Cognitive Processing Speed across the Lifespan: Beyond the Influence of Motor Speed.
Traditional neuropsychological measurement of cognitive processing speed with tasks such as the Symbol Search and Coding subsets of the WAIS-IV, consistently show decline with advancing age. This is potentially problematic with populations where deficits in motor performance are expected, i.e., in aging or stroke populations. Thus, the aim of the current study was to explore the contribution of hand motor speed to traditional paper-and-pencil measures of processing speed and to a simple computer-customized non-motor perception decision task, the Inspection Time (IT) task. Participants were 67 young university students aged between 18 and 29 (59 females), and 40 older adults aged between 40 and 81 (31 females) primarily with a similar education profile. As expected, results indicated that age group differences were highly significant on the motor dexterity, Symbol Search and Coding tasks. However, no significant differences or correlations were seen between age groups and the simple visual perception IT task. Furthermore, controlling for motor dexterity did not remove significant age-group differences on the paper-and-pencil measures. This demonstrates that although much of past research into cognitive decline with age is confounded by use of motor reaction times as the operational measure, significant age differences in cognitive processing also exist on more complex tasks. The implications of the results are crucial in the realm of aging research, and caution against the use of traditional WAIS tasks with a clinical population where motor speed may be compromised, as in stroke.


Accuracy of conversion formula for effect sizes: A Monte Carlo simulation.
In meta-analysis, effect sizes often need to be converted into a common metric. For this purpose conversion formulas have been constructed; some are exact, others are approximations whose accuracy has not yet been systematically tested. We performed Monte Carlo simulations where samples with pre-specified population correlations between the x and y-variables were drawn from a normally distributed population. A number of commonly used effect size measures and statistics were calculated from each sample. Using several available conversion formula these statistics were converted into Pearson r and Cohen's d and compared to r and d calculated directly from the original data. Converted values were systematically lower than the directly calculated values. While conversions to d were quite accurate, some of the conversions to r resulted in large biases. These systematic errors can in most cases be adjusted for by simply multiplying the converted values with a corresponding correction factor.


Continuous blood pressure measurement in rats with aortic baroreceptor deafferentation.
The purpose of this study was to determine if once-daily arterial pressure measurements are a reliable estimate of actual time-averaged arterial pressure in neurogenic hypertensive rats. Male rats were subjected to either aortic baroreceptor deafferentation (ABD, n = 10) or sham operation (SO, n = 10). One to 3 mo later, arterial pressure (AP) was recorded from a chronic indwelling catheter in each rat for 72 continuous hours. Subsequently, AP was determined once a day (10- to 30-min recording periods) in each rat for an additional 3 consecutive days. Continuous recording yielded an average mean arterial pressure (MAP) of 104 +/- 2 mmHg in SO rats and an average mean MAP of 120 +/- 3 mmHg in ABD rats. Standard deviation of MAP measured every 5 min for 24 consecutive hours (as an index of pressure lability) was 8.0 +/- 0.4 mmHg in SO rats and 14.4 +/- 1.3 mmHg in ABD rats. Both of the above differences were statistically significant (P less than 0.05). The average MAP from daily measurements in the same rats was 107 +/- 3 mmHg in SO rats and 124 +/- 3 mmHg in ABD rats. Average pressure values were not statistically different for the two measurement techniques in either group of rats. Overall, there existed a significant correlation (r = 0.64, P less than 0.01) between MAP measured continuously and daily in the 20 rats studied. We conclude that daily direct measurement of MAP in conscious ABD rats yields a satisfactory estimate of actual time-averaged MAP in these rats despite their markedly increased MAP lability.


Synthesis of Cs-symmetrical C60 tetra-adducts via reactions of C60Cl6 with CH-acids and enol silyl ester.
Here we report the synthesis of novel fullerene derivatives with attached aliphatic residues based on the previously unknown reactions of chlorofullerene C60Cl6 with CH-acids and silyl enol ether.


The cancer multi-disciplinary team from the coordinators' perspective: results from a national survey in the UK.
The MDT-Coordinators' role is relatively new, and as such it is evolving. What is apparent is that the coordinator's work is pivotal to the effectiveness and efficiency of an MDT. This study aimed to assess the views and needs of MDT-coordinators. Views of MDT-coordinators were evaluated through an online survey that covered their current practice and role, MDT chairing, opinions on how to improve MDT meetings, and coordinators' educational/training needs. 265 coordinators responded to the survey. More than one third of the respondents felt that the job plan does not reflect their actual duties. It was reported that medical members of the MDT always contribute to case discussions. 66.9% of the respondents reported that the MDTs are chaired by Surgeons. The majority reported having training on data management and IT skills but more than 50% reported that they felt further training is needed in areas of Oncology, Anatomy and physiology, audit and research, peer-review, and leadership skills. MDT-Coordinators' role is central to the care of cancer patients. The study reveals areas of training requirements that remain unmet. Improving the resources and training available to MDT-coordinators can give them an opportunity to develop the required additional skills and contribute to improved MDT performance and ultimately cancer care. Finally, this study looks forward to the impact of the recent launch of a new e-learning training programme for MDT coordinators and discusses implications for future research.


A general method for assaying homo- and hetero-transglycanase activities that act on plant cell-wall polysaccharides.
Transglycanases (endotransglycosylases) cleave a polysaccharide (donor-substrate) in mid-chain, and then transfer a portion onto another poly- or oligosaccharide (acceptor-substrate). Such enzymes contribute to plant cell-wall assembly and/or re-structuring. We sought a general method for revealing novel homo- and hetero-transglycanases, applicable to diverse polysaccharides and oligosaccharides, separating transglycanase-generated (3)H-polysaccharides from unreacted (3)H-oligosaccharides--the former immobilized (on filter-paper, silica-gel or glass-fiber), the latter eluted. On filter-paper, certain polysaccharides [e.g. (1→3, 1→4)-β-D-glucans] remained satisfactorily adsorbed when water-washed; others (e.g. pectins) were partially lost. Many oligosaccharides (e.g. arabinan-, galactan-, xyloglucan-based) were successfully eluted in appropriate solvents, but others (e.g. [(3)H]xylohexaitol, [(3)H]mannohexaitol [(3)H]cellohexaitol) remained immobile. On silica-gel, all (3)H-oligosaccharides left an immobile 'ghost' spot (contaminating any (3)H-polysaccharides), which was diminished but not prevented by additives e.g. sucrose or Triton X-100. The best stratum was glass-fiber (GF), onto which the reaction-mixture was dried then washed in 75% ethanol. Washing led to minimal loss or lateral migration of (3)H-polysaccharides if conducted by slow percolation of acidified ethanol. The effectiveness of GF-blotting was well demonstrated for Chara vulgaris trans-β-mannanase. In conclusion, our novel GF-blotting technique efficiently frees transglycanase-generated (3)H-polysaccharides from unreacted (3)H-oligosaccharides, enabling high-throughput screening of multiple postulated transglycanase activities utilising chemically diverse donor- and acceptor-substrates.


Prospective diagnostic accuracy assessment of the HemosIL HS D-dimer to exclude pulmonary embolism in emergency department patients.
Chest pain and shortness of breath are among the most common symptoms requiring immediate evaluation. Testing for pulmonary embolism (PE) has become easier and widespread due to D-dimer blood tests. Safe use of these tests is only possible if sensitivity is high and they are used in non-high probability patients. We evaluated diagnostic performance of the HemosIL HS D-dimer, which despite FDA approval in 2005, has been minimally reported in prospective standard clinical care. We used a prospective observational study design to follow patients in a single center with the HemosIL HS ordered for symptoms of possible PE with positive test result if >243 ng/ml. The outcome was PE or deep venous thrombosis (DVT) at the time of presentation or subsequent 45 days determined by structured evaluation of imaging tests, phone, or medical record follow-up in all patients. 529 patients received a D-dimer and 4.7% were ultimately diagnosed with PE or DVT. The sensitivity of the HemosIL HS was 96.0% (95% CI; 79.6 to 99.9%) specificity was 65.7% (95% CI; 61.4 to 69.8%) and likelihood ratio negative was 0.06 (95% CI; 0.01 to 0.42). The probability of PE in patients with a negative D-dimer was 1/332 or 0.3% (95% CI; 0.01% to 1.67%). The receiver operator curve had an area under the curve of 0.87 and supported the current cut-point as optimal. The HemosIL HS D-dimer had high sensitivity, very low negative post-test probability and is useful in excluding PE in the acute care setting.


Measuring unfolding of proteins in the presence of denaturant using fluorescence correlation spectroscopy.
IFABP is a small (15 kDa) protein consisting mostly of antiparallel beta-strands that surround a large cavity into which ligands bind. We have previously used FCS to show that the native protein, labeled with fluorescein, exhibits dynamic fluctuation with a relaxation time of 35 micros. Here we report the use of FCS to study the unfolding of the protein induced by guanidine hydrochloride. Although the application of this technique to measure diffusion coefficients and molecular dynamics is straightforward, the FCS results need to be corrected for both viscosity and refractive index changes as the guanidine hydrochloride concentration increases. We present here a detailed study of the effects of viscosity and refractive index of guanidine hydrochloride solutions to calibrate FCS data. After correction, the increase in the diffusion time of IFABP corresponds well with the unfolding transition monitored by far ultraviolet circular dichroism. We also show that the magnitude of the 35 micros phase, reflecting the conformational fluctuation in the native state, decreases sharply as the concentration of denaturant increases and the protein unfolds. Although FCS experiments indicate that the unfolded state at pH 2 is rather compact and native-like, the radius in the presence of guanidine hydrochloride falls well within the range expected for a random coil.


Pleasure or Health? The Role of Mental Simulation in Desire and Food Choices.
Many times, desire possesses us and impedes us from making healthier food choices. From a grounded cognition perspective, we investigated the role of two types of mental simulation (process and outcome) in desire and food choice to understand the processes that modulate them and find strategies that encourage healthier food choices. In addition to these explicit measures, we used two implicit methods to measure approach-avoidance tendencies and visual attention. Our results showed that imagining the consumption of vice and virtue foods increased desire for the product imagined and seemed to favor the choice of a vice food. However, at an implicit level, the motivation to approach and avoid food products was neutral. Imagining the post-consumption of a vice food decreased desire for the imagined food and although it tempted people at an implicit level, it made people more prone to choose a virtue food. When a vice food was imagined, attentional bias increased for all types of food regardless of the simulation. When a virtue food was imagined, there was no effect on choice, motivation nor attentional bias. In conclusion, simply imagining certain foods is a potential solution for promoting healthier and thoughtful choices.


Low-level laser irradiation promotes proliferation of cryopreserved adipose-derived stem cells.
To evaluate the effect of low-level laser irradiation on proliferation and viability of murine adipose-derived stem cells previously submitted to cryopreservation. Adipose-derived stem cells were isolated from inguinal fat pads of three mice, submitted to cryopreservation in fetal bovine serum with 10% dimethylsulfoxide for 30 days and then thawed and maintained in normal culture conditions. Culture cells were either irradiated or not (control) with an InGaAIP diode laser at zero and 48 hours, using two different energy densities (0.5 and 1.0J/cm2). Cell proliferation was evaluated by trypan blue exclusion method and MTT assay at intervals of zero, 24, 48, and 72 hours after the first laser application. Cell viability and apoptosis of previously cryopreserved cells submitted to laser therapy were evaluated by flow cytometry. The Irradiated Groups (0.5 and 1.0J/cm2) showed an increased cell proliferation (p<0.05) when compared to the Control Group, however no significant difference between the two energy densities was observed. Flow cytometry revealed a percentage of viable cells higher than 99% in all groups. Low-level laser irradiation has stimulatory effects on the proliferation of adipose-derived stem cells previously submitted to cryopreservation.


Evaluation of brain natriuretic peptide in the diagnosis of heart failure.
A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.


Physical attractiveness and reproductive success in humans: Evidence from the late 20 century United States.
Physical attractiveness has been associated with mating behavior, but its role in reproductive success of contemporary humans has received surprisingly little attention. In the Wisconsin Longitudinal Study (1244 women, 997 men born between 1937 and 1940) we examined whether attractiveness assessed from photographs taken at age ~18 predicted the number of biological children at age 53-56. In women, attractiveness predicted higher reproductive success in a nonlinear fashion, so that attractive (second highest quartile) women had 16% and very attractive (highest quartile) women 6% more children than their less attractive counterparts. In men, there was a threshold effect so that men in the lowest attractiveness quartile had 13% fewer children than others who did not differ from each other in the average number of children. These associations were partly but not completely accounted for by attractive participants' increased marriage probability. A linear regression analysis indicated relatively weak directional selection gradient for attractiveness (β=0.06 in women, β=0.07 in men). These findings indicate that physical attractiveness may be associated with reproductive success in humans living in industrialized settings.


Interaction between stimulus contrast and pre-saccadic crowding.
Objects that are briefly flashed around the time of saccades are mislocalized. Previously, robust interactions between saccadic perceptual distortions and stimulus contrast have been reported. It is also known that crowding depends on the contrast of the target and flankers. Here, we investigated how stimulus contrast and crowding interact with pre-saccadic perception. We asked observers to report the orientation of a tilted Gabor presented in the periphery, with or without four flanking vertically oriented Gabors. Observers performed the task either following a saccade or while maintaining fixation. Contrasts of the target and flankers were independently set to either high or low, with equal probability. In both the fixation and saccade conditions, the flanked conditions resulted in worse discrimination performance-the crowding effect. In the unflanked saccade trials, performance significantly decreased with target-to-saccade onset for low-contrast targets but not for high-contrast targets. In the presence of flankers, impending saccades reduced performance only for low-contrast, but not for high-contrast flankers. Interestingly, average performance in the fixation and saccade conditions was mostly similar in all contrast conditions. Moreover, the magnitude of crowding was influenced by saccades only when the target had high contrast and the flankers had low contrasts. Overall, our results are consistent with modulation of perisaccadic spatial localization by contrast and saccadic suppression, but at odds with a recent report of pre-saccadic release of crowding.


Gamma rays and bleomycin nick DNA and reverse the DNase I sensitivity of beta-globin gene chromatin in vivo.
The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA (Villeponteau et al., Cell 39:469-478, 1984). This hypothesis predicts that nicking of the DNA within any such chromosomal domain in vivo will relax the DNA and lead to loss of the special DNase I-sensitive state. Here we have tested this prediction by using gamma irradiation and bleomycin treatment to cleave DNA within intact chicken embryo erythrocytes. Both treatments cause reversal of DNase I sensitivity. Moreover, reversal occurs at approximately one nick per 150 kilobase pairs for both agents despite their entirely unrelated modes of cell penetration and DNA attack. These results suggest that the domain of DNase I sensitivity surrounding the beta-globin genes comprises 150 kilobase pairs of chromatin under torsional stress and that a single DNA nick in this region is sufficient to reverse the DNase I sensitivity throughout the entire domain.


[The role of the vitreous in the pathogenesis of age-related macular degeneration].
Age-related macular degeneration (AMD) is the main cause of severe visual decease in elderly people in the industrialised countries. AMD is a multifactorial disease with only limited therapeutic options before anti-VEGF treatment was introduced. In spite of all the progress no long-term healing is possible. Actually, the vitreous is being investigated as a possible co-factor in the pathogenesis of AMD. Numerous authors demonstrated a higher incidence of vitreoretinal adhesion in exudative AMD by considering age, genetic and environmental factors. The essential question is whether the therapeutic release of vitreoretinal adhesion could affect the development and progress of AMD. Up to now only case reports and case series have demonstrated a positive effect on disease progress. An ongoing multicentre, prospective, comparative, randomised, double-blind clinical trial with enzymatic vitreolysis is now evaluting the effect of vitreoretinal release on the progress of AMD. The results are necessary to evaluate whether vitreoretinal release is a therapeutic option for the future.


Interrupting Sitting Time in Postmenopausal Women: Protocol for the Rise for Health Randomized Controlled Trial.
Many older adults spend the majority of their waking hours sitting, which increases their risk of chronic diseases. Given the challenges that many older adults face when engaging in moderate-to-vigorous physical activity, understanding the health benefits of decreasing sitting time and increasing the number of sit-to-stand transitions is needed to address this growing public health concern. The aim of this 3-arm randomized controlled trial is to investigate how changes in sitting time and brief sit-to-stand transitions impact biomarkers of healthy aging and physical, emotional, and cognitive functioning compared with a healthy attention control arm. Sedentary and postmenopausal women (N=405) will be recruited and randomly assigned to 1 of the 3 study conditions for 3 months: healthy living attention control (Healthy Living), reduce sitting time (Reduce Sitting), and increase sit-to-stand transitions (Increase Transitions). Assessments conducted at baseline and 3 months included fasting blood draw, blood pressure, anthropometric measurements, physical functioning, cognitive testing, and 7 days of a thigh-worn accelerometer (activPAL) and a hip-worn accelerometer (ActiGraph). Blood-based biomarkers of healthy aging included those associated with glycemic control (glycated hemoglobin, fasting plasma insulin and glucose, and homeostatic model assessment of insulin resistance). Recruitment began in May 2018. The intervention is ongoing, with data collection expected to continue through the end of 2022. The Rise for Health study is designed to test whether 2 different approaches to interrupting sitting time can improve healthy aging in postmenopausal women. Results from this study may inform the development of sedentary behavior guidelines and interventions to reduce sitting time in older adults. ClinicalTrials.gov NCT03473145; https://clinicaltrials.gov/ct2/show/NCT03473145. DERR1-10.2196/28684.


Recover the food-energy-water nexus from COVID-19 under Sustainable Development Goals acceleration actions.
The interwoven relationship between food, energy, and water (FEW) is described as the FEW nexus. The COVID-19 pandemic has interrupted the FEW nexus and impeded the progress of FEW-related Sustainable Development Goals (SDGs) (SDG 2: Zero Hunger; 6: Clean Water and Sanitation; 7: Affordable and Clean Energy). We aim to find solutions to recover the FEW nexus from COVID-19. First, we discussed the challenges faced by FEW amid COVID-19. Second, we observed responses of the FEW nexus under COVID-19's interference. Finally, we proposed the solutions that guide the FEW nexus in recovery from the pandemic by mining 164 FEW-related SDG Acceleration Actions. The key solutions include 1) building or upgrading FEW facilities and infrastructure, 2) improving nature's contribution to the FEW nexus, 3) developing digital technologies, 4) innovating the source and production of FEW, and 5) promoting community production and transforming the lifestyle. Our work highlights the importance of feasible and accelerated actions that recover the FEW nexus in the post-pandemic era.


Trace DNA from insect skins: a comparison of five extraction protocols and direct PCR on chironomid pupal exuviae.
Insect skins (exuviae) are of extracellular origin and shed during moulting. The skins do not contain cells or DNA themselves, but epithelial cells and other cell-based structures might accidentally attach as they are shed. This source of trace DNA can be sufficient for PCR amplification and sequencing of target genes and aid in species identification through DNA barcoding or association of unknown life stages. Species identification is essential for biomonitoring programs, as species vary in sensitivities to environmental factors. However, it requires a DNA isolation protocol that optimizes the output of target DNA. Here, we compare the relative effectiveness of five different DNA extraction protocols and direct PCR in isolation of DNA from chironomid pupal exuviae. Chironomidae (Diptera) is a species-rich group of aquatic macroinvertebrates widely distributed in freshwater environments and considered a valuable bioindicator of water quality. Genomic DNA was extracted from 61.2% of 570 sampled pupal exuviae. There were significant differences in the methods with regard to cost, handling time, DNA quantity, PCR success, sequence success and the ability to sequence target taxa. The NucleoSpin(®) Tissue XS Kit, DNeasy(®) Blood and Tissue kit, and QuickExtract(™) DNA Extraction Solution provided the best results in isolating DNA from single pupal exuviae. Direct PCR and DTAB/CTAB methods gave poor results. While the observed differences in DNA isolation methods on trace DNA will be relevant to research that focuses on aquatic macroinvertebrate ecology, taxonomy and systematics, they should also be of interest for studies using environmental barcoding and metabarcoding of aquatic environments.


Increased resistance to oxidative stress in transgenic tobacco plants overexpressing bacterial serine acetyltransferase.
Plant expression cassettes containing the Escherichia coli cysE gene alleles (encoding SAT) were constructed. After the Agrobacterium-mediated transformation of tobacco, we identified stable transformed plants containing several-fold higher SAT activity in comparison to the control plant. Determination of non-protein thiol contents indicated two- to threefold higher cysteine and glutathione levels in some of these transgenic plants. The maximal elevation of the cysteine level was about fourfold while that of GSH was about twofold higher than in the controls. The most striking physiological consequence of the modification of sulfur metabolite levels in the transgenic plants, however, was their several-fold increased resistance to oxidative stress generated by exogenous hydrogen peroxide.


Proteolytic removal of core histone amino termini and dephosphorylation of histone H1 correlate with the formation of condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development.
During the sexual cycle in Tetrahymena, the germ-line micronucleus gives rise to new macro- and micronuclei, whereas the former somatic macronucleus ceases transcription, becomes highly condensed, and is eventually eliminated from the cell. With polyclonal antibodies specific for acetylated forms of histone H4, immunofluorescent analyses have demonstrated that transcriptionally active macronuclei stain positively at all stages of the life cycle except during conjugation, when parental macronuclei become inactive and are eliminated from the cell. In this report using affinity-purified antibodies to either the acetylated or unacetylated amino-terminal domain of H4, immunofluorescent analyses suggest that the acetylated amino-terminal tails of H4 are proteolytically removed in "old" macronuclei during this period. This suggestion was further confirmed by biochemical analysis of purified old macronuclei that revealed several polypeptides with molecular mass 1-2 kD less than that of intact core histones. These species, which are unique to old macronuclei, are not newly synthesized and fail to stain with either acetylated or unacetylated H4 antibodies. Microsequence analysis clearly shows that these polypeptides are proteolytically processed forms of core histones whose amino-terminal "tails" (varying from 13 to 21 residues) have been removed. During the same developmental period, histone H1 is dephosphorylated rapidly and completely in old macronuclei. These results strongly suggest that the developmentally regulated proteolysis of core histones and dephosphorylation of histone H1 participate in a novel pathway leading to the formation of highly condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development.


The gestural repertoire of the wild chimpanzee.
Great ape gestural communication is known to be intentional, elaborate and flexible; yet there is controversy over the best interpretation of the system and how gestures are acquired, perhaps because most studies have been made in restricted, captive settings. Here, we report the first systematic analysis of gesture in a population of wild chimpanzees. Over 266 days of observation, we recorded 4,397 cases of intentional gesture use in the Sonso community, Budongo, Uganda. We describe 66 distinct gesture types: this estimate appears close to asymptote, and the Sonso repertoire includes most gestures described informally at other sites. Differences in repertoire were noted between individuals and age classes, but in both cases, the measured repertoire size was predicted by the time subjects were observed gesturing. No idiosyncratic usages were found, i.e. no gesture type was used only by one individual. No support was found for the idea that gestures are acquired by 'ontogenetic ritualization' from originally effective actions; moreover, in detailed analyses of two gestures, action elements composing the gestures did not closely match those of the presumed original actions. Rather, chimpanzee gestures are species-typical; indeed, many are 'family-typical', because gesture types recorded in gorillas, orangutans and chimpanzee overlap extensively, with 24 gestures recorded in all three genera. Nevertheless, chimpanzee gestures are used flexibly across a range of contexts and show clear adjustment to audience (e.g. silent gestures for attentive targets, contact gestures for inattentive ones). Such highly intentional use of a species-typical repertoire raises intriguing questions for the evolution of advanced communication.


The surgical management of insulinoma.
Insulinoma is the most common endocrine tumor of the pancreas. Over 90% of the insulinomas are benign and single, and can be cured by simple excision. Depending on the location, insulinomas can be enucleated, might require partial or distal pancreatectomy or pancreaticoduodenectomy. Five cases with insulinoma successfully treated by surgical intervention, two by enuclation, two by distal pancreatectomy and splenectomy, and preservation of the spleen have been summarized. The management of insulinoma involves the diagnosis, localization of the tumor and treatment. Insulinomas are rare tumors of the pancreas. Nevertheless, it is the most common endocrine tumor of the pancreas. Specifically arising from the beta cells, of the islets of Langerham, that produce insulin (fig.1). Its incidence is one in 250,000 inhabitants. It can be seen at any age, but is more frequent in females between 4 and 82 years of age, with a mean of 45.5 years. Insulinomas are evenly distributed between the head, body and tail of the pancreas. Over 90% are benign and single and can be cured by simple excision. Depending on the location insulinomas can be enucleated, might require partial or distal pancreatectomy or a pancreaticoduodenectomy. Ten percent could be malignant when metastasis to peripancreatic lymph nodes or to the liver is detected. The course of the patient with malignant insulinoma is an indolent one. The release of insulin leads to fasting hypoglycemia producing confusion, loss of consciousness, coma or convulsions. The hypoglycemia in turn can induce the release of cathecolamines producing tachycardia, tremulousness and diaphoresis. The Whipple's triad must be present for the diagnosis of insulinoma; symptoms of hypoglycemia, glucose level below 50 mgs/dl and relief of symptoms by the administration of glucose. In large series the interval between the onset of symptoms and a definitive diagnosis of insulinoma was 37 months, with a range of 0 to 14 years.


Factors inducing falling in schizophrenia patients.
[Purpose] The purpose of this study is to investigate the factors causing falling among patients with schizophrenia hospitalized in psychiatric hospitals. [Subjects and Methods] The study subjects were divided into either those having experienced a fall within the past one year (Fall group, 12 patients) and those not having experienced a fall (Non-fall group, 7 patients), and we examined differences between the two groups. Assessment items measured included muscle strength, balance ability, flexibility, body composition assessment, Global Assessment of Functioning scale (GAF), the antipsychotic drug intake, and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS). [Results] As a result, significant differences were observed in regard to One leg standing time with eyes open, Time Up and Go Test (TUGT), and DIEPSS Sialorrhea between the Fall group and the Non-fall group. [Conclusion] These results suggest that a decrease in balance ability was significantly correlated with falling in schizophrenia patients.


Sexual activity in ankylosing spondylitis.
To assess the sexual activity of patients with ankylosing spondylitis, correlating it with disease activity and functional indices. Thirty-two patients with ankylosing spondylitis and 32 healthy controls were assessed regarding pain, fatigue, sexual activity (by use of pictures of seven sexual positions), disease activity (by use of Bath Ankylosing Spondylitis Disease Activity Index - BASDAI), and functional capacity (by use of Bath Ankylosing Spondylitis Functional Index - BASFI). After the interview, the patients were divided into two groups: group A (with sexual activity) and group B (no sexual activity). Group B showed statistical association with longer disease duration (P = 0.01), and higher BASFI (P = 0.0007) and BASDAI (P = 0.03) scores. No correlation was observed between age and functional capacity. Man lying on his back and woman on top was the most frequent, enjoyable and least painful position. The position with the woman on her back and a man lying on top was the least chosen. Control individuals reported a higher frequency of sexual activity, longer duration of intercourse, and less pain and fatigue; the reported frequency of orgasms, however, was similar in both groups. The chronic nature of ankylosing spondylitis, with poor functional capacity and higher disease activity, interferes with sexual intercourse. When sexual activity was possible, orgasm and sexual satisfaction did not differ from those of healthy controls.


Integrating single-molecule experiments and discrete stochastic models to understand heterogeneous gene transcription dynamics.
The production and degradation of RNA transcripts is inherently subject to biological noise that arises from small gene copy numbers in individual cells. As a result, cellular RNA levels can exhibit large fluctuations over time and from one cell to the next. This article presents a range of precise single-molecule experimental techniques, based upon RNA fluorescence in situ hybridization, which can be used to measure the fluctuations of RNA at the single-cell level. A class of models for gene activation and deactivation is postulated in order to capture complex stochastic effects of chromatin modifications or transcription factor interactions. A computational tool, known as the finite state projection approach, is introduced to accurately and efficiently analyze these models in order to predict how probability distributions of RNA change over time in response to changing environmental conditions. These single-molecule experiments, discrete stochastic models, and computational analyses are systematically integrated to identify models of gene regulation dynamics. To illustrate the power and generality of our integrated experimental and computational approach, we explore cases that include different models for three different RNA types (sRNA, mRNA and nascent RNA), three different experimental techniques and three different biological species (bacteria, yeast and human cells).


Specificity for human hemoglobin enhances Staphylococcus aureus infection.
Iron is required for bacterial proliferation, and Staphylococcus aureus steals this metal from host hemoglobin during invasive infections. This process involves hemoglobin binding to the cell wall of S. aureus, heme extraction, passage through the cell envelope, and degradation to release free iron. Herein, we demonstrate an enhanced ability of S. aureus to bind hemoglobin derived from humans as compared to other mammals. Increased specificity for human hemoglobin (hHb) translates into an improved ability to acquire iron and is entirely dependent on the staphylococcal hemoglobin receptor IsdB. This feature affects host-pathogen interaction as demonstrated by the increased susceptibility of hHb-expressing mice to systemic staphylococcal infection. Interestingly, enhanced utilization of human hemoglobin is not a uniform property of all bacterial pathogens. These results suggest a step in the evolution of S. aureus to better colonize the human host and establish hHb-expressing mice as a model of S. aureus pathogenesis.


Analyzing the 2019 Chilean social outbreak: Modelling Latin American economies.
In this work, we propose a quantitative model for the 2019 Chilean protests. We utilize public data for the consumer price index, the gross domestic product, and the employee and per capita income distributions as inputs for a nonlinear diffusion-reaction equation, the solutions to which provide an in-depth analysis of the population dynamics. Specifically, the per capita income distribution stands out as a solution to the extended Fisher-Kolmogorov equation. According to our results, the concavity of employee income distribution is a decisive input parameter and, in contrast to the distributions typically observed for Chile and other countries in Latin America, should ideally be non-negative. Based on the results of our model, we advocate for the implementation of social policies designed to stimulate social mobility by broadening the distribution of higher salaries.


Production of starch foams by twin-screw extrusion: effect of maleated poly(butylene adipate-co-terephthalate) as a compatibilizer.
Free-radical-initiated grafting of maleic anhydride (MA) onto poly(butylene adipate-co-terephthalate) (PBAT), a biodegradable aliphatic-aromatic copolyester, was performed by reactive extrusion. 2,5-Dimethyl-2,5-di(tert-butylperoxy)hexane was used as the free-radical initiator. The peroxide concentration was varied between 0.0 and 0.5 wt % at 3.0 wt % MA concentration; the MA concentration was varied between 1.0 and 5.0 wt % at 0.5 wt % peroxide concentration. The reaction temperature was maintained at 185 degrees C for all experiments. Under these conditions, between 0.194% and 0.691% MA was grafted onto the polyester backbone. Size-exclusion chromatography, melt flow index, intrinsic viscosity measurements, thermal gravimetric analysis, and differential scanning calorimetry were used to characterize the maleated copolyester. Increasing the initiator concentration at a constant MA concentration of 3% resulted in an increase in the grafting of MA while decreasing the molecular weight of the resulting polymer. Increasing the feed MA concentration also increased the grafting percentage. The maleation of the polyester proved to be very efficient in promoting strong interfacial adhesion with high amylose cornstarch in starch foams as prepared by melt blending. Thus, the use of maleated copolyester as a compatibilizer between starch and PBAT allowed the reduction of the density of resulting starch foams to approximately 21 kg/m3 and improved the resilience from 84% to as high as 95%. Also, the resulting starch foams exhibited improved hydrophobic properties in terms of lower weight gain and higher dimensional stability on moisture sorption.


The impact of frailty in critically ill patients after trauma: A prospective observational study.
As our population ages, older adults are increasingly exposed to trauma. Frailty could be a useful measure to identify patients at risk of a poor outcome. This study aimed to determine the impact of frailty in an Australian trauma intensive care unit (ICU) population. A prospective observational study of critically ill trauma patients ≥50 years of age. Frailty was determined on admission to the ICU using the frailty phenotype. Demographic and hospital data were collected, and patients were followed up at 6 and 12 months. The primary outcome was 12-month mortality, and multiple regression was used to determine associated factors. One hundred thirty-eight patients were included, whose mean age was 68 years; 78.2% (108/138) were classified as major trauma (Injury Severity Score >12). Twenty-two percent (30/138) of patients were identified as frail. Patients with frailty were significantly older: however, they were less severely injured and required lower rates of surgical interventions and mechanical ventilation. Frailty was independently associated with mortality at 6 and 12 months (odds ratio: 5.9, 95% confidence interval: 1.9-18.1 and odds ratio: 7.3, 95% confidence interval: 2.5-21.9, respectively). Patients with frailty had lower measures of global functioning (Glasgow Outcome Scale-Extended frail 3 [1-5] vs nonfrail 6 [(5-7], p = 0.002) and health status (Euro Qol 5Q-5D-5L utility score 0.6 [0.5-0.7] vs 0.7 [0.6-0.9], p = 0.02) at 12 months than patients without frailty. Frailty is a useful predictor of poor outcomes in critically ill trauma patients. ACTRN12615000039583.


Functionality of C(4,4) carbon nanotube as molecular detector.
Alterations in the electronic transport properties of C(4,4) single walled carbon nanotube when an agent is introduced to the outer surface are investigated theoretically. Several chemical agents in this context are investigated. The calculations are performed in two steps: First an optimized geometry for the functionalized carbon nanotube is obtained using semi-empirical calculations at the PM3 level, and then the transport relations are obtained using non equilibrium green-function approach. Gaussian and Transiesta-C simulation packages are used in the calculations correspondingly. The "electrodes" are chosen to be ideal geometry of the particular carbon nanotube, eliminating current quantization effects due to contact region. By varying chemical potential in the electrode regions, an I-V curve is traced for each particular functionalisation. Conductance in carbon nanotubes show a strong dependence on the geometry and aromaticity, both are which altered when the suitable agent is introduced. This dependence results in rather dramatic response in the I-V trace, the current is reduced significantly, and quantization effects are observed, even for a single molecule. However due to chemically stable nature, not all agents form a chemical bond to the surface. Overall, the material is a promising candidate for detector equipment.


A Prospective, Randomized Comparison of Traditional and Accelerated Approaches to Postoperative Rehabilitation following Autologous Chondrocyte Implantation: 2-Year Clinical Outcomes.
To determine the safety and efficacy of "accelerated" postoperative load-bearing rehabilitation following matrix-induced autologous chondrocyte implantation (MACI). A randomized controlled study design was used to investigate clinical outcomes in 70 patients following MACI, in conjunction with either accelerated or traditional approaches to postoperative weight-bearing (WB) rehabilitation. Both interventions sought to protect the implant for an initial period and then incrementally increase WB. Under the accelerated protocol, patients reached full WB at 8 weeks postsurgery, compared to 11 weeks for the traditional group. Clinical outcomes were assessed presurgery and at 3, 6, 12, and 24 months postsurgery. A significant effect (P < 0.017) for time existed for all clinical measures, demonstrating improvement up to 24 months in both groups. A significant interaction effect (P < 0.017) existed for pain severity and the 6-minute walk test, with accelerated group patients reporting significantly less severe pain and demonstrating superior 6-minute walk distance over the period. Although there was a significant group effect (P < 0.017) for maximal active knee extension range in favor of the accelerated regime, no further significant differences existed. There was no incidence of graft delamination up to 24 months that resulted directly from the 3-month postoperative rehabilitation program. The accelerated load-bearing approach that reduced the length of time spent ambulating on crutches produced comparable if not superior clinical outcomes up to 24 months postsurgery in the accelerated rehabilitation group, without compromising graft integrity. This accelerated regime is safe and effective and demonstrates a faster return to normal function postsurgery.


The role of interleukin-2 in combination adenovirus gene therapy for head and neck cancer.
Interleukin-2 (IL-2) gene therapy alone and in combination with the herpes thymidine kinase gene (tk) was used to evaluate immunological responses and antitumor effects in head and neck cancer. Established floor of mouth squamous cell carcinomas in C3H/HeJ mice were directly injected with recombinant adenoviral vectors carrying both therapeutic and control genes. One week after adenoviral gene transfer, only the animals treated with combination IL-2+tk or tk alone demonstrated significant tumor regression. Residual tumors were harvested for microscopic evaluation and immunohistochemistry staining, which revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL-2. To evaluate the systemic immune effects of IL-2, animals treated with single or combination gene therapy received a second site challenge with parental tumor cells or a heterologous but syngeneic sarcoma cell line. Mice treated with combination IL-2 and tk demonstrated a protective systemic immunity specific to the parental tumor cell line, whereas no systemic immune response was evident in mice receiving IL-2 alone. In a separate experiment, a range of concentrations of the adenovirus IL-2 vector were used to treat established tumors. Even with the maximal single-dose adenovirus concentration, IL-2 alone was ineffective as a single therapy. These results support the use of adenovirus-mediated gene transfer of IL-2 as an effective immunotherapy when used adjuvantly with the tk "suicide gene".


The dual role of nod-like receptors in mucosal innate immunity and chronic intestinal inflammation.
Nucleotide-binding and oligomerization domain NOD-like receptors (NLRs) are highly conserved cytosolic pattern recognition receptors that play, in combination with toll-like receptors, a critical role in innate immunity and inflammation. These proteins are characterized by a central oligomerization domain termed nucleotide-binding domain, and a protein interaction domain containing leucine-rich repeats. Some NLRs, including NOD1 and NOD2, sense the cytosolic presence of conserved bacterial molecular signatures and drive the activation of mitogen-activated protein kinase and the transcription factor NF-κB. A different set of NLRs induces caspase-1 activation through the assembly of large protein complexes known as inflammasomes. Activation of NLR proteins results in secretion of pro-inflammatory cytokines and subsequent inflammatory responses. The critical role of NLRs in innate immunity is underscored by the fact that polymorphisms within their genes are implicated in the development of several immune-mediated diseases, including inflammatory bowel disease. Over the past few years, the role of NLRs in intestinal homeostasis has been highlighted, however the mechanism by which dysfunction in these proteins leads to aberrant inflammation is still the focus of much investigation. The purpose of this review is to systematically evaluate the function of NLRs in mucosal innate immunity and understand how genetic or functional alterations in these components can lead to the disruption of intestinal homeostasis, and the subsequent development of chronic inflammation.


Future of immunotherapy in pancreas cancer and the trials, tribulations and successes thus far.
Pancreas ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival rate of 10%. Currently, chemotherapy remains the standard of care for systemic treatment. Immunotherapy with checkpoint inhibitors unfortunately has not been found to be effective in the treatment of PDAC to date, likely due to the highly desmoplastic and immunosuppressive tumor microenvironment (TME). Treatment targeting pathways against the immunosuppressive mechanisms of PDAC are of mounting interest to improve outcomes in PDAC. In this review, we discuss prior efforts and the current state of immunotherapy in PDAC. We will also review the emerging targets and treatments with significant clinical potential for the treatment of PDAC such as: CD40 pathway, the adenosine pathway, the CXCR4/CXCL12 axis, the CCR2/CCL2 axis, IDO pathway, and others.


Effects of a web-based decision aid regarding diagnostic self-testing. A single-blind randomized controlled trial.
Currently, there are many diagnostic self-tests on body materials available to consumers. The aim of this study was to assess the effect of an online decision aid on diagnostic self-testing for cholesterol and diabetes on knowledge among consumers with an intention to take these tests. A randomized controlled trial was designed. A total of 1259 consumers with an intention to use a diagnostic cholesterol or diabetes self-test were selected from an existing Dutch Internet panel. The intervention group was invited to view an online decision aid offering general information on self-testing and test-specific information on cholesterol and diabetes self-testing, including indications for testing, how to perform the test and interpreting the result. The placebo condition consisted of a limited information sheet. Multiple regression analysis showed that the knowledge level in the diabetes arm was higher in the intervention group than in the control group (B = 0.657; 95% CI, 0.011-1.303), as was the number of participants with an informed choice (OR, 1.672; 95% CI, 1.134-2.465). No differences were found in the cholesterol arm. Consumers who are considering doing a self-test should have access to independent information on self-testing and be encouraged to read this information. Dutch Trial Register: NTR 3149.


Ligamentous, chondral, and osteochondral ankle injuries in athletes.
There is a broad spectrum of intra- and extra-articular pathologies that may result in chronic pain and loss of function after an ankle sprain in an athlete. Multiple concurrent intra- and extra-articular pathologies are common. The complex anatomy in the ankle and foot may result in overlap of the clinical features of these various conditions. Contemporary imaging modalities facilitate accurate diagnosis and appropriate and timely management. This review focuses on the particular mechanisms of injury in individual sports, the imaging manifestations of ankle ligament injuries, posttraumatic ankle synovitis, meniscoid lesions, soft-tissue impingement, and ankle joint chondral and osteochondral lesions, with an emphasis on their clinical relevance in athletes.


Clinical and phenotypical characteristics of submucosal invasive carcinoma in non-ampullary duodenal cancer.
The rare incidence of submucosal invasive non-ampullary duodenal carcinoma has led to scant information in literature; therefore, we compared the clinicopathological features between submucosal invasive carcinoma (SM-Ca), mucosal carcinoma (M-Ca), and advanced carcinoma (Ad-Ca). We retrospectively analyzed 165 patients with sporadic non-ampullary duodenal carcinomas (SNADCs) from four institutions between January 2003 and December 2018. The SNADCs were divided to three groups according to histological diagnosis: SM-Ca, M-Ca, and Ad-Ca. The clinicopathological characteristics and mucin phenotypes were compared between groups. Among the 165 SNADCs, 11 (7%) were classified as SM-Ca, 70 (42%) as M-Ca, and 84 (51%) as Ad-Ca. We found that all SM-Ca (P = 0.013) and most Ad-Ca (P = 0.020) lesions were located on the oral-Vater; however, an almost equal distribution of M-Ca lesions was found between the oral- and anal-Vater. No significant difference was observed between the tumor diameter of M-Ca and SM-Ca; however, 45% (5/11) of SM-Ca were ≤10 mm. A total of 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were classified as intestinal phenotype; whereas most M-Ca were classified as intestinal phenotype (67%, 8/12). SM-Ca lesions were all located on the oral-Vater and were highly associated with the gastric mucin phenotype, which were different from the features of most M-Ca.


Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response.
Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and could potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, we characterized how aging induces changes in immunological signatures that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment both locally and regionally in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improved healing and restored therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair. This article is protected by copyright. All rights reserved.


Racial disparities in survival after diagnosis of prostate cancer in Kentucky, 2001-2010.
Whether the African American race remains a significant predictor of poorer prostate cancer survival after adjusting for other sociodemographic and treatment-related factors remains unclear. We examined whether disparities in survival among 18,900 African American and Caucasian men diagnosed with prostate cancer in Kentucky remained after adjusting for health insurance (payor source), cancer treatment, cancer stage at diagnosis, prostate-specific antigen (PSA) level, smoking status, and Appalachian region. After adjusting for these predictors, African American men living in Kentucky had poorer prostate cancer survival after 5 years (hazard ratio [HR] = 1.33; 95% confidence interval = 1.11, 1.59) and 10 years (HR = 1.39; 95% CI = 1.18, 1.28) of follow-up, and for the entire follow-up period (HR = 1.41; 95% CI = 1.26, 1.65) compared to their Caucasian counterparts. Thus, health insurance status, cancer treatment, cancer stage at diagnosis, PSA level at diagnosis, smoking status, and geographic location did not explain the racial gap in survival in Kentucky.


Assessment of staffing needs for registered nurses and licensed practical nurses at primary care units in Brazil using Workload Indicators of Staffing Need (WISN) method.
The balance between supply and demand for primary health care (PHC) services is one of the main challenges to the health system in Brazil. In this context, the application of planning methods could benefit the decision-making process for human resources organizations. Hence, the objective of this study was to assess the staffing needs for registered nurses (RNs) and licensed practical nurses (LPNs) at PHC services using the WISN method. The Workload Indicators of Staffing Need (WISN) methodology was applied at 13 Primary Care Units (PCU) located in the city of São Paulo, Brazil. It included 87 RNs and 174 LPNs, and used data from 2017 to 2019. The WISN results found that RNs were under high workload pressure at 10 PCUs (77%) in 2017 and 2018, with a decrease to 8 PCUs (61%) in 2019. For LPNs, high workload pressure increased from 2 PCUs (15%) in 2017 to 13 PCUs (100%) in 2018, with a decrease to 11 (85%) in 2019. The assessment of staffing needs for RNs and LPNs at the PCUs included in the study identified a consistent deficit in the number of professionals, and high workload pressure in most services throughout the study period.


A PTEN-related 5-phosphatidylinositol phosphatase localized in the Golgi.
Phosphoinositides play important roles as signaling molecules in different cell compartments by regulating the localization and activity of proteins through their interaction with specific domains. The activity of these lipids depends on which sites on the inositol ring are phosphorylated. Signaling pathways dependent on phosphoinositides phosphorylated at the D3 position of this ring (3-phosphoinositides) are negatively regulated by 3-phosphoinositide-specific phosphatases that include PTEN and myotubularin. Using the conserved PTEN catalytic core motif, we have identified a new protein in the Dictyostelium genome called phospholipid-inositol phosphatase (PLIP), which defines a new subfamily of phosphoinositide phosphatases clearly distinct from PTEN or other closely related proteins. We show that PLIP is able to dephosphorylate a broad spectrum of phosphoinositides, including 3-phosphoinositides. In contrast to previously characterized phosphoinositide phosphatases, PLIP has a preference for phosphatidylinositol 5-phosphate, a newly discovered phosphoinositide. We found that PLIP is localized in the Golgi, with its phosphatase domain facing the cytoplasmic compartment. PLIP null cells created via homologous recombination are unable to effectively aggregate to form multicellular organisms at low cell densities. The presence of PLIP in the Golgi suggests that it may be involved in membrane trafficking.


Altered cognitive function of prefrontal cortex during error feedback in patients with irritable bowel syndrome, based on FMRI and dynamic causal modeling.
Patients with irritable bowel syndrome (IBS) have increased activity in the insula and reduced activation of the dorsolateral prefrontal cortex (DLPFC) in response to visceral stimulation. We investigated whether they have latent impairments in cognitive flexibility because of dysfunction in the DLPFC and insula and altered connectivity between brain regions. We analyzed data from 30 individuals with IBS (15 men; age, 21.7 ± 3.0 y) diagnosed based on Rome III criteria, along with 30 individuals matched for age, sex, and education level (controls). Event-related functional magnetic resonance imaging of the brain was performed to evaluate cognitive flexibility and was assessed by the Wisconsin Card Sorting Test, in which subjects are allowed to change choice criteria, defined as set-shifting in response to error feedback. Brain images were analyzed with statistical parametric mapping 5 and 8 software and dynamic causal modeling. Subjects with IBS had significantly more Nelson perseverative errors (P < .05) and set-maintenance difficulties (P < .05) than controls. They also showed significantly decreased activity of the right DLPFC (Brodmann's area 9; P < .001) and right hippocampus (P < .001), and significantly increased activity of the left posterior insula (P < .001) at error feedback during set-shifting. Dynamic causal modeling analysis during set-shifting revealed significantly less connectivity from the DLPFC to pre-supplementary motor area in subjects with IBS, compared with controls (P = .012). Individuals with IBS have latent impairments in cognitive flexibility as a result of altered activity of the DLPFC, insula, and hippocampus, and impaired connectivity between the DLPFC and pre-supplementary motor area.


Durability of serologic response after lamivudine treatment of chronic hepatitis B.
Forty subjects with chronic hepatitis B and hepatitis B e antigen (HBeAg) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses. Patient follow-up began a median of 4.3 months after completion of therapy in previous trials. At months 2, 4, 6, 9, and 12 of year 1, and every 6 months thereafter, we tested for HBeAg and hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT). After a median (range) of 36.6 (4.8-45.6) months of follow-up monitoring, HBeAg seroconversion was demonstrated at the last visit by 77% (30 of 39) of patients. In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials, the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64%. Nine (9 of 40, 23%) patients were HBsAg negative at the last assessment. Seventy-four percent (17 of 23) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit. Eight patients (8 of 40, 20%) initiated retreatment for reappearance of HBV markers, and 7 showed biochemical and/or virologic improvement (including regained HBeAg seroconversion in 2). No safety issues of concern emerged. In conclusion, most HBeAg responses achieved during lamivudine therapy were durable, and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine. Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression.


Derivation and maintenance of mouse haploid embryonic stem cells.
Ploidy represents the number of chromosome sets in a cell. Although gametes have a haploid genome (n), most mammalian cells have diploid genomes (2n). The diploid status of most cells correlates with the number of probable alleles for each autosomal gene and makes it difficult to target these genes via mutagenesis techniques. Here, we describe a 7-week protocol for the derivation of mouse haploid embryonic stem cells (hESCs) from female gametes that also outlines how to maintain the cells once derived. We detail additional procedures that can be used with cell lines obtained from the mouse Haplobank, a biobank of >100,000 individual mouse hESC lines with targeted mutations in 16,970 genes. hESCs can spontaneously diploidize and can be maintained in both haploid and diploid states. Mouse hESCs are genomically and karyotypically stable, are innately immortal and isogenic, and can be derived in an array of differentiated cell types; they are thus highly amenable to genetic screens and to defining molecular connectivity pathways.


The hereditary angioedema syndromes.
Hereditary angioedema (HAE) is a rare genetic disorder primarily caused by mutations in the SERPING1 gene encoding the C1 inhibitor (C1INH) that leads to plasma deficiency, resulting in recurrent attacks of severe swelling. In the current issue of the JCI, Haslund et al. show that in a subset of patients with type I HAE, mutated C1INH encoded by HAE-causing SERPING1 acts upon wildtype (WT) C1INH in a dominant-negative manner and forms intracellular C1INH aggregates. These aggregates lead to a reduction in the levels of secreted functional C1INH, thereby manifesting in the condition that allows the disease state. Interestingly, administration of WT SERPING1 gene is able to restore the levels of secreted C1INH, thereby opening up a novel mechanism justifying gene therapy for HAE.


Uterine kisspeptin receptor critically regulates epithelial estrogen receptor α transcriptional activity at the time of embryo implantation in a mouse model.
Embryo implantation failure is a major cause of infertility in women of reproductive age and a better understanding of uterine factors that regulate implantation is required for developing effective treatments for female infertility. This study investigated the role of the uterine kisspeptin receptor (KISS1R) in the molecular regulation of implantation in a mouse model. To conduct this study, a conditional uterine knockout (KO) of Kiss1r was created using the Pgr-Cre (progesterone receptor-CRE recombinase) driver. Reproductive profiling revealed that while KO females exhibited normal ovarian function and mated successfully to stud males, they exhibited significantly fewer implantation sites, reduced litter size and increased neonatal mortality demonstrating that uterine KISS1R is required for embryo implantation and a healthy pregnancy. Strikingly, in the uterus of Kiss1r KO mice on day 4 (D4) of pregnancy, the day of embryo implantation, KO females exhibited aberrantly elevated epithelial ERα (estrogen receptor α) transcriptional activity. This led to the temporal misexpression of several epithelial genes [Cftr (Cystic fibrosis transmembrane conductance regulator), Aqp5 (aquaporin 5), Aqp8 (aquaporin 8) and Cldn7 (claudin 7)] that mediate luminal fluid secretion and luminal opening. As a result, on D4 of pregnancy, the lumen remained open disrupting the final acquisition of endometrial receptivity and likely accounting for the reduction in implantation events. Our data clearly show that uterine KISS1R negatively regulates ERα signaling at the time of implantation, in part by inhibiting ERα overexpression and preventing detrimentally high ERα activity. To date, there are no reports on the regulation of ERα by KISS1R; therefore, this study has uncovered an important and powerful regulator of uterine ERα during early pregnancy.


A motion sequence fusion technique based on PCA for activity analysis in body sensor networks.
Human movement analysis by means of mobile sensory platforms is an ever-growing area with promise to revolutionize delivery of healthcare services. An effective data fusion technique is essential for understanding the inertial information obtained from distributed sensor nodes. In this paper, we develop a data fusion model based on the concept of principal component analysis. Unlike traditional fusion techniques which deal with statistical feature space, our model operates on motion transcripts, where each movement is represented as a sequence of basic building blocks called primitives. We describe how our model transforms transcripts of different nodes into a unified transcript by integrating the most relevant primitives of movements. Finally, we demonstrate the performance of our transcript fusion model for action recognition using real data collected from three subjects.


Diagnostic Value of Clinical Features to Distinguish Enteric Fever From Other Febrile Illnesses in Bangladesh, Nepal, and Pakistan.
Enteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan. Outpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients. We enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0-74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6-65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8-77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4-95.5) and specificity of 13.6% (95% CI, 9.8-17.5). Clinical features do not accurately distinguish blood culture-confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity.


Real-time metabolomics on living microorganisms using ambient electrospray ionization flow-probe.
Microorganisms such as bacteria and fungi produce a variety of specialized metabolites that are invaluable for agriculture, biological research, and drug discovery. However, the screening of microbial metabolic output is usually a time-intensive task. Here, we utilize a liquid microjunction surface sampling probe for electrospray ionization-mass spectrometry to extract and ionize metabolite mixtures directly from living microbial colonies grown on soft nutrient agar in Petri-dishes without any sample pretreatment. To demonstrate the robustness of the method, this technique was applied to observe the metabolic output of more than 30 microorganisms, including yeast, filamentous fungi, pathogens, and marine-derived bacteria, that were collected worldwide. Diverse natural products produced from different microbes, including Streptomyces coelicolor , Bacillus subtilis , and Pseudomonas aeruginosa are further characterized.


A novel universal small-molecule detection platform based on antibody-controlled Cas12a switching.
Molecular diagnostics play an important role in illness detection, prevention, and treatment, and are vital in point-of-care test. In this investigation, a novel CRISPR/Cas12a based small-molecule detection platform was developed using Antibody-Controlled Cas12a Biosensor (ACCBOR), in which antibody would control the trans-cleavage activity of CRISPR/Cas12a. In this system, small-molecule was labeled around the PAM sites of no target sequence(NTS), and antibody would bind on the labeled molecule to prevent the combination of CRISPR/Cas12a, resulting the decrease of trans-cleavage activity. Biotin-, digoxin-, 25-hydroxyvitamin D3 (25-OH-VD3)-labeled NTS and corresponding binding protein were separately used to verify its preformance, showing great universality. Finally, one-pot detection of 25-OH-VD3 was developed, exhibiting high sensitivity and excellent specificity. The limit of detection could be 259.86 pg/mL in serum within 30 min. This assay platform also has the advantages of low cost, easy operation (one-pot method), and fast detection (∼30 min), would be a new possibilities for the highly sensitive detection of other small-molecule targets.


Maternal obesity and pregnancy outcome.
The increasing prevalence of maternal obesity worldwide provides a major challenge to obstetric practice from preconception to postpartum. Maternal obesity can result in unfavorable outcomes for the woman and fetus. Maternal risks during pregnancy include gestational diabetes and chronic hypertension leading to preeclampsia. The fetus is at risk for stillbirth and congenital anomalies. Intrapartum care, normal and operative deliveries, anesthetic and operative interventions in the obese demand extra care. Obesity in pregnancy can also affect health later in life for both mother and child. For women, these risks include heart disease and hypertension. Children have a risk of future obesity and heart disease. Women and their offspring are at increased risk for diabetes. Obstetrician-gynecologists should be well informed to prevent and treat this epidemic. Interventions directed at weight loss and prevention of excessive weight gain during pregnancy must begin in the preconception period.


Long Non-Coding RNA LOXL1-AS1 Enhances Colorectal Cancer Proliferation, Migration and Invasion Through miR-708-5p/CD44-EGFR Axis.
Colorectal cancer (CRC), the third most common cancer worldwide, involves a physiological and pathological long non-coding RNA (lncRNA) paradigm shift. It has been reported that the lncRNA LOXL1-AS1 affects tumor development for many kinds of cancers, but its functions and mechanisms in CRC remain unknown. Expression levels of LOXL1-AS1 and miR-708-5p within CRC tissues and cell lines were measured using qRT-PCR. The performance of gain-of-function and loss-of-function assays was aimed at examining the effects of LOXL1-AS1 and miR-708-5p; colony formation and cell viability assays were carried out to measure cell multiplication; and Transwell migration and wound-healing assays were carried out for the measurement of cell migration and invasion. Luciferase reporter assay was used to verify the interactions between LOXL1-AS1 and miR-708-5p and between miR-708-5p and the CD44-EGFR signaling pathway. Finally, expression of CD44 and EGFR proteins was measured by Western blot and immunofluorescence assays. In this study, we reveal that the regulation of lncRNA LOXL1-AS1 occurs within CRC based on the correlation with poor clinical outcomes. LOXL1-AS1 knockdown along with miR-708-5p overpresentation in CRC cell lines inhibited cell multiplication, migration, and invasion. The inhibiting effect of LOXL1-AS1 knockdown on CRC was reversed by upregulating the CD44-EGFR signal pathway. From the perspective of mechanism, LOXL1-AS1 imposes sponging upon miR-708-5p and thereby promotes the CD44-EGFR signal pathway in CRC cells. This study demonstrated that lncRNA LOXL1-AS1 enhances multiplication, migration, invasion, and progression of CRC by sponging miR-708-5p to regulate the CD44-EGFR signal pathway.


Role of prostaglandins in neuroinflammatory and neurodegenerative diseases.
Increasing data demonstrates that inflammation participates in the pathophysiology of neurodegenerative diseases. Among the different inflammatory mediators involved, prostaglandins play an important role. The effects induced by prostaglandins might be mediated by activation of their known receptors or by nonclassical mechanisms. In the present paper, we discuss the evidences that link prostaglandins, as well as the enzymes that produce them, to some neurological diseases.


Salt-wasting congenital adrenal hyperplasia: detection and characterization of mutations in the steroid 21-hydroxylase gene, CYP21, using the polymerase chain reaction.
We have characterized mutations in the steroid 21-hydroxylase gene (CYP21) in salt-wasting congenital adrenal hyperplasia (SW-CAH) subjects, healthy control subjects, and affected sibling pairs with SW-CAH. To identify point mutations in CYP21, we have used an improved polymerase chain reaction methodology that allows analysis of the entire CYP21 gene. In addition, we have used polymerase chain reaction to search for abnormally spliced mRNAs resulting from putatively abnormal CYP21 genes transfected into COS1 cells. We found that all 26 SW-CAH subjects from whom DNA could be completely analyzed, had mutations that could account for the 21-hydroxylase enzyme deficiency. These mutations included CYP21 gene deletion, conversion to the inactive CYP21P form, point mutations leading to amino acid substitutions or stop codons, small gene deletions, and a point mutation in intron-2 that leads to an abnormally spliced mRNA. The point mutation in intron-2 was directly shown to activate a cryptic splice site 19 basepairs from exon-3 of CYP21 and thereby cause a reading frame mutation. This CYP21 mutation was frequently found in our white SW-CAH subjects, while the frequency of this mutation was extremely low in a racially matched control population. Furthermore, affected sibling pairs shared this mutation in all cases examined. The results presented should have important applications for the prenatal diagnosis of CAH.


A new method for the stereoselective synthesis of alpha-substituted serine amino acid analogues.
[reaction: see text]. A new method was developed for the stereoselective synthesis of alpha-substituted serine amino acids. The strategy utilizes a common enantiomerically enriched intermediate obtained through an enzymatic desymmetrization. A variety of amino acids were synthesized in good ee's through nucleophilic acetylide addition reactions and palladium-catalyzed Sonogashira couplings.


Anak Krakatau triggers volcanic freezer in the upper troposphere.
Volcanic activity occurring in tropical moist atmospheres can promote deep convection and trigger volcanic thunderstorms. These phenomena, however, are rarely observed to last continuously for more than a day and so insights into the dynamics, microphysics and electrification processes are limited. Here we present a multidisciplinary study on an extreme case, where volcanically-triggered deep convection lasted for six days. We show that this unprecedented event was caused and sustained by phreatomagmatic activity at Anak Krakatau volcano, Indonesia during 22-28 December 2018. Our modelling suggests an ice mass flow rate of ~5 × 106 kg/s for the initial explosive eruption associated with a flank collapse. Following the flank collapse, a deep convective cloud column formed over the volcano and acted as a 'volcanic freezer' containing ~3 × 109 kg of ice on average with maxima reaching ~1010 kg. Our satellite analyses reveal that the convective anvil cloud, reaching 16-18 km above sea level, was ice-rich and ash-poor. Cloud-top temperatures hovered around -80 °C and ice particles produced in the anvil were notably small (effective radii ~20 µm). Our analyses indicate that vigorous updrafts (>50 m/s) and prodigious ice production explain the impressive number of lightning flashes (~100,000) recorded near the volcano from 22 to 28 December 2018. Our results, together with the unique dataset we have compiled, show that lightning flash rates were strongly correlated (R = 0.77) with satellite-derived plume heights for this event.


Photodynamic therapy for nodular basal cell carcinoma up to 5 mm located on high-risk area: effectiveness and long-term follow-up results.
Response rates evaluation of photodynamic therapy (PDT) for nodular basal cell carcinoma (BCC) treatment located on high-risk and low-risk areas of the face. Two groups of nodular BCC were selected, debulked, and received 20% methyl aminolevulinate (MAL) hydrochloride cream. After 3 hours, the first irradiation was performed (20 min, 150 J/cm2). Then, the cream was re-applied, and a second irradiation was performed after 1.5 hours (20 min, 150 J/cm2). Clearance at 30 days and recurrence-free survival rate were evaluated. The clearance at 30 days after PDT was 89% for the low-risk area group and 87% for the high-risk group. The recurrence-free survival at 60 months was 82% and 85% for the high-risk and low-risk groups, respectively. No significant differences were observed between groups nor for clearance at 30 days, nor recurrence-free follow-up. These results make the PDT an option for nodular BCC less than 5 mm located in high-risk areas.


A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.
Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.


Smart technology for healthcare: Exploring the antecedents of adoption intention of healthcare wearable technology.
Technological advancement and personalized health information has led to an increase in people using and responding to wearable technology in the last decade. These changes are often perceived to be beneficial, providing greater information and insights about health for users, organizations and healthcare and government. However, to date, understanding the antecedents of its adoption is limited. Seeking to address this gap, this cross-sectional study examined what factors influence users' adoption intention of healthcare wearable technology. We used self-administrated online survey to explore adoption intentions of healthcare wearable devices in 171 adults residing in Hong Kong. We analyzed the data by Partial least squares - structural equation modelling (PLS-SEM). The results reveal that perceived convenience and perceived irreplaceability are key predictors of perceived usefulness, which in turn strengthens users' adoption intention. Additionally, the results also reveal that health belief is one of the key predictors of adoption intention. This paper contributes to the extant literature by providing understanding of how to strengthen users' intention to adopt healthcare wearable technology. This includes the strengthening of perceived convenience and perceived irreplaceability to enhance the perceived usefulness, incorporating the extensive communication in the area of healthcare messages, which is useful in strengthening consumers' adoption intention in healthcare wearable technology.


[Depressive disorders in gastroenterology: problems in the treatment of chronic duodenal obstruction].
Among 190 patients suffering from chronic duodenal obstruction (CDO) the authors identified 66 patients whose somatic disturbances were manifestations of mental disease, usually depression. They formed a section "primary functional forms of CDO" in the classification scheme. Additionally some of these cases were complicated by nonspecific lymphadenitis and entered a group of mechanical forms of CDO. The use of psychotropic drugs in both cases considerably improved the prognosis of the disease. Sensthopathic feelings in the abdomen in such cases were attributable to vegetative motor disorders of the upper portions of the gastrointestinal tract ascertained by instrumental examination.


Correlation Between Cued Fear Memory Retrieval and Oscillatory Network Inhibition in the Amygdala Is Disrupted by Acute REM Sleep Deprivation.
The basolateral amygdaloid complex (BLA) is critically involved in emotional behaviors, such as aversive memory formation. In particular, fear memory after cued fear conditioning is strongly associated with the BLA, whereas both the BLA and hippocampus are essential for contextual fear memory formation. In the present study, we examined the effects of acute (3 h) sleep deprivation (SD) on BLA-associated fear memory in juvenile (P24-32) rats and performed in vitro electrophysiology using whole-cell patch clamping from the basolateral nucleus (BA) of the BLA. BA projection neurons exhibit the network oscillation, i.e., spontaneous oscillatory bursts of inhibitory transmission at 0.1-3 Hz, as previously reported. In the present study, SD either before or after fear conditioning (FC) disturbed the acquisition of tone-associated fear memory without significant effects on contextual fear memory. FC reduced the power of the oscillatory activity, but SD did not further reduce the oscillation power. Oscillation power was correlated with tone-associated freezing rate (FR) in SD-free fear-conditioned rats, but this relation was disrupted in SD treated group. Rhythm index (RI), the rhythmicity of the oscillation, quantified by autocorrelation analysis, also correlated with tone-associated FR in the combined data, including FC alone and FC with SD. These results suggest that slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.


Polypharmacy and Drug Interactions in the COVID-19 Pandemic.
The COVID-19 pandemic generated a great impact on health systems. We compared evolution, polypharmacy, and potential drug-drug interactions (P-DDIs) in COVID-19 and non-COVID-19 hospitalizations during first wave of pandemic. Prescriptions for hospitalized patients ≥ 18 years (COVID-19 and non-COVID-19 rooms) between April and September 2020 were included. The computerized medical decision support system SIMDA and the physician order entry system Hdc.DrApp.la were used. Patients in COVID-19 rooms were divided into detectable and non-detectable, according to real-time reverse transcription polymerase chain reaction (RT-PCR). Number of drugs, prescribed on day 1, after day 1, and total; polypharmacy, excessive polypharmacy, and P-DDIs were compared. 1,623 admissions were evaluated: 881 COVID-19, 538 detectable and 343 non-detectable, and 742 non-COVID-19. Mortality was 15% in COVID-19 and 13% in non-COVID-19 (RR [non-COVID-19 vs. COVID-19]: 0.84 [95% CI] [0.66-1.07]). In COVID-19, mortality was 19% in detectable and 9% in non-detectable (RR: 2.07 [1.42-3.00]). Average number of drugs was 4.54/patient (SD ± 3.06) in COVID-19 and 5.92/patient (±3.24) in non-COVID-19 (p<0.001) on day 1 and 5.57/patient (±3.93) in COVID-19 and 9.17/patient (±5.27) in non-COVID-19 (p<0.001) throughout the hospitalization. 45% received polypharmacy in COVID-19 and 62% in non-COVID-19 (RR: 1.38 [1.25-1.51]) and excessive polypharmacy 7% in COVID-19 and 14% in non-COVID-19 (RR: 2.09 [1.54-2.83]). The frequency of total P-DDIs was 0.31/patient (±0.67) in COVID-19 and 0.40/patient (±0.94) in non-COVID-19 (p=0.022). Hospitalizations in the COVID-19 setting are associated with less use of drugs, less polypharmacy and less P-DDIs. Detectable patients had higher mortality.


The use of a chitosan dressing with silver in the management of paediatric burn wounds: a pilot study.
Traditional burn dressings demonstrate unfavourable tendencies of shrinking when wet and failing to maintain their integrity when manipulated. To overcome these obstacles, gel-forming fibre dressings have emerged as an alternative. Our objective was to observe the clinical properties and healing ability in the setting of burn wounds in a paediatric centre of a chitosan-based dressing containing silver. A sample of 12 partial-thickness burns in 10 children were identified for treatment with the chitosan-based silver dressing. The dressings were moistened before application, and monitored for any shrinkage on application. Patients were monitored for healing at outpatient follow-up visits and the dressings were allowed to separate as healing occurred. We treated 12 burns in 10 children with an average age of 5.2 years. The burns had an average proportion of total body surface area (TBSA) of 3.6 % and involved the trunk and all extremities. Wounds healed mostly or completely in an average of 8.3 days. Dressings retained their size when wet and integrity when removed. No burns were found to be infected at any point in the study. The chitosan-based dressing offered an optimal environment for moist wound management, and did not demonstrate the shrinkage or disintegration that diminishes the clinical usability of widely used hydrofibre dressings. The burns healed within an expected period of time, and did not undergo any infectious processes. Based on the results of this pilot study, the chitosan-based silver dressing is deserving of further study as an alternative to traditional burn dressings.


Recognizing Recurrence of Melanoma in an Emergency Department Patient: A Case Study.
Malignant melanoma incidence is rising faster than any other malignancy. Recurrent disease can occur in as many as 10% of patients diagnosed with primary malignant melanoma. In-transit melanoma is a type of locoregional disease that materializes when the cancer recurs as dermal and subdermal nodules found between the primary site and the lymph node drainage basin. Patients may not recognize the lesions as in-transit melanoma, and they may present to the emergency department for another matter completely. Ultimately, once recurrence is suspected, there must be a swift referral to oncology. Lack of recognition of this unique skin lesion could prove to be fatal. As frontline providers of care, emergency nurse practitioners should be alert to the characteristics of these lesions and the history that supports this dermatological condition.


[Bibliographic study of publishing on management activity of nursing in mental health].
Aiming at studying the mental health nurse's management activity as an instrument in the work process, a bibliographic study on nursing publications from 1988 to 1997 which concerned that topic was carried out. By reading and critically analyzing 8 articles and 19 selected theses and dissertations, the major characteristics of such practice were identified, namely: mental health nurses are responsible for the nursing team and care according to the logic determined by the institution; their actions are not planned, coordinated or evaluated; management activities take most of their time and direct nursing care is given by the auxiliary nursing team whilst in extra-hospital services, direct and group care are more frequent.


An Automatized Deep Segmentation and Classification Model for Lumbar Disk Degeneration and Clarification of Its Impact on Clinical Decisions.
Cross-sectional database study. The purpose of this study was to develop a successful, reproducible, and reliable convolutional neural network (CNN) model capable of segmentation and classification for grading intervertebral disc degeneration (IVDD), as well as quantify the network's impact on doctors' clinical decision-making. 5685 discs from 1137 patients were graded separately by four experienced doctors according to the Pfirrmann classification. A ground truth (GT) was established for each disc in accordance with the decision of the majority of doctors. The U-net model is used for segmentation. 1815 discs from 363 patients were used to train and test the U-net. The Inception V3 model is employed for classification. All discs were separated into two distinct sets: 90% in a training set and 10% in a test set. The performance metrics of these models were measured. Reliability tests were performed. The impact of CNN assistance on doctors was assessed. Segmentation accuracy was .9597 with a .8717 Jaccard Index and a .9314 Sorensen Dice coefficient. Classification accuracy is .9346, and the F1 score is .9355. The intraclass correlation coefficient (ICC) and kappa values between CNN and GT were .95-.97. With CNN's assistance, the success rates of doctors increased by 7.9% to 22%. The fully automated network outperformed doctors markedly in terms of accuracy and reliability. The results of CNN were comparable to those of other recent studies in the literature. It was determined that CNN's assistance had a substantial positive effect on the doctor's decision.


Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?
Angiogenesis is defined as the formation of new blood vessels from preexisting vessels and has been characterized as an essential process for tumor cell proliferation and viability. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve tumor of nutrients and oxygen, primarily through blockade of VEGF/VEGFR signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, alone or in combination with chemotherapy or other targeted therapies. But this success had only limited impact on overall survival of cancer patients and rarely resulted in durable responses. Given the recent success of immunotherapies, combinations of anti-angiogenics with immune checkpoint blockers have become an attractive strategy. However, implementing such combinations will require a better mechanistic understanding of their interaction. Due to overexpression of pro-angiogenic factors in tumors, their vasculature is often tortuous and disorganized, with excessively branched leaky vessels. This enhances vascular permeability, which in turn is associated with high interstitial fluid pressure, and a reduction in blood perfusion and oxygenation. Judicious dosing of anti-angiogenic treatment can transiently normalize the tumor vasculature by decreasing vascular permeability and improving tumor perfusion and blood flow, and synergize with immunotherapy in this time window. However, anti-angiogenics may also excessively prune tumor vessels in a dose and time-dependent manner, which induces hypoxia and immunosuppression, including increased expression of the immune checkpoint programmed death receptor ligand (PD-L1). This review focuses on revisiting the concept of anti-angiogenesis in combination with immunotherapy as a strategy for cancer treatment.


[Study of eating habits in a female population comparing groups with and without food-related diseases].
To analyze female subjects in the rural setting to detect food-related disorders and factors associated with these. To isolate these factors and prevent the development of food-related disorders in Primary Health Care. Also to assess continuity in the alterations in the general, sub-clinical and bulimic populations. SCOPE AND SUBJECTS: 127 women with absence of dysfunctions: 57 sub-clinical and 63 bulimics, all from south-western Spain. Those adolescents at risk of dysfunctions would present positive results in pathological personality traits; therefore, their identification in Primary Health Care would avoid the transition to complete forms and would be favour the theory of the continuum. Significant differences were found between sub-clinical and bulimic women for mean age and age of onset of eating-related difficulties. Subjects without eating-related dysfunctions have a lower body mass index (BMI) than sub-clinical ones and the latter have less than bulimic subjects, both now and in the past. The objective and subjective history of excess weight was recorded for all three populations, together with eating-related behaviour and the various symptoms suggesting personality disorders, and data on their consumption of toxic substances. In our sample, 30% of the population obtained scores above the cut-off value in the two scales used, so they could be considered at risk for having food-related dysfunctions and it is necessary to take action at the level of Primary Health Care, as it is in the transition from childhood to adolescence that diets are begun to be followed because of an excessive assessment of weight and it is in this sphere that early action can be taken.


Testing the ability of plants to access potassium from framework silicate minerals.
The availability of K, essential for plant growth, from syenite (a silicate rock in which potassium feldspar is the dominant mineral; >90wt%), and phlogopite mica has been demonstrated using carefully designed plant growth pot experiments in which the only added source of K was the mineral of interest, with no loss of nutrients through drainage. Using pure quartz sand as a soil, both growth (increase in diameter) of leek plants and K-content of the plant material showed a dose-dependent positive response to the application (114-43000mgK/pot) of milled syenite with increases in plant diameter of 0.5-0.7mm/week, increasing with application rate. Phlogopite mica (114-6000mgK/pot) supported the highest observed increase in diameter (approx. 1mm/week) and plant K-content, both similar to that observed for a positive control (KCl). These experiments demonstrate that plants can obtain K for growth from milled syenite, in which feldspar is the dominant K-bearing mineral, and confirm previous observations that micas can be an effective source of K.


Reliability of radionuclide gastroesophageal reflux studies using visual and time-activity curve analysis: inter-observer and intra-observer variation and description of minimum detectable reflux.
Radionuclide studies have gained wide acceptance in the evaluation of infants and children with gastroesophageal reflux (GER). For correct interpretation of scan results, knowledge of inter-observer and intra-observer variability and minimum detectable reflux volume is essential. In this study, we evaluated the methodological issues underlying the visual assessment of GER and time activity curve analysis. An in vitro model of stomach and oesophagus was established to determine the minimum detectable reflux by placing various volumes and concentrations representing the diluted activity in the stomach. In the clinical part 99 patients were imaged for 1 h after oral administration of 99mTc sulfur colloid. Eleven patients were excluded from the study either due to incomplete clinical data or suboptimal image quality. Frames of 16 s each, and time-activity curves which were generated after drawing regions of interest from the oesophagus, were read three times by an experienced nuclear medicine physician and a resident in training. On the phantom study, the concentration, volume and duration were the determining factor for the visualization of reflux. In the clinical part, the overall incidence of GER in 88 patients was 69%. The mean intra- and inter-observer reproducibility (kappa values) was 0.76 and 0.7065, respectively. Agreement was slightly higher in the analysis of time-activity curves (0.767 and 0.731). Our results indicate that GER may be reproducibly analysed on scintigraphy by the same and different observers with varying levels of training. Its visualization is associated with reflux duration, volume and dilution factor of radioactivity.