Transcription factor EGR2 controls homing and pathogenicity of TH17 cells in the central nervous system.
CD4+ T helper 17 (TH17) cells protect barrier tissues but also trigger autoimmunity. The mechanisms behind these opposing processes remain unclear. Here, we found that the transcription factor EGR2 controlled the transcriptional program of pathogenic TH17 cells in the central nervous system (CNS) but not that of protective TH17 cells at barrier sites. EGR2 was significantly elevated in myelin-reactive CD4+ T cells from patients with multiple sclerosis and mice with autoimmune neuroinflammation. The EGR2 transcriptional program was intricately woven within the TH17 cell transcriptional regulatory network and showed high interconnectivity with core TH17 cell-specific transcription factors. Mechanistically, EGR2 enhanced TH17 cell differentiation and myeloid cell recruitment to the CNS by upregulating pathogenesis-associated genes and myelomonocytic chemokines. T cell-specific deletion of Egr2 attenuated neuroinflammation without compromising the host's ability to control infections. Our study shows that EGR2 regulates tissue-specific and disease-specific functions in pathogenic TH17 cells in the CNS.


Are animal models predictive for human postmortem muscle protein degradation?
A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.


Significance of a Non-Thermal Plasma Treatment on LDPE Biodegradation with Pseudomonas Aeruginosa.
The use of plastics has spanned across almost all aspects of day to day life. Although their uses are invaluable, they contribute to the generation of a lot of waste products that end up in the environment and end up polluting natural habitats such as forests and the ocean. By treating low-density polyethylene (LDPE) samples with non-thermal plasma in ambient air and with an addition of ≈4% CO₂, the biodegradation of the samples can be increased due to an increase in oxidative species causing better cell adhesion and acceptance on the polymer sample surface. It was, however, found that the use of this slight addition of CO₂ aided in the biodegradation of the LDPE samples more than with solely ambient air as the carbon bonds measured from Raman spectroscopy were seen to decrease even more with this change in gas composition and chemistry. The results show that the largest increase of polymer degradation occurs when a voltage of 32 kV is applied over 300 s and with a mixture of ambient air and CO₂ in the ratio 25:1.


A novel deletion of the entire alpha globin locus causing alpha-thalassemia-1 in a northern European family.
alpha-Thalassemia, though one of the most common genetic abnormalities in humans, is uncommon outside of tropical or subtropical regions of the world. The authors describe a family of northern European ancestry with a clinical presentation consistent with alpha-thalassemia-1, or deletion of both alpha globin genes on chromosome 16 in cis. Genomic mapping studies show that the deletion in this family spans 36.5-40 kbp and removes the entire alpha globin locus. This represents a novel deletion causing alpha-thalassemia-1, here termed "--RT." The 5' breakpoint is localized near the 5' breakpoints of previously described deletions in Thai and Filipino persons, consistent with this being an unstable region of chromosome 16.


The use of environmental exposure chambers in studies related to ocular surface effects.
The potential of allergen challenges using environmental exposure facilities in allergic conjunctivitis drug development and more recently its implication on the diagnosis of the united airways concept have been emphasized in the recent literature. This study aims to present an overview of new and important data in this field. Standardized methodologies for ocular surface assessment during allergen challenges were described. The Total Ocular Symptom Score (TOSS) is the main validated questionnaire used for the assessment of ocular surface during allergen challenges. It combines patient and investigator assessments for more accurate conjunctival response and was extensively used in clinical research and daily practice. Environmental Exposure Chambers (EECs) studies aim to conduct tight-controlled challenges to a stable and well defined allergen airborne concentration, closer to natural exposure to evaluate the efficacy of nonpharmaceutical and antiallergic treatments. Recent studies showed a good correlation between ocular symptoms elicited by EEC and those assessed during natural exposure. These validated methods allow to investigate the efficacy of novel pharmacotherapies for allergic conjunctivitis and allergen immunotherapy (AIT) in a real-world model of allergen exposure. This study aims to summarize novel data regarding the impact of EECs in studying pathophysiology and drug efficacy in the context of existing clinical protocols related to ocular surface effects. In this regard, studies comparing conjunctival response during natural and EEC exposures in patients with pollen-induced conjunctivitis aimed to demonstrate better outcomes in tight-controlled exposures mimicking natural exposure. Because allergen challenges are widely implemented in allergy treatment, this article will focus on the most important outcomes and the evolution of treatments for allergic conjunctivitis.


Ulcerated Hemangioma - Surveillance Only.
Infantile hemangiomas are reported in 10-12% of children less than 1 year of age, with ulceration in about 5-13% of cases. Little is known about the mechanism of this disease and explanations are still being looked for. We present a 4-month-old female infant with haemangioma on the left buttock; the hemangioma was noticed at 2 weeks of age, progressively enlarging and ulcerated.


Manganese supplementation reduces high glucose-induced monocyte adhesion to endothelial cells and endothelial dysfunction in Zucker diabetic fatty rats.
Endothelial dysfunction is a hallmark of increased vascular inflammation, dyslipidemia, and the development of atherosclerosis in diabetes. Previous studies have reported lower levels of Mn(2+) in the plasma and lymphocytes of diabetic patients and in the heart and aortic tissue of patients with atherosclerosis. This study examines the hypothesis that Mn(2+) supplementation can reduce the markers/risk factors of endothelial dysfunction in type 2 diabetes. Human umbilical vein endothelial cells (HUVECs) were cultured with or without Mn(2+) supplementation and then exposed to high glucose (HG, 25 mm) to mimic diabetic conditions. Mn(2+) supplementation caused a reduction in monocyte adhesion to HUVECs treated with HG or MCP-1. Mn(2+) also inhibited ROS levels, MCP-1 secretion, and ICAM-1 up-regulation in HUVECs treated with HG. Silencing studies using siRNA against MnSOD showed that similar results were observed in MnSOD knockdown HUVECs following Mn(2+) supplementation, suggesting that the effect of manganese on monocyte adhesion to endothelial cells is mediated by ROS and ICAM-1, but not MnSOD. To validate the relevance of our findings in vivo, Zucker diabetic fatty rats were gavaged daily with water (placebo) or MnCl2 (16 mg/kg of body weight) for 7 weeks. When compared with placebo, Mn(2+)-supplemented rats showed lower blood levels of ICAM-1 (17%, p < 0.04), cholesterol (25%, p < 0.05), and MCP-1 (28%, p = 0.25). These in vitro and in vivo studies demonstrate that Mn(2+) supplementation can down-regulate ICAM-1 expression and ROS independently of MnSOD, leading to a decrease in monocyte adhesion to endothelial cells, and therefore can lower the risk of endothelial dysfunction in diabetes.


Intrinsically disordered regions are poised to act as sensors of cellular chemistry.
Intrinsically disordered proteins and protein regions (IDRs) are abundant in eukaryotic proteomes and play a wide variety of essential roles. Instead of folding into a stable structure, IDRs exist in an ensemble of interconverting conformations whose structure is biased by sequence-dependent interactions. The absence of a stable 3D structure, combined with high solvent accessibility, means that IDR conformational biases are inherently sensitive to changes in their environment. Here, we argue that IDRs are ideally poised to act as sensors and actuators of cellular physicochemistry. We review the physical principles that underlie IDR sensitivity, the molecular mechanisms that translate this sensitivity to function, and recent studies where environmental sensing by IDRs may play a key role in their downstream function.


Dissecting the Effect of Temperature on Hyperthermophilic Pf2001 Esterase Dimerization by Molecular Dynamics.
Pf2001 esterase (Pf2001) from Pyrococcus furiosus has hyperthermophilic properties and exerts a biocatalytic function in a dimeric state. Crystal structures revealed that the structural rearrangement of the cap domain is responsible for the Pf2001 dimer formation. However, the details of the cap domain remodeling and the effects of temperature on the dimerization process remain elusive at the molecular level, taking into account that experimental methods are difficult to capture the dynamic process of dimerization to some extent. Herein, four dimer models based on the monomeric crystal structure (PDB ID: 5G59) were constructed to investigate the conformational transition details and temperature effects in the dimerization by conventional molecular dynamics and accelerated molecular dynamics simulations. Our simulation results indicate that the monomer undergoes a conformational change into a "preparatory state" at high temperatures, which is more favorable for its transformation into a stable dimer. The subsequent free energy landscape analysis further identifies four intermediate states (from separated state to dimeric state) and discloses that a more accessible α-helix driven by stronger hydrophobic interactions induces a rearrangement of the cap domain, displaying a "tic-tac-toe" activation feature that is important for stabilizing the dimer interface and facilitating the formation of hydrophobic pockets. In addition, the electrostatic potential surface analysis illustrates that the weaker electrostatic repulsion (Lys and Arg) in the dimer interface at high temperatures is also a key factor for dimer stabilization. Altogether, our results can provide molecular-level insight into the dimer formation process of hyperthermophilic esterase and would be useful to understand the enzymatic specificity of α/β-hydrolase.


Congenital ankyloglossia with deviation of the epiglottis and larynx: symptoms and respiratory function in adults.
We operated on 38 adult patients with congenital ankyloglossia with deviation of the epiglottis and larynx. The results were as follows. 1) Most patients had Angle's class III malocclusion, irregular alignment of the upper teeth, and high hard palate. 2) Fifty percent of the patients in our study population had obstructive respiratory failure. Their vital capacity increased significantly after the operation, but changes of forced expiratory volume in 1 second were not prominent. 3) Subjective symptoms of this disease were stiffness of the shoulders, a cold feeling in the extremities, an obstructed feeling in the throat, insomnia, fatigue, dry skin, irritability and/or anxiety, and nervousness. These improved postoperatively. 4) Objective symptoms included snoring, muscle cramps, difficulty in playing wind instruments, hoarseness, and incorrect articulation. The objective symptoms, except for incorrect articulation, improved postoperatively.


Preparation of hybrid soda-lime/quartz glass chips with wettability-patterned channels for manipulation of flow profiles in droplet-based analytical systems.
Profile switching of two-phase flows is often required in microfluidic systems. Manipulation of flow profiles can be realized by control of local surface energy of micro channel through wettability-patterning of channel surface. This article presents a facile approach for wettability-patterning of the micro channels of glass chips. Commercially available octadecyltrichlorosilane (OTS) was used to hydrophobilize the channels via the formation of OTS self-assembly monolayer (SAM), and a UV-source that mainly emits deep UV-light of 254 and 185 nm was employed to degrade the in-channel formed OTS-SAM. The architecture of soda-lime glass/quartz glass hybrid chip was designed to facilitate the deep UV-light effective degrading the OTS-SAM. The established approach, together with the side-by-side laminar-flow patterning technique, was applied to prepare various finely patterned channel networks for different tasks of flow profile switching. The micro device capable of conducting the profile switch from W/O droplets to two separated continuous phases was demonstrated to perform on-chip quick liquid-liquid extraction for the determination of partition coefficients of pharmaceuticals.


High electron mobility in thin films formed via supersonic impact deposition of nanocrystals synthesized in nonthermal plasmas.
Thin films comprising semiconductor nanocrystals are emerging for applications in electronic and optoelectronic devices including light emitting diodes and solar cells. Achieving high charge carrier mobility in these films requires the identification and elimination of electronic traps on the nanocrystal surfaces. Herein, we show that in films comprising ZnO nanocrystals, an electron acceptor trap related to the presence of OH on the surface limits the conductivity. ZnO nanocrystal films were synthesized using a nonthermal plasma from diethyl zinc and oxygen and deposited by inertial impaction onto a variety of substrates. Surprisingly, coating the ZnO nanocrystals with a few nanometres of Al2O3 using atomic layer deposition decreased the film resistivity by seven orders of magnitude to values as low as 0.12 Ω cm. Electron mobility as high as 3 cm(2) V(-1) s(-1) was observed in films comprising annealed ZnO nanocrystals coated with Al2O3.


Photosensitive Melanopsin-Containing Retinal Ganglion Cells in Health and Disease: Implications for Circadian Rhythms.
Melanopsin-containing retinal ganglion cells (mRGCs) represent a third class of retinal photoreceptors involved in regulating the pupillary light reflex and circadian photoentrainment, among other things. The functional integrity of the circadian system and melanopsin cells is an essential component of well-being and health, being both impaired in aging and disease. Here we review evidence of melanopsin-expressing cell alterations in aging and neurodegenerative diseases and their correlation with the development of circadian rhythm disorders. In healthy humans, the average density of melanopsin-positive cells falls after age 70, accompanied by age-dependent atrophy of dendritic arborization. In addition to aging, inner and outer retinal diseases also involve progressive deterioration and loss of mRGCs that positively correlates with progressive alterations in circadian rhythms. Among others, mRGC number and plexus complexity are impaired in Parkinson's disease patients; changes that may explain sleep and circadian rhythm disorders in this pathology. The key role of mRGCs in circadian photoentrainment and their loss in age and disease endorse the importance of eye care, even if vision is lost, to preserve melanopsin ganglion cells and their essential functions in the maintenance of an adequate quality of life.


VISTA deficiency protects from immune complex-mediated glomerulonephritis by inhibiting neutrophil activation.
V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is a negative checkpoint regulator of T cells. We assessed VISTA deficient mice in the murine nephrotoxic nephritis models of acute and chronic immune-complex mediated glomerulonephritis. We show that VISTA deficiency protects from crescentic glomerulonephritis, with no effect on the nephritogenic adaptive immune response. The early neutrophil influx was unaffected but proteinuria was reduced suggesting a reduction in neutrophil activation. In vivo, there was reduced neutrophil degranulation in VISTA deficienct mice and, in vitro, VISTA-deficient neutrophils had an impaired response to immune complexes but not to fMLP or PMA. Mice with a genetic deficiency of neutrophils due to myeloid-specific deletion of myeloid cell leukemia 1 (Mcl-1) were also protected from crescentic glomerulonephritis, indicating an essential role for neutrophils. Therefore, VISTA deficiency inhibits neutrophil activation by immune complexes and neutrophil-dependent crescentic glomerulonephritis. This suggests that VISTA is a therapeutic target for inflammatory disease. However, this would need to be balanced against a potential enhancing effect on autoimmunity.


Human Papilloma Virus-Associated Lips Verrucous Carcinoma in HIV-Infected Male.
Human papillomavirus (HPV) infection, widely known as the necessary cause of cervical cancer, has been established as a major etiologic factor for head and neck cancer (HNC). HIV-infected individuals are at higher risk of HPV-associated cancers than the general population. We describe a 45-year-old man with HIV and HPV coinfection, who presented progressively enlarging verrucous neoformations of the lips. The final diagnosis of verrucous carcinoma was delayed. Early detection of HPV lesions in oral mucosa and HPV screening activities could be important in improving the diagnostic sensitivity for the HIV-infected patients with oral cancer.


Comparison of brain activation via tooth stimulation.
The aim of this study was to evaluate the sensation of each tooth type at the cortical level. The tactical sensation from teeth plays an important role in controlling the masticatory system. However, the role of each tooth type has not been determined. Functional near-infrared spectroscopy (fNIRS) was used to detect changes in cerebral blood flow in the somatosensory cortex of 12 healthy volunteers. Painless vibrotactile stimuli were applied to 8 teeth (left maxillary and mandibular incisors, canines, 1(st) premolars, or 1(st) molars). The somatosensory cortex was activated during stimulation of all teeth. A comparison of cortical activation revealed significantly greater activation during stimulation of the maxillary and mandibular first molars. However, no significant differences were seen between any other teeth. These results indicate that the first molar is the most sensitive tooth type at the cortical level, and provide basic data on the relationship between input from individual tooth type and brain activation. These data could be useful for understanding the neural mechanisms of individual tooth types.


Excellent adsorption performance of dibenzothiophene on functionalized low-cost activated carbons with different oxidation methods.
Low-cost activated carbon (KAC) was functionalized by HNO3, (NH4)2S2O8 and air oxidation, respectively, to remove dibenzothiophene (DBT) from model fuel. The changes in physical and chemical properties of these activated carbons were characterized by thermal analysis, elemental analysis, nitrogen adsorption apparatus, Raman spectra, scanning electron microscope and Boehm's titration method. HNO3 and (NH4)2S2O8 oxidation result in a significant decrease in pore structure, while air oxidation only causes slight pore reduction due to the re-activation by O2. The oxygen-containing functional groups (OFGs) increase markedly after oxidative modification, in which (NH4)2S2O8 oxidation is considered as the most efficient method with respect to the introduction of OFGs. HNO3 and (NH4)2S2O8 oxidation are more selective to generate carboxyls and lactones, whereas air oxidation creates more phenols, carbonyls and ethers. The DBT adsorption capacity follows the order: NAC (HNO3-oxidized KAC) > OAC (air-oxidized KAC) > KAC > SAC ((NH4)2S2O8-oxidized KAC), implying the introduction of OFGs is beneficial for the DBT adsorption process, especially for selectivity, but excessive OFGs have a negative effect on the removal of DBT. Thus, to achieve high DBT adsorption performance, there should be a trade-off between the micropore volume and the OFGs amount.


Combined petrosal approach for a huge retroclival meningioma preserving the cranial nerves.
Surgery for petroclival meningioma is challenging because cranial nerve preservation during tumor removal can be very complex. For small- to medium-sized tumors, the anatomical relationship between tumor and neurovascular structures can be assessed before surgery. However, in large tumors, cranial nerves usually cannot be seen in preoperative images. The authors present a case of a 65-year-old woman who presented with gait disturbance and hearing loss and was diagnosed with huge retroclival meningioma involving the cavernous sinus, Meckel's cave, and internal acoustic meatus. In this video, they explain the radiographical, anatomical, and surgical considerations and demonstrate the surgical technique. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21221.


Admission white blood cell count predicts short-term clinical outcomes in patients with uncomplicated Stanford type B acute aortic dissection.
Inflammation has been shown to be related with acute aortic dissection (AAD). The present study aimed to evaluate the association of white blood cell counts (WBCc) on admission with both in-hospital and long-term all-cause mortality in patients with uncomplicated Stanford type B AAD. From 2008 to 2010, a total of 377 consecutive patients with uncomplicated type B AAD were enrolled and then followed up. Clinical data and WBCc on admission were collected. The primary end points were in-hospital death and long-term all-cause death. The in-hospital death rate was 4.2%, and the long-term all-cause mortality rate was 6.9% during a median follow-up of 18.9 months. WBCc on admission was identified as a risk factor for in-hospital death by univariate Cox regression analysis as both a continuous variable and a categorical variable using a cut off of 11.0 × 109 cell/L (all P < 0.05). After adjusting for age, sex and other risk factors, elevated admission WBCc was still a significant predictor for in-hospital death as both a continuous variable [hazard ratio (HR): 1.052, 95% CI: 1.024-1.336, P = 0.002] and a categorical variable using a cut off of 11.0 × 109 cell/L (HR: 2.056, 95% CI: 1.673-5.253, P = 0.034). No relationship was observed between WBCc on admission and long-term all-cause death. Our results indicate that elevated WBCc upon admission might be used as a predictor for increased risk of in-hospital death in uncomplicated type B AAD. There might be no predictive value of WBCc for the long-term survival of type B AAD.


Self-Assembled Lanthanum Oxide Nanoflakes by Electrodeposition Technique for Resistive Switching Memory and Artificial Synaptic Devices.
In recent years, many metal oxides have been rigorously studied to be employed as solid electrolytes for resistive switching (RS) devices. Among these solid electrolytes, lanthanum oxide (La2 O3 ) is comparatively less explored for RS applications. Given this, the present work focuses on the electrodeposition of La2 O3 switching layers and the investigation of their RS properties for memory and neuromorphic computing applications. Initially, the electrodeposited La2 O3 switching layers are thoroughly characterized by various analytical techniques. The electrochemical impedance spectroscopy (EIS) and Mott-Schottky techniques are probed to understand the in situ electrodeposition, RS mechanism, and n-type semiconducting nature of the fabricated La2 O3 switching layers. All the fabricated devices exhibit bipolar RS characteristics with excellent endurance and stable retention. Moreover, the device mimics the various bio-synaptic properties such as potentiation-depression, excitatory post-synaptic currents, and paired-pulse facilitation. It is demonstrated that the fabricated devices are non-ideal memristors based on double-valued charge-flux characteristics. The switching variation of the device is studied using the Weibull distribution technique and modeled and predicted by the time series analysis technique. Based on electrical and EIS results, a possible filamentary-based RS mechanism is suggested. The present results assert that La2 O3 is a promising solid electrolyte for memory and brain-inspired applications.


Synthesis, anticancer activity and UPLC analysis of the stability of some new benzimidazole-4,7-dione derivatives.
In this work, a sensitive analytical method to study the stability of two new series of synthesized heterocyclic compounds, the benzimidazole-4,7-diones 5 and N-oxide benzimidazole-4,7-dione derivatives 6 was established and validated. These derivatives were developed as potential anticancer substances to be activated under hypoxic conditions. At this point we were concerned with establishing their stability in some specific environments for further biological studies. For that, we developed and validated an RP-UPLC method. Next, selected compounds were tested in vitro for possible anticancer activity. Their effect on A549 tumour cell lines under normoxia and hypoxia conditions was determined by a WST-1 test. Four of the examined compounds (compounds 5a-c and 6c) showed very good antiproliferative effects and three of them (compounds 6a, 6b and 6d) were specific for hypoxia conditions. The hypoxia/normoxia cytotoxic coefficient of compound 6b is close to that of tirapazamine--a reference compound in our experiments--and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole).


Atrial Arrhythmias and Electroanatomical Remodeling in Patients With Left Ventricular Assist Devices.
The incidence, predictors, and impact of atrial arrhythmias along with left atrial structural changes in patients with left ventricular assist devices (LVADs) remain undetermined. All patients who underwent LVAD implantation from 2008 to 2015 at the University of Chicago Medical Center were included. Electronic medical records, electrocardiograms, echocardiograms, and cardiac electrical device interrogations were reviewed. The association of arrhythmias and clinical covariates with survival was evaluated by Kaplan-Meier and Cox proportional hazards analyses. A total of 331 patients were followed for a median of 330 days (range 0-2306 days). Mean age was 57.8±12.8 years, 256 participants (77.3%) were male, mean left ventricular ejection fraction was 20±6.6%, and 124 (37.5%) had ischemic cardiomyopathy. Atrial arrhythmias (53.8%) were highly prevalent and frequently coexisted before LVAD implantation: atrial fibrillation (AF) in 45.9%, atrial flutter in 13.9%, atrial tachycardia in 6.9%, and atrioventricular nodal reentrant tachycardia in 1.2%. New-onset AF was documented in 14 patients (7.8% of patients without prior AF) after the first 30 days with an LVAD. Increasing age, renal insufficiency, and lung disease were predictors of new-onset AF after LVAD implantation. Of patients with paroxysmal AF, 43% had no further AF after LVAD. Left atrial size and volume index improved with LVAD (P<0.005). History of persistent AF, atrial tachycardia, ventricular arrhythmia, coronary artery bypass, and low albumin were associated with decreased survival. Atrial arrhythmias are significantly prevalent in patients who require LVAD and are associated with increased mortality; however, LVADs induce favorable atrial structural and electrical remodeling.


In vitro selection and evolution of functional proteins by using ribosome display.
We report here a system with which a correctly folded complete protein and its encoding mRNA both remain attached to the ribosome and can be enriched for the ligand-binding properties of the native protein. We have selected a single-chain fragment (scFv) of an antibody 10(8)-fold by five cycles of transcription, translation, antigen-affinity selection, and PCR. The selected scFv fragments all mutated in vitro by acquiring up to four unrelated amino acid exchanges over the five generations, but they remained fully compatible with antigen binding. Libraries of native folded proteins can now be screened and made to evolve in a cell-free system without any transformation or constraints imposed by the host cell.


Academic Impact of COVID-19 in Collegiate Athletes.
The COVID-19 pandemic caused a pause to nearly all sporting activities in the spring of 2020, and collegiate athletes at the National Collegiate Athletic Association (NCAA)-affiliated universities whose sporting seasons were affected by the pandemic were granted an extra year of athletic eligibility. This study was conducted to determine how collegiate athletes planned to use an additional year of eligibility granted by the NCAA. The authors conducted a cross-sectional survey of 632 athletes from two universities in the Midwestern United States, between August and September 2021. The athletes completed an anonymous, nine-item survey to assess the effect of the pandemic on the athletic season, athletic eligibility, and potential change in an academic or professional career. Chi-square tests, generalized linear mixed models, and adjusted odds ratio were used for the analyses. The participation rate was 74.5% (471 of 632). Nearly 63% (290 of 461) of the athletes received an additional year of eligibility because of the pandemic, with 193 (66.6%) planned to use their extra year for scholastic development. Male athletes (65.3% vs. 34.7%; χ2[1, n = 290] = 11.66, p < 0.001, Φ = 0.20), Division II athletes (59.6% vs. 40.4%; χ2[1, n = 290] = 13.93, p < 0.001, Φ = 0.22), and athletes who had not previously used redshirt (73.1% vs. 26.9%; χ2[1, n = 290] = 4.79, p = 0.029, Φ = 0.32) where more likely to use their extra year of eligibility academically. Our findings suggested that most of the athletes planned to use their extra year of eligibility to pursue further scholastic or professional development, highlighting the positive part of the COVID-19 pandemic. Future studies should investigate how these findings relate to athletes from universities in different geographical locations and intra-division schools.


Migraine and breast cancer risk: a prospective cohort study and meta-analysis.
The evidence for an association between migraine and breast cancer risk is inconclusive. While female sex hormones have been proposed as one underlying mechanism, data on sex hormone levels in migraineurs are sparse. We prospectively evaluated the association between migraine and breast cancer risk among 115378 Nurses' Health Study II participants using Cox proportional hazards models. Differences in endogenous sex hormone levels according to migraine status were assessed among 2034 premenopausal women using linear regression. We performed a meta-analysis of studies investigating the association between migraine and invasive breast cancer risk published through October 2013. All statistical tests were two-sided. Seventeen thousand six hundred ninety-six women (15.3%) reported a physician's diagnosis of migraine at baseline. Over 20 years of follow-up, 833 in situ and 3091 invasive breast malignancies occurred. Migraine was not associated with total (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.88 to 1.04), in situ (HR = 0.97, 95% CI = 0.82 to 1.15), or invasive breast cancer risk (HR = 0.95, 95% CI = 0.87 to 1.04). Endogenous sex hormone levels did not differ according to migraine status. In the meta-analysis, migraine was associated with a lower risk of breast cancer overall (pooled risk ratio [RR] = 0.84, 95% CI = 0.73 to 0.98). However, this inverse association was apparent only among case-control studies (pooled RR = 0.72, 95% CI = 0.66 to 0.79), and not among cohort studies (pooled RR = 0.98, 95% CI = 0.87 to 1.10). In this large cohort study, migraine was not associated with breast cancer risk or differences in endogenous sex hormone levels. While case-control studies suggest an inverse association between migraine and breast cancer risk, prospective cohort studies do not support an association in pooled analyses.


Failure to stop autocorrect errors in reading aloud increases in aging especially with a positive biomarker for Alzheimer's disease.
The present study examined the effects of aging and CSF biomarkers of Alzheimer's disease (AD) on the ability to control production of unexpected words in connected speech elicited by reading aloud. Fifty-two cognitively healthy participants aged 66-86 read aloud 6 paragraphs with 10 malapropisms including 5 on content words (e.g., "window cartons" that elicited autocorrect errors to "window curtains") and 5 on function words (e.g., "thus concept" that elicited autocorrections to "this concept") and completed a battery of neuropsychological tests including a standardized Stroop task. Reading aloud elicited more autocorrect errors on function than content words, but these were equally correlated with age and Aβ1-42 levels. The ability to stop autocorrect errors declined in aging and with lower (more AD-like) levels of Aβ1-42, and multiplicatively so, such that autocorrect errors were highest in the oldest-old with the lowest Aβ1-42 levels. Critically, aging effects were significant even when controlling statistically for Aβ1-42. Finally, both autocorrect and Stroop errors were correlated with Aβ1-42, but only autocorrect errors captured unique variance in predicting Aβ1-42 levels. Reading aloud requires simultaneous planning and monitoring of upcoming speech. These results suggest that healthy aging leads to decline in the ability to intermittently monitor for and detect conflict during speech planning and that subtle cognitive changes in preclinical AD magnify this aging deficit. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Evolution of Dopant-Concentration-Induced Magnetic Exchange Interaction in Topological Insulator Thin Films.
To date, the quantum anomalous Hall effect has been realized in chromium (Cr)- and/or vanadium(V)-doped topological insulator (Bi,Sb)2Te3 thin films. In this work, we use molecular beam epitaxy to synthesize both V- and Cr-doped Bi2Te3 thin films with controlled dopant concentration. By performing magneto-transport measurements, we find that both systems show an unusual yet similar ferromagnetic response with respect to magnetic dopant concentration; specifically the Curie temperature does not increase monotonically but shows a local maximum at a critical dopant concentration. We attribute this unusual ferromagnetic response observed in Cr/V-doped Bi2Te3 thin films to the dopant-concentration-induced magnetic exchange interaction, which displays evolution from van Vleck-type ferromagnetism in a nontrivial magnetic topological insulator to Ruderman-Kittel-Kasuya-Yosida (RKKY)-type ferromagnetism in a trivial diluted magnetic semiconductor. Our work provides insights into the ferromagnetic properties of magnetically doped topological insulator thin films and facilitates the pursuit of high-temperature quantum anomalous Hall effect.


Phase structure and molecular dynamics of liquid-crystalline side-on organosiloxane tetrapodes.
X-ray diffraction and proton NMR relaxation measurements were carried out on two liquid-crystalline organosiloxane tetrapodes with side-on mesogenic groups, exhibiting nematic and smectic- C phases, and on a monomeric analog. Packing models for the mesophases exhibited by these systems are proposed on the basis of x-ray diffraction data. As a consequence of microsegregation, the aromatic cores are packed in between two sublayers formed by a mixture of interdigitated aliphatic and siloxane chains. The mixed sublayers are characteristic for the tetrapodes with side-on mesogenic groups presented in this work and have not been observed in tetrapodes with terminally attached mesogens. The tilt angle in the smectic- C phase is found very large, i.e., approximately 61 degrees -62 degrees . Notably, smectic- C clusters are present also in the whole temperature range of the nematic phase. NMR relaxometry yields T(1)-1 dispersions clearly different from those of conventional calamitics. The influence of molecular tendency to form interdigitated structures is evidenced by frequency-dependent relaxation rate in the isotropic phase-indicating the presence of ordered clusters far above the phase transition-and by the diminished role of molecular self-diffusion in ordered phases. Nematiclike director fluctuations are the dominating relaxation mechanism whereas the translational displacements are strongly hindered by the interdigitation of dendrimer arms.


Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer.
The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.


4-(5-Hy-droxy-meth-yl-2-meth-oxy-phen-oxy)benzoic acid.
The title compound, C(15)H(14)O(5), crystallizes with two independent mol-ecules in the asymmetric unit in which the benzene rings are inclined at dihedral angles of 79.4 (1) and 84.2 (1)°. In the crystal, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into double chains propagating in [001].


Dynamic Analysis to Enhance the Performance of a Rotating-Disk-Based Triboelectric Nanogenerator by Injected Gas.
A rotating-disk-based triboelectric nanogenerator (TENG) generating electrical energy from wind usually includes a propeller. TENGs are widely used because their high frequency of rotation allows them to generate a relatively high output current. Deep analysis of the gas flow in a TENG is essential to improve its energy conversion efficiency. However, previous studies have isolated the propeller and the TENG as separate entities that harvest wind energy and generate electrical energy, respectively. Most studies focused on each entity because considering both the dynamics and the TENG operation together is an intricate process. This paper introduces a dynamic analysis of the gas flow by dividing it into four vertical and horizontal directions and carrying out a COMSOL simulation to verify the pressure on the propeller and the flow of the gas. The electrical outputs are measured while varying the height and angle of the inlet and the number of wings on the propeller. After optimization, the P-TENG generated a high output power density of 283.95 mW/m2, which can light up 205 light-emitting diodes and drive a commercial small electronic appliance. In addition, optimizing the P-TENG through a variety of analyses allowed it to provide sustainable power to a self-powered wireless sensor system.


Structure, function, and regulation of a subfamily of mouse zinc transporter genes.
Zinc is an essential metal for all eukaryotes, and cells have evolved a complex system of proteins to maintain the precise balance of zinc uptake, intracellular storage, and efflux. In mammals, zinc uptake appears to be mediated by members of the Zrt/Irt-like protein (ZIP) superfamily of metal ion transporters. Herein, we have studied a subfamily of zip genes (zip1, zip2, and zip3) that is conserved in mice and humans. These eight-transmembrane domain proteins contain a conserved 12-amino acid signature sequence within the fourth transmembrane domain. All three of these mouse ZIP proteins function to specifically increase the uptake of zinc in transfected cultured cells, similar to the previously demonstrated functions of human ZIP1 and ZIP2 (Gaither, L. A., and Eide, D. J. (2000) J. Biol. Chem. 275, 5560-5564; Gaither, L. A., and Eide, D. J. (2001) J. Biol. Chem. 276, 22258-22264). No ZIP3 orthologs have been previously studied. Furthermore, this first systematic comparative study of the in vivo expression and dietary zinc regulation of this subfamily of zip genes revealed that 1) zip1 mRNA is abundant in many mouse tissues, whereas zip2 and zip3 mRNAs are very rare or moderately rare, respectively, and tissue-restricted in their accumulation; and 2) unlike mouse metallothionein I and zip4 mRNAs (Dufner-Beattie, J., Wang, F., Kuo, Y.-M., Gitschier, J., Eide, D., and Andrews, G. K. (2003) J. Biol. Chem. 278, 33474-33481), the abundance of zip1, zip2, and zip3 mRNAs is not regulated by dietary zinc in the intestine and visceral endoderm, tissues involved in nutrient absorption. These studies suggest that all three of these ZIP proteins may play cell-specific roles in zinc homeostasis rather than primary roles in the acquisition of dietary zinc.


Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.
Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance--i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding.


Impact of duration of adjuvant chemotherapy in radically resected patients with T4bN1-3M0/TxN3bM0 gastric cancer.
To provide evidence regarding the postoperative treatment of patients with T4bN1-3M0/TxN3bM0 gastric cancer, for which guidelines have not been established. Patients who had undergone curative resection between 1996 and 2014 with a pathological stage of T4bN1-3M0/TxN3bM0 for gastric cancer were retrospectively analyzed; staging was based on the 7th edition of the American Joint Committee on Cancer staging system. The clinicopathological characteristics, administration of adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and multivariate analyses of prognostic factors were conducted. The chemotherapeutic agents mainly included fluorouropyrimidine, platinum and taxanes, used as monotherapy, doublet, or triplet regimens. Patterns of first recurrence were categorized as locoregional recurrence, peritoneal dissemination, or distant metastasis. The 5-year overall survival (OS) of the whole group (n = 176) was 16.8%, and the median OS was 25.7 mo (95%CI: 20.9-30.5). Lymphovascular invasion and a node positive rate (NPR) ≥ 0.8 were associated with a poor prognosis (P = 0.01 and P = 0.048, respectively). One hundred forty-seven (83.5%) of the 176 patients eventually experienced recurrence; the most common pattern of the first recurrence was distant metastasis. The prognosis was best for patients with locoregional recurrence and worst for those with peritoneal dissemination. Twelve (6.8%) of the 176 patients did not receive adjuvant chemotherapy, while 164 (93.2%) patients received adjuvant chemotherapy. Combined chemotherapy, including doublet and triplet regimens, was associated with a better prognosis than monotherapy, with no significant difference in 5-year OS (17.5% vs 0%, P = 0.613). The triplet regimen showed no significant survival benefit compared with the doublet regimen for 5-year OS (18.5% vs 17.4%, P = 0.661). Thirty-nine (22.1%) patients received adjuvant chemotherapy for longer than six months; the median OS in patients who received adjuvant chemotherapy for longer than six months was 40.2 mo (95%CI: 30.6-48.2), significantly longer than the 21.6 mo (95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than six months (P = 0.001). Patients with T4bN1-3M0/TxN3bM0 gastric cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant chemotherapy for longer than six months improved outcomes for them.


Rationing and competition in the Dutch health-care system.
In this paper we examine the goals and effects of health-care policy in the Netherlands over the period 1980--2000. During this period Dutch health-care policy is marked by a peculiar combination of increasingly stringent cost-containment policies alongside a persistent pursuit of market-oriented reforms. The main goal of cost containment was to keep labour costs down under the restriction of universal equal access to health care. Supply and price control policies were quite successful in achieving cost containment, but in due course prolonged quantity rationing began to jeopardise universal physical access to health services. The main goal of market-oriented health-care reforms is to increase the system's efficiency and its responsiveness to patient's needs, while maintaining equal access. The feasibility of the reforms crucially hinges on the realisation of adequate methods of risk adjustment, product classification and quality measurement, an appropriate consumer information system and an effective competition policy. Realising these preconditions requires a lengthy and cautious implementation process. Although considerable progress has been made in setting the appropriate stage for regulated competition in Dutch health care, the role of the market is still limited.


Spectral estimation optical coherence tomography for axial super-resolution.
The depth reflectivity profile of Fourier domain optical coherence tomography (FD-OCT) is estimated from the inverse Fourier transform of the spectral interference signals (interferograms). As a result, the axial resolution is fundamentally limited by the coherence length of the light source. We demonstrate that using the autoregressive spectral estimation technique instead of the inverse Fourier transform, to analyze the spectral interferograms can improve the axial resolution. We name this method spectral estimation OCT (SE-OCT). SE-OCT breaks the coherence length limitation and improves the axial resolution by a factor of up to 4.7 compared with FD-OCT. Furthermore, SE-OCT provides complete sidelobe suppression in the depth point-spread function, further improving the image quality. We demonstrate that these technical advances enables clear identification of corneal endothelium anatomical details ex vivo that cannot be identified using the corresponding FD-OCT. Given that SE-OCT can be implemented in the FD-OCT devices without any hardware changes, the new capabilities provided by SE-OCT are likely to offer immediate improvements to the diagnosis and management of diseases based on OCT imaging.


Glycoproteins of human parainfluenza virus type 3: affinity purification, antigenic characterization and reconstitution into lipid vesicles.
Monoclonal antibodies to the envelope glycoproteins, HN and F, of human parainfluenza virus type 3 were coupled to a Sepharose 4B matrix and used for affinity purification of the viral glycoproteins. The purity of the glycoproteins was demonstrated by SDS-PAGE followed by fluorography or silver staining. The antigenicity of the glycoproteins was determined by immunization of rabbits; polyclonal rabbit antisera demonstrated inhibition of functional activities of the virus glycoproteins. The F glycoprotein, when reconstituted into lipid vesicles, showed distinct spike-like projections similar to those of intact virions.


Genetic Diversity of Verticillium dahliae Isolates From Mint Detected with Genotyping by Sequencing.
Verticillium wilt is the most important disease threatening the commercial production of mint grown for essential oil. An important long-term goal for mint breeders is the production of cultivars with resistance to Verticillium wilt. Before that can be accomplished, a better understanding of the genetic variation within and among populations of Verticillium dahliae is needed. We characterized the extent of phenotypic and genetic diversity present in contemporary and archival populations of V. dahliae from mint fields in Oregon and other production regions of the United States using genotyping by sequencing, PCR assays for mating type and pathogenic race, vegetative compatibility group (VCG) tests, and aggressiveness assays. We report that the population in the Pacific Northwest can be described as one common genetic group and four relatively rare genetic groups. Eighty-three percent of the isolates belonged to VCG2B, and all isolates possessed the MAT1-2 idiomorph and were characterized as pathogenic race 2. These results indicate low levels of genetic diversity and a negligible risk of sexual recombination in populations of this host-adapted pathogen population. Knowledge of the genetic structure of V. dahliae in the Pacific Northwest will inform breeders about the diversity of pathogenicity factors that may need to be considered in their breeding programs.


New Exact Quantization Condition for Toric Calabi-Yau Geometries.
We propose a new exact quantization condition for a class of quantum mechanical systems derived from local toric Calabi-Yau threefolds. Our proposal includes all contributions to the energy spectrum which are nonperturbative in the Planck constant, and is much simpler than the available quantization condition in the literature. We check that our proposal is consistent with previous works and implies nontrivial relations among the topological Gopakumar-Vafa invariants of the toric Calabi-Yau geometries. Together with the recent developments, our proposal opens a new avenue in the long investigations at the interface of geometry, topology and quantum mechanics.


Evaluation of tibial osteopathy occurrence in neurofibromatosis type 1 Italian patients.
Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age-matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high-signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype. Patients of both groups were subdivided by gender and re-evaluated for these items. Statistical comparison was carried out between the two groups of patients for each feature. We collected data on type of treatment and on the clinical conditions of NF1-TO patients after follow-up. Patient's age at NF1 diagnosis was significantly younger in NF1-TO subjects compared with NF1 subjects without TO, and the incidence of T2H was significantly reduced in NF1-TO males compared with NF1 males without TO. The presence of TO does not imply that there is an increased risk of developing typical complications of NF1 (e.g., optic pathway glioma, plexiform neurofibroma, etc.), however, it does allow us to make an earlier diagnosis of NF1.


Interregulation of CDKA/CDK1 and the Plant-Specific Cyclin-Dependent Kinase CDKB in Control of the Chlamydomonas Cell Cycle.
The cyclin-dependent kinase CDK1 is essential for mitosis in fungi and animals. Plant genomes contain the CDK1 ortholog CDKA and a plant kingdom-specific relative, CDKB. The green alga Chlamydomonas reinhardtii has a long G1 growth period followed by rapid cycles of DNA replication and cell division. We show that null alleles of CDKA extend the growth period prior to the first division cycle and modestly extend the subsequent division cycles, but do not prevent cell division, indicating at most a minor role for the CDK1 ortholog in mitosis in Chlamydomonas. A null allele of cyclin A has a similar though less extreme phenotype. In contrast, both CDKB and cyclin B are essential for mitosis. CDK kinase activity measurements imply that the predominant in vivo complexes are probably cyclin A-CDKA and cyclin B-CDKB. We propose a negative feedback loop: CDKA activates cyclin B-CDKB. Cyclin B-CDKB in turn promotes mitotic entry and inactivates cyclin A-CDKA. Cyclin A-CDKA and cyclin B-CDKB may redundantly promote DNA replication. We show that the anaphase-promoting complex is required for inactivation of both CDKA and CDKB and is essential for anaphase. These results are consistent with findings in Arabidopsis thaliana and may delineate the core of plant kingdom cell cycle control that, compared with the well-studied yeast and animal systems, exhibits deep conservation in some respects and striking divergence in others.


Single center experience of 39 patients with preoperative portal vein thrombosis among 404 adult living donor liver transplantations.
Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) involves technical difficulty. The aim of this research was to analyze their preoperative diagnosis of PVT, operative procedures, and postoperative courses of patients with preoperative PVT. Thirty-nine patients of 404 adult patients (9.7%) undergoing LDLT in our hospital from 1996 June to 2004 December had PVT at their transplantation. Twenty-nine patients had intractable ascites, 21 had gastrointestinal bleeding, and 18 had encephalopathy. The thrombus was located in the portal trunk in 23, in the portal trunk and superior mesenteric vein (SMV) in 7, and developed into the SMV and the splenic vein in 8. The occlusive grade was partial in 29, and complete in 10 patients. The thrombus was removed by a simple technique, and eversion and/or incision technique, or total removal of the portal vein (PV). The PV was reconstructed with the thrombectomized native PV, with an interposed vein graft, or porto-caval hemitransposition. Advanced PVT had a significant impact on blood loss and hospital mortality. Three out of 10 patients with residual PVT required radiological and/or surgical intervention after transplantation. In conclusion, thorough planning is essential for a successful LDLT outcome for patients with preexisting PVT.


[Differential reactivities of three kinds of carbon dioxide absorbents with high concentration of sevoflurane].
The differential reactivities of three kinds of carbon dioxide absorbents, sodalime, Sodalime A and Baralyme with 5% sevoflurane were investigated in a closed system under administration of 5% carbon dioxide. The degradation products in the closed system were determined by gas chromatography and the temperature of the glass container which was filled with each carbon dioxide absorbent was monitored. The degradation products, P1, P3 and P5 were produced by every carbon dioxide absorbents even after one-hour circulation. Especially P3 and P5 were produced by Baralyme more than the others after two or four-hour circulation. The significant differences of the temperature among glass containers were not recognized. Previously we found that the reactivity of Sodalime A is the highest among the three kinds of carbon dioxide absorbents when low concentration of sevoflurane (2 or 3%) is used. Possible explanation for this result is that the increasing temperature of glass container filled with each carbon dioxide absorbent is different from each other, and Sodalime A is the highest. The reactivity was thought to depend on the temperature of glass container. However, with this high concentration of sevoflurane (5%), Baralyme has the highest reactivity. Baralyme contains higher proportion of KOH which has the highest reactivity with sevoflurane than the other constituents of carbon dioxide absorbents. The reactivity of sodalime, Sodalime A and Baralyme with 5% sevoflurane was thought to depend not on their temperature but on their chemical constitutions. These results suggested that the using high concentration sevoflurane with Baralyme should be reconsidered.


Chinese medicine injection qingkailing for treatment of acute ischemia stroke: a systematic review of randomized controlled trials.
Qingkailing (QKL) injection was a famous traditional Chinese patent medicine, which was extensively used to treat the acute stages of cerebrovascular disease. The aim of this study was to assess the quantity, quality and overall strength of the evidence on QKL in the treatment of acute ischemic stroke. Methods. An extensive search was performed within MEDLINE, Cochrane, CNKI, Vip and Wan-Fang up to November 2011. Randomized controlled trails (RCTs) on QKL for treatment of acute stroke were collected, irrespective of languages. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards, and RevMan5 was used for data analysis. Results. 7 RCTs (545 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that QKL combined with conventional treatment was more effective in effect rate, and the score of MESSS and TNF-α level compared with conventional treatment alone, but there was no significant difference in mortality of two groups. Only one trial reported routine life status. There were four trials reported adverse events, and no obvious adverse event occurred in three trials while one reported adverse events described as eruption and dizziness.


Aspirin inhibits highly invasive prostate cancer cells.
Cell adhesion, proteolytic degradation and cell migration are interrelated processes responsible for the invasion and metastasis of cancer. One of the crucial molecules involved in cancer metastasis is urokinase-type plasminogen activator (uPA). An elevated concentration of uPA is a strong indicator of poor prognosis. In addition to the proteolytic activity of uPA, which degrades the extracellular matrix, uPA also binds to its receptor (uPAR) and controls cell adhesion and migration through the reorganization of actin cytoskeleton. We have recently demonstrated that constitutively active nuclear factor-kappa B (NF-kappaB) is responsible for the increased secretion of uPA and that inhibition of NF-kappaB suppresses secretion of uPA and cell migration of highly invasive cancer cells. Aspirin and other nonsteroidal anti-inflammatory drugs have been recently shown to have a chemopreventive effect in colon and pancreatic cancers. Here we show that aspirin inhibits NF-kappaB, resulting in the suppression of uPA secretion from the highly invasive human prostate cancer cells PC-3. Furthermore, aspirin inhibited migration of PC-3 cells, suggesting an effect on the uPA-uPAR signaling complex. Finally, aspirin suppressed adhesion of PC-3 cells to fibronectin (FN), which binds to an alpha3beta1 integrin receptor, and to vitronectin (VN), which binds to alphavbeta3 integrin receptor. Altogether, our data suggests that aspirin inhibits the formation of uPA-uPAR-FN-alpha3beta1 and uPA-uPAR-VN-alphavbeta3 complexes, resulting in the suppression of cell adhesion and cell motility of the highly invasive prostate cancer cells PC-3. These results indicate that aspirin may contribute directly to reducing invasion and metastasis of prostate cancers by inhibiting cell migration and invasion.


Comprehensive Insights into the Family of Atomically Thin 2D-Materials for Diverse Photocatalytic Applications.
2D materials with their fascinating physiochemical, structural, and electronic properties have attracted researchers and have been used for a variety of applications such as electrocatalysis, photocatalysis, energy storage, magnetoresistance, and sensing. In recent times, 2D materials have gained great momentum in the spectrum of photocatalytic applications such as pollutant degradation, water splitting, CO2 reduction, NH3 production, microbial disinfection, and heavy metal reduction, thanks to their superior properties including visible light responsive band gap, improved charge separation and electron mobility, suppressed charge recombination and high surface reactive sites, and thus enhance the photocatalytic properties rationally as compared to 3D and other low-dimensional materials. In this context, this review spot-lights the family of various 2D materials, their properties and their 2D structure-induced photocatalytic mechanisms while giving an overview on their synthesis methods along with a detailed discussion on their diverse photocatalytic applications. Furthermore, the challenges and the future opportunities are also presented related to the future developments and advancements of 2D materials for the large-scale real-time photocatalytic applications.


Rhabdomyolysis complicating unrecognized hypophosphatemia in an alcoholic patient.
Rhabdomyolysis occurring as a complication of hypophosphatemia has been infrequently described. A 58-year-old male with a history of daily alcohol consumption presented with two generalized tonic clonic seizures secondary to hypovolemic hyponatremia. He was volume-resuscitated, and antiepileptic medication was administered. After three days of hospitalization, the patient developed severe rhabdomyolysis despite the absence of further seizure activity. Serum phosphate levels were depressed. He was treated with intravenous mannitol, alkaline diuresis, and intravenous and oral phosphate supplementation. He recovered uneventfully. Hypophosphatemia can potentially lead to multisystem organ dysfunction including severe rhabdomyolysis. It is, therefore, important to maintain a low threshold for measuring serum phosphate levels in patients admitted to hospital.


Acute myocardial infraction and pulmonary embolism in a same patient with COVID -19: a rare association.
Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 is associated with a hypercoagulable state leading to increased incidence of thromboembolism. However, it is exceedingly rare to see presence of both arterial and venous thromboembolism simultaneously. Herein, we report an unusual presentation of a 39-year-old male with recently diagnosed COVID -19 who initially had acute myocardial infarction secondary to thrombotic occlusion of right coronary artery followed by acute pulmonary embolism. Health care providers should be aware of this uncommon yet possible co-existence of two life-threatening manifestations in order to prevent fatal consequences.


Comparison of the apoptosis-inducing abilities of various protein synthesis inhibitors in U937 cells.
We compared the abilities of ricin, diphtheria toxin, cycloheximide, and anisomycin to induce apoptosis, using human myeloid leukemia U937 cells at the concentration of each toxin at which almost complete protein synthesis inhibition was attained within 3 h. Among these toxins, anisomycin was found to be the most potent apoptosis inducer. After a 6-h exposure to anisomycin (1 microg/ml), nearly 95% of the cells had apoptotic nuclear morphological changes, while 53%, 30%, and 10% of the cells showed apoptotic changes after exposure to ricin (0.1 microg/ml), diphtheria toxin (10 microg/ml), and cycloheximide (10 microg/ml), respectively. Furthermore, a rapid increase in caspase-3-like activity was observed in anisomycin-treated cells. A similar increase in caspase-3-like activity was also observed in ricin-treated cells on a slower time schedule. However, only a slight increase in the protease activity was induced by diphtheria toxin or cycloheximide even after 6 h of incubation. Since both ricin and anisomycin are known to act on 28S ribosomal RNA, our results suggest that this action mechanism may be responsible for their potent apoptosis induction, and protein synthesis inhibition alone is not sufficient to induce apoptosis.


Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay.
We developed a quantitative enzyme immunoassay (EIA) for antibody to hepatitis E virus (HEV) by using truncated HEV capsid protein expressed in the baculovirus system to improve seroepidemiology, to contribute to hepatitis E diagnosis, and to enable vaccine evaluations. Five antigen lots were characterized; we used a reference antiserum to standardize antigen potency. We defined Walter Reed antibody units (WR U) with a reference antiserum by using the four-parameter logistic model, established other reference pools as assay standards, and determined the conversion factor: 1 WR U/ml = 0.125 World Health Organization unit (WHO U) per ml. The EIA performed consistently; median intra- and inter-test coefficients of variation were 9 and 12%, respectively. The accurate minimum detection limit with serum diluted 1:1,000 was 5.6 WR U/ml; the test could detect reliably a fourfold antibody change. In six people followed from health to onset of hepatitis E, the geometric mean antibody level rose from 7.1 WR U/ml to 1,924.6 WR U/ml. We used the presence of 56- and 180-kDa bands by Western blotting as a confirmatory test and to define true-negative and -positive serum specimens. A receiver-operating characteristics plot identified 30 WR U/ml as an optimum cut-point (sensitivity, 86%; specificity, 89%). The EIA detected antibody more sensitively than a commercially available test. The EIA was transferred to another laboratory, where four operators matched reference laboratory results for a panel of unknowns. Quantitation of antibody to HEV and confirmation of its specificity by Western blotting make HEV serology more meaningful.


Medically Assisted Procreation and Fast-Moving Developments in Science and Law: Ethical and Legal Issues in Heterologous Procreation in Italy.
Significance for public healthContinual scientific progress is making new applications available, with significant medical, ethical, legal and social implications, not only for the persons directly concerned. In the area of medically assisted procreation, the use of heterologous techniques is able to overcome problems of sterility or infertility for those requesting access to methods of this kind. On the other hand, legislation is required to regulate the many correlated issues, also with regard to other parties such as ova or sperm donors and the offspring resulting from the use of these techniques: the protection of the health of the offspring; the management of laboratory results obtained during donor selection tests; the protection of confidentiality; the donor-child traceability; the number of donations; and individuals' rights to be fully informed about their biological origins are just some of the questions confirming that the implications of new procreation techniques are not restricted merely to the couples who access them.


Do you know this syndrome? Werner syndrome.
Werner syndrome is a rare autosomal recessive disorder, caused by mutations in the WRN gene. Clinical findings include: senile appearance, short stature, grey hair, alopecia, bird-like face, scleroderma-like skin changes, skin ulcers, voice abnormalities, cataracts, osteoporosis, type 2 diabetes mellitus, ischemic heart disease and hypogonadism. The syndrome begins to become apparent in adolescence but it is usually diagnosed in the third or fourth decade of life. Since the patients usually die by the age of 40-50 years related to malignant neoplasms or atherosclerotic complications, they should be closely followed and treated for complications.


The ethics of randomized placebo-controlled trials of antidepressants with pregnant women: a systematic review.
To determine whether placebo-controlled randomized clinical trials of antidepressant medications with pregnant participants are ethically justified. We searched PUBMED, PsychINFO, and Cochrane databases for articles related to the ethical justification of randomized placebo-controlled trials involving pregnant women and for all research articles for the treatment of depression during pregnancy, using the keys words depression, antidepressive agents, pregnancy, clinical trials, placebo, and ethics. We based our ethical framework on current literature on the ethics of maternal-fetal medicine and research and the requirements of argument-based ethics. We selected studies in which maternal, fetal, and neonatal health outcomes associated with antidepressant exposure were reported. We integrated evidence-based reasoning and argument-based ethics to address four questions to determine whether what is known as normative equipoise (evidence-based reasoning requires uncertainty about which clinical management is superior) exists: 1) Is there evidence of efficacy of antidepressant use during pregnancy? 2) Is there documented causality of serious, far-reaching, and irreversible clinical harm to the fetal or neonatal patient? 3) Is there documented causality of serious, far-reaching, and irreversible harm to depressed pregnant women in a placebo arm? 4) Are there no or only rare documented occurrences of less serious injury to the fetal or neonatal patient? Evidence-based answers to these questions support the judgment that normative equipoise exists with respect to randomized placebo-controlled trials of antidepressants with pregnant participants. Randomized placebo-controlled trials of antidepressant medications during pregnancy are ethically justified. Well-conducted and ethically justified trials of antidepressants should improve the quality of care provided to depressed pregnant women and thus address a major public health problem.


A Mixed Methods Assessment of Self- Management Needs and Preferences of People with Type 2 Diabetes Mellitus in China.
Consistent and effective self-management is a major challenge for people with diabetes and long-term effects can be difficult to sustain despite the many interventions. Interventions often fail to take patients' perceptions of self-management into account from their perspective. Exploring the needs preferences and the influencing factors of self-management in patients can improve the effectiveness of self-management. This study used a mixed research approach, exploring patient needs and preferences through web crawl methods and using qualitative interviews to explore the logic of preferences. 1605 data were obtained from 4 online health communities through web crawlers. Data were coded using grounded theory to analyze self-management needs. The codes were also coded for frequency statistics and ranked to explain the self-management preferences. The second phase explained the logic of the ranked distribution of preferences through one-on-one interviews with 22 patients. This study summarized six self-management needs of people with diabetes through web crawler data, among which medication management and conflict between disease and daily life were the most important concerns of patients. The reasons why patients are particularly concerned about these two needs were explored through qualitative interviews, and it was found that patients' concerns about medication were mainly due to the following three aspects: the effect of drugs is direct and obvious, medication use makes life less complicated, and progressive side effects. The patients' concerns about the conflict between disease and daily life are often caused by the following three aspects: diabetes impacts social roles, disease complicates life, and reducing the impact of the disease on life. The self-management needs of Chinese diabetics have six themes. Medication management, conflict between disease and daily life, diet, diabetes knowledge, blood glucose monitoring and exerciseIn order of frequency of mention and possible preference: medication management, conflict between disease and daily life were the most frequent needs, while diet, knowledge about diabetes, blood glucose monitoring and exercise were their least frequent needs.Understanding the individual's perception and understanding of diabetes self-management and the expression of the patient's daily life situations can guide the medical team to optimize collaboration on personalized care plans.


Predicting regulation of the phosphorylation cycle of KaiC clock protein using mathematical analysis.
Abstract The cyanobacterial clock protein KaiC regulates the circadian cycle by exhibiting rhythms in transcription, translation, and phosphorylation. KaiC phosphorylation persists in circadian cycling even under transcription-less conditions and was reconstituted in vitro by incubating KaiC, KaiA, and KaiB. This presents a novel perspective for circadian oscillation occurring due to interactions between clock proteins. Using mathematical models, the authors investigated the mechanism for the transcription-less KaiC phosphorylation cycle. They developed a simple model based on the possible KaiC behavior, which is experimentally suggested by Kitayama et al. (2003, EMBO J, 22:2127-2134). They hypothesized that the KaiC-KaiA complex formation, followed by a decrease in free KaiA molecules, may attenuate the KaiC phosphorylation rate, and it acts as negative feedback in the system. However, this model was shown not to be adequate to generate the KaiC phosphorylation cycle. The authors developed the general version of the model and determined the necessary condition to generate the KaiC phosphorylation cycle. Linear stability analysis revealed that oscillations can occur when the distance of feedback between the recipient reaction and the effector is far enough. Furthermore, they classified negative feedback regulations in the closed system into 2 types: destabilizing inhibition and stabilizing inhibition. Based on this result, the authors predicted that, in addition to the identified states of KaiC, another unknown state must be present between KaiC phosphorylation and the complex formation. By incorporating the unknown state into the previous model, they realized the periodic pattern reminiscent of the KaiC phosphorylation cycle in computer simulation. This result implies that the KaiC-KaiA complex formation requires more than 1 step of posttranslational modification, including phosphorylation or conformational change of KaiC.


[New developments in the surgical treatment of breast cancer].
Adecuate surgical treatment is mandatory in order to achieve cure in patients with breast cancer. Breast surgeons have to choice the best surgical technique over the breast and over the axillary nodes. Two new surgical aproaches have been implemented in the last decade: oncoplastic conservative surgery and sentinel lymph node biopsy. Oncoplastic surgery provides oncologic safety results and good cosmetic outcome. In this paper the technical steps and indications of different oncoplastic techniques in conservative breast surgery are review. Concerning to axillary surgery sentinel lymph node biopsy is the gold standard. However there are several controversial points in sentinel node biopsy referring to indications, identification and histological findings.


Maturation enhances the sensitivity of ovine cerebral arteries to the ATP-sensitive potassium channel activator lemakalim.
A wide variety of previous studies have demonstrated that arterial reactivity and contractility change dramatically during maturation. In light of recent findings that binding sites for glibenclamide, a ligand for ATP-sensitive potassium (KATP) channels, become more abundant with age in many tissues, the present studies examine the hypothesis that maturational changes in vascular reactivity involve changes in arterial electrophysiologic characteristics. To test this hypothesis, we determined the dose-response relation to lemakalim, a selective activator of KATP channels, in isolated endothelium-denuded segments of the second (2B, internal diameter approximately 200 microns) and fourth (4B, internal diameter approximately 125 microns) branches of middle cerebral arteries taken from newborn (3-7 d old) and adult sheep. At 100 microM, lemakalim completely relaxed serotonin-induced tone in all arteries. However, -log ED50 values were 29 to 43 times greater in adult (2B, 7.15 +/- 0.38; 4B, 6.61 +/- 0.42) than in newborn (2B, 5.52 +/- 0.25; 4B, 5.15 +/- 0.24) segments. Correspondingly, Hill values were significantly smaller in adults (2B, 0.47 +/- 0.17; 4B, 0.71 +/- 0.30) than in newborns (2B, 1.40 +/- 0.35; 4B, 3.30 +/- 0.92). These findings demonstrate that KATP channels are less sensitive to activation in newborn than in adult cerebral arteries. Given the important influence of KATP channels on vascular tone, and their possible role in many cardiovascular responses, the present data suggest that maturational increases in the activity of KATP channels contribute significantly to age-related changes in cerebrovascular contractility.


Lymphokine control of in vivo immunoglobulin isotype selection.
Several specific conclusions can be drawn from these studies: 1. IL-4 is required for the generation of both primary polyclonal and secondary antigen-specific IgE responses in vivo. 2. IL-4 is required to maintain established, ongoing, antigen-specific and polyclonal IgE responses. 3. Most, but not all, polyclonal IgE production during a secondary immune response is IL-4-dependent. Memory B cells that have already switched to IgE at the DNA level may no longer require stimulation with IL-4 to be induced to secrete IgE. 4. The generation of a secondary IgE response is not dependent upon the presence of IL-4 during primary immunization. However, if IL-4 is not present during primary immunization, it is required during secondary immunization for the generation of an IgE response. 5. IL-4 does not appear to be required for the generation of in vivo IgG1 responses, and in at least some instances, does not contribute significantly to the generation of IgG1 responses in vivo. 6. A late-acting form of T-cell help other than IL-4 appears to be required for the generation of an IgE, but not an IgG1 response. 7. An antibody that inhibits IL-4 binding to IL-4 receptors affects Ig isotype selection in the same way as an antibody that neutralizes IL-4. 8. IFN-gamma can act in both spontaneous and induced immune responses to suppress IgE production. 9. IFN-gamma can also suppress IgG1 production and stimulate IgG2a production. However, IFN-gamma appears to suppress polyclonal IgG1 responses more than antigen-specific IgG1 responses, and it enhances, but is not required for, the generation of IgG2a responses. 10. IFN-alpha appears to resemble IFN-gamma in its ability to inhibit IgE and enhance IgG2a responses in GaM delta-injected mice, but it requires the presence of IFN-gamma to suppress IgG1 production in these mice. 11. Both IFN-alpha and IFN-gamma appear to be able to decrease IgE production in some human patients. 12. There is no direct evidence that IL-5 contributes to the generation of in vivo antibody responses. Two general conclusions may also be drawn.(ABSTRACT TRUNCATED AT 400 WORDS)


Influence of Primary Tumor Resection on Survival of Patients With Metastatic Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Population-Based, Propensity-Matched Analysis.
It remains unclear whether primary tumor resection improves survival in patients with metastatic Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Therefore, our study attempted to investigate the prognostic value of primary tumor resection on metastatic AEG. In total, 4200 patients diagnosed with metastatic AEG were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were categorized into two groups according to the performance of primary tumor resection. Pearson's chi-square test, Kaplan-Meier survival curve, and Cox regression analysis were conducted in this study. In addition, propensity-score matching was conducted to match 323 patients who received primary tumor resection and another 323 patients without. Multivariate Cox regression analysis demonstrated that primary tumor resection was a significant prognostic factor in patients with metastatic AEG before matching. Moreover, in the matched cohort, metastatic AEG patients receiving primary tumor resection had significantly longer overall survival (hazard ratio [HR]: .54, 95% confidence interval [CI]: .46-.64, P < .001) and cancer-specific survival (HR: .53, 95% CI: .45-.63, P < .001). Subgroup analysis similarly revealed that primary tumor resection was significantly associated with better survival in most subgroups. The present population-based study identified that primary tumor resection led to significantly superior survival in patients with metastatic AEG. These findings are likely to contribute to the development of individualized therapy in metastatic AEG.


A theoretical model for oxygen transport in skeletal muscle under conditions of high oxygen demand.
Oxygen transport from capillaries to exercising skeletal muscle is studied by use of a Krogh-type cylinder model. The goal is to predict oxygen consumption under conditions of high demand, on the basis of a consideration of transport processes occurring at the microvascular level. Effects of the decline in oxygen content of blood flowing along capillaries, intravascular resistance to oxygen diffusion, and myoglobin-facilitated diffusion are included. Parameter values are based on human skeletal muscle. The dependence of oxygen consumption on oxygen demand, perfusion, and capillary density are examined. When demand is moderate, the tissue is well oxygenated and consumption is slightly less than demand. When demand is high, capillary oxygen content declines rapidly with axial distance and radial oxygen transport is limited by diffusion resistance within the capillary and the tissue. Under these conditions, much of the tissue is hypoxic, consumption is substantially less than demand, and consumption is strongly dependent on capillary density. Predicted consumption rates are comparable with experimentally observed maximal rates of oxygen consumption.


AlCl3-promoted highly regio- and diastereoselective [3 + 2] cycloadditions of activated cyclopropanes and aromatic aldehydes: construction of 2,5-diaryl-3,3,4-trisubstituted tetrahydrofurans.
The AlCl(3)-catalyzed [3 + 2] cycloaddition reaction of diethyl trans-2,3-disubstituted cyclopropane-1,1-dicarboxylates and aromatic aldehydes was carried out under mild conditions to provide a series of diethyl 2,5-diaryl-4-benzoyltetrahydrofuran-3,3-dicarboxylates in moderate to good yields with excellent diastereoselectivities. While common 2,5-cis products were obtained with electron-neutral or electron-poor aryl aldehydes, the much less common 2,5-trans products were obtained in excellent diastereoselectivities when electron-rich aryl aldehydes were used. The relative configurations of those typical products were confirmed by X-ray crystallographic analyses.


[The Alzheimer's disease: how to estimate the impact of the pathology and the treatment?].
The Alzheimer's disease (AD) is a neuro-degenerative pathology which establishes at present the most frequent cause of dementia. The therapeutic which we have actually are symptomatic treatments which do not modify the evolution of the disease. A clinical and cognitive evaluation is sufficient mostly to estimate the efficiency of these symptomatic treatments. The development of treatments to modify the natural evolution of AD (disease modifying) requires the implementation of innovative therapeutic tries with a significant number of subjects, a long period of observation and where the only clinical criteria of evaluation seem insufficient. The use of biomarkers of plasma, cerebrospinal fluid, or neuro-imaging could play an important role to estimate their efficiency. However, at present no biomarker is validated as surrogate endpoint. It seems today indispensable to use them in the therapeutic tries so as to validate and standardize their methods of acquisition, measure and analysis.


Sticky complexes: carboxylic acid-functionalized N-phenylpyridin-2-ylmethanimine ligands as anchoring domains for copper and ruthenium dye-sensitized solar cells.
Four members of a series of N-phenylpyridin-2-ylmethanimine ligands (L) decorated with carboxylic acid functionalities have been prepared. The ligand design allows a copper(i) complex [CuL(2)](+) to bind to a TiO(2) surface through the simultaneous use of two carboxylate anchoring domains. Complexes of the type [CuL(2)][PF(6)], [CuL(NCMe)(2)][PF(6)] and [Ru(bpy)(2)L][PF(6)](2) have been synthesized and characterized by (1)H and (13)C NMR and electronic absorption spectroscopies, mass spectrometry and, for four of the complexes, single crystal X-ray diffraction. Dye-sensitized solar cells (DSCs) have been fabricated using the new complexes and the performances of the dyes assessed. The copper(I) complexes show good surface coverage and tuning of the electrolyte and the electronic properties of the ligands is now required to enhance the efficiencies of the DSCs.


Use of nonsteroidal antiinflammatory drugs in dental practice. A review.
Nonsteroidal antiinflammatory drugs (NSAIDs) are drugs commonly prescribed in dental practice for the management of pain and swelling. Of these substances, paracetamol and ibuprofen are the most widely used. Their mechanism of action is based on the inhibition of cyclooxygenase, and therefore of prostaglandin synthesis. All of these drugs present a similar mechanism of action, as a result of which their side effects are also similar. The most frequent range from mild (e.g., nausea or vomiting) to serious gastric problems (such as gastric bleeding or perforation). Other side effects include an increased risk of vascular accidents (particularly acute myocardial infarction), renal toxicity secondary to a decrease in perfusion, and the risk of abnormal bleeding tendency due to the antiplatelet effect of these drugs. Their use is contraindicated in the third trimester of pregnancy, due to the induction of premature ductus arteriosus closure. The present study reviews the information currently available on NSAIDs, with special emphasis on those aspects related to dental practice.


Smaller Australian raptors have greater urban tolerance.
Urbanisation is occurring around the world at a rapid rate and is generally associated with negative impacts on biodiversity at local, regional, and global scales. Examining the behavioural response profiles of wildlife to urbanisation helps differentiate between species that do or do not show adaptive responses to changing landscapes and hence are more or less likely to persist in such environments. Species-specific responses to urbanisation are poorly understood in the Southern Hemisphere compared to the Northern Hemisphere, where most of the published literature is focussed. This is also true for raptors, despite their high diversity and comparably high conservation concern in the Southern Hemisphere, and their critical role within ecosystems as bioindicators of environmental health. Here, we explore this knowledge gap using community science data sourced from eBird to investigate the urban tolerance of 24 Australian raptor species at a continental scale. We integrated eBird data with a global continuous measure of urbanisation, artificial light at night (ALAN), to derive an urban tolerance index, ranking species from positive to negative responses according to their tolerance of urban environments. We then gathered trait data from the published literature to assess whether certain traits (body mass, nest substrate, habitat type, feeding guild, and migratory status) were associated with urban tolerance. Body size was negatively associated with urban tolerance, as smaller raptors had greater urban tolerance than larger raptors. Out of the 24 species analysed, 13 species showed tolerance profiles for urban environments (positive response), and 11 species showed avoidance profiles for urban environments (negative response). The results of this study provide impetus to conserve native habitat and improve urban conditions for larger-bodied raptor species to conserve Australian raptor diversity in an increasingly urbanised world.


Characterization of long-term monolayer cultures of human granulosa cells from follicles of different size and exposed in vivo to clomiphene citrate and hCG.
To determine the effects of prolonged hCG treatment in vitro upon granulosa cells from follicles of various sizes previously exposed to clomiphene citrate and hCG in vivo, progesterone and relaxin concentrations of spent media were correlated with light microscopic and ultrastructural characteristics. Intact, freshly dispersed cells were characterized by numerous lipid droplets, elliptical mitochondria with tubular or lamellar cristae, moderate rough-surfaced endoplasmic reticulum (RER), sparse smooth-surfaced endoplasmic reticulum (SER), and few Golgi. After 10-24 days in culture, 2 morphologically distinct cell types, 'granulosa-type' and 'luteal-type', were noted at the light microscopic level. Ultrastructurally, lipid droplets decreased in number, mitochondria became pleomorphic, RER became more prominent and dilated, and Golgi became more widely dispersed. Tubular SER became abundant and annular nexuses became more numerous after hCG treatment in vitro. Granulosa cells generated from all follicles responded to hCG treatment with significantly increased progesterone secretion after 4 days in culture. Relaxin was not detectable in any sample of medium. This study shows that human granulosa cells from 15-25-mm follicles retain their differentiated function of progesterone secretion in long-term culture and recover responsiveness to hCG in vitro, as demonstrated by enhanced progesterone secretion and development of prominent SER and increased annular nexuses.


Induction of human cytochrome P450 3A4 by the irreversible myeloperoxidase inactivator PF-06282999 is mediated by the pregnane X receptor.
1. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide (PF-06282999) is a member of the thiouracil class of irreversible inactivators of human myeloperoxidase enzyme and a candidate for the treatment of cardiovascular disease. PF-06282999 is an inducer of CYP3A4 mRNA and midazolam-1'-hydroxylase activity in human hepatocytes, which is consistent with PF-06282999-dose dependent decreases in mean maximal plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) of midazolam in humans following 14-day treatment with PF-06282999. 2. In the present study, the biochemical mechanism(s) of CYP3A4 induction by PF-06282999 was studied. Incubations in reporter cells indicated that PF-06282999 selectively activated human pregnane X receptor (PXR). Treatment of human HepaRG cells with PF-06282999 led to ∼14-fold induction in CYP3A4 mRNA and 5-fold increase in midazolam-1'-hydroxylase activity, which was nullified in PXR-knock out HepaRG cells. TaqMan® gene expression analysis of human hepatocytes treated with PF-06282999 and the prototypical PXR agonist rifampin demonstrated increases in mRNA for CYP3A4 and related CYPs that are regulated by PXR. 3. Docking studies using a published human PXR crystal structure provided insights into the molecular basis for PXR activation by PF-06282999. Implementation of PXR transactivation assays in a follow-on discovery campaign should aid in the identification of back-up compounds devoid of PXR activation and CYP3A4 induction liability.


The nature of adolescents' relationships with their "very important" nonparental adults.
As part of a larger program of research on the nature of adolescents' relationships with very important nonparental adults (hereafter referred to as "VIPs"), a community sample of 243 eleventh graders (mean age = 16.6 years) was surveyed, and a subgroup of 55 adolescents and their VIPs were interviewed about the nature and quality of their relationships. Results showed that (a) adolescent-VIP relationships were a normative component of adolescent development, not a result of problems in adolescents' lives; (b) adolescent-VIP relationships were generally of high quality (e.g., high support, low conflict, and high mutuality); (c) there were significant differences between kin and nonkin VIPs in terms of the duration of relationships and frequency of contact, but not in the quality of relationships; and (d) VIPs whom adolescents designated as extremely important were distinguished from other VIPs in terms of providing a higher level of social support and a higher frequency of contact. Theoretical and practical implications of these findings are discussed.


Increase of large granular lymphocytes in human ejaculate containing antisperm antibodies.
Using flow cytometry, we studied the expression of the CD16 antigen by lymphocytes present in human semen samples from three groups of patients: 60 fertile men attending for vasectomy, 60 sterile patients without antisperm antibodies (ASA) and 18 immunological sterile patients with ASA in their ejaculate. No significant difference was found in the concentration of leukocytes or subpopulations of these cells (monocytes, lymphocytes and granulocytes) between fertile, sterile without ASA and immunological sterile groups. However, we detected a predominance of macrophages/monocytes within the population of seminal leukocytes. No statistically significant difference was found in the absolute number of T and B lymphocytes between the three groups studied. However, a significant increase in the number of CD16+ lymphocytes was observed in the ejaculate of sterile patients with ASA as compared to the other groups. This finding might establish an important parameter in the follow-up and prognosis of patients with immunological sterility.