Pancreaticogastrostomy as a fistula mitigating strategy for a high-risk pancreatic anastomosis following pancreaticoduodenectomy.
Clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) has been associated with soft gland texture and/or small pancreatic duct. We hypothesized that selective use of pancreaticogastrostomy (PG) over pancreaticojejunostomy (PJ) in those scenarios would decrease the rate of CR-POPF. Review of prospective database of all PD's performed at a single institution between 2009 and 2019 was performed. The pancreatic remnant was deemed "high risk" if soft gland and/or small duct were present. PJ was performed in 199 (147 "low-risk" and 52 "high-risk") cases, and 110 patients (all "high-risk") had a PG. Overall CR-POPF rate was 11.9% with no difference between the groups. Risk-stratified analysis within PJ group showed CR-POPF rate of 5.4% versus 36% in "low-risk" versus "high risk" scenarios, respectively; the use of PG significantly decreased CR-POPF rate (9.1%, p < 0.0001). Gastrointestinal bleeding was more likely to occur following PG than PJ. Soft gland texture and gastrointestinal bleeding were the strongest predictors of CR-POPF in PJ and PG groups, respectively. Selective use of PG after PD in "high-risk" scenarios mitigates the risk of CR-POPF. Increased rate of gastrointestinal bleeding calls for further refinement of the technique and heightened postoperative vigilance.


Human chorionic gonadotropin--like material: presence in normal human tissues.
With the use of radioreceptor assay for gonadotropin and a beta-chain radioimmunoassay for human chorionic gonadotropin (hCG), we have been able to demonstrate the presence of hCG-like material in all normal human tissues tested. This activity was completely absorbed by a hCHG-antibody affinity column and was demonstrated to have altered carbohydrate content by studies showing this material did not bind to concanavalin A (con A)-Sepharose affinity columns. In identical studies greater than 90% of placental hCG was bound to con A. However, if placental hCG is rendered carbohydrate free it also does not bind to con A. It is known that carbohydrate-free hCG is cleared rapidly from the circulation and thus possesses little or no biological potency in vivo. Accordingly, we hypothesize: (1) that this hCG-like material in normal tissues has the protein structure of hCG but does not possess the carbohydrate moieties of placental hCG and probably has little or no bioactivity in vivo and (2) that the trophoblastic cell is not unique in its ability to synthesize hCG but has developed the ability to glycosylate hCG, transforming a ubiquitous cellular protein into a hormone, hCG might better be called human cellular gonadotropin.


Glomerular lesions in benign essential hypertension. A study of eight biopsy specimens with laboratory evidence suggestive of glomerular abnormalities.
We performed renal biopsies on eight patients who had benign essential hypertension but laboratory abnormalities suggestive of glomerulonephritis. Persistent microscopic hematuria was detected in four patients, proteinuria in five, RBC casts in two, and decreased glomerular filtration in seven. In all eight biopsy specimens, we detected hyaline arterionephrosclerosis, focal glomerular obsolescence, and segmental, afibrillar thickening of glomerular basement membranes. Direct immunofluorescence studies performed on all eight samples were negative for immunoglobulins, complement, and fibrinogen. Although the patients in our study had laboratory findings suggestive of glomerulonephritis, the morphologic changes were indicative of benign essential hypertension.


Focused and divided attention in each half of space with disconnected hemispheres.
The effects of spatial location and strategy of attention on the processing of speech messages were investigated in ten right-handed subjects and four persons with complete forebrain commissurotomy and one case of right hemispherectomy. Lists of simultaneous but different words, with one of each pair spoken by a male and the other by a female, were monitored for target words. The lists were presented to the left ear, the right ear and to both ears (central) in separate conditions. Unimanual responses were made to targets in either voice (divided attention) or to only one of the voices (focused attention). The performance of the clinical subjects was generally less efficient than that of the controls. In contrast to intact subjects, they responded to more distractor and unattended items. They also showed a nonsignificant tendency for better processing of right rather than centrally-presented words. With right-sided presentation two clinical subjects, with extracallosal damage to the right cortex, were unable to divide attention and responded to only one of the voices. These results implicate an intact corpus callosum for efficient use of attention strategies as well as hemispheric differences in the control of attention.


Internal validity of the physical activity index over 26 years in middle-aged and older men.
To determine the internal validity of the physical activity index (PAI). Three time periods over a 26-year period (1965/68 examination, n = 7911; 1980/82 examination, n = 2054; 1991/93 examination, n = 3425). Honolulu, Hawaii. Middle-aged to older Japanese-American men. PAI, other physical activity measures, body mass index (BMI), tricep skinfold thickness, subscapular skinfold thickness, and HDL cholesterol. PAI levels was associated significantly with levels of other physical activity measures at all time periods. Higher PAI level was associated with lower BMI at the baseline examination (1965/68), lower subscapular skinfold thickness at the 1965/68 and 1980/82 examinations, lower tricep skinfold thickness at all examinations, and higher HDL cholesterol at the 1980/82 examination. Change in PAI level from 1965/68 to 1980/82 was associated with change in BMI, subscapular, and tricep skinfold thickness levels, but there were no significant associations between change in PAI level and change in BMI, skinfold thicknesses, or HDL cholesterol levels from 1980/82 to 1991/93. PAI level is a relatively valid estimate of overall daily energy expenditure that may be an acceptable general measure across the middle-to-late stages of life. The PAI may also be sensitive enough to discern a shift toward less physical demanding activities as a population becomes older, although further studies should be conducted to better determine its validity in older populations.


Chronic pancreatitis and pseudocyst formation secondary to carcinoid tumor of the pancreas.
The incidence of chronic pancreatitis has been increasing in the western world. Although chronic alcohol abuse accounts for 90% of adult cases, the physician must be aware of the multiplicity of causes for chronic pancreatitis. We present a case of obstruction of the pancreatic duct and chronic pancreatitis caused by a primary carcinoid tumor.


Latent shape image learning via disentangled representation for cross-sequence image registration and segmentation.
Cross-sequence magnetic resonance image (MRI) registration and segmentation are two essential steps in a variety of medical image analysis tasks. And have attracted considerable research interest. However, they remain challenging due to domain shifts between different sequences. This study is aiming at proposing a novel method via disentangled representations, latent shape image learning (LSIL), for cross-sequence image registration and segmentation. Images from different sequences were firstly decomposed into a shared domain-invariant shape space and a domain-specific appearance space via an unsupervised image-to-image translation approach. A latent shape image learning model is then built on the disentangled shape representations to generate latent shape images. A series of experiments including cross-sequence image registration and segmentation were performed to qualitatively and quantitatively verify the validity of our method. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were adopted as our evaluation metrics. The performance of our method was evaluated based on 2 datasets total of 50 MRIs. The experimental results showed the superiority of the proposed framework over the state-of-the-art cross-sequence registration and segmentation approaches. The proposed method shows the mean DSCs of 0.711 and 0.867, respectively, in cross-sequence registration and segmentation. We proposed a novel method based on representation disentangling to solve the cross-sequence registration and segmentation problem. Experimental results prove the feasibility and generalization of the generated latent shape images. The proposed method demonstrates significant potential for use in clinical environments of missing sequences. The source code is available at https://github.com/wujiong-hub/LSIL .


Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis.
Pathogenic muscle-specific tyrosine kinase (MuSK)-specific IgG4 autoantibodies in autoimmune myasthenia gravis (MG) are functionally monovalent as a result of Fab-arm exchange. The development of these unique autoantibodies is not well understood. We examined MG patient-derived monoclonal autoantibodies (mAbs), their corresponding germline-encoded unmutated common ancestors (UCAs), and monovalent antigen-binding fragments (Fabs) to investigate how affinity maturation contributes to binding and immunopathology. Mature mAbs, UCA mAbs, and mature monovalent Fabs bound to MuSK and demonstrated pathogenic capacity. However, monovalent UCA Fabs bound to MuSK but did not have measurable pathogenic capacity. Affinity of the UCA Fabs for MuSK was 100-fold lower than the subnanomolar affinity of the mature Fabs. Crystal structures of two Fabs revealed how mutations acquired during affinity maturation may contribute to increased MuSK-binding affinity. These findings indicate that the autoantigen drives autoimmunity in MuSK MG through the accumulation of somatic mutations such that monovalent IgG4 Fab-arm-exchanged autoantibodies reach a high-affinity threshold required for pathogenic capacity.


Hyaluronan interactions with cationic surfactants - Insights from fluorescence resonance energy transfer and anisotropy techniques.
Interactions of hyaluronan with micelles formed by cationic surfactants were studied by the time-resolved measurement of fluorescence resonance energy transfer (FRET) using perylene and fluorescein as probes. Two surfactants were studied - Cetyltrimethylammonium bromide (CTAB) and Septonex. In pure micellar solutions, the same values of FRET efficiency were found for both surfactants, but values for the binding of the probe pair were lower for Septonex micelles than in the case of CTAB. This was attributed to steric effects of the carbethoxy group in the Septonex polar head. Upon the addition of hyaluronan, decreased FRET efficiency and increased binding were detected in comparison with pure surfactants. To resolve the structure of the formed aggregates, steady state and time-resolved fluorescence anisotropy was employed as an additional technique. All results indicated that cationic micelles bind to hyaluronan forming a pearl necklace structure with micelles of smaller size compared to pure surfactant. Besides theoretical interest, the studied polyelectrolyte-surfactant system may be interesting for the formulation of drug delivery systems.


Succinate dehydrogenase activity in cultured human skin fibroblasts and amniotic fluid cells. A methodological study.
Through a methodological evaluation, reliable histochemical and biochemical methods for succinate dehydrogenase activity in cultured human skin fibroblasts and amniotic fluid cells were developed. The histochemical method includes a cleaning of the cultured cells in 1 mM malonate in 0.9% NaCl, air-drying and fixation in acetone (5 min at -20 degrees C), coating of cells with CoQ10 (0.2 mg/ml in ether/acetone) and incubation for 1 h at 37 degrees C in 50 mM succinate and 0.5 mg/ml Nitro BT in 200 mM phosphate buffer, pH 7.6 PMS as an intermediate electron carrier was found inferior to exogenous CoQ10. Both types of cells exhibit equal activity. In the biochemical method homogenizing was performed in 50 mM Tris-HCl buffer, pH 7.5, and 200 mM sucrose. The standard incubation was 2.0 mM INT and 10 mM succinate in 10 mM Tris-HCl buffer, pH 7.5 for 1 h at 37 degrees C. The apparent Km values for INT and succinate were estimated to 0.39 mM and 0.13 mM, respectively, while I0.5 for malonate was 0.46 mM. Activity in amniotic fluid cells was 18.1 pkat/mg protein and in human skin fibroblasts 20.3 pkat/mg protein. Specificity of the methods was tested by use of a Chinese hamster fibroblast strain B9 known to be succinate dehydrogenase deficient in addition to various control experiments. Congruent results were obtained with the two methods.


CCK and GLP-1 response on enteroendocrine cells of semi-dynamic digests of hydrolyzed and intact casein.
A semi-dynamic gastrointestinal device was employed to explore the link between protein structure and metabolic response upon digestion for two different substrates, a casein hydrolysate and the precursor micellar casein. As expected, casein formed a firm coagulum that remained until the end of the gastric phase while the hydrolysate did not develop any visible aggregate. Each gastric emptying point was subjected to a static intestinal phase where the peptide and amino acid composition changed drastically from that found during the gastric phase. Gastrointestinal digests from the hydrolysate were characterized by a high abundancy of resistant peptides and free amino acids. Although all gastric and intestinal digests from both substrates induced the secretion of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in STC-1 cells, GLP-1 levels were maximum in response to gastrointestinal digests from the hydrolysate. The enrichment of protein ingredients with gastric-resistant peptides by enzymatic hydrolysis is proposed as strategy to deliver protein stimuli to the distal gastrointestinal tract to control food intake or type 2 diabetes.


The impact of primary Gleason grade on biochemical outcome following brachytherapy for hormone-naive Gleason score 7 prostate cancer.
Although the perception exists that biochemical outcome in patients with a Gleason score of 7 with dominant pattern 4 histology is inferior to that of patients with a Gleason score of 7 with a primary Gleason grade of 3, conflicting conclusions have been reported for radical prostatectomy and brachytherapy. In this study, we evaluate the effect of the dominant histologic pattern in Gleason score 7 prostate cancer on biochemical progression-free survival after brachytherapy. Between April 1995 and October 2001, 273 consecutive patients underwent permanent interstitial brachytherapy without androgen deprivation therapy for clinical T1c-T3a NxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathological lymph node staging. All patients underwent brachytherapy more than 3 years before analysis. Biochemical progression-free survival was defined by a prostate specific antigen (PSA) cut point < or = 0.4 ng/mL after nadir or by the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition. The median follow-up was 4.7 years. Clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included primary Gleason grade; clinical T stage; pretreatment PSA level; risk group; percent positive biopsy results; perineural invasion; patient age; isotope; supplemental external-beam radiation therapy; prostate volume; brachytherapy planning volume; percent of the target volume receiving 100%, 150%, and 200% of the prescribed dose (V100/150/200); minimum percent of the prescribed dose covering 90% of the target volume (D90); tobacco consumption; hypertension; and diabetes. For the entire cohort, the actuarial 8-year biochemical progression-free survival rate was 94.5% and 94.8% using a PSA cut point < or = 0.4 ng/mL after nadir and the ASTRO consensus definition, respectively. For biochemically disease free patients, the median posttreatment PSA level was < 0.1 ng/mL. When the group was stratified by the dominant histologic pattern, no statistical difference in outcome was noted for any of the evaluated parameters. In forward conditional Cox regression analysis, pretreatment PSA level and percent positive biopsy results were statistically significant predictors of biochemical outcome. In hormone-naive patients with a Gleason score of 7, prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival and is independent of Gleason 3 + 4 versus 4 + 3 histology.


Patient Coded Severity and Payment Penalties Under the Hospital Readmissions Reduction Program: A Machine Learning Approach.
The objective of this study was to examine variation in hospital responses to the Centers for Medicare and Medicaid's expansion of allowable secondary diagnoses in January 2011 and its association with financial penalties under the Hospital Readmission Reduction Program (HRRP). Medicare administrative claims for discharges between July 2008 and June 2011 (N=3102 hospitals). We examined hospital variation in response to the expansion of secondary diagnoses by describing changes in comorbidity coding before and after the policy change. We used random forest machine learning regression to examine hospital characteristics associated with coded severity. We then used a 2-part model to assess whether variation in coded severity was associated with readmission penalties. Changes in severity coding varied considerably across hospitals. Random forest models indicated that greater baseline levels of condition categories, case-mix index, and hospital size were associated with larger changes in condition categories. Hospital coding of an additional condition category was associated with a nonsignificant 3.8 percentage point increase in the probability for penalties under the HRRP (SE=2.2) and a nonsignificant 0.016 percentage point increase in penalty amount (SE=0.016). Changes in patient coded severity did not affect readmission penalties.


55 years together-our life with yeasts.
The authors look back at their life together in yeast research, the influences that shaped it, certain challenges and changes in laboratory and funding policies.


Biocompatibility evaluation of tissue-engineered decellularized scaffolds for biomedical application.
Biomaterials based on seeding of cells on decellularized scaffolds have gained increasing interest in the last few years and suggested to serve as an alternative approach to bioengineer artificial organs and tissues for transplantation. The reaction of the host toward the decellularized scaffold and transplanted cells depends on the biocompatibility of the construct. Before proceeding to the clinical application step of decellularized scaffolds, it is greatly important to apply a number of biocompatibility tests in vitro and in vivo. This review describes the different methodology involved in cytotoxicity, pathogenicity, immunogenicity and biodegradability testing for evaluating the biocompatibility of various decellularized matrices obtained from human or animals.


[Cytokine assays for pterygium].
To study the roles of tumor necrosis factor (TNF-alpha) and platelet-derived growth factor (PDGF) in pathogenesis of pterygium. Radioimmunoassay and bioactivity assay were used to measure the levels of TNF-alpha and PDGF in tissue culture supernatant of pterygium specimens obtained from 30 patients. The levels of TNF-alpha and PDGF in tissue culture supernatant of pterygium were significantly higher than that of normal conjunctival specimens (t = 2.827, P < 0.01; t = 3.011, P < 0.01), and there was a significant difference between progressive and quiescent cases (t = 2.374, P < 0.05; t = 2.712, P < 0.05). The abnormal secretion of TNF-alpha and PDGF may be related to the pathogenesis of pterygium.


Diarylheptanoids/sorafenib as a potential anticancer combination against hepatocellular carcinoma: the p53/MMP9 axis of action.
Hepatocellular carcinoma (HCC) is a serious and potentially fatal form of cancer associated with liver damage. New anticancer drugs are increasingly needed due to the increasing number of cancer cases every year. In this study, diarylheptanoids (DAH) from Alpinia officinarum were examined for their antitumor activity against DAB-induced HCC in mice, as well as their ability to reduce liver damage. Assays for cytotoxicity were conducted using MTT. The DAB-induced HCC Swiss albino male mice were given DAH and sorafenib (SOR) either as single treatments or in combination, and the effects on tumour development and progression were monitored. Malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were evaluated along with biomarkers of liver enzymes (AST, ALT, and GGT). The apoptosis-related gene (CASP8), the apoptosis-related gene (p53), the anti-inflammatory genes (IL-6), the migration-related gene matrix metalloprotease-9 (MMP9), and the angiogenesis-related gene vascular endothelial growth factor (VEGF) were assessed using qRT-PCR in the hepatic tissue. As a final step, DAH and SOR were docked with CASP8 and MMP9 via molecular docking to propose potential mechanisms of action. Our results revealed that the combination of DAH and SOR has a potent inhibitory effect on the growth and viability of the HepG2 cell line. The outcomes demonstrated that DAH and SOR-treated HCC-bearing mice displayed a reduction in the tumour burden and liver damage as demonstrated by (1) parameters of repaired liver function; (2) low levels of hepatic MDA; (3) elevated levels of hepatic T-SOD; (4) p53, IL-6, CASP8, MMP9, and VEGF downregulation; and (5) enhanced hepatic structure. The best results were revealed in mice that were co-treated with DAH (given orally) and SOR (given intraperitoneally). The docking study also proposed that both DAH and SOR could inhibit CASP8 and MMP9's oncogenic activities and had a high affinity for these enzymes. In conclusion, according to study findings, DAH enhances SOR antiproliferative and cytotoxic effects and identifies their molecular targets. Furthermore, the results revealed that DAH was able to boost the anticancer effects of the drug SOR and reduce liver damage caused by HCC in mice. This suggests that DAH could be a potential therapeutic agent against liver cancer.


Skin simulators for dermatological procedures.
A variety of skin simulators are available on which to practice procedures; however, choice of a suboptimal substitute compromises realism and productive practice. Skin simulators for basic dermatological procedures are reviewed. The authors' anecdotal experience with various skin simulators for different procedures is shared. The following simulators are suggested: an unripe banana for elliptical excision, pork belly for undermining, pork belly for simple interrupted and buried suture, capped needle on a human shoulder for intramuscular injection, ripe tomato or hotdog with skin for intradermal injection, eggplant for shave biopsy, pork belly for punch biopsy, plastic tape over a dark surface for cryosurgery, and beef liver for electrosurgery. Flaps are best practiced with foam sandwiched between foam tape or artificial anatomical models created specifically for this purpose. The utility of one simulator over another was not compared in a controlled study. Efficient, realistic skin simulators are readily available for practice, which should enhance the safety of the practitioner and improve outcomes of novices.


Human exposure to metals in consumer-focused fused filament fabrication (FFF)/ 3D printing processes.
Fused filament fabrication (FFF) or 3D printing is a growing technology used in industry, cottage industry and for consumer applications. Low-cost 3D printing devices have become increasingly popular among children and teens. Consequently, 3D printers are increasingly common in households, schools, and libraries. Because the operation of 3D printers is associated with the release of inhalable particles and volatile organic compounds (VOCs), there are concerns of possible health implications, particularly for use in schools and residential environments that may not have adequate ventilation such as classrooms bedrooms and garages, etc. Along with the growing consumer market for low-cost printers and printer pens, there is also an expanding market for a range of specialty filaments with additives such as inorganic colorants, metal particles and nanomaterials as well as metal-containing flame retardants, antioxidants, heat stabilizers and catalysts. Inhalation of particulate-associated metals may represent a health risk depending on both the metal and internal dose to the respiratory tract. Little has been reported, however, about the presence, speciation, and source of metals in the emissions; or likewise the effect of metals on emission processes and toxicological implications of these 3D printer generated emissions. This report evaluates various issues including the following: metals in feedstock with a focus on filament characteristics and function of metals; the effect of metals on the emissions and metals detected in emissions; printer emissions, particle formation, transport, and transformation; exposure and translation to internal dose; and potential toxicity on inhaled dose. Finally, data gaps and potential areas of future research are discussed within these contexts.


[Nystagmus. Clinical characteristics and therapeutic options].
This article presents an overview of the pathophysiology of nystagmus and the differential diagnostics of congenital and acquired nystagmus. In addition, the principles of conservative, surgical and pharmacotherapy treatment options are described. The pathophysiological basis of nystagmus deepens the understanding of the etiology of the individual forms of nystagmus. The therapeutic approach to calming of nystagmus aims at an extension of the foveation time, which has the most significant impact on visual acuity. In congenital nystagmus this can be carried out by optimization of the retinal image, prisms or by bilateral surgical muscle repositioning to use the phenomenon of a null or neutral zone. In acquired nystagmus the off-label use of centrally acting medications can sometimes be helpful to calm the nystagmus and the associated oscillopsia.


BOLD Response is more than just magnitude: Improving detection sensitivity through capturing hemodynamic profiles.
Typical fMRI analyses often assume a canonical hemodynamic response function (HRF) that primarily focuses on the peak height of the overshoot, neglecting other morphological aspects. Consequently, reported analyses often reduce the overall response curve to a single scalar value. In this study, we take a data-driven approach to HRF estimation at the whole-brain voxel level, without assuming a response profile at the individual level. We then employ a roughness penalty at the population level to estimate the response curve, aiming to enhance predictive accuracy, inferential efficiency, and cross-study reproducibility. By examining a fast event-related FMRI dataset, we demonstrate the shortcomings and information loss associated with adopting the canonical approach. Furthermore, we address the following key questions: 1) To what extent does the HRF shape vary across different regions, conditions, and participant groups? 2) Does the data-driven approach improve detection sensitivity compared to the canonical approach? 3) Can analyzing the HRF shape help validate the presence of an effect in conjunction with statistical evidence? 4) Does analyzing the HRF shape offer evidence for whole-brain response during a simple task?


Response of Saos-2 osteoblast-like cells to laser surface texturing, sandblasting and hydroxyapatite coating on CoCrMo alloy surfaces.
Cobalt chrome alloys are commonly used in orthopaedic implants where high stiffness and wear resistance are required. This study proposes Laser Surface Texturing (LST) as a cost-effective mean for producing bioinspired surface textures in order to improve the performance of CoCrMo orthopaedic implants. Cobalt-chrome alloy disks were modified using three different LST strategies: i) micro-scale texturing using a nanosecond laser source; (ii) micro-scale texturing with an ultrashort laser source and (iii) bioinspired sub-micron scale texturing with an ultrashort laser source. The modified disks were characterized and compared to blasted, hydroxyapatite coated and polished surface finishes. Saos-2 osteoblast-like cells were seeded on the different surfaces and their proliferation and morphology was assessed. The laser modification increases the surface energy of the CoCrMo alloy disks when compared to their untreated counterparts. The bioinspired sub-micron textured surfaces exhibited the highest cell metabolic activity on day 7 of the MTT assay.


Periostin and bone marrow fibrosis.
Periostin is a secreted protein that shares structural homology with the insect axon guidance protein fasciclin 1. Periostin is expressed predominantly in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses. We have shown previously that periostin is a novel component of subepithelial fibrosis in bronchial asthma. Here, we investigated the relationship between periostin and bone marrow (BM) fibrosis. Periostin was expressed in the stroma and stromal cells of BM fibrosis specimens and to a great extent its expression levels correlated closely to the grade of fibrosis, as estimated by silver staining. However, in the present study, we found no relationship between plasma periostin levels and the extent of BM fibrosis. We also demonstrated that periostin is secreted by human BM hTERT stromal cells and that its secretion is enhanced by TGF-beta, a cytokine produced by clonal proliferation of megakaryocytes and/or monocytes. These results indicate that periostin is a component of BM fibrosis and that it may play a role in the disease progression.


[Management of sialorrhea in mentally retarded children by salivary denervation (6 cases) (author's transl)].
Sialorrhea in mentally handicapped children makes rehabilitation difficult and may provoke dyspneic spells. We have interrupted in 6 cases the parasympathetic innervation to the major salivary glands by a bilateral intratympanic neurectomy of Jacobson's nerve and chorda tympani. Results were satisfactory in 2/3 of cases.


The evolutionary history of the transposable element Penelope in the Drosophila virilis group of species.
We have used phylogenetic techniques to study the evolutionary history of the Penelope transposable element in the Drosophila virilis species group. Two divergent types of Penelope have been detected, one previously described, clade I, and a new one which we have termed clade III. The phylogeny of some copies of the Penelope clade I element was partially consistent with the species phylogeny of the D. montana subphylad, suggesting cospeciation and allowing the estimation of the evolutionary rate of Penelope. Divergence times of elements found in different species are younger than the age of the species, suggesting horizontal transfer events.


Working in health access programme (WHAP): initial results.
Academic achievement and social class are positively related and applications to medical schools reflect a class-based bias favouring middle-class candidates. Applying a measure that is class-free could be useful as an indicator of a potential good health professional may widen the pool of applicants. In the Working in Health Access Programme (WHAP), we report on the potential usefulness of such a measure. In addition, we describe a programme for raising awareness of higher education (HE) and careers in health care. Pupils attending schools with low HE participation rates sat a battery of psychometric tests assessing both cognitive and non-cognitive skills. A total of 2349 pupils sat the tests and 1000 of them took part in the subsequent activities. These pupils are being followed up and have obtained their Standard Grade (Year 11) examination results. Although social class influenced cognitive skills, it had no influence on non-cognitive abilities. Pupils with high levels of cognitive ability were found in all classes, including the most deprived. Both the testing and the awareness-raising programme were successful. Additional information was obtained on factors influencing the participants' choices of career. Psychometric assessment could act as an early indicator for identifying potential in young people. For pupils with both cognitive and non-cognitive attributes that might indicate they would be successful in veterinary or human medicine, appropriate advice regarding subject choices for school examinations and future careers could be provided.


Effect of guanidine on release of noradrenaline from the perfused spleen of the cat.
1 Guanidine increased noradrenaline (NA) output at 5 Hz by 3 to 6 fold, and doubled it at 30 Hz. Onset of maximum activity was slow, and reversal was also slow. Output of NA induced by potassium, sodium deprivation, or tyramine was not affected. 2 NA output was doubled at low concentrations (1 to 2 mM) of guanidine, but maximal effect was obtained at 4 mM. At 10 mM, spontaneous release was occasionally observed. 3 The effect of guanidine on NA release was related to the external calcium concentration. Outputs which previously have been shown to be insignificant at 5 Hz in 0.25 and 0.75 mM calcium-Krebs solution were markedly enhanced by guanidine. Guanidine enhanced release at all calcium concentrations up to 7.5 mM, but maximum output was obtained at 2.5 mM. 4 Guanidine had no effect on the recovery of intra-arterially infused NA. 5 The effects of guanidine and tetraethyl-ammonium (TEA) on NA release at 5 Hz were additive. 6 Guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 5 and 10 Hz, and the NA output increased nearly 2.5 fold after repeated stimulation of the nerves. Guanidine was less effective in reversing the inhibitory effects of guanethidine on NA release at 30 Hz. 7 Guanidine did not affect release of catecholamines (CA) from the perfused cat adrenal gland by splanchnic nerve stimulation. 8 It is suggested that guanidine enhances NA release partly by increasing the influx of calcium into the neurone during an action potential, and also by interfering with intracellular binding of calcium.


Systematic review with meta-analysis: outcomes of pregnancy in patients with autoimmune hepatitis.
Autoimmune hepatitis (AIH) is common in females of childbearing age. Although some studies have provided information about the outcomes of pregnancy, there remains uncertainty regarding conclusions. To comprehensively explore the interactions between pregnancy and AIH. Databases including PubMed, Embase, Cochrane Library and Science Citation Index Expanded were searched to collect available studies in relation to pregnancy in AIH patients (from inception to 28 August 2021). Pooled data were calculated using a random effects model with standardised mean difference (SMD), or risk ratio (RR), and 95% confidence intervals (CI). Twelve studies were considered eligible for meta-analysis. Data from 26 case reports/series were extracted for systematic review. AST level in AIH patients was significantly lower during pregnancy (SMD = -0.41, 95% CI = [-0.70, -0.12]; SMD = -1.60, 95% CI = [-2.76, -0.44]) and loss of biochemical remission occurred more frequently in post-partum (RR = 0.31, 95% CI = [0.19, 0.52]). Patients with portal hypertension or without established remission before conception presented as high-risk subgroups and the incidence of pre-term delivery was higher in these groups compared to other AIH patients (RR = 9, 95% CI = [1.22, 51.1]; RR = 0.05, 95% CI = [0.004, 0.38]). In population-based comparison, pre-term birth (RR = 2.45, 95% CI = [1.66, 3.62]) also occurred more often in AIH patients compared with the general population. Successful pregnancy is a reasonable expectation in AIH. However, hepatic biochemistry should be monitored closely in both the puerperium and the post-partum period. Though some patients may present higher risk, with carefully selected therapeutic manipulation and multi-disciplinary care, the majority of mothers and infants should achieve uneventful outcomes.


Retracted: Analysis of Coronary Artery Lesion Degree and Related Risk Factors in Patients with Coronary Heart Disease Based on Computer-Aided Diagnosis of Coronary Angiography.
[This retracts the article DOI: 10.1155/2021/2370496.].


The role of hypoxia in the differentiation of P19 embryonal carcinoma cells into dopaminergic neurons.
Nervous system development at early stage is in hypoxic environment. Very little is known about the role of hypoxia in neuronal development. P19 embryonal carcinoma (EC) cells are a widely used model for studying early neuronal development. In this study we investigated the roles of hypoxia in differentiation of dopaminergic neurons derived from P19 EC cells. Results demonstrate that hypoxia increases the percentage of differentiated neurons, especially neurons of dopaminergic phenotype. To investigate the potential mechanism involved in hypoxia promoted differentiation of dopaminergic neurons, we measured the expression of hypoxia-inducible factor 1alpha (HIF-1alpha), based on its characteristic response to hypoxia. The result shows that HIF-1alpha mRNA level in P19 EC cells increases after hypoxia treatment. It is known that HIF-1alpha regulates the expression of tyrosine hydroxylase (TH) gene through binding to its promoter. Therefore, we propose that the underlying mechanism for hypoxia promoted differentiation of dopaminergic neurons was mediated by HIF-1alpha up-regulation under hypoxia.


TAT-PEP Alleviated Cognitive Impairment by Alleviating Neuronal Mitochondria Damage and Apoptosis After Cerebral Ischemic Reperfusion Injury.
Paired immunoglobulin-like receptor B (PirB) was identified as a myelin-associated inhibitory protein (MAIP) receptor that plays a critical role in axonal regeneration, synaptic plasticity and neuronal survival after stroke. In our previous study, a transactivator of transcription-PirB extracellular peptide (TAT-PEP) was generated that can block the interactions between MAIs and PirB. We found that TAT-PEP treatment improved axonal regeneration, CST projection and long-term neurobehavioural recovery after stroke through its effects on PirB-mediated downstream signalling. However, the effect of TAT-PEP on the recovery of cognitive function and the survival of neurons also needs to be investigated. In this study, we investigated whether pirb RNAi could alleviate neuronal injury by inhibiting the expression of PirB following exposure to oxygen-glucose deprivation (OGD) in vitro. In addition, TAT-PEP treatment attenuated the volume of the brain infarct and promoted the recovery of neurobehavioural function and cognitive function. This study also found that TAT-PEP exerts neuroprotection by reducing neuronal degeneration and apoptosis after ischemia-reperfusion injury. In addition, TAT-PEP improved neuron survival and reduced lactate dehydrogenase (LDH) release in vitro. Results also showed that TAT-PEP reduced malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity and reduced reactive oxygen species (ROS) accumulation in OGD-injured neurons. The possible mechanism was that TAT-PEP could contribute to the damage of neuronal mitochondria and affect the expression of cleaved caspase 3, Bax and Bcl-2. Our results suggest that PirB overexpression in neurons after ischaemic-reperfusion injury induces neuronal mitochondrial damage, oxidative stress and apoptosis. This study also suggests that TAT-PEP may be a potent neuroprotectant with therapeutic potential for stroke by reducing neuronal oxidative stress, mitochondrial damage, degeneration and apoptosis in ischemic stroke.


Enhancement of methane production by anaerobic digestion of corn straw with hydrogen-nanobubble water.
Hydrogen-nanobubble water was proposed to enhance methane production by anaerobic digestion (AD) with corn straw. The effects of H2-nanobubble water (H2-NBW) amounts (0%, 20%, 40%, 60%, 80%, and 100%) on methane production characteristics of corn straw were explored. The results showed that the methane yields were increased by 11.54%∼25.29% compared with the control group(CK), and the maximum cumulative methane production reached to 254.36 mL·g-VS-1 when the H2-NBW addition was of 60%. Interestingly, the maximum methane concentration increased by 4.37% compared with CK. H2-NBW addition can destroy the cellulose structure of corn straw, reduce the crystallinity of cellulose, and promote the hydrolysis. The degradation rate of cellulose and hemicellulose were increased by 20%∼33% and 13% ∼25.7% respectively, and the removal rate of TS and VS were increased by 6.82%-27.93% and 8.52%-21.47%, respectively. The modified Gompertz equation fitted the cumulative methane production curves very well, with high correlation coefficients (R2 > 0.992).


Automatic Measurement of Maximal Diameter of Abdominal Aortic Aneurysm on Computed Tomography Angiography Using Artificial Intelligence.
The treatment of abdominal aortic aneurysm relies on surgical repair and the indication mainly depends on its size evaluated by the maximal diameter (Dmax). The aim of this study was to evaluate a new automatic method based on artificial intelligence to measure the Dmax on computed tomography angiography. A fully automatic segmentation of the vascular system was performed using a hybrid method combining expert system with supervised deep learning. The aorta centreline was extracted from the segmented aorta and the aortic diameters were automatically calculated. Results were compared to manual segmentation performed by two human operators. The median absolute error between the two human operators was 1.2 mm (IQR 0.5-1.9). The automatic method using the deep learning algorithm demonstrated correlation with the human segmentation, with a median absolute error of 0.8 (0.5-4.2) mm and a coefficient correlation of 0.91 (P < 0.001). Although validation in larger cohorts is required, this method brings perspectives to develop new tools to standardize and automate the measurement of abdominal aortic aneurysm Dmax in order to help clinicians in the decision-making process.


Integrated metabolomics and network pharmacology revealing the mechanism of arsenic-induced hepatotoxicity in mice.
Endemic arsenic (As) poisoning is a severe biogeochemical disease that endangers human health. Epidemiological investigations and animal experiments have confirmed the damaging effects of As on the liver, but there is an urgent need to investigate the underlying mechanisms. This study adopted a metabolomic approach using UHPLC-QE/MS to identify the different metabolites and metabolic mechanisms associated with As-induced hepatotoxicity in mice. A network pharmacology approach was applied to predict the potential target of As-induced hepatotoxicity. The predicted targets of differential metabolites were subjected to a deep matching for elucidating the integration mechanisms. The results demonstrate that the levels of ALT and AST in plasma significantly increased in mice after As exposure. In addition, the liver tissue showed disorganized liver lobules, lax cytoplasm and inflammatory cell infiltration. Metabolomic analysis revealed that As exposure caused disturbance to 40 and 75 potential differential metabolites in plasma and liver, respectively. Further investigation led to discovering five vital metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis and nicotinate and nicotinamide metabolism pathways. These pathways may responded to As-induced hepatotoxicity primarily through lipid metabolism, apoptosis, and deoxyribonucleic acid damage. The network pharmacology suggested that As could induce hepatotoxicity in mice by acting on targets including Hsp90aa1, Akt2, Egfr, and Tnf, which regulate PI3K Akt, HIF-1, MAPK, and TNF signaling pathways. Finally, the integrated metabolomics and network pharmacology revealed eight key targets associated with As-induced hepatoxicity, namely DNMT1, MAOB, PARP1, MAOA, EPHX2, ANPEP, XDH, and ADA. The results also suggest that nicotinic acid and nicotinamide metabolisms may be involved in As-induced hepatotoxicity. This research identified the metabolites, targets, and mechanisms of As-induced hepatotoxicity, offering meaningful insights and establishing the groundwork for developing antidotes for widespread As poisoning.


miR-101 inhibits cholangiocarcinoma angiogenesis through targeting vascular endothelial growth factor (VEGF).
Recent evidence has suggested an important role of miRNAs in liver biology and diseases, although the implication of miRNAs in cholangiocarcinoma remains to be defined further. This study was designed to examine the biological function and molecular mechanism of miR-101 in cholangiocarcinogenesis and tumor progression. In situ hybridization and quantitative RT-PCR were performed to determine the expression of miR-101 in human cholangiocarcinoma tissues and cell lines. Compared with noncancerous biliary epithelial cells, the expression of miR-101 is decreased in 43.5% of human cholangiocarcinoma specimens and in all three cholangiocarcinoma cell lines used in this study. Forced overexpression of miR-101 significantly inhibited cholangiocarcinoma growth in severe combined immunodeficiency mice. miR-101-overexpressed xenograft tumor tissues showed decreased capillary densities and decreased levels of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). The VEGF and COX-2 mRNAs were identified as the bona fide targets of miR-101 in cholangiocarcinoma cells by both computational analysis and experimental assays. miR-101 inhibits cholangiocarcinoma angiogenesis by direct targeting of VEGF mRNA 3'untranslated region and by repression of VEGF gene transcription through inhibition of COX-2. This study established a novel tumor-suppressor role of miR-101 in cholangiocarcinoma and it suggests the possibility of targeting miR-101 and related signaling pathways for future therapy.


Chromatographic separation of activated and unactivated forms of aldose reductase.
Chromatography of bovine kidney aldose reductase using Matrex Orange A affinity gel results in the separation of the unactivated and activated enzyme forms. The former washes through the column, while the latter is eluted with an NADPH step-gradient. The separated enzyme forms display Vmax and Km glycolaldehyde values, and relative sensitivities to inhibition by the aldose reductase inhibitor AL-1576 (spiro[2,7-difluorofluorene-9,4'-imidazolidine]-2',5'- dione), that are similar to those reported previously for the individual forms. However, because Vmax is 17-fold lower for the unactivated enzyme, the purification of aldose reductase via NADP(H) elution from a dye-ligand affinity matrix can result in the selective purification of only the activated enzyme form. These results have direct implications for the study of potential aldose reductase inhibitors, and may explain why linear double-reciprocal plots are commonly observed for enzyme prepared in this manner, while nonlinear plots are seen in other cases.


Radiomic analysis of MRI for prediction of response to induction chemotherapy in nasopharyngeal carcinoma patients.
To establish and validate radiomic models for response prediction to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) using the radiomic features from pretreatment MRI. This retrospective analysis included 184 consecutive NPC patients, 132 in the primary cohort and 52 in the validation cohort. Radiomic features were derived from contrast-enhanced T1-weighted imaging (CE-T1) and T2-weighted imaging (T2-WI) for each subject. The radiomic features were then selected and combined with clinical characteristics to build radiomic models. The potential of the radiomic models was evaluated based on its discrimination and calibration. To measure the performance of these radiomic models in predicting the treatment response to IC in NPC, the area under the receiver operating characteristic curve (AUC), and sensitivity, specificity, and accuracy were used. Four radiomic models were constructed in the present study including the radiomic signature of CE-T1, T2-WI, CE-T1 + T2-WI, and the radiomic nomogram of CE-T1. The radiomic signature of CE-T1 + T2-WI performed well in distinguishing response and non-response to IC in patients with NPC, which yielded an AUC of 0.940 (95% CI, 0.885-0.974), sensitivity of 83.1%, specificity of 91.8%, and accuracy of 87.1% in the primary cohort, and AUC of 0.952 (95% CI, 0.855-0.992), sensitivity of 74.2%, specificity of 95.2%, and accuracy of 82.7% in the validation cohort. MRI-based radiomic models could be helpful for personalised risk stratification and treatment in NPC patients receiving IC.


A non-extracting procedure for the determination of meloxicam in plasma samples by HPLC-diode array detection.
The bioequivalence of two formulations of 15 mg tablets of meloxicam (CAS 71125-38-7), Meloxicam (LaborMed Pharma) and a commercially available preparation as reference in 24 healthy male and female Caucasian volunteers was assessed based on a validated non-extractive HPLC-DAD method. The sample preparation procedure was based on protein precipitation with a mixture of methanol/acetonitrile, trifluoacetic acid and sodium sulfate solution. Piroxicam (CAS 36322-90-4) was used as internal standard. The stepwise gradient elution profile of the chromatographic method allows injection of a high volume of the sample (500 microL) with the focusing of both analytes in a Chromolith Performance RP-18e column. The mobile phase constituents are methanol and aqueous 20 mmol/L Na2HPO4 buffer solution brought to pH = 6 with H3PO4. A flow-rate of 2 mL/min achieves a complete chromatographic run (including column equilibration) within 12 min. UV detection at 356 nm allowed a quantitation limit around 30 ng/mL. Bioequivalence study was based on an open-label, randomized, two-period, two-sequence, single dose, crossover design with a 2-week wash-out period between consecutive oral administrations. The main pharmacokinetic parameters (C(max), t(max), t 1/2, AUD and AUC(0-infinity)) were considered as evaluation criteria for the bioequivalence of the test drug against the reference.


Consequences of transforming measures of efficacy for acute therapies: 5-HT agonists as a worked example.
To examine whether the distributions of active and placebo response rates change after transformation into therapeutic gains, numbers needed to treat, and therapeutic ratios for 51 published clinical trials of 5-HT(1B/1D) agonists in the acute treatment of migraine. Acute migraine therapies have been compared using meta-analysis. Before pooling the results of noncontemporaneous clinical trials for meta-analysis, reconciliation of active response rates with concurrent placebo controls is done because of fluctuations in placebo response rates. The 3 common methods of reconciliation are to find for each clinical trial the therapeutic gain, the number needed to treat, or the therapeutic ratio. Raw active and placebo response rates were tabulated and displayed as histograms. The distributions of the therapeutic gains, numbers needed to treat, and therapeutic ratios were similarly plotted. These distributions were then compared with normal distributions using chi-squared goodness-of-fit methodology. The distribution of active response rates was consistent with a normal distribution (passing a goodness-of-fit test). Placebo response rates were not normally distributed. The distribution of therapeutic gains failed a test of normality (P=.018), as did the numbers needed to treat (P <.001); the skews of these distributions were toward opposite ends of the scale for relative efficacy. The therapeutic ratios also failed a test for normality, but passed a test for log-normal distribution. Choice of transformation is a potential source of bias in meta-analysis of acute migraine therapies.


Neurologic Emergencies at the Extremes of Age.
The diagnosis and management of neurologic conditions are more complex at the extremes of age than in the average adult. In the pediatric population, neurologic emergencies are somewhat rare and some may require emergent consultation. In older adults, geriatric physiologic changes with increased comorbidities leads to atypical presentations and worsened outcomes. The unique considerations regarding emergency department presentation and management of stroke and altered mental status in both age groups is discussed, in addition to seizures and intracranial hemorrhage in pediatrics, and Parkinson's disease and meningitis in the geriatric population.


Study of Antihypertensive Activity of Anvillea radiata in L-Name-Induced Hypertensive Rats and HPLC-ESI-MS Analysis.
This study aimed to evaluate the effect of the aqueous extract of Anvillea radiate (A. radiata) aerial parts (AEAR) on arterial blood pressure in normotensive and hypertensive rats. The effect of the acute and sub-chronic administration of AEAR on the following blood pressure parameters: systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) was evaluated in normotensive and L-NAME induced hypertensive rats. In the second experiment, the vasorelaxant effect of AEAR was assessed in isolated aortic rings from rats with functional endothelium pre-contracted with epinephrine (EP) or KCl, and six antagonists/ inhibitors were used to explore the mechanisms of action involved in the vasorelaxant effect. In order to determine the phytochemical contents of Anvillea radiata, HPLC-ESI-MS analysis was conducted. Daily oral administration of AEAR (100 mg/kg) provoked a significant decrease in SBP, MBP, and DBP without affecting HR in hypertensive rats. In addition, AEAR (0.08-0.64 mg/ml) revealed a vasorelaxant effect in thoracic aortic rings pre-contracted by EP (10 μM) or KCl (80 mM). This effect was reduced in the presence of Nifedipine, L-Name or Methylene blue. The polyphenolic compounds of AEAR were determined. This study revealed that AEAR possesses a potent antihypertensive activity and its vasorelaxant activity seems to be mediated through Ca2+ channels, direct nitric oxide (NO), and NO/cGMP pathways. Chlorogenic acid and caffeic acid identified in A. radiata could be at least partially responsible for the antihypertensive activity of this extract.


DeepACP: A Novel Computational Approach for Accurate Identification of Anticancer Peptides by Deep Learning Algorithm.
Cancer is one of the most dangerous diseases to human health. The accurate prediction of anticancer peptides (ACPs) would be valuable for the development and design of novel anticancer agents. Current deep neural network models have obtained state-of-the-art prediction accuracy for the ACP classification task. However, based on existing studies, it remains unclear which deep learning architecture achieves the best performance. Thus, in this study, we first present a systematic exploration of three important deep learning architectures: convolutional, recurrent, and convolutional-recurrent networks for distinguishing ACPs from non-ACPs. We find that the recurrent neural network with bidirectional long short-term memory cells is superior to other architectures. By utilizing the proposed model, we implement a sequence-based deep learning tool (DeepACP) to accurately predict the likelihood of a peptide exhibiting anticancer activity. The results indicate that DeepACP outperforms several existing methods and can be used as an effective tool for the prediction of anticancer peptides. Furthermore, we visualize and understand the deep learning model. We hope that our strategy can be extended to identify other types of peptides and may provide more assistance to the development of proteomics and new drugs.


The progressive ratio and fixed ratio 1 schedules of cocaine self-administration in rats convey the same information.
Progressive ratio (PR) schedules of drug delivery are used to determine the 'motivational' state of an animal and drug 'reinforcing efficacy'. This widely held interpretation is supported mainly by the observation that the PR breakpoint (BP) is proportional to the unit dose of self-administered drug. The compulsion zone theory of cocaine self-administration was applied to determine whether it can explain the pattern of lever-pressing behavior and cocaine injections under the PR schedule in rats. This theory states that cocaine induces lever pressing when levels are below the satiety threshold and above the priming/remission threshold. Rats were trained to self-administer cocaine on a fixed ratio FR1 schedule over a range of cocaine unit doses. Then they were switched to a PR schedule. Typical for the self-administration under a PR schedule, long post-injection pauses occurred when calculated cocaine levels were in the satiety zone. The compulsion zone theory interprets BP simply as the maximal number of responses which rats can perform after an injection while cocaine levels remain within the compulsion zone. The thresholds delineating the compulsion zone were very stable and independent of the self-administration schedule. PR and fixed ratio schedules convey the same pharmacokinetic/pharmacodynamic information, i.e., these two schedules are invariant.


Frontal midline theta related to learning in a simulated driving task.
The occurrence of frontal midline theta activity (4-7 Hz) was studied in a simulated driving task during consecutive phases of goal-directed behaviour. Electrical activity of the forebrain (Fz) was analysed in a simulated traffic situation in which the subject had to find the correct way to drive a car through a set of roads in a computer game. The occurrence of theta activity was analysed during seven consecutive sections of the game. The results showed that the occurrence of theta activity increased during learning--successful behaviour produced more theta than unsuccessful behaviour. In some sections of the game the percentage of theta was larger than in others. It is suggested that the theta activity reflects relaxed concentration after mastering the game.


Pulmonary carcinoids. Immunohistochemical demonstration of brain-gut peptides.
Antisera raised against serotonin, gastrin, somatostastin, motilin, bombesin, calcitonin, secretin, glucagon, ACTH, neurotensin, and pancreatic polypeptide carboxyterminal hexapeptide were employed to immunohistochemically stain seven pulmonary carcinoids. Argentaffin and argyrophil stains were also performed on all cases. Serotonin-like immunoreactivity was present in four tumors, pancreatic polypeptide-like immunoreactivity in four tumors, bombesin-like immunoreactivity in two tumors and ACTH-like immunoreactivity in one tumor. The cells shown to contain neuroendocrine products constituted a minority cell population in all tumors except the ACTH-immunoreactive tumor. This study suggests that pulmonary carcinoids, like their abdominal counterparts, contain a variety of neuroendocrine products, and may produce more than one neuroendocrine product. Serotonin and pancreatic polypeptide-like immunoreactivity were the most prevalent neuroendocrine products demonstrable in this study.


Effectiveness of combined thoracoscopic-laparoscopic esophagectomy: comparison of postoperative complications and midterm oncological outcomes in patients with esophageal cancer.
During esophagectomy, laparoscopy can be used together with thoracoscopy, but it is not known whether a combined thoracoscopic-laparoscopic procedure is associated with fewer postoperative complications than open esophagectomy, and without compromising oncological outcome. This was a longitudinal cohort study that included 185 esophageal cancer patients, including 72 who underwent combined thoracoscopic-laparoscopic esophagectomy (TLE), 34 who underwent thoracoscopic esophagectomy (TE), and 79 who underwent open esophagectomy (OE) between January 2002 and May 2010. The main outcome measures were postoperative respiratory and overall complications. The secondary outcome was 2-year relapse-free survival (RFS). Respiratory complications occurred in 9 patients who underwent TLE, 13 who underwent TE, and 31 who underwent OE. TLE was associated with fewer respiratory complications (TLE vs. OE: odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09-0.53 and TE vs. OE: OR, 0.71; 95% CI 0.29-1.76). Overall complications occurred in 34 patients who underwent TLE, 20 who underwent TE, and 54 who underwent OE. TLE was associated with fewer overall complications (TLE vs. OE: OR, 0.47; 95% CI 0.23-0.94 and TE vs. OE: OR, 0.51; 95% CI 0.21-1.25). The 2-year RFS rates were similar among the three groups: 71.6% for TLE, 57.7% for TE, and 58.3% for OE (TLE vs. OE: hazard ratio, 0.65; 95% CI 0.35-1.20 and TE vs. OE: hazard ratio, 0.91; 95% CI 0.45-1.82). Unlike TE, TLE was associated with fewer postoperative complications than was OE, with no compromise of 2-year RFS. A randomized controlled trial with longer follow-up is needed.


Contributions of GABAergic and glutamatergic mechanisms to isoflurane-induced suppression of thalamic somatosensory information transfer.
Indications for a pivotal role of the thalamocortical network in producing the state of anesthesia have come from in vivo animal studies as well as imaging studies in humans. We studied possible synaptic mechanisms of anesthesia-induced suppression of touch perception in the rat's thalamus. Thalamocortical relay neurons (TCNs) receive ascending and descending glutamatergic excitatory inputs via NMDA and non-NMDA receptors (AMPAR) and are subjected to GABA(A)ergic inhibitory input which shapes the sensory information conveyed to the cortex. The involvement of these synaptic receptors in the suppressive effects of the prototypic volatile anesthetic isoflurane was assessed by local iontophoretic administration of receptor agonists/antagonists during extracellular recordings of TCNs of the ventral posteromedial nucleus responding to whisker vibration in rats anesthetized with isoflurane concentrations of approximately 0.9 vol.% (baseline) and approximately 1.9 vol.% (ISO high). ISO high induced a profound suppression of response activity reflected by a conversion of the sustained vibratory responses to ON responses. Administration of NMDA, AMPA, or GABA(A)R antagonists caused a reversal to sustained responses in 88, 94 and 88% of the neurons, respectively, with a recovery to baseline levels of response activity. The data show that the block of thalamocortical transfer of tactile information under ISO high may result from an enhancement of GABA(A)ergic inhibition and/or a reduction of glutamatergic excitation. Furthermore, they show that the ascending vibratory signals still reach the thalamic neurons under the high isoflurane concentration, indicating that this input is resistant to isoflurane while the attenuation of excitation may be brought about at the corticothalamic glutamatergic facilitatory input.


Latent microvolt T-wave alternans in survivors of unexplained cardiac arrest unmasked by epinephrine challenge.
The arrhythmogenic substrate in survivors of unexplained cardiac arrest (UCA) has not been defined. To test the hypothesis that patients with UCA have latent repolarization abnormalities, in particular T-wave alternans (TWA), which may be unmasked with epinephrine (EPI) challenge. We prospectively studied 10 UCA survivors (46 ± 9 years) and 11 first-degree relatives (FDRs) of sudden death victims (37 ± 14 years). Patients with UCA underwent standard clinical testing, which was normal. FDRs had normal clinical history and testing. All subjects underwent an EPI infusion (0.05, 0.1, and 0.2 μg/(kg·min), 5 minutes each dose) while recording continuous digital 12-lead electrocardiograms. Corrected QT interval and QT variability index were evaluated at each EPI dose. TWA magnitude (V(alt)) was assessed at each dose by using the spectral method. Positive (+) TWA at each dose was defined as V(alt) > 0 with k ≥ 3 in 1 or more 128-beat segment in ≥2 electrocardiogram leads. A novel metric, TWA burden, reflecting V(alt) integrated over time (s), was also evaluated for each EPI dose. There was no difference between UCA survivors and FDRs with respect to heart rate, QT, corrected QT interval, or QT variability index at baseline or during EPI. At baseline, +TWA was similar between UCA survivors and FDRs (10% vs 0%; P = NS). During EPI, +TWA was more prevalent in UCA survivors than in FDRs (80% vs 18%; P = .009). TWA burden was greater in UCA survivors than in FDRs during EPI 0.1 (P = .039) and EPI 0.2 μg/(kg·min) (P = .009). UCA survivors are more likely to demonstrate latent TWA compared with FDRs, which becomes manifest with EPI. This novel finding provides evidence for an arrhythmogenic substrate in UCA survivors.


The Psychometric Properties of the Brief COPE Among Young Adults.
Background and Process: Although the Brief COPE is a widely used instrument to measure coping, its factor structure is understudied in young adults. The purpose of this article was to determine the psychometric properties of the dispositional version of the Brief COPE among young adults. Methods: Two hundred young adults completed the dispositional version of the Brief COPE. Measures of depression, anxiety, and stress tested predictive validity. Confirmatory factor analyses and exploratory structural equation modeling were conducted. Results: The final model achieved good fit (minimum discrepancy/degrees of freedom [CMIN/df] = 1.59; comparative fit index [CFI] = .93; standardized root mean square residual [SRMR] = .07). Three second-order factors were identified: adaptive (α = .81), support (α = 78), and disengaged coping (α = 71). Adaptive and disengaged coping were differentially associated with mental health outcomes. Conclusions: The results are consistent with a growing body of evidence to support the construct validity of the Brief COPE.


Bcl-2 silencing attenuates hypoxia-induced apoptosis resistance in pulmonary microvascular endothelial cells.
Pulmonary arterial hypertension (PAH) is a life-threatening disorder that ultimately causes heart failure. While the underlying causes of this condition are not well understood, previous studies suggest that the anti-apoptotic nature of pulmonary microvascular endothelial cells (PMVECs) in hypoxic environments contributes to PAH pathogenesis. In this study, we focus on the contribution of Bcl-2 and hypoxia response element (HRE) to apoptosis-resistant endothelial cells and investigate the mechanism. PMVECs obtained from either normal rats or apoptosis-resistant PMVECs obtained from PAH rats were transduced with recombinant lentiviral vectors carrying either Bcl-2-shRNA or HRE combined Bcl-2-shRNA, and then cultured these cells for 24 h under hypoxic (5% O2) or normoxic (21% O2) conditions. In normal PMVECs, Bcl-2-shRNA or HRE combined with Bcl-2-shRNA transduction successfully decreased Bcl-2 expression, while increasing apoptosis as well as caspase-3 and P53 expression in a normoxic environment. In a hypoxic environment, the effects of Bcl-2-shRNA treatment on cell apoptosis, and on Bcl-2, caspase-3, P53 expression were significantly suppressed. Conversely, HRE activation combined with Bcl-2-shRNA transduction markedly enhanced cell apoptosis and upregulated caspase-3 and P53 expression, while decreasing Bcl-2 expression. Furthermore, in apoptosis-resistant PMVECs, HRE-mediated Bcl-2 silencing effectively enhanced cell apoptosis and caspase-3 activity. The apoptosis rate was significantly depressed when Lv-HRE-Bcl-2-shRNA was combined with Lv-P53-shRNA or Lv-caspase3-shRNA transduction in a hypoxic environment. These results suggest that HRE-mediated Bcl-2 inhibition can effectively attenuate hypoxia-induced apoptosis resistance in PMVECs by downregulating Bcl-2 expression and upregulating caspase-3 and P53 expression. This study therefore reveals critical insight into potential therapeutic targets for treating PAH.


Sympathetic innervation is essential for metabolic homeostasis and pancreatic beta cell function in adult rats.
Obesity is associated with an imbalance in the activity of the autonomic nervous system (ANS), specifically in the organs involved in energy metabolism. The pancreatic islets are richly innervated by the ANS, which tunes the insulin release due to changes in energy demand. Therefore, changes in the sympathetic input that reach the pancreas can lead to metabolic dysfunctions. To evaluate the role of the sympathetic ends that innervate the pancreas, 60-day-old male Wistar rats were subjected to sympathectomy (SYM) or were sham-operated (SO). At 120 day-old SYM rats exhibited an increase in body weight, fat pads and metabolic dysfunctions. Decreases in the HOMA-IR and reductions in insulin release were observed both in vivo and in vitro. Furthermore, the SYM rats exhibited altered pancreatic islet function in both muscarinic and adrenergic assays and exhibited high protein expression of the alpha-2 adrenergic receptor (α2AR). Because α2AR has been linked to type 2 diabetes, these findings demonstrate the clinical implications of this study.


Interactions Between the Nematode Heterorhabditis amazonensis JPM4 and the Predator Macrolophus basicornis: Two Natural Enemies of Tuta absoluta Native to South America.
Entomopathogenic nematodes (EPNs) and predatory mirids are among the most effective natural enemies for the control of Tuta absoluta, a key pest of tomato worldwide. In the case of South America, the native EPN Heterorhabditis amazonensis and the predator Macrolophus basicornis (Stal) coexist in tomato. The intraguild interactions of two ENPs, H. amazonensis JPM4 and the widely used Steinernema carpocapsae, with the predator M. basicornis, were studied in laboratory setups with the objective of evaluating the potential interactions between them. We hypothesized that the two natural enemies do not interact negatively. The first nymphal stage of the predator was not affected when exposed to tomato leaves directly sprayed with both EPNs, which we attributed to the small size of its stylet. Individuals treated with H. amazonensis JPM4 had low mortality rates in all developmental stages with a maximum of 1.3%. Mortality was higher when the predator was exposed to S. carpocapsae (28% for adults) and correlated positively with increasing developmental stages. In prey choice tests between larvae infected with H. amazonensis and uninfected larvae, M. basicornis fed indistinctively showing no clear preference. When presented with choice larvae infected with S. carpocapsae, the consumption of healthy larvae was higher. In a no-choice prey acceptance experiment, M. basicornis preyed on both healthy and infected larvae with no difference in larvae consumed. Predators that had fed from infected larvae did not exhibit signs of nematode infection and survived. Our results indicate that the South American native H. amazonensis JPM4 and M. basicornis do not show a negative interaction and are promising candidates for combined use in T. absoluta biological control.


Ethical principles in critical care medicine.
This article identifies the ethical principles that have guided medicine since antiquity: beneficence, primum non nocere, patient autonomy, and respect for life and the quality of life. The author's basic premise is that many recently publicized ethical dilemmas are really not dilemmas--the knowledge of what is good or evil is not confused, contradictory, or absent. Instead, medicine's concern and responsibility to its patients is being clouded by legal, governmental, or societal concerns.


Hybrid external fixation for tibial plateau fractures: clinical and biomechanical correlation.
The biomechanical data support the use of tensioned wire fixation to stabilize complex fractures of the proximal tibia. The authors will show that the stability of a four-wire construct is comparable to the gold standard of dual plating internal fixation techniques. Using these techniques, many recent investigators have demonstrated improved clinical results, with average knee scores for most patients ranging from 85 to 90.


Observation of dimethylaminoethyl methacrylate-myoglobin binding reaction using laser spray mass spectrometry.
Covalent bonds are often created by a reaction between chemicals and protein before causing various adverse effects in a cell. Dimethylaminoethyl methacrylate (DMAEMA), which has moderate toxicity, causes skin inflammation and throat irritation. For this study, we investigated a reaction mechanism between myoglobin and (DMAEMA) using a new analytical tool developed at our laboratory: laser spray mass spectrometry technique. It was found that initially DMAEMA was added to the amino group of protein by the Michael addition mechanism; the added DMAEMA was hydrolyzed to methacrylic acid using an autocatalytic system. The results of this study indicate the feasibility of the laser spray technique in analyses of reaction dynamics.


Evaluation of fetal MRI in a South African referral centre.
The Department of Radiology at Groote Schuur Hospital, Cape Town, South Africa, has been performing fetal magnetic resonance imaging (MRI) since 2007. Fetal MRI findings have not previously been analysed to correlate them with antenatal and postnatal findings. To determine the most common indication for fetal MRI, and to correlate antenatal MRI with antenatal ultrasound (US), postnatal imaging and postmortem findings. This was a retrospective study of imaging carried out between January 2006 and December 2011. Seventy fetal MRI cases with complete antenatal and postnatal medical records were included. Antenatal US and antenatal MRI were compared, and also compared with the postnatal imaging findings. Stata 12 was used to analyse the data, and Spearman's test to test the agreement between the results. Intracranial pathology was the most common indication for fetal MRI, with ventriculomegaly being the commonest indication determined from prenatal US. There was 72% agreement between antenatal US and fetal MRI. Postnatal findings showed 28% agreement with antenatal US and 39% agreement with fetal MRI. Intracranial pathology was the major indication for fetal MRI. There was good agreement between prenatal US and fetal MRI but poor agreement between antenatal and postnatal findings, largely as a result of resolution of ventriculomegaly.


Should Targeted Biopsy be Performed in Patients Who Have Only Pi-rads 3 Lesions?
To determine whether clinical or radiological parameters can predict clinically significant prostate cancer (csPC) in patients with the Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions. Data were obtained from 247 patients with PI-RADS 3 lesions on mpMRI and who had received a software guided transperineal/transrectal MRI/transrectal ultrasonography (MRI/TRUS) fusion prostate biopsy with concomitant standard systematic 12-core biopsy following mpMRI in the prostate cancer and prostate biopsy database of Turkish Urooncology Association, between 2016 and 2020. The cut-off values of clinical parameters were determined using receiver operating characteristic (ROC) curve analysis. Simple and multiple logistic regression analyses were performed to determine the clinical parameters in predicting csPC. A total of 56 patients (22.6%) had prostate cancer, 23 (9.3%) of whom had csPC. In the lesion- based analysis, cancer detection rates (CDRs) of each lesion in targeted biopsy were found to be 6% and 5% for ISUP GG 1 and ISUP GG ≥ 2, respectively. In the patient-based analysis, clinically insignificant CDRs were significantly higher in systematic biopsy compared with targeted biopsy, whereas no significant difference was found in terms of clinically significant CDRs (p = 0.020 and p=0.422, respectively). The cut-off values were determined as 48.3 mL (AUC [95% CI] = 0.68 [0.53-0.82]) for prostate volume, and 0.213 ng/mL/mL (AUC [95% CI] = 0.64 (0.51-0.77]) for PSAD in predicting csPC. In the multiple logistic regression analysis, only PSAD was found to be an independent risk factor in predicting csPC (OR [95% CI]: 3.56 [1.15-10.91], p = 0.024). Since PSAD > 0.20 ng/mL/mL was found to be positive independent risk factor in predicting csPC, in the absence of advanced radiological parameters, PSAD could be used for the biopsy decision in patients with PI-RADS 3 lesions.


Diagnostic accuracy of the Finnish Diabetes Risk Score (FINDRISC) for undiagnosed T2DM in Peruvian population.
To assess the diagnostic accuracy of the Finnish Diabetes Risk Score (FINDRISC) for undiagnosed T2DM and to compare its performance with the Latin-American FINDRISC (LA-FINDRISC) and the Peruvian Risk Score. A population-based study was conducted. T2DM and undiagnosed T2DM were defined using oral glucose tolerance test (OGTT). Risk scores assessed were FINDRISC, LA-FINDRISC and Peruvian Risk Score. Diagnostic accuracy of risk scores was estimated using the c-statistic and the area under the ROC curve (aROC). A simplified version of FINDRISC was also derived. Data from 1609 individuals, mean age 48.2 (SD: 10.6), 810 (50.3%) women, were collected. A total of 176 (11.0%; 95%CI: 9.4%-12.5%) were classified as having T2DM, and 71 (4.7%; 95%CI: 3.7%-5.8%) were classified as having undiagnosed T2DM. Diagnostic accuracy of the FINDRISC (aROC=0.69), LA-FINDRISC (aROC=0.68), and Peruvian Risk Score (aROC=0.64) was similar (p=0.15). The simplified FINDRISC, with 4 variables, had a slightly better performance (aROC=0.71) than the other scores. The performance of FINDRISC, LA-FINDRISC and Peruvian Risk Score for undiagnosed T2DM was similar. A simplified FINDRISC can perform as well or better for undiagnosed T2DM. The FINDRISC may be useful to detect cases of undiagnosed T2DM in resource-constrained settings.


Melatonin modulates monochromatic light-induced GHRH expression in the hypothalamus and GH secretion in chicks.
To study the mechanism by which monochromatic lights affect the growth of broilers, a total of 192 newly hatched broilers, including the intact, sham-operated and pinealectomy groups, were exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for 2 weeks. The results showed that the GHRH-ir neurons were distributed in the infundibular nucleus (IN) of the chick hypothalamus. The mRNA and protein levels of GHRH in the hypothalamus and the plasma GH concentrations in the chicks exposed to GL were increased by 6.83-31.36%, 8.71-34.52% and 6.76-9.19% compared to those in the chicks exposed to WL (P=0.022-0.001), RL (P=0.002-0.000) and BL (P=0.290-0.017) in the intact group, respectively. The plasma melatonin concentrations showed a positive correlation with the expression of GHRH (r=0.960) and the plasma GH concentrations (r=0.993) after the various monochromatic light treatments. After pinealectomy, however, these parameters decreased and there were no significant differences between GL and the other monochromatic light treatments. These findings suggest that melatonin plays a critical role in GL illumination-enhanced GHRH expression in the hypothalamus and plasma GH concentrations in young broilers.


Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis.
To characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. In this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2-3 months after treatment and then every 3-6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression-free survival (LPFS) based on ADT. Patients had a median follow-up of 116 days (interquartile range [IQR], 69-231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6-239.0] vs 40.6 [IQR, 26.0-66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%-89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%-100%) probability of LPFS. Tumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.


Dietary isoleucine affects muscle fatty acid and amino acid profiles through regulating lipid metabolism and autophagy in hybrid catfish (Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂).
The present study explored the impacts of Ile on muscle fatty acid and amino acid profiles, lipid metabolism, and autophagy in hybrid catfish. Seven isonitrogenous (387.8 g/kg protein) semi-purified diets were formulated to contain 5.0 (control), 7.5, 10.0, 12.5, 15.0, 17.5, and 20.0 g Ile/kg diet respectively. The fish (initial weight of 33.11 ± 0.09 g) were randomly assigned to 7 groups for a 56-day trial. Each group has 3 replicates with 30 fish per replicate, fed at 08:00 and 18:00 each day. Results showed that muscle protein and lipid, C14:0, C18:0, C22:0, C14:1, C18:1n-9, polyunsaturated fatty acid (PUFA), Arg, Ile, Ala, Cys, Gly, Tyr, essential amino acid (EAA), and total amino acid (TAA) contents and flavor amino acid (FAA)/TAA in muscle had positive linear and/or quadratic responses to dietary Ile levels (P < 0.05). Fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL) activities had positive linear and/or quadratic responses, but carnitine palmitoyl transferase 1 (CPT1) activity had a negative response with increasing dietary Ile levels (P < 0.05). The mRNA expressions of FAS, SCD, ACC, LPL, fatty acid binding protein 4 (FABP4), FATP1, sterol response element-binding protein 1c (SREBP-1c), sequestosome 1 (SQSTM1), and adenosine 5'-monophosphate-activated protein kinase (AMPK) had positive linear and/or quadratic responses to dietary Ile levels (P < 0.05). The mRNA expressions of hormone-sensitive lipase (HSL), CPT1, peroxisome proliferator-activated receptor α (PPARα), PPARγ, uncoordinated 51-like kinase 1 (ULK1), beclin1 (Becn1), autophagy-related protein 9α (Atg9α), Atg4b, Atg7, autophagy marker light chain 3 B (LC3B), and SQSTM1 in muscle had negative linear and/or quadratic responses to dietary Ile levels (P < 0.05). The p-AMPK and ULK1 protein levels, and p-AMPK/AMPK were decreased by 12.5 g Ile/kg in the diet (P < 0.05). Finally, SQSTM1 protein level had the opposite effect (P < 0.05). The above results indicate that dietary Ile improves fish muscle fatty acid and amino acid profiles potentially via respectively regulating lipid metabolism and autophagy. The Ile requirement of hybrid catfish (33 to 72 g) were estimated to be 12.63, 13.77, 13.75, 11.45, 10.50, 12.53 and 12.21 g/kg diet based on the regression analysis of protein, lipid, SFA, PUFA, FAA, EAA, and TAA muscle contents, respectively.


Characterizing fine-root traits by species phylogeny and microbial symbiosis in 11 co-existing woody species.
Understanding the differences in fine-root traits among different species is essential to gain a detailed understanding of resource conservation and acquisition strategies of plants. We aimed to explore whether certain root traits are consistent among subsets of species and characterize species together into meaningful community groups. We selected 11 woody species from different microbial symbiotic groups (ectomycorrhiza, arbuscular mycorrhiza, and rhizobia) and phylogenetic groups (broad-leaved angiosperms and coniferous gymnosperms) from the cool temperate forests of Nagano, Japan. We measured root architectural (branching intensity), morphological (root tissue density and specific root length), chemical (N and K concentrations), and anatomical (total stele and total cortex) traits. Significant differences were observed in all root traits, although many species did not differ from one another. Branching intensity was found to be the greatest variation in the measured root traits across the 11 woody species. The results of a principal component analysis of root traits showed a distinct separation between angiosperms and gymnosperms. We identified clusters of species based on their multidimensional root traits that were consistent with the different phylogenetic microbial association groups. Gymnosperm roots may be more resource conservative, while angiosperm roots may be more acquisitive for water and nutrients. We consider that the advances in root traits combination will make a breakthrough in our ability to differentiate the community groups rather than individual root trait.


Numerical assessment of the impact of a flow wire on its velocity measurements.
Blood flow velocities can be measured using a Doppler flow wire. This numerical study evaluates the impact of a 0.014" flow wire on the measured frequencies in a straight artery with diameters of 3 mm and 4 mm, under steady and pulsatile flow conditions. Simulations were performed with the wires positioned differently in the artery (perfectly centred and at an offset of 0.5 mm from the wall) and with different types of wire (tilted and straight). Measurements were taken at range gates from 4 mm to 10 mm. During simulations using a 3-mm vessel under pulsatile flow conditions, the relative error between the measured and reference maximum frequency (occurring in absence of the wire) decreased from 17.7% to 11.6% (with a mean value of 14.9%). During simulations using an off-centre 1.5 degree tilted wire, the mean error was approximately 5%. Therefore, our study suggests that that a centrally positioned flow wire is unfavourable for measuring flow velocities.


Resveratrol Attenuates the Disruption of Lipid Metabolism Observed in Amyloid Precursor Protein/Presenilin 1 Mouse Brains and Cultured Primary Neurons Exposed to Aβ.
To examine whether resveratrol (RSV), an activator of silent mating-type information regulation 2 homolog 1 (SIRT1), can reverse the disruption of lipid metabolism caused by β-amyloid peptide (Aβ), APP/PS1 mice or cultured primary rat neurons were treated with RSV, suramin (inhibitor of SIRT1), ZLN005, a stimulator of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), or PGC-1α silencing RNA. In the brains of the APP/PS1 mice, expressions of SIRT1, PGC-1α, low-density lipoprotein receptor (LDLR) and very LDLR (VLDLR) were reduced at the protein and, in some cases, mRNA levels; while the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein E (ApoE), total cholesterol and LDL were all elevated. Interestingly, these changes were reversed by administration of RSV, while being aggravated by suramin. Furthermore, activation of PGC-1α, but inhibition of SIRT1, decreased the levels of PCSK9 and ApoE, while increased those of LDLR and VLDLR in the neurons exposed to Aβ, and silencing PGC-1α, but activation of SIRT1, did not influence the levels of any of these proteins. These findings indicate that RSV can attenuate the disruption of lipid metabolism observed in the brains of APP mice and in primary neurons exposed to Aβ by activating SIRT1, in which the mechanism may involve subsequently affecting PGC-1α.


On the role of vestibulo-ocular reflex plasticity in recovery after unilateral peripheral vestibular lesions.
Although adaptive plasticity is a well-known feature of the vestibulo-ocular reflex (VOR), deficits in VOR performance after unilateral labyrinthectomy are poorly compensated in a large percentage of cats. To assess whether VOR plastic capabilities are affected by labyrinthectomy, forced oscillation in front of a patterned surround was imposed in unilaterally labyrinthectomized cats. This experimental paradigm has been shown to be very effective in inducing adaptive VOR gain changes in intact animals. We demonstrate that plasticity of VOR gain is still present both in acute and chronic stages following vestibular lesions. By contrast, forced oscillation did not significantly alter the lesion-induced asymmetry of responses. We conclude that VOR gain control mechanisms are not used to their fullest possible extent in a large percentage of animals suffering unilateral vestibular damage.


Deep learning applied to EEG source-data reveals both ventral and dorsal visual stream involvement in holistic processing of social stimuli.
Perception of social stimuli (faces and bodies) relies on "holistic" (i.e., global) mechanisms, as supported by picture-plane inversion: perceiving inverted faces/bodies is harder than perceiving their upright counterpart. Albeit neuroimaging evidence suggested involvement of face-specific brain areas in holistic processing, their spatiotemporal dynamics and selectivity for social stimuli is still debated. Here, we investigate the spatiotemporal dynamics of holistic processing for faces, bodies and houses (adopted as control non-social category), by applying deep learning to high-density electroencephalographic signals (EEG) at source-level. Convolutional neural networks were trained to classify cortical EEG responses to stimulus orientation (upright/inverted), separately for each stimulus type (faces, bodies, houses), resulting to perform well above chance for faces and bodies, and close to chance for houses. By explaining network decision, the 150-200 ms time interval and few visual ventral-stream regions were identified as mostly relevant for discriminating face and body orientation (lateral occipital cortex, and for face only, precuneus cortex, fusiform and lingual gyri), together with two additional dorsal-stream areas (superior and inferior parietal cortices). Overall, the proposed approach is sensitive in detecting cortical activity underlying perceptual phenomena, and by maximally exploiting discriminant information contained in data, may reveal spatiotemporal features previously undisclosed, stimulating novel investigations.


Interpersonal synchronization of movement intermittency.
Most animal species group together and coordinate their behavior in quite sophisticated manners for mating, hunting, or defense purposes. In humans, coordination at a macroscopic level (the pacing of movements) is evident both in daily life (e.g., walking) and skilled (e.g., music and dance) behaviors. By examining the fine structure of movement, we here show that interpersonal coordination is established also at a microscopic - submovement - level. Natural movements appear as marked by recurrent (2-3 Hz) speed breaks, i.e., submovements, that are traditionally considered the result of intermittency in (visuo)motor feedback-based control. In a series of interpersonal coordination tasks, we show that submovements produced by interacting partners are not independent but alternate tightly over time, reflecting online mutual adaptation. These findings unveil a potential core mechanism for behavioral coordination that is based on between-persons synchronization of the intrinsic dynamics of action-perception cycles.


Desire, envy and punishment: a Matsigenka emotion schema in illness narratives and folk stories.
Accumulating evidence suggests that folktales in some societies are characterized by a culturally constructed underlying emotional structure, or Cultural Emotion Schema. In this paper we argue that Matsigenka illness narratives and folk stories share an underlying emotion schema, in which death and suffering result from conflicts between strong-willed individuals prompting anger and aggression. Analysis of illness narratives collected by Izquierdo in the Matsigenka community of Kamisea in the Peruvian Amazon between 1996 and 1999 reveals a common pattern in which envy and frustration lead to the belief in sorcery as the main cause of illness and death. This pattern contrasts with the typical stories of a previous generation collected by the Johnsons among the Matsigenka of Shimaa and other Matsigenka researchers, where sorcery beliefs were virtually absent. Our argument is that important changes in ecology, community, politics, and religion have led to a systematic rise in feelings of envy and frustration, and that these have increased the likelihood that sorcery accusations will occur. We explore the likelihood that such beliefs increase as egalitarian peoples become more crowded into settlements where they are likely to experience greater inequality, more competition for resources and increased societal and personal stress.


Resident-reported brachytherapy experience in ACGME-accredited radiation oncology training programs.
To describe resident-reported experience in brachytherapy in Accreditation Council of Graduate Medical Education-accredited radiation oncology training programs over the last 5 years. Archived reports of Accreditation Council of Graduate Medical Education final resident case logs from the last 5 years were reviewed and summarized. Brachytherapy was categorized according to the dose rate (low dose rate vs. high dose rate), technique (interstitial vs. intracavitary), and primary tumor site. Linear regression was used to test for trends. The mean number of total brachytherapy procedures performed per resident in the last 5 years has decreased from 80.8 in 2006-2007 to 71.0 in 2010-2011, but the trend is not statistically significant. The average number of intracavitary procedures has remained steady. The average resident experience with interstitial brachytherapy has decreased in a statistically significant manner. The average number of interstitial procedures has decreased by 25%. The average number of interstitial procedures reported by residents has decreased by 25%. The community charged with training residents in interstitial brachytherapy should consider methods to ensure that residents obtain sufficient experience in the future.


Effects of tryptophan mutation on the deprotonation and reprotonation kinetics of the Schiff base during the photocycle of bacteriorhodopsin.
The rates of deprotonation and reprotonation of the protonated Schiff base (PSB) are determined during the photocycle of nine bacteriorhodopsin mutants in which Trp-10, 12, 80, 86, 137, 138, 182 and 189 are individually substituted by either phenylalanine or cysteine. Of all the mutants, the replacement of Trp-86, Trp-182, and Trp-189 by phenylalanine and Trp-137 by cysteine is found to significantly alter the rate of the deprotonation, but not that of the reprotonation process. As compared with ebR, the Trp-86 mutation dramatically increases the rate of deprotonation of the PSB while the Trp-182 mutation greatly decreases this rate. Temperature dependence studies on the rate constants of the deprotonation demonstrate that the different energetic and entropic effects of the mutation are responsible for the observed different kinetic behavior of the Trp-86 and Trp-182 mutants as compared with that of ebR. In the case of Trp-86 mutant, a large decrease in both energy and entropy of activation suggests that the mutation of this tryptophan residue opens up the protein structure as a result of eliminating the hydrogen-bonding group on its side chain by a phenylalanine substitution. A correlation is observed between the proton pumping yield and the relative amplitudes of the slow deprotonation component but not with rate constants of the rise or decay process at constant pH. These results are best discussed in terms of the heterogeneity model (with parallel cycle) rather than back reaction model.


Dermatofibrosarcoma Protuberans in Children.
Paediatric dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue malignant tumour which displays aggressive local behaviour and has low metastatic potential. The diagnosis is often delayed as DFSP is usually mistaken for other skin conditions, particularly in the early stages of disease. DFSP tends to follow an indolent course after the initial presentation with what is often described as a "rubbery lump". As the disease progresses, the lump tends to enlarge, change colour, and exhibit a more nodular consistency. In rare cases, DFSP can present as an ulcerated exophytic lesion or a depressed area of skin, making diagnosis even more challenging. A high index of suspicion is warranted for early diagnosis, and referral to a specialist unit with expertise in both oncologic resection and reconstruction. DFSP tumours arise from the dermis and grow with finger-like projections. Therefore, in cosmetically sensitive or functionally important locations, an excision and analysis technique that assesses all excision margins is the gold standard of care. Slow Mohs technique performed with en bloc excision is a well-tolerated option for oncologic resection of the tumour. Mohs technique can also be considered but can be challenging in children for reasons explained below. As an alternative, depending on the anatomical location, tumours can be excised with a wide local excision. While an excision technique that incorporates the deep fascia with a 3-cm peripheral margin is acceptable in adults, planning of the excision margin in children should involve consideration of preoperative imaging with MRI, site of the tumour, age, and physical built of the child. Patients should be offered all treatment options considering the local outcomes, available expertise, and cost. A multidisciplinary approach and good communication between team members is crucial. Close collaboration with a pathologist who is familiar with sectioning technique that allows margin control is of paramount importance. Soft tissue reconstruction should be performed immediately after oncologic clearance, although a staged approach may be required. Adjuvant radiotherapy should be avoided in children due to the long-term risk of secondary malignancies and potential for growth disruption.