Assessing potential predisposition of elementary school children to heart disease.
Physical well-being has been designated a top priority for the children in the Clovis (California) Unified School District. In an effort to diminish coronary risk factors and encourage a healthy life style, a health assessment battery was developed for students in grades 1 through 6. The battery included measurements in height, weight, blood pressure, sit and reach flexibility, and skin-fold test for body fat composition. More than 5000 students were administered the tests by a health assessment team consisting of two nurses, three physical education resource teachers, and two clerical staff members. A random sample of 100 males and 100 females at each grade level was utilized for the statistical analysis. The correlation between body fat and weight was .80 (p v .05) in the fifth and sixth grades. Body fat was positively correlated with both systolic and diastolic measures of blood pressure. The coefficient averaged .21 (p v .05) over the 6 grades for systolic and .22 (p .05) over the 6 grades for diastolic blood pressure. Future plans call for the development of a longitudinal profile of students, as well as establishing district norms for the test battery.


Recombination during transformation as a source of chimeric mammalian artificial chromosomes in yeast (YACs).
Mammalian DNAs cloned as artificial chromosomes in yeast (YACs) frequently are chimeras formed between noncontiguous DNAs. Using pairs of human and mouse YACs we examined the contribution of recombination during transformation or subsequent mitotic growth to chimeric YAC formation. The DNA from pairs of yeast strains containing homologous or heterologous YACs was transformed into a third strain under conditions typical for the development of YAC libraries. One YAC was selected and the presence of the second was then determined. Co-penetration of large molecules, as deduced from co-transformation of markers identifying the different YACs, was > 50%. In approximately half the cells receiving two homologous YACs, the YACs had undergone recombination. Co-transformation depends on recombination since it was reduced nearly 10-fold when the YACs were heterologous. While mitotic recombination between homologous YACs is nearly 100-fold higher than for yeast chromosomes, the level is still much lower than observed during transformation. To investigate the role of commonly occurring Alu repeats in chimera formation, spheroplasts were transformed with various human YACs and an unselected DNA fragment containing an Alu at one end and a telomere at the other. When unbroken YACs were used, between 1 and 6% of the selected YACs could incorporate the fragment as compared to 49% when the YACs were broken. We propose that Alu's or other commonly occurring repeats could be an important source of chimeric YACs. Since the frequency of chimeras formed between YACs or a YAC and an Alu-containing fragment was reduced when a rad52 mutant was the recipient and since intra-YAC deletions are reduced, rad52 and possibly other recombination-deficient mutants are expected to be useful for YAC library development.


Is It Possible to induce Artificial Caries-affected Dentin using the Same Protocol to Primary and Permanent Teeth?
This in vitro study compared the mineral loss of natural and artificially-created caries-affected dentin in primary and permanent teeth using the same protocol to induce caries lesions. Twenty molars presenting natural occlusal dentin caries lesions (10 primary-PriC and 10 perma-nent-PermC; control group), and 20 sound molars (10 primary -PripH and 10 permanent-PermpH; experimental group), were selected. Occlusal cavities were prepared in teeth of the experimental group that were submitted to pH-cycling for 14 days to simulate caries-affected dentin. All specimens were longitudinally sectioned and prepared in order to obtain Knoop micro-hardness values from 15 to 250 urn depth, starting in bottom of center of natural lesions or cavities. The microhardness (KHN) data were submitted to three-way repeated measures analysis of variance (ANOVA) and Tukey's tests (α = 0.05). Considering all depths, there was no statistically significant differences (p > 0.05) between the mineral loss of the control (PriC = 30.9 ± 6.4 and PermC = 40.8 ± 8.6) and experimental (PripH = 27.3 ± 11.1 and PermpH = 35.5 ± 14.0) groups, neither between primary and permanent teeth. The mineral loss of the artificially-created caries-affected dentin is similar to that from naturally developed dentin caries lesions. The pH-cycling model may be a suitable method to simulate caries-affected dentin in both permanent and primary teeth.


Phonological recoding in error detection: a cross-sectional study in beginning readers of Dutch.
The present cross-sectional study investigated the development of phonological recoding in beginning readers of Dutch, using a proofreading task with pseudohomophones and control misspellings. In Experiment 1, children in grades 1 to 3 rejected fewer pseudohomophones (e.g., wein, sounding like wijn 'wine') as spelling errors than control misspellings (e.g., wijg). The size of this pseudohomophone effect was larger in grade 1 than in grade 2 and did not differ between grades 2 and 3. In Experiment 2, we replicated the pseudohomophone effect in beginning readers and we tested how orthographic knowledge may modulate this effect. Children in grades 2 to 4 again detected fewer pseudohomophones than control misspellings and this effect decreased between grades 2 and 3 and between grades 3 and 4. The magnitude of the pseudohomophone effect was modulated by the development of orthographic knowledge: its magnitude decreased much more between grades 2 and 3 for more advanced spellers, than for less advanced spellers. The persistence of the pseudohomophone effect across all grades illustrates the importance of phonological recoding in Dutch readers. At the same time, the decreasing pseudohomophone effect across grades indicates the increasing influence of orthographic knowledge as reading develops.


Localised sarcoptic mange in dogs: a retrospective study of 10 cases.
The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.


Pre- and Post-Treatment Imaging of Primary Central Nervous System Tumors in the Molecular and Genetic Era.
Recent advances in the molecular and genetic characterization of central nervous system (CNS) tumors have ushered in a new era of tumor classification, diagnosis, and prognostic assessment. In this emerging and rapidly evolving molecular genetic era, imaging plays a critical role in the preoperative diagnosis and surgical planning, molecular marker prediction, targeted treatment planning, and post-therapy assessment of CNS tumors. This review provides an overview of the current imaging methods relevant to the molecular genetic classification of CNS tumors. Specifically, we focused on 1) the correlates between imaging features and specific molecular genetic markers and 2) the post-therapy imaging used for therapeutic assessment.


Effect of Supplementation of Sorghum Silage in Weanling Fillies During the Dry Period in Brazil.
Young horses reach nearly 90% of their final height in the first year of life. However, to achieve their genetic potential, it is necessary to receive adequate nutrition during this period of rapid growth. The objective of this study was to evaluate the effect of supplementation of sorghum silage during a period of limited pasture forage availability, on the body development, and health of Mangalarga Marchador (MM) weanling fillies. Fourteen healthy MM 6-month-old fillies were randomly assigned to one of two groups: GS (consuming silage) and GH (consuming grass hay (Cynodon spp) in addition to 1.5% of body weight (BW) in dry matter (DM) of a fortified corn-based concentrate (17% CP [crude protein]), which was fed in individual stalls divided into two feedings/day for both groups. After concentrate feedings, the experimental groups remained loose in drylot pens of 50 m2, where the assigned forages were fed ad libitum with free access to salt and water. Group feed intake of the forages was recorded. It was assumed they were consuming a forage:concentrate ratio of 50:50. To assess development, the animals were weighed and measured for height at the withers and croup, body length, girth, and cannon bone circumference. The physical condition of animals, including BW, rectal temperature, mucous membrane color, and body condition score were assessed as well as serum biochemical analyses of creatinine, urea, total protein, gamma glutaminotransferase, aspartate aminotransferase, alkaline phosphatase, glucose, magnesium, calcium, and phosphorus concentrations were evaluated. The weights, morphometric measurements, clinical evaluation, and blood collections were done on the first day and every 21 days during the 84 days trial period. The growth performance and serum were subjected to analysis of variance for repeated measures, factoring treatment, and collection period. Despite higher (P < .05) DM and CP intakes by the GH fillies than those GS, there were no treatment effects (P > .05) on any of the development or health parameters measured. The use of sorghum silage as forage source for 84 days during the dry season had no negative impact on the body development and health of MM fillies (6-9 months of age) that were also fed 1.5% BW of a commercial concentrate balanced for growth.


The Xenopus Emx genes identify presumptive dorsal telencephalon and are induced by head organizer signals.
We have isolated and studied the expression pattern of Xemx1 and Xemx2 genes in Xenopus laevis. Xemx genes are the homologues of mouse Emx genes, related to Drosophila empty spiracles. They are expressed in selected regions of the developing brain, particularly in the telencephalon, and, outside the brain, in the otic vesicles, olfactory placodes, visceral arches and the developing excretory system. We also report on experiments concerning the tissue and molecular signals responsible for their activation in competent ectoderm. Xemx genes are activated in ectoderm conjugated with head organizer tissue, but not with tail organizer tissue. Furthermore, they are not activated in animal cap either by noggin or by Xnr3, thus suggesting that a different inducer or the integration of several signals may be responsible for their activation.


Immunoreactive gonadotropin-releasing hormone (Gn-RH) during maturation in the rat: Ontogeny of regional hypothalamic differences.
The developmental appearance of immunoreactive gonandotropin releasing hormone (Gn-RH) was measured by radioimmunoassay in male and female rats from the 12th day of gestation to adulthood. Gn-RH content of the whole hypothalamus of both sexes increased from birth to 21 days of age. By the 28th day, Gn-RH content in females had approximately reached adult levels, while that in males continued to increase. Adult male rats exhibited significantly higher levels than adult females. The ontogeny of the regional differences previously observed in cycling female rats (4) was also studied. Regional analysis of Gn-RH development was characterized in the anterior hypothalamus by the rapid attainment of adult levels by day 7. In striking contrast, in the mid-hypothalamic region, Gn-RH content increased gradually, rising dramatically just prior to vaginal opening. The developmental pattern of Gn-RH content is consistent with the maturation of those hypothalamic structures concerned with synthesis, transport and storage of Gn-RH. The regional patterns observed may thus represent sequential maturation of the neural pathways involved.


Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis.
Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy. The β-CDs/CeO2 NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression. The average particle size of the blank β-CDs/CeO2 NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce3+/Ce4+ valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of H2O2 efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@β-CDs/CeO2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO2 NPs exhibited excellent therapeutic effect. This study may pave the way for the application of nanozyme β-CDs/CeO2 NPs as a powerful tool for psoriasis therapy.


An analysis of the outcomes of treatment of small cell lung cancer in the elderly.
Many cases of small cell lung cancer will occur in the elderly population but optimal management of the disease in this age group remains uncertain. To evaluate treatment of small cell lung cancer in the elderly in Australia and to compare treatment received and outcomes with those of younger patients. To draw insights from these observations into the optimal management of small cell lung cancer in the elderly. A retrospective review of treatment charts and case notes for 51 elderly patients and 102 younger patients was undertaken. Elderly patients had similar baseline parameters with respect to disease stage and performance status. Elderly patients were mostly treated uniformly with combination chemotherapy, but suffered more dose reductions than younger patients. Benefits of chemotherapy were seen even in patients with poor performance status. Despite the dose reductions, response rates and survival times for elderly patients were usually similar to younger patients. Combination chemotherapy is beneficial to elderly patients with small cell lung cancer. Optimal therapy for the elderly may be different from that for younger patients and should be defined through prospective randomised clinical trials.


A Decentralized Framework for Multi-Agent Robotic Systems.
Over the past few years, decentralization of multi-agent robotic systems has become an important research area. These systems do not depend on a central control unit, which enables the control and assignment of distributed, asynchronous and robust tasks. However, in some cases, the network communication process between robotic agents is overlooked, and this creates a dependency for each agent to maintain a permanent link with nearby units to be able to fulfill its goals. This article describes a communication framework, where each agent in the system can leave the network or accept new connections, sending its information based on the transfer history of all nodes in the network. To this end, each agent needs to comply with four processes to participate in the system, plus a fifth process for data transfer to the nearest nodes that is based on Received Signal Strength Indicator (RSSI) and data history. To validate this framework, we use differential robotic agents and a monitoring agent to generate a topological map of an environment with the presence of obstacles.


[Comparison of Recovery Phase CT Features between Mild/moderate and Severe/critical Coronavirus Disease 2019 Patients].
Objective To investigate the computed tomographc(CT)features of mild/moderate and severe/critical cases of coronavirus disease 2019(COVID-19)in the recovery phase. Methods Totally 63 discharged patients in Wuhan,China,who underwent both chest CT and reverse transcription-polymerase chain reaction(RT-PCR)from February 1 to February 29,2020,were included.With RT-PCR as a gold standard,the performance of chest CT in diagnosing COVID-19 was assessed.Patients were divided into mild/moderate and severe/critical groups according to the disease conditions,and clinical features such as sex,age,symptoms,hospital stay,comorbidities,and oxygen therapy were collected.CT images in the recovery phase were reviewed in terms of time from onset,CT features,location of lesions,lobe score,and total CT score. Results There were 37 patients in the mild/moderate group and 26 in the severe/critical group. Compared with the mild/moderate patients,the severe/critical patients had older age [(43±16) years vs. (52±16) years; t=2.10, P=0.040], longer hospital stay [(15±6)d vs. (19±7)d; t=2.70, P=0.009], higher dyspnea ratio (5.41% vs. 53.85%; χ2=18.90, P<0.001), lower nasal oxygen therapy ratio (81.08% vs. 19.23%;χ2=23.66, P<0.001), and higher bi-level positive airway pressure ventilation ratio (0 vs. 57.69%; χ2=25.62, P<0.001). Time from onset was (23±6) days in severe/critical group, significantly longer than that in mild/moderate group [(18±7) days] (t=3.40, P<0.001). Severe/critical patients had significantly higher crazy-paving pattern ratio (46.15% vs.10.81%;χ2=4.24, P=0.039) and lower ground-glass opacities ratio (15.38% vs. 67.57%; χ2=16.74, P<0.001) than the mild/moderate patients. The proportion of lesions in peripheral lung was significantly higher in mild/moderate group than in severe/critical group (78.38% vs.34.61%; χ2=13.43, P<0.001), and the proportion of diffusely distributed lesions was significantly higher in severe/critical group than in mild/moderate group (65.38% vs.10.81%; χ2=20.47, P<0.001). Total CT score in severe/critical group was also significantly higher in severe/critical group than in mild/moderate group [11 (8,17) points vs. 7 (4,9) points; Z=3.81, P<0.001]. Conclusions The CT features in the recovery stage differ between mild/moderate and severe/critical COVID-19 patients.The lung infiltration is remarkably more severe in the latter.


Targeting the Microenvironment in Advanced Colorectal Cancer.
Colorectal cancer (CRC) diagnosis often occurs at late stages when tumor cells have already disseminated. Current therapies are poorly effective for metastatic disease, the main cause of death in CRC. Despite mounting evidence implicating the tumor microenvironment in CRC progression and metastasis, clinical practice remains predominantly focused on targeting the epithelial compartment. Because CRCs remain largely refractory to current therapies, we must devise alternative strategies. Transforming growth factor (TGF)-β has emerged as a key architect of the microenvironment in poor-prognosis cancers. Disseminated tumor cells show a strong dependency on a TGF-β-activated stroma during the establishment and subsequent expansion of metastasis. We review and discuss the development of integrated approaches focused on targeting the ecosystem of poor-prognosis CRCs.


Growth hormone (GH)-releasing hormone increases the expression of the dominant-negative GH isoform in cases of isolated GH deficiency due to GH splice-site mutations.
An autosomal dominant form of isolated GH deficiency (IGHD II) can result from heterozygous splice site mutations that weaken recognition of exon 3 leading to aberrant splicing of GH-1 transcripts and production of a dominant-negative 17.5-kDa GH isoform. Previous studies suggested that the extent of missplicing varies with different mutations and the level of GH expression and/or secretion. To study this, wt-hGH and/or different hGH-splice site mutants (GH-IVS+2, GH-IVS+6, GH-ISE+28) were transfected in rat pituitary cells expressing human GHRH receptor (GC-GHRHR). Upon GHRH stimulation, GC-GHRHR cells coexpressing wt-hGH and each of the mutants displayed reduced hGH secretion and intracellular GH content when compared with cells expressing only wt-hGH, confirming the dominant-negative effect of 17.5-kDa isoform on the secretion of 22-kDa GH. Furthermore, increased amount of 17.5-kDa isoform produced after GHRH stimulation in cells expressing GH-splice site mutants reduced production of endogenous rat GH, which was not observed after GHRH-induced increase in wt-hGH. In conclusion, our results support the hypothesis that after GHRH stimulation, the severity of IGHD II depends on the position of splice site mutation leading to the production of increasing amounts of 17.5-kDa protein, which reduces the storage and secretion of wt-GH in the most severely affected cases. Due to the absence of GH and IGF-I-negative feedback in IGHD II, a chronic up-regulation of GHRH would lead to an increased stimulatory drive to somatotrophs to produce more 17.5-kDa GH from the severest mutant alleles, thereby accelerating autodestruction of somatotrophs in a vicious cycle.


N-Doped Sandwich-Structured Mo2C@C@Pt Interface with Ultralow Pt Loading for pH-Universal Hydrogen Evolution Reaction.
Designing a unique electrochemical interface to exhibit Pt-like activity and good stability is indispensable for the efficient hydrogen evolution reaction (HER). Herein, we synthesize well-defined Mo2C@NC@Pt nanospheres with a sandwich-structured interface through a facile organic-inorganic pyrolysis and following reduction process. The obtained Mo2C@NC@Pt heterostructures with ultralow Pt loading are composed of well-dispersed Mo2C nanoparticles (NPs) inner layer, N-doped carbon layer, and ultrafine Pt NPs outer layer. Electrochemical measurements demonstrate that Mo2C@NC@Pt heterostructures not only exhibit superior HER activities than commercial Pt/C with small overpotentials of only 27, 47, and 25 mV to achieve a current density of 10 mA cm-2 in acidic, alkaline, and neutral media, respectively, but also possess favorable long-term stability in pH-universal solution. The improved reaction kinetics of Mo2C@NC@Pt heterostructures are mainly attributed to the unique sandwich-structured interface with well-defined Mo2C NPs encapsulated by carbon layers and Pt NPs well-dispersed on the carbon support, synergistic effects among Mo2C NPs, NC, and Pt NPs, high specific surface area, and N-doping into the catalysts. This facile approach not only provides a new pathway for preparing well-defined carbides but also gives insight into the development of low-Pt catalysts for the efficient HER.


Cooperative and submolecular dissipation mechanisms of sliding friction in complex organic systems.
Energy dissipation in single asperity sliding friction was directly linked to submolecular modes of mobility by intrinsic friction analysis, involving time-temperature superposition along with thermodynamic stress and reaction rate models. Thereby, polystyrene served as a representative tribological sample for organic and amorphous complex systems. This study reveals the significance of surface and subsurface (alpha-, beta-, and gamma-) relaxational modes, which couple under appropriate external conditions (load, temperature, and rate) with shear induced disturbances, and thus gives rise to material specific frictional dissipation. At low pressures and temperatures below the glass transition point, the phenyl pendant side groups of polystyrene, known for their preferential orientation at the free surface, were noticed to be the primary channel for dissipation of kinetic sliding-energy. While this process was found to be truly enthalpic (activation energy of 8 kcalmol), energy dissipation was shown to possess both enthalpic and cooperative entropic contributions above the loading capacity of the surface phenyl groups (9.9 kcalmol) or above the glass transition. Apparent Arrhenius activation energies of frictional dissipation of 22 and 90 kcalmol, respectively, and cooperative contributions up to 80% were found. As such, this study highlights issues critical to organic lubricant design, i.e., the intrinsic enthalpic activation barriers of mobile linker groups, the evaluation of cooperative mobility phenomena, and critical tribological parameters to access or avoid coupling between shear disturbances and molecular actuators.


Problematic internet use and internet searches for medical information: the role of health anxiety.
Individuals frequently use the Internet to search for medical information. For some individuals, repeated searches for medical information on the Internet exacerbate health anxiety. Researchers have termed this phenomenon "cyberchondria" and have suggested that cyberchondria might relate to the excessive use of the Internet for other purposes as well. The present study examined associations among Internet searches for medical information, health anxiety, and problematic Internet use (PIU) using a large sample of medically healthy community adults located in the United States (N=430). As predicted, respondents who experienced increased health anxiety following Internet searches for medical information reported significantly greater PIU than respondents for whom such searches either had no impact on or decreased their health anxiety. This effect was not attributable to the frequency of health-related online searching behavior or negative affect. Conceptual and therapeutic implications are discussed.


Women who quit maquiladora work on the U.S.-Mexico border: assessing health, occupation, and social dimensions in two transnational electronics plants.
This cohort study of 725 women examined the health, occupational, and social factors that contribute to quitting work in two transnational electronics maquiladoras (assembly plants) in Tijuana, Mexico. The estimated cumulative probabilities of quitting were 68% and 81% by 1 and 2 years of employment. After adjusting for other factors, women who had a history of smoking or surgery and those who returned to work after a paid leave due to illness were more likely to quit. In contrast, women with a history of chronic illness had lower quitting rates. The nationality of the company and the work shift also significantly influenced quitting rates, but demographic characteristics and health care visits did not have a significant effect. Women selectively leave maquiladora employment, often due to health-related events. The healthy worker effect is difficult to measure in a mobile population with high turnover.


Febrile convulsions: electroencephalographic changes related to rectal temperature.
Nine children had simultaneous continuous electroencephalographic monitoring and temperature recording immediately after febrile convulsions. Background electroencephalographic rhythms did not alter with temperature and with one exception, seizure discharges occurred only during sustained high pyrexia.


In vitro pharmacodynamics of moxifloxacin versus levofloxacin against 4 strains of Streptococcus pneumoniae: 1 wild type, 2 first-step parC mutants, and 1 pump mutant.
Levofloxacin binds topoisomerase IV, whereas moxifloxacin preferentially binds DNA gyrase. Most 1st-step pneumococcal mutants have alterations in the parC gene of topoisomerase IV. Because of differential binding affinity, moxifloxacin may have superior activity against 1st-step mutants compared with levofloxacin. The purpose of this work was to compare rates and extent of bacterial killing of genetically characterized Streptococcus pneumoniae with moxifloxacin and levofloxacin. Four strains of S. pneumoniae were used: a wild type, 2 first-step parC mutants, and a pump mutant. Using an in vitro pharmacodynamic model run in duplicate, we exposed bacteria to unbound moxifloxacin and levofloxacin peaks of 2 and 4.5 mg/L, respectively, which emulated clinical dosing. Additional experiments were done in which the area under the curve (AUC)/MIC ratio of 1 agent was matched to the competing drug's clinical dose AUC/MIC ratio. Time kill curves were analyzed for rate and extent of bacterial kill and regrowth. Pre- and postexposure MIC and polymerase chain reaction (PCR) testing were done. Moxifloxacin and levofloxacin displayed similar rates and extent of bacterial kill for the wild type, efflux pump type, and parC mutant 27-1361B. Moxifloxacin initially achieved a faster rate of kill, regardless of the AUC/MIC ratio, against parC mutant 7362 (P < 0.05) but not an advantage in time to 3 log kill. Postexposure MIC values were elevated for strain 7362 in 2 moxifloxacin experiments and 1 levofloxacin experiment. Post-PCR analysis revealed new gyrA mutations for all 3 isolates. Both moxifloxacin and levofloxacin are effective against multiple strains of S. pneumoniae.


Vergence Profile and Prevalance of Non-Strabismic Vergence Anomalies Among School Children in Abia State, Nigeria.
To determine the prevalence of non-strabismic vergence anomalies and their relationship with age, gender, and school level in children aged 10-16 years Method: A cross-sectional study was conducted among 537 children (255 male, 282 females; mean age 13.0 ± 2.0, years) selected from nine schools using stratified, cluster, and random sampling. The participants completed a Convergence Insufficiency Symptom Survey (CISS) and eye examinations, including the measurement of visual acuity, non-cycloplegic refraction, cover test, near point of convergence, fusional vergences, accommodative functions, and ocular health evaluation. All binocular tests were performed following the subjective refraction with the corrective lenses in place, if prescribed. The prevalence of low suspect, high suspect, and definite convergence insufficiency was 9.6%, 5.8%, and 4.1%, respectively. Other prevalence estimates included convergence excess (2.9%), fusional vergence dysfunction (2.6%), basic exophoria (1.7%), basic esophoria (2.8%), divergence insufficiency (0.8%), and divergence excess (0.6%). The prevalence of high suspect (p < 0.01) and definite (p < 0.01) convergence insufficiency was significantly higher in older than younger children, and as expected, in secondary more so than primary school children (p = 0.01). There was no statically significant association between gender and various vergence anomalies. The study showed that vergence anomalies are common vision conditions among Abia State school children. Given the importance of visual skills in learning and academic achievements, there is a need to develop screening and management strategies that will target those visual conditions to prevent educational and social progress being affected.


Effect of target-enriched multiplex polymerase chain reaction on patient outcomes and costs during the 2013-14 influenza season.
The US Centers for Disease Control and Prevention recommends the initial use of rapid antigen influenza diagnostic test (RIDT) for the detection of influenza A (H1N1-09). Nasopharyngeal samples were tested from 246 patients for H1N1-09 using target-enriched multiplex polymerase chain reaction (TEM-PCR), of which 163 were additionally tested via RIDT. RIDTs had a sensitivity of 18.7% compared with TEM-PCR as the reference standard. Patients with false-negative RIDTs were withheld from 111 days of oseltamivir and 65 days of isolation. Patients negative for H1N1 via TEM-PCR had antiviral therapy immediately stopped, thereby evading 408 days of oseltamivir and 315 days of unnecessary isolation. This cost avoidance saved US$208,982.


[Skin disorders and job fitness assessment].
Assessment of fitness for employment represents the final phase of the risk evaluation and health surveillance carried out during pre-employment and periodical medical examination. Dermatoses are frequent diseases both in the general population and workers, therefore job fitness assessment for workers with skin problems will frequently fall within the occupational health area. The physician must verify whether or not the dermatosis is an occupational disease and must adopt preventive measures to avoid any worsening or relapse of the clinical situation due to occupational factors. This article gives suggestions for correct management of occupational and non-occupational skin diseases in the workplace, with practical examples of job fitness assessment. We first examined the role of the occupational physician in the evaluation of occupational risk factors that can induce work-related dermatoses or aggravate other dermatoses. We then discussed the factors that must be considered during assessment of fitness for employment when dermatoses are present. Finally, we examined practical examples of occupational or non-occupational dermatoses that can cause functional limitations, factors that can influence job fitness evaluation, and the possible role of allergological tests. Several dermatoses can be aggravated or caused by occupational factors (e.g. atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, keratinization disorders, lichen planus, physical urticaria). Close cooperation between the dermatologist and the occupational physician is very important in order to make an etiological diagnosis that is necessary for the job fitness assessment. It is difficult to define definitive criteria for the assessment of fitness for employment; in this article only some suggestions are made and they can vary according to the different situations.


Somatomedin A in human serum, determined by radioreceptor assay.
Somatomedin A was determined by radioreceptor assay in serum from patients with various disorders. The mean values of somatomedin A in serum from 20 adult subjects, 21 patients with acromegaly, and 17 patients with hypopituitary dwarfism were 1.08 +/- 0.08, 3.02 +/- 0.33 and 0.44 +/- 0.03 U/ml, respectively. In children below 2 years of age, low levels were found (mean 0.40 +/- 0.04 U/ml). Normal levels were found in patients with Turner's syndrome and primary hypothyroidism, increased levels in uraemic patients, and decreased levels in Laron dwarfs.


Burnout in the Pharmaceutical Activity: The Impact of COVID-19.
Pharmacists are among the healthcare professionals involved in the response to the COVID-19 pandemic, maintaining essential services. In the context of restrictions and reorganization of human resources, as a result of policies recently applied to the health sector, following international guidelines, and given the scarcity of data on burnout in pharmaceutical activity, it was considered highly relevant to promote a nationwide survey aiming to collect more complete evidence on the burnout syndrome and to understand how pharmacists have viewed their work and the people they worked closely with. The study aimed to assess the occurrence of pharmacist burnout and determine outcomes for each of its dimensions; identify potentially associated characteristics; and determine profiles and critical limits. A cross-sectional observational study conducted by a multidisciplinary panel from the Portuguese Pharmaceutical Society (PPS). Professionals from community and hospital pharmacies who were at the forefront of the COVID-19 response were involved in (i) confirming the need and pertinence for conducting this research, (ii) identifying the main factors leading to pharmaceutical emotional distress ("burnout"), and (iii) disseminating the survey. The questionnaire was designed for digital voluntary, confidential, and anonymous participation and divided into four segments of data collection: (i) demographics, (ii) employment and workplace characterization, (iii) pandemic impact on labor activity, and (iv) burnout assessment (as described ahead). An electronic survey was addressed to all PPS members, and an account was created solely to manage the questionnaire data for the research team. The web-based and user-friendly platform Google Forms supported the data capture and provided an intuitive interface for validated data entry. In a population of 15,565 pharmacists (members of the PPS), the minimum recommended sample size (Epi Info software), with a 5% margin of error and a 99.9% confidence interval, should be 1,012 individuals. A total of 1,362 pharmacists participated in the study. Of these, 91.4% (n = 1,246) were involved in direct patient care activity and 7.7% (n = 106) in non-direct patient care activity.


Isolation of a CDC25 family gene, MSI2/LTE1, as a multicopy suppressor of ira1.
We have identified MSI2 as a gene of Saccharomyces cerevisiae which, when on a multicopy vector, suppresses the heat shock sensitivity caused by the loss of the IRA1 product, a negative regulator of the RAS protein. The multicopy MSI2 also suppresses the heat shock sensitivity of cells with the RAS2val19 mutation but not those with the bcy1 mutation, suggesting that the MSI2 protein may interfere with the activity of the RAS protein. The sequence analysis of MSI2 reveals that it is identical to LTE1 belonging to the CDC25 family: CDC25, SCD25 and BUD5, each of which encodes a guanine nucleotide exchange factor for the ras superfamily gene products. Deletion of the entire MSI2 coding region reveals that MSI2 is not essential but the disruptant shows a cold-sensitive phenotype. Under the non-permissive conditions, more than 70% of the msi2 disruptants arrested at telophase as large budded cells with two nuclei divided completely and elongated spindles, indicating that the msi2 deletion is a cell division cycle mutation. These results suggest that MSI2 is involved in the termination of M phase and that this process is regulated by a ras superfamily gene product.


Probing nanomechanical interactions of SARS-CoV-2 variants Omicron and XBB with common surfaces.
The emergence of SARS-CoV-2 variants has further raised concerns about viral transmission. A fundamental understanding of the intermolecular interactions between the coronavirus and different surfaces is needed to address the transmission of SARS-CoV-2 through respiratory droplet-contaminated surfaces or fomites. The receptor-binding domain (RBD) of the spike protein is a key target for the adhesion of SARS-CoV-2 on the surface. To understand the effect of mutations on adhesion, atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) was used to quantify the interactions between wild-type, Omicron, and XBB with several surfaces. The measurement revealed that RBD exhibits relatively higher forces on paper and gold surfaces, with the average force being 1.5 times greater compared to that on plastic surface. In addition, the force elevation on paper and gold surfaces for the variants can reach ∼28% relative to the wild type. These findings enhance our understanding of the nanomechanical interactions of the virus on common surfaces.


Joint Multi-Leaf Segmentation, Alignment, and Tracking for Fluorescence Plant Videos.
This paper proposes a novel framework for fluorescence plant video processing. The plant research community is interested in the leaf-level photosynthetic analysis within a plant. A prerequisite for such analysis is to segment all leaves, estimate their structures, and track them over time. We identify this as a joint multi-leaf segmentation, alignment, and tracking problem. First, leaf segmentation and alignment are applied on the last frame of a plant video to find a number of well-aligned leaf candidates. Second, leaf tracking is applied on the remaining frames with leaf candidate transformation from the previous frame. We form two optimization problems with shared terms in their objective functions for leaf alignment and tracking respectively. A quantitative evaluation framework is formulated to evaluate the performance of our algorithm with four metrics. Two models are learned to predict the alignment accuracy and detect tracking failure respectively in order to provide guidance for subsequent plant biology analysis. The limitation of our algorithm is also studied. Experimental results show the effectiveness, efficiency, and robustness of the proposed method.


[Extra-articular elbow fractures].
Only some fractures of the humerus-shaft or the shaft of radius and ulna can be called extra-articular fractures of the elbow. These fractures occur mostly in the still growing bone or in bones with abnormal structure. The treatment consists in adults in open reduction and osteosynthesis, in adolescents and children percutaneous methods of fixation can be recommended. Conservative and early functional treatment are only indicated in very few cases. Lesions of nerves and vessels are relatively common.


Surfactant-assisted-water-exposed versus surfactant-aqueous-solution-exposed electrospinning of novel super hydrophilic Polycaprolactone-based fibers: Cell culture studies.
Blend electrospun scaffolds composed of Polycaprolactone and Pluronic are suitable for bone tissue engineering due to their excellent biocompatibility and hydrophilicity. However, exceeding from certain amounts of Pluronic, surface enrichment of this polymer leads to segregation of Pluronic chains within the fiber, endangering the integrity and mechanical properties of the scaffold. In this article, a novel method of blend electrospinning has been employed using a parallel water supply, positioning the Pluronic chains on the surface, thus enhancing the miscibility within the fibers. Water uptake test revealed the super hydrophilicity of obtained scaffolds. Atr-FTIR and X-ray photoelectron spectroscopy verified a higher percentage of Pluronics on the surface in comparison with conventional blend electrospinning. Tensile test demonstrated improved mechanical properties of the modified scaffolds. The results of cytocompatibility tests have also revealed enhanced viability of cells on these scaffolds confirming their great promise for clinical applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1204-1212, 2019.


Musculoskeletal disorders and work-related musculoskeletal diseases among nursery school teachers: analysis in a sample in the city of Venice.
Objectives. Musculoskeletal disorders (MSD) represent one of the most relevant occupational problems. School teachers and particularly nursery school teachers (NST) are reported to have a high prevalence of MSD. We aimed to estimate frequency of MSD in a sample of NST and to bring out cases of work-related musculoskeletal disorders (WRMSD) among these workers. Design. Cross-sectional prevalence study. Setting and participants. NST applying to the trade union patronage between December 2015 and December 2017 for problems of absence from work for health reasons have been proposed the compilation of the Italian version of the Nordic Questionnaire for musculoskeletal disorders. NST who reported MSD underwent medical examination performed by an occupational physician. In accordance with current legislation, certification of occupational disease was completed when a plausible occupational origin of the pathology could be identified. Main outcome measures. MSD and WRMSD prevalence. Results. Questionnaires were completed by 82 NST: 75 (91.5% of the sample) reported at least one MSD. 71 NST underwent medical examination. In 32 subjects (39% of the sample) a diagnosis of musculoskeletal pathology was formulated. Based on work history, 20 cases of probable occupational pathology were reported. Occupational etiology was ascertained for 12 subjects (14.6%): 11 cases of lumbar discopathy / lumbar disc herniation and 1 case of both lumbar disc herniation and tendinopathy of shoulder rotator cuff. Conclusion. Prevalence of musculoskeletal disorders was high and the most frequently affected body sites were similar to those reported in the literature, confirming NST as a group at risk for developing both MSD and WRMSD. Results indicate the importance of taking primary and secondary prevention actions to protect the health of NST.


Effect of ultrasonic and sonic activation of root canal sealers on the push-out bond strength and interfacial adaptation to root canal dentine.
To evaluate the effect of ultrasonic and sonic activation of two root canal sealers on interfacial adaptation and push-out bond strength (BS) to root canal dentine. The root canals of seventy-eight roots of maxillary canines were prepared with NiTi rotary instruments under irrigation with 2.5% NaOCl and 17% EDTA. Canals were filled by lateral condensation of gutta-percha and AH Plus (n = 39) or MTA Fillapex (n = 39). Three subgroups (n = 13) were formed according to sealer activation: no activation (NA), sonic activation (SA, 20 s) and ultrasonic activation (US, 20 s). In three specimens of each subgroup, 0.1% rhodamine B was added to the sealer. Three 1-mm-thick slices were obtained from each root third. The first and second were used for push-out BS test and the third for a qualitative analysis of interfacial adaptation (gaps) and voids by confocal laser scanning microscopy (CLSM). Intratubular penetration of rhodamine B-labelled sealer was also assessed by CLSM. Data were analysed by two-way anova and Tukey's test (α = 0.05). AH Plus (2.58 ± 1.21) had higher push-out BS than MTA Fillapex (1.45 ± 0.71) (P = 0.000). UA (2.64 ± 1.44) had higher BS (P = 0.000) than NA (1.58 ± 0.73) and SA (1.83 ± 0.85), which did not differ significantly from each other (P = 0.3303). The coronal third had higher BS (2.48 ± 1.49) than the middle (2.08 ± 0.94) (P = 0.0003) and apical (1.48 ± 0.58) (P = 0.00) thirds. For both sealers, UA was associated with a more homogeneous filling material with better interfacial adaptation and greater quantity, density and length of tags in dentinal tubules. When UA was used, the tags had similar quantity, density and length to those formed without activation, but interfacial gaps and voids were observed. Ultrasonic activation was associated with higher BS values, deeper intratubular penetration and greater interfacial adaptation to root dentine than sonic activation and no activation techniques, AH Plus had higher BS values than MTA Fillapex irrespective of the type of activation.


Successful management of pediatric high anisometropia using traditional treatment methods: a case series.
To report visual results in pediatric patients with high anisometropia following aggressive amblyopia treatment using traditional methods. Charts of one physician, JM, were reviewed at a major university medical center for all patients with anisometropia of eight diopters or greater. Patients ranged from children with severe unilateral high myopia due to retinopathy of prematurity to one infant with severe microphthalmos, acoria, and congenital cataract. Four patients were identified. Final Snellen acuities were reported from the patient's last clinic examination. Average follow-up period was four years. Final visual acuities of involved eyes ranged from line Snellen 20/60 to 20/20. One patient with severe microphthalmos, congenital acoria, congenital cataract, and anisometropia of 40 diopters achieved a final Snellen visual acuity of 20/40 OS. No patients developed visual loss in the normal eye due to patching. No patients were lost to follow-up. Based on our observations, excellent visual outcomes may be achieved in pediatric patients with high anisometropia by aggressive use of conventional occlusion and refractive methods.


Futile and Potentially Inappropriate Interventions: Semantics Matter.
In 1997, the Society for Critical Care Medicine (SCCM) published a statement regarding futile and inadvisable treatments. Recently, five critical care organizations published a consensus statement supporting and expanding upon the 1997 SCCM statement, and the SCCM issued a companion statement defining futile and potentially inappropriate interventions. In all of these statements, there is agreement that the term futile should be used only when an intervention cannot accomplish the intended physiologic goal. The organizations provide recommendations for optimizing communication, however even when clinicians use excellent communication techniques, there are times when competing ethical considerations mean that a surrogate persists in requesting an intervention that the clinician does not believe is justified. In such cases, clinicians should not label the requested intervention as futile, because doing so is disrespectful to patients and families, overly empowers clinicians, and stifles communication. When clinicians believe that they are justified in declining such a request due to differences in values or beliefs, they should refer to the requested treatment as "potentially inappropriate," indicating that the disagreement is based on values, and that any decision to withhold the requested intervention is preliminary until reviewed through a fair process.


Current education versus peer-education on walking in type 2 diabetic patients based on Health Belief Model: a randomized control trial study.
Diabetes is a disease with several metabolic and organic symptoms. Physical activity plays a key role in controlling type 2 diabetes. Several researches confirm that educational strategies can lead to healthy behaviors and its continuation is effective and can indicate what type of relationship with the client is better. The purpose of this study is comparing the Effect of Current Education and Peer-Education on Walking in Type 2 Diabetic Patients based on Health Belief Model (HBM). This was a clinical trial (RCT) study done on 80 people with type 2 diabetes. Patients were divided into two groups, Current education and Peer education groups. Data were collected using a questionnaire based on the health belief model, a checklist related to patients' practice and recording patients' HbA1c, 2HPP and FBS levels. Results were documented before and three months after intervention. The patients participated in 2 educational classes during three months of intervention, as the follow-up of the intervention. Mean scores for HBM Model variables, i.e. perceived susceptibility, perceived severity, perceived benefit and self-efficacy, were significantly increased in the peer education group compared to current education group after intervention. Also, behavioral walking, rates of HbA1c and FBS and 2HPP levels were improved significantly among the peer education group. Applying walking training program developed for diabetic patients and its implementation by the peers in order to control blood sugar using the health belief model is very useful and effective. During implementation of these control programs, monitoring and follow-up training is recommended.


Naturally occurring variation in cardiovascular traits among inbred mouse strains.
The objective of this study was to characterize genetic variation in complex cardiovascular traits in two commonly used inbred mouse strains. We performed echocardiography, graded treadmill exercise, tail cuff plethysmography, and telemetry (heart rate, activity, temperature) in age- ( approximately 9 weeks) and sex-matched A/J and C57BL/6J (B6) inbred mice. B6 mice had significantly larger end-diastolic dimension (3.31+/-0.42 mm versus 2.83+/-0.31 mm) and left ventricle mass (46.2+/-14.1 versus 32.7+/-11.5 g) than A/J mice. This relative hypertrophy was eccentric (relative wall thickness ratios: 0.30+/-0.01 versus 0.32+/-0.01) and was not associated with a difference in systolic blood pressure (122.0+/-13.2 versus 123.1+/-20.8 mmHg). Left ventricle fractional shortening (39.1+/-6.2 versus 47.1+/-6.9%) and heart rate (433+/-55 versus 524+/-45 beats per minute) were significantly lower in B6 versus A/J, respectively, resulting in similar resting echocardiographic cardiac indices (0.58+/-0.19 versus 0.50+/-0.17 ml/min/g). Maximum exercise time on a treadmill was significantly greater in B6 than in A/J mice (9.6+/-3.4 versus 4.4+/-1.9 minutes). Telemetry showed that body temperature was generally greater and heart rate lower in B6 than A/J; the relation with activity was more complex. These data suggest that relative to A/J, B6 mice have a phenotype characteristic of the "athlete's heart," that is, eccentric, physiologic hypertrophy, slower heart rates, and increased exercise endurance. This systematic characterization of functionally related cardiovascular traits in A/J and C57BL/6J mice revealed numerous differences whose genetic bases can be dissected with recombinant inbred, recombinant congenic, and chromosome substitution strains.


"Pop-off" technic. The ultrastructure of paraffin-embedded sections.
Stained paraffin embedded sections sometimes contain a precise area that warrants further investigation at an ultrastructural level. A technic is described whereby an area in question may be reembedded into plastic and sectioned for examination under the electron microscope. The decoverslipped paraffin section is "popped-off" into an inverted BEEM capsule. Suspected viral inclusions in sections may be identified or ruled out with this technic. Special stains, especially heavy metal applications, not able to be utilized in conventional plastic embedding may be reembedded into plastic. The metallic granules may be visualized ultrastructurally without further grid staining. This method is especially helpful for cell smears and cell monolayers since they may be the only material available for study. Although ultrastructural detail is often poor, one does have the ability to study the identical section under both the light and the electron microscopes.


The evaluation and interpretation of cervical cytology: application of the likelihood ratio concept.
The Papanicolaou smear (Pap test), used for the detection and prevention of neoplastic lesions of the cervix, is known to have both false negative and false positive results. Proper handling of the diagnostic uncertainty resulting from these errors demands quantification of flaws. Traditionally, sensitivity, specificity and predictive values are used for that aim. In this study another approach is advocated, namely the use of the likelihood ratio. For cervical cytology this ratio is the quotient of the probability of a Pap class within the diseased population to the probability of that same Pap class within the non-diseased group. This approach enables the characterization of each Pap class separately, and is therefore much better for clinical interpretation of the result. It is also a superior approach for quality assessment.


New flavonol glycosides from the leaves of Caragana brachyantha.
Two new flavonol glycosides, brachysides C and D, together with three known flavonol glycosides, were isolated from the leaves of Caragana brachyantha. The structures of brachysides C and D were elucidated on the basis of detailed spectroscopic analysis as quercetin 5-O-[α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside]-7-O-[α-L-rhamnopyranoside] and quercetin 5-O-[α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside]-7-O-[α-L-rhamnopyranoside]-4'-O-[α-L-rhamnopyranoside], respectively. The presence of flavonol tetra- and triglycosides bearing a sugar moiety at position 5 was the first report from this genus Caragana.


Field-Free Atmospheric Pressure Photoionization-Liquid Chromatography-Mass Spectrometry for the Analysis of Steroids within Complex Biological Matrices.
A comparison study is presented in which the relative performance of a new orthogonal geometry field-free atmospheric pressure photoionization (FF-APPI) source was evaluated against both electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) for the analysis of a small panel of clinically relevant steroids, spiked within various complex biological matrices. Critical performance factors like sensitivity and susceptibility to matrix effects were assessed using a simple, isocratic, high-throughput LC-MS workflow. FF-APPI was found to provide the best performance in terms of both sensitivity and detection limit for all of the steroids included in the survey. Order-of-magnitude sensitivity advantages were realized for some low polarity analytes including both estradiol and estrone. A robust linear regression, post extraction addition method was used to evaluate the relative impact of matrix effects upon each ionization method using protein precipitated human serum, plasma and Surine (simulated urine) as standard clinical matrices. Under conditions optimized for sensitivity, both the field-free APPI and APCI sources were found to provide similarly high resistance to matrix suppression effects, while ESI performance was impacted the most dramatically. For the prototype FF-APPI source, a strong relationship was established between optimizable source parameters and the degree of ion suppression observed. Through careful optimization of vaporization temperature and nebulizer gas pressure it was possible to significantly reduce or even eliminate the impact of matrix effects, even for high-throughput LC-MS methods.


Co-localization of integrins and matrix metalloproteinases in the extracellular matrix of chondrocyte cultures.
Beta1-integrins were found in the cartilage matrix, suggesting their implication in the assembly of its architectural scaffold, but the mechanism for this event is not yet clear. Matrix metalloproteinases (MMPs) may be involved in an integrin-shedding mechanism and matrix beta1-integrins may act to alter MMP activity. To begin to address this question, this study was designed to determine whether beta1-integrins and MMPs are colocalized in the chondrocytes or in the extracellular matrix of cartilage. We investigated high-density cultures of limb buds of 12-day-old mouse embryos by double immunofluorescence, immunoelectron microscopy and by coimmunoprecipitation assays in order to examine the localization of beta1-integrins and matrix metalloproteinases (MMP-1, MMP-3 and MMP-9) in cartilage. It was found, that all investigated MMPs and beta1-integrins were specifically co-localized in high-density cartilage cultures. Immunogold and immunofluorescence labelling of both beta1-integrins and MMPs were observed not only at the surface of chondrocytes but mainly also in the pericellular space and distributed between collagen fibrils in the extracellular matrix (ECM) as well. Results of immunoprecipitation experiments suggest a functional association of MMPs and beta1-integrins in chondrocytes as already described for other cell types. Further investigations are needed to elucidate the functional association between beta1-integrins and MMPs in chondrocytes.


Pharmacokinetics and tissue distribution of 4,5-dimethoxycanthin-6-one and its major metabolites in rats.
4,5-Dimethoxycanthin-6-one and 5-hydroxy-4-methoxycanthin-6-one are the active ingredients of P. quassiodes. In the present work, a LC-MS/MS method was developed for the determination of 4,5-dimethoxycanthin-6-one and its major metabolites 5-hydroxy-4-methoxycanthin-6-one (M1) and 4-hydroxy-5-methoxycanthin-6-one (M2) in rat plasma and tissues, and applied to study their pharmacokinetics and tissue distribution after intramuscular administration of 4,5-dimethoxycanthin-6-one to rats. By protein precipitation with methanol for plasma samples and liquid-liquid extraction with ethyl acetate for tissue samples, the analytes were separated on an ODS C18 column with a mobile phase consisted of methanol and water (0.1% formic acid), and quantified by a MS detector in positive multiple reaction monitoring (MRM) mode. MS transitions were m/z 281.0→167.1 for 4,5-dimethoxycanthin-6-one, m/z 267.0→168.1 for M1 and M2, m/z 251.0→195.1 for 3-methylcanthin-2,6-dione (IS). The pharmacokinetic results indicate that 4,5-dimethoxycanthin-6-one is absorbed rapidly (Tmax=5.4-6.4min), distributed rapidly and widely in the order of liver>kidney≈lung≈large intestine≈small intestine, and eliminated quickly (t1/2z=64.9-77.7min) following the intramuscular administration. Furthermore, M1 and M2 were detected only in rat plasma and liver at the indicated times after the intramuscular administration.


[Impact of streptozotocininduced hyperglycemia on anxiety level and physical fatigue of Wistar rats].
The aim of the study was to evaluate type 2 diabetes medicamental biomodel in 70-days experiment. Control group animals were provided with water ad libitum throughout the experiment, experimental group animals for the first two weeks were provided with 20% solution of fructose ad libitum instead of water. On the 15th day, experimental group animals (average body weight 257±8 g) were injected abdominally with streptozotocin (STZ) in dosage 40 mg/kg of body weight. For the next three weeks on the 22nd, 28th and 36th days, glucose level in blood taken from the tail vein was measured using portable electrochemical glucometer. On the 37th day animals with blood glucose level 11.0 mmol/L or higher were included in experimental group for further research. On the 44th and 60th day control measurements of glucose level were conducted. On the 70th day animals were taken out of experiment by decapitation under ether anesthesia. The concentration of glucose, glycosylated hemoglobin, triglycerides, cholesterine, HLD and LDL were measured in blood serum. Additionally anxiety level of animals was evaluated before and after STZ injection using Elevated plusmaze. The comparison of physical fatigue of control and experimental groups was performed using treadmill. On the 37th day blood glucose concentration of control group animals was 6.6±0.4 mmol/L. 33% of animals (13 of 40) with glucose level 11.0 mmol/L or higher formed the experimental group (average glucose level 16.2±1.3 mmol/L), other 27 rats had normal glucose level. The anxiety level of diabetic rats was higher than in control group. Diabetic rats showed significantly lower physical fatigue than control rats. On the 44th and 60th day of experiment glucose level in experimental rats from group 2 (15.5±1.4 и 14.8±1.2 mmol/L) was significantly higher than of control animals (7.0±0.5 и 6.8±0.3 mmol/L). Glycated hemoglobin level in blood serum of diabetic group (7.2±0.7%) was significantly higher than of control group (3.3±0.2%). This proves the progression of stable long-term hyperglycemia. According to results represented model can be used for initial experimental evaluation of tested antidiabetic biologically active substances.


Serotonin, glutamate and glycerol are released after the injection of hypertonic saline into human masseter muscles - a microdialysis study.
Chronic myalgia is associated with higher muscle levels of certain algesic biomarkers. The aim of this study was to investigate if hypertonic saline-induced jaw myalgia also leads to release of such biomarkers and if there were any sex differences in this respect. Healthy participants, 15 men and 15 aged-matched women (25.7 ± 4.3 years) participated. Intramuscular microdialysis into masseter muscles was performed to sample serotonin (5-HT), glutamate, lactate, pyruvate, glucose and glycerol. After 2 hours 0.2 mL hypertonic saline (58.5 mg/mL) was injected into the masseter on one side and 0.2 mL isotonic saline (9 mg/mL) into the contralateral masseter close to the microdialysis catheter. Microdialysis continued for 1 hour after the injections. Pressure pain thresholds (PPT) and pain were assessed before and after injections. The median (IQR) peak pain intensity (0-100 visual analogue scale) after hypertonic saline was 52.5 (38.0) and after isotonic saline 7.5 (24.0) (p < 0.05). 5-HT, glutamate and glycerol increased after hypertonic saline injection (p < 0.05). Lactate, pyruvate and glucose showed no change. PPT after microdialysis was reduced on both sides (p < 0.05) but without side differences. Pain after hypertonic saline injection correlated positively to 5-HT (p < 0.05) and negatively to glycerol (p < 0.05). 5-HT, glutamate and glycerol increased after a painful hypertonic saline injection into the masseter muscle, but without sex differences. Since increased levels of 5-HT and glutamate have been reported in chronic myalgia, this strengthens the validity of the pain model. Glycerol warrants further investigations.


Insomnia and other sleep-related problems during the remission period of the COVID-19 pandemic: A large-scale survey among college students in China.
This study aimed to evaluate the sleep-related problems and predictors of probable clinical insomnia among college students during the COVID-19 remission period in China. 146,102 college students from 22 colleges/universities in Guangdong province participated in this study from 1th to 15th June, 2020. Self-administered questionnaires were used to assess demographic characteristics. Sleep-related problems, depression and anxiety symptoms were measured by Youth Self-Rating Insomnia Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7, respectively. The prevalence of difficulty in initiating sleep, difficulty in maintaining sleep, early morning awakening, sleep insufficiency, unrefreshing sleep and daytime functioning impairment were 7.2%, 3.4%, 3.5%, 9.6%, 14.6%, and 7.6%, respectively. 16.9% students had varying degrees of insomnia and 6.3% were considered as displaying probable clinical insomnia. Moreover, being urban residents, having a history of physical or mental illness, and probable clinical depression or anxiety were significant risk factors of probable clinical insomnia, while college senior degree and 7-8 hours' sleep duration per day was the protective factor for probable clinical insomnia. Unrefreshing sleep was the most prominent sleep problem among college students during COVID-19 remission in China. Good sleep hygiene practices are strongly suggested to develop in the time of prolonged home isolation.


Size-dependent expression of cyclooxygenase-2 in sporadic colorectal adenomas relative to adenomas in patients with familial adenomatous polyposis.
Several studies have indicated that administration of non-steroidal anti-inflammatory drugs (NSAID) to patients with familial adenomatous polyposis (FAP) results in a regression of colorectal adenomas through inhibition of cyclooxygenase-2 (COX-2). It is thought that sporadic colorectal adenomas might also be useful targets for the chemoprevention of colorectal cancer, but a marked effect of NSAID on the regression of sporadic adenomas has not been observed. We investigated the immunohistochemical expression of COX-2 in sporadic tubular adenomas (n = 100) from 63 patients and in tubular adenomas (n = 121) from 12 patients with FAP, in order to determine if chemoprevention might be more successful in sporadic adenomas once they have reached a certain size. COX-2 scores were significantly lower (P < 0.0001) in small (< 5 mm in diameter) adenomas than in large (> or = 5 mm) adenomas. This was observed in both sporadic cases and in cases involving patients with FAP. With regard to small (< 5 mm) adenomas, significantly higher (P = 0.02) COX-2 scores were obtained in adenomas resulting from FAP than sporadic adenomas. The variation in COX-2 expression observed among sporadic adenomas of different sizes should be taken into account when making decisions regarding attempts at chemoprevention using NSAID. Sporadic adenomas 5 mm or larger with upregulated COX-2 expression are potentially useful targets for the antiproliferative effects of NSAID.


Transabdominal ultrasonographic evaluation of fetal well-being in the late-term mare and cow.
In the equine practice, attempts have been made to examine the fetus in the second and third trimester of pregnancy but all of the available methods have limitations. Until now, transabdominal ultrasonography has been regarded as the most informative examination. This method allows us to measure fetal heart rate, fetal activity as well as the quality and quantity of the fetal fluids. A modified biophysical profile for horses was used by several researchers in the USA from the 1990s as a gold standard. However, it is not sensitive enough and, in the authors' experience, professionals can face difficulties during its application (e.g. for measuring aortic diameter and fetal breathing movements). In cows, this method was first used for this purpose by a Canadian research group in 2007. They reported that transabdominal ultrasound was promising but showed low sensitivity in this species. The present studies show that birth weight cannot be predicted from fetal aortic diameter measurement in cows as suggested by other researchers. Transabdominal ultrasound needs special equipment (2-3.5 MHz convex transducer) and basic ultrasonographic knowledge; however, we suggest that in most cases it can be performed with the dam placed in a stock and without shaving the examination area. The method provides useful information within 30-40 minutes, enabling the examiner to determine whether or not the fetus is alive and to recognise placentitis or twins. This technique also allows measuring the combined thickness of the uteroplacental unit, and the authors' ongoing study showed higher normal values in Lipizzaner mares compared to values in other breeds. In conclusion, with the help of advanced techniques, simple and low-cost methods should be developed for the evaluation of the pregnant dam and its fetus to assess fetal viability in the veterinary practice.


Virus susceptibility analyses from a phase IV clinical trial of inhaled zanamivir treatment in children infected with influenza.
A zanamivir postapproval efficacy study was conducted in children (n = 279) in Japan during three influenza seasons. Pharyngeal swab specimens (n = 714) were obtained for detailed resistance analysis. From 371 cultured viruses, 3 viruses (A/H1N1) from two subjects showed reduced susceptibility to zanamivir at day 1 (before treatment), 1 had an N74S amino acid substitution (fold shift, 46), and 2 (day 1 and day 2) had a Q136K amino acid substitution (fold shifts, 292 and 301). Q136K was detected only in cultured virus and not in the swab. From the remaining 118 cultured viruses obtained during or after treatment with zanamivir, no shifts in virus susceptibility were detected. Neuraminidase (NA) population sequencing showed that viruses from 12 subjects had emergent amino acid substitutions, but 3 with susceptibility data were not zanamivir resistant. The remainder may be natural variants. Further analysis is planned. Hemagglutinin (HA) sequencing showed that viruses from 20 subjects had 9 HA amino acid substitutions that were previously implicated in resistance to neuraminidase inhibitors in in vitro assays or that were close to the receptor binding site. Their role in in vivo resistance appears to be less important but is not well understood. NA clonal sequence analysis was undertaken to determine if minority species of resistant viruses were present. A total of 1,682 clones from 90 subjects were analyzed. Single clones from 12 subjects contained amino acid substitutions close to the NA active site. It is unclear whether these single amino acid substitutions could have been amplified after drug pressure or are just chance mutations introduced during PCR.


An active learning-enabled annotation system for clinical named entity recognition.
Active learning (AL) has shown the promising potential to minimize the annotation cost while maximizing the performance in building statistical natural language processing (NLP) models. However, very few studies have investigated AL in a real-life setting in medical domain. In this study, we developed the first AL-enabled annotation system for clinical named entity recognition (NER) with a novel AL algorithm. Besides the simulation study to evaluate the novel AL algorithm, we further conducted user studies with two nurses using this system to assess the performance of AL in real world annotation processes for building clinical NER models. The simulation results show that the novel AL algorithm outperformed traditional AL algorithm and random sampling. However, the user study tells a different story that AL methods did not always perform better than random sampling for different users. We found that the increased information content of actively selected sentences is strongly offset by the increased time required to annotate them. Moreover, the annotation time was not considered in the querying algorithms. Our future work includes developing better AL algorithms with the estimation of annotation time and evaluating the system with larger number of users.


Decision model for the acute treatment of mania.
Decision making in psychiatric diagnosis and treatment has not been evaluated systematically. The authors present a model for treatment of an acute manic episode using a decision analysis software program. Six treatment options were put into the model: lithium, valproate, carbamezepine, electroconvulsive therapy, clonazepam, and neuroleptics. Each treatment was evaluated on three factors, efficacy, tolerability, and cost, using data from the literature and pharmacy and billing information. Output from the computer program identified three top choices among the six options: valproate, carbamazepine, and lithium, with valproate emerging as the first choice using the data we inputted.


Diabrotica virgifera virgifera on South-Northern expansion drive?
As Wudtke and colleagues predicted and Hummel and colleagues later confirmed, the Western corn rootworm Diabrotica v. virgifera LeConte (Coleoptera: Chrysomelidae) (WCR) had shown the ability to expand northward from South and Eastern into Central Europe. Decades earlier WCR had done the same in North America. Yet, European entomologists erroneously assumed they would be somehow magically protected from such aggressive moves of WCR. Meanwhile we know better: Southern Germany is infested, and also many East European countries are victims of these Northern and also Eastern advances. In Germany, neither speed nor extent of such advances is well defined. Jumping advances similar to earlier spreading episodes may be the rule, but they are not well predictable. In this report, we argue for a persistent northbound trend of WCR.


Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer.
Capecitabine (Xeloda), Roche Laboratories Inc., Nutley, NJ) is an orally administered fluoropyrimidine carbamate that serves as a prodrug of 5-fluorouracil (5-FU), an integral component of chemotherapy (CT) regimens for metastatic colorectal cancer (mCRC). As the drug is orally administered, capecitabine permits greater convenience and flexibility in dosing by eliminating the need for continuous infusion and its potential complications. In phase 3 trials, capecitabine has been used as an alternative to 5-FU, both as a monotherapy and in combination with agents such as oxaliplatin (as XELOX), with good efficacy and tolerability. Combination therapy with capecitabine and irinotecan (XELIRI), however, has produced more variable results, with some dose combinations and schedules resulting in excessive and/or unexplained treatment-related toxicity. Recent initiatives using lower doses of capecitabine and irinotecan, as well as alternative dosing schedules, have resulted in more favorable outcomes (efficacy and tolerability), even in combination with targeted-agents such as bevacizumab. Dose reduction in elderly populations and in those with moderate renal impairment also appears to be important for minimizing toxicity with XELIRI regimens. Although additional phase 3 studies are needed, XELIRI may be an effective base CT regimen, allowing a greater number of treatment options for tumor control in patients with mCRC.


Internet of Things-based sustainable environment management for large indoor facilities.
Due to global warming and climate change, the poultry industry is heavily impacted, especially the broiler industry, due to the sensitive immune system of broiler chickens. However, the continuous monitoring and controlling of the farm's environmental parameters can help to curtail the negative impacts of the environment on chickens' health, leading to increased meat production. This article presents smart solutions to such issues, which are practically implemented, and have low production and operational costs. In this article, an Internet of Things (IoT) based environmental parameters monitoring has been demonstrated for the poultry farmhouse. This system enables the collection and visualization of crucially sensed data automatically and reliably, and at a low cost to efficiently manage and operate a poultry farm. The proposed IoT-based remote monitoring system collects and visualizes environmental parameters, such as air temperature, relative humidity (RH), oxygen level (O2), carbon dioxide (CO2), carbon monoxide (CO), and ammonia (NH3) gas concentrations. The wireless sensor nodes have been designed and deployed for efficient data collection of the essential environmental parameters that are key for monitoring and decision-making process. The hardware is implemented and deployed successfully at a site within the control shed of the poultry farmhouse. The results revealed important findings related to the environmental conditions within the poultry farm. The temperature inside the control sheds remained within the desired range throughout the monitoring period, with daily average values ranging from 32 °C to 34 °C. The RH showed slight variations monitoring period, ranging from 65% to 75%, with a daily average of 70%. The O2 concentration exhibited an average value of 17% to 18.5% throughout the monitoring period. The CO2 levels showed occasional increases, reaching a maximum value of 1,100 ppm. However, this value was below the maximum permissible level of 2,500 ppm, indicating that the ventilation system was effective in maintaining acceptable CO2 levels within the control sheds. The NH3 gas concentration remained consistently low throughout the duration, with an average value of 50 parts per million (ppm).


Dissect: detection and characterization of novel structural alterations in transcribed sequences.
Computational identification of genomic structural variants via high-throughput sequencing is an important problem for which a number of highly sophisticated solutions have been recently developed. With the advent of high-throughput transcriptome sequencing (RNA-Seq), the problem of identifying structural alterations in the transcriptome is now attracting significant attention. In this article, we introduce two novel algorithmic formulations for identifying transcriptomic structural variants through aligning transcripts to the reference genome under the consideration of such variation. The first formulation is based on a nucleotide-level alignment model; a second, potentially faster formulation is based on chaining fragments shared between each transcript and the reference genome. Based on these formulations, we introduce a novel transcriptome-to-genome alignment tool, Dissect (DIScovery of Structural Alteration Event Containing Transcripts), which can identify and characterize transcriptomic events such as duplications, inversions, rearrangements and fusions. Dissect is suitable for whole transcriptome structural variation discovery problems involving sufficiently long reads or accurately assembled contigs. We tested Dissect on simulated transcripts altered via structural events, as well as assembled RNA-Seq contigs from human prostate cancer cell line C4-2. Our results indicate that Dissect has high sensitivity and specificity in identifying structural alteration events in simulated transcripts as well as uncovering novel structural alterations in cancer transcriptomes. Dissect is available for public use at: http://dissect-trans.sourceforge.net.


Fast detection of Staphylococcus aureus using thiol-functionalized WS2 quantum dots and Bi2O2Se nanosheets hybrid through a fluorescence recovery mechanism.
Ultrafast and sensitive detection of Staphylococcus aureus (S. aureus), a harmful Gram-positive human pathogenic bacterium, by two-dimensional layered materials continues to be a challenge. Herein, we have studied the sensing of S. aureus using a tungsten disulfide (WS2) quantum dot (QD) and bismuth oxyselenide (Bi2O2Se) nanosheet (NS) hybrid through their unique optical functionalities. The WS2 QDs of a mean diameter of 2.5 nm were synthesized by liquid exfoliation. Due to the quantum confinement and functional groups, the WS2 QDs exhibit high fluorescence (FL) yield under UV excitation. The addition of Bi2O2Se NSs resulted in the adsorption of WS2 QDs on their surface, resulting in quenching of the FL emission due to nonfluorescent complex formation between the WS2 QDs and Bi2O2Se NSs. A specific sequencing single-standard DNA (ssDNA) aptamer, which identifies and explicitly binds with S. aureus, was attached to the defect sites of the WS2 QDs for selective detection. The thiol-modified ssDNA aptamers attach covalently to the WS2 QD defect sites, which was confirmed by Raman and X-ray photoelectron spectroscopy (XPS). The interaction of S. aureus with the aptamer functionalized WS2 QDs weakens the van der Waals interaction between the WS2 QDs and Bi2O2Se NSs, which results in the detachment of the WS2 QDs from the Bi2O2Se NS surface and restores the FL intensity of the WS2 QDs, thus allowing the efficient detection of S. aureus. Similar measurements with non-targeted bacteria show that the system is quite selective towards S. aureus. Our FL-based biosensor has a linear response in the range of 103-107 CFU mL-1 (colony formation unit mL-1) with a detection limit of 580 CFU mL-1. We have observed a fast response time of 15 minutes for sensing, which is superior to the previous reports. The proposed system was tested in human urine and can detect S. aureus in human urine samples selectively, proving its potential in real-life applications. The reported approach is versatile enough for sensing other biomolecules and metal ions by choosing suitable receptors.


Toxic and genotoxic effects of Roundup on tadpoles of the Indian skittering frog (Euflictis cyanophlyctis) in the presence and absence of predator stress.
Glyphosate, a post emergent herbicide, has become the backbone of no-till agriculture and is considered safe for animals. However, the impact of glyphosate on non-target organisms, especially on amphibians, is the subject of major concern and debate in recent times. We examined the toxic and genotoxic effects of Roundup, a commercial formulation of glyphosate, in the tadpoles of the Indian skittering frog (Euflictis cyanophlyctis). Roundup at different concentrations (0, 1, 2, 3, 4 and 8mg acid equivalent (ae)/L), tested in a 2×6 factorial design in the presence and absence of predator stress, induced concentration-dependent lethality in tadpoles. The 96-h LC50 for Roundup in the absence and presence of predator stress were 3.76mgae/L and 3.39mgae/L, respectively. The 10-day LC50 value for Roundup was significantly lower, 2.12mgae/L and 1.91mgae/L in the absence and presence of predator stress, respectively. Lower concentrations of Roundup (1, 2 and 3mgae/L) induced the formation of micronuclei (MN) in the erythrocytes of tadpoles at 24-h (F3,56=10.286, p<0.001), 48-h (F3,56=48.255, p<0.001), 72-h (F3,56=118.933, p<0.001) and 96-h (F3,56=85.414, p<0.001) in a concentration-dependent manner. Presence of predator stress apparently increased the toxicity and genotoxicity of Roundup; but these effects were not statistically significant. These findings suggest that Roundup at environmentally relevant concentrations has lethal and genotoxic impact on E. cyanophlyctis; which may have long-term fitness consequence to the species.


Baseline Renal Function Tests and Adverse Outcomes in Pregnant Patients With Chronic Hypertension.
To examine the relationship between baseline renal function tests in pregnant patients with chronic hypertension and adverse pregnancy outcomes. This was a retrospective cohort study of women with a singleton pregnancy and chronic hypertension with assessment of renal function (urine protein-to-creatinine ratio and serum creatinine) before 20 weeks of gestation. The primary outcome was severe preeclampsia at less than 34 weeks of gestation. Secondary outcomes were severe preeclampsia at any gestational age, any preeclampsia, preterm birth at less than 35 weeks of gestation, composite perinatal outcome (perinatal death, assisted ventilation, cord pH less than 7, 5-minute Apgar score 3 or less, or neonatal seizures), and small for gestational age. The association between baseline renal function and the primary outcome was assessed with receiver operating characteristic (ROC) curves and objective cutoffs determined. Outcomes were compared between those with values above and below the cutoffs using univariable and multivariable analyses. Seven hundred fifty-five pregnant women with chronic hypertension had baseline renal function assessment. The urine protein-to-creatinine ratio and creatinine cutoffs for severe preeclampsia at less than 34 weeks of gestation were 0.12 or greater and 0.75 mg/dL or greater, respectively. The area under the ROC curves for severe preeclampsia at less than 34 weeks of gestation was 0.74 (95% confidence interval [CI] 0.7-0.8) for urine protein-to-creatinine ratio and 0.67 (95% CI 0.6-0.8) for creatinine. A urine protein-to-creatinine ratio 0.12 or greater was associated with an increased risk of developing severe preeclampsia at less than 34 weeks of gestation (16.4% compared with 2.6%, adjusted odds ratio [OR] 7.5, 95% CI 3.9-14.6) as was a creatinine 0.75 mg/dL or greater (15.7% compared with 4.6%, adjusted OR 3.5, 95% CI 1.9-6.3). Severe preeclampsia at less than 34 weeks of gestation occurred in only 1.6% of patients if their baseline tests were below both cutoffs. Baseline assessment of renal function can be used as a risk stratification tool in pregnant patients with chronic hypertension.


Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin osteoporosis in vitro.
Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.


The role of 14-3-3ε interaction with phosphorylated Cdc25B at its Ser321 in the release of the mouse oocyte from prophase I arrest.
The protein kinase A (PKA)/Cdc25B pathway plays a critical role in maintaining meiotic arrest in mouse oocytes. However, the molecular mechanism underlying this interchange is not known. In this study, we assessed the role of 14-3-3ε interaction with phosphorylated Cdc25B at its Ser321 as the mouse oocyte is released from prophase I arrest. The 14-3-3ε isoform is a highly conserved protein with various regulatory roles, including maintenance of meiotic arrest. Cdc25B phosphatase is also a key cell cycle regulator. 14-3-3ε binds to Cdc25B-WT, which was abrogated when Ser321 of Cdc25B was mutated to Ala. In addition, we found that 14-3-3ε and Cdc25B were co-localized. Cdc25B was translocated from the cytoplasm to the nucleus shortly before germinal vesicle breakdown (GVBD) during the primary oocyte stage of oogenesis. However, mutation of Ser321 to Ala completely abolished the cytoplasmic localization of Cdc25B. Furthermore, oocytes co-expressing of Cdc25B-WT or Cdc25B-Ser321D and 14-3-3ε were unable to undergo GVBD. In contrast, co-expression of 14-3-3ε and Cdc25B-Ser321A induced GVBD and allowed the process to continue. Down-regulation of 14-3-3ε caused partial meiotic resumption. Taken together, these data indicate that Ser321 of Cdc25B is the specific binding site for 14-3-3ε binding, and that 14-3-3ε is the significant factor in Cdc25B regulation during meiotic resumption of GV stage.


Analytical and Preparative Scale Separation of Enantiomers of Chiral Drugs by Chromatography and Related Methods.
While the amino acids, enzymes and hormones are chiral, chirality plays significant role in the life of plants, animals, as well as the human being. Chirality of molecules is important in various industries, such as pharmaceutical, agricultural, food, electronics, etc. Chiral drugs may have different bioavailability, distribution, biotransformation and excretion, as well as quantitatively and/or qualitatively different pharmacological or toxic properties. Enantiomerically pure chiral drugs have been increasingly developed for the pharmaceutical market due to their superiority from the viewpoints of potency and safety. This is supported by the development of new methods for enantioselective production of the chiral compounds, as well as by the capability of the enantioselective analytical methods to allow a detection and quantification of minor enantiomeric impurity in the presence of another enantiomer in a large excess. The aim of the present review is to provide a short summary of the basic principles of chiral separations on an analytical and preparative scale. In addition, some selected applications for analytical techniques, such as gas chromatography, supercritical fluid chromatography, high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography for the separation of enantiomers of chiral pharmaceuticals published in the last two years are also discussed.


Impact of first-line treatment on outcomes of Ewing sarcoma of the spine.
The optimal first-line treatment for primary Ewing sarcoma (ES) of the spine is unclear, especially when the patients present with acute neurological deficits. This study aimed to retrospectively analyze the effect of first-line treatment with surgery or chemotherapy on neurological and survival outcomes of ES of the spine. 39 patients treated between January 2005 and December 2016 were included in the present analysis. 29 (74.4%) presented with symptomatic spinal cord compression at diagnosis. 21 patients were submitted to primary surgery followed by chemotherapy and local radiotherapy, while 18 patients received induction chemotherapy before surgery and/or local radiotherapy. Neurological deficit before and after treatment, event-free survival and overall survival were analyzed. The results indicated that chemotherapy as the first-line treatment could achieve similar results as primary surgery in preserving neurological function, even in case of major neurological deficits. Compared with primary surgery, induction chemotherapy contributed to a higher rate of en bloc resection with a microscopic negative margin (R0) of primary tumor (72.7% vs. 28.6%, P < 0.05). Multivariate Cox regression analyses revealed that initial chemotherapy was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.215; 95% confidence interval, 0.077-0.596; P = 0.003) and overall survival (hazard ratio, 0.288, 95% confidence interval, 0.098-0.852; P = 0.024). In conclusion, our study suggests that first-line treatment of ES of the spine should be induction chemotherapy, even in case of major neurological deficits.


Perinatal outcome with HELLP/partial HELLP complicating hypertensive disorders of pregnancy. An Indian rural experience.
A total of 615 women with hypertensive disorders during pregnancy were the study subjects. Of these, 145 (23.58%) women had HELLP or partial HELLP (only one or two of the three components H,EL, LP). Overall, eight (1.3%), i.e. five out of 399 primigravida (1.2%) and three of the 216 multigravida (1.3%), had complete HELLP and the remaining 137 (22.2%) had partial HELLP. Of the 399 primigravida with hypertensive disorders, 107 (26.5%) had partial HELLP, statistically significantly more (p<0.002) than the 30 out of the 216 (13.8%) multigravida. In 210 (44.6%) out of 470 women with hypertension without HELLP/partial HELLP, labour was induced and the perinatal mortality rate (PMR) was 138.9 (58.06 in term and 363.63 in pre-term cases), and in the other 260 women in whom labour was not induced, PMR was 96.15 (in term cases 74.07 and in pre-term 120). Among the women with HELLP/partial HELLP (145), out of the 64 women in whom labour was induced, the PMR was 359.37 (235.29 in term and 500 in pre-term) and of those in whom labour was not induced (81), PMR was 209.87 (106 in term cases and 352.94 in pre-term). All the eight women with the full HELLP syndrome had labour induced, the PMR in these cases was 500. Overall, in women with HELLP/partial HELLP, the PMR was 275.8 and in the remainder with hypertensive disorders without HELLP/partial HELLP, it was 114.89.


Cocaine Hydrochloride Structure in Solution Revealed by Three Chiroptical Methods.
Structure and flexibility of natural compounds determine their biological activity. In the present study, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA) spectra of cocaine hydrochloride in aqueous solutions were measured and related to the structure with the aid of density functional theory (DFT) computations. Additional measurements in deuterated environment made assignment of vibrational bands easier. The results suggest that the prevalent cocaine conformation in solution differs from that adopted in hydrochloride crystal. The spectroscopic results and computational analysis are consistent with X-ray structures of known cocaine-receptor complexes, in which the compound adopts a variety of conformations. All three kinds of chiroptical spectra exhibited significantly greater conformational sensitivity than unpolarized absorption or Raman scattering. The ROA technique provided the largest number of well-resolved bands, bearing rich structural information.


Variants in the Kisspeptin-GnRH Pathway Modulate the Hormonal Profile and Reproductive Outcomes.
Kisspeptin has been identified as a key regulatory protein in the release of gonadotropin-releasing hormone (GnRH), which subsequently increases gonadotropin secretion during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. The effects of variants in the KISS1, KISS1R, and GNRHR genes and their possible association with assisted reproduction outcomes remain to be elucidated. In this study, we used next-generation sequencing to investigate the associations of the genetic diversity at the candidate loci for KISS1, KISS1R, and GNRHR with the hormonal profiles and reproductive outcomes in 86 women who underwent in vitro fertilization treatments. Variants in the KISS1 and KISS1R genes were associated with luteinizing hormone (rs35431622:T>C), anti-Mullerian hormone (rs71745629delT), follicle-stimulating hormone (rs73507529:C>A), and estradiol (rs73507527:G>A, rs350130:A>G, and rs73507529:C>A) levels, as well as with reproductive outcomes such as the number of oocytes retrieved (s35431622:T>C), metaphasis II oocytes (rs35431622:T>C), and embryos (rs1132506:G>C). Additionally, variants in the GNRHR UTR3' (rs1038426:C>A, rs12508464:A>C, rs13150734:C>A, rs17635850:A>G, rs35683646:G>A, rs35610027:C>G, rs35845954:T>C, rs17635749:C>T, and rs7666201:C>T) were associated with low prolactin levels. A conjoint analysis of clinical, hormonal, and genetic variables using a generalized linear model identified two variants of the KISS1 gene (rs71745629delT and rs1132506:G>C) that were significantly associated with hormonal variations and reproductive outcomes. The findings suggest that variants in KISS1, KISS1R, and GNRHR genes can modulate hormone levels and reproductive outcomes.


Efficacy of Tuina in chronic low back pain with anxiety: study protocol for a randomised controlled trial.
Chronic low back pain (cLBP) is one of the largest and most frequent public health problems worldwide. Tuina is a physical therapy commonly used in China to treat musculoskeletal diseases. Compared with traction, there is little high-quality scientific evidence that can demonstrate the effectiveness of Tuina in the treatment of patients with cLBP. Therefore, the purpose of this clinical trial is to evaluate the effect of massage on cLBP patients compared with traction. This is a single-centre, assessor-blinded and analyst-blinded prospective randomised controlled trial with two parallel arms. Ninety-four patients with cLBP will be recruited. Three treatments were given every week for a total of 4 weeks. In the Traction group, participants were given traction therapy in the Tuina group, participants will receive a four-step physiotherapy including kneading, rolling, plucking and oblique pulling. The outcomes will be measured at baseline, at the end of treatment, as well as 1 and 2 months after treatment. The primary outcome will be the Hamilton Anxiety Scale after 12 sessions of treatment. The secondary outcomes will be the Visual Analogue Scale, the medical outcomes study Short Form 36, Serum Quantitative Index and genetic testing after 12 sessions of treatment. The study was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated with Shanghai University of Traditional Chinese Medicine. ChiCTR2200065448.