[Evolution of the blood products distribution in France - detailed analysis in a regional blood transfusion centre].
The present increase of blood products distribution raises some adaptation questions. To understand this evolution, it is necessary to assure patients needs satisfaction. The study focuses on years 1997 to 2007. All blood products and hospitals are taken into account. The possible impact of size and clinical specialties is analyzed for the main hospitals. The evolution varies according to blood product: continuous drop for autologous red cells and plasmas, drop and rise for homologous red cells and platelets with a turnaround in 2001-2002, reverse and more chaotic movement for homologous plasmas. These movements are the result of public hospitals, with an upsurge of the medium sized ones. Private hospitals go down for all blood products, with a concentration on the larger ones. Surgical hospitals fall from 3 to 4% for all blood products, while medical ones rise of 3% for homologous red cells, 27% for platelets and fall of 10% for homologous plasmas. Private mixed hospitals fall for all blood products, while public ones rise for homologous red cells and platelets. Evolution understanding of blood products distribution requires precisions about the kind of products and the hospitals status and specialties: medical, surgical, even obstetrical or urgency-related. The present trend is a rise for public hospitals and medical specialties, which are both the largest. Blood transfusion needs will thus go on rising in the years to come.


Investigating Determinants and Evaluating Deep Learning Training Approaches for Visual Acuity in Foveal Hypoplasia.
To describe the relationships between foveal structure and visual function in a cohort of individuals with foveal hypoplasia (FH) and to estimate FH grade and visual acuity using a deep learning classifier. Retrospective cohort study and experimental study. A total of 201 patients with FH were evaluated at the National Eye Institute from 2004 to 2018. Structural components of foveal OCT scans and corresponding clinical data were analyzed to assess their contributions to visual acuity. To automate FH scoring and visual acuity correlations, we evaluated the following 3 inputs for training a neural network predictor: (1) OCT scans, (2) OCT scans and metadata, and (3) real OCT scans and fake OCT scans created from a generative adversarial network. The relationships between visual acuity outcomes and determinants, such as foveal morphology, nystagmus, and refractive error. The mean subject age was 24.4 years (range, 1-73 years; standard deviation = 18.25 years) at the time of OCT imaging. The mean best-corrected visual acuity (n = 398 eyes) was equivalent to a logarithm of the minimal angle of resolution (LogMAR) value of 0.75 (Snellen 20/115). Spherical equivalent refractive error (SER) ranged from -20.25 diopters (D) to +13.63 D with a median of +0.50 D. The presence of nystagmus and a high-LogMAR value showed a statistically significant relationship (P < 0.0001). The participants whose SER values were farther from plano demonstrated higher LogMAR values (n = 382 eyes). The proportion of patients with nystagmus increased with a higher FH grade. Variability in SER with grade 4 (range, -20.25 D to +13.00 D) compared with grade 1 (range, -8.88 D to +8.50 D) was statistically significant (P < 0.0001). Our neural network predictors reliably estimated the FH grading and visual acuity (correlation to true value > 0.85 and > 0.70, respectively) for a test cohort of 37 individuals (98 OCT scans). Training the predictor on real OCT scans with metadata and fake OCT scans improved the accuracy over the model trained on real OCT scans alone. Nystagmus and foveal anatomy impact visual outcomes in patients with FH, and computational algorithms reliably estimate FH grading and visual acuity.


Epinephrine Use in Endoscopic Ear Surgery: Quantitative Safety Assessment.
The management of bleeding in exclusive endoscopic ear surgery (EES) is largely dependent on epinephrine use. However, to date its suitability and safety have not been assessed. The aim of the present study would be to assess the safety profile of topical application and/or local infiltrationof diluted epinephrine during EES regarding the intra- and postoperative periods. We hypothesize that epinephrine may be safely used during EES. Retrospective analysis of 90 EES cases performed at the University Hospital of Modena, Italy. Patient's charts and video recordings of the operations were assessed. Epinephrine was used in all cases for hemostatic purposes as following: (1) diluted epinephrine (1:200,000) injection: mean 1.2 mL (range: 0-3.5) corresponding to 0.006 mg (range 0-0.018), and (2) topical application (1:1,000) directly in the surgical field: mean 7 cottonoids (range: 0-18) corresponding to mean 0.56 mg (range: 0-1.44). No major cardiovascular adverse effects were assessed. Only 2 intraoperative hypertensive events were recorded. One sensorineural hearing loss was observed in a case of cholesteatoma involving the stapes; no facial palsy occurred during the study period. The combined use of local injection and topical epinephrine is a safe and effective strategy to control bleeding in exclusive EES, when used within the dilutions and quantities reported in this study.


Alzheimer's disease: immunoreactivity of neurofibrillary tangles with anti-neurofilament and anti-paired helical filament antibodies.
The origin of the paired helical filaments (PHF) that accumulate in human neurons during aging and in Alzheimer's disease and their relationship to normal neurofilaments remain unclear. The observation that a rabbit antiserum to highly enriched PHF fractions specifically labeled PHF in Alzheimer neurofibrillary tangles but showed no reaction with neurofilaments or other normal cytoskeletal proteins led us to compare this antiserum to two monoclonal antibodies, RT97 and BF10, previously found to cross-react with tangles and with the 210,000 and 155,000 mol. wt. neurofilament proteins, respectively. Both alpha-PHF serum and the neurofilament monoclonals strongly immunolabel almost all neurofibrillary tangles in Alzheimer cortical sections. Double-immunolabeling studies show that both reagents recognize the same tangles and usually show identical patterns of staining of intraneuronal fibrous material. Following prolonged extraction of cortex in sodium dodecyl sulfate, a step which removes normal neurofilaments but leaves PHF intact, almost all isolated tangles retain strong immunoreactivity with alpha-PHF serum at an intensity which is slightly reduced from that in cortical sections. In contrast, only a small number of isolated tangles are stained strongly by RT97 and BF10; most show much decreased or no reactivity with these monoclonal neurofilament antibodies. This differential immunoreactivity was confirmed by double-labeling studies. Tangles prepared under gentle extraction conditions show strong reactivity with alpha-PHF antibodies but again only a small number are strongly labeled by RT97 and BF10. We conclude that neurofibrillary tangles in Alzheimer's disease are heterogeneous as regards their filamentous content and contain both antigens cross-reacting with neurofilaments and antigens which are apparently unique to PHF and not shared with normal neurofilaments.


Heterogeneous susceptibility to metronidazole and clarithromycin of Helicobacter pylori isolates from a single biopsy in adults is confirmed in children.
The aim of this study was to assess the resistance to metronidazole and clarithromycin of individual colonies of Helicobacter pylori from a single biopsy taken from 14 adults and 14 children. The Etest was used to determine the minimum inhibitory concentrations (MICs) of these two antimicrobial drugs for ten individual H. pylori colonies isolated from each initial gastric biopsy culture. We confirmed the heterogeneity in metronidazole and clarithromycin resistance in children as seen in adults before anti-H. pylori treatment. The number of resistant individual colonies ranged from two to nine depending on the subject. All individual colonies from the same biopsy that were resistant to clarithromycin were genetically identical according to randomly amplified polymorphic DNA testing and exhibited the same point mutation according to polymerase chain reaction-restriction fragment length polymorphism.


Biogeochemistry of selenium and its impact on food chain quality and human health.
In areas where soils are low in bioavailable selenium (Se), potential Se deficiencies cause health risks for humans. Though higher plants have been considered not to require this element, the experience with low-Se soils in Finland has provided evidence that the supplementation of commercial fertilizers with sodium selenate affects positively not only the nutritive value of the whole food chain from soil to plants, animals and humans but also the quantity of plant yields. The level of Se addition has been optimal, and no abnormally high concentrations in plants or in foods of animal origin have been observed. Se levels in serum and human milk indicate that the average daily intake has been within limits considered to be safe and adequate. In fact, plants act as effective buffers, because their growth is reduced at high Se levels. They also tend to synthesize volatile compounds in order to reduce excess Se. On the other hand, when added at low concentrations, Se exerts a beneficial effect on plant growth via several mechanisms. As in humans and animals, Se strengthens the capacity of plants to counteract oxidative stress caused by oxygen radicals produced by internal metabolic or external factors. At proper levels it also delays some of the effects of senescence and may improve the utilization of short-wavelength light by plants. High additions are toxic and may trigger pro-oxidative reactions. Thus, the present supplementation of fertilizers with Se can be considered a very effective and readily controlled way to increase the average daily Se intake nationwide.


Impact of the '2 week wait' directive for suspected cancer on service provision in a symptomatic breast clinic.
The '2 week wait' directive (Health Service Circular (HSC) 1998/242) guaranteeing that 'everyone with suspected breast cancer will be able to see a specialist within two weeks of their general practitioner (GP) deciding they need to be seen urgently' is a unique audited approach to access for the British National Health Service, the effects of which have been assessed in a non-academic symptomatic breast clinic. New GP referrals (n = 607) were reviewed prospectively in two comparable 3-month intervals, beginning 1 April 1998 and 1 April 1999, to determine the probability of a breast cancer diagnosis from the referral letter and the effects of the directive on waiting times for appointments and utilization of clinics. The urgency of referral was not specified in 53 per cent of GP referrals. For the 'urgent' cases (25 per cent of all new referrals) the probability of a final diagnosis of breast cancer was 0.19. The breast specialists prospectively achieved a rate of 0.26 from 99 per cent of the same referral letters. 'Urgent' referrals did not wait significantly longer in 1999 (median 9 versus 10 days) but waiting times for new appointments overall increased (13 versus 16 days; P < 0.01), and this was greatest for 'routine' [14] versus 21 days; P < 0.001). These changes were caused by an increase in the number of clinic appointments, due to significant increases in median number of visits to diagnosis or discharge and clinic non-attendance in 1999, resulting in overbooking. Telephonic communications were associated with faster median access times (fax 8 days; telephone 2 days), relative to mailed [19] days) (P < 0.01). Breast specialists were better overall at assessing the probability of a breast cancer diagnosis. The waiting time for 'urgent' appointments was unchanged following HSC 1998/242, but there was an increased wait for other patients, especially those assessed as having a lower probability of cancer.


Effect of route of administration and distribution on drug action.
The extent and time course of drug action can be markedly affected by the route of drug administration into the patient as well as the pattern of drug distribution within the patient. Drugs which are rapidly cleared by hepatic processes will show a decreased extent of availability following oral administration due to metabolism of drug on its first pass through the liver. The magnitude of this first pass will depend on the blood flow to the liver and the intrinsic clearing ability of the liver (i.e., the ability of the organ to eliminate the drug independent of the rate at which drug is brought to the organ). Drug distribution in the patient will depend on the blood flow to various sites in the body as well as the partition coefficient of the drug between the blood and the distributive organs. Protein binding both in the plasma and in the tissues will markedly affect this distribution. However, free drug concentrations are generally relieved to be the effective determinant in drug therapy. Often a redistribution due to changes in protein binding will have little effect on the therapeutic efficacy since, although total drug distribution changes, free concentrations in the plasma remain essentially similar.


Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: a matched case-control study.
This study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas. In type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls. The 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3-4.3, P=0.004) with glibenclamide; 2-fold (0.9-4.6, P=0.099) with glipizide; 2.9-fold (1.6-5.1, P=0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7-1.7, P=0.385) with glimepiride, 0.4-fold (0.7-1.3, P=0.192) with gliclazide, and 0.4-fold (0.7-1.1, P=0.09) with either. Initiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents.


Recent Advances in the Management of Migraine in Older Patients.
Although the prevalence of migraine tends to decrease in the fifth to sixth decades of life, there are still a significant number of patients > 65 years of age who experience migraine or have new-onset migraine. Because these older patients are often excluded from clinical trials, there are fewer evidence-based treatment guidelines for them. Migraine treatment in the older population requires careful consideration of changes in medication metabolism and increased medical comorbidities. Furthermore, older patients can present with an atypical migraine phenotype and have a higher rate of secondary headache, which may lead to a delay in diagnosis and subsequent treatment. Classic preventive treatments for migraine, including tricyclic antidepressants, antiepileptic drugs, and beta blockers, often have intolerable side effects. In addition, the presence of coronary artery disease, stroke, and peripheral arterial disease precludes the use of typical rescue medications such as triptans. As such, there has been a dire need for novel acute and preventive treatments for older adults. The purpose of this review is to provide an update on novel acute and preventive treatments for migraine in the older population. The advantages of these therapies include their efficacy, favorable side-effect profile, particularly in patients with atherosclerotic disease, as well as their tolerability.


Food quality effects on life history traits and fitness in the generalist herbivore Daphnia.
Life table experiments were conducted on the generalist suspension feeder Daphnia galeata, using as food the two green algae (Chlorophyta) Scenedesmus acutus and Oocystis lacustris. Oocystis was hypothesized to be a lower quality food because it is convered with a thick sheath, believed to reduce digestibility. Results showed that Oocystis is a lower quality food for Daphnia, but only at relatively low food concentrations (0.15 mg C/L) and not at higher concentrations (1.0 mg C/L). At 0.15 mg C/L, Daphnia intrinsic rate of increase (r) when grown on Oocystis was only half that when grown on Scenedesmus. Daphnia r was similar at 0.15 mg C/L Oocystis and 0.075 mg C/L Scenedesmus, indicating that Daphnia requires twice as much Oocystis as Scenedesmus to achieve the same fitness. Intrinsic rate of increase was lower on Oocystis mainly because age at first reproduction was greatly delayed compared to that on Scenedesmus (13.6 vs 7.3 d). In addition, juvenile growth and survivorship were reduced on Oocystis compared with Scenedesmus. Clutch sizes were similar on the two foods, indicating that once individuals reached adulthood, the two foods were similar in quality. In contrast, at high food concentrations (1.0 mg C/L), the two algae were similar in quality for both juveniles and adults, and r was not significantly different on the two foods. Ingestion and assimilation rate experiments whowed that Daphnia consumes the two algae at identical rates, and that adults assimilate the two algae at similar rates. However, juveniles assimilate Oocystis at much lower rates than Scenedesmus, possibly accounting for reduced juvenile growth and delay in age at maturity at low concentrations. Thus, Daphnia exhibits an ontogenetic shift in its ability to utilize Oocystis, and this can result in "juvenile bottlenecks" in which survival and growth of young age classes are of critical importance in determining population dynamics. Because food quality effects were manifested primarily in juveniles and at low concentrations, food quality effects in nature will depend on phytoplankton abundance and age-structure of Daphnia populations.


miR‑218 functions as a tumor suppressor gene in cervical cancer.
Previous microRNA (miR) microarray analysis revealed that miR‑218 is downregulated in cervical cancer tissues. The present study aimed to further evaluate the expression of miR‑218 in cervical cancer specimens, determine the association between its expression with disease progression, and investigate the roles of miR‑218 in cervical cancer cells. Tissue specimens were obtained from 80 patients with cervical squamous cell carcinoma, 30 patients with high‑grade cervical intraepithelial neoplasia [(CIN) II/III] and 15 patients with low‑grade CIN (CINI); in addition, 60 plasma samples were obtained from patients with cervical cancer, and 15 normal cervical tissue specimens and 30 plasma samples were obtained from healthy women. These samples were used for analysis of miR‑218 expression via reverse transcription‑-quantitative PCR. In addition, tumor cells were transfected with miR‑218 mimics, human papillomavirus (HPV)16 E6/E7 small interfering RNA, or their respective negative controls to determine the viability, colony formation, migration and invasion of cells using MTT, colony formation, wound healing and Transwell assays, respectively. Target genes of miR‑218 were bioinformatically predicted and analyzed using Gene Ontology (GO) terms. The results revealed that miR‑218 was downregulated in the tumor tissues and plasma of patients with cervical cancer, with expression associated with the advanced clinicopathological characteristics of patients, including HPV positivity, tumor size, blood vessel invasion and lymph node metastasis. Furthermore, miR‑218 overexpression reduced tumor cell viability and xenograft growth, and suppressed tumor cell migration and invasion. HPV was detected in 75% of the 80 patients with cervical cancer, and HPV positivity was inversely associated with miR‑218 expression. In addition, bioinformatics analysis predicted that roundabout guidance receptor 1 (ROBO1) was a target gene of miR‑218; miR‑218 overexpression significantly reduced ROBO1 levels. Furthermore, GO analysis revealed that ROBO1 was involved in regulating cell proliferation, adhesion and migration, and the cell cycle. In conclusion, the findings of the present study suggested that miR‑218 may possess antitumor activities in cervical cancer.


Mom's shadow: structure-from-motion in newly hatched chicks as revealed by an imprinting procedure.
The ability to recognize three-dimensional objects from two-dimensional (2-D) displays was investigated in domestic chicks, focusing on the role of the object's motion. In Experiment 1 newly hatched chicks, imprinted on a three-dimensional (3-D) object, were allowed to choose between the shadows of the familiar object and of an object never seen before. In Experiments 2 and 3 random-dot displays were used to produce the perception of a solid shape only when set in motion. Overall, the results showed that domestic chicks were able to recognize familiar shapes from 2-D motion stimuli. It is likely that similar general mechanisms underlying the perception of structure-from-motion and the extraction of 3-D information are shared by humans and animals. The present data shows that they occur similarly in birds as known for mammals, two separate vertebrate classes; this possibly indicates a common phylogenetic origin of these processes.


[Multiple familial follicular hamartoma (author's transl)].
Multiple cystic and proliferative follicular lesions localized on the face and the genitalia of several members of an Italian family are described. Transmission seems to be autosomal dominant, with weak penetration and variable expressivity.


Potential anticancer effects of cyclo(-Pro-Tyr) against N-diethyl nitrosamine induced hepatocellular carcinoma in mouse through PI3K/AKT signaling.
The oceans are considered as magnificent source of bioactive metabolites, of which marine sponges associated organisms are being the most effective producers of various bioactive molecules. We previously reported that cyclo(-Pro-Tyr) (CPT), a dipeptide from marine sponge Callyspongia fistularis associated Bacillus pumilus AMK1 bacteria for its anti-proliferative activity through down regulating PI3K signaling and inducing mitochondrial mediated apoptosis in HepG2 cells. Further we emphasize to study the role of CPT against hepatocellular carcinoma (HCC) induced by N-diethylnitrosamine (DEN) in male swiss albino mice in vivo. In this study, HCC was induced by the administration of DEN (75 mg/kg b.wt) dissolved in saline once/week for 3 weeks, then 100 mg/kg b.wt for another successive 3 weeks and observed for 18 weeks. CPT (100 mg/kg b.wt) treatment was started after 14 weeks of DEN induction. The obtained results demonstrated that CPT altered DEN induced oxidative stress by decreasing serum SGOT and SGPT followed increment in the antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. This was accompanied by decreased accumulation of glycoconjugates and argyophilic nucleolar organizing regions in the treatment groups. Further, CPT significantly reduced the levels of phospho-PI3Kinase p85 and phospho-AKT and upregulation of PTEN compared with DEN induced group. Besides this, decreased expression of Bcl-2 and increased expression of Bax, Caspase 3, and p53 was observed in CPT treated mice. Therefore, the anticancer mechanism of CPT against DEN induced HCC may be associated with the regulation of the PI3K/AKT signaling pathway, which ultimately stimulates apoptosis.


LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1.
We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells. The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8+ T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8+ T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot. KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3'-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8+ T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8+ T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1. LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.


Assay of ditiocarb sodium and its methyl ester in mouse plasma by column-switching HPLC.
To establish a column-switching high pressure liquid chromatograpy (CSHPLC) with direct injection for determination of ditiocarb sodium (DTC) and its methyl ester (DTC-Me) in mouse plasma. After automated online pretreating column enrichment and clear-up, DTC-Me was flushed and chromatographed on an ordinary reversed-phase analytical column, and monitored by UV at lambda absorption = 276 nm. DTC was methylated before determination. No potential interfering peaks were identified. The calibration curves of both analytes were linear within the range of 0.1-150 mg.L-1. The correlation coefficients of DTC and DTC-Me were 0.9998 and 0.9995, respectively. The detection limit was 25 micrograms.L-1 and the coefficient of variation in the assay was within 7% for both compounds. The average recoveries were in the range of 95.28 -100.06%. A typical application was presented for mouse after i.v. DTC 50 mg.kg-1. The rapid CSHPLC method with direct injection can be used for the study of pharmacokinetics of DTC and DTC-Me.


Tritiated thymidine as a broad spectrum initiator in transplacental two-stage carcinogenesis, with phorbol as promoter.
A single subcutaneous injection of 200 mu Ci [3H] thymidine into pregnant BALD/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in overall tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two-stage carcinogenicity studies to determine the organ specificity of different promoting agents.


Correlation between retinal nerve fiber layer thickness and IOP variation in glaucoma suspects and patients with primary open-angle glaucoma.
To analyze the relationship between retinal nerve fiber layer thickness (RNFLT) and intraocular pressure (IOP) variation in glaucoma suspects (GS) and patients with primary open-angle glaucoma (POAG). Thirty-one GS and 34 POAG patients underwent ophthalmologic examination and 24-h IOP measurements. GS had IOPs ranging from 19 to 24 mmHg and/or suspicious appearance of the optic nerve. POAG patients had reproducible abnormal visual fields. We only included patients who presented with short-term IOP fluctuation >6 mm Hg (∆IOP). Only one eye per patient was included through a randomized process. Peripapillary RNFLT was assessed by spectral-domain optical coherence tomography. We correlated RNFLT with IOP parameters. Mean IOP was similar between GS and POAG groups (15.6 ± 3.47 vs 15.6 ± 2.83 mmHg, p = 0.90) as was IOP peak at 6 AM (21.7 ± 3.85 vs 21.3 ± 3.80 mmHg, p = 0.68). Statistically significant negative correlations were found in POAG group between IOP at 6 AM and RNFLT in global (rs = -0.543; p < 0.001), inferior (rs = -0.540; p < 0.001), superior (rs = -0.405; p = 0.009), and nasal quadrants (rs = -0.561; p < 0.001). Negative correlations were also found between ∆IOP and RNFLT in global (rs = -0.591; p < 0.001), and all other sectors (p < 0.05). In GS IOP at 6 AM correlated only with inferior quadrant (rs = -0.307; p = 0.047). IOP at 6 AM and ∆IOP had negative correlations with RNFLT quadrants in POAG. In GS this correlation occurred between IOP at 6 AM and inferior quadrant. These findings may indicate potential risk factors for glaucoma progression.


Configurational changes in rat liver nuclear chromatin caused by azo dyes.
The effects of azo dyes on the chromatin configuration of isolated rat-liver nuclei were examined by electron microscopy for elucidation of the mechanism of dye-stimulated in vitro RNA synthesis. Sunset Yellow FCF had no effect on the incorporation of [3H]UTP into RNA but amaranth and Ponceau 3R stimulated incorporation approximately two- and 3.5-fold, respectively. Sunset Yellow FCF did not produce any major alteration in liver nuclei. Isolated liver nuclei treated with amaranth or Ponceau 3R showed dissociation of heterochromatin and the nucleoli lost their fine-granular structure acquiring a coarse-granular configuration. The dense structure of heterochromatin in liver nuclei treated with Ponceau 3R was completely dissociated and appeared as a lace-like configuration. These results suggest that both Ponceau 3R and amaranth stimulate in vitro RNA synthesis by causing the dissociation of heterochromatin in isolated rat-liver nuclei.


Obesity identified by discharge ICD-9 codes underestimates the true prevalence of obesity in hospitalized children.
To define inpatient care of obese children with or without an obesity diagnosis. A total of 29,352 inpatient discharges (18,459 unique inpatients) from a tertiary children's hospital were analyzed. Body mass index (BMI) was calculated from measured height and weight. "Obesity" was defined as BMI >or=95th percentile by using Centers for Disease Control and Prevention 2000 growth charts. "Diagnosed obesity" was defined by primary, secondary or tertiary International Classification of Diseases, Ninth Revision codes for "obesity" or "overweight." Analyses controlled for multiple inpatient records per individual. A total of 5989 discharges from the hospital (20.4%) were associated with obesity, but only 512 discharges (1.7%) indicated obesity as a diagnosis. An obesity diagnosis identified only 5.5% of inpatient days for obese inpatients. Obese patients with an obesity diagnosis (Ob/Dx) had fewer hospital discharges per person and shorter lengths of stay than obese patients without an obesity diagnosis (Ob/No Dx). Patients with Ob/Dx had higher odds of mental health, endocrine, and musculoskeletal disorders than non-obese inpatients, but Ob/No Dx patients generally did not. Inpatient obesity diagnoses underestimate inpatient utilization and misidentify patterns of care for obese children. Extreme caution is warranted when using obesity diagnoses to study healthcare utilization by obese children.


Development of a new body weight estimation method using head CT scout images.
Imaging examinations are crucial for diagnosing acute ischemic stroke, and knowledge of a patient's body weight is necessary for safe examination. To perform examinations safely and rapidly, estimating body weight using head computed tomography (CT) scout images can be useful. This study aims to develop a new method for estimating body weight using head CT scout images for contrast-enhanced CT examinations in patients with acute ischemic stroke. This study investigates three weight estimation techniques. The first utilizes total pixel values from head CT scout images. The second one employs the Xception model, which was trained using 216 images with leave-one-out cross-validation. The third one is an average of the first two estimates. Our primary focus is the weight estimated from this third new method. The third new method, an average of the first two weight estimation methods, demonstrates moderate accuracy with a 95% confidence interval of ±14.7 kg. The first method, using only total pixel values, has a wider interval of ±20.6 kg, while the second method, a deep learning approach, results in a 95% interval of ±16.3 kg. The presented new method is a potentially valuable support tool for medical staff, such as doctors and nurses, in estimating weight during emergency examinations for patients with acute conditions such as stroke when obtaining accurate weight measurements is not easily feasible.


Determining polarity and dislocation core structures at atomic level for epitaxial AlN/(0001)6H-SiC from a single image in HRTEM.
The polarity of epitaxial AlN film grown on (0001)6H-SiC and dislocation core structures in the film have been studied using a 200 kV LaB6 high-resolution transmission electron microscope of point resolution about 0.2 nm. A posterior image processing technique, the image deconvolution, was utilized to transform a single [21¯1¯0] image that does not intuitively represent the structure into the projected structure map. The adjacent Al and N projected atomic columns with the interatomic distance 0.109 nm can be distinguished from each other by analyzing the image contrast change with the sample thickness based on the pseudo-weak phase object approximation. This makes possible to derive the polarity and core structures of partial dislocations in the epitaxial AlN film at atomic level from a single image without relying on any other additional structure information. The atomic configurations for two partial dislocations containing a 10-atom ring and a 12-atom ring, respectively, have been attained. The method is available for II-VI and other III-V compounds. Its principle and procedure are briefly introduced.


Subjective ultrasound assessment, the ADNEX model and ultrasound-guided tru-cut biopsy to differentiate disseminated primary ovarian cancer from metastatic non-ovarian cancer.
To compare subjective ultrasound assessment and the ADNEX model with ultrasound-guided tru-cut biopsy to differentiate disseminated primary ovarian cancer from metastatic non-ovarian cancer. This was a prospective study including 143 consecutive women with disseminated malignancy of unknown primary origin, with a pelvic tumor/carcinosis. Women underwent either transvaginal or transrectal ultrasound as well as transabdominal ultrasound examination followed by tru-cut biopsy. The ultrasound examiner assessed tumor morphology, spread in the pelvis and abdomen, and predicted tumor origin as primary ovarian or metastatic using both subjective assessment and the ADNEX model. Histology from tru-cut biopsy served as the gold standard for assessment of diagnostic accuracy. Biopsy adequacy and the complication rate were assessed. Tru-cut biopsy was performed transvaginally in 131/143 (92%) women. Two women needed inpatient care (one had abdominal wall hematoma, and one infection). Biopsy resulted in a conclusive diagnosis in 126/143 (88%) women, amongst whom cytoreductive surgery was performed in 30/126 confirming the diagnosis in all cases. Non-ovarian metastatic cancer was found in 37/126 (29%) women and primary ovarian cancer in 89/126 (71%) women. Subjective ultrasound evaluation had a sensitivity of 82% (73/89) and a specificity of 70% (26/37) in predicting primary ovarian cancer. The ADNEX model had an area under the receiver-operating characteristics curve of 0.891 (95% CI, 0.794-0.946) (in women with an ovarian lesion, n = 104). Tumor origin was associated with age, CA 125, previous neoplasia, presence of omental cake and tumor mobility. Subjective ultrasound assessment and the ADNEX model can both be used to predict whether a pelvic tumor is metastatic and of non-ovarian origin, indicating the need for tru-cut biopsy, which is associated with very few complications and will provide a conclusive diagnosis in nine out of 10 women. Copyright © 2015 ISUOG.


Diagnostic accuracy and discriminative power of biparametric versus multiparametric MRI in predicting muscle-invasive bladder cancer.
Investigate and compare the diagnostic accuracy and discriminative power of biparametric MRI (bp-MRI) and multiparametric MRI (mp-MRI) in predicting muscle-invasive bladder cancer (MIBC) based on Vesical Imaging-Reporting and Data System (VI-RADS) scoring and evaluate potentially influencing factors on both protocols' accuracy. This retrospective study included 54 bladder cancer (BC) patients who underwent bladder MRI and histo-pathological assessment. Three readers independently reviewed the MRI studies and assigned a 1-5 score for T2-weighted, diffusion-weighted, and dynamic contrast-enhanced images. Then, bp-MRI and mp-MRI final VI-RADS scores were recorded for each BC. Diagnostic tables, chi-square test, kappa score (k), logistic regression, receiver operating characteristics (ROC) curves, areas under the curves (AUCs), and VI-RADS cut-off values were calculated. A Delong test was performed for ROC curve comparison. A P-value<0.05 was considered significant. In predicting MIBC, bp-MRI and mp-MRI had comparable diagnostic accuracy with insignificant differences for the three readers (P = 0.364,0.718,0.702). Radiologists' experience, and tumors' size and morphology had insignificant effect on bp-MRI accuracy (P = 0.086, 0.392,0.294), respectively. Tumors' size significantly influenced mp-MRI accuracy (P = 0.039). Bp-MRI and mp-MRI had comparable discriminative power with insignificant differences for all readers (P > 0.05). Using VI-RADS > 3 cut-off value improved the discriminative power of bp-MRI. Excellent inter-reader agreement in VI-RADS scoring for bp-MRI (k range, 0.814-0.867) and mp-MRI (k range, 0.787-0.859) was observed. Bp-MRI and mp-MRI demonstrated comparable diagnostic accuracy and discriminative power in predicting MIBC. The accuracy of bp-MRI was not influenced by radiologists' experience, or tumors' size and morphology.


Stimulus rate determines regional brain blood flow in striate cortex.
Intravenous bolus administration of oxygen 15-labeled water and positron emission tomography were used to measure changes in brain blood flow induced by two modes of photic stimuli over a wide range of repetition rates. These stimuli (patterned-flash and reversing checkerboard) were chosen in order to determine whether stimulus luminance or stimulus frequency was responsible for previously observed increases in blood flow in the striate cortex during photic stimulation. The response curves of blood flow change as a function of stimulus rate were nearly identical for both stimuli. These results suggest that elementary stimulus variables, such as repetition rate, can have a major effect on local cerebral responses, as measured with positron emission tomography and other radiotracer methods.


Influences of periodontal and mandibular-joint receptors on reflex sensitivity of human jaw-closing muscles.
Reflex sensitivity from stimulating the chin or the dental arch of the mandible and the influences of periodontal and mandibular joint receptors on jaw muscles were investigated by experiments with and without anaesthesia. The findings showed that periodontal receptors exert an inhibitory influence on motoneural excitability of jaw-closing muscles and facilitate alpha-motoneurones of the digastric muscle and that the silent period following a jaw jerk is partly caused by inhibition of alpha-motoneurones of jaw-closing muscles due to activity of periodontal receptors. The ratio of reflex activity in temporal and masseter muscles appeared to depend on the position of the applied stimulus. The mandibular joint receptors appear to play a major part in distributing active muscle-force over these muscles.


Alteration of striatal [11C]raclopride and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine uptake precedes development of methamphetamine-induced rotation following unilateral 6-hydroxydopamine lesions of medial forebrain bundle in rats.
We studied the positron emission tomography (PET) tracer distributions of ligands for dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and of the dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than at 3 days after the 6-OHDA lesions. The brains of 6-OHDA-treated rats were analyzed by tissue dissection following i.v. bolus of each tracer at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [11C]Raclopride, but not [11C]SCH23390, showed higher accumulation in the striatum on the lesion side than on the non-lesion (intact) side both at 3 days and 3 weeks postlesion. On the other hand, lower accumulation of [18F]FDOPA was observed in the striatum on the lesion side at 3 days postlesion and in both the striatum and cerebral cortex on the lesion side at 3 weeks postlesion. Our studies demonstrate that an increase in [11C]raclopride and a decrease in [18F]FDOPA uptake in the denervated striatum is evident even at 3 days after the 6-OHDA lesions when the methamphetamine-induced rotational behavior is not established.


Nutritional status, iron-deficiency-related indices, and immunity of female athletes.
Nutritional status, iron-deficiency-related biochemical indices, and immunologic patterns of female Judo athletes and control subjects were evaluated. The subjects' 3-d food records showed that 41.0 kcal/kg of energy was consumed daily and the contributions of protein, fat, and carbohydrate to total energy intake were 12.5%, 29.2%, and 58.3%, respectively. The reported vitamin intakes of athletic subjects were above those of the recommended daily allowance, however, calcium and iron intakes were less than 100% of the recommended daily allowance. Intakes of energy, protein, phosphate, vitamin B1, and vitamin B2 were higher in the athletes than in the control subjects. Analysis using the Nutrient Adequacy Ratio and the Index of Nutritional Quality showed that athletic subjects had more desirable patterns than the control subjects. There was no any indication of anemia, which often occurs as a result of hemodilution in strenuously trained athletes. The subjects' immunologic patterns showed a slight immunosuppression. Iron, vitamin B1, niacin intakes were positively correlated with immunoglobulin (Ig) G levels in the athletes. The relation between nutrient intakes and the immune systems of endurance-trained athletes needs further investigation.


Rewarding properties of visual stimuli.
The behavioral functions of rewards comprise the induction of learning and approach behavior. Rewards are not only related to vegetative states of hunger, thirst and reproduction but may also consist of visual stimuli. The present experiment tested the reward potential of different types of still and moving pictures in three operant tasks involving key press, touch of computer monitor and choice behavior in a laboratory environment. We found that all tested visual stimuli induced approach behavior in all three tasks, and that action movies sustained consistently higher rates of responding compared to changing still pictures, which were more effective than constant still pictures. These results demonstrate that visual stimuli can serve as positive reinforcers for operant reactions of animals in controlled laboratory settings. In particular, the coherently animated visual stimuli of movies have considerable reward potential. These observations would allow similar forms of visual rewards to be used for neurophysiological investigations of mechanisms related to non-vegetative rewards.


[Mechanical bending strength of explanted ex vivo bone cements compared with in vitro samples].
The mechanical properties of acrylic bone cements are an important factor in determining an efficient load transmission between prosthesis and bone to guarantee the long-term stability in cemented hip arthroplasty. Palacos and Refobacin Palacos specimens from 21 aseptically loosened femoral compoments of cemented hip arthroplasties manufactured by the first to third generation cementing technique have been mechanically tested in a standardised four-point bending test (ISO 5833). In vitro manufactured Palacos and Refobacin Palacos specimens served as a control group. The fatigue fracture surfaces were morphologically analysed with light microscopy. Under in vitro conditions manufactured specimens had higher values of bending strength, with the exception of blood contaminated ones, compared to ex vivo specimens. Ex vivo specimens of the second and third generation cementing technique had higher values than specimens of the first generation. Acrylic bone cements are subjected to a multifactorial material fatigue in vivo. Here, the art and quality of cementing technique is of eminent importance in determining the long-term stability of cemented hip arthroplasty.


Differential fixation of poly(L-arginine) and poly(L-lysine) by tannic acid and its application to the fixation of collagen in electron microscopy.
A differential fixation of poly(L-arginine) and poly(L-lysine) has been demonstrated by means of cellulose acetate electrophoresis and colorimetric titration. Electrophoresis showed that at pH 3.0 and concentrations between 0.025% and 2% the reagent interacts with poly(L-arginine) but not with poly(L-lysine). At pH 7.5, however, poly(L-lysine) also reacts, although at a higher concentration of tannic acid than was required to fix poly(L-arginine) at this pH. Colorimetric titration revealed that for poly(L-arginine) the reaction with tannic acid commences at pH 3.0 and is complete at pH 4.1 whereas for poly(L-lysine) the reaction commences at pH 3.5 and is complete at pH 4.9. It is suggested that the reaction is predominantly electrostatic. The results are discussed in relation to the use of tannic acid as a protein fixative in electron microscopy.


Hodgkin's disease of the thoracic vertebrae.
Hodgkin's disease rarely occurs in the spine, which is usually a setting for the advanced form of the disease. To describe an unusual case of isolated, primary spinal Hodgkin's disease and to draw attention to this disease as a possible diagnosis in patients with mixed inflammatory cell infiltrate lesions located in the thoracic spine. A case report of a 28-year-old woman who presented with back pain and progressive weakness in the lower extremities as a result of spinal cord compression from Hodgkin's disease of the thoracic vertebrae. We report a new case of spinal cord compression resulting from Hodgkin's disease of the thoracic vertebrae. Decompression surgery was performed in the patient, followed by antibiotic treatment. Antibiotic therapy temporarily improved inflammation and fever. However, magnetic resonance imaging (MRI) evaluation showed that the inflammatory reaction in the lesion was not completely resolved. The disease progressed and later investigations revealed Hodgkin's disease, which improved with a course of chemotherapy and radiation. Hodgkin's disease should be considered in the differential diagnosis of spinal neoplastic lesions with clinical features similar to spondylitis. Because MRI evaluation showed that the vertebral disc was maintained in this case, the presence of a tumor rather than inflammation should have been suspected.


Major threats to early safety after transcatheter aortic valve implantation in a contemporary cohort of real-world patients.
Despite considerable advances in the last decade, major adverse events remain a concern after transcatheter aortic valve implantation (TAVI). The aim of this study was to provide a detailed overview of their underlying causes and contributing factors in order to identify key domains for quality improvement. This observational, prospective registry included all patients undergoing TAVI between 31 December 2015 and 1 January 2020 at the St. Antonius Hospital in Nieuwegein and the University Medical Centre in Utrecht. Outcomes of interest were all-cause mortality, stroke, major bleeding, life-threatening or disabling bleeding, major vascular complications, myocardial infarction, severe acute kidney injury and conduction disturbances requiring permanent pacemaker implantation within 30 days after TAVI, according to the Valve Academic Research Consortium‑2 criteria. Of the 1250 patients who underwent TAVI in the evaluated period, 146 (11.7%) developed a major complication. In 54 (4.3%) patients a thromboembolic event occurred, leading to stroke in 36 (2.9%), myocardial infarction in 13 (1.0%) and lower limb ischaemia in 11 (0.9%). Major bleeding occurred in 65 (5.2%) patients, most frequently consisting of acute cardiac tamponade (n = 25; 2.0%) and major access-site bleeding (n = 21; 1.7%). Most complications occurred within 1 day of the procedure. Within 30 days a total of 54 (4.3%) patients died, the cause being directly TAVI-related in 30 (2.4%). Of the patients who died from causes that were not directly TAVI-related, 14 (1.1%) had multiple hospital-acquired complications. A variety of underlying mechanisms and causes form a wide spectrum of major threats affecting early safety in 11.7% of patients undergoing TAVI in a contemporary cohort of real-world patients.


Advances in Discovering Deubiquitinating Enzyme (DUB) Inhibitors.
Deubiquitinating enzymes, or DUBs, comprise a family of proteases that regulate ubiquitination dynamics. Since their discovery, genetic and functional studies have nominated DUBs as a promising class for drug discovery across diverse therapeutic areas. Consequent probe and drug discovery efforts over the past 15 years have resulted in over 50 reported inhibitors and advances in DUB structural studies, assay formats, and chemical biology tools. Accumulating knowledge from these studies has enabled several important recent breakthroughs. In this review, we highlight recent successes in solving DUB-ligand co-structures and the development of rigorously characterized potent and selective inhibitors. We posit that these advances in pharmacological targeting of DUBs establish the enzyme family as targetable and provide a framework for other DUBs programs. Accordingly, we envision increasingly rapid progress in the development of potent and selective inhibitors for a wide range of DUBs and advancement of DUB-targeting drugs to the clinic.


Long-term effects of non-excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs.
We previously showed that acute delivery of non-excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (HF). In the present study we examined the long-term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HF. Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls. In control dogs, LV end-diastolic volume (EDV) and LV end-systolic volume (ESV) increased (64+/-5 ml vs. 75+/-6 ml, P=0.003; 46+/-4 ml vs. 57+/-4 ml, P=0.003; respectively), and ejection fraction (EF) decreased (28+/-1% vs. 23+/-1%, P=0.001) over the course of 3 months of follow-up. In contrast, CCM-treated dogs showed a smaller increase in EDV (66+/-4 vs. 73+/-5 ml, P=0.01), no change in ESV, and an increase in EF from 31+/-1 to 34+/-2% (P=0.04) after 3 months of therapy. In dogs with HF, long-term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HF.


Predictive factors for extraction site hernia after laparoscopic right colectomy.
Incisional hernia at the extraction site (ESIH) is a common complication after laparoscopic colorectal resections. The aim of this study was to evaluate the prevalence and potential risk factors for ESIH in a large cohort study having standardized technique. A cross-sectional study was performed including all patients who underwent elective laparoscopic right or extended right colectomy for cancer from November 2006 to October 2013 using a standard technique. All patients have been followed up for a minimum of 1 year with abdominal CT scan. A total of 292 patients were included with a median follow-up of 42 months. Twenty patients (6.8 %) developed ESIH. Obesity (odds ratio (OR) = 3.76, 95 % confidence interval (CI) 1.39-10.15; p = 0.009) and incision length (OR 2.86, 95 % CI 1.077-7.60; p = 0.035) significantly predisposed to the development of ESIH. This study identified that the risk of ESIH is significant after colonic resections and there are several risk factors responsible for the development of ESIH.


CT Angiography Manual Multiplanar Vessel Diameter Measurement vs. Semiautomated Perpendicular Area Minimal Caliber Computation of Internal Carotid Artery Stenosis.
Objective: To determine the diagnostic agreement of CT angiography (CTA) manual multiplanar reformatting (MPR) stenosis diameter measurement and semiautomated perpendicular stenosis area minimal caliber computation of extracranial internal carotid artery (ICA) stenosis. Methods: We analyzed acute cerebral ischemia CTA at our tertiary stroke center in a 12-month period. Prospective NASCET-type stenosis grading for each ICA was independently performed using (1) MPR to manually determine diameters and (2) perpendicular stenosis area with minimal caliber semiautomated computation to grade luminal constriction. Corresponding to clinically relevant NASCET strata, results were grouped into severity ranges: normal, 1-49%, 50-69%, and 70-99%, and occlusion. Results: We included 647 ICA pairs from 330 patients (median age of 74 [66-80, IQR]; 38-92 years; 58% men; median NIHSS 4 [1-9, IQR]). MPR diameter and semiautomated caliber measurements resulted in stenosis grades of 0-49% in 143 vs. 93, 50-69% in 29 vs. 27, 70-99% in 6 vs. 14, and occlusion in 34 vs. 34 ICAs (p = 0.003), respectively. We found excellent reliability between repeated manual CTA assessments of one expert reader (ICC = 0.997; 95% CI, 0.993-0.999) and assessments of two expert readers (ICC = 0.972; 95% CI, 0.936-0.988). For the semiautomated vessel analysis software, both intrarater reliability and interrater reliability were similarly strong (ICC = 0.981; 95% CI, 0.952-0.992 and ICC = 0.745; 95% CI, 0.486-0.883, respectively). However, Bland-Altman analysis revealed a mean difference of 1.6% between the methods within disease range with wide 95% limits of agreement (-16.7-19.8%). This interval even increased with exclusively considered vessel pairs of stenosis ≥1% (mean 5.3%; -24.1-34.7%) or symptomatic stenosis ≥50% (mean 0.1%; -25.7-26.0%). Conclusion: Our findings suggest that MPR-based diameter measurement and the semiautomated perpendicular area minimal caliber computation methods cannot be used interchangeably for the quantification of ICA steno-occlusive disease.


Pathologic basis and treatment considerations in chronic kidney disease-related hypertension.
Chronic kidney disease (CKD) is both a cause and an effect of hypertension and is multifactorial in its origin. Beyond volume expansion, CKD-related hypertension is without defining characteristics of any consistency. Consequently, the order in which antihypertensive medications are given to the CKD patient with hypertension is arbitrary, although prescription practice is for the most part mindful of the need for multiple drug classes with at least one of them being a diuretic. It is not without reason that blood pressure goals in the hypertensive CKD patient are set at lower levels than those for patients with essential hypertension, but it remains to be determined how much the blood pressure should be decreased in the CKD patient.


Labels of insecticides to which Oregon honey bee (Apis mellifera L.) hives could be exposed do not align with federal recommendations in their communication of acute and residual toxicity to honey bees.
Teaching pesticide applicators how to determine a product's toxicity to honey bees (Apis mellifera L.) by understanding the label is a way to reduce honey bee exposure to pesticides. Applicators are currently taught how to interpret labels that follow the United States Environmental Protection Agency's (USEPA's) recommendations for how this toxicity should be communicated. To effectively educate applicators, it must be determined if labels follow USEPA recommendations in how they communicate toxicity to honey bees, and if they do not, what patterns exist in these deviations from the recommendations (hereafter, deviations). As a case study, we analyzed the USEPA master labels of insecticides used in 16 situations where there is concern over Oregon honey bee colony exposure to pesticides. Of the 232 labels analyzed, 31.5% deviated from USEPA recommendations in at least one way. Labels of both commercial and garden products deviated from USEPA recommendations. Products with labels that deviated from USEPA recommendations were found across application situation and active ingredient subgroup. The percentage of products per application situation and per chemical subgroup whose label deviated from USEPA recommendations varied. The most common deviation represented a direct contradiction between the statement used and the toxicity class of the product's active ingredient. Applicators will be underprepared to interpret the pesticide labels they see in the field if they are exclusively taught how to interpret labels that follow USEPA recommendations. Applicators should be taught how to interpret a product label that uses non-USEPA-recommended statements to communicate toxicity to honey bees. © 2019 Society of Chemical Industry.


ACR white paper: task force on timing of oral boards in diagnostic radiology.
The direction that the American Board of Radiology intends to follow relative to the diagnostic radiology oral board examination has risen quickly up the list of fundamental challenges for the radiology community. The formation of an ACR task force to study these changes was necessary, because this issue carries a high stake for the future of the profession and the patients we serve. After a careful review of the potential impacts, the committee discovered that consensus would be difficult to achieve relative to the merits of these changes. Accordingly, this white paper is focused objectively on the potential impacts on radiologists, practices, academic institutions, the ACR itself, and the ACR's membership. It is suggested that these concepts be used as starting points for future discussion and consideration of potential action.


Set-up error validation with EPID images: Measurements vs Egs_cbct simulation.
In this study, the egs_cbct code's ability to replicate an electronic portal imaging device (EPID) is explored. We have investigated head and neck (H&N) setup verification on an Elekta Precise linear accelerator. It is equipped with an electronic portal imaging device (EPID) that can capture a set of projection images over different gantry angles. Cone-beam computed tomography (CBCT) images were reconstructed from projection images of two different setup scenarios. Projections of an Anthropomorphic Rando head phantom were also simulated by using the egs_cbct Monte Carlo code for comparison with the measured projections.Afterwards, CBCT images were reconstructed from this data. Image quality was evaluated against a metric defined as the image acquisition interval (IAI). It determines the number of projection images to be used for CBCT image reconstruction. From this results it was established that phantom shifts could be determined within 2 mm and rotations within one degree accuracy using only 20 projection images (IAI = 10 degrees). Similar results were obtained with the simulated data. In this study it is demonstrated that a head and neck setup can be verified using substantially fewer projection images. Bony landmarks and air cavities could still be observed in the reconstructed Rando head phantom. The egs_cbct code can be used as a tool to investigate setup errors without tedious measurements with an EPID system.


Direct Oxidation of Aliphatic C-H Bonds in Amino-Containing Molecules under Transition-Metal-Free Conditions.
By employing a simple, inexpensive, and transition-metal-free oxidation system, secondary C-H bonds in a series of phthaloyl protected primary amines and amino acid derivatives were oxidized to carbonyls with good regioselectivities. This method could also be applied to oxidize tertiary C-H bonds and modify synthetic dipeptides.


Betamethasone-dixyrazine combination versus high-dose metoclopramide as antiemetic treatment in doxorubicin and cisplatin chemotherapy.
In a prospective randomized and double-blind cross-over study, a new antiemetic regimen consisting of betamethasone (1 x 8 mg) and dixyrazine (a phenothiazine derivative) (4 x 10 mg) was compared with a standard high-dose metoclopramide (4 x 1 mg/kg) schedule for antiemetic treatment in doxorubicin and cisplatin chemotherapy. 100 consecutive patients (62 without prior experience of chemotherapy and 38 with prior experience) entered the study and were followed during 1-4 courses of chemotherapy. Effect and side effect parameters were recorded on questionnaires for patients and nurses using the visual analog scale for quantification. The correlation between the two ways of recording (self-scoring versus recording by nursing staff) was very high, both for effect variables (nausea and vomiting) and the adverse reactions (sedation and extrapyramidal reactions). The median number of courses per patient was 3.0 (range 1-4) and altogether 299 courses were studied. Full emetic protection was achieved in 58% with betamethasone-dixyrazine and in 34% with high-dose metoclopramide regardless of prior patient experience or the cytostatic agents administered. With doxorubicin regimens, betamethasone-dixyrazine gave full protection in 80% compared to 40% for metoclopramide. Cisplatin regimens were a greater challenge and protection against nausea and vomiting was achieved only in 27% with betamethasone-dixyrazine and in 18% with metoclopramide. Adverse reactions were a significant problem with metoclopramide: restlessness 33%, akathisia 19%, parkinsonism 16%, and acute dystonia 3%. Sedation was the same with the two regimens (80%).


Perspectives of older adults, caregivers, healthcare providers on frailty screening in primary care: a systematic review and qualitative meta-synthesis.
Screening is often recommended as a first step in frailty management. Many guidelines call to implicate frailty screening into practice in the primary care setting. However, few countries or organizations implement it. Understanding and clarifying the stakeholders' views and issues faced by the implementation is essential to the successful implementation of frailty screening. However, the systematic review on stakeholders' views of frailty screening in primary care is decidedly limited. Our objective was to explore the perspective of older adults, caregivers, and healthcare providers on frailty screening and determine the enablers and barriers to implementing frailty screening in primary care. A systematic search of six databases and other resources was conducted following JBI's three-step search strategy. The search resulted in 7362 articles, of which 97 were identified for further assessment according to the inclusion criteria. After the full-text screening, quality assessment and data extraction were carried out using the tools from Joanna Briggs Institute (JBI). Moreover, reviewers used the approach of meta-aggregative of JBI to analyze data and synthesis the findings. Six studies were included. A total of 63 findings were aggregated into 12 categories and then further grouped into three synthesized findings:1) capacity of healthcare providers and older adults; 2) opportunity in the implementation of frailty screening; 3) motivation in the implementation of frailty screening. These themes can help identify what influences the implementation of screening from the perspective of stakeholders. This meta-synthesis provides evidence on the barriers and enablers of frailty screening in primary care, from the aspects of psychological, physical, social, material, etc. However, stakeholder perspectives of frailty screening have not been adequately studied. More research and efforts are needed to explore the influencing factors and address the existing barriers.


Engagement of gcFKBP5/TRAF2 by spring viremia of carp virus to promote host cell apoptosis for supporting viral replication in grass carp.
Spring viremia of carp virus (SVCV) causes severe morbidity and mortality in grass carp (Ctenopharyngodon idellus) in Europe, America and several Asian countries. We found that FKBP5 (FK506-binding protein 5) is an SVCV infection response factor; however, its role in the innate immune mechanism caused by SVCV infection remains unknown. This study cloned gcFKBP5 (grass carp FKBP5) and made its mimic protein structure for function discussion. We found that gcFKBP5 expression in the primary innate immune organs of grass carp, including intestine, liver and spleen, was highly upregulated by SVCV in 24 h, with a similar result in fish cells by poly(I:C) treatment. gcFKBP overexpression aggravates viral damage to cells and increases viral replication. Furthermore, SVCV engages gcFKBP5 interacting with TRAF2 (tumour necrosis factor receptor-associated factor 2) to promote host cell apoptosis for supporting viral replication. The enhanced viral replication seems not to be due to the repression of IFN and other antiviral factors as expected. For the first time, these data show the pivotal role of gcFKBP5 in the innate immune response of grass carp to SVCV infection.


Effectiveness of an intensive, school-based intervention for teen mothers.
This study evaluated the effectiveness of a secondary teen pregnancy prevention intervention that includes school-based social work services coordinated with comprehensive health care for teen mothers and their children. A prospective cohort study compared subsequent births to teen mothers followed for at least 24 months or until age 20 years (whichever was longer) compared with matched subjects from state data. Analyses were based on intent to treat and included chi(2), survival, and cost-benefit analysis. Subjects included 63 girls (97% eligible, 99% African-American, mean age 16 years). A propensity-matched comparison group (n = 252) did not differ from subjects. Participation in program components was good: (1) group meetings: 76%; (2) case management: 95%; (3) coordinated medical care: 63%. The majority of subjects used contraception (93%), with greater use of medroxyprogesterone associated with participation in coordinated medical care (80% vs. 50%, p = .0145). Subsequent births were more common in the comparison group (33%) than among subjects (17%) (p = .001), and survival curves were significantly different (p = .007) (hazard ratio = 2.5). There was a trend toward fewer births with increased participation in medical care (p = .08) and case management (p = .08) but not with group meetings. Cost savings were calculated as $19,097 per birth avoided or $5,055 per month. The intervention was effective in reducing subsequent births to teens; however selection bias of school enrollment cannot be excluded by this study. The cost savings of delayed births outweigh the expenses of this intensive model.


Adaptive conductive electrotherapeutic scaffolds for enhanced peripheral nerve regeneration and stimulation.
While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches. In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models. This work was supported by K. Lisa Yang Center for Bionics at MIT.


Research on highway traffic flow prediction model and decision-making method.
In order to solve the problem of traffic congestion in a certain area, this paper develops a set of traffic optimization decision system. For analyzing the actual traffic conditions and calculating the traffic volume, density and traffic speed, a traffic prediction model is established and updated iteratively to modify the prediction model parameters. Based on this model, the congestion degree is estimated at the current road section, thus, an intelligent decision-making and the coordinated optimization methods are proposed. Moreover, this paper implements some application experiments on the isometric road of a three-intersection and obtains better prediction results of traffic density and traffic speed on the three-section highway. At the same time, compared with other existing prediction methods, the prediction model presented in this paper not only has higher accuracy, shorter prediction time and stronger anti-interference ability, but also has better effect on vehicle diversion. In addition, it also greatly relieves the traffic pressure on the road, maximizes the complementary advantages between intersections, and balances the good cooperation between each intersection.


Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression.
N6-methyladenosine (m6A), the most abundant and reversible modification of mRNAs in eukaryotes, plays pivotal role in breast cancer (BC) tumorigenesis and progression. Circular RNAs (circRNAs) can act as tumor promoters or suppressors by microRNA (miRNA) sponges in BC. However, the underlying mechanism of circRNAs in BC progression via regulating m6A modulators remains unclear. Prognostic m6A RNA methylation regulators were identified in 1065 BC patients from The Cancer Genome Atlas (TCGA) project. Differentially expressed (DE) miRNAs and DE circRNAs were identified between BC and normal samples in TCGA and GSE101123, respectively. MiRNA-mRNA interactive pairs and circRNA-miRNA interactive pairs were verified by MiRDIP and Circular RNA Interactome. GSEA, KEGG, and ssGSEA were executed to explore the potential biological and immune functions between HNRNPC-high and HNRNPC-low expression groups. qRT-PCR and Western blot were used to quantify the expression of HNRNPC and circBACH2 in MCF-7 and MDA-MB-231 cells. The proliferation of BC cells was assessed by CCK-8 and EdU assay. 2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients. Then, the regulatory network of circRNA-miRNA-m6A modulators was constructed, which consisted of 2 DE m6A modulators (HNRNPC and YTHDF3), 12 DE miRNAs, and 11 DE circRNAs. Notably, BC patients with high expression of HNRNPC and low expression of hsa-miR-944 were correlated with late clinical stages and shorter survival times. Besides, the results from the KEGG inferred that the DE HNRNPC was associated with the MAPK signaling pathway in BC. Moreover, the circBACH2 (hsa_circ_0001625) was confirmed to act as hsa-miR-944 sponge to stimulate HNRNPC expression to promote BC cell proliferation via MAPK signaling pathway, thus constructing a circBACH2/hsa-miR-944/HNRNPC axis in BC. Our findings decipher a novel circRNA-based m6A regulatory mechanism involved in BC progression, thus providing attractive diagnostic and therapeutic strategies for combating BC.


Abdominal pain in athletes.
Abdominal pain in an athlete may be due to an intra-abdominal injury or abdominal disease unrelated to athletics; both are uncommon. Because such processes may be life-threatening, awareness of their typical patterns is imperative for all involved in sports medicine. Evaluation of an athlete with abdominal pain is thus directed at deciding if the athlete has significant abdominal disease, and then using appropriate diagnostic methods to determine the specific process.


Increased mortality for colorectal cancer patients with preexisting diabetes mellitus: an updated meta-analysis.
Although the preexisting diabetes mellitus (DM) is known to have a high risk for death in many cancers, its impact on the mortality for the colorectal cancer (CRC) patients is still uncertain. In this study, we conducted a meta-analysis to explore an association of DM with the survival for the CRC patients. We made a relative data search from the public available databases including Medline and Embase with a cutoff date to Jan 31, 2017. Pooled hazard ratios (HRs) were calculated using either a fixed or random effect model. Trim and fill analysis was conducted to test and adjust for publication bias. Subgroup analyses were also performed for overall survival and all-cause mortality when stratified by tumor stage, geographical region, duration of follow-up, gender and subsite of cancer. Twenty-one eligible cohorts including 1,025,034 patients were identified and included in this meta-analysis review. The sample size for each analysis was ranged from 207 to 771,297 patients. It is revealed that with the preexisting DM, the CRC patients had a significantly increased all-cause mortality (pooled adjusted HR: 1.23; 95% CI: 1.11, 1.37) and decreased overall survival (pooled adjusted HR: 1.25, 95% CI: 1.19-1.31). But no difference was found for adjusted cancer-specific survival for the CRC patients with the preexisting DM compared with subjects without DM. These associations almost remained consistent after trim and fill adjustment and across those outcomes when stratified by site of cancer, tumor stage, population geography, study design, duration of follow-up, data resource or gender. This meta-analysis review indicates that preexisting diabetes mellitus in CRC patients is severely associated with the worse overall survival but not with cancer-specific survival.


Isotropic systems of medium-chain mono- and diglycerides for solubilization of lipophilic and hydrophilic drugs.
The aim of this study was to investigate isotropic mono- and diglyceride-based (MCMDG) systems, which are potential vehicles for injectable products containing both hydrophilic and lipophilic drugs. For two-component systems, MCMDG was mixed with various masses of water. For three-component systems, the samples were prepared by mixing propylene glycol or glycerol formal or short-chain alcohols with MCMDG prior to the addition of water. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. Solubilities of levamisole phosphate (hydrophilic) and abamectin (lipophilic) were determined in the isotropic formulations using high-performance liquid chromatography assay. The isotropic region in the two-component systems had a water content of up to 18% at 25 degrees C. Solvents such as propylene glycol (PG), glycerol formal (FG), and ethyl alcohol increased the isotropic region. The area of isotropic region in these three-component systems increased with increasing temperature. The area of the isotropic region became larger with decreasing dielectric constant and solubility parameter of the series of short-chain alcohols, except n-butyl alcohol, at 25 degrees C. The systems exhibited Newtonian behavior. The solubility of both hydrophilic and lipophilic drugs was high in formulations at 25 degrees C. It was concluded that more water was solubilized in MCMDG/short-chain alcohols/water systems, and the isotropic region in the short-chain alcohol systems enlarged compared with MCMDG/PG/water or MCMDG/GF/water systems, except the n-butyl alcohol system. Hydrophilic and lipophilic drugs solubilize in the systems. The isotropic formulations containing MCMDG may represent an alternative to more traditional formulations for injectable formulations containing both lipophilic and hydrophilic drugs.


Bioinspired ketoprofen-incorporated polyvinylpyrrolidone/polyallylamine/ polydopamine hydrophilic pressure-sensitive adhesives patches with improved adhesive performance for transdermal drug delivery.
Inspired by the natural mussel adhesive mechanism, three different materials-polydopamine (PDA), polyvinylpyrrolidone (PVP), and polyallylamine (PAM)-were used to make innovative pressure-sensitive adhesives (PSAs) for transdermal delivery of ketoprofen. PDA was synthesized under alkaline conditions using a self-polymerization reaction and was exploited as a cross-linking agent due to its biocompatibility. The adhesive performance, physicochemical properties, drug content, and drug permeation through the skin were examined. Moreover, in vivo skin irritation and skin adhesion performance were investigated. PVP/PAM/PDA PSAs showed a significantly higher adhesion to human skin compared with commercial patches owing to the interaction between the catechol groups presented on the patches and the skin. In addition, the patches were stable for six months. Consequently, the PVP/PAM/PDA patches exhibited outstanding tissue adhesiveness, enabling universal tissue adherence while causing no skin tissue irritation or inflammatory reaction.


Magnetic solid phase extraction sorbents using methyl-parathion and quinalphos dual-template imprinted polymers coupled with GC-MS for class-selective extraction of twelve organophosphorus pesticides.
A novel magnetic dual-template molecularly imprinted polymer (DMIP) was prepared with methyl-parathion and quinalphos as templates. For comparison, a series of single-template polymers with only methyl-parathion (MPMIP) or quinalphos (QPMIP) as template as well as a non-imprinted polymer (NIP) in the absence of the template, were synthesized using the same procedure of DMIP. The obtained MIPs were characterized by scanning electron microscopy(SEM), Fourier transform infrared (FT-IR) spectroscopy, vibrating sample magnetometer (VSM), and X-ray diffraction (XRD). The properties including kinetic effect, thermodynamic effect, selectivity, and reusability of MIPs were investigated . Only DMIP possessed high affinity and good recognition for all twelve OPPs including quinalphos, isazophos, chlorpyrifos-methyl, chlorpyrifos, methidathion, triazophos, profenofos, fenthion, fenitrothion, methyl-parathion, parathion, and paraoxon in comparison to MPMIP, QPMIP, or NIP. Moreover, DMIP was used as magnetic solid phase extraction (MSPE) sorbent for the pre-concentration of twelve OPPs in cabbage samples. The developed DMIP-MSPE-GC-MS method showed high sensitivity, low LODs (1.62-13.9 ng/g), fast adsorption equilibrium (10 min), and acceptable spiked recoveries (81.5-113.4%) with relative standard deviations (RSD) in the range 0.05-7.0% (n = 3). The calibration plots were linear in the range 10-800 ng/mL with coefficients of determination (R2) better 0.99 for all twelve compounds. These results suggest that the DMIP is applicable for rapid determination and high throughput analysis of multi-pesticide residues. Graphical abstract.


Structural and functional basis of mammalian microRNA biogenesis by Dicer.
MicroRNA (miRNA) and RNA interference (RNAi) pathways rely on small RNAs produced by Dicer endonucleases. Mammalian Dicer primarily supports the essential gene-regulating miRNA pathway, but how it is specifically adapted to miRNA biogenesis is unknown. We show that the adaptation entails a unique structural role of Dicer's DExD/H helicase domain. Although mice tolerate loss of its putative ATPase function, the complete absence of the domain is lethal because it assures high-fidelity miRNA biogenesis. Structures of murine Dicer•-miRNA precursor complexes revealed that the DExD/H domain has a helicase-unrelated structural function. It locks Dicer in a closed state, which facilitates miRNA precursor selection. Transition to a cleavage-competent open state is stimulated by Dicer-binding protein TARBP2. Absence of the DExD/H domain or its mutations unlocks the closed state, reduces substrate selectivity, and activates RNAi. Thus, the DExD/H domain structurally contributes to mammalian miRNA biogenesis and underlies mechanistical partitioning of miRNA and RNAi pathways.


Shear-induced release of disabled herpes simplex virus from baby-hamster kidney cells.
A new process route is proposed to increase the production yield of disabled herpes simplex virus type 1 (HSV-1 DIS). Infected baby-hamster kidney (BHK) cells were subjected to a range of shear rates between 3.69 x 10(3) s(-1) and 51.3 x 10(3) s(-1) in the gap between a pair of co-axial cylinders. Analysis of the supernatant fractions of sheared material established that optimal virus release was achieved by exposing the infected cells to a shear rate of 42.7 x 10(3) s(-1) for a period of 1 min. Compared with the current laboratory process, the titre of HSV-1 DIS was increased over 30-fold, from about 1 x 10(6) to 30 x 10(6) pfu (plaque-forming units)/ml. Evaluation of the supernatant fractions by flow cytometry, total protein assay, PAGE and dot-blot assays showed no evidence of cell disruption, supporting the hypothesis that shear-induced release of the cell-membrane-bound virus was achieved without compromising downstream purification. The proposed method is scalable, and since no additional chemicals are required, it provides an attractive option for enhanced recovery of virus particles for therapeutic applications.


Reduced aortic elastic properties in a child with Takayasu arteritis: case report and literature review.
Takayasu arteritis (TA) is a chronic inflammatory vasculitis of the aorta and its major branches with a very low incidence in Europe and North America. Our objective was to determine the elastic properties of the affected ascending and descending aortic walls non-invasively in a 14-year-old Iraqi girl with a 3-year history of fever, fatigue, malaise and diffuse pain. Ultrasound and magnetic resonance angiography showed marked thickening of the aortic wall, dilatation of the aortic arch, and decreased luminal diameters of the abdominal aorta and both subclavian arteries, consistent with TA. Ascending and descending aortic elastic properties such as distensibility and stiffness index were markedly reduced compared to a group of healthy controls (n=39): ascending aortic distensibility was 20 kPa(-1) x 10(-3) versus 63+/-23 kPa(-1) x 10(-3) in controls, and the ascending aortic stiffness index 9.6 versus 3.5+/-1.3 in controls. Although the patient's general condition improved rapidly on oral prednisolone and azathioprine and inflammatory parameters normalised within 3 weeks, the aortic elastic parameters did not change during the first 2 weeks of anti-inflammatory treatment. Unfortunately, no further follow-up was possible. In patients with Takayasu arteritis, non-invasive quantification of reduced aortic elastic properties can help to assess aortic involvement, and possibly to follow disease activity and vascular response to therapy.


Parochial prosocial religions: Historical and contemporary evidence for a cultural evolutionary process.
In our response to the 27 commentaries, we refine the theoretical claims, clarify several misconceptions of our framework, and explore substantial disagreements. In doing so, we (1) show that our framework accommodates multiple historical scenarios; (2) debate the historical evidence, particularly about "pre-Axial" religions; (3) offer important details about cultural evolutionary theory; (4) clarify the term prosociality; and (4) discuss proximal mechanisms. We review many interesting extensions, amplifications, and qualifications of our approach made by the commentators.


The scale of Nigeria's involvement in the trans-national illegal pangolin trade: Temporal and spatial patterns and the effectiveness of wildlife trade regulations.
The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) prohibits commercial trans-national trade in pangolin specimens. However, African pangolins are continually trafficked to Asia for traditional medicine, with Nigeria considered a key hub. Using reported Nigeria-linked pangolin seizure data and interviews with Nigerian law enforcement officials, we a) characterised Nigeria's involvement in global pangolin trafficking January 2010-September 2021, particularly observing trafficking trends after pangolin's CITES Appendix I listing; b) estimated the minimum number of pangolins whose scales are in Nigeria-linked seizures January 2010-September 2021, and; c) assessed ongoing efforts within Nigeria to curb pangolin trafficking. Nigeria-linked seizures involved 190,407 kg of pangolin derivatives (99.9% scales) from a minimum of 799,343 pangolins (95% confidence interval; 625,944-996,353) of four species (see caveats in Methods). All shipments confiscated in transit were destined for Asia, with a rapid increase in the mass of maritime shipments over time. Furthermore, stockpiling of pangolin derivatives for overseas shipment is perhaps a prominent trafficking model in Nigeria. Nigeria's law enforcement efforts improved from 2017, the same year Nigeria apparently began playing a hub role. The impact of pangolin's CITES Appendix I listing on pangolin trafficking was unclear, as the marked rise in seizures from 2017 when the listing became effective, coincided with improvements in Nigerian law enforcement efforts. COVID-19-induced travel restrictions likely reduced trafficking activities in 2020 but activities may have fully resumed in 2021. This study provides new information to inform effective enforcement and policy formulation efforts to protect African pangolins.


Nitrous oxide emissions from the oxidation tank of a pilot activated sludge plant.
This study discusses the results of the continuous monitoring of nitrous oxide emissions from the oxidation tank of a pilot conventional wastewater treatment plant. Nitrous oxide emissions from biological processes for nitrogen removal in wastewater treatment plants have drawn great attention over the last years, due to the high greenhouse effect. However, even if several studies have been carried out to quantify nitrous oxide emission rates from different types of treatment, quite wide ranges have been reported. Only grab samples or continuous measurements over limited periods were considered in previous studies, which can account for the wide variability of the obtained results. Through continuous monitoring over several months, our work tries to fill this gap of knowledge and get a deeper insight into nitrous oxide daily and weekly emission dynamics. Moreover, the influence of some operating conditions (sludge age, dissolved oxygen concentration in the oxidation tank, nitrogen load) was studied to determine good practices for wastewater treatment plant operation aiming at the reduction of nitrous oxide emissions. The dissolved oxygen set-point is shown to play a major role in nitrous oxide emissions. Low sludge ages and high nitrogen loads are responsible for higher emissions as well. An interesting pattern has been observed, with quite negligible emissions during most of the day and a peak with a bell-like shape in the morning in the hours of maximum nitrogen load in the plant, correlated to the ammonia and nitrite peaks in the tank.


High affinity dopamine reuptake inhibitors as potential cocaine antagonists: a strategy for drug development.
The addictive and euphorogenic effects of cocaine are thought to result primarily from inhibition of dopamine reuptake. Although the potency of cocaine-like drugs as inhibitors of DA reuptake is highly correlated with their potency as reinforcers in animals, several potent DA reuptake blockers (bupropion, nomifensine, benztropine, and mazindol) have not been reported to produce addiction or euphoria in humans. Based on these observations in humans, DA reuptake inhibitors are classified into two groups; type 1 blockers, which produce addiction and euphoria, and type 2 blockers, which do not. Given that type 1 and type 2 blockers act at the same site (the DA transporter), the author suggests that type 2 agents may antagonize the effects of cocaine, and might prove useful in the treatment of cocaine addiction.


Downregulating the canonical Wnt/β-catenin signaling pathway attenuates the susceptibility to autism-like phenotypes by decreasing oxidative stress.
Although a growing body of evidence supports the importance of the Wnt/β-catenin signaling pathway and oxidative stress in the pathogenesis of autism, it is unclear whether a relationship exists between the Wnt/β-catenin pathway and oxidative homeostasis. The present study examines the effects of sulindac, a small molecule inhibitor of the Wnt/β-catenin signaling pathway, on the oxidative status of rats that are prenatally exposed to valproic acid (VPA), which is used in an animal model of autism. Our data show that sulindac treatment downregulated the canonical Wnt/β-catenin signaling pathway by enhancing the expression of Glycogen Synthase Kinase 3β and attenuating the expression of β-catenin in comparison to levels in VPA-treated rats. Concomitantly, a marker of lipid peroxidation, 4-hydroxynonenal, was reduced as well. Sulindac treatment ameliorated the pain threshold, repetitive/stereotypic activity, learning and memory abilities and behavioral abnormalities of rats in our autism model. Our working model suggests that the upregulation of the Wnt/β-catenin signaling pathway induced by VPA administration during early pregnancy produces an imbalance of oxidative homeostasis that facilitates susceptibility to autism. This information may be instrumental in designing appropriate therapeutic regimens with small molecule inhibitors of the Wnt/β-catenin pathway for the treatment of autism-like behavioral phenotypes.


How much segmentation is needed in the health care marketplace? An exploratory study of HMO and non-HMO customers.
The health care landscape has changed dramatically. Consumers now seek plans whose benefits better fit their health care needs and desires for access to providers. This exploratory survey of more than 1,000 HMO and non-HMO customers found significant differences with respect to their selection processes for health plans and providers, and their expectations regarding access to and communication with health care providers. While there are some similarities in factors affecting choice, segmentation strategies are necessary to maximize the appeal of a plan, satisfy customers in the selection of physicians, and meet their expectations regarding access to those physicians.


Origin of Dryopteris shibipedis (Dryopteridaceae), a fern species extinct in the wild.
Dryopteris shibipedis was once treated as an extinct species in the Red List (2007) by the Japanese Ministry of the Environment, but 'rediscovered' in the Tsukuba Botanical Garden. To clarify its origin, using 'overlooked' cultivated stocks we analyzed nuclear PgiC intron sequences. As the PgiC genotype of D. shibipedis can be explained by a combination of alleles of D. kinkiensis and those of D. pacifica, the hypothesis of hybrid origin of the species is supported.


Open supracondylar femur fractures with bone loss in the polytraumatized patient - Timing is everything!
Open supracondylar femur fractures are rare, complex injuries which occur in polytrauma patients and are complicated by bone loss, contamination, compromised soft tissues, and poor host condition. The purpose of this study is to demonstrate a successful treatment protocol for these challenging injuries. A consecutive series of 15 open supracondylar femur fractures in 14 polytrauma patients (ages 16-75, mean 41) were treated at one Level I trauma centre by a single surgeon. Fracture patterns included seven AO/OTA Type C2 and eight Type C3 fractures. All fractures were open and classified by Gustillo/Anderson as type IIIA (10 fractures) and type IIIB (five fractures). Stage I was performed within 24h and included thorough open fracture care and early definitive fixation with a laterally based locking device and antibiotic bead placement. Stage II was performed several months later (average 3.6 months) when the soft tissue envelope had revascularized and the polytrauma patient had recovered from their other injuries. Stage II consisted of either an anterior incision or subvastus approach to the distal femur, bone grafting, BMP application, and addition of medial column support to create rigid fixation. All fractures (15/15) healed uneventfully. Union was determined by absence of pain and radiographic union in 3/4 cortices. Mean time to union was 4 months. There were no deep infections and alignment was maintained (average tibiofemoral angel of 5° of valgus) although several limbs were complicated by knee stiffness. Healing of open supracondylar femur fractures with critical sized bone defects requires diligent surgical timing in order to optimise the host and wound bed. Thorough initial debridement and early definitive fixation halt ongoing soft tissue injury, restores length and alignment, and allow for sterilisation of the wound. After patients have recovered from their other injuries and the soft tissue sleeve has revascularized, bone grafting with BMP supplementation and medial column plating allows for rigid fixation of the femur and offers the biology these fracture patterns require for successful union without infection.


Bovine leukemia virus detection in humans: A systematic review and meta-analysis.
To review the available studies on the frequency of detection of the bovine leukemia virus in human samples, a systematic review with meta-analysis of the scientific literature was carried out, including papers published in English, Spanish, and Portuguese in 5 multidisciplinary databases. We collected information from different populations following a detailed and reproducible search protocol in which two researchers verified the inclusion and exclusion criteria. We identified 759 articles, of which only 33 met the inclusion criteria. Analyzed studies reported that the presence of the virus was measured in human samples, such as paraffin-embedded breast tissue and peripheral blood from 10,398 individuals, through serological and molecular techniques. An overall virus frequency of 27% (Ranging between 17 and 37%) was observed, with a high-frequency data heterogeneity between studies. The presence of this virus in different human biological samples suggests the need to investigate further its transmission route to humans and its potential role in developing and progressing diseases.


Isolation and characterization of the unusual lipopolysaccharide component, 2-amino-2-deoxy-2-N-(27-hydroxyoctacosanoyl)-3-O-(3-hydroxy- tetradecanoyl)-gluco-hexuronic acid, and its de-O-acylation product from the free lipid A of Rhizobium trifolii ANU843.
Two new, unusual lipid A components have been isolated and characterized from the free lipid A of Rhizobium trifolii ANU843. 2-Amino-2-deoxy-2-N-(27-hydroxyoctacosanoyl)-3-O-(3-hydroxy- tetradecanoyl)-gluco-hexuronic acid and its de-O-acylation product were purified from the chloroform/methanol extract of a mild acid hydrolysate of the lipopolysaccharide by chromatography on C18 reverse-phase columns and layers. The compositions of the two compounds were determined by releasing the acyl components by exhaustive acid-catalyzed methanolysis and identifying them as their methyl esters by gas chromatography and gas chromatography/mass spectrometry. The sugar component was identified by converting it to the alditol acetate derivative of glucosamine in a two-step reduction and identifying it as such by gas chromatography/mass spectrometry. The linkages of the fatty acyl components to the sugar residue and the configuration of the sugar component was confirmed by 1H and 13C NMR spectroscopy. The complete structures of the two compounds were further confirmed by fast atom bombardment mass spectrometry. It is still unsure whether the de-O-acylated derivative was formed from the di-acyl compound by de-O-acylation during acid hydrolysis. These structures represent the first report of 2-amino-2-deoxy-gluco-hexuronic acid in the free lipid A of a Gram-negative bacterium and confirms our earlier contention (Hollingsworth, R.I., and Carlson, R. W. (1989) J. Biol. Chem. 264, 9000-9303) of the involvement of 27-hydroxyoctacosanoic acid in the structure of the lipopolysaccharide of Rhizobium trifolii ANU843.


Sagittal craniosynostosis, Dandy-Walker malformation, and hydrocephalus: a unique multiple malformation syndrome.
The Dandy-Walker malformation and craniosynostosis have each been described as isolated occurrences and as components of multiple malformation syndromes. The purpose of this report is to delineate the characteristics of a multiple malformation syndrome of Dandy-Walker malformation and sagittal craniosynostosis. The inheritance pattern appears to be autosomal dominant.