Functional analysis of a novel parasitic nematode-specific protein of Setaria digitata larvae in Culex quinquefasciatus by siRNA mediated RNA interference.
Functional analysis of animal parasitic nematode genes is often quite challenging due to the unavailability of standardised in vitro culture conditions and lack of adequate tools to manipulate these genes. Therefore, this study was undertaken to investigate the suitability of Culex quinquefasciatus, as an in vivo culture platform for Setaria digitata larvae and RNA interference (RNAi), as a post-transcriptional gene silencing tool to study the roles of a vital gene that encodes a novel parasitic nematode-specific protein (SDNP). The red colour fluorescence detected following RNAi injection to the thorax of C. quinquefasciatus indicated the uptake of dsRNA by S. digitata larvae. The reduction of SDNP transcripts in siRNA treated larvae compared to non-treated larvae, as determined by qPCR, indicated that the siRNA pathway is operational in S. digitata larvae. The observation of motility reductions and deformities during the development indicated the association of SDNP in larvae locomotion and development processes, respectively. The irregularities in the migration of larvae in mosquitoes and elevated survival rates of mosquitoes compared to their untreated counterparts indicated reduced parasitism of S. digitata larvae in mosquitoes upon targeted downregulation of SDNP by siRNA treatment. SDNP plays vital roles in muscle contraction, locomotion, development processes, larval development and parasitism of S. digitata. Its ubiquitous presence in parasitic nematodes and its absence in their hosts provide a tantalising prospect of the possibility of targeting SDNP for future development of anthelmintic drugs. The susceptibility of the larval stages of S. digitata for RNAi in Culex quinquefasciatus was also demonstrated for the first time in this study.


Gliovascular interface abnormality in mice with endothelial cell senescence.
In the brain, neurons, glial cells, vascular endothelial cells (ECs), and mural cells form a functional structure referred to as the neurovascular unit (NVU). The functions of the NVU become impaired with aging. To gain insight into the mechanism underlying the aging-related changes in the NVU, we characterized in the present study the gliovascular interface in transgenic mice expressing a dominant-negative form of the telomeric repeat-binding factor 2 (TERF2) specifically in ECs using the Tie2 promoter. In these transgenic mice, senescence occurred in the cerebral ECs and was accompanied by upregulation of the mRNAs of proinflammatory cell adhesion molecules and cytokines. It is noteworthy that in the deep layers of the cerebral cortex, astrocytes exhibited an increase in the signals for S100β as well as a decrease in the polarization of the water channel aquaporin-4 (AQP4) to the perivascular endfeet of the astrocytes. Mechanistically, the perivascular localization of dystroglycan and its ligand, laminin α2, was decreased, and their localization correlated well with the perivascular localization of AQP4, which supports the notion that their interaction regulates the perivascular localization of AQP4. The diminished perivascular localization of laminin α2 may be attributed to its proteolytic degradation by the matrix metalloproteinase-2 released by senescent ECs. Pericyte coverage was increased and negatively correlated with the decrease in the perivascular localization of AQP4. We propose that aging-related changes in ECs induce a mild morphological alteration of astrocytes and affect the localization of AQP4 at the gliovascular interface.


[Effects of shenyan yiqiye on experimental membranous glomerulonephritis in rabbits].
The cationic bovine serum albumin (C-BSA) was used for duplicating experimental animal model of membranous glomerulonephritis with chronic renal failure. Shenyan Yiqiye (SYYQY) was adopted for treatment. The results showed that, in the therapeutic group, the urine protein and serum creatinine were reduced as compared with those in pathological group, P < 0.01. The parameter of morphometric analysis of glomeruli such as mean diameter, mean perimeter, mean surface area, mean volume, mean cross sectional area were all decreased, P < 0.01, the number of glomerular proliferative cells and thickness of glomerular capillary wall were all attenuated, P < 0.01, as compared with those in the pathological group. It suggested that SYYQY might alleviate the glomeruli lesions and benefit the renal functions.


Synthesis of Pyrrolidinium-Type Poly(ionic liquid) Membranes for Antibacterial Applications.
Pyrrolidinium-type small molecule ionic liquids (ILs), poly(ionic liquid) (PIL) homopolymers, and their corresponding PIL membranes were synthesized and used for antibacterial applications. The influences of substitutions at the N position of pyrrolidinium cation on the antimicrobial activities against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were studied by minimum inhibitory concentration (MIC). The antibacterial efficiency of both the small molecule ILs and PIL homopolymers increased with the increase of the alkyl chain length of substitutions. Furthermore, PIL homopolymers show relatively lower MIC values, indicating better antimicrobial activities than those of the corresponding small molecule ILs. However, the antibacterial properties of the PIL membranes are contrary to corresponding ILs and PIL homopolymers, which reduce with the increase of alkyl chain length. Furthermore, the resultant PIL membranes show excellent hemocompatibility and low cytotoxicity toward human cells, demonstrating clinical feasibility in topical applications.


Insulin-induced translocation of glucose transporters to the plasma membrane precedes full stimulation of hexose transport.
Insulin stimulation of hexose transport in 3T3-L1 adipocytes was studied at 27 degrees C. At this temperature, the transport of 2-deoxyglucose was stimulated 8-fold, with a half-time of 9.5 min. Under the same conditions, the increase in cell surface glucose transporters, as measured by labeling in the intact cell with galactose oxidase and tritiated borohydride, was only 2.6-fold. Moreover, the half-times for the increase in cell surface glucose transporters and for the decrease in transporter number in the intracellular pool were both 4 min. Thus, these processes clearly precede the full stimulation of transport. These data are in agreement with immunolocalization studies of the glucose transporter in this cell line and further support the hypothesis that a second mechanism besides translocation is involved in the stimulation of hexose transport by insulin [Blok, J., Gibbs, E. M., Lienhard, G. E., Slot, J. W., & Gueze, H. J. (1988) J. Cell Biol. 106, 69-76]. The findings presented here indicate that neither the translocation of glucose transporters to, nor their subsequent insertion into, the plasma membrane is the rate-limiting step in the stimulation of hexose transport by insulin. Rather, there is a second mechanism of activation, which is rate limiting and occurs after the transporter is in the plasma membrane.


Quantitative Brain Amyloid Measures Predict Time-to-Progression from Amnestic Mild Cognitive Impairment to Alzheimer's Disease.
This study was designed to investigate factors that predict progression from amnestic mild cognitive impairment (aMCI) to probable Alzheimer's disease (AD). We studied the usefulness of quantitative assessment of amyloid burden measured by Florbetapir PET scan. The study cohort consisted of aMCI participants older than 65 and those with available Florbetapir PET scan at diagnosis from the ADNI database (http://adni.loni.usc.edu). To assess the prognostic impact of amyloid burden, a staging system based on the global SUVr of the PET scan was applied. We defined the stages as: stage I, negative amyloid scan; stage II, positive amyloid in 1st tertile; stage III, positive amyloid in 2nd tertile; and stage IV, positive amyloid in 3rd tertile. Of 250 eligible aMCI subjects (age 74.1±5.4, female n = 105), 71 (28.4%) were diagnosed with probable AD within 3 years. Higher amyloid stages showed faster cognitive decline by Kaplan-Meier analysis. In multivariate Cox analysis, with stage I as a reference, the hazard ratio (HR) increased as the stage increased: stage II (HR, 4.509; p = 0.015), stage III (HR, 7.616; p = 0.001), and stage IV (HR, 9.421; p < 0.001). Along with amyloid stage, ApoE ɛ4 (HR, 1.943; p = 0.031), score of CDR-SB (HR, 1.845; p < 0.001) and ADAS 11 (HR, 1.144; p < 0.001), and hippocampal volume (HR, 0.002; p = 0.005) were also identified as predictors of dementia progression in aMCI subjects. Large amyloid burden measured from amyloid PET scan could be a predictor of faster cognitive decline in aMCI patients.


Low T cell responses to human herpesvirus 8 in patients with AIDS-related and classic Kaposi sarcoma.
Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and is strongly associated with infection with human herpesvirus 8 (HHV-8; also known as "KS-associated herpesvirus"). We hypothesized that KS is linked to deficiencies in specific anti-HHV-8 T cell immunity. We studied asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n = 23) and patients with HIV-related or classic KS (n = 29). We used an interferon- gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses. We found that patients with KS responded to these peptides less often and had much lower HHV-8-specific T cells counts than did asymptomatic HHV-8 carriers (P = .001 and P = .0004, respectively), regardless of CD4 T cell count or HHV-8 load. The frequency of Epstein-Barr virus-specific T cells was similar in both groups. Our results suggest that HIV-related and classic KS are associated with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data provide new insight into HHV-8 cellular immunity.


Blockade of joint inflammation and secondary hyperalgesia by L-NAME, a nitric oxide synthase inhibitor.
Acute arthritis is associated with pain-related behavior, joint swelling and increased joint temperature. Arthritic animals exhibit a significant decrease in paw withdrawal latency 4, 5, 6, 7 and 8 h after induction of inflammation, when compared with baseline values, indicative of secondary hyperalgesia. Intra-articular injection of a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), resulted in a complete reversal of heat hyperalgesia and prevented further increase in joint swelling and temperature, while injection of either isotonic saline or the inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME) after induction of arthritis had no effect on any of these parameters. Intra-articular injection of 7-nitro-indazole (7-NINA), a selective neuronal NOS inhibitor, reversed the heat hyperalgesia for about 1 h but did not inhibit the increase in joint swelling or temperature. These results suggest an important role for nitric oxide (NO) in mediating peripheral nociceptive transmission and inflammation.


Rizatriptan in migraine.
The prevalence of migraine is high, affecting a significant proportion of the adult population during their most productive years of life and promoting impairment of their normal daily activities. Although guidelines for the acute treatment of migraine are available, outcome parameters are sometimes still below the expectations of both patients and physicians. Triptans represented an advance in clinical practice and have become the most well-studied class of medication for migraine. These agents present class I evidence for efficacy. However, they differ with regard to several of their clinical parameters, including onset of relief and consistency of response. Rizatriptan is a selective agonist of the 5-hydroxytryptophan(1B/1D )receptors, with proven superiority over placebo, ergotamine and selected oral triptans, demonstrating a good profile of safety and tolerability.


Progranulin Protects against Hyperglycemia-Induced Neuronal Dysfunction through GSK3β Signaling.
Type II diabetes affects over 530 million individuals worldwide and contributes to a host of neurological pathologies. Uncontrolled high blood glucose (hyperglycemia) is a major factor in diabetic pathology, and glucose regulation is a common goal for maintenance in patients. We have found that the neuronal growth factor progranulin protects against hyperglycemic stress in neurons, and although its mechanism of action is uncertain, our findings identified Glycogen Synthase Kinase 3β (GSK3β) as being potentially involved in its effects. In this study, we treated mouse primary cortical neurons exposed to high-glucose conditions with progranulin and a selective pharmacological inhibitor of GSK3β before assessing neuronal health and function. Whole-cell and mitochondrial viability were both improved by progranulin under high-glucose stress in a GSK3β-dependent manner. This extended to autophagy flux, indicated by the expressions of autophagosome marker Light Chain 3B (LC3B) and lysosome marker Lysosome-Associated Membrane Protein 2A (LAMP2A), which were affected by progranulin and showed heterogeneous changes from GSK3β inhibition. Lastly, GSK3β inhibition attenuated downstream calcium signaling and neuronal firing effects due to acute progranulin treatment. These data indicate that GSK3β plays an important role in progranulin's neuroprotective effects under hyperglycemic stress and serves as a jumping-off point to explore progranulin's protective capabilities in other neurodegenerative models.


Bilateral Basal Ganglia Infarction After Intranasal Use of Cocaine: A Case Report.
We present a case of a young man who developed bilateral basal ganglia infarct after intranasal use of cocaine. Cerebral ischemic infarcts are a known complication of cocaine use. This complication is rare and has been reported in the past with cocaine and concomitant use of other drugs such as heroin and amphetamines.


Use of a geographic information system (GIS) for targeting radon screening programs in South Dakota.
Because (222)Rn is a progeny of (238)U, the relative abundance of uranium may be used to predict the areas that have the potential for high indoor radon concentration and therefore determine the best areas to conduct future surveys. Geographic Information System (GIS) mapping software was used to construct maps of South Dakota that included levels of uranium concentrations in soil and stream water and uranium deposits. Maps of existing populations and the types of land were also generated. Existing data about average indoor radon levels by county taken from a databank were included for consideration. Although the soil and stream data and existing recorded average indoor radon levels were sparse, it was determined that the most likely locations of elevated indoor radon would be in the northwest and southwest corners of the state. Indoor radon levels were only available for 9 out of 66 counties in South Dakota. This sparcity of data precluded a study of correlation of radon to geological features, but further motivates the need for more testing in the state. Only actual measurements should be used to determine levels of indoor radon because of the strong roles home construction and localized geology play in radon concentration. However, the data visualization method demonstrated here is potentially useful for directing resources relating to radon screening campaigns.


Human eye ocular component analysis for refractive state and refractive surgery.
To analyze the clinical factors influencing the human vision corrections via the changing of ocular components of human eye in various applications; and to analyze refractive state via a new effective axial length. An effective eye model was introduced by the ocular components of human eye including refractive indexes, surface radius (r1, r2, R1, R2) and thickness (t, T) of the cornea and lens, the anterior chamber depth (S1) and the vitreous length (S2). Gaussian optics was used to calculate the change rate of refractive error per unit amount of ocular components of a human eye (the rate function M). A new criterion of myopia was presented via an effective axial length. For typical corneal and lens power of 42 and 21.9 diopters, the rate function Mj (j=1 to 6) were calculated for a 1% change of r1, r2, R1, R2, t, T (in diopters) M1=+0.485, M2=-0.063, M3=+0.053, M4=+0.091, M5=+0.012, and M6=-0.021 diopters. For 1.0 mm increase of S1 and S2, the rate functions were M7=+1.35, and M8=-2.67 diopter/mm, respectively. These rate functions were used to analyze the clinical outcomes in various applications including laser in situ keratomileusis surgery, corneal cross linking procedure, femtosecond laser surgery and scleral ablation for accommodation. Using Gaussian optics, analytic formulas are presented for the change of refractive power due to various ocular parameter changes. These formulas provide useful clinical guidance in refractive surgery and other related procedures.


Talking with patients about environmental health: the "I talk" mnemonic.
We conducted a survey regarding engagement in environmental health in an urban community. Although many people were concerned that environmental pollution affects health, talking about this with healthcare providers was an infrequent action. We propose a mnemonic--"I talk"--to guide nurses in inviting discussion about environment and health.


Refractory CSF leakage following untethering surgery performed 10 months after birth for enlarging terminal myelocystocele associated with OEIS complex.
Terminal myelocystocele (TMC) is an occult spinal dysraphism characterized by cystic dilatation of the terminal spinal cord in the shape of a trumpet (myelocystocele) filled with cerebrospinal fluid (CSF), which herniates into the extraspinal subcutaneous region. The extraspinal CSF-filled portion of the TMC, consisting of the myelocystocele and the surrounding subarachnoid space, may progressively enlarge, leading to neurological deterioration, and early untethering surgery is recommended. We report a case of a patient with TMC associated with OEIS complex consisting of omphalocele (O), exstrophy of the cloaca (E), imperforate anus (I), and spinal deformity (S). The untethering surgery for TMC had to be deferred until 10 months after birth because of the delayed healing of the giant omphalocele and the respiration instability due to hypoplastic thorax and increased intra-abdominal pressure. The TMC, predominantly the surrounding subarachnoid space, enlarged during the waiting period, resulting in the expansion of the caudal part of the dural sac. Although untethering surgery for the TMC was uneventfully performed with conventional duraplasty, postoperative CSF leakage occurred, and it took three surgical interventions to repair it. External CSF drainage, reduction of the size of the caudal part of the dural sac and use of gluteus muscle flaps and collagen matrix worked together for the CSF leakage. Preoperative enlargement of the TMC, together with the surrounding subarachnoid space, can cause the refractory CSF leakage after untethering surgery because the expanded dural sac possibly increases its own tensile strength and impedes healing of the duraplasty. Early untethering surgery is recommended after recovery from the life-threatening conditions associated with OEIS complex.


[Case report of disseminated nocardiosis complicated in an elderly person with pneumoconiosis].
Nocardia is typically regarded as an opportunistic infection, with pulmonary nocardiosis frequently disseminated to organs hematogenous by, and nearly half of these cases resulting in complicated nocardia brain abscess. Disseminated nocardia has a dismal prognosis with high mortality, and should be checked for multiple organs including the brain when nocardiosis is diagnosed. We describe the successful treatment of nocardia brain abscesses in an immunocompetent older people with pneumoconiosis by combining trimethoprim-sulfamethoxazole and ciprofloxacin. Patients had no history of fever, headache, or respiratory symptoms such as cough, or sputum until the acute hemiplegia episode. Nocardia infection is not as rare as generally assumed and should be considered as a possibility in the elderly due to its high mortality.


Essential fatty acids and modern lifestyle: a reappraisal.
Controversy surrounds the effects of dietary fish oil supplementation on atherosclerosis. Three studies were undertaken, where Vervet monkeys were fed either a Western atherogenic diet (WAD) or a high carbohydrate diet (HCD). The first study indicated that enhanced atherosclerosis may be the result of an imbalance of fatty acids in plasma and tissue lipids as eicosapentaenoic acid (EPA; C20:5 ω3) was increased with fish oil (FO) supplementation at the expense of arachidonic acid (AA; C20:4 ω6). The second study investigated the effect of diet on the metabolism of EPA. Disappearance of EPA, after EPA loading, was delayed in Vervets on the WAD in comparison with those on the HCD. Results of this study indicate that diet is able to modulate EPA metabolism, and that the beneficial effects of a HCD on plasma lipoprotein concentrations can be augmented by EPA supplementation. The third study investigated the combined effect of a supplement that contained different ratios and dosages of gamma-linolenic acid (GLA; C18:3 ω6) and EPA during ingestion of the WAD. Based on a favourable response to plasma lipoprotein cholesterol and a phosphatidylcholine fatty acid metabolism with increases in both EPA and dihomogamma-linolenic acid (DGLA; C20:3 ω6), we conclude that a 4:1 ω6/ω3 fatty acid supplement at 200 mg/day would be the optimum supplement in our animal model. The long-term effects of this supplement on lipoprotein metabolism and atherosclerosis in the non-human primate model, is currently under investigation.


Xanthogranulomatous cholecystitis masquerading as gallbladder cancer: can it be diagnosed preoperatively?
Background. Xanthogranulomatous cholecystitis (XGC) is often misdiagnosed as gallbladder cancer (GBC). We aimed to determine the preoperative characteristics that could potentially aid in an accurate diagnosis of XGC masquerading as GBC. Methods. An analysis of patients operated upon with a preoperative diagnosis of GBC between January 2008 and December 2012 was conducted to determine the clinical and radiological features which could assist in a preoperative diagnosis of XGC. Results. Out of 77 patients who underwent radical cholecystectomy, 16 were reported as XGC on final histopathology (Group A), while 60 were GBC (Group B). The incidences of abdominal pain, cholelithiasis, choledocholithiasis, and acute cholecystitis were significantly higher in Group A, while anorexia and weight loss were higher in Group B. On CT, diffuse gallbladder wall thickening, continuous mucosal line enhancement, and submucosal hypoattenuated nodules were significant findings in Group A. CT findings on retrospect revealed at least one of these findings in 68.7% of the cases. Conclusion. Differentiating XGC from GBC is difficult, and a definitive diagnosis still necessitates a histopathological examination. An accurate preoperative diagnosis requires an integrated review of clinical and characteristic radiological features, the presence of which may help avoid radical resection and avoidable morbidity in selected cases.


Coronary endothelium-dependent and independent vasomotor responses in patients with hypertrophic cardiomyopathy.
It is well known that coronary flow reserve (CFR) is decreased in patients with hypertrophic cardiomyopathy (HCM), but it is unclear whether coronary endothelial function is impaired. Coronary endothelial function and CFR in the coronary macro- and microcirculation was evaluated in 14 patients with HCM and 11 control subjects. Acetylcholine (ACh), bradykinin (BK) and papaverine were infused into the left coronary artery. Coronary cross-sectional area was determined by quantitative coronary angiography and coronary blood flow (CBF) was determined by the product of the coronary cross-sectional area and CBF velocity measured by an intracoronary Doppler guidewire. Acetylcholine at 100 microg induced diffuse coronary spasms of the left anterior descending coronary arteries in 3 of the patients with HCM. The changes in the diameter of the left anterior descending coronary artery and the increases in CBF induced by BK (0.2, 0.6, and 2.0 microg/min) did not differ between the 2 groups. CFR was lower in the HCM group than in the control group (p<0.01). Moreover, the ratio of BK-induced CBF increase to papaverine-induced CBF increase was comparable between the 2 groups. Endothelium-dependent vasodilation of the epicardial and resistance coronary arteries induced by BK was preserved despite the decreased CFR in patients with HCM.


Contact lens-related microbial keratitis: Part II: Pathophysiology.
The literature is reviewed concerning the pathophysiologic effects of contact-lens wear, the microbiology of contact-lens wear, the change in microflora with contact-lens wear, the contamination of contact lenses and contact-lens products, patient compliance, and corneal interaction with the contact lens. Hypoxia and hypercapnia are the most significant changes in the cornea as a result of contact-lens wear. Changes take place in the conjunctival flora in patients with contact lenses. Compliance of patients and contamination of contact lenses and contact-lens products are significant risk factors. The corneal interaction with the contact lens can overwhelm the protective mechanisms of the cornea, increasing the ability of microbes to adhere to the cornea and progress to microbial keratitis. Some of the factors associated with microbial keratitis are modifiable and should stimulate the contact-lens industry to develop better contact lenses and contact lens products and also permit ophthalmologists to obtain better informed consent from their patients.


Nutrient cycles and resource management: implications for the choice of wastewater treatment technology.
We look at the most important issues of the global nitrogen and phosphorus cycle and conclude that the nutrients from human metabolism are of no importance for the global nitrogen cycle and of minor importance for the global phosphorus cycle. However, for water pollution control, N and P from the human metabolism are of extreme importance. Nitrogen is mainly an issue for coastal waters, whereas P is an issue for freshwater and coastal areas alike. It is by now generally recognised that coastal ecosystems are exceedingly important for human well-being and at the same time highly endangered. The recycling issue is of high importance in areas where nutrient application is low due to economic constraints. NoMix technology (urine source separation) holds a large promise to become an efficient mainstream technology. The largest short-term potential is found in densely populated areas in coastal areas without existing infrastructure and in areas with nutrient deficiency, especially in urban areas with a large nutrient potential. We believe, however, that these technologies will, with time, also become competitive in Europe.


Pretreatment risk factors and importance of comorbidity for overall survival, complete remission, and early death in patients with acute myeloid leukemia.
The objective of this single-center study was to determine the pretreatment risk factors and influence of comorbidity on outcome in patients with acute myeloid leukemia (AML). The research involved 145 patients with AML during a 58-month follow-up period. The results suggest that the most significant predictor of poor overall survival (OS) is an adverse karyotype (P = 0.007), while for poor rate of complete remission (CR) it is age ≥55 years, and for early death the most significant predictor is comorbidity, as scored by the Hematopoetic Cell Transplantation Comorbidity Index (HCT-CI), P = 0.001. When we divided the patients into two groups: aged ≥55 years and aged <55 years, these predictors differed. In the group aged ≥55 years the most significant predictor of OS (P = 0.013) and for early death (P = 0.003) was HCT-CI (P = 0.013), while in the younger group it was karyotype (P < 0.001). The most significant predictor of CR in the elderly was increased serum lactate dehydrogenase (LDH) level (P = 0.045). In the younger patients, the most significant predictor of CR was leukocytosis (P = 0.001) and for early death it was infection as the comorbidity (P = 0.007). We point out the importance of comorbidity for OS and early death, as well as the impact of infection in patients with AML.


Application of Least-Squares Support Vector Machines for Quantitative Evaluation of Known Contaminant in Water Distribution System Using Online Water Quality Parameters.
In water-quality, early warning systems and qualitative detection of contaminants are always challenging. There are a number of parameters that need to be measured which are not entirely linearly related to pollutant concentrations. Besides the complex correlations between variable water parameters that need to be analyzed also impairs the accuracy of quantitative detection. In aspects of these problems, the application of least-squares support vector machines (LS-SVM) is used to evaluate the water contamination and various conventional water quality sensors quantitatively. The various contaminations may cause different correlative responses of sensors, and also the degree of response is related to the concentration of the injected contaminant. Therefore to enhance the reliability and accuracy of water contamination detection a new method is proposed. In this method, a new relative response parameter is introduced to calculate the differences between water quality parameters and their baselines. A variety of regression models has been examined, as result of its high performance, the regression model based on genetic algorithm (GA) is combined with LS-SVM. In this paper, the practical application of the proposed method is considered, controlled experiments are designed, and data is collected from the experimental setup. The measured data is applied to analyze the water contamination concentration. The evaluation of results validated that the LS-SVM model can adapt to the local nonlinear variations between water quality parameters and contamination concentration with the excellent generalization ability and accuracy. The validity of the proposed approach in concentration evaluation for potassium ferricyanide is proven to be more than 0.5 mg/L in water distribution systems.


Effects of Implant Diameter on Implant Stability and Osseointegration in the Early Stage in a Dog Model.
Purpose: To determine the optimal implant diameter under limited bone width by comparing the effects of implants with different diameters on implant stability, peri-implant bone stability, and osseointegration. In addition, to evaluate the reliability of resonance frequency analysis (RFA) in detecting osseointegration and marginal bone level (MBL). Materials and Methods: Mandibular premolars and first molars of seven beagle dogs were extracted. After 8 weeks, their mandibular models and radiographic information were collected to fabricate implant templates. Implant sites were randomly divided into three groups according to diameter: Ø3.3, Ø4.1, and Ø4.8 mm. Implant stability quotient (ISQ) measurement and radiographic evaluation were performed after surgery (baseline) and at 4, 8, and 12 weeks. Three dogs were euthanized at 4 weeks to observe osteogenesis and implant-tissue interface biology. Four dogs were euthanized at 12 weeks to observe osseointegration. Hard tissue sections were prepared to analyze osteogenesis (fluorescence double labeling) and osseointegration (methylene blue-acid fuchsin staining). Results: At baseline and at 4, 8, and 12 weeks, the ISQ values of Ø4.1- and Ø4.8-mm implants did not differ (P > .05), but both had higher values than the Ø3.3-mm implants (P < .05). The mean marginal bone resorption (MBR) associated with Ø3.3-, Ø4.1-, and Ø4.8-mm implants was 0.65 ± 0.58 mm, 0.37 ± 0.28 mm, and 0.73 ± 0.37 mm, respectively. The buccal MBR of Ø4.8-mm implants was significantly higher than that of Ø4.1-mm implants (P < .05). The bone-to-implant contact (BIC) percentage at 12 weeks did not differ for any group (P > .05). The correlation coefficients between the ISQ and MBL of the Ø3.3-, Ø4.1-, and Ø4.8-mm implants were -0.84 (P < .01), -0.90 (P < .001), and -0.93 (P < .001), respectively, while that between the ISQ and BIC was 0.15 (P > .05). Conclusions: During the early healing stage, the performance of Ø4.1- and Ø4.8-mm implants in terms of implant stability was better than that of Ø3.3-mm implants. Implant diameter may not influence BIC percentage. RFA can be used to evaluate implant stability and MBL but is not suitable to assess the degree of osseointegration.


INTRASPECIFIC PHYLOGEOGRAPHY OF NORTH AMERICAN HIGHLAND FISHES: A TEST OF THE PLEISTOCENE VICARIANCE HYPOTHESIS.
The highland fish fauna of eastern North America consists of Appalachian and Ozark centers of endemism separated by the intervening Glacial Till Plains. Clades within these areas are more closely related phylogenetically to each other than to clades occurring in the intervening formerly glaciated region, suggesting that the Pleistocene glaciations fragmented a widespread highland region and its associated fauna. Alternatively, it is possible that these faunal assemblages predate the glaciations or that recent dispersals may have been more important than vicariance in determining faunal compositions. We examined the relationships among mitochondrial DNA (mtDNA) haplotypes within five clades of highland fishes, each with a distribution suggestive of a Pleistocene vicariance event. Darters of the subgenera Litocara and Odontopholis have distributions and mtDNA relationships that are consistent with the Pleistocene integration and burial of the Teays-Mahomet valley, a major drainage of the early Pleistocene. The distribution and mtDNA relationships among subspecies of Erimystax dissimilis are not consistent with Pleistocene vicariance, but relationships among Appalachian haplotypes are consistent with the late Pleistocene integration of the modern Ohio River system. Both Cottus carolinae and the Fundulus catenatus species group have representatives in the Mobile basin consistent with pre-Pleistocene divergences. Three haplotype clusters were found in C. carolinae, corresponding to the Appalachian, Ozark, and upper Kanawha River populations. However, Appalachian and Ozark F. catenatus populations are paraphyletic with respect to each other. This, coupled with a relatively low degree of sequence divergence, suggests that no long-term barriers to gene flow exist for C. carolinae and F. catenatus. These three distinct phylogeographic patterns indicate that Pleistocene vicariance is not the only explanation for the Appalachian-Ozark distribution of highland fish communities.


Hemispheric Differences in Functional Interactions Between the Dorsal Lateral Prefrontal Cortex and Ipsilateral Motor Cortex.
Background: The dorsolateral prefrontal cortex (DLPFC) in both hemispheres have a central integrative function for motor control and behavior. Understanding the hemispheric difference between DLPFC and ipsilateral motor cortex connection in the resting-state will provide fundamental knowledge to explain the different roles DLPFC plays in motor behavior. Purpose: The current study tested the interactions between the ipsilateral DLPFC and the primary motor cortex (M1) in each hemisphere at rest. We hypothesized that left DLPFC has a greater inhibitory effect on the ipsilateral M1 compared to the right DLPFC. Methods: Fourteen right-handed subjects were tested in a dual-coil paired-pulse paradigm using transcranial magnetic stimulation. The conditioning stimulus (CS) was applied to the DLPFC and the test stimulus (TS) was applied to M1. Interstimulus intervals (ISIs) between CS and TS were 2, 4, 6, 8, 10, 15, 20, 25, and 30 ms. The result was expressed as a percentage of the mean peak-to-peak amplitude of the unconditioned test pulse. Results: There was stronger inhibitory effect for the left compared to the right hemisphere at ISIs of 2 (p = 0.045), 10 (p = 0.006), 15 (p = 0.029) and 20 (p = 0.024) ms. There was no significant inhibition or facilitation at any ISI in the right hemisphere. Conclusions: The two hemispheres have distinct DLPFC and M1 cortico-cortical connectivity at rest. Left hemisphere DLPFC is dominant in inhibiting ipsilateral M1.


Activators of protein kinase C depolarize insulin-secreting cells by closing K+ channels.
Carbohydrate stimuli of insulin secretion depolarize the pancreatic B cell and the B-cell line RINm5F by inhibiting ATP-sensitive K+ channels. We examined the possibility that this effect is mediated by activation of protein kinase C. In RINm5F cells, the triose D-glyceraldehyde evoked a rapid increase of the mass of 1,2-diacylglycerol, the endogenous activator of protein kinase C. This effect is mainly due to de novo synthesis of the lipid from glycolytic intermediates, as glyceraldehyde carbon was incorporated into 1,2-diacylglycerol within 1 min of exposure to 14C-labelled glyceraldehyde. The effects of two exogenous activators of kinase C, 4-beta-12-phorbol-myristate 13-acetate (PMA) and 1,2-didecanoylglycerol (DC10) on single K+ channel currents were examined in RINm5F cell-attached membrane patches. Both PMA and DC10 depolarized the cells and decreased the open-state probability of the ATP-sensitive K+ channels. These actions were not due to changes in cellular ATP content, since PMA, like glyceraldehyde, failed to alter cellular ATP. As is the case for glyceraldehyde, PMA and DC10 raised cytosolic free Ca2+ [( Ca2+]i) and stimulated insulin secretion. Both of these effects are inhibited in the absence of external Ca2+. This, and the attenuation of the [Ca2+]i rise by verapamil, suggest that all three stimuli raise [Ca2+]i by promoting Ca2+ influx through voltage-gated channels in turn leading to insulin secretion. As the exogenous activators of protein kinase C mimic the effects of glyceraldehyde, it is proposed that the carbohydrate-mediated production of 1,2-diacylglycerol constitutes the link between metabolism and membrane depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)


Cotranslational insertion of selenocysteine into formate dehydrogenase from Escherichia coli directed by a UGA codon.
The structural gene (fdhF) for the 80-kDa selenopolypeptide of formate dehydrogenase (formate:benzyl viologen oxidoreductase, EC 1.2.--.--) from Escherichia coli contains an in-frame UGA codon at amino acid position 140 that is translated. Translation of gene fusions between N-terminal parts of fdhF with lacZ depends on the availability of selenium in the medium when the hybrid gene contains the UGA codon; it is independent of the presence of selenium when an fdhF portion upstream of the UGA position is fused to lacZ. Transcription does not require the presence of selenium in either case. By localized mutagenesis, the UGA codon was converted into serine (UCA) and cysteine (UGC and UGU) codons. Each mutation relieved the selenium dependency of fdhF mRNA translation. Selenium incorporation was completely abolished in the case of the UCA insertion and was reduced to about 10% when the UGA was replaced by a cysteine codon. Insertion of UCA yielded an inactive fdhF gene product, while insertion of UGC and UGU resulted in polypeptides with lowered activities as components in the system formerly known as formate hydrogenlyase. Altogether the results indicate that the UGA codon at position 140 directs the cotranslational insertion of selenocysteine into the fdhF polypeptide chain.


The effects of direction similarity in visual working memory: Behavioural and event-related potential studies.
Object similarity can improve visual working memory (VWM) performance in the change-detection task, but impair the recognition performance when it occurs at retrieval of VWM in the recognition task. The effect of direction similarity is an issue that has not been well resolved. Furthermore, electrophysiological evidence in support of the mechanisms that underlie the effects of similarity is still scarce. In the current study, we conducted three behavioural experiments to examine the effects of direction similarity on memory performance with regard to both the encoding and retrieval phases of VWM and one event-related potential (ERP) experiment to explore the neural signatures of direction similarity in VWM. Our behavioural studies indicated that direction similarity improved performance when it occurred at the encoding phase but impaired performance when it occurred at the retrieval phase. Moreover, the ERP experiment showed that the amplitude of the contralateral delay activity (CDA) increased with the increasing set size for similar but not dissimilar directions. In addition, the CDA amplitude for similar directions was lower than that for dissimilar directions at set size 2. Taken together, these findings suggest that direction similarity at encoding has a positive effect on VWM performance and at retrieval has a negative effect. Given that VWM capacity depends on information load and the number of objects, the positive effect of similarity may be attributed to reduced information load of memory objects.


[Killing effect of Huaier combined with DC-CIK on nude mice bearing colon cancer HT29 stem cells in vivo].
To compare the therapeutic effects of different treatment methods on the nude mice bearing colon cancer HT29 cells. BalB/C nude mice colon cancer stem cell models were established and randomly divided into the following four groups, with 8 nude mice in each group: blank control group, DC-CIK group, Huaier group, and Huaier combined with DC-CIK group (combined treatment group). The mice in DC-CIK group and combined treatment group received 1×10⁶ DC-CIK cells treatment by tail vein injectionafter the tumor stem cells were inoculated for 4 days,2 times a week for three weeks. The mice in Huaier group and combined treatment group received intragastric administration at the dose of 20 g/60 kg body weight, 0.2 mL/time, once a day for a total of three weeks. The mice in control group received equal volume of normal saline. Tumor size and body weight of nude mice were measured every 2 days during treatment for three weeks in each group. After the treatment, the nude mice were sacrificed to measure the tumor weight and the tumor inhibition rate was calculated. The RT-PCR method was used to detect the expression levels of the key genes in the signal pathway. After the end of the treatment, the quality of the tumor in the Huaier group, DC-CIK group and combined treatment group was significantly lower than that in the control group; the quality in combined treatment group was significantly lower than that in Huaier group and DC-CIK group.Among them, the tumor inhibition rate reached 46.77% in the combined treatment group. In respect of changes in expression levels of key genes in the signaling pathway, the mRNA expression levels of key genes PI3KR1 and Akt in PI3K/Akt pathway, key genes Wnt1 and CTTNB1 in Wnt/β-catenin pathway, and key genes Notch1, Notch2, Notch3 in Notch pathway in the combined treatment group were lower than those in DC-CIK group and Huaier group. The Huaier combined with DC-CIK group showed best therapeutic effect among different treatment methods for HT29 stemcell colon tumors in nude mice, providing a new idea for clinical treatment of colon cancer.


Issues in stinging insect allergy immunotherapy: a review.
The treatment of insect allergy by desensitization still continues to present with some unanswered questions. This review will focus mainly on articles that have dealt with these issues in the past 2 years. With the publication in 2007 of Allergen Immunotherapy: a practice parameter second update, many of the key issues were reviewed and summarized. Other recent studies deal with omalizumab pretreatment of patients with systemic mastocytosis and very severe allergic reactions to immunotherapy. It would appear that venom immunotherapy is somewhat unique compared to inhalant allergen immunotherapy in that premedication prior to rush protocols may not be necessary and that intervals of therapy may be longer than with allergen immunotherapy. The use of concomitant medications such as beta-blockers may be indicated in special situations. Angiotensin-converting enzyme inhibitors can be stopped temporarily before venom injections to prevent reactions. The issue of when to discontinue immunotherapy remains unsettled and should be individualized to patient requirements. The newest revision of the Immunotherapy Parameters provides much needed information concerning successful treatment with immunotherapy of Hymenoptera-sensitive patients.


Role of receptor aggregation in triggering IgE-mediated reactions.
The first event in the IgE-mediated triggering of basophils and mast cells is the binding of serum IgE to membrane IgE receptors; quantitative relationships have been found among the serum IgE concentration, the number of IgE molecules per cell, the total receptor number, and the degree of endogenous receptor occupancy. Once bound, these antibody molecules must be cross-linked by multivalent antigen to activate the cell. Receptor juxtaposition is necessary throughout both activation and desensitization of these cells. Two types of desensitization occur. Antigen-specific desensitization alters only the function of certain IgE molecules; the cell can respond normally to other antigens. Specific desensitization is not reversed by removal of the antigen. Also, the affected antibody-receptor complexes remain on the cell surface, can rebind antigen, but cannot trigger the cell. Nonspecific desensitization is less well understood but is directly related to the number of cross-links on the basophils. Inasmuch as the cells become insensitive to all IgE-mediated stimuli, the total depletion of some intermediate has been postulated. In the presence of calcium the stimulated cells normally degranulate and release mediators. We have shown that for the simple antigens, both the release process and desensitization are a function of the number of cross-links present on the cell surface, and we have generated a mathematical model that quantitatively fits the experimental data. Thus, after many studies that span decades, the role of receptor aggregation in triggering mast cells and basophils is becoming qualitatively and quantitatively defined.


In the eyes of the beholder: cognitive appraisals as mediators of the association between interparental conflict and youth maladjustment.
Although the association between interparental conflict and youth maladjustment has been established, processes underlying this relationship are less understood. In this investigation, children's conflict appraisals were examined as mediating variables. In Study 1, 1,893 6th graders reported their perceptions of conflict and appraisals of threat and self-blame. Youth and teachers reported on externalizing and internalizing problems. In Study 2, 416 married parents from the larger sample reported their conflict and youth maladjustment. Children's appraisals of coping efficacy also were examined. Perceived threat, self-blame, and coping efficacy were salient mediators of overt conflict and triangulation, particularly for internalizing problems. Findings indicate that children's beliefs about interparental conflict play an important role in their adjustment to this family stressor.


Seroma formation after mastectomy: pathogenesis and prevention.
Post mastectomy seroma remains an unresolved quandary as the risk factors for its formation have still not been identified. Seromas of the axillary space following breast surgery can lead to significant morbidity and delay in the initiation of adjuvant therapy. Various techniques and their modifications have been practiced and published in English literature, but there seems to be no consensus. In this article, all aspects of seroma formation from pathogenesis to prevention including drug therapies have been discussed.


Hepatitis C in childhood.
The approach of a pediatric hepatologist in managing children with hepatitis C virus (HCV) differs from adult practice, because the pediatric hepatologist is dealing with the beginning of a chronic illness in which long-term outcomes will not occur for 20 or 40 years, and it is not possible to predict in the early stages of the infection which patients have a more sinister prognosis. The prevalence of chronic HCV in children is low, but varies between different countries in the Asia-Pacific region. In most countries, screening of blood products for HCV has virtually eliminated the risk of post-transfusion HCV, so that in Australia children aged less than 11 years will not have acquired HCV from blood transfusion or extracorporeal membrane oxygenation. The risk of perinatal transmission of this virus is only about 6%, but this remains virtually the only source of HCV transmission for children in most countries. While available data are limited, mild histological changes are present in the majority of children with hepatitis C, and cirrhosis is rare. Unfortunately, long-term natural history studies of the course of HCV infection in children have not been reported. Individual decisions on antiviral treatment are more difficult in childhood, not because the treatment is any less effective or because of the severity of side-effects (which tend to be less severe than for adults), but because the long-term outcome of infection is unclear. At present, treatment should be confined to those with significant hepatic fibrosis and continued moderate to severe necroinflammatory change. Measures to prevent HCV infection in childhood center on whether, as recently suggested, elective cesarean section may reduce the risk of transmission. Despite the presence of HCV-RNA in some breast milk samples, there is no evidence that breast-feeding confers any risk of HCV infection.


[Churg-Strauss syndrome with rectal localization and exudative enteropathy].
The authors report the case of a 61-year old patient with a Churg-Strauss syndrome revealed by abdominal pain. Investigations showed a diffuse inflammatory digestive tract involvement, documented by endoscopy associated with protein-losing enteropathy. Deep rectal biopsy revealed vasculitis in an otherwise macroscopically normal rectum. Faced with acute and life-threatening course of disease, emergency medical treatment with steroids and cyclophosphamide led to rapid regression of clinical, biological and radiological abnormalities.


In vitro mesenchymal stem cell response to a CO2 laser modified polymeric material.
With an ageing world population it is becoming significantly apparent that there is a need to produce implants and platforms to manipulate stem cell growth on a pharmaceutical scale. This is needed to meet the socio-economic demands of many countries worldwide. This paper details one of the first ever studies in to the manipulation of stem cell growth on CO2 laser surface treated nylon 6,6 highlighting its potential as an inexpensive platform to manipulate stem cell growth on a pharmaceutical scale. Through CO2 laser surface treatment discrete changes to the surfaces were made. That is, the surface roughness of the nylon 6,6 was increased by up to 4.3μm, the contact angle was modulated by up to 5° and the surface oxygen content increased by up to 1atom %. Following mesenchymal stem cell growth on the laser treated samples, it was identified that CO2 laser surface treatment gave rise to an enhanced response with an increase in viable cell count of up to 60,000cells/ml when compared to the as-received sample. The effect of surface parameters modified by the CO2 laser surface treatment on the mesenchymal stem cell response is also discussed along with potential trends that could be identified to govern the mesenchymal stem cell response.


Impact of isoflurane on malignant capability of ovarian cancer in vitro.
Metastatic recurrence of ovarian cancer is the foremost cause of postoperative mortality. With recent research indicating that inhalation of anaesthetics may influence cancer cell behaviour, this study investigated the effects of isoflurane on the expression of tumorigenic markers and proliferative capacity in ovarian cancer cells. Ovarian cancer (SK-OV3) cells were cultured and then exposed to 2% isoflurane for 2 h. The expression of markers involved in cell proliferation, angiogenesis, and migration were assessed up to 24 h after treatment using immunofluorescence staining, western blotting, and flow cytometry. The effects of isoflurane on in vitro angiogenesis and migration were also determined. Isoflurane exposure significantly increased insulin-like growth factor (IGF)-1 and IGF-1R expression, cell cycle progression, and cell proliferation in SK-OV3 cells. Increased expression of the angiogenic markers vascular endothelial growth factor (VEGF) by 56% (P<0.05) and angiopoietin-1 by 62% (P<0.05) was also observed 24 h after isoflurane exposure together with an enhanced in vitro angiogenesis. Cell migration was significantly increased after exposure to isoflurane together with increased production of both matrix metalloproteinases 2 and 9 (both P<0.05) by almost five-fold relative to control. These effects were abolished when IGF-1R signalling was blocked either by neutralizing antibody or by small interfering RNA. Our data indicate that isoflurane increases the malignant potential of ovarian cancer cells through the up-regulation of markers associated with the cell cycle, proliferation, and angiogenesis. This study warrants further investigations.


42 W femtosecond Yb:Lu2O3 regenerative amplifier.
We report on a femtosecond high-power regenerative amplifier based on Yb:Lu2O3. Exploiting the excellent thermo-mechanical properties of this material, we were able to achieve up to 64.5 W in continuous-wave regime, limited only by the available pump power. In pulsed operation, 42 W of average output power at a repetition rate of 500 kHz with 780 fs long pulses could be demonstrated, resulting in a pulse peak power of ∼100 MW. The spectrum was centered at 1034 nm with an FWHM of 2.4 nm, potentially allowing for even shorter pulses. At the maximum output power the beam was nearly TEM00, with an M2 value of 1.2 in both axes.


Effects of Patient Navigation on Patient Satisfaction Outcomes.
Patient navigation (PN) may reduce cancer health disparities. Few studies have investigated the effects of PN on patient-reported satisfaction with care or assessed patients' satisfaction with navigators. The objectives of this study are to test the effects of PN on patient satisfaction with cancer care, assess patients' satisfaction with navigators, and examine the impact of barriers to care on satisfaction for persons with abnormal cancer-related screening tests or symptoms. Study participants included women and men with abnormal breast, cervical, or colorectal cancer screening tests and/or symptoms receiving care at 18 clinics. Navigated (n=416) and non-navigated (n=292) patients completed baseline and end-of-study measures. There was no significant difference between navigated and non-navigated patients in change in patient satisfaction with cancer care from baseline to exit. African-American (p<0.001), single (p=0.03), low income (p<0.01), and uninsured patients (p<0.001) were significantly less likely to report high patient satisfaction at baseline. A significant effect was found for change in satisfaction over time by employment status (p=0.04), with full-time employment showing the most improvement. The interaction between satisfaction with navigators and satisfaction with care over time was marginally significant (p=0.08). Baseline satisfaction was lower for patients who reported a barrier to care (p=0.02). Patients reporting other-focused barriers (p=0.03), including transportation (p=0.02), had significantly lower increases in satisfaction over time. Overall, results suggested that assessing barriers to cancer care and tailoring navigation to barrier type could enhance patients' experiences with health care. PN may have positive effects for healthcare organizations struggling to enhance quality of care.


Horner's syndrome: Herald of a ticking bomb.
Horner's syndrome is a clinical syndrome caused by damage to the cervical sympathetic ganglia. We discuss a case with classic signs of Horner's syndrome in an intravenous drug user with a right septic subclavian artery pseudoaneurysm. This case highlights that with the increasing intravenous drug use, this rare presentation of HS may become more common.


DPT Student Perceptions of the Physical Therapist Assistant's Role: Effect of Collaborative Case-Based Learning Compared to Traditional Content Delivery and Clinical Experience.
Doctor of physical therapy (DPT) student learning about role delineation of physical therapist assistants (PTAs) is essential to ethical and legal practice. Survey assessment of three DPT student cohorts compared collaborative interprofessional case-based learning with PTA students to traditional curriculum delivery strategies. Control cohorts were assessed one time. The intervention group was assessed pre-intervention, immediately post-intervention, and after completing a full-time clinical experience. The case-based learning covered 46% of survey content, allowing for the assessment of content-specific material and potential learning through collaboration. Following the educational intervention, the intervention group improved significantly in areas inside and outside the case-based study content, outscoring both control groups on 25-34% of the survey items. Following the clinical experience, the intervention group declined answer accuracy for patient evaluation and treatment implementation, suggesting unlearning. Improvement in the administrative section was observed after the clinical experience. Perceptions of the tasks within the PTA role were diminished while tasks outside the scope of practice appeared clarified following the clinical experience. While case-based collaborative intraprofessional learning proves effective in student learning about the PTA role, changes following the clinical experience raise questions about the influence of the clinical environment on learning and the practical application of recently learned knowledge.


Pancreatic steatosis and metabolic pancreatic disease: a new entity?
Overweight and obesity are some of the most important health challenges. Many diseases are related to these metabolic disorders, and, among them, the pancreatic fat accumulation, also called "pancreatic steatosis" or "nonalcoholic fatty pancreas", seems to have an emerging role in different conditions. There are different method to evaluate the fat content in the pancreas, such as histology, different imaging techniques and endoscopic ultrasound, but there is no gold standard for the correct diagnosis and for the identification of "inter/intralobular" and "intra-acinar" pancreatic fat. However, the fat storage in the pancreas is linked to chronic inflammation and to several conditions, such as acute and chronic pancreatitis, type 2 diabetes mellitus and pancreatic cancer. In addition, pancreatic fat accumulation has also been demonstrated to play a role in surgical outcome after pancreatectomy, in particular for the development of postoperative pancreatic fistula. Different possible therapeutic approaches have been proposed, but there is still a lack of evidence. The aim of this review is to report the current evidence about the relationship between the obesity, the pancreatic fat accumulation and its potential role in pancreatic diseases.


[Mid-stream versus bladder puncture urine in the diagnosis of urinary tract infection in pregnant patients].
150 healthy women being pregnant in the 1st, 2nd and 3rd trimester were examined. From the same content of urinary bladder suprapubic puncture urine (BPU) and mid-stream urine (MSU) were collected. The results concerning microbiological and microscopical analysis of urine proofs were compared. For qualitative and quantitative germ analysis MSU is sufficiently clean enough. In 95.3 there is a good correspondence of the microbiological results of both proofs. Exceptionally in 4.7% the MSU-results were not confirmed by BPU. With respect to the findings in sediment there is no good correspondence of the results. In case of sterile bladder content the BPU sediment - findings are significantly more frequent normal and significantly more seldom abnormal than in MSU. The sediment findings in MSU are more frequent false positive than in BPU. In case of an infected bladder content there are no significant differences in the sediment findings of both techniques in taking urine proofs. The rate of normal sediment findings in case of an infected bladder content is unrealistic high: In MSU in 11% and in BPU in 26%. For microbiologic germ diagnosis MSU and BPU proofs are equivalent. But, for detection or for exclusion of urinary tract infections the sediment finding is poorly pathognomonic for a urinary tract infection. A normal sediment finding does not exclude the existance of an urinary tract infection. Therefore, in the system of prenatal care we should waive of the sediment finding as a guide for the diagnosis of urinary tract infections.


Fluorescein angiography of retinal vascular involution after intravitreal injection of ranibizumab for retinopathy of prematurity.
To describe the involution patterns of vessel growth of retina through fluorescein angiography (FA) of children, who had been under treatment up to 1y previously intravitreal ranibizumab (IVR) as monotherapy for retinopathy of prematurity (ROP). This is a retrospective study. The medical information and FA of 17 children (34 eyes) whose area of avascular retina from the ora serrata was more than two disc diameters (DD) were analyzed. Among 34 eyes, all were the presence of finger-shaped vessels and arteriolar-venular shunts (100%, 34/34 eyes). Popcorn abnormalities were found in most of the eyes (94.1%, 32/34 eyes). Furthermore, in many cases (23.5%, 8/34 eyes), there were leakage persisting in the region of the junction between avascular and vascular retina. In contrast, just 2 eyes (5.9%) showed damage of retinal capillary bed and 3 eyes (8.8%) showed large area of retinal pigment epithelium (RPE) atrophy. Although IVR can be very effective in ROP, we should remain cautious as infants may remain avascular peripheral retinas and abnormal vessel. FA allows accurate visualization of vessel abnormalities in eyes with ROP, which will be helpful to affect assessment of disease activity and therapeutic effect.


Association of daily physical activity level with health-related factors by gender and age-specific differences among Korean adults based on the sixth (2014-2015) Korea national health and nutrition examination survey
This study examined the effects of daily physical activity level on health-related factors according to gender and identified age-specific differences among Korean adults. Using data from the Korea National Health and Nutrition Examination Survey VI (2014-2015), we selected adults aged 19-64 years who participated in both a health examination and health interview survey. The study included 6,457 participants 19-64 years of age (2,611 men, 3,846 women). Assessment of the differences in health-related factors according to age and physical activity in men and women by repeated two-way analysis of variance (ANOVA) revealed significant interaction effects on total cholesterol (TC) and triglyceride (TG) levels and diastolic blood pressure (DBP) in male participants, but there were no significant interaction effects for any health-related factors in female participants. The group of female participants aged 40-64 years with daily physical activity levels over 200 kcal showed a significantly increased prevalence of 46% for dyslipidemia compared to that in female participants with daily physical activity levels below 200 kcal. Physical activity was positively correlated with weight and high-density lipoprotein cholesterol (HDL-C) levels in men 19-39 years of age, compared to weight, waist circumference (WC), body mass index (BMI), and DBP in men 40-64 years of age, and weight, WC, BMI, glycated hemoglobin (HbA1c) and triglyceride (TG) levels in women 19-39 years of age. In women 40- 64 years of age, physical activity was especially significantly positively correlated with weight, BMI, HDL-C and negatively correlated with fasting glucose and TG levels. In male and female participants, the 40-64-year age group showed negative results for health-related factors compared to those in the 19-39-year age group. The higher the weight, WC, BMI, the higher is the physical activity level. Physical activity levels were significantly positively correlated with health-related variables.


Multichannel measurements of C. elegans largest Lyapunov exponents using optical diffraction.
Dynamic diffraction (DOD) is a form of microscopy that allows the dynamic tracking of changing shapes in a 1D time series. DOD can capture the locomotion of a nematode while swimming freely in a 3D space, allowing the locomotion of the worm to more closely mimic natural behavior than in some other laboratory environments. More importantly, we are able to see markers of chaos as DOD covers dynamics on multiple length scales. This work introduces a multichannel method to measure the dynamic complexity of microscopic organisms. We show that parameters associated with chaos, such as the largest Lyapunov exponent (LLE), the mean frequency, mutual information (MI), and the embedding dimension, are independent of the specific point sampled in the diffraction pattern, thus demonstrating experimentally the consistency of our dynamic parameters sampled at various locations (channels) in the associated optical far-field pattern.


MicroRNA 21 Emerging Role in Diabetic Complications: A Critical Update.
Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies are essential. MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic posttranscriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as low-grade inflammation. Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.


Pancreatic Elastography From Acoustic Radiation Force Impulse Imaging for Evaluation of Diabetic Microangiopathy.
The purposes of this study were to compare pancreatic shear-wave velocity (SWV) in subjects with and those without diabetic microvascular complications and to investigate the feasibility of pancreatic SWV in evaluating diabetic microangiopathy. SWV measurements were prospectively performed in 115 patients with diabetes mellitus and 115 healthy persons by use of acoustic radiation force impulse imaging. Patients with diabetes were divided into subgroups with and without microangiopathy. Pancreatic SWV was compared in three groups. Factors associated with increased SWV were studied. Pancreatic SWV increased significantly in the subgroups with diabetes mellitus compared with the control group (p < 0.01). Especially, the SWV in the pancreatic body was significantly higher when microangiopathy was present (p < 0.01). In patients with diabetes, microangiopathy (standardized β = 0.208, p = 0.022), age (standardized β = 0.265, p = 0.004), and total cholesterol level (standardized β = 0.223, p = 0.011) were positively and markedly correlated with high SWV in the pancreatic body. The increased SWV in the pancreatic body was significantly related to the presence of microangiopathy. It is feasible to use SWV in the pancreatic body to evaluate diabetic microangiopathy.


Achieving and maintaining venous access for home parenteral nutrition.
Once chronic intestinal failure is established and home parenteral nutrition has become necessary, the patient's life is literally dependent on secure long-term central venous access, other than in the small group in whom intestinal transplantation is both appropriate and available. Means to preserve venous access are therefore crucial. Recent papers have explored the nature of the complications that occur (in epidemiological, clinical and microbiological contexts), and have considered management strategies to prevent problems and generally to reduce morbidity. Interesting new data on patient attitudes to domiciliary care and the effects of these on outcomes are also presented. Home parenteral nutrition has a relatively high technical complication rate, but remains a safer option than intestinal transplantation. Meticulous attention to aseptic techniques, and patient-centred training and support can nevertheless improve outcomes and prolong the useful life of intravenous nutrition access devices.


Elafin is a biomarker of graft-versus-host disease of the skin.
Graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation, affects the skin, liver, and gastrointestinal tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large-scale quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, with enzyme-linked immunosorbent assay in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma concentrations of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio, 1.78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD.


Antiretroviral therapy in HIV-infected adolescents: clinical and pharmacologic challenges.
With the currently available combined antiretroviral therapy regimens, durable suppression of viral replication, preservation of immune function and normalizing life expectancy, are all becoming achievable goals. Teenagers and young adults living with HIV present unique clinical and pharmacologic challenges to optimizing antiretroviral treatment outcomes. Areas covered: In this expert review of the topic, we examine recent clinical trial data and draw on our program's 25 year experience working with both perinatally and behaviorally HIV infected adolescents. Expert commentary: In order to be effective, the antiretrovirals we provide must be combined with multidisciplinary interventions and ongoing socio-behavioral support to ensure treatment adherence and prevent the emergence of viral resistance.


The Practice of Feedback in Health Professions Education in the Hierarchical and Collectivistic Culture: a Scoping Review.
The global trend in student assessment is moving towards outcome-based assessment that requires multiple systematic data points and continuous feedback. However, in hierarchical and collectivistic cultures, one-way communication is practised more often, leading to less dialogical feedback. This scoping review explored feedback practice in Asian educational setting. Based on the 17 articles selected, the findings were categorised into four themes, i.e. inhibiting or facilitating factors of feedback, influences of cultural factors on feedback, discrepancies between students' and teachers' perceptions of feedback and impact of feedback. Hierarchical and collectivist cultural aspects, such as preference for group feedback, are pertinent to feedback practice, which likely influence the readiness for programmatic assessment.


Localization of kinetoplast DNA maxicircle transcripts in bloodstream and procyclic form Trypanosoma brucei.
Over 80% of the maxicircle and numerous minicircles of Trypanosoma brucei kinetoplast DNA have been cloned. The uncloned maxicircle segment contains few restriction endonuclease cleavage sites, varies in size among strains, and may be unstable in conventional cloning systems. cDNA prepared to bloodstream or procyclic trypomastigote RNA hybridized to all but one maxicircle segment, but did not hybridize to minicircles. Fourteen maxicircle transcripts were detected in RNA from both bloodstream and procyclic trypomastigotes. The coding sequences for these transcripts were localized and account for most of the maxicircle. One region of the maxicircle, which borders the variable region, was not found to be transcribed. We conclude that the maxicircle is largely but not completely transcribed in both bloodstream and procyclic trypomastigotes, whereas minicircle transcription is minimal or absent in these stages. Qualitative transcriptional differences which could account for mitochondrial respiratory differences between the bloodstream and procyclic trypomastigotes were not observed.


[Respiratory failure from upper airway collapse following anterior cervical spine surgery].
To determine the frequencies of variables that might predispose to upper airway collapse in a series of patients undergoing anterior cervical spine surgery. Retrospective review of the medical records of 204 patients who underwent anterior cervical spine neurosurgery between 2003 and 2009. We gathered information on perioperative variables that might be related to upper airway collapse, on whether intensive care unit admission was planned or not, and on the moment when obstruction developed. Partial obstruction occurred in 7 cases (3.4%); 4 (1.9%) resolved with tracheal intubation and 3 (1.5%) required emergency tracheostomy. None of the variables were significantly associated with the development of postoperative upper airway obstruction in these patients. Upper airway obstruction after anterior cervical spine surgery is an unforeseen event and the emergency assessment of the airway may not coincide with the assessment of the anesthetist during the preanesthetic visit. This event may constitute an emergency for which preparation times and resources may differ from those available when this complication is foreseen. The problem for the anesthetist is not the impossibility of tracheal intubation but rather the difficulty of ventilating through a facial mask or supraglottic device, possibly with life-threatening consequences.


Efficacy of team-based financial incentives for smoking cessation in the workplace.
Worksite smoking cessation programs offer accessibility of the target population, availability of occupational health support, and the potential for peer pressure and peer support. The purpose of this study was to identify the efficacy of the financial incentives given to various teams in the workplace. St. Paul's Hospital's employees were enrolled. Each team of employees consisted of smoking participants and non-smoking fellow workers from the same department. The financial incentive of 50000 won (about $45) was rewarded to the team for each successful participant-not to individual members-after the first week and then after one month. If the smokers in the team remained abstinent for a longer time period, the team was given an incentive of 100000 won for each successful participant after 3 and 6 months. A total 28 smoking participants and 6 teams were enrolled. Self-reported abstinence rates validated by urinary cotinine test at 3, 6, and 12 months after the initial cessation were 61%, 54%, and 50%, respectively. Smokers with high nicotine dependence scores or those who began participation 1 month after enrollment initiation had a lower abstinence rate at 3 months, but not at 6 and 12 months. Participants who succeeded at smoking cessation at 12 months were more likely to be older and have a longer smoking duration history. The financial incentives given to teams could be promising and effective to improve long-term rates of smoking cessation. This approach could use peer pressure and peer support in the workplace over a longer period.


Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 1-Defining populations at risk.
Thrombosis is a well-recognized phenomenon in dogs and cats with a significant impact on morbidity and mortality. Despite growing awareness of thrombosis and increased use of antithrombotic therapy, there is little information in the veterinary literature to guide the use of anticoagulant and antiplatelet medications. The goal of Domain 1 was to explore the association between disease and thrombosis in a number of conditions identified as potential risk factors in the current veterinary literature, to provide the basis for prescribing recommendations. A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. Revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated included immune-mediated hemolytic anemia, protein-losing nephropathy, pancreatitis, glucocorticoid therapy, hyperadrenocorticism, neoplasia, sepsis, cerebrovascular disease, and cardiac disease. Academic and referral veterinary medical centers. Of the diseases evaluated, a high risk for thrombosis was defined as dogs with immune-mediated hemolytic anemia or protein-losing nephropathy, cats with cardiomyopathy and associated risk factors, or dogs/cats with >1 disease or risk factor for thrombosis. Low or moderate risk for thrombosis was defined as dogs or cats with a single risk factor or disease, or dogs or cats with known risk factor conditions that are likely to resolve in days to weeks following treatment. Documented disease associations with thrombosis provide the basis for recommendations on prescribing provided in subsequent domains. Numerous knowledge gaps were identified that represent opportunities for future study.


A step forward in health-related IoT cybersecurity: remarks on the proposal for a liability for defective products directive.
This article outlines the efforts of the European Union in health-related IoT (H-IoT) cybersecurity. The first part identifies cyber threats that are specific to H-IoT. The second part covers the overall regulatory picture and briefly addresses both existing law and legislative initiatives. The third part discusses the Proposal for a Liability for Defective Products Directive and the measures it contains that relate directly to H-IoT.


Association of renal resistance index and arterial stiffness on clinical outcomes in patients with mild-to-moderate renal dysfunction and presence or absence of heart failure with preserved ejection fraction.
The renal arterial resistance index (RI) and the brachial-ankle pulse wave velocity (baPWV) are known as indicators of renal vascular resistance/systemic vascular damage and systemic arterial stiffness. The clinical significance of those parameters on clinical outcomes is poorly known in patients with and without heart failure with preserved ejection fraction (HFpEF). Baseline clinical data and the RI assessed by renal Doppler data, baPWV were obtained in patients with (HFpEF group, n = 60) and without HFpEF (non-HFpEF group, n = 51) who had a reduced estimated glomerular filtration rate (eGFR) of > 30 and < 60 mL/min/1.73 m2). We investigated the association between the RI and baPWV and major clinical outcomes including hospitalization for heart failure, cardiovascular death, myocardial infarction or unstable angina or other cardiovascular events and death from another cause. The RI and baPWV were greater in the HFpEF group than in the non-HF group (0.75 ± 0.07 vs. 0.69 ± 0.08, p < 0.001; 2002 ± 430 vs. 1762 ± 300 cm/s, p = 0.001). The RI correlated significantly with baPWV in the HFpEF (r = 0.382, p = 0.003) and non-HFpEF groups (r = 0.414, p = 0.002). During the median follow-up period of 54 months, major clinical outcomes occurred in 41 (36.9%) patients. The RI value, statin use and the presence of HFpEF were major factors for predicting clinical outcomes by multivariate analysis. Among the patients who had mild-to-moderate renal dysfunction, an increased RI and baPWV were observed in HFpEF patients as compared to non-HFpEF patients, but the baPWV similarly correlated with the RI value regardless of HFpFE patients or not. The strong association between the high RI value and presence of HFpEF and major clinical outcomes, suggests that not only the presence of HFpEF but also the high RI value may help to identify the high-risk patients leading to poor clinical outcomes.


The value of ultrasound harmonic imaging in the diagnostics of gall bladder cholesterol polyps.
The aim of the study was to assess the value of harmonic imaging in US evaluation of gall bladder cholesterol polyps. Material comprises 40 patients with pathology of gall bladder diagnosed in US examination. 10 patients from this group with gall bladder cholesterol polyps diagnosed in US were included into the study. In each patient supplementary US examination in the harmonic mode was performed. The quality of images in the harmonic mode was better. The walls of the gall bladder were more distinct. The polyps were more evident on harmonic images. THI enable more precise measurements of the polyps. In three cases in the standard mode the inspissated bile was found in gall bladder, and in those patients polyps were difficult to assess. Examination of those patients in the harmonic mode excluded the presence of the bile sludge, and facilitates the assessment of the polyps. In four patients on harmonic images more polyps were found than in the standard mode. In the harmonic mode the level of artifacts generated by the body wall is reduced and contrast resolution is increased due to reduction in noise level. The visualization of gallbladder is improved in the harmonic mode. The assessment of gallbladder polyps in the harmonic mode is easier. The polyps are easily seen, assessment of their margins and size is facilitated by harmonic imaging. The number of polyps revealed in US examination is larger in the harmonic mode.


In-Situ X-ray Tomography Study of Cement Exposed to CO2 Saturated Brine.
For successful CO2 storage in underground reservoirs, the potential problem of CO2 leakage needs to be addressed. A profoundly improved understanding of the behavior of fractured cement under realistic subsurface conditions including elevated temperature, high pressure and the presence of CO2 saturated brine is required. Here, we report in situ X-ray micro computed tomography (μ-CT) studies visualizing the microstructural changes upon exposure of cured Portland cement with an artificially engineered leakage path (cavity) to CO2 saturated brine at high pressure. Carbonation of the bulk cement, self-healing of the leakage path in the cement specimen, and leaching of CaCO3 were thus directly observed. The precipitation of CaCO3, which is of key importance as a possible healing mechanism of fractured cement, was found to be enhanced in confined regions having limited access to CO2. For the first time, the growth kinetics of CaCO3 under more realistic well conditions have thus been estimated quantitatively. Combining the μ-CT observations with scanning electron microscopy resulted in a detailed understanding of the processes involved in the carbonation of cement.


The minimum local anesthetic concentration of ropivacaine for caudal analgesia in children.
Ropivacaine is a new long-acting amino-amide local anesthetic. The concentrations of ropivacaine used in caudal analgesia range from 0.1% to 0.5%. The purpose of this study was to determine the minimum local analgesic concentration of ropivacaine to provide caudal analgesia in children. In a prospective, randomized, double-blinded clinical study, we studied 26 ASA grade I patients aged 1 to 5 yr who were scheduled for hypospadias operation under general anesthesia with caudal ropivacaine analgesia. General anesthesia was maintained with an end-tidal enflurane concentration of 0.8% in 100% oxygen (0.5 minimum alveolar anesthetic concentration [MAC]). Each child received 1 mL/kg of ropivacaine solution through a caudal catheter. The first child received ropivacaine 0.2%, and subsequent concentrations were determined by the analgesic response of the previous patient to the initial skin incision by use of Dixon's up-and-down sequential allocation. The testing interval was set at 0.025%. The minimum local analgesic concentration of ropivacaine for caudal analgesia under general anesthesia with 0.5 MAC enflurane was 0.11% (95% confidence interval [CI], 0.09%-0.12%), and the 95% effective concentration was 0.13% (95% CI, 0.12%-0.21%). In conclusion, the minimum local analgesic concentration of ropivacaine to provide effective caudal analgesia in children under general anesthesia with 0.5 MAC enflurane was found to be 0.11% (95% CI, 0.09%-0.12%). Ropivacaine is a new long-acting amino-amide local anesthetic. The concentrations of ropivacaine used in caudal analgesia ranged from 0.1% to 0.5%. This study determined the minimum local analgesic concentration of ropivacaine to establish effective caudal analgesia under general anesthesia with 0.5 minimum alveolar anesthetic concentration enflurane in children.


The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma.
The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.


Role of the semi-conserved histidine residue in the light-sensing domain of LitR, a MerR-type photosensory transcriptional regulator.
The LitR/CarH protein family transcriptional regulator is a new type of photoreceptor based on the function of adenosyl B12 (AdoB12) as a light-sensitive ligand. Here, we studied a semi-conserved histidine residue (His132) in the light-sensing (AdoB12-binding) domain at the C-terminus of LitR from a thermophilic Gram-negative bacterium, Thermus thermophilus HB27. The in vivo mutation of His132 within LitR caused a reduction in the rate of carotenoid production in response to illumination. BIAcore analysis revealed that the illuminated-LitRH132A possesses high DNA-binding activity compared to the wild-type protein. The subunit structure analysis showed that LitRH132A performed an incomplete subunit dissociation. The ability of LitRH132A to associate with AdoB12 was reduced compared with that of the wild-type protein in an equilibration dialysis experiment. Overall, these results suggest that His132 of LitR is involved in the association with AdoB12 as well as the light-sensitive DNA-binding activity based on oligomer dissociation.


The glycolytic enzyme PFKFB3 determines bone marrow endothelial progenitor cell damage after chemotherapy and irradiation.
Bone marrow (BM) endothelial progenitor cell (EPC) damage of unknown mechanism delays the repair of endothelial cells (EC) and recovery of hematopoiesis after chemo-radiotherapy. We found increased levels of the glycolytic enzyme PFKFB3 in the damaged BM EPC of patients with poor graft function, a clinical model of EPC damage-associated poor hematopoiesis after allogeneic hematopoietic stem cell transplantation. Moreover, in vitro the glycolysis inhibitor 3-(3-pyridinyl)- 1-(4-pyridinyl)-2-propen-1-one (3PO) alleviated the damaged BM EPC from patients with poor graft function. Consistently, PFKFB3 overexpression triggered BM EPC damage after 5-fluorouracil treatment and impaired hematopoiesis-supporting ability in vitro. Mechanistically, PFKFB3 facilitated pro-apoptotic transcription factor FOXO3A and expression of its downstream genes, including p21, p27, and FAS, after 5-fluorouracil treatment in vitro. Moreover, PFKFB3 induced activation of NF-κB and expression of its downstream adhesion molecule E-selectin, while it reduced hematopoietic factor SDF-1 expression, which could be rescued by FOXO3A silencing. High expression of PFKFB3 was found in damaged BM EC of murine models of chemo-radiotherapy-induced myelosuppression. Furthermore, a murine model of BM EC-specific PFKFB3 overexpression demonstrated that PFKFB3 aggravated BM EC damage, and impaired the recovery of hematopoiesis after chemotherapy in vivo, effects which could be mitigated by 3PO, indicating a critical role of PFKFB3 in regulating BM EC damage. Clinically, PFKFB3-induced FOXO3A expression and NF-κB activation were confirmed to contribute to the damaged BM EPC of patients with acute leukemia after chemotherapy. 3PO repaired the damaged BM EPC by reducing FOXO3A expression and phospho-NF-κB p65 in patients after chemotherapy. In summary, our results reveal a critical role of PFKFB3 in triggering BM EPC damage and indicate that endothelial-PFKFB3 may be a potential therapeutic target for myelosuppressive injury.


Effect of short-term splitting of gamma-ray doses on changes in haemopoietic stem cell number in bone marrow and on mortality of whole-body irradiated mice.
Split-dose irradiation of mice with two doses of 0.5 Gy given at 2 to 5 h interval damages haemopoietic stem cells (CFU-S) less than single exposure to 1 Gy. Also in comparison with whole-body single exposure of mice to a high sublethal dose of 7 Gy, splitting this dose into two doses of 3.5 Gy given at 4-h interval brought about more rapid recovery of CFU-S in femoral bone marrow and of bone marrow cellularity. At 360 days after irradiation with 7 Gy gamma-rays, a secondary decrease in CFU-S was apparent in bone marrow, which was more profound in the single-exposure group than in the group given split doses amounting to 7 Gy. The protective effect of short-term dose splitting was also evident in an investigation of mortality of irradiated mice. The LD50/30 value in mice exposed to a single dose of gamma-rays (8.3 Gy) increased to 10.5 Gy, when the dose was split (two doses, 4-h interval).


Induction potency of various beta-lactam derivatives in gram-negative rods.
The induction potency of various beta-lactams as well as that of 'nonspecific' inducers such as the media employed or body fluids were studied in gram-negative clinical isolates and in their resistant corresponding counterparts. In all wild-type isolates quite a few beta-lactams (mainly cefoxitin and imipenem) shared the ability to induce the chromosomal beta-lactamase, whereas all beta-lactams - including 6-APS and 7-CPS clavulanic acid, and sulbactam (both beta-lactamase inhibitors), exhibited strong induction potency in their corresponding resistant counterparts. Moreover, all resistant counterparts exhibited the phenomenon of 'nonspecific' induction, whereas the wild-type strains did not. Interestingly, in both Proteus vulgaris 4917 W and Providencia rettgeri 862 W wild-type strains most beta-lactam compounds were potent inducers, thus providing an explanation for resistance against beta-lactamase-unstable compounds. The addition of subinhibitory concentrations of the quinolone compound enoxacin or chloramphenicol did not influence the phenotypic beta-lactamase expression, neither in wild-type strains nor in their resistant counterparts, whereas the addition of clindamycin or gentamicin resulted in a marked decrease of enzyme production in cephalosporinase overproducers, the P. vulgaris and the P. rettgeri isolates.


Properties of invertase immobilized on the poly(ethylene-co-vinyl alcohol) hollow fiber membrane.
Invertase was ionically immobilized on the poly(ethylene-co-vinyl alcohol) hollow fiber inside surface, which was aminoacetalized with 2-dimethylaminoacetaldehyde dimethyl acetal. Immobilization and enzyme reaction were carried out by letting the respective solutions pass or circulate through the inside of the hollow fiber, and the activity of invertase was determined by the amount of glucose produced enzymatically from sucrose. Immobilization conditions were examined with respect to the enzyme concentration and to the time, and consequently the preferable conditions at room temperature were found to be 5 microg/mL of enzyme concentration and 4 h of immobilization time. Under those conditions the immobilization yield and the ratio of the activity of the immobilized invertase to that of the native one were 89 and 80%, respectively. For both repeating and continuous usages, the activity fell to ca. 60% of the initial activity in the early stage and after that almost kept that value. The apparent Michaelis constant K(m)(') for the immobilized invertase decreased with increasing the flow rate of the substrate solution, to be close to the value for the native one. Furthermore, the possibility of the separation of the enzymatically formed glucose from the reaction mixture through the hollow fiber membrane was preliminarily examined.


SELFISH LARVAE: DEVELOPMENT AND THE EVOLUTION OF PARASITIC BEHAVIOR IN THE HYMENOPTERA.
Queens of hymenopteran social parasites manipulate the workers of other social species into raising their offspring. However, nonconspecific brood care may also allow the parasite larvae to control their own development to a greater extent than possible in nonparasitic species. An evolutionary consequence of this may be the loss of the parasite's worker caste if the larvae can increase their fitness by developing into sexuals rather than workers. We argue that this loss is particularly likely in species in which there is little inclusive fitness benefit in working. Retention of a worker caste correlates with characteristics that increase the fitness of working relative to becoming a sexual, such as worker-production of males, high intracolony relatedness, and seasonal environments where the hosts of potential parasite queens are not always available. Further evidence strongly suggests that when the worker caste is evolutionarily lost in perennial species like ants, it disappears rapidly and through a reduction in caste threshold and queen size, so that parasite larvae become queens with less food than required to produce host workers. This evolutionary process, however, appears to lower overall population fitness, resulting in workerless parasite species having small populations and being geographically restricted. Conversely, in annual species like bees and wasps, workerless social parasitism evolves with no size reduction in queens, which is consistent with an expected lower level of queen/offspring conflict.


Current treatment options for restless legs syndrome.
Restless legs syndrome (RLS) is a common but often underdiagnosed neurological disorder characterised by an imperative desire to move the extremities associated with paraesthesias, motor restlessness, worsening of symptoms at rest in the evening or at night and, as a consequence, sleep disturbances particulary. Additionally, most patients with RLS have periodic limb movements during sleep and relaxed wakefulness. The aetiology of RLS remains unknown. Treatment of RLS is generally symptomatic, a causal therapy is possible only in the secondary forms. Dopaminergic agents including levodopa and dopamine agonists such as pergolide, pramipexole, cabergoline and ropinirole are regarded as the treatment of choice for idiopathic RLS, however, the development of augmentation of symptoms, especially under levodopa therapy, may be a major problem. Except in special circumstances, opioids and anticonvulsants such as gabapentin or benzodiazepines, are regarded as second-line treatment. In secondary RLS, the underlying illness should first be treated, although dopaminergic drugs may also be helpful.