Quality of Life of Patients With Chronic Venous Insufficiency of the Lower Extremities Before and After Endovascular Laser Ablation: A Prospective Pilot Study Using the Chronic Venous Insufficiency Quality of Life Questionnaire 20 (CIVIQ-20).
Background Chronic venous insufficiency of the lower extremities is a condition in which blood stagnates in the venous system, causing symptoms of pain, fatigue, leg edema, and cramps. Although this disease progresses slowly and is not fatal, its symptoms lead to a decline in quality of life, affecting the patient's work. One of the current surgical treatment methods for patients with indications for surgical removal of the saphenous vein is endovenous laser ablation (EVLA). After EVLA, besides evaluating the effectiveness of surgery, and the rate of complications, one of the aspects that need attention is improving quality of life. The objective of this study was to assess the quality of life of patients with chronic venous insufficiency of the lower extremities before and after endovascular laser intervention, analyzing changes in ChronIc Venous Insufficiency Quality of Life Questionnaire 20 (CIVIQ-20) scores in each domain of quality of life. Methodology A total of 41 patients with chronic venous insufficiency of the lower extremities were enrolled in this study, who were classified as C2 to C6 and were treated by endovenous laser ablation. QoL was measured by using the ChronIc Venous Insufficiency Quality of Life Questionnaire 20 (CIVIQ-20) questionnaire pre- and post-operatively. Pain scores and clinical severity were also evaluated using the visual analog scale (VAS) and the venous clinical severity score (VCSS) one month after EVLA. Results The mean age was 52.17 ± 11.23 years. The mean duration of symptoms was 7.29 ± 3.58 years, the median laser ablation time was 40 minutes, and the mean time to return to normal activities was 5.7 ± 1.8 days. The CIVIQ-20 score at baseline was 47.8 ± 7.4 and 31.1 ± 3.9 after one-month laser ablation. The quality of life has significantly improved after intervention using laser treatment (p < 0.001). The VAS and VCSS scores after laser treatment were lower than the baseline (p < 0.001). In our study, there was a statistically significant correlation between the change of CIVIQ-20 and the change of VCSS (r = 0.63, p < 0.001). Conclusion CIVIQ-20 is a reliable toolkit to assess the quality of life of patients with chronic venous insufficiency of the lower extremities. The patient's quality of life improved markedly after the intervention.


An innovative MWCNTs/DOX/TC nanosystem for chemo-photothermal combination therapy of cancer.
Chemotherapy and photothermal therapy can be efficiently integrated to achieve enhanced antitumor efficacy by using carbon nanotubes (CNTs) which are super in delivering drug and converting near infrared radiation (NIR) into heat. We previously developed an innovative TAT-chitosan functionalized MWCNTs (MWCNTs/TC) based drug delivery system for doxorubicin (DOX) and preliminarily investigated its release profile and antitumor effect. In the present study, the application potential of MWCNTs/DOX/TC in chemo-photothermal combination therapy was further explored. The in vitro drug release, photothermal effect, cellular uptake and cytotoxicity were assessed. The in vivo anti-tumor effect of MWCNTs/DOX/TC was further evaluated by noninvasive bioluminescence imaging. It was demonstrated that this innovative drug delivery system not only realized a conspicuously sustained release of DOX, but also retained the optical properties of MWCNTs for a high photothermal effect upon NIR irradiation, and exhibited remarkably enhanced anti-tumor efficacy through the synergistic function of chemotherapy and photothermal ablation.


Comparative Study on Proton Conductivity and Mechanism Analysis of Two Imidazole Modified Imine-Based Covalent Organic Frameworks.
This work elucidates the potential impact of intramolecular H-bonds within the pore walls of covalent organic frameworks (COFs) on proton conductivity. Employing DaTta and TaTta as representative hosts, it was observed that their innate proton conductivities (σ) are both unsatisfactory and σ(DaTta)<σ(TaTta). Intriguingly, the performance of both imidazole-loaded products, Im@DaTta and Im@TaTta is greatly improved, and the σ of Im@DaTta (0.91×10-2 S cm-1 ) even surpasses that of Im@TaTta (3.73×10-3 S cm-1 ) under 100 °C and 98 % relative humidity. The structural analysis, gas adsorption tests, and activation energy calculations forecast the influence of imidazole on the H-bonded system within the framework, leading to observed changes in proton conductivity. It is hypothesized that intramolecular H-bonds within the COF framework impede efficient proton transmission. Nevertheless, the inclusion of an imidazole group disrupts these intramolecular bonds, leading to the formation of an abundance of intermolecular H-bonds within the pore channels, thus contributing to a dramatic increase in proton conductivity. The related calculation of Density Functional Theory (DFT) provides further evidence for this inference.


Influence of the extracellular matrix on the regulation of cardiac fibroblast behavior by mechanical stretch.
Fibroblasts are responsible in large part for production, organization, and turnover of the extracellular matrix (ECM), thereby regulating the fibrotic content of the heart. Excessive fibrosis, which has been associated with certain forms of hemodynamic overload such as hypertension, is thought to result in increased ventricular chamber stiffness, and eventual heart failure. As such, the role of mechanical stretch in regulating fibroblast activity is crucial to our understanding of healthy and diseased hearts. However, little is known about the effects of alterations in the composition of the ECM in regulating mechanotransduction in cardiac fibroblasts. In order to address this question, rat cardiac fibroblasts were cultured on silastic membranes coated with different ECM substrates, and cyclically stretched for various durations. Experiments were designed to assess the activation of signaling pathways, as well as changes in collagen production, cellular proliferation, and morphology. Mitogen activated protein kinase (MAP kinase) was most rapidly activated, and collagen I expression was most abundant, in cells stretched on randomly organized collagen, and uncoated charged membranes. Regardless of the nature of the ECM substrate, stretched cells decreased proliferation, however, this effect was most marked in cells stretched on randomly organized collagen. Finally, cells stretched on all ECM substrates increased their surface area, but this was observed most significantly in cells adherent to aligned collagen, randomly organized collagen, and uncoated, charged membranes. Taken together, these results suggest cardiac fibroblasts may differentially interpret a mechanical stimulus, in terms of both signal transduction, and specific long-term events such as gene transcription, based on the composition and organization of the ECM.


[The prognostic role of Ki-67 in childhood low-grade glioma].
Gliomas currently represent a group of uncommon diseases originating from glial elements. According to their biologic features they can be distinguished in low-grade gliomas--not very aggressive and with a poor tendency to progression--and high-grade gliomas--with a greater proliferative drive and aggressiveness. Such definitions outline two distinct disease types, which profoundly differ as for epidemiological, clinical, diagnostic and molecular features. The introduction of biomolecular techniques has provided a deeper knowledge of low-grade gliomas: the use of new molecular markers, such as Ki-67, makes it possible to study peculiar features of the neoplasm, with strong prognostic implications. Nonetheless, in the literature there is still no agreement on their role, nor on their prognostic validity in pediatric age, also because the criteria that are currently used for adult patients haven't still been codified for pediatric age.


Synthesis and characterisation of transition metal halide complexes of the xylyl-distibine, 1,2-bis(dimethylstibanylmethyl)benzene.
Complexes of the title ligand with Cu(I), Ag(I), Au(I), Pd(II), Pt(II), Rh(III), and rare examples with Ni(II) and Co(III) have been prepared and characterised by analysis, IR, UV-vis, 1H, 63Cu and 59Co NMR spectroscopy and ES+ mass spectrometry as appropriate. The structures of [Cu[1,2-C6H4(CH2SbMe2)2]2]BF4, [PtCl2[1,2-C6H4(CH2SbMe2)2]], [M[1,2-C6H4(CH2SbMe2)2]2][PF6]2 (M = Pd or Pt), and [NiI[1,2-C6H4(CH2SbMe2)2]2]ClO4 have been determined, and the varying chelate bite and conformations of the xylyl backbone in these structures are discussed. Despite the unfavourable seven-membered chelate ring and the large soft antimony donors, 1,2-C6H4(CH2SbMe2)2 proves to be a surprisingly good ligand for late transition metals in medium oxidation states.


Sequential intravenous/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection.
In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.


Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal Stem Cells.
Light is a non-invasive tool that is widely used in a range of biomedical applications. Techniques such as photopolymerization, photodegradation, and photouncaging can be used to alter the chemical and physical properties of biomaterials in the presence of live cells. Long-wave UV light (315 nm-400 nm) is an easily accessible and commonly used energy source for triggering biomaterial changes. Although exposure to low doses of long-wave UV light is generally accepted as biocompatible, most studies employing this wavelength only establish cell viability, ignoring other possible (non-toxic) effects. Since light exposure of wavelengths longer than 315 nm may potentially induce changes in cell behavior, we examined changes in gene expression of human mesenchymal stem cells exposed to light under both 2D and 3D culture conditions, including two different hydrogel fabrication techniques, decoupling UV exposure and radical generation. While exposure to long-wave UV light did not induce significant changes in gene expression regardless of culture conditions, significant changes were observed due to scaffold fabrication chemistry and between cells plated in 2D versus encapsulated in 3D scaffolds. In order to facilitate others in searching for more specific changes between the many conditions, the full data set is available on Gene Expression Omnibus for querying.


Diversity and spatiotemporal distribution of larval odonate assemblages in temperate neotropical farm ponds.
Farm ponds help maintain diversity in altered landscapes. However, studies on the features that drive this type of property in the Neotropics are still lacking, especially for the insect fauna. We analyzed the spatial and temporal distribution of odonate larval assemblages in farm ponds. Odonates were sampled monthly at four farm ponds from March 2008 to February 2009 in a temperate montane region of southern Brazil. A small number of genera were frequent and accounted for most of the dominant fauna. The dominant genera composition differed among ponds. Local spatial drivers such as area, hydroperiod, and margin vegetation structure likely explain these results more than spatial predictors due to the small size of the study area. Circular analysis detected seasonal effect on assemblage abundance but not on richness. Seasonality in abundance was related to the life cycles of a few dominant genera. This result was explained by temperature and not rainfall due to the temperate climate of the region studied. The persistence of dominant genera and the sparse occurrence of many taxa over time probably led to a lack in a seasonal pattern in assemblage richness.


[Elderlies in street situation or social vulnerability: facilities and difficulties in the use of computational tools].
This study aimed to identify the advantages and difficulties encountered by older people living on the streets or social vulnerability, to use the computer or internet. It is an exploratory qualitative research, in which five elderlies, attended on a non-governmental organization located in the city of São Paulo, have participated. The discourses were analyzed by content analysis technique and showed, as facilities, among others, to clarify doubts with the monitors, the stimulus for new discoveries coupled with proactivity and curiosity, and develop new skills. The mentioned difficulties were related to physical or cognitive issues, lack of instructor, and lack of knowledge to interact with the machine. The studies focusing on the elderly population living on the streets or in social vulnerability may contribute with evidence to guide the formulation of public policies to this population.


Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα.
Encephalomyocarditis virus (EMCV), like hepatitis C virus (HCV), requires phosphatidylinositol 4-kinase IIIα (PI4KA) for genome replication. Here, we demonstrate that tyrphostin AG1478, a known epidermal growth factor receptor (EGFR) inhibitor, also inhibits PI4KA activity, both in vitro and in cells. AG1478 impaired replication of EMCV and HCV but not that of an EMCV mutant previously shown to escape PI4KA inhibition. This work uncovers novel cellular and antiviral properties of AG1478, a compound previously regarded only as a cancer chemotherapy agent.


The Effect of Intraoperative N-Acetylcysteine on Hepatocellular Injury During Laparoscopic Bariatric Surgery. A Randomised Controlled Trial.
The combination of pneumoperitoneum and intraoperative retraction of the left lobe of the liver leads to hepatocellular injury during laparoscopic gastric surgery. Fatty livers are more susceptible to ischaemic insults. This trial investigated whether the antioxidant N-acetylcysteine (NAC) reduced liver injury during laparoscopic sleeve gastrectomy (LSG). Patients undergoing LSG were randomised (single blinded) to receive intraoperative NAC infusion or standard anaesthetic treatment. Blood samples were taken before and after surgery (days 0 to 4). Primary endpoints included serum aminotransferases. Secondary measures were C-reactive protein, weight cell count (WCC), cytokines (interleukin 6 and 10) and cytokeratin-18 as markers of apoptosis. Intraoperative liver biopsy samples were assessed using a locally developed injury score. Twenty patients (14 females, mean age 44.5 (SEM ± 2.9) years, mean BMI 60.8 (SEM ± 2.4) kg/m(2)) were recruited (NAC n = 10, control n = 10). The trial was stopped early after a planned interim analysis. Baseline liver function was similar. The peak rise in liver enzymes was on day 1, but levels were not significantly different between the groups. Rates of complications and length of stay were not significantly different. Secondary outcome measures, including white cell count (WCC), cytokines and cytokeratin (CK)-18 fragments, were not different between groups. Liver injury scores did not differ significantly. NAC did not reduce intraoperative liver injury in this small number of patients. The heterogenous nature of the study population, with differences in co-morbidities, body mass index and intraabdominal anatomy, leads to a varied post-operative inflammatory response. Significant hepatocyte injury occurs through both necrosis and apoptosis.


Feasibility of Internet training for care staff of residents with dementia: the CARES program.
This study evaluated an Internet-based training module, CARES(®) (Connect with the resident; Assess behavior; Respond appropriately; Evaluate what works; Share with the team), to determine its feasibility for certified nursing assistants (CNAs) in three nursing homes and one assisted living facility. Pre- and posttest questionnaires were administered to 40 CNAs to determine improvements in dementia care knowledge and perceptions of competence in dementia care. Dementia care knowledge improved significantly after CARES training. More than 85% of the sample agreed or strongly agreed that the CARES protocol improved mastery, improved care competency, and reduced stress related to care of residents with dementia. Open-ended feedback indicated that CARES provided CNAs with new information and skills pertaining to dementia care. The results suggest that Internet-based programs such as CARES represent time- and cost-efficient methods to deliver dementia care training in long-term care settings.


Something of a curate's egg: comments on Adrian Harvey's An epoch in the annals of national sport.
This short review is an attempt to establish the balance of strengths and weaknesses in Harvey's essay. Its strengths seem to be principally two: (i) although he exaggerates its significance, Harvey is right to draw attention to the vibrant football culture that grew up in the Sheffield area in the 1850s and 60s; (ii) he is also right (and so is Goulstone) to point to the evidence for matches between pub sides of equal though variable numbers in the early nineteenth century. To my knowledge, this evidence is new and alters our understanding of the development of football in that period. However, the weaknesses in Harvey's case arguably outweigh its strengths. For example, he misconstrues the meaning of 'football' in medieval and early modern sources, wrongly assuming that the term referred to an entirely kicking game. Furthermore, Harvey's grounds for rejecting the influence of the public schools, especially Eton, on Sheffield football are flimsier than the admittedly scarce counter-evidence. Most importantly of all, Harvey shows a limited awareness of the variety of types of football that there were in these islands in the early nineteenth century and fails to situate his claims adequately in relation to the wider literature. In this connection, in his desire to downplay the role of the public schools, he neglects altogether the sociologically plausible suggestion that the initial bifurcation of rugby and soccer can be traced to Rugby-Eton rivalry in the 1840s.


Revalidation of Synonymy between Nesotriatoma flavida and N. bruneri (Hemiptera, Reduviidae, Triatominae).
We analyzed the external morphology and the external male genitalia of specimens of Nesotriatoma flavida of a laboratory colony founded with specimens from Guanahacabiles in Pinar del Río Province in the west of Cuba in 1980. This species was at first identified as different from N. bruneri and then later considered synonymous. We proposed to revise the morphological characters with which these species were considered as different and then later synonymous, such as the fossula spongiosa or spongy grooves, length of the first antenna segment, relationship length of eye to interocular distance, the form of the phallosome, phallosome support, and the endosome processes. The results of the analyses of these characters in the specimens of our colony, and of the corresponding works where the separation and synonymy of these species has been proposed, allow us to sustain the revalidation of the synonymy between N. flavida and N. bruneri. Based on the body external morphology and the male external genitalia of N. flavida it is concluded that N. flavida and N. bruneri are synonymous species.


Overexpression of long non-coding RNA LINC00982 suppresses cell proliferation and tumor growth of papillary thyroid carcinoma through PI3K-ATK signaling pathway.
Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan-Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.


Changes of brachial flow-mediated vasodilation in different ischemic stroke subtypes.
The relationship between endothelial dysfunction and stroke subtypes is unclear. We prospectively measured brachial flow-mediated vasodilation (FMD) in 143 patients with acute ischemic stroke and 40 controls. The overall stroke patients had impaired FMD, but only lacunar infarction had significantly impaired FMD vs the controls. Impaired FMD was an independent predictor for lacunar infarction. Ischemic stroke is associated with endothelial dysfunction, which is more conspicuous in lacunar infarction.


A study of patients whose mode of food intake changed during long-term bedside care.
Hatakeyama M, Shirahase M, Suzuki S, Morita K, Yamashita S. A study of patients whose mode of food intake changed during long-term bedside care. Jpn J Compr Rehabil Sci 2023; 14: 60-68. The objective of this study was to determine the characteristics of patients who exhibited changes in their food intake level (as determined by the Food Intake Level Scale [FILS] score) while hospitalized for long-term bedside care. The subjects were 264 patients hospitalized for long-term bedside care. The FILS was used to assess the subjects' mode of food intake on the admission and survey dates. The FILS score was used to divide the patients into three stages: no oral intake, combined oral intake and alternative nutrition, and exclusively oral intake; the patients whose FILS stage on the survey date was different from that on the admission date were examined to determine whether there were any characteristic tendencies with regard to their age, sex, length of hospital stay, level of long-term care needed, primary illness, and dysphagia rehabilitation. Overall, 6.8%, 9.8%, and 4.5% of the subjects showed improvement in the FILS stage, experienced deterioration of the FILS stage, and transitioned to exclusively oral intake, respectively. Further, 33.3% of the improved-FILS stage group were in their ≥90s. The results of the exact binomial test with the entire study cohort as the population proportion showed that there were significantly more females in the improved-FILS group. In addition, 83.3% of those who improved from no oral intake to exclusively oral intake had cerebrovascular disease. No difference in the length of hospital stay and level of long-term care needed was observed in either the improved-FILS or deteriorated-FILS group in comparison to their proportions in the entire study cohort. In the entire study cohort, a greater proportion of the subjects in the improved-FILS group underwent indirect or direct swallowing training than those in the deteriorated-FILS group; the improved-FILS group had no subjects who were assigned to watchful waiting. Most patients who exhibited marked positive changes in their mode of food intake were females or patients with cerebrovascular disease. However, no characteristic attributes were observed among those whose FILS stage deteriorated.


[Arterioportal fistula and hemobilia in a patient with hepatic transplant].
The case of a 36-year old male liver transplant recipient hospitalized for upper digestive hemorrhage, jaundice and pain in the right hypochondrium is herein reported. Two hepatic biopsies had been performed 60 and 7 days prior to admission. Bleeding was observed to be from the biliary tract by endoscopy and an arterioportal fistula in the right hepatic lobe by echo-doppler and arteriography was seen. Treatment with selective embolization by arteriography was satisfactory with biliary tract drainage not being required. Doppler echography was used to control the evolution of the patient.


HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers.
The serotonin 2C (HTR2C) and 1A (HTR1A) receptors have been involved in suicide-related behaviors. We studied gene variants of both receptors in suicide attempters and completers. The sample was composed of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide, 312 German healthy subjects, 152 Italian suicide attempters (major depression n = 68 and bipolar disorder n = 84), and 131 Italian healthy volunteers. HTR2C (SNP: rs547536, rs2192372, rs6318, rs2428707, rs4272555, rs1801412) and HTR1A (SNP: rs1423691, rs878567, and rs6295) variants were analyzed in the German sample. HTR2C rs6318 and HTR1A rs6295 were analyzed in the Italian sample. Haplotype analysis in relation to suicidal behaviors did not reveal any significant association. Single markers and haplotypes were not or only marginally associated with other related features, such as violence of suicide attempt, family history for suicide attempt or State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the notion that HTR2C and HTR1A gene variants are major contributors to suicide-, anger-, or aggression-related behaviors in our sample.


Severe allergic blepharoconjunctivitis induced by a dye for eyelashes and eyebrows.
To report a case of severe allergic blepharoconjunctivitis induced by a dye for eyebrows and eyelashes. A 38-year-old healthy female was examined one day after dyeing her eyebrows and eyelashes with a black cream dye intended for this purpose (FDA-approved). The patient complained of severe eye itching, redness, and epiphora. Vision was 20/40 in both eyes; a moderate edema of the eyebrows and eyelid margins was noted. The conjunctiva was severely hyperemic with papillary reaction and chemosis. The corneas, anterior chambers, irides, lenses, and posterior segments were normal. The patient was treated with Dexamethasone 0.1% and ocular lubrication. After five days of treatment, the ocular symptoms improved, her vision returned to 20/20 in both eyes, and the ocular examination was within normal limits. FDA-approved dyes for eyebrows and eyelashes can sometimes irritate the ocular surface.


Characterization of the thrombin generation profile in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.


Non-attendance and drop-out in cardiac rehabilitation among patients with ischaemic heart disease.
Previous studies have shown drop-out from cardiac rehabilitation (CR) to have prognostic influence on morbidity and mortality among patients with ischaemic heart disease (IHD). We aimed to identify and clarify patients' reasons for non-attendance and drop-out from CR. A total of 872 consecutive patients with acute myocardial infarction and/or after percutaneous coronary intervention or coronary artery bypass surgery were asked by conventional mail to fill in a self-completion questionnaire on their choice of post-hospital CR and their reasons for drop-out or for non-attendance. Age, employment and marital status had a statistically significant influence on the overall course of CR. Younger age, affiliation with the labour market and living alone were related to a higher drop-out from CR in univariate analysis. We found no evidence of a gender difference among the patients who withdrew. Lack of time was stated as the prevailing reason for non-attendance and withdrawal from CR programmes among employed patients and in people aged 65 years or younger. Patients above 75 years of age asked for additional differentiation of exercise levels; currently two levels are offered. Or they found CR meaningless given their physical condition or their overall life situation. In patients with IHD, age, marital status and employment status play a role in the patient's attendance or drop out from CR. Different physical conditions, lack of time, too great a distance from residence to hospital, transport problems and lack of understanding of the benefits of CR explain why patients refuse to participate in or drop-out from CR. supported by grant from The Danish Ministry of Health. not relevant.


Pain and its interference with daily activities in medical oncology outpatients.
Pain prevalence at various stages of cancer ranges from 27% to 60% for outpatients. Yet, how pain is managed in this patient group is poorly understood. The primary objective was to assess pain prevalence and intensity, and its interference with daily activities, in medical oncology outpatients. The secondary objectives were the adequacy of analgesic pain treatment and to identify independent predictors for moderate to severe pain. A cross-sectional study. Oncology outpatient clinics of 7 Dutch regional hospitals. Four hundred twenty-eight medical oncology outpatients were assigned to the study. Pain prevalence and interference of pain with daily activities were assessed using the Brief Pain Inventory. Adequacy of analgesic treatment was determined by calculating the Pain Management Index (PMI). Descriptive statistics, non-parametric tests, and logistic regression analysis were conducted. More than one third of all participants reported pain (39%). Eighty-three patients (20%) had moderate to severe pain (NRS 5-10). Analgesic treatment was inadequate in more than half of the patients with pain (62%). Interference of pain with daily activities increased with increased intensity, yet even 10%-33% of patients suffering mild pain reported high interference with daily activities. High current pain intensity and high interference with general daily activities predicted moderate to severe pain. No characteristics of nonparticipants were available. Pain remains a significant problem in medical oncology outpatients, and often pain is insufficiently managed. Patients with a high pain intensity were more at risk to experience pain related interference with daily activities, but even some patients suffering mild pain experienced this. As adequate pain relief for up to 86% of the patients with cancer should be feasible, pain in medical oncology outpatients is still undertreated. Taking into account the interference of pain with daily activities and predictors of pain will facilitate cancer pain management. The study has been approved by the Medical Ethics Committee (CMO) in all 7 hospitals (METC protocol number 2011/020) and has been registered by the Dutch Trial register (NTR): NTR2739.


A single-cell gene expression atlas of human follicular aspirates: Identification of leukocyte subpopulations and their paracrine factors.
Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA-seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can directly impact granulosa cell function by activating their receptors (e.g., cytokines and secretory ligands) and are involved in tissue remodeling (e.g., MMPs, ADAMs, ADAMTSs, and TIMPs) and angiogenesis (e.g., VEGFs, PGF, FGF, IGF, and THBS1) in ovulatory follicles. Consistent with the findings from the scRNA-seq data, the leukocyte-specific expression of CD68, IL1B, and MMP9 was verified in follicle tissues collected before and at defined hours after hCG administration from regularly cycling women. Collectively, this study demonstrates that this data can be used as an invaluable resource for identifying important leukocyte-derived factors that promote follicular cell function, thereby facilitating ovulation and luteinization in women.


Effect of ethanol on metarhodopsin II formation is potentiated by phospholipid polyunsaturation.
The role of phospholipids in modulating the effect of ethanol on membrane receptor activation was investigated by studying the extent of metarhodopsin II (MII) formation in vesicles formed POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and PDPC (1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine) and in native rod outer segment disk membranes as a function of ethanol concentration. The equilibrium concentration of MII, the G protein-activating form of photoactivated rhodopsin, was found to increase as a function of ethanol concentration in all three bilayers. Phospholipid composition had a marked effect on ethanol potency, with the presence of polyunsaturated phospholipid acyl chains increasing ethanol potency by 40%. The effects of ethanol on lipid acyl chain packing in POPC and PDPC were investigated using frequency domain anisotropy decay measurements of the fluorescent membrane probe 1,6-diphenyl-1,3,5-hexatriene. Enhanced formation of MII due to the presence of ethanol was correlated with the effects of ethanol on acyl chain packing properties. These findings support a phospholipid-mediated mechanism for the action of ethanol in modulating integral membrane receptor conformation.


Yamaguchi Facial Expression-Making Task in Alzheimer's Disease: A Novel and Enjoyable Make-a-Face Game.
To assess the ability to make emotional facial expressions, we newly developed the Yamaguchi facial expression-making task (Y-FEMT). We recruited 20 normal controls and 61 outpatients: 10 with amnestic mild cognitive impairment (aMCI), 34 with mild Alzheimer's disease (AD), and 17 with moderate AD. In the Y-FEMT, smile and anger expressions were made by arranging face parts. We examined the relationship between each Y-FEMT score and the Mini-Mental State Examination (MMSE) score or overlapping figure identification test (Fig-test). The Total score (0-20) was nearly achieved in controls (18.9 ± 1.4) and declined with AD progression (aMCI 17.2 ± 2.4, mild AD 15.7 ± 2.6, moderate AD 12.3 ± 2.7). The Anger score (0-10) was significantly lower than the Smile score (0-10) in mild and moderate AD (p = 0.007 and p = 0.006, respectively). The Structure score (0-6 each) correlated well with both the MMSE score (r = 0.44, p < 0.001) and Fig-test (r = 0.45, p < 0.001), whereas the Expression score (0-4 each) correlated only with the MMSE score (r = 0.33, p = 0.01). The Subjective scores (0-4), evaluated by 10 therapists, highly correlated with the Total score. Additionally, the Y-FEMT promoted laughter and a convivial atmosphere. The Y-FEMT pleasantly assessed the ability to make emotional facial expressions without special equipment. Furthermore, the Y-FEMT may provide helpful clues for caregivers to achieve good communication with AD patients for better care.


Differential ontogeny of divalent cation effects on rat brain delta-, mu-, and kappa-opioid receptor binding.
The effect of the divalent cations, Mn2+, Mg2+ and Ca2+ on rat forebrain delta-, mu- and kappa-receptor binding was examined during postnatal development. It was found that delta-receptor binding, assessed with [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) (+ 10 nM D-Ala2- MePhe4-Gly-ol5-enkephalin (DAMGE)), was stimulated by the 3 cations in a dose- and developmental time-dependent manner. delta-Binding was most sensitive to the cations during the first week postnatal, prior to the appearance of high-affinity delta-binding. In contrast, inhibition of mu-receptor binding ([3H]DAMGE) by divalent cations appeared early in development and remained constant throughout the postnatal period. Divalent cation inhibition of kappa-binding ([3H]ethylketocyclazocine ([3H]EKC) + 100 nM DAMGE and 100 nM DADLE) appeared after the second week postnatal. These results demonstrate that the characteristics and postnatal development of divalent cation modulation of mu-, delta- and kappa-binding is distinctly different. Thus, the neonate may be a good model system to examine the binding properties and functions of delta- and kappa-receptor subtypes.


Bioethanol production from Chlorella vulgaris ESP-31 grown in unsterilized swine wastewater.
The potential of microalgae to remove nutrients from swine wastewater and accumulate carbohydrates was examined. Chlorella sorokiniana AK-1 and Chlorella vulgaris ESP-31 were grown in 10% unsterilized swine wastewater and obtained a maximum carbohydrate content and productivity of 42.5% and 189 mg L-1d-1, respectively. At 25% wastewater and 25% BG-11 concentration, the maximum carbohydrate productivity and total nitrogen removal efficiency of C. vulgaris ESP-31 were improved to 266 mg L-1d-1 and 54.2%, respectively. Further modifications in light intensity, inoculum size, and harvesting period enhanced the biomass growth, carbohydrate concentration, and total nitrogen assimilation to 3.6 gL-1, 1.8 gL-1, and 92.2%, respectively. Ethanol fermentation of the biomass resulted in bioethanol yield and concentration of 84.2% and 4.2 gL-1, respectively. Overall, unsterilized swine wastewater was demonstrated as a cost-effective nutrient source for microalgal cultivation which further increases the economic feasibility and environmental compatibility of bioethanol production with concomitant swine wastewater treatment.


Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents.
Thirty-one patients with hepatocellular carcinoma (HCC) were given either an intraarterial injection of iodized poppyseed oil (Lipiodol) alone (group A, n = 6), an emulsion of iodized oil and doxorubicin hydrochloride (Adriamycin) (group B, n = 15), or chemoembolization with the same emulsion followed by gelatin sponge (Gelfoam) particles (group C, n = 10). Hepatic resection was subsequently performed. The frequencies of complete necrosis of tumor in the main lesion, daughter tumors, tumor thrombus, and foci of intracapsular invasion were evaluated in the cut surface of the resected specimen. Group C demonstrated the best therapeutic effects, showing complete necrosis of the main lesion in 83% (P less than .01), daughter tumors in 53% (P less than .01), tumor thrombus in 17%, and foci of intracapsular invasion in 67%. These results are superior to those reported previously for chemoembolization without iodized oil. Group B showed better results than group A, but the difference was not significant. Iodized oil alone (group A) had practically no therapeutic effect but was helpful in differentiating small HCC from regenerative nodules.


A novel effect of the new antileukemic drug, 2-chloro-2'-deoxyadenosine, in human lymphocytes.
2-chloro-2'-deoxyadenosine (Cl-dAdo) is a potent drug against hairy cell leukemia and other lymphomas. Its effects on the metabolism of labeled deoxycytidine (5-[3H]dCyd) and deoxythymidine ([3H]dThd) were investigated in short term cultures of human lymphocytes. In the presence of Cl-dAdo, a more pronounced inhibition of DNA synthesis was found, accompanied with a much higher accumulation of radioactivity in dTTP than in dCTP. This difference disappeared in the presence of exogenous dThd. Analysis of intracellular metabolites of 5-[3H]dCyd showed an increase in [3H]dCTP used for liponucleotide biosynthesis and a decrease in [3H]dUMP formation in the presence of Cl-dAdo, suggesting the possible inhibition of dCMP deaminase.


Microsurgical Treatment of a Petrotentorial Dural Arteriovenous Fistula: The Vein, the Whole Vein, and Nothing but the Vein: 2-Dimensional Operative Video.
Dural arteriovenous fistulas (dAVFs) consist of abnormal anastomoses between 1 or multiple meningeal arteries to meningeal veins, venous sinuses, or subarachnoid veins.1 dAVFs account for 10% to 15% of all intracranial arteriovenous lesions.2 dAVFs can be challenging to treat with various approaches that include microsurgical ligation, endovascular embolization (transarterial or transvenous), and stereotactic radiosurgery. All these treatments share the common goal of disconnecting the draining vein from the fistulous point. We present a case of a 43-yr-old male who presented with progressive headaches and was found to have an incidental Zipfel type 3A3 right petrotentorial dAVF on catheter angiography. The patient underwent a right retrosigmoid craniotomy and clipping of 2 separate venous outflows. The case illustrates the principle that multiple venous outflows can exist in dAVF and a thorough analysis of the venous phase of the angiogram as well as corresponding inspection of the fistula at the time of surgical exploration is a necessity to avoid partial obliteration. The patient remained neurologically intact postoperatively and had complete resolution of his fistula on postoperative angiography. We review the neuroimaging, operative video, and technical nuances and provide a short literature review on the topic.4 The patient gave informed consent for the procedure and verbal consent for this publication. The patient consented to the publication of their image.


Vitamin E or vitamin A protects chickens against E. coli infection.
The supplementation of either vitamin E (300 mg./kg. diet) or vitamin A (60,000 I.U./kg. diet) to a standard chick ration increased the protection of six week old immunized chickens against E coli infection, decreasing mortality from about 40% to 5%. The combination of the two vitamins, however, did not give as much protection as either vitamin alone. Vitamin E or A did not protect chicks from weight loss and severe morbidity due to infection, but slightly increased the rate of recovery.


Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. I. Distribution and cellularity of the bone marrow in normal dogs.
Marrow cellularity in adult beagles (1-2 yr old) is highest in centrally located bones, with values between 8000 and 12,000 nucleated cells per sq mm. It decreases gradually towards the peripheral parts of the body, reaching values below 1000 per sq mm in bones distal to the elbow and knee. The first tail segment always contains some active marrow. The fifth segment has only stromal elements. In spongy bones fat cells appear to be distributed at random among the blood-forming elements. In the middle part of the femur the fatty marrow predominates in the center of the cylinder, while the subendosteal area is very cellular. The proximal and distal ends of the femur are more cellular than the middle. The small standard deviation of the cellularity in the spongy bones of the trunk and in the proximal and middle part of the humerus makes these sites areas of choice for quantitative studies of marrow regeneration. The large variations in cellularity of the marrow in the radius and tibia of young adult dogs make these sites unsuitable for such studies. The distribution of active and fatty marrow in dogs is similar to that of humans. The differential count of active marrow is quite constant between different dogs and in the various sites of each animal.


P2-006 profiles of receptors for specialized lipid mediators on synoviocyte from osteoarthritis.
【Background】 As specialized pro-resolving mediators (SPM) derived from fatty acids are detectable in synovial fluids in osteoarthritis (OA), they appear to take some roles for disease pathogenesis. Receptors for SPMs have been found, such as leukotriene B4 receptor (BLT1), formyl peptide receptor 2 (FPR2), and chemokine like receptor 1 (CMKLR1). 【Purpose】 To identify the significance of receptors for SPMs on the cells in synovial tissue from OA joints. 【Methods】 Expression of BLT1, FPR2 and CMKLR1 on synoviocytes from OA patients (45.5% women, mean age 69 years, mean BMI 27.9 kg/m(2)) and macrophage were analysed by flow cytometry and quantitative PCR. 【Results】 FPR2 and CMKLR1 are found on synoviocyte, in which mean expression by flow cytometry were 8.5% and 6.2%, respectively, but BLT1 was less than 2.0%, although all of them decreased by keeping incubation. LPS treatment increased rather FPR2, but not so much CMKLR1, on synoviocytes and macrophage. 【Conclusion】 There are FPR2 or CMKLR1 positive cells in synovial tissues, and especially FPR2 seems to have a certain function under inflammatory conditions.


[Need for primary care training in rare diseases].
The problem of the need for primary care (PC) training in rare diseases (RD) is approached through a qualitative research study that tries to define its relevance and to identify the need for RD training in PC. By means of naturalistic research methods (in-depth interviews and group dynamics), we tried to discover the personal and professional connotations of PC training in RD in the rural and urban areas of the Community of Madrid, Spain. The areas explored by means of structured interview were: challenges and RD definition; professional experience with RD; relevance of PC for RD; training and information in RD; needs and demands for RD in PC. We found no differences between the rural and urban groups nor between different professional categories. The RD concept was relatively unknown and difficulties arose in understanding the magnitude and overall importance of these diseases. Nor did the RD concept express the severity or the repercussions of these diseases. RDs awoke little professional interest, in contrast with the human interest aroused. The professionals interviewed thought that undergraduate training was sufficient, and rejected postgraduate training as unnecessary and unfeasible. The search for active information through Internet was the best way to obtain data to optimize criteria for patient referral. As such, the Information System for Rare Diseases in Spanish (Sistema de Información de Enfermedades Raras en Español, SIERE) (http://iier.isciii.es/er) meets the demands for information.


Single-marker and multi-marker mixed models for polygenic score analysis in family-based data.
Genome-wide association studies have proven successful but they remain underpowered for detecting variants of weaker effect. Alternative methods propose to test for association by using an aggregate score that combines the effects of the most associated variants. The set of variants that are to be aggregated may come from either of two modeling approaches: single-marker or multi-marker. The goal of this paper is to evaluate this alternative strategy by using sets of single-nucleotide polymorphisms identified by the two modeling approaches in the simulated pedigree data set provided for the Genetic Analysis Workshop 18. We focused on quantitative traits association analysis of diastolic blood pressure and of Q1, which served to control the statistical significance of our results. We carried out all analyses with knowledge of the underlying simulation model. We found that the probability to replicate association with the aggregate score depends on the single-nucleotide polymorphism set size and, for smaller sets (≤100), on the modeling approach. Nonetheless, assessing the statistical significance of these results in this data set was challenging, likely because of linkage because we are analyzing pedigree data, and also because the genotypes were the same across the replicates. Further methods need to be developed to facilitate the application of this alternative strategy in pedigree data.


Bayesian Hierarchical Graph Neural Networks With Uncertainty Feedback for Trustworthy Fault Diagnosis of Industrial Processes.
Deep learning (DL) methods have been widely applied to intelligent fault diagnosis of industrial processes and achieved state-of-the-art performance. However, fault diagnosis with point estimate may provide untrustworthy decisions. Recently, Bayesian inference shows to be a promising approach to trustworthy fault diagnosis by quantifying the uncertainty of the decisions with a DL model. The uncertainty information is not involved in the training process, which does not help the learning of highly uncertain samples and has little effect on improving the fault diagnosis performance. To address this challenge, we propose a Bayesian hierarchical graph neural network (BHGNN) with an uncertainty feedback mechanism, which formulates a trustworthy fault diagnosis on the Bayesian DL (BDL) framework. Specifically, BHGNN captures the epistemic uncertainty and aleatoric uncertainty via a variational dropout approach and utilizes the uncertainty information of each sample to adjust the strength of the temporal consistency (TC) constraint for robust feature learning. Meanwhile, the BHGNN method models the process data as a hierarchical graph (HG) by leveraging the interaction-aware module and physical topology knowledge of the industrial process, which integrates data with domain knowledge to learn fault representation. Moreover, the experiments on a three-phase flow facility (TFF) and secure water treatment (SWaT) show superior and competitive performance in fault diagnosis and verify the trustworthiness of the proposed method.


Hydrogen-Bonding Trends in a Bithiophene with 3- and/or 4-Pyridyl Substituents.
To improve the charge-carrier transport capabilities of thin-film organic materials, the intermolecular electronic couplings in the material should be maximized. Decreasing intermolecular distance while maintaining proper orbital overlap in highly conjugated aromatic molecules has so far been a successful way to increase electronic coupling. We attempted to decrease the intermolecular distance in this study by synthesizing cocrystals of simple benzoic acid coformers and dipyridyl-2,2'-bithiophene molecules to understand how the coformer identity and pyridine N atom placement affected solid-state properties. We found that with the 5-(3-pyridyl)-5'-(4-pyridyl)-isomer, the 4-pyridyl ring interacted with electrophiles and protons more strongly. Synthesized cocrystal powders were found to have reduced average crystallite size in reference to the parent compounds. The opposite was found for the intermolecular electronic couplings, as determined via density functional theory (DFT) calculations, which were relatively large in some of the cocrystals.


Knee loading stimulates cortical bone formation in murine femurs.
Bone alters its architecture and mass in response to the mechanical environment, and thus varying loading modalities have been examined for studying load-driven bone formation. The current study aimed to evaluate the anabolic effects of knee loading on diaphyseal cortical bone in the femur. Using a custom-made piezoelectric loader, 0.5-N loads were laterally applied to the left knee of C57/BL/6 mice at 5, 10, 15, and 20 Hz for 3 minutes per day for 3 consecutive days. Animals were sacrificed for examination 13 days after the last loading. The contralateral femur was used as a non-loading control, and the statistical significance of loading effects was evaluated with p < 0.05. Although diaphyseal strains were measured as small as 12 mustrains, bone histomorphometry clearly demonstrated frequency-dependent enhancement of bone formation. Compared to a non-loading control, bone formation on the periosteal surface was significantly enhanced. The loading at 15 Hz was most effective in elevating the mineralizing surface (1.7 x; p < 0.05), mineral apposition rate (1.4 x; p < 0.001), and bone formation rate (2.4 x; p < 0.01). The loading at 10 Hz elevated the mineralizing surface (1.4 x; p < 0.05), mineral apposition rate (1.3 x; p < 0.01), and bone formation rate (1.8 x; p < 0.05). The cross-sectional cortical area and the cortical thickness in the femoral diaphysis were significantly increased by loading at 10 Hz (both 9%) and 15 Hz (12% and 13%, respectively). The results support the anabolic effects of knee loading on diaphyseal cortical bone in the femur with small in situ strain, and they extend our knowledge on the interplay between bone and joints. Strengthening the femur contributes to preventing femoral fractures, and the discovery about the described knee loading might provide a novel strategy to strengthen osteoporotic bones. Further analyses are required to understand the biophysical and molecular mechanism behind knee loading.


CT- or sonography-guided biopsy of the liver in the presence of ascites: frequency of complications.
The presence of ascites has been considered a contraindication to percutaneous biopsy of the liver. To determine the validity of this assumption, we performed percutaneous biopsies of the liver under CT or sonographic guidance in 28 patients who had ascites and in 28 patients who did not have ascites and compared the complication rates in the two groups. Twenty-two patients (79%) in the group with ascites and 19 patients (68%) in the group without ascites had biopsies to determine the cause or extent of chronic liver disease. The remainder were oncologic patients who had biopsies to determine the cause of a focal hepatic mass. The complication rate in the patients who had ascites (32%) was less than that in the patients who did not have ascites (43%) (the difference did not reach statistical significance, p less than .30). In the ascites group, complications included transient hypotension (five patients), a mild-to-moderate fall in hematocrit (three patients), and a small leak of ascites from the biopsy site (one patient). In the control group, minor complications included transient hypotension (three patients), a mild-to-moderate fall in hematocrit (seven patients), and a small subcapsular hematoma (one patient). One major complication occurred in the control group: a patient required a blood transfusion because of the fall in his hematocrit. We conclude that the complication rate in liver biopsies guided by CT or sonography in the presence of ascites is not higher than similar biopsies done in the absence of ascites. Ascites should not be considered a contraindication for performing such biopsies.


The effect of temazepam on assessment of severity of obstructive sleep apnea by polysomnography.
To determine the effect of temazepam on assessment of the severity of obstructive sleep apnea (OSA) by polysomnography (PSG). Analysis of diagnostic laboratory-PSG studies was performed in OSA patients who were administered temazepam (10 mg) to facilitate sleep ("temazepam group", n = 73) and in OSA patients (matched for age, gender, body mass index and study date) in whom temazepam was not administered ("control group", n = 73). Sleep- and respiratory-related variables were compared between the groups for the (i) first 3 h of study following temazepam in the temazepam group (when peak blood concentration is expected) or following lights out in the control group, and (ii) entire study duration. Within the first 3 h, no differences in sleep-related variables were observed between the groups. Over the entire study duration, the temazepam group had a reduced total sleep time compared to the control group, likely due to the overnight sleep difficulties that led to its use. Whether measured during the first 3 h of study or over the entire study duration, no significant differences were detected between the groups for any respiratory-related variable, including apnea hypopnea index, arousal index, oxygen desaturation, apnea index, hypopnea index, and event duration. When patients were considered in terms of OSA severity, decreased arousal index was noted in the temazepam group over the entire study duration, but only in those with severe OSA. Oral administration of 10 mg of temazepam during the course of PSG does not systematically affect assessment of the severity of OSA by PSG.


Lubrication approximation for microparticles moving along parallel walls.
Lubrication expressions for the friction coefficients of a spherical particle moving in a fluid between and along two parallel solid walls are explicitly evaluated in the low-Reynolds-number regime. They are used to determine lubrication expression for the particle free motion under an ambient Poiseuille flow. The range of validity and the accuracy of the lubrication approximation are determined by comparing with the corresponding results of the accurate multipole procedure. The results are applicable for thin, wide, and long microchannels, or quasi-two-dimensional systems.


RESPONSE TO NATURAL ENVIRONMENTAL HETEROGENEITY: MATERNAL EFFECTS AND SELECTION ON LIFE-HISTORY CHARACTERS AND PLASTICITIES IN MIMULUS GUTTATUS.
Recent studies in plant populations have found that environmental heterogeneity and phenotypic selection vary at local spatial scales. In this study, I ask if there is evolutionary change in response to environmental heterogeneity and, if so, whether the response occurs for characters or character plasticities. I used vegetative clones of Mimulus guttatus to create replicate populations of 75 genotypes. These populations were planted into the natural habitat where they differed in mean growth, flowering phenology, and life span. This phenotypic variation was used to define selective environments. There was variation in fitness (flower production) among genotypes across all planting sites and in genotype response to the selective environment. Offspring from each site were grown in the greenhouse in two water treatments. Because each population initially had the same genetic composition, variation in the progeny between selective environments reveals either evolutionary change in response to environmental heterogeneity or environmental maternal effects. Plants from experimental sites that flowered earlier, had shorter life spans and were less productive, produced offspring that had more flowers, on average, and were less plastic in vegetative allocation than offspring of longer-lived plants from high-productivity areas. However, environmental maternal effects masked phenotypic differences in flower production. Therefore, although there was evidence of genetic differentiation in both life-history characters and their plasticities in response to small-scale environmental heterogeneity, environmental maternal effects may slow evolutionary change. Response to local-scale selective regimes suggests that environmental heterogeneity and local variation in phenotypic selection may act to maintain genetic variation.


Density functional theory calculations establish the experimental evidence of the DX center atomic structure in CdTe.
The In DX center and the DX-like configuration of the Cd host atom in CdTe are investigated using density functional theory. The simultaneous calculation of the atomic structure and the electric field gradient (EFG) allows one to correlate the theoretically predicted structure of the DX center with an experimental observable, namely, the EFG obtained from radioactive 111In/111Cd probe atoms in In doped CdTe. In this way, the experimental identification of the DX center structure is established.


Identification and expression analysis of starch branching enzymes involved in starch synthesis during the development of chestnut (Castanea mollissima Blume) cotyledons.
Chinese chestnut (Castanea mollissima Blume) is native to China and distributes widely in arid and semi-arid mountain area with barren soil. As a perennial crop, chestnut is an alternative food source and acts as an important commercial nut tree in China. Starch is the major metabolite in nuts, accounting for 46 ~ 64% of the chestnut dry weight. The accumulation of total starch and amylopectin showed a similar increasing trend during the development of nut. Amylopectin contributed up to 76% of the total starch content at 80 days after pollination (DAP). The increase of total starch mainly results from amylopectin synthesis. Among genes associated with starch biosynthesis, CmSBEs (starch branching enzyme) showed significant increase during nut development. Two starch branching enzyme isoforms, CmSBE I and CmSBE II, were identified from chestnut cotyledon using zymogram analysis. CmSBE I and CmSBE II showed similar patterns of expression during nut development. The accumulations of CmSBE transcripts and proteins in developing cotyledons were characterized. The expressions of two CmSBE genes increased from 64 DAP and reached the highest levels at 77 DAP, and SBE activity reached its peak at 74 DAP. These results suggested that the CmSBE enzymes mainly contributed to amylopectin synthesis and influenced the amylopectin content in the developing cotyledon, which would be beneficial to chestnut germplasm selection and breeding.


Impact of imprecise household location on effective coverage estimates generated through linking household and health provider data by geographic proximity: a simulation study.
Geographic proximity is often used to link household and health provider data to estimate effective coverage of health interventions. Existing household surveys often provide displaced data on the central point within household clusters rather than household location. This may introduce error into analyses based on the distance between households and providers. We assessed the effect of imprecise household location on quality-adjusted effective coverage of child curative services estimated by linking sick children to providers based on geographic proximity. We used data on care-seeking for child illness and health provider quality in Southern Province, Zambia. The dataset included the location of respondent households, a census of providers, and data on the exact outlets utilized by sick children included in the study. We displaced the central point of each household cluster point five times. We calculated quality-adjusted coverage by assigning each sick child to a provider's care based on three measures of geographic proximity (Euclidean distance, travel time, and geographic radius) from the household location, cluster point, and displaced cluster locations. We compared the estimates of quality-adjusted coverage to each other and estimates using each sick child's true source of care. We performed sensitivity analyses with simulated preferential care-seeking from higher-quality providers and randomly generated provider quality scores. Fewer children were linked to their true source of care using cluster locations than household locations. Effective coverage estimates produced using undisplaced or displaced cluster points did not vary significantly from estimates produced using household location data or each sick child's true source of care. However, the sensitivity analyses simulating greater variability in provider quality showed bias in effective coverage estimates produced with the geographic radius and travel time method using imprecise location data in some scenarios. Use of undisplaced or displaced cluster location reduced the proportion of children that linked to their true source of care. In settings with minimal variability in quality within provider categories, the impact on effective coverage estimates is limited. However, use of imprecise household location and choice of geographic linking method can bias estimates in areas with high variability in provider quality or preferential care-seeking.


Cardiac Point-of-Care Ultrasound: State-of-the-Art in Medical School Education.
The development of small, user friendly, handheld ultrasound devices has stimulated the growth of cardiac point-of-care ultrasound (POCUS) for the purpose of rapid, bedside cardiac assessment. Medical schools have begun integrating cardiac POCUS into their curricula. In this review the authors summarize the variable approaches taken by several medical training programs with respect to duration of POCUS training, prerequisite knowledge, and methods of delivering these skills (including e-learning, hands-on training, and simulation). The authors also address issues related to the need for competency evaluation and the limitations of the technology itself. The studies reviewed suggest that undergraduate education is a viable point at which to introduce basic POCUS concepts.


Utilization of Crowdfunding for Cataract and LASIK Procedures.
To study the nature of crowdfunding campaigns for common ophthalmologic procedures. Cross sectional, retrospective study of campaigns on GoFundMe.com from January 1st, 2021 to July 31st, 2021. All domestic and international campaigns referring to cataract and intraocular lens placement or LASIK procedures, excluding those with non-ophthalmologic conditions or campaigns for multiple conditions. Descriptive analysis of campaigns including condition, country of origin of patient, total and median value raised, total and median value sought, age of the patient, funding goal met, insurance status when possible. Total and median funds raised and sought, international versus domestic campaigns, success rate for campaigns, percent of campaigns involving children, percent of campaigns mentioning insurance. 137 campaigns were identified, 67.9% (93/137) were for cataract and 32.1% (44/137) were for LASIK. 13.1% (18/137) of campaigns were international. 7.3% (10/137) campaigns were successful at reaching fing goals. Of successful campaigns, 70.0% (7/10) were for cataract and 30.0% (3/10) were for LASIK. Total value raised (in USD) was $131,763, where $106,593 was for cataract and $25,170 was for LASIK. The median value sought overall was $5,000, where the median sought for cataract procedures was $5,000 and the median for LASIK was $4,000. The median value raised was $395. 5.8% (8/137) of campaigns mentioned minors. 12.5% (1/8) of campaigns for children or minors successfully met funding goals compared to 7.0% (9/129) adult campaigns. The total funds raised for children or minors was $9,224 with a goal of $41,050. The total funds raised for adults was $122,539 out of a goal of $775,617. 14.6% (20/137) campaigns mentioned insurance coverage, of which 85% (17/20) were for cataract and 15.0% (3/20) were for LASIK. Premium lenses (toric, multifocal, etc.) were mentioned in 1.1% of cataract campaigns (1/93) as being cost prohibitive. Crowdfunding is ineffective as a means for patients to raise funds for ophthalmic procedures. The broad range of financial requests within campaigns indicates a large patient knowledge gap in cost for procedures.


Reanalysis of P2X7 receptor expression in rodent brain.
P2X receptors are cationic-selective ion channels gated by extracellular ATP. There are seven subunits (P2X1-7), the first six of which are expressed throughout the peripheral and central nervous systems. P2X7 receptors are rapidly upregulated and activated as a result of inflammatory stimuli in immune cells, where they act not only as cationic channels but uniquely couple with rapid release of proinflammatory cytokines, cytoskeletal rearrangements, and apoptosis or necrotic cell death. The P2X7 receptor has been termed the cytolytic non-neuronal P2X receptor because it had not been detected in neurons until recently when it has been immunolocalized to several brain regions, particularly the hippocampus, and has been suggested to be involved in presynaptic modulation of transmitter release. Because its expression in brain neurons may have substantial functional implications, we have performed detailed immunocytochemical, immunoblot, and immunoprecipitation studies on brain and non-neuronal tissue using all currently available antibodies. We first examined rats, but staining patterns were inconsistent among antibodies; we therefore studied mice for which there are two P2X7 knock-out mice constructs available, one expressing the LacZ transgene. We found that P2X7 receptor protein is strongly and reliably detected in the submandibular gland and lung of wild-type mice but not in either of the P2X7-/- mice. However, we failed to find evidence for P2X7 receptor protein in hippocampal neurons or their input-output projections. Either the P2X7 protein in the hippocampus is below the limits of detection by the currently available methods or it is not present.


Effect of flint corn processing method and roughage level on finishing performance of Nellore-based cattle.
This study was conducted to evaluate the effects of flint corn processing method (CPM) and level of NDF from roughage (rNDF) on performance, carcass characteristics, and starch utilization by finishing Nellore-based cattle fed high-concentrate, flint corn-based diets. In this study, 112 Nellore type bulls (initial BW 384.07 ± 29.53 kg and 24-36 mo of age) were individually fed using Calan gates or individual pens. The animals were used in a randomized complete block design in a 2 × 4 factorial arrangement with 2 CPM, high-moisture flint corn (HMC) or finely ground dry flint corn (FGC), with 1 of 4 levels of rNDF, 3, 8, 13, and 18% (DM basis), using sugarcane silage (SS) as roughage. Bulls were adapted to the finishing diet over a 21-d period and fed for a total of 81 d. Fecal starch (FS) concentration was determined on d 46 and 74 of the feeding period. There was a quadratic effect of rNDF on final BW ( < 0.01) and ADG ( = 0.01). Optimal concentrations of rNDF were estimated using the first derivative of second order polynomials, indicating that final BW and ADG were maximized with 13.3 and 13.0% rNDF, respectively. An interaction was observed between CPM and rNDF ( = 0.05) for DMI, with peak DMI occurring at 11.3 and 13.7% rNDF with FGC and HMC, respectively. Cattle fed HMC had 13.9% greater G:F ( < 0.01) compared with those fed FGC (0.172 vs. 0.151, respectively). There were quadratic effects of rNDF on HCW ( = 0.04) and ME intake ( < 0.01); heaviest carcass weights were estimated, in both cases, to be achieved with 12.8% rNDF. A quadratic effect of rNDF for renal, pelvic, and inguinal fat weight ( = 0.04) was observed, with a peak estimated to occur at 12.6% rNDF. An interaction between CPM and rNDF also was observed for FS ( < 0.05). Bulls fed FGC with 3% rNDF had greater FS content, and FS linearly decreased as concentration of rNDF increased. For bulls fed HMC, FS was 3.0% of DM and was unaffected by rNDF in the diet. Lower FS from bulls fed HMC suggests that availability of starch from flint corn was greater than that of FGC. For Nellore-based cattle fed a flint corn-based diet containing SS and 8% whole lint cottonseed, performance was optimized with 12.8% rNDF. In the absence of cottonseed addition to diets, optimal performance would be expected with about 14.5% rNDF.


Static dynamics approach to relaxation modes and times for deformed polymers.
We discuss relaxation of conformational fluctuations around deformed polymer states. To this end, Brownian dynamics simulations of bead-spring models including a finite extensibility of the springs as well as excluded volume and hydrodynamic interactions between the beads have been performed. Complete spectra of relaxation times as well as corresponding relaxation modes are obtained from the simulation data by applying the static dynamics formalism, which rigorously describes the initial decay of correlations between the bead positions. As shown here, this procedure amounts to using a generalized Rouse-Zimm-like model which is governed by linear effective equations of motion having the same initial decay of correlations as the full nonlinear bead-spring model used in the simulations. In thermal equilibrium, the well-known scaling laws in the presence of excluded volume and hydrodynamic interactions between the beads are recovered, but, in addition, the static dynamics method also yields numeric values for the nonuniversal prefactors of the respective laws. The method is equally applicable to a broad range of problems, where the polymer is deformed by the action of flows or forces. Two examples of recent interest are considered: a tethered polymer pulled at its free end and one which is stretched by a uniform flow. It is shown that in both cases, the relaxation process is dominated by a finite extensibility of the springs.


Parental expectations regarding postschool social attainments of adolescents with autism spectrum disorders in Singapore.
This study sought to understand the parental expectations of social attainments in the postschool years. The parents of 20 adolescents with autism spectrum disorders (ASD) attending special schools were interviewed. Most expected their children would be working in sheltered workshops or unemployed. All parents indicated that their children would live with them until they were unable to provide appropriate care, and nearly half expressed wishes for relatives to care for them thereafter. None expected any independent access to the community. Analysis of the interviews suggested that the adolescents' learning and behavior, parental concerns, availability of formal resources, and societal factors influenced parents' expectations. Implications for working with Asian populations and for service delivery in Singapore are discussed.


Bacterial adhesion: genetics, biogenesis, and role in pathogenesis of fimbrial adhesins of Escherichia coli.
Microbial pathogenicity is a complex phenomenon encompassing many varied mechanisms. There are, however, several common strategies that pathogenic organisms use to sustain themselves and overcome host barriers. In one of these strategies, the first step is the firm adhesion of the microorganism to host cells. Adhesion is frequently mediated by organelles called fimbriae. A surprising variety of fimbrial adhesins have been found in Escherichia coli, and several have been extensively characterized. The genetics and regulation of the various fimbrial structures are reviewed, and strategies for preventing the adhesion of harmful bacteria to host surfaces are discussed.


Effects of Chronic and Acute Pulmonary Hyperinflation on Phrenic Nerve Conduction in Patients with COPD.
In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (p < 0.05), but similar amplitude of motor compound muscle action potential (cMAP) was observed in stable COPD patients vs. matched controls (p < 0.05). However, in COPD patients with resting pulmonary hyperinflation as reliably detected by substantial Inspiratory Capacity reduction (<80% pred.), the mean bilateral latency was longer vs. COPD patients without pulmonary hyperinflation (p < 0.02). During COPD exacerbation, in contrast with mean latency, the mean amplitude of phrenic nerves cMAP improved at discharge when compared with in-hospital admission (p < 0.05). In stable COPD patients the velocity of phrenic nerve conduction was impaired mostly in the presence of pulmonary hyperinflation, while during COPD exacerbation where dynamic pulmonary hyperinflation abruptly occurs, the reversible decrease of cMAP amplitude does suggest a temporary, acute axonal damage of phrenic nerves, potentially contributing to diaphragmatic dysfunction in these circumstances.


The concentration of thyroid hormones and activities of iodothyronine deiodinases are altered in human brain gliomas.
We have determined the cellular concentration of thyroxine (T4) and triiodothyronine (T3) and the activities of two brain iodothyronine deiodinases, type II (5'-D2) and type III (5-D3), in two types of tissues --tumour (26) and non-tumour (5), derived either from human gliomas with various histological malignancies or from non-tumoural surrounding brain tissue. As it has been established, all patients before the surgery had the Non-Thyroidal Illness Syndrome (NTIS). The concentration of serum T3 was therefore significantly decreased in all the examined patients. It was over 2.5 times lower than that before surgery and 4.0 times lower at surgery than that seen in healthy controls. The serum concentration of T4 was found to be below normal range in 4/26 cases and in low levels of normal range in 6/26 cases, whereas TSH serum concentration in all patients was within normal range. The concentrations of T3 and T4 (expressed as pg of hormone/mg tissues protein) in 22/26 brain tissue samples were significantly lower in gliomas than in 5 non-tumoural brain tissue samples. As expected, the alternation in brain 5'D II activity in gliomas was seen in most cases with astrocytomas (5/8 cases), gliosarcomas (8/8 cases) and glioblastoma multiforme (10/10 cases). In general, the mean enzyme activity in tumour tissue was significantly higher than that found in non-tumoural tissue of human brain (21.79 fmol of newly generated T3/h/mg of protein vs. 4.88 fmol of T3/h/mg protein, respectively). The highest 5'D2 activity with a range from 10.82 to 45.96 (mean 23.61 fmol T3/h/mg protein) was found in gliosarcomas. The activity of 5-D3 was increased (in 8/8 cases of gliosarcoma and in 9/10 cases of glioblastoma multiforme) or decreased (in 3/3 cases of astrocytoma II, 5/5 cases of astrocytoma III) when compared to mean activity of this enzyme found in non-tumoural brain tissue. In summary, our results suggest that the concentration of brain iodothyronines and metabolism of thyroid hormones in the examined human brain tumours are altered. These changes may be related to malignant progression.


An important role of endogenous insulin on exocrine pancreatic secretion in rats.
We have investigated a physiological role of endogenous insulin on exocrine pancreatic secretion stimulated by a liquid meal as well as exogenous secretin and cholecystokinin octapeptide (CCK-8) in conscious rats. Each rat was prepared with a chronic pancreatic fistula and an indwelling catheter in a jugular vein. Oral ingestion of a liquid meal (5 ml) resulted in significant increases in pancreatic secretion, including volume, bicarbonate, and amylase output, in these rats. A rabbit anti-insulin serum (1.0 ml) given intravenously completely blocked the postprandial exocrine pancreatic secretion, whereas a normal rabbit serum did not influence the pancreatic secretion in the same rats. When pancreatic secretion was stimulated by intravenous administration of both secretin and CCK-8 in three different doses, including 0.015, 0.03, and 0.06 clinical unit and microgram.kg-1.h-1, respectively, volume, bicarbonate, and amylase output increased significantly in a dose-dependent manner. This increase in pancreatic secretion was also completely blocked by a rabbit anti-insulin serum, whereas it was not influenced by a normal rabbit serum. The amount of the antiserum employed abolished the postprandial increases in plasma insulin concentration. We conclude that endogenous insulin plays an important role on the regulation of postprandial pancreatic secretion in rats. Furthermore, for the stimulatory action of the two intestinal hormones secretin and CCK-8 on the pancreatic exocrine secretion, endogenous insulin is need.


Differences in Cancer-Specific Mortality of Right- Versus Left-Sided Colon Adenocarcinoma: A Surveillance, Epidemiology, and End Results Database Analysis.
Studies have shown an increased risk for all-cause mortality with right-sided colon cancer (RCC) as compared with left-sided colon cancer (LCC). However, these studies were unable to directly account for mortality events unrelated to cancer, known as other-cause mortality. We investigated the difference in cancer-specific mortality (CSM) between RCC and LCC at localized, regional, and metastatic stages, according to the Fine and Gray proportional hazards model, while accounting for other-cause mortality as a competing risk. Using the SEER database, we identified 90,635 patients with LCC (ie, involving the splenic flexure, descending, sigmoid, and rectosigmoid colon) and 112,679 patients with RCC (ie, involving the cecum, ascending, hepatic flexure, and transverse colon) diagnosed from 1998 to 2013. We performed a competing risk analysis for CSM using the Fine and Gray proportional hazard model, adjusting for age, sex, race, tumor grade, surgery status, year of diagnosis, and tumor laterality, with two-sided testing and a statistical significance threshold of 0.05. Compared with LCC, RCC demonstrated statistically significant decreased CSM at the localized stage (adjusted hazards ratio [AHR], 0.865; P < .001), equivalent CSM at the regional stage (AHR, 0.990; P = .440), and increased CSM at the metastatic stage (AHR, 1.175; P < .001). Using a competing risk model, we have shown that RCC, compared with LCC, is associated with lower CSM at the localized stage, equivalent CSM at the regional stage, and higher CSM at the metastatic stage. This pattern may correlate with variation in genetic factors, including known decreased prevalence of microsatellite instability in RCC with regional and metastatic disease.


Effect of the electrostatic microenvironment on the observed redox potential of electroactive supramolecular bioconjugates.
The present work describes our studies of the influence of the electrostatic microenvironment on the observed oxidation-reduction potential of redox-labeled supramolecular bioconjugates. Our experimental results show that the charge of the protein (streptavidin), determined by the pH, strongly influences the redox potential of the incorporated ferrocene centers. This is due to the electrostatic contributions from the fixed charges in the protein that affect the relative stability of the redox species involved in the electroactive label. In addition, the ionic strength plays a central role in screening the stabilizing or repulsive interactions, thus further influencing the magnitude of the apparent redox potential. This dependence of the redox potential on pH and ionic strength was described in quantitative terms by following a similar approach to that previously used for interpreting the behaviour of electron transfer proteins. This work provides a framework to understand, rationalize and predict variations in redox potentials of electroactive centers incorporated into different soft matter-based complex environments, like supramolecular bio-architectures. The potential of the approach was demonstrated through creation of a pH-tunable bioelectrochemical interface with switchable behavior based entirely on redox-active supramolecular bioconjugates.


Clinical Trials in Non-Small Cell Lung Cancer with Biomarker-Driven Treatment Allocation: Ready or Not, Here We Come.
Lung cancer is the leading cause of cancer mortality. Great advances in non-small cell lung cancer therapy have been seen in the last decade, beginning with the success in treating lung cancer harboring EGFR mutations and ALK-gene rearrangements. The potential of these biomarker-driven therapies has propelled research in biomarker targeted approaches to the forefront of lung cancer research. The successful development of immunotherapeutic agents targeting PD-L1 and PD-1 with an associated non-genomic biomarker has opened a new front in the effort for targeted approaches. Although early-phase lung cancer studies have hinted at the potential to use biomarkers to select patients for allocation to treatment in the conduct of clinical trials, data from late-phase studies have tempered expectations. The data leave unclear the wisdom of routinely restricting enrollment on lung cancer clinical trials to biomarker restricted populations, particularly non-genomic biomarkers.


Hyperopic automated lamellar keratoplasty: complications and visual results.
To examine the long-term safety and efficacy of hyperopic automated lamellar keratoplasty (H-ALK) for correction of primary hyperopia and for consecutive hyperopia following overcorrected myopic refractive surgery. A prospective study was done on 67 eyes of 50 consecutive patients who underwent H-ALK between March 17, 1993, and August 18, 1995. Hyperopic automated lamellar keratoplasty was performed for primary hyperopia in 25 eyes (group 1) and for consecutive hyperopia after myopic refractive surgery in 42 eyes (group 2, radial keratotomy, 41 eyes, and myopic automated lamellar keratoplasty, 1 eye). The eyes were followed up for a mean+/-SD of 19.2+/-12.8 months (range, 3-49 months), 58 (87%) of them with 6 months' follow-up, and 45 (67%) of them with at least 1 year's follow-up. Twenty-one eyes were followed up for 2 to 4 years. The overall mean+/-SD preoperative spherical equivalent was +2.87+/-1.28 diopters (D). The mean+/-SD postoperative spherical equivalent was -0.03+/-1.42 D at 3 months, -0.42+/-2.25 D at 6 months, -0.55+/-3.00 D at 1 year, -1.58+/-1.53 D at 2 years, and -0.35+/-1.79 D at the last follow-up. A mean myopic shift of 0.50 D was noted between 3 months and 1 year, and of 1.00 D between 1 and 2 years. Hyperopia was meaningfully reduced and visual acuity was improved by H-ALK, especially for patients with primary hyperopia. Long-term refractive instability, however, is a serious problem with this procedure. In this series, 11 (26%) of 42 eyes in which H-ALK was performed for consecutive hyperopia developed iatrogenic keratoconus. Based on this study, the long-term instability of H-ALK and the high incidence of iatrogenic keratoconus following the procedure should discourage its use, especially for consecutive hyperopia following radial keratotomy.


Economic issues: toward a cost-effective approach to the management of febrile neutropenia in Japan.
The cost of treating neutropenic patients unexplained fever is of significant concern in Japan because of the depressed economy and the aging population. Development of a standardized treatment methodology specifically tailored to the situation in Japan will make the treatment more efficient for health care institutions, will allow for improved monitoring of practices and costs, and will result in better patient care. It is essential, however, that the welfare of the patients be the utmost priority--cost savings is not sufficient in the absence of a significant impact on morbidity and mortality.


Clinical features and treatment results in children with hemangioma.
Ataş E, Koç O, Artık HA. Clinical features and treatment results in children with hemangioma. Turk J Pediatr 2017; 59: 254-260. Hemangioma is a frequent disease which has a proliferative and involution phase. In this single center retrospective study, we evaluated clinical and therapeutic features of hemangiomas in children (n: 49). The median (range) age at onset and at admission were 21 days (10 days-156 months) and 7 months (0.25-192 months), respectively. The localization of lesions was: head region (n: 28; 57.2%), trunk (n: 8; 16.3%) trunk, limb (n: 8; 16.3%), and neck region (n: 5; 10.2%) neck region. Seventeen patients (34.7%) were treated. Following treatments were used: propranolol alone in 12 (24.5%) patients, steroid alone in 2 (4.1%) patients, prednisone plus propranolol in 2 (4.1%) patients, and propranolol plus surgery in 1 (2.0%) patient. The number of hemangioma (n > 1) (p = 0.026, OR = 9.5, 95% CI 1.3-69.2) and treatment other than observation (p = 0.008, OR = 10.5, 95% CI 1.8-59.1) were significant predictors in the univariate analysis; treatment other than observation was an independent predictor for clinical response (p = 0.014, OR = 9.8, 95% CI 1.5-90.9).


Operable persistent photoconductivity of Bi2S3 nested nano-networks.
Recently, hierarchical nanostructures have attracted increasing attention because of their large specific surface area and abundant physical characteristics. Here we propose a hierarchical Bi2S3 nested nano-network (Bi2S3-3N) with an excellent thermally-stable lattice structure, which is prepared by topotactic transformation. Experimental results revealed that for the first time, Bi2S3-3N possesses an interesting nature of the repetitively-operable persistent photoconductivity, which is believed to stem from the releasing of photo-stimulated carriers captured by deep-level traps. This work shows great potential of topotactic transformed Bi2S3 hierarchical nanostructures in practical applications like functional porous nanoarchitectures, bistable optical-switching, photo detectors, memory, etc.


[Malherbe's calcified epithelioma. Review of 80 cases].
The authors review a series of 80 Benign Calcifying Epitheliomas (BCE), and describe their main clinical, histologic and prognostic features, in comparison with those reported in the literature. BCE or pilomatrixoma arises from the hair matrix, and represents approximately 1/1,000 of all skin tumors. Statistically, it is found more frequently among children under the age of 10 years and anatomic locations are mostly located on the face and upper limb. These benign tumors tend to develop slowly in subcutaneous tissue, and their treatment consists of simple surgical excision, except in some instances, where signs of more aggressive behavior can be found.


Homochiral [2.2]Paracyclophane Self-Assembly Promoted by Transannular Hydrogen Bonding.
[2.2]paracyclophane (pCp), unlike many π-building blocks, has been virtually unexplored in supramolecular constructs. Reported here is the synthesis and characterization of the first pCp derivatives capable of programmed self-assembly into extended cofacial π-stacks in solution and the solid state. The design employs transannular (intramolecular) hydrogen bonds (H-bonds), hitherto unstudied in pCps, between pseudo-ortho-positioned amides of a pCp-4,7,12,15-tetracarboxamide (pCpTA) to preorganize the molecules for intermolecular H-bonding with π-stacked neighbors. X-ray crystallography confirms the formation of homochiral, one-dimensional pCpTA stacks helically laced with two H-bond strands. The chiral sense is dictated by the planar chirality (Rp or Sp ) of the pCpTA monomers. A combination of NMR, IR, and UV/Vis studies confirms the formation of the first supramolecular pCp polymers in solution.


Recommendations for hypofractionated whole-breast irradiation.
This recommendation consensus for hypofractionated whole-breast radiotherapy (RT) was organized by the Brazilian Society of Radiotherapy (SBRT) considering the optimal scenario for indication and safety in the technology applied. All controversies and contraindication matters (hypofractionated RT in patients who underwent chemotherapy [CT], hypofractionated RT in lymphatic drainage, hypofractionated RT after mastectomy with or without immediate reconstruction, boost during surgery, hypofractionated RT in patients under 50 years old, hypofractionated RT in large breasts, hypofractionated RT in histology of carcinoma in situ [DCIS]) was discussed during a meeting in person, and a consensus was reached when there was an agreement of at least 75% among panel members. The grade for recommendation was also suggested according to the level of scientific evidence available, qualified as weak, medium, or strong. Thus, this consensus will aid Brazilian radiotherapy experts regarding indications and particularities of this technique as a viable and safe alternative for the national reality.


Substrate Compliance Directs the Osteogenic Lineages of Stem Cells from the Human Apical Papilla via the Processes of Mechanosensing and Mechanotransduction.
It is well recognized that the interaction between stem cells and their physical microenvironment plays a fundamental role in controlling cell behaviors and directing lineage commitment, which eventually determines cell fate. Any change in the physical characteristics of the extracellular matrix in terms of topography, geometry, and stiffness has a strong effect on this interaction. Nevertheless, the precise biomechanism that regulates the responses of stem cells to the biophysical properties of substrates is not fully understood. In this study, we generated a series of polydimethylsiloxane (PDMS) substrates with different stiffness properties and explored the whole process involved in the determination of osteogenic lineage in stem cells from the human apical papilla (hSCAPs) in response to substrate stiffness. We first found that the hSCAPs responded to different substrate stiffnesses by changing their cell morphologies and cytoskeletons (via changes in α-tubulin and β-tubulin in microtubules and F-actin in microfilaments). We then found that the hSCAPs secreted more fibronectin in response to the stiffer substrates. We next found that fibronectin interacted with focal adhesion kinase (FAK) and paxillin in the FA plaques, and moreover, the expressions of FAK and paxillin were enhanced as the substrate stiffness increased. We further found that FAK and paxillin directly interacted with β-catenin. Furthermore, the accumulation of β-catenin in the nuclear region was strengthened as the substrate stiffness increased. We finally detected the changes of Lef-1 and TCF-1 in osteogenic-induced hSCAPs and found that their expressions were enhanced as the substrate stiffness increased. Lef-1 and TCF-1, as the transcriptional factors in the nucleus, potentially bound to the promoter region of Runx2 and might ultimately determine the osteogenic lineage in hSCAPs. These results indicate the important effect of stiffness in the microenvironment on the osteogenic lineage of hSCAPs and increase the understanding of the biomechanisms involved in the molecular signal cascade during mechanosensing, mechanotransduction, and stem cell differentiation, which will be useful in the biological fields of cell-matrix/cell-cell interactions and tissue engineering/regenerative medicine.


Drug exsorption from blood into the gastrointestinal tract.
Drugs are exsorbed from the blood across the gastrointestinal membranes by passive or active processes. In the case of a passive transport mechanism, the exsorption of drugs depends on the concentration gradients between the serosal and mucosal sides. The extent of secretion (exsorption) is determined by numerous factors such as extent of binding to serum proteins, distribution volume, lipophilicity, pKa and molecular size of drugs, and the blood flow rate in the gut. Specific transport systems such as P-glycoprotein (P-gp), organic cation and organic anion transporters are found to be involved in active intestinal secretion of drugs. Intestinal secretory transport systems reduce the extent of drug absorption sometimes resulting in low oral bioavailability. It is, therefore, important to know whether poor drug absorption is due to the involvement of specialized secretory transport systems. Modulation of intestinal secretory transport can be a means to enhance absorption of drugs with low oral bioavailability if exsorption of drugs is based on active secretion pathways that are open for control from the "outside".


Model of the brain tumor-Pumilio translation repressor complex.
The Brain Tumor (Brat) protein is recruited to the 3' untranslated region (UTR) of hunchback mRNA to regulate its translation. Recruitment is mediated by interactions between the Pumilio RNA-binding Puf repeats and the NHL domain of Brat, a conserved structural motif present in a large family of growth regulators. In this report, we describe the crystal structure of the Brat NHL domain and present a model of the Pumilio-Brat complex derived from in silico docking experiments and supported by mutational analysis of the protein-protein interface. A key feature of the model is recognition of the outer, convex surface of the Pumilio Puf domain by the top, electropositive face of the six-bladed Brat beta-propeller. In particular, an extended loop in Puf repeat 8 fits in the entrance to the central channel of the Brat beta-propeller. Together, these interactions are likely to be prototypic of the recruitment strategies of other NHL-containing proteins in development.