Gender as a factor of susceptibility to infection in experimental hydatidosis.
We developed an experimental model of hydatidosis in BALB/c mice with six groups, a group of females and another group of males was infected with PSC of Echinococcus, granulosus. Another two groups were gonadectomised and infected with PSC. and another two groups were healthy controls. They were all bled and sacrificed after sixteen weeks post-infection. The cysts in the abdominal cavity were count, and samples were taken from liver. A microscopic study was made of the tissue around the cyst to evaluate the chronic inflammatory response. In addition the seric levels of estradiol and testosterone by means of radioimmunoassay (RIA) were determined. The results were that the females presented a greater number of cysts in liver than the males, in addition the levels to estradiol almost rose to the double in males and females after 16 weeks post-infection, and the testosterone diminished. The granulomatous response around the cysts was greater in the females than in the males. The gonadectomization affected the susceptibility to the infection in females, diminishing in number of hepatic cysts found. One concluded that the females are more susceptible to the infection by metacestode of E. granulosrus, than the males. The female displayed one better granulomatous answer than the males. Nevertheless this was not sufficient to eliminate the parasite or to inhibit its growth. The levels of estradiol and testosterone undergo an imbalance, observing that estradiol increased in chronic stages of the infection whereas the testosterone diminishes, which would indicate to us that probably the parasite causes hormonal imbalance in chronic stages, to be able to remain by long periods in its host.


The effect of three bufadienolide cardiac glycosides on contraction of isolated rat jejunum.
Three cardiac glycosides were screened for pharmacological effects on isolated rat jejunum. The contraction of rat jejunum with epoxyscillirosidin, a non-cumulative bufadienolide, and cotyledoside and tyledoside D, both cumulative neurotoxic bufadienolides were compared with methacholine. The results indicate that all three bufadienolides cause contraction of jejunal smooth muscle. When combined with atropine (1 x 10(-6) M) the response of epoxyscillirosidin and tyledoside D decreased, indicating suppression of a cholinergic response caused by the cardiac glycosides.


Evaluation of Plasma Asprosin Concentration in Patients with Coronary Artery Disease.
The goal of this study is to investigate the association between diagnosis and severity of coronary artery disease (CAD) and Asprosin level. Patients diagnosed with CAD who underwent conventional coronary angiography for the first time were included in the present study. The patients were divided into four groups, each consisting of 20 individuals, as medical group, single coronary lesion group, double coronary lesion group, and multiple coronary lesions group. Serum Asprosin values and Gensini scores of the groups were compared in terms of compliance. In this study, Asprosin values were found to be significantly higher in the multiple coronary lesions group than in the medical, single coronary, and double coronary lesion groups (P<0.05). In the double coronary lesion group, Asprosin values were significantly higher (P<0.05) than the in the medical and single coronary lesion groups. It was also found that Asprosin values did not differ at significant levels in the medical and single coronary lesion groups (P>0.05). It was determined that the increases in Asprosin values and Gensini scores were compatible with each other. The present study showed that the increases in serum Asprosin levels, along with the increases in the number of coronary arteries with critical stenosis, might be a marker in diagnosing and determining the severity of CAD.


Oxacillin or cefalotin treatment of hospitalized children with cellulitis.
Cellulitis is an important cause of hospitalization in pediatrics. Because Staphylococcus aureus is the main pathogen of cellulitis, medicinal therapeutics should take the changing resistance profile of this organism into consideration. The aim of this study was to evaluate the progression and outcomes of children hospitalized for cellulitis and treated with oxacillin or cefalotin. This retrospective cohort study enrolled 218 children, hospitalized between 2001 and 2008 in Salvador, Northeast Brazil. All were diagnosed with cellulitis and treated with oxacillin or cefalotin (≥100 mg/kg/day). The median age was 2 years and 56.9% were males. Frequencies of signs and symptoms used in the clinical diagnoses were as follows: swelling (91.3%), redness (81.7%), warmth (47.2%), and tenderness (31.7%). All patients were discharged due to clinical recovery and the mean length of hospitalization was 7 ± 4 days. None of the patients died, needed intensive care, or had sequelae. By comparing the daily frequency of clinical findings during hospitalization, significant decreases were found in the frequencies of fever (admission day [42.2%], first day [20.8%], second day [12.9%], third day [8.3%], fourth day [6.1%]), toxemia, irritability, somnolence, vomiting, tachycardia, and need for intravenous hydration. In conclusion, oxacillin or cefalotin remain the drugs of choice for treating uncomplicated cellulitis in regions where community-acquired methicillin-resistant S. aureus is infrequent (<10%).


Humoral immunity in humanized mice: a work in progress.
Humanized mice historically have not been good models of human humoral immunity induced by either infection or immunization. However, newer versions of humanized mice generated in severely immunodeficient mice with a targeted disruption of the IL2Rγc gene have recently been reported to produce antigen-specific class-switched human antibodies, with some demonstrating neutralizing activities. Here we review the growing ability of humanized mice to support the study of human humoral immune responses, discussing the current and future potential of these models as well as their current limitations.


The promoter and enhancer of the inactive chicken beta-globin gene contains precisely positioned nucleosomes.
Core histone octamers reconstituted in vitro onto DNA fragments containing the chicken beta-globin gene promoter are precisely positioned with respect to the underlying DNA sequence [1]. Here we show that this is also true of the chicken beta-globin gene enhancer. These nucleosome binding sites are also employed within transfected COS cell nuclei, where the chicken beta-globin gene is transcriptionally inactive. Similar results were found in vivo, where positioned nucleosomes were detected over the inactive beta-globin promoter in chicken brain cells and 5-day red blood cells, and over the inactive beta-globin enhancer in brain cells. In contrast, the promoter and enhancer regions were found to be nucleosome-free in 15-day erythrocytes where the beta-globin gene is active. We argue that these results suggest a role for positioned nucleosomes in the regulation of the transcription of the chicken beta-globin gene.


Asymmetric catalytic ene-cyclization approach to 2-fluoro-19-nor-1,25-dihydroxyvitamin D(3) A-ring analog with significant transactivation activity.
1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)2D3) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for the treatment of cancer and psoriasis. However, little information has been available on the binding conformation of the 1alpha,25(OH)2D3 molecule and its analogs with the vitamin D receptor (VDR). Therefore, we synthesized 2alpha-fluorinated A-ring analogs of 19-nor-1alpha,25(OH)2D3 in order to investigate the VDR-binding conformation of the A-rings on the basis of the (19)F NMR analysis. The 2alpha-fluoro-19-nor-1alpha,25-dihydroxyvitamin D3 A-ring analog thus synthesized via a asymmetric catalytic carbonyl-ene cyclization, shows significant activity in transactivation.


αPIX Is a Trafficking Regulator that Balances Recycling and Degradation of the Epidermal Growth Factor Receptor.
Endosomal sorting is an essential control mechanism for signaling through the epidermal growth factor receptor (EGFR). We report here that the guanine nucleotide exchange factor αPIX, which modulates the activity of Rho-GTPases, is a potent bimodal regulator of EGFR trafficking. αPIX interacts with the E3 ubiquitin ligase c-Cbl, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation. We show that EGF stimulation induces αPIX::c-Cbl complex formation. Simultaneously, αPIX and c-Cbl protein levels decrease, which depends on both αPIX binding to c-Cbl and c-Cbl ubiquitin ligase activity. Through interaction αPIX sequesters c-Cbl from EGFR and this results in reduced EGFR ubiquitination and decreased EGFR degradation upon EGF treatment. However, quantitatively more decisive for cellular EGFR distribution than impaired EGFR degradation is a strong stimulating effect of αPIX on EGFR recycling to the cell surface. This function depends on the GIT binding domain of αPIX but not on interaction with c-Cbl or αPIX exchange activity. In summary, our data demonstrate a previously unappreciated function of αPIX as a strong promoter of EGFR recycling. We suggest that the novel recycling regulator αPIX and the degradation factor c-Cbl closely cooperate in the regulation of EGFR trafficking: uncomplexed αPIX and c-Cbl mediate a positive and a negative feedback on EGFR signaling, respectively; αPIX::c-Cbl complex formation, however, results in mutual inhibition, which may reflect a stable condition in the homeostasis of EGF-induced signal flow.


Survey to define informational needs of patients undergoing surgery for Crohn's anal fistula.
There are many surgical treatments used in Crohn's anal fistula, although none is perfect. Decisions about surgery in this condition may be preference sensitive. The aim of this study was to identify what information patients would like in order to make treatment decisions and to explore experiences of making decisions in this setting. A survey was designed based upon qualitative interviews and input from patients and clinicians. It included a long list of informational items to be ranked on a scale of importance, a control preference scale, the decision regret scale, and items exploring preferred information formats. This was distributed through 10 English hospitals to patients with recent surgical treatment for Crohn's anal fistula. Results were analysed using principal component analysis, to identify key informational needs, and other appropriate descriptive statistics. In total 92 questionnaires were returned (response rate 41.8%); 48 (52.5%) respondents were women and 54 (58.7%) had undergone seton insertion. Principal component analysis identified three information needs: wound and aftercare, effect on perianal symptoms, severity of surgery. Decision-making preferences showed a desire to participate in decision-making. Median decision regret score was 25/100 (i.e., low). The preferred format for sharing information to support decision-making was from the surgeon, 80/92 (87.0%), and from a booklet, 58/92 (63.0%). Key informational needs in this condition are wound and after care, effect on perianal symptoms, and severity of surgery. Patients would like this information to help engage in shared decision-making.


[Meptazinol, a new analgesic. Hemodynamic and respiratory effects].
In a prospective, randomized double-blind study the hemodynamic and respiratory effects of i.v. meptazinol, a new synthetic narcotic agonist-antagonist analgesic given in 2 dosages (2 mg/kg and 4 mg/kg), were compared over 15 min to a control group that received 0.9% saline solution as placebo. In a total of 80 patients scheduled for elective aortocoronary bypass surgery, the study was performed before and during general anesthesia and during extracorporeal circulation (ECC). A dose-dependent increase in mean arterial pressure (MAP) and total systemic resistance (TSR) were the predominant hemodynamic effects of meptazinol before and during anaesthesia (Tables 1 and 2). Within the study period no change in heart rate (HR) or cardiac index (CI) could be observed. Directly measured left ventricular parameters revealed a significant increase in left ventricular pressure (LVEDP, and dp/dtmax (Fig. 1). During ECC meptazinol injection was followed by a dose-dependent increase in perfusion pressure, indicating a direct vasoconstrictive effect; no influence on the capacitance system ("venous pooling") could be observed (Fig. 2). In the spontaneously breathing, premedicated patients (morphine hydrochloride 0.15 mg/kg and flunitrazepam 0.03 mg/kg) paO2 increased and paCO2 decreased, especially after injection of the higher dosage of meptazinol; there was no influence on intrapulmonary right-to-left shunting (Qs/Qt).(ABSTRACT TRUNCATED AT 250 WORDS)


CNS effects of a CCR5 inhibitor in HIV-infected subjects: a pharmacokinetic and cerebral metabolite study.
We conducted a pharmacokinetic and in vivo cerebral (1)H magnetic resonance spectroscopy ((1)H-MRS) study to assess CSF exposure and cerebral metabolite ratios (CMRs) following maraviroc intensification. HIV-infected neurologically asymptomatic adults receiving tenofovir, emtricitabine and lopinavir/ritonavir with plasma HIV RNA <50 copies/mL were eligible and received intensified therapy with 150 mg of maraviroc twice daily. (1)H-MRS was performed in several cerebral locations, including the right basal ganglia (RBG), to assess CMRs, including N-acetyl aspartate/creatine (NAA/Cr), at baseline and after 14 days. Subsequently, on day 15, blood samples were obtained to determine plasma concentrations of maraviroc pre-dose (C(trough)) and then paired blood and CSF samples were collected at 4 or 6 h post-dose. Associations between maraviroc exposure, clinical parameters and changes to CMRs were evaluated. ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT00982878). Twelve subjects (75% male) participated with a mean (SD) CD4+ cell count of 503 (199) cells/μL. Mean (SD) maraviroc plasma concentrations at pre-dose, 4 h post-dose and 6 h post-dose were 337 (74), 842 (174) and 485 (100) ng/mL and CSF concentrations at 4 h post-dose and 6 h post-dose were 7.5 (1.3) and 5.1 (1.2) ng/mL. The mean maraviroc CSF : plasma ratio (range) was 1.01% (0.57%-1.61%). An increase of 14.8% was observed for the RBG NAA/Cr ratio, which was significantly associated with higher maraviroc plasma C(trough) (P = 0.05, r = 0.61), but not CSF concentration (P = 0.16, r = 0.46). After 14 days of maraviroc intensification, small increases in cerebral metabolite markers of neuronal integrity (NAA/Cr ratios) were observed and are associated with maraviroc plasma C(trough).


Cap-snatching mechanism in yeast L-A double-stranded RNA virus.
The 5' cap structure (m(7)GpppX-) is an essential feature of eukaryotic mRNA required for mRNA stability and efficient translation. Influenza virus furnishes its mRNA with this structure by a cap-snatching mechanism, in which the viral polymerase cleaves host mRNA endonucleolytically 10-13 nucleotides from the 5' end and utilizes the capped fragment as a primer to synthesize viral transcripts. Here we report a unique cap-snatching mechanism by which the yeast double-stranded RNA totivirus L-A furnishes its transcript with a cap structure derived from mRNA. Unlike influenza virus, L-A transfers only m(7)Gp from the cap donor to the 5' end of the viral transcript, thus preserving the 5' α- and β-phosphates of the transcript in the triphosphate linkage of the final product. This in vitro capping reaction requires His154 of the coat protein Gag, a residue essential for decapping of host mRNA and known to form m(7)Gp-His adduct. Furthermore, the synthesis of capped viral transcripts in vivo and their expression were greatly compromised by the Arg154 mutation, indicating the involvement of Gag in the cap-snatching reaction. The overall reaction and the structure around the catalytic site in Gag resemble those of guanylyltransferase, a key enzyme of cellular mRNA capping, suggesting convergent evolution. Given that Pol of L-A is confined inside the virion and unable to access host mRNA in the cytoplasm, the structural protein Gag rather than Pol catalyzing this unique cap-snatching reaction exemplifies the versatility as well as the adaptability of eukaryotic RNA viruses.


Assessing decentering: validation, psychometric properties, and clinical usefulness of the Experiences Questionnaire in a Spanish sample.
Decentering is defined as the ability to observe one's thoughts and feelings in a detached manner. The Experiences Questionnaire (EQ) is a self-report instrument that originally assessed decentering and rumination. The purpose of this study was to evaluate the psychometric properties of the Spanish version of EQ-Decentering and to explore its clinical usefulness. The 11-item EQ-Decentering subscale was translated into Spanish and psychometric properties were examined in a sample of 921 adult individuals, 231 with psychiatric disorders and 690 without. The subsample of nonpsychiatric participants was also split according to their previous meditative experience (meditative participants, n=341; and nonmeditative participants, n=349). Additionally, differences among these three subgroups were explored to determine clinical validity of the scale. Finally, EQ-Decentering was administered twice in a group of borderline personality disorder, before and after a 10-week mindfulness intervention. Confirmatory factor analysis indicated acceptable model fit, sbχ(2)=243.8836 (p<.001), CFI=.939, GFI=.936, SRMR=.040, and RMSEA=.06 (.060-.077), and psychometric properties were found to be satisfactory (reliability: Cronbach's α=.893; convergent validity: r>.46; and divergent validity: r<-.35). The scale detected changes in decentering after a 10-session intervention in mindfulness (t=-4.692, p<.00001). Differences among groups were significant (F=134.8, p<.000001), where psychiatric participants showed the lowest scores compared to nonpsychiatric meditative and nonmeditative participants. The Spanish version of the EQ-Decentering is a valid and reliable instrument to assess decentering either in clinical and nonclinical samples. In addition, the findings show that EQ-Decentering seems an adequate outcome instrument to detect changes after mindfulness-based interventions.


Cloning, properties and tissue distribution of natriuretic peptide receptor-A of euryhaline eel, Anguilla japonica.
During the course of cloning and characterization of natriuretic peptide receptor-A (NPR-A) from the euryhaline fish eel, Anguilla japonica, we identified a splice variant with unique structural properties that affect ligand-inducible intrinsic guanylate cyclase activity. The variant, generated from a splice between a cryptic donor site and the normal acceptor site, lacked nine amino acid residues (VFTKTGYYK) in the kinase-like regulatory domain. This deletion of a very short segment resulted in the complete loss of the ligand inducibility of the cyclase activity. The nine-amino acid segment may therefore be useful as a target for studies aimed at clarifying the mechanism of activation of the guanylate cyclase domain. Characterization of the normal form of eel NPR-A also led to the following interesting findings. Although eel NPR-A had a domain structure very similar to that of mammalian counterparts, it lacked the third cysteine residue in the extracellular domain which is conserved among mammalian NPR-A molecules. The eel receptor bound both amidated and nonamidated eel atrial natriuretic peptide (eANP) with high affinity but, when assayed for ligand-inducible cGMP generation, it responded efficiently only to physiological concentrations of the amidated ligand, suggesting that the biologically active form is the amidated eANP, and the nonamidated form acts as a partial antagonist; similarly, nonhomologous rat ligands behaved like antagonists toward the eel receptor in the concentration range 0.1-10 nm. The receptor message was found to be relatively abundant in the osmoregulatory organs such as the gill, kidney, intestine and urinary bladder.


Radiotherapy plus rituximab as first-line regimen for localized follicular lymphoma.
Early-stage follicular lymphoma (FL) can be cured with involved-field radiotherapy (IF-RT); however, many patients relapse in non-irradiated areas. A combined association with chemotherapy could increase treatment efficacy, but toxic effects could be unacceptable. In vitro synergistic effect between rituximab (R) and RT has been observed, but clinical data are limited. We retrospectively analyzed 41 early-stage FL patients receiving R and IF-RT as first-line treatment. We administered R 375mg/m2 weekly for four courses, before or after IF-RT (median dose 24 Gy). Primary outcome was PFS, secondary endpoints were CR rate, OS and safety. All patients achieved CR, after a median follow-up of 46 months only three patients relapsed after 18, 26 and 42 months; estimated 5-year PFS was 90%. We suggest R in association with IF-RT could represent a feasible first-line treatment option for early-stage FL and could increase efficacy without additional toxicity compared to available data about RT alone.


Evidence-Based Choice of P2Y12 Inhibitors in End Stage Renal Disease Patients: A Mini-Review.
Chronic kidney disease has been identified as an independent cardiovascular risk factor. The morbidity and mortality due to cardiovascular disease are higher among chronic kidney disease patients when compared with patients with normal kidney function. Although P2Y12 inhibitors (eg. clopidogrel) are associated with increased survival rates after a myocardial infarction, most of the clinical trials excluded End-Stage Renal Disease (ESRD) patients. Besides, non-responders to P2Y12 inhibitors have been identified as at risk of cardiovascular adverse events and non-responder prevalence is higher among ESRD than in any other population. Recent data questioned the benefits from P2Y12 inhibitors among chronic kidney disease patients. This systematic review aimed to describe pharmacokinetics (PK) and pharmacodynamics (PD) evidence data among 3 widely prescribed P2Y12 inhibitors. Clopidogrel and prasugrel are bioactivated by the cytochromes P450 (CYP) while ticagrelor is already active. PD data used different assays among which the VerifyNow® which showed intravariability before and after dialysis. The potential explanation of modulated PK/PD parameters among ESRD patients will be addressed. Absorption as well as metabolism is diminished in ESRD patients. It could potentially lead to absence of clopidogrel or prasugrel bioactivation or ticagrelor accumulation. Evidence-based recommendation regarding the best option for antiaggregation secondary to percutaneous intervention in this high risk population is still lacking.


Infliximab treatment for Crohn's disease in a patient with IgA nephropathy.
We describe herein a case of IgA nephropathy in a 34-year-old woman with Crohn's disease (CD) treated with infliximab. CD first appeared at the age of 15 years. An elemental diet was started for remission maintenance. Ten years later, the patient suffered from a recto-vaginal fistula and subtotal colectomy with stoma formation was performed. At the age of 33 years, the patient was investigated for painless macroscopic hematuria and proteinuria. Renal biopsy revealed IgA nephropathy. Mizoribine was started but proteinuria persisted. Due to diarrhea she was admitted to our hospital, and scheduled maintenance therapy with infliximab was initiated. After the first infliximab infusion, the patient presented significant clinical improvement in both diarrhea and proteinuria with concomitant decrease of C-reactive protein to normal levels and proteinuria ~1 g/day. This represents the first report of infliximab treatment in a patient with IgA nephropathy associated with CD and clarifies the importance of tumor necrosis factor-alpha (TNFα) in immunity to renal disease. Further studies are needed to draw firm conclusions for the safety of infliximab in patients with IgA nephropathy.


Nifedipine-induced hypotension and myocardial ischemia in refractory angina pectoris.
Combined nitrate/beta-blocker/nifedipine therapy is commonly used to treat refractory angina pectoris. We have observed "paradoxical" myocardial ischemia in ten patients with refractory angina (seven receiving combined beta-blocker and nitrate therapy, and three receiving nitrate treatment alone) in whom nifedipine (mean dosage, 92 mg/day; range, 60 to 120 mg/day) induced a decrease in blood pressure, angina pectoris (10/10 patients), and ischemic ECG changes (7/10 patients). These ten patients, all of whom regularly reported angina within 20 to 30 minutes of nifedipine ingestion, were prospectively studied before and after usual nifedipine dose administration, while blood pressures, heart rate, and ECGs were recorded. Mean systolic BP fell from 109 to 94 mm Hg after nifedipine (P less than .001, paired t test); mean heart rate increased from 64 to 68 beats per minute (P less than .05); seven patients developed transient ECG changes (five with ST-T wave depression and two with ST-T wave elevation) during the hypotensive period. Nifedipine may provoke angina and myocardial ischemia in certain patients with refractory angina pectoris receiving concomitant beta-blocker and nitrate therapy.


Tetracyclic Triterpenoids, Steroids and Lignanes from the Aerial Parts of Oxypetalum caeruleum.
The MeOH extract from dried aerial parts of Oxypetalum caeruleum (Apocynaceae) plants yielded seventeen compounds, including four new tetracyclic triterpenoids, one pregnane glycoside, two lignane glycosides, and ten known compounds. The structures of the new compounds were established using NMR, MS spectroscopic analysis and chemical evidence.


Imaging and radiometric properties of microlens arrays.
The imaging and radiometric properties of erect lens arrays made up of small biconvex microlenses are derived from a ray analysis. The lens arrays provide erect, unit magnification images. The relationship between the radii of curvature, the lens thickness, and the one-to-one conjugate distance is derived for both the single-layer case and a double-layer structure, which contains field lenses. Radiometric properties of the microlens and the array are derived for both structures. The results are compared to experimentally measured values obtained from arrays fabricated by a photothermal process.


Molecular targeted therapy of glioblastoma.
Glioblastomas are intrinsic brain tumors thought to originate from neuroglial stem or progenitor cells. More than 90% of glioblastomas are isocitrate dehydrogenase (IDH)-wildtype tumors. Incidence increases with age, males are more often affected. Beyond rare instances of genetic predisposition and irradiation exposure, there are no known glioblastoma risk factors. Surgery as safely feasible followed by involved-field radiotherapy plus concomitant and maintenance temozolomide chemotherapy define the standard of care since 2005. Except for prolonged progression-free, but not overall survival afforded by the vascular endothelial growth factor antibody, bevacizumab, no pharmacological intervention has been demonstrated to alter the course of disease. Specifically, targeting cellular pathways frequently altered in glioblastoma, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), the p53 and the retinoblastoma (RB) pathways, or epidermal growth factor receptor (EGFR) gene amplification or mutation, have failed to improve outcome, likely because of redundant compensatory mechanisms, insufficient target coverage related in part to the blood brain barrier, or poor tolerability and safety. Yet, uncommon glioblastoma subsets may exhibit specific vulnerabilities amenable to targeted interventions, including, but not limited to: high tumor mutational burden, BRAF mutation, neurotrophic tryrosine receptor kinase (NTRK) or fibroblast growth factor receptor (FGFR) gene fusions, and MET gene amplification or fusions. There is increasing interest in targeting not only the tumor cells, but also the microenvironment, including blood vessels, the monocyte/macrophage/microglia compartment, or T cells. Improved clinical trial designs using pharmacodynamic endpoints in enriched patient populations will be required to develop better treatments for glioblastoma.


Tie my hands, tie my eyes.
Previous studies have demonstrated that motor abilities allow us not only to execute our own actions and to predict their consequences, but also to predict others' actions and their consequences. But just how deeply are motor abilities implicated in action observation? If an observer is prevented from acting while witnessing others' actions, will this impact on their making sense of others' behavior? We recorded proactive eye movements while participants observed an actor grasping objects. The participants' hands were either freely resting on the table or tied behind their back. Proactivity of gaze behavior was dramatically impaired when participants observed others' actions with their hands tied. Since we don't literally perceive actions with our hands, the effect may be explained by the hypothesis that effective observation of action depends not only on motor abilities but on being in a position to exercise them. This suggests, for the first time, that actions are observed best when we are actually in the position to perform them.


Population genetics of Haemophilus influenzae serotype a in three Canadian provinces.
Haemophilus influenzae serotype a (Hia) is an important pathogen since the introduction of vaccines for control of disease due to serotype b strains. Using a sodC-based polymerase chain reaction, Hia can be divided into 2 phylogenetic divisions, each with their own unique multilocus sequence types. Most Canadian Hia belongs to clonal division I and the ST-23 clonal complex. The recently described hypervirulent clone of ST-4 was found in a single Canadian isolate. Therefore, surveillance of invasive H. influenzae disease should include serotyping to detect Hia and multilocus sequence typing to detect hypervirulent clones.


Patient-centered Bedside Education and Traditional Jewish Law and Ethics.
Bedside rounds have long been a time-honored component of medical education. Recently, there have been various recommendations that residency-training programs further incorporate bedside teaching into clinical curricula. To compare these current attitudes regarding bedside education with the position of traditional Jewish law and ethics. Relevant medical journal articles and traditional Jewish sources were reviewed. Halacha (the corpus of traditional Jewish law and ethics) gives greater focus to a patient-centered rather than student-centered bedside education experience. Residency training programs should give greater consideration to the importance of a patient-centered bedside education experience.


Developmental Toxicity of Surface-Modified Gold Nanorods in the Zebrafish Model.
nanotechnology is one of the fastest-growing areas, and it is expected to have a substantial economic and social impact in the upcoming years. Gold particles (AuNPs) offer an opportunity for wide-ranging applications in diverse fields such as biomedicine, catalysis, and electronics, making them the focus of great attention and in parallel necessitating a thorough evaluation of their risk for humans and ecosystems. Accordingly, this study aims to evaluate the acute and developmental toxicity of surface-modified gold nanorods (AuNRs), on zebrafish (Danio rerio) early life stages. in this study, zebrafish embryos were exposed to surface-modified AuNRs at concentrations ranging from 1 to 20 μg/mL. Lethality and developmental endpoints such as hatching, tail flicking, and developmental delays were assessed until 96 h post-fertilization (hpf). we found that AuNR treatment decreases the survival rate in embryos in a dose-dependent manner. Our data showed that AuNRs caused mortality with a calculated LC50 of EC50,24hpf of AuNRs being 9.1 μg/mL, while a higher concentration of AuNRs was revealed to elicit developmental abnormalities. Moreover, exposure to high concentrations of the nanorods significantly decreased locomotion compared to untreated embryos and caused a decrease in all tested parameters for cardiac output and blood flow analyses, leading to significantly elevated expression levels of cardiac failure markers ANP/NPPA and BNP/NPPB. our results revealed that AuNR treatment at the EC50 induces apoptosis significantly through the P53, BAX/BCL-2, and CASPASE pathways as a suggested mechanism of action and toxicity modality.


Kinetic study of the quenching reaction of singlet oxygen by carotenoids and food extracts in solution. Development of a singlet oxygen absorption capacity (SOAC) assay method.
A kinetic study of the quenching reaction of singlet oxygen (1O2) with eight kinds of carotenoids and α-tocopherol was performed in ethanol/chloroform/D2O (50:50:1, v/v/v) solution at 35 °C. The overall rate constants, kQ (=kq+kr, physical quenching+chemical reaction), for the reaction of carotenoids with 1O2 were measured, using the competition reaction method, where endoperoxide was used as a singlet oxygen generator, 2,5-diphenyl-3,4-benzofuran (DPBF) as an UV-vis absorption prove, and α-tocopherol as a standard compound. The rate constants, kQ (S) and kQ (t1/2), were determined by analyzing the first-order rate constant (S) and the half-life (t1/2) of the decay curve of DPBF with carotenoids, respectively, showing good accordance with each other. Similar measurements were performed for tomato and carrot extracts. From the results, a new assay method that can quantify the singlet oxygen absorption capacity (SOAC) of antioxidants, including carotenoids, α-tocopherol, and vegetable extracts, has been proposed.


Predictive molecular markers of response to epidermal growth factor receptor(EGFR) family-targeted therapies.
Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting this pathway are necessary to select patients more likely to respond, and importantly, to avoid treating patients likely to suffer a worse outcome with therapy compared to standard of care. Determination of EGFR by immunohistochemistry(IHC) is not strongly predictive of response to EGFR-targeted therapy in CRC and NSCLC. EGFR gene mutations in the tyrosine kinase(TK) binding domain are predictive of response to EGFR tyrosine kinase inhibitors(TKIs) in NSCLC, and the acquisition of a point mutation in a gene encoding an amino acid in an adjacent area, T790M, is predictive of resistance. However, novel irreversible EGFR inhibitors such as BIBW-2992 and HKI-272 may retain activity in tumours with T790M mutations. It is well established in CRC that mutations in KRAS are predictive of resistance to EGFR pathway inhibition, and may predict for a poorer outcome with therapy. Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. Functional genomics elucidation of drug resistance pathways using RNA interference (RNAi) techniques may provide novel therapeutic approaches in disease resistant to EGFR pathway targeting and accelerate predictive biomarker development.


Ruthenium-indenylidene complexes: powerful tools for metathesis transformations.
Ruthenium-indenylidene complexes represent a class of robust and efficient pre-catalysts for olefin metathesis reactions. In this feature article, we provide an overview of the various complexes belonging to this family and summarise their use in various applications. The relation between the nature of ancillary ligands around the metal coordination sphere of these complexes and their catalytic activity is also discussed.


Life-threatening COVID-19 presenting as stroke with antiphospholipid antibodies and low ADAMTS-13 activity, and the role of therapeutic plasma exchange: A case series.
We present a case series of three patients with COVID-19 who were admitted to our intensive care unit due to acute respiratory distress syndrome, brain infarction, pulmonary embolism, and antiphospholipid antibodies. We applied therapeutic plasma exchange on all cases. On intensive care unit admission, all patients had low (<10) Glasgow Coma Scale, and central nervous imaging showed multiple brain infarctions. COVID-19 was confirmed by reverse transcriptase polymerase chain reaction assays. Patients underwent rescue therapeutic plasma exchange using the Spectra OptiaTM Apheresis System (Terumo BCT Inc., USA), which operates with acid-citrate dextrose anticoagulant as per Kidney Disease Improving Global Outcomes 2019 guidelines. A dose of 1.5 plasma volume was used for the first dose and then 1 plasma volume daily for a total of five doses. Plasma was replaced with Octaplas LG® (Octapharma AG, USA), which is an artificial fresh frozen plasma product that has undergone viral inactivation by prion reduction technology. We administered ARDS-net/prone positioning ventilation, empiric antiviral treatment, therapeutic anticoagulation, and intensive care unit supportive care. Laboratory tests showed lymphocytopenia; elevated levels of D-dimer, fibrinogen, total bilirubin, C-reactive protein, lactate dehydrogenase, and ferritin; as well as low levels of ADAMTS-13 activity and antibody. Serology tests depicted positive IgM and IgG antiphospholipid antibodies (anti-cardiolipin and anti-β2-glycoprotein I antibodies). No side effects of therapeutic plasma exchange were recorded. After the completion of therapeutic plasma exchange, patients improved clinically and gradually recovered neurologically (after 27-32 days). To conclude, in life-threatening COVID-19, especially when immune dysregulation features such as antiphospholipid antibodies exist, therapeutic plasma exchange could be an effective rescue therapy.


Peritoneoscopy in chronic hepatitis. A retrospective evaluation of its role in the management of the asymptomatic patient.
The course of chronic hepatitis was retrospectively evaluated in 26 patients in whom both peritoneoscopy and liver biopsy were initially performed. At entry all patients were clinically asymptomatic and showed mild or moderate histological and chemical abnormalities, so that none of them needed steroid treatment. The duration of the follow-up ranged from 24-82 months. At the end of follow-up liver biopsy was obtained in all patients. In a few patients peritoneoscopy was also ultimately performed. In six patients in whom initially chronic persistent hepatitis (CPH) was diagnosed both by peritoneoscopy and liver biopsy, the subsequent course of the disease was benign. In all the nine patients in whom initially peritoneoscopy suggested CPH, in contrast to the histological diagnosis of chronic aggressive hepatitis (CAH), chemical and morphological parameters of liver disease activity did not worsen to require steroid treatment. In five of six patients in whom both liver biopsy and peritoneoscopy initially showed CAH, chemical and morphological abnormalities progressed so that steroids had to be initiated. Finally in four of five patients in whom initially peritoneoscopy showed CAH and liver biopsy CPH, steroid treatment was ultimately required because of chemical and morphological worsening. In conclusion peritoneoscopy may be a useful aid in the management of the asymptomatic patient with moderate chemical and histological features of chronic liver disease.


[Case report of MRSA sepsis required two valve replacement twice a year--trying case with hyperthermal extracorporeal circulation].
We report a case in conjunction with MRSA sepsis, who needed re-mitral valve replacement (re-MVR) and re-tricuspid valve imposition (re-TVI), and who was successfully treated with a number of antibiotics in conjunction with hyperthermal extracorporeal circulation. Initially, we performed MVR and tricuspid valve superimposition on a 62-year-old woman lationing under the MRSA sepsis condition to control against heart failure. However, she developed a fever following the first operation, and MRSA was detected from her blood cultivation. She thus underwent treatment employing many kinds of antibiotics. A thickened C.E. valve at the tricuspid valve cardiac echogram suggested PVE, we performed a second operation of re-MVR and re-TVI about a year after the first operation. We used a tangl of antibiotics during the operation, adding Vancomycin into the extracorporeal circulation, and utilized hyperthermal extracorporeal circulation. This patient's postoperative course was uneventful, with no recurrence arising at 23 months after the second operation.


Hypoxic stress and hypoxia-inducible factors in leukemias.
To cope with hypoxic stress, ancient organisms have developed evolutionally conserved programs centered on hypoxia-inducible transcriptional factors (HIFs). HIFs and their regulatory proteins have evolved as rheostats to adapt cellular metabolism to atmospheric oxygen fluctuations, but the amplitude of their transcriptional programs has tremendously increased along evolution to include a wide spectrum of physiological and pathological processes. The bone marrow represents a notable example of an organ that is physiologically exposed to low oxygen levels and where basal activation of hypoxia signaling appears to be intrinsically wired within normal and neoplastic hematopoietic cells. HIF-mediated responses are mainly piloted by the oxygen-labile α subunits HIF1α and HIF2α, and current literature suggests that these genes have a functional specification that remains to be fully defined. Since their identification in the mid 90s, HIF factors have been extensively studied in solid tumors, while their implication in leukemia has lagged behind. In the last decades however, many laboratories have addressed the function of hypoxia signaling in leukemia and obtained somewhat contradictory results. Suppression of HIFs expression in different types of leukemia has unveiled common leukemia-promoting functions such as stimulation of bone marrow neoangiogenesis, maintenance of leukemia stem cells and chemoresistance. However, genetic studies are revealing that a definition of HIF factors as bona fide tumor promoters is overly simplistic, and, depending on the leukemia subtype, the specific oncogenic event, or the stage of leukemia development, activation of hypoxia-inducible genes may lead to opposite consequences. With this article we will provide an updated summary of the studies describing the regulation and function of HIF1α and HIF2α in blood malignancies, spanning from acute to chronic, lymphoid to myeloid leukemias. In discussing these data, we will attempt to provide plausible explanations to contradictory findings and point at what we believe are areas of weakness in which further investigations are urgently needed. Gaining additional knowledge into the role of hypoxia signaling in leukemia appears especially timely nowadays, as new inhibitors of HIF factors are entering the clinical arena for specific types of solid tumors but their utility for patients with leukemia is yet to be determined.


Metallic beam developments for the SPIRAL 2 project.
The SPIRAL 2 facility, currently under construction, will provide either stable or radioactive beams at high intensity. In addition to the high intensity of stable beams, high charge states must be produced by the ion source to fulfill the RFQ LINAC injection requirements: Q/A = 1/3 at 60 kV ion source extraction voltage. Excepting deuterons and hydrogen, most of the stable beam requests concern metallic elements. The existing 18 GHz electron cyclotron resonance ion source (ECRIS) Phoenix V2 designed at LPSC Grenoble has been used for the tests and will be the source for the SPIRAL 2 commissioning. The tests performed at LPSC for calcium ((40)Ca(14+) and (40)Ca(16+)), nickel ((58)Ni(19+)), and sulfur ((32)S(11+)) are described and discussed. Due to the very high charge states required, the oven method has been chosen. An intensity of 1 pμA has been reached for those elements. The performance and the beam stability have been studied using different buffer gases, and some ionization efficiency preliminary results are given.


[Aromatase gene expression and its modifying factors in breast tumor tissue].
Aromatase (CYP 19) gene expression was studied in 70 breast tumors. When RNA-dot-blot or rt-polymerase chain reaction were used expression frequency was 60.4 and 91.7%, respectively. An analysis of individual variants of non-coding exon of aromatase gene confirmed that, unlike normal mammary tissue, tumor switched from activation of exon I.4 ("sensitive" to glucocorticoids) to exons II ("sensitive" to cAMP) or I.3. This difference was relatively somewhat more pronounced in the Russian material. Direct correlation between aromatase enzymatic activity and expression of exons II and I.3 in tumor tissue appeared more significant than that of aromatase gene coding site. An evaluation of the expression of adenylate cyclase G-protein alpha-subunit genes established an inverse correlation between expression of Gi2a and exon I.3. Breast tumors with elevated basal aromatase activity were more sensitive to aromatase inhibitors (letrozole, 4-OHA) in vitro although no relationship between use of CYP19 (aromatase) 5' exon variant and in vitro inhibition of aromatase was detected. A correlation was observed between expression of aromatase gene and variants of its 5' exon, on the one hand, and age, tumor grade, steroid receptor presence and tumor lymphocytic infiltration, on the other. To summarize, local estrogen production in breast tumor tissue is regulated by a wide range of factors expression both aromatase gene influencing and its enzymatic activity, thus providing leverage on both.


[Duodenal bleeding revealing a renal cell carcinoma].
The pancreas is an uncommon site of metastasis from renal cell carcinoma. The metastasis is generally diagnosed during the follow-up of patients who underwent nephrectomy for renal cell carcinoma. In our observation, duodenal bleeding led to the diagnosis of both pancreatic metastasis and renal carcinoma. The diagnosis of pancreatic metastasis should be suspected when a pancreatic mass is associated with past or synchronous renal carcinoma. The outcome after resection of pancreatic metastasis is better than after resection of pancreatic adenocarcinoma. Surgical resection of pancreatic metastasis should be considered when possible.


[Percutaneous surgery for lithiasis: results and perspectives. Apropos of 390 operations].
Percutaneous nephrolithotomy (PCNL) has radically changed the treatment of renal stones. The indications for this technique have been modified by the development and refinement of extracorporeal lithotripsy (ECL). The authors present their experience of 390 PCNL performed between 1984 and 1991, for solitary stones in 75% of cases. There were only 11 cases of failed puncture (3.8%). The overall morbidity was 18% with only 4.4% of major complications, i.e. life threatening or requiring reoperation. There were two deaths (0.5%). Stones were completely eliminated in 80.25% of patients, after a second operation (PCNL or other technique) in 32 cases (11%). 45 staghorn calculi were treated with 11% of complications and a 51% complete cure rate. The mean hospital stay was 6 days (2 to 30). PCNL is a safe and reliable technique. Its indications have decreased (6.5% of our patients treated for renal stones), but it still retains a place in the therapeutic approach to patients with renal stones.


Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) tumors have a nutrient-poor, desmoplastic, and highly innervated tumor microenvironment. Although neurons can release stimulatory factors to accelerate PDAC tumorigenesis, the metabolic contribution of peripheral axons has not been explored. We found that peripheral axons release serine (Ser) to support the growth of exogenous Ser (exSer)-dependent PDAC cells during Ser/Gly (glycine) deprivation. Ser deprivation resulted in ribosomal stalling on two of the six Ser codons, TCC and TCT, and allowed the selective translation and secretion of nerve growth factor (NGF) by PDAC cells to promote tumor innervation. Consistent with this, exSer-dependent PDAC tumors grew slower and displayed enhanced innervation in mice on a Ser/Gly-free diet. Blockade of compensatory neuronal innervation using LOXO-101, a Trk-NGF inhibitor, further decreased PDAC tumor growth. Our data indicate that axonal-cancer metabolic crosstalk is a critical adaptation to support PDAC growth in nutrient poor environments.


Fatty acid concentration of plasma, muscle, adipose and liver from beef heifers fed an encapsulated n-3 polyunsaturated fatty acid supplement.
Increasing the content of polyunsaturated fat in the human diet is a priority for reducing cardiovascular disease and cancer risks. Beef has the potential to contribute to the polyunsaturated fat content in the human diet; however, ruminants cannot synthesise many long-chain fatty acids de novo; they require dietary supplementation. The objectives of the current study were to evaluate (i) the effect of a partially rumen protected n-3 long-chain polyunsaturated fatty acid (LC-PUFA) dietary supplement on the fatty acid composition of muscle (Longissimus dorsi), adipose and liver tissues of beef heifers and (ii) the usefulness of blood plasma as a predictor of tissue concentrations of specific fatty acids. Charolais crossbred heifers (n = 20) were assigned to one of two isolipid dietary treatments namely palmitic acid (control) or an n-3 LC-PUFA supplement for a 91-day period. Blood plasma and adipose tissue samples were taken to determine the temporal effect of these diets on fatty acid composition (days 0, 10, 35 and 91), while liver and muscle samples were taken following slaughter. Dietary lipid source did not influence animal growth rate or body condition score. At day 91, the percentage differences between control and n-3 LC-PUFA heifers in concentrations of eicosapentaenoic acid were +61, +176 and +133 % in liver, muscle and adipose, respectively. For docosahexaenoic acid, at the same time point, the percentage differences were +57, +73 and +138 % for liver, muscle and adipose, respectively. Medium-to-strong positive correlation coefficients were evident for liver and plasma fatty acids, in particular, there were positive relationships with concentrations of total saturated fatty acid (SFA), total n-6 PUFA and total n-3 PUFA. This trend also extended to both the ratio of PUFA to SFA (slope (β1) = 0.56 ± 0.167, intercept (β0) = 0.56, R2 = 0.61, P < 0.05) and the ratio of n-6 to n-3 PUFA (β1 = 0.15 ± 0.054, β0 = 0.24, R2 = 0.52, P < 0.05). A strong correlation was also detected in the ratio of n-6 to n-3 in plasma and muscle tissue of heifers fed the n-3 LC-PUFA diet (β1 = 0.53 ± 0.089, β0 = -0.31, R2 = 0.83, P < 0.001). The results of this study show that the n-3 LC-PUFA can be readily increased through targeted supplementation and that plasma concentrations of n-3 LC-PUFA are useful predictors of their concentrations in a number of economically important tissues.


Approach for estimating microbial growth and the biodegradation of hydrocarbon contaminants in subsoil based on field measurements: 1. Model development and verification.
An approach was developed to represent the microbial growth and corresponding biodegradation of hydrocarbons (HCs) during the natural attenuation process based on field measurements of in situ microbial biomass and residual HC concentrations in unsaturated subsurface soil. A kinetic model combining Monod and logistic kinetics represents microbial growth under the limitation of HCs as substrates and environmental factors at actual contaminated sites by the introduction of two new kinetic parameters, the effective rate and the self-limiting coefficient of microbial growth. The correspondence between microbial growth and the biodegradation of HCs in the soil is obtained by dividing the amount of HC and the corresponding degrading microbial groups into two classes: saturated HCs as inert components and aromatic HCs that form a contamination plume as dissolved components. The respiratory quinones were used as indicators of microbial biomass. The biodegradation capacity of contaminated sites was evaluated by the maximum microbial biomass obtained by field measurements, which is considered as the integrated results from measurements of HCs, degrading kinetics, and environmental factors at the site. The feasibility of the proposed approach was verified at two hypothetical contaminated sites. The results suggested that the proposed approach is feasible for application at actual HC-contaminated sites.


Properties of Fixed-Fixed Models and Alternatives in Presence-Absence Data Analysis.
Assessing the significance of patterns in presence-absence data is an important question in ecological data analysis, e.g., when studying nestedness. Significance testing can be performed with the commonly used fixed-fixed models, which preserve the row and column sums while permuting the data. The manuscript considers the properties of fixed-fixed models and points out how their strict constraints can lead to limited randomizability. The manuscript considers the question of relaxing row and column sun constraints of the fixed-fixed models. The Rasch models are presented as an alternative with relaxed constraints and sound statistical properties. Models are compared on presence-absence data and surprisingly the fixed-fixed models are observed to produce unreasonably optimistic measures of statistical significance, giving interesting insight into practical effects of limited randomizability.


Mapping of the Motor Cortex.
The resection of brain tumors located within or near the eloquent tissue has a higher risk of postoperative neurological deficits. The primary concerns include loss of sensory and motor functions in the contralateral face, upper and lower extremities, as well as speech deficits. Intraoperative neurophysiological monitoring (IONM) techniques are performed routinely for the identification and preservation of the functional integrity of the eloquent brain areas during neurosurgical procedures. The IONM modalities involve sensory, motor, and language mapping, which helps in the identification of the boundaries of these areas during surgical resection. Cortical motor Mapping (CmM) technique is considered as a gold-standard technique for mapping of the brain. We present the intraoperative CmM technique, including anesthesia recommendations, types of electrodes, as well as stimulation and recording parameters for successful monitoring.


Influence of smoking on hormone secretion in obese and lean female smokers.
Smoking exerts influences on the secretion of several hormones which are abnormal in obesity. Previous studies have mainly been performed in non-obese men, and data from non-obese and obese women are scarce. The aim of the present study was therefore to identify the effect of smoking on hormone secretions in obese and lean female smokers. The study was performed in 10 obese and 8 lean, premenopausal, healthy smokers. All subjects were tested once under experimental and once under control conditions (not smoking) in randomized order. The women smoked two non-filtered cigarettes during 4 minutes each. Blood pressure and heart rate were measured 30 minutes before smoking, at the start of smoking (time 0) and then after 5, 10, 20, 30, 45 and 60 minutes. Blood samples were taken for determination of serum concentrations of adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and thyroid stimulating hormone (TSH) at the same time points except at 5 minutes. Heart rate rose in both groups during smoking. Systolic and diastolic blood pressure was increased only in the obese subjects. Cortisol and ACTH increased in both groups, while TSH, PRL and GH were unchanged in both groups. We conclude that lean and obese smoking women seem to respond rather similarly to smoking in the hemodynamic and endocrine variables measured in this report with the possible exception of blood pressure where the obese women tended to show more pronounced increases.


Treatment of Head and Neck Venous Malformations with Sodium Tetradecyl Sulfate.
The purpose of this study was to discuss the clinical outcomes and complications of treating venous malformations with sclerotherapy, with sodium tetradecyl sulfate as the sclerosing agent. Case series with planned data collection. Amiralam Hospital-a referral otolaryngology-head and neck surgery hospital affiliated with Tehran University of Medical Sciences. A total of 345 patients with venous malformations were treated with sclerotherapy with sodium tetradecyl sulfate 3% (1 mL for every 1 cm3 of the lesion). The venous malformation location, treatments before the current sclerotherapy with sodium tetradecyl sulfate, the number of sclerotherapy sessions, and complications resulting from sclerotherapy were recorded. Follow-up assessments were done for a minimum of 1 year following the procedure. A favorable outcome was defined as a 50% decrease in the lesion size based on clinical and radiologic assessments. A total of 759 injection sessions were documented, ranging from 1 to 6 injections per patient (mean = 3.1). The follow-up duration ranged from 12 to 84 months (mean = 55 months). Based on clinical assessment, a 50% reduction of size was reported for 95.6% of the patients. According to the imaging before and after the procedures, a 50% reduction of size was seen among 67.3% of the patients. The results of the study showed that the use of sodium tetradecyl sulfate as a sclerosing substance can effectively reduce the size of venous malformation lesions.


Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6.
Induction of endoplasmic reticulum (ER) stress and apoptosis by elevated exogenous saturated fatty acids (FAs) plays a role in the pathogenesis of β-cell dysfunction and loss of islet mass in type 2 diabetes. Regulation of monounsaturated FA (MUFA) synthesis through FA desaturases and elongases may alter the susceptibility of β-cells to saturated FA-induced ER stress and apoptosis. Herein, stearoyl-CoA desaturase (SCD)1 and SCD2 mRNA expression were shown to be induced in islets from prediabetic hyperinsulinemic Zucker diabetic fatty (ZDF) rats, whereas SCD1, SCD2, and fatty acid elongase 6 (Elovl6) mRNA levels were markedly reduced in diabetic ZDF rat islets. Knockdown of SCD in INS-1 β-cells decreased desaturation of palmitate to MUFA, lowered FA partitioning into complex neutral lipids, and increased palmitate-induced ER stress and apoptosis. Overexpression of SCD2 increased desaturation of palmitate to MUFA and attenuated palmitate-induced ER stress and apoptosis. Knockdown of Elovl6 limited palmitate elongation to stearate, increasing palmitoleate production and attenuating palmitate-induced ER stress and apoptosis, whereas overexpression of Elovl6 increased palmitate elongation to stearate and palmitate-induced ER stress and apoptosis. Overall, these data support the hypothesis that enhanced MUFA synthesis via upregulation of SCD2 activity can protect β-cells from elevated saturated FAs, as occurs in prediabetic states. Overt type 2 diabetes is associated with diminished islet expression of SCD and Elovl6, and this can disrupt desaturation of saturated FAs to MUFAs, rendering β-cells more susceptible to saturated FA-induced ER stress and apoptosis.


Risk factors for gastrointestinal symptoms. The Danish Gulf War Study.
Compared with controls, up to six years after their return, Danish Gulf War Veterans have a significantly higher prevalence of self-reported gastrointestinal symptoms characterized by constant or occasional recurrent diarrhoea and frequent rumbling of the stomach within the preceding 12 months. The aim of this study was to clarify whether these symptoms could be attributed to physical, chemical or biological exposures. Some 686 subjects who had been deployed in the Persian Gulf within the period August 2 1990 until December 31 1997 were included in a prevalence study using retrospective data on exposure; the control group comprised 257 subjects matched according to age, gender and profession. All participants underwent clinical and paraclinical examinations, and were interviewed by a physician based on a previously completed questionnaire. Among Gulf War Veterans the prevalence of gastrointestinal symptoms was 9.1% vs 1.7% among controls, p < 0.001. Of 24 physical, chemical or biological exposures, 15 were significantly, p < 0.05, associated with the outcome in bivariate analyses. After multivariate adjustment, two exposure variables were significantly associated with the outcome: Burning of waste or manure and exposure to insecticides against cockroaches; tooth brushing using water contaminated with chemicals or pesticides, and bathing in or drinking contaminated water, were nearly significant, p < 0.10. A group of 74 subjects had 3-4 of these exposures, and a prevalence of 18.9%; 164 subjects had 2 exposures and a prevalence of 12.8%, 270 subjects with one symptom had a prevalence of 7.4%, and 153 subjects without any of these exposures had a prevalence of 2.0%, a prevalence comparable to that of controls. The associations were not explained by differences in psychiatric symptoms, age or gender. Our results suggest that, 1) a large proportion of long-term gastrointestinal problems among Gulf War Veterans can be attributed to specific exposures, 2) it should be possible to avoid a large proportion of long-term gastrointestinal symptoms in future similar missions by committed interventive measures.


Link between the EZH2 noncanonical pathway and microtubule organization center polarization during early T lymphopoiesis.
EZH2 plays an essential role at the β-selection checkpoint of T lymphopoiesis by regulating histone H3 lysine 27 trimethylation (H3K27me3) via its canonical mode of action. Increasing data suggest that EZH2 could also regulate other cellular functions, such as cytoskeletal reorganization, via its noncanonical pathway. Consequently, we investigated whether the EZH2 noncanonical pathway could be involved in early T-cell maturation, which requires cell polarization. We observed that EZH2 localization is tightly regulated during the early stages of T-cell development and that EZH2 relocalizes in the nucleus of double-negative thymocytes enduring TCRβ recombination and β-selection processes. Furthermore, we observed that EZH2 and EED, but not Suz12, colocalize with the microtubule organization center (MTOC), which might prevent its inappropriate polarization in double negative cells. In accordance with these results, we evidenced the existence of direct or indirect interaction between EED and α-tubulin. Taken together, these results suggest that the EZH2 noncanonical pathway, in association with EED, is involved in the early stages of T-cell maturation.


En route to coordination chemistry under confined conditions in a porous capsule: Pr3+ with different coordination shells.
The highly charged nanocontainer capsule of the type [pentagon]12[linker]30 identical with [(Mo)Mo5O21(H2O)6]12[Mo2O4(SO4)]30 with 20 nanosized pores and channels allows the entrance of cations like Pr3+: the latter are positioned at two different sites and have two different coordination shells, corresponding to a coordination chemistry under confined conditions; a fascinating aspect is that capsule encapsulated water shells fixed by hydrogen bonds act formally as polydentate ligands.


Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma.
The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma. Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was assessed using Student's t test, the Chi-square test and the log-rank test. In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43% (30/42) (chi(2) = 10.06, P < 0.005), and 9 (21.43%) of the 42 patients showed no gross residual disease after surgery. Blood loss and operative time were significantly decreased in the study group as compared with those in the control group (665.24 +/- 37.61 ml: 849.31 +/- 41.20 ml, t(1) = 33.21, P(1) < 0.001; 4.23 +/- 0.21 hours: 6.15 +/- 0.38 hours, t(2) = 28.92, P(2) < 0.01). In the study group, the mean survival time and the median overall survival were 33.66 months (95% CI, 24.73 to 42.58) and 26.00 months (95% CI, 19.22 to 32.78), respectively. The median disease-free interval was 18.20 months. In the control group, the mean survival time and the median overall survival were 32.38 months (95% CI, 24.92 to 39.84) and 25.00 months (95% CI, 22.80 to 27.20), respectively. The median disease-free interval was 14.20 months. The overall survival rates were not significantly different between the two groups (chi(2) = 6.48, P > 0.05). Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.


Anamorphic optical systems using programmable spatial light modulators.
Anamorphic optical systems with different horizontal and vertical magnifications are constructed by using programmable anamorphic lenses written on a magneto-optic spatial light modulator.


Multifunctional properties of RANKL/RANK in cell differentiation, proliferation and metastasis.
It is known that there are close relationships between bone destruction and tumor growth in bone metastasis. RANKL is a central factor in bone metastasis, inducing osteoclastogenesis mediated by its receptor RANK. Recent reports demonstrate that RANKL has important roles in organogenesis stimulating proliferation and differentiation of epithelial and stroma cells. RANKL is induced not only by cytokines and hormones but also by UV-irradiation, inflammation and carcinogens. Expression of RANK and RANKL is found in several human cancer cell lines, and RANK signaling stimulates proliferation, migration and epithelial-mesenchymal transition of cancer cells, which may be involved in metastasis via an autocrine/paracrine mechanism. RANKL regulates the number of Tregs that produce RANKL, which may affect cancer metastasis. In this review we discuss the multifunctional roles of RANKL/RANK in osteoclastogenesis, organogenesis, and the metastasis and tumorigenesis of cancer cells.


Protein engineering modulates the transport properties and ion selectivity of the pores formed by staphylococcal gamma-haemolysins in lipid membranes.
Staphylococcal gamma-haemolysins are bicomponent toxins in a family including other leucocidins and alpha-toxin. Two active toxins are formed combining HlgA or HlgC with HlgB. Both open pores in lipid membranes with conductance, current voltage characteristics and stability similar to alpha-toxin, but different selectivity (cation instead of anion). Structural analogies between gamma-haemolysins and alpha-toxin indicate the presence, at the pore entry, of a conserved region containing four positive charges in alpha-toxin, but either positive or negative in gamma-haemolysins. Four mutants were produced (HlgA D44K, HlgB D47K, HlgB D49K and HlgB D47K/D49K) converting those negative charges to positive in HlgA and HlgB. When all charges were positive, the pores had the same selectivity and conductance as alpha-toxin, suggesting that the cluster may form an entrance electrostatic filter. As mutated HlgC-HlgB pores were less affected, additional charges in the lumen of the pore were changed (HlgB E107Q, HlgB D121N, HlgB T136D and HlgA K108T). Removing a negative charge from the lumen made the selectivity of both HlgA-HlgB D121N and HlgC-HlgB D121N more anionic. Residue D121 of HlgB is compensated by a positive residue (HlgA K108) in the HlgA-HlgB pore, but isolated in the more cation-selective HlgC-HlgB pore. Interestingly, the pore formed by HlgA K108T-HlgB, in which the positive charge of HlgA was removed, was as cation selective as HlgC-HlgB. Meanwhile, the pore formed by HlgA K108T-HlgB D121N, in which the two charge changes compensated, retrieved the properties of wild-type HlgA-HlgB. We conclude that the conductance and selectivity of the gamma-haemolysin pores depend substantially on the presence and location of charged residues in the channel.


Elastofibroma: diagnosis and treatment of six cases.
Elastofibroma is a rare, benign pseudotumor that arises from connective tissue, most commonly found at the right scapular tip. These tumors usually can be distinguished from malignant soft-tissue tumors by their anatomical location and also through imaging techniques. Although elastofibroma is rare, it is important for surgeons to be aware of this diagnosis to prevent unnecessary biopsies and unnecessary operations. We report a series of six patients, four of whom were female, with a median age of 62.5 years, diagnosed with and treated for elastofibroma. Five of the six patients had unilateral lesions, while one patient had bilateral elastofibromas. All unilateral lesions were found on the right side. The elastofibroma in five of six patients was located on the subscapular tip, the remaining patient's elastofibroma was found on the chest wall external to the pleural surface. The pathogenesis of this lesion is discussed, as recent evidence suggests a neoplastic origin to elastofibroma. Additionally, cellular changes occurring in elastofibroma may reflect the pathogenesis of other disorders of elastic fibers.


High efficacy of tumor-targeting Salmonella typhimurium A1-R on a doxorubicin- and dactolisib-resistant follicular dendritic-cell sarcoma in a patient-derived orthotopic xenograft PDOX nude mouse model.
Follicular dendritic-cell sarcoma (FDCS) is a rare and recalcitrant disease. In the present study, a patient-derived orthotopic xenograft (PDOX) mouse model of FDCS was established in the biceps muscle of nude mice. The FDCS PDOX was resistant to both doxorubicin (DOX) and NVP-BEZ235, dactolisib (BEZ) an experimental agent which is a dual pan-phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor. However, in contrast to DOX and BEZ, the FDCS PDOX was sensitive to the tumor-targeting bacterial strain, Salmonella typhimurium A1-R (S. typhimurium A1-R). The combination of S. typhimurium A1-R and either DOX or BEZ did not increase the antitumor efficacy of S. typhimurium A1-R, indicating that DOX and BEZ were not active in this PDOX model. The efficacy of S. typhimurium A1-R in this recalcitrant FDCS gives strong impetus to move bacterial therapy to clinical trials for this disease. The findings of the present study are of particular importance since it demonstrates that S. typhimurium A1-R is effective in a PDOX model of FDCS established from a patient who failed DOX therapy.


Well-Tempered Metadynamics Simulations Predict the Structural and Dynamic Properties of a Chiral 24-Atom Macrocycle in Solution.
Inspired by therapeutic potential, the molecular engineering of macrocycles is garnering increased interest. Exercising control with design, however, is challenging due to the dynamic behavior that these molecules must demonstrate in order to be bioactive. Herein, the value of metadynamics simulations is demonstrated: the free-energy surfaces calculated reveal folded and flattened accessible conformations of a 24-atom macrocycle separated by barriers of ∼6 kT under experimentally relevant conditions. Simulations reveal that the dominant conformer is folded-an observation consistent with a solid-state structure determined by X-ray crystallography and a network of rOes established by 1H NMR. Simulations suggest that the macrocycle exists as a rapidly interconverting pair of enantiomeric, folded structures. Experimentally, 1H NMR shows a single species at room temperature. However, at lower temperature, the interconversion rate between these enantiomers becomes markedly slower, resulting in the decoalescence of enantiotopic methylene protons into diastereotopic, distinguishable resonances due to the persistence of conformational chirality. The emergence of conformational chirality provides critical experimental support for the simulations, revealing the dynamic nature of the scaffold-a trait deemed critical for oral bioactivity.


The international status of lung transplantation.
Lung transplantation has continued to increase yearly, but is now beginning to plateau possibly due to the stagnant donor pool. Emphysema/COPD continues to be the leading transplant diagnosis and infection, rejection and BO are the leading causes of recipient deaths. Actuarial survival statistics show that bilateral transplants have a slightly higher survival rate than single lung transplants with the difference widening the further out from transplantation one gets. The 6-year survival rate for all lung transplants was 40%.


Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.
The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).


Induction of acute and chronic pancreatitis with the use of the toxin of the scorpion Tityus serrulatus: experimental model in rats.
We observed that the purified venom of the Tityus serrulatus scorpion (T1 fraction), injected i.v. in rats, in a single dose of 0.5 mg/kg, produces: acute pancreatitis, characterized by degranulation and acinar cell vacuolization, necrosis and an inflammatory reaction, 24, 48 and 96 hours after the injection; chronic pancreatitis, characterized by interstitial fibrosis, lymphocyte infiltration, ductal and ductular dilation, acinar cell atrophy, periductal ductular hyperplasia, 20 days after injection: hyperplasia of Langerhans' islets and nesidioblastosis, associated to chronic pancreatitis. The absence of deaths in the experimental group is an interesting finding: the dose used preserved the animals from death and allowed the safe follow-up of the progression of the provoked pancreatitis. The results led us to conclude that the toxin of Tityus serrulatus scorpion is an agent of considerable efficacy in the induction of pancreatitis in rats providing an experimental model of acute and chronic form of this disease.


Altered calmodulin activity in fluphenazine-resistant mutant strains. Pleiotropic effect on development and cellular organization in Volvox carteri.
Genetically altered calmodulin activity in spontaneously derived mutant strains, which were selected for resistance to the toxic effect of a specific inhibitor, the phenothiazine drug fluphenazine, is demonstrated. Partially purified calmodulin preparations from wild-type and fluphenazine-resistant strains of the multicellular alga Volvox carteri, were tested for the ability to activate Ca2+-ATPase of the erythrocyte membranes, and the inhibition of this stimulatory activity by fluphenazine. Unlike the preparation obtained from wild-type cells, mutant calmodulin is shown to be insensitive to fluphenazine inhibition, in one case, and calmodulin from another strain was found to be inactive in vitro, i.e. it did not activate Ca2+-ATPase. The pleiotropic phenotype of the spontaneously derived mutant strains involved aberrant multicellular organization and hormone-independent commitment of the multipotent asexual reproductive cells, gonodia, to sexual development. These results clearly implicate calmodulin in the control of development and morphogenesis in this simple multicellular eukaryote. In addition, intracellular inhibition of calmodulin in wild-type cells is shown to block the morphogenic process of embryo inversion and to arrest motility. The availability of mutant calmodulin will facilitate further investigation of the role of this ubiquitous regulatory protein in the control of development and differentiation in multicellular eukarytes, as well as the fine structure/function relationship with regard to calmodulin modulation of a wide variety of cellular processes.


False-positive MIBG uptake in pneumonia in a patient with stage IV neuroblastoma.
A 32-month-old female child with a history of stage IV favorable biology neuroblastoma with a 123-I MIBG (metaiodobenzylguanidine scan) avid adrenal mass, with retroperitoneal nodal extension and bony metastasis, was in complete remission after intense multimodal therapy. Seventeen months after diagnosis a surveillance 123-I MIBG scan showed abnormal tracer uptake in the midzone of the right thorax. Chest x-ray and CT scan confirmed right upper lobe consolidation corresponding to the tracer uptake. Chest x-ray after antibiotics showed resolution of the abnormality. 123-I MIBG scan 3 months later showed no abnormal uptake. False-positive MIBG uptake in pneumonia has not been previously reported.


Aging and effects of ultraviolet A exposure may be quantified by fluorescence excitation spectroscopy in vivo.
The fluorescence properties of skin chromophores such as tryptophan and collagen cross-links might be useful markers of aging and photoaging. As the fluorescence of pepsin-digestible collagen cross-links was found to increase with aging and decrease with photoaging we investigated the characteristics of this dependence. In vivo fluorescence excitation spectra (emission at 380 nm) of SKH hairless mouse model skin are characterized by two bands centered near 295 nm and 335 nm due, respectively, to epidermal tryptophan moieties and pepsin-digestible collagen cross-links. Several groups of hairless mice were followed over a period of 18 mo to document changes in skin fluorescence with aging. Other groups of animals were exposed to either broad band or narrowband ultraviolet A radiation to determine the effects of ultraviolet A exposure on the fluorescence of the dermal collagen cross-links and to determine an action spectrum for the induced changes. We also found that the intensity of pepsin-digestible collagen cross-links in vivo increases linearly with age and that the fluorescence of epidermal tryptophan decreases linearly with age. We found that the fluorescence of pepsin-digestible collagen cross-links decreases immediately following exposure to ultraviolet A whereas epidermal tryptophan fluorescence increases. Both changes were dose dependent but the increase in tryptophan fluorescence occurred exclusively in young animals (2--6 mo old). We found that the ultraviolet-induced fluorescence decrease of pepsin-digestible collagen cross-links is wavelength specific. The action spectrum for the ultraviolet A effect on the in vivo fluorescence of pepsin-digestible collagen cross-links shows a distinct maximum at 335 nm that corresponds to the maximum in the fluorescence excitation spectrum due to pepsin-digestible collagen cross-links. Our results seem to indicate that in vivo fluorescence of epidermal tryptophan moieties and collagen cross-links in the dermal matrix may serve as markers for skin aging, for photoaging, and for immediate assessment of exposure to ultraviolet A radiation.


Nonlinearity and fractality in the variability of cardiac period in the lizard, Gallotia galloti: effects of autonomic blockade.
Both nonlinear and fractal properties of beat-to-beat R-R interval variability signal (RRV) of freely moving lizards (Gallotia galloti) were studied in baseline and under autonomic nervous system blockade. Nonlinear techniques allowed us to study the complexity, chaotic behavior, nonlinearity, stationarity, and regularity over time of RRV. Scaling behavior of RRV was studied by means of fractal techniques. The autonomic nervous system blockers used were atropine, propranolol, prazosin, and yohimbine. The nature of RRV was linear in baseline and under beta-, alpha(1)- and alpha(2)-adrenoceptor blockades. Atropine changed the linear nature of RRV to nonlinear and increased its stationarity, regularity and fractality. Propranolol increased the complexity and chaotic behavior, and decreased the stationarity, regularity, and fractality of RRV. Both prazosin and yohimbine did not change any of the nonlinear and fractal properties of RRV. It is suggested that 1) the use of both nonlinear and fractal analysis is an appropriate approach for studying cardiac period variability in reptiles; 2) the cholinergic activity, which seems to make the alpha(1)-, alpha(2)- and beta-adrenergic activity interaction unnecessary, determines the linear behavior in basal RRV; 3) fractality, as well as both RRV regularity and stationarity over time, may result from the balance between cholinergic and beta-adrenergic activities opposing actions; 4) beta-adrenergic activity may buffer both the complexity and chaotic behavior of RRV, and 5) neither the alpha(1)- nor the alpha(2)-adrenergic activity seem to be involved in the mediation of either nonlinear or fractal components of RRV.


To cut or not to cut, that is the question: A review of the anatomy, the technique, risks, and benefits of an episiotomy.
Childbirth can be a traumatic experience on the female body. Some techniques may be implemented to make the process smoother and decrease the potential lacerations that can occur. Episiotomies have been used by obstetricians and midwives to help make the fetal decent down the vaginal canal less turbulent. A physician must use his best judgment on when it is necessary to make this incision and what form of incision to make. Before making an incision one must understand the female external and internal anatomy and thoroughly comprehend the stages of birth to understand how and what complications can occur. Even though an episiotomy is a minor incision, it is still a surgical incision nonetheless and as with any form of surgery there are both risks and benefits that are to be considered. Nevertheless, episiotomies have proven to help ease births that are complicated by shoulder dystocia, prevent severe lacerations, and decrease the second stage of labor. The following comprehensive review provides a description of the female anatomy, as well as an extensive description of why, when, and how an episiotomy is done. Clin. Anat. 30:362-372, 2017. © 2017 Wiley Periodicals, Inc.


Dupuytren's contracture in pensioners at the Royal Hospital Chelsea.
Dupuytren's disease of the hands was present in 55 (13.75%) of the 400 elderly ex-servicemen living at the Royal Hospital Chelsea. Five men (9.1%) reported the condition in either a parent or sibling, but none was aware of an affected child. The prevalence of heavy drinking, non-insulin dependent diabetes or manual occupation was statistically the same in those with or without the condition. Overall, both hands were equally affected, but they differed in severity in 29 men. In milder cases the left hand was the more severely affected (grades 1 and 2); the reverse was true when the difference in severity was greater (grade 3). Since the original description of Dupuytren's disease [1] attempts have been made to link it with a variety of other conditions. These have included trauma, alcoholism and cirrhosis, [2] epilepsy [3] and diabetes mellitus [4]. A genetic link is accepted [5]. The condition is more common in men than women and becomes increasingly common with advancing age [6]. The prevalence in elderly men has been reported as high as 28.9%, rising to 64.3% in surveys of affected families [7]. There are still many physicians who, with a knowing wink when they spot that one of their patients has a Dupuytren's contracture, mentally register that he is an alcoholic. This paper is an attempt to disprove this fairy story. It describes a survey of Dupuytren's disease in a population of elderly men drawn from all parts of the United Kingdom and Ireland.


Identification of a novel HIV-1 circulating recombinant form (CRF62_BC) in western Yunnan of China.
We report here a novel HIV-1 circulating recombinant form (CRF62_BC) that was isolated from three epidemiologically unlinked individuals [one from an injecting drug user (IDU); two from heterosexuals] in Dehong prefecture of western Yunnan province. CRF62_BC harbored two subtype B segments in the pol and vpu-env regions in a subtype C backbone. Subregion tree analysis demonstrated that subtype B regions originated from a Thai-B (subtype B') lineage and the subtype C region was from an India C lineage. CRF62_BC is the fourth CRF composed of subtypes B' and C known to date after CRF07_BC, CRF08_BC, and CRF57_BC, which were originally found among IDUs in China. The emergence of CRF62_BC may indicate the continual generation of new recombinant strains in various high-risk populations in western Yunnan. This may complicate the development of effective vaccines to limit the HIV-1 epidemic and increase the difficulty of AIDS prevention and control in China.


A call for randomized controlled cost-effectiveness analysis of percutaneous transluminal coronary angioplasty.
A rapidly evolving technology, percutaneous transluminal coronary angioplasty, is increasingly favored over bypass surgery for treating some types of coronary stenosis because of its less traumatic invasion, better recovery response, and lower initial cost. However, substantially higher failure rates in initial procedures offset PTCA's savings to an unknown extent and cloud analysis of its overall impact. Lack of randomized clinical data precludes valid cost-effectiveness comparison of the technologies at this time. Criteria for establishing valid data and evaluations of currently available data are described in this paper.


A Preventative Respiratory Protocol to Identify Trauma Subjects at Risk for Respiratory Compromise on a General In-Patient Ward.
Patients are at risk for respiratory complications after sustaining blunt chest trauma, yet contradictory evidence exists about the utility of prophylactic respiratory therapy to reduce respiratory complications in this population. This study assessed the effectiveness of a proactive respiratory protocol on an in-patient ward to identify trauma patients at risk for pulmonary complications, administer appropriate therapies, and prevent deterioration requiring transfer to the ICU. Trauma patients received a respiratory therapy evaluation at the time of admission to a general in-patient ward at a Level 1 trauma center. If subjects met protocol inclusion criteria, they received prophylactic respiratory treatments, primarily MetaNeb therapy, Vest therapy, or EzPAP. Multiple phases were included to evaluate the effectiveness of the protocol, with 50 subjects in each phase: a pre-protocol phase before adoption of the protocol; phase 1, which was found to have low physician adherence and overly broad inclusion criteria; and phase 2, with improved adherence and narrower inclusion criteria. Study inclusion criteria mirror the protocol criteria from phase 2: ≥3 rib fractures; pulmonary contusion; exacerbation of COPD, asthma, or other lung disease; or age ≥65 y with expected immobility of ≥48 h. The respiratory protocol was associated with an elimination of unplanned admissions to the ICU. After controlling for injury severity and other important clinical factors, receiving the protocol significantly decreased hospital stay by approximately 1.5 d. More subjects were admitted from the emergency department directly to the ward, avoiding the ICU. Bronchodilator use also decreased, although the result did not reach statistical significance. Study results suggest that a preventive respiratory protocol had a beneficial effect on patient outcomes; receiving the protocol reduced hospital days and eliminated unplanned admission to the ICU.


Boosting carbon quantum dots/fullerene electron transfer via surface group engineering.
The design of novel nanostructures with tailored opto-electronic properties is a crucial step for third-generation photovoltaics, and the development of cheap and environmentally compatible materials is still a challenge. Carbon quantum dots (CQDs) emerged as promising candidates but usually a low processability and poor electron-donor properties hampered their photovoltaic applications. We tackle these issues through the synthesis and photophysical characterization of N-doped CQDs functionalized with different thiophene-containing groups. Functionalization was aimed at enhancing the electron donating properties of the carbon dots and improving the solubility in nonpolar solvents. The increased solubility in organic solvents allowed us to investigate the photoinduced interactions of the functionalized carbon dots with the fullerene derivative PCBM in solution and in solid blends. The investigation was carried out by cyclic voltammetry, photoluminescence spectroscopy and electron paramagnetic resonance (EPR). The remarkable oxidation potential shift of the functionalized carbon dots with respect to the pristine materials and the HOMO-LUMO energies strongly suggest them as good electron donors towards PCBM. The electron transfer process between CQDs and PCBM resulted in efficient fluorescence quenching in solution and in total quenching in solid blends. By using EPR spectroscopy in the solid blends, we demonstrated the efficient electron transfer by observing the photoinduced formation of a PCBM radical anion in the presence of functionalized CQDs. Time-resolved EPR allowed us to identify differences in the charge transport efficiency for different CQD:PCBM blends. The enhanced processability of CQDs with PCBM and the promising charge-generation and separation properties pave the way to the development of "all-carbon" photovoltaic devices.


Methods of nutritional assessment and functional capacity in the identification of unfavorable clinical outcomes in hospitalized patients with cancer: a systematic review.
Malnutrition has a negative impact on patients with cancer. Identifying risk, nutritional status, and functional capacity can contribute to adequate and early nutritional therapy, which can reduce unfavorable clinical outcomes. To evaluate and summarize the main instruments of nutritional assessment and functional capacity and associate their results with clinical outcomes in hospitalized patients with cancer. A systematic search was performed in the PubMed/MEDLINE, Embase, SciELO, and LILACS databases. Studies in which researchers evaluated and compared screening, nutritional assessment, and functional capacity instruments and their associations with clinical outcomes were included. The data were extracted by 2 independent reviewers. A total of 29 studies met the inclusion criteria (n = 20 441 individuals). The Nutritional Risk Screening-2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA) were the most common tools used for nutritional assessment. High nutritional risk according to the NRS-2202 and worse nutritional status according to the PG-SGA and Subjective Global Assessment were positively associated with a longer hospital stay and mortality. Low functional capacity, according to handgrip strength, was associated with longer hospital stay and nutrition impact symptoms. Tools such as the NRS-2002, PG-SGA, Subjective Global Assessment, and handgrip strength assessment are efficacious for assessing unfavorable clinical outcomes in hospitalized patients with cancer.


Oxysterols in human circulation: which role do they have?
Oxysterols are oxygenated derivatives of cholesterol that are intermediates in cholesterol excretion pathways. They may also be regarded as transport forms of cholesterol and introduction of an additional hydroxyl group facilitates flux of cholesterol across cell membranes and the blood-brain barrier. According to current concepts, oxysterols are also mediating a number of cholesterol-induced metabolic effects. The recent discovery of nuclear receptors with an affinity for oxysterols has given support to this concept. Nuclear receptors such as liver X receptor alpha do have a role in cholesterol homeostasis, but there is still only indirect evidence that oxysterols are the physiological ligands. In this overview we report some recent advancements in our knowledge about the origin and metabolic fate of the quantitatively most important oxysterols occurring in the circulation. In addition, we discuss the possibility that some of these oxysterols may activate liver X receptors and regulate cholesterol homeostasis.


Discrete vector spatial solitons in a nonlinear waveguide array.
A vector discrete diffraction managed soliton system is introduced. The vector model describes propagation of two polarization modes interacting in a nonlinear waveguide array with varying diffraction via the cross-phase modulation coupling. In the limit of strong diffraction we derive averaged equations governing the slow dynamics of the beam's amplitudes, and their stationary (in the form of bright-bright vector bound state) and traveling wave solutions are found. Through an extensive series of direct numerical simulations, interactions between diffraction-managed solitons for different values of velocities, diffraction, and cross-phase modulation coefficient are studied. We compare each collision case with its classical counterpart (constant diffraction) and find that in both the scalar and vector diffraction management cases, the interaction picture involves beam shaping, fusion, fission, nearly elastic collisions, and, in some cases, multihump structures. The collision scenario is found, in both the scalar and vector diffraction managed cases, to be rather different from the classical case.


Immunological detection of the Weligama coconut leaf wilt disease associated phytoplasma: Development and validation of a polyclonal antibody based indirect ELISA.
Weligama coconut leaf wilt disease (WCLWD) causes heavy losses in the coconut cultivations of southern Sri Lanka. The in-house developed and validated indirect ELISA was based on specific polyclonal antibodies raised in female New Zealand White rabbits, against partially purified WCLWD associated phytoplasma. This ELISA has the potential to distinguish secA PCR confirmed, WCLWD associated phytoplasma positive palms from phytoplasma free palms at high accuracy (93%) and sensitivity (92.7%), but with marginal specificity (79%). The calculated ELISA cross reactivity index (CRI) values were low for sugarcane white leaf (7%) and sugarcane grassy shoot (8%) infected leaves, but with marked highCRIfor both Bermuda grass white leaf (69%) and areca nut yellow leaf (70%) infected leaves. SecA gene based phylogenetic relationships of the WCLWD associated phytoplasma with these other locally prevalent phytoplasma strains elucidated this immunological cross reactivity, which was further reiterated by virtual restriction fragment length polymorphism analysis. Based on scanning electron microscopy, this study provides additional visual evidence, for the presence of phytoplasmas in WCLWD infected tissues.