Somatosensory input to the ventrolateral thalamic region in the macaque monkey: potential substrate for parkinsonian tremor.
In the present study, we determined the anatomic relationships between somatosensory and motor pathways within ventrolateral (VL) thalamic nuclei of the motor thalamus of macaque monkeys. In labeling experiments, four macaque monkeys (Macaca mulatta) received injections of biotinylated dextran amine and wheat germ agglutinin conjugated to horseradish peroxidase into the cerebellar nuclei or internal segment of the globus pallidus and cervical segments of the spinal cord, respectively. Each tracer was visualized in brain sections by sequentially using a different chromogen. Labeled terminals were plotted and superimposed on adjacent brain sections processed for Nissl substance, acetylcholinesterase, and the antigens for calbindin and Cat-301 to reveal thalamic nuclei. The labeled cerebellar terminals were distributed throughout the posterior VL (VLp), whereas the labeled pallidothalamic terminals were concentrated in the anterior VL and the ventral anterior nucleus. The spinothalamic input was directed mostly to the ventral posterior complex and cells just caudal to it. In addition, the patches of spinothalamic terminations intermingled and partly overlapped with the cerebellothalamic, but not with the pallidothalamic terminations within VLp. The regions of overlap of somatosensory and cerebellar inputs within the VLp of the present study appear to correspond to the reported locations of the tremor-related cells in parkinsonian patients. Thus, the overlapping spinothalamic and cerebellar inputs may provide a substrate for the altered activity of motor thalamic neurons in such patients.


Ophthalmic manifestations of multiple myeloma.
The ophthalmic manifestations of multiple myeloma can be seen in practically every ocular structure. Ocular findings may be the first manifestations of the disease. It may also occur as one of the extramedullary manifestations of the disease or as the first sign of insufficient chemotherapy. Multiple myeloma may cause ocular pathology by direct infiltration or as extramedullary plasmacytomas resulting in displacement or compression of tissues, by causing hyperviscosity syndrome, and by immunoglobulin light chain deposition in ocular tissues. To outline the ophthalmic manifestations of multiple myeloma. Information about multiple myeloma and ophthalmic manifestations was obtained from original journal articles, review articles, case reports and standard postgraduate textbooks. Ophthalmic manifestations include proptosis, diplopia, lid ecchymosis, xanthomatosis, conjunctival and corneal crystalline and non-crystalline deposits, scleritis, episcleritis, secondary glaucoma, ciliary body cysts, ciliochoroidal effusion, uveal plasmacytoma, hyperviscosity retinopathy, retinal vasculitis, detachment of sensory retina and retinal pigment epithelium, and neuro-ophthalmic manifestations. In multiple myeloma, it is necessary to take a closer look at the ophthalmic manifestations, both because of their local morbidity and because they might act as a reservoir for proliferation of myeloma cells and eventual systemic relapse. Early detection may permit safer and effective treatment. All patients with multiple myeloma should thus undergo thorough ophthalmic examination at the time of initial diagnosis and during follow-up.


Human-induced land use changes and phosphorus limitation affect soil microbial biomass and ecosystem stoichiometry.
Soil and microbial biomass carbon (C), nitrogen (N), and phosphorus (P) play an important role in soil nutrient dynamics in biogeochemical cycles of terrestrial ecosystems. However, increased human activities as a result of agricultural intensification on soil nutrients and microbial C:N:P stoichiometry are poorly understood in this fragile forest-savanna transition agroecosystem. This study aimed to (i) assess soil and microbial C, N, and P stoichiometry in different land use systems, and (ii) examine the effect of soil and microbial C, N, and P stoichiometry on soils susceptible to human-induced land use changes. A total of 82 composite soil samples at a depth of 0-20 cm were sampled from forest, savanna, grassland, fallow and cropland for laboratory analysis. The results revealed that the concentrations of C, N, and P were low in Fallow and Cropland compared to other land use systems. Analysis of variance in microbial C, N, and P stoichiometric ratios revealed a significant decreasing tendency compared to soil C:N, C:P and N:P ratios with no statistical significance (p < 0.05). The C:P and N:P ratios were low compared to the C:N ratio in land uses. A significant positive correlation was observed between MBC and MBN (0.95; p < 0.01), and with C and N (0.69; p < 0.01). There were significant interactive effects of land use on soil and microbial variables. The estimated microbial C:N:P stoichiometric ratios (21:2:1) were well constrained in the study area. The transition from Forest to Cropland resulted in 64%, 52%, and 71% reduction in C, N, and P, respectively. This implies that phosphorus is the main factor limiting productivity. The low availability of phosphorus in these tropical soils may have resulted in low C:P and N:P ratios. Therefore, we conclude that our results highlight the importance of phosphorus limitation on ratios of microbial C:P and N:P in landuse systems. Nutrient inputs such as fertilizers, manure and crop residues should be applied to croplands to improve soil and microbial C, N and P levels. Further, effects of land use on soil nutrient status and stoichiometry at 1-meter depth will be considered in our future work.


Performance and intestinal microbiota of chickens receiving probiotic in the feed and submitted to antibiotic therapy.
The purpose of this study was to verify the ability of a probiotic in the feed to maintain the stability of the gut microbiota in chickens after antibiotic therapy and its association with growth performance. One thousand six hundred twenty 1-day-old Cobb male were housed in floor pens (36 pens, 45 birds/pen) and were fed corn-/soya bean meal-based diets supplemented with or without probiotic (Bacillus subtilis) during the entire rearing phase. From 21 to 24 days of age (three consecutive days), the chickens were submitted to antibiotic therapy via drinking water (bacitracin and neomycin) in order to mimic a field treatment and induce dysbiosis. Growth performance was monitored until 42 days of age. At 2, 4 and 6 days after antibiotic therapy, three chickens from each pen were euthanized and the contents of the small intestine and caeca were collected and pooled. The trial was conducted with four treatments and nine replicates in a 2 × 2 factorial arrangement for performance characteristics (with and without probiotic × with and without antibiotic therapy); for the intestinal microbiota, it was in a 2 × 2 × 3 factorial arrangement (with and without probiotic × with and without antibiotic therapy × 2, 4 and 6 days after the antibiotic therapy) with three replicates per treatment. Terminal restriction length polymorphism (T-RFLP) analysis showed that the structure of gut bacterial community was shaped by the intestinal segment and by the time after the antibiotic therapy. The number of 16S rDNAs copies in caecum contents decreased with time after the therapeutic treatment. The antibiotic therapy and dietary probiotic supplementation decreased richness and diversity indexes in the caecal contents. The improved performance observed in birds supplemented with probiotic may be related to changes promoted by the feed additive in the structure of the intestinal bacterial communities and phylogenetic groups. Antibiotic therapy modified the bacterial structure, but did not cause loss of broiler performance.


Engineered streptavidin monomer and dimer with improved stability and function.
Although streptavidin's high affinity for biotin has made it a widely used and studied binding protein and labeling tool, its tetrameric structure may interfere with some assays. A streptavidin mutant with a simpler quaternary structure would demonstrate a molecular-level understanding of its structural organization and lead to the development of a novel molecular reagent. However, modulating the tetrameric structure without disrupting biotin binding has been extremely difficult. In this study, we describe the design of a stable monomer that binds biotin both in vitro and in vivo. To this end, we constructed and characterized monomers containing rationally designed mutations. The mutations improved the stability of the monomer (increase in T(m) from 31 to 47 °C) as well as its affinity (increase in K(d) from 123 to 38 nM). We also used the stability-improved monomer to construct a dimer consisting of two streptavidin subunits that interact across the dimer-dimer interface, which we call the A/D dimer. The biotin binding pocket is conserved between the tetramer and the A/D dimer, and therefore, the dimer is expected to have a significantly higher affinity than the monomer. The affinity of the dimer (K(d) = 17 nM) is higher than that of the monomer but is still many orders of magnitude lower than that of the wild-type tetramer, which suggests there are other factors important for high-affinity biotin binding. We show that the engineered streptavidin monomer and dimer can selectively bind biotinylated targets in vivo by labeling the cells displaying biotinylated receptors. Therefore, the designed mutants may be useful in novel applications as well as in future studies in elucidating the role of oligomerization in streptavidin function.


Antiplasmodial compounds from Cochlospermum tinctorium.
Fractionation of an ethanol extract of roots of Cochlospermum tinctorium afforded five compounds: 3-O-E-p-coumaroylalphitolic acid (1), cochloxanthin (2), dihydrocochloxanthin (3), alphitolic acid (4), and 1-hydroxytetradecan-3-one (5). This is the first example of a 1-hydroxyalkan-3-one obtained from plant material after gentle workup. The antiplasmodial activities of the compounds were determined, and the IC(50) value of 3-O-E-p-coumaroylalphitolic acid was 2.3 microM.


New synthetic approach to yttrium hydroxoacetates, structural characterization, and use as a precursor for coated conductors.
A novel synthetic approach is given for the preparation of a metal-organic lanthanide sol-gel precursor solution and its application for the production of coated conductors. Besides all other problems concerning the technical process itself, the key to a successful deposition of oxide layers is the choice of the precursor solution and the understanding of the mechanism of deposition. Moreover, the isolation and characterization of the species involved in the reaction is very important. Regarding the complex process occurring during the formation of the surface layer, it is obvious that the best choice should have a compound already containing the final composition of the layer. Two compounds of composition [Y(OAc)3(H2O)2]2 and [Y(OAc)3]2(H2O) were isolated from their precursor solution and characterized by X-ray structural analysis. A short outlook will give an insight into the possible bonding mechanisms of the surface layer. These experiments were made with the mixed metal-oxide system yttrium-stabilized zirconium oxide, which is widely used as a substrate for superconducting oxides. A study of the structure of hydrated yttrium acetates, by single-crystal X-ray diffraction, infrared spectra, and elemental analysis demonstrates that there are two separate structures for hydrated yttrium acetates, which play a role as an intermediate in the building of ceramic oxide layers for coated conductors.


MrsRF: an efficient MapReduce algorithm for analyzing large collections of evolutionary trees.
MapReduce is a parallel framework that has been used effectively to design large-scale parallel applications for large computing clusters. In this paper, we evaluate the viability of the MapReduce framework for designing phylogenetic applications. The problem of interest is generating the all-to-all Robinson-Foulds distance matrix, which has many applications for visualizing and clustering large collections of evolutionary trees. We introduce MrsRF (MapReduce Speeds up RF), a multi-core algorithm to generate a t x t Robinson-Foulds distance matrix between t trees using the MapReduce paradigm. We studied the performance of our MrsRF algorithm on two large biological trees sets consisting of 20,000 trees of 150 taxa each and 33,306 trees of 567 taxa each. Our experiments show that MrsRF is a scalable approach reaching a speedup of over 18 on 32 total cores. Our results also show that achieving top speedup on a multi-core cluster requires different cluster configurations. Finally, we show how to use an RF matrix to summarize collections of phylogenetic trees visually. Our results show that MapReduce is a promising paradigm for developing multi-core phylogenetic applications. The results also demonstrate that different multi-core configurations must be tested in order to obtain optimum performance. We conclude that RF matrices play a critical role in developing techniques to summarize large collections of trees.


Preparation of core-shell magnetic molecularly imprinted polymer nanoparticle for the rapid and selective enrichment of trace diuron from complicated matrices.
A novel magnetic MIPs (DUMIPs) was prepared by surface molecular imprinting method using superparamagnetic core-shell nanoparticle (Fe3O4@SiO2) as the sacrificial support matrix, herbicide diuron as template, α-methacrylic acid as the functional monomer, trimethylolpropane trimethacrylate as the crosslinker, azobisisobutyronitrile as the initiator, and acetonitrile as the porogen. Highly cross-linked porous surface and excellent magnetic property were characterized by Fourier-transform infrared spectroscopy, transmission electron microscopy, and vibrating sample magnetometer, respectively. The adsorption capacity of DUMIPs was 8.1 mg g-1, 2.6-fold over its corresponding non-imprinted polymers (DUNIPs). The adsorption in DUMIPs was considered as multilayer adsorption and posed high affinity to diuron, due to the better fitting to Freundilich isotherm. Competitive recognition study demonstrated DUMIPs had highly selective binding diuron. DUMIPs, as an influential sorbent has been used for selective extraction of diuron from environmental samples (paddy field water, paddy soil and grain seedlings) and the elution was determined by high efficiency liquid chromatography (HPLC). In this analytical method, various factors affecting the extraction efficiency such as pH, sorbent dosage, utilization efficiency and volumes of eluent were simultaneously investigated. Under the optimal conditions, the linearity of the method obtained is in the range of 0.02-10.0 mg L-1. The limit of detection is 0.012 mg L-1. In four spiked levels (0.04, 0.2, 1.0, and 4.0 mg kg-1), the recoveries of diuron in real samples are in the range of 83.56%-116.10% with relative standard deviations in the range of 1.21-6.81%. Importantly, compared to C18-SPE column, the MMIPs exhibited convenient separation by external magnetic field, strong clean-up capacity, and selective enrichment for diuron. Thus, the DUMIPs-based method is great potential for efficient sample preparation in the determination of trace amounts of diuron residues in complex matrices.


Is the Course of COVID-19 Different during Pregnancy? A Retrospective Comparative Study.
The COVID-19 pandemic has challenged health systems around the world. Maternal-foetal medicine, which has been particularly affected, must consider scientific data on the physiological processes occurring in the pregnant woman's body to develop relevant standards of care. Our study retrospectively compared the clinical and laboratory characteristics of 52 COVID-19 pregnant patients with 53 controls. Most of the pregnant patients required medical attention during the third trimester and therefore we propose that vaccination is needed prior to the 30th week of pregnancy. We found no differences between the 2 groups in the course of illness classification system, days of hospital stay, need for oxygen supplementation, need for mechanical ventilation, and ICU admission. Moreover, clinical manifestations and imaging findings were comparable. Pregnant patients needed a greater oxygen flow rate and required high flow oxygen therapy more frequently. Considering pregnancy-related physiological adaptations, we found that COVID-19 infection in pregnant patients is associated with higher levels of inflammatory markers, apart from serum ferritin, than in non-pregnant women, and concluded that biomarkers of cardiac and muscle injury, as well as kidney function, may not be good predictors of COVID-19 clinical course in pregnant patients at the time of admission, but more research needs to be conducted on this topic.


The use of elemental sulphur as organic alternative to control pH during composting of olive mill wastes.
High values of pH may represent a limitation for the agricultural use of the composts, not only when used as soil-less substrate but also as soil amendment in high pH soils. The addition of elemental S during the maturation phase of the composting process was evaluated as suitable method to reduce pH of the composts under the organic agriculture regulations. A compost prepared with two phase olive mill waste (OMW) and sheep litter (SL) was used to study the effect of elemental sulphur addition on the pH of the composting mixture. Initially, different bench scale experiments were designed in order to study the influence of moisture, sulphur concentration, and incubation temperature on the sulphur oxidation rate and thus on the pH of the compost. A concentration of 0.5% in sulphur (dry weight basis) and moisture of 40% were proposed as the optimum conditions to decrease the compost pH by 1.1 units without increasing in EC to levels that may suppose a limitation for its agricultural use. Finally, these optimum experimental conditions found at bench scale were tested at full scale in a commercial composting plant treating the same organic materials by windrowing. The pH values of the composting mixture were reduced by one unit after 2 weeks following the addition of elemental S causing no negative effects on the final compost quality.


Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma.
Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then distributing cytokine cues to elicit type 2 immune effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery.


Demonstration in vitro that eucaryotic initiation factor 3 is active but that a cap-binding protein complex is inactive in poliovirus-infected HeLa cells.
Protein synthesis initiation factor preparations from poliovirus-infected HeLa cells have reduced ability to initiate translation on capped mRNA. The defect in initiation factors has been variously attributed to inactivation of eucaryotic initiation factor 3 (eIF3), eIF4B, or a cap-binding protein (CBP) complex. We have developed a series of in vitro protein synthesis assays to show that eIF3 is active but a CBP complex activity is inactivated after poliovirus infection. eIF3 activity, when determined in the presence of purified CBP complex, is present in sucrose gradients of factors from both infected and uninfected cells. CBP complex activity, determined in the presence of eIF3 from poliovirus-infected cells, is present in uninfected cells only and comigrates on sucrose gradient with an activity which restores the ability of crude initiation factors from infected cells to translate capped globin mRNA. This is the first demonstration by a fractionated translation system that an activity which is attributable to CBP complex is inactivated in poliovirus-infected cells. The results also indicate that eIF3 is undetectable or has greatly reduced activity in the absence of CBP complex.


Soft Hydrogel Actuator for Fast Machine-Learning-Assisted Bacteria Detection.
We demonstrate that our bio-electrochemical platform facilitates the reduction of detection time from the 3-day period of the existing tests to 15 min. Machine learning and robotized bioanalytical platforms require the principles such as hydrogel-based actuators for fast and easy analysis of bioactive analytes. Bacteria are fragile and environmentally sensitive microorganisms that require a special environment to support their lifecycles during analytical tests. Here, we develop a bio-electrochemical platform based on the soft hydrogel/eutectic gallium-indium alloy interface for the detection of Streptococcus thermophilus and Bacillus coagulans bacteria in various mediums. The soft hydrogel-based device is capable to support bacteria' viability during detection time. Current-voltage data are used for multilayer perceptron algorithm training. The multilayer perceptron model is capable of detecting bacterial concentrations in the 104 to 108 cfu/mL range of the culture medium or in the dairy products with high accuracy (94%). Such a fast and easy biodetection is extremely important for food and agriculture industries and biomedical and environmental science.


Internal carotid artery dissection: MR imaging features and clinical-radiologic correlation.
To analyze the usefulness of magnetic resonance (MR) imaging techniques and diagnostic sensitivity in internal and carotid artery dissection (ICAD) and to correlate these findings with those of other imaging modalities and with clinical signs. Thirty-one patients with ICAD underwent MR imaging within 2-40 days (mean, 13 days) after onset of clinical symptoms. All patients initially underwent Doppler sonography; 15 patients underwent additional angiographic studies. T1-weighted fat-suppressed MR images most accurately demonstrated intramural hematoma in the internal carotid artery (ICA) in all patients. Kinking or coiling of the ICA was found in nine (29%) patients. Hyperintense signal was seen on T1- and T2-weighted images in the carotid canal or in the cavernous sinus in two-thirds of the patients. Findings characteristic of ICAD were seen on 13 of 16 angiograms. MR imaging most accurately demonstrated ICAD. The high rate of kinking and coiling in the carotid artery suggests that these anatomic conditions may be predisposing factors.


Efficacy of varicose vein surgery with preservation of the great safenous vein.
To evaluate the efficacy of surgical treatment of varicose veins with preservation of the great saphenous vein. We conducted a prospective study of 15 female patients between 25 and 55 years of age with clinical, etiologic, anatomic and pathophysiologic (CEAP) classification 2, 3 and 4. The patients underwent surgical treatment of primary varicose veins with great saphenous vein (GSV) preservation. Doppler ultrasonography exams were carried out in the first and third months postoperatively. The form of clinical severity of venous disease, Venous Clinical Severity Score (VCSS) was completed before and after surgery. We excluded patients with history of deep vein thrombosis, smoking or postoperatively use of elastic stockings or phlebotonics. All patients had improved VCSS (p <0.001) and reduction in the diameter of the great saphenous vein (p <0.001). There was a relationship between VCSS and the GSV caliber, as well as with preoperative CEAP. There was improvement in CEAP class in nine patients when compared with the preoperative period (p <0.001). The varicose vein surgery with preservation of the great saphenous vein had beneficial effects to the GSV itself, with decreasing caliber, and to the symptoms when the vein had maximum caliber of 7.5 mm, correlating directly with the CEAP. The decrease in GSV caliber, even without complete abolition of reflux, leads to clinical improvement by decreasing the reflux volume.


Development and characterization of phyto-vesicles of wedelolactone for hepatoprotective activity.
Wedelolactone is isolated from the dried leaves of Eclipta alba (L.) and reported to be effective as a potential hepatoprotective, antibacterial and anti hemorrhagic. Pharmacokinetic studies of wedelolactone reveal its poor absorption through the intestine. The objective of the present study is to enhance bioavailability of wedelolactone by its complexation with phosphatidyl choline and then formulating it as phyto-vesicles for hepatoprotective activity. The complex of wedelolactone rich fraction was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, thin layer chromatography (TLC), UV, IR and NMR spectroscopy. The complex was further converted into phyto-vesicles and characterized. The hepatoprotective potential of phyto-vesicles was compared with complex, wedelolactone rich fraction and physical mixture of wedelolactone rich fraction and phosphatidyl choline by in vitro method. The results revealed that hepatoprotective activity is better in case of phyto-vesicles as compared to the complex, physical mixture and the wedelolactone itself. Enhanced bioavailability of the wedelolactone complex may be due to the amphiphillic nature of the complex, which greatly enhance the water and lipid solubility of the compound. The present study clearly indicates the superiority of phyto-vesicles over the complex and wedelolactone, in terms of better absorption and improved hepatoprotective activity.


Live and heat-killed probiotic Lactobacillus casei Lbs2 protects from experimental colitis through Toll-like receptor 2-dependent induction of T-regulatory response.
Inflammatory bowel disease (IBD) is a group of inflammatory disorders of the intestine caused by dysregulated T-cell mediated immune response against commensal microflora. Probiotics are reported as therapeutically effective against IBD. However, variable efficacy of the live probiotic strains, difference in survival and persistence in the gut between the strains and the lack of insight into the mechanisms of probiotic action limit optimal therapeutic efficacy. Our aims were to evaluate the lactobacillus strains isolated from the North Indian population for the generation of regulatory cells and cytokines in the intestine, to study their effects on pro-inflammatory mediators in the mouse model of inflammatory bowel disease and to explore the underlying mechanisms of their actions. Among the selected lactobacillus strains, Lactobacillus casei Lbs2 (MTCC5953) significantly suppressed lipopolysaccharide-induced pro-inflammatory cytokine (TNF-alpha, IL-6) secretion. Both live and heat-killed Lbs2 polarized Th0 cells to T-regulatory (Treg) cells in vitro, increased the frequency of FoxP3(+) Treg cells in the mesenteric lymph nodes (MLNs) and alleviated macroscopic and histopathological features of colitis in probiotic-fed mice. Moreover, the levels of IL-12, TNF-alpha and IL-17A were suppressed, while IL-10 and TGF-beta levels were augmented in the colonic tissues of Lbs2-treated mice. The induced Treg (iTreg) cells secreted IL-10 and TGF-beta and exerted suppressive effects on the proliferation of effector T-cells. Adoptive transfer of iTreg cells ameliorated the disease manifestations of murine colitis and suppressed the levels of TNF-alpha and IL-17A. Finally, Lbs2 effects were mediated by Toll-like receptor 2 (TLR2) activation on the dendritic cells. This study identified live and heat-killed Lbs2 as putative therapeutic candidates against IBD and highlighted their Toll-like receptor 2-dependent immunomodulatory and regulatory function.


[A Case of Bilateral Lymph Node Metastases of Rectal Cancer Treated with Chemotherapy and Surgery].
We present a case of bilateral lymph node metastases of rectal cancer treated with chemotherapy and surgery. The patient was a 65-year-old man with upper rectal cancer. Laparoscopic low anterior resection(LAR)was performed. Pathological findings were tub2>por>muc, pT3, ly2, v3, pN2, pM0. Six months after surgery, the CEA level was elevated. CT and PET-CT confirmed bilateral metastasis to the lymph nodes. Five courses of FOLFOX4 plus bevacizumab were administered, and then, we performed laparoscopic bilateral lymph node dissection. Pathological assessments confirmed scarring and fibrosis, that is, a pathological complete response(pCR)was achieved. Two years and 6 months after surgery, no recurrence was detected. After chemotherapy or chemoradiotherapy, we should perform surgery to prevent local recurrence, especially to the lateral lymph nodes.


[Puerperal fever. A survey of an epidemic using a case-controlled study].
Puerperal fever caused by group A streptococci (GAS) is a most serious infection deriving from the birth canal after childbirth or caesarian section and is manifest by fever and/or local signs of infections. Secundary infections in the umbilicus or skin can occur in the newborn child. As approximately 5% of the Danish population are carriers of GAS in nose, throat, rectum and/or vagina the risk of infection is present especially in childbirth. GAS epidemics in the community result in increased risk of hospital-acquired GAS infections. In the literature it is recommended to take action and implement preventive strategies when two simultaneous cases occur in one department. We describe the course of seven GAS infections in six patients (two children) in the same obstetric ward over a seven-week period, the elucidation by case-control analysis and the implementation of preventive measures. The importance of good hygienic practices is highlighted.


High-Throughput UPLC-MS Method for the Determination of N-Acetyl-l-Cysteine: Application in Tissue Distribution Study in Wistar Rats.
N-Acetylcysteine (NAC) is the N-acetyl derivative of the amino acid l-cysteine and is extensively used as a medicine to treat a variety of diseases. High-throughput ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method has been developed for the quantitative assessment of N-acetyl-l-cysteine. The method was further applied to study the distribution of the intraperitoneal injected drug into different tissues and plasma of Wistar rats, including liver, kidney, heart, lungs and spleen. The drug was having highest concentration in plasma and liver followed by kidney, lungs, heart and spleen. Method validation studies suggested being linear in the range of 1-15 µg mL(-1) for liver, kidney, heart, lungs and spleen and 1-120 µg mL(-1) for the plasma. The limit of detection and limit of quantitation were found to be 0.20 and 0.66 µg mL(-1), respectively. The recovery studies suggested that in all the cases, the obtained recovery was in the range of 98.51-101.88%. Our analyses provide a validated UPLC-MS method for the determination of NAC and its successful application for the analysis in plasma and tissues obtained from Wistar rats.


Predictors of frequent middle school health room use.
Disproportionately high use of school health room (HR) services by small groups of users has been reported. This study investigated predictors of frequent HR use in two suburban middle schools involving 1089 students who made at least one HR visit during a single academic year. Subsets of high and low users were compared using logistic regression. Predictor variables included gender, grade, academic ability, and existence of a chronic health condition. Although demographic characteristics of the study schools varied significantly, a pattern of increasing HR use associated with progressive lowering of academic ability was demonstrated in both schools. Existence of a chronic health condition was associated with increased HR use, even when controlling for routine medication visits. Gender and grade were not predictive. These findings suggest that HR use reflects more than medical concerns. Patterns of HR use by students with chronic health conditions deserve additional study to determine whether current strategies to meet their needs are adequate.


Multiscale Interface Effect on Homogeneous Dielectric Structure of ZrO₂/Teflon Nanocomposite for Electrowetting Application.
Electrowetting-on-dielectric is a preferred option in practical applications of the electrowetting phenomenon but limited by dielectric and breakdown performances of the dielectric layer. In the present work, a ceramic/polymer nanocomposite as a novel dielectric layer is developed to intensify the overall electrowetting performances by multiscale interface effect. Hereinto, surface fluoro-modified ZrO₂ nanoparticles (mZrO₂) are dispersed well in AF 1600 matrix to form a mZrO₂@AF 1600 nanocomposite. The small addition of mZrO₂ improves the dielectric constant of the nanocomposite, and the experimental value is larger than the theoretical value calculated by Maxwell⁻Garnett model, but fits well with the Rahaman⁻Khastgir model. The molecular dynamics simulations with the explicit model further verify the interfacial effect. Meanwhile, double contact angle modulation and higher breakdown field strength (Eb) are obtained. For the three-layer sandwich structure, both the top and bottom AF 1600 layer decrease the surface roughness for better electrowetting reproducibility and wider wettability modulation. The Forlani⁻Minnaja theory related to the empirical relationship between Eb and thickness of dielectric layer fit well with the monolayer structure, but cannot be applied in multi-layer structures. A new relationship is proposed to guide the design of dielectric multi-layers with high breakdown field strength.


Preferential activation of the vagal nodose nociceptive subtype by TRPA1 agonists in the guinea pig esophagus.
The TRPA1 receptor is directly activated by a wide range of chemicals including many endogenous molecules relevant for esophageal pathophysiology. We addressed the hypothesis that the TRPA1 agonists differentially activate esophageal nociceptive subtypes depending on their embryological source (neural crest or epibranchial placodes). Single cell RT-PCR and whole cell patch clamp recordings were performed on the vagal neurons retrogradely labeled from the guinea pig esophagus. Extracellular recordings were made in the isolated innervated esophagus preparation ex vivo. Single cell RT-PCR revealed that the majority of the nodose (placodes-derived) and jugular (neural crest-derived) TRPV1-positive esophageal nociceptors express TRPA1. Single fiber recording showed that the TRPA1 agonists allyl-isothiocyanate (AITC) and cinnamaldehyde were effective in inducing robust action potential discharge in the nerve terminals of nodose nociceptors, but had far less effect in jugular nociceptors (approximately fivefold less). Higher efficacy of the TRPA1 agonists to activate nodose nociceptors was confirmed in the isolated esophagus-labeled vagal neurons in the whole cell patch clamp studies. Similarly to neural crest-derived vagal jugular nociceptors, the spinal DRG nociceptors that are also neural crest-derived were only modestly activated by allyl-isothiocyanate. We conclude that the TRPA1 agonists are substantially more effective activators of the placodes-derived than the neural crest-derived esophageal nociceptors. Our data predict that in esophageal diseases the presence of endogenous TRPA1 activators will be preferentially signaled by the vagal nodose nociceptors.


Hypothesis-based weight of evidence: a tool for evaluating and communicating uncertainties and inconsistencies in the large body of evidence in proposing a carcinogenic mode of action--naphthalene as an example.
Human health risk assessment consists of bringing to bear a large body of in vitro, animal, and epidemiologic studies on the question of whether environmental exposures to a substance are a potential risk to humans. The body of scientific information is typically less than definitive and often contains apparent contradictions. Often various possible conclusions about potential human risks may be drawn from the data and these may vary from very strong to tenuous. The task, therefore, is to communicate the uncertainties in the inferences from the data effectively, giving proper consideration to contrary data and alternative scientifically plausible interpretations. We propose an approach, Hypothesis-Based Weight of Evidence (HBWoE), to organize, evaluate, and communicate the large body of available relevant data on a given chemical, using naphthalene as an example. The goal for our use of the term "weight of evidence" (WoE) is broad in that we express the relative degrees of credence that should be placed in alternative possible interpretations of the naphthalene data and hypothesized carcinogenic modes of action (MoAs), expressed in a way that shows how such credence is tied to specific scientific interpretations, considering consistencies, inconsistencies, and contradictions within the data set.


The role of morning basal serum cortisol in assessment of hypothalamic pituitary-adrenal axis.
The use of morning basal serum cortisol levels as an alternative to dynamic testing for assessment of hypothalamic-pituitary-adrenal (HPA) axis has previously been reported. The purpose of this study was to determine the lower and upper cutoff values that would obviate subsequent HPA axis testing. A single-centre, retrospective study from a tertiary care endocrinology clinic was conducted, analyzing data from 106 adult individuals referred for HPA axis testing who had undergone a 0800-0900 morning basal serum cortisol test followed by a standard dose (250 μg) adrenocorticotropin (ACTH) stimulation test. The ability of morning basal serum cortisol values to predict post-ACTH 30 or 60 minute peak cortisol value of >500 or >550 nmol/L was investigated. A morning basal cutoff of <128 nmol/L is sufficient for predicting a post-ACTH value<550 nmol/L, and morning basal cutoff levels of >243 nmol/L and >266 nmol/L predict peak post-ACTH values of >500 and >550 nmol/L respectively, obviating the need for dynamic testing. Regression analysis further demonstrated the log-linear relationship between morning basal and peak levels, while also finding a significant decrease in peak post-ACTH levels for patients diagnosed with secondary hypothyroidism (76 nmol/L lower, p=0.003) or secondary hypogonadism (61 nmol/L lower, p=0.02). These data suggest that the risk of cortisol deficiency is significantly higher in individuals with additional pituitary insufficiencies. The odds ratios for cortisol deficiency in patients with history of isolated secondary hypothyroidism was 3.41 (p=0.015), with isolated secondary hypogonadism was 4.77 (p=0.002) and with both was 7.45 (p=0.0002). Morning basal serum cortisol levels show promise as an effective screening test for HPA insufficiency for most patients. Clinicians should consider the high probability of HPA insufficiency in patients with one or more pituitary insufficiencies.


Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.
Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.


Outcomes of an Interdisciplinary Transitional Care Quality Improvement Project on Self-Management and Health Care Use in Patients With Heart Failure.
Heart failure (HF) accounts for most U.S. Medicare hospital admissions. The purpose of the current study was to evaluate the effectiveness of a care transitions quality improvement (QI) intervention on self-management and readmission rates in older adults with HF. A quasi-experimental, descriptive study was conducted with 66 patients with HF in three medical units in a 489-bed Midwestern acute care hospital. The intervention included a nurse coach visit and follow up, pharmacy medication education and reconciliation, and HF clinic referral. Outcomes were assessed within 48 hours of admission and 30 days after discharge using the Self-Care of Heart Failure Index and medical record review. Following implementation, readmission rates decreased from 24% to 13%. Participants demonstrated a greater improvement in use of self-management strategies to control symptoms than the non-intervention group (p < 0.02) and more readily identified their symptoms of HF (p < 0.04). The evolution of population health, with increasing numbers of older adults living at home with complex chronic conditions, will require establishment of active partnerships among pharmacists, physicians, nurse specialists, home care nurses, and patients. [Journal of Gerontological Nursing, 43(1), 23-31.].


Wear resistance of cast dental Ti-Fe alloys.
Binary Ti-Fe alloys with 5-25 mass% Fe were prepared, and subjected to reciprocating wear test. The aim of this study was to investigate the relationship between mechanical properties and the wear resistance of titanium and Ti-Fe alloys. The dimensions (length, width and depth) of wear marks on Ti-Fe alloys were less than those observed on pure Ti specimen. Wear resistance of Ti-Fe alloys was better than that of pure titanium. It was established that hardness was the main factor that influenced wear resistance of Ti-Fe alloys. Single β Ti-Fe alloys showed better wear resistance than α+β Ti-Fe alloys. Increase in concentration of Fe in the β phase of Ti-Fe alloys leads to improved wear resistance of the alloy. Ti-Fe alloys with 11-15 mass% Fe form ideal candidates for fabrication of dental titanium alloys with excellent wear resistance.


[Effect of lateral septal nucleus damage on the photoperiodic changes in the reproductive system of male rats].
The experiments on the juvenile male Wistar rats (4-5 weeks old) were carried out to show the effects of damage of the lateral septal nucleus (LSN) on the gonads of rats caged under different photoperiodic regimes: natural change of light and dark phases of the day, constant light and darkness for 24 hours. A short (week) exposition of rats to the permanent light or darkness stimulates or inhibits gonads, respectively. Lesion of LSN in rats caged under permanent light or darkness inhibits the morpho-functional state of the reproductive system and hormone-producing function of testes. The changes are much more pronounced in rats caged under permanent darkness. The possible mechanisms of LSN influence on the photoperiodic changes of the reproductive system of male rats are under discussion.


Streamlined determination of processive run length and mechanochemical coupling of nucleic acid motor activities.
Quantitative determination of enzymatic rates, processivity and mechanochemical coupling is a key aspect in characterizing nucleotide triphosphate (NTP)-driven nucleic acid motor enzymes, for both basic research and technological applications. Here, we present a streamlined analytical method suitable for the determination of all key functional parameters based on measurement of NTP hydrolysis during interaction of motor enzymes with the nucleic acid track. The proposed method utilizes features of kinetic time courses of NTP hydrolysis that have not been addressed in previous analyses, and also accounts for the effect of protein traps used in kinetic experiments on processivity. This analysis is suitable for rapid and precise assessment of the effects of mutations, physical conditions, binding partners and other effectors on the functioning of translocases, helicases, polymerases and other NTP-consuming processive nucleic acid motors.


Preliminary results of online classification of upper limb motions from around-shoulder muscle activities.
Recently, detecting upper-limb motion intention for prosthetic control purpose attracted growing research attention. In most of the studies, recordings of forearm muscle activities were used as the signal sources, from which the intention of wrist and hand motions were detected using pattern recognition technology. However, most daily-life upper limb activities need coordination of the shoulder-arm-hand complex. The disadvantage of relying only on the local information to recognize a whole body coordinated motion is that misrecognition could easily happen, so that steady and reliable continuous motions could not be realized. Moreover, using forearm muscle activities would limit the use of the system for higher level amputation patients. Therefore, in this study we aimed to explore the feasibility of using an online classification algorithm to test the intention detection in real time. Experiments were conducted to record around-shoulder muscle activity using EMG and acceleration sensors. Then, a neural network was trained using these data, and finally tested online in a set of tests. Results showed that, from 5 channels of Electromyogram (EMG) and 4 channels of accelerometers, it is possible to discriminate 3 different grips and 5 reaching direction of arm.


Anesthesia for interventional pulmonology.
Anesthesia for pulmonological interventions is a demanding challenge. This article discusses recent innovations and the implications for periinterventional anesthetic management. Interventional pulmonology is a rapidly expanding specialty with very complex diagnostic and therapeutic approaches that include oncological staging, treatment of obstructive and restrictive lung diseases, recanalization of endobronchial obstructions, and retrieval of foreign bodies. With the development of advanced diagnostic and therapeutic interventions, the application is extended to critically ill patients. Current evidence focusing on the anesthetic techniques is presented here. The development of new pulmonological methods requires a tailored anesthesiological approach. Their specific impact must be taken into account to ensure patient safety, goal-oriented outcome diagnostics and -quality, successful interventions, and patient comfort.


Competent in evidence-based practice (EBP): validation of a measurement tool that measures EBP self-efficacy and task value in speech-language therapy students.
Worldwide speech-language therapy (SLT) students are educated in evidence-based practice (EBP). For students to use EBP in their future day-to-day clinical practice, they must value EBP as positive and must feel confident in using it. For curricula developers it is therefore important to know the impact their teaching has on these aspects of students' motivational beliefs. To develop and validate a measurement tool to assess EBP task value and self-efficacy in SLT students. A 20-item questionnaire was developed based on a review of the literature and an additional group interview with speech-language therapists. Face validity of the questionnaire was established using a Delphi panel consisting of six EBP lecturers. Dutch bachelor SLT students (n = 149) with a different level of EBP knowledge and skills filled in the newly developed questionnaire. Reliability (internal consistency) was assessed using Cronbach's alpha and internal validity using a principal component analysis (PCA). Construct validity was assessed by comparing the bachelor SLT student scores with a group of m students (n = 15) who were highly experienced in EBP. The PCA showed that the questionnaire consists of two components, representing EBP task value and self-efficacy, both with good reliability (Cronbach's α = 0.83 and 0.79, respectively). The hypothesis that master's students would score significantly higher on both components than bachelor SLT students was met. The study provides evidence on the internal consistency and construct validity of this questionnaire to evaluate EBP task value and self-efficacy in SLT students. As is common with new measures, more research is needed to evaluate further its psychometric properties.


Intraventricular haemorrhage in premature infants: a study from Oman.
In a prospective study at Sultan Qaboos University Hospital, 95 premature infants with birthweights equal or less than 1500 g were screened for intraventricular haemorrhage (IVH) using cranial ultrasound. Nineteen (20 per cent) were found to have developed IVH. Eight out of fourteen variables studied showed a significant difference between infants who did and those who did not develop IVH. These variables were Apgar score at 1 and 5 min, mechanical ventilation (IPPV), blood transfusion, receiving boluses of sodium bicarbonate for correction of metabolic acidosis, the degree of acidosis, the degree, and duration of hypercarbia (CO2 > 8 kPa).


A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites.
Levosimendan is a pyridazinone-dinitrile derivative, emerged as a potent cardiotonic agent with dual inotropic and vasodilator activities in higher animals. This is a calcium (Ca2+) sensitizing cardiotonic agent, which has been shown to exert positive inotropic effects without increasing intracellular Ca2+ transient. This avoids Ca2+ overload that leads to arrhythmias and myocyte injuries, and do not increase the energy consumption for handling Ca2+ and has shown good activity against congestive heart failure (CHF), due to its increased myocardial contractility by stabilizing the calcium bound conformation of troponin C. Levosimendan also acts as a pulmonary and systemic vasodilator. The combination of positive inotropic and vasodilator activity has been beneficial in increasing cardiac output and decreasing left ventricular end-diastolic pressure, pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance in CHF patients. The cardiac target protein of levosimendan and troponin C, is Ca2+-binding protein. This raises the possibility that levosimendan may interact with smooth muscle proteins, such as, calmodulin, and regulatory myosin light chains. Levosimendan relaxes coronary arteries and lowers Ca2+. The lowering of Ca2+ by levosimendan is consistent with opening of K+ channels and causes relaxation that is independent of Ca2+. However, most of the Ca2+ sensitizers may impair cardiac diastolic function as a result of increased Ca2+ sensitivity of the myofilaments. Levosimendan has not only improved the cardiac systolic function but also the diastolic relaxation in CHF.


Optical imaging guided- 'precision' biopsy of skin tumors: a novel approach for targeted sampling and histopathologic correlation.
Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused 'precision biopsy' technique that correlates clinical-dermoscopy-RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy-RCM-histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22-91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for 'feature correlation' of structures on dermoscopy or RCM, and five (20.8%) for 'correlation of new/unknown' RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction.


A Simple Methodology to Estimate the Diffusion Coefficient in Pervaporation-Based Purification Experiments.
A procedure to estimate the diffusion coefficient in solution⁻diffusion models of hydrophilic membranes used in pervaporation-based purification experiments is presented. The model is based on a series solution of the general permeation problem. It considers a membrane that can be filled with water or with the feed solution before the measurement. Furthermore, the length of the tubing between the permeation cell and the place of cold traps is also addressed. To illustrate the parameter estimation procedure, we have chosen the data for the separation of water and ethanol by chitosan membranes. It is shown that the diffusion coefficient can be estimated effectively from the time course of the transported mass and by the analysis of certain well defined time lags of the permeation curve.


Amoxycillin/clavulanate versus amoxycillin in recurrent otitis media and therapeutic failure in children.
A total of 102 children with recurrent otitis media or therapeutic failure after treatment with phenoxymethyl penicillin were entered into a double-blind study with parallel groups, comparing treatment with amoxycillin/clavulanate suspension (Spektramox) for 7 days with amoxycillin suspension (Imacillin) for 10 days. Bacterial and clinical investigations were performed. A total of 91 patients were evaluated for efficacy at the first follow-up visit (10-12 days after start of treatment). Amoxycillin/clavulanate and amoxycillin showed equally high, satisfactory treatment results, i.e. more than a 90% response. Similarly, there was no statistically significant difference between the treatment groups at the second follow-up visit (about 30 days after start of treatment). Bacteriological cultures from the nasopharynx showed equal distribution of Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae between the study groups. Elimination of the initially occurring pathogens was equal in the two study groups with the exception of B. catarrhalis which was eliminated to a significantly higher extent with amoxycillin/clavulanate. Both drugs were well tolerated. In patients with recurrent otitis media or therapeutic failure, treatment with amoxycillin/clavulanate for 7 days results in high, satisfactory clinical effects and is comparable to treatment with amoxycillin for 10 days.


In silico analyses of a new group of fungal and plant RecQ4-homologous proteins.
Bacterial and eukaryotic RecQ helicases comprise a family of homologous proteins necessary for maintaining genomic integrity during the cell cycle and DNA repair. There is one known bacterial RecQ helicase, and five eukaryotic RecQ helicases that have been described: RecQ1p, RecQ4p, RecQ5p, Bloom, and Werner. While the biochemical functions of Bloom and Werner helicases are well understood, the same is not true for RecQ4p helicase. RecQ4p mutations lead to pathologies like Rothmund-Thompson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS). Until now, RecQ4p helicases had only been described in metazoans, and their presence in organisms like fungi and plants were not known. Thus far only one RecQ-homologous protein (Sgs1p), similar to Bloom helicase, has been described in fungal genomes. In the present study we employed an in silico approach, and successfully identified and characterized a second RecQ helicase from the genomes of different fungal and two plant species that shows similarity to metazoan RecQ4 proteins. An in-depth phylogenetic analysis of these new fungal and plant RecQ4-like sequences (termed Hrq1p) indicated that they are orthologous to the metazoan RecQ4p. We employed hydrophobic cluster analysis (HCA) and three-dimensional modeling of selected Hrq1p sequences to compare conserved regions among Hrq1p, human RecQ4p and bacterial RecQp. The results indicated that Hrq1p sequences, as previously observed for metazoan RecQ4 proteins, probably act in genomic maintenance and/or chromatin remodeling in fungal and plant cells.


Optimizing combination therapies with existing and future CML drugs.
Small-molecule inhibitors imatinib, dasatinib and nilotinib have been developed to treat Chromic Myeloid Leukemia (CML). The existence of a triple-cross-resistant mutation, T315I, has been a challenging problem, which can be overcome by finding new inhibitors. Many new compounds active against T315I mutants are now at different stages of development. In this paper we develop an algorithm which can weigh different combination treatment protocols according to their cross-resistance properties, and find the protocols with the highest probability of treatment success. This algorithm also takes into account drug toxicity by minimizing the number of drugs used, and their concentration. Although our methodology is based on a stochastic model of CML microevolution, the algorithm itself does not require measurements of any parameters (such as mutation rates, or division/death rates of cells), and can be used by medical professionals without a mathematical background. For illustration, we apply this algorithm to the mutation data obtained in [1], [2].


An empirical comparison of SPM preprocessing parameters to the analysis of fMRI data.
We present the results from two sets of Monte Carlo simulations aimed at evaluating the robustness of some preprocessing parameters of SPM99 for the analysis of functional magnetic resonance imaging (fMRI). Statistical robustness was estimated by implementing parametric and nonparametric simulation approaches based on the images obtained from an event-related fMRI experiment. Simulated datasets were tested for combinations of the following parameters: basis function, global scaling, low-pass filter, high-pass filter and autoregressive modeling of serial autocorrelation. Based on single-subject SPM analysis, we derived the following conclusions that may serve as a guide for initial analysis of fMRI data using SPM99: (1) The canonical hemodynamic response function is a more reliable basis function to model the fMRI time series than HRF with time derivative. (2) Global scaling should be avoided since it may significantly decrease the power depending on the experimental design. (3) The use of a high-pass filter may be beneficial for event-related designs with fixed interstimulus intervals. (4) When dealing with fMRI time series with short interstimulus intervals (<8 s), the use of first-order autoregressive model is recommended over a low-pass filter (HRF) because it reduces the risk of inferential bias while providing a relatively good power. For datasets with interstimulus intervals longer than 8 seconds, temporal smoothing is not recommended since it decreases power. While the generalizability of our results may be limited, the methods we employed can be easily implemented by other scientists to determine the best parameter combination to analyze their data.


Changemakers as digital makers: Connecting and co-creating.
This paper presents data from two international projects focused on the interaction between changemaking and digital making in university students. The data is drawn from the contributions of 63 university students located in the United States, Romania, Spain, Belgium, Norway, Denmark and England. Using a design thinking methodology and a thematic analysis of student responses, the aim was to understand how the creative use of immersive technologies, such as augmented and virtual reality, might create an environment for changemaking practices in an international context. Findings suggest that students demonstrated not only enhanced digital skills and student engagement but increased cultural competence and global mindfulness. International digital collaboration can create conditions for students to develop changemaker attributes and identify as changemakers within the spheres of entrepreneurship and education, preparing them to be a force for change in the world.


Empowering differential networks using Bayesian analysis.
Differential networks (DN) are important tools for modeling the changes in conditional dependencies between multiple samples. A Bayesian approach for estimating DNs, from the classical viewpoint, is introduced with a computationally efficient threshold selection for graphical model determination. The algorithm separately estimates the precision matrices of the DN using the Bayesian adaptive graphical lasso procedure. Synthetic experiments illustrate that the Bayesian DN performs exceptionally well in numerical accuracy and graphical structure determination in comparison to state of the art methods. The proposed method is applied to South African COVID-19 data to investigate the change in DN structure between various phases of the pandemic.


A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth.
Deletion of 3p12-22 is frequent in multiple cancer types, indicating the presence of critical tumor-suppressor genes (TSGs) at this region. We studied a novel candidate TSG, CMTM7, located at the 3p22.3 CMTM-gene cluster, for its tumor-suppressive functions and related mechanisms. The three CMTM genes, CMTM6, 7 and 8, are broadly expressed in human normal adult tissues and normal epithelial cell lines. Only CMTM7 is frequently silenced or downregulated in esophageal and nasopharyngeal cell lines, but uncommon in other carcinoma cell lines. Immunostaining of tissue microarrays for CMTM7 protein showed its downregulation or absence in esophageal, gastric, pancreatic, liver, lung and cervix tumor tissues. Promoter CpG methylation and loss of heterozygosity were both found contributing to CMTM7 downregulation. Ectopic expression of CMTM7 in carcinoma cells inhibits cell proliferation, motility and tumor formation in nude mice, but not in immortalized normal cells, suggesting a tumor inhibitory role of CMTM7. The tumor-suppressive function of CMTM7 is associated with its role in G1/S cell cycle arrest, through upregulating p27 and downregulating cyclin-dependent kinase 2 (CDK2) and 6 (CDK6). Moreover, CMTM7 could promote epidermal growth factor receptor (EGFR) internalization, and further suppress AKT signaling pathway. Thus, our findings suggest that CMTM7 is a novel 3p22 tumor suppressor regulating G1/S transition and EGFR/AKT signaling during tumor pathogenesis.


Laboratory-confirmed bloodstream infection in systemic lupus erythematosus: Risk profiling and short-term mortality.
To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients.Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013-2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.


Is There an Ethical Mandate to Practice Without Proper Personal Protective Equipment?
In the spring of 2020, a novel virus known as COVID-19 (coronavirus disease 2019) was introduced to the human population, and the world faced a global pandemic with far-reaching consequences. One of the most difficult challenges that nurses faced in the midst of the crisis was the lack of proper personal protective equipment (PPE). The lack of PPE left health care professionals with a complicated ethical dilemma: Is there an ethical duty to care for patients in the absence of proper PPE? This article seeks to help the individual nurse (a) understand the ethical dilemma and the tensions that it brings, (b) look to the literature for guidance, and (c) understand how individuals can apply these ethical principles. After careful analysis, the recommendation is for the individual nurse to make a thorough assessment of their personal situation. This will include consideration for their family, community, financial responsibilities, legal protections, organizational policies, and personal health risk. Finally, this article serves as a call to organizations and professional leaders to increase their support of frontline health care workers and provide the individual nurse with the information they need in order to make sound decisions.


A preoperative education class reduces length of stay for total knee replacement patients identified at risk of an extended length of stay.
To establish whether attendance at an education class prior to total hip or knee replacement surgery as part of an enhanced recovery after surgery pathway could decrease length of hospital stay. A single-site, retrospective cohort study comparing length of stay in hospital for patients who attended and did not attend an education class prior to hip or knee replacement surgery. Patients were stratified into 3 groups according to the predicted likelihood of an extended inpatient hospital stay using the Risk Assessment Predictor Tool. Mean length of stay reduced by 0.37 days for patients who received hip replacement (n = 590) (95% confidence interval (95% CI) -0.74, -0.01, p = 0.05) and by 0.77 days for patients who underwent knee replacement (n = 643) (95% CI -1.23, -0.31, p = 0.001) following attendance at a preoperative education class. Patients undergoing knee replacement who were considered at high risk of an extended hospital stay stayed, on average, 2.59 days less in hospital after attending the class (mean length of stay: 4.52 (standard deviation (SD) 1.26) vs 7.11 (SD 4.18) days (95% CI -4.62, -0.54, p < 0.02). This study supports the inclusion of a preoperative education session in this context for both hip and knee replacement procedures, and indicates that this may be most beneficial for patients undergoing knee replacement who are at risk of an extended length of stay.


Obesity and public policy.
There is a pressing need to reduce both the prevalence and impact of obesity. This review begins with a discussion of the roles of treatment and prevention. Two overriding issues, weight bias and the addictive nature of food, are covered because of their importance not only to the individuals affected but also to public policy. We then cover promising policy areas in which changes can be implemented to support healthy behaviors: school policy, food marketing, food labeling and packaging, and taxes on unhealthy foods. The roles of the food industry and federal, state, and local governments are also discussed.


[Expression, purification of recombinant cationic peptide AIK in Escherichia coli and its antitumor activity].
AIK is a novel cationic peptide with potential antitumor activity. In order to construct the AIK expression vector by Gateway technology, and establish an optimal expression and purification method for recombinant AIK, a set of primers containing AttB sites were designed and used to create the AttB-TEV-FLAG-AIR fusion gene by overlapping PCR. The resulting fusion gene was cloned into the donor vector pDONR223 by attB and attP mediated recombination (BP reaction), then, transferred into the destination vector pDESTl 5 by attL and attR mediated recombination (LR reaction). All the cloning was verified by both colony PCR and DNA sequencing. The BL21 F. coli transformed by the GST-AIR expression plasmid was used to express the GST-AIK fusion protein with IPTG induction and the induction conditions were optimized. GST-AIR fusion protein was purified by glutathione magnetic beads, followed by rTEV cleavage to remove GST tag and MTS assay to test the growth inhibition activity of the recombinant AIR on human leukemia HL-60 cells. We found that a high level of soluble expression of GST-AIK protein (more than 30% out of the total bacterial proteins) was achieved upon 0.1 mmol/L ITPG induction for 4 h at 37 °C in the transformed BL21 F. coli with starting OD₆₀₀ at 1.0. Through GST affinity purification and rTEV cleavage, the purity of the resulting recombinant AIK was greater than 95%. And the MTS assays on HL-60 cells confirmed that the recombinant AIK retains an antitumor activity at a level similar to the chemically synthesized AIK. Taken together, we have established a method for expression and purification of recombinant AIK with a potent activity against tumor cells, which will be beneficial for the large-scale production and application of recombinant AIK in the future.


Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site- -a clinical research center study.
As part of a phase III multicenter study, the pharmacokinetics and metabolism of a permeation-enhanced testosterone (T) transdermal (TTD) system and the influence of application site were investigated in 34 hypogonadal men (21-65 yr of age). After an 8-week androgen washout period, two TTD systems were applied to the back for 24 h. Serum concentrations of total T, bioavailable testosterone (BT), dihydrotestosterone (DHT), and estradiol (E2) increased from hypogonadal levels into the respective normal physiological ranges and declined to baseline levels within 24 h after system removal. Peak concentrations occurred approximately 8 h after application for T and BT and at 13 h for DHT and E2. The baseline-subtracted time-average steady state concentrations (C'ss) for T and BT were 18.1 +/- 7.49 (+/- SD) and 9.08 +/- 3.99 nmol/L, respectively. DHT/T and E2/T ratios, derived from the C'ss values, were 0.063 +/- 0.018 and 0.0033 +/- 0.0018, comparable to the precursor-product conversion ratios reported in healthy men. The estimated half-lives of each hormone were: T, 1.29 +/- 0.71 h; BT, 1.21 +/- 0.75 h; DHT, 2.83 +/- 0.97 h; and E2, 3.53 +/- 1.93 h. The influence of application site was then evaluated by applying two TTD systems for 24 h to the abdomen, back, chest, shin, thigh, or upper arm, according to a sequential cross-over design. Hormone profiles were qualitatively similar at each site, but C'ss values showed significant differences (by ANOVA, P < 0.0001). Based on the BT levels, the rank ordering of the sites were: back > thigh > upper arm > abdomen > chest > shin. DHT/T and E2/T ratios showed negligible site to site variation and were comparable to the results from the initial study. Estimates of T input, based on hormone levels and analysis of the systems used, averaged 4-5 mg/day for the abdomen, back, thigh, and upper arm and were lower and more variable for the chest and shin. Individual C'ss values for T and BT increased linearly with the T input rates (derived from used system analysis) across all studies (n = 235; r = 0.564 for T and r = 0.754 for BT). From these data, T and BT clearance rates were estimated for each patient, averaging 1248 +/- 518 and 2435 +/- 778 L/day, respectively. T clearance rates were proportional to the BT/T ratio (nonsex hormone-binding globulin-bound fraction). On the basis of these studies, the optimal sites of TTD system application were identified as the back, thigh, upper arm, and abdomen


The future of gastroenterology: patient choice, patient voice.
The policy context for patient choice and public and patient involvement (PPI) in the NHS is set out. Both have become increasingly prominent since 2000. A series of NHS systems and policies have been put in place to enable greater patient choice in the belief that the exercise of choice by patients will influence providers to improve quality. This has had some success in elective surgery. One focus has been the publication of outcome data and this may have led to quality improvement through the inherent competitiveness of professionals and institutions. PPI has suffered from a series of unsuccessful reorganisations of patient involvement organisations but has ensured that most health bodies include patient representatives. Capturing patient experience and providing information to enable patient choice have been constantly developed over this time. A particular framework developed by Angela Coulter is used to review current levels of patient engagement in Inflammatory Bowel Disease (IBD), exploring the extent to which patient choice and patient voice are supported and enhanced within current IBD services locally and in national IBD strategy.1 A 2017 vision of the way in which IBD services might maximise patient choice and patient voice is put forward, based on the adoption of present good practice and current service developments, followed by a few rather more radical thoughts about possibilities for after 2017.


Genetic mapping of QTLs for drought tolerance in chickpea (Cicer arietinum L.).
Chickpea yield is severely affected by drought stress, which is a complex quantitative trait regulated by multiple small-effect genes. Identifying genomic regions associated with drought tolerance component traits may increase our understanding of drought tolerance mechanisms and assist in the development of drought-tolerant varieties. Here, a total of 187 F8 recombinant inbred lines (RILs) developed from an interspecific cross between drought-tolerant genotype GPF 2 (Cicer arietinum) and drought-sensitive accession ILWC 292 (C. reticulatum) were evaluated to identify quantitative trait loci (QTLs) associated with drought tolerance component traits. A total of 21 traits, including 12 morpho-physiological traits and nine root-related traits, were studied under rainfed and irrigated conditions. Composite interval mapping identified 31 QTLs at Ludhiana and 23 QTLs at Faridkot locations for morphological and physiological traits, and seven QTLs were identified for root-related traits. QTL analysis identified eight consensus QTLs for six traits and five QTL clusters containing QTLs for multiple traits on linkage groups CaLG04 and CaLG06. The identified major QTLs and genomic regions associated with drought tolerance component traits can be introgressed into elite cultivars using genomics-assisted breeding to enhance drought tolerance in chickpea.


Litoribacter ruber gen. nov., sp. nov., an alkaliphilic, halotolerant bacterium isolated from a soda lake sediment.
A novel alkaliphilic, halotolerant, rod-shaped bacterium, designated strain YIM CH208(T), was isolated from a soda lake in Yunnan, south-west China. The taxonomy of strain YIM CH208(T) was investigated by a polyphasic approach. Strain YIM CH208(T) was Gram-negative, strictly aerobic and non-motile and formed red colonies. Optimal growth conditions were 28°C, pH8.5 and 0.5-2.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the isolate formed a distinct line within a clade containing the genus Echinicola in the phylum Bacteroidetes and was related to the species Echinicola pacifica and Rhodonellum psychrophilum, with sequence similarity of 91.7 and 91.6 % to the respective type strains. The DNA G+C content was 45.1 mol%. The major respiratory quinone was menaquinone-7 (MK-7). The predominant cellular fatty acids were iso-C(17 : 1)ω9c (19.9 %), C(15 : 0) 3-OH (12.1 %), iso-C(17 : 0) 3-OH (11.3 %), summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c; 10.7 %) and C(17 : 1)ω6c (8.7 %). On the basis of the phenotypic, chemotaxonomic and phylogenetic data, strain YIM CH208(T) represents a novel species of a new genus, for which the name Litoribacter ruber gen. nov., sp. nov. is proposed. The type strain of Litoribacter ruber is YIM CH208(T) (=ACCC 05414(T) =KCTC 22899(T)).


Oral habits in a group of consecutively treated orthodontic patients, using standardized video recordings for diagnosis.
To investigate the prevalence and correlation of soft tissue dysfunctions documented by standardized video recordings in a group of orthodontic patients and to evaluate orthodontic treatment changes. The presence of an oral habit was evaluated from standardized pre- and post-treatment video recordings of 80 consecutive patients (30 boys and 50 girls, mean age 12.2 ± 1.7 years). Any digit-sucking habit was noted during a routine interview. Pre- and post-treatment cephalograms were traced to assess sagittal and vertical jaw and incisor relationships. Correlations and differences were tested for statistical significance using the t-test and Odds-ratio. 56.3% had one or more habits before treatment. The total prevalence fell during treatment. A clear correlation was found between digit sucking and atypical tongue activity. Pre-treatment cephalograms showed that patients with a habit had a larger overjet, smaller overbite, more proclined and protruded incisors, a greater ANB angle and a greater inter-maxillary angle (ML/NL) than those without a habit. Cephalometric differences between the groups after orthodontic treatment were much less pronounced. Those with an oral habit also showed a tendency for increased treatment time/number of visits. Standardized video recordings improved the reliability of the recordings of the oral soft tissue dysfunctions. Their overall reduction after the end of orthodontic treatment coincided with a normalization of the sagittal skeletal and dental variables.


Isolation and preliminary characterization of a soluble nitrate reductase from the sulfate reducing organism Desulfovibrio desulfuricans ATCC 27774.
Desulfovibrio desulfuricans ATCC 27774 is a sulfate reducer that can adapt to nitrate respiration, inducing the enzymes required to utilize this alternative metabolic pathway. Nitrite reductase from this organism has been previously isolated and characterized, but no information was available on the enzyme involved in the reduction of nitrate. This is the first report of purification to homogeneity of a nitrate reductase from a sulfate reducing organism, thus completing the enzymatic system required to convert nitrate (through nitrite) to ammonia. D. desulfuricans nitrate reductase is a monomeric (circa 70 kDa) periplasmic enzyme with a specific activity of 5.4 K(m) for nitrate was estimated to be 20 microM. EPR signals due to one [4Fe-4S] cluster and Mo(V) were identified in dithionite reduced samples and in the presence of nitrate.


An evaluation of 30-km cycling time trial (TT30) pacing strategy through time-to-exhaustion at average TT30 pace.
A paucity of research is available on the optimal pacing strategy for cycling events longer than 4 km. Anecdotal evidence suggests that an even pacing strategy is most suitable; however, controlled studies have only determined that a slow start is more suitable than a fast start pacing strategy. Currently, it is unclear which strategy is more effective for endurance cycling time trials. This study sought to identify differences in 30-km cycling time trial (TT30) performance related to pacing strategies by comparing individually chosen pacing strategy with time-to-exhaustion (TE) at the average power output achieved during TT30. Eight moderately trained male cyclists (Vo2max = 50.9 +/- 5.2 mlxkgxmin) performed 2 TT30 tests and 2 TE tests at the average power output of TT30 on a Velotron cycle ergometer at the same time of day, separated by at least 48 hours. During TT30, participants generally chose to use a 'fast start' pacing strategy, cycling at a speed relative to the TT average (TTAvg) of 103.1 +/- 2.2% during the first 5 km. There was no significant difference in performance time between the TE test and TT30. Starting pace (TT0-5) was significantly correlated with finishing pace (TT25-30) (r = -0.91; p < 0.01) and TE (r = 0.85; p < 0.01). Subjects cycling at a relative starting speed (RS0-5) >105% had a significantly longer TE than subjects cycling at <105%, whereas TT30 performance time was not different between the two groups. The present investigation provided indirect evidence that a fast start pacing strategy decreases finishing speed and overall performance in TT30, and increased TT performance can be achieved by selecting a starting pace no more than 5% above TTAvg.


High-resolution soft X-ray beamline ADRESS at the Swiss Light Source for resonant inelastic X-ray scattering and angle-resolved photoelectron spectroscopies.
The concepts and technical realisation of the high-resolution soft X-ray beamline ADRESS operating in the energy range from 300 to 1600 eV and intended for resonant inelastic X-ray scattering (RIXS) and angle-resolved photoelectron spectroscopy (ARPES) are described. The photon source is an undulator of novel fixed-gap design where longitudinal movement of permanent magnetic arrays controls not only the light polarization (including circular and 0-180 degrees rotatable linear polarizations) but also the energy without changing the gap. The beamline optics is based on the well established scheme of plane-grating monochromator operating in collimated light. The ultimate resolving power E/DeltaE is above 33000 at 1 keV photon energy. The choice of blazed versus lamellar gratings and optimization of their profile parameters is described. Owing to glancing angles on the mirrors as well as optimized groove densities and profiles of the gratings, the beamline is capable of delivering high photon flux up to 1 x 10(13) photons s(-1) (0.01% BW)(-1) at 1 keV. Ellipsoidal refocusing optics used for the RIXS endstation demagnifies the vertical spot size down to 4 microm, which allows slitless operation and thus maximal transmission of the high-resolution RIXS spectrometer delivering E/DeltaE > 11000 at 1 keV photon energy. Apart from the beamline optics, an overview of the control system is given, the diagnostics and software tools are described, and strategies used for the optical alignment are discussed. An introduction to the concepts and instrumental realisation of the ARPES and RIXS endstations is given.


Anaerobic power and achievement of VO2 plateau in pre-pubertal boys.
A low anaerobic power has been proposed as a factor that may be limiting the achievement of a plateau in VO2 of children who perform maximal aerobic power tests. This study examined the frequency of plateau achievement in pre-pubertal children and compared VO2max, peak (PP) and mean (MP) anaerobic power in subjects who either achieved a plateau (PLAT) or did not (NO PLAT). Eighteen healthy pre-pubertal (Tanner Stage, pubic hair = 1) males (age = 9.1 1.6 yrs, ht = 134.4 +/- 9.7cm, wt = 33.3 +/- 9.2kg, VO2max = 40.0 +/- 6.7 ml x kg(-1) min(-1)) were tested. All subjects completed a 30 sec Wingate Anaerobic Test and a McMaster aerobic protocol to volitional fatigue on a cycle ergometer. Only 33% of the subjects met the PLAT criterion. No differences were found for PP or MP between those who achieved a plateau and those who did not (PLAT: PP= 6.3 +/- 0.8W/kg and MP = 5.2 +/- 0.7W/kg; NO PLAT: PP= 6.3 +/- 1.2 W/kg and MP = 5.2 +/- 1.3 W/kg). We conclude that anaerobic power is not a factor limiting the achievement of a plateau in VO2 of pre-pubertal boys who perform maximal aerobic power tests.


[Cervical recurrence in the pathologically negative neck (pNO): finding a needle in a haystack].
Recurrence in the pathologically negative neck (pN0) is one of the most striking events occurring in head and neck tumors. It is not even mentioned in many neck dissection studies. The presence of micrometastases has been suggested as an explanation for this event. In accordance to a recent study performed in our institution, we bring up this controversial issue. A definitive explanation for recurrence in the pN0 has not yet been proposed.


Flexible parallel implementation of logic gates using chaotic elements.
We demonstrate the basic principles for the direct and flexible implementation of all basic logical operations utilizing low dimensional chaos. Then we generalize the concept to high dimensional chaotic systems, and show the parallelism inherent in such systems. As a case study we implement the proposed parallel computing architecture to obtain parallelized bit-by-bit addition with a two-dimensional chaotic neuronal and a three-dimensional chaotic laser model.


Identification of dyes on single textile fibers by HPLC-DAD-MS.
An HPLC-DAD-MS method is described to analyze textile dyes in different dye classes (reactive, basic, acid, direct, disperse). The described method is sensitive enough to analyze single fibers with a length of a few millimeters or less, which makes it suitable for forensic analyses. The current paper describes the information content of the acquired data as well as the results of a validation study, in which the repeatability, specificity, and limit of detection of the method were assessed by repeated measurements of nine different dyes in the mentioned dye classes. The mass accuracy (deviation generally <2 ppm) and absorbance spectra were found to be highly stable in several measurements over a period of 8 weeks. Deviation in retention times were observed and attributed to small experimental effects and a precolumn blockage. The results show that dye analysis is possible for most fibers with a minimum length of one or a few millimeters.


First-order transition between a small gap semiconductor and a ferromagnetic metal in the isoelectronic alloy FeSi1-xGex.
The contrasting ground states of isoelectronic, isostructural FeSi and FeGe are explained within an extended local density approximation scheme (LDA+U) by an appropriate choice of the Coulomb repulsion U on the Fe sites. A minimal two-band model with interband interactions leads to a phase diagram for the alloys FeSi1-xGex. A mean field approximation gives a first-order transition between a small gap semiconductor and a ferromagnetic metal as a function of magnetic field, temperature, and concentration x. Unusually the transition from metal to insulator is driven by broadening, not narrowing, the bands and it is the metallic state that shows magnetic order.


Fever of Unknown Origin in a 17-Year-Old Girl.
Fever of unknown origin (FUO) is defined as fever (>101°F) that lasts more than three weeks and for which a cause is not found within seven days of hospital evaluation. FUO has a broad list of differentials - infection, inflammatory diseases, and malignancy. A detailed history and meticulous clinical examination with thorough and stepwise investigations lead to a diagnosis in only two-thirds of cases. In this article, we present a 17-year-old adolescent girl, with no significant past medical history, who presented with FUO during the COVID pandemic. A high index of suspicion and extensive investigations revealed the final diagnosis.


Cutaneous lupus erythematosus: update of therapeutic options part II.
In the first part of the review, topical agents and first-line systemic treatment options for cutaneous lupus erythematosus were discussed whereas in the second part, recent information on efficacy, dosage, and side effects for further systemic treatment options are described in detail. In contrast to other immunosuppressive agents, such as azathioprine, cyclophosphamide, and cyclosporine, methotrexate has recently received more attention in the treatment of the disease. Further second-line treatment includes retinoids, dapsone, and mycophenolate mofetil. Because of severe side effects or high costs, other agents, such as thalidomide or high-dose intravenous immunoglobulins, are reserved for severe recalcitrant CLE. Biologics, ie, rituximab, have been used to treat systemic lupus erythematosus; however, in CLE, most biologics have only been applied in single cases. In addition to successful treatment, induction of CLE subtypes by biologics has been reported. In conclusion, many treatment options exist for CLE, but not many are supported by evidence from randomized controlled trials.


Prevalence of traumatic dental injuries in India: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to estimate the prevalence of traumatic dental injuries (TDI) in India. The secondary objective was to evaluate the prevalence rate according to the differences in gender, age, regions, type of TDI and risk factors associated with TDI. The PubMed, LILACS, Web of Science, Cochrane, CINHAL, and Scopus databases, along with the Public Health Electronic Library, TRoPHI and DoPHER were searched from 1st March to 15thApril 2019 without any restriction of language and year of publication. The qualitative synthesis was done regarding the demographics, study methods, cause of trauma, geographic location, increased overjet and inadequate lip coverage. The meta-analysis was undertaken with STATA-14 software (USA). The pooled prevalence of TDI was calculated using data extracted from 48 studies included in qualitative synthesis and meta-analysis. A sub-group meta-analysis was done by extraction of the data for age groups of 6 years and >6 years. The pooled prevalence of TDI in Indian population was 13 cases in 100 individuals. The prevalence of TDI for age groups of ≤6 was 15% (males, 15%; females, 16%) and for >6 years was 12% (males, 13%; females, 8%). The most common cause of TDI was falls, and most frequent location was home. The odds ratio for occurrence of TDI and inadequate lip-coverage was 3.35 and overjet greater than 3 mm was 3.53. The pooled prevalence of TDI was 13% and slightly higher in children less than 6 years of age. Inadequate lip coverage and increased overjet are the risk factors associated with TDI. Heterogeneity was observed among the studies in terms of design, variables recorded, sampling, study methods and statistical methods. Majority of them also suffered from moderate to high risk of bias.


Effect of ultrasound contrast agent dose on the duration of focused-ultrasound-induced blood-brain barrier disruption.
It has been shown that focused ultrasound (FUS) is capable of noninvasive and reversible disruption of the blood-brain barrier (BBB) at target regions when applied in the presence of ultrasound contrast agent (UCA). The purpose of this study was to investigate the effects of UCA dose on the reversibility of BBB disruption induced by the same acoustical power of FUS. Sonications were applied at an ultrasound frequency of 1 MHz with a 5% duty cycle and a repetition frequency of 1 Hz. The brains of 66 male Sprague-Dawley rats were subjected to sonications with three doses of UCA. BBB integrity was evaluated via femoral vein injection of Evans Blue (EB) while the rats were anesthetized. The relationship between UCA dose and the region of EB extravasation was evaluated at an acoustic power of 1.43 W. The BBB disruption, as indexed by the amount of EB extravasation, was the largest immediately after the sonications. The quantity of Evans blue extravasation decreased as a function of time at various UCA doses. This study demonstrates that the appropriate dose of UCA not only enhance the BBB opening but also effectively aid in controlling the duration of BBB disruption.


[The cystic fibrosis gene: mutation and the function of CFTR protein].
The spectrum of mutations identified in cystic fibrosis patients includes a major defect (delta F508), found in 70% of CF chromosomes from French patients, and a large number of infrequent mutations. This significant heterogeneity of molecular defects precludes large scale screening for the disease at the time being. The presumptive structure of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), the membrane protein encoded by the CF gene, is briefly recalled. The role this protein is thought to play in the regulation of chloride ion transport across epithelial membranes is discussed, along with the new insights into the molecular mechanisms of CF gained as a result of identification of the CF gene.


Relationship Between Quality of Care and Patient Care Outcomes for Postoperative Pain in Major Orthopedic Surgery: Analytical and Cross-Sectional Study.
The quality of care provided for the management of postoperative pain and patient outcomes are key criteria for healthcare institutions. This study aimed to determine the relationship between the quality of care provided for the alleviation of postoperative pain experienced among patients undergoing major orthopedic surgery and the patient care outcomes. The study was designed as an analytical and cross-sectional study. The rates of pain severity and sleep interference, activity interference, affective experiences, and adverse effects due to postoperative pain were higher in female patients than in male patients. A significant positive correlation was identified between the quality of postoperative pain care and the perception of care (p < .05). Implementing nursing interventions to improve pain management and increase the quality of care appears to be vital elements for reducing adverse effects caused by pain and increasing the satisfaction with postoperative pain care.


Verification of performance specifications for a US Food and Drug Administration-approved molecular microbiology test: Clostridium difficile cytotoxin B using the Becton, Dickinson and Company GeneOhm Cdiff assay.
US Food and Drug Administration (FDA)-approved diagnostic tests based on molecular genetic technologies are becoming available for an increasing number of microbial pathogens. Advances in technology and lower costs have moved molecular diagnostic tests formerly performed for research purposes only into much wider use in clinical microbiology laboratories. To provide an example of laboratory studies performed to verify the performance of an FDA-approved assay for the detection of Clostridium difficile cytotoxin B compared with the manufacturer's performance standards. We describe the process and protocols used by a laboratory for verification of an FDA-approved assay, assess data from the verification studies, and implement the assay after verification. Performance data from the verification studies conducted by the laboratory were consistent with the manufacturer's performance standards and the assay was implemented into the laboratory's test menu. Verification studies are required for FDA-approved diagnostic assays prior to use in patient care. Laboratories should develop a standardized approach to verification studies that can be adapted and applied to different types of assays. We describe the verification of an FDA-approved real-time polymerase chain reaction assay for the detection of a toxin gene in a bacterial pathogen.


Alcohol consumption and the risk of bladder cancer in the Framingham Heart Study.
The association between alcohol consumption and bladder cancer is controversial. We used data from 10,125 participants in the Framingham Heart Study to assess the association between total and beverage-specific alcohol consumption and the risk of bladder cancer. For each case of bladder cancer, up to five control subjects were selected and matched on major confounders using a risk set method. We used conditional logistic regression to assess the risk of bladder cancer according to categories of alcohol consumption. During a mean follow-up of 27.3 +/- 10.1 years, there were 126 incident cases of bladder cancer. There was no statistically significant association between alcohol consumption and risk of bladder cancer (P(trend) =.3). In beverage-specific analyses, beer consumption was associated with a reduced risk of bladder cancer (P(trend) =.03), whereas wine (P(trend) =.7) and spirit (P(trend) =.2) consumption were not. Our data suggest that total and beverage-specific alcohol consumption are not associated with an increased risk of bladder cancer.