Recombinant Bacille Calmette-Guérin coexpressing Ag85B-IFN-γ enhances the cell-mediated immunity in C57BL/6 mice.
The only available vaccine against pulmonary tuberculosis is Bacille Calmette-Guérin (BCG). As the efficacy reported of the vaccine is not up to the mark, there is an urgent need to develop improved anti-tuberculosis vaccines. Antigen 85B (Ag85B) is a very promising vaccine candidate molecule of Mycobacterium tuberculosis and interferon (IFN)-γ and has been considered the most attractive correlate of protective immunity. The aim of this study was to construct a novel recombinant BCG (rBCG) to secrete Ag85B and mouse IFN-γ under control of the Mycobacterial heat shock protein 60 (hsp60) promoter and the antigen signal sequence. Second aim of the present study is to evaluate the immune response in C57BL/6 elicted by the new rBCG. Expression of the fusion protein was readily detectable by western blotting and IFN-γ bioactivity was detected indirectly by enzyme-linked immunosorbent assay (ELISA). Compared with BCG, rBCG::Ag85B-IFN-γ was substantially more active in inducing the production of IFN-γ and tumor necrosis factor (TNF)-α from mouse splenocytes. ELISA analysis for IgG, IgG1 and IgG2c showed that rBCG::Ag85B-IFN-γ induced higher titer of Ag85B and facilitated Th1 type immune response. rBCG::Ag85B-IFN-γ also improved nitric oxide production levels and enhanced antigen-specific splenocyte proliferation. Moreover, rBCG::Ag85B-IFN-γ induced human monocytes such as THP-1 cells to enhance expression of CD80, CD86, CD40 and HLA-DR. Flow cytometry analysis confirmed that rBCG::Ag85B-IFN-γ significantly activated CD4+ T cells. Assessing combinations of IFN-γ, TNF-α and interleukin-2 at the single-cell level by multiparameter flow cytometry, we found that rBCG::Ag85B-IFN-γ improved the multifunctional T cells level in comparison to BCG. In conclusion, the present study indicates that rBCG::Ag85B-IFN-γ increases cell mediated immune response and is a potential candidate vaccine for immunotherapeutic protocols against pulmonary tuberculosis.


Evaluation of the Antimicrobial Activity of Cationic Polymers against Mycobacteria: Toward Antitubercular Macromolecules.
Antimicrobial resistance is a global healthcare problem with a dwindling arsenal of usable drugs. Tuberculosis, caused by Mycobacterium tuberculosis, requires long-term combination therapy and multi- and totally drug resistant strains have emerged. This study reports the antibacterial activity of cationic polymers against mycobacteria, which are distinguished from other Gram-positive bacteria by their unique cell wall comprising a covalently linked mycolic acid-arabinogalactan-peptidoglycan complex (mAGP), interspersed with additional complex lipids which helps them persist in their host. The present study finds that poly(dimethylaminoethyl methacrylate) has particularly potent antimycobacterial activity and high selectivity over two Gram-negative strains. Removal of the backbone methyl group (poly(dimethylaminoethyl acrylate)) decreased antimycobacterial activity, and poly(aminoethyl methacrylate) also had no activity against mycobacteria. Hemolysis assays revealed poly(dimethylaminoethyl methacrylate) did not disrupt red blood cell membranes. Interestingly, poly(dimethylaminoethyl methacrylate) was not found to permeabilize mycobacterial membranes, as judged by dye exclusion assays, suggesting the mode of action is not simple membrane disruption, supported by electron microscopy analysis. These results demonstrate that synthetic polycations, with the correctly tuned structure are useful tools against mycobacterial infections, for which new drugs are urgently required.


Kink-formation kinetics and submonolayer density of magic two-dimensional islands in molecular beam epitaxy.
The nucleation and growth of compact two-dimensional islands having a regular shape and edges consisting of atomically straight kink-free segments is studied analytically and with kinetic Monte Carlo (KMC) simulations. In the analytical model the islands grow by a cyclic process of deposition of single atomic rows along the island edges. Two ends of an incomplete row are the kink sites where adatoms incorporate into the crystal. Adatoms attached to the island edge are able to migrate along the edge and detach back to the terrace before reaching the kinks. Completion of the rows corresponds to a sequence of the magic island sizes. It is assumed that a one-dimensional nucleus of the next atomic row (a pair of kinks) forms when two adatoms meet each other at the edge of the magic island. It follows from the model that at certain growth conditions the island density is independent of the deposition flux and increases with the increasing growth temperature. The predictions of the analytical model are in good agreement with results of KMC simulations. Computer simulations also show that the island size distribution gradually changes with the increasing detachment probability from the monomodal distribution with a peak around the mean island size to a sequence of monotonously decreasing peaks at magic sizes.


Immunohistochemical studies of cyclic guanosine monophosphate and nuclear function.
In previous immunohistochemical studies, it has been found that all nuclei contain cyclic (c)GMP, which occurs in discrete aggregates and in the nucleolus. We have studied the nature of the cGMP aggregates in isolated mouse fetal nuclei using a specific immunofluorescent technique. These aggregates correspond to the areas of condensation of DNA, demonstrable by either Felugen's or acridine orange stain. Treatment with DNAase eliminated DNA and cGMP staining. Staining for RNA, with a human anti-RNA antibody, demonstrated RNA to be distributed diffusely throughout the nucleus and not preferentially in the areas of discrete cGMP aggregates. The diffuse stain for nuclear RNA was eliminated by pretreatment with RNAase but not DNAase, but aggregates of cGMP were not affected by pretreatment with RNAase. Sites of active RNA synthesis were determined by autoradiography using [3H]uridine, and did not correspond to the aggregates of cGMP. The relationship of cGMP to nucleolar function was examined in the endothelial cells of the isthmus and ampulla of the rat fallopian tube. Previous studies have shown that in proestrous, a period of increased RNA synthesis, nucleoli detectable by staining for RNA appear in the endothelial cells lining the fallopian tube. After immunofluorescent staining, we found prominent accumulation of cGMP in the nucleoli. During other phases of the cycle, there is an absence of nucleoli detectable by staining for RNA, and an absence of nucleolar cGMP. After we treated hypophysectomized or oophorectomized rats with estrogen, which is known to increase nucleolar RMA synthesis in the fallopian tube and endometrium, nucleoli in the endothelial cells of the rat fallopian tube and uterus stained strongly for cGMP. In conclusion, our studies suggest that the discrete aggregates of nuclear cGMP are associated with a fraction of DNA uninvolved in RNA synthesis. In contrast, cGMP appears in the nucleolus during a period of increased RNA synthesis, suggesting a role for cGMP in regulating nucleolar synthesis and processing of RNA.


Unexpected sounds inhibit the movement of the eyes during reading and letter scanning.
Novel sounds that unexpectedly deviate from a repetitive sound sequence are well known to cause distraction. Such unexpected sounds have also been shown to cause global motor inhibition, suggesting that they trigger a neurophysiological response aimed at stopping ongoing actions. Recently, evidence from eye movements has suggested that unexpected sounds also temporarily pause the movements of the eyes during reading, though it is unclear if this effect is due to inhibition of oculomotor planning or inhibition of language processes. Here, we sought to distinguish between these two possibilities by comparing a natural reading task to a letter scanning task that involves similar oculomotor demands to reading, but no higher level lexical processing. Participants either read sentences for comprehension or scanned letter strings of these sentences for the letter 'o' in three auditory conditions: silence, standard, and novel sounds. The results showed that novel sounds were equally distracting in both tasks, suggesting that they generally inhibit ongoing oculomotor processes independent of lexical processing. These results suggest that novel sounds may have a global suppressive effect on eye-movement control.


Association between exposure to antimicrobial household products and allergic symptoms.
Antimicrobial chemicals are used in a variety of household and personal care products. Exposure to antimicrobial household products has been hypothesized to lead to allergic diseases in children. We investigated antimicrobial household product exposure and allergic symptoms in Korean children. An antimicrobial exposure (AE) score was derived. To examine the symptoms of allergic diseases (current wheeze, current rhinitis, and current eczema) in the past 12 months, we used a questionnaire based on the core module of the International Study of Asthma and Allergies in Children. Complete data for the analysis were available for 25,805 of the 35,590 (72.5%) children. The prevalence of current allergic diseases was as follows: wheeze, 5.6%; allergic rhinitis, 32.6%; and eczema, 17.7%. The mean (standard deviation) AE score was 14.3 (9.3) (range: 0-40). Compared with subjects with a low AE score (reference), subjects with a high AE score (fourth quartile) were more likely to have symptoms of wheezing and allergic rhinitis (adjusted odds ratio [aOR] for wheezing 1.24, 95% confidence interval [CI], 1.05-1.45, p for trend=0.24; aOR for allergic rhinitis 1.30, 95% CI, 1.20-1.40, p<0.01). These findings suggest that frequent use of antimicrobial household products was associated with current wheeze and current allergic rhinitis.


The effects of CO2 and nutrient fertilisation on the growth and temperature response of the mangrove Avicennia germinans.
In order to understand plant responses to both the widespread phenomenon of increased nutrient inputs to coastal zones and the concurrent rise in atmospheric CO2 concentrations, CO2-nutrient interactions need to be considered. In addition to its potential stimulating effect on photosynthesis and growth, elevated CO2 affects the temperature response of photosynthesis. The scarcity of experiments testing how elevated CO2 affects the temperature response of tropical trees hinders our ability to model future primary productivity. In a glasshouse study, we examined the effects of elevated CO2 (800 ppm) and nutrient availability on seedlings of the widespread mangrove Avicennia germinans. We assessed photosynthetic performance, the temperature response of photosynthesis, seedling growth and biomass allocation. We found large synergistic gains in both growth (42 %) and photosynthesis (115 %) when seedlings grown under elevated CO2 were supplied with elevated nutrient concentrations relative to their ambient growing conditions. Growth was significantly enhanced under elevated CO2 only under high-nutrient conditions, mainly in above-ground tissues. Under low-nutrient conditions and elevated CO2, root volume was more than double that of seedlings grown under ambient CO2 levels. Elevated CO2 significantly increased the temperature optimum for photosynthesis by ca. 4 °C. Rising CO2 concentrations are likely to have a significant positive effect on the growth rate of A. germinans over the next century, especially in areas where nutrient availability is high.


Time course of renal glutathione levels in experimental Fanconi syndrome: an enzyme-based approach.
Time-dependent alterations in glutathione (GSH) concentration and the activities of several key enzymes of GSH metabolism were studied in a rat model of experimental Fanconi syndrome induced by i.p. injection of sodium maleate (400 mg/kg BW). The changes in the parameters tested were monitored 0, 2, 4, and 12 h after sodium maleate administration. A significant decrease in renal GSH level was observed 2 and 4 h after sodium maleate treatment (27% and 38% of control values, respectively). The renal GSH depletion did not appear to be due to the decreased production rate or to an increased degradation of the tripeptide. This suggestion is based on the findings that the activities of the GSH synthesis (gamma-glutamyl cysteine synthetase and glutathione reductase) and those of the catabolic pathways (gamma-glutamyl transpeptidase) were unaltered at the same time points. The unchanged activity of gamma-glutamyl transpeptidase also suggests preserved luminal membrane integrity in experimental Fanconi syndrome. The decreased activity of glutathione peroxidase, which utilizes GSH as a cosubstrate in the course of inactivation of free radicals, in the first hours after treatment could facilitate lipid peroxidation reactions in this model of acute renal failure. The observed changes in all parameters tested were transient, with recovery to baseline levels in a period of 12 h after sodium maleate administration. At the same time a pronounced functional impairment still existed. The beneficial effect of fast recovery of renal GSH level on the functional and morphological restitution in experimental Fanconi syndrome is suggested.


[Congenital poikilodermas].
We discuss the diagnoses and differential diagnoses of the various forms of congenital poikiloderma. In addition, we differentiate this disease from dysplastic syndromes, progeria, and connotal metabolic disorders.


Understanding the contamination of food with mineral oil: the need for a confirmatory analytical and procedural approach.
The contamination of food by mineral oil hydrocarbons (MOHs) found in packaging is a long-running concern. A main source of MOHs in foods is the migration of mineral oil from recycled board into the packed food products. Consequently, the majority of food manufacturers have taken protective measures, e.g., by using virgin board instead of recycled fibres and, where feasible, introducing functional barriers to mitigate migration. Despite these protective measures, MOHs may still be observed in low amounts in certain food products, albeit due to different entry points across the food supply chain. In this study, we successfully apply gas chromatography coupled to mass spectrometry (GC-MS) to demonstrate, through marker compounds and the profile of the hydrocarbon response, the possible source of contamination using mainly chocolate and cereals as food matrices. The conventional liquid chromatography-one-dimensional GC coupled to a flame ionisation detector (LC-GC-FID) is a useful screening method, but in cases of positive samples it must be complemented by a confirmatory method such as, for example, GC-MS, allowing a verification of mineral oil contamination. The procedural approach proposed in this study entails profile analysis, marker identification, and interpretation and final quantification.


Omega-3 Consumption During Pregnancy to Support Optimal Outcomes.
Long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFA), including docosahexaenoic acid, are components of cellular membranes that affect biological functioning. Most pregnant women consume inadequate amounts of n-3 LCPUFA and inadequately convert linolenic acid into docosahexaenoic acid. The purpose of this article is to educate nursing professionals on the importance of n-3 LCPUFA consumption during pregnancy and highlight the critical role of nursing professionals in supporting optimal consumption for improved metabolic, antioxidant, and anti-inflammatory potential.


The use of a geographical information system in historical demography.
The plethora of digital data has caused a dramatic rise in the use of demographic databases for the analysis of modern populations. This paper discusses the use of an analogue and digital dataset within the framework of a proprietary Geographical Information System (ARC/INFO) in recent historical demography.


The evolution of cervical cancer screening.
There are few medical success stories in history as significant as the reduction in cervical cancer incidence. Through the collaborative efforts of dedicated scientific pioneers, the past century has witnessed remarkable advancement that began with the detection of exfoliated cancer cells through cytologic examination to widespread implementation of cervical cancer screening programs to the discovery of the link between cervical cancer and human papillomavirus (HPV). Current screening methods apply HPV-based testing, and artificial intelligence-based screening systems utilizing digitalized cytology images are being used in a continuous effort to optimize the accuracy and efficiency of the Papanicolaou test. This review summarizes the major milestones in cervical cancer screening history to emphasize its evolution as the World Health Organization aims for the global elimination of cervical cancer.


Effect of Abdominal Aortic Aneurysm Size on Mid-Term Mortality After Endovascular Repair.
Previous studies have suggested that large preoperative AAA size may impact late survival after elective EVAR. It is unclear, however, whether this association applies to patients with smaller AAA between 5.0-5.5 cm, who constitute a substantial portion of patients undergoing elective EVAR. The purpose of this study was to delineate the effect of AAA size between 5.0 and 5.5 cm on mid-term mortality after EVAR by analyzing a large national cohort, the Vascular Quality Initiative (VQI) database. Using the Vascular Quality Initiative (VQI) national database, patients who underwent EVAR for intact AAA between 2003 and 2018 were identified and stratified based on maximal AAA diameter into 3 groups: Group 1 (4.0 cm ≤ AAA <5.0 cm); Group 2 (5.0 cm ≤ AAA < 5.5 cm); and Group 3 (AAA ≥ 5.5 cm). Cox proportional hazard model and propensity score matching method were used to estimate AAA size effect on all-cause mortality at 1, 3, and 5 years after EVAR while adjusting for potential confounders. The study included 32,398 patients, of whom 81% were men with a mean age of 74. The most common group who underwent EVAR was Group 2 (5.0 cm ≤ AAA < 5.5 cm). Larger AAA size was associated with male sex (75% versus 79% versus 84%, for Groups 1, 2, and 3 respectively; P < 0.0001) and with coronary artery disease (27% versus 29% versus 31%, for Groups 1, 2, and 3 respectively, P< 0.0001); but was negatively associated with active smoking (33% versus 31% versus 30%, for Groups 1, 2, and 3, respectively, P< 0.001). While 10% of the largest and smallest AAA groups (Groups 3 and 1, respectively) were symptomatic, only 5% of patients in Group 2 were symptomatic (P < 0.01). Adjusted Cox proportional hazard modeling revealed that patients in Group 2 were at significantly lower risk of 5-year mortality when compared to patients in Group 3 (HR 0.66, 95% CI 0.61-0.72, P< 0.01), while similar in risk when compared to patients in Group 1 (HR 1.11, 95% CI 0.93-1.32, P= 0.26). Our analysis found that over 40% of EVAR in the national VQI cohort were performed for AAA < 5.5 cm, with the greatest number of patients undergoing EVAR at AAA size 5.0-5.5cm. Patients with AAA size 5.0-5.5 cm had better 5-year survival outcomes than patients with AAA ≥ 5.5 cm, and similar survival to patients with small AAA between 4.0-5.0 cm.


InP nanowire array solar cells achieving 13.8% efficiency by exceeding the ray optics limit.
Photovoltaics based on nanowire arrays could reduce cost and materials consumption compared with planar devices but have exhibited low efficiency of light absorption and carrier collection. We fabricated a variety of millimeter-sized arrays of p-type/intrinsic/n-type (p-i-n) doped InP nanowires and found that the nanowire diameter and the length of the top n-segment were critical for cell performance. Efficiencies up to 13.8% (comparable to the record planar InP cell) were achieved by using resonant light trapping in 180-nanometer-diameter nanowires that only covered 12% of the surface. The share of sunlight converted into photocurrent (71%) was six times the limit in a simple ray optics description. Furthermore, the highest open-circuit voltage of 0.906 volt exceeds that of its planar counterpart, despite about 30 times higher surface-to-volume ratio of the nanowire cell.


Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review.
Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54-1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67-0.97). Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians.


Sprint-interval but not continuous exercise increases PGC-1α protein content and p53 phosphorylation in nuclear fractions of human skeletal muscle.
Sprint interval training has been reported to induce similar or greater mitochondrial adaptations to continuous training. However, there is limited knowledge about the effects of different exercise types on the early molecular events regulating mitochondrial biogenesis. Therefore, we compared the effects of continuous and sprint interval exercise on key regulatory proteins linked to mitochondrial biogenesis in subcellular fractions of human skeletal muscle. Nineteen men, performed either 24 min of moderate-intensity continuous cycling at 63% of WPeak (CE), or 4 × 30-s "all-out" cycling sprints (SIE). Muscle samples (vastus lateralis) were collected pre-, immediately (+0 h) and 3 (+3 h) hours post-exercise. Nuclear p53 and PHF20 protein content increased at +0 h, with no difference between groups. Nuclear p53 phosphorylation and PGC-1α protein content increased at +0 h after SIE, but not CE. We demonstrate an exercise-induced increase in nuclear p53 protein content, an event that may relate to greater p53 stability - as also suggested by increased PHF20 protein content. Increased nuclear p53 phosphorylation and PGC-1α protein content immediately following SIE but not CE suggests these may represent important early molecular events in the exercise-induced response to exercise, and that SIE is a time-efficient and possibly superior option than CE to promote these adaptations.


The provision of therapy mattresses for pressure ulcer prevention.
Preventing pressure ulcers is complex and involves skin care, the provision of therapy mattresses, repositioning, the management of incontinence and adequate nutritional support. This article describes a model of therapy mattress provision that is based on non-powered products. Evaluating the efficiency of this model is challenging, due to the complexities of care, but Safety Thermometer data and incidents reports offer reassurance that non-powered therapy mattresses can provide adequate pressure ulcer prevention. Therapy mattress provision is only one of the five interventions and these are described in details to give readers a fuller picture of the model used at the author's trust.


MiR-30a targets IL-1α and regulates islet functions as an inflammation buffer and response factor.
Diabetes is an inflammatory disease. Inflammation plays an important role in islet functions. However, the exact mechanisms by which inflammation affects islet functions remain unclear. In this study, we investigated the regulatory effects of miR-30a on inflammation and islet functions. The results indicate that miR-30a serves as an inflammation-resolving buffer factor by targeting interleukin 1a (IL-1α) in immune cells and in islet cells, which might play an important role in inflammation homeostasis. miR-30a ameliorates islet functions in an inflammatory micro-environment by targeting the IL-1α/nuclear factor kappa B (NFKB) p65 subunit (p65)/p62 (SQSTM1)/insulin axis, which can be developed into a novel antidiabetic approach. miR-30a serves as a promising inflammation-response biomarker in inflammatory diseases and is possibly activated by the toll-like receptor 4 (TLR4)/IL-1α/NFKB pathways. However, the exact molecular mechanisms by which miR-30a regulates inflammation and islet functions as well as the potential applications in transitional medicine require further elucidation.


HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery.
Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery.


Discrete breathers in an electric lattice with an impurity: Birth, interaction, and death.
We have simulated aspects of intrinsic localized modes or discrete breathers in a modulated lumped transmission line with nonlinear varactors and a defect unit cell. As the inductance or capacitance of this cell is increased, a transition from instability to stability takes place. Namely, there exist threshold values of the inductance or capacitance of a lattice impurity for a breather to be able to attach to. A resistive defect can also anchor a breather. Moreover, by either gradually lowering all the source resistances, or else increasing the modulation frequency, multiple secondary ILMs can be spontaneously generated at host sites (with only a single inductive or capacitive defect). Further, if two impurities are subcritically spaced (the separation increasing with the amplitude of the modulation voltage), a breather can pop up midway, with no breathers at the impurity sites themselves. Finally, an ILM can pull closer its neighbors on both sides, only to perish once these ILMs have gotten sufficiently close. To our knowledge, these effects have not been reported for any discrete nonlinear system.


[The effect of the depolymerization and disintegration of the microtubular system on the cytoskeleton of untransformed and transformed cells].
How important are the changes of microtubule control for the realization of actin cortex changes during neoplastic transformation? To answer this question we studied the actin cytoskeleton and intermediate filaments condition after colcemid destruction or taxol disintegration of microtubule system in non-transformed cells BALB/c 3T3 and in the same cells transformed by Ha-ras gene. We have come to a conclusion that the differences between non-transformed and transformed cells in the actin cytoskeleton organization remain the same after specific inhibitor action on the microtubules; after the microtubules are destroyed the differences between the two cell types appear in the intermediate filament organization; there are reasons to assume that changes in the actin cortex structure may play the central role in morphological transformation expression.


Biochemomechanics of intraluminal thrombus in abdominal aortic aneurysms.
Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.


[Percutaneous echo-guided drainage and sclerotherapy of symptomatic renal cysts: critical comparison with laparoscopic treatment].
Nowadays, the minimally invasive treatment of symptomatic renal cyst has been progressively gaining wide acceptance while classic open surgery has been almost abandoned. It is a still controversial which minimally invasive approach provides the major advantages and results. Fifty-two patients with symptomatic simple renal cyst underwent ultrasound guided percutaneous drainage and sclerotherapy (ethanol 95 degrees) and 20 patients underwent laparoscopic unroofing of simple renal cysts in our department. No major complication was recorded with both the techniques. Even if we reported a higher recurrence rate (82%) with sclerotherapy than that with laparoscopic treatment (5%) we consider the percutaneous drainage a valid approach because it is a safe, easy and at low cost procedure.


Copper enhances cellular and network excitabilities, and improves temporal processing in the rat hippocampus.
Copper, an ion with many important metabolic functions, has also been proposed to have a role as modulator on neuronal function, mostly based on its effects on voltage- and neurotransmitter-gated conductance as well as on neurological symptoms of patients with altered copper homeostasis. Nevertheless, the mechanisms by which copper exerts its neuromodulatory effects have not been clearly established in a functional neuronal network. Using rat hippocampus slices as a neuronal network model, the effects of copper in the range of 10-100 nm were tested on the intrinsic, synaptic and network properties of the CA1 region. Most of the previously described effects of this cation were in the micromolar range of copper concentrations. The current results indicate that copper is a multifaceted neuromodulator, having effects that may be grouped into two categories: (i) activity enhancement, by modulating synaptic communication and action potential (AP) conductances; and (ii) temporal processing and correlation extraction, by improving reliability and depressing inhibition. Specifically it was found that copper hyperpolarizes AP firing threshold, enhances neuronal and network excitability, modifies CA3-CA1 pathway gain, enhances the frequency of spontaneous synaptic events, decreases inhibitory network activity, and improves AP timing reliability. Moreover, copper chelation by bathocuproine decreases spontaneous network spiking activity. These results allow the proposal that copper affects the network activity from cellular to circuit levels on a moment-by-moment basis, and should be considered a crucial functional component of hippocampal neuronal circuitry.


Osteomyelosclerosis, anemia and extramedullary hematopoiesis in mice lacking the transcription factor NFATc2.
Nuclear factors of activated T cells (NFAT) are transcription factors that are central to cytokine production in activated T cells and regulate the development and differentiation of various tissues. NFATc2 is expressed in hematopoietic stem cells and regulated during myeloid commitment in a lineage-specific manner. The biological role of NFATc2 in hematopoiesis is, however, unclear. In the present study, we analyzed steady-state hematopoiesis in young (<3 months) and old (>12 months) mice lacking NFATc2. Complete blood counts were performed in the peripheral blood, bone marrow and spleen. Using cytological and histological analyses, the blood cell differential was determined. Colony-formation assays were used to determine the differentiation potential of hematopoietic cells. Bone cell cultures were derived from the bone marrow, and bone remodeling markers were determined in the serum. NFATc2(-/-) mice older than 12 months were anemic and thrombocytopenic. The bone marrows of these mice showed a markedly reduced number of hematopoietic cells, of which megakaryocytic and erythroid lineages were most affected. While the number of hematopoietic progenitor cells in NFATc2-deficent bone marrow was reduced, the myeloid differentiation potential of these cells remained intact. Aged NFATc2(-/-) mice showed ossification of their bone marrow space and developed extramedullary hematopoiesis in the spleen. Ex vivo differentiation assays revealed an intrinsic defect of NFATc2-deficient stromal cells, in which NFATc2(-/-) osteoblasts differentiated more efficiently than wild-type cells, whereas osteoclast differentiation was impaired. Our data suggest that NFATc2 may play a role in the maintenance of steady-state hematopoiesis and bone remodeling in adult organisms.


Steroidogenic factor-1 is an essential transcriptional activator for gonad-specific expression of promoter I of the rat prolactin receptor gene.
The expression of the prolactin receptor is under the control of two putative tissue-specific (PI, gonads; PII, liver) and one common (PIII) promoters (Hu, Z. Z., Zhuang, L., and Dufau, M. L. (1996) J. Biol. Chem. 271, 10242-10246). The three promoter regions were co-localized to the rat chromosomal locus 2ql6, in the order 5'-PIII-PI-PII-3'. To investigate the mechanisms of gonad-specific utilization of PI, the promoter domain, regulatory cis-elements, and trans-factors were identified in gonadal cells. The promoter domain localized to the 152-base pair 5' of the transcriptional start site at -549 is highly active in gonadal cells but has minimal activity in hepatoma cells. It contains a steroidogenic factor 1 (SF-1) element (-668) that binds the SF-1 protein of nuclear extracts from gonadal cells and is essential for promoter activation. A CCAAT box (-623) contributes minimally to basal activity in the absence of the SF-1 element, and two adjacent TATA-like sequences act as inhibitory elements. Thus, PI belongs to a class of TATA-less/non-initiator gene promoters. These findings demonstrate an essential role for SF-1 in transcriptional activation of promoter I of the prolactin receptor gene, which may explain the tissue-specific expression of PI in the gonads but not in the liver and the mammary gland.


Importance of dynamic surface tension to the residual water content of fabrics.
At the end of the final spin cycle of the laundry process, the residual moisture content (RMC) of fabric is directly related to the dynamic surface tension of the residual water in the fabric. The LaPlace equation for capillary rise predicts that the capillary rise of solutions in a capillary is proportional to the surface tension at the air-liquid interface. If fabric can be considered to be a large ensemble of capillaries due to interfiber spacing, then the RMC of fabrics will be directly related to the surface tension of residual solution in the fabric. The use of a tailored rinse additive has the potential to decrease the surface tension of solution significantly, thus leading to a decrease in the residual water content of the fabric. It is expected that as the surfactant concentration increases the surface tension decreases. Hence, the RMC of fabrics must decrease with increasing surfactant concentration. However, a peak is observed in the RMC of fabrics before the critical micelle concentration (CMC) is reached. Prior to the CMC, it is proposed that a sudden adsorption of surfactant is occurring on the fabric surface leading to a decrease in bulk monomer concentration. The decrease in free monomer concentration should result in an increase in the equilibrium surface tension of the residual solution leading to a concomitant increase in RMC. Because the dynamic surface tension is measured on a short time scale (on the order of milliseconds), there will be less adsorption of monomer onto the newly created air-liquid interface of the bubbles during the measurement process. This decrease in adsorption should lead to a pronounced increase in the dynamic surface tension. This indeed was observed. The RMC correlates very well with the dynamic surface tension of the residual solution.


Immunosenescence and hurdles in the clinical management of older HIV-patients.
People living with HIV (PLWH) who are treated with effective highly active antiretroviral therapy (HAART) have a similar life expectancy to the general population. Moreover, an increasing proportion of new HIV diagnoses are made in people older than 50 y. The number of older HIV-infected patients is thus constantly growing and it is expected that by 2030 around 70% of PLWH will be more than 50 y old. On the other hand, HIV infection itself is responsible for accelerated immunosenescence, a progressive decline of immune system function in both the adaptive and the innate arm, which impairs the ability of an individual to respond to infections and to give rise to long-term immunity; furthermore, older patients tend to have a worse immunological response to HAART. In this review we focus on the pathogenesis of HIV-induced immunosenescence and on the clinical management of older HIV-infected patients.


A caffeine-sensitive Ca2+ store modulates K+-evoked secretion in chromaffin cells.
Catecholamine release from bovine adrenal medulla chromaffin cells superfused with a Krebs-N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid solution was monitored on-line with an electrochemical detector. Caffeine (10 mM) progressively depressed the magnitude of secretory responses to depolarizing pulses of 70 mM K+ and 2 mM Ca2+ (70 K+/2 Ca2+) in cells superfused with a Krebs-N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid solution containing 0 mM Ca2+ + 0.5 mM EGTA; blockade reached 80% at the third 70 K+/2 Ca2+ challenge given in the presence of caffeine. A similar effect was obtained when, instead of continuous superfusion, prepulses of caffeine were applied (10 mM for 60 s). The blocking effects of caffeine on K+-induced secretion depended on the time of exposure to the drug: the longer the exposure time the greater the blockade. The recovery of the K+ secretory responses previously impaired by caffeine was always gradual and followed a staircase mode. This contrasts with the effects of caffeine on various parameters measuring Ca2+ entry through Ca2+ channels, which did not parallel its effects on K+-evoked secretion. The secretion data, however, are compatible with the disappearance and recovery of an intracellular Ca2+ concentration signal triggered by K+ in single chromaffin cells loaded with fura 2 and treated with 10 mM caffeine. Thus, contrary to previous views, the depression of secretion by caffeine does not seem to be associated with inhibition of extracellular Ca2+ entry through Ca2+ channels. These functional data are, rather, compatible with the view that the degree of filling of a caffeine-sensitive intracellular Ca2+ store might regulate the extent of exocytosis. When emptied, such a store might act as a sink for the external Ca2+ entering through Ca2+ channels during cell depolarization, thus decreasing the intracellular Ca2+ concentration available for exocytosis.


Safe criteria and procedure for kangaroo care with intubated preterm infants.
Kangaroo care (KC) was safely conducted with mechanically ventilated infants who weighed less than 600 grams and were less than 26 weeks gestation at birth. These infants, ventilated for at least 24 hours at the time of the first KC session, were considered stable on the ventilator at low settings (intermittent mandatory ventilation < 35 breaths per minute and FiO2 < 50%), had stable vital signs, and were not on vasopressors. A protocol for implementation of KC with ventilated infants that uses a standing transfer, with two staff members assisting to minimize the possibility of extubation, is presented. Also discussed is the positioning of the ventilator tubing during KC. This protocol was implemented without any accidental extubation throughout an experimental research study. The criteria and protocol were compared to those available in published reports and revealed many similar elements, providing additional support for the recommended protocol. No adverse events occurred with the criteria and protocol reported here, suggesting that they can be adopted for broader use.


Structural basis of l-tryptophan-dependent inhibition of release factor 2 by the TnaC arrest peptide.
In Escherichia coli, elevated levels of free l-tryptophan (l-Trp) promote translational arrest of the TnaC peptide by inhibiting its termination. However, the mechanism by which translation-termination by the UGA-specific decoding release factor 2 (RF2) is inhibited at the UGA stop codon of stalled TnaC-ribosome-nascent chain complexes has so far been ambiguous. This study presents cryo-EM structures for ribosomes stalled by TnaC in the absence and presence of RF2 at average resolutions of 2.9 and 3.5 Å, respectively. Stalled TnaC assumes a distinct conformation composed of two small α-helices that act together with residues in the peptide exit tunnel (PET) to coordinate a single L-Trp molecule. In addition, while the peptidyl-transferase center (PTC) is locked in a conformation that allows RF2 to adopt its canonical position in the ribosome, it prevents the conserved and catalytically essential GGQ motif of RF2 from adopting its active conformation in the PTC. This explains how translation of the TnaC peptide effectively allows the ribosome to function as a L-Trp-specific small-molecule sensor that regulates the tnaCAB operon.


Human factors applications in the design of decision support systems for population health: a scoping review.
Public health professionals engage in complex cognitive tasks, often using evidence-based decision support tools to bolster their decision-making. Human factors methods take a user-centred approach to improve the design of systems, processes, and interfaces to better support planning and decision-making. While human factors methods have been applied to the design of clinical health tools, these methods are limited in the design of tools for population health. The objective of this scoping review is to develop a comprehensive understanding of how human factors techniques have been applied in the design of population health decision support tools. The scoping review will follow the methodology and framework proposed by Arksey and O'Malley. We include English-language documents between January 1990 and August 2021 describing the development, validation or application of human factors principles to decision support tools in population health. The search will include Ovid MEDLINE: Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE 1946-present; EMBASE, Scopus, PsycINFO, Compendex, IEEE Xplore and Inspec. The results will be integrated into Covidence. First, the abstract of all identified articles will be screened independently by two reviewers with disagreements being resolved by a third reviewer. Next, the full text for articles identified as include or inconclusive will be reviewed by two independent reviewers, leading to a final decision regarding inclusion. Reference lists of included articles will be manually screened to identify additional studies. Data will be extracted by one reviewer, verified by a second, and presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Ethics approval is not required for this work as human participants are not involved. The completed review will be published in a peer-reviewed, interdisciplinary journal.


[Morphofunctional changes of dendritic cells induced by sulfated polysaccharides of brown algae].
The effects of various sulfated polysaccharides of brown algae Fucus evanescens, Saccharina cichorioides and Saccharina japonica on the morphofunctional changes of dendritic cells have been investigated using flow cytometry and phase-contrast microscopy. The dendritic cells are characterized by larger sizes, vacuolated cytoplasm, eccentrically located nucleus, and also by the presence of numerous cytoplasmic pseudopodia of various shapes. They express surface markers, indicating their maturation (CD83, CD11c, HLA-DR, CD86). Increased production of immunoregulatory (IL-12) and proinflammatory TNF-a, IL-6) cytokines (by dendritic cells polarizes the development of the Th-1 type immune response.


Strengthening aging content in the baccalaureate social work curricula: what students have to say.
Encouraging student's interest and preparing them for social work practice with older adults is increasingly important in view of the demographic changes that are taking place. This article describes a study that engages BSW students in a discussion of best models for promoting gerontological social work curriculum infusion. Using two focus groups, the authors explore barriers to student interest and potential strategies to recruit students for gerontological social work. Fear of their own decline and mortality, lack of exposure to older adults and aging issues emerge as the primary reasons for aversion to working with older adults. Strategies to promote student interest, organize curricula, and create an inclusive learning context are discussed.


Cardiorespiratory response to free suspension simulating the situation between fall and rescue in a rock climbing accident.
Many factors contribute to the risk of late death after successful rescue in a rock climbing accident. One factor may be hemodynamic and respiratory compromise by free suspension in a rope between fall and rescue. The risk probably results from using a chest harness alone or the combination of a chest harness and a sit harness. No trials on the acute cardiorespiratory response to free suspension in rock climbing have been reported so far. The effect of 3 min free suspension in a chest harness or in a sit harness on cardiopulmonary parameters was investigated in a randomized, cross-over trial in six healthy volunteers in a simulated rock climbing accident. Measurements were performed before and during the suspension at an altitude of 171 m. No statistical change in cardiopulmonary parameters was observed after free suspension in the sit harness. After free suspension in the chest harness, mean forced vital capacity decreased by 34.3% and mean forced expiratory volume decreased by 30.6%. No statistical change of arterial oxygen saturation occurred and mean end-tidal carbon dioxide increased by 11.5%. Mean heart rate decreased by 11.7%, mean systolic blood pressure decreased by 27.6%, mean diastolic blood pressure decreased by 13.1%, and mean cardiac output decreased by 36.4%. The p value for all reported changes was <0.05. We conclude that free suspension in a chest harness leads to a dramatic impairment of hemodynamics and respiration. This may contribute to the risk of a fatal outcome if rescue is not timely.


Concise total synthesis of (-)-myxalamide A.
The MIDA touch: A concise and highly convergent protecting-group-free total synthesis of (-)-myxalamide A involves a stereoselective vinylogous Mukaiyama aldol reaction of a vinylketene silyl N,O-acetal, together with a one-pot Stille/Suzuki-Miyaura cross-coupling reaction using Burke's N-methyliminodiacetic acid (MIDA) boronate to connect left- and right-hand fragments of the molecule (see scheme).


Endophytic Beauveria bassiana induces biosynthesis of flavonoids in oilseed rape following both seed inoculation and natural colonization.
Cultivation of oilseed rape Brassica napus is pesticide-intensive, and alternative plant protection strategies are needed because both pesticide resistance and legislation narrow the range of effective chemical pesticides. The entomopathogenic fungus Beauveria bassiana is used as a biocontrol agent against various insect pests, but little is known about its endophytic potential and role in plant protection for oilseed rape. First, we studied whether B. bassiana can establish as an endophyte in oilseed rape, following seed inoculation. To evaluate the plant protection potential of endophytic B. bassiana on oilseed rape, we next examined its ability to induce plant metabolite biosynthesis. In another experiment, we tested the effect of seed inoculation on seedling survival in a semi-field experiment. Beauveria bassiana endophytically colonized oilseed rape following seed inoculation, and, in addition, natural colonization was also recorded. Maximum colonization rate was 40%, and generally increased with inoculation time. Seed inoculation did not affect the germination probability or growth of oilseed rape, but B. bassiana inoculated seeds germinated more slowly compared to controls. Endophytic colonization of B. bassiana induced biosynthesis of several flavonoids in oilseed rape leaves under controlled conditions. In the experiment conducted in semi-field conditions, inoculated seedlings had slightly higher mortality compared to control seedlings. Beauveria bassiana showed endophytic potential on oilseed rape via both natural colonization and seed inoculation, and it induced the biosynthesis of flavonoids. However, its use as an endophyte for plant protection against pests or pathogens for oilseed rape remains unclear. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors.
Metformin (MET) has recently emerged as a potentially active agent in cancer prevention and treatment. MET is thought to exert its antitumor effects either via modification of systemic metabolism or through cell-autonomous effects (e.g., activation of AMPK and inhibition of the mTOR pathway). Preliminary findings of the PRIME-NET study suggest that the addition of MET to treatment with everolimus (EVE) and/or somatostatin analogs (SSAs) can provide clinical benefit in diabetic neuroendocrine tumor (NET) patients. In light of this and other retrospective evidence of MET's anticancer activity in NETs, prospective studies are needed. A pilot, single-arm, open-label, prospective study (MetNET-2 trial, NCT02823691) was designed to evaluate the safety of MET in combination with lanreotide in well-differentiated gastrointestinal (WD GI) and lung NETs.


Archaeal fibrillarin-Nop5 heterodimer 2'-O-methylates RNA independently of the C/D guide RNP particle.
Archaeal fibrillarin (aFib) is a well-characterized S-adenosyl methionine (SAM)-dependent RNA 2'-O-methyltransferase that is known to act in a large C/D ribonucleoprotein (RNP) complex together with Nop5 and L7Ae proteins and a box C/D guide RNA. In the reaction, the guide RNA serves to direct the methylation reaction to a specific site in tRNA or rRNA by sequence complementarity. Here we show that a Pyrococcus abyssi aFib-Nop5 heterodimer can alone perform SAM-dependent 2'-O-methylation of 16S and 23S ribosomal RNAs in vitro independently of L7Ae and C/D guide RNAs. Using tritium-labeling, mass spectrometry, and reverse transcription analysis, we identified three in vitro 2'-O-methylated positions in the 16S rRNA of P. abyssi, positions lying outside of previously reported pyrococcal C/D RNP methylation sites. This newly discovered stand-alone activity of aFib-Nop5 may provide an example of an ancestral activity retained in enzymes that were recruited to larger complexes during evolution.


Auditory noise increases the allocation of attention to the mouth, and the eyes pay the price: An eye-tracking study.
We investigated the effect of auditory noise added to speech on patterns of looking at faces in 40 toddlers. We hypothesised that noise would increase the difficulty of processing speech, making children allocate more attention to the mouth of the speaker to gain visual speech cues from mouth movements. We also hypothesised that this shift would cause a decrease in fixation time to the eyes, potentially decreasing the ability to monitor gaze. We found that adding noise increased the number of fixations to the mouth area, at the price of a decreased number of fixations to the eyes. Thus, to our knowledge, this is the first study demonstrating a mouth-eyes trade-off between attention allocated to social cues coming from the eyes and linguistic cues coming from the mouth. We also found that children with higher word recognition proficiency and higher average pupil response had an increased likelihood of fixating the mouth, compared to the eyes and the rest of the screen, indicating stronger motivation to decode the speech.


Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical slow oscillation and associated local fast activity.
The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia reflects synchronized network activity composed of alternating active and silent (ON/OFF) phases at the local network and cellular level. The SO itself shows self-organized spatiotemporal dynamics as it appears to originate at unique foci on each cycle and then propagates across the cortical surface. During sleep, this rhythm is relevant for neuroplastic processes mediating memory consolidation especially since its enhancement by slow, rhythmic electrical fields improves subsequent recall. However, the neurobiological mechanism by which spontaneous or enhanced SO activity might operate on memory traces is unknown. Here we show a series of original results, using cycle to cycle tracking across multiple neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal dynamics of the SO are complex, showing interfering propagation patterns in the anterior-to-posterior plane. These patterns compete for expression and tend to alternate following phase resets that take place during the silent OFF phase of the SO. Applying sinusoidal electrical field stimulation to the anterior pole of the cerebral cortex progressively entrained local field, gamma, and multi-unit activity at all sites, while disrupting the coordination of endogenous SO activity. Field stimulation also biased propagation in the anterior-to-posterior direction and more notably, enhanced the long-range gamma synchrony between cortical regions. These results are the first to show that changes to slow wave dynamics cause enhancements in high frequency cortico-cortical communication and provide mechanistic clues into how the SO is relevant for sleep-dependent memory consolidation.


A simple but reliable method for measuring 3D Achilles tendon moment arm geometry from a single, static magnetic resonance scan.
Current methods for measuring in vivo 3D muscle-tendon moment arms generally rely on the acquisition of magnetic resonance imaging (MRI) scans at multiple joint angles. However, for patients with musculoskeletal pathologies such as fixed contractures, moving a joint through its full range of motion is not always feasible. The purpose of this research was to develop a simple, but reliable in vivo 3D Achilles tendon moment arm (ATMA) technique from a single static MRI scan. To accomplish this, for nine healthy adults (5 males, 4 females), the geometry of a cylinder was fit to the 3D form of the talus dome, which was used to estimate the talocrural flexion/extension axis, and a fifth-order polynomial fit to the line of action of the Achilles tendon. The single static scan in vivo 3D ATMA estimates were compared to estimates obtained from the same subjects at the same ankle joint angles using a previously validated 3D dynamic MRI based in vivo ATMA measurement technique. The ATMA estimates from the single scan in vivo 3D method (52.5mm±5.6) were in excellent agreement (ICC=0.912) to the validated in vivo 3D method (51.5mm±5.1). These data show reliable in vivo 3D ATMA can be obtained from a single MRI scan for healthy adult populations. The single scan, in vivo 3D ATMA technique provides researchers with a simple, but reliable method for obtaining subject-specific ATMAs for musculoskeletal modelling purposes.


Somatosensory evoked potentials from dermatomal stimulation as an indicator of L5 and S1 radiculopathy.
Dermatomal somatosensory evoked potential (DSEP) results for L5 and S1 were contrasted with electromyography (EMG) results for 50 patients referred to the electrodiagnosis laboratory to document the presence of radiculopathy. Stimulation sites were over the dorsum of the foot at the distal fifth metatarsal for the S1 dermatome and at the web space of the first and second toe for the L5 dermatome. Recordings were made at PZ reference to FZ. Spinal cord or cauda responses could not be detected. Both EMG and DSEP were contrasted to myelography or lumbar computerized tomography results on 31 patients. Side-to-side amplitude differences proved too variable to be of use. Sixty-five percent of abnormal DSEP results were on the basis of side-to-side latency criterion, and 35% were on the basis of an absent unilateral response. When compared to EMG and anatomic studies DSEP showed less accuracy and sensitivity. The specificity of the two tests was similar. Using both positive EMG and anatomic studies to define radiculopathy, there were 27% false negative tests and 9% false positive tests. An 86% root level correlation was found between EMG and DSEP. Dermatomal somatosensory evoked potential studies add little to the diagnosis of radiculopathy.


Independent Association of Overhydration with All-Cause and Cardiovascular Mortality Adjusted for Global Left Ventricular Longitudinal Systolic Strain and E/E' Ratio in Maintenance Hemodialysis Patients.
Fluid overload is common and associated with morbidity and mortality in patients with end-stage renal disease. The relationship between fluid overload and cardiac function is complex, and whether fluid overload is associated with adverse outcomes in patients undergoing hemodialysis (HD) independently of systolic and diastolic function of the left ventricle (LV) remains unclear. The present study aimed to investigate the relationship between overhydration and all-cause and cardiovascular (CV) mortality after adjusting for LV function in 178 maintenance HD patients. The relative hydration status (overhydration/ extracellular water, ∆HS) was measured using a body composition monitor, and then used to assess the fluid status. A ∆HS ≥7% was defined as fluid overload. Global left ventricular longitudinal systolic strain (GLS), and the early filling and early diastolic mitral annular velocity (E/E') ratio were assessed using speckle-tracking and tissue Doppler echocardiography. During a mean follow-up period of 2.7 years, 24 patients died, including 11 CV deaths. An increased ∆HS was significantly associated with all-cause and CV mortality in the univariate analysis. This prognostic significance remains after multivariate adjusting for GLS and E/E' ratio for all-cause (HR, 1.123; 95% CI, 1.063-1.186; p-value < 0.001) and CV (HR, 1.088; 95% CI, 1.005-1.178; p-value =0.037) mortality. Moreover, ∆HS significantly improved the prognostic value beyond conventional clinical and echocardiographic parameters. A higher ∆HS was independently associated with increased all-cause and CV mortality after adjusting for systolic and diastolic function of the LV. This suggests that ∆HS may be a relevant target for improving outcomes in maintenance HD patients.


Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression.
Peroxisome proliferator-activated receptor (PPAR) δ is implicated in the carcinogenesis of several types of cancer. However, the therapeutic efficacy of PPARδ ligands against cancer progression is unclear. Here, we showed that PPARδ modulates the migration and invasion of melanoma cells by up-regulating Snail expression. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly increased the migration and invasion of highly metastatic A375SM cells, but not that of low metastatic A375P cells. The migration- and invasion-promoting effects of PPARδ on A375SM cells was associated with increased Snail expression, which was accompanied by a decrease in E-cadherin expression. Furthermore, a significant concentration- and time-dependent increase in the levels of Snail mRNA and protein was observed in A375SM cells (but not A375P cells) treated with GW501516. The effects of GW501516 were almost completely abrogated by a small interfering RNA against PPARδ, suggesting that PPARδ mediates the effects of GW501516. Activation of PPARδ in SK-MEL-2 and SK-MEL-5 (but not SK-MEL-3) melanoma cell lines also led to significant increases in the expression of Snail mRNA and protein, which mirrored the invasive and migratory potential of these cell lines. These results suggest that PPARδ promotes the aggressive phenotype observed in highly metastatic melanoma cells by up-regulating Snail.


The Ambiguous Role of γδ T Lymphocytes in Antitumor Immunity.
γδ T cells play a role in immune surveillance because they recognize stress-induced surface molecules and metabolic intermediates that are frequently dysregulated in transformed cells. Hence, γδ T cells have attracted much interest as effector cells in cell-based immunotherapy. Recently, however, it has been realized that γδ T cells can also promote tumorigenesis through various mechanisms including regulatory activity and IL-17 production. In this review we outline both the pathways involved in cancer cell recognition and killing by γδ T cells as well as current evidence for their protumorigenic activity in various models. Finally, we discuss strategies to improve the tumor reactivity of γδ T cells and to counteract their protumorigenic activities, which should open improved perspectives for their clinical application.


Recurrent Hydropneumothorax After COVID-19.
A 60-year-old male with a past medical history of heart failure with reduced ejection fraction, obstructive sleep apnea, atrial flutter, and hypertension initially presented to the emergency department with a chief complaint of shortness of breath. He was diagnosed with COVID-19-induced acute hypoxic respiratory failure. Before his presentation to the emergency department, he was treated with a brief course of hydroxychloroquine, azithromycin, and prednisone. His initial hospitalization was relatively uncomplicated. He then presented back to the emergency department approximately five months later with chief complaints of continued dyspnea and increased work of breathing. On this presentation, he was noted to have a right-sided pneumothorax with a moderate right-sided pleural effusion. The effusion was drained through CT (computed tomography)-guided catheter insertion. Pleural fluid culture and sensitivity were negative, and a cartridge-based nucleic acid amplification test (CBNAAT) was not performed. He was discharged a few days later to home. Over the next several weeks, the patient had recurrent admissions and chest tube placements for unresolving hydropneumothorax. He eventually had a right-sided posterolateral thoracotomy performed. The tissue sample from the thoracotomy was noted to have positive gram staining for fungal hyphae consistent with aspergillosis. This was initially considered a contaminant and not treated with antifungal medication. Unfortunately, after the thoracotomy, the patient continued to have complications including subcutaneous emphysema and recurring hydropneumothoraces. He was taken for another procedure after a repeat CT showed intercostal herniation of the pleura between the fifth and sixth ribs. The herniation was excised, and the pleura was repaired. This pleural tissue was then sent to pathology and noted to have non-caseating granulomas consistent with aspergillosis. At this time, the patient was started on voriconazole. After initiating this medication, the patient's last chest x-ray showed stable findings of his chronic disease process with no new or worsening hydropneumothorax.


Opioids and Chronic Pain: Impact of the NIH Pathways to Prevention Evidence-Based Workshop Program.
The National Institutes of Health (NIH) Office of Disease Prevention (ODP) sponsors Pathways to Prevention (P2P), an evidence-based scientific workshop program that helps advance prevention research. Each P2P workshop is presided over by an independent expert panel and informed by a systematic evidence review, scientific presentations, and public input. Post-workshop activities include collaborating with federal agency partners to develop an action plan for addressing key research gaps. Primary outcomes of P2P workshops include developing a research agenda and creating or enhancing initiatives to implement the agenda. In 2014, ODP partnered with the NIH Pain Consortium and two NIH institutes to convene "The Role of Opioids in the Treatment of Chronic Pain." This workshop assessed the state-of-the-science on the long-term effectiveness, safety, and harms of opioid use for managing chronic pain. In 2021, ODP initiated an assessment of the outcomes and impact of the Opioids P2P workshop. We applied an evaluation framework and a mixed methods approach encompassing web analytics, bibliometric assessment, grant portfolio analysis, policy assessment, and key informant interviews. Our data showed that the workshop attracted a broad audience, and its published reports had high impact. The workshop also helped inform over 100 new research projects through grants funded by three federal agencies, as well as national legislation and practice guidelines from influential organizations. In sum, the Opioids P2P workshop and follow-up activities have identified gaps in scientific knowledge, informed clinical practice, and catalyzed change on a national level for addressing the prescription opioid crisis.


Antibody reactivity of a standardized human serum protein solution against a spectrum of microbial pathogens and toxins: comparison with fresh frozen plasma.
In this study, we compared a standardized solution of human serum protein (HSP) and fresh frozen plasma (FFP) with regard to the antibody specificity against a number of microbial pathogens and some important pathogenicity factors of bacterial pathogens. Due to the clinical use of HSP and FFP for therapeutical plasma exchange, we have chosen a spectrum of microbial pathogens for serological analysis that is critical in clinical settings. With the enzyme-linked immunosorbent assay technique, we could show that HSP contains marked IgG antibody reactivity against antigens of Escherichia coli, Campylobacter jejuni, Enterobacter sakazakii, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Chlamydia pneumoniae, and Candida albicans. Although no IgM antibodies against the pathogens tested could be detected in HSP, moderate IgA reactivity was found against 4 of 12 microbial antigens. Immunoblot analysis demonstrated specific IgA and IgG responses against the endoproteinase Glu-C and the superantigens enterotoxin A and B of S. aureus, the IgA-protease of Neisseria gonorrhoeae, and Shiga toxin 2 of enterohemorrhagic E. coli. By using 3 different HSP batches in parallel, we could demonstrate antibody reactivity against important microbial pathogens and toxins. This antibody profile is essentially more homogeneous than that of 3 batches of FFP.


Training nu-support vector regression: theory and algorithms.
We discuss the relation between epsilon-support vector regression (epsilon-SVR) and nu-support vector regression (nu-SVR). In particular, we focus on properties that are different from those of C-support vector classification (C-SVC) and nu-support vector classification (nu-SVC). We then discuss some issues that do not occur in the case of classification: the possible range of epsilon and the scaling of target values. A practical decomposition method for nu-SVR is implemented, and computational experiments are conducted. We show some interesting numerical observations specific to regression.


Characteristics of patients with COPD in three motivational stages related to smoking cessation.
To characterize patients with chronic obstructive pulmonary disease (COPD) in different motivational stages related to smoking cessation. 633 smoking COPD patients from 67 general practices participated in a cross-sectional study. The patients were compared with respect to health indicators, demographics, self-efficacy, nicotine dependence, attitudes, and action plans. In line with previous Dutch results, smokers in precontemplation associated significantly fewer advantages with smoking cessation than smokers contemplating quitting and preparing to quit. Preparers had significantly higher self-efficacy expectations about quitting than the other smokers. Patients preparing to quit suffered from more COPD complaints than precontemplators. Smokers contemplating quitting and preparing to quit developed more plans to turn intentions to quit into action. More than 50% of the smokers with COPD are amenable to smoking cessation support. Preparers and contemplators did not differ as much as previous studies found. It would be advantageous to tailor COPD counseling to two distinct groups (unmotivated smokers and smokers motivated to quit), to discuss the advantages of quitting with unmotivated smokers, and to increase self-efficacy, and action planning for smokers motivated to quit. COPD patients are amenable to counseling to quit smoking. Addressing COPD complaints may contribute to greater motivation.


Current perspective. Diabetic vascular disease: from endothelial dysfunction to atherosclerosis.
Cardiovascular complications are the leading cause of death in diabetes. Over the past decade a number of studies have addressed the underlying mechanisms. Derangements of endothelial function, also referred to as endothelial dysfunction, have emerged to be the crucial early step in the development of atherosclerosis and are also involved in plaque progression and clinical emergence. Endothelial dysfunction is a condition of impaired endothelium-dependent vasodilation and most important of "endothelial activation", characterized by a proinflammatory, proliferative, and procoagulatory milieu that promotes initiation and complications of atherogenesis. A synergistic cross-talk among the conventional cardiovascular risk factors associated with diabetes contributes to disruption of endothelial integrity and accelerated atherosclerosis. This review will focus on the multifactorial nature of endothelial dysfunction in diabetes, the relationship between endothelial dysfunction, conventional cardiovascular risk factors and atherosclerosis, and the therapeutic options to improve endothelial function.


A systematic review of diversity, equity, and inclusion and antiracism training studies: Findings and future directions.
A growing number of organizations are prioritizing diversity, equity, and inclusion (DEI) and antiracism in the workplace, including investing resources in DEI or antiracism training. However, such trainings vary widely in curriculum, objectives, delivery, and evaluation, with little known about the efficacy of existing trainings. The aim of this systematic review is to evaluate training characteristics, measures, and results of peer-reviewed studies (published between 2000 and 2022) testing DEI or antiracism trainings. Studies were identified using Google Scholar, JSTOR, and a university library database. Key search terms included "diversity, equity, and inclusion training"; "antiracism training"; and "effect," "impact," "outcome," or "evaluation." The search yielded N = 15 DEI training studies and N = 8 antiracism training studies. The majority of studies (75% of antiracism training; 66.6% of DEI training) utilized a one-time training session. Content, objectives, measures, and impact varied widely across studies. Randomized designs were uncommon (13%), and over 70% of studies had majority female participants. Findings highlight several strategies to advance the field of DEI and antiracism training, such as shifting curriculum from targeting individual knowledge to supporting behavioral and organizational change, providing longitudinal training, standardizing outcomes of interest, and implementing rigorous evaluation methods.


[Some questions on the author of Qian Jin Yi Fang].
It is said that the alleged author of Qian Jin Yi Fang, a supplement to Bei Ji Qian Jin Yao Fang is SUN Si-miao. It is claimed that, based on the relevant historical materials, there are overlapping contents, principle differences in the academic ideas between the two books. Moreover, there are differences between the texts of Qian Jin Yi Fang cited by Wai Tai Mi Yao and the modern version of Qian Jin Yi Fang, all these texts are not from the original Qian Jin Yi Fang. It can be concluded that the author of Qian Jin Yi Fang is not SUN Si-miao.


Linking health effects to PM components, size, and sources.
A number of physicochemical factors contribute to the adverse cardiopulmonary effects associated with exposure to ambient PM. It has become increasingly clear that mass concentration alone may not be the best indices for associating health effects with exposure to PM. Recent epidemiology and animal toxicology data have examined the role of particle size and components on cardiopulmonary effects. In addition, collaborative efforts in North America and Europe have examined the in vitro and in vivo toxicity of size-fractionated particles collected in a variety of urban and rural sites. The ability of these latter studies and other investigations to develop source apportionment findings will become increasingly important for policy makers and regulators in their deliberations.


Studies of spermatogenesis in the hepaticae. I. Ultrastructure of the vierergruppe in Marchantia.
Spermatids of the liverwort Marchantia polymorpha were shown by analysis of thin-sections to contain a four-layered organelle, the Vierergruppe, lying between the flagellar bases above and a subjacent mitochondrial body. The uppermost layer consists of parallel tubules structurally similar to those of the axoneme. Some of the tubules extend beyond the four-layered region to form a long ribbon-like appendage. The second layer consists of low, vertical, membranous fins connected by numerous short links to the tubules above. The third layer, limited above and below by two horizontal membranes, consists of vertical partitions, apparently continuous with the fins. The fourth and lowermost layer consists of narrow parallel tubules aligned beneath alternate partitions. The long axes of the lower three layers are parallel to each other and lie at an angle of 48 degrees to the tubule axis of the uppermost stratum. A graphic representation of a three-dimensional scale model interpreting organelle structure is given. The Vierergruppe supersedes Dreiergruppe interpretation in most if not all of the bryophytes studied to date.


Freak waves in the linear regime: a microwave study.
Microwave transport experiments have been performed in a quasi-two-dimensional resonator with randomly distributed conical scatterers. At high frequencies, the flow shows branching structures similar to those observed in stationary imaging of electron flow. Semiclassical simulations confirm that caustics in the ray dynamics are responsible for these structures. At lower frequencies, large deviations from Rayleigh's law for the wave height distribution are observed, which can only partially be described by existing multiple-scattering theories. In particular, there are "hot spots" with intensities far beyond those expected in a random wave field. The results are analogous to flow patterns observed in the ocean in the presence of spatially varying currents or depth variations in the sea floor, where branches and hot spots lead to an enhanced frequency of freak or rogue wave formation.


A Novel and Non-Cytotoxic Self-Healing Supramolecular Elastomer Synthesized with Small Molecular Biological Acids.
A novel and non-cytotoxic self-healing supramolecular elastomer (SE) is synthesized with small-molecular biological acids by hydrogen-bonding interactions. The synthesized SEs behave as rubber at room temperature without additional plasticizers or crosslinkers, which is attributed to the phase-separated structure. The SE material exhibits outstanding self-healing capability at room temperature and essential non-cytotoxicity, which makes it a potential candidate for biomedical applications.


The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome.
In this study we examined the possible correlation between insulin metabolism and outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women who were entered into the study in a consecutive fashion. Following performance of the CIGMA (continuous infusion of glucose with model assessment) test, 17 women were classified as insulin resistant and 25 women as non-insulin resistant. Each woman received up to two cycles of low-dose follicle stimulating hormone (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70 cycles performed. The insulin resistant PCOS women required more gonadotrophin and a longer time to achieve follicular maturation. By multiple regression gonadotrophin consumption correlated best with CIGMA value but not with fasting insulin concentration or body mass index. In the insulin resistant PCOS women 10 out of 29 cycles were cancelled due to a multifollicular response, while only one of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the non-insulin resistant PCOS women. In conclusion, in PCOS women insulin resistance seems to be an unfavourable condition resulting in an elevated cancellation rate and a low conception rate following low-dose FSH stimulation.


Vascular elasticity of systemic lupus erythematosus patients is associated with steroids and hydroxychloroquine treatment.
We studied the large and small artery elasticity (AE) and systemic vascular resistance (SVR) of systemic lupus erythematosus (SLE) patients according to treatment profile. Forty-one SLE patients (90% female, mean age 48.7 +/- 2.4 years) were compared to 96 healthy controls. The large and small AE and the SVR were derived from radial artery waveforms (model CR-2000, HDI Inc.). Patients were categorized into groups according to treatment: steroid (12), hydroxychloroquine (HCQ) (9), steroid+HCQ (16), and no-steroids-no-HCQ (4). The steroid group had reduced large AE and increased SVR as compared to the HCQ group (8.3 mmHg x mL x 10 and 18.4 dyne x sec x 10(-3) versus 13.7 and 14.4, respectively). Mean large AE and the SVR of the HCQ group was similar to that of the controls (11.8 mmHg x mL x 10 and 14.5 dyne x sec x 10(-3), respectively). Mean large AE and SVR of the steroid+HCQ group were better than the steroid group (10.4 mmHg x mL x 10 and 16.0 dyne x sec x 10(-3)). Patients that received steroids had higher rates of hypertension (36%) and diabetes (1%) compared to rest of the patients (15% and 0%, respectively). Small AE, blood pressure, CRP, and SLEDAI were similar between the groups. Among SLE patients, steroid treatment was associated with the highest degree of vascular damage, and HCQ was associated with the lowest degree of vascular damage. It is possible that the steroids are responsible in part to the increased large-vessel manifestations observed in these patients, and that HCQ might have a protective effect on the vessel wall.


[Physical development of schoolchildren in the city of Moscow during the recent decade and a related assessment].
Data on the long-term and short-term monitoring over the growth and development of schoolchildren in the city of Moscow during the second half of the last century are presented (including around 10,000 persons). According to the purpose-oriented 40-year observations of the growing generation in Moscow, the accelerated physical development started in the 60-ies with its peak falling on the middle 70-ies; the elements of deceleration set on in the 80-ies and continued through the 90-ies. As for now, a deficit of the body weight, reduced width and span parameters and a decreased power abilities as well as shifts of the menarche time in girls towards an older age are typical of contemporary schoolchildren in Moscow. The detected trends are common regularities typical of children in all Russia's big cities.


[Duplex and transcranial sonography in the preoperative evaluation of cerebrovascular circulation before heart operations].
Fifty unselected patients undergoing open heart surgery (OHS) were examined by duplex and transcranial Doppler sonography. Two high degree (greater than 75%) carotid stenosis were found in 70 carotid arteries of 35 patients with coronary artery disease. Fourteen vessels had unmistakable signs of extracranial vascular disease whilst 54 carotid arteries were identified as normal. Two high degree (greater than 75%) carotid stenosis were found in 30 vessels of 15 patients with valvular disease. Seven other vessels had a low grade stenosis or excessive atheroma, whereas 21 were identified as normal. The rate of about 5-10% asymptomatic high grade carotid stenosis in patients undergoing OHS justifies routine noninvasive examination of the cerebral circulation by duplex and transcranial Doppler sonography. Patients with high grade stenosis are offered a follow-up preventive programme against cerebral infarction, which consists of 3 steps: 1. anti-platelet aggregating drugs, 2. periodic control examinations by duplex and transcranial Doppler sonography, and 3. continued evaluation of indication for carotid endarterectomy.


TSG-6: A multifunctional protein with anti-inflammatory and tissue-protective properties.
Tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) is an inflammation-associated secreted protein that has been implicated as having important and diverse tissue protective and anti-inflammatory properties, e.g. mediating many of the immunomodulatory and beneficial activities of mesenchymal stem/stromal cells. TSG-6 is constitutively expressed in some tissues, which are either highly metabolically active or subject to challenges from the environment, perhaps providing protection in these contexts. The diversity of its functions are dependent on the binding of TSG-6 to numerous ligands, including matrix molecules such as glycosaminoglycans, as well as immune regulators and growth factors that themselves interact with these linear polysaccharides. It is becoming apparent that TSG-6 can directly affect matrix structure and modulate the way extracellular signalling molecules interact with matrix. In this review, we focus mainly on the literature for TSG-6 over the last 10 years, summarizing its expression, structure, ligand-binding properties, biological functions and highlighting TSG-6's potential as a therapeutic for a broad range of disease indications.


[Prenatal diagnosis of 1p36.3 microdeletion in a fetus with complex heart defect].
To analyze a fetus presenting with complex heart defect and assess the recurrence risk. Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism-based array (SNP-array) were used to analyze the fetus and his parents. SNP-array has detected a 6.9 Mb microdeletion at 1p36.33-p36.23 in the fetus. Chromosomal and FISH analyses indicated that the father of the fetus had a karyotype of 46,XY,t(1;14)(p36.3;p12), and that the fetus has inherited an abnormal chromosome 1 derived from the paternal translocation. SNP-array combined with GTG banding and FISH can help to detect cryptic translocation, microdeletion or microduplication of chromosomes and is valuable to assess the recurrence risk for the affected family.


Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans.
Caenorhabditiselegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop a C. elegans-Candidaparapsilosis infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (C.parapsilosis (sensustricto), Candidaorthopsilosis and Candidametapsilosis) caused infection resulting in C. elegans killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in C. elegans-Candida infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of cnc-4, cnc-7, and fipr-22/23. Overall, the C. elegans-C. parapsilosis infection model can be used to model C. parapsilosis host-pathogen interactions.


Methods for measurement of muscle function. Methodological aspects, reference values for children, and clinical applications.
In children isometric muscle force can be measured with acceptable reproducibility by using a simple hand-held dynamometer. Reference values for 10 different muscle groups are given for children aged 3.5-15 years. If age and weight are known, the force can be predicted. The most pronounced differences between the dominant and the non-dominant side were found in the elbow flexors, 3 of the 6 age groups showing greater force on the dominant side, and in the wrist extensors, the 2 oldest age groups being stronger on the dominant side. Sex differences were present as early as 9.5-11 years of age, boys being stronger than girls. Isokinetic muscle torque of the dorsiflexors of the ankle increased with age. Reference values are given for peak torque in children 6, 9, 12, and 15 years of age. The most intense force development occurs between 12 and 15 years of age in boys, and earlier in girls. Sex differences appear in early puberty. In young children the dominant leg was the stronger at the highest velocities. In the older children the non-dominant leg was the stronger at low velocities. Isokinetic measurements are time-consuming and require experience, and should be regarded as complementary to isometric testing. In muscle groups that are too weak to overcome gravity isometric and isokinetic methods cannot be used. Functional tests of motor ability are especially useful in patients with severely impaired muscle function when other test methods are inadequate or difficult to evaluate. The natural course of Duchenne muscular dystrophy was followed in 16 boys by means of functional tests, isometric tests, isokinetic tests of concentric muscle contraction, and manual tests. Of these only the isokinetic method proved unreliable, possibly because of difficulty in activating the muscles at different speeds. The function of adductor pollicis was studied by supramaximal electrical stimulation of the ulnar nerve. Force-frequency curves and reference values for relaxation rate and half contraction time to tetanus for children aged 9, 12, and 15 years are presented. The half contraction time to tetanus was briefer in the older children than in the younger. The relative force developed at a stimulation of 10 Hz increased with age. Apart for the increase in muscle force with increasing age, no other differences emerged between the different age groups. No sex differences were found. The electrical stimulation test is rather painful, and only about 60% of the children persevered to the end of the test.(ABSTRACT TRUNCATED AT 400 WORDS)


Achieving safe, effective, and durable Zika virus vaccines: lessons from dengue.
Newly proposed candidate Zika virus vaccines might or might not succeed in raising safe, effective, and durable protection against human Zika virus infections or syndromes. Analyses of a clinically tested and licensed dengue vaccine that failed to protect seronegative individuals from breakthrough or enhanced dengue infections suggest that poor T-cell immunity might have contributed to protection failure. Because of the similarity of Zika and dengue viruses, an analogous unwanted outcome might occur with some Zika virus vaccine designs. A successful Zika virus vaccine requires challenge experiments that are done at long intervals after immunisation and that identify protection as the absence of viraemia and the absence of an anamnestic antibody response. T-cell immunity might be an essential component of safe, efficacious, and durable Zika virus vaccines.


Additive Manufacturing of Honeybee-Inspired Microneedle for Easy Skin Insertion and Difficult Removal.
With natural evolution, honeybee stinger with microbarbs can easily penetrate and trap in the skin of hostile animals to inject venom for self-defense. We proposed a novel three-dimensional additive manufacturing method, namely magnetorheological drawing lithography, to efficiently fabricate a bioinspired microneedle imitating a honeybee stinger. Under the assistance of an external magnetic field, a parent microneedle was directly drawn on the pillar tip, and tilted microbarbs were subsequently formed on the four sides of the parent microneedle. Compared with the barbless microneedle, the microstructured barbs enable the bioinspired microneedle for easy skin insertion and difficult removal. The extraction-penetration force ratio of the bioinspired microneedle was triple that of the barbless microneedle. The stress concentration at the barbs helps to reduce the insertion force of the bioinspired microneedle by minimizing the frictional force, whereas it increases the adhesion force by interlocking the barbs in the tissue during retraction. Such finds may provide an inspiration for further design of barbed microtip-based microneedles for tissue adhesion, transdermal drug delivery, biosignal recording, and so on.


Left atrial thrombus causing pulmonary embolism by passing through an atrial septal defect.
A 66-year-old woman admitted with dyspnea on exertion had atrial fibrillation and left ventricular dysfunction. Echocardiography revealed an atrial septal defect (ASD) and a soft, easily deformable thrombus in the dilated left atrium. The atrial mass suddenly disappeared on the 10th day after admission, and contrast-enhanced chest computed tomography and pulmonary blood flow scintigraphy showed that the thrombus had detached from the left atrium, floated into the right atrium through the ASD and caused pulmonary embolism. This is the first documented case of a left atrial thrombus causing pulmonary embolism by passing through an ASD. When an ASD is present, it is important to consider not only paradoxical thromboembolism (from the right to the left atrium), but also pulmonary embolism caused by thromboembolism from the left to the right atrium.


Effect of truck operating weight on heavy-duty diesel emissions.
Heavy-duty diesel vehicles are substantial contributors of oxides of nitrogen (NO(x)) and particulate matter (PM) while carbon monoxide and hydrocarbon (HC) emissions from diesel vehicles receive less attention. Truck emissions inventories have traditionally employed average fuel economy and engine efficiency factors to translate certification into distance-specific (g/mi) data, so that inventories do not take into account the real effects of truck operating weight on emissions. The objective of this research was to examine weight corrections for class 7 and 8 vehicles (over 26 000 lb (11 793 kg) gross vehicle weight) from a theoretical point of view and to present a collection of original data on the topic. It was found by combining an empirical equation with theoretical truck loads that the NO(x) emissions increased by approximately 54% for a doubling of test weight. Emissions data were gathered from specific tests performed using different test weights and using various test schedules, which can consist of cycles or routes. It was found experimentally that NO(x) emissions have a nearly linear correlation with vehicle weight and did not vary much from vehicle to vehicle. NO(x) emissions were also found to be insensitive to transient operation in the test schedule. The observed trends correlate well with the theory presented, and hence, the NO(x) emissions can be predicted reasonably accurately using the theory. If NO(x) data were considered in fuel-specific (g/gal) units, they did not vary with the test weight. HC emissions were found to be insensitive to the vehicle weight. CO and PM emissions were found to be a strong function of weight during transient operation. Under transient operation, the CO emissions value increased by 36% for an increase in test weight from 42 000 (19 051 kg) to 56 000 lb (25 401 kg). However, CO and PM were found to be insensitive to the vehicle weight during nearly steady-state operation.


[Psychomotor and intellectual development in 52 children with congenital hypothyroidism screened at birth. Factors likely to have an effect on prognosis].
Follow-up was obtained for at least 4 years in 52 children (40 F, 12 M) who presented with congenital hypothyroidism, detected by TSH screening at 5 days of age and persisting at the 3th-5th postnatal week. Eight had athyreosis, 33 an ectopic thyroid gland and 11 an anatomically normal thyroid. Treatment began at day 29 +/- 12 (1 SD) with I-T4 solution, 5-7 micrograms/kg/day and was followed in order to obtain immediately T4 and FT4 blood levels in the high normal range, with normal TSH at least from age 6 months. Mental development was evaluated at age 0.5, 1 and 2 years with the Brunet-Lézine scale, and at 4 years with the Termann-Merill test. Thirty of them were reevaluated at age 7 years with the WISC-R test. The results of these tests were all in the normal range, with individual differences, the range being 85 to 145 at 4 years and 95 to 133 at 7 years, not different from those obtained in age-matched controls and in the normal siblings of the patients at 4. The WISC-R test at 7 years did not show differences between verbal and performance levels. Its results were correlated with those of the TM test performed at age 4 years in the same 30 patients: r = 0.75, p less than 0.01. School level at 7 years was normal for age in these 30 hypothyroid children.(ABSTRACT TRUNCATED AT 250 WORDS)


Nipah virus attachment glycoprotein stalk C-terminal region links receptor binding to fusion triggering.
Membrane fusion is essential for paramyxovirus entry into target cells and for the cell-cell fusion (syncytia) that results from many paramyxoviral infections. The concerted efforts of two membrane-integral viral proteins, the attachment (HN, H, or G) and fusion (F) glycoproteins, mediate membrane fusion. The emergent Nipah virus (NiV) is a highly pathogenic and deadly zoonotic paramyxovirus. We recently reported that upon cell receptor ephrinB2 or ephrinB3 binding, at least two conformational changes occur in the NiV-G head, followed by one in the NiV-G stalk, that subsequently result in F triggering and F execution of membrane fusion. However, the domains and residues in NiV-G that trigger F and the specific events that link receptor binding to F triggering are unknown. In the present study, we identified a NiV-G stalk C-terminal region (amino acids 159 to 163) that is important for multiple G functions, including G tetramerization, conformational integrity, G-F interactions, receptor-induced conformational changes in G, and F triggering. On the basis of these results, we propose that this NiV-G region serves as an important structural and functional linker between the NiV-G head and the rest of the stalk and is critical in propagating the F-triggering signal via specific conformational changes that open a concealed F-triggering domain(s) in the G stalk. These findings broaden our understanding of the mechanism(s) of receptor-induced paramyxovirus F triggering during viral entry and cell-cell fusion. The emergent deadly viruses Nipah virus (NiV) and Hendra virus belong to the Henipavirus genus in the Paramyxoviridae family. NiV infections target endothelial cells and neurons and, in humans, result in 40 to 75% mortality rates. The broad tropism of the henipaviruses and the unavailability of therapeutics threaten the health of humans and livestock. Viral entry into host cells is the first step of henipavirus infections, which ultimately cause syncytium formation. After attaching to the host cell receptor, henipaviruses enter the target cell via direct viral-cell membrane fusion mediated by two membrane glycoproteins: the attachment protein (G) and the fusion protein (F). In this study, we identified and characterized a region in the NiV-G stalk C-terminal domain that links receptor binding to fusion triggering via several important glycoprotein functions. These findings advance our understanding of the membrane fusion-triggering mechanism(s) of the henipaviruses and the paramyxoviruses.