Polyethylene Glycol-Mediated Synthesis of Cubic Iron Oxide Nanoparticles with High Heating Power.
Iron oxide magnetic nanoparticles (IOMNPs) have been successfully synthesized by means of solvothermal reduction method employing polyethylene glycol (PEG200) as a solvent. The as-synthesized IOMNPs are poly-dispersed, highly crystalline, and exhibit a cubic shape. The size of IOMNPs is strongly dependent on the reaction time and the ration between the amount of magnetic precursor and PEG200 used in the synthesis method. At low magnetic precursor/PEG200 ratio, the cubic IOMNPs coexist with polyhedral IOMNPs. The structure and morphology of the IOMNPs were thoroughly investigated by using a wide range of techniques: TEM, XRD, XPS, FTIR, and RAMAN. XPS analysis showed that the IOMNPs comprise a crystalline magnetite core bearing on the outer surface functional groups from PEG200 and acetate. The presence of physisorbed PEG200 on the IOMNP surface is faintly detected through FT-IR spectroscopy. The surface of IOMNPs undergoes oxidation into maghemite as proven by RAMAN spectroscopy and the occurrence of satellite peaks in the Fe2p XP spectra. The magnetic studies performed on powder show that the blocking temperature (TB) of IOMNPs is around 300 K displaying a coercive field in between 160 and 170 Oe. Below the TB, the field-cooled (FC) curves turn concave and describe a plateau indicating that strong magnetic dipole-dipole interactions are manifested in between IOMNPs. The specific absorption rate (SAR) values increase with decreasing nanoparticle concentrations for the IOMNPs dispersed in water. The SAR dependence on the applied magnetic field, studied up to magnetic field amplitude of 60 kA/m, presents a sigmoid shape with saturation values up to 1700 W/g. By dispersing the IOMNPs in PEG600 (liquid) and PEG1000 (solid), it was found that the SAR values decrease by 50 or 75 %, indicating that the Brownian friction within the solvent was the main contributor to the heating power of IOMNPs.


Effects of environmental stress on the architecture and permeability of the rat mesenteric microvasculature.
This study was performed to determine the effects of environmental stress on the leakage to albumin and architecture of microvessels in the rat mesentery. One group of rats (Group A, n = 6) were examined immediately upon arrival at the animal care facility. Groups B (n = 24) and C (n = 32) were housed in rooms with high and low personnel activity, respectively, for up to 7 weeks. Group D (n = 18) was housed in the high activity room for 2, 3, or 4 weeks followed by the low activity room. Rats in the low activity room for 3-4 weeks showed robust microvascular networks within 25% to 50% of the mesenteric windows (each window consisting of the tissue extending between two adjacent feeding arterioles in the mesentery), whereas rats in Group B only showed fragile vessels at the edges of the mesenteric windows within fat deposits. Groups A and C demonstrated little mesenteric fat and few fragile vessels, in contrast to group B. Group D showed increased mesenteric networks and decreased mesenteric fat as recovery progressed. The microvascular networks of 6 rats, randomly selected from Group C, showed few venular leaks following perfusion with fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). Such leaks were abundant in the mesenteric microvasculature of 3 rats randomly selected from Group B. This study demonstrates that environmentally induced stress alters the architecture and leakage to albumin of the rat mesenteric microvasculature, and emphasizes the importance of closely monitoring the environment of experimental animals.


New approach to global Mittag-Leffler synchronization problem of fractional-order quaternion-valued BAM neural networks based on a new inequality.
In this paper, a novel kind of neural networks named fractional-order quaternion-valued bidirectional associative memory neural networks (FQVBAMNNs) is formulated. On one hand, applying Hamilton rules in quaternion multiplication which is essentially non-commutative, the system of FQVBAMNNs is separated into eight fractional-order real-valued systems. Meanwhile, the activation functions are considered to be quaternion-valued linear threshold ones which help to reduce the unnecessary computational complexity. On the other hand, based on fractional-order Lyapunov technology, a new fractional-order derivative inequality is established. Mainly by employing the new inequality technique, constructing three novel Lyapunov-Krasovskii functionals (LKFs) and designing simple linear controllers, the global Mittag-Leffler synchronization problems are investigated and the corresponding criteria are acquired for the system of FQVBAMNNs and its special cases such as fractional-order complex-valued BAM neural networks (FCVBAMNNs) and fractional-order real-valued BAM neural networks (FRVBAMNNs), respectively. Finally, two numerical examples are given to show the effectiveness and availability of the proposed results.


Lipase-catalyzed esterification of palm-based 9,10-dihydroxystearic acid and 1-octanol in hexane--a kinetic study.
The esterification of palm-based 9,10-dihydroxystearic acid (DHSA) and 1-octanol in hexane as catalyzed by lipase from Rhizomucor meihei (Lipozyme IM) followed Michaelis-Menten kinetics. The esterification reaction follows a Ping-Pong, Bi-Bi mechanism. The maximum rate was estimated to be 1 micromol min(-1) mg(-1) catalyst in hexane at 50 degrees C, and the Michaelis-Menten constants for DHSA and 1-octanol were 1.3 M and 0.7 M, respectively.


Corrigendum to "Colonic basidiobolomycosis presenting with intestinal obstruction and a normal eosinophil count" [IDCases 17 (2019) e00565].
[This corrects the article DOI: 10.1016/j.idcr.2019.e00565.].


Monitoring Indicators of Universal Access to Accessible and Safe Anesthetic and Surgical Care in a Peruvian Region: An Ambispective Study.
The Lancet Commission on Global Surgery indicators for monitoring anesthetic and surgical care allow the identification of access barriers, evaluate the safety of surgeries, facilitate planning, and assess changes over time. The primary objective was to measure these indicators in all health facilities of a Peruvian region in 2020. This was an ambispective observational study to measure the anesthetic and surgical care indicators in Piura, a region in Peru, between January 2020 and June 2021. Public and private health facilities in the Piura region that performed surgical care or had specialists from any surgical specialty participated in the study. Data were collected from all regional health facilities that provided surgical care to estimate the density of surgical workforce. Likewise, the percentage of the population with access to an operating room within 2 h was estimated using georeferenced tools. Finally, a public database was accessed to determine the surgical volume, the percentage of the regional population protected with health insurance. In 2020, 88.4% of the inhabitants of this Peruvian region had access to timely essential surgery. There were 18.4 surgical specialists and 1174 surgeries per 100,000 populations, and 91% of the population had health insurance. In addition, there was a rate of 2.1 working operating rooms per 100,000 inhabitants in 2021. This Peruvian region presented an increasing trend with respect to the population's access to essential and timely surgical care, and health insurance coverage. However, the workforce distribution was inequitable among the provinces of the region, the surgical volume was reduced, and timely access was hindered because of the SARS-CoV-2 pandemic.


Cost-effectiveness of 5 fraction and partial breast radiotherapy for early breast cancer in the UK: model-based multi-trial analysis.
We estimated the cost-effectiveness of 4 radiotherapy modalities to treat early breast cancer in the UK. In a subgroup of patients eligible for all modalities, we compared whole-breast (WB) and partial breast (PB) radiotherapy delivered in either 15 (WB15F, PB15F) or 5 fractions (WB5F, PB5F). In a subgroup ineligible for PB radiotherapy, we compared WB15F to WB5F. We developed a Markov cohort model to simulate lifetime healthcare costs and quality-adjusted life years (QALYs) for each modality. This was informed by the clinical analysis of two non-inferiority trials (FAST Forward and IMPORT LOW) and supplemented with external literature. The primary analysis assumed that radiotherapy modality influences health only through its impact on locoregional recurrence and radiotherapy-related adverse events. In the primary analysis, PB5F had the least cost and greatest expected QALYs. WB5F had the least cost and the greatest expected QALYs in those only eligible for WB radiotherapy. Applying a cost-effectiveness threshold of £15,000/QALY, there was a 62% chance that PB5F was the cost-effective alternative in the PB eligible group, and there was a 100% chance that WB5F was cost-effective in the subgroup ineligible for PB radiotherapy. Hypofractionation to 5 fractions and partial breast radiotherapy modalities offer potentially important benefits to the UK health system.


Identification of H1 visual interneuron in Drosophila by [3H]2-deoxyglucose uptake during stationary flight.
High-resolution 2-deoxyglucose (2-DG) neuronal activity labeling is used to identify a visual interneuron in Drosophila by its stimulus-specific uptake of [3H]2-DG during stationary flight in a well-characterized behavioral situation. With a single rotating stripe as visual stimulus a neuron is heavily labeled that has not been described in Drosophila before but is homologous to the extensively studied H1 visual interneuron of larger diptera. Labeling of this cell is inconspicuous in Drosophila if the animal is stimulated with a rotating striped drum.


Dithiothreitol elicits epileptiform activity in CA1 of the guinea pig hippocampal slice.
Dithiothreitol (DTT) is a sulfhydryl reducing agent used as a radioprotectant. Exposure of hippocampal slices for 30 min to 0.5 mM DTT irreversibly increased the orthodromic population spike amplitude, promoted repetitive firing and induced spontaneous epileptiform activity in the CA1 subfield. The same concentration of the oxidized form of DTT did not increase hippocampal excitability. Although the slope of the population synaptic response to afferent stimulation (popPSP) was unchanged by DTT, the duration of the popPSP was prolonged. Recurrent inhibition was unaffected. DTT probably exerts its effects through an irreversible chemical reaction with cellular components. Possible mechanisms of DTT-induced epileptiform activity are discussed.


Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma using high-performance liquid chromatography-tandem mass spectrometry.
A HPLC-MS-MS method to measure amprenavir in human seminal plasma has been developed and validated. The procedure uses stable, isotopically labeled 13C6-amprenavir as an internal standard and 100 microl of sample. The method is accurate (bias less than or equal to 7.2%) and precise (within- and between-day RSDs less than or equal to 4.2%) over the dynamic range of 30-4,000 ng/ml. Recently, this simple and sensitive method was used to determine amprenavir concentrations in seminal samples collected from HIV-1 positive subjects receiving amprenavir antiretroviral therapy as part of a multicenter clinical trial.


Optimisation of Calophyllum inophyllum seed oil nanoemulsion as a potential wound healing agent.
Efficient delivery systems of Calophyllum inophyllum seed oil (CSO) in the form of nanoemulsion were optimised to enhance its stability and ensure its therapeutic efficiency as a potential agent for various biomedical applications. Response Surface Methodology (RSM) was used to determine the effects of independent variables (oil, surfactant, water percentage and homogenisation time) on physicochemical characteristics, including droplet size, polydispersity index and turbidity. The optimised CSO nanoemulsion (CSONE) has a 46.68 nm particle size, 0.15 Polydispersity index value and 1.16 turbidity. After 4 weeks of storage at 5 ± 1 °C and 25 ± 1 °C, the CSONE was physically stable. The optimised CSO nanoemulsion showed enhancement in cell viability and wound healing in baby hamster kidney a clone BHK-21 (BSR) cells as compared to the CSO. The wound healing property of CSONE was higher than CSO. Thus, our in vitro wound healing results demonstrated that CSO in the nanoemulsion form can promote wound healing by enhancing the proliferation and migration of epidermal cells. The coarse emulsion of Calophyllum inophyllum seed oil nano emulsion was prepared using high shear homogeniser techniques. The optimised CSONE with the droplet size of 46.68 nm was prepared from a mixture of CSO, Tween 80, and high pure water (HPW), then used for the biological investigation. The in vitro cell monolayer scratch assay revealed that CSONE in the lowest concentration of CSO resulted in 100% wound closure after 48 hrs. The optimised CSO nanoemulsion was found to be a promising and effective approach in the treatment of wounds by boosting the proliferation and migration of epidermal cells.


Neoplasms of the peripheral nervous system.
Neoplasms of the peripheral nervous system arise from the cellular sheath surrounding the nerve trunks, that is, the pluripotential Schwann cells and related cells, and rarely affect the feet. When present, they are most frequently associated with the autosomal dominantly inherited neurofibromatosis 1. This condition has been related to chromosome 17, and it appears, from in vitro experiments, to involve defects in tyrosine metabolism. Hence, the most common neoplasm is the neurofibroma. Distinct criteria have been established for a diagnosis of neurofibromatosis 1, so that a single pedal neurofibroma may not represent this complex. However, if the complex is present, it is necessary to consider the possibility of malignant transformation to a neurofibrosarcoma. Although malignant peripheral nerve neoplasms are extremely rare in the feet, they may arise in the context of neurofibromatosis 1, or independently. Other benign or malignant schwannomas may (rarely) also arise in the feet. Surgical excision of benign lesions, according to established standards for tumor surgery, is usually curative, but a detailed personal and familial history, along with adjunctive radiologic procedures and biopsy, is necessary to determine the nature of the lesion. Since (endocrine and) other abnormalities may complicate neurofibromatosis 1, surgical procedures must not be undertaken until the patient has been medically cleared and is carefully monitored. A high mortality rate is associated with malignant peripheral neurogenic tumors, especially those arising in the context of neurofibromatosis 1. It should be recalled that neurologic manifestations in the foot may represent non-neoplastic conditions as well as peripheral nerve tumors (or other tumors involving those nerves) that are proximal to the foot and ankle area.


[Effect of haw leaf extract and its preparation on polymorphonuclear leucocyte adhesion during HUVEC anoxia/reoxygenation injury].
To study the effect and molecular mechanism of two haw leaf extracts, Vitexin-rhamnoside (VR) and Vitexin-glucoside (VG), and their preparation, Aoshaen injection (AI), on the polymorphonuclear leucocyte (PMN) adhesion during human umbilical vein endothelial cell (HUVEC) anoxia/reoxygenation (A/R) injury. The cell model of A/R injury duplicated by breaking off the oxygen supplying of HUVEC for 60 min followed with reoxygenating for 30 min (phase 1) or 240 min (phase 2) was taken as the experimental objective. The effects of testing drugs (VR, VG and AI) on PMN adhesion in the model cells were measured by enzyme immunoassay, and their effects on PMN superficial adhesion molecule CD11/CD18 expression were measured by flow cytometer respectively. After 60 min of anoxia, HUVEC was shrunk and deformed. The adhesion between PMN and HUVEC significantly revealed at phase 1 in the model group, but it was fewer in the normal cell group, and also lesser in the groups treated with various drugs. The condition of cell adhesion revealed at phase 2 was the similar to that at phase 1. All testing drugs, VR, VG and AI, showed inhibitory effect on the cell adhesion at either phase 1 or phase 2, showing a certain dose-effect relationship. The expression of CD11/ CD18 was also inhibited by the testing drugs, and a good dose-effect relation was shown by VG and AI. At the resting condition, there are almost no expression of CD11/CD18 molecule, but it could be enhanced by incubating PMN with supernate of A/R injured HUVEC culture, and more marked at phase 1. Adding the test drugs into the supernate could inhibit the enhancing of CD11/CD18 molecule expression and reduce the PMN-HUVEC adhesion, which may be one of the molecular mechanisms of haw leaf extracts and their preparation in protecting heart against A/R injury.


Effect of the antiepileptic drug sodium valproate on glutamine and glutamate metabolism in isolated human kidney tubules.
We studied the effects of sodium valproate, a widely used antiepileptic drug and a hyperammonemic agent, on L-[1-14C]glutamine and L-[1-14C]glutamate metabolism in isolated human kidney-cortex tubules. Valproate markedly stimulated glutamine removal as well as the formation of ammonia, 14CO2, pyruvate, lactate and alanine, but it inhibited glucose synthesis; the increase in ammonia formation was explained by a stimulation by valproate mainly of flux through glutaminase (EC 18.104.22.168) and to a much lesser extent of flux through glutamate dehydrogenase (EC 126.96.36.199). By contrast, valproate did not stimulate glutamate removal or ammonia formation, suggesting that the increase in flux through glutamate dehydrogenase observed with glutamine as substrate was secondary to the increase in flux through glutaminase. Accumulation of pyruvate, alanine and lactate in the presence of valproate was less from glutamate than from glutamine. Inhibition by aminooxyacetate of accumulation of alanine from glutamine caused by valproate did not prevent the acceleration of glutamine utilization and the subsequent stimulation of ammonia formation. It is concluded from these data, which are the first concerning the in vitro metabolism of glutamine and glutamate in human kidney-cortex tubules, that the stimulatory effect of valproate is primarily exerted at the level of glutaminase in human renal cortex.


Acute kidney injury in necrotizing enterocolitis predicts mortality.
Morbidity and mortality with necrotizing enterocolitis (NEC) remains a significant challenge. Acute kidney injury (AKI) has been shown to worsen survival in critically ill neonates. To our knowledge, this study is the first to evaluate the prevalence of AKI and its impact on outcomes in neonatal NEC. We carried out a single-center retrospective chart review of all neonates treated for NEC between 2003 and 2015 (N = 181). AKI is defined as a rise in serum creatinine (SCr) from a previous trough according to neonatal modified KDIGO criteria (stage 1 = SCr rise 0.3 mg/dL or SCr 150 < 200%, stage 2 = SCr rise 200 < 300%, stage 3 = SCr rise ≥300%, SCr 2.5 mg/dL or dialysis). Primary outcome was in-hospital mortality and secondary outcomes were hospital length of stay (LOS) and need for and type of surgery. Acute kidney injury occurred in 98 neonates (54%), with 39 stage 1 (22%), 31 stage 2 (18%), and 28 stage 3 (16%), including 5 requiring dialysis. Non-AKI and AKI groups were not statistically different in age, weight, Bell's NEC criteria, and medication exposure (vasopressors, vancomycin, gentamicin, or diuretic). Neonates with AKI had higher mortality (44% vs 25.6%, p = 0.008) and a higher chance of death (HR 2.4, CI 1.2-4.8, p = 0.009), but the effect on LOS on survivors did not reach statistical significance (79 days, interquartile range [IQR] 30-104 vs 54 days, IQR 30-92, p = 0.09). Overall, 48 (27.9%) patients required surgical intervention. This study shows that AKI not only occurs in over half of patients with NEC, but that it is also associated with more than a two-fold higher mortality, highlighting the importance of early recognition and potentially early intervention for AKI.


An investigation of ultrasound effect on digestate solubilization and methane yield.
In this study, different ultrasound power intensities of 0.05-0.21kW/L (4.13-16.52kWh/kg TS) were applied at a frequency of 20kHz and for durations of 5-20min to digestate obtained from a domestic wastewater treatment plant. The ultrasonic effect on digestate solubilization was revealed by increased levels of soluble Chemical Oxygen Demand (sCOD), soluble Total Organic Carbon (sTOC), and soluble Total Nitrogen (sTN) released into the solution. The highest material release was achieved at an ultrasonic energy intensity of 0.21kWh/L. Furthermore, the ultrasonic effect on CH4 production was studied using the anaerobic digestion process. The application of ultrasound at 0.05-0.21kWh/L provided 1.6-2.3-fold increase in net CH4 production. Analysis of the energetics of the system showed that only about 4 and 11% of the energy input was recovered in terms of additional CH4 production at 0.21 and 0.05kWh/L, respectively. A comprehensive cost-benefit analysis of the system is required for making a conclusion on the feasibility of the system, and such analysis should include environmental, economic, and societal benefits of the system, among others.


Relationship between body mass and gastro-oesophageal reflux symptoms: The Bristol Helicobacter Project.
To examine the relationship between body mass and gastro-oesophageal reflux in a large population-representative sample from the UK. Cross-sectional population-based study, as part of a randomized controlled trial of eradication of Helicobacter pylori infection, in Southwest England. Subjects In all, 10 537 subjects, aged 20-59 years, were recruited from seven general practices. Subjects provided data on frequency and severity of dyspeptic symptoms and anthropometric measurements were taken. Relationship between overweight (body mass index [BMI] >/=25 kg/m(2) and </=30 kg/m(2)) or obesity (BMI >30 kg/m(2)) and frequency and severity of heartburn and acid regurgitation. Body mass index was strongly positively related to the frequency of symptoms of gastro-oesophageal reflux. The adjusted odds ratios (OR) for frequency of heartburn and acid regurgitation occurring at least once a week in overweight participants compared with those of normal weight were 1.82 (95% CI: 1.33-2.50) and 1.50 (95% CI: 1.13-1.99) respectively. Corresponding OR (95% CI) relating to obese patients were 2.91 (95% CI: 2.07-4.08) and 2.23 (95% CI: 1.44-3.45) respectively. The OR for moderate to severe reflux symptoms were raised in overweight and obese subjects but not to the same extent as frequency of symptoms and only the relationship between obesity and severity of heartburn reached conventional statistical significance: OR = 1.19; 95% CI: 1.07-1.33. Being above normal weight substantially increases the likelihood of suffering from heartburn and acid regurgitation and obese people are almost three times as likely to experience these symptoms as those of normal weight.


A Pilot Study Examining Physical and Social Warmth: Higher (Non-Febrile) Oral Temperature Is Associated with Greater Feelings of Social Connection.
An emerging literature suggests that experiences of physical warmth contribute to social warmth-the experience of feeling connected to others. Thus, thermoregulatory systems, which help maintain our relatively warm internal body temperatures, may also support feelings of social connection. However, the association between internal body temperature and feelings of connection has not been examined. Furthermore, the origins of the link between physical and social warmth, via learning during early experiences with a caregiver or via innate, co-evolved mechanisms, remain unclear. The current study examined the relationship between oral temperature and feelings of social connection as well as whether early caregiver experiences moderated this relationship. Extending the existing literature, higher oral temperature readings were associated with greater feelings of social connection. Moreover, early caregiver experiences did not moderate this association, suggesting that the physical-social warmth overlap may not be altered by early social experience. Results provide additional support for the link between experiences of physical warmth and social warmth and add to existing theories that highlight social connection as a basic need on its own.


Autism and Asperger's disorder: are they movement disorders involving the cerebellum and/or basal ganglia?
Autism and Asperger's disorder (AD) are childhood developmental disorders of unknown aetiology. Autism and AD share several behavioural features, and it is not clear whether they are distinct disorders or variants of the same disorder. Recent studies indicate that disordered movement may be another feature of autism and AD, and that this may reflect dysfunction within the frontostriatal and/or cerebellar motor circuits. While disordered movement in autism and AD has been examined in a variety of ways, it is relatively under-researched compared to the cognitive, affective, and behavioural disturbances seen in these disorders. This review examines the role of the frontostriatal and cerebellar motor systems in the behavioural features of autism and AD, with gait as a proxy, and discusses difficulties with their diagnosis and their possible pathogenesis.


Can we predict a delirium after cardiac surgery? A validation study of a delirium risk checklist.
Delirium is a common temporary mental disorder that often occurs in patients who undergo cardiac surgery. It is important to prevent the negative side effects of delirium by identifying high-risk patients before surgery. Koster and colleagues designed a risk model to identify patients with an increased risk of postoperative delirium after cardiac surgery. The aim of this study was to validate the risk model for delirium and further improve the risk model. A delirium risk checklist containing predictors associated with postoperative delirium was used during the preoperative outpatient screening in 329 patients. The delirium observation screening scale was used preoperatively and postoperatively to assess delirium. Compared with the model of Koster and colleagues age greater than 70 years and a history of delirium were confirmed as statistically significant predictors of postoperative delirium, while cognitive impairment and alcohol abuse were almost significant factors. The European system for cardiac operative risk evaluation (EuroSCORE), comorbidity and type of surgery could not predict a postoperative delirium again. The area under the curve of this model was 0.79 (95% confidence interval (CI) 0.73-0.86; P<0.001). Based on the data of this study the model was improved with the following independent predictors of postoperative delirium: age, more than one comorbidity, history of delirium and a lower standardised mini mental state examination score as with an area under the curve of 0.79 (95% CI 0.73-0.85; P<0.001). The risk model could not be fully validated. It is difficult to validate a risk model over time; there are different circumstances such as the increased focus on the prevention of delirium.


Persistent Barriers to Colorectal Cancer Screening Completion Amid Centralized Outreach: A Mixed Methods Study.
To understand patient experiences and persistent barriers to colorectal cancer (CRC) screening amid centralized outreach at urban family medicine practices. Following a pragmatic trial assessing mailed fecal immunochemical test (FIT) outreach, we invited a subset of participants to complete a semi-structured qualitative interview and structured questionnaire. Single urban academic healthcare system. Sixty patients who were eligible and overdue for CRC screening at the time of trial enrollment. Using Andersen's Behavioral Model, we developed an interview guide to systematically assess factors shaping screening decisions and FIT uptake. Close-ended responses were analyzed using descriptive statistics. Qualitative data were analyzed using the constant comparative method. Most participants (82%) self-reported that they had ever completed any modality of CRC screening, and nearly half (43%) completed the mailed FIT during the trial. Most patients (60%) preferred FIT to colonoscopy due to its private, convenient, and non-invasive nature; however, persistent barriers related to screening beliefs including fear of test results and cancer treatment still prevented some patients from completing any form of CRC screening. Mailed FIT can overcome many structural barriers to CRC screening, yet clear communication and follow-up amid centralized outreach are essential. For some patients, tailored outreach or navigation to address screening-related fears or other screening beliefs may be needed to ensure timely completion of CRC screening.


Computer vision coaching microsurgical laboratory training: PRIME (Proficiency Index in Microsurgical Education) proof of concept.
Computer vision (CV) feedback could be aimed as a constant tutor to guide ones proficiency during microsurgical practice in controlled environments. Five neurosurgeons with different levels of microsurgical expertise performed simulated vessel dissection and micro-suture in an ex vivo model for posterior computer analysis of recorded videos. A computer program called PRIME (Proficiency Index of Microsurgical Education) used in this research recognized color-labeled surgical instruments, from downloading videos into a platform, with a range of motion greater than 3 mm, for objective evaluation of number of right and left hand movements. A proficiency index of 0 to 1 was pre-established in order to evaluate continuous training improvement. PRIME computer program captured all hand movements executed by participants, except for small tremors or inconsistencies that have a range of motion inferior to 3 mm. Number of left and right hand movements were graphically expressed in order to guide more objective and efficacious training for each trainee, without requiring body sensors and cameras around the operating table. Participants with previous microsurgical experience showed improvement from 0.2 to 0.6 (p < 0.05), while novices had no improvement. Proficiency index set by CV was suggested, in a self-challenge and self-coaching manner. PRIME would offer the capability of constant laboratory microsurgical practice feedback under CV guidance, opening a new window for oriented training without a tutor or specific apparatus regarding all levels of microsurgical proficiency. Prospective, large data study is needed to confirm this hypothesis.


Stopping-power ratio estimation for proton radiotherapy using dual-energy computed tomography and prior-image constrained denoising.
Dual-energy computed tomography (DECT) is a promising technique for estimating stopping-power ratio (SPR) for proton therapy planning. It is known, however, that deriving electron density (ED) and effective atomic number (EAN) from DECT data can cause noise amplification in the resulting SPR images. This can negate the benefits of DECT. This work introduces a new algorithm for estimating SPR from DECT with noise suppression, using a pair of CT scans with spectral separation. The method is demonstrated using phantom measurements. An iterative algorithm is presented, reconstructing ED and EAN with noise suppression, based on Prior Image Constrained Denoising (PIC-D). The algorithm is tested using a Siemens Definition AS+ CT scanner (Siemens Healthcare, Forchheim, Germany). Three phantoms are investigated: a calibration phantom (CIRS 062M), a QA phantom (CATPHAN 700), and an anthropomorphic head phantom (CIRS 731-HN). A task-transfer function (TTF) and the noise power spectrum are derived from SPR images of the QA phantom for the evaluation of image quality. Comparisons of accuracy and noise for ED, EAN, and SPR are made for various versions of the algorithm in comparison to a solution based on Siemens syngo.via Rho/Z software and the current clinical standard of a single-energy CT stoichiometric calibration. A gamma analysis is also applied to the SPR images of the head phantom and water-equivalent distance (WED) is evaluated in a treatment planning system for a proton treatment field. The algorithm is effective at suppressing noise in both ED and EAN and hence also SPR. The noise is tunable to a level equivalent to or lower than that of the syngo.via Rho/Z software. The spatial resolution (10% and 50% frequencies in the TTF) does not degrade even for the highest noise suppression investigated, although the average spatial frequency of noise does decrease. The PIC-D algorithm showed better accuracy than syngo.via Rho/Z for low density materials. In the calibration phantom, it was superior even when excluding lung substitutes, with root-mean-square deviations for ED and EAN less than 0.3% and 2%, respectively, compared to 0.5% and 3%. In the head phantom, however, the SPR accuracy of the PIC-D algorithm was comparable (excluding sinus tissue) to that derived from syngo.via Rho/Z: less than 1% error for soft tissue, brain, and trabecular bone substitutes and 5-7% for cortical bone, with the larger error for the latter likely related to the phantom geometry. Gamma evaluation showed that PIC-D can suppress noise in a patient-like geometry without introducing substantial errors in SPR. The absolute pass rates were almost identical for PIC-D and syngo.via Rho/Z. In the WED evaluations no general differences were shown. The PIC-D DECT algorithm provides scanner-specific calibration and tunable noise suppression. It is vendor agnostic and applicable to any pair of CT scans with spectral separation. Improved accuracy to current methods was not clearly demonstrated for the complex geometry of a head phantom, but the suppression of noise without spatial resolution degradation and the possibility of incorporating constraints on image properties, suggests the usefulness of the approach.


Piperine: researchers discover new flavor in an ancient spice.
Studies with animals that are deficient in the vanilloid (capsaicin) receptor TRPV1 have confirmed the pivotal role that TRPV1 has in the development of post-inflammatory hyperalgesia, and enhanced TRPV1 expression has been described in various human disorders. Natural products have provided several lead structures for the development of vanilloid ligands. A recent study shows that piperine, the irritant principle in black pepper, is more efficient than capsaicin in the desensitization of human TRPV1, which suggests that this pharmacological aspect of vanilloids can be dissociated from its potency. This finding raises the intriguing possibility that piperine can be used as a chemical template for the design of improved TRPV1 agonists.


The microRNA-212/132 cluster regulates B cell development by targeting Sox4.
MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the prepro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in accelerated B cell recovery after antibody-mediated B cell depletion. We find that Sox4 is a target of miR-132 in B cells. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from overexpression of miR-132 alone, thus suggesting that miR-132 may regulate B lymphopoiesis through Sox4. In addition, we show that the expression of miR-132 can inhibit cancer development in cells that are prone to B cell cancers, such as B cells expressing the c-Myc oncogene. We have thus uncovered miR-132 as a novel contributor to B cell development.


Paroxysmal movement disorders and episodic ataxias.
This chapter summarizes clinical symptoms of some paroxysmal dyskinesias (PDs) of infancy and childhood, as well as episodic ataxias. PDs refer to a complex group of disorders whose main feature is the occurrence of sudden, intermittent attacks of abnormal postures and involuntary movements. PDs can sometimes be symptomatic (secondary PDs), but usually an underlying cerebral lesion is not present (primary PDs). Some of the primary PDs are transient, such as benign paroxysmal torticollis of infancy. Chronic PDs are subdivided into nonkinesigenic (Mount and Reback type), kinesigenic (Kertesz type), and exercise-induced (Lance type) but cases that overlap with these types are on record. They are autosomal dominant inherited conditions. The myofibrillogenesis regulator-1 gene is responsible for nonkinesigenic PDs. To date, the genetic basis of kinesigenic PDs remains unknown. Several clinical entities associated epilepsy with PDs, such as infantile convulsions and choreoathetosis (ICCA). Exercise-induced PD type can be produced by mutations in the SLC2A1 gene that encodes Glut1 (glucose transporter type1). Episodic ataxias are inherited disorders of intermittent ataxia. The attacks are brief and triggered by abrupt exercise and emotional stimulus. Between attacks, palpebral and hand muscle myokymia is often seen in episodic ataxia type 1 (EA1). In episodic ataxia type 2 (EA2) interictal nystagmus is usually present. Some of these latter patients develop progressive ataxia with vermian atrophy. This disorder is associated with mutations in the human Ca channel alfa 1 subunit CACN1A4 gene.


Brain connectivity meets reservoir computing.
The connectivity of Artificial Neural Networks (ANNs) is different from the one observed in Biological Neural Networks (BNNs). Can the wiring of actual brains help improve ANNs architectures? Can we learn from ANNs about what network features support computation in the brain when solving a task? At a meso/macro-scale level of the connectivity, ANNs' architectures are carefully engineered and such those design decisions have crucial importance in many recent performance improvements. On the other hand, BNNs exhibit complex emergent connectivity patterns at all scales. At the individual level, BNNs connectivity results from brain development and plasticity processes, while at the species level, adaptive reconfigurations during evolution also play a major role shaping connectivity. Ubiquitous features of brain connectivity have been identified in recent years, but their role in the brain's ability to perform concrete computations remains poorly understood. Computational neuroscience studies reveal the influence of specific brain connectivity features only on abstract dynamical properties, although the implications of real brain networks topologies on machine learning or cognitive tasks have been barely explored. Here we present a cross-species study with a hybrid approach integrating real brain connectomes and Bio-Echo State Networks, which we use to solve concrete memory tasks, allowing us to probe the potential computational implications of real brain connectivity patterns on task solving. We find results consistent across species and tasks, showing that biologically inspired networks perform as well as classical echo state networks, provided a minimum level of randomness and diversity of connections is allowed. We also present a framework, bio2art, to map and scale up real connectomes that can be integrated into recurrent ANNs. This approach also allows us to show the crucial importance of the diversity of interareal connectivity patterns, stressing the importance of stochastic processes determining neural networks connectivity in general.


Sociopsychological factors affecting the human response to noise exposure.
Community noise is reported to be the most often mentioned undesirable neighborhood condition in a recent U.S. Census survey. Understanding community response to noise involves the measurement of a number of complex acoustic and nonacoustic variables and establishing the chain of relationships between physical exposure, perception, annoyance, and acceptability responses and finally complaint behavior. The perceived loudness of a noise is the most important acoustic parameter influencing annoyance and complaints, and the simple dBA unit can be used to integrate spectral characteristics of complex sounds in community studies. Although energy averaging such as Leq or Ldn can be used to describe multiple noise exposures over time, the variable trade-off relationships between number and level of exposures are somewhat obscured by such summary measures. However, they are still the best available descriptors and, until more accurate ones are developed, can be used to measure community noise environments. Perception of an identical noise exposure can vary according to the physiological noise sensitivity of a person and the activity context in which the noise is heard. Although the acoustic quality of the noise itself usually explains about 10 to 25 per cent of the variability in annoyance responses, sociopsychological variables measured in field studies account for 35 to 50 per cent of the variations in human annoyance responses. Three of the most important nonacoustic factors are the connotative fear effects of the noise signal, the feeling that those responsible for the noise are misfeasant in not reducing the noise, and the feeling that harmful health effects are produced by the noise. When residents report great fear, a high misfeasance, and marked health effects, about 90 per cent report a high annoyance level whether their noise exposure level is above 90 Ldn or 65 to 70 Ldn. In contrast, if the feelings are a low fear level, a low degree of misfeasance, and minimal health effects, only 3 to 10 per cent give high annoyance responses. Complaint behavior, although based on intensity of annoyance, is modified by a number of other sociopsychological factors and often is an unreliable indicator of an environmental problem.


Transcutaneous ultrasound-facilitated coronary thrombolysis during acute myocardial infarction.
In preclinical experiments, the combination of transcutaneous, low-frequency ultrasound and thrombolytic therapy has shown improved patency rates over thrombolytics alone. A total of 25 patients with myocardial infarction were treated with a thrombolytic agent and adjunctive transcutaneous ultrasound. No unanticipated major adverse events were observed.


4DCT ventilation function image-based functional lung protection for esophageal cancer radiotherapy.
4DCT (four-dimensional computed tomography) can effectively obtain functional lung ventilation images for patients and integrate them into radiotherapy treatment planning. Studies have not been performed on esophageal cancer, and there is no clear consensus on the optimal functional lung threshold for functional lung. Functional lung images were generated for 11 patients with esophageal cancer. The correlation between the dose-volume parameters of functional lung (FL) as defined by different thresholds and the change of PFT/PDFT (pulmonary [diffusion] function test) metrics before and after radiotherapy were evaluated. FL-sparing planning was generated for each patient to preserve the functional lung and compared to conventional anatomical CT (non-sparing) planning. There was a significant positive correlation between the FL0.8 (defined Jacobian value ≤ 0.8), FL0.84, and FL0.9 dose-volume parameters and ΔFEV1/FVC (reduction before and after radiotherapy), and the FL0.8‑V30 correlation was the strongest (r = 0.819, P < 0.01). The FL-sparing planning had a target area conformity index and homogeneity index comparable to the non-sparing planning (P > 0.05). For FL, the FL-sparing planning achieved lower FL-MLD (6.30 ± 2.14 Gy vs. 7.83 ± 2.70 Gy), V10 (17.13 ± 7.70% vs. 27.40 ± 9.48%), and V20 (6.96 ± 3.85% vs. 11.63 ± 7.19%) compared to the non-sparing planning (P < 0.05), while heart and spinal cord doses were not significantly different between the two planning groups. The 4DCT-based FL irradiation dose for esophageal cancer was significantly associated with a decrease in FEV1/FVC. The optimal FL defined as a Jacobian value ≤ 0.8 or about 21% of the whole lung volume may be a good choice. FL-sparing planning significantly reduced the FL dose without compromising target area coverage.


Effect of dietary fiber and growth hormone on colonic adaptation in short bowel syndrome treated by enteral nutrition.
Colon adaptation can partially compensate for the reduced capacity of nutrient absorption in patients with short bowel syndrome (SBS). The aim of this study was to assess the effect of combined treatment with enteral nutrition (EN), dietary fiber, and recombinant human growth hormone (rhGH) on promoting colonic adaptation. A group of 40 male Sprague-Dawley rats undergoing up to 80% to 85% small intestine resection were randomly assigned to four groups of 10 rats each: enteral nutrition (EN, the control); enteral nutrition/dietary fiber (EF); enteral nutrition/rhGH (EG); and enteral nutrition/dietary fiber/rhGH (EFG). All groups received isonitrogenous, isocaloric enteral feeding for 21 days. Body weight, daily nitrogen balance, colonic morphology, DNA, insulin-like growth factor-1/IGF-1 receptor (IGF-1)/IGF-1R) expression were determined. Morphologic adaptation of the colon (including increased mucosal thickness and plica height, enlarged surface area, increased hyditloid cells) was observed on postoperative day 21. GH is superior to fiber in several aspects: increasing colon diameters (0.46 +/- 0.03 vs. 0.38 +/- 0.02 cm, P < 0.05), villous height (356 +/- 23 vs. 307 +/- 21 microm, P < 0.05) and total surface area (15,222 +/- 1344 vs. 13,178 +/- 1727 microm(2), P < 0.05). Increased DNA content-1.66 +/- 0.13 (EG) and 1.71 +/- 0.13 (EGF) vs. 1.28 +/- 0.11(EF), P < 0.05-in the colon was also found in the EG and EGF groups. GH administration led to a significant increase in plasma IGF-1 (439.6 +/- 88.3 ng/ml in the EG group, 455.4 +/- 107.4 ng/ml in the EGF group) and growth hormone (9.29 +/- 6.49 ng/ml in the EG group, 9.68 +/- 3.26 ng/ml in the EGF group) as compared to the EN group (IGF-1, 328.7 +/- 68.1 ng/ml; GH, 5.81 +/- 2.41 ng/ml) and the EF group (IGF-1, 356.4 +/- 52.1 ng/ml; GH, 6.51 +/- 4.66 ng/ml). Analysis of IGF-1 and IGF-1 receptor mRNA also demonstrated a significantly higher IGF-1 mRNA in the EG and EFG groups than in the EN and EF groups. Colon functional adaptation was also associated with accelerated absorptive function of water in the EF, EG, and EGF groups. Improved nutritional status (body weight, nitrogen retention, plasma protein) were seen in the EG and EGF groups. Dietary fiber, in combination with growth factor, synergistically promoted colon adaptation in the SBS animal model and facilitated maintenance of daily nutritional needs in rodents.


Volume of the posterior hippocampus mediates age-related differences in spatial context memory and is correlated with increased activity in lateral frontal, parietal and occipital regions in healthy aging.
Healthy aging is associated with episodic memory decline, particularly in the ability to encode and retrieve object-context associations (context memory). Neuropsychological and neuroimaging studies have highlighted the importance of the medial temporal lobes (MTL) in supporting episodic memory across the lifespan. However, given the functional heterogeneity of the MTL, volumetric declines in distinct regions may impact performance on specific episodic memory tasks, and affect the function of the large-scale neurocognitive networks supporting episodic memory encoding and retrieval. In the current study, we investigated how MTL structure may mediate age-related differences in performance on spatial and temporal context memory tasks, in a sample of 125 healthy adults aged 19-76 years old. Standard T1-weighted MRIs were segmented into the perirhinal, entorhinal and parahippocampal cortices, as well as the anterior and posterior hippocampal subregions. We observed negative linear and quadratic associations between age and volume of the parahippocampal cortex, and anterior and posterior hippocampal subregions. We also found that volume of the posterior hippocampus fully mediated the association between age and spatial, but not temporal context memory performance. Further, we employed a multivariate behavior partial-least-squares analysis to assess how age and regional MTL volumes correlated with brain activity during the encoding and retrieval of spatial context memories. We found that greater activity within lateral prefrontal, parietal, and occipital regions, as well as within the anterior MTL was related to older age and smaller volume of the posterior hippocampus. Our results highlight the heterogeneity of MTL contributions to episodic memory across the lifespan and provide support for the posterior-anterior shift in aging, and scaffolding theory of aging and cognition.


Nonglandular leaf trichomes as short-term inducible defense of the grey alder, Alnus incana (L.), against the chrysomelid beetle, Agelastica alni L.
The grey alder compensates leaf area losses due to insect grazing by continuously producing new leaves throughout the vegetative period. Different degrees of defoliation were attained experimentally by a controlled release of the oligophagous beetle Agelastica alni on arbitrarily selected trees from a homogenous population of young alders. The reduction in leaf area per tree significantly influenced the density of leaf trichomes, assessed 10-30 days later, on newly sprouting leaves only. Cross-correlations between leaf area reduction and trichome density were strongest for leaves which completed unfolding 14-21 days after damage. Dualchoice assays suggested a negative influence of trichomes on oviposition rate of A. alni. Removal of trichomes by shaving demonstrated the highly significant effect of trichomes on feeding behavior of adults and larvae in dual-choice assays. The role of the induced increase in trichome density as a possible short-term defense reaction against herbivorous insects is discussed.


Impact of UV Modifying Factors on the Incidence of Keratinocyte Carcinomas in Solid Organ Transplant Recipients: A Systematic Review.
Solid organ transplant recipients (SOTR) are at an increased risk for developing keratinocyte carcinomas (KC). Four ultraviolet (UV) modifying factors have been identified that impact the incidence of KC: Fitzpatrick Skin Type (FST), race, sun exposure, and sun-protective factors. We conducted a systematic review to summarize the association between UV modifying factors and the incidence of KC in SOTR. We systematically searched PubMed, Scopus, and Web of Science databases, and after screening for inclusion and exclusion criteria, we included 13 studies with 6,910 solid organ transplant recipients in our analysis. Our review found that lower FST (I-II), white and Latinx populations, lack of regulated sunscreen application, and occupational and residential sun exposure are individual risk factors among solid organ transplant recipients for KC incidence. Although previous studies showed an in-creased SCC:BCC ratio, some studies found a contradictory increased BCC:SCC ratio. Limitations include few research studies that analyze these UV modifying factors and a lack of incorporating both varying immunosuppressant factors and transplantation follow-up times. These findings support the need for dermatological advice in increased risk patient demographic populations, lower FST and white and Latinx populations, and subsequently moderating sun exposure and protective factors.


Ordinary chat and therapeutic conversation: phatic communication and mental health nursing.
This paper offers a definition of 'phatic communication' and identifies examples of it. The paper also illustrates how a knowledge of such communication is useful for mental health nurses in conversation with their clients and colleagues. The importance of turn taking in conversations is also discussed in a cultural context. Various examples of phatic communication are offered.


Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives.
Sulfur-containing compounds are considered as attractive pharmacophores for discovery of new drugs regarding their versatile properties to interact with various biological targets. Quantitative structure-activity relationship (QSAR) modeling is one of well-recognized in silico tools for successful drug discovery. In this work, a set of 38 sulfur-containing derivatives (Types I-VI) were evaluated for their in vitro anticancer activities against 6 cancer cell lines. In vitro findings indicated that compound 13 was the most potent cytotoxic agent toward HuCCA-1 cell line (IC50 = 14.47 μM). Compound 14 exhibited the most potent activities against 3 investigated cell lines (i.e., HepG2, A549, and MDA-MB-231: IC50 range = 1.50-16.67 μM). Compound 10 showed the best activity for MOLT-3 (IC50 = 1.20 μM) whereas compound 22 was noted for T47D (IC50 = 7.10 μM). Subsequently, six QSAR models were built using multiple linear regression (MLR) algorithm. All constructed QSAR models provided reliable predictive performance (training sets: Rtr range = 0.8301-0.9636 and RMSEtr = 0.0666-0.2680; leave-one-out cross validation sets: RCV range = 0.7628-0.9290 and RMSECV = 0.0926-0.3188). From QSAR modeling, chemical properties such as mass, polarizability, electronegativity, van der Waals volume, octanol-water partition coefficient, as well as frequency/presence of C-N, F-F, and N-N bonds in the molecule are essential key predictors for anticancer activities of the compounds. In summary, a series of promising fluoro-thiourea derivatives (10, 13, 14, 22) were suggested as potential molecules for future development as anticancer agents. Key structure-activity knowledge obtained from the QSAR modeling was suggested to be advantageous for suggesting the effective rational design of the related sulfur-containing anticancer compounds with improved bioactivities and properties.


Changing obstetric practices associated with decreasing incidence of meconium aspiration syndrome.
To describe changes in neonatal and obstetric practices that may have contributed to the decreasing incidence of meconium aspiration syndrome in our population during this time. We compared neonatal and obstetric characteristics of 61 infants diagnosed with meconium aspiration syndrome with 1365 infants born through moderate or thick meconium-stained amniotic fluid at more than 37 weeks' completed gestation. Data were prospectively collected, and all respiratory diagnoses were concurrently made. Three distinct birth year groups were analyzed based on changing obstetric practice paradigms. Meconium aspiration syndrome decreased nearly four-fold from 1990-1992 to 1997-1998 (5.8% to 1.5% of meconium-stained infants more than 37 weeks; P <.003). The only change in neonatal characteristics was a 33% decrease in births more than 41 weeks with a reciprocal 33% increase in births 38-39 weeks during 1997-1998. Significant changes in obstetric practice included more frequent diagnosis of nonreassuring fetal heart rate patterns, greater use of amnioinfusion, and increased cesarean delivery rate in 1997-1998. By logistic regression analysis, the only consistent risk factor for meconium aspiration syndrome across all three epochs was the presence of tracheal meconium. Reduction in post-term delivery was the most important factor in reducing meconium aspiration syndrome.


Molecular characterization and protective immunity of rhoptry protein 35 (ROP35) of Toxoplasma gondii as a DNA vaccine.
Toxoplasma gondii rhoptry proteins (TgROPs) have been considered the main targets and indicator molecules for immune diagnosis and prophylaxis because they present during the initial process of invasion. The aim of this study was to evaluate the protective effect of a TgROP35 DNA vaccine on experimental mice subjected to T. gondii challenge. The effect of intramuscularly injecting the genetic vaccine pVAX-ROP35 into BALB/c mice was evaluated, by first inserting the TgROP35 sequence into the pVAX I eukaryotic expression vector. The levels of IgG, IgG1 and IgG2a in pVAX-ROP35-vaccinated animals were integrally increased. Cytokine profile analyses revealed that IFN-γ, IL-2 and IL-10 levels were significantly increased, while there were no significant differences in IL-4 expression between the pVAX-ROP35 immunized and control groups. Additionally, we found that immunization with pVAX-ROP35 significantly prolonged the survival time (13.90 ± 1.97 days) of mice after challenge infection with the virulent T. gondii RH strain compared with that in non-vaccinated control animals (mice died within 10 days). Moreover, the number of brain cysts (1450 ± 287) in the animals subjected to pVAX-TgROP35 vaccination decreased remarkably (P < 0.05) compared to that in the blank control mice (2333 ± 473). Furthermore, the size of brain cysts in the pVAX-TgROP35 group was significantly smaller than that in the blank control, PBS and pVAXI groups. The findings indicated that intense cell-mediated and humoural immunity was triggered and that defence mechanisms against T. gondii were partially induced after vaccination by TgROP35.


Dual dynamic bonds approach for polyurethane recycling and self-healing of emulsified asphalt.
To recycle polyurethane and extend the service life of polyurethane-modified emulsified asphalt, this study developed novel perspectives for a lower carbon-footprint and cleaner preparation of recyclable polyurethane (RWPU) and its modified emulsified asphalt (RPUA-x) by using self-emulsification and dual dynamic bonds. Particle dispersion and zeta potential tests reflected that the emulsions of RWPU and RPUA-x existed excellent dispersion and storage stability. Microscopic and thermal analyses indicated that RWPU possessed dynamic bonds and maintained thermal stability below 250 °C as anticipated. Concurrently, RWPU provided RPUA-x with a strong physical cross-linking network, and a homogeneous phase was observed in RPUA-x after drying. Self-healing and mechanical evaluation results revealed that the regeneration efficiencies of RWPU were 72.3 % (stress) and 100 % (strain), respectively, and the stress-strain healing efficiency of RPUA-x was >73 %. The energy dissipation performance and plastic damage principle of RWPU were investigated using cyclic tensile loading. The multiple self-healing mechanisms of RPUA-x were revealed through microexamination. Furthermore, the viscoelasticity of RPUA-x and variations in flow activation energy were determined based on Arrhenius fitting from dynamic shear rheometer tests. In conclusion, disulfide bonds and hydrogen bonds endow RWPU with remarkable regenerative properties and grant RPUA-x with both asphalt diffusion self-healing and dynamic reversible self-healing capabilities.


Synergistic Effect of Reverse Drilling and Bone Dust on Femoral Tendon-Bone Healing After Anterior Cruciate Ligament Reconstruction in a Rabbit Model.
Anterior cruciate ligament (ACL) injuries and bone tunnel enlargement (BTE) after ACL reconstruction (ACLR) remain frequent issues. Bone dust (BD) produced by tunnel preparation with osteogenic ability and reverse drilling (RD), an easy compaction technique, make it accessible to enhance tendon-bone healing in the clinic. RD and BD synergistically promote tendon-bone healing by improving peritunnel bone and preventing BTE in femurs. Controlled laboratory study. In total, 96 New Zealand White rabbits underwent ACLR. The semitendinosus tendon was freed before medial parapatellar arthrotomy. After the native ACL was transected, bone tunnels were prepared through the footprint of the native ACL. All animals were randomly assigned to 1 of 4 groups according to different tunnel preparation methods: group 1 (irrigation after extraction drilling [ED]; control group), group 2 (irrigation after RD), group 3 (no irrigation after ED), and group 4 (no irrigation after RD). BD was harvested by irrigating tunnels and was characterized by morphology and size. The specimens underwent microarchitectural, histological, and biomechanical evaluations at 4, 8, and 12 weeks postoperatively. Micro-computed tomography demonstrated more peritunnel bone and less BTE in the femurs of group 4 compared with the other groups. Histologically, BD possessed osteogenic activity in bone tunnels postoperatively. Meanwhile, group 4 regenerated a higher amount of the tendon-bone interface and more peritunnel bone than group 1. Biomechanically, group 4 showed higher failure loads and stiffness than group 1. However, peritunnel bone loss, active osteoclasts, and significant BTE were found in the femurs of group 1 and group 3 at 12 weeks postoperatively, while no strong correlation was found between BTE and inflammatory cytokines. Scanning electron microscopy and particle size analysis suggested that BD produced by ED and RD had no difference in size. Tendon-bone healing was facilitated by the synergistic effect of RD and BD in femurs. This study provides a more accessible and effective surgical strategy to promote tendon-bone healing after ACLR by increasing peritunnel bone and preventing BTE in femurs.


An updated narrative review on the management of the most common oncological and hematological emergencies.
Oncological emergencies are defined as an acute life-threatening event in a patient with a tumor occurring as part of their complex treatment regimen or secondarily to their underlying malignancy. These events can occur at any time from the initial diagnosis of their cancer to end-stage disease. These oncological emergencies are broadly classified into four major categories; metabolic, structural, hematological and treatment-related causes; and can be encountered in any clinical setting, ranging from primary care physician and emergency department visits to a variety of subspecialty environments. This study aims to cover an in-depth review of the underlying pathogenesis, clinical presentation, and updated management protocol of most common emergencies belonging to the above-mentioned categories. An all-language literature search was conducted on 15th October 2021 and 10th March 2022, limited to 5 years on PubMed database using the following search strings: oncological emergencies, malignant spinal cord compression, febrile neutropenia, hyperviscosity syndrome, superior vena cava syndrome, immune related adverse events, tumor lysis syndrome, hypercalcemia of malignancy, corrected calcium, malignant pericardial effusion and chemotherapy extravasation.


Long non-coding RNA regulation of epithelial-mesenchymal transition in cancer metastasis.
Metastasis is a multistep process starting with the dissemination of tumor cells from a primary site and ending with secondary tumor development in an anatomically distant location. The epithelial-mesenchymal transition (EMT), a process that endows epithelial tumor cells with mesenchymal properties including reduced adhesion and increased motility, is considered a critical step driving the early phase of cancer metastasis. Although significant progress has been made in understanding the molecular characteristics of EMT, the intracellular mechanisms driving transition through the various stages of EMT remain unclear. In recent years, an increasing number of studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in tumor metastasis through modulating EMT. LncRNAs and their associated signaling networks have now emerged as new players in the induction and regulation of EMT during metastasis. Here we summarize the recent findings and characterizations of several known lncRNAs involved in the regulation of EMT. We will also discuss the potential use of these lncRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets to slow down or prevent metastatic spread of malignant tumors.


Long-term persistence of CD4(+) but rapid disappearance of CD8(+) T cells expressing an MHC class I-restricted TCR of nanomolar affinity.
Most T cells have T cell receptors (TCR) of micromolar affinity for peptide-major histocompatibility complex (MHC) ligands, but genetic engineering can generate TCRs of nanomolar affinity. The affinity of the TCR used, m33, for its cognate non-self peptide-MHC-I complex (SIYRYYGL-K(b)) is 1,000-fold higher than of the wild-type TCR 2C. The affinity of m33 for the self-peptide dEV-8 on K(b) is only twofold higher. Mouse CD8(+) T cells transduced with an m33-encoding retrovirus showed binding of SIY-K(b) and potent function in vitro, but in vivo these T cells disappeared within hours after transfer into syngeneic hosts without causing graft-versus-host disease (GVHD). Accordingly, in cases where such CD8-dependent self-reactivity might occur in human adoptive T cell therapies, our results show that a peripheral T-cell deletion mechanism could operate to avoid reactions with the host. In contrast to CD8(+) T cells, we show that CD4(+) T cells expressing m33 survived for months in vivo. Furthermore, the m33-transduced CD4(+) T cells were able to mediate antigen-specific rejection of 6-day-old tumors. Together, we show that CD8(+) T cell expressing a MHC class I-restricted high-affinity TCR were rapidly deleted whereas CD4(+) T cells expressing the same TCR survived and provided function while being directed against a class I-restricted antigen.


Dopamine-stimulated cyclic AMP and binding of [3H] dopamine in acini from dog pancreas.
Dispersed acini from dog pancreas were used to examine the ability of dopamine to increase cyclic AMP cellular content and the binding of [3H] dopamine. Cyclic AMP accumulation caused by dopamine was detected at 1.10(-8) M and was half-maximal at 7.9 +/- 3.4 10(-7) M. The increase at 1.10(-5) M, (7.5-fold) was equal to the half-maximal increase caused by secretin at 1.10(-9) M. Haloperidol, a dopaminergic receptor antagonist inhibited cyclic AMP accumulation caused by dopamine. The IC50 value for haloperidol, calculated from the inhibition of cyclic AMP increase caused by 1.10(-5) M dopamine was 2.3 +/- 0.9.10(-6) M. Haloperidol did not alter basal or secretin-stimulated cyclic AMP content. [3H] Dopamine binding was studied on the same batch of cells as cyclic AMP accumulation. At 37 degrees C, it was rapid, reversible, saturable and stereospecific. The Kd value for high affinity binding sites was 0.43 +/- 0.1.10(-7) M and 4.7 +/- 1.6.10(-7) M for low affinity binding sites. The concentration of drugs necessary to inhibit specific binding of dopamine by 50% was 1.2 +/- 0.4.10(-7) M epinine, 4.1 +/- 1.8.10(-6) M fluphenazine, 8.0 +/- 1.6.10(-6) M haloperidol, 4.2 +/- 1.2.10(-6) M cis-flupenthixol, 2.7 +/- 4.0.10(-5) M trans-flupenthixol, less than 1.10(-5) M apomorphine, sulpiride, naloxone and isoproterenol.


Horseradish peroxidase: a tool for study of the neuroendocrine cell and other peptide-secreting cells.
The versatility of horseradish peroxidase is its usefulness both as an antigenic marker and as a probe molecule. We have demonstrated in the neuroendocrine cell that an HRP-bound antibody offers a high order of resolution for determining in which cellular compartment an antigen is located and where it is not. When native peroxidase is applied as an intracellular probe, it labels organelles associated with endocytosis in retrograde axonal transport and with the lysosomal system in both retrograde and orthograde axonal transport. The investigation that remains is the application of lectin-bound HRP to determine the pathways of membrane flow at the time when the neuroendocrine cell is stimulated to synthesize, transport, and secrete its peptide. For example, we are interested to know (1) whether internalized axon terminal membrane tagged with wheat germ agglutinin-HRP is channeled to all Golgi saccules engaged in the production of secretory granules in salt stimulated supraoptic neurons; and (2) if internalized cell membrane of the supraoptic cell body is tagged with wheat germ agglutinin-HRP and channeled to GERL, will this membrane be transferred from GERL to secretory granules, lysosomes in the cell body and axon, the axonal endoplasmic reticulum, and to autophagic/crinophagic vacuoles in axon terminals of salt-stressed supraoptic neurons? These additional studies should provide a more comprehensive, morphological picture of membrane flow in a neuroendocrine cell that is responding to the metabolic demands placed upon it.


Effects of below- and aboveground competition from the vines Lonicera japonica and Parthenocissus quinquefolia on the growth of the tree host Liquidambar styraciflua.
Detrimental effects of vines on tree growth in successional environments have been frequently reported. Little is known, however, about the relative importance of below and aboveground competition from vines on tree growth. The objective of this study was to quantify and compare the growth responses of Liquidambar styraciflua saplings to below and/or aboveground competition with the exotic evergreen vine, Lonicera japonica (Japanese honeysuckle), and the native deciduous vine, Parthenocissus quinquefolia (Virginia creeper). Soil trenching and/or vine-trellising were used to control the type of vine competition experienced by trees. Comparisons among untrenched treatments tested for effects of belowground competition. Comparisons among trenched treatments tested for effects of aboveground competition. After two growing seasons, Lonicera japonica had a greater effect on the growth of L. styraciflua than did P. quinquefolia. This effect was largely due to root competition, as canopy competition only had a negative effect on tree growth when it occurred in combination with root competition. Leaf expansion was consistently and similarly affected by all treatments which involved belowground competition.


Intensive Care Unit-acquired Weakness: A Frequent but Under-recognized Threat.
How to cite this article: Sapra H. Intensive Care Unit-acquiredWeakness: A Frequent but Under-recognized Threat. Indian J Crit Care Med 2021;25(9):969-971.


In vivo targeting of ERG potassium channels in mice and dogs by a positron-emitting analogue of fluoroclofilium.
The antiarrhythmic clofilium is an efficient blocker of hERG1 potassium channels that are strongly expressed in the heart. Therefore, derivatives of clofilium that emit positrons might be useful tools for monitoring hERG1 channels in vivo. Fluoro- clofilium (F-clofilium) was synthesized and its channel-blocking properties were determined for hERG1 and hEAG1 channels expressed in HEK?293 cells and in Xenopus oocytes. When applied extracellularly in the whole-cell patch-clamp configuration, F-cloflium exhibited a slower onset of block when compared with clofilium, presumably owing to its lower membrane permeability. When applied in the inside-out configuration at the intracellular membrane side, it blocked hEAG1 channels almost as efficiently as clofilium (IC50 1.37 nM and 0.83 nM, respectively). Similar results were obtained for hERG1, showing F-clofilium is a potent hERG1 and hEAG1 channel blocker once it has reached the intracellularly accessible target site at the channel. Using the (18)F-labeled analog we studied the in vivo binding and distribution of F-clofilium in mice and a dog. Greatest activity was found in kidneys and bones. A small but significant enrichment of activity in the dog myocardium known for its expression of cERG1 channels allowed to depict the myocardium of a living dog by PET. Thus, F-clofilium is a useful tool for imaging hERG channels in living organisms.


Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling.
The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology. EGFR is activated by ligand binding, triggering receptor dimerization, activation of kinase activity, and intracellular signaling. EGFR is transiently confined within various plasma membrane nanodomains, yet how this may contribute to regulation of EGFR ligand binding is poorly understood. To resolve how EGFR nanoscale compartmentalization gates ligand binding, we developed single-particle tracking methods to track the mobility of ligand-bound and total EGFR, in combination with modeling of EGFR ligand binding. In comparison to unliganded EGFR, ligand-bound EGFR is more confined and distinctly regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurs preferentially in tetraspanin nanodomains, and disruption of tetraspanin nanodomains impairs EGFR ligand binding and alters the conformation of the receptor's ectodomain. We thus reveal a mechanism by which EGFR confinement within tetraspanin nanodomains regulates receptor signaling at the level of ligand binding.


Characteristics of difficult-to-place youth in state custody: a profile of the Exceptional Care Pilot Project population.
This study examines the characteristics of Texas youth designated as 'most difficult to place' recipients of service under the "Exceptional Care Pilot Project" (N = 46). Findings include, among others, high levels of comorbid psychiatric disturbance (> 3 diagnostic groupings), physical (78.3%) and sexual (88%) maltreatment, and placement breakdowns (m = 4.8 therapeutic placements). This initial profile of the population provides a base for helping other states identify and plan for the needs of their most troubled youth.


Surface Patterning for the Control of Receptor Clustering and Molecular Forces of Integrin-Mediated Adhesions.
Surface nanopatterning allows for the creation of spatially controlled binding sites for extracellular matrix ligands and the modulation of receptor binding sites. Here we describe the preparation of gold nanopatterned substrates using diblock micellar nanolithography to immobilize integrin ligands at defined spacing and combined with molecular tension sensors to measure molecular forces as function of integrin lateral clustering.


Spatial distribution of soil nutrients and ephemeral plants underneath and outside the canopy of Porlieria chilensis shrubs (Zygophyllaceae) in arid coastal Chile.
Soil nutrients and density and biomass of annual plants underneath and outside the canopy of Porlieria chilensis shrubs were measured at the end of the growing season in a protected arid coastal site in Chile. Levels of soil nitrogen, phosphorus and organic matter were significantly higher underneath than outside the canopies of shrubs. Almost 4 times as many plants occurred outside than underneath shrubs, but no significant differences in total aboveground biomass were found. Several species had higher densities and/or biomass outside rather than underneath shrubs, whereas others showed the oppsite trend. Species richness was lower underneath P. chilensis canopy. The spatial microdistribution of ephemeral species may be explained by differential water and nutrient requirements. Comparison of the patterns observed in our protected site versus surrounding unprotected areas supports the generalization that man, by removing shrubs and trees, has changed a previous heterogeneous spatial distribution of nutrients to a more homogenous one.


Experiences of genetic counselors in referring young and metastatic breast cancer patients to support services: A needs assessment.
Conduct a needs assessment to explore the experiences, barriers, and needs of genetic counselors (GCs), who counsel and refer young and metastatic breast cancer (BC) patients to support services, in order to develop resources to address any noticeable gaps. GCs providing care to BC patients were eligible to complete the survey. Support services were defined as resources to address patient-centered healthcare, emotional, and quality-of-life needs. Most participants (n = 117) reported familiarity with cancer prevention services (93%); fewer were familiar with services secondary to a BC diagnosis (e.g., fatigue=16% and sexual health=24%). The volume of GCs indicating familiarity with support services increased significantly as work experience increased for seven services. Many (>50%) never referred patients to most (9/12) support services, excluding cancer prevention, mental health, and financial issues. Open-ended responses highlighted that GCs considered referrals to be outside their scope of practice or that healthcare systems prevent GCs from making referrals. GCs may benefit from curated resources and materials, especially for support services secondary to a BC diagnosis, to better support their patients. Collaboration of GCs with other health professionals through integrative care programs may decrease burdens to accessing support services.


High-content analysis of α-synuclein aggregation and cell death in a cellular model of Parkinson's disease.
Alpha-synuclein (α-SYN) aggregates represent a key feature of Parkinson's disease, but the exact relationship between α-SYN aggregation and neurodegeneration remains incompletely understood. Therefore, the availability of a cellular assay that allows medium-throughput analysis of α-SYN-linked pathology will be of great value for studying the aggregation process and for advancing α-SYN-based therapies. Here we describe a high-content neuronal cell assay that simultaneously measures oxidative stress-induced α-SYN aggregation and apoptosis. We optimized an automated and reproducible assay to quantify both α-SYN aggregation and cell death in human SH-SY5Y neuroblastoma cells. Quantification of α-SYN aggregates in cells has typically relied on manual imaging and counting or cell-free assays, which are time consuming and do not allow a concurrent analysis of cell viability. Our high-content analysis method for quantification of α-SYN aggregation allows simultaneous measurements of multiple cell parameters at a single-cell level in a fast, objective and automated manner. The presented analysis approach offers a rapid, objective and multiparametric approach for the screening of compounds and genes that might alter α-SYN aggregation and/or toxicity.


Synthesis, cellular uptake and structure-activity relationships for potent cytotoxic trichloridoiridium(III) polypyridyl complexes.
The complexes fac-[IrCl(3)(DMSO)(pp)] 1a-5a may be prepared by stepwise reaction of IrCl(3) x 3H(2)O with the appropriate polypyridyl ligand (pp=bpy, phen, dpq, dppz, dppn) and DMSO in CH(3)OH solution in the dark. The fac isomers of 1a-5a are stable in light-protected CD(2)Cl(2) solution but, with the exception of 5a, isomerize rapidly to a mixture of the fac and mer isomers in the presence of light. In contrast, solutions of the fac isomers in the polar solvents D(2)O and CD(3)OD are stable under such conditions. The isomer mer-[IrCl(3)(DMSO-kappa S)(phen)] 2b was, however, isolated by slow evaporation of an H(2)O/CH(3)OH solution of 2a and characterized by X-ray structural analysis. UV/Vis and CD studies of the interaction of 1a-5a with calf thymus DNA are in accordance with an effective absence of intercalation. (1)H NMR studies indicate that the complexes react slowly with compounds containing soft S donor atoms (e. g. N-acetylmethionine) but do not react with the guanine base of 5'-GMP(2-). The complexes 2a-5a are potent in vitro cytotoxic agents toward the human cell lines MCF-7 and HT-29 and their IC(50) values are dependent on the size of the polypyridyl ligand in the order phen, dpq>dppz>dppn. For instance IC(50) values of 5.5 (0.9), 0.8 (0.3) and 0.21 (0.11)microM were established for 3a-5a against MCF-7 cells and 6.1 (0.7), 1.5 (0.2) and 1.3 (0.4)microM against HT-29 cells. These values correlate with the cellular uptake efficiency which, on exposure to 10 microM solutions, reaches its highest levels (19.3(0.8) and 37.4(8.9) ng Ir/mg protein for MCF-7 and HT-29, respectively) for the dppn compound 5a.


Age at onset, childhood psychopathology, and 2-year outcome in psychotic bipolar disorder.
The relationships of age at onset and childhood psychopathology to 2-year clinical and functional outcomes in first-admission patients with bipolar I disorder were examined. Patients with bipolar I disorder (N=123) presenting with psychotic symptoms were followed over a 2-year period. Age at onset was stratified into <19 and >or=19 years. Childhood psychopathology was categorized as behavior problems, other psychopathology, and none. Functional and clinical outcomes were rated with standard measures. Childhood psychopathology and age at onset were independently related to poorer functional and clinical outcome. In the multivariate models that included psychopathology, age at onset, sex, and education, early age at onset was related to incomplete remission, and childhood psychopathology was related to functional outcome. Childhood psychopathology and age at onset contribute independently to outcomes of bipolar disorder. Childhood psychopathology is a much stronger predictor of functioning than age at onset.


Ovarian volume is more closely related to the different manifestations of polycystic ovary syndrome than follicle number per ovary.
Polycystic ovary (PCO), a diagnostic component of polycystic ovary syndrome (PCOS), requires either an ovarian volume (OV) criterion or a follicle number per ovary (FNPO) criterion. This study investigated the association of OV and FNPO criteria with various manifestations of PCOS. This cross-sectional study was conducted at a university hospital among 100 patients newly diagnosed with PCOS (according to the revised Rotterdam criteria). Fasting blood samples were collected to measure glucose, total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), lipid, insulin, and hemoglobin A1c levels. An oral glucose tolerance test was performed. Transabdominal or transvaginal ultrasound of the ovaries was done, depending on patients' marital status. All investigations were conducted in the follicular phase of the menstrual cycle. OV >10 mL and/or FNPO ≥12 indicated PCO. A homeostasis model assessment of insulin resistance (IR) value ≥2.6 indicated IR, and metabolic syndrome (MS) was defined according to the international harmonization criteria. Seventy-six participants fulfilled the OV criterion, 70 fulfilled the FNPO criterion, and 89 overall had PCO. Both maximum OV and mean OV had a significant correlation with TT levels (<italic>r</italic>=0.239, <italic>p</italic>=0.017 and <italic>r</italic>=0.280, <italic>p</italic>=0.005, respectively) and the LH/FSH ratio (<italic>r</italic>=0.212, <italic>p</italic>=0.034 and <italic>r</italic>=0.200, <italic>p</italic>=0.047, respectively). Mean OV also had a significant correlation with fasting insulin levels (<italic>r</italic>=0.210, <italic>p</italic>=0.036). Multivariate binary logistic regression analysis showed that IR (odds ratio [OR], 9.429; 95% confidence interval [CI], 1.701 to 52.271; <italic>p</italic>=0.010) and MS (OR, 7.952; 95% CI, 1.821 to 34.731; <italic>p</italic>=0.006) had significant predictive associations with OV alone, even after adjustment for age and body mass index. OV may be more closely related to the androgenic and metabolic characteristics of PCOS than FNPO.


S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5.
Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD. RNA and protein levels of SEPTIN5 showed a significant decrease in human temporal cortex in relation to the increasing degree of AD-related neurofibrillary pathology. Conversely, an increase in the phosphorylation of the functionally relevant SEPTIN5 phosphorylation site S327 was observed already in the early phases of AD-related neurofibrillary pathology, but not in the cerebrospinal fluid of individuals fulfilling the criteria for mild cognitive impairment due to AD. According to the mechanistic assessments, a link between SEPTIN5 S327 phosphorylation status and the effects of SEPTIN5 on amyloid precursor protein processing and markers of autophagy was discovered in mouse primary cortical neurons transduced with lentiviral constructs encoding wild type SEPTIN5 or SEPTIN5 phosphomutants (S327A and S327D). C57BL/6 J mice intrahippocampally injected with lentiviral wild type SEPTIN5 or phosphomutant constructs did not show changes in cognitive performance after five to six weeks from the start of injections. However, SEPTIN5 S327 phosphorylation status was linked to changes in short-term synaptic plasticity ex vivo at the CA3-CA1 synapse. Collectively, these data suggest that SEPTIN5 and its S327 phosphorylation status play a pivotal role in several cellular processes relevant for AD.


Colorectal cancer with synchronous unresectable liver metastases: resecting the primary tumor improves survival.
The optimal treatment strategy of patients affected by colorectal cancer (CRC) with synchronous unresectable liver metastases (SULM) is at present undefined. It is not known if a palliative primary tumor resection followed by chemotherapy could have a survival benefit compared to upfront chemotherapy (CT). The aim of the study is to analyze the safety and effectiveness of both therapeutic strategies in a group of patients treated at one institution. A prospectively collected database was queried for patients affected by colorectal cancer with synchronous unresectable liver metastases between January 2004 and December 2018, defining and comparing 2 groups: patients treated by chemotherapy alone (group 1) vs patients who underwent primary tumor resection with or without a first line chemotherapy (group 2). The primary end point was Overall Survival (OS), estimated by the Kaplan-Meier method. One hundred sixty-seven patients were included: 52 in group 1 and 115 in group 2, median follow-up 48 months (range 25-126). A difference of 14 months in overall survival was observed between group 2 compared to group 1 (28 vs 14 months respectively; p < 0.001). Furthermore, overall survival increased in patients who underwent liver metastases resection (p < 0.001) or percutaneous radiofrequency ablation after surgery (p < 0.001). With the limits of a retrospective analysis, the study shows that surgical resection of the primary tumor has a significant impact on survival compared to chemotherapy alone. Randomized controlled trials are needed to confirm these data.


The development of a framework of entrustable professional activities for the intern year in Ireland.
Entrustable Professional Activities (EPAs) are units of professional practice that capture essential competencies in which trainees must become proficient before undertaking them independently. EPAs provide supervisors with a solid justification for delegating an activity to trainees. This study aimed to develop and ensure face validity of a set of EPAs for junior doctors in the first year of clinical practice in the Republic of Ireland. An iterative eight stage consensus building process was used to develop the set of EPAs. This process was based on international best practice recommendations for EPA development. A series of surveys and workshops with stakeholders was used to develop a framework of EPAs and associated competencies. An external stakeholder consultation survey was then conducted by the Irish Medical Council. The framework of EPAs was then benchmarked against the 13 core EPAs developed by the Association of American Medical Colleges (AAMC). A framework of seven EPAs, and associated competencies resulted from this study. These EPAs address all core activities that junior doctors should be readily entrusted with at the end of the intern year, which is the first year of clinical practice in the Republic of Ireland. Each EPA contains a series of defined competencies. The final EPAs were found to be comparable to the AAMC core EPAs for entering residency. A framework of EPAs for interns in Ireland that are appropriate for the intern year has been developed by key stakeholders. The implementation of the EPAs in practice is the next step, and is likely to result in an improved intern training process and increased patient safety.


One-pot synthesis of antibacterial chitosan/silver bio-nanocomposite hydrogel beads as drug delivery systems.
Silver nanoparticles were synthesized in situ during the formation of physically crosslinked chitosan hydrogel beads using sodium tripolyphosphate as the crosslinker. The aim of the study was to investigate whether these nanocomposite beads have the potential to be used in drug delivery applications. The formation of silver nanoparticles (AgNPs) in the hydrogels was confirmed by X-ray diffraction and scanning electron microscopy studies. Furthermore, the antibacterial and swelling properties of the beads were studied. The nanocomposite hydrogels demonstrated good antibacterial effects against Escherichia coli and Staphylococcus aureus bacteria. AgNPs caused an increase in the swelling capacity of the beads. In vitro drug release test was carried out to prove the effectiveness of this novel type of nanocomposite beads as a controlled drug delivery system. Prolonged and more controlled drug releases were observed for AgNPs containing chitosan beads, which increased by the increase in AgNPs content.


The ethnopharmacological literature: An analysis of the scientific landscape.
The research into bioactive natural products originating from medicinal plants, fungi and other organisms has a long history, accumulating abundant and diverse publications. However no quantitative literature analysis has been conducted so far. Here we analyze the bibliometric data of ethnopharmacology literature and relate the semantic content to the publication and citation data so that the major research themes, contributors, and journals of different time periods could be identified and evaluated. Web of Science (WoS) was searched to identify relevant publications. The Analyze function of WoS and bibliometric software (VOSviewer) were utilized to perform the analyses. Until the end of November 2018, 59,576 publications -linked to 'ethnopharmacology' indexed by WoS, published since 1958 in more than 5600 journals, and contributed by over 20,600 institutions located in more than 200 countries/regions, were identified. The papers were published under four dominating WoS categories, namely pharmacology/pharmacy (34.4%), plant sciences (28.6%), medicinal chemistry (25.3%), and integrative complementary medicine (20.6%). India (14.6%) and China (13.2%) were dominating the publication space. The United States and Brazil also had more than 8.0% contribution each. The rest of the top ten countries/regions were mainly from Asia. There were around ten-fold more original articles (84.6%) than reviews (8.4%). Ethnopharmacological research has a consistent focus on food and plant sciences, (bio)chemistry, complementary medicine and pharmacology, with a more limited scientific acceptance in the socio-cultural sciences. Dynamic global contributions have been shifting from developed countries to economically and scientifically emerging countries in Asia, South America and the Middle East. Research on recording medicinal plant species used by traditional medicine continues, but the evaluation of specific properties or treatment effects of extracts and compounds has increased enormously. Moreover increasing attention is paid to some widely distributed natural products, such as curcumin, quercetin, and rutin.


Comparison of the Differences in Survival Rates between the 7th and 8th Editions of the AJCC TNM Staging System for Gastric Adenocarcinoma: a Single-Institution Study of 5,507 Patients in Korea.
The aims of this study were to compare the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manuals on tumor, node, and metastasis (TNM) staging systems and to evaluate whether the 8th edition represents a better refinement of the 7th staging system, when applied for the classification of gastric cancers. A total of 5,507 gastric cancer patients, who underwent treatment from January 1989 to December 2013 at a single institute, were included. We compared patient survival rates across the disease groups classified according to the 7th and 8th editions of the AJCC TNM staging systems. Stage migration was observed in 6.4% (n=355) of the patients. Of these, 3.5% (n=192) and 2.9% (n=158) of patients showed a higher stage and lower stage, respectively. According to the 8th edition of the AJCC TNM staging criteria, the 5-year overall survival rates of the patients with stage IIIB and IIIC showed a significant difference (40.8% vs. 20.2%, P<0.001) whereas no significant differences in the 5-year overall survival rates were observed according to the 7th edition criteria (37.6% vs. 33.2%, P=0.381). Restaging stage III cancers according to the 8th edition of the AJCC TNM classification criteria improved survival rate discrimination, particularly, in institutes where the stage III patients were not distinctly categorized.


Sonohysterography.
Sonohysterography can distinguish focal from diffuse pathology reliably and has become a crucial imaging test in the triage of PMB and in premenopausal patients with dysfunctional uterine bleeding or infertility. Polyps and submucosal fibroids are the most common focal findings during SHG. In postmenopausal patients, detection and accurate localization of findings, rather than lesion characterization, are the primary goals of the procedure. Most, if not all, focal lesions in this patient population require tissue diagnosis, even when the imaging features suggest benign lesions.


Physiological roles and transport mechanisms of boron: perspectives from plants.
Boron, an orphan of the periodic table of the elements, is unique not only in its chemical properties but also in its roles in biology. Its requirement in plants was described more than 80 years ago. Understandings of the molecular basis of the requirement and transport have been advanced greatly in the last decade. This article reviews recent findings of boron function and transport in plants and discusses possible implication to other organisms including humans.


A multicenter anaphylaxis registry in Korea: Clinical characteristics and acute treatment details from infants to older adults.
Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged <18 years. In children and adolescents, foods (84.8%) were the most common cause of anaphylaxis, followed by drugs (7.2%); in adults, drugs (58.3%) were the most common cause, followed by foods (28.3%) and insect venom (8.1%). The onset time was ≤10 min in 37.6% of patients. Among the 351 cases registered via the emergency department (ED) of participating hospitals, epinephrine was administered to 63.8% of patients. Among those receiving epinephrine in the ED, 13.8% required 2 or more epinephrine shots. Severe anaphylaxis accounted for 23.5% cases (38.1% in adults; 13.7% in children); patients with drug and insect venom-induced anaphylaxis had higher rates of severe anaphylaxis. This multicenter registry provides data on anaphylaxis for all age groups for the first time in Asia. The major causes and severity of anaphylaxis were remarkably different according to age group, and the acute treatment features of anaphylaxis in the EDs were examined in detail.


ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of tumor.
This study reports a tumor-specific ROS-responsive nanoplatform capable of the combination of nitric oxide (NO)-based gas therapy and sensitized photodynamic therapy (PDT). The nanoplatform is constructed on porous coordination network (PCN), which contains NO donor L-Arg and is concurrently coated with cancer cell membrane (L-Arg@PCN@Mem). Under near infrared light (NIR) irradiation, L-Arg@PCN@Mem produces plenty of reactive oxygen species (ROS) directly for PDT therapy, while a part of ROS take the role of oxidative to converse L-Arg into NO for combined gas therapy. The results indicate that the transformation of ROS to NO can enhance PDT efficacy in hypoxic tumors owing to the ability of NO in freely diffusing into deep hypoxic tumor site. Moreover, homologous targeting function originated from the coating of cancer cells membrane further improves the tumor treatment effect owing to the biotargeting toward homologous tumors. This L-Arg@PCN@Mem nanoplatform provides a new therapy paradigm of overcoming the hypoxia barrier of tumor therapy, and holds great potential for the treatment of tumor and NO-related diseases.