Neutron interference from a split-crystal interferometer.
The first successful operation of a neutron interferometer with a separate beam-recombining crystal is reported. This result was achieved at the neutron interferometry setup S18 at the ILL in Grenoble by a collaboration between TU Wien, ILL, Grenoble, and INRIM, Torino. While previous interferometers have been machined out of a single-crystal block, in this work two crystals were successfully aligned on nanoradian and picometre scales, as required to obtain neutron interference. As a decisive proof-of-principle demonstration, this opens the door to a new generation of neutron interferometers and exciting applications.


Measurement of mechanical properties on gap healing in a rabbit osteotomy model until the remodeling stage.
The most important issue in the assessment of fracture healing is to acquire information about the restoration of the mechanical integrity of bone. Many researchers have attempted to monitor stiffness either directly or indirectly for the purpose of assessing strength, as strength has been impossible to assess directly in clinical practice. The purpose of this study was thus to determine the relationship between bending stiffness and strength using mechanical testing at different times during the healing process. Unilateral, transverse, mid-tibial osteotomies with a 2-mm gap were performed in 28 rabbits. The osteotomy site was stabilized using a double-bar external fixator. The animals were divided into four groups (n=7/group/time point; 4, 6, 8 and 12 weeks). A series of images from micro-computed tomography of the gap was evaluated to detect the stage of fracture healing and a 4-point bending test was performed to measure stiffness and strength. Relative stiffness and strength values were also acquired from calculation of ratios relative to those of the non-osteotomized contralateral bones. Formation of cortex and medullary canal at the gap was seen in the 12-week group and would represent the remodeling stage. In addition, the relationship between stiffness and strength remained almost linear until at least 12 weeks. However, stiffness recovered much more rapidly than strength. Strength was not fully restored until the later stages of fracture healing. However, the current study demonstrated that stiffness could be monitored as a surrogate marker of strength until at least the remodeling stage.


[Reduction techniques for minimally invasive plate osteosynthesis].
The technique of fracture treatment by minimally invasive plate osteosynthesis (MIPO) is today part of the treatment repertoire of any experienced trauma surgeon. The minimization of any additional iatrogenic damage to the tissues and the preservation of the osteogenic fracture hematoma are the decisive differences to open reduction and internal fixation (ORIF). The MIPO technique is particularly applied in metaphyseal and diaphyseal fractures, which cannot be treated with intramedullary nails as well as in fractures with critical soft tissue covering and complex fractures with metaphyseal extension fractures. In metaphyseal and diaphyseal fractures a distinction must always be made between relatively simple (A/B1 type) and more complex (B2/3 and C type) fracture forms. In simple fracture forms, which are treated with minimally invasive plate osteosynthesis, an anatomical (or at least gap-free) reduction should be strived for. In contrast, in more complex metaphyseal and diaphyseal fractures achievement of correct functional alignment (correct axis, length and rotation) is the goal of reduction. The minimally invasive approach by the trauma surgeon in MIPO fracture treatment is mainly defined by the selected gentle reduction technique. Because the fracture zone cannot be directly viewed, good knowledge of the anatomy and careful surgical planning including reduction on an adequate image basis are of decisive importance. This article introduces the principles of the reduction techniques in minimally invasive plate osteosynthesis and their practical application is described in detail.


The face does predict the brain--midline facial and forebrain defects uncovered during the investigation of nasal obstruction and rhinorrhea. Case report and a review of holoprosencephaly and its classifications.
When the embryonic forebrain (the prosencephalon) fails to sufficiently divide into the two cerebral hemispheres, holoprosencephaly (HPE) results. This disorder can result in various skull and facial defects with brain abnormalities of varying severity. These brain defects ultimately dictate the prognosis. This varies from death in utero, to normal or near normal brain development. In these less severe cases, otherwise normally developing babies are born with rarely seen midfacial cleft deformities, giving away a structural brain deformity. We report a case of an otherwise developmentally normal seven-year-old boy who was being assessed for nasal obstruction and rhinorrhea. Investigation directed by a high index of suspicion uncovered an occult case of holoprosencephaly.


Automatic graph-cut based segmentation of bones from knee magnetic resonance images for osteoarthritis research.
In this paper, a new, fully automated, content-based system is proposed for knee bone segmentation from magnetic resonance images (MRI). The purpose of the bone segmentation is to support the discovery and characterization of imaging biomarkers for the incidence and progression of osteoarthritis, a debilitating joint disease, which affects a large portion of the aging population. The segmentation algorithm includes a novel content-based, two-pass disjoint block discovery mechanism, which is designed to support automation, segmentation initialization, and post-processing. The block discovery is achieved by classifying the image content to bone and background blocks according to their similarity to the categories in the training data collected from typical bone structures. The classified blocks are then used to design an efficient graph-cut based segmentation algorithm. This algorithm requires constructing a graph using image pixel data followed by applying a maximum-flow algorithm which generates a minimum graph-cut that corresponds to an initial image segmentation. Content-based refinements and morphological operations are then applied to obtain the final segmentation. The proposed segmentation technique does not require any user interaction and can distinguish between bone and highly similar adjacent structures, such as fat tissues with high accuracy. The performance of the proposed system is evaluated by testing it on 376 MR images from the Osteoarthritis Initiative (OAI) database. This database included a selection of single images containing the femur and tibia from 200 subjects with varying levels of osteoarthritis severity. Additionally, a full three-dimensional segmentation of the bones from ten subjects with 14 slices each, and synthetic images with background having intensity and spatial characteristics similar to those of bone are used to assess the robustness and consistency of the developed algorithm. The results show an automatic bone detection rate of 0.99 and an average segmentation accuracy of 0.95 using the Dice similarity index.


Multiple sclerosis.
Multiple sclerosis is the most common disabling neurologic disease affecting young adults and adolescents in the United States. The first objective of this article is to familiarize nonspecialists with the cardinal features of multiple sclerosis and our current understanding of its etiology, epidemiology, and natural history. The second objective is to explain the approach to diagnosis. The third is to clarify current evidence-based treatment strategies and their roles in disease modification. The overall goal is to facilitate the timely evaluation and confirmation of diagnosis and enhance effective management through collaboration among primary physicians, neurologists, and other care providers who are confronted with these formidably challenging patients.


Detection of reassortant influenza B strains from 2004 to 2015 seasons in Barcelona (Catalonia, Spain) by whole genome sequencing.
Influenza B viruses (FLUBV) have segmented genomes which enables the virus to evolve by segment reassortment. Since the divergence of both FLUBV lineages, B/Victoria/2/87 (FLUBV/VIC) and B/Yamagata/16/88 (FLUBV/YAM), PB2, PB1 and HA have kept the same ancestor, while some reassortment events in the other segments have been reported worldwide. The aim of the present study was to find out reassortment episodes in FLUBV strains detected in cases attended at Hospital Universitari Vall d'Hebron and Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) from 2004 to 2015 seasons. From October 2004 to May 2015, respiratory specimens were received from patients with respiratory tract infection suspicion. Influenza detection was carried out by either cell culture isolation, immunofluorescence or PCR-based assays. A RT-PCR was performed to distinguish both lineages by agarose gel electrophoresis. Whole genome amplification was performed using the universal primer set by Zhou et al. in 2012, and subsequently sequenced using Roche 454 GS Junior platform. Bioinformatic analysis was performed to characterise the sequences with B/Malaysia/2506/2007 and B/Florida/4/2006 corresponding sequences as reference of (B/VIC) and (B/YAM), respectively. A total of 118 FLUBV (75 FLUBV/VIC and 43 FLUBV/YAM), from 2004 to 2006, 2008-2011 and 2012-2015 seasons, were studied. The whole genome of 58 FLUBV/VIC and 42 FLUBV/YAM viruses was successfully amplified. Based on HA sequences, most FLUBV/VIC viruses (37; 64%) belonged to clade 1A (B/Brisbane/60/2008) except to 11 (19%), which fell within clade 1B (B/HongKong/514/2009) and 10 (17%) to B/Malaysia/2506/2004. Nine (20%) FLUBV/YAM viruses belonged to clade 2 (B/Massachusetts/02/2012), 18 (42%) to clade 3 (B/Phuket/3073/2013) and 15 (38%) fell within Florida/4/2006. Numerous intra-lineage reassortments in PB2, PB1, NA and NS were found in 2 2010-2011 viruses. An important inter-lineage reassortment event from 2008 to 2009 (11), 2010-2011 (26) and 2012-2013 (3) FLUBV/VIC (clade 1) strains to FLUBV/YAM (clade 3) was found, in addition to 1 reassortant NS in 2010-2011 B/VIC virus. Intra- and inter-lineage reassortment episodes were revealed by WGS. While PB2-PB1-HA remained in complex, NP and NS reassortant viruses were found in both lineages. Despite reassorment events are not often, the characterisation only by HA and NA sequences might be underestimating their detection.


Population extinctions driven by climate change, population size, and time since observation may make rare species databases inaccurate.
Loss of biological diversity through population extinctions is a global phenomenon that threatens many ecosystems. Managers often rely on databases of rare species locations to plan land use actions and conserve at-risk taxa, so it is crucial that the information they contain is accurate and dependable. However, small population sizes, long gaps between surveys, and climate change may be leading to undetected extinctions of many populations. We used repeated survey records for a rare but widespread orchid, Cypripedium fasciculatum (clustered lady's slipper), to model population extinction risk based on elevation, population size, and time between observations. Population size and elevation were negatively associated with extinction, while extinction probability increased with time between observations. We interpret population losses at low elevations as a potential signal of climate change impacts. We used this model to estimate the probability of persistence of populations across California and Oregon, and found that 39%-52% of the 2415 populations reported in databases from this region are likely extinct. Managers should be aware that the number of populations of rare species in their databases is potentially an overestimate, and consider resurveying these populations to document their presence and condition, with priority given to older reports of small populations, especially those at low elevations or in other areas with high vulnerability to climate or land cover change.


Development of a model with which to predict the life expectancy of patients with spinal epidural metastasis.
The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable. The Cox proportional hazards model was used to make a prediction model. To validate the model, Efron optimism correction by bootstrapping was performed. Retrospective data of patients treated for a spinal metastasis were used. Possible predictive factors were defined based on clinical experience and the literature. Statistical methods and clinical knowledge were also used to reveal an optimal set of predictors of survival. Data from patients treated at the Department of Radiation Oncology for spinal metastasis between 1998 and 2005 were evaluated. The case notes of 219 patients form the base of this study. In the final model, only 5 variables were required to predict the survival of a patient with spinal metastasis: sex, location of the primary lesion, intentional curative treatment of the primary tumor, cervical location of the spinal metastasis, and Karnofsky performance score. Examples with different predictors are given. The R(2) (N) index of Nagelkerke was 0.36 (95% confidence interval [95% CI], 0.28-0.48) and the c-index 0.72 (95% CI, 0.68-0.77). A reliable and simple model with which to predict the survival of a patient with spinal epidural metastasis is presented. Without the need for extensive investigations, survival can be predicted and only 5 easily obtainable parameters are required.


The phenotypic and behavioral defects can be transferred from zinc-exposed nematodes to their progeny.
In despite of the essential functions of zinc as trace element for humans, toxic effects will be pronounced while organisms are exposed to high levels of zinc. However, whether the multiple biological toxicities caused by zinc exposure could be transferred to progeny is still largely unknown. In the present study, we explored the model organism, Caenorhabditis elegans, to analyze the multiple toxicities from zinc exposure and their possibly transferable properties. Our results indicate that the zinc exposure could result in multiple biological defects by affecting the endpoints of life span, development, reproduction, locomotion behavior and chemotaxis plasticity. Zinc exposure could specially cause the appearance of uncoordinated (UNC) animals. In addition, Zn exposure could result in the stress responses in most of the tissues in exposed nematodes. Moreover, these phenotypic and behavioral toxicities could be transferred from zinc-exposed nematodes to their progeny. The fold changes of hsp16-2-gfp expression in embryos of progeny animals suggest that the zinc toxicity might be deposited in eggs of nematodes. We summarized these defects into two groups according to their transferable properties. Therefore, our data suggest that zinc exposure can result in multiple toxicities and these multiple biological defects can be largely transferred to progeny in C. elegans.


The association of acute rejection vs recurrent glomerular disease with graft outcomes after kidney transplantation.
It has been shown that glomerulonephritis (GN) recurrence affects graft survival more than acute rejection. Thus, we assessed allograft survival after biopsy-confirmed diagnosis of acute rejection or recurrent GN in current era of immunosuppression. Allograft survival following a biopsy diagnosis of acute rejection or recurrent GN was determined in adult kidney transplant recipients from 1994 to 2013. A total of 306 patients (35%) with IgA, 298 (35%) with FSGS, 177 (21%) with lupus nephritis, and 81 (9%) with membranous nephropathy were followed for a median of 6.3 years. Among the 862 transplant recipients with primary GN, allograft loss was similar following a biopsy diagnosis of acute rejection or recurrent glomerular disease (11.5 vs 14.2/100 person-years, P = .15). Differences in allograft survival emerged after 2.5 years following recurrent disease, with significantly higher graft failure in patients with FSGS, MN, or LN compared with IgA after recurrence of disease (16.7 vs 7.5/100 person-years, P = .05). The advantage in allograft survival for IgA patients did not achieve significance after acute rejection (P = .10 for IgA vs FSGS, MN, and LN). Allograft survival was similar after disease recurrence or acute rejection after kidney transplant in patients with ESRD due to GN.


Does dengue and COVID-19 co-infection have worse outcomes? A systematic review of current evidence.
In dengue-endemic regions, the co-infection with SARS-CoV-2 and dengue is a significant health concern. Therefore, we performed a literature search for relevant papers in seven databases on 26 Spetember 2021. Out of 24 articles, the mortality rate and intensive care unit (ICU) admission were 19.1% and 7.8%, respectively. The mean hospital stay was 11.4 days. In addition, we identified two pregnancies with dengue and COVID-19 co-infection; one ended with premature rupture of membrane and intrauterine growth restriction fetus, while the other one ended with maternal mortality and intrauterine fetal death. COVID-19 and dengue co-infection had worse outcomes regarding mortality rates, ICU admission, and prolonged hospital stay. Thus, wise-decision management approaches should be adequately offered to these patients to enhance their outcomes. Establishing an early diagnosis might be the answer to reducing the estimated significant burden of these conditions.


17 Beta-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell cultures.
Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17beta-estradiol (E2) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. HepG2 cells were exposed for 24 h to DCA (350 micromol/L). Cell viability, aspartate aminotransferase and lactate dehydrogenase activity and apoptosis were measured as indices of cell toxicity. The effect of DCA was compared to that observed using either a hydrophilic bile acid, ursodeoxycholic acid (UDCA; 100 micromol/L), or E2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 micromol/L) or mixtures of E2/DCA or UDCA/DCA. The same experiments were performed using WRL-68 cells that, at variance with HepG2, express a higher level of nuclear estrogen receptor. High concentrations of E2 and UDCA prevented DCA-induced decrease in cell viability, increase in enzyme activity and apoptosis evaluated both by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. In addition, DCA-related apoptosis, assessed by caspase activity, was also prevented by E2 (P < 0.01) in physiological (1-10 nmol/L) doses. The cytoprotective effects of E2 and UDCA was also observed in the WRL-68 cell line. 17Beta-Estradiol prevents DCA-induced cell damage in HepG2 and WRL-68 cell lines to an extent comparable to UDCA. The hypothesis that the protective effect of E2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.


Internal validation of the renal pelvic score: a novel marker of renal pelvic anatomy that predicts urine leak after partial nephrectomy.
To internally validate the renal pelvic score (RPS) in an expanded cohort of patients undergoing partial nephrectomy (PN). Our prospective institutional renal cell carcinoma database was used to identify all patients undergoing PN for localized renal cell carcinoma from 2007 to 2013. Patients were classified by RPS as having an intraparenchymal or extraparenchymal renal pelvis. Multivariate logistic regression models were used to examine the relationship between RPS and urine leak. Eight hundred thirty-one patients (median age, 60 ± 11.6 years; 65.1% male) undergoing PN (57.3% robotic) for low (28.9%), intermediate (56.5%), and high complexity (14.5%) localized renal tumors (median size, 3.0 ± 2.3 cm; median nephrometry score, 7.0 ± 2.6) were included. Fifty-four patients (6.5%) developed a clinically significant or radiographically identified urine leak. Seventy-two of 831 renal pelvises (8.7%) were classified as intraparenchymal. Intrarenal pelvic anatomy was associated with a markedly increased risk of urine leak (43.1% vs 3.0%; P <.001), major urine leak requiring intervention (23.6% vs 1.7%; P <.001), and minor urine leak (19.4% vs 1.2%; P <.001) compared with that in patients with an extrarenal pelvis. After multivariate adjustment, RPS (intraparenchymal renal pelvis; odds ratio [OR], 24.8; confidence interval [CI], 11.5-53.4; P <.001) was the most predictive of urine leak as was tumor endophyticity ("E" score of 3 [OR, 4.5; CI, 1.3-15.5; P = .018]), and intraoperative collecting system entry (OR, 6.1; CI, 2.5-14.9; P <.001). Renal pelvic anatomy as measured by the RPS best predicts urine leak after open and robotic partial nephrectomy. Although external validation of the RPS is required, preoperative identification of patients at increased risk for urine leak should be considered in perioperative management and counseling algorithms.


Multicentre cohort study of acute cholecystitis management during the COVID-19 pandemic.
To analyse acute cholecystitis (AC) management during the first pandemic outbreak after the recommendations given by the surgical societies estimating: morbidity, length of hospital stay, mortality and hospital-acquired SARS-CoV-2 infection rate. Multicentre-combined (retrospective-prospective) cohort study with AC patients in the Community of Madrid between 1st March and 30th May 2020. 257 AC patients were involved in 16 public hospital. Multivariant binomial logistic regression (MBLR) was applied to mortality. Of COVID-19 patients, 30 were diagnosed at admission and 12 patients were diagnosed during de admission or 30 days after discharge. In non-COVID-19 patients, antibiotic therapy was received in 61.3% of grade I AC and 40.6% of grade II AC. 52.4% of grade III AC were treated with percutaneous drainage (PD). Median hospital stay was 5 [3-8] days, which was higher in the non-surgical treatment group with 7.51 days (p < 0.001) and a 3.25% of mortality rate (p < 0.21). 93.3% of patients with SARS-CoV-2 infection at admission were treated with non-surgical treatment (p = 0.03), median hospital stay was 11.0 [7.5-27.5] days (p < 0.001) with a 7.5% of mortality rate (p > 0.05). In patients with hospital-acquired SARS-CoV-2 infection, 91.7% of grade I-II AC were treated with non-surgical treatment (p = 0.037), with a median hospital stay of 16 [4-21] days and a 18.2% mortality rate (p > 0.05). Hospital-acquired infection risk when hospital stay is > 7 days is OR 4.7, CI 95% (1.3-16.6), p = 0.009. COVID-19 mortality rate was 11.9%, AC severity adjusted OR 5.64 (CI 95% 1.417-22.64). In MBLR analysis, age (OR 1.15, CI 95% 1.02-1.31), SARS-CoV-2 infection (OR 14.49, CI 95% 1.33-157.81), conservative treatment failure (OR 8.2, CI 95% 1.34-50.49) and AC severity were associated with an increased odd of mortality. In our population, during COVID-19 pandemic, there was an increase of non-surgical treatment which was accompanied by an increase of conservative treatment failure, morbidity and hospital stay length which may have led to an increased risk hospital-acquired SARS-CoV-2 infection. Age, SARS-CoV-2 infection, AC severity and conservative treatment failure were mortality risk factors.


Stereoselective determination of mepivacaine in human serum using a brush-type chiral stationary phase and solid-phase extraction.
A stereoselective high-performance liquid chromatography assay method was developed for the quantitation of R-(+)- and S-(-)-mepivacaine in human serum. The assay uses a Pirkle brush-type (S)-tert.-leucine, (R)-1-(alpha-naphthyl)ethylamine stationary phase (Sumichiral OA-4700, 250 x 4 mm I.D.) at ambient temperature with a mobile phase of hexane-ethylenedichloride-absolute methanol (85:10:5, v/v) for the separation of R-(+)- and S-(-)-mepivacaine. The eluents were monitored using UV detection at 220 nm. Isolation of the analytes from serum was performed using a 1-ml C18 solid-phase extraction cartridge with high recovery and selectivity. The detection limits were 100 ng/ml for each enantiomer and the limits of quantitation were 150 ng/ml for both enantiomers. Linear calibration curves in the 150-2400 ng/ml range showed good correlation coefficients (r > 0.9994, n = 3). Precision and accuracy of the method were within 2.1-5.3 and 2.0-3.6%, respectively, for R-(+)-mepivacaine and 2.7-5.7% and 1.7-4.2%, respectively, for S-(-)-mepivacaine.


Ancillary tests for hepatobiliary neoplasms: what we know and what we need to know.
Ancillary tests are commonly used in the surgical pathology setting for diagnosing challenging neoplastic diseases of the liver and biliary tract, while histology and clinical correlation remain to be critically important. With continuous discoveries, more and more useful ancillary tests have become available, which can help distinguish between malignant and benign hepatocellular neoplasms, malignant and benign biliary tract entities, and intrahepatic and metastatic carcinomas. This review will focus on existing and emerging biomarkers (such as glutamine synthetase, organic anion transporting polypeptide 1B3, insulin-like growth factor-II mRNA binding protein-3, S100P, SMAD4, enhancer of zeste homolog 2, albumin, hepatocyte nuclear factor-1β, etc.) that can be used for the diagnosis, classification and prognostication of hepatobiliary neoplasms.


Instability of Efavirenz Metabolites Identified During Method Development and Validation.
Accurate quantification of efavirenz metabolites in patient samples is required to investigate their potential contribution to efavirenz adverse events. This study aimed to validate a LC-MS/MS method to quantify and investigate the stability of efavirenz and metabolites in human plasma. Compounds were extracted from plasma by supported liquid extraction and resolved on a C18 column. Validation was performed following FDA bioanalytical method validation guidelines. Stability under common conditions of sample pre-treatment and storage were assessed. Efavirenz and 8-hydroxyefavirenz were stable for all conditions tested. 7-Hydroxyefavirenz and 8,14-dihydroxyefavirenz were not stable in plasma at room temperature for 24 h (46%-69% loss), -20°C for 90 days (17%-50% loss), or 60°C for 1 h (90%-95% loss). Efavirenz and 8-hydroxyefavirenz concentrations in HIV/AIDS patient (n=5) plasma prepared from pre-treated (60°C for 1 h) whole blood varied from 517-8564 ng/mL and 131-813 ng/mL, respectively. 7-Hydroxyefavirenz and 8,14-dihydroxyefavirenz concentrations were below validated lower limits of quantification (0.25 and 0.5 ng/mL, respectively), most likely due to sample pre-treatment. This is the first report of 7-hydroxyefavirenz and 8,14-dihydroxyefavirenz instability under conditions commonly used in preparation of samples from HIV/AIDS patients. Alternative biosafety measures to heat pre-treatment must therefore be used for accurate quantification of plasma 7-hydroxyefavirenz and 8,14-dihydroxyefavirenz.


Yield-enhancing quantitative trait loci (QTLs) from wild species.
Wild species of crop plants are increasingly being used to improve various agronomic traits including yield in cultivars. Dense molecular maps have enabled mapping of quantitative trait loci (QTLs) for complex traits such as yield. QTLs for increased yield have been identified from wild relatives of several crop plants. Advanced backcross QTL analysis has been used to identify naturally occurring favorable QTL alleles for yield and minimize the effect of unwanted alleles from wild species. Yield QTLs from wild species are distributed on almost all chromosomes but more often in some regions. Many QTLs for yield and related traits derived from different wild accessions or species map to identical chromosomal regions. QTLs for highly correlated yield associated traits are also often co-located implying linkage or pleiotropic effects. Many QTLs have been detected in more than one environment and in more than one genetic background. The overall direction of effect of some QTLs however, may vary with genetic context. Thus, there is evidence of stable and consistent major effect yield-enhancing QTLs derived from wild species in several crops. Such QTLs are good targets for use in marker assisted selection though their context-dependency is a major constraint. Literature on yield QTLs mapped from wild species is summarized with special reference to rice and tomato.


Clinical studies of advanced glycation end product inhibitors and diabetic kidney disease.
Current treatment of the nephropathy complication of diabetes mellitus is suboptimal in halting the progression of the complex disease. Among the irreversible effects of sustained hyperglycemia is the heightened formation of advanced glycation end products (AGEs). The role of AGEs in diabetic nephropathy has been established by years of basic research. This article reports progression through human studies of the few AGE inhibitors that have reached clinical development, including pimagedine, pyridoxamine, and alagebrium.


Differential Fragmentation of Mobility-Selected Glycans via Ultraviolet Photodissociation and Ion Mobility-Mass Spectrometry.
The alternative dissociation pathways initiated by ultraviolet photodissociation (UVPD) compared with collision-induced dissociation (CID) may provide useful diagnostic fragments for biomolecule identification, including glycans. However, underivatized glycans do not commonly demonstrate strong UV absorbance, resulting in low fragmentation yields for UVPD spectra. In contrast to UVPD experiments that leverage covalent modification of glycans, we detail the capacity of metal adduction to yield comparatively rich UVPD fragmentation patterns and enhance separation factors for an isomeric glycan set in a drift tube ion mobility system. Ion mobility and UVPD-MS spectra for two N-acetyl glycan isomers were examined, each adducted with sodium or cobalt cations, with the latter providing fragment yield gains of an order of magnitude versus sodium adducts. Furthermore, our glycan analysis incorporated front-end ion mobility separation such that the structural glycan isomers could still be identified even as a mixture and not simply composite spectra of isomeric standards. Cobalt adduction proved influential in the glycan separation by yielding an isomer resolution of 0.78 when analyzed simultaneously versus no discernable separation obtained with the sodium adducts. It is the combined enhancement of both isomeric drift time separation and isomer distinction with improved UVPD fragment ion yields that further bolster multivalent metal adduction for advancing glycan IM-MS experiments. Graphical Abstract .


Anxiety disorders, depression and incontinence in preschool children-A population-based study.
The aim was to examine associations of specific anxiety disorders, depressive symptoms, and incontinence in a representative, population-based sample of preschool children. All preschool children of a defined geographical area examined before school-entry were included. Parents completed a questionnaire including the Preschool Feelings Checklist (PFC), eight questions referring to nocturnal enuresis (NE), daytime urinary incontinence (DUI), fecal incontinence (FI) and constipation, and 30 items regarding Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) diagnostic criteria of separation anxiety disorder (SAD), social phobia (SOC), specific phobia (PHOB), and generalized anxiety disorder (GAD). Data of 1206 children (mean age = 5.7 years; 53.5% boys) are presented. 34.6% of incontinent children had an anxiety disorder based on DSM-5 criteria and 13.3% had clinically relevant depressive symptoms (measured by the PFC). Rates of incontinence overall were 14.1% (11.9% NE, 3.1% DUI, and 1.8% FI) and 6.3% for constipation. Rates of SOC and PHOB were increased in NE (20.8% and 25.4%), DUI (39.3% and 34.5%) and FI (35.3% and 50.0%) compared to continent children (13.5% and 17.2%). Children with constipation had higher rates of SOC, PHOB, and GAD than those without. Compared to continent children (9.7%), depressive symptoms were more frequent in children with NE (26.8%), DUI (50.0%), and FI (61.9%). Anxiety disorders and depressive symptoms are common in children with incontinence. The most specific DSM-5 disorders associated with incontinence are SOC and PHOB, which can be incapacitating and may require treatment. Due to the high rates of anxiety disorders, it is important to screen all children with incontinence, for example, with specific questionnaires.


Smooth graph learning for functional connectivity estimation.
Functional connectivity (FC) estimated from functional magnetic resonance imaging (fMRI) signals is important in understanding neural representation and information processing in cortical networks. However, due to a lack of "ground truth" FC pattern, the reliability and robustness of FC estimates are usually examined in downstream FC analysis tasks, such as performing participant's identification (also known as "fingerprinting"). In this paper, we propose to learn FC via a smooth graph learning framework. In particular, we treat each time frame of the fMRI time series as a graph signal on an underlying functional brain graph, and estimate the smooth graph functional connectivity (SGFC) by learning the weighted graph adjacency matrix based on graph signal smoothness assumption. We demonstrate that our approach gives rise to a natural and sparse graph representation of FC from which reliable graph measures can be extracted. Reliability of SGFC is evaluated in the context of fingerprinting and compared to correlation FC (CFC). SGFC achieves higher fingerprinting accuracy across several different experiment settings; the improvement is even more significant when a shorter fMRI scanning length is used for FC estimation. In addition to being reliable, we also validate the cognitive relevance of SGFC by using it to predict fluid intelligence. Finally, in evaluating topological measures of the sparse graph, SGFC reveals a more small-world and modular structure compared to CFC. Together, our results suggest that the smooth graph learning framework produces a naturally sparse, reliable, and cognitive-relevant representation of functional connectivity.


Classical phenotyping and deep learning concur on genetic control of stomatal density and area in sorghum.
Stomatal density (SD) and stomatal complex area (SCA) are important traits that regulate gas exchange and abiotic stress response in plants. Despite sorghum (Sorghum bicolor) adaptation to arid conditions, the genetic potential of stomata-related traits remains unexplored due to challenges in available phenotyping methods. Hence, identifying loci that control stomatal traits is fundamental to designing strategies to breed sorghum with optimized stomatal regulation. We implemented both classical and deep learning methods to characterize genetic diversity in 311 grain sorghum accessions for stomatal traits at two different field environments. Nearly 12,000 images collected from abaxial (Ab) and adaxial (Ad) leaf surfaces revealed substantial variation in stomatal traits. Our study demonstrated significant accuracy between manual and deep learning methods in predicting SD and SCA. In sorghum, SD was 32%-39% greater on the Ab versus the Ad surface, while SCA on the Ab surface was 2%-5% smaller than on the Ad surface. Genome-Wide Association Study identified 71 genetic loci (38 were environment-specific) with significant genotype to phenotype associations for stomatal traits. Putative causal genes underlying the phenotypic variation were identified. Accessions with similar SCA but carrying contrasting haplotypes for SD were tested for stomatal conductance and carbon assimilation under field conditions. Our findings provide a foundation for further studies on the genetic and molecular mechanisms controlling stomata patterning and regulation in sorghum. An integrated physiological, deep learning, and genomic approach allowed us to unravel the genetic control of natural variation in stomata traits in sorghum, which can be applied to other plants.


Detailed Characterization of the Cooperative Binding of Piperine with Heat Shock Protein 70 by Molecular Biophysical Approaches.
In this work, for the first time, details of the complex formed by heat shock protein 70 (HSP70) independent nucleotide binding domain (NBD) and piperine were characterized through experimental and computational molecular biophysical methods. Fluorescence spectroscopy results revealed positive cooperativity between the two binding sites. Circular dichroism identified secondary conformational changes. Molecular dynamics along with molecular mechanics Poisson Boltzmann surface area (MM/PBSA) reinforced the positive cooperativity, showing that the affinity of piperine for NBD increased when piperine occupied both binding sites instead of one. The spontaneity of the complexation was demonstrated through the Gibbs free energy (∆G < 0 kJ/mol) for different temperatures obtained experimentally by van't Hoff analysis and computationally by umbrella sampling with the potential of mean force profile. Furthermore, the mean forces which drove the complexation were disclosed by van't Hoff and MM/PBSA as being the non-specific interactions. In conclusion, the work revealed characteristics of NBD and piperine interaction, which may support further drug discover studies.


Ketone body metabolism in diabetic and non-diabetic heart failure.
Heart failure (HF) is one of the most common cardiovascular diseases, causing large disease and economic burden worldwide. Impaired metabolic balance has been confirmed as a significant aspect of HF, and alteration of substrate utilization plays a vital role in the development of HF. Diabetes mellitus is strictly related with HF, and patients with diabetes show a higher mortality and morbidity of HF. Furthermore, HF patients and animals with diabetes behave different characteristics of metabolic pattern and substrate utilization comparing to those without diabetes. Recently, ketone body has been demonstrated as an alternative energy source in HF, which may improve myocardial energy supply and thus be adaptive for HF. Studies measured ketone body oxidation and production of ketone body metabolism in different groups of patients and animal models. This review focuses on the alteration of ketone body metabolism during HF and compares different results between diabetic and non-diabetic HF and the potential mechanism.


Long-term follow-up of renal transplantation in type 1 and type 2 diabetic patients.
This study evaluated the long-term outcome of renal transplantation in type 1 (n = 25) and type 2 (n = 18) diabetic patients. Overall postoperative survival at 1 year was 69% in type 1 diabetes and 75% in type 2; at 5 years it was 62% in type 1 diabetes and 58% in type 2. Death was due mainly to cardiovascular disease (60%) and septic gangrene (20%). Outcome was examined in terms of graft function, which was poor in the majority (86%) of patients who died. Patients with fatal outcome suffered major vascular complications prior to renal transplantation and frequently had impaired graft function. Metabolic control was better in patients with good graft function (HbA1c < 6.2%) than in those with poor or no function of kidney transplant (HbA1c > 9.8%). In the absence of severe vascular complications renal transplantation may be the treatment of choice for both type 1 and type 2 diabetic patients with end-stage renal disease. Otherwise, renal transplantation is not able to improve the prognosis of patients with a history of severe vascular complications prior to renal replacement therapy.


Temporal trend of leprosy in a region of high endemicity in the Brazilian Northeast.
to analyze the temporal trend and epidemiological patterns of leprosy indicators in Sobral, a municipality countryside of the state of Ceará, from 2001 to 2016. a time series study based on data from the Department of Informatics of the Unified Health System. The time trend analysis was performed using the join point regression model. There were 2,220 new cases of leprosy in Sobral from 2001 to 2016. Of these, 158 (7.2%) in children younger than 15 years of age, the proportion of new male cases was 52.8% (1,162), cases with grade 2 were 7.0% (156), and proportion of cases diagnosed by contact examination 5.7% (126). leprosy remains hyperendemic in adults and children, demonstrating the character of neglected disease. Analysis of the temporal trend allowed to verify that the instability in the detection coefficients, reflect operational problems in the organization of the services.


Safety of the adjustable pressure ventricular valve in magnetic resonance imaging: problems and solutions.
We performed magnetic resonance imaging in 30 patients with hydrocephalus with Sophy adjustable pressure valves (PAVS). A pressure check following the MRI study showed a significant proportion with pressure valve changes, which could easily be readjusted by percutaneous manipulation. The value of the PAVS and its safety during MRI examinations are discussed.


Healthcare Costs Among Patients with Psoriasis Treated with Ixekizumab Versus Secukinumab in Real-World Settings Over 24 Months.
The aim of this study was to compare healthcare costs between ixekizumab (IXE)-treated and secukinumab (SEC)-treated patients with psoriasis over a 24-month follow-up period in the United States. Patients with psoriasis diagnosis were identified from IBM Watson Health MarketScan® Research Databases; those with one or more claim for index drug (IXE or SEC) between March 1, 2016 and October 31, 2019 were included. Included patients were ≥ 18 years old and had continuous enrollment with medical and pharmacy benefits ≥ 6 months before and ≥ 24 months after index date. Patients were classified as IXE or SEC users based on drug received at index. Per patient per month (PPPM) all-cause, psoriasis-related, and index drug costs for IXE and SEC users were estimated over 24 months of follow-up. Institute for Clinical and Economic Review (ICER) discount factors were applied to adjust pharmacy costs. Index drug costs were additionally adjusted for adherence. Inverse probability of treatment weighting was used to address cohort imbalances. Chi-square/t tests were used to compare IXE versus SEC users; p value < 0.05 was considered statistically significant. Overall, 1461 patients (IXE users, n = 471; SEC users, n = 990) were included. IXE versus SEC users had higher weighted PPPM all-cause, psoriasis-related, and index drug costs (p ≤ 0.001). IXE versus SEC users had comparable ICER-adjusted mean PPPM all-cause costs (US$4172 ± 3349 vs US$3978 ± 2619; p = 0.227) and psoriasis-related costs (US$2950 ± 1332 vs US$2899 ± 1152; p = 0.447). After applying ICER and adherence adjustments, index drug costs were similar between IXE and SEC users (US$3794 ± 1822 vs US$3766 ± 1973; p = 0.795). All-cause and psoriasis-related costs were comparable between IXE and SEC users after ICER adjustments; index drug costs were similar after ICER and adherence adjustments.


Impact of Polyethylene Thickness on Clinical Outcomes and Survivorship in Medial Mobile-Bearing Unicondylar Knee Arthroplasty.
The thickness of the polyethylene bearing in medial unicondylar knee arthroplasty (UKA) is determined by the depth of the tibial resection, degree of correctable deformity, and balance of the knee. The purpose of this study is to evaluate whether polyethylene thickness in medial mobile-bearing UKA impacts clinical outcomes and survivorship. A retrospective review from 2004 to 2017 identified patients who underwent a primary mobile-bearing medial UKA with 2-year minimum follow-up or revision. A total of 2305 patients (3030 knees) met inclusion criteria. Patients were divided in 2 groups: thin bearing (group 1): 3-mm or 4-mm bearing and thick bearing (group 2): ≥ 5 mm. The thin group consisted of 2640 knees (87%), whereas the thick group had 390 knees (13%). Preoperative and postoperative demographics, range of motion, Knee Society scores, complications, and reoperations were evaluated. Mean follow-up was 5.2 years (range, 0.5 to 12.6). There was no significant difference between groups in postoperative range of motion or Knee Society scores (P > .05). Manipulations were performed in 1.3% of patients and not significantly different between groups. The all-cause revision rate for group 1 was 4.02% and group 2 was 4.58% (P = .6). Revision rates for tibial aseptic loosening were significantly higher in group 2 (1.8%) than those in group 1 (0.7%) (P = .04). There was no significant difference in failure rates between groups for tibial collapse or fracture, femoral aseptic loosening, arthritic progression, bearing dislocation, or other cause of revision. This study demonstrated that thicker bearings in medial UKA increased the risk of tibial aseptic loosening, but not all-cause failures or clinical outcomes.


Frequency of pseudo-Gaucher cells in diagnostic bone marrow biopsies from patients with Ph-positive chronic myeloid leukaemia.
Pseudo-Gaucher cells (PGC) are a characteristic finding in Ph-positive CML, and prolongation of survival was observed when PGC were detected within the bone marrow. However, the conspicuous variation in the reported frequencies indicates the necessity for analysis of their natural occurrence in the bone marrow from untreated CML patients. A total of 833 diagnostic bone marrow biopsies from patients with Ph-positive CML were examined for PGC by 7 observers. Proof of PGC was based on systematic examination of Giemsa-stained slides with and without polarization at high magnification. Birefringence within the cytoplasm turned out to be highly specific for PGC. The risk of overlooking PGC was at least 80% when the number of these storing histiocytes was 70 per slide or less, and at least 50% when the total amount per slide was < or = 250. This high risk of failure explained the disagreement among the authors. An intensive investigation by at least two observers is mandatory if results are to be evaluated in research. Under the conditions used in this study, the natural frequency of PGC within the bone marrow from untreated patients with a Ph-positive CML is much higher than assumed to date, amounting to about 70%. On the basis of these findings, the prognostic importance of PGC in CML must be evaluated critically.


A missense mutation in the NF2 gene results in moderate and mild clinical phenotypes of neurofibromatosis type 2.
Since the identification of the NF2 tumor suppressor gene in 1993, various mutations have been found in NF2-related tumors and in lymphocytes from NF2 patients. Most of the reported mutations result in truncated gene products. Missense mutations affecting the tumor suppressor are rare. These missense mutations would provide valuable information for the understanding of the function of the tumor suppressor, since they should affect critical parts of the protein. In this study we describe a novel point mutation in exon 15 of the NF2 gene, which is found in lymphocyte DNA of two NF2 patients from one family. This mutation is expected to result in a substitution of Pro for Gln at codon 538. Though both of the two patients developed bilateral vestibular schwannomas, the first patient showed onset of the disease at the age of 31 years and presented with various central, peripheral and abdominal tumors, while the second patient showed later onset of clinical symptoms (at age 52 years) and presented with only two additional small spinal tumors.


Brief embryonic strychnine exposure in zebrafish causes long-term adult behavioral impairment with indications of embryonic synaptic changes.
Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that a short embryonic exposure to a neurotoxicant can alter development of neural synapses and lead to changes in adult behavior.


Effects of aging, Parkinson's disease, and dopaminergic medication on response selection and control.
We examined effects of short-term and long-term dopaminergic medication in Parkinson's disease on conflict monitoring or response selection processes. These processes were examined using event-related potentials (ERPs), while subjects performed a stimulus-response (S-R) compatibility task. An extended sample of young and elderly controls, Parkinson's disease patients with a medication history (PDs) and initially diagnosed, drug-naïve de novo PD patients (de novo PDs) were enrolled. Both PD groups were measured twice (on and off-medication or before and 8 weeks after medication onset). The results show that dopaminergic intervention selectively reduced the pathologically enhanced response selection in compatible S-R relations. This medication effect was already evident after short-term treatment, not differing from long-term treatment and performance in elderly controls. Contrary, age-related attenuations of the N2 in incompatible S-R relations, probably reflecting impaired conflict processing or response control, are unaffected by medication. The results suggest that compatible and incompatible S-R relations demand different neuronal mechanisms within the basal ganglia, as only the former are affected by agonizing the dopaminergic system.


Radioprotection of targeted and bystander cells by methylproamine.
Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to (137)Cs γ-ray/X-ray irradiation and He(2+) microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for (137)Cs γ-rays and X-rays but not for He(2+) charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He(2+) ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He(2+) ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.


Pre- and post-weaning performance of artificially reared calves. II. The effects of milk substitute and milk substitute-whey diets on the performance of calves with particular reference to the selection of calves with improved growth potential from their blood composition a week after birth.
Sixteen Friesland bull calves were divided into two groups and raised artificially in an early weaning system. The liquid feeding of one group consisted of a commercial milk substitute and that of the other group of a 50:50 milk substitute-whey mixture. Blood samples were taken at regular intervals, starting one week after birth, and analysed for packed cell volume (PCV), blood glucose and haemoglobin (Hb); serum albumin, total protein, urea, inorganic phosphate (Pi), Ca, Mg, Na and K. The liquid portion of the diet had no significant effect on either the blood composition of the calves or on their performance (mass gain, dry matter intake and feed conversion) at the end of the experimental period (week 13). The only significant difference (P less than 0,05) between the two groups was the body mass of the calves at weaning. There were significant changes in the concentrations of most blood constituents with age (P less than 0,001 for Hb, PCV, albumin, globulin, Pi and K; P less than 0,01 for urea and Ca). A significant correlation (P less than 0,05) was also found between the calves' growth rates from 1 to 13 weeks and the concentration of globulin at one week of age. The regression of growth rate from 1 to 13 weeks with the blood constituents, globulin, Hb, PCV, Pi, Mg and Ca at one week of age accounted for 67,4% of the variance among calves. The evidence suggests that the above types of liquid feeding in an early weaning system would not significantly affect the composition of the blood of calves when sampled approximately six weeks or more after weaning, provided a predictive assessment of subsequent growth performance.


Morphological and optical features of the apposition compound eye of Monochamus alternatus Hope (Coleoptera: Cerambycidae).
The Japanese pine sawyer beetle, Monochamus alternatus Hope (Coleoptera: Cerambycidae) is currently the most destructive forest pest as it transmits the pine wilt nematode Bursaphelenchus xylophilus. Morphological, optical features and dark/light adaptational changes of the compound eyes of M. alternatus adults were examined by light, scanning and transmission electron microscopy. The eye of M. alternatus is apposition type and contains 489-712 ommatidia, depending on the beetle's body size. Each ommatidium features a large corneal lens, composed of a thick inner lens (ILU) and a thin outer lens unit (OLU); an acone-type of cone of four cone cells, a semi-fused type of rhabdom formed by eight retinular cells (two central cells: R7-R8 surrounded by six peripheral cells: R1-R6). Dark/light adaptational changes affect size and shape of the cones as well as the rhabdom's cross-sectional area and outline, to optimize the amount of light that reaches the photopigment. The compound eyes of M. alternatus have an F-number of 0.94, an interommatidial angle of 5.34°, an eye parameter P of 4.98 μm rad and a ratio of acceptance to interommatidial angle of 0.45. The eye is characterized by relatively poor spatial resolution, but can be expected to exhibit high absolute sensitivity and contrast in dim light.


HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.
Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.


Correction: Changes in historical typhoid transmission across 16 U.S. cities, 1889-1931: Quantifying the impact of investments in water and sewer infrastructures.
[This corrects the article DOI: 10.1371/journal.pntd.0008048.].


Oxidative stability of high oleic sunflower oil during deep-frying process of purple potato Purple Majesty.
The behaviour of high oleic sunflower oil in deep frying process of purple potato Purple Majesty has been evaluated simulating a fast food cooking process. This oil was used for 8h/day for 6 days, filling up from the 2nd day. A discontinuous and prolonged procedure was tested. Free Fatty Acidity (FFA), Peroxide Value (PV), Total Polar Compounds (TPC), Fatty Acid (FA) composition, Volatile Organic Compounds (VOC) have been determined at different times in thermo-oxidized (T-OX) oil, and in frying oil. The FFA in T-OX oil samples showed values in the range 0.09%-0.24%, whereas in the frying oil values varied in a range between 0.09% and 0.16%. TPCs values varied from 1.76% to 38.24% in T-OX oils, whereas in frying oil used for frying purple potatoes (FOPP) showed values in the range from 1.76 to 29.13%. The peroxides values did not follow a regular pattern, both during thermo-oxidation and during frying. Among the Long Chain Fatty Acids (LCFAs), oleic acid was the most represented (84.13%). Short chain fatty acids (SCFAs) amount was 0.34% (octanoic acid). Medium chain fatty acids (MCFA) amount was 4.45% (palmitic acid). During the thermo-oxidation, the poly-unsaturated fatty acids (PUFA) amount decreased during the 48 h of heat treatment, reaching an amount of 6.21%. This determined the increase in short chain fatty acids (SCFA). Trans fatty acids increased with the frying time. Unsaturated fatty acids (UFA) reached the value of 90.19%; SFA was 9.79%, and octanoic acid was 0.20%. A correlation between TPC vs UFA/SFA and TPC vs C18:2/C16:0 was observed in the frying oil. The most abundant volatile compounds in frying oil (from 0 to 48 h) were the aldehydes produced by decomposition of hydroperoxides of oleic and linoleic acids.


Association between diabetes mellitus, prediabetes and risk, disease progression of Parkinson's disease: A systematic review and meta-analysis.
Previous studies reported inconsistent results regarding association between diabetes mellitus (DM), prediabetes and risk, disease progression of Parkinson's disease (PD). The meta-analysis was made to investigate association between DM, prediabetes and risk, disease progression of PD. Literatures investigating association between DM, prediabetes and risk, disease progression of PD were searched in these databases: PubMed and Web of Science. Included literatures were published before October 2022. STATA 12.0 software was used to compute odds ratios (ORs)/relative risks (RRs) or standard mean differences (SMDs). DM was associated with a higher risk of PD, compared to non-diabetic participants with a random effects model (OR/RR = 1.23, 95% CI 1.12-1.35, I 2 = 90.4%, p < 0.001). PD with DM (PD-DM) was associated with a faster motor progression compared to PD without DM (PD-noDM) with a fixed effects model (RR = 1.85, 95% CI 1.47-2.34, I 2 = 47.3%, p = 0.091). However, meta-analysis for comparison in change rate of United Rating Scale (UPDRS) III scores from baseline to follow-up time between PD-DM and PD-noDM reported no difference in motor progression between PD-DM and PD-noDM with a random effects model (SMD = 2.58, 95% CI = -3.11 to 8.27, I 2 = 99.9%, p < 0.001). PD-DM was associated with a faster cognitive decline compared to PD-noDM with a fixed effects model (OR/RR = 1.92, 95% CI 1.45-2.55, I 2 = 50.3%, p = 0.110). In conclusion, DM was associated with a higher risk and faster disease decline of PD. More large-scale cohort studies should be adopted to evaluate the association between DM, prediabetes and PD.


Age-related differences in network structure and dynamic synchrony of cognitive control.
Cognitive trajectories vary greatly across older individuals, and the neural mechanisms underlying these differences remain poorly understood. Here, we investigate the cognitive variability in older adults by linking the influence of white matter microstructure on the task-related organization of fast and effective communications between brain regions. Using diffusion tensor imaging and electroencephalography, we show that individual differences in white matter network organization are associated with network clustering and efficiency in the alpha and high-gamma bands, and that functional network dynamics partly explain individual differences in cognitive control performance in older adults. We show that older individuals with high versus low structural network clustering differ in task-related network dynamics and cognitive performance. These findings were corroborated by investigating magnetoencephalography networks in an independent dataset. This multimodal (fMRI and biological markers) brain connectivity framework of individual differences provides a holistic account of how differences in white matter microstructure underlie age-related variability in dynamic network organization and cognitive performance.


Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.
To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. Retrospective cohort study with prospectively collected data between June 2011 and January 2019. Seventeen academic hospitals in the United States. We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. None. We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.


Ankrd7, a novel gene specifically expressed in Sertoli cells and its potential roles in Sertoli cell maturation.
The somatic Sertoli cells play an essential role in testis determination and spermatogenesis by providing nutrition and structural support. In the current study, we report on the novel Ankrd7 gene that contains five ankyrin repeat domains. This gene was specifically expressed in Sertoli cells and was regulated in a maturation-dependent manner. Its expression was restricted to testicular tissue, and its mRNA could be detected in testes at as early as 14 dpp (days post partum) using RT-PCR analysis. In both testicular tissue sections and in vitro cultured Sertoli cells, the Ankrd7 protein was localized to the nucleus of the Sertoli cell. Immuno-histochemistry and immunocytochemistry investigations showed that the protein was detectable in testicular tissues at 20 dpp, at which time Sertoli cells were gradually differentiating into their mature cellular form. These results suggest that Ankrd7 is probably involved in the process of Sertoli cell maturation and in spermatogenesis.


An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy.
Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics, the resistance against approved therapy remains an issue of concern. The resistance against the therapy is widely reported due to factors like clonal selection, involvement of multiple developmental pathways, and majorly defective mismatch repair (MMR) mediated by O6- methylguanine DNA methyltransferase (MGMT). Phytotherapy is one of the most effective alternatives to overcome resistance. It involves plant-based compounds, divided into several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds comprised in these classes are extracted or processed from certain plant sources. They can target various proteins of molecular pathways associated with the progression and survival of GBM. Phytocompounds have also shown promise as immunomodulatory agents and are being explored for immune checkpoint inhibition. Therefore, research and innovations are required to understand the mechanism of action of such phytocompounds against GBM to develop efficacious treatments for the same. This review gives insight into the potential of phytochemical-based therapeutic options for GBM treatment.


Effect of prolactin on maintenance of prelactating human mammary gland in vitro.
Human mammary tissue from a female at the end of the second trimester of pregnancy was studied in organ culture in a chemically defined medium. Sampling was carried out at 1, 2 and 3 weeks. Without hormones, there was nearly total lobuloalveolar degeneration in all specimens at all times. Addition of insulin, hydrocortisone and ovine prolactin, in combination at a concentration of 5 mug per ml each, did not affect the extent of degeneration. Raising the concentration of prolactin to 50 mug per ml resulted in greatly improved lobulo-alveolar maintenance in all specimens and continued epithelial cell DNA synthesis for up to 3 weeks in vitro.


Anatomical hamstring tendons ACL reconstruction with the "linking rings" technique.
Hamstring tendons (HTs) are one of the most commonly used autografts for anterior cruciate ligament (ACL) reconstruction (ACLR). However, the tendon-to-bone healing of the HTs grafts within the bone tunnels has always been a concern. Periosteum contains pluripotent stem cells with osteogenic and chondrogenic potential which can allow a direct, stronger and faster healing of the HTs graft within the bone tunnels. In this technical note, we present a modification of anatomical ACLR with the semitendinosus tendon (ST) graft and periosteum augmentation using the "linking rings" technique. The ST is harvested together with periosteum from its distal insertion. An additional free periosteal flap is harvested from the proximal tibia, below the ST insertion. The two free ends of the ST are then linked with a strong non-resorbable suture forming a ring and then folded again creating a quadruple construct with two loops at each end. The periosteum is then wrapped and sutured around the quadruple ST graft on both sides of the linking rings near the femoral and tibial tunnel opening. A technical pearl is to use one artery clamp inside the double rings at the graft ends, pull apart simultaneously and equal the tension between the strands. Another technical pearl is to not pull the periosteum to obtain the flaps, but to use instead a periosteal elevator to preserve the cambium layer which contains the pluripotent stem cells.


Laparoscopic assisted ERCP in patient with Roux-en-Y gastric bypass. A case report.
Choledocholithiasis in Roux-en-Y patients is a therapeutic challenge for both surgeons and endoscopists. In fact, typical procedures, such as ERCP, can't be performed due to the altered anatomy of the patient. Nowadays, procedures on this kind of patient are performed not only in specialized bariatric centers, but, due to the increasing number of patients undergoing bariatric surgery, are starting to become more common even in smaller and non-specialized centers that don't possess the same expertise and technology. We present the case of a 33-year-old patient, who had already undergone bariatric surgery, and presented to our department with a diagnosis of choledocholithiasis. Due to the altered anatomy the patient was treated through a laparoscopic assisted ERCP. A review of the need and proper timing for a cholecystectomy in this kind of patient, in order to prevent choledocholithiasis, is discussed. Moreover, a review of the literature regarding the possible treatments of this pathology in bariatric patients underlines the presence of other treatments, beyond the one performed in our department, that can be performed even in small non-specialized centers. Prophylactic cholecystectomy is not recommended in bariatric surgery. Laparoscopic assisted-ERCP is a safe and feasible intervention which is to be preferred, even if B-ERCP and EDGE are two valid alternatives.


Passive avoidance deficit following intracerebroventricular administration of cholecystokinin tetrapeptide amide in rats.
The effect of cholecystokinin tetrapeptide amide (CCK-4) injected into the lateral cerebral ventricle on memory processes was examined by a one-trial passive avoidance test in the rat. CCK-4 injection 30 and 60 min before the first retention test caused a shortened latency to response, and its chronic infusion into the lateral ventricle at a rate of 2 micrograms/day shortened the latency of the response to the level of almost complete amnesia. CCK-4 also reduced arginine-vasopressin effect on memory processes when administered simultaneously 30 min before the first retention test, but its amnestic action is short-lasting and antagonized by relatively small amounts of cholecystokinin octapeptide (CCK-8). In addition, the shortened latency to response was admitted to be not always associated with the motility effect of CCK-4.


Effect of different root canal irrigants on push-out bond strength of two novel root-end filling materials.
The aim of this in vitro study was to evaluate push-out bond strength of different root-end filling materials using various irrigant solutions. A push-out bond strength test was performed to evaluate the bond strength of two experimental root-end filling materials: namely, nano-hybrid mineral trioxide aggregate (MTA) and polymethyl methacrylate (PMMA) cement filled with 20% weight nano hydroxyapatite (nHA) fillers compared to conventional MTA. The irrigant solutions employed were sodium hypochlorite (NaOCl) in concentrations 1%, 2.5% and 5.25% and 2% chlorhexidine gluconate (CHX) followed by application of 17% ethylene diamine tetra-acetic acid (EDTA). A freshly extracted sixty single-rooted human maxillary central incisors were used. The crowns were removed, the canal apex was widened to simulate immature teeth. Each type of irrigation protocols was performed. After application and setting of the root-end filling materials, a slice of one mm thickness was cut transversely from the apical end of each root. Specimens were stored for 1 month in artificial saliva and were subjected to a push-out test to evaluate the shear bond strength. Data were analyzed using two-way ANOVA and Tukey test. The experimental nano-hybrid MTA showed the highest significant push-out bond strength values when irrigated by NaOCl at several concentrations (1%, 2.5% and 5.25%) (P< 0.05). Meanwhile, irrigation with 2% CHX resulted in highest bond strength values in nano-hybrid white MTA (18 MPa) and PMMA filled with 20% weight nHA (17.4 MPa) with nonsignificant difference between them (p = 0.25). In each root-end filling material, irrigation with 2% CHX led to the highest significant bond strength, followed by NaOCl 1%, while the least significant bond strength was produced after irrigation with NaOCl 2.5% and 5.25% (P< 0.05). Considering the limitations of this study, it may be concluded that the application of 2% CXH and 17% EDTA provides superior push-out bond strength to root canal dentin compared with irrigation with NaOCl irrigants and 17% EDTA, experimental nano-hybrid MTA root-end filling material provides enhanced shear bond strength than conventional micron-sized MTA root-end filling material.


The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson's Disease.
As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson's disease. The latest reports have indeed revealed that rotenone promotes Parkinson's in humans, but studies aiming to show congruent effects in zebrafish (Danio rerio) are lacking. Material and Methods. In this context, the aim of the present study was to demonstrate how chronic administration of rotenone for 3 weeks impairs the locomotor activity and sociability and induces oxidative stress in zebrafish. There were no statistically significant differences following the analysis of their social interaction and locomotor tests (p > 0.05). However, several exceptions have been noted in the control, rotenone, and probiotics groups when we compared their locomotor activity during the pretreatment and treatment interval (p < 0.05). We further assessed the role of rotenone in disturbing the detoxifying system as represented by three enzymes known as superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Despite the fact that there were no statistically significant changes within SOD and GPx levels between the control group and rotenone, probiotics, and rotenone + probiotics (p > 0.05), relevant changes have been observed between the analyzed groups (p < 0.05 and p < 0.005, respectively). On the other hand, significant differences (p < 0.05) have been observed for MDA when we analyzed the data between the control group and the other three groups. Our results suggest that rotenone can be successfully used to trigger Parkinson's disease-related symptomatology in zebrafish.


Regulation mechanism of plant response to heavy metal stress mediated by endophytic fungi.
Endophytic fungi exist widely in plants and play an important role in the growth and adaptation of plants. They could be used in phytoremediation techniques against heavy metal contaminated soil since beneficial microbial symbionts can endow plants with resistance to external heavy metal stresses. This review summarized the regulation mechanism of plant response to heavy metal stress mediated by endophytic fungi. Potential endophytic fungi in enhancing plant's adaption to heavy metal stresses include arbuscular mycorrhizal fungi, dark septate endophytic fungi, plant growth promoting endophytic fungi. The mechanisms involve coevolution strategy, immune regulation and detoxification transport to improve the ability of plants to adapt to heavy metal stress. They can increase the synthesis of host hormones and maintaining the balance of endogenous hormones, strengthen osmotic regulation, regulate carbon and nitrogen metabolism, and increase immune activity, antioxidant enzyme and glutathione activity. They also help to improve the detoxification transport and heavy metal emission capacity of the host by significantly producing iron carrier, metallothionein and 1-aminocyclopropane-1-carboxylic acid deaminase. The combination of endophytic fungi and hyperaccumulation plants provides a promising technology for the ecological restoration of heavy metal contaminated soil. Endophytic fungi reserves further development on enhancing host plant's adaptability to heavy metal stresses.


The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene.
Neutral lipid storage disease is caused by mutations in the CGI-58 or the PNPLA2 genes. Lipid storage can be detected in various cell types including blood granulocytes. While CGI-58 mutations are associated with Chanarin-Dorfman syndrome, a condition characterized by lipid storage and skin involvement (ichthyosis), mutations in the patatin-like phospholipase domain-containing protein 2 gene (PNPLA2) were reported with skeletal and cardiac muscle disease only. We describe clinical, myopathological, magnetic resonance imaging (MRI), and genetic findings of six patients carrying different recessive PNPLA2 mutations. Pulse-chase labeling of control and patient cells with supplementation of clenbuterol, salmeterol, and dexamethasone was performed in vitro. The patients share a recognizable phenotype with prominent shoulder girdle weakness and mild pelvic girdle and distal muscle weakness, with highly elevated creatine kinase (CK) and cardiomyopathy developing at later stages. Muscle histology invariably reveals massive accumulation of lipid droplets. New muscle or whole-body MRI techniques may assist diagnosis and may become a useful tool to quantify intramuscular lipid storage. Four novel and two previously reported mutations were detected, affecting different parts of the PNPLA2 gene. Activation of hormone-sensitive lipase by beta-adrenergic substances such as clenbuterol appears to bypass the enzymatic block in PNPLA2-deficient patient cells in vitro. PNPLA2 deficiency is a slowly progressive myopathy with onset around the third decade. Cardiac involvement is relatively common at a later stage. Muscle MRI may detect increased lipid in a characteristic distribution, which could be used for monitoring disease progression. Beta-adrenergic agents may be beneficial in improving triacylglycerol breakdown in patients with PNPLA2 mutations.


Easiness, usefulness and intention to use a MOOC in nursing.
The growing ageing population and the increasing prevalence of non-communicable diseases call for innovation and healthcare mastered professional skills. Emerging digital learning contents envisioning to complement education, lifelong learning and in-service training. The use of digital platforms allows nurses to access contents in several formats, enabling the required pedagogical autonomy and personal time management. This allows nurses to enrol in education wherever accessible, reducing personal and professional costs and ensuring high-quality standards. To assess students and nurses' easiness, usefulness and intention to use a Massive Open Online Course (MOOC) as an educational resource to enhance self-management intervention skills in COPD patients. An exploratory, descriptive and transversal study was conducted. Participants were nursing students, registered nurses and rehabilitation nurses. A questionnaire supported by Davis Technology Acceptance Model and on the determinants of the ease-of-use perception of Venkatesh was applied. An EFA was performed and two dimensions were obtained (perceived easiness and global quality of the course and perceived usefulness and intention to use the MOOC) and groups were compared in these dimensions. From the total participants (n = 93), 65.6% were nursing students, 15.1% were Portuguese nurses and 19.4% were Portuguese rehabilitation nurses. The perceived easiness and global quality score of the course were 4.70 (SD = 0.314) and the perceived usefulness and intention to use the MOOC was 4.73 (SD = 0.346). Rehabilitation nurses, who are older, scored higher than nurses and students (χ2(2, n = 93) = 8.43, p = .015, ε2 = 0.092). The dropout rate was 25%. The MOOC showed usefulness and nurses' intention to use this educational resource in future education and yielded high average rates of perceived easiness and global quality. These massive courses unlock new opportunities for nursing education and to lifelong learning in nursing, enhancing safety and quality of the healthcare services in supporting patients to achieve a better quality of life.


Antitumor effects of an engineered and energized fusion protein consisting of an anti-CD20 scFv fragment and lidamycin.
Antibody-based fusion proteins are the next generation of antibody therapies for cancer and other diseases. CD20 antigen, which is overexpressed on cell membranes in nearly 95% of cases of B-cell Non-Hodgkin's Lymphoma, is an attractive target for the therapy of B-lymphoid malignancies. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic that now has entered phase II clinical trials. In this study, we prepared an engineered fusion protein, scFv-LDP, consisting of an anti-CD20 scFv fragment and the apoprotein LDP of LDM using DNA recombination. After purification and refolding, scFv-LDP was found to bind specifically to CD20-positive lymphoma cells using ELISA and indirect immunofluorescent cytochemical staining assays. The energized fusion protein scFv-LDP-AE was obtained using molecular reconstitution of the active chromophore AE of LDM and scFv-LDP. MTT assay revealed potent cytotoxicity of scFv-LDP-AE to CD20-positive Raji and Daudi cells, with IC(50) values of 1.21×10(-11) and 6.24×10(-11) mol L(-1), respectively. An in vivo subcutaneous xenograft model of CD20-positive B cell lymphoma in BALB/c (nu/nu) mice was also utilized. Drugs were given intravenously on day 14 and 21 after tumor transplantation. In terms of maximal tolerated doses, scFv-LDP-AE at 0.3 mg kg(-1) suppressed tumor growth by 79.3%, and LDM at 0.05 mg kg(-1) by 68.6% (P<0.05). Results suggested scFv-LDP-AE could be a potential candidate for tumor-targeting therapy.


Ten year experience of bioabsorbable mesh support in pectus excavatum repair.
We reviewed 10 years experience in the treatment of this deformity using a retro-sternal bioabsorbable mesh in place of a metallic device to lift and stabilise the sternum. Moreover, the mesh supports the thoracic and upper abdominal wall reconstruction. From January 1990 to December 2000, in our Thoracic Surgery Unit, 65 patients with PE were assessed for surgical repair, mean age 16+/- 3.5 years, fronto sagittal thoracic index (FSTI) 0.21, ranging from 0.15-0.33. Twenty-three of them underwent surgical correction after initial assessment, 22 were deferred and sent to physiotherapy. At a subsequent assessment, five of the patients sent to physiotherapy were deemed to require surgery. Of the 28 patients who underwent surgery, 2 (10%) presented a mild recurrence of PE after 1 year (0.30<FSTI>0.34), meanwhile all other patients maintained a FSTI>0.34. For all patients the improvement in FSTI was statistically significant, p = 0.001. Patients satisfaction after 24 months was thus shared: excellent 18 patients (65%), good seven patients (25%), fair one patient (3.5%) and poor two patients (7%). No major complications were observed in preoperative period. Patients mobilisation was soon achieved thanks to the postoperative pain control and the absence of retro-sternal metallic support. The introduction of bioabsorbable mesh in the Robicsek technique is a safe procedure related to a high percentage of success. The high tolerance of the material reduces the inflammatory reaction. Moreover, the procedure prevents patients from having complications caused by retro-sternal device dislodgment, avoiding a second intervention for device reposition and reducing the postoperative chest pain achieving an early patient mobilisation. In the end a complete reconstruction of the upper abdomen wall has been produced.


Cardiovascular risks of periodontitis and oral hygiene indicators in patients with diabetes mellitus.
Periodontitis is a common chronic inflammatory disease prevalent in diabetes. The aim of this study was to evaluate periodontitis and poor oral hygiene as independent risk factors for either cerebral or myocardial infarction in the diabetes population. This retrospective cohort study included 17,009 patients with diabetes who had participated in a nationwide health-screening programme, including oral health examination, during 2002-2003 in South Korea. Presence of periodontitis, tooth loss and carious teeth were assessed by professional dentists, and the number of tooth brushings per day was evaluated through self-reported questionnaires. The primary study outcome was the development of cerebral or myocardial infarction, based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes, up to 31 December 2015. The study enrolled 17,009 patients with diabetes. Over the mean 11.64 years of follow-up, 1341 patients presented with either cerebral or myocardial infarction. On multivariable Cox proportional hazards regression analysis, presence of periodontitis was an independent risk factor for either cerebral or myocardial infarction [adjusted hazard ratio (HR): 1.17, 95% confidence interval (CI): 1.02-1.34; P = 0.030]. An increased number of carious teeth (≥5) was also associated with risk of cerebral or myocardial infarction (adjusted HR: 1.67, 95% CI: 1.20-2.32; P = 0.002), whereas frequent tooth brushing (≥2 times/day) was negatively associated with risk of cerebral or myocardial infarction (adjusted HR: 0.79, 95% CI: 0.70-0.90; P < 0.001) compared with tooth brushing ≤1 time/day. Early identification and intervention of periodontal disease may be effective in reducing cardiovascular complications in the diabetes population, and improved oral hygiene would probably be associated with lower cardiovascular risk in diabetes.


Rheological Behavior of Glycyrrhiza glabra (Licorice) Extract as a Function of Concentration and Temperature: A Critical Reappraisal.
In the present study, rheological properties of twelve different licorice root extracts were evaluated using a rotational viscometer as a function of soluble solids content (15-45 °Bx) and temperature (30-70 °C). Response Surface Methodology was used to understand the relationships between the parameters. The experimental data were then fit into mathematical models. The results, for the first time, revealed that the licorice solutions had non-Newtonian shear-thinning behaviors with flow behavior indexes of 0.24 to 0.91, depending on the licorice extract samples, temperature, and °Bx. These observations were different from those reported in the literature and the present study elaborated on reasons for such observations. Further, the shear-thinning behavior generally increased by increasing the °Bx and decreasing the temperature. In addition, the power-law model was found to be suitable for predicting the experimental data. The newly revealed information can be particularly important in designing the unit operations for licorice extract processing.


Rotational positional error-corrected linear set-up margin calculation technique for lung stereotactic body radiotherapy in a dual imaging environment of 4-D cone beam CT and ExacTrac stereoscopic imaging.
Accurate calculation of set-up margin is a prerequisite to arrive at the most optimal clinical to planning target volume margin. The aim of this study was to evaluate the compatibility of different on-board and in-room stereoscopic imaging modalities by calculating the set-up margins (SM) in stereotactic body radiotherapy technique accounting and unaccounting for rotational positional errors (PE). Further, we calculated separate SMs one based on residual positional errors and another based on residual + intrafraction positional errors from the imaging data obtained in a dual imaging environment. A total of 22 lung cancer patients were included in this study. For primary image guidance, four-dimensional cone beam computed tomography (4-D CBCT) was used and stereoscopic ExacTrac was used as the auxiliary imaging. Following table position correction (TPC) based on the initial 4-D CBCT, another 4-D CBCT (post-TPC) and a pair of stereoscopic ExacTrac images were obtained. Further, during the treatment delivery, a series of ExacTrac images were acquired to identify the intrafraction PE. If a, b and c were the observed translational shifts in lateral (x-axis), longitudinal (y-axis) and vertical direction (z-axis) and α, β and γ were the rotational shifts in radians about the same axes, respectively, then the resultant translational vectors (A, B and C) were calculated on the basis of translational and rotational values. Set-up margins were calculated using residual errors post-TPC only and also using intrafraction positional errors in addition to the residual errors. Residual and residual + intrafraction SM were calculated from a dataset of 82 CBCTs and 189 ExacTrac imaging sessions. CBCT-based mean ± SD shifts in translational and rotational directions were 0.3 ± 1.8 mm, 0.1 ± 1.8 mm, - 0.4 ± 1.6 mm, 0.1 ± 0.4°, 0.0 ± 1.0° and 0.3 ± 0.7°, respectively, and for ExacTrac - 0.1 ± 1.8 mm, 0.2 ± 2.4 mm, - 0.6 ± 1.8 mm, 0.1 ± 1.2°, - 0.2 ± 1.3° and - 0.1 ± 0.6°, respectively. Residual SM without considering the rotational correction in x, y and z directions were 5.0 mm, 4.5 mm and 4.4 mm; rotation-corrected SM were 4.4 mm, 4.0 mm and 5.5 mm, respectively. Residual plus intrafraction SM were 5.5 mm, 6.6 mm and 6.2 mm without considering the rotational corrections, whereas they were 5.0 mm, 6.3 mm and 6.2 mm with rotational errors accounted for. Accurate calculation of set-up margin is required to find the clinical to planning target volume margin. Primary and auxiliary imaging margins fall in the range of 4.0 to 5.5 mm and 5.0 to 7.0 mm, respectively, indicating a higher SM for X-ray-based planar imaging techniques over three-dimensional cone beam images. This study established the degree of mutual compatibility between two different kinds of widely used set-up imaging modalities, on-board CBCT and in-room stereoscopic imaging ExacTrac. It also describes the technique to calculate the residual and residual plus intrafraction SM and its variation in a dual imaging environment accounting for rotational PE in stereotactic body radiotherapy of lung.


Local scale genetic structure in coral populations: a signature of selection.
Coastal marine reserves in general, and coral reef reserves in particular, are typically composed of scattered patches separated by uninhabited areas. Due to the sessile mode of life of adult corals, larval connectivity is often the only agent of gene flow between reef localities. In this study we examined the connectivity between populations of the common scleratinian coral Stylophora pistillata at the northern tip of the Gulf of Aqaba (Red Sea), using the rDNA ITS (internal transcribed spacer) as a molecular marker. Sequence comparisons among recruits indicated very similar, equally-diverse, assemblages of recruits in both the northern (highly affected by anthropogenic disturbances) and southern (less affected) study sites, implying a high larval connectivity or common sources of larval supply. By contrast, sequence diversity observed among adults declined sharply from southern to northern sites, accompanied by genetic differentiation of the respective populations. Based on Fu's Fs-test of selective neutrality, it may be suggested that various post-settlement selective regimes, presumably more intense in the northern sites, provide a reasonable explanation for the observed patterns of genetic diversity. The suggested hypothesis is supported by the sharper decline in sequence diversity found between recruits and adults in the northern sites. This study exemplifies the necessity to consider local selective factors, in addition to larval connectivity, when managing marine reserves.


Chrysin restores PDGF-induced inhibition on protein tyrosine phosphatase and reduces PDGF signaling in cultured VSMCs.
Previous studies have shown that an increased intake of dietary flavonoids is associated with a decreased risk of cardiovascular diseases (CVDs). PDGF is a major mitogen for vascular smooth muscle cell (VSMC) and participates in the pathogenesis of many CVDs. The study investigated whether the flavone chrysin affected PDGF functions in VSMCs and neointma formation in rat artery. We found that chrysin concentration-dependently inhibited PDGF-induced proliferation and chemotaxis and reduced PDGF signaling in VSMCs. Chrysin attenuated H(2)O(2) signaling and PDGF-induced reactive oxygen species production and NADPH oxidase activation but did not interfere with PDGF binding to VSMCs. The further analyses revealed that chrysin relieved PDGF-induced inhibition on activity of protein tyrosine phosphatase (PTP) and reduced PDGF-induced oxidation of PTP cysteinyl active site. Moreover, it inhibited PDGF receptor autophosphorylation induced by low-dose vanadate (an inhibitor for PTP). The effect of chrysin, but not of the flavonoid (-)-epigallocatechin-3-gallate and antioxidant N-acetylcysteine, on PDGF signaling and PTP activity was reversed by depletion of intracellular glutathione (GSH), suggesting an involvement of chrysin on GSH/glutaredoxin system for PTP reactivation. Finally, to demonstrate the effectiveness of chrysin in vivo, we showed that oral administration of chrysin before and after angioplasty could reduce neointima formation in balloon-injured carotid artery in rats. In conclusion, we provide here evidence that chrysin can regulate intracellular PTP activity during PDGF signaling, inhibits PDGF-induced VSMC proliferation and chemotaxis, and reduces arterial intima hyperplasia in vivo.


Establishment of a stable complex formed from whey protein isolate and chitosan and its stability under environmental stresses.
This study aimed to investigate the stability of a complex formed with whey protein isolate (WPI) and chitosan under environmental stress. The optical density, particle size, zeta potential, chemical characteristics, electrostatic interactions, and surface morphology were evaluated for the stable complexes; the optimum conditions for the generation of the stable complex were 0.2% (wt/wt) whey protein with 0.05% (wt/wt) chitosan at pH 5.7. Under these conditions, the complex particle size was 217.8 ± 11.3 nm and the zeta potential was 16.7 ± 0.92 mV. The complex was formed through electrostatic interactions between the amine groups of chitosan (-NH3+) and carboxyl groups of whey protein (-COO-), and contained a porous network interspaced by heterogeneously sized vacuoles. The complex displayed stable physiochemical characteristics under environmental stresses including NaCl (0-75 mM) or sugar (0-5%) at ambient temperature and upon heating for 15 min at 25-65 °C, up to 65 °C for 30 min. Moreover, the complex could be stably stored for 30 d at 4 °C and for 20 d at 25 °C. The present results provide theoretical insights into the industrial production of chitosan-protein complexes and for microencapsulation of sensitive food or medicinal ingredients to increase their intestinal absorption.


Probabilistic causation and the explanatory role of natural selection.
The explanatory role of natural selection is one of the long-term debates in evolutionary biology. Nevertheless, the consensus has been slippery because conceptual confusions and the absence of a unified, formal causal model that integrates different explanatory scopes of natural selection. In this study we attempt to examine two questions: (i) What can the theory of natural selection explain? and (ii) Is there a causal or explanatory model that integrates all natural selection explananda? For the first question, we argue that five explananda have been assigned to the theory of natural selection and that four of them may be actually considered explananda of natural selection. For the second question, we claim that a probabilistic conception of causality and the statistical relevance concept of explanation are both good models for understanding the explanatory role of natural selection. We review the biological and philosophical disputes about the explanatory role of natural selection and formalize some explananda in probabilistic terms using classical results from population genetics. Most of these explananda have been discussed in philosophical terms but some of them have been mixed up and confused. We analyze and set the limits of these problems.