[Assessment of efficacy of reconstructive operations on carotid arteries in combination of stenosis and pathological tortuosity].
The purpose of this study was to assess efficacy of reconstructive operations on carotid arteries in patients presenting with stenosis of the internal carotid artery (ICA) combined with its pathological tortuosity. We analysed our experience in surgical treatment of 84 patients with pathological tortuosity of the ICA combined with atherosclerotic stenosis. The study included patients with ICA stenosis ≥60% (any type of the atherosclerotic plaque) and with any degree of cerebrovascular insufficiency (CVI), or with ICA stenosis <60% (type I-III atherosclerotic plaque) with degree II-IV CVI in a combination with either S- or C-shaped tortuosity of the ICA, kinking or coiling, with the linear blood flow rate ≥110 cm/s and turbulence of blood flow. Only six (7.1%) patients of the 84 (100%) presented with no clinical signs of CVI and were found to have a past medical history free from episodes of cerebral circulation impairments. The ratio of asymptomatic/symptomatic patients was as follows: in group 1 - 12 (58.7%)/19 (61.3%), in group 2 - 27 (81.8%)/6 (18.2%), and in group 3 - 10 (50%)/10 (50%). Six months after surgery, the asymptomatic/symptomatic patients ratio was as follows: in group 1 - 22 (70.9%)/9 (29.1%), in group 2 - 28 (84.8%)/5 (15.2%), p=0.045, and in group 3 - 9 (45%)/11 (55%), p=0.024. In group 3, one (5%) patient developed thrombosis of the reconstruction zone with the development of ischaemic-type acute cerebral circulation impairment. Twelve months after surgery the ratio in the groups did not change. Of twelve patients with degree IV chronic CVI, four (33.3%) were found to have partial regression of the focal neurological symptomatology. Surgical method of treatment of patients with ICA stenos combined with pathological tortuosity proved efficient and safe both for asymptomatic patients and patients with clinical manifestations of CVI. Significantly better results were observed in the group subjected to eversion carotid endarterectomy with resection of the excessive ICA, with brining down and reimplantation into the ostium as compared with carotid endarterectomy with a patch and as compared with ICA resection with prosthetic repair.


Radiotherapy for localized relapse in patients with non-Hodgkin's lymphoma: a preliminary report.
To evaluate the usefulness of radiotherapy for relapse of non-Hodgkin's lymphoma (NHL) at a localized site. Of 79 patients with relapsed intermediate- or high-grade NHL, 13 patients (16.5%) with a localized relapse were analyzed retrospectively. Five patients were treated with radiotherapy alone and eight were treated with radiotherapy plus conventional chemotherapy (CHOP or other combinations). Radiotherapy was delivered to the involved field to a mean total dose of 34.1 Gy (range, 21-51 Gy). The 5-year overall and disease-free survival rates were 80.2% and 76.2%, respectively. Four patients relapsed subsequently. After further salvage therapy, two patients died of NHL and two were alive without active disease. Radiotherapy may be an important component of treatment for selected patients with NHL who relapse at a localized site.


Protein interaction with hydrogel contact lenses.
The first event observed at the interface between a contact lens and tear fluid is protein adsorption. Tears have a rich and complex composition, allowing a wide range of interactions and competitive processes. The majority of studies avail-able on protein adsorption have focused on blood/plasma/serum protein on solid surfaces. However, recently the interaction of tear proteins with contact lenses has become an important field of research following the widespread use of contact lenses in many physiological and pathological conditions. Protein adsorption on contact lenses is the overall result of various types of in-teractions between the different components present, i.e. the chemical composition and the surface charge, the structure of the protein molecules, the nature of the medium (tears) and many other solutes present in tears. The chemical structure of contact lenses and their physical and biological behavior are considered, followed by tear film structure and biochemistry. Finally, the nature and mechanism of protein adsorption on contact lenses, factors affecting adsorption and attempts to reduce protein ad-sorption are reviewed. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 1-19).


Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers.
Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell's MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production.


Controlled trial of antilymphocyte globulin in cadaveric transplantation.
Since January 1974, alternate cadaveric renal transplants were treated with antilymphocyte globulin (Behringwerke) om addotopm to prednisone and azathioprine. Thirty patients were treated in this way. 53% of patients receiving ALG had a functioning graft at six months as opposed to 40% in the control group. This difference is not significant. All other parameters were approximately equal in the two groups. No serious side effects of ALG treatment were observed.


Reduced hepatic aquaporin-9 and glycerol permeability are related to insulin resistance in non-alcoholic fatty liver disease.
Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance. Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m(-2)) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P(gly)) was measured by stopped-flow light scattering. AQP9 was the most abundantly (P<0.0001) expressed aquaglyceroporin in human liver (AQP9>>>AQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P(gly) and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI. AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD.


Infectious entry pathway of adenovirus type 2.
Internalization of the infectious fraction of human adenovirus type 2 into HeLa cells was followed by a quantitative internalization assay. Treatments known to selectively block receptor-mediated endocytosis reduced the internalization of infectious virus to an extent close to the reduction of endocytosis of transferrin. This suggests that one of the first steps in the infectious cycle of adenovirus type 2 is internalization by the coated-pit and -vesicle pathway.


[Functional remission of people with serious mental illness (SMI): psychometric properties of a new ROM-instrument].
Instruments are used for routine outcome monitoring of patients with severe mental illness in order to measure psychiatric symptoms, care needs and quality of life. By adding an instrument for measuring functional remission a more complete picture can be given of the complaints, the symptoms and general functioning, which can give direction to providing care for patients with severe mental illness. To describe the development and testing of a new instrument of functional remission (FR) among people with a psychotic disorder or another serious mental disorder (SMI) as an addition to the symptomatic remission (SR), according to international criteria. The FR-assessment involves assessment by a mental health professional who conducts a semi-structured interview with the patient and his or her family and/or uses patient files relating to the three areas of functioning: daily living and self-care; work, study and housekeeping; and social contacts. These areas are rated on a three-point scale of 0: independent; 1: partially independent; 2: dependent. The assessment covers a period of six months, in accordance with the measurement of symptomatic remission and should be part of regular routine outcome monitoring (ROM) procedures. The FR-instrument was used in 2012 with 840 patients from eight Dutch mental care institutions and included a one-year follow-up among 523 patients (response 62%). The results showed that the instrument is relatively easily to complete. It was also relevant for clinical practice, although further research is needed because of the raters' low response. Intra- and inter-rater reliability, discriminating and convergent validity, and sensitivity to change were rated sufficient to good. If the FR-instrument becomes part of regular ROM-procedures and is used as a measure of societal participation, it could be a useful addition to current measures of symptomatic remission.


[Lymphatic filariasis: a potentially eradicable disease]
The recent demonstration that single-dose ivermectin, diethylcarbamazine, or a combination of these drugs can profoundly suppress Wuchereria bancrofti and Brugia malayi microfilaremia for periods of six months to two years has led to renewed hope that transmission can be interrupted and lymphatic filariasis eradicated. Based in part on the availability of these new chemotherapeutic tools, the International Task Force for Disease Eradication recently identified lymphatic filariasis as one of the few diseases that could potentially be eradicated. Thus, control programs based on mass treatment (whether supplemented or not by vector control) have begun to be implemented in some endemic areas. We provide a brief review of available anti-filarial drugs for use in humans, including their tolerance and efficacy.


Regulatory ILC2-Role of IL-10 Producing ILC2 in Asthma.
Over the past two decades, a growing body of evidence observations have shown group two innate lymphoid cells (ILC2) to be critical drivers of Type 2 (T2) inflammatory responses associated with allergic inflammatory conditions such as asthma. ILC2 releases copious amounts of pro-inflammatory T2 cytokines-interleukin (IL)-4, IL-5, IL-9, and IL-13. This review provides a comprehensive overview of the newly discovered regulatory subtype of ILC2 described in murine and human mucosal tissue and blood. These KLRG1+ILC2 have the capacity to produce the anti-inflammatory cytokine IL-10. Papers compiled in this review were based on queries of PubMed and Google Scholar for articles published from 2000 to 2023 using keywords "IL-10" and "ILC2". Studies with topical relevance to IL-10 production by ILC2 were included. ILC2 responds to microenvironmental cues, including retinoic acid (RA), IL-2, IL-4, IL-10, and IL-33, as well as neuropeptide mediators such as neuromedin-U (NMU), prompting a shift towards IL-10 and away from T2 cytokine production. In contrast, TGF-β attenuates IL-10 production by ILC2. Immune regulation provided by IL-10+ILC2s holds potential significance for the management of T2 inflammatory conditions. The observation of context-specific cues that alter the phenotype of ILC warrants examining characteristics of ILC subsets to determine the extent of plasticity or whether the current classification of ILCs requires refinement.


Possible Quantum Paramagnetism in Compressed Sr_{2}IrO_{4}.
The effect of compression on the magnetic ground state of Sr_{2}IrO_{4} is studied with x-ray resonant techniques in the diamond anvil cell. The weak interlayer exchange coupling between square-planar 2D IrO_{2} layers is readily modified upon compression, with a crossover between magnetic structures around 7 GPa mimicking the effect of an applied magnetic field at ambient pressure. Higher pressures drive an order-disorder magnetic phase transition with no magnetic order detected above 17-20 GPa. The persistence of strong exchange interactions between J_{eff}=1/2 magnetic moments within the insulating IrO_{2} layers up to at least 35 GPa points to a highly frustrated magnetic state in compressed Sr_{2}IrO_{4}, opening the door for realization of novel quantum paramagnetic phases driven by extended 5d orbitals with entangled spin and orbital degrees of freedom.


Transcriptomics of MASLD Pathobiology in African American Patients in the Washington DC Area †.
Metabolic-dysfunction-associated steatotic liver disease (MASLD) is becoming the most common chronic liver disease worldwide and is of concern among African Americans (AA) in the United States. This pilot study evaluated the differential gene expressions and identified the signature genes in the disease pathways of AA individuals with MASLD. Blood samples were obtained from MASLD patients (n = 23) and non-MASLD controls (n = 24) along with their sociodemographic and medical details. Whole-blood transcriptomic analysis was carried out using Affymetrix Clarion-S Assay. A validation study was performed utilizing TaqMan Arrays coupled with Ingenuity Pathway Analysis (IPA) to identify the major disease pathways. Out of 21,448 genes in total, 535 genes (2.5%) were significantly (p < 0.05) and differentially expressed when we compared the cases and controls. A significant overlap in the predominant differentially expressed genes and pathways identified in previous studies using hepatic tissue was observed. Of note, TGFB1 and E2F1 genes were upregulated, and HMBS was downregulated significantly. Hepatic fibrosis signaling is the top canonical pathway, and its corresponding biofunction contributes to the development of hepatocellular carcinoma. The findings address the knowledge gaps regarding how signature genes and functional pathways can be detected in blood samples ('liquid biopsy') in AA MASLD patients, demonstrating the potential of the blood samples as an alternative non-invasive source of material for future studies.


Modulation of the Hoffmann reflex by rapid muscle contraction or release.
The inhibition of the H-reflex of the Soleus (Sol) muscle that takes place during and after voluntary release of Sol muscle has been attributed to presynaptic inhibition of autogenetic spindle afferences. In the present study, the time-relationship between onset of H-reflex depression and termination of Sol contraction was investigated to ascertain whether the reflex inhibition is linked to the command to release, or whether it is an accompanying phenomenon connected to changes in the neural outflow from the periphery. A parallel investigation was carried out on the temporal characteristics of the facilitation of the H-reflex that precedes onset of Sol contraction, in an attempt to point at the different functional organization of the two motor tasks. Voluntary releases from a bilateral isometric plantar torque, or bilateral plantar flexions, were performed in response to an acoustic stimulus, in a reaction time (RT) situation. The intervals from the starting signal to complete termination, or to beginning, of the Sol EMG were measured. The H-reflex was evoked at random during the tasks in one leg and its amplitude was referred in time to the end, or to the onset, of the EMG recorded from the contralateral Sol muscle. The RTs of the termination of Sol EMG had an average duration of about 100 ms, being some 20 ms shorter than those of the onset of EMG. In the release-task, the H-reflex amplitude was higher than that of the controls during the holding phase, and started to decrease about 20 ms before the cessation of the EMG.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the diagnostic performance of imaging criteria for HCCs ≤ 3.0 cm on gadoxetate disodium-enhanced MRI.
Imaging-based diagnostic systems play important roles in hepatocellular carcinoma (HCC). We aimed to compare the diagnostic performance of recently updated imaging criteria for HCCs ≤ 3.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging (MRI). 493 nodules (399 HCCs, 24 other malignancies, 70 benign) 1.0-3.0 cm from 400 patients, including 322 male (mean age 59.3 ± 9.4 years) and 78 female (mean age 61.2 ± 9.0 years), at risk for HCC who underwent gadoxetate disodium-enhanced MRI between July 2015 and December 2016 were retrospectively evaluated. Final diagnosis was determined histopathologically or clinically. The sensitivity and specificity in diagnosing HCC of the latest versions of four imaging criteria [Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC)] were compared using generalized estimating equations. In 331 only pathologically diagnosed nodules, the sensitivities of both the APASL (86.8%) and KLCA-NCC criteria (85.4%) were significantly higher than the sensitivities of the EASL (71.8%) and LR-5 (71.1%) criteria (p < 0.001 for each pairwise comparison). However, the specificity of LR-5 was significantly higher than that of APASL (92.2% vs. 70.6%, respectively; p = 0.011) but did not differ significantly from the specificities of EASL (84.3%; p = 0.634) and KLCA-NCC (78.4%; p = 0.107). Of the four international imaging criteria, LI-RADS and EASL showed high specificity but suboptimal sensitivity for diagnosing HCCs ≤ 3 cm. However, APASL and KLCA-NCC had a higher sensitivity but a lower specificity than LI-RADS and EASL.


Noradrenergic inhibition of canine gallbladder contraction and murine pancreatic secretion during stress by corticotropin-releasing factor.
Gastrointestinal secretory and motor responses are profoundly altered during stress; but the effects of stress and its mediator(s) on the two major gut functions, exocrine pancreatic secretion and gallbladder motility, are unknown. We therefore developed two animal models that allowed us to examine the effects of acoustic stress on canine gallbladder contraction and restraint stress on rat exocrine pancreatic secretion. Acoustic stress inhibited cholecystokinin-8 (CCK)- and meal-induced gallbladder contraction, and restraint stress inhibited basal and CCK/secretin-stimulated pancreatic secretion. These inhibitory responses were mimicked by cerebral injection of corticotropin-releasing factor (CRF) and abolished by the CRF antagonist, alpha-helical CRF-(9-41). The effects of stress and exogenous CRF were simulated by intravenous infusion of norepinephrine but prevented by ganglionic, noradrenergic, and alpha-adrenergic but not beta-adrenergic receptor blockade. Vagotomy, adrenalectomy, and--in rats--hypophysectomy did not alter the effects produced by stress and CRF. These results indicate that endogenous CRF released in response to different stressors in distinct species inhibits canine gallbladder contraction and murine exocrine pancreatic secretion via activation of sympathetic efferents. Release of norepinephrine appears to be the final common pathway producing inhibition of biliary and pancreatic digestive function during stress mediated by cerebral CRF.


Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer.
MTA1 has been identified as a metastasis-promoting gene, and its gene expression is correlated with serosal invasion and lymph node metastasis in the gastrointestinal and esophageal cancers. We examined MTA1 mRNA expression levels in 13 cell lines and 23 tumor tissues of pancreatic cancer by quantitative reverse transcription polymerase chain reaction. MTA1 mRNA expression was found in all the cell lines, however its levels were not correlated with the metastatic pontential of each cell line representing hematogenous distant metastasis. In the pancreatic cancer tissues, the overexpression of MTA1 mRNA (tumor/normal ratio >/=1) was observed in 12 out of 23. Pancreatic cancer tissues overexpressing MTA1 mRNA (T/N ratio >/=1) tended to have higher incidence of lymph node metastasis. These results together with previous findings in the gastrointestinal and esophageal cancers suggest that MTA1 might be involved in the progression, particularly in lymph node metastasis of pancreatic cancer.


Antimutagenic activity of natural xanthophylls against aflatoxin B1 in Salmonella typhimurium.
Carotenoids (carotenes and xanthophylls) are excellent antioxidants with antimutagenic and anticarcinogenic properties. They occur naturally in some foods such as carrots, red tomatoes, butter, cheese, paprika, palm oil, corn kernels, Marigold petals, annatto, and red salmon. In the present study, we used the Salmonella plate incorporation test to examine the effect of xanthophylls extracted from Aztec Marigold (Tagetes erecta) on the AFB1 mutagenicity, using tester strain YG1024. The effect of lutein on the DNA-repair system in YG1024 was investigated by a pre-incubation test. In a dose-response curve of AFB1, the mutagenic potency was 1,031 revertants/nmol. The dose of 0.5 microgram AFB1/ plate was chosen for the antimutagenicity studies. Pure lutein and xanthophylls from Aztec Marigold flower (oleoresin and xanthophyll plus) inhibited the mutagenicity of AFB1 in a dose-dependent manner. The pigments were more efficient at inhibiting the AFB1 mutagenicity than pure lutein. The percentages of inhibition on AFB1 mutagenicity were 37, 66, and 76% for lutein, oleoresin, and xanthophyll plus at the dose of 2 micrograms/plate, respectively. Lutein had a modest effect on the DNA-repair system of YG1024. In spectrophotometric studies, a new absorption peak was detected at 378 nm when lutein and AFB1 were incubated together, and lutein reacted with AFB1 metabolites. The results suggest that the inhibitory mechanism of lutein against AFB1 mutagenicity is most probably the result of a combination of the following events: formation of a complex between lutein and AFB1, direct interaction between lutein and AFB1 metabolites, and finally that the lutein may also affect the metabolic activation of AFB1 by S9 and the expression of AFB1-modified Salmonella DNA.


Anti-inflammatory, free radical scavenging and alpha-glucosidase inhibitory activities of Hamelia patens and its chemical constituents.
Context Hamelia patens Jacq. (Rubiaceae) is traditionally used to treat wounds, inflammation and diabetes. However, there is still a lack of scientific evidence to support these applications. Objective The objective of this study is to evaluate the anti-inflammatory, antioxidant and antidiabetic activities of Hamelia patens, and identify its bioactive compounds. Materials and methods Four extracts were obtained by maceration and liquid-liquid extraction: HEX, DCM-EtOAc, MeOH-EtOAc and MeOH-Aq. The anti-inflammatory effect was evaluated orally on rat paw carrageenan-induced oedema over 6 h (50, 200 and 500 mg/kg), and topically in mouse ear oedema induced by 12-tetradecanoylphorbol-13-acetate (TPA) after 4 h (0.5 and 1 mg/ear). We also evaluated myeloperoxidase levels in ear tissue, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and in vitro α-glucosidase inhibition. The chemical compounds were separated by column chromatography and identified by spectroscopic analysis. Results We found that the oral administration of the HEX extract at 500 and 200 mg/kg significantly decreased the carrageenan-induced inflammation after 1 and 3 h, respectively. The MeOH-EtOAc extract significantly inhibited myeloperoxidase activity (83.5%), followed by the DCM-EtOAc extract (76%), β-sitosterol/stigmasterol (72.7%) and the HEX extract (55%), which significantly decreased oedema induced by TPA at both doses, giving a similar effect to indomethacin. We also found that the MeOH-EtOAc, MeOH-Aq and DCM-EtOAc extracts showed good DPPH scavenging activity (IC50 values of 18.6, 93.9 and 158.2 μg/mL, respectively). The HEX extract showed the lowest α-glucosidase inhibition (an IC50 value of 26.07 μg/mL), followed by the MeOH-EtOAc extract (an IC50 value of 30.18 μg/mL), β-sitosterol/stigmasterol (IC50 34.6 μg/mL) and compound A ((6E,10E,14E,18E)-2,6,10,14,18,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, an IC50 value of 114.6 μg/mL), which were isolated for the first time from Hamelia patens. Discussion and conclusion Hamelia patens possesses anti-inflammatory, antioxidant and α-glucosidase inhibitory activities, which support its traditional use. These effects can be attributed to the identified compounds.


Liberation from Dialysis Dependence in a Patient with HIV-Associated Nephropathy (HIVAN) after Combined Antiretroviral Therapy (cART).
Prior to the advent of combined antiretroviral therapy (cART), human immunodeficiency virus-associated nephropathy (HIVAN) was inevitably associated with rapidly progressive renal failure and dialysis dependence. HIV-1 seropositive patients often met with untimely deaths due to complications of end-stage renal disease (ESRD), opportunistic infections, or other HIV-related end-organ failure. Although the association between cART and improved outcomes in HIVAN has been recognized for over 20 years, no randomized trials have specifically examined this effect to date. In terms of reversal of dialysis-dependent renal failure after cART initiation, only a handful of case reports exist. The authors report a case of a 44-year-old Latino male requiring thrice-weekly haemodialysis in the setting of biopsy-proven HIVAN who was able to stop dialysis in 7 months after being initiated on cART.


Tetrafluoropyridyl (TFP): a general phenol protecting group readily cleaved under mild conditions.
Phenols are extremely valuable building blocks in the areas of pharmaceuticals, natural products, materials and catalysts. In order to carry out modifications on phenols, the phenolic oxygen is routinely protected to prevent unwanted side reactions. Presently many of the protecting groups available can require harsh conditions, specialist equipment, expensive or air/moisture-sensitive reagents to install and remove. Here we introduce the use of the tetrafluoropyridyl (TFP) group as a general protecting group for phenols. TFP can be installed in one step with no sensitivity to water or air, and it is stable under a range of commonly employed reaction conditions including acid and base. The TFP protecting group is readily cleaved under mild conditions with quantitative conversion to the parent phenol, observed in many cases in less than 1 hour.


[Cerebral syndrome in chronic nonspecific lung diseases].
An analysis of the results of clinico-electrophysiological examinations of 89 patients suffering from chronic nonspecific inflammatory diseases of the lungs with involvement of the nervous system is presented. The clinical syndromes of the nervous system affections in patients with chronic inflammatory pulmonary diseases are specified. Of importance in the pathogenesis of these affections are progressing hypoxia, intoxication, edema of the brain and the meninges, and the effects of the infectious factors on the vascular walls and the nervous cells.


Bankruptcy analysis with self-organizing maps in learning metrics.
We introduce a method for deriving a metric, locally based on the Fisher information matrix, into the data space. A self-organizing map (SOM) is computed in the new metric to explore financial statements of enterprises. The metric measures local distances in terms of changes in the distribution of an auxiliary random variable that reflects what is important in the data. In this paper the variable indicates bankruptcy within the next few years. The conditional density of the auxiliary variable is first estimated, and the change in the estimate resulting from local displacements in the primary data space is measured using the Fisher information matrix. When a self-organizing map is computed in the new metric it still visualizes the data space in a topology-preserving fashion, but represents the (local) directions in which the probability of bankruptcy changes the most.


Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model.
Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1) disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor) or muscleblind, or by RNA interference (RNAi)-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis.


Serum Cystatin C as an Indicator of Renal Function and Mortality in Liver Transplant Recipients.
Chronic kidney disease (CKD) is an important comorbidity after liver transplantation (LT); however, reliable tools with which to evaluate these patients are limited. In this work, we examine the extent to which the addition of serum cystatin C improves glomerular filtration rate (GFR) estimation and mortality prediction, in comparison to various GFR-estimating equations. The GFR was measured in LT recipients by iothalamate clearance. Concurrent serum cystatin C was assayed in banked serum samples. Performance of GFR-estimating equations with and without cystatin C, including the modification of diet in renal disease and CKD-epidemiology collaboration formulas was assessed. The proportional hazards regression analysis was performed to determine the association between serum cystatin C and mortality. A total of 586 iothalamate results were obtained in 401 patients after a mean of 4 years after LT. When compared to measured GFR, the formula with both creatinine and cystatin C, namely, CKD-epidemiology cr-cys, outperformed those with either marker alone. Performance of creatinine-based models was similar to one another. Serum cystatin C, by itself or as a part of an estimated GFR, was a significant predictor of mortality. Serum cystatin C has an important role in enhancing accuracy of GFR estimation and predicting mortality in LT recipients.


Legionella pneumophila type II secretion dampens the cytokine response of infected macrophages and epithelia.
The type II secretion (T2S) system of Legionella pneumophila is required for the ability of the bacterium to grow within the lungs of A/J mice. By utilizing mutants lacking T2S (lsp), we now document that T2S promotes the intracellular infection of both multiple types of macrophages and lung epithelia. Following infection of macrophages, lsp mutants (but not a complemented mutant) elicited significantly higher levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-10, IL-8, IL-1β, and MCP-1 within tissue culture supernatants. A similar result was obtained with infected lung epithelial cell lines and the lungs of infected A/J mice. Infection with a mutant specifically lacking the T2S-dependent ProA protease (but not a complemented proA mutant) resulted in partial elevation of cytokine levels. These data demonstrate that the T2S system of L. pneumophila dampens the cytokine/chemokine output of infected host cells. Upon quantitative reverse transcription (RT)-PCR analysis of infected host cells, an lspF mutant, but not the proA mutant, produced significantly higher levels of cytokine transcripts, implying that some T2S-dependent effectors dampen signal transduction and transcription but that others, such as ProA, act at a posttranscriptional step in cytokine expression. In summary, the impact of T2S on lung infection is a combination of at least three factors: the promotion of growth in macrophages, the facilitation of growth in epithelia, and the dampening of the chemokine and cytokine output from infected host cells. To our knowledge, these data are the first to identify a link between a T2S system and the modulation of immune factors following intracellular infection.


Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: predefined 2-year follow-up study.
The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 6 months; however, maintenance glucocorticoid requirements and long-term outcomes are unknown. A total of 140 patients with new-onset ANCA-associated vasculitis without severe glomerulonephritis or alveolar haemorrhage were randomised to receive reduced-dose prednisolone (0.5 mg/kg/day) plus rituximab (375 mg/m2/week×4) or high-dose prednisolone (1 mg/kg/day) plus rituximab. After achieving remission, patients received the rituximab maintenance therapy (1 g/6 months). A total of 134 patients were analysed. Among patients who achieved remission with the protocolised treatments, the majority of patients in the reduced-dose group (89.7%) and 15.5% in the high-dose group discontinued prednisolone (median time to withdrawal, 150 and 375 days, respectively). During 24-month trial period, two patients in the reduced-dose group (2.8%) died, while five patients in the high-dose group (7.6%) died (p=0.225). Relapse occurred in nine patients in the reduced-dose group (13.0%) (two major and seven minor) and five in the high-dose group (7.6%) (two major and three minor) (p=0.311). Serious adverse events (SAEs) were less frequent in the reduced-dose group (36 events in 19 patients, 27.5%) than in the high-dose group (54 events in 30 patients, 46.2%) (p=0.025). At 24 months, frequencies of relapse did not differ between the groups, and SAEs were less frequent in the reduced-dose group due to the lower event rate in the 6-month induction phase. The bias to myeloperoxidase-ANCA positivity (85.8%) in the trial population should be noted. NCT02198248.


Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response.
Prediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging. Among HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival. During follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score <12) and low risk of HCC (score < 7/22) with 3-yrs HCC incidence of 18.96%, 5.50% and 1.65%, respectively. The integrated time-dependent area under the ROC curve (i-AUC) was 0.76 in our patients and 0.61 in the validation cohort. The externally validated HEPATHER HCC score has good short-term predictive performance in HCV- patients who achieved SVR12 after DAAs allowing to identify high-risk patients in whom HCC screening may be cost-effective and low-risk patients in whom HCC screening may be superfluous in the first 3 years after SVR.


Influence of Ala54Thr polymorphism of fatty acid-binding protein 2 on histological alterations and insulin resistance of non alcoholic fatty liver disease.
A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the influence of Ala54Thr polymorphism in the FABP2 gene on the histological alterations of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Thirty subjects with the presence of biopsy-proven NAFLD were enrolled for this study. Glucose, Insulin, Insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, resistin, leptin, adiponectin, interleukin-6 and TNF-alfa serum levels were measured at basal time. A tetrapolar bioimpedance, BMI, waist circumference, waist to hip ratio, blood pressure and a prospective serial assessment of nutritional intake with 3 days written food records were examined. Genotype of Ala54Thr FABP2 gene polymorphism was studied. The mean age was 41.6 +/- 11 years and the mean BMI 29.2 +/- 6.6 with 24 males (80%) and 6 females (20%). Fifteen patients (50%) had the genotype Ala54/Ala54 (wild type group) and 15 (50%) patients Ala54/Thr54 (13 patients) or Thr54/Thr54 (2 patients) (mutant type group). Both genotype groups have the similar anthropometric parameters. Serum aspartate aminotransferase and alcaline phosfatase were higher in wild type group than mutant type group, with an unclear explanation. Dietary intake was similar in both groups. A non-statistical significant low levels of adiponectin in mutant group was observed. No differences were detected among other adipokines. There were no differences between genotypes in histological results of inflammation (portal or lobular inflammation) or grade of steatosis or fibrosis. In conclusion, the present study demonstrates that the polymorphism Ala54Thr of FABP in patients with NAFLD doesn't predict liver histological changes, nor both insulin resistance and serum adipokines variations.


[State of the blood coagulating system in the treatment of puerperal infections using semisynthetic penicillins and cephaloridine].
The effect of some semi-synthetic penicillins, such as methicillin and oxacillin and cephalosporings, such as cephaloridin on the condition of the blood coagulation system in 85 patients with postnatal mastitis and endomyometritis was studied. It was shown that the above antibiotics had no significant effect on the parameters of the blood coagulating system. A decrease in the fibrinogen level was found in the mastitis patients treated with semi-synthetic penicillins and cephaloridin. An increase in the prothrombins index in the patients treated with methicillin oxacillin was shown. The use of the semi-synthetic penicillins and cephaloridin for the therapy of the puerpera with endomyometritis resulted in prolongation of the recalcification period. A decrease in the fibrinolytic activity most pronounced in therapy with cephaloridin was also found. Therefore, the above changes in the blood coagulating system of the puerpera with postnatal infections subjected to short-term treatment courses were insignificant and required no special correction.


Improving screening for cystic fibrosis-related diabetes at a pediatric cystic fibrosis program.
Despite guidelines recommending an annual oral glucose tolerance test (OGTT) for all patients with cystic fibrosis (CF) aged ≥ 10 years, screening rates for cystic fibrosis-related diabetes (CFRD) remained low at our center. The aim of this project was to implement an outpatient system to provide effective, evidence-based screening for CFRD at a pediatric CF program. Development of a system to improve outpatient screening for CFRD included structured education, communication with families, and processes for scheduling laboratory appointments. The primary outcome measure was the proportion of eligible patients seen at the clinic who received an OGTT by the subsequent clinic appointment. The proportion of patients without CFRD in our program who received an OGTT within the previous 12 months was also tracked longitudinally. The outpatient screening rate for CFRD increased from 2% of eligible patients seen at the clinic during the 18 weeks before the start of our initiative to 78% during the 18 weeks after the start of our initiative (P < .001). The screening rate was also increased from the corresponding date range the previous year, when only 35% of eligible patients received an OGTT (P < .001). The overall percentage of patients without CFRD in our program who received an OGTT in the previous 12 months increased from 47% to 71% after implementation of our initiative (P = .003). A systematic, quality improvement approach effectively increased the rate of outpatient screening for CFRD at a pediatric CF program.


A realist evaluation of the management of a well-performing regional hospital in Ghana.
Realist evaluation offers an interesting approach to evaluation of interventions in complex settings, but has been little applied in health care. We report on a realist case study of a well performing hospital in Ghana and show how such a realist evaluation design can help to overcome the limited external validity of a traditional case study. We developed a realist evaluation framework for hypothesis formulation, data collection, data analysis and synthesis of the findings. Focusing on the role of human resource management in hospital performance, we formulated our hypothesis around the high commitment management concept. Mixed methods were used in data collection, including individual and group interviews, observations and document reviews. We found that the human resource management approach (the actual intervention) included induction of new staff, training and personal development, good communication and information sharing, and decentralised decision-making. We identified 3 additional practices: ensuring optimal physical working conditions, access to top managers and managers' involvement on the work floor. Teamwork, recognition and trust emerged as key elements of the organisational climate. Interviewees reported high levels of organisational commitment. The analysis unearthed perceived organisational support and reciprocity as underlying mechanisms that link the management practices with commitment. Methodologically, we found that realist evaluation can be fruitfully used to develop detailed case studies that analyse how management interventions work and in which conditions. Analysing the links between intervention, mechanism and outcome increases the explaining power, while identification of essential context elements improves the usefulness of the findings for decision-makers in other settings (external validity). We also identified a number of practical difficulties and priorities for further methodological development. This case suggests that a well-balanced HRM bundle can stimulate organisational commitment of health workers. Such practices can be implemented even with narrow decision spaces. Realist evaluation provides an appropriate approach to increase the usefulness of case studies to managers and policymakers.


Preterm Cervical Ripening in humans.
Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Despite the current treatment procedures, the incidence of PTB has not changed in the past thirty years. Incomplete understanding of the biological and patophysiological mechanisms underlying preterm delivery is the major obstacle to prevent PTB. Cervical ripening is necessary for vaginal delivery and understanding of preterm cervical ripening is required for developing new treatment strategies. Several important substances such as HMGB1 and its receptors, CRH and its receptors and numerous cytokines are localized in the cervix and undergo distinct changes in labour. Other important -molecules, such as CRH, CRH-BP, CRH-R1, CRH-R2, HMGB1, TLR2, TLR4, IL-10, IL-12, are localized in the cervical epithelium, also indicating their role in the process of cervical ripening during labour. Furthermore, CRH stimulates IL-8 secretion from both preterm and term cervical fibroblasts. Recent studies from our group show that major -inflammatory changes occur in the cervix at labour irrespective of gestational age. This indicates that cervical ripening at both term and preterm is an inflammatory process even if no infection is present. However, preterm cervical ripening still entails some differences from term cervical ripening, for example in the down-regulation of mRNA expression of Toll-like receptors (TLR-2 and TLR-4) and IL-12, higher levels of IL-10 in cervical epithelium, and presents different secretion patterns of cervical fibroblasts. Moreover, preterm cervical ripening, like preterm delivery itself, is a multifactorial disorder with pathways which are partly different from those involved in PPROM and infected preterm labour.


Pilot randomized trial of a telephone-delivered physical activity and weight management intervention for individuals with lower extremity amputation.
Obesity and inactivity are common and burdensome for people with lower extremity amputation (LEA). The extent to which home-based physical activity/weight management programs are effective and safe for people with LEA is unknown. Translating effective interventions for understudied disability groups is needed. To test the feasibility, acceptability, and safety of a weight management and physical activity intervention and obtain preliminary efficacy estimates for changes in weight, body composition, and physical functioning. Eligibility criteria included: LEA ≥1 year prior, 18-69 years of age, overweight or obese and living in the Seattle area. The intervention arm received self-monitoring tools (e.g., pedometer, scale) and written materials, a single exercise counseling home visit by a physical therapist, and up to 11 telephone calls from a health coach over 20 weeks that involved motivational interviewing to set specific, attainable, and measurable goals. The self-directed control group received the same tools and materials but no home visit or coaching calls. Nineteen individuals consented to participate, 15 were randomized (mean age = 56, 73% male, 80% transtibial amputation) and 11 completed 20-week follow-up assessments. The intervention was acceptable and safe. Coached participants had greater decreases in waist circumference (mean difference between groups over 20 weeks, baseline values carried forward: -4.3 cm, 95% CI -8.2, -0.4, p = 0.03) and fat mass (-2.1 kg, 95% CI -3.8, -0.4, p = 0.02). The home-based intervention was promising in terms of efficacy, safety and acceptability. Inclusion of multiple trial centers and increased use of technology may facilitate recruitment and retention.


Regional heterogeneity of cerebral hemodynamics in mild neonatal encephalopathy measured with multichannel near-infrared spectroscopy.
Neuromonitoring at the bedside is the key to understand the pathophysiological mechanisms of brain injury associated with neonatal encephalopathy. The current practice is to monitor the forehead using a noninvasive cerebral oximetry-it remains unknown to what extent cerebral hemodynamics in other brain regions is different to the frontal region. A multichannel near-infrared spectroscopy (NIRS) system was used to monitor neonates (n = 14) with fetal acidosis and mild neonatal encephalopathy at four brain regions (the frontal, posterior, left temporal, and right temporal lobes). The data were compared to delineate the regional difference in (1) cerebral hemodynamics and (2) pressure autoregulation. For both analyses, wavelet transform coherence was applied. We observed frontal-posterior heterogeneity as indicated by significantly lower coherence between these two regions (p = 0.02). Furthermore, areas with regional magnetic resonance imaging (MRI)-detected lesions showed greater hemodynamic variations compared to non-affected areas (p = 0.03), while cerebral autoregulation was not affected and showed no difference. Cerebral hemodynamics in mild neonatal encephalopathy is heterogeneous across different brain regions, while cerebral autoregulation remains intact. These findings indicate the robustness of the wavelet measure of cerebral autoregulation in this population, but need to be further investigated in the presence of severe injury. This proof-of-concept study is the first to investigate the regional difference of cerebral hemodynamics and autoregulation in mild neonatal encephalopathy. Study findings confirm that brain functions are complex in the developing neonatal brain and that cerebral hemodynamics are region specific in newborns with frontal-posterior heterogeneity among brain regions probed by multichannel NIRS. Regional MRI lesions were associated with differences across NIRS regional channels among the affected side. Cerebral autoregulation with multichannel NIRS is not affected by regional MRI abnormalities.


Effects of Concurrent and Terminal Visual Feedback on Ankle Co-Contraction in Older Adults during Standing Balance.
This preliminary investigation studied the effects of concurrent and terminal visual feedback during a standing balance task on ankle co-contraction, which was accomplished via surface electromyography of an agonist-antagonist muscle pair (medial gastrocnemius and tibialis anterior muscles). Two complementary mathematical definitions of co-contraction indices captured changes in ankle muscle recruitment and modulation strategies. Nineteen healthy older adults received both feedback types in a randomized order. Following an analysis of co-contraction index reliability as a function of surface electromyography normalization technique, linear mixed-effects regression analyses revealed participants learned or utilized different ankle co-contraction recruitment (i.e., relative muscle pair activity magnitudes) and modulation (i.e., absolute muscle pair activity magnitudes) strategies depending on feedback type and following the cessation of feedback use. Ankle co-contraction modulation increased when concurrent feedback was used and significantly decreased when concurrent feedback was removed. Ankle co-contraction recruitment and modulation did not significantly change when terminal feedback was used or when it was removed. Neither ankle co-contraction recruitment nor modulation was significantly different when concurrent feedback was used compared to when terminal feedback was used. The changes in ankle co-contraction recruitment and modulation were significantly different when concurrent feedback was removed as compared to when terminal feedback was removed. Finally, this study found a significant interaction between feedback type, removal of feedback, and order of use of feedback type. These results have implications for the design of balance training technologies using visual feedback.


Right ventricular endomyocardial fibrosis.
Endomyocardial fibrosis is a variety of restrictive cardiomyopathy, in which endocardium of one or both ventricles is thickened markedly with involvement of underlying myocardium. Partial obliteration of ventricular cavities by fibrous tissue and thrombus causes diastolic dysfunction with increased resistance to ventricular filling. Systolic function is well preserved till late stages. Biventricular or isolated left ventricular involvement is common. Isolated right ventricular involvement is relatively uncommon. Case reports on endomyocardial fibrosis have declined in literature. In India, endomyocardial fibrosis is mainly reported from Kerala. A case of right ventricular endomyocardial fibrosis from West Bengal is reported here. Isolated right sided endomyocardial fibrosis, massive right atrial enlargement, complete disorganization of tricuspid valve, massive pericardial effusion, normal absolute eosinophil count and its sporadic occurrence outside 15 degrees of the equatorial belt were interesting features in this case of endomyocardial fibrosis. X-ray features were typical of pericardial effusion masking underlying endomyocardial fibrosis. Endomyocardial fibrosis is a neglected research field. It needs more attention from biomedical researchers.


Ultra-High-Pressure Ion Chromatography with Suppressed Conductivity Detection at 70 MPa Using Columns Packed with 2.5 μm Anion-Exchange Particles.
The use of ultrahigh pressures in combination with columns packed with 2.5 μm microporous and supermacroporous (perfusive) stationary phase particles coated with nanobeads has been successfully explored in ion chromatography with online eluent generation and suppressed conductivity detection. Isocratic separations of inorganic anions and organic acids yielding reduced plate heights as low as 2.1 were achieved, corresponding to efficiencies up to 190000 plates/m, using an optimized system configuration with respect to injection parameters, considering volume and mass loadability, and extra-column dispersion. Viscous-heating effects have been assessed for PEEK-lined stainless steel columns operated at 70 MPa, and effects of thermal gradients on separation efficiency and retention are demonstrated. Whereas the PEEK-lined column hardware acts to some extent as an insulator, a 10% increase in plate number could be obtained when applying a still-air column oven configuration. In the forced-air mode, an increase in retention was observed for polyvalent ions. Finally, the kinetic performance limits of ultrahigh-pressure ion chromatography applying 2.5 μm particle-packed columns operated at 70 MPa were compared to conventional ion-chromatography technology using columns packed with 4 μm particles operated at a maximum pressure of 35 MPa. Downscaling the particle size and increasing the operating pressure led to a maximum time gain with a factor of 3.4, without compromising separation efficiency (N = 10000).


[German language physician rating sites].
In physician rating sites (PRS), patients are able to share their experiences and indicate their satisfaction in qualitative and quantitative form. This information should support other patients in the search for a suitable physician and can serve as a form of anonymous feedback for physicians. Medical association representatives are often concerned that such reviews primarily aim at defamation. Furthermore, there are various aspects of medical work that cannot be adequately evaluated solely through the patients. In the United States of America, the majority of such previous reviews were shown to be positive. It has yet to be examined in the German and English speaking regions where distinct criteria presently allow patients to express their satisfaction through PRS. Based on the systematic review of patient satisfaction questionnaires, a set of criteria was created that represents the dimensions of patient satisfaction. German and English language physician rating sites were systematically researched using the Internet search machines "Google" and "Yahoo". The identified PRS were then evaluated with the help of the aforementioned set of criteria. In order to survey the tendency of the amount and content of reviews, a stratified sample of members of the Panel Doctor's Association in Hamburg and Thuringia was generated. A total of 298 randomly selected physicians were searched for in 6 German-language PRS regarding potential reviews. Some of the key features of the relation-ship between physicians and patients, such as medical competence, information, and consultation, were surveyed by more than three-fourths of the German-speaking PRS; however, other features such as communication were only sampled by one. As opposed to formal points of view, office facilities and organisation were assessed by all PRS. General reviews on treatment success and satisfaction were displayed in more than half of the reviews. Between 75% and 98% of physicians from the random sampling could be found in one of the 6 German language physician rating sites. Of the randomly sampled physicians, between 3% and 28% were evaluated by at least one patient. On average, the ratings for the total sample (on a scale of 1=good to 3=poor) ranged from 1.1 to 1.5, which clearly represents a positive trend. There were no differences found in terms of quantity and quality of ratings, or concerning the identifiability of physicians in the cases of Thuringia and Hamburg. The various PRS vary significantly in the selection and explanation of criteria for the evaluation of medical quality and, respectively, patient satisfaction. The specific selection and explanation of certain evaluation criteria could have a lasting effect on the understanding of physician quality and patient self-conception in the case of increased utilisation of PRS. The lack of standards for medical evaluation for PRS as well as poorly differentiated reviews, since reviews were usually positive, generally speak for the need for full text comments on PRS. This would enable peer-to-peer communication amongst users, especially regarding the practical relevance of evaluation criteria. Through this interaction between PRS users, user-oriented standards can be established and the advanced use of physician rating sites can be promoted.


Availability of Mental Health Services Prior to Health Care Reform Insurance Expansions.
This study sought to examine psychiatrists' perceptions of gaps in the availability of mental health and substance use services and their ability to spend sufficient time and provide enough visits to meet patients' clinical needs. A cross-sectional probability survey of U.S. psychiatrists was fielded during September through December 2013 by using practice-based research methods, including distribution by priority mail. Psychiatrists (N=2,800) were randomly selected from the American Medical Association Physician Masterfile, and 1,188 of the 2,615 (45%) with deliverable addresses responded. Of those, 93% (N=1,099) reported currently treating psychiatric patients, forming the sample for this study. Thirty percent or more of psychiatrists reported being unable to provide or find a source for each of the following services in the past 30 days: psychotherapy, housing, supported employment, case management or assertive community treatment, and substance use treatment. Approximately 20% reported being unable to provide or find a source for inpatient treatment, psychosocial rehabilitation, general medical care, pharmacologic treatment, and child and adolescent treatment. Approximately half (52%) of psychiatrists reported not having enough time during patient visits, affecting 28% of patients. More than one-third (37%) reported being unable to provide enough visits to meet patients' clinical needs, affecting 24% of patients. Psychiatrists reported constrained availability of a range of mental health, substance use, and general medical services. In order for the Affordable Care Act to realize the promise of increased access to care, the infrastructure for mental health and substance use treatment, workforce, and services delivery may require significant enhancement.


Risk, Determinants, and Pharmacologic Treatment of Depression Following Acute Ischemic Stroke.
Background and Purpose: We assessed risk and determinants of new-onset depression in acute ischemic stroke (AIS) patients of all ages and no known history of depression. Additionally, we assessed patterns of post-stroke depression (PSD) treatment with pharmacotherapy. Methods: Retrospective cohort study of de-identified Marketscan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Datasets for adults age ≥18 years admitted with AIS from July 1, 2016-July 1, 2017. We created Kaplan-Meier curves of cumulative risk of PSD up to 1.5 years following index AIS admission. We performed Cox regression to report hazard ratios for determinants of PSD up to 1.5 years following AIS. We summarized proportions treated with pharmacotherapy and identified the most commonly prescribed medications. Results: Of 8089 AIS patients, 1059 were diagnosed with PSD. At 1 year, cumulative risk of PSD was 13.4% (standard error .4) and 15.3% (standard error .5) at 1.5 years. History of anxiety was most strongly associated with PSD and discharge home least. Among those with PSD, 68.8% were prescribed an antidepressant and 8.4% an antipsychotic. The most commonly prescribed antidepressant was sertraline (28.5%). Conclusions: Among AIS patients of all ages, there is a persistently elevated cumulative risk of new diagnosis of PSD in the 1.5 years following AIS. Of the >2/3 treated with an antidepressant, sertraline was most commonly prescribed. Screening and treatment strategies for PSD require further study.


Computer-aided discovery of anti-inflammatory thiazolidinones with dual cyclooxygenase/lipoxygenase inhibition.
New anti-inflammatory agents possessing dual cyclooxygenase/lipoxygenase (COX/LOX) inhibition were discovered by computer-aided prediction of biological activity for 573 virtually designed chemical compounds. Prediction of biological activity was performed by PASS, and prediction results were analyzed with PharmaExpert software. Nine 2-(thiazole-2-ylamino)-5-phenylidene-4-thiazolidinone derivatives differing by the phenyl group substitution were selected for synthesis and experimental testing as potential COX/LOX inhibitors. Eight tested compounds exhibited anti-inflammatory activity in the carrageenin-induced paw edema. It was shown that seven tested compounds (77.8%) were LOX inhibitors, seven compounds were COX inhibitors (77.8%), and six tested compounds (66.7%) were dual COX/LOX inhibitors. Analysis of lipophilicity of the compounds showed a negative correlation with inhibition of edema formation. The binding modes of the most active compounds of this series (2-(thiazole-2-ylamino)-5-( m-chlorophenylidene)-4-thiazolidinone for COX-1 and COX-2, and 2-(thiazole-2-ylamino)-5-( m-nitrophenylidene)-4-thiazolidinone for 15-LOX) were proposed on the basis of docking studies.


Comparison of user volume control settings for portable music players with three earphone configurations in quiet and noisy environments.
Listening to music is one of the most common forms of recreational noise exposure. Previous investigators have demonstrated that maximum output levels from headphones can exceed safe levels. Although preferred listening levels (PLL) in quiet environments may be at acceptable levels, the addition of background noise will add to the overall noise exposure of a listener. Use of listening devices that block out some of the background noise would potentially allow listeners to select lower PLLs for their music. Although one solution is in-the-ear earphones, an alternative solution is the use of earmuffs in conjunction with earbuds. There were two objectives to this experiment. The first was to determine if an alternative to in-the-ear earphones for noise attenuation (the addition of earmuffs to earbuds) would allow for lower PLLs through a portable media player (PMP) than earbuds. The second was to determine if a surrounding background noise would yield different PLLs than a directional noise source. This was an experimental study. Twenty-four adults with normal hearing. PLLs were measured for three earphone configurations in three listening conditions. The earphone configurations included earbuds, canal earphones, and earbuds in combination with hearing protection devices (HPDs). The listening conditions included quiet, noise from one loudspeaker, and noise from four surrounding loudspeakers. Participants listened in each noise and earphone combination for as long as they needed to determine their PLL for that condition. Once the participant determined their PLL, investigators made a 5 sec recording of the music through a probe tube microphone. The average PLLs in each noise and earphone combination were used as the dependent variable. Ear canal level PLLs were converted to free-field equivalents to compare to noise exposure standards and previously published data. The average PLL as measured in the ear canal was 74 dBA in the quiet conditions and 84 dBA in the noise conditions. Paired comparisons of the PLL in the presence of background noise for each pair of earphone configurations indicated significant differences for each comparison. An inverse relationship was observed between attenuation and PLL whereby the greater the attenuation, the lower the PLL. A comparison of the single noise source condition versus the surrounding noise condition did not result in a significant effect. The present work suggests that earphones that take advantage of noise attenuation can reduce the level at which listeners set music in the presence of background noise. An alternative to in-the-ear earphones for noise attenuation is the addition of earmuffs to earbuds.


[Oscillations and trigger phenomena in fructose-2,6-bis-phosphate metabolism. A mathematical model].
A mathematical model describing metabolism of fructose-2,6-bisphosphate (F2, 6P2), which is a powerful mediator in glycolysis, is investigated. The model takes into account inhibitory effect of F2, 6P2 and fructose-6-phosphate (F6P) on protein kinase, which phosphorylates the bifunctional enzyme fructose-6-phosphate-2-kinase/fructose-2,6-bisphosphatase. Such a mechanism of enzyme chemical modification in the presence of F2, 6P outflow from the F6P in equilibrium with F2, 6P2 cycle, caused by nonspecific phosphatases, can display trigger phenomena and sustained oscillations in F2, 6P2 metabolism and in the whole glycolytic system. The results obtained suggest that earlier models of the generation of glycolytic oscillations should be revised.


[Organisational and legal issues of medical rehabilitation for patients with occupational diseases caused by dust].
The study based on Rehabilitation Center No 2 in Rostov region covered 100 male patients with dust obstructive bronchitis. The authors considered organisational and legal problems of medical rehabilitation for patients with occupational diseases caused by dust. The authors also specified and suggested stages of individual medical rehabilitation and efficiency criteria for rehabilitation, exeplified by dust obstructive bronchitis patients. Data show that creation and accomplishment of individual medical rehabilitation programs for dust obstructive bronchitis patients enable to optimize rehabilitation process, provide continuity of medical rehabilitation, evaluate efficiency of rehabilitation measures on each step of medical rehabilitation. Higher efficiency of rehabilitation is achieved by individual rehabilitation added by nebulizer treatment, efferent therapy, psychologic correction and specialized education for chronic patients with obstructive lung diseases.


The impact of cystic duct tube on the onset time of postoperative bile leakage after hepatectomy: A propensity score-matched analysis.
The cystic duct tube (C-tube) was used to reduce bile leakage (BL) incidence after hepatectomy. Nevertheless, delayed BL is sometimes experienced even using C-tube. This study investigates the impact of C-tube use on the onset time of post-hepatectomy BL. Data from 455 consecutive patients who underwent hepatectomy without biliary reconstruction between November 2007 and July 2020 were analyzed retrospectively. A C-tube was used for intraoperative biliary injury or in consideration of BL risk. BL was divided into two groups according to the postoperative onset time: early onset and late onset. To assess the association between C-tube use and BL, propensity score matching in a 1:1 ratio was performed to match BL risk factors between the C-tube and no-C-tube groups. BL occurred in 30 (6.6%) of the 455 included patients. C-tubes were used in 51 patients (11.2%) with open hepatectomy, high-risk hepatectomy, massive blood loss, long operation time, or prophylactic drain placement. After propensity score matching, BL occurred in 17 of 102 patients (16.7%). Early-onset BL occurred significantly less frequently in the C-tube group than in the no-C-tube group (3.9% vs. 15.7%, p = 0.046); however, late-onset BL was more common in the C-tube group (9.8% vs. 3.9%, p = 0.24). Six of seven patients (85.7%) with BL with C-tube use developed BL after C-tube removal. C-tube drainage may reduce early-onset BL in cases having risk factors for BL. Conversely, since late-onset BL often occurs after C-tube removal, attention should be paid to those cases.


The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics.
Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population.


Personal and partner measures in stages of consistent condom use among African-American heterosexual crack cocaine smokers.
Participants' personal condom use measures and those of their last sex partner's were examined in five stages of change for consistent condom use among 449 urban sexually active, heterosexual, African-American crack smokers. The measures included participants' personal and their last sex partner's perceived responsibility, personal and perceived negative attitudes, and participants' self-efficacy to use condoms. The relationships between the measures and the stages were examined using analyses of variance and multivariate logistic regression. Over 90% of participants did not use condoms, consistently. Two-thirds of the inconsistent users were in the precontemplation stage. The rest were equally divided between the contemplation and preparation stages. Personal responsibility outperformed other measures in initial intention to become a regular condom user; partner's perceived responsibility dominated continued intention and actual consistent condom use. Negative attitudes and self-efficacies had strong relationships to the stages of consistent condom use in univariate analyses but these relationships became substantially weaker when the responsibility, attitude, and self-efficacy concepts were entered simultaneously into multivariate analyses.


Anti-pertussis toxin IgG and anti-filamentous hemagglutinin IgG production in children immunized with pertussis acellular vaccine and comparison of these titers with the sera of pertussis convalescent children.
Serum was taken from 195 infant pertussis patients several times at appropriate intervals, and antibodies to pertussis toxin and filamentous hemagglutinin were evaluated by the ELISA. The geometric mean titers were low for both IgG antibodies at the onset of the disease, and rose to about 30 U/ml for both antibodies in the convalescent sera. All convalescent sera showed high titers of anti-PT IgG antibody. Paired serum samples were collected from 685 children before and four weeks after the second primary dose of immunization with the component vaccine. The titers were less than 1.0 and 1.8 U/ml for anti-PT and anti-FHA IgG, respectively for pre-immunization, and 22 and 66 U/ml for anti-PT and anti-FHA IgG, respectively for after immunization. When children six months of age were immunized with the component vaccine, good antibody responses were seen and no significant differences of antibody response by age were observed. There were 71 children who were immunized twice with the component vaccine and were considered to be exposed to infection by household members. Nine children out of 71 had weak or typical attacks of pertussis, and the attack rate was about 13% (9/71). It was concluded that the newly developed vaccine is suitable for children with respect to immunogenicity, and it was assumed that 20 to 30 ELISA U/ml of anti-PT and anti-FHA IgG is sufficient for protection from pertussis.


The variability in CYP3A4 activity determines the metabolic kinetic characteristics of ketamine.
Ketamine is a psychotropic drug that can cause significant neurological symptoms and is closely linked to the activity of the CYP3A4 enzyme. This study aimed to examine the diversity of CYP3A4 activity affects the metabolism of ketamine, focusing on genetic variation and drug-induced inhibition. We used a baculovirus-insect cell expression system to prepare recombinant human CYP3A4 microsomes. Then, in vitro enzyme incubation systems were established and used UPLC-MS/MS to detect ketamine metabolite. In rats, we investigated the metabolism of ketamine and its metabolite in the presence of the CYP3A4 inhibitor voriconazole. Molecular docking was used to explore the molecular mechanism of inhibition. The results showed that the catalytic activity of CYP3A4.5, .17, .23, .28, and .29 significantly decreased compared to CYP3A4.1, with a minimum decrease of 3.13%. Meanwhile, the clearance rate of CYP3A4.2, .32, and .34 enhanced remarkably, ranging from 40.63% to 87.50%. Additionally, hepatic microsome incubation experiments revealed that the half-maximal inhibitory concentration (IC50) of voriconazole for ketamine in rat and human liver microsomes were 18.01 ± 1.20 µM and 14.34 ± 1.70 µM, respectively. When voriconazole and ketamine were co-administered, the blood exposure of ketamine and norketamine significantly increased in rats, as indicated by the area under the concentration-time curve (AUC) and maximum concentration (Cmax). The elimination half-life (t1/2Z) of these substances was also prolonged. Moreover, the clearance (CLz/F) of ketamine decreased, while the apparent volume of distribution (Vz/F) increased significantly. This might be attributed to the competition between voriconazole and ketamine for binding sites on the CYP3A4 enzyme. In conclusion, variations in CYP3A4 activity would result in the stratification of ketamine blood exposure.


Interleukin-22 promotes aerobic glycolysis associated with tumor progression via targeting hexokinase-2 in human colon cancer cells.
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.


Predictors of outcome for telephone and face-to-face administered cognitive behavioral therapy for depression.
Cognitive behavioral therapy (CBT) can be delivered efficaciously through various modalities, including telephone (T-CBT) and face-to-face (FtF-CBT). The purpose of this study was to explore predictors of outcome in T-CBT and FtF-CBT for depression. A total of 325 depressed participants were randomized to receive eighteen 45-min sessions of T-CBT or FtF-CBT. Depression severity was measured using the Hamilton Depression Rating Scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9). Classification and regression tree (CART) analyses were conducted with baseline participant demographics and psychological characteristics predicting depression outcomes, HAMD and PHQ-9, at end of treatment (week 18). The demographic and psychological characteristics accurately identified 85.3% and 85.0% of treatment responders and 85.7% and 85.0% of treatment non-responders on the HAMD and PHQ-9, respectively. The Coping self-efficacy (CSE) scale predicted outcome on both the HAMD and PHQ-9; those with moderate to high CSE were likely to respond with no other variable influencing that prediction. Among those with low CSE, depression severity influenced response. Social support, physical functioning, and employment emerged as predictors only for the HAMD, and sex predicted response on the PHQ-9. Treatment delivery method (i.e. telephone or face-to-face) did not impact the prediction of outcome. Findings suggest that the predictors of improved depression are similar across treatment modalities. Most importantly, a moderate to high level of CSE significantly increases the chance of responding in both T-CBT and FtF-CBT. Among patients with low CSE, those with lower depressive symptom severity are more likely to do well in treatment.


Synchrony of nuclear replication in individual hyphae of Aspergillus nidulans.
The synchrony of nuclear replication in individual, multinucleate hyphae of Aspergillus nidulans has been investigated. Samples were taken from cultures of germinating conidiospores, and the relative frequency of hyphae containing two to eight nuclei was determined. Because the conidiospores are mononucleate, complete synchrony will yield populations of hyphae containing only 2(n) nuclei, n being the number of doublings after germination. The appearance of hyphae with total numbers of nuclei other than 2(n) will indicate lack of synchrony. The relative frequency of hyphae not having 2(n) nuclei will depend on the degree of synchrony in the individual hyphae; numerical aspects of this relation are discussed. In two different strains, replication of the nuclei in any one hypha was highly synchronized when the dry weight doubling time was 1.4 to 1.8 hr. As the doubling time was made longer by changing the nitrogen or carbon source, synchrony was progressively lost. At the slowest growth rate tested, the interval between the division of the fastest and the slowest nucleus equaled 48% of the dry weight doubling time. The active replication of some nuclei in a hypha where other nuclei were resting suggested that nuclear duplication in this eukaryotic organism may be controlled by specific initiators.


A mutant of Chlamydomonas reinhardtii that lacks the flagellar outer dynein arm but can swim.
A new type of Chlamydomonas mutant, which lacks the outer dynein arm but can swim, was isolated. Sodium dodecyl sulphate/polyacrylamide gel electrophoresis showed that four of the ten high-molecular-weight bands of dynein present in the wild-type axoneme are missing or diminished in the mutant axoneme. The mutant has a swimming rate of about 35 micrometers/s and a flagellar beat frequency of about 25 Hz, both of which are about 1/2.5 to 1/3 of those of the wild type. The mutant flagella beat with an asymmetric, cilia-type pattern, similar to the forward-swimming mode of the flagellar beating pattern of the wild type. However, unlike wild-type flagella, the mutant flagella never beat with a symmetrical waveform: when the cells were stimulated by intense light, the mutant transiently stopped beating its flagella, whereas the wild-type cell transiently swam backwards with the two flagella beating with a symmetrical waveform. Both wild-type and mutant cells could be demembranated by Nonidet P40 and their swimming reactivated by addition of Mg-ATP in the virtual absence of Ca2+. Double reciprocal plots of the beat frequency against ATP concentrations showed a linear relationship for both strains, yielding maximal frequencies of 44 Hz (wild-type) and 23 Hz (mutant). The mutant axonemes can be reactivated only when the Ca2+ concentration is lower than 10(-6) M: at pCa4, the wild-type axonemes beat with a symmetrical waveform, but the mutant axonemes showed no movement. These findings indicate that the outer dynein arm is dispensable for flagellar beating of the asymmetric waveform (forward-swimming mode), but not for beating of the symmetrical waveform (backward-swimming mode), and thus suggest the importance of the outer dynein arm in the switching of flagellar waveforms.


Autologous chondrocyte implantation with collagen bioscaffold for the treatment of osteochondral defects in rabbits.
Osteochondral injury is therapeutically irreversible within current treatment parameters. Autologous chondrocyte implantation (ACI) promises to regenerate hyaline articular cartilage, but conventional ACI is plagued by complications determined by periosteal grafting. Here we propose the utilization of collagen membrane in ACI as an effective bioscaffold for the regeneration of osteochondral lesions. Using a rabbit model of osteochondral injury, we have inoculated autologous chondrocytes onto a type I/III collagen scaffold [so-called matrix-induced ACI (MACI)] and implanted into 3-mm osteochondral knee defects. All untreated defect histology showed inferior fibrocartilage and/or fibrous tissue repair. In our time-course study, ACI with type I/III collagen membrane regenerated cartilage with healthy osteochondral architecture in osteochondral defects at 6 weeks. At 12 weeks, articular cartilage regeneration was maintained, with reduced thickness and proteoglycan compared with the adjacent cartilage. Both 6-week (p < 0.01) and 12-week (p < 0.05) ACI with collagen membrane showed significant improvement as compared with untreated controls. To further examine the efficacy of cartilage regeneration by ACI, we conducted a dose-response study, using chondrocytes at various cell densities between 10(4) and 10(6) cells/cm(2). The results showed that cell density had no effect on outcome histology, but all cell densities were significantly better than untreated controls (p < 0.01) and cell-free collagen membrane treatment (p < 0.05). In short, our data suggest that autologous chondrocyte-seeded type I/III collagen membrane is an effective method for the treatment of focal osteochondral knee injury in rabbits.


The importance of community-specific survey data in understanding behavioral and social drivers of COVID-19 vaccination: Lessons learned from urban neighborhoods in four United States cities.
This descriptive study examined patterns and trends in coronavirus (COVID-19) vaccination rates and drivers among people living, working, or socializing in urban neighborhoods of predominantly Black and Hispanic communities and compared them with the results of two national surveys. Data for these communities came from a routine survey conducted as part of the Equity-first Vaccination Initiative (EVI) in urban neighborhoods within four United States (U.S.) cities during four phases of the pandemic between July 2021 and April 2022. Our sample included 5,970 responses, which were weighted to account for design effects and compositional differences among surveyed people across the four periods. We wanted to compare the results from the EVI survey to nationally representative surveys, therefore, we did not demographically weight the sample to look like the national surveys. As a result, the EVI survey included larger proportions of people identifying with non-white racial and ethnic groups than those groups' proportions of the national population per the last U.S. Census (African American or Black: 49.8% vs. 13.7%, Hispanic or Latino/Latinx 36.5% vs. 18.9%, respectively). More EVI respondents reported concern about vaccines and fewer reported trust in COVID-19 information key messengers than national averages. The EVI survey found variation in the proportions as well as the magnitude and directionality of increases or decreases in beliefs about vaccination safety and effectiveness, the influence of religious beliefs, and intentions to get vaccinated. These differences highlight the granular insight that community-specific data can help better tailor interventions to communities disproportionately impacted by disease.


Fosfomycin: a good alternative drug for prostate biopsy prophylaxis the results of a prospective, randomized trial with respect to risk factors.
To determine the risk factors and the efficiency of rectal swab samples to prevent infectious complications in prostate biopsy, and compare fosfomycin with ciprofloxacin use in prophylaxis. Between May and October 2014, pre-biopsy risk factors and their effect in ciprofloxacin and fosfomycin prophylaxis were determined. Pre-biopsy urinalysis, urine culture and rectal swab samples were obtained from all of the patients. Rectal swabs were obtained upon admission, and biopsy was performed in the following 3-7 days. The place of rectal swab samples and efficiency of fosfomycin use was evaluated. Pre-biopsy rectal swabs were obtained from 110 patients who revealed 60.9% fluoroquinolone resistance (FQR), and 32.7% fluoroquinolone sensitivity (FQS). Fosfomycin resistance was present in 3 patients. Ciprofloxacin use in last 6 months was the only risk factor for FQR. Antibiotic prophylaxis was given to both groups with and without risk factors, according to swab results, and no infective complications were observed. Among the group where fosfomycin was used empirically, one patient had an infection needing hospitalization, however this constitutes no statistical difference between the Group that fosfomycin used empirically or according to swab results (p=0.164). In prostate biopsy prophylaxis, ciprofloxacin may be used liberally in patients without risk factors, but it should be given according to the rectal swab results in the patients with risk, and fosfomycin may be used independently of risk factors and rectal swab results.


[Complications of elective esophago-gastro-duodenoscopy (EGDS). Personal experience and literature review].
Although upper gastrointestinal (GI) endoscopy is reasonably safe, it is not perfectly so. The complication rate is about 0.1% for EGDS. Aim of this study is to schedule and evaluate all possible complications, starting from personal experience in Operative Unit of Surgical Endoscopy. We evaluated all EGDS performed at the Operative Unit of Surgical Endoscopy of Policlinico in Palermo between January 2000 and January 2008. A single staff of endoscopists performed diagnostic and therapeutic exam. All complications were tabulated and scheduled to identify possible risk factors or indicators procedure- or patient-related. 5.258 patients (43.6 %) experienced temporary and self-limiting hypoxia (SaO2 < 85%); we report totally 18 complications (0.15%), according to literature data: 2 hypopharinx perforations (0.016%), 2 middle esophagus perforation (either with death of patients = 0.016%), 3 post-biopsy hematomas of the gastric wall (0.02%) and 2 duodenal wall (0.016%) 6 (0.04%) post-polypectomy bleeding, 1 abscess post-percutaneous endoscopic gastrostomy (PEG) (0.008%) and 1 accidentally PEG remove (0.008%). EGDS-related complications may occur and cannot be prevented completely even in expert hands however, early recognition and proper management will lead to better outcome. Because of the complexity of endoscopic procedures has increased, endoscopists need to be aware of all possible procedure-related complications and should use strategies to minimize it. Endoscopic complications will inevitably occur if an endoscopist does many procedures. The knowledge of potential complications and their expected frequency can lead to improved risk-benefit analysis by physicians and patients as well as true informed consent by patients. Early recognition of complications and prompt intervention may minimize patient morbidity.


Tactile discrimination of grating orientation: fMRI activation patterns.
Grating orientation discrimination is employed widely to test tactile spatial acuity. We used functional magnetic resonance imaging (fMRI) to investigate the neural circuitry underlying performance of this task. Two studies were carried out. In the first study, an extensive set of parietal and frontal cortical areas was activated during covert task performance, relative to a rest baseline. The active regions included the postcentral sulcus bilaterally and foci in the left parietal operculum, left anterior intraparietal sulcus, and bilateral premotor and prefrontal cortex. The second study examined selective recruitment of cortical areas during discrimination of grating orientation (a task with a macrospatial component) compared to discrimination of grating spacing (a purely microspatial task). The foci activated on this contrast were in the left anterior intraparietal sulcus, right postcentral sulcus and gyrus, left parieto-occipital cortex, bilateral frontal eye fields, and bilateral ventral premotor cortex. These findings not only confirm and extend previous studies of the neural processing underlying grating orientation discrimination, but also demonstrate that a distributed network of putatively multisensory areas is involved.


Exogenous Application of Harpin Protein Hpa1 onto Pinellia ternata Induces Systemic Resistance Against Tobacco Mosaic Virus.
The harpin protein Hpa1 has various beneficial effects in plants, such as promoting plant growth and inducing pathogen resistance. Our previous study found that Hpa1 could significantly alleviate the mosaic symptoms of tobacco mosaic virus (TMV) in Pinellia ternata, indicating that Hpa1 can effectively stimulate resistance. Here, the potential mechanism of disease resistance and field applicability of Hpa1 against TMV in P. ternata were further investigated. The results showed that 15 µg ml-1 Hpa1 had stronger antiviral activity than the control, and its protective effect was better than its curative effect. Furthermore, Hpa1 could significantly induce an increase in defense-related enzyme activity, including polyphenol oxidase, peroxidase, catalase, and superoxide dismutase, as well as increase the expression of disease resistance-related genes (PR1, PR3, PR5, and PDF1.2). Concurrently, Hpa1 significantly increased the content of some disease resistance-related substances, including hydrogen peroxide, phenolics, and callose, whereas the content of malondialdehyde was reduced. In addition, field application analysis demonstrated that Hpa1 could effectively elicit a defense response against TMV in P. ternata. Our findings propose a mechanism by which Hpa1 can prevent TMV infection in Pinellia by inducing systemic resistance, thereby providing an environmentally friendly approach for the use of Hpa1 in large-scale applications to improve TMV resistance in Pinellia.


The inhibition by fluorocitrate of rat liver mitochondrial and extramitochondrial aconitate hydratase.
1. The effects of synthetic fluorocitrate were studied on: (a) the oxidation of citrate and cis-aconitate by rat liver mitochondria; (b) the activity of the aconitate hydratase found in the liver cell sap; (c) the activity of the aconitate hydratase solubilized from liver mitochondria. 2. Fluorocitrate was found to be a potent inhibitor of oxidation of citrate but only a weak inhibitor of oxidation of cis-aconitate: 6.7mum-fluorocitrate (containing 4% of the inhibitory isomer) caused 94% inhibition of the oxidation of citrate (2mm) whereas 1.0mm-fluorocitrate was necessary to provoke the same inhibition when cis-aconitate (2mm) was the substrate. The degree of inhibition varied in relation to the respiratory state of mitochondria when fluorocitrate was added. The inhibition could be partially reversed by cis-aconitate. 3. The aconitate hydratase extracted from the mitochondria was much less inhibited by fluorocitrate than was the mitochondria-bound enzyme, and the aconitate hydratase found in the cell sap was even less sensitive. 0.3mm-Fluorocitrate was required to cause 50% inhibition of the reaction citrate-->cis-aconitate, catalysed by the aconitate hydratase extracted from the mitochondria, and 1.2m-fluorocitrate for the extramitochondrial enzyme. For both enzymes the reaction citrate-->cis-aconitate was 2-3 times more sensitive to fluorocitrate than was the reaction isocitrate-->cis-aconitate. The inhibition was of the competitive type for both reactions.


Surgical treatment of appendiceal adenocarcinoid (goblet cell carcinoid).
Adenocarcinoid of the appendix is an infrequent tumor with histologic features of both adenocarcinoma and carcinoid tumor. Although its malignant potential remains unclear, adenocarcinoids seem to be biologically more aggressive than conventional carcinoids. The aim of this study was to analyze long-term results of surgical treatment for appendiceal adenocarcinoid. A retrospective review (1991-2003) identified seven patients (median age 72, range 27-81 years) treated for appendiceal adenocarcinoid. The clinical data of these patients were reviewed. Follow-up was complete for all patients (median 60 months, range 24-108 months). Most cases presented with associated acute appendicitis (71%). First intention surgery consisted of appendectomy (m = 6) and right hemicolectomy (m = 1). In three patients, additional surgical procedures were performed (right colectomy). Indications for colectomy were tumor size (three cases) associated with appendectomy margin invasion in one case. One patient with lymph node and peritoneal involvement experienced recurrence 9 months after hemicolectomy and died of the disease at 2 years. One patient subsequently died of colon carcinoma 6 years after adenocarcinoid treatment. Five patients were alive without disease at the time of the last follow-up. Synchronous or metachronous colon carcinomas developed in three patients (43%). Our results suggest that appendectomy alone could be used for appendiceal adenocarcinoid provided that the tumor (1) is less than 1 cm; (2) does not extend beyond the appendix adventitia; (3) has less than 2 mitoses/10 high power fields; and (4) has surgical margins that are tumor free. Otherwise, carcinologic right colectomy seems to be indicated. The risk for developing colorectal adenocarcinoma seems to be extremely high in patients treated for appendiceal adenocarcinoid and warrants close follow-up with colonoscopic screening.