Photosensitive fits elicited by TV animation: an electroencephalographic study.
We carried out a clinical and electroencephalographic (EEG) study to reveal the pathophysiology of acute symptoms elicited by a TV animation program. Clinical data and EEG were obtained from 20 patients ranging in age from 6 to 30 years. A pattern presentation and an intermittent photic stimulation were performed. Of 20 patients, 13 had a convulsion and seven had other symptoms, mainly nausea and/or vomiting. A photoparoxysmal response (PPR) was confirmed in 12 of 13 patients (92.3%) who had a convulsion. Only one of seven patients (14.3%) without a convulsion showed a PPR. The incidence of PPR was significantly higher in patients with convulsion than those without convulsion. There were no significant differences in the family history of convulsion, gender, parameters associated with TV watching and basic EEG between the two groups. All patients with PPR had a convulsion or consciousness disturbance. Acute symptoms, such as convulsion and impairment of consciousness, are supposed to be based on photosensitivity.


Systemic administration of kainic acid produces elevations in TRH in rat central nervous system.
Several studies have suggested that the concentration of thyrotropin releasing hormone (TRH) in the central nervous system (CNS) is influenced by the level of CNS activation. Hibernation in the ground squirrel and estivation in the lungfish result in region-specific decreases in TRH concentrations. Repeated electroconvulsive shock (ECS) and amygdaloid kindling have been shown to result in elevations of TRH in limbic brain regions. In the present study, limbic seizures induced by systemic administration of kainic acid resulted in substantial increases in the TRH content of posterior cortex and of dorsal and ventral hippocampus, and in moderate elevations in anterior cortex, amygdala/piriform cortex and corpus striatum. Maximal elevations in TRH were observed 2-4 days after kainic acid administration, and by 14 days TRH levels were similar to control values, with the exception of the dorsal hippocampus, which exhibited more prolonged elevations in TRH levels. Prior exposure to limbic seizure activity attenuated the magnitude of TRH elevation in response to a second administration of kainic acid in the posterior cortex but in no other region. These results indicate that seizure-related processes or events influence TRH systems in the CNS. Neuronal populations involved in limbic seizure induced damage may be involved in the modulation of posterior cortical TRH levels.


Pancreatic Neuroendocrine Neoplasias in Multiple Endocrine Neoplasia Type 1 Are Predominantly Located in the Dorsal Anlage: An Endoscopic Ultrasound Study.
Pancreatic neuroendocrine neoplasias (pNENs) frequently occur in multiple endocrine neoplasia type 1 (MEN1). Their distribution referring to embryology, that is, the pancreatic anlagen, has not been investigated yet. In the time between 1998 and 2019, we studied the distribution of pNENs in MEN1 concerning the embryologic origin of the pancreas, that is, the dorsal versus ventral anlage using endoscopic ultrasound in 117 MEN1 patients: 56 women, 61 men; aged 40 years (standard deviation, 14 years) at first endoscopic ultrasound. In 105 patients, a total of 628 pNENs were detected. They were located in the pancreatic tail: 231; pancreatic body: 177; pancreatic head/uncinate process: 220. Of the latter, 22 were located in the ventral anlage, 176 in the dorsal anlage, and 22 remained undefined. In summary, just 3.5% of all detected pNENs were located in the ventral anlage, 93.0% in the dorsal anlage, and 3.5% could not be assigned. Our study indicates that the vast majority of pNENs in MEN1 is located in the dorsal anlage, whereas the ventral anlage of the pancreas seems to be to a large extend spared from pNENs. Implications for new surgical strategies might be considered.


Alcohol, iron-associated oxidative stress, and cancer.
Oxidative stress is recognized to play an important role in the initiation and promotion events of carcinogenesis. Alcoholic liver disease is associated with significant oxidative stress as well as the hepatic accumulation of iron, a transition element also documented to initiate oxidative stress. The combined prooxidant potential of ethanol and iron is at least additive and possibly synergistic with respect to inducing hepatocellular oxidative stress and antioxidant depletion. One cellular consequence of sustained oxidative stress and redox imbalance resulting from the combined actions of alcohol and iron is lipid peroxidation, resulting in the production of aldehydic products such as 4-hydroxy-2-nonenal, which has been linked to site-specific mutations of the p53 gene. In addition, the accumulation of iron in hepatic macrophage isolated from laboratory animals chronically ingesting alcohol is associated with activation of nuclear factor-kappa B and production of tumor necrosis factor-alpha, providing a proinflammatory cellular environment also favorable for initiation and promotion of carcinogenesis. Consequently, there is persuasive evidence that the potential of ethanol and iron to induce oxidative stress may be an important pathogenic mechanism for the increased occurrence of hepatocellular carcinoma in individuals with hepatic iron overload who ingest alcohol.


Resolution of inflammation during multiple sclerosis.
Multiple sclerosis (MS) is a frequent autoimmune demyelinating disease of the central nervous system (CNS). There are three clinical forms described: relapsing-remitting multiple sclerosis (RRMS), the most common initial presentation (85%) among which, if not treated, about half will transform, into the secondary progressive multiple sclerosis (SPMS) and the primary progressive MS (PPMS) (15%) that is directly progressive without superimposed clinical relapses. Inflammation is present in all subsets of MS. The relapsing/remitting form could represent itself a particular interest for the study of inflammation resolution even though it remains incomplete in MS. Successful resolution of acute inflammation is a highly regulated process and dependent on mechanisms engaged early in the inflammatory response that are scarcely studied in MS. Moreover, recent classes of disease-modifying treatment (DMTs) that are effective against RRMS act by re-establishing the inflammatory imbalance, taking advantage of the pre-existing endogenous suppressor. In this review, we will discuss the active role of regulatory immune cells in inflammation resolution as well as the role of tissue and non-hematopoietic cells as contributors to inflammation resolution. Finally, we will explore how DMTs, more specifically induction therapies, impact the resolution of inflammation during MS.


18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy.
We investigated whether baseline [18F] Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each 18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline 18F-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC.


Preparation of 14,15-secoestra-1,3,5(10)-trien-15-ynes, inhibitors of estradiol dehydrogenase.
The conversion of estrone to 14,15-secoestratrien-15-ynes, inactivators of estradiol dehydrogenase from human term placenta, is described. The optically pure precursor 7-acetoxy-octahydro-2-phenanthrenecarboxylic acid methyl ester is prepared from estrone in five steps and 40% yield. The unsubstituted propargylic secoestratriene diol, a mechanism-based inactivator of estradiol dehydrogenase, and the corresponding acetylenic ketone, an affinity label inactivator of the same enzyme, arise from the phenanthrene ester in three and four steps. The propargylic secoestratriene diol also competes with [3H]estradiol for binding to calf uterus estrogen receptor and possesses weak uterotrophic activity.


Visualization of in vivo protein-protein interactions in plants.
Molecular processes depend on the concerted and dynamic interactions of proteins, either by one-on-one interactions of the same or different proteins or by the assembly of larger protein complexes consisting of many different proteins. Here, not only the protein-protein interaction (PPI) itself, but also the localization and activity of the protein of interest (POI) within the cell is essential. Therefore, in all cell biological experiments, preserving the spatio-temporal state of one POI relative to another is key to understanding the underlying complex and dynamic regulatory mechanisms in vivo. In this review, we examine some of the applicable techniques to measure PPIs in planta as well as recent combinatorial advances of PPI methods to measure the formation of higher order complexes with an emphasis on in vivo imaging techniques. We compare the different methods and discuss their benefits and potential pitfalls to facilitate the selection of appropriate techniques by providing a comprehensive overview of how to measure in vivo PPIs in plants.


Reasons for late presentation of cleft deformity in Nepal.
To determine the causes of late presentation of patients with cleft lip and palate in Nepal. Cross-sectional survey using interviews of patients' parents. The study was carried out between April 1999 and September 1999 in Western Regional Hospital (WRH), Pokhara, Nepal, a secondary care center. All patients with cleft lip and palate coming to WRH outpatient department or coming for surgery were included in the study. Those without parents were excluded. A total of 53 patients were included. Forty-two (79%) presented after 3 months. The most common reasons were lack of knowledge of availability of repair (31%), lack of accessibility of care (29%), and lack of finances (24%). In Nepal, the majority of patients with cleft present late, mainly because of a lack of awareness of cleft services, the remoteness of available services, or a lack of finances. These obstacles can be largely surmounted through itinerant services.


Localization of tubular uptake segment of filtered Cystatin C and Aprotinin in the rat kidney.
The renal tubular uptake of 125I-Aprotinin (*Ap) is on average located more superficially than its filtration site, causing transfer of some of *Ap filtered in deep to more superficial cortical zones. 125I-Cystatin C (*Cy) showed less uptake in deep cortical zones than Ap, suggesting a longer and/or a more superficial tubular uptake site. To test that hypothesis and to quantify the outward transfer of the filtered polypeptides, we estimated the tubular uptake pattern of the tracers in perfusion fixed rat kidneys after intravenous injection of *Cy and *Ap. Autoradiographs were made from 10 mum thick slices of Microfil nephron casts from outer (OC), middle (MC) and inner (IC) cortical zones to quantify cortical border-crossing *Ap transfer. Single nephron glomerular filtration rate (snGFR) was estimated as the zonal uptake of *Ap corrected for *Ap transfer, divided by its time-integrated plasma concentration and the zonal number of glomeruli. *Ap and *Cy uptake fell exponentially along the proximal convoluted tubule (PCT), indicating an uptake proportional to luminal concentration. Uptake in IC exceeded that in MC and OC nephrons. The per cent PCT length with *Cy uptake (67.2 +/- 1.6) exceeded that of *Ap (54.6 +/- 1.8). The zonal border-crossing PCT length (29-34% of total PCT) from deep to more superficial cortical zones transferred 4-6% more *Cy than *Ap. Greater tubular uptake length of *Cy than of *Ap causes more cortical border-crossing of *Cy. The zonal snGFR estimated from Aprotinin uptake corrected for border-crossing agreed well with that obtained with the Hanssen ferrocyanide technique.


Analysis of the VIQ scores of families of three or more Orkney brothers.
Classification of the boys in 48 families of three or more brothers according to their Moray House Test (VIQ) scores awarded at age 11 +/- 1 1/2 years in 1947-75 confirms the postulated existence of a total of nine male phenotypes for this X-linked trait in the score range < 70 to 140 points. The phenotypic means lie close to the sequence 69(8)133. Recombination is shown to occur. An additive effect of three alleles at each of two X-chromosome loci is the most likely simple scheme. An iterative approach matching the observed mixtures of proposed genotypes in the families with probabilities for variable levels of homozygosity, non-crossover/crossover heterozygosity, and maternal meiotic recombination yields a best goodness of fit where this last is 20%.


Efficacy and safety of electroacupuncture treatment in the prevention of negative moods in healthy young men after 30 h of total sleep deprivation: study protocol for a single-center, single-blind, parallel-arm, randomized clinical trial.
Sleep deprivation (SD) among young adults is a major public health concern. In humans, it has adverse effects on mood and results in serious health problems. Faced with SD, persons may take precautionary measures to try and reduce their risk. The aim of this study is to evaluate the efficacy and safety of electroacupuncture (EA) for the prevention of negative moods after SD. In addition, we will do a comparison of the effects of EA on mood after SD at different time points. This randomized controlled trial (RCT) will be performed at the First Affiliated Hospital of Changchun University of Chinese Medicine in China. The Standards for Reporting Interventions in Clinical Trials of Acupuncture 2010 will be strictly adhered to. Forty-two healthy male volunteers will be distributed into acupoints electroacupuncture (AE) group, non-acupoints electroacupuncture (NAE) control group, or blank control group. This trial will comprise 1-week baseline (baseline sleep), 1-week preventative treatment, 30-h total sleep deprivation (TSD), and 24-h after waking follow-up period. Participants in the AE group and the NAE control group during the preventative treatment period will be administered with EA treatment once daily for 1 week. Participants in the blank control group will not be administered with any treatment. The primary outcome will be the Profile of Mood States (POMS) Scale. Secondary outcome measures will include changes in the Noldus FaceReader (a tool for automatic analysis of facial expressions) and Positive and Negative Affect Schedule (PANAS) Scale. Total sleep deprivation will be 30 h. During the 30-h TSD period, participants will be subjected to 11 sessions of assessment. Adverse events will be recorded. This study is designed to evaluate the efficacy and safety of EA for the prevention of negative moods after SD. The results of this trial will allow us to compare the effects of EA on mood after SD at different time points. Moreover, the findings from this trial will be published in peer-reviewed journals. Chinese Clinical Trial Registry Chi2000039713 . Registered on 06 November 2020.


Brain network characteristics and cognitive performance in motor subtypes of Parkinson's disease: A resting state fMRI study.
Parkinson's disease (PD) is a heterogeneous disorder with great variability in motor and non-motor manifestations. It is hypothesized that different motor subtypes are characterized by different neuropsychiatric and cognitive symptoms, but the underlying correlates in cerebral connectivity remain unknown. Our aim is to compare brain network connectivity between the postural instability and gait disorder (PIGD) and tremor-dominant (TD) subtypes, using both a within- and between-network analysis. This cross-sectional resting-state fMRI study includes 81 PD patients, 54 belonging to the PIGD and 27 to the TD subgroup. Group-level spatial maps were created using independent component analysis. Differences in functional connectivity were investigated using dual regression analysis and inter-network connectivity analysis. An additional voxel-based morphometry analysis was performed to examine if results were influenced by grey matter atrophy. The PIGD subgroup scored worse than the TD subgroup on all cognitive domains. Resting-state fMRI network analyses suggested that the connection between the visual and sensorimotor network is a potential differentiator between PIGD and TD subgroups. However, after correcting for dopaminergic medication use these results were not significant anymore. There was no between-group difference in grey matter volume. Despite clear motor and cognitive differences between the PIGD and TD subtypes, no significant differences were found in network connectivity. Methodological challenges, substantial symptom heterogeneity and many involved variables make analyses and hypothesis building around PD subtypes highly complex. More sensitive visualisation methods combined with machine learning approaches may be required in the search for characteristic underpinnings of PD subtypes.


Is there an association between maternal pap test use and adolescent human papillomavirus vaccination?
To identify the association between mother's recent receipt of a Pap test and daughter's uptake and completion of the three-shot human papillomavirus (HPV) vaccination series. We used cross-sectional data from the 2008 to 2010 Behavioral Risk Factor Surveillance System from 9 U.S. states and Puerto Rico and logistic regression models to examine the association between mother's receipt of a Pap test in the past 3 years and daughter's uptake and completion of the three-shot HPV vaccination series among adolescent girls aged 9-17 years (N = 4,776). Approximately one-quarter of adolescent girls began the HPV vaccination series, and 13.6% completed the three-shot series. Uptake and completion were more likely among girls whose mothers had obtained a Pap test within the past 3 years-for HPV uptake, odds ratio: 1.342, 95% confidence interval: 1.073-1.692; for HPV completion, odds ratio: 1.904; 95% confidence interval: 1.372-2.721-but the relationship between mother's recent Pap test and vaccine uptake was explained by the mother's use of a personal doctor and obtaining a routine physical examination in the past year. HPV vaccination uptake and completion were more likely among adolescent girls whose mothers obtained a recent Pap test. Interventions designed to educate mothers on the importance of HPV vaccination and to facilitate relationships between physicians and mothers may prove successful at increasing HPV vaccination among adolescent girls.


Post natal side effects in rats induced by hypolipidaemic treatment during pregnancy.
Maternal, foetal and peri- and post-natal toxicity studies of a hypolipidaemic agent, 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methyl propionic acid (WIN 35833), were performed on different animal species during animal evaluation of this new drug. In teratology studies in rats, mice and rabbits, no adverse effects were detected following drug exposure during the organogenesis period. In peri-natal studies, a neonatal abnormality related to treatment just before term was shown in rats. This modification, previously observed with other hypolipidaemic drugs, seems to be species specific and characteristic of compounds in the aryloxyalkanoic acid series.


The clinical efficacy of the minimally invasive treatment of Mason type II radial head fractures using intramedullary fixation with double titanium elastic nails.
Radial head fractures (RHFs) occur most frequently among all elbow fractures. Current treatments pose several limitations for the Mason type II radial head fractures. This study was performed to evaluate the clinical efficacy of a new minimally invasive treatment for Mason type II radial head fractures using intramedullary fixation with double titanium elastic nails. Between January 2018 and December 2019, our group used double titanium elastic intramedullary nails as a minimally invasive treatment for 32 cases of Mason II type radial head fractures. After the treatments, we summarized and conducted a retrospective analysis to evaluate the surgical operation itself, the quality of the fracture reductions, the fracture healing, and any complications. The Mayo elbow function scores (MEPS) and the visual analog scale (VAS) pain scores were used to evaluate the clinical efficacy of this approach. All the patients recovered from their surgeries without any complications. We followed all the cases for an average of 12 months. The elbow extension range of motion was 5 degrees (range: 0-15 degrees), the elbow flexion range of motion was 140 degrees (range: 135-146 degrees), and the average forearm pronation range of motion was 84.1 degrees (range: 78-90 degrees). The average forearm supination range of motion was 80.4 degrees (range: 75-85 degrees). All the fractures healed (a 100% healing rate), the MEPS score was 96.7 (range: 85-100), and the MEPS ratings of excellent and good were both 100%. The VAS pain scores ranged from 0-1. The minimally invasive treatment of Mason type II radial head fractures using intramedullary fixation with double elastic nails proved to be a simple approach with a relatively short operation time. It required only a small incision with little trauma and had few complications, so it is worth consideration for wider use.


Results of conservative surgery for middle ear cholesteatoma.
A retrospective study was carried out to analyze treatment results for cholesteatoma at the University of Iowa Hospitals and Clinics. All patients undergoing primary surgical treatment from January 1, 1969 to December 31, 1973 were followed through October 1976. Treatment failures were based on the occurrence of postoperative cholesteatoma. The probability of being disease free for periods up to five years after original surgery was then estimated for each type of operation. Postoperative cholesteatoma occurred after atticotomy in 17%, intact canal wall mastoidectomy in 35%, and modified radical mastoidectomy in 9%. The postoperative cholesteatoma rate in the group having intact canal wall mastoidectomy was more than twice as high for those patients under age nine. The likelihood of being disease free five years after intact canal wall surgery was estimated to be 36% using the life table method. Disease recurrence was significantly higher after intact canal wall surgery compared to other surgical methods. The effectiveness of this method should be evaluated in a randomized, prospective manner to minimize patient selection and treatment bias.


Experience of the homecare of children on automatic peritoneal dialysis during the COVID-19 outbreak: A qualitative descriptive study.
To describe the home care experience, challenges and coping strategies of caregivers with children on automatic peritoneal dialysis (PD) in mainland China during the early stage of the COVID-19 outbreak. A qualitative descriptive approach was adopted. Semi-structured telephone interviews were conducted among 14 families with children on automatic peritoneal dialysis from February 2nd to 10th, 2020. The care routine, stress and coping strategies of caregivers of children on peritoneal dialysis were collected. The data were analysed using thematic analysis. Four key themes were defined: (1) concerns about PD treatment intertwined with worries about COVID-19; (2) retaining a sense of normality in the middle of the challenges; (3) staying safe; and (4) staying positive and carrying on. Families with children on automatic PD addressed the stress from COVID-19 and its containment measures by closely adhering to COVID-19 preventative measures, actively adjusting mentality and maintaining a sense of normality during the outbreak. This implies that healthcare staff need to be more aware of the complex medical needs of families with children on automatic PD, advocate for them and facilitate their navigation through the repurposed healthcare system.


Theoretical justification for distal foot power equation.
The distal foot power equation is a simple yet powerful tool for estimating the power dissipation or generation within the foot even while modeling it as a rigid body. It was introduced over two decades ago, but has seen a resurgence of use in recent years. Nevertheless, the theoretical justification for this formula has thus far been limited. It is difficult to properly use any equation and interpret the results from analyses using it without a solid understanding of how it is derived as well as its underlying assumptions. In this communication, a thorough derivation of the distal foot power equation is provided first for the case where the foot is interacting with a rigid ground without sliding and then second generalized for situations when the foot may slide relative to a deformable ground surface. For the first case, the derivation makes clear that distal foot power represents the power due to the deviation of the foot from a rigid body state for the portion of the foot between its mass center (or other point of reference) and the center of pressure. For the second case, distal foot power represents not only the internal deformation power of the foot, but also the power due to sliding of the foot on the ground and the power due to deformation of the ground near the point of contact.


Efficacy of two formulations of afoxolaner (NexGard® and NexGard Spectra®) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe.
A multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland. Client-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions. Treatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment. This clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.


Treatment of Drug-Resistant Tuberculosis.
The treatment of drug-resistant tuberculosis (TB) is complicated and has evolved significantly in the past decade with the advent of rapid molecular tests and updated evidence-based guidelines of the World Health Organization and other organizations. The latest recommendations incorporate the use of new drugs and regimens that maximize efficacy and minimize toxicity to improve treatment outcomes for the patients. This article provides an overview of the latest published strategies for clinical and programmatic management of drug-resistant TB.


Density-Dependent Material and Failure Criteria Equations Highly Affect the Accuracy and Precision of QCT/FEA-Based Predictions of Osteoporotic Vertebral Fracture Properties.
About 700,000 vertebral fractures occur in the US as a result of bone loss. Quantitative computed tomography (QCT)-based finite element analysis (FEA) is a promising tool for fracture risk prediction that is becoming attractive in the clinical setting. The goals of this study were (1) to perform individual and pooled specimen optimization using inverse QCT/FEA modeling to obtain ash density-elastic modulus equations incorporating the whole vertebral body and accounting for all variables used during FE modeling, and (2) to determine the effect of material equations and failure criteria on the accuracy and precision of mechanical properties. Fifty-four (54) human vertebrae were used to optimize material equations based on experimental outcomes and, together with a previously proposed material equation, were implemented in our models using three different failure criteria to obtain fracture loads. Our robust QCT/FEA approach predicted 78% of the failure loads. Material equations resulted in poor accuracy in the predicted stiffness, yet yielded good precision and, more importantly, strong correlations with fracture loads. Both material and fracture criterion equations are equally important in estimating accurate and precise QCT/FEA predictions. Results suggest that both elastic modulus and fracture criterion equations should be validated against experimental outcomes to better explain the response of the tissue under various conditions.


Combined action of acivicin and D-galactosamine on pyrimidine nucleotide metabolism in hepatoma cells.
The glutamine antagonist acivicin, L-(alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, strongly reduced CTP and GTP contents in AS-30D rat hepatoma cells in suspension. UTP only dropped to 63% of the respective control after 4 hr; however, by combining acivicin with the uridylate-trapping sugar analogue D-galactosamine, a synergistic decrease in UTP contents to 7% of control was induced. Incorporation of 14CO2 into purine and pyrimidine nucleotides followed by radio-high performance liquid chromatography showed marked inhibition of purine and pyrimidine biosynthesis de novo; the latter was reduced to 35% of control. The inhibitory potency of acivicin on glutamine-dependent carbamoyl-phosphate synthetase and consequently on de novo uracil nucleotide formation was also reflected by the complete suppression of the D-galactosamine-induced rise in total uridylate. Induction of UTP deficiency by interference with the first and rate-limiting step in pyrimidine biosynthesis de novo together with a trapping of uridylate by D-galactosamine may provide a promising approach to the chemotherapy of hepatocellular carcinoma.


Choroidal thickness profile in Retinitis Pigmentosa - Correlation with outer retinal structures.
To compare the choroidal thickness (CT) of subjects with Retinitis Pigmentosa (RP) with age-matched healthy subjects and to correlate the visual acuity with retinal parameters including central macular thickness (CMT), inner segment/outer segment junction (IS/OS junction) integrity, external limiting membrane (ELM) integrity and choroidal thickness in subjects with RP. Eighty-eight eyes (69 patients) with typical RP and 188 eyes of 104 healthy subjects were enrolled between September 2012 and January 2013. All subjects underwent a comprehensive ocular examination including choroidal imaging using enhanced depth imaging with spectral domain optical coherence tomography. Outcome measures were CT difference between RP and age-matched healthy subjects; and correlation of various factors such CMT, IS/OS junction integrity, ELM integrity, and CT with visual acuity. Among RP subjects, mean age was 31.39 ± 13.4 years with a mean BCVA of 0.99 ± 0.94 logMAR. Mean spherical equivalent was -0.6 ± 1.6D. Mean CMT was 148.48 ± 119 μm. Mean subfoveal CT was 296.9 ± 72 μm. Mean IS/OS and ELM integrity was 42.2 ± 46.6% and 43.75 ± 45.7%, respectively. The mean age was 40.0 ± 13.5 years with a mean spherical equivalent of 0.18 ± 0.6D for the normal age-matched healthy group. Mean subfoveal CT was 283.1 ± 47.8 μm. CT at various locations in patients of various ages in the RP group did not show any statistical significant difference (P = ≫0.05) in comparison with age-matched healthy subjects. On multivariate regression, ELM percentage integrity had the strongest association with best corrected visual acuity, followed by IS/OS junction percentage integrity. Subfoveal choroidal thickness had very weak correlation with visual acuity as well other retinal parameters. There was a significant difference in the outer retinal structure integrity (p = 0.002) and CMT (p = 0.02) between the eyes with good (⩾20/200) and poor vision (<20/200), but not in subfoveal choroidal thickness (p = 0.3). Our study results did not show any significant difference in choroidal thickness between subjects with RP and age-matched healthy subjects. Choroidal thickness correlated better with the age but not with the vision or outer retinal structures in eyes with RP. Outer retinal structure integrity and CMT had a better correlation with visual acuity.


Central venous oxygen saturation: analysis, clinical use and effects on mortality.
The aim of this literature review was to provide a clear definition of central venous oxygen saturation (ScvO₂), highlight the differences between ScvO₂ and mixed venous oxygen saturation (SvO₂), show how it can be used clinically and the effect central venous oxygen saturation has on mortality. Many articles concentrate on the individual aspects of ScvO₂, such as its use in early goal-directed therapy, but few provide a full overview of what it means, how to interpret results and how it can be used clinically. Keywords were searched for including central venous oxygen saturation ScvO₂ mixed venous oxygen saturations ScvO₂ early goal-directed therapy sepsis and mortality. Where possible only publications within the last 10 years were used but key publications were not excluded if they were out with this time frame. Central venous oxygen saturation (ScvO₂) is a very important measurement which can be easily taken in a critical care environment by both medical and nursing staff. It provides an understanding of the patient's oxygen delivery, oxygen consumption and cardiac output. It has a key role within early goal-directed therapy and has been shown to decrease mortality when taken and analysed appropriately. This literature review will highlight to nursing staff within the critical care environment the importance of central venous oxygen saturation measurement and interpretation. By raising awareness of the importance of this measurement it is hoped nursing staff will be proactive in both taking this test and analysing the results, therefore facilitating better care for the septic, critically ill patient and improving outcomes for these patients.


Synthesis and turnover of folates in plants.
Folates are essential cofactors for one-carbon transfer reactions, which are central to plant metabolism. Plants synthesize folates de novo, and are key sources of dietary folate for humans. Research into plant folates therefore impacts human nutrition. Biochemical progress, the sequencing of the Arabidopsis genome, and EST databases are now painting a clear picture of the folate synthesis pathway in plants and its surprising compartmentation. Moreover, new analytical advances will help to elucidate plant folate turnover and transport, which are practically unexplored.


Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin.
Male rabbit germ cells were labelled by intratesticular injection of [3H]-thymidine (3H-T). In sperms of control animals, radioactivity was first demonstrated between the 40th and 43rd day after labelling, corresponding to preleptotene spermatocytes. In rabbits treated with 22.5 mg/kg methylmethane sulfonate (MMS), significant radioactivity was shown in sperms collected from day 19 ownwards. These cells derived from spermatocyes and early spermatids at the time of labelling. 3H-T incorporation into these cell populations represents unscheduled DNA synthesis (UDS), a repair process initiated after chemical damage of germ cell DNA. After i.v. injection of 20 mg/kg cyclophosphamide, an alkylating agent that must be activated, labelled sperms were found 28--37 days after treatment. This shows that UDS took place in spermatocytes during the pachytene and zygotene stages. Adriamycin (1.0 and 3.0 mg/kg) induced UDS during pachytene and zygotene stages of spermatogenesis. Sperm counts decreased during spermatogonial stages by a factor of about ten in cyclophosphamide and adriamycin treated rabbits. It was not changed after MMS-treatment.


The SARS-CoV-2 pandemic impact on rhinology research: A survey of the American Rhinologic Society.
The COVID-19 pandemic has radically shifted healthcare operations within hospitals and universities across the globe. However, the effect of the COVID-19 pandemic on research endeavors and clinical trials is unclear. This study investigates the impact of the COVID-19 pandemic on basic science and clinical research within the rhinology community. A cross-sectional study was designed utilizing an 8-question survey to identify changes to rhinology research. Questions evaluated the impact of the COVID-19 pandemic on administrative research support and staffing, basic science research, clinical trials and resident research involvement. Seventy-one participants responded to the survey (8.5% response rate). Most respondents noted changes in IACUC/IRB approval (faster, 33%; slower, 31%). Of those who employed laboratory personnel, 64% were able to continue staff employment with full salary. The majority of animal research and in vitro studies were halted (64% and 56%, respectively), but animal care and cell line maintenance were allowed to continue. Clinical trial enrollment was most commonly limited to COVID derived studies (51%). Forty-seven percent of respondents noted increased resident research participation. The rapid spread of the SARS-CoV-2 virus has markedly impacted rhinology-related research. Maintaining safe workplace practices as restrictions are lifted will hopefully mitigate the spread of the virus and allow research productivity to resume.


A brief method for assessing social development: structure, reliability, stability, and developmental validity of the Interpersonal Competence Scale.
The Interpersonal Competence Scale (ICS-T) is a set of brief rating scales for teachers and parents. It consists of 18 items that assess social and behavioural characteristics of children and youths. The ICS-T yields three primary factors: AGG (argues, trouble at school, fights), POP (popular with boys, popular with girls, lots of friends), and ACA (spelling, math). Subsidiary factors include AFF (smile, friendly), OLY (appearance, sports, wins), and INT (shyness, sad, worry). The psychometric properties of the scale (internal structure, reliability, long-term stability) are presented and evaluated over successive ages. The scale factors have been linked to contemporaneous observations of behavior and social network membership. Developmental validity of the ICS-T includes the significant prediction of later school dropout and teenage parenthood. The ICS-T scale is described, along with instructions for use and scoring.


[Cervical lymph node involvement in carcinomas of the mobile tongue in Tunisia. Retrospective study of 135 cases].
To report the profile of histologic cervical nodes involvement associated with mobile tongue squamous cell carcinoma. Our retrospective study concerned patients treated from 1978 to 1998 by cervical neck dissection for mobile tongue carcinoma. A population of 135 patients (90 M/45 F, sex-ratio 2) with a 53.5 mean age (19 to 75) is analyzed. Clinical palpable nodes were present in 68 cases (50%) mainly submental-submaxillar (54). Histologic examination showed a node involvement in 54 cases without (32 cases) or with capsular rupture (22 cases) mainly in the jugulo-carotidian chain (46/54). Among the 67 clinically N0 patients collected after 1990, 22 patients (33%) exhibited an histological involvement vs 32/68 (47%) for the group presenting palpable cervical nodes for the whole period. Histologic node involvement seemed to be linked to the clinical status, node size and TNM stage. Cervical lymph node treatment needs to be systematic in mobile tongue carcinoma. The probability of histologic involvement is linked to the loco-regional extent of disease and influences the prognosis. In N0 patients, neck dissection is required because of the frequency of histological involvement, particularly when loss to follow-up may be expected.


Epidemiology of aplastic anemia: a prospective multicenter study.
Aplastic anemia is a rare and severe disease. Its incidence varies considerably worldwide. We aimed at describing the epidemiology of this disease, including the incidence, mortality and survival trends, in a well-defined population. Since 1980, a case-control surveillance study of aplastic anemia has been carried out by a cooperative group, in the metropolitan area of Barcelona. Inclusion is dependent on the patient having at least two of the following features: white blood cell count < or = 3.5 x 10(9)/L, platelet count < or = 50 x 10(9)/L, hemoglobin <10 g/L or hematocrit of <30%; when only one of these last two criteria is fulfilled, a reticulocyte count of < or = 30 x 10(9)/L is also required. The bone marrow biopsy has to be compatible with the diagnosis of aplastic anemia. Between 1980 and 2003, a total of 235 cases of aplastic anemia were identified. The overall incidence was 2.34 per million inhabitants per year and the incidence increased with age. Most of the cases were classified as severe or very severe aplastic anemia. Survival rates at 3 months, and at 2 and 15 years after the diagnosis were 73%, 57%, and 51%, respectively. Advanced age and more severe disease at the time of diagnosis were associated with a lower survival rate. There was a trend to a better 2-year survival rate among patients treated with bone marrow transplantation. Forty-nine cases (20.8%) were exposed to drugs reported to be associated with aplastic anemia, and 21 (8.9%) to toxic agents. The incidence of aplastic anemia in Barcelona is low but the case fatality rate is high. Advanced age and severe disease at the time of diagnosis were associated with decreased survival.


Increased visfatin expression is associated with nuclear factor-kappa B and phosphatidylinositol 3-kinase in periodontal inflammation.
Visfatin is an adipocytokine that plays a role in regulating periodontal inflammation by as yet identified mechanisms. It has been suggested that visfatin mediates inflammation via activation of the nuclear factor-kappa B (NF-κB) and phosphatidylinositol 3-kinase (PI3k) signaling pathways which play a role in the inhibition of neutrophil apoptosis. The aim of this study was to investigate the expression of visfatin, NF-κB (NF-κB1 and NF-κB2), PI3k, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) in the tissue of healthy individuals and patients with periodontitis. Tissue biopsy samples were obtained from 21 patients with chronic periodontitis and from the gingiva of 19 healthy individuals undergoing crown lengthening. The mRNA expression levels of visfatin, NF-κB, PI3k, TNF-α, and IL-1β were evaluated by quantitative real-time PCR (qPCR). Also, visfatin protein expression was measured by immunohistochemistry. Both qPCR and immunohistochemistry results revealed that the visfatin expression was higher in the tissues with periodontitis than in healthy tissues (P < 0.01). Similarly, the mRNA expression levels of NF-κB2, PI3k, and IL-1β were higher in tissues with periodontitis than in healthy gingival tissues (P < 0.01). Visfatin was positively correlated with the levels of NF-κB1 (r = 0.549, P < 0.05), NF-κB2 (r = 0.636, P < 0.05), PI3k (r = 0.682, P < 0.01), TNF-α (r = 0.558, P < 0.05), and IL-1β (r = 0.686, P < 0.01) in the tissues with periodontitis. Our results demonstrated that increased visfatin was associated with the expression of NF-κB and PI3k which may play a role in the pathogenesis of periodontitis. We suggest that increased visfatin may contribute to the inhibition of neutrophil apoptosis via the NF-κB and PI3k signaling pathways. Understanding the role of visfatin in periodontitis will enable the development of new treatment methods for inflammation.


Effect of dietary betaine supplementation on lipogenesis gene expression and CpG methylation of lipoprotein lipase gene in broilers.
Experiments were conducted to investigate the effect of betaine supplementation on mRNA expression levels of lipogenesis genes and CpG methylation of lipoprotein lipase gene (LPL) in broilers. From 22 days of age, 78 broilers were feed basal diet without betaine and basal diet supplemented with 0.1% betaine, respectively, and at 56 and 66 days of age, the traits of 15 chickens (7 males and 8 females) of each group were recorded and abdominal fat pads were collected. The mRNA expression levels of several lipogenesis gene were analyzed by semi-quantitative RT-PCR and real-time quantitative RT-PCR (qPCR), respectively. The CpG methylation profile at the promoter region of LPL gene in 66-day-old broilers was determined by bisulfite sequencing. The average daily gain and percent abdominal fat traits were slightly improved in 56-day-old and 66-day-old broilers after dietary supplementation of betaine to diet. After adding 0.1% betaine to diet, the mRNA levels of fatty acid synthase (FAS) and adipocyte-type fatty acid-binding protein genes in abdominal adipose were significantly decreased in 56-day-old broilers, and those of LPL and FAS genes in abdominal adipose were significantly decreased in 66-day-old broilers comparing with the control group (P < 0.05 and P < 0.001). Moreover, in 66-day-old broilers fed 0.1% betaine diet, a different CpG methylation pattern was observed: the CpG dinucleotides of 1st, 6th, 7th, 8th and from 10th to 50th were less methylated; however, those of 2nd, 5th and 9th were more heavily methylated. The results suggest that transcription of some lipogenesis genes was decreased by betaine supplementation and betaine may decrease LPL mRNA expression by altering CpG methylation pattern on LPL promoter region.


Localization performance correlates with binaural fusion for interaurally mismatched vocoded speech.
Bilateral cochlear implant users often have difficulty fusing sounds from the two ears into a single percept. However, measuring fusion can be difficult, particularly with cochlear implant users who may have no reference for a fully fused percept. As a first step to address this, this study examined how localization performance of normal hearing subjects relates to binaural fusion. The stimuli were vocoded speech tokens with various interaural mismatches. The results reveal that the percentage of stimuli perceived as fused was correlated with localization performance, suggesting that changes in localization performance can serve as an indicator for binaural fusion changes.


An unusual displacement of the cervical plate to the inner surface of the hypopharynx.
Unlocking and penetration of the screws and displacement or breakage of the plates are some commonly reported complications associated with the cervical implants. It is imperative to provide immediate surgical intervention along with a complete workup. Timely diagnosis and management can reduce further complications and morbidities.


Ecotoxicological evaluation of the UV-filter octocrylene (OC) in embryonic zebrafish (Danio rerio): Developmental, biochemical and cellular biomarkers.
Octocrylene (OC), an UV-filter (OUVF) is used in many cosmetic products to protect the skin against the harmful effects of UV radiation. Octocrylene has been detected in the environment and become an emerging contaminant of concern. However, the eco-toxicological data on octocrylene and their molecular effects and mechanism of action on freshwater fish are very limited. In this research work, the potential toxicity of octocrylene and its mechanisms on morphology, antioxidant and AChE activity, apoptosis, and histopathological changes were investigated in embryonic zebrafish (Danio rerio) at different concentrations (5, 50 and 500 μg/L). Embryos/larvae (96 hpf) treated with 50 and 500 μg/L of OC caused developmental abnormalities, and decreased hatching rate and heartbeat rate. The oxidative damage (LPO) and antioxidant enzyme (SOD, CAT and GST) activities were apparently elevated (P < 0.05) at the highest test concentration (500 μg/L). However, acetylcholinesterase (AChE) activity was significantly inhibited at the highest test concentration. Also, OC induced apoptosis in a dose-dependent manner. The zebrafish exposed to 50 and 500 μg/L showed histopathological changes including elongated yolk sac, swim bladder inflammation, muscle cell degeneration, retinal damage and pyknotic cells. In conclusion, octocrylene has induced oxidative stress at environmentally relevant concentrations leading to developmental toxicity, neurotoxicity, and histopathological damage in zebrafish embryos/larvae.


Evaluation of essential clinical components and features of current acne global grading scales.
Acne research is hindered by the absence of a universal, consistently applied standard for severity grading. Acne experts recently identified 4 essential clinical components and 2 features for an ideal acne global grading scale (AGGS). This study evaluated current AGGSs against consensus criteria previously identified as necessary. AGGSs were identified by systematic literature search and then evaluated independently by 4 raters against criteria (components and subcomponents; features and subfeatures) identified as essential. Eighteen AGGSs fulfilled selection criteria. Three scored 1 full SD above the mean for categorical scores. We also identified highest-ranked AGGSs for subcategory scores. Only English-language scales were selected. Efficiency and acceptance were not evaluable. Although no singular scale fulfilled all essential criteria, this study did identify highly ranked AGGSs. Incorporation and rationalization of their components and features should facilitate development of an ideal standard.


Characterization of tTA and its functional domain in tetracycline repressor-mediated gene repression system.
To elucidate of role(s) of tTA as a repressor in the tTA-mediated gene repression system, we introduced mutations into the acidic domain of VP16 and examined the effects of such various mutations. In the transient repression experiment, a region containing 34 amino acids of the activation domain of VP16 (412-456) which interacts with TFIIB was found to be necessary and sufficient for the tTA-mediated repression of gene expression. However, in the experiment to investigate the fact that tTA-regulated repression is related to the activation function of VP 16, we found that the repression abilities of tTA derivatives did not correlate exactly with their activation abilities. Therefore, we conclude that increased mass of VP16 in tTA might be also important for efficient repression in addition to functional domain of VP16.


Measurements and micro-mechanical modelling of the response of sintered titanium foams.
Titanium foams of relative density in the range 0.35-0.50 are tested in quasi-static compression, tension and shear. The response is ductile in compression but brittle, and weaker, in shear and tension. Virtual foam microstructures are generated by an algorithm based on Voronoi tessellation of three-dimensional space, capable of reproducing the measured size distribution of the pores in the foam. Finite Element (FE) simulations are conducted to explore the mechanical response of the material, by analysing the elasto-plastic response of a statistical volume element (SVE). The simulations correctly predict the ductile compressive response and its dependence on relative density.


Selective REcruitmeNt of plant DNA polymerases by geminivirus.
Geminiviruses reprogram host machineries to ensure their own propagation. They do not encode any DNA polymerase. Furthermore, the absence of direct evidence about the precise role of any host-encoded DNA polymerase has made geminivirus replication an enigma. Wu et al. recently resolved this puzzle by revealing that geminiviruses utilize plant DNA polymerase α and δ to drive their replication.


Influence of serum proteins on erythrocyte uptake of digoxin and digitoxin.
My purpose was to find out whether changes in serum protein content (albumin and gamma globulin) influenced erythrocyte uptake of glycosides and the capacity of erythrocytes to equilibrate glycoside levels when there are changes in protein binding. Heparinized human blood was incubated with 3H-digoxin, 6 ng/ml, and 3H-digitoxin, 44 ng/ml for 15 min. After centrifugation, distribution between plasma and erythrocytes was determined by liquid scintillation. Ratios between erythrocyte and plasma concentrations were 0.84 and 0.11 for digoxin and digitoxin. Replacing plasma by a protein-free isotonic solution led to increased erythrocyte uptake by 15% and 540% for digoxin and digitoxin. Erythrocyte uptake for both drugs was also determined in varying amounts of albumin (0 to 120 gm/l) and gamma globulin (0 to 25 gm/l). Only albumin influenced the erythrocyte uptake of these drugs. Calculations of free and bound plasma levels for both drugs showed that free digitoxin increased when albumin concentrations were equal to or less than 10 gm/l and remained constant (3%) for albumin concentrations between 15 and 120 gm/l. Free digoxin plasma levels rise when the albumin concentration is equal to or less than 15 gm/l and do not change at albumin levels between 30 and 120 gm/l. These data indicate that blood components play an important role in equilibrating changes in free digoxin and digitoxin levels.


Propolis reverses acetaminophen induced acute hepatorenal alterations: a biochemical and histopathological approach.
The present study has been conducted to evaluate the curative effect of propolis extract, a honey bee-hive product, against acetaminophen (APAP) induced oxidative stress and dysfunction in liver and kidney. Animals were challenged with APAP (2 g/kg, p.o.) followed by treatment of propolis extract (100 and 200 mg/kg, p.o.) once only after 24 h. Release of transaminases, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin were increased, whereas hemoglobin and blood sugar were decreased after APAP administration. Antioxidant status in both the liver and kidney tissues were estimated by determining the glutathione, malondialdehyde content and activities of the CYP enzymes, which showed significant alterations after APAP intoxication. In addition, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase, and major cell contents (total protein, glycogen and cholesterol) were also altered due to APAP poisoning. Propolis extract successfully reversed the alterations of these biochemical variables at higher dose. Improvements in hepatorenal histoarchitecture were also consistent with biochemical observations. The results indicated that ethanolic extract of propolis has ability to reverse APAP-induced hepatorenal biochemical and histopathological alterations probably by increasing the antioxidative defense activities due to various phenolic compounds present in it.


Immune profiling of the progression of a BALB/c mouse aerosol infection by Burkholderia pseudomallei and the therapeutic implications of targeting HMGB1.
The role of damage-associated molecular pattern HMGB1 signalling in a murine BALB/c model of severe respiratory melioidosis (Burkholderia pseudomallei infection) was explored in this study. Time course experiments were performed. It was established that HMGB1 was released in concert with increasing weight of organs and increasing concentration of liver enzymes in the blood a short time after cytokine release. Differences in the cytokine response between organs were observed, where the lungs contained higher concentrations of chemokines and interleukin 17, while the spleen produced more interferon-gamma, which is essential in the host defence against B. pseudomallei. This is evidence as to why the disease is seemingly more severe in the respiratory form. The effect of depleting HMGB1 using an antibody was also evaluated. It was found that this treatment significantly reduced bacterial load in the liver, spleen, and, to a greater degree, in the lungs. Cytokine quantification indicated that this reduction in bacterial load is likely due to the treatment reducing the release of a variety of pro-inflammatory cytokines. It is concluded that anti-HMGB1 treatment would be effective alongside other therapeutics, where it would reduce the characteristic over-inflammation associated with late stage infection.


Physiological implications of mammalian ferritin-binding proteins interacting with circulating ferritin and a new aspect of ferritin- and zinc-binding proteins.
Serum ferritin levels are relatively low (<1 µg/ml) and serum ferritin generally disappears rapidly from the circulation (t 1/2 < 10 min). There are various mammalian ferritin-binding proteins (FBPs) in the blood. Ferritin is cleared by direct uptake by ferritin receptors and by indirect receptor-mediated uptake of FBP complexed with ferritin. Mammalian ferritin binds both heme and iron, and binding occurs through two mechanisms: direct binding with ferritin to H-kininogen and anti-ferritin autoantibody, and indirect heme-mediated binding of fibrinogen and apolipoprotein B to ferritin. Anti-ferritin autoantibody and fibrinogen are proposed to be common mammalian FBPs, as is α2-macroglobulin. FBP-ferritin binding may affect blood coagulation and influence iron metabolism, oxidative condition, angiogenesis, inflammatory condition and immune response. Aside from apolipoprotein B, FBPs bind zinc ion to form antioxidant and anti-inflammatory agents. The possible simultaneous uptake of zinc ion with FBP-ferritin complex is likely to attenuate iron- and/or heme-mediated oxidative damage and inflammatory response.


A Cross-Sectional Survey of HIV Testing and Prevalence in Twelve Brazilian Correctional Facilities.
Prior studies have reported higher HIV prevalence among prisoners than the general population in Brazil, but data have been derived from single prisons. The aim of this study was to evaluate HIV testing practices, prevalence and linkage to care among inmates in a network of 12 prisons. We administered a questionnaire to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV and syphilis testing from January to December 2013. We evaluated factors associated with HIV testing and infection using multivariable logistic regression models. Six months after HIV testing, we assessed whether each HIV-infected prisoner was engaged in clinical care and whether they had started antiretroviral therapy. We recruited 3,362 inmates, of whom 2,843 (85%) were men from 8 prisons, and 519 (15%) were women from 4 prisons. Forty-five percent of participants reported never having been tested for HIV previously. In multivariable analysis, the variables associated with previous HIV testing were lack of a stable partner (adjusted odds ratio [AOR]: 1.38; 95% CI: 1.18-1.60), completed more than four years of schooling (AOR 1.40; 95% CI: 1.20-1.64), history of previous incarceration (AOR: 1.68; 95% CI: 1.43-1.98), history of mental illness (AOR 1.52; 95% CI: 1.31-1.78) and previous surgery (AOR 1.31; 95% CI: 1.12-1.52). Fifty-four (1.6%) of all participants tested positive for HIV; this included 44 (1.54%) men and 10 (1.92%) women. Among male inmates, HIV infection was associated with homosexuality (AOR 6.20, 95% CI: 1.73-22.22), self-report of mental illness (AOR 2.18, 95% CI: 1.13-4.18), history of sexually transmitted infections (AOR 3.28, 95% CI: 1.64-6.56), and syphilis sero-positivity (AOR 2.54, 95% CI: 1.20-5.39). Among HIV-infected individuals, 34 (63%) were unaware of their HIV status; only 23 of these 34 (68%) newly diagnosed participants could be reached at six month follow-up, and 21 of 23 (91%) were engaged in HIV care. HIV testing rates among prison inmates are low, and the majority of HIV-infected inmates were unaware of their HIV diagnosis. Incarceration can be an opportunity for diagnosis and treatment of HIV among vulnerable populations who have poor access to health services, but further work is needed on transitional HIV care for released inmates.


[Effect of diets with easily assimilated carbohydrates on the lipid composition of tissues of young rats with alloxan diabetes].
The blood serum, liver, cerebral and pancreatic tissues of 250 rats aged 1 to 1.5 mos. were investigated. Alloxan diabetes caused profound changes in the lipid composition of various tissues, the most noticeable ones in the pancreas. Of all easily assimilable carbohydrates used as admixtures to a common ration fructose followed by xylite and sorbitol produced the most unfavorable effect on lipid metabolism. The best results were obtained by adding up glucose.


Characterization of the novel HLA-DRB1*11:04:21 allele by sequencing-based typing.
HLA-DRB1*11:04:21 differs from HLA-DRB1*11:04:01 by one nucleotide substitution in codon 69 in exon 2.


Quantitative radioautographic studies on exponentially growing cultures of Escherichia coli. The distribution of parental DNA, RNA, protein, and cell wall among progeny cells.
Exponentially growing cultures of E. coli were examined by quantitative radioautographic techniques to determine the distribution of labeled DNA, RNA, protein, and cell wall among the progeny cells of successive generations. It was found that DNA is in large structures, non-randomly distributed in the progeny. About one-half of the cells have four such structures and approximately one-half contain these four structures plus four smaller ones. These structures show remarkable stability. Fewer than 3.5 per cent of the large structures break in one division time. Protein, RNA, and cell wall are all distributed randomly among progeny cells. The number of units of each component that show random segregation must be 200 or more.


Morphological maturation of the mouse brain: An in vivo MRI and histology investigation.
With the wide access to studies of selected gene expressions in transgenic animals, mice have become the dominant species as cerebral disease models. Many of these studies are performed on animals of not more than eight weeks, declared as adult animals. Based on the earlier reports that full brain maturation requires at least three months in rats, there is a clear need to discern the corresponding minimal animal age to provide an "adult brain" in mice in order to avoid modulation of disease progression/therapy studies by ongoing developmental changes. For this purpose, we have studied anatomical brain alterations of mice during their first six months of age. Using T2-weighted and diffusion-weighted MRI, structural and volume changes of the brain were identified and compared with histological analysis of myelination. Mouse brain volume was found to be almost stable already at three weeks, but cortex thickness kept decreasing continuously with maximal changes during the first three months. Myelination is still increasing between three and six months, although most dramatic changes are over by three months. While our results emphasize that mice should be at least three months old when adult animals are needed for brain studies, preferred choice of one particular metric for future investigation goals will result in somewhat varying age windows of stabilization.


Temperature dependence of the interaction of prazosin with lipid Langmuir monolayers.
The influence of temperature on membrane-prazosin interactions was studied. Prazosin, a quinazoline derivative of 2-furoylpiperazine, is a classic antihypertensive and antiarrhythmic drug. A mixed cholesterol/phospholipid monolayer at the water/air interface was employed as a simplified biomembrane model. Brewster angle microscopy (BAM) was used to visualize the monolayer morphology. It was found that prazosin penetrates Langmuir monolayers and modifies the interactions between membrane components, causing monolayer fluidization. An increase in temperature facilitates penetration of prazosin into the monolayers. Prazosin interacts preferentially with phosphatidylcholine and modifies the morphology of the condensed phase domains of DPPC. In the presence of prazosin, monolayers collapse at lower surface pressures. The difference between the collapse pressures of monolayers on water with and without prazosin increases with temperature.


Application of Graphene as Candidate Biomaterial for Synthetic Keratoprosthesis Skirt.
Synthetic keratoprostheses are required for visual rehabilitation in patients with end-stage corneal blindness. This study aimed to assess the biocompatibility of graphene material and its potential as a novel synthetic keratoprosthesis skirt material for corneal tissue engineering. Human corneal stromal fibroblasts were cultured on material surfaces including pristine graphene film, graphene foam, pristine titanium (Ti) discs, and tissue culture plastic surface (TCPS). Cell attachment was assayed by immunostaining of paxillin and vinculin. Cell viability and proliferation were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Click iT 5-ethynyl-2'-deoxyuridine (EdU) assays. The growth of fibroblasts on three-dimensional graphene foam was examined by scanning electron microscopy, and cytokine release was analyzed by enzyme-linked immunosorbent assay. Graphene films were implanted into rabbit corneal stromal pockets and examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography, in vivo confocal microscopy, and histology. Pristine graphene demonstrated good biocompatibility with human stromal fibroblasts in terms of cell adhesion, viability, and proliferation. Cells on graphene films showed higher number than on TCPS control. Cells grown on graphene had 10% more proliferation than on Ti. The expression levels of IL-6 and IL-8 were reduced when cells were seeded on graphene foam as compared to Ti and graphene film. Implantation of graphene film into rabbit stroma (n = 6) did not show any signs of infection, neovascularization, or inflammation. Graphene displayed excellent short-term biocompatibility with corneal cells and tissue. This demonstrates that graphene can be developed as a tissue engineering material for use in cornea.


Rapid removal of sulfamethoxazole from simulated water matrix by visible-light responsive iodine and potassium co-doped graphitic carbon nitride photocatalysts.
An environment-friendly iodine and potassium co-doped g-C3N4 (IKC3N4) photocatalyst was synthesized via the co-pyrolysis of urea and potassium iodate. Various characterization techniques were employed to evaluate the physical, thermal and chemical characteristics of the as-synthesized photocatalyst. Sulfamethoxazole (SMX) was used as a representative antibiotic pollutant. SMX removal by IK-C3N4 photocatalysts exceeded 99% (∼23 times higher than that of pure g-C3N4) within 45 min of visible light irradiation. The kinetics of SMX removal was analyzed with respect to solution pH, photocatalyst dosage and initial SMX concentration. Experimental data was found to fit the pseudo-first order kinetics and the Langmuir-Hinshelwood kinetics. The reuse of the photocatalyst up to 3 consecutive photodegradation cycles gave a minimal decline in SMX removal while the structure and the crystallinity of the nanomaterials remained unchanged. Overall, morphology engineering of conventional bulk graphitic carbon nitride can produce highly efficient photocatalysts for the decontamination of antibiotics in the aqueous environment.


Imputation accuracy for genomic selection using embryo biopsy samples in Gir.
The aim of this study was to establish a platform for genomic selection of in vitro-fertilized (IVF) Gir embryos. Multiple displacement amplification (MDA)-based embryo biopsy samples were genotyped, and genomic estimated breeding values (GEBV) for milk yield (305MY) were calculated. The concordance of GEBV and accuracy between embryo biopsies and the respective liveborn were assessed. Imputation was performed using two panels (Z-Chip and Bovine HD, Illumina) based on a database of 73,110 lactating cow's database and pedigree files from 147,131 animals. Biopsied embryos had similar pregnancy rates (39% vs 40%), pregnancy loss rates (18% vs 20%), and pregnancy length compared to Control embryos. After genotyping, low call rate means were detected for biopsy samples compared to the respective calf samples (0.80 vs 0.98). Imputation presented 0.83 (Z-Chip) and 0.96 (HD) accuracy (CORRanim). Embryo GEBV accuracy levels were higher in BovineHD imputation (0.82) than Z-Chip imputation (0.55) or no imputation (0.62), and the correlation between embryo/calf pairs' accuracy was 0.85 for BovineHD imputation, 0.11 for Z-Chip imputation, and 0.02 for no imputation. GEVB estimates correlation between embryo/calf pairs was 0.87 for BovineHD imputation, 0.80 for Z-Chip imputation, and 0.41 before imputation. The call rate of embryo samples did not affect the correlation between embryo/calf pairs for accuracy and GEBV before and after BovineHD imputation. Embryos obtained on the same farm presented GEBV 305MY differences of up to 800 kg, emphasizing the expected impact of embryo genomic selection for the Gir breed.


Studying task-related activity of individual neurons in the human brain.
Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative phase, we discuss informed consent, equipment setup and behavioral testing. During the intraoperative phase, we discuss the procedure for microelectrode recordings. Because patients are often awake during these procedures, this protocol can be performed in conjunction with behavioral tasks for studying a variety of cognitive functions. We describe the protocol in detail and provide two examples of expected results. In addition, we discuss the potential difficulties and pitfalls related to intraoperative studies. This protocol takes ∼1.5 h to complete.


Negative affect impedes perceptual filling-in in the uniformity illusion.
The notion of cognitive penetrability, i.e., whether perceptual contents can in principle be influenced by non-perceptual factors, has sparked a significant debate over methodological concerns and the correct interpretation of existing findings. In this study, we combined predictive processing models of visual perception and affective states to investigate influences of affective valence on perceptual filling-in in extrafoveal vision. We tested how experimentally induced affect would influence the probability of perceptual filling-in occurring in the uniformity illusion (N = 50). Negative affect led to reduced occurrence rates and increased onset times of visual uniformity. This effect was selectively observed in illusionary trials, requiring perceptual filling-in, and not in control trials, where uniformity was the veridical percept, ruling out biased motor responses or deliberate judgments as confounding variables. This suggests an influential role of affective status on subsequent perceptual processing, specifically on how much weight is ascribed to priors as opposed to sensory evidence.


The double trouble of metabolic diseases: the diabetes-cancer link.
The recent recognition of the clinical association between type 2 diabetes (T2D) and several types of human cancer has been further highlighted by reports of antidiabetic drugs treating or promoting cancer. At the cellular level, a plethora of molecules operating within distinct signaling pathways suggests cross-talk between the multiple pathways at the interface of the diabetes-cancer link. Additionally, a growing body of emerging evidence implicates homeostatic pathways that may become imbalanced during the pathogenesis of T2D or cancer or that become chronically deregulated by prolonged drug administration, leading to the development of cancer in diabetes and vice versa. This notion underscores the importance of combining clinical and basic mechanistic studies not only to unravel mechanisms of disease development but also to understand mechanisms of drug action. In turn, this may help the development of personalized strategies in which drug doses and administration durations are tailored to individual cases at different stages of the disease progression to achieve more efficacious treatments that undermine the diabetes-cancer association.


Medication communication between nurses and patients during nursing handovers on medical wards: a critical ethnographic study.
Communication is central to safe medication management. Handover is a routine communication forum where nurses provide details about how patients' medications are managed. Previous studies have investigated handover processes as general communication forums without specific focus on medication information exchange. The effects of social, environmental and organisational contexts on handover communication and medication safety have not been explored. To examine dominant and submissive forms of communication and power relations surrounding medication communication among nurses, and between nurses and patients during handover. A critical ethnographic approach was utilised to unpack the social and power struggles embedded in handover practices. The study was conducted in two medical wards of a metropolitan teaching hospital in Melbourne, Australia from January to November 2010. All registered nurses employed in the medical wards during the study time were eligible for participation. Patients were eligible if they were able to communicate with nurses about how their medications were managed. In total, 76 nurses and 27 patients were recruited for the study after giving written consent for participation. Participant observations, field interviews, video-recordings and video reflexive focus groups were conducted. Fairclough's critical discourse analytic framework guided data analysis. Nurse coordinators' group handovers in private spaces prioritised organisational and biomedical discourses, with little emphasis on evaluating the effectiveness of medication treatment. The ward spatial structure provided an added complexity to how staff allocation occurred. Handovers involving patients in the public spaces at the bedside facilitated a partnership model in medication communication. Nurses exercised discretion during bedside handovers by discussing sensitive information away from the bedside. Handovers across different wards during patient transfers caused communication breakdowns because information was not exchanged between bedside nurses. Nurse coordinators need to relinquish organisational control of the handover practice and appreciate the contribution of bedside nurses to patient information exchange. Bedside nurses need to be provided with opportunities to raise questions during the group handover. Designated meeting spaces need to be provided to reduce interruptions to the group handover process.


Species specificity in the responsiveness of chick embryo neural tube explants to target-conditioned medium.
Explants from the metencephalic region of 40-h chick embryo neural tubes containing the trigeminal (V) motor nucleus were cultured in appropriate target muscle-conditioned media (MCM) derived from chick, quail and rat embryos. Enhanced neuritic outgrowth was found only in the presence of chick MCM, indicating that this early, initial responsiveness to target-released materials within this system is species-specific.


On the physiology of grooming in a pigtail macaque.
Several functions of social grooming have been proposed, including building affiliative bonds between group members, and reducing tension or anxiety. In this case study, heart rate (HR) of a single adult female pigtail macaque living in a social group was monitored in several behavioral contexts to examine the relationship between grooming and HR level, an indicator of autonomic nervous system activity. The subject was implanted as a part of another study with a multichannel telemetry system which monitored several physiological variables. Physiological and behavioral data were collected over a nine day period. Heart rate during agonistic interactions was significantly higher than during other categories of behavior, and sleep HR significantly lower. When the subject received grooming from others, HR was significantly lower than during self grooming or initiating grooming to others, as well as during other behaviors. HR showed significant declines during bouts of receiving groom (up to 20 bpm), but not during bouts of initiating or self grooming. Following aggression, HR decline was greatest while receiving grooming. There were also HR differences for methods of grooming: stroking but not other methods related to decreases in HR.


Delayed seed dispersal in Pinus torreyana (Torrey pine).
Torrey pine exhibits a pattern of seed release intermediate between an open and closed-cone species. It was found that the cones open at maturity, but that seed fall from some cones continues for up to 13 years. Approximately 77% of the total seed crop was present in age classes one or more years past the time of seed maturity.Serotiny is thought to evolve in response to fire, and partial serotiny at the population level has been attributed to circumstances in which the strong selective pressure of fire is relaxed. We hypothesize that delayed seed dispersal in Torrey pine is a stable trait which is the result of a pattern of large relatively rare crown fires separated by intervals longer than one generation. The reduced serotiny observed in other conifers on headlands and islands in California seems consistent with our hypothesis.


Nucleotides and nucleolipids derivatives interaction effects during multi-lamellar vesicles formation.
In this paper a micellar interface, constituted by the cationic surfactant CTAB, in presence of 1,2-epoxydodecane and nucleotides was used for catanionic multi-lamellar vesicles (MLVs) formation. The micellar solution of CTAB is able to disperse the 1,2 epoxydodecane in the micellar core promoting the reaction of this reagent with the nucleotide attracted by the positive surface charge of the micellar aggregates. The alkylation of AMP and UMP nucleotides leads to the synthesis of nucleolipids. The behaviour of the supramolecular structures formed depends on the starting reagents (AMP, UMP and AMP+UMP) and on the assembly capabilities of the products. In particular nucleotides and nucleotides derivatives interaction effects are evaluated during the multi-lamellar vesicles formation. NMR spectroscopy and UV-vis measurements performed on MLVs showed strong aryl interactions. Interestingly, NMR spectra revealed prevailing stacking interactions between complementary nucleolipids. The assembly of complementary nucleotides affects the course of the reaction during the MLVs formation. Moreover the MLVs supramolecular stability has been tested by means of turbidity and UV-vis measurements. In particular, an enhanced stability has been found in systems prepared with complementary nucleotides confirming that in these systems the self-assembly process is influenced by nucleolipids interactions. Furthermore by following the hypocromic effect during the micellar catalysis, we showed that even in the earlier stages of the reaction significant differences are detectable.


Liver in a dish.
There exists a worldwide shortage of donor livers for transplant. This may not pose a problem in the future, as Takebe et al. have recently grown functional "liver buds" from stem cells in a dish.


Small-angle x-ray scattering study of human serum low-density lipoproteins with differential reactivity for an arterial proteoglycan.
The structure and thermal behavior of human serum low-density lipoproteins showing either a high or a low reactivity against a proteoglycan isolated from human arteries have been found to be different from each other. It is suggested that modifications in the lipoprotein surface structure induced by the physical state of the neutral lipids could modulate the affinity of the macromolecule for the arterial component.


NO RELATIONSHIP BETWEEN INTELLIGENCE AND FACIAL ATTRACTIVENESS IN A LARGE, GENETICALLY INFORMATIVE SAMPLE.
Theories in both evolutionary and social psychology suggest that a positive correlation should exist between facial attractiveness and general intelligence, and several empirical observations appear to corroborate this expectation. Using highly reliable measures of facial attractiveness and IQ in a large sample of identical and fraternal twins and their siblings, we found no evidence for a phenotypic correlation between these traits. Likewise, neither the genetic nor the environmental latent factor correlations were statistically significant. We supplemented our analyses of new data with a simple meta-analysis that found evidence of publication bias among past studies of the relationship between facial attractiveness and intelligence. In view of these results, we suggest that previously published reports may have overestimated the strength of the relationship and that the theoretical bases for the predicted attractiveness-intelligence correlation may need to be reconsidered.


Polyhydroxyalkanoates production with mixed microbial cultures: from culture selection to polymer recovery in a high-rate continuous process.
Polyhydroxyalkanoates (PHA) production with mixed microbial cultures (MMC) has been investigated by means of a sequential process involving three different stages, consisting of a lab-scale sequencing batch reactor for MMC selection, a PHA accumulation reactor and a polymer extraction reactor. All stages were performed under continuous operation for at least 4 months to check the overall process robustness as well as the related variability of polymer composition and properties. By operating both biological stages at high organic loads (8.5 and 29.1 gCOD/Ld, respectively) with a synthetic mixture of acetic and propionic acid, it was possible to continuously produce PHA at 1.43 g/Ld with stable performance (overall, the storage yield was 0.18 COD/COD). To identify the optimal operating conditions of the extraction reactor, two digestion solutions have been tested, NaOH (1m) and NaClO (5% active Cl2). The latter resulted in the best performance both in terms of yield of polymer recovery (around 100%, w/w) and purity (more than 90% of PHA content in the residual solids, on a weight basis). In spite of the stable operating conditions and performance, a large variation was observed for the HV content, ranging between 4 and 20 (%, w/w) for daily samples after accumulation and between 9 and 13 (%, w/w) for weekly average samples after extraction and lyophilization. The molecular weight of the produced polymer ranged between 3.4 × 10(5) and 5.4 × 10(5)g/mol with a large polydispersity index. By contrast, TGA and DSC analysis showed that the thermal polymer behavior did not substantially change over time, although it was strongly affected by the extraction agent used (NaClO or NaOH).


Association of polymorphism in cytochrome P450 2C9 with susceptibility to head and neck cancer and treatment outcome.
The present case-control study involving 750 cases and equal number of healthy controls investigates the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemotherapy or combination of radio-chemotherapy. The frequency of heterozygous or homozygous genotypes of CYP2C9*2 & CYP2C9*3, which leads to the poor metabolizer (PM) genotype was significantly higher in HNSCC cases when compared to the healthy controls resulting in significantly increased risk in the cases. Tobacco use in the form of tobacco smoking or tobacco chewing was found to increase the risk several fold in cases when compared to the non-tobacco users. Likewise, alcohol intake in cases with variant genotypes of CYP2C9*2 or CYP2C9*3 also significantly increased the HNSCC risk in cases when compared to non-alcohol users. Further, majority of the cases carrying variant alleles of both CYP2C9*2 or CYP2C9*3 were found to respond poorly to the chemotherapy or combination of radio-chemotherapy. The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome.


Medical litigation in oral surgery practice: lessons learned from 20 lawsuits.
The aim of this study was to investigate all the lawsuits related to oral surgery practice over a period of three years, and to analyze the different causes of litigation. Inclusion criteria involved all the closed cases that proved malpractice against an oral and maxillofacial surgeon or involved a dentist who performed an oral and maxillofacial surgical procedure. The most common causes of litigation were oro-antral communication, neurological deficit, and bleeding. The study presented the lessons learned from 20 cases, and concluded that most of the lawsuits in oral surgery practice can be prevented either through preoperative measures or by dealing with the impact of the surgical error through good patient rapport and communication.


Survival and analysis of predictors of mortality in patients undergoing replacement renal therapy: a 20-year cohort.
optimal management of end-stage renal disease (ESRD) in hemodialysis (HD) patients should be more studied because it is a serious risk factor for mortality, being considered an unquestionable global priority. we performed a retrospective cohort study from the Nephrology Service in Brazil evaluating the survival of patients with ESRD in HD during 20 years. Kaplan-Meier method with the Log-Rank and Cox's proportional hazards model explored the association between survival time and demographic factors, quality of treatment and laboratory values. Data from 422 patients were included. The mean survival time was 6.79 ± 0.37. The overall survival rates at first year was 82,3%. The survival time correlated significantly with clinical prognostic factors. Prognostic analyses with the Cox proportional hazards regression model and Kaplan-Meier survival curves further identified that leukocyte count (HR = 2.665, 95% CI: 1.39-5.12), serum iron (HR = 8.396, 95% CI: 2.02-34.96), serum calcium (HR = 4.102, 95% CI: 1.35-12.46) and serum protein (HR = 4.630, 95% CI: 2.07-10.34) as an independent risk factor for the prognosis of survival time, while patients with chronic obstructive pyelonephritis (HR = 0.085, 95% CI: 0.01-0.74), high ferritin values (HR = 0.392, 95% CI: 0.19-0.80), serum phosphorus (HR = 0.290, 95% CI: 0.19-0.61) and serum albumin (HR = 0.230, 95% CI: 0.10-0.54) were less risk to die. survival remains low in the early years of ESRD treatment. The present study identified that elevated values of ferritin, serum calcium, phosphorus, albumin, leukocyte, serum protein and serum iron values as a useful prognostic factor for the survival time.


BDNF-induced local protein synthesis and synaptic plasticity.
Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and long-term potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-γ (PLC-γ) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre- and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short- and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.


Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice.
Accumulating evidence suggests the origin of juvenile myelomonocytic leukemia (JMML) is closely associated with fetal development. Nevertheless, the contribution of embryonic progenitors to JMML pathogenesis remains unexplored. We hypothesized that expression of JMML-initiating PTPN11 mutations in HSC-independent yolk sac erythromyeloid progenitors (YS EMPs) would result in a mouse model of pediatric myeloproliferative neoplasm (MPN). E9.5 YS EMPs from VavCre+;PTPN11D61Y embryos demonstrated growth hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and hyperactive RAS-ERK signaling. Mutant EMPs engrafted the spleens of neonatal recipients, but did not cause disease. To assess MPN development during unperturbed hematopoiesis we generated CSF1R-MCM+;PTPN11E76K ;ROSAYFP mice in which oncogene expression was restricted to EMPs. Yellow fluorescent protein-positive progeny of mutant EMPs persisted in tissues one year after birth and demonstrated hyperactive RAS-ERK signaling. Nevertheless, these mice had normal survival and did not demonstrate features of MPN. YS EMPs expressing mutant PTPN11 demonstrate functional and molecular features of JMML but do not cause disease following transplantation nor following unperturbed development. Developmental Dynamics 246:1001-1014, 2017. © 2017 Wiley Periodicals, Inc.


Factors associated with the intention to use vitamin D supplements: quantitative study among a sample of elderly people in a medium-sized town in the Netherlands.
The objective of this study was to assess which factors are related to the intention of elderly people to use vitamin D supplements.A questionnaire that was based on several theories, feedback of experts, and personal interviews with members of the target group was distributed among a random sample of 497 elderly people in a medium-sized town in the Netherlands (response 46%). Variables measured included perceived susceptibility, severity and control with respect to developing a vitamin D deficiency or getting a bone fracture, and beliefs, perceived social norms, modeling, self-efficacy, and intention with respect to the use of vitamin D supplements. Univariate analyses of variance, chi-square tests, stepwise multiple regression, and stepwise logistic regression analysis were performed. Respondents reporting a high intention had more positive attitudes and normative beliefs, higher self-efficacy expectations with respect to using vitamin D supplements, and more often used other supplements than respondents with a low intention. Subjects who already used vitamin D supplements were more often female and already familiar with the advice and had more positive attitudes and normative beliefs than nonusers. It was concluded that many elderly people have high intentions to start using vitamin D supplements as soon as they hear about the advice. A health promotion campaign to promote the use of vitamin D supplements should aim at making elderly people familiar with the Health Council of the Netherlands' advice. Furthermore, the campaign should place emphasis on changing attitudes, perceived social norms, and self-efficacy expectations toward vitamin D supplement use.


Does Student Loan Debt Hinder Community Well-Being?
How the growth in student debt is impacting the well-being of the larger community is explored using U.S. county level data. Using tax return data from the Internal Revenue Service (IRS) we find that higher levels of student debt tends to be associated with lower levels of community well-being. Specifically, lower rates of home ownership, higher rental market stress, lower rates of entrepreneurship and poorer health behaviors. While the decision to take on student debt is an individual decision, local communities are uniquely positioned to help students make decisions around taking on debt and repayment options.


Complete elimination of hostplant quinolizidine alkaloids by larvae of a polyphagous lycaenid butterfly, Callophrys rubi.
Caterpillars of the lycaenid butterfly Callophrys rubi accept a variety of hostplants. When fed inflorescences or leaves of Genista tinctoria (a natural hostplant) or Lupinus polyphyllus (a non-host), the larvae completely eliminate quinolizidine alkaloids ingested from their food in their frass. No alkaloids are stored. Infestation by the parasitoid wasp Distatrix sancus (Braconidae) did not affect alkaloid elimination. The presence of an effective anti-toxin system is discussed with reference to the evolution of hostplant relationships in the genus Callophrys. There is no evidence that in the secondarily myrmecoxenous larvae of C. rubi hostplantderived chemical defense takes the place of former myrmecophily.


Systematic comparison of multi-omics survival models reveals a widespread lack of noise resistance.
As observed in several previous studies, integrating more molecular modalities in multi-omics cancer survival models may not always improve model accuracy. In this study, we compared eight deep learning and four statistical integration techniques for survival prediction on 17 multi-omics datasets, examining model performance in terms of overall accuracy and noise resistance. We found that one deep learning method, mean late fusion, and two statistical methods, PriorityLasso and BlockForest, performed best in terms of both noise resistance and overall discriminative and calibration performance. Nevertheless, all methods struggled to adequately handle noise when too many modalities were added. In summary, we confirmed that current multi-omics survival methods are not sufficiently noise resistant. We recommend relying on only modalities for which there is known predictive value for a particular cancer type until models that have stronger noise-resistance properties are developed.


Changes in tissue levels of glutathione, extent of lipid peroxidation, and activity of glutathione peroxidase in transplantable murine lymphoma.
The reduced glutathione (GSH) levels in the hepatic tissues, extent of lipid peroxidation in the liver, kidney and brain, and alterations in the activity of glutathione peroxidase (GPX) in the hepatic tissues were monitored in mice bearing a transplantable ascitic lymphoma. These markers showed substantial alterations during the height of tumour progression when compared to controls. The GSH level, extent of lipid peroxidation, and GPX activity increased sharply after approximately 2 weeks following inoculation of ascitic cells. This was followed by a steady decline in all markers and death occurred around day 32 after inoculation.


Acute response of social functioning in dysthymic patients with desipramine.
Despite some evidence that short-term antidepressant treatment improves social dysfunction in depressed patients, little is known about the response of specific social impairments in dysthymic patients to antidepressant medication. We examined the effect of acute (10 weeks), open-label desipramine (DMI) treatment on social functioning in subjects with DSM-III-R dysthymia. Social functioning was assessed with the social adjustment scale self-report (SAS-SR) at baseline and at week 10. Compared with DMI nonresponders DMI responders showed significantly greater improvement in overall social functioning (F2,45 = 5.46, P < 0.0001) and in enjoyment of leisure time (F2,45 = 14.38, P < 0.0001) on the SAS-SR. Dysthymic patients who respond to DMI improve significantly in social functioning. Diminished capacity to enjoy leisure time may be a state marker of depression in some chronically depressed patients.