Ex vivo-expanded bone marrow stem cells home to the liver and ameliorate functional recovery in a mouse model of acute hepatic injury.
Stem cell transplantation provides a theoretical approach for liver regeneration medicine; it may promote liver regeneration and self-repair. However, the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated. This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl4 injury. Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation, characterized by cytoflow immunofluorescence, and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl4. The integration of bone marrow cells into the liver was examined microscopically, and plasma hepatic enzymes were determined biochemically. Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells. Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl4-treated mice. Densitometry showed increased in situ cell proliferation (50+/-14 vs 20+/-3 cells/high-power field, P<0.05) and albumin expression (149+/-25 vs 20+/-5 cells/high-power field, P<0.05) in the liver, as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls. Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically-injured liver. Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.


Spindle Assembly: Two Spindles for Two Genomes in a Mammalian Zygote.
A single bipolar spindle was thought to form around both parental genomes in zygotes initiating the first division. A recent study challenges this predominant view by showing that two independent spindles assemble to prevent parental genome mixing in mouse zygotes.


In Vivo MRI Assessment of Experimental Schistosomiasis.
A new study using magnetic resonance imaging (MRI) evaluated successfully the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis in schistosomiasis. However, there are some drawbacks that need special attention. This preliminary data opens new opportunities to understand and monitor liver fibrosis in schistosomiasis and other fibrogenic diseases.


How do young children expect others to address resource inequalities between groups?
Age-related changes in young children's expectations for others' resource allocation decisions were investigated. Children ages 3 to 6years (N=80) were introduced to an inequality of resources between two groups. Participants gave their expectations for (a) how a member of the group with more resources (advantaged group) and a member of the group with fewer resources (disadvantaged group) would evaluate the inequality (okay or not okay), (b) which group each of the two individuals would prefer (ingroup or outgroup), and (c) how each of the two individuals would allocate subsequent resources between the groups. Findings revealed children's differing expectations for how others would address resource inequalities based on group status. Children expected that if the disadvantaged group member evaluated the inequality negatively then he or she would reduce the disparity. But children expected that if the advantaged group member evaluated the inequality positively then he or she would increase the disparity. Furthermore, 5- and 6-year-olds, but not 3- and 4-year-olds, expected individuals to seek more for their ingroup if they preferred their ingroup over the outgroup. Different from previous research on children's own resource allocation decisions, these findings reveal the circumstances under which children expect others to perpetuate or attenuate resource inequalities between groups.


Multi-teacher knowledge distillation based on joint Guidance of Probe and Adaptive Corrector.
Knowledge distillation (KD) has been widely used in model compression. But, in the current multi-teacher KD algorithms, the student can only passively acquire the knowledge of the teacher's middle layer in a single form and all teachers use identical a guiding scheme to the student. To solve these problems, this paper proposes a multi-teacher KD based on joint Guidance of Probe and Adaptive Corrector (GPAC) method. First, GPAC proposes a teacher selection strategy guided by the Linear Classifier Probe (LCP). This strategy allows the student to select better teachers in the middle layer. Teachers are evaluated using the classification accuracy detected by LCP. Then, GPAC designs an adaptive multi-teacher instruction mechanism. The mechanism uses instructional weights to emphasize the student's predicted direction and reduce the student's difficulty learning from teachers. At the same time, every teacher can formulate guiding scheme according to the Kullback-Leibler divergence loss of the student and itself. Finally, GPAC develops a multi-level mechanism for adjusting spatial attention loss. this mechanism uses a piecewise function that varies with the number of epochs to adjust the spatial attention loss. This piecewise function classifies the student' learning about spatial attention into three levels, which can efficiently use spatial attention of teachers. GPAC and the current state-of-the-art distillation methods are tested on CIFAR-10 and CIFAR-100 datasets. The experimental results demonstrate that the proposed method in this paper can obtain higher classification accuracy.


Selection of Ideal Candidates for Surgical Salvage of Head and Neck Squamous Cell Carcinoma: Effect of the Charlson-Age Comorbidity Index and Oncologic Characteristics on 1-Year Survival and Hospital Course.
Salvage surgery for recurrent head and neck squamous cell carcinoma (HNSCC) carries substantial risks of morbidity and mortality. Risk factors for death within 1 year should be better defined. To report preoperative oncologic prognostic factors predictive of short-term (<1 year) survival after salvage surgery in patients with HNSCC, to assess whether preoperative age and comorbidity predicts 1-year mortality, and to report hospital courses after salvage surgery within 1 year. A retrospective medical record review of 191 patients with recurrent HNSCC treated with salvage surgery from January 1, 2003, through December 31, 2013, at a tertiary academic center. Surgical salvage of HNSCC (larynx, oral cavity, oropharynx, or hypopharynx) with curative intent. Primary outcome was survival 1 year after salvage surgery. Secondary outcomes were length of inpatient hospital stay, days of admissions, and skilled nursing facility disposition within 1 year stratified by survival status. Presalvage Charlson-Age Comorbidity Index (CACI) was calculated. Associations among CACI, oncologic risk factors, and risk of death within 1 year after salvage surgery are investigated using multivariable analysis. Of 191 patients studied, 53 (27.7%) died within 1 year after salvage surgery. Patients who died within 1 year had more total inpatient admissions (P < .001), longer total length of stay (P < .001), and higher risk of discharge to a skilled nursing facility (P < .001) and spent 17.3% (interquartile range, 5.2-36.3) of their remaining days in the hospital. Independent risk factors for death within 1 year are CACI (relative risk [RR], 1.43; 95% CI, 1.16-1.76), primary T3 or T4 stage (RR, 2.34; 95% CI, 1.27-4.31), and disease-free interval of less than 6 months (RR, 5.61; 95% CI, 1.78-16.7). Medical comorbidity and age as measured by the CACI, primary T3 or T4 stage, and short disease-free interval must be considered in selecting patients ideal for surgical salvage surgery for recurrent HNSCC. Patients with these risk factors should be more strongly considered for palliative measures.


Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.
Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression.


Site of palmitoylation of a phospholipase C-resistant glycosylphosphatidylinositol membrane anchor.
The site of palmitoylation of the phosphatidylinositol moiety of the glycosyl-phosphatidylinositol membrane anchor of Trypanosoma brucei procyclic acidic repetitive protein was studied by using periodate oxidation. Analysis of the products by g.c.-m.s. allowed the assignment of 40 and 60% of the palmitate to the 2-position and the 3-position respectively of the myo-inositol ring.


Hoarseness - what is the voice trying to tell you?
Most episodes of hoarseness are benign and self limiting. This article describes the causes and management of hoarseness in adults, outlines the features of common causes of voice disturbance in adults, and highlights a number of red flags that should trigger urgent referral. Patients with hoarseness lasting more than 3 weeks require specialist assessment to visualise the larynx.


Comparison of the accuracy of intraocular lens power calculations for cataract surgery in eyes after phototherapeutic keratectomy.
To compare the accuracy of several methods of intraocular lens (IOL) power calculations used for cataract surgery in eyes treated with phototherapeutic keratectomy (PTK) that results in changes in the anterior corneal surface and axial length; these results make power calculations less predictable. We evaluated the medical records of 23 eyes of 13 patients (mean age, 68.8 years; range 62-80 years) who underwent cataract surgery after PTK at Keio University Hospital, Tokyo, Japan. The prediction error, defined as the difference between the estimated postoperative spherical equivalent and the postoperative manifest refraction at the spectacle plane, was calculated using five formulas: SRK/T, Haigis-L, Shammas-PL, Camellin-Calossi, and OKULIX ray tracing software. We compared the median values of the arithmetic and absolute prediction errors among the five formulas. The median arithmetic errors after cataract surgery for the five formulas were 0.70 D (diopter) (range -0.41 to 2.78), -0.96 D (range -2.14 to 0.81), -0.81 D (range -1.89 to 1.15), -0.04 D (range -1.35 to 1.47), and 0.68 D (range -0.61 to 2.50), respectively. The Camellin-Calossi formula is a good option for calculating IOL powers in eyes that underwent PTK.


Glutathione improves the function of porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.
Flush perfusion with low-potassium dextran is the standard strategy in clinical lung preservation. Despite improved outcome, endothelial cell injury and surfactant dysfunction remain a significant problem after lung transplantation. The radical scavenger glutathione has been shown to be responsible for the efficacy of Celsior solution in lung preservation. We tested the hypothesis that the addition of glutathione to low-potassium dextran might further improve graft function by ameliorating ischemia-reperfusion injury. In 12 domestic pigs, lungs were flush preserved with either low-potassium dextran (n = 6) or low-potassium dextran supplemented by 5 mmol glutathione (n = 6). Left single lung transplantation was performed after 24-hour storage in low-potassium dextran at 8 degrees C. After 15 minutes of reperfusion the right main bronchus and pulmonary artery were crossclamped. Hemodynamic and respiratory measures were recorded in 30-minute intervals for a total observation period of 7 hours. Bronchoalveolar lavage fluid was obtained from the native lung and 2 hours after reperfusion from the graft. Bronchoalveolar lavage fluid and surfactant composition, and surfactant function analyses were performed. Neutrophil sequestration was assessed by myeloperoxidase activity assay. Tissue water content was calculated from wet/dry weight ratios at the end of the experiment. In the low-potassium dextran group, 2 animals died during reperfusion. After reperfusion, pulmonary vascular resistance (P = .01) and pulmonary artery pressure remained lower in the glutathione/low-potassium dextran group, which was associated with a higher cardiac output (P = .05) in this group. Also, the oxygenation index at the end of the observation period was higher in the glutathione/low-potassium dextran group compared with the low-potassium dextran group (430 +/- 130 vs 338 +/- 184, respectively; P < .05). The graft water content representing postreperfusion lung edema was not different between the 2 study groups. Alteration of surfactant was less in the glutathione/low-potassium dextran group with a significantly decreased small to large aggregate ratio (P = .03) versus low-potassium dextran group. Myeloperoxidase activity was twice as high in the low-potassium dextran group when compared with the glutathione/low-potassium dextran group (glutathione/low-potassium dextran: 134 +/- 110 mU/g vs low-potassium dextran: 274 +/- 168 mU/g, P = .07). The addition of glutathione to low-potassium dextran preservation solution reveals beneficial effects on vascular function and surfactant composition in transplanted lungs. Therefore, glutathione ameliorates ischemia-reperfusion injury in a preclinical model of lung transplantation. Future studies are needed to evaluate this promising modification in clinical lung transplantation.


A potential smoothing algorithm accurately predicts transmembrane helix packing.
Potential smoothing, a deterministic analog of stochastic simulated annealing, is a powerful paradigm for the solution of conformational search problems that require extensive sampling, and should be a useful tool in computational approaches to structure prediction and refinement. A novel potential smoothing and search (PSS) algorithm has been developed and applied to predict the packing of transmembrane helices. The highlight of this method is the efficient manner in which it circumvents the combinatorial explosion associated with the large number of minima on multidimensional potential energy surfaces in order to converge to the global energy minimum. Here we show how our potential smoothing and search method succeeds in finding the global minimum energy structure for the glycophorin A (GpA) transmembrane helix dimer by optimizing interhelical van der Waals interactions over rigid and semi-rigid helices. Structures obtained from our ab initio predictions are in close agreement with recent experimental data.


Electronic micropipettor: a versatile fluid propulsion and injection device for micro-flow analysis.
The shortage of ready to use small sized liquid propulsion and switching devices for microfluidic cells (micro-cell) is a bottleneck in the dissemination of micro-flow analysis (mu-FA), now that microfluidic electrochemical cells can be designed and assembled in any laboratory by thermal transfer of laser printed masks and CD-Rs. Microprocessor-controlled electronic pipettors, commercially available with minimum capacity of 10 microL, represent a compromise solution between oversized peristaltic pumps and tiny "on a chip" micropumps and valves. The versatility of the electronic pipette coupled with the mu-cell (13-microm deep longitudinal channel) was demonstrated in three operation modes: SIA like, FIA like and direct injection analysis (DIA). Injections of 100 nL K4Fe(CN)6 (0.1 mol L(-1) KCl) define a linear analytical curve (r=0.999) in the range of 5 x 10(-7) to 1.0 x 10(-3) mol L(-1) for flow amperometry at a gold electrode potentiostated at 0.4V versus Ag/AgCl. Methods for the amperometric mu-flow determination of promethazine (FIA like), dipyrone (SIA like) and chlorpromazine (DIA) in pharmaceutical formulations were developed and applied to real samples. Excellent linearity of analytical curves and high repeatability (R.S.D.<3.0%) at the low picomole range was obtained and all results for real samples were in agreement with reference methods. The results reflect the stability and the reliability of the setups envisioned for the electronic pipette coupled with amperometric mu-cell and the validity of the mu-FA methods.


Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability.
To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.


Reconstruction of the denuded nasoseptal flap donor site with a free fascia lata graft: technical note.
The nasoseptal flap provides hearty vascularized tissue for the reconstruction of skull base defects subsequent to expanded endonasal approaches; however, it leads to exposure of the cartilage at the septal donor site producing crusting and discomfort while it remucosalizes. We report an alternative technique to reconstruct the denuded nasal septal donor site by means of a free fascia lata graft. Fascia lata grafting of the nasoseptal flap donor site showed evidence of revascularization 4 weeks after initial surgery. Re-epithelialization was complete 4-12 weeks postoperation. Although the nasoseptal flap provides a versatile reconstructive technique, its harvest results in significant donor site morbidity. A free fascia lata graft accelerates the rate of donor site remucosalization; thus, decreasing the nasal complications.


Risk Factors Associated with Symptomatic Pulmonary Embolism of Catheter Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis.
The aim was to study the risk factors associated with symptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) in the lower limbs treated by catheter directed thrombolysis (CDT) without inferior vena cava filter (IVCF) placement. A total 266 patients with acute/subacute ilio-femoral, ilio-femoropopliteal, and femoropopliteal thrombosis confirmed by computed tomography venography or ultrasound Doppler were studied. All patients were treated with CDT. CTPA (computed tomography pulmonary angiography) examination was performed in all patients before thrombolysis. Patients with clinically suspected symptomatic PE were confirmed by repeated CTPA after treatment. The major outcome of this study was the occurrence of symptomatic PE events during CDT. During CDT, the incidence of symptomatic PE events was 4.9% (13/266). Patients with silent PE had a higher risk of developing symptomatic PE (10/110, 9.1%) than those who had no prior PE (3/156, 1.9%); multivariate analysis confirmed this difference (OR 4.018, 95% CI 1.048-15.402). It was also found that patients with previous heart disease had a higher risk of developing symptomatic PE (11/90, 12.2%) than those with no prior heart disease (2/176, 1.1%). Multivariate analysis confirmed that previous heart disease increased the risk of developing symptomatic PE (OR 10.407, 95% CI 2.228-48.617). One patient who suffered from heart failure and silent PE before CDT died of symptomatic PE (1/13, 7.7%). The risk of developing symptomatic PE is most markedly increased in patients with previous silent PE and heart disease. Selective rather than routine IVCF placement is an appropriate approach.


p53/TP53 Status Assessment in Gastroesophageal Adenocarcinoma.
Chromosomal instability (CIN) is very frequent in gastroesophageal adenocarcinoma (GEA) and it is characterized by TP53 deletions/mutations resulting in p53 nuclear accumulation, as revealed by immunohistochemistry (IHC), which considers the cases with "high" staining levels to be positive. Aiming to improve aberrant TP53 detection, droplet digital PCR (ddPCR) was used to evaluate TP53 deletion in formalin-fixed, paraffin-embedded DNA (FFPE-DNA) and cell-free DNA (cfDNA). To further investigate the mutational TP53 profile, next-generation sequencing (NGS) was performed in a subset of FFPE samples. After combining "low" and "high" IHC staining level groups, the proportion of deletion events was significantly higher compared to the "intermediate" group (72.9% vs. 47.5%, p-value = 0.002). The ddPCR TP53 deletion assay was feasible for cfDNA but only had good agreement (72.7%, Cohen's kappa = 0.48) with the assay performed with FFPE-DNA of the "low-level" group. NGS analysis confirmed that, in the "low-level" group, a high percentage (66.7%) of cases were aberrant, with disruptive mutations that probably led to p53 loss. Data suggested that p53 IHC alone underestimates the CIN phenotype in GEA and that molecular analysis in both solid and liquid biopsies could be integrated with it; in particular, in cases of completely negative staining.


The effect of intralesional interferon gamma on basal cell carcinomas.
This open label study evaluated the effect of nine intralesional injections of two different doses of interferon gamma on basal cell carcinomas in 29 patients. One group of 15 patients received interferon gamma, 0.01 mg (20,000 IU), intralesionally three times a week for 3 weeks. Fourteen patients received interferon gamma, 0.05 mg (100,000 IU), intralesionally in the same dosage schedule. Excisional biopsy specimens 12 weeks after therapy showed no evidence of tumor remaining in 7 of 14 patients (50%) treated with the higher dose of interferon gamma, whereas only 1 of 15 patients (7%) treated with low-dose interferon gamma was cured according to histologic criteria (p = 0.025). Seventy-six percent of patients reported at least one adverse reaction, but most were considered mild by the patient and the investigator.


Fatigue Life of Reciproc and Mtwo instruments subjected to static and dynamic tests.
This study evaluated the influence of flexibility and reciprocating movement on the fatigue life of endodontic instruments subjected to static and dynamic tests. The rotary nickel-titanium instruments used in this study were Reciproc and Mtwo. The instruments were initially subjected to a cantilever-bending test and then to static and dynamic fatigue tests. Reciproc instruments were operated in reciprocating movement, whereas Mtwo instruments were worked in continuous rotation. The means of bending resistance (maximum load in grams) of the instruments were 274.9 for Reciproc and 429 for Mtwo. The mean times (in seconds) to fracture of the instruments subjected to static and dynamic tests were 214.5 (static) and 286.3 (dynamic) for Reciproc and 38.9 (static) and 99 (dynamic) for Mtwo. The Student's t test revealed significant differences in all tests (P < .05). The results of the present study showed longer fatigue life for instruments with higher flexibility, driven by reciprocating movement, and in the dynamic testing model. These findings reinforce the assumption that use of reciprocating movement is a means to prolong the fatigue life of rotary nickel-titanium endodontic instruments during instrumentation of curved canals.


Improved glycemic status, insulin resistance and inflammation after receiving oral oleoylethanolamide supplement in people with prediabetes: a randomized controlled trial.
The anti-inflammatory properties of cannabinoids have been shown. This study was conducted to assess effect of oleoylethanolamide (OEA) supplementation on glycemic status, insulin resistance (IR) and inflammatory factor in pre-diabetic individuals. This double-blind randomized clinical trial was done at Qazvin University of Medical Sciences in which 46 pre-diabetic patients were divided into two equal groups and received one 125 mg OEA capsule in the intervention group (23 subjects) and 125 mg capsule containing wheat flour in placebo group daily for 8 weeks. After collecting demographic information, at the beginning and end of the study, the questionnaires of physical activity, 24-hour food recall were completed and blood glucose (BG), plasma insulin level, IR, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) were measured. Statistical analysis was performed using SPSS software. At the beginning and end of the study, there was no significant difference between the two groups in terms of anthropometric indices, food intake and physical activity (P > 0.05). At the end of the study, consumption of OEA significantly reduced BS, insulin, IR, HbA1c, and CRP (P < 0.05). No significant change was observed in mentioned biochemical factors in placebo group (P > 0.05). Given that OEA supplementation improved the glycemic status, IR and reduced the inflammatory factor, use of this supplement can be introduced as a useful supplement to control pre-diabetes status. The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials ( http://www.IRCT.IR , identifier: IRCT20141025019669N16).


Evaluation of a cost effective technique for treating aquaculture water discharge using Lolium perenne Lam as a biofilter.
Wastewater stabilization ponds generate low cost by-products that are useful for agriculture. The utilization of these by-products for soil amendment and as a source of nutrients for plants requires a high level of sanitation and stabilization of the organic matter, to maintain acceptable levels of soil, water and air quality. In this study, two aquaculture wastewater treatment systems; recirculating system and a floating plant bed system were designed to improve the quality of irrigation water in local communities with low income. In both systems the grass species Lolium perenne Lam was used as a plant biofilter while vegetable specie Amaranthus viridis was used to evaluate the performance of the system and the suitability of the phyto-treated water for irrigation. It was found that the harmful material removal rate for recirculating system was 88.9% for TAN (total ammonia nitrogen), 90% for NO2(-)-N, 64.8% for NO3(-)-N while for floating plant bed system 82.7% for TAN, 82% for NO2(-)-N and 60.5% for NO3(-)-N. Comparative analysis of the efficiency of waste element removal between the two systems revealed that both systems performed well, however, plant growth was not robust for floating plant bed system while recirculating system is energy consuming. Although both systems did not attain sufficient levels of TN (total nitrogen) and TP (total phosphorus) load reduction, the treatment with L. perenne remarkably improved the irrigation water quality. A. viridis plants irrigated with the phyto-treated discharge water had lesser concentrations of heavy metals in their tissues compared to those irrigated with untreated discharge. The control plants irrigated with untreated discharge were also found to be highly lignified with few stems and small leaves.


Photodynamic therapy for choroidal neovascularization in pediatric patients.
To report the use of photodynamic therapy (PDT) for choroidal neovascularization (CNV) in pediatric patients. Five patients (age range, 7-15 years) who underwent PDT for idiopathic CNV (n = 2) or CNV secondary to macular toxoplasmic scar (n = 3) were included in this study. Follow-up ranged from 12 months to 18 months. PDT was performed according to the standard protocol. We evaluated visual acuity, fluorescein leakage from the CNV, greatest linear dimension of the lesion, and occurrence of ocular or systemic adverse events at baseline and during follow-up. No severe or moderate visual loss occurred in all cases during follow-up. PDT reduced CNV leakage in four cases. No serious ocular or systemic adverse events were recorded. Retinal pigment epithelium atrophic changes were observed around the regressed CNV, but they did not appear to cause visual loss. PDT was safe for pediatric patients, and visual acuity was substantially stable after one or few treatments. Further follow-up is needed to assess if retinal pigment epithelium atrophic changes around the regressed CNV, possibly related to PDT, could affect vision in the long term.


Multitopic 3,2':6',3''-terpyridine ligands as 4-connecting nodes in two-dimensional 4,4-networks.
The tetratopic 1,4-bis(2-phenylethoxy)-2,5-bis(3,2':6',3''-terpyridin-4'-yl)benzene (1) and 1,4-bis(3-phenylpropoxy)-2,5-bis(3,2':6',3''-terpyridin-4'-yl)benzene (2) ligands have been prepared and fully characterised. Combination of ligand 1 or 2 and [M(hfacac)2]·xH2O (M = Cu, x = 1; M = Zn, x = 2) under conditions of crystal growth by layering led to the formation of [Cu2(hfacac)4(1)] n ·3.6n(1,2-Cl2C6H4)·2nCHCl3, [Zn2(hfacac)4(1)] n ·nMeC6H5·1.8nCHCl3, [Cu2(hfacac)4(2)] n ·nMeC6H5·2nH2O, [Cu2(hfacac)4(2)] n ·2.8nC6H5Cl and [Cu2(hfacac)4(2)] n ·2n(1,2-Cl2C6H4)·0.4nCHCl3·0.5nH2O. For each compound, single-crystal X-ray analysis revealed the assembly of a planar (4,4)-net in which the tetratopic ligands 1 or 2 define the nodes. The metal centres link two different bis(3,2':6',3''-tpy) ligands via the outer pyridine rings; whereas copper(ii) has N-donors in a trans-arrangement, zinc(ii) has them in cis. This difference between the copper(ii) and zinc(ii) coordination polymers modifies the architecture of the assembly without changing the underlying (4,4)-network.


Treatment of Molluscum Contagiosum with Imiquimod in the United States: A Retrospective Cross-Sectional Study.
Since there are concerns that imiquimod is being overprescribed for children with molluscum despite its limited efficacy, we used data from two nationally representative surveys to determine the rate at which imiquimod was being prescribed for molluscum contagiosum in the United States. From 1999-2010, there were an estimated 6.4 million visits for molluscum (95% CI: 5.5, 7.3 million), and imiquimod was prescribed at 7.0% of these visits (95% CI: 3.4, 11). Given the low frequency of patients being treated with imiquimod for molluscum, the concerns of its overuse may be unfounded.


Cyclooxygenase-2 facilitates dengue virus replication and serves as a potential target for developing antiviral agents.
Cyclooxygenase-2 (COX-2) is one of the important mediators of inflammation in response to viral infection, and it contributes to viral replication, for example, cytomegalovirus or hepatitis C virus replication. The role of COX-2 in dengue virus (DENV) replication remains unclear. In the present study, we observed an increased level of COX-2 in patients with dengue fever compared with healthy donors. Consistent with the clinical data, an elevated level of COX-2 expression was also observed in DENV-infected ICR suckling mice. Using cell-based experiments, we revealed that DENV-2 infection significantly induced COX-2 expression and prostaglandin E2 (PGE2) production in human hepatoma Huh-7 cells. The exogenous expression of COX-2 or PGE2 treatment dose-dependently enhanced DENV-2 replication. In contrast, COX-2 gene silencing and catalytic inhibition sufficiently suppressed DENV-2 replication. In an ICR suckling mouse model, we identified that the COX-2 inhibitor NS398 protected mice from succumbing to life-threatening DENV-2 infection. By using COX-2 promoter-based analysis and specific inhibitors against signaling molecules, we identified that NF-κB and MAPK/JNK are critical factors for DENV-2-induced COX-2 expression and viral replication. Altogether, our results reveal that COX-2 is an important factor for DENV replication and can serve as a potential target for developing therapeutic agents against DENV infection.


1-D and 2-D NMR-based metabolomics of earthworms exposed to endosulfan and endosulfan sulfate in soil.
One-dimensional (1-D) and two-dimensional (2-D) nuclear magnetic resonance (NMR)-based metabolomics was used to investigate the toxic mode of action (MOA) of endosulfan, an organochlorine pesticide, and its degradation product, endosulfan sulfate, to Eisenia fetida earthworms in soil. Three soil concentrations (0.1, 1.0 and 10.0 mg/kg) were used for both endosulfan and endosulfan sulfate. Both earthworm coelomic fluid (CF) and tissues were extracted and then analyzed using (1)H and (1)H-(13)C NMR techniques. A similar separation trajectory was observed for endosulfan and endosulfan sulfate-exposed earthworms in the mean principal component analysis (PCA) scores plot for both the earthworm CF and tissue extracts. A neurotoxic and apoptotic MOA was postulated for both endosulfan and endosulfan sulfate exposed earthworms as significant fluctuations in glutamine/GABA-glutamate cycle metabolites and spermidine were detected respectively. This study highlights the application of NMR-based metabolomics to understand molecular-level toxicity of persistent organochlorine pesticides and their degradation products directly in soil.


ChIPCodis: mining complex regulatory systems in yeast by concurrent enrichment analysis of chip-on-chip data.
Eukaryotic genes are often regulated by multiple transcription factors (TFs). Depending on the interactions among different TFs the expression of a gene can be tuned to respond to diverse environmental conditions. Chip-on-chip experiments provide a snapshot of which TF are in vivo bound to which genes in a particular condition, and have been applied to characterize the regulatory code of yeast under several experimental settings. ChIPCodis mines this data to provide new insights about how the expression of a particular group of genes is regulated. For a given list of yeast genes ChIPCodis determines which combinations of TFs are significantly over-represented in a series of environmental conditions. http://chipcodis.dacya.ucm.es


Role of the glycosyl-phosphatidylinositol anchor in the intracellular transport of a transmembrane protein in Madin-Darby canine kidney cells.
In order to compare the trafficking of proteins with different membrane anchors, we have constructed and expressed three different recombinant forms of neutral endopeptidase (NEP) in MDCK cells. The wild type form of NEP (WT-NEP) is attached to the plasma membrane by a single N-terminal membrane spanning domain, whereas the glycosylphosphatidylinositol-anchored form of the protein (GPI-NEP) contains a C-terminal GPI anchor. A double anchored form of NEP (DA-NEP) was also constructed, that contains both the original N-terminal membrane spanning domain and a C-terminal GPI anchor. We show here that WT-NEP, GPI-NEP and DA-NEP, which are all apically targeted in MDCK cells, behave differently when subjected to Triton X-100 solubilisation: despite the presence of the transmembrane anchor DA-NEP behaves as a GPI-anchored protein. This suggests that the GPI anchor of DA-NEP is dominant over the transmembrane anchor of the native protein to determine its pattern of solubility in Triton X-100.


Assessment of Knowledge, Attitude, and Practice of Iranian Nurses towards Toothbrush Maintenance and Use.
Since nurses are considered a role model in society, they should have sufficient knowledge, attitude, and practice in the field of oral hygiene. This study was aimed to assess the nurses' knowledge, practice, and attitude towards toothbrush maintenance and use. In this cross-sectional study, 325 nurses working in hospitals affiliated to Kermanshah University of Medical Sciences were randomly recruited. Data collection tools included a demographic information form and a researcher-made questionnaire on knowledge, attitude, and practice regarding toothbrush maintenance and use. Data were analyzed by SPSS software using descriptive and inferential statistics (Mann-Whitney U and Kruskal-Wallis H). The mean scores of nurses' knowledge, attitude, and practice were 59.2 ± 16.4, 64.2 ± 20.6, and 51.4 ± 17.0 out of 100, respectively. There was no statistically significant relation between nurses' knowledge, attitude, and practice and their gender, age, level of education, and work experience. Nurses had moderate knowledge, attitude, and practice regarding toothbrush maintenance and use, which is not very desirable given their role model. Therefore, training courses are recommended to be held to increase the nurses' knowledge, attitude, and practice regarding toothbrush maintenance and use.


Incidence, timing, location, risk factors, and nomogram of lower extremity deep venous thrombosis after acute carbon monoxide poisoning.
Data on lower extremity deep venous thrombosis (DVT) following acute carbon monoxide (CO) poisoning are lacking. This study aimed to identify the incidence rate, timing, locations, risk factors, and nomogram of lower extremity DVT after acute CO poisoning. A total of 203 patients with acute CO poisoning from October 2019 to April 2021 were included in this retrospective study. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with lower extremity DVT. Nomogram was drawn and area under the curve (AUC) was calculated to predict lower extremity DVT. Overall, 14.3% (29/203) had lower extremity DVT, with incidence rates of 2.5% (5/203) for proximal DVT and 11.8% (24/203) for distal DVT. The lower extremity DVTs involved intermuscular vein in 28 patients, popliteal vein in 5 patients, and posterior tibial vein in 3 patients. The mean time from end of exposure to diagnosis of lower extremity DVT was 1.24 days. Among 29 lower extremity DVT cases, 6 (23.1%) DVT cases had thrombolysis. Multivariate logistic regression analysis revealed that long coma duration (P < 0.001) and high D-dimer levels (P < 0.001) were significantly associated with lower extremity DVT. The discrimination of nomogram was good with AUC of 0.93 (95% CI, 0.89-0.98). Clinicians should be aware of and concerned with lower extremity DVT after acute CO poisoning, especially in patients with long coma duration and high D-dimer levels.


A global perspective on risk factors for frailty in community-dwelling older adults: A systematic review and meta-analysis.
Frailty has become an important determinant of a series of adverse health outcomes. We explored the risk factors for frailty in older adults in the community from a global perspective and explore whether there are ethnic differences in these risk factors. The systematic review and meta-analysis (PROSPERO registration number: CRD42022323342) was searched using six electronic databases, including PubMed, Embase, the Cochrane Library, Web of Science, PsycINFO (EBSCO) and CINAHL (EBSCO) from inception to October 2021. We assessed study eligibility by inclusion and excluded criteria. Cohort studies included were assessed according to the Newcastle-Ottawa Scale. Cross-sectional studies were assessed by the bias risk evaluation standard recommended by the Agency for Health care Research and Quality. The results were reported by a narrative synthesis and pooled analyses. Statistical analyses were performed in Review Manager 5.3 software. We reviewed 10870 studies, and 62 studies were included. The results showed a significant association between multidomain risk factors and the frailty of global older adults, including demographic factors, health-related factors, and physical factors. Marital status, depression, risk of malnutrition, history of falls and disease-related symptoms are also risk factors for frailty among older people in Asia. Multiple domain factors were associated with frailty among older people around the world. Compared with the rest of the world, Asian populations are exposed to more risk factors for frailty. Therefore, health care providers should consider the characteristics of risk factors for frailty in this region when formulating intervention measures related to frailty.


Treatment options for vancomycin-resistant enterococcal infections.
Serious infection with vancomycin-resistant enterococci (VRE) usually occurs in patients with significantly compromised host defences and serious co-morbidities, and this magnifies the importance of effective antimicrobial treatment. Assessments of antibacterial efficacy against VRE have been hampered by the lack of a comparator treatment arm(s), complex treatment requirements including surgery, and advanced illness-severity associated with a high crude mortality. Treatment options include available agents which don't have a specific VRE approval (chloramphenicol, doxycycline, high-dose ampicillin or ampicillin/sulbactam), and nitrofurantoin (for lower urinary tract infection). The role of antimicrobial combinations that have shown in vitro or animal-model in vivo efficacy has yet to be established. Two novel antimicrobial agents (quinupristin/ dalfopristin and linezolid) have emerged as approved therapeutic options for vancomycin-resistant Enterococcus faecium on the basis of in vitro susceptibility and clinical efficacy from multicentre, pharmaceutical company-sponsored clinical trials. Quinupristin/dalfopristin is a streptogramin, which impairs bacterial protein synthesis at both early peptide chain elongation and late peptide chain extrusion steps. It has bacteriostatic activity against vancomycin-resistant E. faecium [minimum concentration to inhibit growth of 90% of isolates (MIC(90)) = 2 microg/ml] but is not active against Enterococcus faecalis (MIC(90 )= 16 microg/ml). In a noncomparative, nonblind, emergency-use programme in patients who were infected with Gram-positive isolates resistant or refractory to conventional therapy or who were intolerant of conventional therapy, quinupristin/dalfopristin was administered at 7.5 mg/kg every 8 hours. The clinical response rate in the bacteriologically evaluable subset was 70.5%, and a 65.8% overall response (favourable clinical and bacteriological outcome) was observed. Resistance to quinupristin/dalfopristin on therapy was observed in 6/338 (1.8%) of VRE strains. Myalgia/arthralgia was the most frequent treatment-limiting adverse effect. In vitro studies which combine quinupristin/dalfopristin with ampicillin or doxycyline have shown enhanced killing effects against VRE; however, the clinical use of combined therapy remains unestablished. Linezolid, an oxazolidinone compound that acts by inhibiting the bacterial pre-translational initiation complex formation, has bacteriostatic activity against both vancomycin resistant E. faecium (MIC(90) = 2 to 4 microg/ml) and E. faecalis (MIC(90) = 2 to 4 microg/ml). This agent was studied in a similar emergency use protocol for multi-resistant Gram-positive infections. 55 of 133 evaluable patients were infected with VRE. Cure rates for the most common sites were complicated skin and soft tissue 87.5% (7/8), primary bacteraemia 90.9% (10/11), peritonitis 91.7% (11/12), other abdominal/pelvic infections 91.7% (11/12), and catheter-related bacteraemia 100% (9/9). There was an all-site response rate of 92.6% (50/54). In a separate blinded, randomised, multicentre trial for VRE infection at a variety of sites, intravenous low dose linezolid (200mg every 12 hours) was compared to high dose therapy (600 mg every 12 hours) with optional conversion to oral administration. A positive dose response (although statistically nonsignificant) was seen with a 67% (39/58) and 52% (24/46) cure rate in the high- and low-dose groups, respectively. Adverse effects of linezolid therapy have been predominantly gastrointestinal (nausea, vomiting, diarrhoea), headache and taste alteration. Reports of thrombocytopenia appear to be limited to patients receiving somewhat longer courses of treatment (>14 to 21 days). Linezolid resistance (MIC > or = 8 microg/ml) has been reported in a small number of E. faecium strains which appears to be secondary to a base-pair mutation in the genome encoding for the bacterial 23S ribosome binding site. At present a comparative study between the two approved agents for VRE (quinupristin/dalfopristin and linezolid) has not been performed. Several investigational agents are currently in phase II or III trials for VRE infection. This category includes daptomycin (an acidic lipopeptide), oritavancin (LY-333328; a glycopeptide), and tigilcycline (GAR-936; a novel analogue of minocycline). Finally, strategies to suppress or eradicate the VRE intestinal reservoir have been reported for the combination of oral doxycyline plus bacitracin and oral ramoplanin (a novel glycolipodepsipeptide). If successful, a likely application of such an approach is the reduction of VRE infection during high risk periods in high risk patient groups such as the post-chemotherapy neutropenic nadir or early post-solid abdominal organ transplantation.


Basaloid carcinoma, a rare primary lung neoplasm: report of a case and review of the literature.
Basaloid carcinoma of the lung is a rare primary neoplasm, first described in 1992. Basaloid carcinoma is an aggressive subtype of Non small cell lung cancer, with poor 5-year survival, even in stage I and II resected tumors. Differential diagnosis from small cell, Neuroendocrine large cell and poorly differentiated squamous cell carcinoma is difficult to be made. We report a patient with lung basaloid carcinoma, initially diagnosed and treated as small cell carcinoma. Thoracotomy and resection of the tumor following chemotherapy, established the correct diagnosis.


Transcription and polyadenylation processes during early development of quail embryo.
Transcription of tRNA and mRNA occurs in quail as early as during cleavage while rRNA transcription becomes measurable during blastulation. The polyadenylated fraction content is newly synthesized RNA amounting to 6% during cleavage and blastulation decreases to 3% during gastrulation. Up to 3/4 adenylic residues incorporated into RNA during cleavage are accumulated in the polyadenylated molecules mainly in the form of RNAse-resistant tracts.


Potential anticancer agents: 5-(N-substituted-aminocarbonyl)- and 5-(N-substituted-aminothiocarbonyl)-5,6,7,8-tetrahydrofolic acids.
5-[[N-[(Ethoxycarbonyl)alkyl]amino]carbonyl] (6-9) and the corresponding aminothiocarbonyl (12-15) derivatives of 5,6,7,8-tetrahydrofolic acid were prepared as multisubstrate analogues of the substrate--cofactor adduct in the reactions catalyzed by the folate-mediated one-carbon transfer reactions. Evaluation in vitro showed that 7 (alkyl = hexyl) was cytotoxic to H.Ep.-2 cells (ED50, 4 microM) but noncytotoxic to proliferating L1210 cells. No activity was observed for 7 against the P388 leukemia in mice.


Identification, molecular characterization and phylogenetic analysis of a novel nucleorhabdovirus infecting Paris polyphylla var. yunnanensis.
A novel betanucleorhabdovirus infecting Paris polyphylla var. yunnanensis, tentatively named Paris yunnanensis rhabdovirus 1 (PyRV1), was recently identified in Yunnan Province, China. The infected plants showed vein clearing and leaf crinkle at early stage of infection, followed by leaf yellowing and necrosis. Enveloped bacilliform particles were observed using electron microscopy. The virus was mechanically transmissible to Nicotiana bethamiana and N. glutinosa. The complete genome of PyRV1 consists of 13,509 nucleotides, the organization of which was typical of rhabdoviruses, containing six open reading frames encoding proteins N-P-P3-M-G-L on the anti-sense strand, separated by conserved intergenic regions and flanked by complementary 3'-leader and 5'-trailer sequences. The genome of PyRV1 shared highest nucleotide sequence identity (55.1%) with Sonchus yellow net virus (SYNV), and the N, P, P3, M, G, and L proteins showed 56.9%, 37.2%, 38.4%, 41.8%, 56.7%, and 49.4% amino acid sequence identities with respective proteins of SYNV, suggesting RyRV1 belongs to a new species of the genus Betanucleorhabdovirus.


Non-linear analysis of EEG signals at various sleep stages.
Application of non-linear dynamics methods to the physiological sciences demonstrated that non-linear models are useful for understanding complex physiological phenomena such as abrupt transitions and chaotic behavior. Sleep stages and sustained fluctuations of autonomic functions such as temperature, blood pressure, electroencephalogram (EEG), etc., can be described as a chaotic process. The EEG signals are highly subjective and the information about the various states may appear at random in the time scale. Therefore, EEG signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. The sleep data analysis is carried out using non-linear parameters: correlation dimension, fractal dimension, largest Lyapunov entropy, approximate entropy, Hurst exponent, phase space plot and recurrence plots. These non-linear parameters quantify the cortical function at different sleep stages and the results are tabulated.


Pulse energy measurement at the SXR instrument.
A gas monitor detector was implemented and characterized at the Soft X-ray Research (SXR) instrument to measure the average, absolute and pulse-resolved photon flux of the LCLS beam in the energy range between 280 and 2000 eV. The detector is placed after the monochromator and addresses the need to provide reliable absolute pulse energy as well as pulse-resolved measurements for the various experiments at this instrument. This detector provides a reliable non-invasive measurement for determining flux levels on the samples in the downstream experimental chamber and for optimizing signal levels of secondary detectors and for the essential need of data normalization. The design, integration into the instrument and operation are described, and examples of its performance are given.


The Natural Course of Intermittent Exotropia over a 3-year Period and the Factors Predicting the Control Deterioration.
The natural course of intermittent exotropia and the factors affecting its control has been unclear. We aim to report the natural course of our cohort of 117 Chinese children with intermittent exotropia and to identify baseline parameters that may have predictive value in the control deterioration of the disease. The visual acuity, spherical equivalent, compliance to orthoptic exercise, angle of deviation fusional convergence parameters and Newcastle Control Score were recorded for all children at baseline and at 3 years apart. Patients were divided into two groups according to the change in control over the 3 years: group 1 included patients who had no deterioration or had improvement in disease control; and group 2 were those who had deteriorated control or had undergone surgery. There were 77 patients (66%) in group 1 and 40 (34%) patients in group 2. Comparing the baseline parameters of the two groups, group 1 had statistically significantly smaller angle of deviation, larger fusional reserve, larger fusional recovery, and higher fusional reserve ratio (p < 0.05). Other baseline parameters were similar between the two groups. The baseline fusional parameters may have predictive value in determining the control of intermittent exotropia.


Direct, non-destructive quantitative measurement of an active pharmaceutical ingredient in an intact capsule formulation using Raman spectroscopy.
The active pharmaceutical ingredient (ambroxol) in an intact capsule formulation has been non-destructively quantified using Raman spectroscopy. To improve the problem of insufficient representative sampling inherent in Raman measurements, we have employed a wide area illumination (WAI) scheme that enables much improved sample coverage through a circular excitation laser spot with a 6 mm diameter. One of the anticipated sources of variation for this measurement was variation in the capsule shells. However, the WAI scheme significantly decreased the spectral variation among empty capsules compared to a measurement with a traditional small-spot excitation. Therefore, measurement variations emanating from the capsule shell did not significantly influence the accuracy of the determination of ambroxol concentrations. The resulting standard error of prediction (SEP) using the WAI scheme was comparable to that from previous Raman measurements which used a conventional small-spot excitation and employed a sampling scheme that involved rotation of an ambroxol pellet. It is further noteworthy that the SEP was also similar to that obtained from the use of transmission NIR spectroscopy, which was achieved by collection of spectra of the powdered capsule contents removed from the shell. The proposed Raman measurement using the WAI scheme in this case was sufficient to achieve the quantitative measurement of the active pharmaceutical ingredient (API) content of capsules non-destructively.


Iridium nanoclusters as high sensitive-tunable elemental labels for immunoassays: Determination of IgE and APOE in aqueous humor by inductively coupled plasma-mass spectrometry.
Iridium nanoclusters (IrNCs) stabilized with citrate were synthesized and then the ligand was exchanged by lipoic acid (LA). The IrNCs@LA were bioconjugated through carbodiimide chemistry with specific antibodies to prepare IrNCs-labelled immunoprobes. The IrNCs-immunoprobes were employed in competitive immunoassays for immunoglobulin E (IgE) and apolipoprotein E (APOE) determination by detecting the iridium through inductively coupled plasma - mass spectrometry (ICP-MS). The IrNCs@LA have a 1.89 nm diameter at average and each NC contains 250 Ir atoms. Labelling of specific antibodies with IrNCs was optimized in terms of recognition capabilities and signal amplification by ICP-MS. Amplification and detection limits can be tuned by selecting the IrNCs:Ab molar ratio. An immunoprobe prepared by mixing a 10:1 IrNC:Ab molar ratio was selected for the determination of IgE and APOE in aqueous humor, achieving a signal amplification of 1760 iridium atoms per molecule of the sought protein and limits of detection in the tens of pg mL-1 of protein. The IrNCs-immunoprobes were evaluated for IgE determination in serum samples as well as for IgE and APOE in aqueous humor (from controls subjects and patients affected by primary open angle glaucoma) by ICP-MS, being required just sample dilution as pre-treatment. Results were corroborated with commercial ELISA kits.


Advances in musculoskeletal radiology: multidetector computed tomography.
The clinical potential of multidetector CT is significantly increased because of the possibility of almost instantaneous isotropic reformations in all planes, increased speed and coverage, and easy interpretation. Multidetector CT has a significant role in the correct and quick diagnosis and treatment of emergency department patients. In complex anatomic regions, it is an important diagnostic aid, and it allows exact classification of the bony lesion, which is important for diagnosis, treatment, and prognosis. Multidetector CT visualizes congenital deformities and is useful in oncology. Ongoing developments comprise diagnosis and treatment, preoperative and postoperative planning, and hard-ware imaging. Relatively new but well-known applications of multidetector CT include intraoperative navigation, implant and prosthesis planning and surgery simulation, vertebroplasty, and pedicle screw installations.


Prevalence of resistant hypertension and associated factors in Japanese subjects with type 2 diabetes.
The prevalence of treatment resistant hypertension (RH) depends on methods used for blood pressure (BP) measurements, goals of BP, and therapeutic efforts in terms of medication and adherence. We focused on diabetic subjects and explored the prevalence of RH in primary care practice. In 1737 subjects with type 2 diabetes who continued regular visits, office BP was evaluated by multiple measurements over one year. RH was defined as using more than four antihypertensive drugs or failure to achieve the goal with three antihypertensive drugs from different classes. The RH prevalence was investigated with BP goals <130/80 and 140/90 mmHg. The percentage of subjects who achieved BP goals <130/80 and 140/90 were 70.5% and 93.8% with adherence to medication ≥95%, and the corresponding prevalence rates of RH in treated subjects were 28.4% and 21.8%, respectively. Factors independently associated with RH were age (odds ratio 1.02 [95% CI 1.01-1.04]), body mass index (1.10 [1.06-1.13]), variability in systolic BP (1.06 [1.02-1.09]), triglycerides (2.86 [1.34-6.11]), macroalbuminuria (3.33 [2.03-5.48]), estimated glomerular filtration rate (0.98 [0.97-0.99]), retinopathy (1.91 [1.39-2.61]), and family history of hypertension (1.85 [1.23-2.21]). Worsening albuminuria and glomerular filtration rate enhanced the prevalence of RH in a graded manner. Careful estimation of office BP values over one year with a high achievement of BP goals and adequate adherence revealed that the prevalence of RH in type 2 diabetes is high. RH was characterized by accumulation of cardiovascular genetic and environmental risks.


2nd-generation HIV surveillance and injecting drug use: uncovering the epidemiological ice-berg.
HIV/AIDS surveillance methods are under revision as the diversity of HIV epidemics is becoming more apparent. The so called "2nd generation surveillance (SGS) systems" aim to enhance surveillance by broadening the range of indicators to prevalence, behaviors and correlates, for a better understanding and a more complete and timely awareness of evolving epidemics. Concepts of HIV SGS are reviewed with a special focus on injecting drug users, a major at-risk and hard to reach group in Europe, a region with mainly low or concentrated epidemics. The scope of HIV/AIDS surveillance needs to be broadened following principles of SGS. Specifically for IDUs we propose including hepatitis C data as indicator for injecting risk in routine systems like those monitoring sexually transmitted infections and information on knowledge and attitudes as potential major determinants of risk behavior. The suggested approach should lead to more complete and timely information for public health interventions, however there is a clear need for comparative validation studies to assess the validity, reliability and cost-effectiveness of traditional and enhanced HIV/AIDS surveillance systems.


[Haloalkaliphilic actinomycetes in soils of Mongolian desert steppes].
The abundance of actinomycetes isolated from the soils of Mongolian desert steppes varies from several thousand to hundreds of thousands of CFU/g soil, depending on soil type and isolation medium. Eight actinomycete genera have been found in these soils: Streptomyces, Micromonospora, Saccharopolyspora, Actinomadura, Microtetraspora, Thermomonospora, Nocardia, and Dactylosporangium. The streptomycete complexes of brown desert-steppe and gray-brown desert alkaline soils include halophilic, alkaliphilic, and haloalkaliphilic species that grow most successfully on the media with a salt concentration of 5% and pH 8-9.


MLLT10 in benign and malignant hematopoiesis.
Non-random chromosomal translocations involving the putative transcription factor Mixed Lineage Leukemia Translocated to 10 (MLLT10, also known as AF10) are commonly observed in both acute myeloid and lymphoid leukemias and are indicative of a poor prognosis. Despite the well-described actions of oncogenic MLLT10 fusion proteins, the role of wild-type MLLT10 in hematopoiesis is not well characterized. The protein structure and several interacting partners have been described and provide indications as to the potential functions of MLLT10. This review examines these aspects of MLLT10, contextualizing its function in benign and malignant hematopoiesis.


Alterations in the microenvironment during spreading depression associated with epileptiform activity in the immature neocortex.
Local changes in extracellular ion concentrations were measured with ion-sensitive microelectrodes in slices of mature (greater than 40 days of age) or immature (16-30 days of age) rat neocortex maintained in vitro. Repetitive stimulation resulted in increases in extracellular potassium ([K+]o) to levels of 8.85 +/- 2.1 mM in slices from adult animals and 12.77 +/- 1.8 mM in slices from immature animals. During exposure to picrotoxin, maximum levels were 11.3 +/- 2.6 and 14.8 +/- 2.5 mM in the mature and immature groups, respectively. Picrotoxin (50 microM) induced spontaneous bursts of repetitive spiking, followed by a slow, negative field potential, associated with spreading depression (SD), in slices from immature animals. [K+]o levels increased to 10.2 +/- 3.9 mM during repetitive spike discharges and reached 30.3 +/- 18.5 mM during SDs. Variations in the size of the extracellular space (ES) were examined during SD. The ES was found to reversibly decrease by 39 +/- 4.5%. Clusters of repetitive spikes were associated with 0.1-0.2 mM decreases in [Ca2+]o, whereas 1.12 +/- 0.06 mM decreases were observed during SDs. Decreases in [Na+]o and [Cl-]o of 56 +/- 10 mM and 41 +/- 9 mM, respectively, were observed during SDs suggesting that a net transmembrane movement of water occurred during SDs. These results indicate that changes in [K+]o associated with epileptiform activity in the immature nervous system are quantitatively different from those observed in the mature brain. These large increases in [K+]o may contribute to the prolonged nature of epileptiform discharges in the developing nervous system.


Polycystic kidney disease in the first year of life.
To determine the frequency of autosomal recessive and autosomal dominant polycystic kidney disease (PKD) in infants and to compare the rate of progression of these conditions, we conducted a retrospective survey of 48 patients who were seen with PKD before 1 year of age and who survived the first month of age. Seventeen patients had recessive PKD; six had dominant PKD. Eighteen patients had insufficient data to categorize the type of PKD with certainty. Seven patients were classified as "other"; three had glomerulocystic disease and the remainder had multiple malformation syndromes or tuberous sclerosis. Renal ultrasonography and excretory urography accurately detected 15 of 17 patients with recessive PKD, but only one patient with dominant PKD was correctly diagnosed by excretory urography. The majority of patients in all groups required antihypertensive therapy. The 17 children with recessive PKD have been followed up for 6.1 +/- 4.3 (SD) years. Eight patients are doing well. Two patients have died; five others have required treatment for renal failure. Only one patient has an estimated glomerular filtration rate within the normal range after 6 years of age. Long-term evaluation of most of the patients with dominant PKD is not yet available; however, by age 42 months one patient has required dialysis. To provide optimum genetic counseling and accurate diagnosis for patients with PKD, a combination of careful family evaluation, radiography, and liver or kidney biopsy is required. The outcome of patients who survive the neonatal period appears not to be so grim as previously feared, underscoring the importance of aggressive supportive care and the need for physician and family education.


Hand functions in patients with schizophrenia: A clinical comparison with bipolar disorder and healthy subjects.
Failure to achieve expected level of motor functioning may be a significant contributor to social withdrawal and further attenuation of life quality in patients with schizophrenia. Hand functioning is one of the most crucial entities in that manner. This study aimed to reveal this question by means of comparing patients with schizophrenia and bipolar disorder who are receiving similar antipsychotic psychopharmacological agents along with healthy control subjects. 99 patients with schizophrenia were compared to 40 patients with bipolar disorder matched according to the received pharmacotherapy comprising similar antipsychotics and 81 medication-free socio-demographically matched healthy control subjects. The materials were Hand Functional Index (HFI), Duruoz Hand Index (DHI), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS) along with clinical characteristics. Difference in total scores of DHI and HFI between schizophrenia, bipolar disorder and control groups were extremely significant (p < 0.001). Further post-hoc subgroup analysis revealed that patients with schizophrenia demonstrated higher scores of HFI indicating worse performance when compared to both bipolar disorder and control group. Significantly higher scores of DHI in patients with schizophrenia than healthy controls were noted. Independent from the impact of the medication use, impairment in hand functions was found to be more frequently seen in schizophrenia when compared to patients with bipolar disorder and healthy subjects. It is evident that hand function impairment is seen independent from psychopharmacological side effect, and is recommended to be assessed as a possible preventable and retractable manifestation of schizophrenia.


The coevolution of Euphydryas chalcedona butterflies and their larval host plants : I. Larval feeding behavior and host plant chemistry.
The interactions between the checkerspot butterfly, Euphydryas chalcedona, and two of its principal host plants, Diplacus aurantiacus and Scrophularia californica, were studied to test the hypothesis that feeding behavior in nature reflects food quality in terms of leaf nitrogen and defensive chemical contents. Larvae preferentially fed on Diplacus leaves containing the highest nitrogen: resin ratio in the field and laboratory. Larvae did not feed selectively among Scrophularia leaves, which show little variation in quality. Seasonal timing of feeding activity and larval development rates were closely related to the availability of any Scrophularia leaves and high-quality Diplacus leaves.


The ischemic time window of ectopic endometrial tissue crucially determines its ability to develop into endometriotic lesions.
Endometriosis develop from shed endometrial fragments via retrograde menstruation. This affects the survival, proliferation and vascularization of the tissue and its final ability to form endometriotic lesions. Within this study, uterine tissue samples from donor mice were precultivated for 24 h or 72 h to simulate avascular periods. Their morphology, microvessel density, apoptotic activity and expression of angiogenesis-related proteins were analyzed in vitro. The formation of endometriotic lesions in vivo was assessed after transplantation of precultivated uterine tissue samples to the abdominal wall and dorsal skinfold chambers by means of high-resolution ultrasound, intravital fluorescence microscopy, histology and immunohistochemistry. In vitro, 72-h-precultivated uterine tissue samples exhibit extensive areas of tissue necrosis and high numbers of apoptotic cells as well as a significantly reduced cell and microvessel density. These samples failed to develop into endometriotic lesions. In contrast, the 24-h-precultivated samples showed, that their early vascularization and growth in vivo was improved when compared to controls. This indicates that avascular periods have a strong impact on the survival of ectopic endometrial tissue and the chance for the development of endometriosis.


Decolourisation of mushroom farm wastewater by Pleurotus ostreatus.
Mushroom production on coffee pulp as substrate generates an intense black residual liquid, which requires suitable treatment. In the present study, Pleurotus ostreatus growth in wastewater from mushroom farm was evaluated as a potential biological treatment process for decolourisation as well as to obtain biomass (liquid inoculum). Culture medium components affecting mycelial growth were determined, evaluating colour removal. Laccase activity was monitored during the process. P. ostreatus was able to grow in non diluted WCP. Highest biomass yield was obtained when glucose (10 g/l) was added. The addition of this carbon source was necessary for efficient decolourisation. Agitation of the culture improved biodegradation of WCP as well as fungal biomass production. Laccase and manganese-independent peroxidase activities were detected during fungal treatment of the WCP by P. ostreatus CCEBI 3024. The laccase enzyme showed good correlation with colour loss. Both wastewater colour and pollution load (as chemical oxygen demand) decreased more than 50% after 10 days of culture. Phenols were reduced by 92%.


Starvation---an interesting model for the study of the renin-angiotensin-aldosterone system.
Five obese subjects were studied during prolonged starvation. Then renin aldosterone system and urinary aldosterone excretion were studied during prolonged starvation and refeeding in five obese subjects. An uniform increase in aldosterone urinary excretion was observed in all subjects studied. A progressive increase in renin plasma activity was found in all patients along the starvation period with a striking additional increase after refeeding. The possible factors involved are discussed.


Cloning and in vitro antiapoptotic effects of pig FLIPs.
Cellular FLICE-like protein (cFLIP) inhibits death receptor-mediated apoptosis signal transduction, such as that induced by Fas and TNFR. The present study examined the role of antiapoptotic molecules to protect pig cells from human natural killer (NK) cells in vitro, as a model of delayed-type xenograft rejection. Pig FLIPs were cloned using the TBLASTIN program to search for cDNA fragments of pig FLIPs. The sequence was identified using the dideoxy chain termination method and an ABI PRISM3100 genetic analyzer. The cDNA of pig FLIPs was inserted into the cloning site of the chicken beta-actin promoter (pCXN2). The cDNA was then transfected into pig endothelial cells (PEC), to establish several stable PEC clones containing the cDNA. Expression of the pig FLIP gene was evaluated by reverse-transcriptase polymerase chain reaction, and NK cell-mediated cytolysis assessed, using YT cells (an NK-like cell line). The full-length pig FLIP encoding sequence, total 5'-region to 3'-region, was defined for the first time. PEC transfectants with the FLIP showed moderate expression of FLIPs. Transfection of PEC with plasmids encoding FLIPs inhibited NK cell-mediated PEC lysis. While approximately half of parental PEC were injured by the human NK-like YT cells, the injury rate was relatively lower in the transfectants. Overexpression of the antiapoptotic molecules, pig FLIPs, has the potential for use in protecting graft cells from human NK cells.


Assessment of antiretroviral treatment (ART) care service provision in Tigray Region health centers, North Ethiopia.
Client satisfaction is a vital component and main concern intertwined with strategic decisions in service provisions. To improve efficiency of services, eliciting the opinion of users about the available services and identifying factors associated with dissatisfaction is very critical. Thus, the main objective of this study was to assess the perceived levels of clients' satisfaction with health services at ART clinic level in health centres of Tigray Region in Ethiopia. Cross sectional study was conducted from May to June 2013 in Tigray Region ART clinics. A total of 714 ART care user were included in the study using both purposive and probability sampling technique. Data was collected by using structured questionnaire and the collected data was analysed using Statistical Package for the Social Sciences (SPSS) version 16.0. Crude and Adjusted logistic regression analyses were carried out to identify the associated factors underlying perceived levels of clients' overall satisfaction. Finally, the results were presented with table as well as odds ratio (OR) and 95% confidence interval (CI). A total of 714 study participants were enrolled in this study. An overall satisfaction level of 89.6% was reported by ART care service users. Higher scores of satisfaction of services provisions were reported for courtesy and respect (95.80%) followed by privacy (93.28%). On the other hand, respondents' dissatisfaction was rated 35.32% for toilet cleanliness followed by 26.19% for availability of additional drugs. As for overall satisfaction and associated factors, adjusted logistic regression analyses showed that marital status [AOR = 2.01 (95% CI: 1.11, 3.60)], educational status [AOR = 3.13 (95% CI: 1.15, 8.53)], travel distance to reach health centre [AOR = 3.59 (95% CI: 1.23, 10.50)], toilet cleanliness [AOR = 2.22 (95% CI :1.62, 6.32)], and ART drug availability [AOR = 2.60 (95% CI :1.18, 6.52)] were found to have influence on overall ART service satisfaction status. This study revealed high level of client satisfaction rate and were associated with preventable and modifiable factors such as marital status, educational status, travel distance to reach health centre, toilet cleanliness and ART drug availability. Therefore, countermeasures such as increasing access to ART service, availing clean toilet and ART drugs may further increase client satisfaction level in the region.


The distribution of substance P-containing neurons in the cat Edinger-Westphal nucleus: relationship to efferent projection systems.
The light microscopic localization of substance P-like immunoreactivity (SPLI) was examined in the cat Edinger--Westphal complex using the peroxidase--antiperoxidase method. A high density of cell bodies and processes staining for SPLI were found in the caudal part of the Edinger--Westphal complex (EWc) capping the somatic divisions of the oculomotor nucleus. This distribution continued rostrally into the anteromedian nucleus (AM). Cells labeled with SPLI were also found arranged in a thin layer dorsally capping the oculomotor nucleus, and scattered cells were found in the periaqueductal gray region at the same level. This distribution of SPLI-positive cells was then compared with the distribution of cells in EWc and AM that are retrogradely labeled by horseradish peroxidase or Nuclear Yellow injections into spinal cord, cerebellum, or ciliary ganglion. Injections of horseradish peroxidase into both cervical and lumbar cord labeled a large number of cells throughout the length of EWc and the more rostral AM. A similar pattern of labeling was seen following injections of Nuclear Yellow into the deep cerebellar nuclei. In contrast, cells innervating the ciliary ganglion were found predominantly outside of the Edinger--Westphal complex in AM, the rostral periaqueductal region, and the tegmentum ventral to the oculomotor complex. The distribution of cells projecting to spinal cord or cerebellum and the pattern of SPLI staining was found to closely overlap, evidence that substance P may be contained in cells that give rise to the central projections of the Edinger--Westphal complex.


Viscocanalostomy and phacoviscocanalostomy: long-term results.
To determine the safety and efficacy of viscocanalostomy and cataract extraction by phacoemulsification combined with viscocanalostomy (phacoviscocanalostomy) in the management of medically uncontrolled glaucoma. Department of Ophthalmic Surgery, Warrington Hospital, Warrington, England. This prospective nonrandomized study comprised 101 consecutive eyes of 73 patients with medically uncontrolled glaucoma having viscocanalostomy or phacoviscocanalostomy. Outcomes measured were intraocular pressure (IOP) control, visual acuity, gonioscopy, bleb morphology, and complications associated with surgery. Examinations were performed preoperatively and 1 and 7 days and 1, 3, 6, 9, and 12 months postoperatively and then at 6-month intervals. The mean follow-up was 23.9 months +/- 11 (SD) (range 6 months to 3.5 years). The mean preoperative IOP was 24.9 +/- 5.7 mm Hg on 2.27 +/- 0.8 medications and the mean postoperative IOP at last follow-up, 16.14 +/- 2.9 mm Hg on 0.1 medications. A postoperative IOP of 21 mm Hg or less was achieved in 93% of eyes. In the remaining 7%, an addition of a mean of 1.4 medications achieved an IOP less than 21 mm Hg. No case required further glaucoma surgery. The mean percentage of IOP reduction in eyes having viscocanalostomy alone was 37% and in eyes having phacoviscocanalostomy, 33%. Complications were minor and included 4 small hyphemas, 5 small choroidal detachments, 1 iris prolapse through the phaco incision, and 10 intraoperative microperforations of the trabeculo-Descemet's window. Transient postoperative pressure elevations secondary to topical steroids occurred in 18% of eyes. Viscocanalostomy and phacoviscocanalostomy were safe and effective in the surgical management of glaucoma and combined glaucoma and cataract. There was a low incidence of complications postoperatively and throughout the long-term follow-up.


Perioperative desmopressin prolongs survival in surgically treated bitches with mammary gland tumours: a pilot study.
Desmopressin (1-deamino-8-d-arginine vasopressin, also known as DDAVP) is a safe haemostatic compound capable of inhibiting lymph node and lung metastasis in a mouse model of mammary tumour manipulation and surgical excision. The aim of this study was to test the efficacy and safety of perioperative DDAVP (1microg/kg) in surgically treated bitches with mammary gland tumours (MGT). Twenty-one, otherwise healthy, intact bitches, with malignant MGT stage III or IV were randomly allocated to DDAVP (n=11) or placebo (n=10) groups. En bloc mastectomy of the affected gland/s was performed. DDAVP had a significant beneficial effect on disease-free period (P<0.01) and overall survival time (P<0.05). No side effects were seen in any of the cases. Whatever the mechanism of action, it seems that DDAVP may have a novel use in cancer surgery to minimise spread or survival of residual malignant cells. Additional, large scale controlled trials are required to fully evaluate this adjuvant pharmacological protocol.


Progress in elucidation of molecular pathophysiology of myeloproliferative neoplasms and its application to therapeutic decisions.
Myeloproliferative neoplasms (MPNs) are hematological diseases that are driven by somatic mutations in hematopoietic stem and progenitor cells. These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia. JAK-STAT pathway has played a central role in the disease pathogenesis of MPNs. Mutant JAK2, CALR or MPL constitutively activates JAK-STAT pathway independent of the cytokine regulation. Symptomatic management is the primary goal of MPN therapy in ET and low-risk PV patients. JAK2 inhibitors and interferon-α are the established therapies in MF and high-risk PV patients.


Artificial radionuclides in sediments of the Don River Estuary and Azov Sea.
The Don River Estuary-Azov Sea system is an extension of the shallow continental shelf area of the Black Sea. A large data set of artificial radionuclides in bottom sediments of the Azov Sea has been compiled in order to examine the storage and migration of radionuclides within this highly restricted inland sea and to estimate the annual dose received by individuals in the local population who regularly consume fish. In recent years (1997-1999), the radionuclide content of surface sediments has been: 137Cs < or = 0.5-100 Bq/kg d.w. (mean = 33.8 +/- 25.9 Bq/kg d.w., n = 57), 90Sr = 0.2-5.7 Bq/kg d.w. (mean = 2.1 +/- 1.4 Bq/kg d.w., n = 34) and 239,240Pu = 0.31-0.51 Bq/kg d.w. (n = 2). In general, 137Cs activities increase with distance from the mouth of the Don River and correlate negatively with sediment grain size (r2 = 0.77, n = 21). The annual 137Cs-derived dose received by an individual through the trophic chain water-fish-humans (approximately 10(-6) Sv/yr) is well below regulatory recommended limits, indicating that current levels of radioactivity in the environment pose no threat to commercial fisheries operations for the bordering nations of Russia and Ukraine.


Implementation of artificial neural networks (ANNs) to analysis of inter-taxa communities of benthic microorganisms and macroinvertebrates in a polluted stream.
This study was performed to gain an understanding of the structural and functional relationships between inter-taxa communities (macroinvertebrates as consumers, and microbes as decomposers or preys for the invertebrates) in a polluted stream using artificial neural networks techniques. Sediment samples, carrying microorganisms (eubacteria) and macroinvertebrates, were seasonally collected from similar habitats in streams with different levels of pollution. Microbial community taxa and densities were determined using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and 16S rDNA sequence analysis techniques. The identity and density of macroinvertebrates were concurrently determined. In general, differences were observed on grouping by self-organizing map (SOM) in polluted, clean and recovering sites based on the microbial densities, while the community patterns were partly dependent on the sampling period. A Spearman rank order correlation analysis revealed correlations of several eubacterial species with those of macroinvertebrates: a negative correlation was observed between Acidovorax sp. (from polluted sites) and Gammaridae (mostly from the clean site), while Herbaspirillum sp. and Janthinobacterium sp. appeared to have positive correlations with some macroinvertebrate species. The population dynamics of the tolerant texa, Tubificidae and Chironomidae, appeared to be related with changes in the densities of Acidovorax sp. This study revealed community relationships between macroinvertebrates and microorganisms, reflecting the connectivity between the two communities via the food chain. A further physio-ecological and symbiological study on the invertebrate-microorganism relationships will be required to understand the degradation and utilization of detritus in aquatic ecosystems as well as to elucidate the roles of the inter-taxa in the recovery of polluted aquatic environments.


A knowledge base for tracking the impact of genomics on population health.
We created an online knowledge base (the Public Health Genomics Knowledge Base (PHGKB)) to provide systematically curated and updated information that bridges population-based research on genomics with clinical and public health applications. Weekly horizon scanning of a wide variety of online resources is used to retrieve relevant scientific publications, guidelines, and commentaries. After curation by domain experts, links are deposited into Web-based databases. PHGKB currently consists of nine component databases. Users can search the entire knowledge base or search one or more component databases directly and choose options for customizing the display of their search results. PHGKB offers researchers, policy makers, practitioners, and the general public a way to find information they need to understand the complicated landscape of genomics and population health.Genet Med 18 12, 1312-1314.


A polarization-independent blue phase liquid crystal on silicon with low operation voltage.
A polarization-independent blue phase liquid crystal on silicon (BPLCoS) device with low operation voltage for 2π phase depth is demonstrated. With optimized reflection structure and two reflection films, the incident light may experience multifold optical path and 2π phase depth can be obtained. For the polarization-independence, an inclined electric field made by periodical gradient voltage is applied on the blue phase liquid crystal (BPLC) to match the light propagation direction. With the structure, the operation voltage can be lowered to 5.5 V in simulation and 5.9 V in experiment for 2π phase modulation at 1550 nm. The proposed device shows great potential for communication and imaging systems.


Stimulation of mucosal growth in the rat ileum by bile and pancreatic secretions after jejunal resection.
After proximal small bowel resection, the remaining small intestine undergoes adaptive hyperplasia. The role of bile and pancreatic secretions in stimulating ileal mucosal growth after jejunectomy was studied. Male Sprague-Dawley rats were fed either standard rat chow or a liquid elemental diet, and were divided into four surgical groups: sham-operated; transplantation of the duodenal papilla (containing the bile and pancreatic ducts) into the ileum; 50% proximal small bowel resection (jejunectomy); and combined transplantation of the duodenal papilla into the ileum and 50% proximal small bowel resection. Four weeks after surgery the rats were killed and segments of ileum were assayed for total weight and mucosal weight, and for DNA and protein concentration per centimeter of segment. These measurements of mucosal mass were significantly increased in ileal segments adjacent to the transplanted duodenal papilla both in nonresected and jejunectomized rats, compared with their respective controls. Transplanting the duodenal papilla into the ileum significantly increased growth of the ileal mucosa after jejunectomy. The results indicate that bile and pancreatic secretions flowing into the ileal lumen stimulate mucosal growth and play a direct role in ileal adaptation to jejunal resection.


Prevalence of Cognitive Impairment Among Peritoneal Dialysis Patients, Impact on Peritonitis and Role of Assisted Dialysis.
♦ Chronic renal failure and aging are suggested as risk factors for cognitive impairment (CI). We studied the prevalence of CI among peritoneal dialysis (PD) patients using Montreal Cognitive Assessment (MoCA), its impact on PD-related peritonitis in the first year, and the potential role of assisted PD. ♦ One hundred fourteen patients were newly started on PD between February 2011 and July 2013. Montreal Cognitive Assessment was performed in the absence of acute illness. Data on patient characteristics including demographics, comorbidities, blood parameters, dialysis adequacy, presence of helpers, medications, and the number PD-related infections were collected. ♦ The age of studied patients was 59±15.0 years, and 47% were female. The prevalence of CI was 28.9%. Patients older than 65 years old (odds ratio [OR] 4.88, confidence interval [CI] 1.79 - 13.28 p = 0.002) and with an education of primary level or below (OR 4.08, CI 1.30 - 12.81, p = 0.016) were independent risk factors for CI in multivariate analysis. Patients with PD-related peritonitis were significantly older (p < 0.001) and more likely to have CI as defined by MoCA (p = 0.035). After adjustment for age, however, CI was not a significant independent risk factor for PD-related peritonitis among self-care PD patients (OR 2.20, CI 0.65 - 7.44, p = 0.20). When we compared patients with MoCA-defined CI receiving self-care and assisted PD, there were no statistically significant differences between the 2 groups in terms of age, MoCA scores, or comorbidities. There were also no statistically significant differences in 1-year outcome of PD-related peritonitis rates or exit-site infections. ♦ Cognitive impairment is common among local PD patients. Even with CI, peritonitis rate in self-care PD with adequate training is similar to CI patients on assisted PD.


Treatment of cryptorchidism. Long-term prospective study.
We have presented preliminary findings on a long-term prospective study designed to (1) assess timing of orchiopexy, (2) eliminate unnecessary abdominal exploratory surgery, and (3) determine efficacy of orchiopexy on subsequent fertility and on malignant degeneration. Some suggestions for the management of this common congenital defect can be provided, but long-term results are lacking. A significant drop-out rate from this prospective study is expected with time; therefore, large patient numbers are needed to draw any valid conclusions at the time of postpubertal reassessment.


Photo-functionalized TiO2 nanotubes decorated with multifunctional Ag nanoparticles for enhanced vascular biocompatibility.
Titanium dioxide (TiO2) has a long history of application in blood contact materials, but it often suffers from insufficient anticoagulant properties. Recently, we have revealed the photocatalytic effect of TiO2 also induces anticoagulant properties. However, for long-term vascular implant devices such as vascular stents, besides anticoagulation, also anti-inflammatory, anti-hyperplastic properties, and the ability to support endothelial repair, are desired. To meet these requirements, here, we immobilized silver nanoparticles (AgNPs) on the surface of TiO2 nanotubes (TiO2-NTs) to obtain a composite material with enhanced photo-induced anticoagulant property and improvement of the other requested properties. The photo-functionalized TiO2-NTs showed protein-fouling resistance, causing the anticoagulant property and the ability to suppress cell adhesion. The immobilized AgNPs increased the photocatalytic activity of TiO2-NTs to enhances its photo-induced anticoagulant property. The AgNP density was optimized to endow the TiO2-NTs with anti-inflammatory property, a strong inhibitory effect on smooth muscle cells (SMCs), and low toxicity to endothelial cells (ECs). The in vivo test indicated that the photofunctionalized composite material achieved outstanding biocompatibility in vasculature via the synergy of photo-functionalized TiO2-NTs and the multifunctional AgNPs, and therefore has enormous potential in the field of cardiovascular implant devices. Our research could be a useful reference for further designing of multifunctional TiO2 materials with high vascular biocompatibility.


Associations of Midlife Dietary Patterns with Incident Dementia and Brain Structure: Findings from the UK Biobank Study.
At present, the results on the associations between dietary patterns and risk of dementia are inconsistent, and studies on the associations between dietary patterns and brain structures are limited. We aimed to investigate the associations of midlife dietary patterns with incident dementia and brain structures. On the basis of the UK Biobank Study, we investigated the 1) prospective associations of 4 healthy dietary pattern indices [healthy plant-based diet index (hPDI), Mediterranean diet score (MDS), recommended food score (RFS), and Mediterranean-DASH Intervention for Neurodegenerative Delay Diet (MIND)] with incident dementia (identified using linked hospital data; N = 114,684; mean age, 56.8 y; 55.5% females) using Cox proportional-hazards regressions and the 2) cross-sectional associations of these dietary pattern indices with brain structures (estimated using magnetic resonance imaging; N = 18,214; mean age, 55.9 y; 53.1% females) using linear regressions. A series of covariates were adjusted, and several sensitivity analyses were conducted. A total of 481 (0.42%) participants developed dementia during the average 9.4-y follow-up. Although the associations were not statistically significant, all dietary patterns exerted protective effects against incident dementia (all HRs < 1). Furthermore, higher dietary pattern indices were significantly associated with larger regional brain volumes, including volumes of gray matter in the parietal and temporal cortices and volumes of the hippocampus and thalamus. The main results were confirmed via sensitivity analyses. Greater adherence to hPDI, MDS, RFS, and MIND was individually associated with larger brain volumes in specific regions. This study shows a comprehensive picture of the consistent associations of midlife dietary patterns with risk of dementia and brain health, underscoring the potential benefits of a healthy diet in the prevention of dementia.


Optimization of ultrasound assisted dispersive liquid-liquid microextraction of six antidepressants in human plasma using experimental design.
A simple Ultrasounds Assisted-Dispersive Liquid Liquid Microextraction (UA-DLLME) method is presented for the simultaneous determination of six second-generation antidepressants in plasma by Ultra Performance Liquid Chromatography with Photodiode Array Detector (UPLC-PDA). The main factors that potentially affect to DLLME were optimized by a screening design followed by a response surface design and desirability functions. The optimal conditions were 2.5 mL of acetonitrile as dispersant solvent, 0.2 mL of chloroform as extractant solvent, 3 min of ultrasounds stirring and extraction pH 9.8.Under optimized conditions, the UPLC-PDA method showed good separation of antidepressants in 2.5 min and good linearity in the range of 0.02-4 μg mL(-1), with determination coefficients higher than 0.998. The limits of detection were in the range 4-5 ng mL(-1). The method precision (n=5) was evaluated showing relative standard deviations (RSD) lower than 8.1% for all compounds. The average recoveries ranged from 92.5% for fluoxetine to 110% for mirtazapine. The applicability of DLLME/UPLC-PDA was successfully tested in twenty nine plasma samples from antidepressant consumers. Real samples were analyzed by the proposed method and the results were successfully submitted to comparison with those obtained by a Liquid Liquid Extraction-Gas Chromatography - Mass Spectrometry (LLE-GC-MS) method. The results confirmed the presence of venlafaxine in most cases (19 cases), followed by sertraline (3 cases) and fluoxetine (3 cases) at concentrations below toxic levels.


[Comparative evaluation of tolerance to exercise and various features of cardiodynamics in healthy men and women 20-69 years of age].
The analysis of clinical and polycardiographic findings for 568 healthy males and females provided the basis for development of the criteria for standard exercise tolerance and normal range of cardiac cycle phases in relation to 5 ten-year age groups. With age, physical and mental performance was found to be on the decrease, circulatory adaptation and contractile cardiac reserve deteriorated.


Barriers and enabling factors in weight management of patients with nonalcoholic fatty liver disease: A qualitative study using the COM-B model of behaviour.
Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first-line treatments for NAFLD. We aim to identify barriers and enabling factors in weight management among patients with NAFLD using the capability, opportunity, motivation, behaviour (COM-B) model of behaviour. This study adopted a qualitative design using semistructured interviews analysed with content analysis and the COM-B framework. Interviews were conducted with 27 patients with NAFLD who experienced successful or unsuccessful weight reduction. Our study included 27 participants: 15 participants with successful weight loss (successful weight loss refers to a decrease in body weight ≥7% of the initial body weight for patients with NAFLD) and 12 participants with unsuccessful weight loss. Thirty-five themes (19 barriers and 16 facilitators) were mapped onto the COM-B model as barriers and facilitators to weight management among patients with NAFLD. The key barriers were lack of time and energy, lack of awareness of weight, lack of attention to NAFLD, treating food as a reward or compensation and social entertainment. The key facilitators were having basic weight loss knowledge and skills, strong motivation, attention to NAFLD, unsuccessful weight loss experiences and positive feedback from phased success. In addition to identifying factors consistent with existing studies, this study identified factors that influence weight management in NAFLD patients, such as basic weight loss skills and rational thinking before weight loss, which were not previously reported. This has clinical implications for clinical healthcare providers and health management services for the improvement of education and support regarding lifestyle improvement and weight management in patients with NAFLD. We recruited potential participants from the Bariatric Clinic, Hepatology Clinic and Physical Examination Center of hospitals between March 2021 and October 2021. Twenty-seven patients with NAFLD who had successful or unsuccessful weight loss experiences participated in the study and responded to questions on weight management.