Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers.
Friend of GATA-1 (FOG-1) is a zinc finger protein that has been shown to interact physically with the erythroid DNA-binding protein GATA-1 and modulate its transcriptional activity. Recently, two new members of the FOG family have been identified: a mammalian protein, FOG-2, that also associates with GATA-1 and other mammalian GATA factors; and U-shaped, a Drosophila protein that interacts with the Drosophila GATA protein Pannier. FOG proteins contain multiple zinc fingers and it has been shown previously that the sixth finger of FOG-1 interacts specifically with the N-finger but not the C-finger of GATA-1. Here we show that fingers 1, 5 and 9 of FOG-1 also interact with the N-finger of GATA-1 and that FOG-2 and U-shaped also contain multiple GATA-interacting fingers. We define the key contact residues and show that these residues are highly conserved in GATA-interacting fingers. We examine the effect of selectively mutating the four interacting fingers of FOG-1 and show that each contributes to FOG-1's ability to modulate GATA-1 activity. Finally, we show that FOG-1 can repress GATA-1-mediated activation and present evidence that this ability involves the recently described CtBP co-repressor proteins that recognize all known FOG proteins.


Prevalence and influencing factors of co-morbid depression in patients with type 2 diabetes mellitus: a General Hospital based study.
Depression and diabetes have been recognized as major public health issues in China, however, no studies to date examined the factors associated with the development of depression in patients with diabetes in China. This study aimed to estimate the prevalence of co-morbid depression among adults with type 2 diabetes mellitus (DM) and to examine the influence factors of co-morbid depression in a group of patients with type 2 DM. The study was conducted from March l to May 31, 2012, in the Department of Endocrinology of the First Affiliated Hospital of the General Hospital of the People's Liberation Army (PLA). A systematic random sample of 412 type 2 DM patients aged over 18 years was selected. A structured questionnaire was used for collecting the information about socio-demographic data, lifestyle factors and clinical characteristics. Depression and social support was evaluated by using the Chinese version of Beck Depression Inventory (BDI) and Social Support Rate Scale (SSRS), respectively. Weights and heights were measured. Hemoglobin A1c (HbA1c) was abstracted from each patient directly after the interview. Of the total sample, 142 patients had depression according to the BDI scores (BDI scores ≥14), the prevalence of co-morbid depression in this study population was 5.7 % (142/2500). Of which, 56 had major depression (BDI ≥ 21), and 86 had moderate depression (BDI ≥ 14&BDI < 21). Logistic regression analysis indicated that a high HbA1c level, a high BMI, low quality health insurance, and being single, were significantly associated with the development of depression. However, a family history of diabetes and a high social support level are likely protective factors. The prevalence of co-morbid depression was 5.7 % among Chinese subjects with type 2 DM in this study. High HbA1c level, high BMI score, being single, low social support level, and low quality health insurance were associated with the presence of depression. These findings support a recommendation for routine screening and management in China for depression in patients with diabetes, especially for those in primary care, to reduce the number of the depressed or the misrecognized depressed diabetic patients.


The problem of sexual imbalance and techniques of the self in the Diagnostic and Statistical Manual of Mental Disorders.
This article examines the problematization of sexual appetite and its imbalances in the development of the Diagnostic and Statistical Manual of Mental Disorders (DSM) in the twentieth and twenty-first centuries. The dominant strands of historiographies of sexuality have focused on historicizing sexual object choice and understanding the emergence of sexual identities. This article emphasizes the need to contextualize these histories within a broader frame of historical interest in the problematization of sexual appetite. The first part highlights how sexual object choice, as a paradigm of sexual dysfunctions, progressively receded from medical interest in the twentieth century as the clinical gaze turned to the problem of sexual appetite and its imbalances. The second part uses the example of the newly introduced Female Sexual Interest/Arousal Disorder in the DSM-5 to explore how the Manual functions as a technique for taking care of the self. I argue that the design of the Manual and associated inventories and questionnaires paved the way for their interpretation and application as techniques for self-examination.


Cellular Signaling Pathways in Insulin Resistance-Systems Biology Analyses of Microarray Dataset Reveals New Drug Target Gene Signatures of Type 2 Diabetes Mellitus.
Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis. Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes). The genetic interaction network of both T2DM-associated seeder as well as signature genes generally relates well with the disease condition based on toxicogenomic and data curation. Results: These networks showed significant enrichment of insulin signaling, insulin secretion and other T2DM-related pathways including JAK-STAT, MAPK, TGF, Toll-like receptor, p53 and mTOR, adipocytokine, FOXO, PPAR, P13-AKT, and triglyceride metabolic pathways. We found some enriched pathways that are common in different conditions. We recognized 11-signaling pathways as a connecting link between gene signatures in insulin resistance and T2DM. Notably, in the drug-gene network, the interacting genes showed significant overlap with 13-FDA approved and few non-approved drugs. This study demonstrates the value of systems genetics for identifying 18 potential genes associated with T2DM that are probable drug targets. Conclusions: This integrative and network based approaches for finding variants in genomic data expect to accelerate identification of new drug target molecules for different diseases and can speed up drug discovery outcomes.


Effects of the spin trap agent disodium- [tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (generic NXY-059) on intracerebral hemorrhage in a rabbit Large clot embolic stroke model: combination studies with tissue plasminogen activator.
It has been proposed that the novel spin trap agent disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) may be useful in the treatment of ischemia and stroke. To date, there is little information concerning the safety of NXY-059 when administered in combination with the only Food and Drug Administration-approved pharmacological agent for the treatment of stroke, the thrombolytic tissue plasminogen activator (tPA). Thus, we determined the effects of NXY-059G, a generic form of NXY-059, on hemorrhage and infarct rate and volume when administered alone or in combination with tPA. In addition, we determined whether NXY-059G affected 2 physiological variables, blood glucose levels and body temperature. Male New Zealand White rabbits were embolized by injecting a large blood clot into the middle cerebral artery via a catheter. Five minutes after embolization, NXY-059G (100 mg/kg) was infused intravenously; control rabbits received infusions of saline, the vehicle required to solubilize NXY-059G. In tPA studies, the thrombolytic was administered intravenously starting 60 minutes after embolization (20% bolus injection/80% infusion over 30 minutes). Body temperature and blood glucose levels were measured throughout the study. Postmortem analysis included assessment of hemorrhage and infarct rate, size, and location. In the vehicle control group, the hemorrhage rate after a thromboembolic stroke was 52% (n=23), and this was increased by 67% if tPA was administered (n=15). The rabbits treated with NXY-059G in the absence of tPA had a 79% incidence of hemorrhage (n=19), an increase of 52% over the control group. In the combination drug-treated groups, the NXY-059G/tPA group had a 47% incidence of hemorrhage (n=15). There was a decrease of hemorrhage volume in the NXY-059G+tPA group compared with the other 3 groups included in the study. There was no significant effect of NXY-059G either alone or in combination with tPA on infarct rate or volume. NXY-059G did not significantly alter the physiological variables that were measured. This study suggests that NXY-059G may affect the integrity of the cerebral vasculature when administered immediately after an embolic stroke, as evidenced by an increase in hemorrhage rate. However, when NXY-059G is administered in combination with tPA, it may improve the safety of tPA by reducing the incidence of tPA-induced hemorrhage. The mechanism(s) involved in the NXY-059G-induced increase in hemorrhage rate and reduction of tPA-induced hemorrhage rate remains to be elucidated.


Quantitative Detection of In Vivo Aggregation Degree for Enhanced M2 Macrophage MR Imaging.
In situ self-assembly in vivo can be used in the enhanced diagnosis and therapy of major diseases such as cancer and bacterial infections on the basis of an assembly/aggregation-induced-retention (AIR) effect. However, the aggregation degree (αagg) is a significant parameter for determining the delivery efficiency to lesions in a complex physiological environment and a real-time quantitative calculation of the aggregation degree in vivo is still a great challenge. Here, we developed a magnetic resonance imaging (MRI) method for sensitive and quantitative calculation of αagg with a detection limit of 10-4 M and a bioactivated in vivo assembly (BIVA) magnetic resonance (MR) probe was optimized for enhanced T1-weighted MR imaging of M2 macrophages in tumors. Our MRI quantitative calculation method had a high fitting degree (R2 = 0.987) with the gold standard fluorescence (FL) method. On the basis of the BIVA mechanism of CD206 active targeting and cathepsin B specific tailoring to induce an in situ nanofiber assembly, our optimized BIVA probe exhibited a high intracellular aggregation degree of over 70% and a high in vivo αagg value of over 55%. Finally, the aggregation-enhanced T1 MR signal and the AIR effect both contributed to enhanced T1-weighted MR imaging of M2 macrophages in triple-negative breast cancer. We believe that our αagg real-time quantitative calculation method of MRI will help to further screen and optimize the in vivo enhanced imaging and treatment of the BIVA drug.


Reply to Cafiero et al. Comment on "Kopańska et al. Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research. Int. J. Mol. Sci. 2022, 23, 672".
We have carefully read the Letter to the Editor by Concetta Cafiero, Alessandra Micera, Agnese Re, Beniamino Schiavone, Giulio Benincasa, and Raffaele Palmirotta related to our paper entitled "Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research" [...].


Orientational averaging of light-scattering observables in the J-matrix approach.
The formalism of the quantum theory of angular momentum is used for orientational averaging of the a matrix, the Hermitian tensorJ(+)J, and the direct product T(*)(vv')T(Tmicromicro'). These results are independent of the nature of waves and scatterers. Equations for ?J? and ?J(+)I? are interpreted as specific forms of the generalized Wigner-Eckart theorem for the matrix elements of operators J and J(+)J which are calculated in terms of symmetrical top eigenfunctions. The averaged values of the above three types of tensor are used for the analytical calculation of a complete set of incoherent light-scattering observables, i.e., the total scattering and extinction cross sections and the Mueller matrix elements.


Vanishing bile duct syndrome associated with pazopanib after progression on pembrolizumab.
Pazopanib, a tyrosine kinase inhibitor, has been a standard first-line treatment for metastatic renal cell carcinoma (mRCC). Recent trials combining pazopanib with programmed cell death protein 1 (PD-1) inhibitors, including pembrolizumab, have shown excessive hepatotoxicity. We report a case of fatal hepatotoxicity from vanishing bile duct syndrome (VBDS) associated with pazopanib treatment, in a patient previously exposed to pembrolizumab. This is the first report of pazopanib-induced VBDS. We postulate whether prior exposure to pembrolizumab predisposed towards pazopanib-induction of VBDS, and discuss potential risks of sequential PD-1 inhibitor followed by pazopanib in mRCC, due to prolonged half-lives of PD-1 inhibitors.


Effective removal of heavy metal ions Cd2+, Zn2+, Pb2+, Cu2+ from aqueous solution by polymer-modified magnetic nanoparticles.
We prepared novel Fe(3)O(4) magnetic nanoparticles (MNPs) modified with 3-aminopropyltriethoxysilane (APS) and copolymers of acrylic acid (AA) and crotonic acid (CA). The MNPs were characterized by transmission electron microscopy, X-ray diffraction, infra-red spectra and thermogravimetric analysis. We explored the ability of the MNPs for removing heavy metal ions (Cd(2+), Zn(2+), Pb(2+) and Cu(2+)) from aqueous solution. We investigated the adsorption capacity of Fe(3)O(4)@APS@AA-co-CA at different pH in solution and metal ion uptake capacity as a function of contact time and metal ion concentration. Moreover, adsorption isotherms, kinetics and thermodynamics were studied to understand the mechanism of the synthesized MNPs adsorbing metal ions. In addition, we evaluated the effect of background electrolytes on the adsorption. Furthermore, we explored desorption and reuse of MNPs. Fe(3)O(4)@APS@AA-co-CA MNPs are excellent for removal of heavy metal ions such as Cd(2+), Zn(2+), Pb(2+) and Cu(2+) from aqueous solution. Furthermore, the MNPs could efficiently remove the metal ions with high maximum adsorption capacity at pH 5.5 and could be used as a reusable adsorbent with convenient conditions.


Tardive dyskinesia and antipsychotics: a 5-year longitudinal study of frequency, correlates and course.
The present study comprised a naturalistic, multicentre, 5-year study of course and correlates of tardive dyskinesia (TD). One hundred and sixty-six patients treated with risperidone were included during 1995/96 and followed once a year for 5 years. Mean age at inclusion was 38 years, and mean illness duration was 12 years. Tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale, and each patient's cognitive function was tested with a comprehensive computerised test battery. At study entry, 14% had TD according to a criterion index. Fifty percent were aware of it, but few reported distress. Age and sex did not correlate with TD, but schizophrenia and bipolar diagnoses did. The presence and intensity of TD correlated with all Positive and Negative Syndrome Scale for Schizophrenia symptom dimensions except the affective factor, but not with type of medication or chlorpromazine-equivalent levels. Tardive dyskinesia patients were cognitively impaired in tests reflecting mental speed, but not in other cognitive modalities. Over the 453 patient years of exposure, five patients developed TD and 14 became free of it. Our findings support the view that TD: (i) is a dynamic phenomenon; (ii) is only partly drug-induced; (iii) has a mild course during treatment with modern neuroleptics; and (iv) appears to have some correlation with mental slowness.


Spontaneous silent myocardial ischemia assessed by technetium-99m-sestamibi imaging.
We report on an 80-yr-old patient with a history of inferior myocardial infarction. The patient was injected with 15 mCi of 99mTc-sestamibi when an electrocardiogram revealed new asymptomatic inferolateral ST-segment depressions. A second 99mTc study was performed 72 hr after the initial injection and after ST-segment changes had resolved. Scintigraphic acquisitions using SPECT revealed a large reduction in photon activity in the inferolateral and inferoposterior walls with 70%-80% normalization. Therefore, 99mTc-sestamibi imaging is useful in assessing asymptomatic silent myocardial ischemia.


Freestanding and Sandwich MXene-Based Cathode with Suppressed Lithium Polysulfides Shuttle for Flexible Lithium-Sulfur Batteries.
Flexible lithium-sulfur (Li-S) batteries with high mechanical compliance and energy density are highly desired. This manuscript reported that large-area freestanding MXene (Ti3C2Tx) film has been obtained through a scalable drop-casting method, significantly improving adhesion to the sulfur layer under the continuously bent. Titanium oxide anchored on holey Ti3C2Tx (TiO2/H-Ti3C2Tx) was also produced by the well-controlled oxidation of few-layer Ti3C2Tx, which greatly facilitates lithium ion transport as well as prevents the shuttling of lithium polysulfides. Therefore, the obtained sandwich electrode has demonstrated a high capacity of 740 mAh g-1 at 2 C and a high capacity retention of 81% at 1 C after 500 cycles. Flexible Li-S batteries based on this sandwich electrode have a capacity retention as high as 95% after bending 500 times. This work provides effective design strategies of MXene for flexible batteries and wearable electronics.


Evaluation of endothelial cell changes 1 year after excimer laser in situ keratomileusis.
To investigate changes in the human corneal endothelium after excimer laser in situ keratomileusis for the correction of high myopia. Preoperative and serial postoperative specular microscopy of the central corneal endothelium was performed on 31 patients (45 eyes) (group A) who underwent laser in situ keratomileusis for the correction of myopia ranging from -8.25 to -18.50 diopters. Twenty-one patients (30 eyes) were contact lens wearers (group B), and 10 patients (15 eyes) had never worn contact lenses (group C). The central endothelium was analyzed for cell density, coefficient of variation in cell size, and hexagonality. The preoperative data were compared with those obtained 3, 6, and 12 months after surgery in all groups. In group A, the postoperative mean cell density increased significantly (2.3%) at 6-month follow-up (P = .04); the coefficient of variation decreased at all follow-ups (P < .001); and the percentage of hexagonal cells increased at all follow-ups (P < .05). In group B, there was a significant postoperative increase in cell density at the 3- (2.36%) and 6-month (3.74%) follow-ups (P < .05); the coefficient of variation decreased at all follow-ups (P < .001); and the hexagonality was also significantly higher at all follow-ups than it was before treatment (P < .05). In group C, no significant differences in mean cell density or morphometric indexes were found between preoperative and postoperative values. Laser in situ keratomileusis caused no damage to the central corneal endothelium. The postoperative improvements in endothelial cell density and morphometric indexes are related to postoperative discontinuation of contact lens use.


Optimization of a rapid nonisotopic DNA probe assay for Plasmodium falciparum in the Gambia.
An enzyme-linked synthetic DNA probe which hybridizes to repetitive DNA of Plasmodium falciparum was used in conjunction with a microtiter-based lysis and filtration blood processing procedure. An assay protocol was developed that is more sensitive and robust than previous protocols, which use stored blood and phenol extraction. In comparison with thick smear examination, 33% positive, 60% negative, and 7% conflicting scores were recorded from 390 analyzed clinical samples, and the sensitivity threshold was about 30 parasites per mm3 of blood.


A comparative analysis of angiopoietin 2 immunohistochemical staining in various stages of lung cancer.
The role of Angiopoietin 2 (Ang 2), which is necessary for tumor growth, extension, and metastasis is not fully elucidated. The presented study aimed to investigate the relationship between Ang 2 staining intensity, expression rate in tumor tissue, and the stage of lung cancer. Fifty cases of lung cancer (34 non-small and 16 small cell cases) were included in the study. Immunohistochemistry was done to evaluate Ang 2 staining intensity and expression rate in tumor and stromal cells of lung cancer tissue. Ang 2 was positive for 45 (90%) cases and negative for five (10%) cases (P = 0.04). There was a significant correlation between Ang 2 expression rate of expression and the histologic type of lung cancer (P = 0.033). Ang 2 expression rate in tumor cells of cancer tissues diagnosed with adenocarcinoma was low. There was a significant correlation between Ang 2 expression rate in stromal cells of cancer tissue and the type of lung cancer (P = 0.021). Stromal cell expression rate of Ang 2 in adenocarcinoma was found to be low. As a result, the relationship between lung cancer stage and Ang 2 was documented with this study and the expression rate was found to be lower in adenocarcinomas. By this analysis, we can suggest that angiopoietins may be used as an option for targeted treatment in lung cancer.


Clinical and metabolic aspects of the continuous use of a contraceptive association of ethinyl estradiol (30 microg) and gestodene (75 microg).
This open, prospective, noncomparative study evaluated clinical and metabolic aspects of the use of a contraceptive combination of ethinyl estradiol (30 microg) and gestodene (75 microg) continuously for 24 weeks in 45 women aged 25 +/- 3.7 years. No alterations in weight or blood pressure were observed. Few side effects were recorded. Amenorrhea rates increased from the fourth month of observation onwards, reaching 81.2% by week 24. A reduction in the levels of cholesterol and LDL and an increase in HDL and triglycerides were observed. Insulin levels increased but not significantly, while levels of glycemia remained unchanged. Levels of antithrombin III, fibrinogen and plasminogen activator inhibitor-1 (PAI-1) increased, whereas a reduction was observed in proteins C and S and in prothrombin time (PT). Activated partial thromboplastin time (APTT) remained unchanged. The treatment was associated with satisfactory clinical effects, high rates of amenorrhea after the third treatment cycle, and resulted in metabolic changes similar to those encountered during the classic use of contraceptive pills with monthly interruption for withdrawal bleeding.


Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression.
Gastrointestinal cancer is a group of tumors that affect multiple sites of the digestive system, including the stomach, liver, colon and pancreas. These cancers are very aggressive and rapidly metastasize, thus identifying effective targets is crucial for treatment. Galectin-1 (Gal-1) belongs to a family of glycan-binding proteins, or lectins, with the ability to cross-link specific glycoconjugates. A variety of biological activities have been attributed to Gal-1 at different steps of tumor progression. Herein, we summarize the current literature regarding the roles of Gal-1 in gastrointestinal malignancies. Accumulating evidence shows that Gal-1 is drastically up-regulated in human gastric cancer, hepatocellular carcinoma, colorectal cancer and pancreatic ductal adenocarcinoma tissues, both in tumor epithelial and tumor-associated stromal cells. Moreover, Gal-1 makes a crucial contribution to the pathogenesis of gastrointestinal malignancies, favoring tumor development, aggressiveness, metastasis, immunosuppression and angiogenesis. We also highlight that alterations in Gal-1-specific glycoepitopes may be relevant for gastrointestinal cancer progression. Despite the findings obtained so far, further functional studies are still required. Elucidating the precise molecular mechanisms modulated by Gal-1 underlying gastrointestinal tumor progression, might lead to the development of novel Gal-1-based diagnostic methods and/or therapies.


[Impact of the COVID-19 epidemic on anxiety among the elderly in community].
Objective: To compare the prevalence of anxiety among old people before and during the COVID-19 epidemic in China, and to provide scientific evidence for psychological intervention of the elderly during public health emergencies. Methods: In 2019, the National Psychological Care Project for the Elderly was launched, covering 818 communities across the country, and 188 407 subjects received psychological assessment. In April and May 2020, a convenient sample of 6 467 aged 65 and above subjects were followed up on the anxiety status and its influencing factors during the epidemic period by using structurized questionnaire. Data collection and management were carried out using the national elderly psychological care project data collection platform. McNemar test was used to compare the difference of the prevalence of anxiety among elderly before (October 2019 to January 23, 2020) and during the epidemic (April-May 2020). The difference of the prevalence of anxiety among elderly with different characteristics was compared by chi square test. The influencing factors of anxiety before and during the epidemic situation were analyzed by multivariate logistic regression model. Results: The prevalence of anxiety symptoms in the elderly population was 4.95% (95%CI: 4.42%-5.48%) before the outbreak of COVID-19, and 10.10% (95%CI: 9.36%-10.83%) during the epidemic which was twice as high as before the outbreak. The difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that the risk factors of anxiety symptoms before the outbreak were with one underlying disease (OR=1.57, 95%CI: 1.05-2.37), with two or more underlying diseases (OR=3.10, 95%CI: 2.13-4.51), and the protective factors were with hobbies, good relationship between children, good relationship with spouse, positive aging attitude and good psychological resilience (all P<0.05). The risk factors of developing anxiety symptoms during the epidemic were living in rural areas (OR=1.77, 95%CI: 1.42-2.20), participating in social activities regularly (OR=1.23, 95%CI: 1.02-1.48), having a good relationship with friends (OR=1.42, 95%CI: 1.11-1.82) and were quarantined or people around were quarantined for medical observation (OR=2.80, 95% CI: 1.90-4.13). Conclusion: The COVID-19 epidemic leads to a double increase in anxiety among the elderly. We should pay more attention to the psychological state of the elderly in rural area and who is being quarantined or people around being quarantined for medical observation.


Iron-restricted pair-feeding affects renal damage in rats with chronic kidney disease.
We have previously shown that dietary iron restriction prevents the development of renal damage in a rat model of chronic kidney disease (CKD). However, iron deficiency is associated with appetite loss. In addition, calorie restriction is reported to prevent the development of end-stage renal pathology in CKD rats. Thus, the beneficial effect of iron restriction on renal damage may depend on calorie restriction. Here, we investigate the effect of pair-feeding iron restriction on renal damage in a rat model of CKD. First, to determine the amount of food intake, Sprague-Dawley (SD) rats were randomly given an ad libitum normal diet or an iron-restricted diet, and the food intake was measured. Second, CKD was induced by a 5/6 nephrectomy in SD rats, and CKD rats were given either a pair-feeding normal or iron-restricted diet. Food intake was reduced in the iron-restricted diet group compared to the normal diet group of SD rats for 16 weeks (mean food intake; normal diet group and iron-restricted diet group: 25 and 20 g/day, respectively). Based on the initial experiments, CKD rats received either a pair-feeding normal or iron-restricted diet (20 g/day) for 16 weeks. Importantly, pair-feeding iron restriction prevented the development of proteinuria, glomerulosclerosis, and tubulointerstitial damage in CKD rats. Interestingly, pair-feeding iron restriction attenuated renal expression of nuclear mineralocorticoid receptor in CKD rats. Pair-feeding iron restriction affected renal damage in a rat model of CKD.


Collagen mRNA expression detected by in situ hybridization in keloid tissue.
The keloid fibroblasts exhibited increased extracellular matrix gene expression, and prominent elevated type I procollagen mRNA when compared to control fibroblasts cultured from the uninvolved skin of normal people. It also showed markedly elevated type I/III procollagen mRNA ratios, but no synthesis of type IV procollagen mRNA by keloid fibroblasts was observed. By in situ hybridization in keloid tissue, high levels of type I and type III procollagen mRNAs were detected in most of the fibroblasts, suggesting the presence of a subpopulation responsible for the increased collagen production. The levels of type I and type III procollagen mRNAs in these fibroblasts were clearly elevated compared to control skin specimens. And concentration of type I procollagen mRNA was found more predominantly than was type III. These results suggest that deposition of collagen in keloid could result from activation of certain fibroblasts responsible for type I procollagen production.


Propagation characteristics of a focused laser beam in a strontium barium niobate photorefractive crystal under reverse external electric field.
The propagation characteristics of a focused laser beam in a SBN:75 photorefractive crystal strongly depend on the signal-to-background intensity ratio (R=Is/Ib) under reverse external electric field. In the range 20>R>0.05, the laser beam shows enhanced self-defocusing behavior with increasing external electric field, while it shows self-focusing in the range 0.03>R>0.01. Spatial solitons are observed under a suitable reverse external electric field for R=0.025. A theoretical model is proposed to explain the experimental observations, which suggest a new type of soliton formation due to "enhancement" not "screening" of the external electrical field.


Radiotherapy in the management of Kaposi's sarcoma: comparison of 8 Gy versus 6 Gy.
To evaluate prospectively the efficacy of a single fraction of high-dose radiotherapy in patients with Kaposi's sarcoma. Between 1994 and 2004, 47 patients with Kaposi's sarcoma were treated at Hacettepe University, Department of Radiation Oncology. Thirteen (28%) patients received chemotherapy before radiotherapy and were referred due to recurrent or progressive disease or intolerance to chemotherapy. All lesions were treated locally with a 2-3-cm safety margin with 4-6-MeV electron beams. Radiotherapy consisted of a single fraction of 8 Gy in the first four years and 6 Gy thereafter. The male:female ratio was 4:1. The median age was 61 years (range 18-87). Eight out of 47 patients (17%) had an underlying immunocompromised state, and one had a previous diagnosis of Hodgkin's disease. Of 203 fields treated, 51 and 152 fields were treated with 8 Gy and 6 Gy, respectively. Overall response rates (RR) at 12 months for 8- and 6 Gy were 93% and 86%, which were not statistically different. However, the difference between complete RRs at 12 months (93% and 60% for 8 Gy and 6 Gy respectively) was significant (p<0.0001). Progression-free survival and reirradiation rates were not significantly different. Side effects were tolerable in all but three patients with grade 2-3 fibrosis and edema. Radiotherapy is an effective mode of treatment for Kaposi's sarcoma, and a single dose of 8 Gy is more effective in terms of complete RR compared to 6 Gy, though overall response and progression-free survival rates were similar.


A constitutive form of heat-shock protein 70 is located in the outer membranes of mitochondria from rat liver.
HSP73, the constitutive form of heat-shock protein 70, has been implicated in the translocation of preproteins across the mitochondrial membranes, being required for maintaining mitochondrial preproteins in an import competent conformation. Here we report that highly purified mitochondrial outer membranes contain a protein indistinguishable from HSP73 as a tightly associated peripheral component of the membrane. This membrane form of HSP73 was photolabelled with [alpha-32P]ATP and could be released from the outer membrane with sodium carbonate, but not after incubation of the membranes with salt or with ATP. A sensitive immunoassay with an anti-HSP73 monoclonal antibody, revealed the association of HSP73 with mitochondrial outer membrane vesicles at a level similar to that of preprotein import receptors.


Blood supply of the terminal part of the external branch of the superior laryngeal nerve.
The external laryngeal nerve (ELN) carries motor fibers to the cricothyroid and inferior pharyngeal muscles. Damage to the nerve may cause symptoms such as a monotone voice. One reason for these symptoms may be nerve injury due to inadvertent stretching, ligation or transaction of the nerve during the dissection of the superior pole of the thyroid gland. We hypothesized a new reason for the symptoms, an insufficient arterial blood supply to the nerve, and investigated this hypothesis. From 36 larynges, 52 sides (26 right and 26 left) were dissected under a surgical Zeiss-OpM1 microscope. The arterial branch to the external branch of the superior laryngeal nerve originated from the posterior glandular branch of the superior thyroid artery in 26 (50%) sides, from the anterior glandular branch in 23 (44.23%) sides, from its trunk on one (1.92%) side, from the infrahyoid branch on one (1.92%) side and from the bifurcation of the superior thyroid artery at the level of separation of the anterior and posterior glandular branches on one (1.92%) side. Devascularization of the ELN may lead to dysfunction, so this nerve's varied blood supply should be kept in mind when invasive procedures are performed in this region.


Nonoperative management of complicated diverticular disease.
The complications of diverticular disease of the colon can be divided into those related to inflammatory conditions (diverticular abscess, fistula, and perforation) and those related to noninflammatory conditions (lower gastrointestinal hemorrhage and noninflammatory stricture or obstruction). Nonoperative management of uncomplicated diverticulitis includes bowel rest and antibiotics. For abscesses, percutaneous drainage by radiologic guidance often turns complicated diverticulitis to an uncomplicated condition. In very select instances, fistulas or even perforation may be managed without operation. Strictures may be dilated or stented. Diverticular hemorrhage may be controlled with colonoscopic and angiographic techniques. For colonoscopy, these include cautery, epinephrine injection, and endoclips. For angiography, these include arterial infusion of vasopressin and selective embolization of bleeding vessels. For both diverticulitis and diverticular bleeding, these nonoperative therapeutic modalities may be utilized as a bridge to surgery, or in select instances as a definitive therapy obviating the need for surgery.


Mechanisms of resistance to QoI fungicides in phytopathogenic fungi.
The major threat to crops posed by fungal diseases results in the use by growers of enormous amounts of chemicals. Of these, quinol oxydation inhibitors (QoIs) are probably the most successful class of agricultural fungicides. QoIs inhibit mitochondrial respiration in fungi by binding to the Qo site of the cytochrome bc1 complex, blocking electron transfer and halting ATP synthesis. Unfortunately, the rapid development of resistance to these fungicides and consequent control failure has become increasingly problematic. The main mechanism conferring resistance to QoIs is target site modification, involving mutations in the cytochrome b gene CYTB, such as the substitution of glycine by alanine at position 143 (G143A) that occurs in several phytopathogenic fungi. The impact of other mechanisms, including alternative respiration and efflux transporters, on resistance seems to be limited. Interestingly, in some species QoI resistance is not supported by mutations in CYTB, while in others the structure of the gene is such that it is unlikely to undergo G143A mutations. Better understanding of the biological basis of QoI resistance in a single pathogen species will facilitate the development of resistance diagnostic tools as well as proper anti-resistance strategies aimed at maintaining the high efficacy of these fungicides.


Associations among Ratio of Free Triiodothyronine to Free Thyroxine, Chronic Kidney Disease, and Subclinical Hypothyroidism.
The ratio of free triiodothyronine (FT3) to free thyroxine (FT4) (FT3/FT4), a maker of peripheral thyroxin deiodination, could indicate activity of thyroid hormone. Since positive association between subclinical hypothyroidism (SCH) and chronic kidney disease (CKD) was reported, clarifying the association among FT3/FT4, SCH, and CKD could be an efficient tool to make a strategy for preventing CKD. A cross-sectional study with 1724 Japanese with normal thyroid hormone was conducted. Significant positive association between SCH and CKD was observed; the adjusted odds ratio (OR) and 95% confidence interval (95% CI) was 2.23 (1.38, 3.59). Even though, FT3/FT4 was found to be inversely associated with CKD whereas positively associated with SCH; the adjusted ORs and 95% CIs for 1 standard deviation (SD) increment of FT3/FT4 were 0.51 (0.35, 0.74) for CKD and 2.40 (1.34, 4.29) for SCH, respectively. FT3/FT4 was also found to be positively associated with SCH without CKD but not those with CKD; 1 SD increment of FT3/FT4 were 3.44 (1.72, 6.91) for SCH without CKD and 1.11 (0.40, 3.06) for SCH with CKD, respectively. Although further investigation is necessary, present study indicates that higher activity of peripheral thyroxin deiodination might have beneficial association on absence of CKD even among SCH which is positively associated with CKD.


[Usefulness of the implantable subcutaneous recorder in the diagnosis of recurrent syncope of unknown etiology in patients without structural heart disease and negative tilt test and electrophysiological study].
In up to 38% of the cases, the etiology of syncope difficult to determine. The main obstacle for diagnosis of the causes of syncope lies in the unpredictable frequency of episodes. Development of implantable loop recorders allows long term electrocardiographic monitoring. The aim of this study was to evaluate the usefulness of the implantable loop recorder for the diagnosis of recurrent syncope of unknown origin. From May 1991 to April 1999, a cohort of 176 patients with recurrent syncope was prospectively assessed. Investigations, including Holter monitoring, Tilt Test and electrophysiological study, allowed the determination of the etiology in 161 patients. The remaining 15 patients, without structural cardiac disease were selected for continuous electrocardiographic monitoring using an implantable loop recorder. During follow up after implant, 15 +/- 2 months (X- +/- SEM), 9 patients showed recurrence of symptoms concordant with prior episodes (time: 105 +/- 30 days). In 7 cases records during symptoms were diagnostic (0.47; CI 95%: 0.21-0.73), in 3 cases a diagnosis with documented arrhythmia was achieved, and in 4 other cases a presumptive clinical diagnosis of non-arrhythmic cause was made. In 8 patients, 6 with no recurrences, diagnosis was not possible. There were no complications related to the use of the device. The strategy of long term monitoring with the implantable loop recorder is safe and effective in patients with recurrent syncope of unknown etiology.


[Clinical diagnosis and treatment of 157 cases of vocal leukoplakia].
Objective:To study the clinical characteristics and common etiology of vocal cord leukoplakia, and explore the treatment principle. Method:One hundred and fifty-seven patients with vocal cord leukoplakia were recruited in this study. They were assessed by routine laryngoscope, narrow band imaging (NBI), stroboscope, reflux finding score (RFs) and reflux symptom index (RSI), and given conservative treatment (smoking cessation, alcohol, acid suppression, sound cessation, etc.) and/or surgical treatment. Result:Among 157 patients with leukoplakia of vocal cord, 109 (69.4%) had basically improved or cured after conservative treatment. Forty-eight cases underwent operation. The postoperative pathological diagnosis was mild dysplasia in 2 cases (1.3%), moderate dysplasia in 15 cases (9.6%), severe dysplasia or carcinoma in situ in 19 cases (12.1%), and invasive carcinoma in 12 cases (7.6%). Conclusion:NBI and stroboscopic laryngoscopy showed that most of the leukoplakia of vocal cord was non-malignant in nature, which was not in accordance with the indication of operation. Conservative treatment is effective. Biopsy or operation was indicated in only a few patients. Moreover, most of the patients are accompanied by laryngopharyngeal reflux, and the treatment of acid suppression is effective.


On the relation between mental representation and naming in a child with specific language impairment.
The naming and drawing responses of a child with specific language impairment (age 5.5 years) were used to test the hypothesis that deficient storage in the mental lexicon plays a role in the naming problems associated with SLI. In confrontation- and repeated naming, the child demonstrated frequent semantic substitutions and occasional phonologic substitutions. Stochastic modelling of his repeated naming revealed storage deficits to be a source of these errors. Comparative picture naming, picture drawing allowed exploration of this storage deficit and revealed that, for some semantic naming errors, sparse semantic representations were clearly at fault but for others, sparse phonological input and output representations played a role. Phonological naming errors, in contrast, were typically associated with strong semantic representations. Clinical, theoretical, and methodological contributions of this cognitive neuropsychological case study are discussed.


Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study.
Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship between LVI/PNI and survival of esophageal squamous cell carcinoma (ESCC) is still unclear. We aim to demonstrate the prognostic significance of LVI/PNI in ESCC. A total of 195 ESCC patients underwent curative surgery from 2012 to 2018 was collected in the 2nd Affiliated Hospital of Fujian Medical University. All the patients were divided into four groups based on the status of the neurovascular invasion: (1) neither LVI nor PNI (V0N0); (2) LVI alone (V1N0); (3) PNI alone (V0N1); (4) combined LVI and PNI (V1N1). First, the analysis included the Kaplan-Meier survival estimates with the Log rank test were performed to determine median overall survival (OS) in different groups divided according to the clinical factor, respectively. And the association between OS with multi clinical factors was examined using Cox regression analysis. Next, the risk factors for recurrence in patients with V1N1 were analyzed with univariate and multivariate logistic regression analyses, respectively. The cases in V0N0, V1N0, V0N1, and V1N1 groups were 91 (46.7%), 62 (31.8%), 9 (4.6%) and 33 (16.9%), respectively. The OS in the four groups was different (P < 0.001). The 1-, 3- and 5-year OS in V0N0 group was higher than that in V1N1 group, respectively (1-year OS: 93.4% vs 75.8%, 3-year OS: 53.8 % vs 24.2%, 5-year OS: 48.1% vs 10.5%). The OS in stage I-II for patients with V1N1 was significantly lower than that in the other groups (V0N0, V1N0, V0N1) (P < 0.001). The postoperative adjuvant chemotherapy was a significant impact factor of OS for ESCC patients with V1N1 (P = 0.004). Lymphatic invasion and LVI were significantly prognosis factors associated (P = 0.036, P = 0.030, respectively). The ulcerative type is a risk factor for V1N1 occurance (P = 0.040). The LVI and PNI are important prognosis factors for ESCC patients. ESCC patients with simultaneous lymphangio vascular and perineural invasion (V1N1) showed worse OS than patients with either lymphangio vascular or perineural invasion alone (V1N0 or V0N1) or none (V0N0). In addition, adjuvant chemotherapy may prolong the OS for ESCC patients with V1N1.


Spectroscopy of the double minimum 3 (3)ΠΩ electronic state of 39K85Rb.
We report the observation and analysis of the 3 (3)ΠΩ double-minimum electronic excited state of (39)K(85)Rb. The spin-orbit components (0(+), 0(-), 1, and 2) of this state are investigated based on potentials developed from the available ab initio potential curves. We have assigned the vibrational levels v' = 2-11 of the 3 (3)Π1,2 potentials and v' = 2-12 of the 3(3)Π0(+/-) potential. We compare our experimental observations of the 3 (3)ΠΩ state with predictions based on theoretical potentials. The observations are based on resonance enhanced multiphoton ionization of ultracold KRb in vibrational levels v" = 14-25 of the a (3)Σ(+) state. These a-state ultracold molecules are formed by photoassociation of ultracold (39)K and (85)Rb atoms to the 5(1) state of KRb followed by spontaneous emission to the a state.


Metformin therapy associated with survival benefit in lung cancer patients with diabetes.
The purpose of this study is to summarize the currently available evidence regarding the concerned issue by performing a comprehensive meta-analysis. Relevant publications reporting the association of metformin use with survival of lung cancer patients with diabetes were electronically searched to identify eligible studies. The meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures for disease-free survival(DFS) and overall survival(OS) estimates. A total of 17 individual studies from 10 publications were included in the meta-analysis. Overall, the results revealed a significant association of metformin use with a better survival of lung cancer patients with diabetes(for DFS: HR = 0.65, 95%CI = 0.52-0.83; for OS: HR = 0.78, 95%CI = 0.64-0.93). The subgroup analyses showed similar association in Asian region(for DFS:HR = 0.69, 95%CI = 0.59-0.80; for OS: HR = 0.55, 95%CI = 0.46-0.67) but not in Western region. Such association was also presented in small cell lung cancer (for DFS: HR = 0.54, 95%CI = 0.38-0.77; for OS: HR = 0.52, 95%CI = 0.39-0.69) and in non-small cell lung cancer(for DFS: HR = 0.70, 95%CI = 0.51-0.96; for OS: HR = 0.75, 95%CI = 0.58- 0.97). Analyses stratified by treatment strategy showed a reduction in the risk of cancer-related mortality in patients receiving chemotherapy(for DFS: HR = 0.71, 95%CI = 0.64-0.83; for OS: HR = 0.58, 95%CI = 0.47-0.71) but not in patients receiving chemoradiotherapy. The meta-analysis demonstrated that metformin use was significantly associated with a favorable survival outcome of lung cancer patients with diabetes.


Adaptor protein is essential for insect cytokine signaling in hemocytes.
Growth-blocking peptide (GBP) is an insect cytokine that stimulates a class of immune cells called plasmatocytes to adhere to one another and to foreign surfaces. Although extensive structure-activity studies have been performed on the GBP and its mutants in Lepidoptera Pseudaletia separata, the signaling pathway of GBP-dependent activation of plasmatocytes remains unknown. We identified an adaptor protein (P77) with a molecular mass of 77 kDa containing SH2/SH3 domain binding motifs and an immunoreceptor tyrosine-based activation motif (ITAM)-like domain in the cytoplasmic region of the C terminus. Although P77 showed no capacity for direct binding with GBP, its cytoplasmic tyrosine residues were specifically phosphorylated within seconds after GBP was added to a plasmatocyte suspension. Tyrosine phosphorylation of P77 also was observed when hemocytes were incubated with Enterobactor cloacae or Micrococcus luteus, but this phosphorylation was found to be induced by GBP released from hemocytes stimulated by the pathogens. Tyrosine phosphorylation of the integrin beta subunit also was detected in plasmatocytes stimulated by GBP. Double-stranded RNAs targeting P77 not only decreased GBP-dependent tyrosine phosphorylation of the integrin beta subunit, but also abolished GBP-induced spreading of plasmatocytes on foreign surfaces. P77 RNAi larvae also showed significantly higher mortality than control larvae after infection with Serratia marcescens, indicating that P77 is essential for GBP to mediate a normal innate cellular immunity in insects. These results demonstrate that GBP signaling in plasmatocytes requires the adaptor protein P77, and that active P77-assisted tyrosine phosphorylation of integrins is critical for the activation of plasmatocytes.


A cadaver study appraising accuracy of blind placement of percutaneous tracheostomy.
An attempt was made to place a percutaneous catheter between the first and second cartilaginous rings of the trachea in 20 cadavers presenting for postmortem examination. Only nine of the catheters entered the trachea in the intended space. All catheters which were noted to be difficult to place entered the trachea higher than intended. One third of all catheters punctured the thyroid isthmus.


Mid-Infrared Pumped Laser-Induced Thermal Grating Spectroscopy for Detection of Acetylene in the Visible Spectral Range.
We present mid-infrared laser-induced thermal grating spectroscopy (IR-LITGS) using excitation radiation around 3 µm generated by a simple broadband optical parametric oscillator (OPO). Acetylene as a typical small hydrocarbon molecule is used as an example target species. A mid-infrared broadband OPO pumped by the fundamental output of a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser was used to generate the pump beams, with pulse energies of 6-10 mJ depending on the wavelength. The line width of the OPO idler beam was ∼5 cm(-1), which is large enough to cover up to six adjacent acetylene lines. The probe beam was the radiation of a 532 nm cw solid state laser with 190 mW output power. Signals were generated in atmospheric pressure gas flows of N2, air, CO2 and Ar with small admixtures of C2H2 A detection limit of less than 300 ppm was found for a point measurement of C2H2 diluted in N2 As expected, the oscillation frequency of the IR-LITGS signal was found to have a large dependency on the buffer gas, which allows determination of the speed of sound. Moreover, the results reveal a very strong collisional energy exchange between C2H2 and CO2 compared to the other gases. This manifests as significant local heating. In summary, the MIR-LITGS technique enables spectroscopy of fundamental vibrational transitions in the infrared via detection in the visible spectral range.


[Expressions of COX-2, PKC-α and miR-101 in gastric cancer and their correlations].
To investigate the expressions of miR-101, protein kinase C-α (PKC-α), and cyclooxygenase-2 (COX-2) in gastric cancer (GC) tissue and their correlations. RT-qPCR was used to examine miR-101 expression and Western blotting employed to detect PKC-α and COX-2 expressions in 57 cases of gastric cancer tissues and paired normal gastric mucosal tissues. The gastric cancer tissues showed a significantly lower miR-101 expression (Z=6.102, P<0.05) but significantly higher expressions of COX-2 (Z=14.436, P<0.05) and PKC-α (Z=6.955, P<0.05) than the normal gastric tissues. The expression of COX-2 protein was significantly correlated with the degree of differentiation, invasion depth, lymph node metastasis and TNM stage (P<0.05); PKC-α protein expression was associated with lymph node metastasis and TNM stage (P<0.05). PKC-α expression was positively correlated (r=0.531, P<0.05) and miR-101 expression negatively correlated (r=-0.627, P<0.05) with COX-2 expression in gastric cancer tissues. miR-101, PKC-α and COX-2 all play a role in the tumorigenesis and progression of gastric cancer. miR-101 and PKC-α might be new potential therapeutic targets for inhibiting COX-2 in gastric cancer.


The GIST of concepts.
A unified general theory of human concept learning based on the idea that humans detect invariance patterns in categorical stimuli as a necessary precursor to concept formation is proposed and tested. In GIST (generalized invariance structure theory) invariants are detected via a perturbation mechanism of dimension suppression referred to as dimensional binding. Structural information acquired by this process is stored as a compound memory trace termed an ideotype. Ideotypes inform the subsystems that are responsible for learnability judgments, rule formation, and other types of concept representations. We show that GIST is more general (e.g., it works on continuous, semi-continuous, and binary stimuli) and makes much more accurate predictions than the leading models of concept learning difficulty, such as those based on a complexity reduction principle (e.g., number of mental models, structural invariance, algebraic complexity, and minimal description length) and those based on selective attention and similarity (GCM, ALCOVE, and SUSTAIN). GIST unifies these two key aspects of concept learning and categorization. Empirical evidence from three experiments corroborates the predictions made by the theory and its core model which we propose as a candidate law of human conceptual behavior.


Enhancement of the antipsychotic effect of risperidone by sodium nitroprusside in rats.
Recently, a single injection of the nitric oxide donor sodium nitroprusside (SNP) was found to induce a rapid and sustained antipsychotic effect in treatment-resistant schizophrenia (TRS). Moreover, a single i.p. injection of SNP in rats was found to generate both rapid and persisting changes in brain synaptic plasticity, including enhanced excitatory postsynaptic current responses and spine morphology in layer V pyramidal cells in the medial prefrontal cortex (mPFC) brain slices. Here we used the conditioned avoidance response (CAR) test in rats to investigate the antipsychotic-like efficacy of SNP in combination with low-dose risperidone. In addition, we performed microdialysis experiments in freely moving rats to measure neurotransmitter efflux in the mPFC and the nucleus accumbens (NAc). Risperidone caused only 20% suppression of CAR, which is far below the degree of CAR suppression required to predict a significant clinical antipsychotic effect. Addition of a low dose of SNP to risperidone dramatically enhanced the antipsychotic-like effect to a clinically relevant level. SNP significantly enhanced the risperidone-induced dopamine output in the mPFC but not in the NAc. The increased prefrontal dopamine release induced by the drug combination may also improve cognition as indicated by previous preclinical and clinical studies and, furthermore, via enhanced synaptic spine function and morphology in mPFC generate a both rapid and prolonged antipsychotic and pro-cognitive effect. Our results delineate SNP as a promising new treatment option for schizophrenia, including TRS, when added to currently available antipsychotic medication in order to improve efficacy at maintained or even reduced dosage.


The Dynamic Interface of Viruses with STATs.
Viruses commonly antagonize the antiviral type I interferon response by targeting signal transducer and activator of transcription 1 (STAT1) and STAT2, key mediators of interferon signaling. Other STAT family members mediate signaling by diverse cytokines important to infection, but their relationship with viruses is more complex. Importantly, virus-STAT interaction can be antagonistic or stimulatory depending on diverse viral and cellular factors. While STAT antagonism can suppress immune pathways, many viruses promote activation of specific STATs to support viral gene expression and/or produce cellular conditions conducive to infection. It is also becoming increasingly clear that viruses can hijack noncanonical STAT functions to benefit infection. For a number of viruses, STAT function is dynamically modulated through infection as requirements for replication change. Given the critical role of STATs in infection by diverse viruses, the virus-STAT interface is an attractive target for the development of antivirals and live-attenuated viral vaccines. Here, we review current understanding of the complex and dynamic virus-STAT interface and discuss how this relationship might be harnessed for medical applications.


Inhibition of the Na+/K+-ATPase by cardiac glycosides suppresses expression of the IDO1 immune checkpoint in cancer cells by reducing STAT1 activation.
Despite extensive basic and clinical research on immune checkpoint regulatory pathways, little is known about the effects of the ionic tumor microenvironment on immune checkpoint expression and function. Here we describe a mechanistic link between Na+/K+-ATPase (NKA) inhibition and activity of the immune checkpoint protein indoleamine-pyrrole 2',3'-dioxygenase 1 (IDO1). We found that IDO1 was necessary and sufficient for production of kynurenine, a downstream tryptophan metabolite, in cancer cells. We developed a spectrophotometric assay to screen a library of 31 model ion transport-targeting compounds for potential effects on IDO1 function in A549 lung and MDA-MB-231 breast cancer cells. This revealed that the cardiac glycosides ouabain and digoxin inhibited kynurenine production at concentrations that did not affect cell survival. NKA inhibition by ouabain and digoxin resulted in increased intracellular Na+ levels and downregulation of IDO1 mRNA and protein levels, which was consistent with the reduction in kynurenine levels. Knockdown of ATP1A1, the ɑ1 subunit of the NKA and target of cardiac glycosides, increased Na+ levels to a lesser extent than cardiac glycoside treatment and did not affect IDO1 expression. However, ATP1A1 knockdown significantly enhanced the effect of cardiac glycosides on IDO1 expression and kynurenine production. Mechanistically, we show that cardiac glycoside treatment resulted in curtailing the length of phosphorylation-mediated stabilization of STAT1, a transcriptional regulator of IDO1 expression, an effect enhanced by ATP1A1 knockdown. Our findings reveal cross talk between ionic modulation via cardiac glycosides and immune checkpoint protein expression in cancer cells with broad mechanistic and clinical implications.


Polymer-Coated Magnetic Microspheres Conjugated with Growth Factor Receptor Binding Peptides Enable Cell Sorting.
The separation and sorting of human cells is an important step in the bioprocessing of cell-based therapeutics. Heterogeneous mixtures of cells must be sorted to isolate the desired cell type and purify the final product. This process is often achieved by antibody-based sorting techniques. In this work, we demonstrate that magnetic microspheres may be functionalized with peptides that selectively bind to cells on the basis of their relative concentration of specific surface proteins. Five-micrometer-magnetic microspheres were coated with the synthetic copolymer PVG (poly(poly(ethylene glycol)methyl ether methacrylate-ran-vinyl dimethyl azlactone-ran-glycidyl methacrylate) and functionalized with the vascular endothelial growth factor receptor binding peptide (VRBP), which binds to the vascular endothelial growth factor receptor (VEGFR). These microspheres exhibited low cytotoxicity and bind to cells depending on their relative surface protein expression. Finally, coated, magnetic microspheres were used to separate heterogeneous populations of cells dependent on their VEGFR expression through magnetic-assisted cell sorting (MACS), demonstrating that peptide-based cell sorting mechanisms may be useful in the bioprocessing of human-cell-based products.


Evaluation of reliability and reproducibility of dental indices.
Evaluation of periodontal therapy involves the use of several oral indices to describe the health status of hard and soft tissues. It was the objective of the present study to evaluate the reliability and reproducibility of some of these indices. A calibration and standardization session was designed to calibrate 10 examiners and a "gold standard" (an experienced examiner) in evaluating the following indices: the Volpe-Manhold calculus index (VM), the Lobene stain index (SI), a non-invasive modification of the Löe-Silness gingival index (GI), the papillary bleeding score (PBS) of Loesche, and the plaque index (PI) of Quigley-Hein as modified by Turesky. For each index, the average intraclass correlation was calculated between two subject visits. The highest intraclass correlation, 0.94, was found for PBS. The intraclass correlation for PI was 0.70 and for VM, 0.65. The lowest intraclass correlations were for stain, 0.47, and GI, 0.25. Intra-subject correlations between the 2 visits were good for all indices, but were best for PBS, followed by VM. PBS seems to be the most reliable index (both intra- and inter-examiner) for measuring the oral health status and is therefore recommended for use in clinical studies.


Presence of neuron-specific enolase and somatostatin in human parathyroid tissues.
The association of parathyroid abnormalities with apudomas prompted us to examine parathyroid tissues for the presence of neuron-specific enolase and somatostatin. Enolase was present in extracts of 29 out of 29 parathyroid specimens; tissue content was significantly higher in adenoma than in hyperplasia tissues (p less than 0.005). Somatostatin was present in 14 of 33 specimens. Immunoreactive somatostatin measured in tissue extracts' fluids coeluted on Sephacryl chromatography along with synthetic somatostatin-14 in studies of two parathyroid carcinoma specimens. Since neuron-specific enolase has been found only in neural and neuroendocrine cells, our results suggest that human parathyroid glands may contain neuroendocrine elements. The differential content of neuron-specific enolase in adenoma versus hyperplasia specimens may be diagnostically useful in selected cases. The significance of the presence of somatostatin in some but not all parathyroid tumors requires further investigation. Taken together with our prior findings of gastrin and pancreatic polypeptide in some human parathyroid glands, we postulate that human parathyroid tumors contain neural crest elements.


The peroneal tubercle: description, classification, and relevance to peroneus longus tendon pathology.
The size and configuration of the peroneal tubercle has been implicated in the pathogenesis of peroneal tendon tears and tenosynovitis. The purpose of this study was to determine the size and prevalence of the peroneal tubercle and devise a classification scheme according to the structure of the tubercle. One hundred and seventeen calcanei were selected from 59 human skeletons in an osteological collection (one calcaneus was missing). Three were excluded because of the poor condition, leaving 114 calcanei. The peroneal tubercle was measured in length, height, and depth and its structure subjectively described as flat, prominent, concave, or tunnel for each specimen when present. This study revealed a peroneal tubercle prevalence of 90.4% (103) in 114 calcanei. The average length, height, and depth of the tubercle were 13.04 mm (range 3.61 mm to 26.66 mm), 9.44 mm (range 3.67 mm to 23.40 mm), and 3.13 mm (range 1 to 10), respectively. The peroneal tubercle was classified structurally as flat in 44 (42.7%), prominent in 30 (29.1%), concave in 28 (27.2%), and tunnel in one (1.0%). This data may further help to understand the size and assorted configurations of the peroneal tubercle and how they relate to peroneus longus tendon pathology.


Immune mechanisms in oral lichen planus.
Oral lichen planus (OLP) is a T cell-mediated inflammatory disease of the oral mucosa that has been extensively researched over many years but as yet the mechanisms of pathogenesis are still not fully understood. Whilst the specific aetiological factors driving OLP remain ambiguous, evidence points to the development of a chronic, dysregulated immune response to OLP-mediating antigens presented by innate immune cells and oral keratinocytes leading to increased cytokine, chemokine and adhesion molecule expression. These molecules recruit T cells and mast cells to the diseased site and orchestrate a complex interplay between cells that culminates in keratinocyte cell death, mucosal basement membrane destruction and long-term chronicity of the disease. The main lymphocytes involved are thought to be CD8+ cytotoxic and CD4+ Th1 polarised T cells although recent evidence indicates the involvement of other Th subsets such as Th9, Th17 and Tregs, suggesting that a more complex immune cell relationship exists during the disease process. This review provides an overview of the immune mechanisms at play in OLP pathogenesis with particular emphasis on the role of the different Th subsets and how these recent discoveries may guide research towards identifying potential therapeutic targets.


Potential sites of action of TNPA: a dopamine-2 receptor agonist.
The purpose of this study was to correlate potential mechanisms with site(s) of action for TNPA-induced ocular hypotension. In response to R(-)-2, 10, 11-trihydroxy-N-propyl-noraporphine hydrobromide (TNPA, 75 microg), a D2 dopamine receptor agonist, the intraocular pressure decreased by 4.5 and 8 mm Hg at 1 and 2 hr, respectively, as measured by pneumatonometry. The levels of norepinephrine in aqueous humor, as determined by high performance liquid chromatography with electrochemical detection, were reduced by 38% and 79% at 1 and 2 hr, respectively, following topical application of TNPA (75 microg). Following pretreatment with raclopride (750 microg), a D2 receptor antagonist, and a subsequent challenge with TNPA (75 microg), the depression of intraocular pressure and levels of norepinephrine induced by TNPA (75 microg, 2 hr) were antagonized. In order to examine sites of action, immunohistochemistry of D2 dopamine receptors was performed in the ciliary body of normal and sympathetically denervated rabbits utilizing a goat polyclonal D2 receptor IgG and anti-goat IgG-FITC. Results from immunolocalization experiments demonstrated that D2 receptors are present on postganglionic sympathetic nerves in the ciliary body of normal rabbits but minimally detectable in that of sympathectomized rabbits. It is concluded that immunohistochemical identification of D2 receptors in the ciliary body associated with the suppression of aqueous norepinephrine levels by topical application of the D2 receptor agonist, TNPA, provide strong evidence of prejunctional (neuronal) site of action of TNPA. Antagonism of TNPA-induced ocular hypotension by raclopride coupled with the immunohistochemical and norepinephrine data suggest that D2 dopamine receptors are located on postganglionic sympathetic neurons in the ciliary body.


Big brains are not enough: performance of three parrot species in the trap-tube paradigm.
The trap-tube task has become a benchmark test for investigating physical causality in vertebrates. In this task, subjects have to retrieve food out of a horizontal tube using a tool and avoiding a trap hole in the tube. Great apes and corvids succeeded in this task. Parrots with relative brain volumes comparable to those of corvids and primates also demonstrate high cognitive abilities. We therefore tested macaws, a cockatoo, and keas on the trap-tube paradigm. All nine parrots failed to solve the task. In a simplified task, trap tubes with a slot inserted along the top were offered. The slot allowed the birds to move the reward directly with their bills. All but one individual solved this task by lifting the food over the trap. However, the parrots failed again when they were prevented from lifting the reward, although they anticipated that food will be lost when moved into the trap. We do not think that the demanding use of an external object is the main reason for the parrots' failure. Moreover, we suppose these parrots fail to consider the trap's position in the beginning of a trial and were not able to stop their behaviour and move the reward in the trap's opposite direction.


Are there age differences in the executive component of working memory? Evidence from domain-general interference effects.
Young and older adults performed verbal and spatial storage-only and storage-plus-processing working memory tasks while performing a secondary finger tapping task, and the effects on both the maximum capacity (measured as the longest series correct) and the reliability (measured as the proportion of items correct) of working memory were assessed. Tapping tended to produce greater disruption of working memory tasks that place greater demands on executive processes (i.e., storage-plus-processing tasks compared to storage-only span tasks). Moreover, tapping produced domain-general interference, disrupting both verbal and spatial working memory, providing further support for the idea that tapping interferes with the executive component of the working memory system, rather than domain-specific maintenance processes. Nevertheless, tapping generally produced equivalent interference effects in young and older adults. Taken together, these findings are inconsistent with the hypothesis that age-related declines in working memory are primarily attributable to a deficit in the executive component.


Communicating Branches of the Facial Nerve: Descriptions and Clinical Considerations.
Major branching patterns of the facial nerve have been extensively studied because damage to branches of the nerve is associated with complications ranging from weakness to paralysis. However, communicating branches of the facial nerve have received far less attention despite being hypothesized as a means of motor recovery following facial nerve injury. The aim of this study was to characterize the frequency of communicating branches of the facial nerve to provide clarity on their anatomy and clinical correlations. Bilateral facial dissections were completed on cadaveric donors (n = 20) to characterize the frequency and location of communicating branches across terminal branches of the facial nerve. Statistical analyses were employed to analyze differences between the location of communications by side and whether the communicating branches were more likely to occur on the left or right side (P < 0.05). Communicating branches were identified among all terminal branches of the facial nerve and their frequencies reported. The highest frequencies of communicating branches were identified between the buccal-to-marginal mandibular and zygomatic-to-buccal branches, at 67.5% (27 comm/40 hemifaces). The second highest frequency was identified between the temporal-to-zygomatic branches in 62.5% (25/40) of donors. The marginal mandibular-to-cervical branches had communicating branches at a frequency of 55% (22/40). Location or sidedness of communicating branches did not significantly differ. Our characterization more accurately defines generalizable areas in which communicating branches are located. These locations of branches, described in relation to nearby landmarks, are fundamental for clinical and surgical settings to improve procedural awareness.


Reliability of temporal summation and diffuse noxious inhibitory control.
The test-retest reliability of temporal summation (TS) and diffuse noxious inhibitory control (DNIC) has not been reported to date. Establishing such reliability would support the possibility of future experimental studies examining factors affecting TS and DNIC. Similarly, the use of manual algometry to induce TS, or an occlusion cuff to induce DNIC of TS to mechanical stimuli, has not been reported to date. Such devices may offer a simpler method than current techniques for inducing TS and DNIC, affording assessment at more anatomical locations and in more varied research settings. The present study assessed the test-retest reliability of TS and DNIC using the above techniques. Sex differences on these measures were also investigated. Repeated measures ANOVA indicated successful induction of TS and DNIC, with no significant differences across test-retest occasions. Sex effects were not significant for any measure or interaction. Intraclass correlations indicated high test-retest reliability for all measures; however, there was large interindividual variation between test and retest measurements. The present results indicate acceptable within-session test-retest reliability of TS and DNIC. The results support the possibility of future experimental studies examining factors affecting TS and DNIC.


Morphological and developmental studies of the snake trypanosome Trypanosoma hydrae Ayala, Atkinson, Vakalis, 1983 in experimentally infected hosts and in culture.
Trypanosoma hydrae from the broad-banded watersnake, Nerodia fasciata confluens, underwent development in the freshwater leech, Placobdella parasitica. Epimastigotes and transitional stages were present only in the crop and gastric caecum. Only one metacyclic form was observed. The potential of leeches as vectors is discussed. Two broad-banded watersnakes were infected by inoculation with culture forms of T. hydrae maintained on NNN medium. Parasitemias varied from 10(5)/ml to 10(6)/ml with dividing forms seen only rarely. A broad and a slender form of T. hydrae are described from the peripheral blood of a watersnake 7 months after an experimental infection.


Hierarchic micro-patterned porous scaffolds via electrochemical replica-deposition enhance neo-vascularization.
Neo-vascularization is a key factor in tissue regeneration within porous scaffolds. Here, we tested the hypothesis that micro-patterned scaffolds, with precisely-designed, open micro-channels, might help endothelial cells to produce intra-scaffold vascular networks. Three series of micro-patterned scaffolds were produced via electrochemical replica-deposition of chitosan and cross-linking. All had regularly-oriented micro-channels (ϕ 500 μm), which differed for the inter-channel spacing, at 600, 700, or 900 μm, respectively. Random-pore scaffolds, using the same technique, were taken as controls. Physical-mechanical characterization revealed high water uptake and favorable elastic mechanical behavior for all scaffolds, slightly reduced in the presence of cross-linking and enhanced with the 700 μm-spaced micro-pattern. At MTT assay, mouse endothelial cell viability was >90% at day 1, 3 and 7, confirmed by visual examination with scanning electron microscopy (SEM). Intra-scaffold cell density, at fluorescence analysis, was higher for the 600 μm-spaced and the 700 μm-spaced micro-patterns over the others. The 700 μm-spaced scaffold was selected for the in vivo testing, to be compared to the random-pore one. Neither type produced an inflammatory reaction; both showed excellent tissue ingrowth. Micro-patterned scaffolds enhanced neo-vascularization, demonstrated by immunofluorescent, semi-quantitative analyses. These findings support the use of micro-patterned porous scaffolds, with adequately spaced micro-channels, to promote neo-vascularization.


Tracking a mass mortality outbreak of pen shell Pinna nobilis populations: A collaborative effort of scientists and citizens.
A mass mortality event is devastating the populations of the endemic bivalve Pinna nobilis in the Mediterranean Sea from early autumn 2016. A newly described Haplosporidian endoparasite (Haplosporidium pinnae) is the most probable cause of this ecological catastrophe placing one of the largest bivalves of the world on the brink of extinction. As a pivotal step towards Pinna nobilis conservation, this contribution combines scientists and citizens' data to address the fast- and vast-dispersion and prevalence outbreaks of the pathogen. Therefore, the potential role of currents on parasite expansion was addressed by means of drift simulations of virtual particles in a high-resolution regional currents model. A generalized additive model was implemented to test if environmental factors could modulate the infection of Pinna nobilis populations. The results strongly suggest that the parasite has probably dispersed regionally by surface currents, and that the disease expression seems to be closely related to temperatures above 13.5 °C and to a salinity range between 36.5-39.7 psu. The most likely spread of the disease along the Mediterranean basin associated with scattered survival spots and very few survivors (potentially resistant individuals), point to a challenging scenario for conservation of the emblematic Pinna nobilis, which will require fast and strategic management measures and should make use of the essential role citizen science projects can play.


The pulmonary artery catheter sleeve--protective or infective?
The use of sterile plastic sleeves to protect pulmonary artery catheters (PAC) may decrease infection risk. The catheter may require manipulation but contamination of the sleeve risks inoculating organisms into the patients. We sought to determine whether the sleeve remains sterile and for how long. We conducted a prospective observational study to culture the components of the PAC in a critically ill population. Upon removal we cultured 1) the PAC tip, 2) the PAC introducer exit site, 3) the PAC introducer hub and 4) a sterile irrigant solution which ran down the inside of the protective sleeve. Demographic, catheter and disease variables were also collected. There were 102 PAC episodes amounting to 3952 catheter hours with a mean duration of catheterisation of 39.1 (24.2) hours. There were 17 positive culture results, of which six were positive sleeve fluid cultures. In three of these patients the exit site was culture positive, and the same organism was isolated as within the sleeve. No patient had a positive blood culture. There was no difference between those with and without a positive sleeve culture in terms of demographic or disease variables. The protective sleeve of the pulmonary artery catheter does not remain sterile and should not be considered as a sterile barrier. We believe that manipulating the PAC within the sleeve carries the risk of inoculating the patient with pathogenic organisms. The duration of sterility remains to be determined.


Cloning of feather-degrading minor extracellular protease from Bacillus cereus DCUW: dissection of the structural domains.
Bacterial extracellular proteases play an important role in cell survival and cell-cell communication. A high-molecular-mass minor extracellular protease (Vpr) from a feather-degrading bacterium, Bacillus cereus DCUW, has been reported by our laboratory. In the present study, we cloned and expressed Vpr in Escherichia coli. Complete nucleotide sequencing of this gene predicted that the protease is a member of the serine protease family, and smart domain analysis revealed that the protease consists of an N-terminal signal sequence for secretion, a subtilisin_N sequence that is a signature for N-terminal processing, a catalytic S_8 peptidase domain, and finally a long C-terminal protease-associated (PA) region containing nine intrinsically disordered subdomains. Four truncated constructs of the Vpr protease were cloned and expressed in E. coli. We found that the catalytic domain (amino acid residues 172-583) is sufficient for protease activity. Maturation of the Vpr protease needed both N-terminal and C-terminal processing. We have demonstrated that the oligomerization property is associated with the C-terminal protease-associated domain and also shown that the substrate-binding specificity to raw feather resides in this domain.


Measurement of Salmonella enterica Internalization and Vacuole Lysis in Epithelial Cells.
Establishment of an intracellular niche within mammalian cells is key to the pathogenesis of the gastrointestinal bacterium, Salmonella enterica serovar Typhimurium (S. Typhimurium). Here we will describe how to study the internalization of S. Typhimurium into human epithelial cells using the gentamicin protection assay. The assay takes advantage of the relatively poor penetration of gentamicin into mammalian cells; internalized bacteria are effectively protected from its antibacterial actions. A second assay, the chloroquine (CHQ) resistance assay, can be used to determine the proportion of internalized bacteria that have lysed or damaged their Salmonella-containing vacuole and are therefore residing within the cytosol. Its application to the quantification of cytosolic S. Typhimurium in epithelial cells will also be presented. Together, these protocols provide an inexpensive, rapid and sensitive quantitative measure of bacterial internalization and vacuole lysis by S. Typhimurium.


Does prevention-focused integration lead to the triple aim? An evaluation of two new care models in England.
To examine the effectiveness of two integrated care models ('vanguards') in Salford and South Somerset in England, United Kingdom, in relation to patient experience, health outcomes and costs of care (the 'triple aim'). We used difference-in-differences analysis combined with propensity score weighting to compare the two care model sites with control ('usual care') areas in the rest of England. We estimated combined and separate annual effects in the three years following introduction of the new care model, using the national General Practice Patient Survey (GPPS) to measure patient experience (inter-organisational support with chronic condition management) and generic health status (EQ-5D); and hospital episode statistics (HES) data to measure total costs of secondary care. As secondary outcomes we measured proxies for improved prevention: cost per user of secondary care (severity); avoidable emergency admissions; and primary care utilisation. Both intervention sites showed an increase in total costs of secondary care (approximately £74 per registered patient per year in Salford, £45 in South Somerset) and cost per user of secondary care (£130-138 per person per year). There were no statistically significant effects on health status or patient experience of care. There was a more apparent short-term negative effect on measured outcomes in South Somerset, in terms of increased costs and avoidable emergency admissions, but these reduced over time. New care models such as those implemented within the Vanguard programme in England might lead to unintended secondary care cost increases in the short to medium term. Cost increases appeared to be driven by average patient severity increases in hospital. Prevention-focused population health management models of integrated care, like previous more targeted models, do not immediately improve the health system's triple aim.


Behavior of mercury emissions from a commercial coal-fired power plant: the relationship between stack speciation and near-field plume measurements.
The reduction of divalent gaseous mercury (Hg(II)) to elemental gaseous mercury (Hg(0)) in a commercial coal-fired power plant (CFPP) exhaust plume was investigated by simultaneous measurement in-stack and in-plume as part of a collaborative study among the U.S. EPA, EPRI, EERC, and Southern Company. In-stack continuous emission monitoring data were used to establish the CFPP's real-time mercury speciation and plume dilution tracer species (SO2, NOX) emission rates, and an airship was utilized as an airborne sampling platform to maintain static position with respect to the exhaust plume centerline for semicontinuous measurement of target species. Varying levels of Hg(II) concentration (2.39-3.90 μg m(-3)) and percent abundance (∼ 87-99%) in flue gas and in-plume reduction were observed. The existence and magnitude of Hg(II) reduction to Hg(0) (0-55%) observed varied with respect to the types and relative amounts of coals combusted, suggesting that exhaust plume reduction occurring downwind of the CFPP is influenced by coal chemical composition and characteristics.


Frontal EEG response to threat, aggressive traits and a family history of alcoholism: a preliminary study.
This study investigated the association between frontal EEG response to threat, a family history of alcoholism (positive history = FHP, negative = FHN), aggressive - antisocial traits and negative affect. EEG in 17 FHP men and 17 FHN men was recorded while resting and while awaiting an electric shock. Compared with FHNs, FHPs showed significantly greater threat-induced decreases in frontal alpha, but no change in frontal beta power. FHNs had significant threat-induced increases in frontal beta power. A measure of aggressive traits, the Buss-Durkee Hostility Assault scale, was also significantly associated with greater threat-induced decreases in frontal alpha power and low reactivity to threat on frontal beta power. The data suggest that familial risk for alcoholism and aggressive traits may be associated with a paradoxical pattern of both increased reactivity (more alpha suppression) and decreased reactivity (no increase in beta power) to threat in frontal cortical regions. However, these results are preliminary and tentative due to limitations arising from the small sample size and the exploratory nature of this study.


Precarity, Inequality, and the Problem of Agency in the Study of the Life Course.
Although long neglected, the themes of inequality and the differentiating consequences of structurally organized constraints and opportunities for individuals have recently become a major theme of scholars in aging and life-course studies. Beyond the evidence of intracohort patterns of cumulative dis/advantage in health and resources, recent societal trends of increasing inequality have added another dimension of theoretical interest and practical urgency to these concerns. These trends have been noteworthy both for the dramatic increase and for their planetary breadth, affecting Asia and Europe as well as America. Both researchers and popular writers have observed the growing importance of the precariat, an emerging subpopulation with tenuous connection to the primary economy encompasses individuals of every age. At the same time, individual agency and related concepts such as "choice" and "decision-making" continue regularly to appear as featured terms in studies of life course and related fields. Such concepts accord a strong explanatory force to the individual, and continue to be widely accepted as unproblematic and legitimate. This article examines the relevance of these two domains of life-course scholarship in analyzing an urgent contemporary problem-struggles associated with the "transition to adulthood" and the situation of young adults. Young people confronting this transition have been the focus of both the celebration of agency and of the growing attention on inequality and adversity and its effects on vulnerable periods and key transitions in the life course. Their situation provides an opportunity to resolve some of the tensions between perspectives that emphasize agency and those that emphasize inequality.


Observation of exciton-phonon sideband in individual metallic single-walled carbon nanotubes.
Single-walled carbon nanotubes (SWCNTs) are quasi-one-dimensional systems with poor Coulomb screening and enhanced electron-phonon interaction, and are good candidates for excitons and exciton-phonon couplings in metallic state. Here we report backscattering reflection experiments on individual metallic SWCNTs. An exciton-phonon sideband separated by 0.19 eV from the first optical transition peak is observed in a metallic SWCNT of chiral index (13,10), which provides clear evidences of excitons in metallic SWCNTs. A static dielectric constant of 10 is estimated from the reflectance spectrum.


Quadrilateral plate fractures of the acetabulum: Classification, approach, implant therapy and related research progress.
The quadrilateral plate (QP) is an essential structure of the inner wall of the acetabulum, an important weight-bearing joint of the human body, which is often involved in acetabular fractures. The operative exposure, reduction and fixation of QP fractures have always been the difficulties in orthopedics due to the special morphological structure and anatomical features of the QP. Fortunately, there have been many effective methods and instruments developed for QP exposure, reduction and fixation by virtue of the combined efforts of numerous orthopedists. At the same time, each method presents with its own advantages and disadvantages, resulting in different prognoses. It is necessary to have a thorough understanding of the anatomy, radiology and fixation techniques of the QP in terms of patient prognosis optimization. In this paper, the anatomical features, definition and classification of QP, operative approach selection, implant internal fixation methods and efficacy were reviewed.


The dynamics of the nurse-patient relationship: introduction of a synthesized theory from the patient's perspective.
The nurse-patient relationship is by many considered the core of nursing. In this paper, a synthesized theory on the dynamics of that relationship is introduced from the patient's perspective. It is described as a dynamic lived reality characterized by a sense of spiritual connection which is experienced as a bond of energy. The highest quality of this connection is the life-giving nurse-patient relationship which is greatly empowering for the patient. The prerequisites for the development of the nurse-patient relationship are perceived nurse caring, wisdom and competence in connecting with people. The dialectic nature of this relationship is discussed as well as the six main phases in the nurse-patient relationship development.


Elastofibroma of scapula: a case report and literature review.
Elastofibromas are benign soft tissue tumors. They occur mostly in the infrascapular region between the thoracic wall, the serratus anterior and the latissimus dorsi muscle, with a prevalence of up to 24% in the elderly. The etiology of this lesion remains uncertain and is a source of ongoing debate. We herein report a 54-year-old female patient, manual worker who presented with bilateral subscapular slow growing tumors for 7 months. Physical examination showed two masses of 4 cm in diameter on the right, and 8 cm on the left, both located inferior to the inferior margin of the scapula. They were more or less firm and mobile on palpation. Computed tomography scan showed large fusiform subscapular soft tissue heterogeneous solid masses with linear areas of low density secondary to fat. The lesions measured 5 cm × 4 cm on the right side and 8 cm × 8 cm on the left. Resection of the largest left tumor was achieved. Macroscopic and histological findings were consistent with elastofibroma.


Circulating tumor cell isolation and diagnostics: toward routine clinical use.
From February 7-11, 2011, the multidisciplinary Lorentz Workshop Circulating Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held in Leiden (The Netherlands) to discuss progress and define challenges and potential solutions for development of clinically useful circulating tumor cell (CTC) diagnostics. CTCs, captured as "liquid biopsy" from blood, for counting and characterization using pathology and molecular assays, are expected to replace metastatic tissue biopsies to be used to predict drug response and resistance and to monitor therapy response and cancer recurrence. CTCs are highly heterogeneous; therefore, cancer type-specific isolation technologies, as well as complex clinical interpretation software, are required.


Photocontrol of the Germination of Onoclea Spores: III. Analysis of Germination Processes by Means of Cycloheximide.
Possible involvement of protein synthesis in the germination of Onoclea sensibilis spores was investigated by temporarily applying 0.1 mm cycloheximide before and after photoinduction. Cycloheximide was shown to inhibit protein synthesis, but not to act as an uncoupler of respiration. When cycloheximide was added before or shortly after photoinduction, spore germination was inhibited with the half-maximal inhibition attained in 30 to 45 minutes and the maximal inhibition in 2 hours of incubation. When the time of the inhibitor treatment was delayed after photoinduction, the spores escape from the inhibitory effect of cycloheximide slowly during the first 8 hours and abruptly thereafter with a half-maximal time of 10 hours. If spores are washed free of exogenous cycloheximide and subsequently irradiated, their ability to germinate can be reinstated in distilled water with a half-maximal time of 12 hours. The kinetics of recovery were identical and of apparent first order, regardless of whether cycloheximide treatments were given before or after photoinduction. These results are interpreted to indicate that the normal course of germination of Onoclea spores requires the continuous synthesis of a short lived enzyme that functions in the germination processes at about 10 hours after photoinduction. The cycloheximide-sensitive step follows in the germination processes an anaerobiosis-sensitive step, but precedes the time of acetocarmine uptake or visible signs of protrusion.


Status epilepticus associated with pregnancy: A cohort study.
Status epilepticus (SE) is a neurological emergency associated with a high mortality rate and long-term cognitive sequelae. Status epilepticus in pregnancy poses a tremendous threat to both mother and fetus, making a correct diagnosis and treatment a challenging task for clinicians. The prevalence, underlying etiology, and outcomes of pregnancy-related SE remain largely unknown. We retrospectively studied all SE episodes (n=366) in patients admitted to our neurological ICU over a period of 8.5years. The patients who developed SE during pregnancy and within 6months after delivery were considered to have pregnancy-related SE. Patients with eclampsia were not included as they were usually cared for in our obstetric unit. Seven patients with pregnancy-related SE were identified (2.1% of all cases of SE), with the majority (85%) occurring de novo except for one patient who had a previous history of epilepsy-related SE due to withdrawal of antiepileptic medication. In terms of etiology, limbic encephalitis and cerebral venous sinus thrombosis were the two main etiologies of de novo SE associated with pregnancy. The overall mortality rate was 28.5% at discharge, and poor outcomes were especially noted in the patients with limbic encephalitis compared to other etiologies. Pregnancy-associated SE is rare and predominantly occurs in patients without a history of epilepsy. An autoimmune etiology should be considered in pregnant patients with de novo SE, which was associated with poor outcomes. Thorough investigations and prompt treatment according to the etiology may be required to improve the final outcomes of both mother and fetus.


Simultaneous bilateral exudative retinal detachment and peripheral necrotizing retinitis as presenting manifestations of concurrent HIV and syphilis infection.
To describe an unusual case of simultaneous bilateral exudative retinal detachment and peripheral necrotizing retinitis as presenting manifestations of concurrent HIV and syphilis infection. A previously healthy 35-year-old Caucasian male was first seen for bilateral sudden visual loss. Ophthalmoscopy showed bilateral exudative retinal detachment involving the posterior pole and a placoid-like area of peripheral necrotizing retinitis in his left eye. Physical examination revealed anal condylomata and aphthous oral lesions. Laboratory investigations confirmed the diagnosis of concurrent HIV and syphilis infection. Ocular lesions resolved in response to anti-syphilitic medication administered for three weeks. This case demonstrates the importance of considering syphilis as a cause of atypical retinitis in the HIV-positive population.


The Relationship between Hepatic High FIB-4 Score and COVID-19 Pneumonia.
We aimed to compare the level of hepatic FIB-4 scores between COVID-19 patients who had pneumonia and COVID-19 patients who had no pneumonia in an attempt to develop a risk assessment after the treatment and recovery of active COVID-19 infection. The study included 80 patients who were consecutively selected and admitted to an internal medicine outpatient clinic for a control examination after COVID-19 infection. Chest tomography was performed on all patients during the COVID-19 infection. Patients were divided into two groups as those with and without lung involvement on CT. COVID-19 infection was diagnosed using real-time reverse transcription-polymerase chain reaction (RT-PCR). The hepatic fibrosis 4 (FIB-4) index score was calculated for each patient. The statistical analyses were performed using Student's t-test and chi-squared tests. We found that the increased hepatic FIB-4 index score in patients with pneumonia group was statistically significant compared to the control group (p < 0.001). The regression analysis showed that the hepatic FIB-4 index has significant prognostic efficiencies in both uni- and multivariate models (p < 0.05). The hepatic FIB-4 index appears to be a simple parameter with a good prognostic value in patients with COVID-19 infection.


Effect of oxidative stress on (3H)N-methylscopolamine binding and production of thiobarbituric acid reactive substances in rat cerebral cortex membranes.
We investigated the effect of lipid peroxidation, in vitro induced by H2O2 or FeSO4 and ascorbic acid, on binding properties of muscarinic receptors in rat cerebral cortex membranes. Simultaneously the concentrations of thiobarbituric acid reactive substances (TBARS) were measured to assess the extent of lipid peroxidation. In conditions of increased TBARS levels the density of (3H)N-methylscopolamine [(3H)NMS] binding sites in rat cerebral cortex membranes was not affected. Decreased numbers of (3H)NMS binding sites observed in the presence of high concentrations of H2O2 (100 and 1000 mmol.l-1) accompanied by a decrease of TBARS levels might be related to a nonspecific effect of H2O2 on cellular proteins.