Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization.
There is compelling support for the contribution of dopamine and the D1R-like (D1R, D5R) receptor subfamily to the behavioral and neural effects of psychostimulant drugs of abuse. The relative roles of D1R and D5R subtypes in mediating these effects are not clear. The objectives of this study are to directly compare (C57BL/6J congenic) D1R knockout (KO) and D5R KO mice for baseline locomotor exploration, acute locomotor responses to cocaine, and locomotor sensitization to repeated cocaine administration, and to examine cocaine conditioned place preference (CPP) in D5R KO. D1R KO, D5R KO, and wild-type (WT) were assessed for baseline open field exploration, locomotor-stimulating effects of 15 mg/kg acute cocaine and sensitized locomotor responses to cocaine after repeated home cage treatment with 20 or 30 mg/kg cocaine. D5R KO and WT were tested for CPP to 15 mg/kg cocaine. D1R KO showed modest basal hyperactivity and increased center exploration relative to WT. Acute locomotor responses to cocaine were consistently absent in D1R KO, but intact in D5R KO. D5R KO showed normal locomotor sensitization to cocaine and normal cocaine CPP. D1R KO failed to show a sensitized locomotor response to 30 mg/kg cocaine. Failure to sensitize in D1R KO was not because of excessive stereotypies. Surprisingly, D1R KO showed a strong trend for sensitization to 20 mg/kg cocaine. D5R KO does not alter acute or sensitized locomotor responses to cocaine or cocaine CPP. D1R KO abolishes acute locomotor response to cocaine, but does not fully prevent locomotor sensitization to cocaine at all doses.


Acquired cystic disease of the kidney in patients on hemodialysis.
Twelve adult patients undergoing hemodialysis for chronic renal failure due to noncystic causes were examined with ultrasonography to assess renal size and cystic changes. Seven of these were examined again one year later. Acquired cystic disease of the kidney was found to be present in ten patients and showed a direct relationship with duration of dialysis. This disease is not a static condition and may show progression or regression over time.


Determination of pseudocontact shifts of low-populated excited states by NMR chemical exchange saturation transfer.
Despite the critical roles of excited states in protein functions, they remain intractable for most structural studies because of their notably low populations. Chemical shifts for "invisible" states in slow exchange with the ground state are intuitively observed using nuclear magnetic resonance (NMR) chemical exchange saturation transfer (CEST) experiments. Here, we present a CEST NMR spectroscopy study for the observation of protein pseudocontact shifts (PCSs) of excited states, which carry valuable angular and distance information about these states. We first validate this approach, dubbed PCS-CEST, in the slow-exchange system of Abp1p SH3-Ark1p labeled with lanthanide ions, where the PCSs of the minor states resemble those of the holo-form ground state as expected. We further demonstrate that pre-existing folding transitional conformations of an FF domain exhibit remarkably lower PCS values than the ground state, which suggests that the low-populated ensemble is unfolded or largely unfolded. A higher resolution of PCSs of the minor states is achieved using our 1D selective CEST experiments. Thus, PCS-CEST provides an exquisite structural probe into the minor but functionally essential excited states.


Co-production of SFO-1 and DHA-1 β-lactamases and 16S rRNA methylase ArmA in clinical isolates of Klebsiella pneumoniae.
To investigate the epidemiology and genetic characteristics of the plasmid-mediated extended-spectrum β-lactamase (ESBL) gene bla(SFO-1) in clinical isolates of ESBL-producing Klebsiella pneumoniae and Escherichia coli. The prevalence of the bla(SFO-1) gene was examined by PCR amplification. Conjugation and transformation experiments were performed and the presence of antimicrobial resistance determinants was investigated by the PCR method. The genetic environments of the bla(SFO-1) and armA genes were determined by direct sequencing of plasmid pHS20. Plasmids were typed by PCR-based replicon typing. PFGE and multilocus sequence typing were performed on SFO-producing strains. Of 158 ESBL-producing strains of K. pneumoniae, 3 (1.9%) carried the bla(SFO-1) gene. All of the SFO-producing isolates belonged to the ST11 epidemic clone, with a single PFGE type and had high-level resistance to third-generation cephalosporins, aminoglycosides and ciprofloxacin. The bla(SFO-1) gene was co-transferred with the armA, aac(6')-Ib-cr and bla(TEM-1) genes by transformation, whereas the armA, bla(DHA-1) and qnrB4 genes were co-transferred by conjugation. The armA genes were located within the composite transposon Tn1548 on two different plasmids in the strain 08-129. The bla(SFO-1) gene was located upstream of an ampR gene from the coding region and flanked by two inverted repeats of IS26. Plasmids carrying bla(DHA-1) were identified as IncFII, while the bla(SFO-1)-bearing plasmids were non-typeable. Although SFO-1 is a low-occurrence ESBL, it has been captured by a plasmid accumulating multiple resistance determinants including armA and aac(6')-Ib-cr, and accompanied by a large DHA-1-bearing IncFII plasmid in a prevalent K. pneumoniae ST11 clone.


Cytoplasmic gamma-actin contributes to a compensatory remodeling response in dystrophin-deficient muscle.
Dystrophin mechanically links the costameric cytoskeleton and sarcolemma, yet dystrophin-deficient muscle exhibits abnormalities in cell signaling, gene expression, and contractile function that are not clearly understood. We generated new antibodies specific for cytoplasmic gamma-actin and confirmed that gamma-actin most predominantly localized to the sarcolemma and in a faint reticular lattice within normal muscle cells. However, we observed that gamma-actin levels were increased 10-fold at the sarcolemma and within the cytoplasm of striated muscle cells from dystrophin-deficient mdx mice. Transgenic overexpression of the dystrophin homologue utrophin, or functional dystrophin constructs in mdx muscle, restored gamma-actin to normal levels, whereas gamma-actin remained elevated in mdx muscle expressing nonfunctional dystrophin constructs. We conclude that increased cytoplasmic gamma-actin in dystrophin-deficient muscle may be a compensatory response to fortify the weakened costameric lattice through recruitment of parallel mechanical linkages. However, the presence of excessive myoplasmic gamma-actin may also contribute to altered cell signaling or gene expression in dystrophin-deficient muscle.


Implementation and evaluation of carousel dispensing technology in a university medical center pharmacy.
The implementation of carousel dispensing technology (CDT) at a university medical center pharmacy and the associated changes in drug distribution are described. An evaluation of CDT was conducted in three phases: before implementation, during implementation, and after implementation. The preimplementation phase consisted of data collection and facility planning leading up to the physical installation. The implementation phase included the physical installation, carousel medication assignment, and user training. The postimplementation phase included data collection and analysis. The data collected were used to compare preimplementation and postimplementation time studies, labor requirements, inventory turns, and accuracy rates. The estimated labor savings comparing the preimplementation and postimplementation time studies for automated dispensing cabinet (ADC) refills, first-dose requests, supplemental cart fill, and medication procurement totaled 2.6 full-time equivalents (FTEs). After departmental reorganization, a net reduction of 2.0 technician FTEs was achieved. The average turnaround time for stat medication requests using CDT was 7.19 minutes, and the percentage of doses filled in less than 20 minutes was 95.1%. After implementing CDT, the average accuracy rate for all dispense requests increased from 99.02% to 99.48%. The inventory carrying cost was reduced by $25,059. CDT improved the overall efficiency and accuracy of medication dispensing in a university medical center pharmacy. Workflow efficiencies achieved in ADC refill, first-dose dispensing, supplemental cart fill, and the medication procurement process allowed the department to reduce the amount of technician labor required to support the medication distribution process, as well as reallocate technician labor to other areas in need.


Preparation of Bovine Serum Albumin (BSA) nanoparticles by desolvation using a membrane contactor: a new tool for large scale production.
Albumin nanoparticles are attractive drug delivery systems as they can be prepared under soft conditions and incorporate several kinds of molecules. The aim of this study was to upscale the desolvation process for preparing Bovine Serum Albumin (BSA) nanoparticles using a membrane contactor. At a first step, the BSA nanoparticles were prepared at small scale using a syringe pump. BSA nanoparticles of 139 nm in size, with a polydispersity index of 0.046, were obtained at the optimal conditions: pH 8.2, 100 mg mL(-1) BSA albumin solution (2 mL), and 1 mL min(-1) flow rate of ethanol addition (8 mL). The upscaling with a membrane contactor was achieved by permeating ethanol through the pores of a Shirasu Porous Glass (SPG Technology Co., Japan) membrane and circulating the aqueous phase tangentially to the membrane surface. By increasing the pressure of the ethanol from 1 to 2.7 bars, a progressive decrease in nanoparticle size was obtained with a high nanoparticles yield (around 94-96%). In addition, the flow rate of the circulating phase did not affect the BSA nanoparticle characteristics. At the optimal conditions (pH 8.2, 100 mg mL(-1) BSA albumin solution, pressure of ethanol 2.7 bars, flow rate of the circulating phase 30.7 mL s(-1)), the BSA nanoparticles showed similar characteristics to those obtained with the syringe pump. Large batches of BSA nanoparticles were prepared up to 10 g BSA. The BSA nanoparticles were stable at least during 2 months at 4 °C, and their characteristics were reproducible. It was then concluded that the membrane contactor technique could be a suitable method for the preparation of albumin nanoparticles at large scale with properties similar to that obtained at small scale.


[Cerebral venous thrombosis in systemic lupus erythematosus. Case report and literature review].
We reviewed a case of cerebral venous thrombosis as the manifestation of systemic lupus erythematosus in a 27-year-old woman whose main symptom was headache, and in which subarachnoid hemorrhage was initially suspected. The angiography revealed thrombosis in the superior longitudinal sinus. The treatment with steroids was satisfactory, with complete resolution of symptoms. We also reviewed the reported cases in medical literature.


Prognostic significance of whole blood viscosity estimated by de Simone's formula in ST-elevation myocardial infarction.
We assessed the predictive value of estimated whole blood viscosity (WBV) in-hospital and long-term cardiovascular outcomes in patients with ST-elevation myocardial infarction (STEMI). One thousand eight hundred and thirty-five STEMI patients were followed up for median 34.6 months. WBV was calculated consistent with the de Simone's formula. In-hospital and long-term major adverse cardiovascular events (MACE) demonstrated an incremental trend in ascending order of WBV tertiles at low and high shear rate. Kaplan-Meier analysis showed a higher occurrence of long-term MACE in third WBV tertiles compared with other tertiles. WBV seems to be a feasible prognostic indicator of short- and long-term cardiovascular adverse events in patients with STEMI. As an easily available parameter, WBV may be utilized in identifying high-risk patients for subsequent MACE.


Modulation of bone microenvironment with zoledronate enhances the therapeutic effects of STI571 and paclitaxel against experimental bone metastasis of human prostate cancer.
Prostate cancer cells metastasize to the bone where their interaction with osteoclasts and osteoblasts can lead to alterations in the structure of the bone. We determined whether the systemic administration of the bisphosphonate, zoledronate, could prevent bone lysis and halt the proliferation of human prostate cancer cells injected into the tibia of nude mice. Zoledronate did not affect the in vitro proliferation of human prostate cancer PC-3MM2 cells. The in vivo administration of zoledronate produced significant bone preservation but did not inhibit the progressive growth of PC-3MM2 cells. The systemic administration of STI571 (imatinib mesylate, Gleevec), an inhibitor of phosphorylation of the platelet-derived growth factor receptor, in combination with paclitaxel, produced apoptosis of tumor cells and bone- and tumor-associated endothelial cells. The systemic administration of zoledronate with STI571 and paclitaxel produced a significant preservation of bone structure, a decrease in tumor incidence and weight, and a decrease in incidence of lymph node metastasis. This therapeutic activity was correlated with inhibition of osteoclast function, inhibition of tumor cell proliferation, and induction of apoptosis in tumor-associated endothelial cells and tumor cells. Cancer is a heterogeneous disease that requires multimodality therapy. The present data recommend the combination of a bisphosphonate agent with protein tyrosine kinase inhibitor and an anticycling drug for the treatment of prostate cancer bone metastasis.


Longitudinal study of foot pressures during real-world walking as infants develop from new to confident walkers.
Onset of walking in infants leads to regular cyclic loading of the plantar foot surface for the first time. This is a critical period for evolving motor skills and foot structure and function. Plantar pressure literature typically studies gait only once walking is established and under conditions that artificially constrain the walking direction and bouts compared to how infants move in the real-world. We therefore do not know how the foot is loaded when self-directed walking is first achieved and whether it changes as walking is practiced. Research question How do pressures on the plantar foot in real-world walking change from new to confident walking? Methods Fifty-seven infants participated in a two-site longitudinal study. Bespoke child-friendly spaces incorporated large pressure platforms and video. Data was collected at two milestones: new (403 days) and confident (481 days) walking. Steps were defined as walking straight or turning medially/laterally. Pressure variables were calculated for eight-foot regions and compared between milestones. Results Confident walking resulted in more steps (median: 18 v 35) and almost twice as many turning steps. During straight-line steps, confident walking increased peak pressures in the medial heel (median: 99.3 v 106.7kPa, p < .05) and lateral forefoot (median: 53.9 v 65.3kPa, p < .001) and reduced medial toe pressure (median: 98.1 v 80.0kPa, p < .05). Relative medial midfoot contact area reduced (median: 12.4 v 11.2%, p < .05) as absolute foot contact increased. A faster transition across stance and a reduced relative contact time in the forefoot were recorded in confident walking. Significance Pressures change rapidly as walking is initiated with significant differences in foot loading evident within an average 77 days. Importantly, these changes differ in straight and turning walking. Continued reliance on assessment of straight-line walking during early stages of ambulation likely fails to characterise 26% of steps experienced by infant feet.


Evaluation of Coriolis Micro Air Sampling to Detect Volatile and Semi-Volatile Organic Compounds.
There are several analytical procedures available for the monitoring of volatile organic compounds (VOCs) in the air, which differ mainly on sampling procedures. The Coriolis micro air sampler is a tool normally designed for biological air sampling. In this paper, the Coriolis micro bio collector is used to evaluate its ability to sample organic contaminants sampling and detecting them when combined GC-MS. We also compare the use of the Coriolis micro with a standardized sampling method, which is the use of a lung box with a Nalophan® bag. The results show that the Coriolis micro sampling method is suitable for the sampling of organic contaminants. Indeed, the Coriolis micro allows to sample and detect mainly semi-volatile molecules, while the lung box/Nalophan® bags allow to sample more volatile molecules (highly volatile and volatile). These results were confirmed in the controlled air lab with a slight difference with the field. The simultaneous use of the both techniques allow to sample and detect a larger number of molecules with specific physicochemical properties to each sampling technique. In conclusion, the Coriolis micro can sample and detect volatile organic compounds present in air. We have shown that the development of alternative sampling methods and the use of non-target analysis are essential for a more comprehensive risk assessment. Moreover, the use of the Coriolis micro allows the detection of emergent molecules around the Thau lagoon.


Comorbid attention-deficit/hyperactivity disorder in borderline patients defines an impulsive subtype of borderline personality disorder.
In order to examine the impulsive profile of a BPD sample with comorbid ADHD, adult patients who met criteria for BPD were assessed for ADHD with the CAADID and the WURS. A high rate of ADHD in the BPD sample was found, with sixty-nine (38.1%) BPD patients diagnosed as having comorbid adult ADHD. BPD-ADHD group had higher rates of general substance use disorder (59.4% vs. 38.4%), antisocial personality disorder (7.2% vs. 0.9%) and obsessive-compulsive personality disorder (21.7% vs. 6.3%). The BPD group without comorbid adult ADHD showed a higher rate of mood disorders (62.5% vs. 37.7%), panic disorders (54.5% vs. 23.1%) and benzodiazepine abuse (18.8% vs. 5.8%). Only in BPD patients without ADHD was comorbid avoidant personality disorder found. BPD patients could be distinguished in two clear subgroups related to the adult ADHD comorbidity. BPD-ADHD patients showed a more homogeneous and impulsive profile while BPD without ADHD comorbidity had more anxiety and depressive disorders.


Why are there ethnic differences in cardio-metabolic risk factors and cardiovascular diseases?
Europe's population is becoming increasingly ethnically diverse, and epidemiological studies indicate that there are remarkable differences in cardio-metabolic risk factors between ethnic groups living in the same area. Variations observed in the distribution of cardiovascular risk factors in these communities may therefore help explain-at least in part-the different burdens on cardiovascular diseases. So far, the underlying pathophysiology leading to ethnic variations in the prevalence of cardio-metabolic risk factors is still poorly understood but it is likely to represent the complex interactions from several innate and environmental factors. Tailored prevention and treatment strategies should therefore be implemented in those "high-risk populations," but data derived from randomized clinical trials are still limited. This article will provide an overview on the role of ethnicity on cardio-metabolic risk factors and cardiovascular diseases, focusing on type 2 diabetes and dyslipidemia based mainly on Dutch and British data.


Studies on analgesic and anti-inflammatory activities of 1-dialkylaminomethyl-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives.
In this study the analgesic and anti-inflammatory activity of 1,2,5-trisubstituted benzimidazole derivatives have been examined. Analgesic activities of these compounds were investigated by using the modified Koster test. Among the compounds synthesized especially compound 1g (1-diethylaminomethyl)-2-(p-chlorophenyl)-5-nitro benzimidazole hydrochloride) has shown higher activity than acetylsalicylic acid (ASA) and indometacin. Compound 1e (1-(diethylaminomethyl)-2-(p-methoxyphenyl)-5-nitro benzimidazole hydrochloride, 1f (1-(diethylaminomethyl)-2-(p-tolyl)-5-nitro benzimidazole hydrochloride and 1i (1-(pipenridinomethyl)-2-(p-methoxyphenyl)-5-nitro benzimidazole hydrochloride) proved as potent as the standard ASA. Therefore the compounds 1e, 1f, 1g and 1i were screened for their anti-inflammatory activities using the carrageenan-induced hind paw edema test. Except 1g all compounds were almost inactive against this model of inflammation compared to indometacin.


The combined effects of vitamin A-deficiency and cigarette smoke on rat tracheal epithelium.
The effects of 1-14 days cigarette smoke inhalation on the morphology of airway epithelium were compared in normal and vitamin A-deficient rats. Control rats for each diet group received 'sham' exposure of air only. The vitamin A-deficient diet caused highly significant decreases in plasma retinol and liver retinyl palmitate (P less than 0.001). Vitamin A-deficiency alone caused a squamous change without stratification which resulted in a slight but statistically significant decrease (P less than 0.005) in the thickness of tracheal epithelium. In rats fed a diet containing an adequate amount of vitamin A (i.e. 4000 iu/kg), cigarette smoke exposure for 14 consecutive days caused cell hyperplasia and hypertrophy and significant thickening of tracheal epithelium (P less than 0.01) without any squamous change. In vitamin A-deficient rats, cigarette smoke caused an epidermoid metaplasia with epithelial thickening in excess of that seen with cigarette smoke alone: i.e. the thickened epithelium was stratified, keratinized and squamous. The increase in thickness was evident after 7 days and maximal after 14 days of smoke exposure whilst the epidermoid change was most pronounced at 7 days. Whilst no secretory cells were detected in the squamous areas, the number of mucous cells in the intervening mucociliary epithelium was greatly increased. Vitamin A-deficiency may, therefore, augment the metaplastic effects of cigarette smoke by favouring an early, florid epidermoid response.


Critical behavior of magnetic polymers in two and three dimensions.
We explore the critical behavior of two- and three-dimensional lattice models of polymers in dilute solution where the monomers carry a magnetic moment which interacts ferromagnetically with near-neighbor monomers. Specifically, the model explored consists of a self-avoiding walk on a square or cubic lattice with Ising spins on the visited sites. In three dimensions we confirm and extend previous numerical work, showing clearly the first-order character of both the magnetic transition and the polymer collapse, which happen together. We present results in two dimensions, where the transition is seen to be continuous. Finite-size scaling is used to extract estimates for the critical exponents and the transition temperature in the absence of an external magnetic field.


Challenging Tumor Heterogeneity with HER2, p16 and Somatostatin Receptor 2 Expression in a Case of EBV-Associated Lymphoepithelial Carcinoma of the Salivary Gland.
Lymphoepithelial carcinoma of the salivary glands (LECSG) is a rare disease in the Western hemisphere that is typically associated with an EBV infection. The molecular mechanisms of LECSG tumorigenesis are poorly understood. Here we report a case of EBV-associated LECSG with an unusual immunophenotype. The tumor exhibited bi-morphic histological features with a mutually exclusive expression of HER2 and p16. The p16-positive domain of the tumor immunohistochemically co-expressed late membrane protein 1 (LMP-1), while the HER2 positive domain did not. Both tumor regions expressed SSTR2. In situ hybridization confirmed the EBV origin of the tumor while extensive immunohistochemical characterization and the recently established RNA-based next generation sequencing panel ("SalvGlandDx" panel) did not reveal evidence for another salivary gland neoplasm. No HPV co-infection was detected by in situ hybridization or PCR-based screenings and no ERBB2 gene amplification was detected by fluorescence in situ hybridization. These findings suggest tumor heterogeneity and lack of genomic aberrations in EBV-associated LECSGs. The heterogenous and unusual immunohistochemical features explain the diagnostic difficulties and simultaneously extend the immunophenotype spectrum of this tumor entity.


Modulation of smooth muscle cell behaviour by platelet-derived factors and the extracellular matrix.
We have studied the combined effects of platelet-derived soluble factors and three types of macromolecular substrata on the proliferation and migration of smooth muscle cells in vitro. Bovine aortic smooth muscle cells were plated onto three-dimensional gels of type I collagen or onto cell-free extracellular matrices deposited on such gels by either bovine aortic endothelial cells or smooth muscle cells. The cells were cultured in the presence of whole-blood serum (WBS) or platelet-poor plasma (PPP). Smooth muscle cell proliferation on type I collagen gels was dependent on the presence of platelet-derived factors, i.e. the cells proliferated in the presence of WBS but not in PPP. In contrast, cell proliferation on the extracellular matrices occurred at the same rate in PPP and WBS. Smooth muscle cells plated onto collagen gels rapidly migrated down into the gel matrix; the percentage of cells migrating was inversely proportional to cell density. The presence of extracellular matrices did not alter the rate of cell migration into the underlying gel matrix. Irrespective of the substratum used, smooth muscle cell migration was independent of platelet-derived or plasma factors and occurred in the absence of proliferation. These results indicate that possible chemotactic, chemokinetic, and/or mitogenic factors produced by the vascular cells and deposited within the extracellular matrix may play an important role in modulating smooth muscle cell behaviour in the vascular wall.


A case of subcutaneous panniculitis-like T-cell lymphoma with haemophagocytosis developing secondary to chemotherapy.
A 45-year-old woman presented with fever, generalized skin lesions and multiple lymphadenopathies. In her past history she had had six courses of cyclophosphamide and cisplatin combination chemotherapy 7 years ago because of an ovarian carcinoma. We found pancytopenia in the peripheral blood examination. Skin biopsy showed diffuse subcutaneous infiltration reminiscent of panniculitis but composed of malignant lymphoid cells that were of T lineage. Bone marrow biopsy showed normocellular myeloid tissue with abundant haemophagocytic macrophages. Subcutaneous panniculitis-like T-cell lymphoma with haemophagocytic syndrome was diagnosed. This is the first case reported of subcutaneous panniculitis-like lymphoma occurring secondary to chemotherapy.


Antifungals: Mechanism of Action and Drug Resistance.
There are currently few antifungals in use which show efficacy against fungal diseases. These antifungals mostly target specific components of fungal plasma membrane or its biosynthetic pathways. However, more recent class of antifungals in use is echinocandins which target the fungal cell wall components. The availability of mostly fungistatic antifungals in clinical use, often led to the development of tolerance to these very drugs by the pathogenic fungal species. Thus, the development of clinical multidrug resistance (MDR) leads to higher tolerance to drugs and its emergence is helped by multiple mechanisms. MDR is indeed a multifactorial phenomenon wherein a resistant organism possesses several mechanisms which contribute to display reduced susceptibility to not only single drug in use but also show collateral resistance to several drugs. Considering the limited availability of antifungals in use and the emergence of MDR in fungal infections, there is a continuous need for the development of novel broad spectrum antifungal drugs with better efficacy. Here, we briefly present an overview of the current understanding of the antifungal drugs in use, their mechanism of action and the emerging possible novel antifungal drugs with great promise.


The influence of health literacy on colorectal cancer screening knowledge, beliefs and behavior.
To determine if health literacy is associated with knowledge of colorectal cancer (CRC) and CRC screening tests, with perceived benefits and barriers to CRC screening, with perceived risk of CRC, with reported self-efficacy for completing CRC screening and with receipt of CRC tests. A convenience sample of 99 subjects completed a health literacy assessment, the Rapid Estimate of Adult Literacy in Medicine (REALM) and a structured interview. Limited or inadequate health literacy was significantly associated with less knowledge about CRC and CRC screening and with more reported barriers to completing fecal occult blood testing (FOBT) and colonoscopy in multivariate analysis. Health literacy was not associated with perceived benefits or reported self-efficacy for completing FOBT or colonoscopy, with perceived risk of developing CRC or with completing CRC tests. However, our small sample size limited our power to detect differences. Patients with limited health literacy have less knowledge about CRC and CRC screening and report more barriers to completing FOBT and colonoscopy. Interventions to improve CRC screening should consider the health literacy of patients, especially when addressing barriers to screening. Future studies are needed to better define the role of health literacy in CRC screening.


[Epidemiological assessment of the system of indices characterizing the quality of vaccine preparations].
The authors discuss the methodology and the method of formation of the medico-technical requirements to newly-elaborated or modified vaccine preparations. The following are considered among the principal parameters responsible for the formation of the quality of the vaccines: the prophylactic activity, the extent of the injurious effect, the technological and the exploitation properties. A close association of these parameters in the determination of the quality of the vaccine and the dependence of the efficacy of its use on the character of the epidemic situation was shown. A possibility of using the method of calculation of the efficacy of immunization for detection of the main (leading) parameters of the quality of the vaccine elaborated which should be used in composing the medico-technical requirements. It is emphasize that one of the principal directions of the investigations is the elaboration and the assessment of the correctness of the immunological and laboratory methods of standardization and control of the methods of objective measurement of the parameters forming the quality of the vaccine preparations.


Coprescription of antibiotics and asthma drugs in children.
In children, antibiotics as well as asthma drugs are frequently prescribed. We investigated the effects of the codispensing of antibiotics and asthma drugs to children. Using a health insurance database, we examined dispensing and codispensing of antibiotics and asthma drugs for the period of a 1 year in 892 841 Belgian children aged <18 years. For a 1-year period, an antibiotic was dispensed to 44.21% of children: 73.05% aged <3 years; 49.62% aged 3 to 7 years; and 34.21% aged 8 to <18 years. An asthma drug was dispensed to 16.04% of children: 44.81% aged <3 years; 17.90% aged 3 to 7 years; and 7.64% aged 8 to <18 years. Overall, an antibiotic was dispensed without an asthma drug to 38.62% of children versus with an asthma drug to 73.50% of children (P < .0001). More frequent dispensing of antibiotics to children who received an asthma drug (odds ratio: 1.90; 95% confidence interval: 1.89-1.91) occurred in all age categories (P < .0001). In 35.64% of children with an asthma drug dispensed, an antibiotic was dispensed on the same day. In all age groups, dispensing of antibiotics is more likely in children who have an asthma drug dispensed in the same year. In all age groups, codispensing of antibiotics and asthma drugs is a common practice. Efforts to decrease antibiotic use in children could be improved by focusing on children who are being treated with asthma drugs.


In Vitro Influence of ZnO, CrZnO, RuZnO, and BaZnO Nanomaterials on Bacterial Growth.
In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria's growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.


Expression of glucosylceramide synthase in invasive ductal breast cancer may be correlated with high estrogen receptor status and low HER-2 status.
Breast cancer is one of the most common causes of cancer-related deaths in women worldwide. Studies on glucosylceramide synthase (GCS) activity suggest that this enzyme has a role in the development of multidrug resistance in many cancer cells. However, few studies have shown the expression of GCS in invasive ductal breast cancer and breast intraductal proliferative lesions. In total, 196 samples from patients with invasive ductal breast cancer and 61 samples of breast intraductal proliferative lesions were collected. Immunohistochemical analyses were conducted to determine the expression of GCS and other related proteins. Expression of GCS was high in estrogen receptor (ER)-positive and HER-2 negative samples. In contrast, the expression of GCS in invasive ductal cancer was significantly lower than that in intraductal proliferative lesions. Our data demonstrates a correlation between the expression of the GCS protein and ER-positive/HER-2 negative breast cancer. Furthermore, in contrast to previous reports, the expression of GCS protein was shown to be much higher in ductal carcinoma in-situ than that in invasive ductal cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1559854430111589.


Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat.
To present the characteristics and the course of a series of anti-hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.


[Rosary-like abnormality of retinal veins:report of a case].
Inherited retinal venous beading is a rare autosomal dominant disorder with variable expressivity. It is characterized by irregular, segmented beading of the retinal veins. Some patients have arteriolar tortuosity. The conjunctiva can be affected by saccular vascular changes. Episodes of acute retinal vascular decompensation are also described. Low to normal leucocyte and neutrophil counts may be an extraocular associated condition. We describe the isolated case of a woman presenting retinal venous beading and conjunctival vascular aneurysms. She has no systemic anomaly and her family members examined are unaffected.


Expression of genes for appetite-regulating peptides in the hypothalamus of genetically selected lean and fat sheep.
The aim was to determine whether genetic selection of sheep for body composition could be accounted for by changes in the level of expression of genes for appetite-regulating peptides in the hypothalamus. We examined gene expression in the hypothalamus of genetically lean, normal and fat ewes (n = 5/group). Plasma growth hormone (GH) and metabolic indicators were measured and gene expression in brains was quantified by in situ hybridization. Body weight and voluntary food intake (VFI) were similar between groups, but lean and fat animals respectively had low and high indices of adiposity. GH levels were higher in lean and fat animals than in controls. In the arcuate nucleus (ARC), neuropeptide Y (NPY) expression/cell was higher in the lean animals than in normal animals, but overall NPY expression was similar in fat and normal animals. Pro-opiomelanocortin (POMC) and leptin receptor (ObRb) expression in the ARC was similar across groups. Orexin (ORX) and melanin-concentrating hormone (MCH) expression was inversely correlated to adiposity, being higher in lean and lower in fat animals. Expression of genes for orexigenic neuropeptides is altered in a consistent way. Energy expenditure is reduced by MCH but increased by ORX, so increased expression of the latter may cause increased energy expenditure in the lean animals and vice versa in the fat animals.


Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets.
Maternal dietary docosahexaenoic acid (DHA) intake is thought to affect development in the offspring. We assessed the impact of maternal dietary DHA on behavior, brain fatty acid (FA) profile, and sickness response of offspring in pigs, a pertinent model for human nutrition. Sows (n = 24) were fed a diet with DHA-rich fish oil (FO) (20 g/kg) or high-oleic acid sunflower oil (HOSF) (20 g/kg) from day 61 of gestation through lactation. At 4 wk of age, 4 piglets per litter were weaned and mixed with piglets from other litters. Behavior was observed in 4- to 8-wk-old piglets, and brain FA composition was analyzed at 4 (n = 15) and 14 (n = 12) wk. Thirteen-week-old piglets (n = 48) were subjected to a lipopolysaccharide (LPS) challenge. Body temperature, plasma cytokines, and motivation to approach a familiar human, indicative of a sickness response, were measured. FO-fed pigs displayed more social activities (+262%, P = 0.02), played more (+61%, P = 0.03), and tended to show fewer oral manipulative behaviors directed at pen mates (-25%, P = 0.06) than did HOSF-fed pigs up to 4 wk after weaning. Brain DHA concentrations were higher in FO- than in HOSF-fed pigs up to 10 wk after supplementation (+10-50%, P < 0.001), although differences declined with age. Body temperature (P < 0.001) and tumor necrosis factor α and interferon γ concentrations (P < 0.05) increased after LPS injection, but no diet effect was found (P > 0.10). LPS-treated pigs were less likely to approach the human than saline-treated pigs in the HOSF-fed (-29%, P = 0.0003), but not in the FO-fed group (-13%, P = 0.11). Maternal DHA beneficially affected offspring social behavior after weaning and mildly attenuated sickness behavior after an inflammatory challenge in pigs. These behavioral changes may be mediated by increased brain DHA proportions.


[Psychosomatic mechanism in pathogenesis bronchial asthma and ulcerous disease].
The objective of this article was to study individual capabilities of intrapsychic processing psycho-traumatic events and their impact on somatic health. Clinical characteristics of bronchial asthma patients and those with ulcerous disease were compared. General pathological background for development of psihosomatic pathology was identified.


L-carnitine ameliorates cancer cachexia in mice by regulating the expression and activity of carnitine palmityl transferase.
Cancer cachexia is characterized by progressive weight loss with the depletion of adipose tissue and skeletal muscle. Impaired fatty acid oxidation mainly resulting from the decrease of carnitine palmitoyltransferase I and II activities in the liver is an important factor that contributes to cancer cachexia . Although recent studies suggest a potential application of L-carnitine in treatment of cancer cachexia, the underlying mechanisms are unknown. In the present study, we aim to assess the effects of L-carnitine on the activity and expression of CPT I and II in the liver of cachectic cancer mice. Our results show that the inoculation of colon-26 adenocarcinoma cells into mice led to cancer cachexia characterized by notable decreases in food intake, gastrocnemius muscle and epididymus fat weight. In addition, the mRNA level and activity of liver carnitine palmitoyltransferase (CPT) I and II, and serum levels of free carnitine and acetylcarnitine were markedly decreased in cachectic mice, accompanied by marked increases in serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). A continuous oral treatment with L-carnitine at 18 mg/kg per day increased dietary uptake, gastrocnemius muscle weight and epididymus fat weight, increased blood glucose and serum albumin levels, and decreased total cholesterol level in cancer cachectic mice, but did not affect tumor growth. These effects of L-carnitine on cancer cachexia mice were accompanied by the upregulation of mRNA level of CPT I and II and increased enzyme activity of CPT I in the liver, as well as the downregulation of serum TNF-α and IL-6 levels. Moreover, free carnitine levels were negatively correlated with serum TNF-α or IL-6 level. These results indicate that L-carnitine ameliorates cancer cachexia by regulating serum TNF-α and IL-6 levels and modulating the expression and activity of CPT in the liver.


Macrophage Depletion Attenuates Acute Renal Damage after Exhaustive Exercise in Mice.
Exhaustive exercise is known to induce acute renal damage. However, the precise mechanisms remain unclear. We investigated the effects of macrophage depletion on exhaustive exercise-induced acute renal damage. Male C57BL/6 J mice were divided into four groups: sedentary with control liposome (n=8), sedentary with clodronate liposome (n=8), exhaustive exercise with control liposome (n=8), and exhaustive exercise with clodronate liposome (n=8). Mice were treated with clodronate liposomes or control liposomes intraperitoneally for 48 h before undergoing exhaustive exercise. Renal function and renal histology were tested at 24 h. The expression levels of kidney injury molecule (KIM)-1 and inflammatory cytokines in kidney tissues were measured by quantitative RT-PCR, and KIM-1 concentration was semi-quantified by immunostaining. As a result, exhaustive exercise increased macrophage infiltration into the kidney. However, clodronate reduced it. Although exhaustive exercise resulted in an increase in KIM-1 mRNA expression levels and concentration, injection of clodronate liposome reduced it. In addition, TUNEL positive apoptotic cells were increased after exercise, but significantly reduced by clodronate. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the kidney after exhaustive exercise. These results suggest that macrophages play a critical role in increasing renal damage by regulating inflammation.


Moderators of remission with interpersonal counselling or drug treatment in primary care patients with depression: randomised controlled trial.
Despite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression. To evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome. A randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score ≤7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome. The percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit. We identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.


Interkingdom and intrakingdom interactions in the microbiome of Heterobasidion fruiting body and associated decayed woody tissues.
We applied macro- (forest stand and forest management) and micro-scale (bacterial and fungal community) analyses for a better understanding of the Heterobasidion pathosystem and associated wood decay process. The core microbiome, as defined by hierarchy analysis and a consistent model, and environmental factors correlation with the community assembly were found to be novel.


Timeliness of abnormal screening and diagnostic mammography follow-up at facilities serving vulnerable women.
Whether timeliness of follow-up after abnormal mammography differs at facilities serving vulnerable populations, such as women with limited education or income, in rural areas, and racial/ethnic minorities is unknown. We examined receipt of diagnostic evaluation after abnormal mammography using 1998-2006 Breast Cancer Surveillance Consortium-linked Medicare claims. We compared whether time to recommended breast imaging or biopsy depended on whether women attended facilities serving vulnerable populations. We characterized a facility by the proportion of mammograms performed on women with limited education or income, in rural areas, or racial/ethnic minorities. We analyzed 30,874 abnormal screening examinations recommended for follow-up imaging across 142 facilities and 10,049 abnormal diagnostic examinations recommended for biopsy across 114 facilities. Women at facilities serving populations with less education or more racial/ethnic minorities had lower rates of follow-up imaging (4%-5% difference, P<0.05), and women at facilities serving more rural and low-income populations had lower rates of biopsy (4%-5% difference, P<0.05). Women undergoing biopsy at facilities serving vulnerable populations had longer times until biopsy than those at facilities serving nonvulnerable populations (21.6 vs. 15.6 d; 95% confidence interval for mean difference 4.1-7.7). The proportion of women receiving recommended imaging within 11 months and biopsy within 3 months varied across facilities (interquartile range, 85.5%-96.5% for imaging and 79.4%-87.3% for biopsy). Among Medicare recipients, follow-up rates were slightly lower at facilities serving vulnerable populations, and among those women who returned for diagnostic evaluation, time to follow-up was slightly longer at facilities that served vulnerable population. Interventions should target variability in follow-up rates across facilities, and evaluate effectiveness particularly at facilities serving vulnerable populations.


Oral immunisation as a strategy for enhancing corneal allograft survival.
To determine optimal conditions for enhancing corneal allograft survival through oral administration of donor specific corneal cells. A mouse model of penetrating keratoplasty was used to evaluate the efficacy and optimal conditions for preventing immunological rejection of corneal allografts. C3H corneal grafts were transplanted orthotopically to CB6F1 recipients and represented mismatches at the entire major histocompatibility complex (MHC) and multiple minor histocompatibility loci. Tissue cultured C3H corneal epithelial and endothelial cells were administered orally to CB6F1 mice before or shortly after the application of orthotopic C3H corneal allografts. Cultured C3H corneal cells were conjugated with the non-toxic B subunit of cholera toxin as a means of preferentially inducing oral tolerance. Ten oral doses of donor cells administered before keratoplasty reduced the incidence of corneal graft rejection from 100% in untreated hosts to 54% in orally tolerised mice. Conjugation of cholera toxin to corneal cells significantly enhanced the efficacy of oral tolerance such that only 9% of the mice fed 10 doses of cholera toxin conjugated cells rejected their corneal grafts. Even a single oral inoculation of corneal cells conjugated to cholera toxin was able to reduce corneal graft rejection by 36%. Oral administration of donor specific cells greatly enhances corneal graft survival. Use of cholera toxin adjuvant markedly enhances the efficacy of oral tolerance such that even a single oral dose of donor cells significantly reduces the incidence of rejection. The results support the clinical feasibility of this novel strategy for preventing immunological rejection of corneal transplants.


Inter-α-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation.
Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous "heavy chains" (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering-based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.


Effects of drug serum of anti-fibrosis I herbal compound on calcium in hepatic stellate cell and its molecular mechanism.
To investigate the effects of anti-fibrosis I herbal compound on intracellular Ca(2+) in activated hepatic stellate cell (HSC) and to try to survey its molecular mechanism in treatment and prevention of hepatic fibrosis and portal hypertension. The activated HSC line was plated on small glass cover slips in 24 wells culture dishes at a density of 5X10(6) /mL, and incubated in RPMI-1640 media for 24 h. After the cells were loaded with Fluo-3/AM, intracellular Ca(2+) was measured with laser scanning confocal microscopy (LSCM). The dynamic changes of intracellular Ca(2+), stimulated by carbon tetrachloride, TGF-beta(1) antibody and the drug serum of anti-fibrosis I herbal compound and under orthogonal design were determined by LSCM. The effect of anti-fibrosis I herbal compound on intracellular Ca(2+) was observed before and after the addition of TGF-(1) antibody. The intracellular Ca(2+) were significantly different in different dosage of carbon tetrachloride anti-fibrosis I formula drug serum, TGF-beta(1) antibody and different turn of these substance, but their interval time between CCl(4) and TGF-beta(1) antibody, CCl(4) and anti-fibrosis I drug serum had no influence on intracellular Ca(2+). The result showed intracellular Ca(2+) wasn't significantly different between rat serum without anti-fibrosis I and untreated group. After carbon tetrachloride stimulation, intracellular Ca(2+) of activated HSC increased significantly when the dosage of CCl(4) from 5 to 15 mmol/L, however, decreased significantly after stimulation by 5-20 microg/mL TGF-beta(1) antibody or 5-20 mL/L drug serum. Moreover, before and after the addition of TGF-beta(1) antibody, intracellular Ca(2+) was significantly different. These results suggested that the molecular mechanism was independent of blocking TGF-beta(1) effects. Anti-fibrosis I herbal compound may treat hepatic fibrosis and decrease portal hypertension by inhibiting activated HSC contractility through decrease of intracellular Ca(2+).


A conserved African swine fever virus IkappaB homolog, 5EL, is nonessential for growth in vitro and virulence in domestic swine.
An African swine fever virus (ASFV) gene with similarity to the cellular inhibitor of NFkappaB (IkappaB) was described in the pathogenic African isolate Malawi Lil-20/1 (ORF 5EL) and a cell-culture-adapted European virus, BA71V (ORF A238L). Recently, this gene was shown to be a functional IkappaB homolog capable of downregulating NFkappaB-regulated gene expression. This observation suggests the gene may be of significance to aspects of ASFV pathogenesis and virulence in domestic swine by interfering with a normal antiviral host response. Here we show, using nucleotide sequence analysis, that 5EL is highly conserved among various African and European pathogenic field isolates and that in all cases its similarity to IkappaB genes is limited to the presence of four low complexity ankyrin repeats in the ASFV gene. The 5EL gene of Malawi Lil-20/1 encodes a 28-kDa protein which was expressed early in virus-infected macrophage cell cultures with maximum levels observed at 3 to 5 hr postinfection. To study gene function, a Malawi Lil-20/1 5EL gene deletion mutant (Delta5EL) was constructed. Growth characteristics of Delta5EL in porcine macrophage cell cultures were indistinguishable from those of the parental virus. And, Delta5EL exhibited an unaltered parental Malawi Lil-20/1 disease and virulence phenotype in domestic swine. Thus, although highly conserved among ASFV isolates, 5EL is nonessential for growth in porcine macrophages in vitro and for viral virulence in domestic swine. A possible role for this gene in transmission of ASFV in nature, a setting which involves the cycling of ASFV between two highly adapted hosts, Ornithodoros ticks and warthogs or bush pigs, in sub-Saharan Africa is discussed.


New frontiers in the oncology of G.I. tract.
Serious, life threatening diseases remain a difficult challenge to conventional treatment methods. In an effort to improve the prognosis of G.I. malignancies, researchers are constantly exploring new treatment modalities. Combined immuno- and chemo-therapy treatment is one such method gaining attention. This article will give a brief background of combined immuno-, chemotherapy treatments, a discussion of one standardized treatment protocol, and a look at the results of the standardized protocol.


Solidification characteristics of solid biofuel densified by two-step torrefaction process.
Coal coke, which is used widely in industrial furnaces, emits large amounts of CO2. To utilize solid biofuels as alternatives to coal coke, the fuel ratio of the biofuels must be improved to generate functions, such as deoxidization, permeability, and carbon pickup. In this study, an innovative densification molding method is proposed; it uses a two-step torrefaction process with a high CO2 reduction effect. The molding method consists of the following two-step torrefaction process at torrefaction temperatures of 463-773 K: In the first step, raw biomass is torrefied to remove some of the volatile matter that inhibits densified molding. In the second step, the torrefied biomass is densified at the above temperature. The purpose of the second torrefaction step is to further enhance the fuel ratio due to the conversion of volatile matter to fixed carbon and to develop the thermal softening of lignin. Solid biofuel densified using a two-step torrefaction process was produced from a Japanese cedar sample, and it was found that its fuel ratio was significantly improved. Furthermore, the mechanism of the adhesive effect during carbonization was elucidated by analyzing the structure of the densified solid biofuel using Raman spectroscopy.


[Characteristics of chronic hepatitis C in patients infected by human immunodeficiency virus].
To know the characteristics of chronic hepatitis C in HIV-infected patients and whether there are differences compared with HIV-negative patients, in order to obtain orientative helpful data for the diagnostic-therapeutic decision making, a usually difficult issue in these patients. Sixty patients with criteria of chronic hepatitis C virus (HCV) criteria were studied. Thirty-three of these patients were coinfected with HIV. The possible associations between the degree of histologic damage and several variables wee studied: age, estimated time of evolution of HCV infection, transaminases, gammaglobulins, GGT, and alcohol consumption. On the other hand, the possible differences regarding the histologic hepatic aggression were assessed. An attempt was made to know whether HIV could negatively influence the evolution of chronic hepatitis C. A direct relationship was observed between hepatic damage, HAI and levels of GOT, GPT, GGT (p < 0.005), and gammaglobulins (p < 0.01). The degree of hepatic fibrosis was directly correlated with the GGT level (mild fibrosis: 47 +/- 34 U/l; severe fibrosis: 86 +/- 60 U/l) (p < 0.05) and the estimated evolution time of infection (p < 0.05). Alcohol consumption was associated with the fibrosis degree (p < 0.01). The degree of histologic damage was similar in the HIV-positive group (HAI: 8.3 +/- 3.6) and HIV-negative patients (HAI: 7.2 +/- 2.8), although the degree of lobular involvement was higher in HIV-positive patients (p < 0.05). Patients with chronic hepatitis C and infected with HIV did not have a higher degree of hepatic damage than HIV-negative patients. GOT, GPT, and gamma globulin levels, as well as a longer evolution time of HCV infection were associated with a higher degree of hepatic histologic activity. Alcohol consumption seemed to be associated with a poorer course of the liver disease in these patients.


Ultrasound quantification of anterior soft tissue thickness fails to predict difficult laryngoscopy in obese patients.
Morbid obesity is associated with difficult laryngoscopy and intubation. In the general population, bedside indices for predicting difficult intubation (i.e. Mallampati classification, thyromental distance, sternomental distance, mouth-opening and Wilson risk score) have poor-to-moderate sensitivity (20-62%) and moderate-to-fair specificity (82-97%). In the obese population, although the risk of difficult intubation after a positive Mallampati test is 34%, it is still not sufficient to be used as a single predictive test. An abundance of pretracheal soft tissue anterior to the vocal cords, as quantified by ultrasound, was a better predictor of difficult laryngoscopy than body mass index (BMI) in Israeli patients. Obesity is a growing problem in the United States: therefore we sought to confirm this finding in the obese population in the United States. We used ultrasound to quantify the neck soft tissue, from the skin to the anterior aspect of the trachea at the vocal cords, in 64 obese patients (BMI > 35). We assessed thyromental distance, mouth-opening, jaw movement, limited neck mobility, modified Mallampati score, abnormal upper teeth, neck circumference, confirmed obstructive sleep apnoea, BMI, age, race and gender as predictors. Twenty patients were classified as difficult laryngoscopy; they were older (47 +/- 9 vs 42 +/- 1 years; P = 0.048; mean +/- SD) and had less soft pretracheal tissue (20.4 +/- 3.0 vs 22.3 +/- 3.8 mm; P = 0.049) than did easy laryngoscopy patients. Multivariate regression indicated that none of the factors was an independent predictor of difficult laryngoscopy. We conclude that the thickness of pretracheal soft tissue at the level of the vocal cords is not a good predictor of difficult laryngoscopy in obese patients in the United States.


Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation.
Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.


Jejunal Injury as a Rare Complication of Percutaneous Nephrolithotomy: Case Report.
Background: Colonic injury represents a rare complication of percutaneous nephrolithotomy (PCNL). Injury of the small bowel is very rare, with only anecdotal case reports in the literature. We report here a rare PCNL complication of jejunal perforation without concomitant colonic injury. Case Presentation: A 45-year-old male underwent PCNL for multiple left kidney stones. At the beginning of the procedure, we faced difficulty in achieving access, but after that the procedure was straightforward and ended smoothly. However, from the third day, the postoperative course became stormy with progressive development of picture of acute peritonitis. Laparotomy was mandatory and jejunal perforation was found and repaired. Conclusion: Although extremely rare, small bowel injury should be kept in mind during planning for percutaneous nephrolithotomy. Prompt diagnosis and active treatment should be undertaken without delay especially if picture of acute peritonitis is developed.


Increased vertical axon numbers in cingulate cortex of schizophrenics.
Data generated from an earlier study have suggested a model in which greater numbers of long, vertical, associative axons may occur in the anterior cingulate cortex of schizophrenic patients relative to control subjects. This hypothesis has now been tested using neuron-specific antibodies raised against the 200-kilodalton neurofilament subunit, a component of neuronal cytoskeleton, to immunostain axons of human postmortem cingulate cortex. A manual method for counting axons in the region of layer II and sublamina IIIA has been designed and applied blindly to parallel control and schizophrenic immunoprocessed specimens. The results show that there are 25% more vertical axons in the schizophrenic than in the control specimens. Preferentially higher numbers of both long vertical axons (62%) and axons associated with blood vessels (52%) have also been noted in the schizophrenic specimens. By contrast, the number of large-caliber horizontal axons was the same in the two groups; therefore, the greater number of vertical axons in schizophrenic specimens does not appear to represent a nonspecific effect. When these data are corrected for the effects of several confounding variables using analysis of covariance, the overall pattern of the results persists. These findings suggest the possibility that there might be an increase of associative inputs into the anterior cingulate cortex of schizophrenic patients, although it is not clear at present whether the differences noted, if replicative, may be primarily or perhaps only secondarily related to the disorder.


Rescue of presumptive viral information from human cells by a helper oncovirus.
We have attempted to rescue presumptive human endogenous retrovirus(es) by using a competent animal oncovirus as a helper. Human melanoma cells (line HMB2) were fused, using polyethylene glycol, with mouse NIH-3T3 cells which had been infected and transformed by the Harvey murine leukaemia and sarcoma virus complex (MLV and MSV). The heteropolykaryons obtained were co-cultivated with fresh NIH-3T3 cells; filtered (Millipore 0.22 micron) medium from these was used to infect further NIH-3T3 cells. In these cells after several passages, vesicular stomatitis virus (VSV) pseudotypes could be produced. These were infectious not only for mouse cells (manifesting the helper MLV), but also for human cells (HeLa, HEC human embryo fibroblasts, HMB2); they were not infectious for CCL64 (mink) or for Vero (African green monkey) cells. The presence of such VSV pseudotypes infectious for human cells indicated that a human ecotropic virus [provisionally named rescued human virus (RHV)] had been rescued by the fusion of human melanoma cells with MLV-infected mouse cells. This was supported by the following evidence. The human-specific pseudotype was neutralized by sheep antisera raised to antigens selected by VSV from human tumour cell lines HMB2, T47D and HeLa. These antisera also aggregated NIH cells infected with MLV and RHV. Mouse antisera raised to antigens present in HIH cells infected with MLV and RHV, in contrast to sera raised to NIH cells infected with MLV only, immunoprecipitated an 85,000 mol. wt. protein band from human cells (HEC, HMB2 and HeLa) surface-labelled with 125I.


Metabolism of ferulic acid via vanillin using a novel CoA-dependent pathway in a newly-isolated strain of Pseudomonas fluorescens.
A soil bacterium, designated Pseudomonas fluorescens AN103, was isolated based on its ability to grow on ferulic acid as a sole source of carbon and energy. In addition, this strain was found to metabolize a number of related phenolic substrates which contained a hydroxyl group at the para position of the aromatic ring. During growth on ferulic acid, transient accumulation of vanillic acid and trace amounts of protocatechuic acid were detected in the culture medium. Washed cells grown on ferulic acid readily oxidized vanillin, vanillic acid and protocatechuic acid, the three putative intermediates of the metabolic pathway. The side-chain cleavage of ferulic acid to produce vanillin was demonstrated in vitro for the first time and this enzyme-catalysed reaction was shown to have an essential requirement for CoASH, ATP and MgCl2. This conversion involved a two-step process involving a CoA ligase followed by the side-chain cleavage. The addition of NAD increased the oxidation of vanillin to vanillic acid and had an overall effect of increasing the rate of ferulic acid cleavage. The application of 13C-NMR studies in vitro revealed acetyl-CoA as the C2 side-chain cleavage product. High levels of inducible ferulate-CoA ligase and NAD-linked vanillin dehydrogenase were detected and a novel pathway for ferulic acid metabolism in this organism is proposed.


Calcitonin gene-related peptide as potential neurotransmitter in guinea pig right atrium.
The potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in cardioacceleratory nonadrenergic noncholinergic (NANC) nerves was examined in the guinea pig right atrium in vitro. In the presence of atropine, a muscarinic antagonist, and atenolol, a beta-adrenoceptor antagonist, transmural nerve stimulation (TNS) of the isolated right atrium caused a positive chronotropic response, which is slow in both onset and decay. This TNS-induced slow response was assumed to be mediated by NANC nerves in the right atrium since tetrodotoxin inhibited the response. Dense distribution of CGRP-like immunoreactive (CGRP-I) nerves was demonstrated in the sinus node. Exogenously applied CGRP exerted a positive chronotropic effect on the isolated right atrium in a dose-dependent manner. Both CGRP-I nerves and NANC response induced by TNS were not affected by surgical sympathectomy and reserpine pretreatment but were abolished by the pretreatment of animals with capsaicin. The results suggest that CGRP is the neurotransmitter of cardioacceleratory NANC nerves in the right atrium of the guinea pig.


Prostatic acid phosphatase reduces thermal sensitivity and chronic pain sensitization by depleting phosphatidylinositol 4,5-bisphosphate.
Prostatic acid phosphatase (PAP) is expressed in nociceptive dorsal root ganglion (DRG) neurons, functions as an ectonucleotidase, and generates adenosine extracellularly. Here, we found that PAP inhibits noxious thermal sensitivity and sensitization that is associated with chronic pain through sustained activation of the adenosine A(1) receptor (A(1)R) and phospholipase C-mediated depletion of phosphatidylinositol 4,5-bisphosphate (PIP(2)). In mice, intrathecal injection of PAP reduced PIP(2) levels in DRGs, inhibited thermosensation through TRPV1, and enduringly reduced thermal hyperalgesia and mechanical allodynia caused by inflammation, nerve injury, and pronociceptive receptor activation. This included inhibitory effects on lysophosphatidic acid, purinergic (ATP), bradykinin, and protease-activated (thrombin) receptors. Conversely, PIP(2) levels were significantly elevated in DRGs from Pap(-/-) mice, and this correlated with enhanced thermal hyperalgesia and mechanical allodynia in Pap(-/-) mice. To directly test the importance of PIP(2) in nociception, we intrathecally injected PIP(2) into mice. This transiently (2 h) elevated PIP(2) levels in lumbar DRGs and transiently (2 h) enhanced thermosensation. Additionally, thermal hyperalgesia and mechanical allodynia were enduringly enhanced when PIP(2) levels were elevated coincident with injury/pronociceptive receptor stimulation. Nociceptive sensitization was not affected if PIP(2) levels were elevated in the absence of ongoing pronociceptive receptor stimulation. Together, our data suggest that PIP(2) levels in DRGs directly influence thermosensation and the magnitude of nociceptive sensitization. Moreover, our data suggest there is an underlying "phosphoinositide tone" that can be manipulated by an adenosine-generating ectonucleotidase. This tone regulates how effectively acute nociceptive insults promote the transition to chronic pain.


Diaphorobacter aerolatus sp. nov., isolated from air, and emended description of the genus Diaphorobacter.
A Gram-stain-negative, non-motile, aerobic rod, designated 8604S-37(T), was isolated from an outdoor air sample collected in Suwon region, Republic of Korea. The isolate was catalase-positive and oxidase-negative. 16S rRNA gene sequence analysis indicated that strain 8604S-37(T) was most closely related to Diaphorobacter nitroreducens NA10B(T) and Diaphorobacter oryzae RF3(T), with which it shared 97.0% 16S rRNA gene sequence similarity. Strain 8604S-37(T) grew at 10-37 °C (optimum 28 °C; no growth occurred at 4 or 40 °C) and pH 5-9 (optimum pH 7). The strain tolerated up to 3% NaCl (w/v) (optimum 0%). The only respiratory quinone was ubiquinone-8 (Q-8). The polar lipid profile comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and one unknown aminolipid. The major fatty acids were C16 : 0, summed feature 3 (comprising C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH), summed feature 8 (C(18 : 1)ω6c and/or C(18 : 1)ω7c) and C(17 : 0) cyclo, and the predominant hydroxy fatty acid was C(10 : 0) 3-OH. Strain 8604S-37(T) exhibited less than 50% DNA-DNA relatedness with Diaphorobacter nitroreducens KACC 13856(T) and Diaphorobacter oryzae KACC 16857(T). The DNA G+C content was 65 mol%. Strain 8604S-37(T) represents a novel species of the genus Diaphorobacter, for which the name Diaphorobacter aerolatus sp. nov. is proposed. The type strain is 8604S-37(T) ( = KACC 16536(T) = NBRC 108926(T)). An emended description of the genus Diaphorobacter is also proposed.


Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6).
Three women with the galactorrhea-amenorrhea syndrome and elevated prolactin concentrations experienced a return of regular ovulatory menses within 37-94 days after starting pyridoxine treatment (200-600 mg/day). In each the galactorrhea ceased and serum prolactin levels were maintained in the normal range while taking pyridoxine. In two other women with prolonged secondary amenorrhea but without hyperprolactinemia or galactorrhea, pyridoxine at dosages up to 600 mg/day did not restore ovulatory menses. Pyridoxine treatment was also ineffective in decreasing profuse galactorrhea in one woman with normal prolactin levels and regular ovulatory menses. In the three women effectively treated with pyridoxine, the galactorrhea returned, serum prolactin levels increased, and the menses ceased after discontinuing pyridoxine. These results imply that pyridoxine, by decreasing the excessive secretion of prolactin, may be useful in the long-term medical management of women with hyperprolactinemia and the galactorrhea-amenorrhea syndrome.


Single-cell proteomics: potential implications for cancer diagnostics.
Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.


Magnetic Reactive Oxygen Species Nanoreactor for Switchable Magnetic Resonance Imaging Guided Cancer Therapy Based on pH-Sensitive Fe5C2@Fe3O4 Nanoparticles.
Reactive oxygen species (ROS) are crucial molecules in cancer therapy. Unfortunately, the therapeutic efficiency of ROS is unsatisfactory in clinic, primarily due to their rigorous production conditions. By taking advantage of the intrinsic acidity and overproduction of H2O2 in the tumor environment, we have reported an ROS nanoreactor based on core-shell-structured iron carbide (Fe5C2@Fe3O4) nanoparticles (NPs) through the catalysis of the Fenton reaction. These NPs are able to release ferrous ions in acidic environments to disproportionate H2O2 into •OH radicals, which effectively inhibits the proliferation of tumor cells both in vitro and in vivo. The high magnetization of Fe5C2@Fe3O4 NPs is favorable for both magnetic targeting and T2-weighted magnetic resonance imaging (MRI). Ionization of these NPs simultaneously decreases the T2 signal and enhances the T1 signal in MRI, and this T2/T1 switching process provides the visualization of ferrous ions release and ROS generation for the supervision of tumor curing. These Fe5C2@Fe3O4 NPs show great potential in endogenous environment-excited cancer therapy with high efficiency and tumor specificity and can be guided further by MRI.


Qualitative psychotherapy research: the journey so far and future directions.
This article documents the evolution of qualitative psychotherapy research over the past 3 decades. Clients' and therapists' accounts of their experiences in psychotherapy provide a window into the psychotherapy relationship and its mechanisms of change. A sizable body of literature has been generated that uses qualitative methods to collect and analyze these accounts and to shed light on the psychotherapy process. It notes changes in the field such as growing numbers of dissertations and publications using qualitative methods as well as a strengthening emphasis on qualitative research within graduate education and research funding bodies. Future recommendations include developing principles for practice from qualitative methods and conducting qualitative meta-analyses. Other recommendations include forming journal review policies that support the publication of qualitative research and that focus on coherence in adapting methods to meet research goals, in light of a study's characteristics and epistemological framework, rather than focusing on sets of procedures.


The design and structural characterization of a synthetic pentatricopeptide repeat protein.
Proteins of the pentatricopeptide repeat (PPR) superfamily are characterized by tandem arrays of a degenerate 35-amino-acid α-hairpin motif. PPR proteins are typically single-stranded RNA-binding proteins with essential roles in organelle biogenesis, RNA editing and mRNA maturation. A modular, predictable code for sequence-specific binding of RNA by PPR proteins has recently been revealed, which opens the door to the de novo design of bespoke proteins with specific RNA targets, with widespread biotechnological potential. Here, the design and production of a synthetic PPR protein based on a consensus sequence and the determination of its crystal structure to 2.2 Å resolution are described. The crystal structure displays helical disorder, resulting in electron density representing an infinite superhelical PPR protein. A structural comparison with related tetratricopeptide repeat (TPR) proteins, and with native PPR proteins, reveals key roles for conserved residues in directing the structure and function of PPR proteins. The designed proteins have high solubility and thermal stability, and can form long tracts of PPR repeats. Thus, consensus-sequence synthetic PPR proteins could provide a suitable backbone for the design of bespoke RNA-binding proteins with the potential for high specificity.


Anterior-entry abdominoperineal resection: a variation in the method of perineal dissection.
For patients with rectal cancer, there is a greater risk of a positive radial margin or local tumor recurrence when an abdominoperineal versus low anterior resection is performed, or when tumors are in an anterior versus nonanterior location. In response, clinical leaders have encouraged perineal dissection in the prone position or in concert with a coccygectomy. We describe anterior-entry abdominoperineal resection, which may minimize the need for such maneuvers and negative patient outcomes. Anterior-entry abdominoperineal resection was provided by one surgeon to 10 patients over an 18-month period. Pelvic dissection used total mesorectal excision techniques. Anteriorly, in men, the perineal dissection occurred between the external anal sphincter and the bulbospongiosus and transversus perinei superficialis muscles. Initial entry into the pelvis occurred anteriorly under direct vision. Rectal specimen quality was graded out of 5 using Quirke methods. There were 8 male and 2 female subjects with a median age of 65 years. Eight of 10 tumors had some component of an anterior location. Seven patients received preoperative radiation. The radial margin was positive in 1 case. Median Quirke score for quality of the surgical specimen was 5 of 5. Anterior-entry abdominoperineal resection follows anatomic planes in the perineum and demands initial entry into the pelvis anteriorly and under direct vision. It may minimize rates of positive radial margins, may be especially suited for tumors with a locally advanced anterior component, and in many patients may avoid the need for perineal dissection in the jackknife position.


Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients.
The Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) project aims to additionally explore the data of the two large, randomized, cooperative-group studies comparing two doses of imatinib (400 mg daily v twice daily) in 1,640 patients with advanced GIST. End points were progression-free survival (PFS) and overall survival (OS). Investigated cofactors included age, sex, performance status (PS), primary tumor site, time from diagnosis, prior therapies, baseline biology, and KIT/PDGFRalpha mutations for a subset of 772 patients. Univariate and multivariate models were used for the analysis. At a median follow-up of 45 months, a small but significant PFS advantage was documented for the high-dose arm. OS was identical in the two arms. The multivariate prognostic models included the following adverse factors: male sex, poor PS, and high baseline neutrophils counts (PFS and OS); low hemoglobin and GIST from small bowel origin (PFS); and advanced age, large tumor size, low albumin level, and prior chemotherapy (OS). In patients analyzed for mutations, patients with wild type, patients with KIT exon 9 mutations, and patients with other mutations had worse prognoses than patients with KIT exon 11 mutations for both end points. The mutation status was the only predictive factor for the PFS benefit attributed to high-dose treatment that resulted in significantly longer PFS (and higher objective response rate) for patients with KIT exon 9 mutations. This analysis confirms a small PFS advantage of high-dose imatinib, essentially among patients with KIT exon 9 mutations, but no OS advantage.


RNA-binding protein Hermes/RBPMS inversely affects synapse density and axon arbor formation in retinal ganglion cells in vivo.
The RNA-binding protein Hermes [RNA-binding protein with multiple splicing (RBPMS)] is expressed exclusively in retinal ganglion cells (RGCs) in the CNS, but its function in these cells is not known. Here we show that Hermes protein translocates in granules from RGC bodies down the growing axons. Hermes loss of function in both Xenopus laevis and zebrafish embryos leads to a significant reduction in retinal axon arbor complexity in the optic tectum, and expression of a dominant acting mutant Hermes protein, defective in RNA-granule localization, causes similar defects in arborization. Time-lapse analysis of branch dynamics reveals that the decrease in arbor complexity is caused by a reduction in new branches rather than a decrease in branch stability. Surprisingly, Hermes depletion also leads to enhanced early visual behavior and an increase in the density of presynaptic puncta, suggesting that reduced arborization is accompanied by increased synaptogenesis to maintain synapse number.


Gastric leishmaniasis in the setting of HIV/AIDS infection at Community Hospital in Southeastern United States.
Visceral leishmaniasis, caused by the Leishmania donovani complex, is responsible for over 20 000 deaths per year. This disease often affects the immunocompromised with an increased prevalence in those with human immunodeficiency virus (HIV). The immunocompromised are not only more susceptible to infection, but disseminated disease including gastric leishmaniasis. This is a case of gastric leishmaniasis occurring in a non-endemic region in a patient with comorbid HIV. The patient is a 39 year old originally from Central America currently living in Southeast Georgia. His history is significant for HIV, alcohol abuse, tobacco dependency and bone marrow biopsy-proven leishmaniasis. He denied any recent travel. At initial presentation, he had abdominal pain, nausea/vomiting, chills and dysphagia along with leukopenia and thrombocytopenia. Treatment with amphotericin B was initiated for his leishmaniasis as well as highly active antiretroviral therapy (HAART). The patient was discharged home on a 3 month course of amphotericin B with continued HAART therapy. Following resolution of his acute symptoms, six months later, the patient developed acute abdominal pain with nausea prompting presentation to the emergency department. Leishmaniasis was found again following bone marrow biopsy and the patient restarted amphotericin B and HAART. Several years later the patient presented again with similar symptoms, this time with accompanying rectal bleeding. The patient received an esophagogastroduodenoscopy and on gastric mucosal biopsy was found to have gastric leishmaniasis. This manuscript highlights the key features of this case, including recognizing leishmaniasis clinically, proving diagnosis through definitive testing and understanding the connection between leishmaniasis and HIV.


Efficacy of oral vaccine against bacterial coldwater disease in ayu Plecoglossus altivelis.
The development of a practical vaccination method against bacterial coldwater disease (BCWD) in ayu Plecoglossus altivelis and the efficacy of oral administration of formalin-killed cells (FKCs) of Flavobacterium psychrophilum was investigated. The FKC was administrated at a dose of 0.1-0.2 g kg(-1) body weight to juvenile ayu (0.5 g body weight) every day for 2 wk or on 5 days over 2 wk. Experimental immersion challenge at 3 and 7 wk after vaccination showed significantly higher survival rates than the controls. The results show the effectiveness of oral vaccination against BCWD in ayu.


Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants.
Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders. The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.


Health behaviors of caregivers of childhood cancer survivors: a cross-sectional study.
Caregiving for childhood cancer survivors may be burdensome for caregivers and affect their physical health and health behaviors. However, studies examining health behaviors in caregivers of childhood cancer survivors are scarce. This study aimed to examine health behaviors of caregivers of childhood cancer survivors by comparing them with those of the general population, and analyze associated factors. This study included 326 caregivers of childhood cancer survivors recruited from 3 major hospitals in South Korea and 1304 controls from the Korean National Health and Nutritional Examination Survey matched for age, sex, and education level. We compared health behaviors between the two groups by using conditional logistic regression analyses, and investigated factors associated with unhealthy behaviors in caregivers by using multiple logistic regression analyses. Caregivers were less likely to be physically inactive (aOR: 0.69, 95% CI: 0.51, 0.92) compared to controls, and this was more evident in women (aOR: 0.65, 95% CI: 0.45, 0.94). However, caregivers were more likely to be binge drinkers (aOR: 2.26, 95% CI: 1.73, 2.97), especially if they were men (aOR: 13.59, 95% CI: 8.09, 22.82). Factors associated with unhealthy behaviors in caregivers differed by the type of behavior. Current smoking risk was lower in female caregivers and in those with more comorbidities. Increasing age, female sex, higher education level, and lower household income were associated with lower risk of binge drinking. Higher household income and anxiety were associated with lower risk of physical inactivity, while depression was associated with higher risk of physical inactivity. Caregivers of childhood cancer survivors were more likely to engage in binge drinking, but less likely to be physically inactive. Strategies to promote adherence to desirable health behaviors in caregivers are needed with consideration of their socioeconomic and clinical factors, such as number of comorbidities.


Effects of Kampo on functional gastrointestinal disorders.
This article reviews the effectiveness of Kampo (traditional Japanese herbal medicine) in the treatment of functional gastrointestinal disorders, especially functional dyspepsia (FD) and irritable bowel syndrome (IBS). The results of four randomized, controlled trials (RCTs) suggested the usefulness of rikkunshito in relieving the subjective symptoms of patients with FD. Rikkunshito significantly improved not only gastric symptoms, such as epigastiric discomfort, but also extra-gastric symptoms, such as general fatigue, when compared with control drugs. The therapeutic effects of rikkunshito were more evident when it was prescribed to patients with "kyosho", i.e., low energy. Two RCTs suggested the efficacy of keishikashakuyakuto for IBS.Basic research studies have demonstrated that these Kampo medicines have multiple sites of action to improve subjective symptoms. For example, rikkunshito improves gastric motility dysfunction, including impaired adaptive relaxation and delayed gastric emptying, gastric hypersensitivity, and anorexia via facilitation of ghrelin secretion. It also exhibits anti-stress effects, i.e., it attenuates stress-induced exacerbation of gastric sensation and anorexia, as well as the hypothalamic-pituitary-adrenocortical axis and sympathetic activation. Keishikashakuyakuto exhibited not only an antispasmodic effect on intestinal smooth muscle, but also antidepressant-like effects. Case series suggest that other Kampo prescriptions are also effective for FD and IBS. However, further studies are necessary to evaluate their efficacy.


Assessment of resistance pathways induced in Arabidopsis thaliana by hypovirulent Rhizoctonia spp. isolates.
Certain hypovirulent Rhizoctonia isolates effectively protect plants against well-known important pathogens among Rhizoctonia isolates as well as against other pathogens. The modes of action involved in this protection include resistance induced in plants by colonization with hypovirulent Rhizoctonia isolates. The qualifications of hypovirulent isolates (efficient protection, rapid growth, effective colonization of the plants, and easy application in the field) provide a significant potential for the development of a commercial microbial preparation for application as biological control agents. Understanding of the modes of action involved in protection is important for improving the various aspects of development and application of such preparations. The hypothesis of the present study is that resistance pathways such as systemic acquired resistance (SAR), induced systemic resistance (ISR), and phytoalexins are induced in plants colonized by the protective hypovirulent Rhizoctonia isolates and are involved in the protection of these plants against pathogenic Rhizoctonia. Changes in protection levels of Arabidopsis thaliana mutants defective in defense-related genes (npr1-1, npr1-2, ndr1-1, npr1-2/ndr1-1, cim6, wrky70.1, snc1, and pbs3-1) and colonized with the hypovirulent Rhizoctonia isolates compared with that of the wild type (wt) plants colonized with the same isolates confirmed the involvement of induced resistance in the protection of the plants against pathogenic Rhizoctonia spp., although protection levels of mutants constantly expressing SAR genes (snc1 and cim6) were lower than that of wt plants. Plant colonization by hypovirulent Rhizoctonia isolates induced elevated expression levels of the following genes: PR5 (SAR), PDF1.2, LOX2, LOX1, CORI3 (ISR), and PAD3 (phytoalexin production), which indicated that all of these pathways were induced in the hypovirulent-colonized plants. When SAR or ISR were induced separately in plants after application of the chemical inducers Bion and methyl jasmonate, respectively, only ISR activation resulted in a higher protection level against the pathogen, although the protection was minor. In conclusion, plant colonization with the protective hypovirulent Rhizoctonia isolates significantly induced genes involved in the SAR, ISR, and phytoalexin production pathways. In the studied system, SAR probably did not play a major role in the mode of protection against pathogenic Rhizoctonia spp.; however, it may play a more significant role in protection against other pathogens.


Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats.
Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management.