Site-specificity and site tenacity in a wolf spider: A serological dietary analysis.
The wolf spider Pardosa ramulosa is a dietary specialist on aquatic insects. Site tenacity of this species was determined by serological analysis of spiders collected on the margins of and at known distances from each of eight closely-spaced pools whose prey compositions were known. Remains of a mosquito species found uniquely in three of these pools were found only in spiders closely associated with them, despite the presence of otherwise suitable pools less than 10 m away. This indicates that spiders stay at specific pools for at least two weeks, the detectability period of this marker species in the assay.The only exception to this site tenacity, except for inadvertant rafting during high tides, is the movement of adult females with egg cases away from pools. This is attributed to selection for avoidance of spiderling cannibalism, rather than a search for sunning or foraging sites as in some other lycosids.The extreme site-tenacity of P. ramulosa is attributed to the high productivity of all pools, such that spiders from the most and least productive pools differ little if at all in fitness, and the high costs of moving to other pools, which are widely dispersed. The situation in crab spiders may be analogous. Conversely high and biologically significant variances in web site productivity, low distances between acceptable web sites, and low moving costs reduce site tenactiy in north temperate second growth orb weavers and a desert funnel web weaver.


Impact of Preconditioning Temperature and Duration Period on Carpogenic Germination of Diverse Sclerotinia sclerotiorum Populations in Southwestern Australia.
The soilborne pathogen Sclerotinia sclerotiorum (Lib.) de Bary is the causal agent of Sclerotinia stem rot, a severe disease of broad-leaf crops including canola/rapeseed (Brassica napus) that can result in significant yield losses. Sclerotia, the hard melanized resting structure of the pathogen, requires preconditioning before carpogenic germination can occur. We investigated the effect of preconditioning temperature (4, 20, 35, 50°C, and field conditions) and duration (0, 30, 60, 120, 179, 240, and 301 days) on germination of S. sclerotiorum sclerotia collected from five canola fields in the southwestern Australia grain belt. The ecological diversity of each population was characterized using mycelial compatibility group (MCG) typing. No response was observed for isolates conditioned at 4°C at any time period, indicating that chilling is not a preconditioning requirement for these isolates. Sclerotia required preconditioning for a minimum of 60 days before any significant increase in germination occurred, with no further increases in germination recorded in response to longer conditioning after 60 days. The highest germination was observed in sclerotia conditioned at 50°C. The MCG results indicated significant diversity within and between populations, suggesting local adaptation to different environments as well as ensuring the ability to respond to seasonal variation between years.


Data defining markers of human neural stem cell lineage potential.
Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in "Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination" (Oikari et al. 2015) [1].


Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long-term open-label safety extension study.
Fenfluramine, which was previously approved as a weight loss drug, was withdrawn in 1997 when reports of cardiac valvulopathy emerged. The present study was conducted in part to characterize the cardiovascular safety profile of low-dose fenfluramine when used in a pediatric population to reduce seizure frequency in patients with Dravet syndrome. Patients 2- to 18-years-old with Dravet syndrome who had completed any of three randomized, placebo-controlled clinical trials of fenfluramine were offered enrollment in this open-label extension (OLE) study. All patients were treated with fenfluramine starting at a dose of 0.2 mg/kg/day (oral solution dosed twice per day), which was titrated to maximal effect with a dose limit of 0.7 mg/kg/day (maximum 26 mg/day) or 0.4 mg/kg/day (maximum 17 mg/day) in patients receiving concomitant stiripentol. Standardized echocardiographic examinations were conducted at Week 4 or 6 and then every 3 months during the OLE study to monitor cardiac valve function and structure and pulmonary artery pressure. The primary end point for the echocardiography analysis was the number of patients who developed valvular heart disease or pulmonary artery hypertension (PAH) during treatment. A total of 232 patients were enrolled in the study. The average age of patients was 9.1 ± 4.7 years, and 55.2% were male. The median duration of treatment with fenfluramine was 256 days (range = 58-634 days), and the mean dose of fenfluramine was 0.41 mg/kg/day. No cases of valvular heart disease or PAH were observed. Longitudinal echocardiography over a median 8.4 months of treatment with fenfluramine suggests a low risk of developing cardiac valvulopathy and PAH when used to treat pediatric patients with Dravet syndrome.


Friction energy harvesting on bismuth tungstate catalyst for tribocatalytic degradation of organic pollutants.
Mechanical energy as the green and sustainable energy source widely distributes in natural environment. In this paper, we successfully realize the conversion of mechanical energy through a friction route on the tribocatalyst of Bi2WO6. Under magnetic stirring, the friction between the PTFE-sealed magnetic bar and the catalyst particles resulted in the electron transfer crossing the contact interface, in which PTFE accepted the electrons and simultaneously the holes were left on the catalyst. The positively charged catalyst was demonstrated through electrostatic attraction and repulsion tests. Like photocatalytic process, the holes on the valence band of Bi2WO6 have strong oxidative ability that can efficiently oxidize organic pollutants. The tribocatalytic tests showed that the Bi2WO6 could eliminate organic dyes under magnetic stirring in dark, and we could further optimize the tribocatalytic performance via regulating the size of magnetic bar and reactor material. Finally, a high stability of tribocatalysis was revealed by the multiple tests. This work not only develops a green tribocatalysis strategy to oxidative purification of organic pollutants, but also provides a possible pathway to convert mechanical energy in environment to chemical energy, such as potential applications in environmental remediation and sustainable energy.


Occurrence of ochratoxin A in Korean red paprika and factors to be considered in prevention strategy.
A large amount-260,000 tons-of red paprika is consumed annually in Korea, where the people prefer hot and pungent to sweet foods. Concern has recently grown among consumers over contamination of paprika powder by mycotoxins; contamination can occur at any stage from pre-harvest to drying, storage, grinding, and eventually transport to the retail market. This study had dual aims: to investigate the current level of contamination of hot peppers by ochratoxin A and to identify the critical control points in the food chain. We measured the ochratoxin A (OTA) content of 200 samples from various sources including supermarkets, an online shopping mall, small stakeholder mills, Hazard Analysis and Critical Control Points (HACCP)-implemented factories, and an import company. Mycotoxin was determined using immunoaffinity column cleanup/HPLC quantification as well as strong anion exchange cleanup/stable isotope dilution assay. Monitoring revealed that approximately 30% of red paprika samples were OTA-positive, indicating a need to establish a maximum level for regulation. We selected two model factories that had adopted HACCP in different ways, and compared data in order to develop guidelines for alleviation of mitigation of the mycotoxin contamination.


Gene expression profiling of allogeneic islet grafts in an experimental mouse model before rejection or tolerance phenotypes arise.
It has been reported that an HY antigen-mismatched islet transplantation can induce peripheral tolerance. However, the factors that initiate the peripheral tolerance are not clear. This study was designed to examine which genes were most important for the induction of peripheral tolerance. Islets from female Balb/c and male C57BL/6 mice were transplanted underneath the left perirenal capsule of female C57BL/6 recipient mice rendered diabetic by intraperitoneal injection of streptozotocin. Before rejection or tolerance phenotypes arose, we harvested islet grafts for cDNA microarray analysis. Minor antigen-mismatched islets transplanted into recipient mice showed no rejection or tolerance phenotypes until 12 days posttransplantation. When we confirmed, decreased functional islet grafts and increased inflammatory cell infiltration. Gene expression profiles revealed differences in expression among groups. Major histocompatibility complex-mismatched islets induced upregulation of 209 genes and downregulation of 10 genes compared with the HY antigen-mismatched islet (2-fold; P < .05). Of these, 3 genes exhibited significant changes in expression levels in Balb/c donor islet grafts compared with C57BL/6 donor islet grafts: Gad1, Gdf10, and Scg2 (P < .01). The present study suggested that 3 genes showed a significant relationship to protection against graft rejection. The identification of these genes may help to understand signaling pathways, involved in the communication between transplanted islet grafts and recipients in vivo.


Effect of Gaussian Smoothing Filter Size for CT-Based Attenuation Correction on Quantitative Assessment of Bone SPECT/CT: A Phantom Study.
This study aims to determine the effect of Gaussian filter size for CT-based attenuation correction (CTAC) on the quantitative assessment of bone SPECT. An experiment was performed using a cylindrical phantom containing six rods, of which one was filled with water and five were filled with various concentrations of K2HPO4 solution (120-960 mg/cm3) to simulate different bone densities. 99mTc-solution of 207 kBq/ml was also included within the rods. SPECT data were acquired at 120 views for 30 s/view. CT for attenuation correction were obtained at 120 kVp and 100 mA. Sixteen different CTAC maps processed with different Gaussian filter sizes (ranging from 0 to 30 mm in 2 mm increments) were generated. SPECT images were reconstructed for each of the 16 CTAC maps. Attenuation coefficients and radioactivity concentrations in the rods were compared with those in the water-filled rod without K2HPO4 solution as a reference. Gaussian filter sizes below 14-16 mm resulted in an overestimation of radioactivity concentrations for rods with high concentrations of K2HPO4 (≥ 666 mg/cm3). The overestimation of radioactivity concentration measurement was 3.8% and 5.5% for 666 mg/cm3 and 960 mg/cm3 K2HPO4 solutions, respectively. The difference in radioactivity concentration between the water rod and the K2HPO4 rods was minimal at 18-22 mm. The use of Gaussian filter sizes smaller than 14-16 mm caused an overestimation of radioactivity concentration in regions of high CT values. Setting the Gaussian filter size to 18-22 mm enables radioactivity concentration to be measured with the least influence on bone density.


Carbon-13 NMR investigations on ribonuclease A.
The proposed interaction between the amino acid residues Asp 14 and His 48 of ribonuclease A has been confirmed by 13C-NMR spectroscopy. The titration behaviour of the resonance of the side-chain carboxyl group of Asp 14 suggests a pKa of 6.5--7.0 for His 48. An equilibrium between different conformation process of His 48. Upon this deprotonation a hydrogen bond between the side-chains of Asp 14 or His 48 and Tyr 25 seems to be formed as is suggested by the behaviour of a tyrosine C zeta resonance assigned to Tyr 25. One phenylalanine resonance broadens and moves upfield on the addition of the inhibitor Cyd-2'-P, being therefore assigned to Phe 120. The behaviour of this resonance suggests that the upfield shift results from the anisotropy of the cytidine ring. Three signals are assigned to the three Phe residues.


Prevalence of wild type transtyrethin cardiac amyloidosis in a heart failure clinic.
Wild type transthyretin amyloidosis (ATTRwt) has gained interest during recent years due to better diagnostic tools and the emergence of treatment options. Little is known about the prevalence of the disease. We aimed to investigate the prevalence in a heart failure population with myocardial hypertrophy. All patients with an ICD code of heart failure living within the catchment area of Umeå University hospital and intraventricular septum >14 mm were offered screening with 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and a clinical work up. Out of 2238 patients with heart failure, 174 patients were found to have a septum >14 mm. Ten patients were already diagnosed with hereditary ATTR cardiomyopathy, 12 patients had ATTRwt cardiomyopathy, 12 patients had known HCM, one patient had AL amyloidosis, and four patients had already undergone a negative DPD scan (DPD uptake grade 0 and 1) within the last 3 years. This left 134 patients who we tried to contact for screening, but 48 patients had either died or declined to participate. Out of 86 screened patients, 13 had a DPD uptake of grade 2 or 3 without other amyloid disease making the total number of patients with ATTRwt in this population 25. Approximately 20% of investigated patients in a cohort with heart failure and increased myocardial wall thickness has ATTRwt. Calculated for the whole population of heart failure patients, the prevalence is just over 1.1%. Comparing this number to the total population would give an estimated prevalence of 1:6000.


Isolated retinal venous macroaneurysm.
Unlike retinal arterial macroaneurysms, retinal venous macroaneurysms are rare. Retrospective studies have previously described venous macroaneurysms predominantly in association with branch retinal vein obstruction. Only 2 cases of isolated retinal venous macroaneurysm without venous occlusion have been described in the literature. The patient being described in this case report has the third isolated nonocclusive venous macroaneurysm to be reported. A healthy 43-year-old white woman presented for a routine eye examination with no history of visual disturbance other than long-standing amblyopia in the left eye (O.S.). An isolated retinal venous macroaneurysm was found on the inferior temporal retinal vein just beyond the optic disc margin. All other retinal findings were normal. One-month and 6-month followup examinations showed the macroaneurysm unchanged. The etiology of the retinal venous macroaneurysm in this case is unknown. This patient has an isolated retinal venous macroaneurysm of unknown etiology. Based on the clinical profile of the patient, it is unlikely, although admittedly not impossible, for this to have resulted from a previous venous occlusive event. The identification and documentation of this extremely rare vascular phenomenon will help improve our understanding of its significance as well as any potential ocular sequela.


GLP-1 agonists for people living with HIV and obesity, is there a potential?
Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV. Clinical experience is limited to two clinical cases of diabetic people with HIV using liraglutide after which a successful weight loss and glycaemic control were observed. None of the adverse events associated with liraglutide and semaglutide usage indicate an additional risk for people with HIV. Extra caution showed be warranted when initiating GLP-1 agonist therapy in people with HIV taking protease inhibitors who have pre-existing risk factors for heart rate variability to reduce the incidence of RP interval prolongation. GLP-1 agonists are metabolized by endopeptidases, and thus do not generate major drug-drug interactions with most drugs, including ARVs. GLP-s agonists are known to inhibit gastric acid secretion, which warrants caution and close monitoring when combined with atazanavir and oral rilpivirine, two ARVs that require low gastric pH for an optimal absorption. Theoretical considerations and a few available clinical observations support semaglutide and liraglutide prescription in people with HIV, with, thus far, no indications of concern regarding efficacy, safety or pharmacological interactions with ARVs.


Calcitonin-producing pancreatic somatostatinoma: report of a case.
A 59-year-old woman was hospitalized due to a 1-year history of diarrhea and weight loss. Echography and computed tomography of the abdomen revealed a 10 x 7 cm solid mass in the tail of the pancreas and gallstones, while selective celiac angiography revealed the presence of a hypervascular mass. High levels of somatostatin and calcitonin were detected in the plasma, 70 pg/ml (normal range <28 pg/ml) and 5550 pg/ml (normal range 37 +/- 8 pg/ml), respectively. This tumor was thus removed by means of a distal pancreatectomy and a splenectomy. After the pancreatic tumor was removed, the elevated levels of plasma somatostatin and calcitonin returned to the normal ranges, and the persistent diarrhea also dramatically disappeared. A postoperative immunohistochemical study showed the tumor cells to be diffusely positive for somatostatin and calcitonin. These results clearly indicate this patient to be a case of calcitonin-producing pancreatic somatostatinoma.


Santonin-related compound 2 inhibits the expression of ICAM-1 in response to IL-1 stimulation by blocking the signaling pathway upstream of I kappa B degradation.
Santonin-related compounds (SRCs) were synthesized from the starting material L-alpha-santonin and tested for the biological activity on the expression of intercellular adhesion molecule-1 (ICAM-1) in response to IL-1 stimulation on human adenocarcinoma cells. One of the bromoketone derivatives termed SRC2 [11S-2 alpha-bromo-3-oxoeudesmanno-13,6 alpha-lactone] strongly inhibited the ICAM-1 expression at an IC(50) value of 5.9 microM, whereas L-alpha-santonin itself was totally inactive up to 100 microM. The blockage of ICAM-1 expression by SRC2 was not due to the direct inhibition of de novo RNA and protein synthesis. The nuclear translocation of NF-kappaB subunit p65 was markedly prevented by SRC2. Moreover, I kappa B alpha degradation upon IL-1 stimulation was strongly inhibited by SRC2. These observations suggest that SRC2 blocks the IL-1 signaling pathway upstream of I kappa B degradation.


Mothers' attitudes and beliefs about infant feeding highlight barriers to exclusive breastfeeding in American Samoa.
In American Samoa, initiation of breastfeeding is almost universal but exclusive breastfeeding, a promising target for obesity prevention, is short in duration. (1) To examine American Samoan mothers' feeding experiences and attitudes and beliefs about infant feeding and (2) to identify potential barriers to exclusive breastfeeding. Eighteen semi-structured interviews were conducted with American Samoan mothers at 16-32 days postpartum. Interviews focused on mother's knowledge and beliefs about infant feeding, how their infants were fed, why the mother had chosen this mode of infant feeding, and how decisions about feeding were made within her social surroundings. A thematic qualitative analysis was conducted to identify salient themes in the data. Intention to exclusively breastfeed did not predict practice; most women supplemented with formula despite intending to exclusively breastfeed. The benefits of breastfeeding were well-recognized, but the importance of exclusivity was missed. Formula-use was not preferred but considered an innocuous "back-up option" where breastfeeding was not possible or not sufficient for infant satiety. Identified barriers to exclusive breastfeeding included: the convenience of formula; perceptions among mothers that they were not producing enough breast milk; and pain while breastfeeding. The important support role of family for infant feeding could be utilized in intervention design. This study identified barriers to exclusive breastfeeding that can be immediately addressed by providers of breastfeeding support services. Further research is needed to address the common perception of insufficient milk in this setting.


Effects of kappa opioid receptor agonists on attention as assessed by a 5-choice serial reaction time task in rats.
In humans, kappa opioid receptor agonists produce, among other effects, sedation and difficulty concentrating, suggesting that they may disrupt attention. The purpose of the present studies was therefore to evaluate the effects of kappa opioid receptor agonists on attention as assessed by a 5-choice serial reaction time task in rats. The kappa opioid receptor agonists (+)-U69,593 (0.1-0.56mg/kg), (+/-)-U50,488 (1.0-5.6mg/kg) and racemic GR89,696 (0.0003-0.01mg/kg) all produced dose-related decreases in the percentage of trials terminated by a correct or incorrect response and increases in the percentage of omissions. In contrast, the peripherally restricted opioid agonist ICI-204,448 was ineffective (1.0-10mg/kg). Moreover, the effects of GR89,696 were stereoselective in that (R)-GR89,696 was approximately equipotent to racemic GR89,696 and approximately 100-fold more potent than (S)-GR89,696. The opioid receptor antagonist naltrexone (0.3-3mg/kg) administered alone had no effects on performance. However, naltrexone, over the dose-range of 0.03-1.0mg/kg, produced a dose-related antagonism of the disruption produced by U69,593 (0.56mg/kg). In contrast, naltrexone, over the dose-range of 0.01-0.3mg/kg produced a dose-related antagonism of morphine (5.6mg/kg). Recent evidence has suggested that kappa opioid receptor agonists decrease dopaminergic and noradrenergic neurotransmission in prefrontal cortex and locus coeruleus. Together with previous findings, the present data indicate that kappa opioid receptor agonists disrupt performance of this attention task by decreasing the probability of responding by specific actions at central kappa opioid receptors, perhaps by decreasing dopaminergic and noradrenergic neurotransmission.


A systematic review of treatment strategies for erythrodermic psoriasis.
Background: Erythrodermic psoriasis (EP) is a severe, rare form of psoriasis that can be life threatening. Treatment of EP is usually based on anecdotal evidence or past clinical experience, which is in part due to the rarity and often emergent nature of this psoriasis subtype.Methods: In December 2018, a keyword search for 'erythrodermic psoriasis' and 'treatment' was conducted. All studies investigating treatment strategies for EP in at least 2 patients were included in this review.Results: The database search yielded 921 results, and 23 studies comprising over 200 patients with EP were included in the final analysis. Biologics including tumor necrosis factor inhibitors (infliximab [n = 4], etanercept [n = 2], and adalimumab [n = 1]), interleukin-17 inhibitors (secukinumab [n = 3], ixekizumab [n = 2], and brodalumab [n = 1]), ustekinumab (n = 4), and guselkumab (n = 1) have been shown to rapidly achieve clinical improvement in patients with EP. The included studies also demonstrated efficacy of systemic agents cyclosporine (n = 4), etretinate (n = 3), and methotrexate (n = 1).Conclusions: A fair number of poor-quality studies support the use of various biologic and systemic therapies in the treatment of EP. Treatment of EP should be based on the severity of the clinical scenario as well as patient comorbidities.


Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin.
The neuropeptide oxytocin is a key modulator of social-emotional behavior and its intranasal administration can influence the functional connectivity of brain networks involved in the control of attention, emotion and reward reported in humans. However, no studies have systematically investigated the effects of oxytocin on dynamic or directional aspects of functional connectivity. The present study employed a novel computational framework to investigate these latter aspects in 15 oxytocin-sensitive regions using data from randomized placebo-controlled between-subject resting state functional MRI studies incorporating 200 healthy subjects. In order to characterize the temporal dynamics, the 'temporal state' was defined as a temporal segment of the whole functional MRI signal which exhibited a similar functional interaction pattern among brain regions of interest. Results showed that while no significant effects of oxytocin were found on brain temporal state related characteristics (including temporal state switching frequency, probability of transitions between neighboring states, and averaged dwell time on each state) oxytocin extensively (n = 54 links) modulated effective connectivity among the 15 regions. The effects of oxytocin were primarily characterized by increased effective connectivity both between and within emotion, reward, salience, attention and social cognition processing networks and their interactions with the default mode network. Top-down control over emotional processing regions such as the amygdala was particularly affected. Oxytocin also increased effective homotopic interhemispheric connectivity in almost all these regions. Additionally, the effects of oxytocin on effective connectivity were sex-dependent, being more extensive in males. Overall, these findings suggest that modulatory effects of oxytocin on both within- and between-network interactions may underlie its functional influence on social-emotional behaviors, although in a sex-dependent manner. These findings may be of particular relevance to potential therapeutic use of oxytocin in psychiatric disorders associated with social dysfunction, such as autism spectrum disorder and schizophrenia, where directionality of treatment effects on causal interactions between networks may be of key importance .


A Guide for the Application of Statistics in Biomedical Studies Concerning Machine Learning and Artificial Intelligence.
With the plethora of machine learning (ML) analyses published in the orthopaedic literature within the last 5 years, several attempts have been made to enhance our understanding of what exactly ML means and how it is used. At its most fundamental level, ML comprises a branch of artificial intelligence that uses algorithms to analyze and learn from patterns in data without explicit programming or human intervention. On the other hand, traditional statistics require a user to specifically choose variables of interest to create a model capable of predicting an outcome, the output of which (1) may be falsely influenced by the variables chosen to be included by the user and (2) does not allow for optimization of performance. Early publications have served as succinct editorials or reviews intended to ease audiences unfamiliar with ML into the complexities that accompany the subject. Most commonly, the focus of these studies concerns the terminology and concepts surrounding ML because it is important to understand the rationale behind performing such studies. Unfortunately, these publications only touch on the most basic aspects of ML and are too frequently repetitive. Indeed, the conclusion of these articles reiterate that the potential clinical utility of these algorithms remains tangential at best in their current form and caution against premature adoption without external validation. By doing so, our perspective and ability to draw our own conclusions from these studies have not advanced, and we are left concluding with each subsequent study that a new algorithm is published for an outcome of interest that cannot be used until further validation. What readers now need is to regress to embrace the principles of the scientific method that they have used to critically assess vast numbers of publications before this wave of newly applied statistical methodology-a guide to interpret results such that their own conclusions can be drawn. LEVEL OF EVIDENCE: Level V, expert opinion.


The impact of binge-like palatable food intake on the endogenous glucagon-like peptide-1 system in female rats.
Binge eating involves consumption of large amounts of food and a loss of control over the amount consumed. The incidence of binge eating disorder is higher in females than males, hinting at important sex differences in binge eating behavior, but the neural underpinnings of binge eating still remain unresolved. Recent work in male rats has shown that a history of binge-like palatable food intake suppresses hindbrain expression of preproglucagon (PPG), the precursor for glucagon-like peptide-1 (GLP-1). Given the roles of GLP-1 in reducing feeding and food reward, this could be a mechanism underlying binge-like eating in rodents. However, whether similar effects occur in female rats is unknown. Here, we tested the hypothesis that a history of binge-like palatable food intake in female rats would reduce PPG expression in the nucleus tractus solitarius (NTS), a key central site of GLP-1 production. Female rats given access to vegetable shortening every fourth day (4D) engaged in binge-like feeding, demonstrated by consuming significantly more shortening during the first hour of fat access compared to counterparts with ad libitum (AL) fat access. After several weeks of fat access under these schedules, PPG and GLP-1 receptor (GLP-1R) expression were measured in the NTS and ileum. Surprisingly, and in contrast to previous findings in male rats, there were no significant differences in expression of PPG or GLP-1R in either site in 4D versus AL rats, nor were there effects on plasma GLP-1 levels. These findings highlight key differences in the effects of binge-like intake on the central GLP-1 system in female compared to male rats.


Effect of intra-operative intravenous lidocaine on opioid consumption after bariatric surgery: a prospective, randomised, blinded, placebo-controlled study.
Peri-operative lidocaine infusion warrants investigation in bariatric surgery because obese patients present different physiological and pharmacological risks. This single-centre, prospective, randomised double-blind placebo-controlled study enrolled obese patients scheduled for laparoscopic bariatric surgery using an enhanced recovery protocol. Patients received either lidocaine (bolus of 1.5 mg.kg-1 , then a continuous infusion of 2 mg.kg-1 .h-1 until the end of the surgery, then 1 mg.kg-1 .h-1 for 1 h in the recovery area) or identical volumes and rates of 0.9% saline. The primary outcome was the consumption of the equivalent of oxycodone consumption over the first 3 postoperative days. Secondary outcomes were: postoperative pain; incidence of nausea and vomiting; bowel function recovery; and lengths of stay in the recovery area and in hospital. Plasma concentrations of lidocaine were measured. On the 178 patients recruited, data were analysed from 176. The median (IQR [range]) equivalent intravenous oxycodone consumption was 3.3 mg (0.0-6.0 [0.0-14.5]) and 5.0 mg (3.3-7.0 [3.3-20.0]) in the lidocaine and saline groups, respectively (difference between medians (95%CI): 1.7 (0.6-3.4) mg; p = 0.004). Length of stay in the recovery area, postoperative pain, nausea and vomiting, day of recovery of bowel function, and length of stay in hospital were not different between groups. Mean (SD) lidocaine plasma concentrations were 2.44 (0.70) µg.ml-1 and 1.77 (0.51) µg.ml-1 at the end of surgery and 1 hour after the end of infusion, respectively. Lidocaine infusion during bariatric surgery resulted in a clinically non-relevant difference in postoperative oxycodone consumption.


Infectious Insecurities: H1N1 and the politics of emerging infectious disease.
Responses to the 2009 H1N1 pandemic, and criticisms of those responses, were framed by issues endemic to the meeting of 'health' and 'security' as governing domains. Offering an editorial introduction to the selection of papers in this special issue, it is suggested that existing scholarship in the emerging field of 'health security' can be categorized according to realist-advocacy, historical-analytic, problematization and critical-inequality approaches. In contributing to this literature through an event-based focus on the pandemic, the papers embrace the opportunity to examine health security architectures acting and interacting 'in the event', to not only speculate over the possible implications of this governing trope, but to review them. Questions of the scales of governance and associated forms of expertise, the implications of differing modes of governance (from preparedness to surveillance to forms of intervention), and the role of health inequalities in the patterning of the pandemic are identified as key themes running across the papers.


Cannulation of the right axillary artery for surgery of acute type A aortic dissection.
The optimal choice of the arterial inflow site during operations for type A aortic dissection is not clearly defined. The aim of the prospective study was to identify whether cannulation of the right axillary artery instead of the femoral artery may improve the results of surgery for acute type A aortic dissection. Seventy consecutive patients were operated on because of acute type A aortic dissection from January 2000 to February 2002. The only difference in surgical strategy was the site of arterial cannulation: the right axillary artery was used in 20 patients [axillary group] and the left femoral artery in 50 patients [femoral group]. All patients had aortic surgery with open distal anastomosis during deep hypothermic arrest and retrograde cerebral perfusion. The mean age was 58.7 +/- 12 years with a range from 28 to 88 years (axillary group, 56.6 +/- 13 years; femoral group, 59.4 +/- 12 years; P = 0.435). Preoperatively evident organ malperfusion was identified in five (25%) patients of the axillary group and in seven (14%) of the femoral group. There was no perioperative death. The hospital mortality rate was 5.0% for the axillary group and 22% for the femoral group (all patients, 17%). Major neurological complications occurred postoperatively in 5% of patients from the axillary group (one out of 20 patients) and in 8% of patients from the femoral group (four out of 50 patients) (all patients, 7%). Cannulation of the right axillary artery improved the outcome of surgery for acute type A aortic dissection. However, postoperative complications occurred after both axillary and femoral artery cannulation.


Inflammatory bowel disease and cannabis: key counseling strategies.
Cannabis use is becoming more frequent in patients with inflammatory bowel disease (IBD). Because of the increased usage, gastroenterologists need to be cognizant of the benefits and risks associated with cannabis use in the IBD-patient population. Recent studies have attempted to determine whether cannabis can improve biomarkers or endoscopic findings of inflammation in patients with IBD, but the results have been inconclusive. However, cannabis has been shown to have an impact on the symptoms and quality of life of individuals with IBD. Despite these benefits, the use of cannabis in IBD is not without risks, including the potential for systemic illness, toxin ingestion and significant drug interactions. In this review article, we use a case-based approach to discuss the critical clinical data that informs us of the benefits and risks of cannabis use in IBD. The endocannabinoid system plays a crucial role in regulating various physiological functions including the gastrointestinal tract. Studies have investigated the impact of cannabis on various medical conditions, including IBD. Clinicians must be aware of the most recent data to properly educate their patients on the benefits and risks of its use.


Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats.
Increasing evidence has revealed a positive correlation between postmenopausal osteoporosis and intervertebral disc degeneration, the underlying mechanism of which might be associated with changes in the vertebral bone and endplate. Alendronate (ALN) can increase bone mass and improve the microstructure of osteoporotic vertebrae, which might be helpful in preserving disc morphology and mechanical properties. This study aims to investigate the effects of ALN on lumbar intervertebral disc degeneration related to osteoporosis using an ovariectomized (OVX) rat model. Thirty female Sprague-Dawley rats aged 3 months were randomly divided into three groups (with 10 rats each) as follows: the Sham group underwent sham surgery; the OVX + ALN group had twice-a-week subcutaneous injections of ALN (15 μg/kg) for 6 months. The OVX + V group received an equivalent volume of saline solution as placebo post-OVX. After animals were sacrificed at 6 months post-OVX, the L3-6 spinal segments were harvested. Bone mineral density (BMD), micro-CT analysis and biomechanical testing were performed to evaluate the bone quality and microstructural changes in the lumbar vertebral bodies. Histological analysis with van Gieson stain and the histological score were used to identify the characteristics of the degenerative discs. The disc height and the thickness of the cartilage endplate were measured and compared. Immunohistochemistry and real-time PCR measurements for aggrecan, type I collagen, type II collagen, and matrix metalloprotease (MMP)-1, MMP-3 and MMP-13 expressions on the disc were performed to assess the underlying molecular signaling changes in matrix metabolism during intervertebral disc degeneration. The OVX + ALN group significantly maintained vertebrae BMD, percent bone volume and biomechanical strength, when compared with the OVX + V group. Histological evaluation suggests that there was no significant difference in disc height between the OVX + ALN and Sham groups, and ALN significantly prevented cartilage endplate thickening and the development of abnormal bony tissues within the cartilage endplate. The histological score in the OVX + ALN group was significantly lower than the OVX + V group, suggesting that ALN treatment was effective in delaying the process of the disc degeneration. The results of molecular analysis revealed a significant increase in aggrecan and type II collagen expressions, but marked reductions in MMP-1, MMP-3 and MMP-13 expressions at both the protein and mRNA levels in the OVX + ALN group. ALN can retard the progression of lumbar intervertebral disc degeneration in OVX rats. The underlying mechanisms might be related to preservation of the structural integrity and function of the adjacent structures, including the vertebrae and endplates, which further links with modulations in extracellular matrix metabolism to protect the disc from degeneration. These results suggest that ALN might be a promising drug agent for preventing lumbar intervertebral disc degeneration related to osteoporosis.


Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double-blind randomized control trial.
Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis.


Overexpression of IgLON cell adhesion molecules changes proliferation and cell size of cortical astrocytes.
IgLON family is a subgroup of the immunoglobulin superfamily cell adhesion molecules and composed of limbic system-associated protein (LAMP), opioid binding cell adhesion molecule (OBCAM), neurotrimin (Ntm) and Kilon. In the present study, we investigated the overexpression of LAMP, OBCAM, Ntm and Kilon on the proliferation and cell size of type-1 astrocytes in vitro. Quantitative analysis using bromodeoxyuridine immunocytochemistry revealed that the expression of OBCAM had greater inhibitory effect on astrocytic proliferation as compared with LAMP, Ntm and Kilon ones. OBCAM overexpression increased the cell size of astrocytes as compared with the control. The treatment of FGF-2 had greater proliferative effect on OBCAM-transfected astrocytes as compared with the control. These results suggest that OBCAM is more potent regulator for controlling the proliferation and cell size of astrocytes as compared with other IgLON proteins possibly through FGF-2 receptor-mediated pathway.


Naloxone-induced analgesia in diabetic mice.
We evaluated the effects of s.c. administration of naloxone in mice with streptozotocin-induced diabetes, compared to those in age-matched naive mice. Naloxone injected s.c. produced a dose-related increase in tail-flick latency in diabetic mice but not in naive mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole, a selective antagonist of delta-opioid receptors. These results indicate that naloxone-induced 'paradoxical' analgesia in diabetic mice may be mediated by delta-opioid receptors.


Postmortem measurement of C-reactive protein and interpretation of results in ketoacidosis.
C-reactive protein (CRP) is a widely used acute phase protein that reacts to various tissue-destroying stimuli. Its forensic applications have been established in prior studies. We show that CRP can be successfully measured even after a long postmortem period, up to 18 days, which has not previously been reported. Information on elevated CRP levels can be very valuable for the forensic pathologist in autopsy cases with scarce findings. The interpretation of results can be very challenging, as the elevation can originate from many different reasons, and due to the biochemical changes in cadavers. One less studied possible reason for elevated CRP is ketoacidosis. Here, we present a study on the effect of both alcoholic and diabetic ketoacidosis on blood CRP elevation in forensic autopsy material. Our results imply that ketoacidosis itself can cause a rise in CRP without other underlying causes, such as infection or trauma. However, more comprehensive studies are required to confirm the relationship between ketoacidosis and CRP level elevation.


Evaluation of fetal cardiac dysrhythmias with two-dimensional, M-mode, and pulsed Doppler ultrasonography.
Forty-three patients with fetal cardiac dysrhythmia were referred to a tertiary ultrasound department for further evaluation. The patients were subdivided according to the type of dysrhythmia diagnosed. All patients with irregular fetal heart rate had a good perinatal outcome. Of the six patients with fetal tachycardia, two required in utero therapy with maternal digoxin, and one of these fetuses had a cardiac tumor. The eleven patients with fetal bradycardia had the worst perinatal outcome, with four deaths occurring. The results suggest that all patients with fetal tachycardia or bradycardia should have a complete fetal cardiac assessment in a center experienced with the management of such cases.


One evidence based protocol doesn't fit all: brushing away ventilator associated pneumonia in trauma patients.
Evaluate change in ventilator associated pneumonia (VAP) and nurse's attitudes, beliefs post implementation of an evidence based practice (EBP) oral hygiene protocol. METHODOLOGY/DESIGN/SETTING: Descriptive pre and post test design in two critical care units in a Level One Trauma Community Hospital. Oral hygiene protocol data was reanalysed to examine effects in medical surgical and trauma subgroups. Oral care practices, attitudes and beliefs among nurses, and VAP rates according to Centers for Disease Control and Prevention guidelines. Trauma rates increased from 6.4% to 10.0% (p=0.346), and medical/surgical rates decreased from 3.3% to 1.0% (p=0.042). Results revealed changes in nurses' beliefs regarding pre-admission colonisation (p=0.027) and having adequate training. Nurses' perception of facility support improved, by having suitable equipment and readily available supplies. Foam swabs with moisture agents at 4hours or less was 88.6% and toothbrush use at 12hours or less was 71%, with significant changes in frequency of oral care post intervention. Trauma patients present with unique characteristics which compromise oral care. Understanding risk and prognostic factors, mechanisms of transmission and systemic inflammatory response are important when implementing EBP protocols. Nurses' attitudes, beliefs are important, and staff adherence considered when initiating EBP changes.


Hydrophilic-amphiphilic transition of the terminal SC5b-8 complement complex through tryptic modification: biochemical and ultrastructural studies.
the SC5b-8 complex of human complement is a hydrophilic molecule of mol. wt 800,000-850,000 that is seen in the electron microscope as an elongated, straight or curved structure of 50-55 nm total length and 8-9 nm width. Tryptic attack on the fluid-phase complex exposes lipid-binding surfaces on the molecule. The trypsinized complex can be incorporated into liposomal lipid bilayers, and the majority of protein is then viewed as ill-defined, larger tufts projecting exterior to the liposomal membrane. These tufts possibly represent clusters of a unit lesion, which consists of two diverging projections, each approximately 25 nm in length. The two projections are possibly joined to each other to give the membrane-bound complex a shape akin to that of an incomplete funnel. Analyses by SDS-polyacrylamide gel electrophoresis show that the polypeptide subunits C5b, C7 and C8 beta entirely resist tryptic degradation in both SC5b-8 and SC5b-9 complement complexes. Limited proteolysis of C6, C8 alpha gamma and C9, and extensive degradation of the S-protein are effected by trypsin. The results are compatible with the concept that proteolytic cleavage of the S-protein in SC5b-8 and SC5b-9 is the cause of the trypsin-dependent, hydrophilic-amphiphilic transition of the terminal, fluid-phase complement complexes.


Isolation and sequence of a cDNA clone for the rat pulmonary surfactant-associated protein (PSP-A).
Pulmonary surfactant is composed mainly of phospholipid and two groups of apoproteins. One of these apoproteins is a family of glycoproteins (pulmonary surfactant-associated protein A, PSP-A). We have isolated and sequenced a cDNA clone encoding for rat PSP-A and the full amino acid sequence has been deduced from the nucleotide sequence. The sequence of 56 amino acids at the N-terminus of PSP-A isolated from rats treated with silica was determined independently, and there is complete agreement with the sequence deduced from the cDNA. Isolated rat alveolar type II cells contain two species of mRNA for this protein.


Cerebrovascular Disease in Pregnancy.
Stroke during pregnancy is a special category of stroke in young women. Although the absolute risk is small, there are diverse causes, including those inherent to the pregnant state, that may have a significant impact on maternal and fetal outcome. Severe pre-eclampsia and eclampsia are commonly associated with ischemic and hemorrhagic stroke, but must not be presumed the sole cause of stroke in pregnant women. Magnesium sulfate is the treatment of choice to prevent eclampsia. Randomized clinical trials in pregnant women are not available to provide guidance for the treatment of ischemic and hemorrhagic stroke in pregnant women. Various antithrombotic agents may be safely used during specific stages of pregnancy for treatment and prevention of ischemic stroke, with low-dose aspirin, unfractionated heparin, and low molecular weight heparin the preferred agents. Low molecular weight heparin may be safer than unfractionated heparin. Treatment of parenchymatous intracerebral hemorrhage and subarachnoid hemorrhage during pregnancy and the puerperium must be individualized. Aneurysms may be treated with neurosurgical clipping or endovascular coiling, depending on neurosurgical considerations. Cesarean or vaginal delivery may be used depending on the timing of delivery, adequacy of aneurysm occlusion, and risk to mother and fetus. Arteriovenous malformations are best treated in a multimodal fashion at a specialized treatment center.


Potentially Inappropriate Medications Pre- and Post-Diagnosis of Major Neurocognitive Disorders Among Older People in Sweden: A Register-Based, 6-Year Longitudinal Study.
The aim of the present study was to investigate how potentially inappropriate medication usage and anti-dementia drug use change from 3 years prior to, up until 3 years post-diagnosis of major neurocognitive disorders among older people living in Sweden. People registered in the Swedish registry for cognitive/dementia disorders from 1 July, 2008 to 31 December, 2017, and aged 68 years or older at diagnosis, were included (n = 67,226). Data were combined with the Swedish Prescribed Drug Registry to obtain information about drugs collected in 6-month periods at Swedish pharmacies from 3 years pre-diagnosis until 3 years post-diagnosis. Potentially inappropriate medications were identified according to Swedish national guidelines. A generalised estimating equation regression model and estimated marginal means were used. Of the 67,226 people included in the study population, 59.2% were women and the mean age ± standard deviation was 81.5 ± 6.4 years, 47.0% lived together with a spouse or partner, and 88.9% were living at home at the time of diagnosis. The proportions of people using potentially inappropriate medications continuously decreased pre- and post-diagnosis, except for antipsychotic drug use, which continuously increased both pre- and post-diagnosis. Moreover, anticholinergic drug use increased pre-diagnosis and declined post-diagnosis. When comparing the periods pre- and post-diagnosis date, the adjusted proportion of people using potentially inappropriate medications was significantly lower post-diagnosis compared with pre-diagnosis, except for the adjusted proportion using antipsychotics, which was significantly higher post-diagnosis, 10.6%, compared with the period before, 3.1% (adjusted odds ratio 3.71; 95% confidence interval 3.59-3.83). The adjusted proportion of people using anticholinergic drugs was significantly lower post-diagnosis, 7.2%, compared with the pre-diagnosis period, 8.9% (adjusted odds ratio 0.80; 95% confidence interval 0.78-0.82). Anti-dementia drug use was significantly higher post-diagnosis, 52.6%, when compared with the pre-diagnosis period, 3.5% (adjusted odds ratio 30.13; 95% confidence interval 29.19-31.10). Overall, the prevalence of people using potentially inappropriate medications decreased and was significantly lower post-diagnosis of major neurocognitive disorders, except for antipsychotics. This indicates that potentially inappropriate medication use should be noticed and reviewed among all older people. The small decrease in the prevalence of anticholinergic drug users and the increasing proportions of people using antipsychotic drugs post-diagnosis are of special concern because of the adverse drug reactions associated with these types of potentially inappropriate medications. Consequently, it is important to identify and regularly question anticholinergic and antipsychotic drug treatment to prevent unnecessary and serious adverse drug reactions among a vulnerable group of people.


Site-specific fluorescent labeling of tubulin.
Fluorescent tubulin can be prepared in which a fluorophore is covalently bound to the protein at only the carboxy terminus of the α-subunit of the αβ-tubulin dimer. This two-step procedure consists of an enzymatic reaction followed by a bioorthogonal chemical reaction. In the first step of the process, the enzyme tubulin tyrosine ligase is used to attach a reactive tyrosine derivative, 3-formyltyrosine, to the protein. In the second step of the procedure, a fluorophore possessing a complementary reactive functional group, such as a hydrazine, hydrazide, or hydroxylamine, is allowed to react with the protein under conditions that are compatible with native tubulin. Polymerization-competent, fluorescently labeled tubulin can be prepared in just a few hours using this protocol. The method described here should be useful for attaching virtually any probe or material to tubulin at this site.


Diagnostic imaging in metastatic lung disease.
Chest radiographs, full lung tomography and computed tomography of the chest provide increasing sensitivity for evaluation of pulmonary metastases. Pulmonary nodules of 5-10 mm diameter are detectable with increasing frequency by use of high kilovoltage chest radiographs. Full lung linear tomography provides an overall accuracy of 72-97% in diagnosis of pulmonary nodules. Chest CT delineates pulmonary nodules as small as 3 mm within 10 mm slice sections. However, as sensitivity increases, specificity diminishes in identifying metastatic nodules. Sensitivity in CT is also reduced by false negative findings due to unequal respiratory cycles. Comparative radiologic-pathologic evaluation of nodule detection proved CT to be the most sensitive screening method for pulmonary metastases. Timing of follow-up studies for pulmonary nodule detection in cancer patients can be determined by tumor growth kinetics; 3-6 month intervals proved to be useful.


Glomerular filtration rate in endurance athletes.
The interpretation of biochemical testing in sportsmen requires caution. Although creatinine-based estimates of glomerular filtration rate (GFR) overcome some shortcomings of serum creatinine, there is scarce information on their use in endurance athletes. We evaluated GFR, estimated by the recommended Modification of Diet in Renal Disease (MDRD) equation in athletes. Seventy-six professional male cyclists, 71 amateur male cyclists, and 65 healthy sedentary matched controls were included in the study. The mean serum creatinine level was significantly higher in the sedentary subjects (81 microM) than in amateur (75 microM; P < 0.001) and professional cyclists (72 microM; P < 0.001), and it was also marginally higher in amateur than in professional cyclists (P = 0.049). The mean estimated GFR value increased throughout the three subgroups, being significantly lower in the sedentary population (98 mL.min.[1.73 m]) than in the subgroups of amateur (109 mL.min.[1.73 m]; P < 0.001) and professional cyclists (113 mL.min.[1.73 m]; P < 0.001), but it did not differ between amateur and professional cyclists (P = 0.116). The average intensity of daily physical exercise, but not the body mass index, was inversely associated with serum creatinine and positively associated with the estimated GFR. The MDRD equation should be used with caution in athletes, and it should consider intensity and type of physical exercise.


Prebirth psychosocial factors as predictors of consistency in contraceptive use among Taiwanese adolescent mothers at 6 months postpartum.
To assess contraceptive behavior and whether pre-birth psychosocial factors could predict consistency in contraceptive use among adolescent mothers at six-month postpartum. Prospective study. 104 Taiwanese adolescent mothers. Participants completed a contraception questionnaire in their third trimester and a postpartum contraception questionnaire at six-month postpartum. Prior to giving birth, the adolescent mothers most commonly answered that condom use (39.8%) was the contraceptive method they planned to use after delivery. It was also more commonly reported in the postpartum to be the method they actually were using (54.3%). Stepwise logistic regression analysis further showed that a more positive contraceptive attitude (odds ratio=1.104) and a higher self-efficacy (odds ratio=1.068) in contraceptive use in the pre-birth period increased the probability that a participant would report that she always used contraceptives in the postpartum period. Nevertheless, a higher score in the pre-birth period in the area of subjective contraceptive norms (odds ratio=0.978) decreased this probability. The final regression model could correctly classify 81.7% of the participants. Health care professionals should provide adolescent mothers with the information they need to improve their attitude and self-efficacy toward contraception before they enter the postpartum period.


Three Dimensional Printing as a Tool For Anatomical Training in Lung Surgery.
Pulmonary anatomy is challenging, due to the high variability and its three-dimensional (3D) shape. While demands in thoracic oncologic surgery are increasing, the transition from open to thoracoscopic surgery is hampering anatomical understanding. This study analyzed the value of a 3D printed lung model in understanding and teaching anatomy. A 3D pulmonary model was created and tested among different levels of proficiency: 10 experienced surgeons, 10 fellow surgeons and 10 junior residents. They were tested in interpretation of anatomy based on thoracic CT-scans, either using the 3D model or a 2D anatomical atlas. Accuracy of the given answers, time to complete the task and the self-reported level of certainty were scored in each group. In the experienced surgeons group there was no difference in between the 2D-model or 3D-model with a high rate of correct answers in both groups, and no differences in time or certainty. Fellow surgeons highly benefitted from the 3D-model with an improved accuracy from 26.6% to 70.0% (p = 0.001). Time to complete the task was shorter (207 versus 122 s, p < 0.0001) and participants were more secure (median of 4 versus 3, p = 0.007). For junior residents time to complete the task was shorter, the level of certainty was higher, but there was no improvement in accuracy. 3D printing may benefit in understanding anatomical relations in the complex anatomy of the bronchiopulmonary tree, especially for surgeons in training and could benefit in teaching anatomy. The online version contains supplementary material available at 10.1007/s40670-023-01807-x.


Sorafenib and entecavir: the dioscuri of treatment for advanced hepatocellular carcinoma?
Hepatitis B virus (HBV) is responsible for 50%-80% of cases of hepatocellular carcinoma (HCC) worldwide. Entecavir (ET) is a potent inhibitor of chronic HBV-DNA polymerase, inhibiting both the priming and elongation steps of viral DNA replication. Sorafenib (SO) has proven efficacy in prolonging survival in patients with advanced HCC. In this frontier report we discuss a possible way to optimize treatment outcomes in patients with HBV and HCC by treatment with ET and SO, on the basis of our practice and published evidence from the literature.


"Walking a tightrope": A grounded theory approach to informal caregiving for amyotrophic lateral sclerosis.
Informal caregivers, mainly family members and friends, provide supportive and palliative care for people with amyotrophic lateral sclerosis (ALS) during their terminal disease course. Informal caregiving for people with ALS continues towards palliative care and end-of-life care with the progression of the disease. In this study, we provide a theoretical understanding of informal caregiving in ALS utilising 23 semi-structured interviews conducted with informal caregivers of people with ALS (pwALS) in Switzerland. Due to the expected death of the care recipient, our grounded theory approach outlines informal caregivers' caregiving work as an effort to secure a balance amongst different caregiving activities, which feed into the final stage of providing palliative care. Overall, our theoretical understanding of ALS informal caregiving work encompasses the core category 'holding the balance' and four secondary categories: 'Organising support', 'being present', 'managing everyday life' and 'keeping up with ALS'. The core category of holding the balance underlines the significance of ensuring care and normalcy even as disease progresses and until the end of life. For the informal caregivers, this balancing act is the key element of care provision to pwALS and therefore guides decisions surrounding caregiving. On this understanding, those caregivers that succeed in holding the balance can provide care at home until death. The balance is heavily influenced by contextual factors of caregiving, for example relating to personal characteristics of the caregiver, or activities of caregiving where the goal is to ensure the quality of life of the pwALS. As there is a heterogeneity of speed and subtype of progression of ALS, our work accounts for multiple caregiving trajectories.


Tunable morphological changes of asymmetric titanium nanosheets with bactericidal properties.
Titanium and titanium alloys are often the most popular choice of material for the manufacture of medical implants; however, they remain susceptible to the risk of device-related infection caused by the presence of pathogenic bacteria. Hydrothermal etching of titanium surfaces, to produce random nanosheet topologies, has shown remarkable ability to inactivate pathogenic bacteria via a physical mechanism. We expect that systematic tuning of the nanosheet morphology by controlling fabrication parameters, such as etching time, will allow for optimisation of the surface pattern for superior antibacterial efficacy. Using time-dependent hydrothermal processing of bulk titanium, we fabricated bactericidal nanosheets with variable nanoedge morphologies according to a function of etching time. A systematic study was performed to compare the bactericidal efficiency of nanostructured titanium surfaces produced at 0.5, 1, 2, 3, 4, 5, 6, 24 and 60 h of hydrothermal etching. Titanium surfaces hydrothermally treated for a period of 6 h were found to achieve maximal antibacterial efficiency of 99 ± 3% against Gram-negative Pseudomonas aeruginosa and 90 ± 9% against Gram-positive Staphylococcus aureus bacteria, two common human pathogens. These surfaces exhibited nanosheets with sharp edges of approximately 10 nm. The nanotopographies presented in this work exhibit the most efficient mechano-bactericidal activity against both Gram-negative and Gram-positive bacteria of any nanostructured titanium topography reported thus far.


Effects of global shape on angle discrimination.
Previous studies have been inconclusive as to whether angle discrimination performance can be predicted by the sensitivity of orientation discrimination mechanisms or by that of mechanisms specialised for angle coding. However, these studies have assumed that angle discrimination is independent of the shape of the object of which the angle is a part. This assumption was tested by measuring angle discrimination using angles that were parts of different triangular shapes. Angle discrimination thresholds were lowest when angles were presented in isosceles triangles (sides forming the angle were of identical length). Performance was significantly poorer when angles were presented in scalene triangles (sides of different lengths) and as much as three times worse when the sides forming the angle varied randomly in length between presentations. Comparing orientation discrimination for single lines with angle discrimination for different stimulus conditions (isosceles, scalene and random triangles) leads to conflicting conclusions as to the mechanisms underlying angle perception: line orientation sensitivity correctly predicts angle discrimination for random triangles, but underestimates angle acuity for isosceles triangles. The fact that performance in angle discrimination tasks is strongly dependant on the overall stimulus geometry implies that geometric angles are computed by mechanisms that are sensitive to global aspects of the stimulus.


Hip fractures in Finland and Great Britain--a comparison of patient characteristics and outcomes.
All hip fracture patients (age <50 years, pathological and subtrochanteric fractures excluded) were registered at admission to hospital and at 4 months (mortality up to 1 year) between 1989 and 1997 in Peterborough District Hospital (2083 patients) and Oulu University Hospital (1702 patients). The mean age at fracture was 80.3 years in Peterborough and 78.3 years in Oulu. Respectively, 69% and 62% of the patients had been living in their own homes, 50% and 54% had been able to walk alone unassisted. In Oulu, the patients were discharged after a mean stay of 7.1 days, most of them to health care centre hospitals (71%) and only 21% to their original place of residence. In Peterborough 81% were discharged to their original place of residence after a mean stay of 15.6 days. At 4 months, 54% were living at their own homes in Peterborough and 44% in Oulu. The overall mortality at 1 year was 27.1% in Peterborough and 24.9% in Oulu.


[Occipital condyle syndrome: the visible part of the iceberg].
Occipital condyle syndrome is a rare clinical disorder, clinically defined by the association of intense occipital headaches and paralysis of the twelfth paired cranial nerve. Its etiology is dominated by metastatic tumor. Imaging is the gold standard for diagnosis allowing to highlight occipital condyle lesion as weel as to find out primary tumor. Treatment is based on pain relief using analgesics, corticosteroids and very often, external radiotherapy. On the other hand, treatment of metastatic tumor is based on cytotoxic chemotherapy, targeted therapies or immunotherapy depending on the molecular profile of the primary tumor.


Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure.
Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.


A hybrid PDMS-Parylene subdural multi-electrode array.
In this paper, we report on a cost effective and simple method for fabricating a flexible multi-electrode array for subdural neural recording. The electrode was fabricated using a PDMS-Parylene bilayer to combine the major advantages of both materials. Mechanical and electrical characterizations were performed to confirm functionality of a 16-site electrode array under various flexed/bent conditions. The electrode array was helically wound around a 3 mm diameter cylindrical tube and laid over a 2 cm diameter sphere while maintaining its recording capability. Experimental results showed impedance values between 300 kΩ and 600 kΩ at 1 kHz for 90 μm diameter gold recording sites. Acoustically evoked neural activity was successfully recorded from rat auditory cortex, confirming in vivo functionality.


Using stable isotope tracing to unravel the metabolic components of neurodegeneration: Focus on neuron-glia metabolic interactions.
Disrupted brain metabolism is a critical component of several neurodegenerative diseases. Energy metabolism of both neurons and astrocytes is closely connected to neurotransmitter recycling via the glutamate/GABA-glutamine cycle. Neurons and astrocytes hereby work in close metabolic collaboration which is essential to sustain neurotransmission. Elucidating the mechanistic involvement of altered brain metabolism in disease progression has been aided by the advance of techniques to monitor cellular metabolism, in particular by mapping metabolism of substrates containing stable isotopes, a technique known as isotope tracing. Here we review key aspects of isotope tracing including advantages, drawbacks and applications to different cerebral preparations. In addition, we narrate how isotope tracing has facilitated the discovery of central metabolic features in neurodegeneration with a focus on the metabolic cooperation between neurons and astrocytes.


Colour Duplex imaging through wound dressings.
Colour flow Duplex scanning is becoming the method of choice to determine patency and haemodynamic status in infrainguinal grafts and native arteries. Due to surgical wounds and ulcers, there are often dressings covering the leg above the vessel to be scanned. There is no data as to the effect of different wound dressings on colour flow Duplex signals. Ten normal superficial femoral arteries were scanned by a blinded operator. Initially the artery was visualised to assess the normal image produced for each artery on B-mode and colour flow ultrasound and a Doppler reading was taken. Then each of five commonly used dressings were applied to the skin above the artery, in random order and the blinded operator graded the signal produced on a linear analogue scale. Primapore, an absorbent material dressing and Spyroflex, a bilaminate membrane dressing, did not transmit ultra-sound at all. Granuflex extra thin allowed a clear B-mode image of each artery to be visualised and an adequate Doppler waveform to be obtained. However colour flow mapping was less than optimal although it was possible in each of the arteries. Opsite and Tegaderm, two thin membrane dressings allowed excellent B-mode and colour flow images, in addition to clear Doppler signals. In patients who require dressings and who may require colour flow Duplex scanning of vessels in the same area, we would suggest the use of a product that permits ultrasound transmission, thus saving the necessity of removing the dressing for the assessment.


Canonical Wnt Pathway Controls mESC Self-Renewal Through Inhibition of Spontaneous Differentiation via β-Catenin/TCF/LEF Functions.
The Wnt/β-catenin signaling pathway is a key regulator of embryonic stem cell (ESC) self-renewal and differentiation. Constitutive activation of this pathway has been shown to increase mouse ESC (mESC) self-renewal and pluripotency gene expression. In this study, we generated a novel β-catenin knockout model in mESCs to delete putatively functional N-terminally truncated isoforms observed in previous knockout models. We showed that aberrant N-terminally truncated isoforms are not functional in mESCs. In the generated knockout line, we observed that canonical Wnt signaling is not active, as β-catenin ablation does not alter mESC transcriptional profile in serum/LIF culture conditions. In addition, we observed that Wnt signaling activation represses mESC spontaneous differentiation in a β-catenin-dependent manner. Finally, β-catenin (ΔC) isoforms can rescue β-catenin knockout self-renewal defects in mESCs cultured in serum-free medium and, albeit transcriptionally silent, cooperate with TCF1 and LEF1 to inhibit mESC spontaneous differentiation in a GSK3-dependent manner.


Comparative ultrastructure of the actinosporean stages of Myxobolus bramae and M. pseudodispar (Myxozoa).
The ultrastructrure of triactinospores and other developmental stages obtained after the experimental infection of the oligochaete Tubifex tubifex with myxospores of Myxobolus bramae and Myxobolus pseudodispar was studied. In both cases, pansporocysts harbouring spores and the remnants of polar bodies were found in the gut epithelium of the tubificids. Other stages were also seen in M. pseudodispar. Capsulogenic cells surrounded the apical part of the sporoplasm in M. bramae whereas they were located separately in M. pseudodispar. The sporoplasm of M. bramae was elongated and was filled with numerous infective cells, whereas secondary cells rarely appeared in the sporoplasm of M. pseudodispar, which contained large groups of beta-glycogen granules. Other M. pseudodispar stages included pansporocysts harbouring pregametic or gametic stages, zygotes, or the initial steps of sporogenesis. The presence of first- and second-order polar bodies indicates the existence of meiosis. In the spores of M. pseudodispar, the presence of desmosome-like junctions between the capsulogenic cells, and hemidesmosome-like junctions between the capsulogenic cells and the inner membrane of the valvogenic cells, is remarkable.


Chronic Inflammatory Demyelinating Polyneuropathy after ChAdOx1 nCoV-19 Vaccination.
Recently several patients, who developed Guillain-Barré syndrome characterized by prominent bifacial weakness after ChAdOx1 nCoV-19 vaccination, were described from different centers. We recently observed a patient who developed a similar syndrome, later in the follow up he showed worsening of the neuropathy two months after the initial presentation. Repeat EMG showed reduced nerve sensory and motor conduction velocities of both upper and lower limbs, and a diagnosis of chronic inflammatory demyelinating polyneuropathy (typical CIDP) was made according to established criteria. Our report expands on the possible outcomes in patients who develop Guillain-Barrè syndrome after COVID-19 vaccinations and suggest that close monitoring after the acute phase is needed in these patients to exclude a chronic evolution of the disease, which has important implications for long-term treatment.


Probability assessment approach to therapeutic drug monitoring: tobramycin.
Pharmacokinetic monitoring is an important therapeutic goal of aminoglycoside therapy. The overall goal of this study was to identify specific patient groups that would derive the maximum benefit from therapeutic drug monitoring services. These groups are patient populations with high probabilities of achieving toxic or subtherapeutic concentrations. Out of a total population of 86 stable, noncritically ill patients, 27 toxic concentrations (trough greater than 2.0 micrograms/mL) occurred in 15 patients. In comparison to patients (n = 46) with therapeutic concentrations (trough less than 2.0 micrograms/mL, peak greater than 4.0 micrograms/mL), these patients were older (64 +/- 11 vs. 54 +/- 18 years; p less than 0.02) and had a higher percentage of females (66.7 vs. 37 percent; p less than 0.05). Those patients with subtherapeutic concentrations (43 concentrations in 25 patients) had higher estimated creatinine clearance values than those with therapeutic concentrations (94 +/- 45 vs. 74 +/- 27 mL/min; p less than 0.005). Probability assessment analysis of the data showed a sevenfold increase in toxic concentrations in patients above 50 years. Females over age 50 had 2.3 times the risk of developing toxic concentrations as males over age 50. In contrast, the development of low concentrations was not predicted by age or sex. Underdosage by greater than or equal to 30 percent was a reasonable predictor (75 percent) of low peak concentrations. Furthermore, toxic concentrations did not occur in patients who were underdosed, justifying dosage increases prior to obtaining serum concentrations in these patients. The group with the highest probability of attaining therapeutic concentrations was males receiving therapeutic doses who were under age 50 (85.5 percent).(ABSTRACT TRUNCATED AT 250 WORDS)


The role of sample preparation in suspect and non-target screening for exposome analysis using human urine.
The use of suspect and non-target screening (SNTS) for the characterization of the chemical exposome employing human biofluids is gaining attention. Among the biofluids, urine is one of the preferred matrices since organic xenobiotics are excreted through it after metabolization. However, achieving a consensus between selectivity (i.e. preserving as many compounds as possible) and sensitivity (i.e. minimizing matrix effects by removing interferences) at the sample preparation step is challenging. Within this context, several sample preparation approaches, including solid-phase extraction (SPE), liquid-liquid extraction (LLE), salt-assisted LLE (SALLE) and dilute-and-shoot (DS) were tested to screen not only exogenous compounds in human urine but also their phase II metabolites using liquid-chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS). Additionally, enzymatic hydrolysis of phase II metabolites was evaluated. Under optimal conditions, SPE resulted in the best sample preparation approach in terms of the number of detected xenobiotics and metabolites since 97.1% of the total annotated suspects were present in samples extracted by SPE. In LLE and SALLE, pure ethyl acetate turned out to be the best extractant but fewer suspects than with SPE (80.7%) were screened. Lastly, only 52.5% of the suspects were annotated in the DS approach, showing that it could only be used to detect compounds at high concentration levels. Using pure standards, the presence of diverse xenobiotics such as parabens, industrial chemicals (benzophenone-3, caprolactam and mono-2-ethyl-5-hydroxyhexyl phthalate) and chemicals related to daily habits (caffeine, cotinine or triclosan) was confirmed. Regarding enzymatic hydrolysis, only 10 parent compounds of the 44 glucuronides were successfully annotated in the hydrolysed samples. Therefore, the screening of metabolites in non-hydrolysed samples through SNTS is the most suitable approach for exposome characterization.


Functional neuroimaging of the 6-OHDA lesion rat model of Parkinson's disease.
We characterized the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat, a well-known acute model of Parkinson's disease (PD), with [(18)F]-fluoro-2-deoxy-d-glucose (FDG) small-animal positron emission tomography (PET), which we compared with a drug-induced rotation behavioral test. In the 6-OHDA model, significant glucose hypometabolism was present in the primary motor cortex, substantia nigra, and pedunculopontine tegmental nucleus on the ipsilateral side. In contrast, neuronal activations were observed in the primary somatosensory cortex and ventral caudate-putamen area after lesioning. Correlation analysis revealed a significant relationship between the behavioral results and the degree of glucose metabolism impairment in the primary motor cortex, substantia nigra, and pedunculopontine tegmental nucleus. In addition, the pedunculopontine tegmental nucleus correlated significantly with the primary somatosensory cortex, the ventral caudate-putamen, the substantia nigra, and the primary motor cortex. Furthermore, the primary motor cortex also showed significant correlations with the substantia nigra. In conclusion, In vivo cerebral mapping of the 6-OHDA-lesioned rats using [(18)F]-FDG PET showed correspondence at the functional levels to the cortico-subcortical network impairment observed in PD patients.


Jejunal invasion of pheochromocytoma pathologically confirmed by endoscopic biopsy.
The authors discuss a case of pheochromocytoma in a 20-year-old man referred for anemia due to gastrointestinal bleeding. Pheochromocytoma uncommonly presents with gastrointestinal bleeding, and a pathologic diagnosis is rarely made without resection of the tumor. Imaging studies demonstrated a mass on the left kidney with metastases to the liver, and high levels of catecholamines in plasma and urine were suggestive of pheochromocytoma. Endoscopic examination of the gastrointestinal tract demonstrated a mass in the proximal jejunum near the ligament of Treitz and a mass with central ulceration in the upper jejunum; biopsy confirmed the pathologic diagnosis of malignant pheochromocytoma with jejunal invasion and metastases to the liver. Gastrointestinal bleeding is one of the manifestations of pheochromocytoma. This is the first case in which endoscopic biopsy determined a pathologic diagnosis of pheochromocytoma.


Integrating Literature-Based Knowledge Database and Expression Data to Explore Molecular Pathways Connecting PPARG and Myocardial Infarction.
Peroxisome proliferator-activated receptor γ (PPARG) might play a protective role in the development of myocardial infarction (MI) with limited mechanisms identified. Genes associated with both PPARG and MI were extracted from Elsevier Pathway Studio to construct the initial network. The gene expression activity within the network was estimated through a mega-analysis with eight independent expression datasets derived from Gene Expression Omnibus (GEO) to build PPARG and MI connecting pathways. After that, gene set enrichment analysis (GSEA) was conducted to explore the functional profile of the genes involved in the PPARG-driven network. PPARG demonstrated a significantly low expression in MI patients (LFC = -0.52; p < 1.84e - 9). Consequently, PPARG could indicatively be promoting three MI inhibitors (e.g., SOD1, CAV1, and POU5F1) and three MI-downregulated markers (e.g., ALB, ACADM, and ADIPOR2), which were deactivated in MI cases (p < 0.05), and inhibit two MI-upregulated markers (RELA and MYD88), which showed increased expression levels in MI cases (p = 0.0077 and 0.047, respectively). These eight genes were mainly enriched in nutrient- and cell metabolic-related pathways and functionally linked by GSEA and PPCN. Our results suggest that PPARG could protect the heart against both the development and progress of MI through the regulation of nutrient- and metabolic-related pathways.


Differential effects of photodynamic therapy on morphologically distinct tumor cells derived from a single precursor cell.
Photodynamic therapy (PDT) involves the administration of a photosensitizer, followed by local illumination of a tumor with a laser (of the appropriate wavelength) to activate a specific drug. However, the cells in a tumor tissue are heterogeneous, in terms of their morphologies and differentiation statuses, even if the tumor consists of progeny developed from a single neoplastic cell. It is not known how tumor cell heterogeneity affects their sensitivity to PDT. Here, we demonstrate that a single tumor cell has the potential to produce a progeny that is heterogeneous in terms of morphology, VEGF secretion, and PDT sensitivity, irrespective of intracellular photosensitizer amount. Understanding tumor cell heterogeneity for clinical applications of PDT will help in the design of new interventions and potentially improve long-term survival of PDT treated patients.


Resonance Raman studies of ETE dehydrogenase (an iron sulfur flavoprotein).
ETF Dehydrogenase is an iron sulfur flavoprotein responsible for the transfer of electrons between electron transfer flavoprotein (ETF) and CoQ of the electron transport chain. We have determined the resonance Raman spectrum of this enzyme observing in the process at least seven of thirteen flavin bands in the 1100cm-1-1600 cm-1 region of the Raman spectrum. The positions of three of these bands, II, IX, and X (see Figure I and Table I for band numbering system) in ETF dehydrogenase is very similar to their positions in aqueous solution of flavins in which water is hydrogen bonded to N-1, N-5, C=0(2), C=0(4), and N-H(3) of flavin. Conversely the positions of the flavin Raman bands are considerably shifted from those of flavin in nonhydrogen bonding solvent. The positions of bands II, IX, and X are nearly identical to those in the flavoprotein glutathione reductase; x-ray structural investigations on this enzyme indicate that there is extensive hydrogen bonding between FAD and protein in this molecule. A previous study in our laboratory has demonstrated that metal complexation at N-5 and C=0(4) with either Ru or Ag produces large shifts in the positions of Raman bands II, VI, IX, and X. None of these shifts are observed in ETF dehydrogenase indicating that there is no direct inner sphere coordination of Fe to flavin. In addition to the Raman bands of flavin observed in our spectrum, we also observe one band that is in the Fe-S stretching region observed for a variety of Fe-S proteins. This band is located at 331 cm-1. The frequency of the band corresponds to the 335 cm-1 band associated with the strongest Fe-S stretching mode in the 4Fe-4S protein ferrodoxin from C. pasterianum. The observed frequency is quite different from that of the 3Fe-3S proteins such as ferrodoxin(II) from D. gigas. Finally, ETF dehydrogenase shows no loss of activity or visual evidence of photodegradation in the laser beam as most other FeS proteins do.


Modular Dual-Mobility Liner Malseating: A Radiographic Analysis.
With dislocation as a leading cause for revision after total hip arthroplasty (THA), modular dual-mobility (MDM) constructs are more commonly used at present in an attempt to decrease postoperative instability. With modularity, there is potential for additional complications, including malseating of the liner. The goal of this study was to perform a radiographic analysis on the incidence of MDM liner malseating. We retrospectively identified 305 patients (305 THAs) who underwent primary THA with an MDM liner from a single manufacturer inserted by a single surgeon. One hundred fifty-six (51%) patients were male. The mean age was 68 years, and the mean body mass index was 31 kg/m2. Only patients with both anteroposterior and cross-table lateral radiographs at a minimum of 6 weeks postoperatively were included. Dislocations and reoperations were determined at 1 year after the procedure. All MDM liners were routinely tested intraoperatively with a "4-quadrant test" to assess for proper seating. Four (4/305, 1.3%) MDM liners were noted to be radiographically malseated at early follow-up with three (3/147, 2.0%) occurring in a thinner two dimentional (2D) ongrowth shell and only one (1/158, 0.6%) observed in a thicker three dimentional (3D) additively manufactured shell. They were inferiorly prominent by a median of 1.2 mm, best seen on the cross-table lateral radiograph. In patients with at least 1-year follow-up, no MDM liners dissociated and no patients sustained a dislocation. Five (1.6%) patients required reoperation unrelated to the acetabular or MDM construct. Surgeons should be aware that malseating of dual-mobility liners may occur. However, with utilization of a consistent surgical technique to test for seating of the liner, the radiographic incidence of MDM liner malseating was low at 1%. Although there were no short-term clinical implications of liner malseating, long-term follow-up is needed.


Augmentation of bone morphogenetic protein-induced bone mass by local delivery of a prostaglandin E EP4 receptor agonist.
Recombinant human bone morphogenetic protein (rhBMP) is viewed as a therapeutic cytokine because of its ability to induce bone. However, the high doses of rhBMP required for bone induction in humans remain a major hurdle for the therapeutic application of this protein. The development of a methodology that would effectively overcome the weak responsiveness to human BMP is highly desired. In the present study, we investigate the ability of a prostaglandin E EP4 receptor selective agonist (EP4A) to augment the bone-inducing ability of BMP in a biodegradable delivery system. A block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG, polymer) was used as the delivery system. Polymer discs containing rhBMP-2 and EP4A were implanted into the left dorsal muscle pouch of mice to examine the dose-dependent effects of EP4A. Fifty mice were divided into 5 groups based on the contents of rhBMP and EP4 in the polymer (group 1; BMP 5 microg EP4A 0 microg, group 2; BMP 5 microg EP4 3 microg, group 3; BMP 5 microg EP4 30 microg, group 4; BMP 5 microg EP4 300 microg, group 5; BMP 0 microg EP4 30 microg, n=10 each). All implants were harvested, examined radiologically, and processed for histological analysis 3 weeks after surgery. On dual-energy X-ray absorptiometry (DXA) analysis, the bone mineral content (BMC) of the ossicles was 6.52+/-0.80 (mg), 9.36+/-1.89, 14.21+/-1.27, and 18.75+/-2.31 in groups 1, 2, 3, and 4 respectively. In terms of BMC, the values of groups 3 and 4 were significantly higher than those of group 1. The mean BMC value of group 4 was approximately 3 times higher than that of group 1. No significant difference in body weight was noted among the groups during the experimental period. In summary, the presence of a prostaglandin E EP4 receptor selective agonist in the carrier polymer enhanced the bone-inducing capacity of rhBMP-2 with no apparent systemic adverse effects.


Diabetic Retinopathy Screening at the Point of Care (DR SPOC): detecting undiagnosed and vision-threatening retinopathy by integrating portable technologies within existing services.
The aim of this study was to determine the prevalence of diabetic retinopathy (DR) in a low socioeconomic region of a high-income country, as well as determine the diagnostic utility of point-of-care screening for high-risk populations in tertiary care settings. This was a cross-sectional study of patients with diabetes attending foot ulcer or integrated care diabetes clinics at two Western Sydney hospitals (n=273). DR was assessed using portable, two-field, non-mydriatic fundus photography and combined electroretinogram/ pupillometry (ERG). With mydriatic photographs used as the reference standard, sensitivity and specificity of the devices were determined. Prevalence of DR and vision-threatening diabetic retinopathy (VTDR) were reported, with multivariate logistic regression used to identify predictors of DR. Among 273 patients, 39.6% had any DR, while 15.8% had VTDR, of whom 59.3% and 62.8% were previously undiagnosed, respectively. Non-mydriatic photography demonstrated 20.2% sensitivity and 99.5% specificity for any DR, with a 56.7% screening failure rate. Meanwhile, mydriatic photography produced high-quality images with a 7.6% failure rate. ERG demonstrated 72.5% sensitivity and 70.1% specificity, with a 15.0% failure rate. The RETeval ERG was noted to have an optimal DR cut-off score at 22. Multivariate logistic regression identified an eGFR of ≤29 mL/min/1.73 m2, HbA1c of ≥7.0%, pupil size of <4 mm diameter, diabetes duration of 5-24 years and RETeval score of ≥22 as strong predictors of DR. There is a high prevalence of vision-threatening and undiagnosed DR among patients attending high-risk tertiary clinics in Western Sydney. Point-of-care DR screening using portable, mydriatic photography demonstrates potential as a model of care which is easily accessible, targeted for high-risk populations and substantially enhances DR detection.


The characteristics of falls in an inpatient traumatic brain injury rehabilitation setting.
To describe the nature of falls in an inpatient traumatic brain injury rehabilitation setting. Falls are the most frequently recorded patient safety incident in the inpatient context. However, higher rates of falls are reported in rehabilitation settings compared to acute care settings. In the rehabilitation setting, patients with a traumatic brain injury have been identified as at a high risk of falling. However to date, research into the nature of falls involving this patient population is limited. Five-year retrospective cohort study design. Falls data from an inpatient traumatic brain injury rehabilitation unit were retrieved from the NSW Ministry of Health Incident Information Management System and patient clinical notes; nursing shift data were retrieved from the local rostering system. The fall rate was 5·18 per 1000 patient bed days. Over a 24-hour period falls (n = 103) occurred in a trimodal pattern. The median fall free period after admission was 14 days and 22% of traumatic brain injury patients had at least one fall. 53% of falls occurred in the patient's bedroom and 57% were attributed to loss of balance. At time of fall, 93% of fallers had impaired mobility and 85% required assistance for transfers. Falls within inpatient traumatic brain injury rehabilitation are a significant and complex clinical issue. While many patients continued to be at risk of falling several months after admission, a repeat faller's first fall occurred earlier in their admission than a single faller's. Generic falls prevention measures are insufficient for preventing falls in the brain injury rehabilitation population. Falls prevention initiatives should target times of high patient activity and situations where there is decreased nursing capacity to observe patients. Rehabilitation clinicians need to be mindful that a patient's risk of falling is not static and in fact, may increase over time.


Aflatoxin B1 residues in eggs of laying hens fed a diet containing different levels of the mycotoxin.
The present study was carried out to evaluate the excretion of aflatoxin B1 residues in eggs of young laying hens fed aflatoxin B1-contaminated rations for 8 weeks. To this end, 96 twenty-week-old hens were randomly distributed into four experimental groups (24 birds per group) and given rations containing either 0 (controls), 100 micrograms, 300 micrograms or 500 micrograms aflatoxin B1/kg feed. Egg aflatoxin B1 residues were determined by thin layer chromatography; two samples per treatment per week were used for analysis. Egg production and average egg weights were not affected (p < 0.05) in the groups receiving aflatoxin B1-contaminated rations. Residues of aflatoxin B1 were detected only in the eggs of hens given 500 micrograms/kg feed, at levels that ranged from 0.05 to 0.16 microgram/kg (average: 0.10 microgram/kg). The results indicate that the feed to eggs aflatoxin B1 transmission ratio was approximately 5000:1, emphasizing the importance of controlling aflatoxin levels in rations for laying hens.


Correction: SP1-activated long noncoding RNA lncRNA GCMA functions as a competing endogenous RNA to promote tumor metastasis by sponging miR-124 and miR-34a in gastric cancer.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.