male Sprague-Dawley rats, 23 months old, were used for the study: the first group consisted of sedentary rats, the second of rats with voluntary exercise from 5 to 23 months and the third was performing involuntary exercise on a treadmill from 5 to 23 months. 2-DE with subsequent mass spectrometrical identification of spots followed by quantification of spots was carried out. Annexin A5, A3, phosphatidylethanolamine-binding protein, guanine nucleotide-binding protein G(I)/G(S)/G(T), 14-3-3 protein gamma, 14-3-3 protein zeta/delta, prohibitin, visinin-like 1, protein phosphatase 1, septin 8, phosphoprotein enriched in astrocytes 15, transcription factor Pur-beta, EEA1 protein, SH3 domain-binding glutamic acid-rich-like protein 2, and cell division cycle 42 showed differential protein levels in the three groups. These results form the basis for functional studies elucidating mechanisms and links between exercise and hippocampal signaling and function.


Prostate tumor cell plasticity: a consequence of the microenvironment.
During each step of prostate cancer metastasis, cancer displays phenotypic plasticity that is associated with the expression of both epithelial and mesenchymal properties or an epithelial to mesenchymal transition. This phenotypic transition is typically in response to microenvironment signals and is the basis for basic cancer cell survival (e.g. motility and invasion versus proliferation). In this review we discuss the loss and gain of E-cadherin expression as a marker of tumor plasticity throughout the steps of metastasis, and particularly focus on dynamic tumor-stromal interaction that induce a cancer cell-associated mesenchymal to epithelial reverting transition in the bone and liver microenvironments.


Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons.
During development, chromatin-modifying enzymes regulate both the timely establishment of cell-type-specific gene programs and the coordinated repression of alternative cell fates. To dissect the role of one such enzyme, the intellectual-disability-linked lysine demethylase 5C (Kdm5c), in the developing and adult brain, we conducted parallel behavioral, transcriptomic, and epigenomic studies in Kdm5c-null and forebrain-restricted inducible knockout mice. Together, genomic analyses and functional assays demonstrate that Kdm5c plays a critical role as a repressor responsible for the developmental silencing of germline genes during cellular differentiation and in fine-tuning activity-regulated enhancers during neuronal maturation. Although the importance of these functions declines after birth, Kdm5c retains an important genome surveillance role preventing the incorrect activation of non-neuronal and cryptic promoters in adult neurons.


Crystal structure of a substrate-engaged SecY protein-translocation channel.
Hydrophobic signal sequences target secretory polypeptides to a protein-conducting channel formed by a heterotrimeric membrane protein complex, the prokaryotic SecY or eukaryotic Sec61 complex. How signal sequences are recognized is poorly understood, particularly because they are diverse in sequence and length. Structures of the inactive channel show that the largest subunit, SecY or Sec61α, consists of two halves that form an hourglass-shaped pore with a constriction in the middle of the membrane and a lateral gate that faces lipid. The cytoplasmic funnel is empty, while the extracellular funnel is filled with a plug domain. In bacteria, the SecY channel associates with the translating ribosome in co-translational translocation, and with the SecA ATPase in post-translational translocation. How a translocating polypeptide inserts into the channel is uncertain, as cryo-electron microscopy structures of the active channel have a relatively low resolution (~10 Å) or are of insufficient quality. Here we report a crystal structure of the active channel, assembled from SecY complex, the SecA ATPase, and a segment of a secretory protein fused into SecA. The translocating protein segment inserts into the channel as a loop, displacing the plug domain. The hydrophobic core of the signal sequence forms a helix that sits in a groove outside the lateral gate, while the following polypeptide segment intercalates into the gate. The carboxy (C)-terminal section of the polypeptide loop is located in the channel, surrounded by residues of the pore ring. Thus, during translocation, the hydrophobic segments of signal sequences, and probably bilayer-spanning domains of nascent membrane proteins, exit the lateral gate and dock at a specific site that faces the lipid phase.


The effect of dietary intake of the acidic protein fraction of bovine colostrum on influenza A (H1N1) virus infection.
Acidic protein levels in the milk decrease markedly as lactation progresses, suggesting that it is an important part of the colostrum. However, little attention has been paid to their biological function. In this study, we isolated the acidic protein fraction of bovine colostrum (AFC, isoelectric point <5) by anion-exchange chromatography, and investigated the effect of its dietary intake on influenza A (H1N1) virus infection. 100% of mice infected with 1 LD50 of the virus survived when administered AFC for 14 days prior to infection, compared with 33% survival when administered phosphate buffered saline (PBS). Moreover, consumption of AFC reduced the weight loss associated with infection. We propose that dietary intake of AFC has a prophylactic effect on influenza A virus infection.


[Somatostatin receptor subtype 2 mRNA expression in human gastric immortalized cell line and tumor cell lines].
Inhibition of somatostatin on cell proliferation via somatostatin receptor subtype 2 (SS-R2), suggested this receptor subtype may be involved in tumor growth. Present study is to demonstrate whether SS-R2 was expressed in tumor cell lines extensively as well as in human gastric epithelia immortalized cell line. Meanwhile, the effect of p53 mutation on SS-R2 expression in gastric cancer cell line was also elucidated. Full-length human somatostatin receptor subtype 2 cDNA was cloned by RT-PCR. Using cDNA as the probe and RT-PCR, expression of mRNA for SS-R2 in 9 cancer cell lines and human gastric immortalized cell line was detected. Data revealed that most cancer cell lines but a pancreatic cancer cell line expressed SS-R2 mRNA. Regardless whether p53 mutation or not in human gastric cancer cell lines, SS-R2 mRNA was transcribed.


Quantitative structure-activity relationships for reactivities of sulfate and hydroxyl radicals with aromatic contaminants through single-electron transfer pathway.
Sulfate radical anion (SO4•-) and hydroxyl radical (OH) based advanced oxidation technologies has been extensively used for removal of aromatic contaminants (ACs) in waters. In this study, we investigated the Gibbs free energy (ΔGSET∘) of the single electron transfer (SET) reactions for 76 ACs with SO4•- and OH, respectively. The result reveals that SO4•- possesses greater propensity to react with ACs through the SET channel than OH. We hypothesized that the electron distribution within the molecule plays an essential role in determining the ΔGSET∘ and subsequent SET reactions. To test the hypothesis, a quantitative structure-activity relationship (QSAR) model was developed for predicting ΔGSET∘ using the highest occupied molecular orbital energies (EHOMO), a measure of electron distribution and donating ability. The standardized QSAR models are reported to be ΔG°SET=-0.97×EHOMO - 181 and ΔG°SET=-0.97×EHOMO - 164 for SO4•- and OH, respectively. The models were internally and externally validated to ensure robustness and predictability, and the application domain and limitations were discussed. The single-descriptor based models account for 95% of the variability for SO4•- and OH. These results provide the mechanistic insight into the SET reaction pathway of radical and non-radical bimolecular reactions, and have important applications for radical based oxidation technologies to remove target ACs in different waters.


Bilateral lung transplant with pulmonary artery reconstruction using donor aorta for pulmonary hypertension with a giant pulmonary arterial aneurysm.
Standard bilateral lung transplantation (BLT) is not feasible for patients with pulmonary arterial hypertension (PAH) complicated with a giant pulmonary arterial aneurysm (PAA). This study aimed to describe the outcomes of BLT with pulmonary artery reconstruction (PAR) using donor aorta for such patients. This is a retrospective single-centre study reviewing PAH patients with a PAA who received BLT with PAR using donor aorta from January 2010 through December 2020. We compared the characteristics and short- and long-term outcomes of recipients receiving PAR (PAR group) with those who had no PAA and received standard BLT (non-PAR group). Nineteen adult PAH patients underwent cadaveric lung transplantation during the study period. Among them, 5 patients with a giant PAA (median pulmonary artery trunk diameter, 69.9 mm) underwent BLT with PAR using donor aorta and the others received standard BLT. Although the operation time tended to be longer in the PAR group compared with the non-PAR group (1239 vs 958 mins, P = 0.087), 90-day mortality (PAR group: 0% vs non-PAR group: 14.3%, P > 0.99), and 5-year survival rate (PAR group: 100% vs non-PAR group: 85.7%, P = 0.74) was comparable between the groups. No dilatation, constriction or infection of the aortic grafts were recorded during the study period with a median follow-up time of 94 months in the PAR group. Lung transplantation with PAR using donor aorta is a valid surgical option for PAH patients complicated with a giant PAA.


Complications associated with the use of gastrointestinal stapling devices.
Complications arising in the intraoperative and postoperative period were assessed over a 2-year period in 132 patients in whom gastroinestinal operations had been performed using the TA-type or GIA-type stapling devices. Specific complications are described and their relationship to the staple-suture technique is evaluated. Bleeding from the anastomotic line is believed to be a complication directly attributable to the technique. Technical errors in the use of the device, as well as mechanical malfunction, can contribute to morbidity or mortality. Methods for avoding staple-related complications are suggested. The history of stapling instruments is reviewed briefly.


Omental fibroma: CT and US findings.
The US, CT, and X-ray findings in a patient with omental fibroma of the lesser omentum are described. Ultrasound showed a solid mass with cystic areas in the central region. At CT the lesion showed peripheral enhancement and central hypodensity. On X-ray studies with barium, there was border distortion in the lesser curvature of the stomach. The mass was resected surgically. A pathologic diagnosis of fibroma was confirmed.


English fluency of the US immigrants: Assimilation effects, cohort variations, and periodical changes.
Using 1% Public-Use Microdata Samples (PUMSs) of the 1980, 1990, and 2000 census and the 2010 American Community Survey (ACS), this study evaluates three simultaneous longitudinal trends in immigrants' English fluency: the assimilation process, variations across arrival cohorts, and periodical changes. The key findings include that the declining initial English fluency among new immigrants reported in a previous study based on 1980 and 1990 data (Carliner, 2000) was reversed in the 1990s and 2000s. Immigrants who arrived during the 2000s have the highest level of English fluency at the year of entry among all cohorts. Immigrants are assimilating. However, changes in social and linguistic environment in the US during the past two decades have suppressed the advancement of immigrants. The decline in the average English attainment from the 1980s to the 1990s reported in a previous study (Pitkin and Myers, 2011) was found to extend to the 2000s. Using new census data, this study updated the current knowledge on immigrants' English fluency by revealing a never documented upward trend among recent immigrants and suppressive period effects from 1990 to 2010.


Studies on the antibody response of mice and humans after immunization with potential influenza virus A (H1N1) vaccines.
The antibody response of mice and adult humans to immunization with subunit vaccines derived from a pair of antigenically distinct influenza A H1N1 viruses isolated in eggs was investigated. Although the haemagglutinin molecule of each virus differed by only three amino acid residues, highly specific antibody responses were elicited in mice as determined by haemagglutination inhibition and radioimmunoprecipitation assays. Results from competitive radioimmunoassays using monoclonal antibodies of known specificity and a study of the reactivity of mouse antisera with H1N1 field strains indicated that the marked differences in the antibody responses to the two vaccines was due to an amino acid substitution in the distal tip of the haemagglutinin molecule. In contrast, crossreactive antibody responses were elicited in humans presumably due to exposure to viruses related to the candidate vaccine prior to vaccination. Although immunogenic differences are apparent in this pair of antigenically distinct viruses in naive laboratory animals, these differences are not apparent following vaccination of humans that had prior exposure to related viruses.


How to manage the left subclavian artery during endovascular stenting of the thoracic aorta.
We performed a systematic review of the literature to establish whether revascularisation of the left subclavian territory is necessary when this artery is covered by a stent. We retrieved data from 99 studies incorporating 4906 patients. Incidences of left-arm ischaemia (0.0% vs 9.2%, p=0.002) and stroke (4.7% vs 7.2%, p<0.001) were significantly less following revascularisation, although mortality (10.5% vs 3.4%, p=0.032) and endoleak incidence (25.8% vs 12.6%, p=0.008) were increased. No significant differences in spinal-cord ischaemia were seen. Revascularisation may reduce downstream ischaemic complications but can cause significant risk. Indications must be carefully considered on an individual patient basis.


Adherence to surveillance colonoscopy guidelines in patients following curative-intent colorectal cancer resection.
Current guidelines recommend that patients who have undergone curative-intent resection for colorectal cancer (CRC) should undergo colonoscopy one year following their surgery or at six months post-operatively if a pre-operative colonoscopy was not performed due to an obstructing lesion. We sought to determine adherence to postoperative surveillance colonoscopy guidelines in our National Cancer Institute designated comprehensive cancer center and potentially identify factors associated with non-adherence. A retrospective review of 100 patients who underwent curative-intent CRC resection was performed between 2013 and 2019. Patients were divided into two groups based upon adherence to surveillance colonoscopy guidelines. Demographic, tumor, and postoperative variables were analyzed. The median age of all patients was 62. Fifty-seven percent of patients were male. Thirty-eight patients underwent surveillance colonoscopy in accordance with current guidelines. Sixty-two patients did not undergo surveillance colonoscopy postoperatively or did so outside of the National Comprehensive Cancer Network guidelines. Factors associated with non-adherence to surveillance colonoscopy included presence of comorbidities, albumin less than 3.5, and performance of a pre-operative colonoscopy. Adherence to surveillance colonoscopy guidelines was low among our patients. Efforts should be directed toward patients at increased risk for non-adherence to surveillance colonoscopy guidelines.


General entry to aspidosperma alkaloids: enantioselective total synthesis of (-)-aspidophytine.
A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a C-H bond activation with a Heck-type coupling, and the stereo-controlled formation of piperidine and pyrrolidine rings as key steps. The feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4-disubstituted cyclohexanedione and 2,3-dimethoxyaniline.


Developmentally regulated expression of VGLUT3 during early post-natal life.
Three subtypes of vesicular glutamate transporters, named VGLUT1-3, accumulate glutamate into synaptic vesicles. In this study, the post-natal expression of VGLUT3 was determined with specific probes and antiserums in the rat brain and compared with that of VGLUT1 and VGLUT2. The expression of VGLUT1 and VGLUT2 increases linearly during post-natal development. In contrast, VGLUT3 developmental pattern appears to have a more or less biphasic profile. A first peak of expression is centered around post-natal day 10 (P10) while the second one is reached in the adult brain. Between P1 and P15, VGLUT3 is observed in the frontal brain (striatum, accumbens, and hippocampus) and in the caudal brain (colliculi, pons and cerebellum). During a second phase extending from P15 to adulthood, the labeling of the caudal brain fades away. The adult pattern is reached at P21. We further analyzed the transient expression of VGLUT3 in the cerebellum and found it to correspond to a temporary expression in Purkinje cells. At P10 VGLUT3 immunoreactivity was present both in the soma and terminals of Purkinje cells (PC), where it colocalized with the vesicular inhibitory amino acid transporter (VIAAT). In agreement with data from the literature [Gillespie, D.C., Kim, G., Kandler, K., 2005. Inhibitory synapses in the developing auditory system are glutamatergic. Nat. Neurosci. 8, 332-338], our results suggest that during the first 2 weeks of post-natal life PC may have the potential to transiently release simultaneously GABA and glutamate.


Effectiveness of electrical stimulation on rehabilitation after ligament and meniscal injuries: a systematic review.
Electrical stimulation (ES) is widely used to strengthen muscles following ligament and meniscal injuries. The aim of this study was to evaluate the effectiveness of ES for rehabilitation after soft tissue injuries of the knee treated surgically or conservatively. Systematic review at the Brazilian Cochrane Center. We searched the Cochrane Central Register of Controlled Trials (2010, Issue 12), Medline (Medical Analysis and Retrieval System Online) via PubMed (1966 to December 2010), Embase (Excerpta Medica database, 1980 to December 2010), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde, 1982 to December 2010), and PEDro (Physiotherapy Evidence Database, 1929 to December 2010). The studies included were randomized controlled trials using ES to increase muscle strength for rehabilitation of patients with soft tissue injuries of the knee. Two authors independently evaluated studies for inclusion and performed data extraction and methodological quality assessment. Seventeen studies evaluating ES after anterior cruciate ligament reconstruction and two studies evaluating ES after meniscectomy were included. There was a statistically significant improvement in quadriceps strength through ES (mean difference, MD: -32.7; 95% confidence interval, CI: -39.92 to -25.48; n = 56) and in functional outcomes (MD -7; -12.78 to -1.22; n = 43) six to eight weeks after surgical reconstruction of the anterior cruciate ligament. There is evidence that ES coupled with conventional rehabilitation exercises may be effective in improving muscle strength and function two months after surgery.


Physical-chemical properties and evaluative fate modelling of 'emerging' and 'novel' brominated and organophosphorus flame retardants in the indoor and outdoor environment.
Several groups of flame retardants (FRs) have entered the market in recent years as replacements for polybrominated diphenyl ethers (PBDEs), but little is known about their physical-chemical properties or their environmental transport and fate. Here we make best estimates of the physical-chemical properties and undertake evaluative modelling assessments (indoors and outdoors) for 35 so-called 'novel' and 'emerging' brominated flame retardants (BFRs) and 22 organophosphorus flame retardants (OPFRs). A QSPR (Quantitative Structure-Property Relationship) based technique is used to reduce uncertainty in physical-chemical properties and to aid property selection for modelling, but it is evident that more, high quality property data are required for improving future assessments. Evaluative modelling results show that many of the alternative FRs, mainly alternative BFRs and some of the halogenated OPFRs, behave similarly to the PBDEs both indoors and outdoors. These alternative FRs exhibit high overall persistence (Pov), long-range transport potential (LRTP) and POP-like behaviour and on that basis cannot be regarded as suitable replacements to PBDEs. A group of low molecular weight alternative BFRs and non-halogenated OPFRs show a potentially better environmental performance based on Pov and LRTP metrics. Results must be interpreted with caution though since there are significant uncertainties and limited data to allow for thorough model evaluation. Additional environmental parameters such as toxicity and bioaccumulative potential as well as functionality issues should be considered in an industrial substitution strategy.


Ubiquitous formation of catalase compound II in hemoglobin-free perfused rat liver and detection of novel spectral species.
Spectral examinations of hemoglobin-free perfused rat livers with a high-sensitivity reflectance spectrophotometer have revealed an accumulation of catalase Compound II to an amount comparable to that of Compound I under the aerobic steady state. This finding is in contrast to a recent proposal that NADPH associated with catalase both prevents and reverses the accumulation of Compound II (Kirkman, H. N., Galiano, S., and Gaetani, G.F. (1987) J. Biol. Chem. 262, 660-666). Furthermore, spectral species with a broad peak extending from 550 to 600 nm were observed in a time range between the methanol-induced decays of Compound I and Compound II. When rats were treated with 3-amino-1,2,4-triazole, catalase Compound I was not detected but spectral species with peaks at 570, 556 and 530 nm were observed. These novel spectral profiles suggest contributions from "peroxy" and "ferryl" forms of cytochrome oxidase.


[Perioperative pharmacological circulatory support in daily clinical routine].
Perioperative phases of hypotension are associated with an increase in postoperative complications and organ damage. Whereas some years ago hemodynamic stabilization was primarily carried out by volume supplementation, in recent years the use and dosing of cardiovascular-active substances has significantly increased. But like intravascular volume therapy, also substances with a cardiovascular effect have therapeutic margins, and thus, potential side effects. This review article discusses indications for each cardiovascular-active agent, weighing up advantages and disadvantages. Special attention is paid to the question how to administrate them: central venous catheter vs. peripheral indwelling venous cannula. The authors come to the conclusion that it is not a question of whether it is principally allowed to apply cardiovascular-active drugs via peripheral veins but more importantly, what should be taken into consideration if a peripheral venous access is used. This article provides concise recommendations.


[Suspension diverticulopexy for Zenker's diverticulum].
Zenker's diverticulum is an unusual condition. Its treatment requires surgery but there is no consensus regarding the various operative techniques. Through an open cervical approach, the diverticulum can be either resected or suspended with or without a concurrent myotomy of the cricopharyngeus muscle. An innovative option is endoscopic trans-oral stapled esophago-diverticulostomy. and method: We retrospectively reviewed a consecutive series of 36 patients operated on between 1988 and 2006. Median age was 77.5 years and M/F sex ratio was 1.4. Through an open neck approach, diverticulectomy without cricopharyngeal myotomy was performed in 7 patients, diverticulectomy with myotomy in 11, and diverticulopexy with myotomy in 18. Morbidity rate was 13.8%. One fistula and one recurrence occurred in both diverticulectomy groups with and without myotomy. There was no morbidity after suspension diverticulopexy which also allowed earlier oral feeding (1 vs. 6 days) and shortened hospitalization (6 vs. 13.5 days). Diverticulopexy with cricopharyngeus myotomy is an effective, reliable, and reproducible technique for the correction of Zenker's diverticula smaller than 5 cm. Diverticulectomy should be reserved for larger diverticula. Technical improvements of transoral stapled diverticulostomy are still required before it can be promoted as an alternative therapy.


Consensus statement on insulin therapy in chronic kidney disease.
Diabetes mellitus (DM) is one of the leading causes of chronic kidney disease (CKD) which eventually leads to insulin resistance and decreased insulin degradation. In patients with diabetic kidney disease (DKD), the overall insulin requirement declines which necessitates the reassessment for individualization, adjustment and titration of insulin doses depending on the severity of kidney disease. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens in patients with DKD. Each insulin regimen (basal, prandial, premix and basal-bolus) was presented and evaluated for dosing and titration based on data from approved medical literatures on chronic kidney disease. These evaluations were then factored into the national context based on the expert committee representatives' and key opinion leaders' clinical experience and common therapeutic practices followed in India. Recommendations based on dosing and titration of insulins has been developed. Moreover, the consensus group also recommended the strategy for dose estimation of insulin, optimal glycaemic targets and self-monitoring in patients with DKD. The consensus based recommendations will be a useful reference tool for health care practitioners to initiate, optimise and intensify insulin therapy in patients with DKD.


Analysis of the psychometric properties of the American Orthopaedic Foot and Ankle Society Score (AOFAS) in rheumatoid arthritis patients: application of the Rasch model.
To tested the reliability and validity of Aofas in a sample of rheumatoid arthritis patients. The scale was applicable to rheumatoid arthritis patients, twice by the interviewer 1 and once by the interviewer 2. The Aofas was subjected to test-retest reliability analysis (with 20 Rheumatoid arthritis subjects). The psychometric properties were investigated using Rasch analysis on 33 Rheumatoid arthritis patients. Intra-Class Correlation Coefficient (ICC) were (0.90<ICC<0.95; p<0.001) for intra-observer reliability and (0.75<ICC<0.91; p<0.001) for inter-observer reliability. Subjects separation rates were 1.9 and 4.75 for the items, showing that patients fell into three ability levels, and the items were divided into six difficulties levels. The Rasch analysis showed that eight items was satisfactory. One erroneous item have been identified, showing percentages above the 5% allowed by the statistical model. Further Rasch modeling suggested revising the original item 8. The results suggest that the Brazilian versions of Aofas exhibit adequate reliability, construct validity, response stability. These findings indicate that Aofas Ankle-Hindfoot scale presents a significant potential for clinical applicability in individuals with rheumatoid arthritis. Other studies in populations with other characteristics are now underway.


TF-CBT Training Augmented with a Self-Care Focus: Understanding Facilitators and Barriers to Treatment Implementation.
Clinicians working with youth exposed to trauma may be at increased risk for experiencing elevated levels of stress and symptoms of secondary traumatic stress, which can negatively impact clinician wellbeing and ultimately contribute to reduced access to quality care for clients. An innovative Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) training incorporating self-care practices (i.e., Practice What You Preach; PWYP) was developed to help facilitate the implementation of TF-CBT and to enhance clinicians' coping and decrease stress. The primary purpose of this study was to determine whether the PWYP-augmented training met three Objectives: (1) increase clinicians' feelings of TF-CBT competency; (2) improve clinicians' coping abilities/reduce clinicians' stress; and (3) increase clinicians' insight into the benefits and/or challenges clients may experience in treatment. An exploratory aim was also developed to identify additional facilitators and barriers of TF-CBT implementation. The written reflections of 86 community-based clinicians who participated in the PWYP-augmented TF-CBT training were examined using qualitative methods. The majority of clinicians indicated increased feelings of competency and improved coping abilities and/or stress levels; almost half mentioned increased insight into clients' experiences. The most frequently mentioned additional facilitators were related to elements of the TF-CBT treatment model. Anxiety/self-doubt was the barrier most frequently mentioned, though all clinicians who mentioned this barrier indicated it lessened or resolved over the course of the training. Incorporating self-care strategies into trainings may serve as a facilitator for TF-CBT implementation by enhancing the competency and well-being of clinicians. The additional insights into barriers and facilitators can be used to further improve the PWYP initiative and future training and implementation efforts.


Normalized Early Postoperative Cortisol and ACTH Values Predict Nonremission After Surgery for Cushing Disease.
Perioperative increases in adrenocorticotropic hormone (ACTH) and cortisol mimic results of corticotropin-releasing hormone (CRH) stimulation testing. This phenomenon may help identify patients with residual adenoma after transsphenoidal surgery (TSS) for Cushing disease (CD). To predict nonremission after TSS for CD. Retrospective case-control study of patients treated at a single center from December 2003 until July 2016. Early and medium-term remission were assessed at 10 days and 11 months. Two hundred and ninety-one consecutive TSS cases from 257 patients with biochemical evidence of CD seen at a clinical center. Normalized early postoperative values (NEPVs) for cortisol and ACTH were calculated as immediate postoperative cortisol or ACTH levels minus preoperative post-CRH-stimulation test levels. Prediction of early nonremission was evaluated using logistic regression. Prediction of medium-term remission was assessed using Cox regression. Predictive ability was quantified by area under the receiver operating characteristic curve (AUROC). NEPVs for cortisol and ACTH predicted early nonremission [adjusted odds ratio (OR): 1.1; 95% confidence interval (CI): 1.0, 1.1; P = 0.016 and adjusted OR: 1.0; 95% CI: 1.0, 1.0; P = 0.048, respectively]. AUROC for NEPV of cortisol was 0.78 (95% CI: 0.61, 0.95); for NEPV of ACTH, it was 0.80 (95% CI: 0.61, 0.98). NEPVs for cortisol and ACTH predicted medium-term nonremission [hazard ratio (HR): 1.1; 95% CI: 1.0, 1.1; P = 0.023 and HR: 1.0; 95% CI: 1.0, 1.0; P = 0.025, respectively]. NEPVs for cortisol and ACTH predicted nonremission after TSS for CD.


Prognostic Value of Metabolic, Volumetric and Textural Parameters of Baseline [18F]FDG PET/CT in Early Triple-Negative Breast Cancer.
(1) Background: triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge primarily affecting young women with poor prognosis. TNBC is currently treated as a single entity but presents a very diverse profile in terms of prognosis and response to treatment. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose ([18F]FDG) is gaining importance for the staging of breast cancers. TNBCs often show high [18F]FDG uptake and some studies have suggested a prognostic value for metabolic and volumetric parameters, but no study to our knowledge has examined textural features in TNBC. The objective of this study was to evaluate the association between metabolic, volumetric and textural parameters measured at the initial [18F]FDG PET/CT and disease-free survival (DFS) and overall survival (OS) in patients with nonmetastatic TBNC. (2) Methods: all consecutive nonmetastatic TNBC patients who underwent a [18F]FDG PET/CT examination upon diagnosis between 2012 and 2018 were retrospectively included. The metabolic and volumetric parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG) and the textural features (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) of the primary tumor were collected. (3) Results: 111 patients were enrolled (median follow-up: 53.6 months). In the univariate analysis, high TLG, MTV and entropy values of the primary tumor were associated with lower DFS (p = 0.008, p = 0.006 and p = 0.025, respectively) and lower OS (p = 0.002, p = 0.001 and p = 0.046, respectively). The discriminating thresholds for two-year DFS were calculated as 7.5 for MTV, 55.8 for TLG and 2.6 for entropy. The discriminating thresholds for two-year OS were calculated as 9.3 for MTV, 57.4 for TLG and 2.67 for entropy. In the multivariate analysis, lymph node involvement in PET/CT was associated with lower DFS (p = 0.036), and the high MTV of the primary tumor was correlated with lower OS (p = 0.014). (4) Conclusions: textural features associated with metabolic and volumetric parameters of baseline [18F]FDG PET/CT have a prognostic value for identifying high-relapse-risk groups in early TNBC patients.


SLAMF1/CD150 expression and topology in prostate and breast cancer cell lines.
SLAMF1/CD150 receptor is aberrantly expressed in malignant hematopoietic cells compared to ubiquitous expression in their normal analogues. However, the data about CD150 expression and function outside the hematopoietic system are limited. The aim of this pilot study was to examine the profile of mRNA expression of CD150 isoforms and the protein topology in highly and low malignant breast (BC) and prostate cancer (PC) cell lines. The study was performed on BC T47D, MDA-MB-231, ВСС/Р and BC/ML cell lines and PC LNCap, Du-145 and PC-3 cell lines. The quantitative polymerase chain reaction was applied for study of CD150 isoforms mRNA expression and flow cytometry was used for determination of protein localization. Analyzed BC cell lines did not express CD150 on the cell surface membrane (csCD150-), but more than 45% of cells were positive for CD150 cytoplasmic reaction (cyCD150+). The cyCD150 expression level in T47D cells of luminal BC subtype was higher than in basal BC cell lines MDA-MB-231, ВСС/Р and BC/ML. The PC cell lines expressed CD150 both on the cell surface and in cytoplasm. The highest number of csCD150+ and cyCD150+ cells was revealed in less aggressive androgen responsive, non-metastatic LNCap cell line. All studied BC and PC cell lines expressed mRNA of canonical transmembrane mCD150 and novel nCD150 isoforms but with different pattern of prevalence. Soluble CD150 isoform was revealed at the low level only in BCC/P BC cell line and LNCap, PC-3 PC cell lines. We have shown that BC and PC cell lines differentially expressed multifunctional receptor CD150 at the mRNA and protein levels that may indicate its association with the degree of their malignancy.


Clinical markers combined with HMGB1 polymorphisms to predict efficacy of conventional DMARDs in rheumatoid arthritis patients.
The efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for rheumatoid arthritis (RA) patients was limited. However, there were no predictive markers for poor csDMARDs outcome. Clinical information of RA patients was collected and the high-mobility group box 1 (HMGB1) polymorphisms (rs4145277, rs2249825, rs1412125 and rs1045411) were examined. Among the 252 patients, 31.0% had no response of csDMARDs. Anti-citrullinated protein antibody (ACPA)-positive, C-reactive protein (CRP) and Disease Activity Score (DAS) 28- erythrocyte sedimentation rate (ESR) were the associated factors, which (DAC:DAS 28 > 4.7 and ACPA-positive and CRP > 7.1 mg/L) was used to predict poor csDMARDs outcome, the sensitivity and specificity was 87.2% and 60.9%, respectively. Among those DAC patients, the refractory RA rate in the rs2249825 GG genotype patients was 83.3%, the specificity was 98.5%. The clinical markers (DAC) and rs2249825 GG genotype can be used to predict poor csDMARDs outcome.


Colocalization of C4d deposits/CD68+ macrophages in rheumatoid nodule and granuloma annulare: immunohistochemical evidence of a complement-mediated mechanism in fibrinoid necrosis.
Rheumatoid nodule (RN) represents a palisading granuloma with central fibrinoid necrosis, which is not only a classical manifestation of rheumatoid arthritis (RA) and part of the American College of Rheumatology (ACR)-criteria, but also is its diagnostic hallmark. The pathogenesis of RN is still not fully understood. At present, only data on serum analyses indicating a complement-mediated pathogenesis in the development of RA are available. Equivalent examinations for RN have not yet been performed. Granuloma annulare (GA) represents another type of palisading granuloma. A special subtype of GA, subcutaneous GA (SGA), is an important differential diagnosis to RN. Therefore, our aim was to examine RN and SGA regarding the complement deposition (C4d) by immunohistochemical means. All RN and GA were stained by hematoxylin/eosin and different special stains. In addition, all specimens were stained immunohistochemically with antibodies against CD68. Five GA and five RN were analyzed immunohistochemically with antibodies against C4d and CD68, and evaluated using single- and doublestaining immunohistochemistry. All RN and GA displayed depositions of C4d within their central necroses and between the surrounding palisading macrophages. Most importantly, C4d/CD68 double staining was visible in the palisading macrophages next to the necroses, while macrophages in the periphery were negative for C4d but positive for CD68. The main difference between RN and GA was a quantitative phenomenon with less positively reacting macrophages in a more incomplete palisade in GA. The positive reactions of all central necroses to C4d and colocalization of CD68 and C4d suggest that a complement-mediated mechanism may be operative in the formation of fibrinoid necrosis. This mechanism may be involved in any form of "fibrinoid necrosis", since no different patterns of C4d/CD68 expression could be observed in GA. This may explain why RG/GA are not distinguishable morphologically.


[EEG contribution to the diagnosis of baclofen overdose].
In a young woman presenting with severe coma, the EEG helped diagnosing baclofen overdose. In this patient, the first EEG showed continuous multifocal pseudoperiodic sharp waves. The diagnosis was confirmed by the plasma dosage providing an 8-fold increase above normal baclofen therapeutic range. Following symptomatic therapy, the patient improved within a few days and the EEG normalised. Few other drugs may be responsible for such EEG changes, namely lithium, cephalosporin, and bismuth. In such cases, EEG contribution to the diagnosis should not be ignored.


Erratum to: 2017 Colorado alphaherpesvirus latency society symposium.
On page 650, the institutional affiliation of Dr. Werner J.D. Ouwendijk was incorrectly listed as Freie Universitaet Berlin. It should instead be Erasmus MC, Rotterdam, The Netherlands.


Expression levels of genes involved in metal homeostasis, physiological adaptation, and growth characteristics of rice (Oryza sativa L.) genotypes under Fe and/or Al toxicity.
Acid sulphate soil contains high amounts of iron (Fe) and aluminum (Al), and their contamination has been reported as major problems, especially in rainfed and irrigated lowland paddy fields. Rice is sensitive to Fe and Al grown in acid soil (pH < 5.5), leading to growth inhibition and grain yield loss. The objective of this study was to evaluate Fe and/or Al uptake, translocation, physiological adaptation, metal toxicity, and growth inhibition in rice genotypes grown in acid soil. Fe and Al in the root tissues of all rice genotypes were enriched depending on the exogenous application of either Fe or Al in the soil solution, leading to root growth inhibition, especially in the KDML105 genotype. Expression level of OsYSL1 in KDML105 was increased in relation to metal uptake into root tissues, whereas OsVIT2 was downregulated, leading to Fe (50.3 mg g-1 DW or 13.1 folds over the control) and Al (4.8 mg g-1 DW or 2.2 folds over the control) translocation to leaf tissues. Consequently, leaf greenness (SPAD), net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (E) in the leaf tissues of genotype KDML105 under Fe + Al toxicity significantly declined by 28.4%, 35.3%, 55.6%, and 51.6% over the control, respectively. In Azucena (AZU; Fe/Al tolerant), there was a rapid uptake of Fe and Al by OsYSL1 expression in the root tissues, but a limited secretion into vacuole organelles by OsVIT2, leading to a maintenance of low level of toxicity driven by an enhanced accumulation of glutathione together with downregulation of OsGR expression level. In addition, Fe and Al restrictions in the root tissues of genotype RD35 were evident; therefore, crop stress index (CSI) of Fe + Al-treated plants was the maximum, leading to an inhibition of gs (53.6% over the control) and E (49.0% over the control). Consequently, free proline, total phenolic compounds, and ascorbic acid in the leaf tissues of rice under Fe + Al toxicity significantly increased by 3.2, 1.2, and 1.5 folds over the control, respectively, indicating their functions in non-enzymatic antioxidant defense. Moreover, physiological parameters including leaf temperature (Tleaf) increment, high level of CSI (>0.6), SPAD reduction, photon yield of PSII (ΦPSII) diminution, Pn, gs, and E inhibition in rice genotype IR64 (Fe/Al-sensitive) under Fe + Al treatment were clearly demonstrated as good indicators of metal-induced toxicity. Our results on Fe- and/or Al-tolerant screening to find out the candidate genotypes will contribute to present screening and breeding efforts, which in turn help increase rice production in the Fe/Al-contaminated acid soil under lowland conditions.


Hemicholinium-3 binding sites in rat brain: a quantitative autoradiographic study.
Quantitative in vitro autoradiography was used to study the distribution of [3H]hemicholinium-3 ([3H]HC-3) binding sites in the rat brain. Regional concentrations of HC-3 binding sites were corrected for regional tissue quenching of tritium in a number of brain structures. Specific binding of 10 nM [3H]HC-3 was highest in the interpeduncular nucleus, followed by the caudate-putamen, olfactory tubercle, amygdala, and the medial and lateral habenulae. There was a high positive correlation between regional HC-3 binding and choline acetyltransferase activity in rat brain; however, a novel pattern of the distribution of cholinergic terminals in the subnuclei of the interpeduncular nucleus was discovered. The apparent Kd in the 1-5 nM range and the pharmacological specificity of the HC-3 binding site agreed with data for choline uptake and for the HC-3 binding site as determined in membrane preparations. HC-3 autoradiography appears to be a useful anatomical marker for cholinergic terminals.


Oral etoposide is active against platinum-resistant epithelial ovarian cancer.
To determine whether etoposide (VP16) is more effective when administered on a chronic schedule, women with clinically defined platinum-resistant epithelial ovarian cancer (EOC) were studied. Thirty-one eligible women were treated with oral VP16. The first seven received a dose that varied depending on their body-surface area, but this proved too toxic, and so a fixed dose of 100 mg orally per day for 14 days every 3 weeks was used for the other subjects. The response rate was 26% (95% confidence interval [CI], 11% to 41%). The 28 women with cancer that had progressed while they were receiving a platinum analog had a response rate of 21% (95% CI, 6% to 36%). Response durations were short. When administered on this chronic schedule, VP16 has activity against platinum-resistant EOC.


Effectiveness of oral aciclovir in preventing maternal chickenpox: A comparison with VZIG.
Although often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. Until April 2022, the UK recommendations were that varicella immunoglobulin (VZIG) should be administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG was recommended if exposure occurred at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox. We identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes. 171/186 (91.9%) of these women received either VZIG or oral aciclovir. Of the 145 women who received VZIG, 53/145 (36.6%) went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p = 0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p = 0.75). These findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed to varicella as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG.


Genes involved in the regulation of vascular homeostasis determine renal survival rate in patients with chronic glomerulonephritis.
Chronic glomerulonephritis (CGN) is one of the most severe kidney diseases. Genes of vascular reactivity are thought to play an important role in development and progression of CGN. In this study, we analyzed association of genes of vascular homeostasis with hypertension and renal survival of CGN patients. The study sample included 238 patients with CGN and 304 healthy subjects of population control. Ten polymorphisms of ten genes of vascular homeostasis were genotyped through polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis and TaqMan assays. Association of the genotypes with renal survival was analyzed by the Kaplan-Meier estimator. Genotypes 311SC and 311SS of the PON2 gene, (-1166)AC and (-1166)CC of the AGTR1 gene, (+46)AA of the ADRB2 gene, and 198KK and 198KN of the EDN1 gene were associated with decreased rate of renal survival of the patients. Polymorphisms S311C PON2, (-1166)A/C AGTR1, (+46)G/A ADRB2, and K198N EDN1 were associated with the accelerated decline in kidney function in the CGN patients.


Radiologic techniques in the treatment of the critically ill trauma patient.
Discussed in this article are portable chest x-ray for imaging abnormalities in pulmonary aeration, pleural disease, and the position of life-support apparatus and abdominal computed tomography and ultrasonography.


Inaccurate protein synthesis in a mutant of Salmonella typhimurium defective in transfer RNA pseudouridylation.
Protein synthesis was studied comparatively in a wild-type strain of Salmonella typhimurium and in hisT mutant cells defective in the pseudouridylation of transfer RNA. From a quantitative point of view, no significant differences between the two types of strain was observed when measuring the rate of protein synthesis during either exponential growth or starvation for histidine. In contrast, the qualitative analysis of proteins by two-dimensional gel electrophoresis showed that histidine-starved hisT cells mistranslate the genetic program at a higher frequency than exponentially growing hisT cells or either starved or unstarved hisT+ cells.


Prolactin receptors: a comparison between chloramine-T and lactoperoxidase iodination.
The binding properties of chloramine-T iodinated oPRL (using a modified iodination procedure) to prolactin receptors of female rat liver membrane particles were compared with those of lactoperoxidase iodinated oPRL. The results indicated that both iodination methods provided 125I-oPRLs which were suitable for receptor binding studies. Our results suggested that chloramine-T 125I-oPRL was even better than lactoperoxidase 125I-oPRL in terms of lower nonspecific binding. The chloramine-T iodinated oPRL was used to study the prolactin receptors in rat ovaries and DMBA induced rat mammary tumors. The results showed that the amount of prolactin receptors in rat ovaries was related to the plasma level of prolactin as it had been reported in liver by other investigators. The study of prolactin receptors in rat mammary tumors indicated that the prolactin receptor content of hormone dependent mammary tumors was much higher than that of hormone independent mammary tumors.


Using palliative and end-of-life simulation to enhance pre-licensure nursing students' emotional intelligence, palliative care knowledge and reflective abilities: A single group, pretest-posttest study.
Nursing students have reported that they lack skills and knowledge in palliative and end-of-life care, and as a result, they faced numerous challenges caring for patients and families receiving palliative and end-of-life care during clinical attachments. To develop a palliative and end-of-life care simulation program and evaluate its effects on nursing students' emotional intelligence, palliative care knowledge and reflective abilities. A single group, pretest-posttest quasi-experimental study. A simulation center in a Singapore university. A convenience sample of 135 third-year undergraduate nursing students. Students attended a two-day simulation program consisting of four scenarios in total. Outcomes were measured before and after the study. Palliative care knowledge was measured using the Palliative Care Knowledge Test, emotional intelligence using the Trait Meta-Mood Scale-24, and reflective abilities using the Groningen Reflective Ability Scale. Outcome and demographic data were analyzed using descriptive and inferential statistics. Total Palliative Care Knowledge Test scores (p = 0.003) and total Trait Meta-Mood Scale-24 scores (p < 0.001) improved significantly, but there was no significant change in Groningen Reflective Ability Scale scores (p = 0.650). Demographic characteristics did not significantly influence most outcome variables. Students' highest education level and experience with caring for a person receiving palliative or end-of-life care significantly affected the posttest scores of the Palliative Care Knowledge Test. Students with prior experience in caring for a person receiving palliative or end-of-life care scored significantly better in the Palliative Care Knowledge Test post-simulation compared to those who did not (p = 0.011). The palliative and end-of-life simulation program significantly improved nursing students' emotional intelligence and palliative care knowledge. Further research is needed on developing a reliable tool to measure nursing students' palliative care knowledge. Future simulations should include structured and deliberate reflection features aside from debriefings to enhance reflective abilities, which is an important nursing competency. More research is needed on the effect of palliative and end-of-life care simulations on emotional intelligence and reflective abilities, and the influence of demographic variables on nursing students' outcomes.


Geniposide ameliorates atherosclerosis by regulating macrophage polarization via perivascular adipocyte-derived CXCL14.
Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis. To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage polarization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT). ApoE-/- mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays. The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE-/- mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geniposide increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells. In summary, our findings suggest that geniposide protects ApoE-/- mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment.


Masculinizing chest surgery for gender affirmation: A retrospective study of outcomes and patient reported satisfaction.
Masculinizing chest surgery is the most common gender-affirming surgery. The objective of our study is to report the surgical and patient reported outcomes of surgery performed by a breast surgery practice. Between June 1, 2017 and December 31, 2019, eighty-one patients underwent surgery at a university-affiliated hospital. This study included a retrospective chart review and an anonymous survey. Seventy-five (93%) patients underwent double incision technique. Complications occurred in 25% of patients and two patients required reoperation within 30 days of surgery. The anonymous survey response rate was 47% (34/72). Patients were asked to rate their satisfaction with the cosmetic appearance and the median score was 90. Quality of life and mental health improvement was reported by most patients. Median follow up was 9 months. Masculinizing chest surgery performed by surgeons trained in breast surgery had a low rate of surgical complications and positive patient reported outcomes.


cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole (BCHMX), its properties and initiation reactivity.
Using the (15)N NMR chemical shifts of nitrogen atoms in nitramino groups of cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole (bicyclo-HMX or BCHMX) and additional 10 nitramines, we have assessed its reactivity in detonation, under the influence of impact, and by action of electric spark. It is stated that the thermal stability of BCHMX is higher than that of 1,3,5-trinitro-1,3,5-triazinane (RDX). The longest NN bond in the BCHMX molecule (1.412(4)A) is the cause for its higher impact reactivity, which is at the level of that of penterythritol tetranitrate (PETN). In the experimentally determined detonation velocity, BCMX can be slightly better performing than RDX. From the standpoint of friction sensitivity, BCHMX is similar to 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). Attention was also focused on the solubility-temperature dependence of BCHMX in acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide, tetrahydrofurane, and nitromethane. X-ray crystallographic study of BCHMX (C(4)H(6)N(8)O(8), M(r)=294.17), has been carried out at the temperature of 150K with the following results: a=8.5430(8), b=6.9480(6), c=8.7780(8)A, alpha=90.0(7) degrees , beta=102.452(11) degrees , gamma=90.0(9) degrees , V=508.777(8)A(3), Z=2, D(x)=1.920 g cm(-3), lambda(Mo Ka)=0.71073A, micro=0.169 cm(-1), F(000)=856, final R=0.0414 for 1254 independent observed reflections. In the BCHMX crystal there were found more short contacts in the molecular crystal of BCHMX data of Gilardi creating extensive supramolecular architecture.


Aerial dispersal in relation to habitat in eight wolf spider species (Pardosa, Araneae, Lycosidae).
In the eight Pardosa species studied, aerial dispersal occurs generally in the young instars. The climatic conditions, particularly wind but also temperature and humidity, affect the occurrence of aerial dispersal. Within the different systematic groups in the genus, species with relatively high and relatively low dispersal capacities occur. These differences in dispersal capacity are discussed in relation with the abundance and stability of the habitat, in which the species are found.


Methadone associated long term hearing loss and nephrotoxicity; a case report and literature review.
Methadone is a long-acting opioid receptor agonist. Reported adverse effects of methadone include constipation, respiratory depression, dizziness, nausea, vomiting, itching, sweating, rhabdomyolysis, QT prolongation, and orthostatic hypotension. Hearing loss has been rarely reported following methadone use, and when reported, long term follow-up is rare. Herein we report a case of methadone poisoning with rhabdomyolysis, acute kidney injury, and persistent hearing loss documented by a 2 year follow up. The patient was a 34 years old male who presented with a reduced level of consciousness and acute hearing loss after suicidal ingestion of 40 mg of methadone while experiencing family-related stresses. He had no prior history of methadone use, abuse, or addiction. Initial laboratory testing was significant for a serum creatinine concentration of 4.1 mg/dl, a mixed metabolic and respiratory acidosis, thrombocytopenia, abnormal hepatic transaminases, and coagulation tests. The patient then developed severe rhabdomyolysis. Also, audiometry showed a bilateral sensorineural hearing loss. The patient required hemodialysis for 11 days while his metabolic abnormalities gradually resolved. However, his hearing loss was persistent, as demonstrated by 2 years of follow up. Our patient simultaneously had kidney failure, rhabdomyolysis, and permanent hearing loss following methadone poisoning. Although rare, ototoxicity and permanent hearing loss may happen in cases of methadone poisoning. While opioid-induced hearing loss is uncommon, methadone toxicity should be taken into account for any previously healthy patient presenting with acute hearing loss with or without rhabdomyolysis.


A Human Long Non-Coding RNA ALT1 Controls the Cell Cycle of Vascular Endothelial Cells Via ACE2 and Cyclin D1 Pathway.
ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2). To date, ALT1 biological roles in human vascular endothelial cells have not been reported. ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3' rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. ALT1 was expressed in human umbilical vein endothelial cells (HUVECs). The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2) was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL) might be involved. The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.


Omega-3 dietary Fatty Acid status of healthy older adults in Tasmania, Australia: an observational study.
To determine the dietary and supplement intake of omega-3 (n-3) polyunsaturated fatty acids (PUFA) of older Tasmanian adults; their plasma n-3 PUFA status and the relationship between n-3 PUFA intake and plasma status. Cross-sectional study. Launceston and surrounding regions, Tasmania, Australia. Seventy-three community-dwelling older adults: 23 men aged 70 ± 6.1 years and 50 women aged 70 ± 6.7 years. A validated, semi-quantitative food frequency questionnaire estimated dietary PUFA intake. The plasma phospholipid fraction of venous blood samples was analysed for fatty acid content. Anthropometric data was recorded. Thirty-five participants (48%) regularly ingested a fish oil supplement. Their plasma n-3 PUFA profile contained significantly more eicosapentaenoic acid (EPA) (odds ratio 3.14; 95% CI 1.37% to 7.30%; p<0.05) and docosahexaenoic acid (DHA) (odds ratio 2.64; 95% CI 1.16% to 6.01%; p<0.05) than non-supplement users. Fish and meat were the main dietary sources of n-3 PUFAs. Participants most commonly consumed fish 3-4 times per week. Significant associations of dietary α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA) and DHA with plasma n-3 PUFAs were noted but not always between dietary and plasma counterparts. Without the use of fish oil supplements, most study participants were unable to meet the recommended daily intake of 0.5g EPA and DHA combined; however, the plasma n-3 PUFA profile of non-supplement-users was still robust compared to other Australian and overseas studies.


Design constraints for the post-human future.
A variety of objections to human germ-line genetic engineering have been raised, such as the claim that we ought not to place individuals at significant risk without their consent. It has also been argued that it is paternalistically objectionable to confer significant benefits on individuals without their consent. As well as imposing risk of harm to non-consenting parties, there is the risk of harm to others. This paper evaluates these and related objections to germ-line genetic engineering. While a complete prohibition on human germ-line genetic engineering is rejected it is argued that acceptable germ-line engineering (a) should at least expand and enrich rather than restrict and constrain the choices for individuals affected, and (b) should not seek to change basic human dispositions and values ('human nature').


New morphological observations on the initial events of Toxoplasma gondii entry into host cells.
Toxoplasma gondii is an obligate intracellular protozoan of worldwide distribution. It is effective in the infection of various homoeothermic animals of economic importance. The process of T. gondii invasion of host cells occurs in less than 20 s by the active mechanism of penetration. First, a mobile junction is formed due to the association between the apical end of the parasite and the host cell surface. Then, the secretion of invasive and docking proteins allows the formation of the mobile junction before the complete internalization of the parasite. Here, using high-resolution microscopy, it was described new morphological observations of the early events of host cell invasion by tachyzoites of T. gondii. Attempts were made to synchronize the interaction process using low temperatures and treatment of the host cells with cytochalasin D, a drug that interferes with the actin dynamics. Images were obtained showing that the parasite and the host cells seem to release small vesicles with diameters varying from 25 to 100 nm. Furthermore, tunneling nanotubes emerge from the host cell surface and interact with the parasite even at long distance. These observations add new details of adhesion and entry events, such as surface projections of the host cell plasma membrane, pseudopods, and nanotubes radiating from the host cell toward the parasite. In addition, scanning microscopy revealed intense vesiculation, with a morphological characteristic of extracellular microvesicles, during the entry of the tachyzoite into the host cell.


Effect of problem-based, self-directed undergraduate education on life-long learning.
To compare how well graduates of a self-directed, problem-based undergraduate curriculum (at McMaster University [MU], Hamilton, Ont.) and those of a traditional curriculum (at the University of Toronto [UT]) who go on to primary care careers keep up to date with current clinical practice guidelines. Analytic survey. Management of hypertension was chosen as an appropriate topic to assess guideline adherence. An updated version of a previously validated questionnaire was mailed to the participants for self-completion. Private primary care practices in southern Ontario. A random sample of 48 MU graduates and 48 UT graduates, stratified for year of graduation (1974 to 1985) and sex, who were in family or general practice in Ontario; 87% of the eligible subjects in each group responded. Overall and component-specific scores; analysis was blind to study group. The overall mean scores were 56 (68%) of a possible 82 for the MU graduates and 51 (62%) for the UT graduates (difference between the means 5, 95% confidence interval 1.9 to 8.2; p < 0.01). Multivariate linear regression analysis of seven factors that might affect questionnaire scores revealed that only the medical school was statistically significant (p < 0.01). The MU graduates had significantly higher mean scores than the UT graduates for two components of the questionnaire: knowledge of recommended blood pressures for treatment (p < 0.05) and successful approaches to enhance compliance (p < 0.005). The trends were similar for the other components but but were not significant. The graduates of a problem-based, self-directed undergraduate curriculum are more up to date in knowledge of the management of hypertension than graduates of a traditional curriculum.


Lost and found dark matter in elliptical galaxies.
There is strong evidence that the mass of the Universe is dominated by dark matter, which exerts gravitational attraction but whose exact nature is unknown. In particular, all galaxies are believed to be embedded in massive haloes of dark matter. This view has recently been challenged by the observation of surprisingly low random stellar velocities in the outskirts of ordinary elliptical galaxies, which has been interpreted as indicating a lack of dark matter. Here we show that the low velocities are in fact compatible with galaxy formation in dark-matter haloes. Using numerical simulations of disk-galaxy mergers, we find that the stellar orbits in the outer regions of the resulting ellipticals are very elongated. These stars were torn by tidal forces from their original galaxies during the first close passage and put on outgoing trajectories. The elongated orbits, combined with the steeply falling density profile of the observed tracers, explain the observed low velocities even in the presence of large amounts of dark matter. Projection effects when viewing a triaxial elliptical can lead to even lower observed velocities along certain lines of sight.


Validating the Executive Personal Finance Scale with Financial Investments and Expectations in University Students.
The validity of the Executive Personal Finance Scale (EPFS) was tested in a sample of 93 undergraduate students (31 men, 62 women; M age = 20.5 years, SD = 1.3, range = 18-24). Scores on the Motivation drive, Organization, and Planning subscales of this scale were associated with having a savings account, owning bank CDs, and self-estimated knowledge about financial matters, while scores on the Impulse control and Motivational drive subscales were associated with expectations for a satisfactory retirement income. The results provide support for the validity of the EPFS.


Ion Mobility Separation of Peptide Isotopomers.
Differential or field asymmetric waveform ion mobility spectrometry (FAIMS) operating at high electric fields fully resolves isotopic isomers for a peptide with labeled residues. The naturally present isotopes, alone and together with targeted labels, also cause spectral shifts that approximately add for multiple heavy atoms. Separation qualitatively depends on the gas composition. These findings may enable novel strategies in proteomic and metabolomic analyses using stable isotope labeling.


Editorial Commentary: Planting a Tree to Create the Shade--Performing Quality Long-term Studies Requires Forethought.
Forecasting the future questions that need to be answered while collecting prospective data makes the design of long-term studies challenging. But, with the current focus in health care to report outcomes, more information will now be prospectively collected, likely providing the necessary data to more critically analyze our results with higher-level of evidence studies.


Nanoparticle's uptake and translocation mechanisms in plants via seed priming, foliar treatment, and root exposure: a review.
Nanotechnology is one of the promising techniques and shares wide ranges of applications almost in every field of life. Nanomaterials are getting continuous attractions due to specific physical and chemical properties and being applied as multifunctional material. The use of nanomaterials/nanoparticles in agriculture sector for crop improvement and protection against various environmental threats have attained greater significance. Size and nature of nanoparticles, mode of application, environmental conditions, rhizospheric and phyllospheric environment, and plant species are major factors that influence the action of nanoparticles. The mode or method of nanoparticle applications to plants is attaining greater attentions. Recently, different methods for nanoparticle applications (seed priming, foliar, and root application) are being used to improve crop growth. It is of quite worth that which method is suitable for nanoparticle application, and how nanoparticles can possibly translocate to various plant tissues from root to shoot or vice versa. These information's are poorly understood and need more investigations to explore the comprehensive mechanism by which nanoparticles make their possible entry through different plant organs and how they transport to regulate various physiological and molecular functions in plant cells. Therefore, this study comprehensively provides the knowledge of nanoparticles uptake via seed priming, foliar exposure, and root application, and their possible translocation mechanism within plants influenced by various factors that has not clearly presented. This study will provide new insights to find out an actual uptake and translocation mechanism of nanoparticles that may help researchers to develop nanoparticle-based new strategies for plants to cope with various environmental challenges. This study also focuses on different soil factors or above ground factors that are involved in nanoparticles uptake and translocation and ultimately their functioning in plants.


Simultaneous quantitation of zidovudine, efavirenz, lopinavir and ritonavir in human hair by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.
Nowadays, zidovudine, efavirenz, lopinavir and ritonavir are important components of the second-line antiretroviral therapeutic regimen of National Free Antiretroviral Treatment Program in China. The measurement of antiretroviral drugs in hair will facilitate for the evaluation of the long-term adherence to highly active antiretroviral therapy. Nevertheless, no study illustrated simultaneous quantitation of the four drugs in hair. The study intended to develop a simple, sensitive and selective method for simultaneous quantitation of the four drugs in hair. The detection employed high liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionization in positive mode. Hair samples were incubated in methanol at 40 °C for 16 h. The method showed the limit of detection at 18, 8, 5 and 6 pg/mg for zidovudine, efavirenz, lopinavir and ritonavir, respectively. The linear range (R2 > 0.99) was 36-5000 pg/mg for zidovudine, 16-5000 pg/mg for efavirenz, 10-50,000 pg/mg for lopinavir and 12-12,500 pg/mg for ritonavir. The intra-day and inter-day coefficients of variation were <15% and the recovery varied from 88.1 to 110.5%. The population analysis revealed that patients with high adherence showed significantly higher drug concentrations in hair than those with low adherence for both AZT and EFV (ps < 0.05). There was high association in drug contents in hair between AZT and EFV or LPV and RTV (ps < 0.05).


Collaboration between schools of social work and university medical centers.
Although the interface involving social work, medicine, and the other health professions occurs primarily in the day-to-day world of practice in hospitals and other health agencies, an equally important opportunity exists for interaction at the university level between schools of social work and schools for health professionals. This artice analyzes one school's effort to build effective interdisciplinary linkages.


Thrombophilia screening in young patients with cryptogenic stroke. Prevalence of gene polymorphisms compared to healthy blood donors and impact on secondary stroke prevention.
The clinical relevance of thrombophilia screening in stroke patients is still a matter of debate, and descriptions of larger patterns of genetic variability are rare. We assessed the frequency of hereditary hypercoagulability in young patients with cryptogenic stroke (n = 44) and in healthy blood donors (n = 282) without prior cardiovascular event. Furthermore, we focused on the impact of thrombophilia screening on secondary stroke prevention. Compared to the control group (19-67 years; median 38.5 years; 64% women), there was a lower prevalence of the FVII-R353Q mutation (p = 0.033) in stroke patients (17-52 years; median 36 years; 59.1% women). Of note, the FVII-R353Q mutation lowers FVII plasma levels, probably reducing the risk of cardiovascular events. The prevalence of the remaining 13 gene polymorphisms did not differ significantly. However, the prevalence of FV Leiden mutation tended to be higher among stroke patients. Overall, extended screening for inherited thrombophilia had an impact on medical stroke prevention in every sixth patient with cryptogenic stroke.