Photocatalytic degradation of bezacryl yellow in batch reactors--feasibility of the combination of photocatalysis and a biological treatment.
A combined process coupling photocatalysis and a biological treatment was investigated for the removal of Bezacryl yellow (BZY), an industrial-use textile dye. Photocatalytic degradation experiments of BZY were carried out in two stirred reactors, operating in batch mode with internal or external irradiation. Two photocatalysts (TiO2P25 and TiO2PC500) were tested and the dye degradation was studied for different initial pollutant concentrations (10-117 mg L(-1)). A comparative study showed that the photocatalytic degradation led to the highest degradation and mineralization yields in a stirred reactor with internal irradiation in the presence of the P25 catalyst. Regardless of the photocatalyst, discoloration yields up to 99% were obtained for 10 and 20 mg L(-1) dye concentrations in the reactor with internal irradiation. Moreover, the first-order kinetic and Langmuir-Hinshelwood models were examined by using the nonlinear method for different initial concentrations and showed that the two models lead to completely different predicted kinetics suggesting that they were completely different.According to the BOD5/ Chemical oxygen demand (COD) ratio, the non-treated solution (20 mg L(-1) of BZY) was estimated as non-biodegradable. After photocatalytic pretreatment of bezacryl solution containing 20 mg/L of initial dye, the biodegradability test showed a BOD5/COD ratio of 0.5, which is above the limit of biodegradability (0.4). These results were promising regarding the feasibility of combining photocatalysis and biological mineralization for the removal of BZY.


The Role of Response Perceptions in Couples' Ongoing Cancer-Related Disclosure.
In efforts to better understand the intricate nature of response, we tested a four-dimension structure of response patterns (measured as support, reciprocity, emotional reaction, and avoidance) as well as four single dimension models within the context of couples managing cancer. All models incorporate dyadic data, including both patient and partner perceptions that relational quality influences response patterns, and response patterns influence ongoing disclosure (measured as breadth and depth). Participants were 95 dyads in which one partner had been diagnosed with cancer. We conducted multilevel analyses using an actor-partner interdependence model. Results supported the four-dimension model as well as individual dimension models. All response types predict within person disclosure. However, only reciprocity predicts the other person's disclosure, and only patient's reports of partner reciprocity predict partner disclosure.


Bibliometric analysis of the literature of randomized controlled trials.
Evidence-based medicine (EBM) is a significant issue and the randomized controlled trial (RCT) literature plays a fundamental role in developing EBM. This study investigates the features of RCT literature based on bibliometric methods. Growth of the literature, publication types, languages, publication countries, and research subjects are addressed. The distribution of journal articles was also examined utilizing Bradford's law and Bradford-Zipf's law. The MEDLINE database was searched for articles indexed under the publication type "Randomized Control Trial," and articles retrieved were counted and analyzed using Microsoft Access, Microsoft Excel, and PERL. From 1990 to 2001, a total of 114,850 citations dealing with RCTs were retrieved. The literature growth rate, from 1965 to 2001, is steadily rising and follows an exponential model. Journal articles are the predominant form of publication, and the multicenter study is extensively used. English is the most commonly used language. Generally, RCTs are found in publications concentrating on cardiovascular disease, cancer, asthma, postoperative condition, health, and anesthetics. Zone analysis and graphical formulation from Bradford's law of scattering shows variations from the standard Bradford model. Forty-two core journals were identified using Bradford's law.


Severe bacteria-associated hemophagocytic lymphohistiocytosis in an extremely premature infant.
Hemophagocytic lymphohistiocytosis (HLH) is a rare condition with high mortality. We report an extremely premature girl, born in the 24th gestational week (BW 732 g), that during her second month developed a severe HLH subsequent to a Serratia marcescens septicemia, with hepatosplenomegaly, cytopenias, hyperbilirubinemia (mostly conjugated, total bilirubin 916 mumol/L), hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia (21266 mug/L), and elevated sIL-2 receptor levels. Genetic analysis revealed no PRF1, STX11 or UNC13D gene mutations. Treatment was provided according to the HLH-2004 protocol with etoposide, dexamethasone, and immunoglobulin, but no cyclosporin because of immature kidneys. She recovered fully from the HLH but developed a severe retinopathy as well as green teeth secondary to the hyperbilirubinemia. We conclude that secondary, bacteria-associated HLH can develop in premature infants, and that HLH can be treated with cytotoxic therapy also in premature infants. It is important to be aware of HLH in premature infants, since it is treatable.


Role of hypothalamic alpha-adrenoceptor activity in fructose-induced hypertension.
The aim of the present study was to investigate the effects of the alpha2-adrenoceptor antagonist yohimbine on blood pressure and heart rate (HR) regulation, as well as on adrenergic and serotoninergic neurotransmission, in fructose hypertensive (F) rats. The anterior hypothalamic area of control (C) and F rats was perfused with Ringer's solution containing 10 and 100 microg/mL yohimbine through a microdialysis concentric probe. The effects of yohimbine on mean arterial pressure (MAP) and HR, as well as on hypothalamic dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) levels, were measured according to perfusion time. Although intrahypothalamic perfusion of yohimbine increased blood pressure in C rats (DeltaMAP 9 +/- 1 and 11 +/- 2 mmHg for 10 and 100 microg/mL yohimbine, respectively; P < 0.05 vs Ringer's perfusion), the alpha-adrenoceptor antagonist did not modify MAP in F. Intrahypothalamic yohimbine had no effect on HR at either concentration tested. Intrahypothalamic perfusion of 10 and 100 microg/mL yohimbine increased DOPAC levels in C rats (135 +/- 6 and 130 +/- 5% of basal levels, respectively; both n = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 +/- 6 and 102 +/- 6% of basal levels, respectively; both n = 6). In both C and F rats, yohimbine administration induced an increase in 5-HIAA dialysate levels. The results of the present study support the notion that alpha2-adrenoceptor tone of the anterior hypothalamus of normotensive rats, which contributes to normal blood pressure regulation, is not involved in the control of HR in either normotensive C or hypertensive F rats. The absence of changes in MAP after yohimbine perfusion in F rats suggests that the alpha2-adrenoceptor tone could be decreased in this group of rats and that this may be responsible for the maintenance of hypertension in this model. Intrahypothalamic perfusion of yohimbine increased DOPAC in the dialysate only in C rats, suggesting changes in presynaptic alpha2-adrenoceptor activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not differ between C and F groups.


"Please keep on beating"-Participation in a Creative Workshop Offers Unexpected Benefits to Women With Takotsubo Cardiomyopathy.
Takotsubo cardiomyopathy (TCM) or "broken heart syndrome" is a rare condition that is more common in women than men, particularly those who are postmenopausal. It mimics a myocardial infarction and psychological factors have been implicated in its etiology as well as being consequences of its presentation. As part of a public engagement project we brought together 8 women (of 12 invited) previously diagnosed with TCM to facilitate a discussion, through participation in a creative workshop-based process, about their illness experience, how they made sense of it, and the meaning it had for them in their lives, and to identify areas of unmet need. Through a range of creative activities we identified that participants had high levels of unmet need in terms of information and psychosocial support. All participants enjoyed the creative process and meeting other people with a diagnosis of TCM. The workshop overall was perceived as empowering. Exploring patient narratives during artist-facilitated workshops is one approach for providing the first steps to addressing unmet need, although the importance of ensuring psychological safety cannot be over-stated.


Association between meibomian gland dysfunction and compliance of topical prostaglandin analogs in patients with normal tension glaucoma.
The aim of this study was to investigate the association between tear film and meibomian gland parameters in patients with normal tension glaucoma (NTG), who underwent topical prostaglandin analog (PGA) monotherapy, and medication compliance. Ocular surface disease index (OSDI), Schirmer's test, tear film break-up time (TBUT), keratoepitheliopathy (KEP) score with fluorescein, and meibomian gland parameters were assessed in 45 eyes of 45 patients with NTG (NTG group), who received topical PGA monotherapy for more than 1 year. The results were compared to those of 40 eyes of 40 normal subjects (control group). Medication compliance was assessed by an 8-item Morisky Medication Adherence Scale (MMAS-8). Multiple logistic regression analysis was used to identify the factors associated with medication compliance. There was a significant difference in OSDI (P = 0.043), Schirmer's test (P < 0.001), TBUT (P < 0.001), KEP score (P = 0.015) and all meibomian gland parameters (all P < 0.001) between two groups. When the NTG group was divided into compliant and non-compliant groups based on the scores of MMAS-8, 30 (75%) patients were classified into the compliant group. Multiple logistic regression analysis revealed that the lid margin score (OR, 0.256; 95% CI, 0.072-0.908, P = 0.035), meibum score (OR, 0.144; 95% CI, 0.023-0.915, P = 0.04), and meibo score (OR, 0.344; 95% CI, 0.140-0.845, P = 0.02) were significant factors associated with compliance in patients with NTG. The meibomian gland parameters showed a negative correlation with medication compliance (all P < 0.005). Malfunction of the meibomian glands can be an important clinical finding associated with compliance of PGA monotherapy in patients with NTG.


Cancer incidence trends among Asian American populations in the United States, 1990-2008.
National cancer incidence trends are presented for eight Asian American groups: Asian Indians/Pakistanis, Chinese, Filipinos, Japanese, Kampucheans, Koreans, Laotians, and Vietnamese. Cancer incidence data from 1990 through 2008 were obtained from 13 Surveillance, Epidemiology, End Results (SEER) registries. Incidence rates from 1990 through 2008 and average percentage change were computed using SEER*Stat and Joinpoint software. The annual percentage change (APC) in incidence rates was estimated with 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates. Rates for non-Hispanic whites are presented for comparison. Prostate cancer was the most common malignancy among most groups, followed by lung, colorectal, liver, and stomach cancers. Breast cancer was generally the most common cancer in women, followed by colorectal and lung cancers; liver, cervix, thyroid, and stomach cancers also ranked highly. Among men, increasing trends were observed for prostate (Asian Indians and Pakistanis: APC 1990-2003 = 2.2, 95% CI = 0.3 to 4.1; Filipinos: APC 1990-1994 = 19.0, 95% CI = 4.5 to 35.4; Koreans: APC 1990-2008 = 2.9, 95% CI = 1.8 to 4.0), colorectal (Koreans: APC 1990-2008 = 2.2, 95% CI = 0.9 to 3.5), and liver cancers (Filipinos: APC 1990-2008 = 1.6, 95% CI = 0.4 to 2.7; Koreans: APC 1990-2006 = 2.1, 95% CI = 0.4 to 3.7; Vietnamese: APC 1990-2008 = 1.6, 95% CI = 0.3 to 2.8), whereas lung and stomach cancers generally remained stable or decreased. Among women, increases were observed for uterine cancer (Asian Indians: APC 1990-2008 = 3.0, 95% CI = 0.3 to 5.8; Chinese: APC 2004-2008 = 7.0, 95% CI = 1.4 to 12.9; Filipina: APC 1990-2008 = 3.0, 95% CI = 2.4 to 3.7; Japanese: APC 1990-2008 = 1.1, 95% CI = 0.1 to 2.0), colorectal cancer (Koreans: APC 1990-2008 = 2.8, 95% CI = 1.7 to 3.9; Laotians: APC: 1990-2008 = 5.9, 95% CI = 4.0 to 7.7), lung cancer (Filipinas: APC 1990-2008 = 2.1, 95% CI = 1.4 to 2.8; Koreans: APC 1990-2008 = 2.1, 95% CI = 0.6 to 3.6), thyroid cancer (Filipinas: APC 1990-2008 = 2.5, 95% CI = 1.7 to 3.3), and breast cancer in most groups (APC 1990-2008 from 1.2 among Vietnamese and Chinese to 4.7 among Koreans). Decreases were observed for stomach (Chinese and Japanese), colorectal (Chinese), and cervical cancers (Laotians and Vietnamese). These data fill a critical knowledge gap concerning the cancer experience of Asian American groups and highlight where increased preventive, screening, and surveillance efforts are needed-in particular, lung cancer among Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and Filipino, Kampuchean, and Vietnamese men.


Pressure support ventilation.
The management of patients with respiratory failure can be challenging. A relatively new technique may be useful in freeing these patients from mechanical ventilation. With a spontaneously taken breath, positive pressure is provided by a ventilator equipped to detect small changes in airway pressure. Pressure support ventilation may mean the difference between an independent life and ventilator dependency.


Effects of high-speed power training on muscle strength and power in patients with multiple sclerosis.
This study examined the effects of a high-speed power training program in peak muscle power and maximal voluntary isometric contraction (MVIC) of knee extensors in patients with relapsing-remitting multiple sclerosis (MS). Forty patients, 20 women (age 42.8 +/- 10.3 yr) and 20 men (age 44.0 +/- 8.7 yr) diagnosed with relapsing-remitting MS were randomly assigned, with respect to sex, to either an exercise group or a control group. Participants from the exercise group performed 12 wk of supervised muscle power training of knee extensors. All subjects were tested for MVIC and peak muscle power at baseline and after the training intervention. A strain gauge was used to measure the MVIC, and peak muscle power was assessed with a linear encoder at five relative loads. The training-related effects were assessed using a t-test. The results showed no significant changes in the control group from baseline to postintervention evaluation. In contrast, the exercise group significantly increased MVIC (10.8%; p < 0.05) and muscle power at 40, 50, 60, 70, and 80% of the MVIC by 21.8, 14.5, 17.3, 19.4, and 22.3%, respectively (p < 0.01), after the training. These findings suggest that 12 wk of high-speed power training improve both MVIC and muscle power at five different loads in patients with relapsing-remitting MS.


Resection of pancreatic ductal adenocarcinoma with synchronous distant metastasis: is it worthwhile?
The purpose of this study is to report prolonged survival in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) managed by chemotherapy and surgery. Between January 2009 and August 2013, 284 patients with metastatic PDAC were managed in our oncologic department. Among them, three (1%) with a single metastasis (liver in two cases and interaorticaval in one case) underwent one- or two-stage surgical resection of the metastasis and the main tumor. Perioperative data were recorded retrospectively, including disease-free and overall survival. The three patients had chemotherapy (FOLFOX or FOLFIRINOX regimen) with objective response or stable disease prior to surgery. Median time between chemotherapy and surgery was 9 (8 to 15) months. Resection consisted in pancreaticoduodenectomy in the three cases. None of the patients had grade III/IV postoperative complications, and median hospital stay was 12 (12 to 22) days. All the patients had postoperative chemotherapy. Only one patient experienced recurrence 11 months after surgery and died after 32.5 months. The two other patients were alive with no recurrence 26.3 and 24.7 months after initial treatment. Radical resection of PDAC with single distant metastases can offer prolonged survival with low morbidity after accurate selection by neoadjuvant chemotherapy.


Precocious atherosclerosis in rheumatoid arthritis: role of traditional and disease-related cardiovascular risk factors.
The risk of cardiovascular (CV) disease increases in patients with rheumatoid arthritis (RA). This is due to a number of different triggers including traditional and disease-related factors. Among established risk factors for CV disease, smoking may exert a more dangerous effect on arterial wall in RA than in the general population by a synergic effect with inflammatory processes of the disease. Although persistent inflammation and immune dysregulation of RA may contribute to favor other well-known CV risk factors, such as dyslipidemia, it is now clear that the disease itself represents an independent risk factor for CV disease by the action of RA chronic inflammatory process as well as humoral and cell-mediated immune mechanisms. There is evidence that CV risk is associated with severity and extension of the disease and it is of interest the fact that the presence of circulating anticyclic citrullinated peptide antibodies appears to be associated with stronger evidence of subclinical atherosclerosis in RA.


Event-related theta activity reflects memory processes in pronoun resolution.
A recent eye-tracking study reported a reverse effect of a noun's lexical frequency in the context of the resolution of coreferring pronouns. Investigating the neurophysiological basis of this effect, the present electroencephalographic study found differential patterns in theta activation when participants read pronouns referring to nouns of different frequency classes. Evoked theta power after pronoun onset increased with the frequency of the critical noun. This finding suggests differential load on memory resources depending on the nouns' frequency. Elevated attention promoting memory encoding for low-frequency words is assumed to facilitate the resolution of pronouns. Location of sources of differential theta activity in the parahippocampal region is accounted for by its role in an association network that mediates memory processes.


Repurposing Simvastatin in Parkinson's Disease Model: Protection Is throughout Modulation of the Neuro-Inflammatory Response in the Substantia nigra.
Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.


Screening for Intestinal Carriage of Extended-spectrum Beta-lactamase-producing Enterobacteriaceae in Critically Ill Patients: Expected Benefits and Evidence-based Controversies.
The rising burden of intensive care unit (ICU)-acquired infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) strengthens the requirement for efficient prevention strategies. The detection of intestinal carriage of ESBL-E through active surveillance cultures (ASC) and the implementation of contact precautions (CP) in carriers are currently advocated in most high-income countries, to prevent cross-transmission and subsequent ESBL-E infections in critically-ill patients. Yet, recent studies have challenged the benefit of ASC and CP in controlling the spread of ESBL-E in ICUs with high compliance to standard hygiene precautions and no ongoing outbreak of ESBL-producing Klebsiella pneumoniae or Enterobacter spp. Besides, given their debated performance to positively predict which patients are at risk of ESBL-E infections, ASC results appear of limited value to rationalize the empirical use of carbapenems in the ICU, emphasizing the urgent need for novel anticipatory and diagnostic approaches. This Viewpoint article summarizes the available evidence on these issues.


Modelling the natural history of Huntington's disease progression.
The lack of reliable biomarkers to track disease progression is a major problem in clinical research of chronic neurological disorders. Using Huntington's disease (HD) as an example, we describe a novel approach to model HD and show that the progression of a neurological disorder can be predicted for individual patients. Starting with an initial cohort of 343 patients with HD that we have followed since 1995, we used data from 68 patients that satisfied our filtering criteria to model disease progression, based on the Unified Huntington's Disease Rating Scale (UHDRS), a measure that is routinely used in HD clinics worldwide. Our model was validated by: (A) extrapolating our equation to model the age of disease onset, (B) testing it on a second patient data set by loosening our filtering criteria, (C) cross-validating with a repeated random subsampling approach and (D) holdout validating with the latest clinical assessment data from the same cohort of patients. With UHDRS scores from the past four clinical visits (over a minimum span of 2 years), our model predicts disease progression of individual patients over the next 2 years with an accuracy of 89-91%. We have also provided evidence that patients with similar baseline clinical profiles can exhibit very different trajectories of disease progression. This new model therefore has important implications for HD research, most obviously in the development of potential disease-modifying therapies. We believe that a similar approach can also be adapted to model disease progression in other chronic neurological disorders.


Cost savings in duodenal ulcer therapy through Helicobacter pylori eradication compared with conventional therapies: results of a randomized, double-blind, multicenter trial. Gastrointestinal Utilization Trial Study Group.
We hypothesized that treatment of duodenal ulcer disease with antibiotic therapy directed toward Helicobacter pylori infection is more cost-effective than therapy with antisecretory agents. A randomized, double-blind, multicenter clinical trial of adult patients with active duodenal ulcer and H. pylori infection was conducted. Patients were randomized to receive 500 mg of clarithromycin 3 times a day plus 40 mg of omeprazole daily for 14 days followed by 20 mg of omeprazole daily for an additional 14 days (group 1), 20 mg of omeprazole daily for 28 days (group 2), or 150 mg of ranitidine hydrochloride twice a day for 28 days (group 3). The use of ulcer-related health care resources was documented during monthly interviews for 1 year after the initial therapy. Clinical success was evaluated 4 to 6 weeks and 1 year after the end of therapy. Of the 819 patients enrolled, 727 completed the study. Group 1 included 243 patients; group 2, 248 patients; and group 3, 236 patients. Patients in group 1 used fewer ulcer-related health care resources during the 1 year after therapy compared with groups 2 and 3 (comparisons are given as group 1 vs group 2 and group 1 vs group 3, respectively): the number of endoscopies performed, 28 vs 76 (P<.001) and vs 71 (P<.001); patients receiving drugs to treat an ulcer, 118 vs 180 (P<.001) and vs 168 (P<.001); clinic visits, 83 vs 135 (P=.05) and vs 161 (P<.001); hospitalizations, 0 vs 5 (P=.045) and vs 6 (P=.02); and length of hospital stay, 0 vs 24 days (P=.04) and vs 37 (P=.04). When ulcer-related costs were defined as the outcome variable in a multivariate linear regression analysis, therapy was determined to have a significant influence on costs (group 1 vs group 2, P<.001; group 1 vs group 3, P=.008). Clinical success rates at the end of the study and cure of H. pylori infection were significantly greater in group 1 compared with groups 2 and 3 (P<.001). Therapy with clarithromycin plus omeprazole provided savings of $1.94 and $2.96 (compared with therapy with omeprazole and with ranitidine hydrochloride, respectively) per dollar spent within the first year after therapy. This incremental cost-benefit translates to savings of $547 or $835 per patient in group 1 (compared with patients in group 2 or group 3, respectively) during the first year after therapy. Combination therapy with clarithromycin and omeprazole resulted in significantly fewer uses of ulcer-related health care resources than conventional antisecretory therapy during a 1-year follow-up and significant savings in associated costs during the same period. Patients who received clarithromycin plus omeprazole also showed a significantly improved clinical outcome compared with patients who received only omeprazole or ranitidine.


Antibody-drug conjugates targeting prostate-specific membrane antigen.
Prostate-specific membrane antigen (PSMA) is an integral, non-shed membrane glycoprotein that is a well-characterized and clinically validated marker of prostate cancer. The expression profile and other biological properties of PSMA make it an attractive target for antibody-drug conjugate (ADC) therapy of prostate cancer, as well as a broad range of other tumors in which PSMA is abundantly expressed within the tumor neovasculature. PSMA-targeted ADCs have been developed using auristatin and maytansinoid drugs, and each ADC has undergone extensive preclinical testing and has completed phase 1 testing in men with advanced prostate cancer. The preclinical and clinical findings have largely substantiated the promise of PSMA as an ADC target. This report summarizes the completed studies, current status, and potential future directions for ADCs that target PSMA.


Evaluation of Cyclin D1 as a Discriminatory Immunohistochemical Biomarker for Idiopathic Pulmonary Fibrosis.
Distinction of idiopathic pulmonary fibrosis (IPF) from other chronic fibrosing interstitial pneumonitides, such as hypersensitivity pneumonitis (HP) and connective tissue diseases, is critical due to varied biological and clinical outcomes. However, their histologic overlaps often pose diagnostic challenges. A recent study suggested an association of herpesvirus saimiri infection with IPF. Productive viral infection is associated with coexpression of pirated mammalian protein cyclin D1, shown to be overexpressed by immunohistochemistry (IHC) in the regenerating alveolar epithelium in IPF but not in normal lungs. We evaluated the diagnostic utility of cyclin D1 to discriminate between IPF and other fibrosing interstitial lung diseases. A retrospective study of cyclin D1 IHC expression in 27 consecutive cases of chronic fibrosing interstitial lung diseases from 2011 to 2017: 12 usual interstitial pneumonia (UIP) pattern; 5 nonspecific interstitial pneumonia pattern; 3 HP pattern; 7 unclassifiable was performed. Five cases of normal lung obtained from lobectomy specimen for malignancy are included as control. Immunoreactivity was graded semiquantitatively on a scale of 0 to 3. Cyclin D1 staining was uniformly strongly positive in all cases evaluated in the study, particularly in proliferating type II pneumocytes in the region of fibrosing areas. There was no statistical difference in the extent of cyclin D1 expression between UIP and non-UIP groups (2.7 vs. 2.5) and IPF versus non-IPF groups (2.7 vs. 2.4). Cyclin D1 expression is lower in control group compared with UIP groups (1.2 vs. 2.7). Cyclin D1 is not a specific marker of UIP pattern/IPF. The high expression of cyclin D1 in lung tissue of fibrosing interstitial pneumonitides regardless of etiology most likely correlates with proliferation in type II pneumocytes.


Comparison of the inhibitory action of natural rotenone and its stereoisomers with various NADH-ubiquinone reductases.
Two stereoisomers of natural rotenone (5'alpha-epirotenone and 5'beta-epirotenone) were synthesized to identify the stereochemical factor of rotenone required for the inhibition and also to probe the structure of the rotenone binding site. The inhibitory action of the stereoisomers was compared with that of rotenone using NADH-ubiquinone reductases from bovine heart submitochondrial particles (SMP), potato tubers (Solanum tuberosum L.) SMP and Escherichia coli (GR19N) membranes. With respect to bovine heart SMP, it was found that the bent form of rotenone is essential for the activity. The modification of the E-ring moiety also affected both the inhibitory potency and the pattern of inhibition. These results indicated that the rotenone-binding site recognizes the whole molecular structure (or shape) of rotenone in a strict sense. Rotenone and 5'beta-epirotenone inhibited the NADH-ubiquinone reductase of bovine heart SMP in a noncompetitive manner against exogenous quinones. In contrast, the inhibition pattern of 5'alpha-epirotenone varied from noncompetitive to competitive as the concentration of quinone increased. These results suggest that rotenone binds close to, but not at a site identical to, the location for ubiquinone in the ubiquinone-catalytic reaction site, whereas the 5'alpha-epirotenone-binding site overlaps that for ubiquinone due to a structural modification of E-ring moiety. Furthermore, the complex inhibition pattern of 5'alpha-epirotenone suggests that there are two quinone-binding sites in NADH-ubiquinone reductase. In contrast, the order of the inhibitory potencies of the three inhibitors with proton-pumping NADH-ubiquinone reductase of potato SMP was the same as that observed for the bovine enzyme. This suggests that the structure of rotenone-binding sites (or ubiquinone-binding sites) of these enzymes are similar. It was further demonstrated that 5'alpha-epirotenone inhibits quinone binding to both proton-pumping and non-proton-pumping NADH-ubiquinone reductases of potato SMP in a competitive manner. With respect to the proton-pumping NADH-ubiquinone reductase of the E. coli membrane, the sensitivity of the enzyme to the inhibitor was remarkably decreased and the difference in the inhibitory potencies of the three inhibitors became ambiguous. In addition, the inhibition pattern of the three inhibitors was competitive against quinone. These results indicated that, contrary to the mammalian enzyme, only part of the rotenone molecule is recognized by the quinone-binding site of this enzyme.


Onasemnogene Abeparvovec (AVXS-101) for the Treatment of Spinal Muscular Atrophy.
Spinal muscular atrophy (SMA) is a debilitating disorder characterized by degeneration of large motor neurons. It is a heterogeneous group of disorders caused by a homozygous deletion in the survival motor neuron (SMN) gene on chromosome 5, resulting in a SMN protein deficiency. Small amounts of SMN protein are also produced by the SMN2 gene, which that differs from SMN1 by a single nucleotide. Spinal muscular atrophy types and phenotypic severity depend on the number of variations of the SMN2 gene and the amount of SMN2 protein produced. Because the SMN protein deficiency is the root cause of the disease, treatment strategies for SMA revolve around increasing SMN protein production. Nusinersen (Spinraza, Biogen, Cambridge, MA) was the only treatment option available for SMA until the FDA approved onasemnogene abeparvovec-xioi (Zolgensma, AveXis Inc, Bannockburn, IL), a one-time-administered adeno-associated viral vector-based gene therapy that delivers the SMN gene to the motor neuron cells. Data from clinical studies show significant improvement in motor milestone achievements and ventilator-free survival but are limited by approximately 5 years' worth of results. This one-time intravenous injection of this new gene therapy also bears a hefty price tag; however, it may be more cost effective in the long run versus the multiple intrathecal administrations needed with nusinersen. Drug access and use are hindered by drug cost, payer reimbursement issues, and lack of long-term data from clinical studies. Questions also remain regarding the safety and efficacy of repeated drug administration for patients with advanced disease.


Treatment of Relapsed/Refractory Acute Myeloid Leukemia.
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled. These advances have paved the way for rational drug development as new "drugable" targets have emerged. Although no new drug has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration "breakthrough" designation granted to venetoclax, and promising agents such as the IDH inhibitors AG-221 and AG-120, the smoothened inhibitor glasdegib and the histone deacetylase inhibitor pracinostat. In our practice, we treat most patients with relapsed/refractory AML on clinical trials, taking into consideration their prior treatment history and response to the same. We utilize targeted sequencing of genes frequently mutated in AML to identify "actionable" mutations, e.g., in FLT3 or IDH1/2, and incorporate small-molecule inhibitors of these oncogenic kinases into our therapeutic regimens whenever possible. In the absence of actionable mutations, we rationally combine conventional agents with other novel therapies such as monoclonal antibodies and other targeted drugs. For fit patients up to the age of 65, we often use high-dose cytarabine-containing backbone regimens. For older or unfit patients, we prefer hypomethylating agent-based therapy. Finally, all patients with relapsed/refractory AML are evaluated for allogeneic HSCT.


A gene expression approach to study perturbed pathways in myositis.
To review new insights into the disease mechanisms of dermatomyositis, inclusion body myositis, and polymyositis gained from large-scale microarray gene expression studies of patient tissue samples. The detection of unexpected gene transcripts using microarrays in inflammatory myopathy tissue has led to the discovery of new types and roles of immune system cells present in muscle in these diseases. Plasmacytoid dendritic cells, the immune system's professional producer of the type 1 interferons alpha and beta, are prominent in dermatomyositis muscle. Plasma cells and myeloid dendritic cells are abundant in polymyositis and inclusion body myositis muscle. Type 1 interferon induction is the single most upregulated pathological pathway genome-wide in dermatomyositis muscle and blood. In individual patients with dermatomyositis and some with polymyositis, a blood type 1 interferon-signature correlates with disease activity. The identification of new cells and pathways in inflammatory myopathies has led to deeper mechanistic understanding of these diseases and potential therapeutic approaches. Through insights gained in gene expression studies, a strong scientific rationale has developed for blockade of the type 1 interferon pathway for treatment of dermatomyositis.


[The PTFE plastic prosthesis as an arterial replacement: experiences over a 5-year period].
Unilateral iliac femoral reconstructions with PTFE are yielding good results-similar to those with Dacron, with patency rates of 75, 67, and 65% at 1, 2 and 3 years, respectively (Kaplan-Meier). PTFE has additional advantages compared with other materials: a) no need of preclotting; b) smooth inner surface-easy thrombectomy in case of thrombosis and c) good handling characteristics. In view of the above-mentioned facts PTFE can be recommended without restriction for unilateral pelvic reconstructions. The functional early results of bilateral aorto-femoral Goretex-Y bifurcation grafts in 50 cases after 2 years are encouraging. Long-term results are still pending. Reports of other groups using this material as aorto-bifemoral substitute are not yet available. The functional results with PTFE for femoro-popliteal grafts are not satisfactory: 35% after 2.5 years. Extra-anatomical bypasses yielded 70% one-year functioning rate. Especially the ring-or spiral-armoured PTFE grafts seem to be suitable for these reconstruction procedures.


We do not need mechanical ventilation any more.
Mechanical ventilation is a lifesaving treatment delivered to patients with a wide spectrum of medical and surgical diseases. However, significant limitations of the clinical application of mechanical ventilation in current practice have emerged, prompting the definition of novel therapeutic perspectives, especially concerning the prevention and treatment of acute respiratory failure. In the past few decades, there has been a consistent scientific and technologic effort to develop alternative strategies to avoid the need for mechanical ventilation. In particular, several studies have explored the feasibility and efficacy of extracorporeal oxygenation and carbon dioxide removal. Furthermore, promising results on the prevention of the occurrence of severe acute respiratory failure have been provided by clinical studies on the noninvasive application of continuous positive airway pressure as well as by experimental investigations in basic science. Therefore, further development in this direction will occur only with a permanent integration and exchange of knowledge among industry, clinicians, and scientific investigators.


Clinical microneedle injection of methyl nicotinate: stratum corneum penetration.
In recent years, microneedles were proposed as a method to painlessly deliver drugs past the stratum corneum. Microneedles have been fabricated in several designs, but limited studies have tested microneedle injections in humans. In this work, we compare microneedle injections with topical application (TA) to investigate if microneedles enhance in vivo drug delivery past the stratum corneum. In vitro tests were used to measure microneedle pressures and injection volumes. In vivo microneedle injections were performed on the volar forearm of 11 healthy volunteers. Two sets of microneedles, pointed and symmetric, were used to develop microneedle/syringe apparatuses that were used to inject approximately 1 microL of 0.1 M methyl nicotinate, and were compared against TA. A Laser Doppler Perfusion Monitor was used to record maximum blood flow and the time to maximum blood flow at the treatment sites. Pointed and symmetric microneedle-injected sites showed a significantly faster time to maximum blood flow than TA. The pointed microneedle injections also resulted in a higher maximum blood flux. Volunteers reported feeling pressure but no pain from the microneedles during the injections. The microneedles aid in bypassing the stratum corneum and enhance drug delivery through it. The design of the microneedle influences its delivery capabilities, because the pointed microneedles seem to be less susceptible to clogging during the injection.


Prescribing power.
Nurses should be able to prescribe items usually dispensed over the counter. It would make it so much easier than having to bother a GP to prescribe eczema cream.


[Phosphorylation of YLR190w by PAP1 PHO85 kinase complex].
A yeast two-hybrid screening by using PAP1 was performed to identify targets for PAP1-PHO85 cyclin-CDK complex. N-terminal fragment of protein YLR190w, a yeast gene encoding a 491 amino acids peptide, was identified, and its coding region was amplified by PCR. The interaction of PAP1 and YLR190w was confirmed by both two-hybrid assay and GST pull-down assay in vitro. The PAP1-PHO85 kinase complex obtained from the immunoprecipitates could phosphorylate GST-YLR190w expressed in E.coli, and the phosphorylation of YLR190w was affected by the phosphate concentration, and the phosphorylation sites of YLR190w were Ser/Thr-Promotif, as revealed by protein mutation assay. In another library screen, YAF9, a yeast homolog of human AF9, was isolated using the two-hybrid system with YLR190w as the bait. It was revealed that interaction of YLR190w and YAF9 was affected by phosphate concentration. When all Ser/Thr in Ser/Thr-Pro motif were mutated to Ala, the interaction of YLR190w (mutant) and YAF9 was weakened, and the effect of phosphate concentration was impaired. Ylr190w was not involved in the PHO system by the acid phosphatase activity assay. Deletion of Ylr190w was constructed by homologous recombination and the doubling time of Ylr190w mutant strain as longer than that of wild type.


Efficacy of the Dynamic Interspinous Assisted Motion system in clinical treatment of degenerative lumbar disease.
The Dynamic Interspinous Assisted Motion (DIAM) system was designed to stabilize degenerative spinal segments without fusion surgery, maintain segment motion and prevent adjacent segment degeneration. The aim of this study was to investigate clinical efficacy of the DIAM system in treatment of degenerative lumbar disease in China. Eight cases of lumbar vertebral instability were treated with the DIAM system at Peking Union Medical College Hospital from June 2006 to January 2008. There were 6 female and 2 male subjects with a mean age of 46.9 years and a range of 40 - 52 years. Radiographs and scores on outcome measures included the visual analogue scale (VAS) for pain and the Oswestry disability index (ODI). These scores were recorded before surgery and after surgery at intervals of 3-month, 6-month, 1-year and the final follow-up visit. The follow-up time ranged from 12 - 31 months, with an average of 20.6 months. There were significant differences between preoperative and postoperative scores at each follow-up evaluation (P < 0.05). However, there was no significant difference between each postoperative follow-up score (P > 0.05). There were significant differences between preoperative and postoperative L4-5 segment activity at each time interval (P < 0.05), but no obvious difference was found within each postoperative follow-up evaluation (P > 0.05). The ODI and VAS score improvements were directly correlated with segment activity (r > 0.7, P < 0.05). The DIAM system appears to be a useful and effective treatment in the surgical management of degenerative lumbar disease in certain patients. However, long-term follow-up is needed to evaluate the clinical outcomes of the device.


Translation of EMS: clinical practice and system oversight from core content study guide to best practices implementation in an Urban EMS system.
Since 2009, the seminal text in emergency medical services (EMS) medicine has been used to guide the academic development of the new subspecialty but direct application of the material into EMS oversight has not been previously described. The EMS/Disaster Medicine fellowship program at our institution scheduled a monthly meeting to systematically review the text and develop a study guide to assist the fellow and affiliated faculty in preparation for the board examination. In addition to the summary of chapter content, the review included an assessment of areas from each chapter subject where our EMS system did not exhibit recommended characteristics. A matrix was developed in the form of a gap analysis to include specific recommendations based on each perceived gap. Initial review and completion dates for each identified gap enable tracking and a responsible party. This matrix assisted the fellow with development of projects for EMS system improvement in addition to focusing and prioritizing the work of other interested physicians working in the system. By discussing expert recommendations in the setting of an actual EMS system, the faculty can teach the fellow how to approach system improvements based on prior experiences and current stakeholders. This collaborative environment facilitates system-based practice and practice-based learning, aligning with ACGME core competencies. Our educational model has demonstrated the success of translating the text into action items for EMS systems. This model may be useful in other systems and could contribute to the development of EMS system standards nationwide.


Cancer incidence in men: a cluster analysis of spatial patterns.
Spatial clustering of different diseases has received much less attention than single disease mapping. Besides chance or artifact, clustering of different cancers in a given area may depend on exposure to a shared risk factor or to multiple correlated factors (e.g. cigarette smoking and obesity in a deprived area). Models developed so far to investigate co-occurrence of diseases are not well-suited for analyzing many cancers simultaneously. In this paper we propose a simple two-step exploratory method for screening clusters of different cancers in a population. Cancer incidence data were derived from the regional cancer registry of Umbria, Italy. A cluster analysis was performed on smoothed and non-smoothed standardized incidence ratios (SIRs) of the 13 most frequent cancers in males. The Besag, York and Mollie model (BYM) and Poisson kriging were used to produce smoothed SIRs. Cluster analysis on non-smoothed SIRs was poorly informative in terms of clustering of different cancers, as only larynx and oral cavity were grouped, and of characteristic patterns of cancer incidence in specific geographical areas. On the other hand BYM and Poisson kriging gave similar results, showing cancers of the oral cavity, larynx, esophagus, stomach and liver formed a main cluster. Lung and urinary bladder cancers clustered together but not with the cancers mentioned above. Both methods, particularly the BYM model, identified distinct geographic clusters of adjacent areas. As in single disease mapping, non-smoothed SIRs do not provide reliable estimates of cancer risks because of small area variability. The BYM model produces smooth risk surfaces which, when entered into a cluster analysis, identify well-defined geographical clusters of adjacent areas. It probably enhances or amplifies the signal arising from exposure of more areas (statistical units) to shared risk factors that are associated with different cancers. In Umbria the main clusters were characterized by high risks for cancers with alcohol and tobacco both as risk factors. Tobacco-only related cancers formed a separate cluster to the alcohol- and tobacco-related sites. Joint spatial analysis or investigation of hypothesized exposures might be used for further investigation into interesting geographical clusters.


Bile-acid binding to isolated rat liver plasma membranes. Failure to find a specific binding site.
Bile-acid transport across the hepatocyte is an active Na-dependent process and specific putative binding sites on liver plasma membrane have been described. We studied cholic-acid binding to isolated liver plasma membranes over a wide concentration range. We found no saturability of binding over a concentration range of 0.001-2000 microM. We did demonstrate saturability of binding over a concentration range (1-30 nM) at pH 6.0 and 4 degrees C, but the saturability was an artifact caused by the increasing concentration of ethanol necessary to avoid precipitation of cholic acid at pH 6.0, 4 degrees C. We were unable to eliminate specific binding by heating the plasma membrane for 3 h at 37 degrees C, as other authors have. Although we were able to show a structural specificity of the bile-acid uptake site on the isolated liver cells, we were unable to demonstrate a specific saturable bile-acid binding site on isolated liver plasma membranes.


Consequences of exposure to ionizing radiation for effector T cell function in vivo.
The adoptive transfer of actuely primed and memory virus-immune CD8+ T cells causes enhanced meningitis in both cyclophosphamide (Cy) suppressed, and unsuppressed, recipients infected with lymphocytic choriomeningitis virus (LCMV). The severity of meningitis is assessed by counting cells in cerebrospinal fluid (CSF) obtained from the cisterna magna, which allows measurement of significant inflammatory process ranging from 3 to more than 300 times the background number of cells found in mice injected with virus alone. Exposure of the donor immune population to ionizing radiation prior to transfer has shown that activated T cells from mice primed 7 or 8 days previously with virus may still promote a low level of meningitis in unsuppressed recipients following as much as 800 rads, while this effect is lost totally in Cy-suppressed mice at 600 rads. Memory T cells are more susceptible and show no evidence of in vivo effector function in either recipient population subsequent to 400 rads, a dose level which also greatly reduces the efficacy of acutely-primed T cells. The results are interpreted as indicating that heavily irradiated cells that are already fully functional show evidence of primary localization to the CNS and a limited capacity to cause pathology. Secondary localization, and events that require further proliferation of the T cells in vivo, are greatly inhibited by irradiation.


Metformin inhibits ganglionic neurotransmission in renal nerves.
Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (delta renal SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.


High-Yield Synthesis of Crystal-Phase-Heterostructured 4H/fcc Au@Pd Core-Shell Nanorods for Electrocatalytic Ethanol Oxidation.
Noble-metal nanomaterials are attracting increasing research interest due to their promising applications in electrochemical catalysis, for example. Although great efforts have been devoted to the size-, shape-, and architecture-controlled synthesis of noble-metal nanomaterials, their crystal-phase-controlled synthesis is still in its infancy. Here, for the first time, this study reports high-yield synthesis of Au nanorods (NRs) with alternating 4H/face-centered cubic (fcc) crystal-phase heterostructures via a one-pot wet-chemical method. The coexistence of 4H and fcc phases is relatively stable, and the 4H/fcc Au NRs can serve as templates for crystal-phase-controlled epitaxial growth of other metals. As an example, bimetallic 4H/fcc Au@Pd core-shell NRs are synthesized via the epitaxial growth of Pd on 4H/fcc Au NRs. Significantly, the 4H/fcc Au@Pd NRs show superior mass activity toward the ethanol oxidation reaction, i.e., 6.2 and 4.9 times those of commercial Pd black and Pt/C catalysts, respectively. It is believed that this new synthetic strategy can be used to prepare other novel catalysts for various promising applications.


Implant Based Breast Reconstruction With Acellular Dermal Matrix: Safety Data From an Open-label, Multicenter, Randomized, Controlled Trial in the Setting of Breast Cancer Treatment.
To evaluate clinical outcomes of using acellular dermal matrix (ADM) with implant based breast reconstructions (IBBRs) in a randomized controlled trial. The use of ADMs in IBBRs is widespread, but link between ADM and complications remain a controversial topic. In view of reports concerning harm, we present 6-months safety data of ADM-assisted IBBR in the setting of breast cancer treatment. An open-label, randomized, controlled trial recruiting patients from 4 centers in Sweden and 1 in UK. Eligible were women with breast cancer planned for mastectomy with immediate IBBR. Participants were randomly allocated to IBBR with or without ADM (Strattice, Branchburg, NJ), with stratification by center in blocks of 6. Main primary endpoint was number of unplanned reoperations at 24 months, and safety expressed as the incidence of adverse events with a 6-month follow-up time for all participants. Analysis were done per protocol using Fisher exact test for complications and reoperations. From start of enrolment on April 24, 2014, to close of trial on May 10, 2017, 135 women were enrolled, of whom 64 with ADM and 65 without ADM were included in the final analysis. Four patients (6%) in each group had reconstructive failure with implant loss, but IBBR with ADM exhibited a trend of more overall complications and reoperations (difference 0·16, 95% CI, -0·01 to 0·32, P = 0·070), and with higher risk of wound healing problems (P = 0·013). With 6-months follow-up for all participants, immediate IBBR with ADM carried a risk of implant loss equal to conventional IBBR without ADM, but was associated with more adverse outcomes requiring surgical intervention. Further investigation of risk factors and patient selection in a long-term follow-up is warranted.


High-rate anaerobic hydrolysis and acidogenesis of sewage sludge in a modified upflow reactor.
Continuous experiments were conducted to study the hydrolysis and acidogenesis of sewage sludge in an upflow reactor with an agitator and a gas-liquid-solid separator. Results of this study showed that 34-78% of volatile suspended solids (VSS) in sewage sludge was hydrolyzed at pH in the range 4.0-6.5, 35 degrees C and 4-24 hours of hydraulic retention time (HRT). About 31-65% of carbohydrate in sewage sludge, 20-45% of protein and 14-24% of lipid were acidified in this reactor. Hydrogen production was favored in lower pH and HRT, whereas methane production was encouraged at higher pH and HRT. Acetate, propionate, butyrate, and i-butyrate were the main aqueous acidogenic products. The distribution of these compounds in the effluent was more sensitive to pH, but was less sensitive to HRT. The maximu specific COD solubilization rate and specific volatile fatty acids production rate were 126 mg-COD/g-VSS x d and 102 mg-VFAIg-VSS x d, respectively. Compared with a CSTR, this modified upflow reactor was shown to be a more promising biosystem for the hydrolysis and acidogenesis of sewage sludge.


Eutectogels as Matrices to Manipulate Supramolecular Chirality and Circularly Polarized Luminescence.
Solvent is regarded as a factor in tuning the supramolecular chirality of self-assemblies. Deep eutectic solvents (DESs) show diverse properties in contrast to other common solvents, which are emerging in fabricating functional aggregates and nanoarchitectures. Nevertheless, the emergence and manipulation of supramolecular chirality in DES still remain mysterious. Exploring supramolecular chirality in DES would produce tunable chiroptical materials considering their feasible preparation process and abundant hydrogen bonding sites. In this work, we explored the occurrence and manipulation of supramolecular chirality in DES. Transfer from inherent chiral DES to solutes in either aggregated or monomeric building units is blocked. However, the chiral assembly of π-conjugated amino acids was realized. Compared to aqueous media, self-assembly in DES hinders the spontaneous structural and chirality evolution that benefit from efficient solvation, where the π-conjugated amino acids were involved as hydrogen bonding donors. DES performs as a dye-friendly matrix to afford chiroptical eutectogels with tunable circularly polarized luminescence, whereby a large dissymmetry g-factor of up to 0.015 was realized. DES behaves as feasible and flexible solvents to fabricate and stabilize functional soft chiral self-assemblies with controllable chiroptical properties.


Treatment options for nonresponders and relapsers to initial therapy for hepatitis C.
As treatment for chronic hepatitis C virus (HCV) infection has advanced over the past decade, efforts have evolved to retreat patients who did not achieve a sustained virologic response to previous antiviral regimens. Retreating nonresponders to interferon alfa monotherapy with a combination of interferon and ribavirin yields a sustained virologic response in 9% to 32% of patients, whereas retreatment with peginterferon alfa plus ribavirin yields a sustained virologic response in up to 30% to 40% of patients. Sustained virologic response is more likely in retreated patients with HCV genotype 2 or 3, low serum HCV RNA levels, and lack of response to prior interferon monotherapy. Retreatment of nonresponders to interferon-ribavirin combination therapy is associated with lower response rates (< or = 20%). Despite treatment advances, the efficacy of current antiviral regimens for nonresponders remains inadequate. The next few years will see more-targeted antiviral regimens for these patients and therapies focused on slowing the progression of liver disease rather than viral eradication.


Branch retinal artery occlusion after diagnostic cardiac catheterization.
A case of right branch retinal artery occlusion (BRAO) due to cholesterol-containing embolus following transfemoral cardiac catheterization is reported. It is extremely rare, however, cardiologists should be alert to any thromboembolic complications during and following cardiac catheterization and choose the suitable approach (either upper extremity or transfemoral).


Reconstructive considerations for limb salvage surgery.
Tumors in the musculoskeletal system are generally treated surgically, although radiation therapy and chemotherapy have greatly improved survival statistics of patients with high-grade sarcomas of the musculoskeletal system. The mainstay in treatment of nearly every primary tumor of the musculoskeletal system is surgical resection for cure. Radiation therapy and chemotherapy continue to be important adjuvants in the overall management of musculoskeletal tumors. Functional limb salvage following radical resection is now possible in most resectable cases by placement of an alloplastic prosthesis, homograft, or autogenous bone for skeletal reconstitution, followed by well-vascularized soft-tissue coverage.


Isolation and Extraction of Monomers from Insoluble Dietary Fiber.
Insoluble dietary fiber is a macromolecular polysaccharide aggregate composed of pectin, glycoproteins, lignin, cellulose, and hemicellulose. All agricultural by-products contain significant levels of insoluble dietary fiber. With the recognition of the increasing scarcity of non-renewable energy sources, the conversion of single components of dietary fiber into renewable energy sources and their use has become an ongoing concern. The isolation and extraction of single fractions from insoluble dietary fiber is one of the most important recent research directions. The continuous development of technologies for the separation and extraction of single components is aimed at expanding the use of cellulose, hemicellulose, and lignin for food, industrial, cosmetic, biomedical, and other applications. Here, to expand the use of single components to meet the new needs of future development, separation and extraction methods for single components are summarized, in addition to the prospects of new raw materials in the future.


Manual curation and reannotation of the genomes of Clostridium difficile 630Δerm and C. difficile 630.
We resequenced the genome of Clostridium difficile 630Δerm (DSM 28645), a model strain commonly used for the generation of insertion mutants. The genome sequence was obtained by a combination of single-molecule real-timeand Illumina sequencing technology. Detailed manual curation and comparison to the previously published genomic sequence revealed sequence differences including inverted regions and the presence of plasmid pCD630. Manual curation of our previously deposited genome sequence of the parental strain 630 (DSM 27543) led to an improved genome sequence. In addition, the sequence of the transposon Tn5397 was completely identified. We manually revised the current manual annotation of the initial sequence of strain 630 and modified either gene names, gene product names or assigned EC numbers of 57 % of genes. The number of hypothetical and conserved hypothetical proteins was reduced by 152. This annotation was used as a template to annotate the most recent genome sequences of the strains 630Δerm and 630. Based on the genomic analysis, several new metabolic features of C. difficile are proposed and could be supported by literature and subsequent experiments.


Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.
To evaluate the postoperative changes in blebs and levels of aqueous monocyte chemotactic protein-1 (MCP-1) after trabeculectomy vs. Ex-PRESS tube shunt surgery. Rabbits were subjected to trabeculectomy or Ex-PRESS tube shunt surgery and observed for up to 3 months. Intraocular pressure (IOP) was measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Bleb morphology was evaluated using photos and anterior-segment optical coherence tomography (OCT). There were no differences in bleb appearance or IOP at any time between the groups. Bleb wall density in the anterior-segment OCT image was significantly lower 1 week after surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in control eyes was 304.1 ± 45.2 pg/mL. In the trabeculectomy group, the mean aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5, 1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90 days after surgery, respectively. In the Ex-PRESS group, the corresponding values were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0 pg/mL. There were no significant differences in the aqueous MCP-1 level between the groups at any time point. The postoperative changes were similar in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal peaks in both groups.


A silver(i)-induced higher-ordered structure based on planar chiral tetrasubstituted [2.2]paracyclophane.
Optically active phenylene-ethynylene dimers with pyridine groups based on a planar chiral 4,7,12,15-tetrasubstituted [2.2]paracyclophane were synthesized. The chiral conformation was controlled by pyridine-Ag(i) coordinations. After Ag(i) coordination, the resulting higher-ordered structure dramatically enhanced the signal intensity of circular dichroism (CD) and decreased that of circularly polarized luminescence (CPL).


Identification and quantification of small exon-containing isoforms in long-read RNA sequencing data.
Small exons are pervasive in transcriptomes across organisms, and their quantification in RNA isoforms is crucial for understanding gene functions. Although long-read RNA-seq based on Oxford Nanopore Technologies (ONT) offers the advantage of covering transcripts in full length, its lower base accuracy poses challenges for identifying individual exons, particularly microexons (≤ 30 nucleotides). Here, we systematically assess small exons quantification in synthetic and human ONT RNA-seq datasets. We demonstrate that reads containing small exons are often not properly aligned, affecting the quantification of relevant transcripts. Thus, we develop a local-realignment method for misaligned exons (MisER), which remaps reads with misaligned exons to the transcript references. Using synthetic and simulated datasets, we demonstrate the high sensitivity and specificity of MisER for the quantification of transcripts containing small exons. Moreover, MisER enabled us to identify small exons with a higher percent spliced-in index (PSI) in neural, particularly neural-regulated microexons, when comparing 14 neural to 16 non-neural tissues in humans. Our work introduces an improved quantification method for long-read RNA-seq and especially facilitates studies using ONT long-reads to elucidate the regulation of genes involving small exons.


[UFT in the treatment of primary lung cancer--5-FU concentration in the tissue and side effects].
The concentrations of FT, 5-FU and uracil in lung cancer tissue, healthy lung tissue and serum were measured in 10 patients with primary lung cancer to whom UFT (600 mg) had been administered for one week. No remarkable difference was found in the concentration of FT between both tissues. The concentration of 5-FU in lung cancer tissue was 0.099 +/- 0.051 microgram/g and significantly higher than the level of 0.009 +/- 0.003 microgram/ml in serum (p less than 0.001) and 0.039 +/- 0.021 microgram/g in normal lung tissue (p less than 0.01). The ratio of 5-FU concentration in cancerous tissue to that in the serum was 11.0, while the ratio of the level in cancerous tissue to that in normal lung tissue was 2.5. The concentration of uracil was much higher in cancerous tissue than in normal lung tissue and serum. Maintenance therapy with UFT proved possible for a long period in 11 primary lung cancer patients with negligible digestive side effects.


The Pattern of Dyslipidemia in Chronic Liver Disease Patients.
Introduction Patients with chronic liver disease are expected to report derangements in serum lipid profiles. Lipid profile monitoring is not a part of the routine management of these patients in our hospital. Few recent studies show how lipid profile varies with the severity of disease and should be considered in the management planning of such patients. The objective of this study was to determine the pattern of dyslipidemia in chronic liver disease patients. Materials and methods A cross-sectional study was conducted involving 171 patients of all genders aged between 18 years and 60 years presenting with chronic liver disease with disease severity graded on Child-Pugh class as A, B, and C. Lipid profile was acquired in all these patients and was compared across various subgroups. Individual serum lipid parameters were graded as normal, high, or very high. Each patient was required to provide written informed consent. Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp. Armonk, NY) was used to analyze data statistically, taking a p-value of ≤0.05 as significant. Results The mean age of patients was 51.2±7.3 years. The male to female ratio came out to be 1.5:1, with 103 (60.2%) male and 68 (39.8%) female patients included in the study. The disease was classified as Child-Pugh A in 20 (11.7%) patients, Child-Pugh B in 67 (39.2%) patients, and Child-Pugh C in 84 (49.1%) patients. Forty-four (25.7%) patients were hypertensive while 62 (36.3%) were diabetic. The mean body mass index (BMI) of these patients was 25.9±2.4 kg/m2. Mean serum values among Child-Pugh A, Child-Pugh B, and Child-Pugh C of low-density lipoproteins (LDL) (113.15±14.08 vs. 95.58±14.25 vs. 53.46±5.90 mg/dl; p-value 0.001), high-density lipoproteins (HDL) (50.60±3.19 vs. 40.70±2.95 vs. 35.40±3.88 mg/dl; p-value 0.001), total cholesterol (174.20±17.33 vs. 164.00±17.82 vs. 128.64±24.73 mg/dl; p-value 0.001), and triglycerides (127.15±8.98 vs. 100.84±27.12 vs. 93.36±25.56 mg/dl; p-value 0.001) decreased significantly with increasing severity of disease. Nineteen (11.1%) patients had hyperlipidemia (serum values of two or more parameters above normal) while 152 (88.9%) patients had normal lipid profile. When stratified, no statistically significant difference was found in the frequency of hyperlipidemia across various subgroups based on the patient's gender, age, duration, and severity of the disease, BMI, or diabetic and hypertensive status. Conclusions A substantial proportion of patients with chronic liver disease had hyperlipidemia which varied with the severity of disease on Child-Pugh classification. Routine monitoring of the lipid profile of such patients is necessary for timely identification and management of dyslipidemia to improve the outcome of such patients. It also suggests an important role of lipid profile in the risk stratification and treatment of chronic liver disease patients and warrants further studies in this regard.


A novel gene, Pi40(t), linked to the DNA markers derived from NBS-LRR motifs confers broad spectrum of blast resistance in rice.
Rice blast disease caused by Magnaporthe grisea is a continuous threat to stable rice production worldwide. In a modernized agricultural system, the development of varieties with broad-spectrum and durable resistance to blast disease is essential for increased rice production and sustainability. In this study, a new gene is identified in the introgression line IR65482-4-136-2-2 that has inherited the resistance gene from an EE genome wild Oryza species, O. australiensis (Acc. 100882). Genetic and molecular analysis localized a major resistance gene, Pi40(t), on the short arm of chromosome 6, where four blast resistance genes (Piz, Piz-5, Piz-t, and Pi9) were also identified, flanked by the markers S2539 and RM3330. Through e-Landing, 14 BAC/PAC clones within the 1.81-Mb equivalent virtual contig were identified on Rice Pseudomolecule3. Highly stringent primer sets designed for 6 NBS-LRR motifs located within PAC clone P0649C11 facilitated high-resolution mapping of the new resistance gene, Pi40(t). Following association analysis and detailed haplotyping approaches, a DNA marker, 9871.T7E2b, was identified to be linked to the Pi40(t) gene at the 70 Kb chromosomal region, and differentiated the Pi40(t) gene from the LTH monogenic differential lines possessing genes Piz, Piz-5, Piz-t, and Pi-9. Pi40(t) was validated using the most virulent isolates of Korea as well as the Philippines, suggesting a broad spectrum for the resistance gene. Marker-assisted selection (MAS) and pathotyping of BC progenies having two japonica cultivar genetic backgrounds further supported the potential of the resistance gene in rice breeding. Our study based on new gene identification strategies provides insight into novel genetic resources for blast resistance as well as future studies on cloning and functional analysis of a blast resistance gene useful for rice improvement.


A nonconventional host-guest cubic assembly based on γ-cyclodextrin and a Keggin-type polyoxometalate.
Supramolecular self-assembly allows components to organize themselves into regular patterns by using non-covalent interactions to find the lowest-energy configuration. However, self-assembling organic and inorganic building blocks together into an ordered framework remains a challenge due to the difficulties in rationally interfacing two dissimilar materials. Herein, we report on the host-guest ensemble of polyoxometalates (POMs) using cyclodextrins (CDs) as the trapping agent to form POM@γ-CD entities. Two unprecedented super cubic isostructures, Co/Cu-PW12O40-γ-CD, were obtained. The self-assembly has been observed both in solution (MS, 1D NMR and 2D DOSY) and in the solid state. Single-crystal X-ray diffraction reveals that in a unit cell, the inner (POM@γ-CD)12 cube is encapsulated by the outer (POM@γ-CD)24 cube. Besides, due to the rather large spherical voids, two (POM@γ-CD)24 cubes are interspersed together. Preliminary investigations of the redox properties of the [PW12O40]3- encapsulated in the γ-cyclodextrins indicate that the redox properties of the trianion are largely retained, yet an additional electrochemical stabilization is observed. The adduct reported here opens the door to a new generation of hybrid materials with tuned structures and customized functionalities.


Biomimetic polymer brushes containing tethered acetylcholine analogs for protein and hippocampal neuronal cell patterning.
This paper describes a method to control neuronal cell adhesion and differentiation with both chemical and topographic cues by using a spatially defined polymer brush pattern. First, biomimetic methacrylate polymer brushes containing tethered neurotransmitter acetylcholine functionalities in the form of dimethylaminoethyl methacrylate or free hydroxyl-terminated poly(ethylene glycol) units were prepared using the "grown from" method through surface-initiated atom transfer radical polymerization reactions. The surface properties of the resulting brushes were thoroughly characterized with various techniques and hippocampal neuronal cell culture on the brush surfaces exhibit cell viability and differentiation comparable to, or even better than, those on commonly used poly-l-lysine coated glass coverslips. The polymer brushes were then patterned via UV photolithography techniques to provide specially designed surface features with different sizes (varying from 2 to 200 μm) and orientations (horizontal and vertical). Protein absorption experiments and hippocampal neuronal cell culture tests on the brush patterns showed that both protein and neurons can adhere to the patterns and therefore be guided by such patterns. These results also demonstrate that, because of their unique chemical composition and well-defined nature, the developed polymer brushes may find many potential applications in cell-material interactions studies and neural tissue engineering.


Cardiovascular magnetic resonance evaluation of patients with transposition of the great arteries following atrial switch surgical correction.
We present a method of imaging patients with surgically corrected transposition of the great arteries using cardiac magnetic resonance imaging and we describe the findings from a typical case. Cardiac magnetic resonance is superior to other imaging methods for patients with complex congenital heart diseases, both for establishing the initial diagnosis and for subsequent follow-up after surgical therapy.


Efficient quantum dot-sensitized solar cells through sulfur-rich carbon nitride modified electrolytes.
For quantum dot sensitized solar cells (QDSSCs), modifying conservative polysulfide electrolytes with polymer additives has been proven as an effective method to control charge recombination processes at the TiO2/QDs/electrolyte interface and to accomplish efficient cell devices. In this respect, the polysulfide electrolyte is modified with polymeric and sulfur-rich graphitic carbon nitride (SGCN) to enhance the photovoltaic performance of QDSSCs. For the first time, SGCN is used to passivate surface trap states and act as the steric hindrance between TiO2/QDs/electrolyte interfaces. The QDSSCs fabricated with GCN and SGCN additives exhibited higher efficiencies, especially improved short-circuit current (JSC) and fill factors (FFs) than those of the liquid electrolyte. Cu-In-S sensitized QDSSCs constructed with GCN and SGCN additives exhibited efficiencies of 6.73% and 7.13%, respectively, whereas the liquid electrolytes delivered an efficiency of 6.16%. Additionally, the applicability of SGCN additives in various Cu-based QDSSCs to enhance their photovoltaic performance is further verified using Cu-In-Se QDSSCs. An increase in the conversion efficiencies of QDSSCs with SGCN additives is possibly due to (1) their electron-rich surface which can act as an obstacle for electron-hole recombination, thereby suppressing the back-transfer of photo-induced electrons to the QD/electrolyte interface; (2) SGCN facilitates the reduction of Sn2- to S2- redox couple, thus providing holes towards the QDs/electrolyte more efficiently. Overall, this work provides an innovative and economic additive to modify polysulfide electrolytes, thereby controlling the TiO2/QDs/electrolyte interfaces of QDSSCs.


Induction chemotherapy followed by concurrent chemotherapy and definitive high-dose radiotherapy for patients with locally advanced non-small-cell lung cancer (stages IIIa/IIIb): a pilot phase I/II trial.
Overall prognosis of patients with locally advanced non-small-cell lung cancer (LAD-NSCLC) is still unfavourable. Different attempts to improve treatment results have been made using combinations of chemotherapy and radiotherapy. The aim of this pilot phase I/II investigation was to test the feasibility and toxicity of a definitive multimodality protocol in patients with irresectable NSCLC stages IIIA (N2) and IIIB. Thirty LAD-NSCLC patients (stages IIIA/IIIB: 3/27; median age: 54 years, range 34-70; male/female: 17/13) who were consecutively enrolled onto our ongoing neoadjuvant multimodality protocol from October 1996 to February 1999 remained inoperable after induction treatment. Three cycles of cisplatin/etoposide (PE) were followed by hyperfractionated accelerated radiotherapy (HF-RTx: 1.5 Gy bid up to a total dose of 45 Gy in 3 weeks) concurrent with one cycle of PE. Definitive local treatment was completed with a small volume boost of 20 Gy (qd), adding up to a total dose of 65 Gy to the primary. Patients were routinely offered prophylactic cranial irradiation (PCI; 30 Gy; 2 Gy qd). Overall toxicity of the definitive CTx/RTx protocol-the main endpoint of this investigation-turned out to be acceptable (oesophagitis grade 3/4: 6/4 patients; pneumonitis grade 3/4: 0/1 patients; no treatment-related deaths). Actuarial survival at 2 years was 31% with a loco-regional control rate of 21%. This regimen turned out to be feasible with acceptable toxicity and will serve as a reference arm in a planned randomised trial in stage IIIB NSCLC, testing the value of surgery in this setting: preoperative induction CTx/RTx followed by surgery versus definitive CTx/RTx.


Effect of DDVP on the histology and AChE kinetics of heart muscles of Rattus norvegicus.
The LD50 of DDVP (Dichloro, dimethyl vinyl phosphate) for Rattus norvegicus was 21.4 mg/kg. b.w. The two sub lethal doses 1 and 3 mg/kg showed many histopathological changes in the working heart muscles and also showed significant necrosis in this S-A node, A-V node and bunble of His of the cardiac conducting system. These sublethal doses of the OP pesticide caused a significant inhibition of AChE. The maximum inhibition was noticed at the highest dose. The enhanced inhibitory constant Km and ACh contents in the heart muscles with the increase of dose showed inhibition of enzyme. The constant Vmax showed competitive nature of inhibition. A significant inhibition of AChE (69%) indicated that DDVP is a strong inhibitor of enzyme in heart.


Chemoautotrophic Potential of the Hydrothermal Vent Tube Worm, Riftia pachyptila Jones (Vestimentifera).
Trophosome tissue of the hydrothermal vent tube worm, Riftia pachyptila (Vestimentifera), contains high activities of several enzymes associated with chemoautotrophic existence. Enzymes catalyzing synthesis of adenosine triphosphate using energy contained in sulfur compounds such as hydrogen sulfide, and two diagnostic enzymes of the Calvin-Benson cycle of carbon dioxide fixation, ribulosebisphosphate carboxylase and ribulose 5-phosphate kinase, are present at high levels in trophosome, but are absent in muscle. These data are consistent with an autotrophic mode of nutrition for this worm, which lives in hydrogen sulfide-rich waters and lacks a mouth and digestive system.


[Time optimized modern shock room management using digital techniques].
Emergency room management means time management. A time and four color based algorithm is described to improve workflow, follow up of diagnostic procedures and initial treatment. As a result introducing the time based interdisciplinary emergency algorithm within 60 minutes all necessary treatment and diagnostic procedures were completed. This algorithm is an effective tool to improve emergency room treatment.


[Genetic analysis reveals misidentification of Mycobacterium lentiflavum as Mycobacterium intracellulare by the COBAS TaqMan MAI test].
To evaluate COBAS TaqMan MAI test misidentification of Mycobacterium lentiflavum as Mycobacterium intracellulare. Preliminary comparative analysis identified 13 clinical isolates used in this study as COBAS Amplicor MAV and MIN-negative but COBAS TaqMan MAI-positive. The COBAS TaqMan MAI test limit of detection and reproducibility were evaluated by tenfold dilution series from 3 x 10(8) CFU/mL. Isolate 16S rDNA nucleotide sequences were compared with Mycobacterium avium and M. intracellulare. Discrepancies were observed between isolates identified as M. lentiflavum by 16S rDNA sequencing and as M. intracellulare by the COBAS TaqMan MAI test. The false-positive results were verified by sequence comparison of a randomly sampled clinical isolate and the M. intracellulare reference strain. Sequence analysis of M. lentiflavum and M. intracellulare 16S rDNA amplification products showed at least 3 mismatches between species. The high identity in the sequence was found for M. intracellulare by COBAS TaqMan MAI. In Japan, commercially available nucleic acid probe- and amplification-based tests cannot identify M. lentiflavum. Correct identification, though challenging, is possible using standard cultivation procedures for colony growth. Misleading results using the COBAS TaqMan MAI kit may lead to erroneous diagnoses.


The N131S mutation in the von Hippel-Lindau gene in a Japanese family with pheochromocytoma and hemangioblastomas.
von Hippel-Lindau (VHL) disease (VHLD) is a hereditary autosomal dominant syndrome that causes various benign and malignant tumors. VHLD is caused by mutations in the VHL tumor suppressor gene. Here, we report a mutation in the VHL gene in a Japanese family with VHLD type 2A, characterized by pheochromocytoma (PHE), and hemangioblastomas (HAB) in both the retina and thoracic spinal cord but without renal cell carcinoma (RCC). We identified a heterozygous A to G point mutation at the second base of codon 131 of the VHL protein (pVHL). This mutation was predicted to convert codon 131 from asparagine to serine (N131S). Although most mutations in VHLD type 2A have been detected in the alpha domain of pVHL, the present mutated amino acid was located at the region encoding the beta domain of pVHL. Previous patients with the N131K or N131T mutation in pVHL developed VHLD type 2B with RCC or VHLD type 1 without PHE, respectively. We also identified somatic loss of heterozygosity (LOH) at chromosome 3p25-26 in the adrenal tumor of the patient. The results of our study suggest that not only the location of mutation but also the altered amino acid may be critical for determining the clinical phenotype of VHLD. LOH was associated with the development of PHE in a patient with the N131S mutation in pVHL.


Self-Powered Real-Time Arterial Pulse Monitoring Using Ultrathin Epidermal Piezoelectric Sensors.
Continuous monitoring of an arterial pulse using a pressure sensor attached on the epidermis is an important technology for detecting the early onset of cardiovascular disease and assessing personal health status. Conventional pulse sensors have the capability of detecting human biosignals, but have significant drawbacks of power consumption issues that limit sustainable operation of wearable medical devices. Here, a self-powered piezoelectric pulse sensor is demonstrated to enable in vivo measurement of radial/carotid pulse signals in near-surface arteries. The inorganic piezoelectric sensor on an ultrathin plastic achieves conformal contact with the complex texture of the rugged skin, which allows to respond to the tiny pulse changes arising on the surface of epidermis. Experimental studies provide characteristics of the sensor with a sensitivity (≈0.018 kPa-1 ), response time (≈60 ms), and good mechanical stability. Wireless transmission of detected arterial pressure signals to a smart phone demonstrates the possibility of self-powered and real-time pulse monitoring system.


HMGA1 is a determinant of cellular invasiveness and in vivo metastatic potential in pancreatic adenocarcinoma.
HMGA1 proteins are architectural transcription factors that are overexpressed in a range of human malignancies, including pancreatic adenocarcinoma. We hypothesized that HMGA1 expression is a determinant of cellular invasiveness and metastasis in pancreatic cancer. Stable silencing of HMGA1 in MiaPaCa2 and PANC1 pancreatic adenocarcinoma cells was achieved by transfection of short hairpin RNA-generating vectors. Additionally, stable overexpression of HMGA1 in MiaPaCa2 cells (characterized by low levels of inherent HMGA1 expression) was achieved. HMGA1 silencing resulted in significant reductions in cellular invasiveness through Matrigel; in cellular matrix metalloproteinase-9 (MMP-9) activity, mRNA levels, and gene promoter activity; and in Akt phosphorylation at Ser(473). Conversely, forced HMGA1 overexpression resulted in significant increases in cellular invasiveness; in cellular MMP-9 activity, mRNA levels, and promoter activity; and in Akt phosphorylation at Ser(473). HMGA1 overexpression-induced increases in invasiveness were MMP-9 dependent. The role of phosphatidylinositol-3 kinase (PI3K)/Akt in mediating HMGA1-dependent invasiveness was elucidated by a specific PI3K inhibitor (LY294002) and constitutively active and dominant-negative Akt adenoviral constructs. Akt-dependent modulation of MMP-9 activity contributed significantly to HMGA1 overexpression-induced increases in invasive capacity. Furthermore, HMGA1 silencing resulted in reductions in metastatic potential and tumor growth in vivo and in tumoral MMP-9 activity. Our findings suggest that HMGA1 may be a novel molecular determinant of invasiveness and metastasis, as well as a potential therapeutic target, in pancreatic adenocarcinoma.


The Role of Targeted Therapy in the Multi-Disciplinary Approach to Colorectal Liver Metastasis.
Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the United States. Among newly diagnosed patients with CRC, 20% will present with metastatic disease and another 25% will develop metastases. The surgical resection of the primary tumor and metastatic disease sites confers the best chance at long-term survival. Unfortunately, many patients will recur after resection or present with unresectable disease. As such, metastatic CRC is commonly treated with a combination of surgery, systemic therapy, and/or liver-directed therapies. Despite best efforts, 5-year survival for unresectable metastatic CRC is only about 20%. CRC is a heterogeneous disease and the underlying genetic differences inform behavior, treatment strategy, and prognosis. Given the limitations of cytotoxic chemotherapy and the growing role of molecular profiling, research has focused on identifying and developing targeted therapies. We herein review how genetic profiling informs prognosis, crucial cell-signaling pathways that play a role in CRC carcinogenesis, and currently approved targeted therapies for metastatic CRC.


[Disorders of erectile potency in diabetes mellitus].
The incidence of erectile dysfunction in patients with long-term diabetes mellitus can be as high as 50%. Diabetic microangiopathy is regarded as the most important pathogenic factor. In this review of a group of 210 impotent patients evaluated and treated at our centre we report on the examination data (angiopathy, neuropathy, psychogenic factors) in 36 patients with diabetes in comparison with the corresponding findings in 169 non-diabetic patients. In 5 patients erectile dysfunction had actually preceded the clinical manifestations of diabetes mellitus. Autoinjection therapy was started in 62% of all the diabetic patients, since this is effective, minimally invasive and, therefore, applicable to a large group of patients. This form of therapy was accepted by 90% of our patients' partners, which is in accordance to the reports in the literature. However, treatment had to be interrupted in 2 out of the 22 patients, owing to lack of cooperation on the part of the sexual partner. No complications were attributable to autoinjection therapy.


Analysis of potential hub genes involved in the pathogenesis of Chinese type 1 diabetic patients.
Type 1 diabetes is an autoimmune disease strongly related to genetic factors. Although studies on T1D susceptibility genes have achieved great progress, the molecular mechanism of T1D remains to be explained. To explore the underlying mechanisms of T1D, bioinformatic analysis based on a microarray database was used to determine the key biomarkers of T1D as well as their biofunctions and interactions. The microarray database GSE55100 was downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were processed by packages in R Software. The database for Annotation, Visualization, and Integrated Discovery (DAVID, version 6.8) was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The protein-protein interaction network was analyzed with the Search Tool for the Retrieval of Interacting Genes (STRING), and the module analysis was performed using Cytoscape. Seventy-eight DEGs and 13 hub genes were identified. The biofunctions and pathways of these DEGs were enriched in immune response, extracellular exosome, cytokine activity and antigen processing and presentation. Thirteen DEGs with MCODE score ≥2 were selected as hub genes including MMP9, ARG1, CAMP, CHI3L1, CRISP3, SLPI, LCN2, PGLYRP1, LTF, RETN, CEACAM1, CEACAM8 and MS4A3. The identification and analyses of the DEGs and hub genes from database GSE55100 provide novel prospectives of the pathogenesis of T1D.


Movement and demographics of Libellula fulva (Odonata, Libellulidae).
Many capture-recapture studies on adult dragonflies have found male-biased sex ratios. However, few have estimated survivorship of males and females separately from data on frequency of recaptures in the field. Even when daily survival and capture probabilities are estimated separately, controversies can arise on whether sex biases in local survival are to be attributed to mortality or permanent emigration from the study site. The knowledge of male and female movements, assessed on an appropriate scale (i.e., within and outside the breeding site), can help address this issue. In this paper, we performed a 4-yr capture-recapture study of two Libellula fulva Müller populations in northwest Italy. Cormack-Jolly-Seber models were used to get unbiased estimates of demographic parameters (daily survival and capture probabilities, sex ratio, mean life span, and population size). Movement parameters were measured directly by georeferencing encounters. Moderate differences in survival, with males surviving better than females, were found in one population and not in the other, suggesting that these differences are not an inherent characteristic of the species. In the population with lower female survival, females were not more vagile than males, thus indicating their lower survival was caused by actual mortality rather than to emigration. In the population with no survival differences between males and females, marked males outnumbered females, but estimated sex ratios were approximately 1:1 or female biased. Therefore, raw field data were misleading because they led to underestimates of the more elusive sex and overestimates of the more detectable one (males). Survival and movement differences detected in the two populations are discussed in the framework of local environmental and demographic factors.


Exogenous Melatonin Enhances Rice Plant Resistance Against Xanthomonas oryzae pv. oryzae.
Rice bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae, is one of the most serious diseases of rice. In this study we found that exogenous melatonin can increase rice resistance to BB. Treatment of rice plants with exogenous melatonin (20 µg/ml) increased nitrate reductase, nitric oxide synthase, and peroxidase activity, enabling high intracellular concentrations of melatonin, nitric oxide, and H2O2. The expression of NPR1, a key regulator in the salicylic acid signaling pathway, was upregulated more than 10-fold when the plants were challenged with melatonin. Similarly, the messenger RNA level of PDF1.2, a jasmonic acid-induced defense marker, was 15 times higher in the treated plants than in the control plants. Moreover, three pathogenesis-related proteins, PR1b, PR8a, and PR9, were upregulated 20-fold in the presence of melatonin. The application of melatonin (100 µg/ml) to soil-grown rice reduced the incidence of BB by 86.21%. Taken together, these results not only provide a better understanding of melatonin-mediated innate immunity to X. oryzae pv. oryzae in rice but also represent a promising cultivation strategy to protect rice against X. oryzae pv. oryzae infection.


Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents.
Recent advances in functional genomics afford the opportunity to interrogate the expression profiles of thousands of genes simultaneously and examine the function of these genes in a high-throughput manner. In this study, we describe a rational and efficient approach to identifying novel regulators of insulin secretion by the pancreatic beta-cell. Computational analysis of expression profiles of several mouse and cellular models of impaired insulin secretion identified 373 candidate genes involved in regulation of insulin secretion. Using RNA interference, we assessed the requirements of 10 of these candidates and identified four genes (40%) as being essential for normal insulin secretion. Among the genes identified was Hadhsc, which encodes short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD), an enzyme of mitochondrial beta-oxidation of fatty acids whose mutation results in congenital hyperinsulinism. RNA interference-mediated gene suppression of Hadhsc in insulinoma cells and primary rodent islets revealed enhanced basal but normal glucose-stimulated insulin secretion. This increase in basal insulin secretion was not attenuated by the opening of the KATP channel with diazoxide, suggesting that SCHAD regulates insulin secretion through a KATP channel-independent mechanism. Our results suggest a molecular explanation for the hyperinsulinemia hypoglycemic seen in patients with SCHAD deficiency.


Lactate thresholds and role of nitric oxide in male rats performing a test with forced swimming to exhaustion.
The present study assessed a complex of biochemical parameters at the anaerobic threshold (AT) in untrained male Wistar rats with different times to exhaustion (Tex ) from swimming. The first group of rats was randomly divided into six subgroups and subjected to a swimming test to exhaustion without a load or with a load of 2%-10% of body weight (BW). In the first group, we established that for untrained rats, the load of 4% BW in the swimming to exhaustion test was optimal for endurance assessment in comparison with other loads. The second group of rats went through a preliminary test with swimming to exhaustion at 4% BW and was then divided into two subgroups: long swimming time (LST, Tex > 240 min) and short swimming time (SST, Tex < 90 min). All rats of the second group performed, for 6 days, an experimental training protocol: swimming for 20 min each day with weight increasing each day. We established that the AT was 3% BW in SST rats and 5% BW in LST rats. The AT shifted to the right on the lactate curve in LST rats. Also, at the AT in the LST rats, we found significantly lower levels of blood lactate, cortisol, and NO.


Association of eIF4E and SPARC Expression with Lymphangiogenesis and Lymph Node Metastasis in Hypopharyngeal Cancer.
Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets. Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis. Compared to lymph node biopsies of healthy controIs, LVD was significantly increased in metastatic lymph nodes as well as in advanced primary tumors. Overexpression of eIF4E and SPARC was demonstrated in all hypopharyngeal cancer specimens. Notably, we observed that increased LVD significantly correlated with the expression of eIF4E as well as SPARC levels. eIF4E- and SPARC-associated signaling pathways may be associated with lymphangiogenesis and could be exploited to counteract the spread of hypopharyngeal cancer cells.