Torrefied biomasses in a drop tube furnace to evaluate their utility in blast furnaces.
Torrefaction and burning characteristics of bamboo, oil palm, rice husk, bagasse, and Madagascar almond were studied and compared with a high-volatile bituminous coal using a drop tube furnace to evaluate the potential of biomass consumed in blast furnaces. Torrefaction at 250 and 300°C for 1h duration was carried out. Analysis using the ash tracer method indicated that the extent of atomic carbon reduction in the biomasses was less than that of atomic hydrogen and oxygen. Torrefaction also lowered the sulfur content in bamboo and oil palm over 33%. An examination of the R-factor and burnout of the samples suggests that more volatiles were released and a higher burnout was achieved with raw and torrefied biomasses at 250°C than at 300°C; however, torrefaction at 300°C is a feasible operating condition to transform biomass into a solid fuel resembling a high-volatile bituminous coal used for blast furnaces.


Effect of human apolipoprotein E isoforms on plasma lipids, lipoproteins and apolipoproteins in apolipoprotein E-deficient mice.
The current study compared the acute effect of human apolipoprotein (apo) E isoforms on plasma lipids, lipoproteins and apolipoproteins 6 h after a bolus intravenous injection of individual isoforms into apo E-deficient mice. We found a large accumulation of remnant particles not only in the d<1.019 g/ml fraction but also in the d = 1.019-1.063 mg/dl fraction in the setting of absence of endogenous mouse apo E. A significant reduction in total cholesterol (49, 47 and 18%) (P<0.005), cholesterol in the d<1.019 g/ml fraction (56, 50 and 18%) and in the d = 1.019-1.063 mg/dl fraction (38, 40 and 17%) was obtained with apo E-3, E-4 and E-2, respectively. Apo E-3 and E-4 showed more pronounced total cholesterol lowering effect than E-2 (P<0.0001). In the d<1.019 g/ml fraction, apo E-3 and E-4 resulted in a marked decrease in apo B-100 (36 and 34%), B-48 (48 and 52%), A-I (48 and 44%) and A-IV (52 and 46%), respectively. The decrease caused by apo E-2 in apo B-100 (19%), B-48 (16%), A-I (18%) and A-IV (33%) was less than that of E-3 or E-4. In the d = 1.019-1.063 g/ml fraction, an apparent decline in apo B-48 (42 and 38%), A-I (39 and 40%) and an increase in apo B-100 (25 and 18%) were observed after apo E-3 and E-4 injection, respectively, while apo E-2 did not cause an appreciable change in these apolipoproteins (-4 to 6%). Compared to normal saline, liver total cholesterol content was increased by 37, 34 and 16% (P<0.05) after apo E-3, E-4 and E-2 injection, respectively. Apo E-3 and E-4 showed the same high affinity binding to mice hepatic LDL receptor, while apo E-2 was severely defective in binding. These findings indicate that apo E polymorphism is an important factor modulating remnant lipoprotein metabolism.


RNA-binding protein HuD reduces triglyceride production in pancreatic β cells by enhancing the expression of insulin-induced gene 1.
Although triglyceride (TG) accumulation in the pancreas leads to β-cell dysfunction and raises the chance to develop metabolic disorders such as type 2 diabetes (T2DM), the molecular mechanisms whereby intracellular TG levels are regulated in pancreatic β cells have not been fully elucidated. Here, we present evidence that the RNA-binding protein HuD regulates TG production in pancreatic β cells. Mouse insulinoma βTC6 cells stably expressing a small hairpin RNA targeting HuD (shHuD) (βTC6-shHuD) contained higher TG levels compared to control cells. Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1c (SREBP1c), a key transcription factor for lipid production. We identified Insig1 mRNA as a direct target of HuD by using ribonucleoprotein immunoprecipitation (RIP) and biotin pulldown analyses. By associating with the 3'-untranslated region (3'UTR) of Insig1 mRNA, HuD promoted INSIG1 translation; accordingly, HuD downregulation reduced while ectopic HuD expression increased INSIG1 levels. We further observed that HuD downregulation facilitated the nuclear localization of SREBP1c, thereby increasing the transcriptional activity of SREBP1c and the expression of target genes involved in lipogenesis; likewise, we observed lower INSIG1 levels in the pancreatic islets of HuD-null mice. Taken together, our results indicate that HuD functions as a novel repressor of lipid synthesis in pancreatic β cells.


Serum neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for predicting high dose methotrexate associated acute kidney injury in children with acute lymphoblastic leukemia.
The present study was aimed at assessing the value of serum NGAL in identifying early acute kidney injury induced by HDMTX. Children aged 1-14 years with newly diagnosed ALL receiving MTX over 3 g/m2 were enrolled. Serum NGAL concentrations, serum creatinine (Scr) and MTX concentrations were measured. The area under the receiver-operating characteristic curve (ROC) was used for evaluating variables' ability of early diagnosis of AKI. A total of 196 courses of 62 patients were assessed, and 22 courses (11.2%) developed AKI. Twenty-four hours serum NGAL concentrations, 24 h Scr ratio, 48 h Scr ratio, CMTX24 h, CMTX48 h, CMTX72 h were significantly higher in patients with AKI. The combination of 24 h Scr ratio and 24 h serum NGAL had higher value for detecting HDMTX induced AKI compared with the 24 h Scr ratio. And the combination had similar value for detecting HDMTX induced AKI compared with the 48 h Scr ratio. After 48 h, CMTX48 h had a satisfying accuracy in predicting AKI. The proportion of post-HDMTX sepsis in patients with AKI was significantly higher than that in patients without AKI. Serum NGAL levels could be used as a marker in identifying the direct kidney tubular damage induced by HDMTX. The combination of 24 h Scr ratio and 24 h serum NGAL had higher value for early diagnosis of HDMTX associated AKI compared with the 24 h Scr ratio.


Differential binding of antidepressants to noradrenaline and serotonin transport sites in central nerve endings.
Imipramine and mianserin are equipotent inhibitors of noradrenaline (NA) uptake in synaptosomes. However, after in vivo administration, NA uptake was inhibited only in synaptosomes from imipramine-treated rats, suggesting that imipramine, or its metabolite desipramine, binds to the NA carrier in a manner outlasting the preparation of synaptosomes, whereas mianserin is washed away. To evaluate binding to the NA carrier, synaptosomes prelabeled with 3H-NA were pretreated with an antidepressant and the release of 3H-NA was then stimulated with unlabeled NA. Any reduction of release was taken as an indication of binding. Pretreatment with desipramine, but not with imipramine or mianserin, reduced 3H-NA release suggesting that desipramine is responsible for NA uptake inhibition in synaptosomes from imipramine-treated rats. Transformation of tertiary into secondary amines seems to be crucial for binding to the NA carrier, as confirmed by the stronger binding of nortriptyline and chlordesipramine compared to amitryptiline and chlorimipramine, respectively. In contrast, tertiary amines bound more strongly than secondary amines to the serotonin carrier. Adult and 8-day old synaptosomes showed similar binding properties towards imipramine and desipraine.


Tillage management to mitigate herbicide loss in runoff under simulated rainfall conditions.
Conservation tillage mitigates soil loss in cropland because plant residues help protect the soil, but effects on pesticide movement in surface runoff are not as straightforward. Effects of soil disturbance on surface runoff loss of chlorimuron and alachlor were evaluated utilizing runoff trays. Soil in the trays was either disturbed (tilled) and kept bare or was not tilled, and existing decomposed plant residue was left on the surface. Rainfall (25mm, 20min) was simulated 1d after alachlor (2.8kg ha(-1)) or chlorimuron (54g ha(-1)) application, and runoff was collected. Runoff fractions were analyzed for herbicide and sediment. Total alachlor loss from bare plots was greater than that in no-tillage plots (4.5% vs. 2.3%, respectively). More than one-third of total alachlor lost from bare plots occurred in the first l of runoff, while no-tillage plots had less runoff volume with a more even distribution of alachlor concentration in the runoff during the rainfall simulation and subsequent runoff period. In contrast, more chlorimuron was lost from no-tillage plots than bare plots (12% vs. 1.5%) even though total runoff volume was lower in the no-tillage plots (10.6mm vs. 13.6mm). This was attributed to dense coverage with partially decomposed plant residue in no-tillage plots (1652kg ha(-1)) that intercepted chlorimuron. It was likely that chlorimuron, a polar compound, was more easily washed off surface plant residues and transported in runoff.


New data on the genus Lathrobium Gravenhorst (Coleoptera: Staphylinidae: Paederinae) of Guangxi, South China.
Lathrobium caiyujiei Lin Peng sp. n. (Guangxi: Jinwanshan N. R.), L. jiuwanshanense Lin Peng sp. n. (Guangxi: Jinwanshan N. R.) and L. zhusha Lin Peng sp. n. (Guangxi: Jinwanshan N. R.) are described and illustrated. Additional records of L. damingense Peng Li, 2013, L. dayaoshanense Peng Li, 2012, L. hujiayaoi Peng Li, 2013, L. maoershanense Peng Li, 2012 and L. zhujianqingi Peng Li, 2012 are reported. Including the new taxa, 227 Lathrobium species are currently known from mainland China.


Tree root-inspired robust superhydrophobic coatings with high permeation for porous structures.
Superhydrophobic coatings have tremendous potential for protecting porous structures from corrosion. However, the weak adhesion and poor abrasion resistance have long been challenges for their real-life applications. Inspired by tree roots, we prepared a robust superhydrophobic coating by spraying fluorinated nanodiamonds (FNDs) on a permeable epoxy coating. The epoxy can not only coat the surface but also permeate deeply inside a porous substrate and consolidate in situ as tree roots in soil. Thus, the structure is thoroughly reinforced where the pull-off strength reaches 9.4 MPa for concrete. On the other hand, the surface is covered with immobilized FNDs, forming a superhydrophobic surface. Thanks to the ultra-hard FNDs, the coating surface has high abrasion resistance and its superhydrophobicity holds even after 100 abrasion cycles. Moreover, it exhibits self-cleaning, anti-icing, and anticorrosion performance. It is promising in protecting various porous structures such as concrete, wood, and untreated corroded steel.


A tale of two clinics--primary health care in refugee settings: lessons from Sudan and Somalia.
The elements and techniques of PHC were not developed in and for refugee situations, and the acute needs and transient situation of refugees sometimes attracts a more traditional medical approach. However, as refugees remain in a host country and their situation stabilizes there, attempts are made to convert to PHC. Refugee health programmes face some unique challenges when attempting this transformation, problems that exist even when PHC techniques were present at the onset of the programme. The challenge is to adapt PHC principles for use in acute and chronic refugee situations, and to find ways to develop a community base for health care programmes while at the same time meeting the acute medical needs unique to refugees.


Reproducible Inter-Personal Brain Coupling Measurements in Hyperscanning Settings With functional Near Infra-Red Spectroscopy.
Despite a huge advancement in neuroimaging techniques and growing importance of inter-personal brain research, few studies assess the most appropriate computational methods to measure brain-brain coupling. Here, we focus on the signal processing methods to detect brain-coupling in dyads. From a public dataset of functional Near Infra-Red Spectroscopy signals (N=24 dyads), we derived a synthetic control condition by randomization, we investigated the effectiveness of four most used signal similarity metrics: Cross Correlation, Mutual Information, Wavelet Coherence and Dynamic Time Warping. We also accounted for temporal variations between signals by allowing for misalignments up to a maximum lag. Starting from the observed effect sizes, computed in terms of Cohen's d, the power analysis indicated that a high sample size ([Formula: see text]) would be required to detect significant brain-coupling. We therefore discuss the need for specialized statistical approaches and propose bootstrap as an alternative method to avoid over-penalizing the results. In our settings, and based on bootstrap analyses, Cross Correlation and Dynamic Time Warping outperform Mutual Information and Wavelet Coherence for all considered maximum lags, with reproducible results. These results highlight the need to set specific guidelines as the high degree of customization of the signal processing procedures prevents the comparability between studies, their reproducibility and, ultimately, undermines the possibility of extracting new knowledge.


Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies.
The purpose of this study is to investigate if female patients with lymphoma demonstrate diminished ovarian reserve prior to initiation of the lymphoma treatment. Sixty-four patients with newly diagnosed lymphoma undergoing controlled ovarian hyperstimulation for fertility preservation were compared with 365 healthy controls undergoing elective oocyte cryopreservation (controlled ovarian hyperstimulation (COH)) and 128 patients with other types of malignancy prompting fertility preservation. The data of all lymphoma patients, all elective, and all the patients with other types of malignancy who met the inclusion criteria and underwent COH for fertility preservation during the study period were retrospectively analyzed. Primary outcomes included serum anti-Müllerian hormone (AMH) levels (ng/mL) and antral follicle count (AFC). Patients in the lymphoma group demonstrated significantly lower AMH levels and AFC and had less oocytes harvested and cryopreserved when compared to healthy controls as well as patients with other malignancies. Patients with lymphoma demonstrate diminished ovarian reserve when compared with healthy controls and patients with other malignancies. This should be taken into consideration when deciding on the dose for COH.


A Nomogram Based on Radiomics with Mammography Texture Analysis for the Prognostic Prediction in Patients with Triple-Negative Breast Cancer.
To develop and validate a radiomics-based nomogram with texture features from mammography for the prognostic prediction in patients with early-stage triple-negative breast cancer (TNBC). The study included 200 consecutive patients with TNBC (training cohort: n = 133, validation cohort: n = 67). A total of 136 mammography-derived textural features were extracted, and LASSO (least absolute shrinkage and selection operator) was applied to select features for building the radiomics score (Rad-score). After univariate and multivariate logistic regression, a radiomics-based nomogram was constructed with independent prognostic factors. The discrimination and calibration power were assessed, and further the clinical applicability of the nomograms was evaluated. Among the 136 mammography-derived textural features, fourteen were used to build the Rad-score after LASSO regression. A radiomics nomogram that incorporates Rad-score and pN stage was constructed. This nomogram achieved a C-index of 0.873 (95% CI: 0.758-0.989) for predicting iDFS (invasive disease-free survival), which outperformed the clinical model. Moreover, it is feasible to stratify patients into high-risk and low-risk groups based on the optimal cut-off point of Rad-score. The validations of the nomogram confirmed favorable discrimination and considerable predictive efficiency. The radiomics nomogram that incorporates Rad-score and pN stage exhibited favorable performance in the prediction of iDFS in patients with early-stage TNBCs.


Transmission of HIV in a dental practice--the facts.
There is compelling evidence that six patients of a Florida dentist were infected with HIV at the dental practice. The strain of HIV in the dentist and patients was virtually identical. There is no evidence that either lapses in infection control or deliberate attempts to infect patients were responsible for this cluster of cases. Recent media analyses have emphasised that handpieces should be taken seriously as a potential source of cross infection but no evidence is available to confirm this as the route in the Florida practice. The unusual circumstances leading up to the detection of this cluster suggest that there could be other undetected cases and clusters.


Prospective comparison of high- and low-spatial-resolution dynamic MR imaging with sensitivity encoding (SENSE) for hypervascular hepatocellular carcinoma.
The purpose of this study was to prospectively evaluate the efficacy of high-spatial-resolution dynamic MRI using sensitivity encoding (SENSE) in detection of hypervascular hepatocellular carcinoma (HCC). Thirty-five patients were included in this prospectively planned study, and 25 patients with 31 HCCs were assigned into three groups and underwent the following sequences: group A (n=11): three-dimensional fast-gradient-echo (3D-FGE) high-spatial-resolution dynamic MRI (HR-MRI) with SENSE; group B (n=10): 3D-FGE low-spatial-resolution dynamic MRI (LR-MRI) with SENSE; and group C (n=14): 3D-FGE/LR-MRI without SENSE. For the quantitative analysis, the lesion-to-liver contrast-to-noise ratio (CNR) between the liver and HCCs was measured. For the qualitative analysis, overall image quality for each group was evaluated with a five-point scale analysis. The sensitivities for detection of HCCs were evaluated. The overall image quality in group A was significantly greater than both groups B and C (P<0.01). The sensitivity of lesion detection on HAP was not significantly higher in group A (100%) than group C (69.2%; P>0.05). In our pilot study on a small number of patients, image quality in HR-MRI with SENSE was superior to LR-MRI. A high detection rate was seen with HR-MRI with SENSE in the patients with hypervascular HCCs.


Prognosis with Incidental Rolandic Spikes.
Investigators from Johns Hopkins University reported a cohort of 27 patients with incidentally-noted rolandic spikes (RS) on EEG.


[Ischiopubic osteochondrosis revealed by an atypical "acute transient synovitis of the hip": A case report].
We report here the case of a 3-year-old patient, who presented a left limp and a total refusal of walking, without any traumatism. Clinical examination revealed a significant pain in the left leg with a limit to the limiting mobilization. Acute phase reactants were slightly elevated. Based on the hip ultrasound, acute transient synovitis of the hip was diagnosed. Following persistent complaints, a hip plain radiography was performed, showing a discreet reshuffle at the right ischiopubic branch. The MRI of the hip revealed a discrete T2 high intensity centered on the right ischiopubic synchondrosis (IPS), corresponding to a Van Neck-Odelberg osteochondrosis. Non-steroidal anti-inflammatory drugs and limited weight bearing enabled significant clinical improvement. The ischiopubic osteochondrosis is a physiological phenomenon, frequent and mostly asymptomatic. However, when associated with pain, it could easily be mistaken for another musculoskeletal or rheumatological disorder. Therefore, it is important to continue investigating more thoroughly any limping that does not have a typical evolution from the presumed diagnosis.


Clinical and metabolomic characterization of Brivanib-Induced hypertension in metastatic colorectal cancer.
Trials of tyrosine kinase inhibitors (TKI) have not demonstrated dramatic benefits in advanced colorectal cancer (CRC), and this may be a function of poor patient selection. TKI-induced hypertension is reportedly a surrogate marker for treatment benefit for some tumor types. Our objective was to determine whether hypertension was associated with benefit in the context of CRC treatment, and also to gain insight on the pathogenesis of TKI-induced hypertension by monitoring associated changes in the circulating metabolome. Clinical data were acquired from clinical trial patients with metastatic CRC randomized to cetuximab ± the TKI brivanib (N = 750). Outcomes were evaluated as a function of treatment-induced hypertension. For metabolomic studies, plasma samples were taken at baseline, as well as at 1, 4, and 12 weeks after treatment initiation. Samples were submitted to gas chromatography-mass spectrometry to identify treatment-related metabolomic changes associated with TKI-induced hypertension, compared to pre-treatment baseline. A model based on changes in metabolite concentrations was generated using orthogonal partial least squares discriminant analysis (OPLS-DA). In the brivanib treated group, 95 patients had treatment-related hypertension within 12 weeks of initiating treatment. TKI-induced hypertension was not associated with a significantly higher response rate, nor was it associated with improved progression-free or overall survival. In metabolomic studies, 386 metabolites were identified. There were 29 metabolites that changed with treatment and distinguished patients with and without TKI-induced hypertension. The OPLS-DA model for brivanib-induced hypertension was significant and robust (R2 Y score = 0.89, Q2 Y score = 0.70, CV-ANOVA = 2.01 e-7). Notable metabolomic features previously reported in pre-eclampsia and associated with vasoconstriction were found. TKI-induced hypertension was not associated with clinical benefit in metastatic CRC. We have identified changes in the metabolome that are associated with the development of worsening brivanib-induced hypertension that may be useful in future efforts of characterizing this toxicity.


Otitis media and hearing loss in the children of the Ruatoki valley: a continuing public health problem.
A longitudinal survey of ear disease using repeated otomicroscopy has demonstrated cases of persistent middle ear effusion, cholesteatoma and perforation in a group of 275 Maori children. The hearing of 194 of the children was assessed, and 25% of them were found to have a hearing loss. It is concluded a public health problem exists with these children. Improved detection and treatment of ear disease and hearing loss in this population is recommended.


Six Sigma can significantly reduce costs of poor quality of the surgical instruments sterilization process and improve surgeon and operating room personnel satisfaction.
Operating room (OR) management is a complex multidimensional activity combining clinical and managerial aspects. This longitudinal observational study aimed to assess the impact of Six-Sigma methodology to optimize surgical instrument sterilization processes. The project was conducted at the operating theatre of our tertiary regional hospital during the period from July 2021 to December 2022. The project was based on the surgical instrument supply chain analysis. We applied the Six Sigma lean methodology by conducting workshops and practical exercises and by improving the surgical instrument process chain, as well as checking stakeholders' satisfaction. The primary outcome was the analysis of Sigma improvement. Through this supply chain passed 314,552 instruments in 2022 and 22 OR processes were regularly assessed. The initial Sigma value was 4.79 ± 1.02σ, and the final one was 5.04 ± 0.85σ (SMD 0.60, 95%CI 0.16-1.04, p = 0.010). The observed improvement was estimated in approximately $19,729 of cost savings. Regarding personnel satisfaction, 150 questionnaires were answered, and the overall score improved from 6.6 ± 2.2 pts to 7.0 ± 1.9 pts (p = 0.013). In our experience the application of the Lean Six Sigma methodology to the process of handling the surgical instruments from/to the OR was cost-effective, significantly decreased the costs of poor quality and increased internal stakeholder satisfaction.


Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Physicochemical Study of an Anhydrous Organic Acidic Cyclohexaphosphate.
The new organic-inorganic hybrid [5-Cl-2-(CH3)C6H3NH3]4H2P6O18 has been synthesized by the slow evaporation method. X-ray diffraction on a single crystal shows that this acidic cyclohexaphosphate crystallized in the monoclinic space group C 2/c with a = 33.89(11) Å, b = 9.16(16) Å, c = 13.68(3) Å, β = 91.35(2)°, V = 4244.9(19) Å3 and Z = 4. 31P MAS-NMR and 13C CP/MAS-NMR results are in accordance with X-ray findings. Fluorescent study shows the blue photoluminescence. Furthermore, FT-IR analysis was studied and the complete vibrational assignments were done. Intermolecular interactions were analyzed using Hirshfeld surface analysis and the associated 2D fingerprint plots.


Morphological characterization of ductular reactions in canine liver disease.
Intrahepatic bile duct proliferation (ductular reaction) was examined histologically, immunohistochemically and ultrastructurally in four cases of canine liver disease, diagnosed as chronic hepatitis, liver fibrosis, cirrhosis and cholangiocellular carcinoma. Ductular reaction was a common finding in all cases. Most of the proliferated bile ducts were similar to normal bile ducts. In addition, duct-like structures occurred, consisting of hepatocytes and of intermediate cells that had phenotypic characteristics of both cholangiocytes and hepatocytes. The proliferated bile ducts were immunohistochemically negative for proliferating cell nuclear antigen (PCNA) and stem cell factor (SCF). The proliferated bile ducts in these four cases of canine liver disease thus showed both typical ductular reactions, such as elongation and tortuosity of the existing bile ducts, and atypical ductular reactions resulting from metaplasia of hepatocytes.


Induction of macrolide-lincosamide-streptogramin B resistance requires ribosomes able to bind inducer.
Plasmids were constructed containing the regulatory regions and N-terminal portions of ermC and of ermD , fused in phase with the coding sequence of the Escherichia coli lacZ gene. ermC and ermD are erythromycin (Em) inducible macrolide-lincosamide-streptogramin B resistance elements derived from Staphylococcus aureus and Bacillus licheniformis, respectively. The fusion plasmids were introduced into B. subtilis and used to study ermC and ermD regulation. In both cases, beta-galactosidase synthesis could be induced by low levels of Em. Induction was prevented by introduction of ole-2, a chromosomal mutation which decreases ribosomal affinity for Em. Induction also did not occur in the presence of intact copies of ermC , suggesting that prior or concomitant methylation of 23S rRNA, a treatment known to decrease ribosomal affinity for Em, was capable of interfering with ermC and ermD induction. These experiments are consistent with the translational attenuation model of ermC regulation, and together with other evidence, suggest that ermD is regulated by a similar mechanism.


Development of tolerance to the anticonvulsant effect of valproate but not to ethosuximide in a rat model of absence epilepsy.
Ethosuximide and valproic acid were tested for 4 and 2 weeks, respectively, in rats showing the spontaneous spike-wave syndrome. Ethosuximide suppressed the syndrome at plasma concentrations of 75-100 micrograms/ml. High doses of valproate (170 mg/kg i.p., t.i.d.), resulting in plasma concentrations of about 500 micrograms/ml, were necessary to suppress the syndrome, but signs of tolerance to the drug developed from day 5. Tolerance was confined to the number of spike-wave complexes, whereas the duration of the discharges was shortened to 60% of the control value, without there being signs of tolerance. It is assumed that increases in cerebral GABA, induced by the high concentration of valproate, counteracted the anti-absence effect of the drug in this model.


Operative treatment of refractory superior vena cava syndrome.
Left sapheno-axillary vein bypass is effective in relieving the signs and symptoms of superior vena cava obstruction. As the operation can be performed easily under local anesthesia, it should probably be used more often than indicated by a review of the literature. The authors present a patient with bronchogenic carcinoma who experienced excellent results.


Antioxidant-oxidant balance and vital parameter alterations in an eukaryotic system induced by aflatoxin B2 exposure.
This study was performed to evaluate the toxic effects of aflatoxin B2 (AFB2) on antioxidant-oxidant balance and vital parameters such as physiological, cytogenetic, and anatomical alterations in Allium cepa L. root tip cells. Toxic effects of AFB2 on vital parameters were investigated by using the changes in weight gain, germination percentage, chromosomal aberrations (CAs), mitotic index (MI), micronucleus frequency (MN), and anatomical structure. Malondialdehyde (MDA) and reduced glutathion (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities in root cells were investigated as antioxidant-oxidant parameters. For this aim, A. cepa bulbs were seperated into five groups as negative control, positive control, and AFB2 treatment groups. In results, while the rate of germination percentage, weight gain, and MI rates decreased, MN and CA frequency increased in AFB2-treated groups compared with the negative control. Most common CAs observed in AFB2-treated groups were fragment and chromosome bridges. It was determined that in 160 μg L-1 AFB2-treated group there was a 70.8% increase in MDA and a 78.1% decrease in GSH level compared with the negative control group and these changes indicate oxidative damage. In 160 μg L-1 AFB2 treatment group, SOD and CAT activities decreased importantly due to inhibition. In anatomical examinations, it was determined that AFB2 treatment caused some anatomical damages in A. cepa root cells such as necrosis, cell deformation, and thickening in cell wall. This study showed that AFB2, which has the least data among aflatoxins, causes serious in vivo toxic effects in A. cepa root cells.


Rapid identification of Candida albicans using 4-methylumbelliferyl N-acetyl-beta-galactosaminide.
Rapid identification of Candida albicans is performed mainly by the germ-tube test. However, recent reports have suggested that up to 5% of C. albicans species can give false negative results. We describe the use of 4-Methylumbelliferyl N-acetyl-beta-D-galactosaminide (4-MAG) conjugate as an alternative to the germ-tube test. Our results indicate that, in comparison to the germ-tube test, the 4-MAG test has a sensitivity of 100% and a specificity of 92%. Candida tropicalis can give false-positive results, and that a further screening test is required to identify this species. Problems reading end-points were not encountered.


Vesicles and cisternae in the trans Golgi apparatus of human fibroblasts are acidic compartments.
Recently we demonstrated that low-pH compartments can be visualized with the electron microscope using a basic congener of dinitrophenol, 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP), which concentrates in acidic compartments and can be detected by immunocytochemistry with a monoclonal anti-dinitrophenol antibody. We now report that DAMP also accumulates in cisternae and vesicles associated with the trans face of the Golgi apparatus. DAMP rapidly leaves this compartment when cells are incubated with the ionophore monensin, which indicates that accumulation is due to the acidic pH in this compartment. Using indirect protein A-gold immunocytochemistry, we localized fibronectin, a major secretory protein in fibroblasts, to the trans Golgi vesicles that took up DAMP. Therefore, the trans cisternae of the Golgi apparatus and forming secretory vesicles have an acidic pH.


Studies in sheep on the absorption of magnesium from a low molecular weight fraction of the reticulo-rumen contents.
1. Six sheep, three animals per diet, were prepared with rumen fistulas and fed on frozen grass or grass-maize pellets to give magnesium intakes of 1.79 and 2.23 g/d respectively. The mean apparent availabilities of Mg in sheep fed on frozen grass and grass-maize pellets were 0.31 and 0.36 respectively. 2. The rumen contents were fractionated by straining the digesta through linen cloth and then differentially centrifuged to give 20,000 g and 100,000 g supernatant fractions. 3. In all sheep, regardless of diet, at 4 and 16 h after a meal, 50 and 60% respectively of the total Mg in the rumen contents was found in strained rumen fluid while 30 and 38% respectively of the total Mg was found in the 100,000 g supernatant fraction. 4. The net absorption of Mg from the temporarily isolated and washed reticulo-rumen was studied using either 100,000 g supernatant fractions of rumen contents from sheep fed on one or other of the two diets, or inorganic buffers containing the same concentration of Mg and other macroelements. 5. The Mg was readily absorbed from the 100,000 g supernatant fraction placed in the rumen with the rate of absorption being 7.3 mumol/l per min (505 mg/d) from the supernatant fraction obtained from sheep fed on frozen grass and 11.3 mumol/l per min (781 mg/d) from the supernatant fraction from sheep fed on grass-maize pellets. In the same sheep, the previously described rates of Mg absorption from the 100,000 g supernatant fraction were similar to those obtained from the comparable inorganic buffers. 6. The effects of varying concentrations of potassium and sodium on the net absorption rate of Mg (as 24Mg) and on the one-way efflux of Mg (as 28Mg) from supernatant fractions or rumen fluid and inorganic buffers were investigated using the temporarily-isolated and washed rumen in three sheep. Although the net absorption rate of 24Mg from supernatant fractions or buffers containing similar K concentrations varied significantly between sheep, a similar percentage decrease in the absorption rates of both 24Mg and 28Mg was found for each sheep as the K concentration was increased. 7. One pair of sheep was fed on the frozen grass and the other pair was fed on the grass-maize pellets. Their daily intakes of K were then increased to 50 g/d for 14 d by intrarumen infusion of potassium chloride. In three of the four sheep the plasma Mg concentration fell within 12 h of the start of the KCl administration.(ABSTRACT TRUNCATED AT 400 WORDS)


Detection of left ventricular dysfunction in ambulatory subjects with the bedside Valsalva maneuver.
The bedside sphygmomanometric determination of the arterial pressure response during the Valsalva maneuver was incorporated into the routine physical examination of ambulatory subjects. Four distinct Valsalva responses were noted: ultrasinusoidal, sinusoidal, absent overshoot, and square wave. The absent overshoot response was further divided into positional and constant types--the latter consistently exhibiting this response regardless of body position. Correlation with resting left ventricular ejection fraction was obtained by radionuclide cineangiography in 200 patients, of whom 81 had left ventricular systolic dysfunction (ejection fraction less than 0.50). Significant differences in the mean left ventricular ejection fraction were found in subjects with an ultrasinusoidal response (0.65 +/- 0.11), sinusoidal response (0.55 +/- 0.15), constant absent overshoot response (0.37 +/- 0.18), and square wave response (0.16 +/- 0.04) to Valsalva maneuver. The sensitivity of an abnormal Valsalva response (absent overshoot or square wave responses) for the bedside detection of left ventricular systolic dysfunction was 69 percent, and the predictive value of an ultrasinusoidal Valsalva response for normal ejection fraction was 93 percent. It is concluded that the high predictive accuracy of the Valsalva maneuver makes this simple bedside technique a valuable method for assessing resting left ventricular function.


Experimental infection of chickens with Cryptosporidium.
To study the clinical and pathological manifestations of Cryptosporidium infections, 24 h-old chickens were inoculated via four routes: orally, nasally, cloacally and by contamination, using 10(5) oocysts of Cryptosporidium in each case. The chickens began to shed oocysts of Cryptosporidium on days 7 to 8 after inoculation. There was no difference in the clinical manifestations or histological damage with respect to the inoculation routes. Various developmental stages of Cryptosporidium were also demonstrated microscopically in the smears or sections of bursa of Fabricii, larynx, trachea and cecal tonsils of inoculated chickens. Although the intestinal mucosa and respiratory tract mucosa were scarcely infected with the parasites, the bursa Fabricii was heavily infected in association with hypertrophy and hyperplasia of the lining epithelial cells.


Usefulness of Sonography in Evaluating Children Suspected of Malrotation: Comparison With an Upper Gastrointestinal Contrast Study.
The purpose of this study was to prospectively evaluate the value of sonography in working up or ruling out malrotation by 3 sonographic features (inversion of the superior mesenteric artery and superior mesenteric vein, the whirlpool sign, and an intraperitoneal transverse duodenum) and comparing it with an upper gastrointestinal (GI) contrast study. A total of 70 pediatric patients who underwent detailed abdominal sonography to rule out intestinal malrotation were included. Twenty-three of them also underwent an upper GI contrast study. Surgery or clinical follow-up was taken as the reference standard. Statistical analysis was performed with the χ(2) test. Twenty-three patients had a diagnosis of malrotation by surgical findings. With the combination of all 3 sonographic features, the sensitivity, specificity, and accuracy of sonography for determining malrotation were 100% (23 of 23), 97.8% (46 of 47), and 98.6% (69 of 70), respectively, whereas the sensitivity, specificity, and accuracy of the upper GI study were 40% (4 of 10), 64.3% (9 of 14), and 56.5% (13 of 23; P < .001). Combined anomalies in 2 patients and complications in 2 patients were also detected by sonography. By combining inversion of the superior mesenteric artery and superior mesenteric vein, the whirlpool sign, and an intraperitoneal transverse duodenum, sonography might be more valuable for accurately working up or ruling out pediatric malrotation than an upper GI contrast study. In addition, sonography could provide extra information, such as combined anomalies and intestinal necrosis, to help management.


Application of microcomputers for recording of patients in the emergency department.
Medical data in the ED can only be approached with computers. A simple, easy and cheap system is described.


CT studies of the liver in vitro: a report on 82 cases with pathological correlation.
Eighty-two liver specimens were studied by both computed tomography (CT) and pathological examination with serial sectioning. In vitro CT studies showed low density structures within 57 normal livers to be due to portal and hepatic vessels but not to bile ducts. A liver with a minimum of 70% fatty infiltration could be diagnosed correctly on CT. Concerning the presence or absence of circumscribed liver disease, sensitivity was 80% and specificity was 84%. With respect to the total number of space occupying liver lesions (n = 364 in 18 specimens), sensitivity was 72%. The smallest metastases detectable on CT were 0.5 cm in diameter, but CT disclosed focal lesions of this small size in only 15% of the cases. In contrast to previously reported in vivo CT studies, metastases were often found to be of higher density than normal liver tissue in vitro.


Dissemination of bla NDM-5 and mcr-8.1 in carbapenem-resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae in an animal breeding area in Eastern China.
Animal farms have become one of the most important reservoirs of carbapenem-resistant Klebsiella spp. (CRK) owing to the wide usage of veterinary antibiotics. "One Health"-studies observing animals, the environment, and humans are necessary to understand the dissemination of CRK in animal breeding areas. Based on the concept of "One-Health," 263 samples of animal feces, wastewater, well water, and human feces from 60 livestock and poultry farms in Shandong province, China were screened for CRK. Five carbapenem-resistant Klebsiella pneumoniae (CRKP) and three carbapenem-resistant Klebsiella quasipneumoniae (CRKQ) strains were isolated from animal feces, human feces, and well water. The eight strains were characterized by antimicrobial susceptibility testing, plasmid conjugation assays, whole-genome sequencing, and bioinformatics analysis. All strains carried the carbapenemase-encoding gene bla NDM-5, which was flanked by the same core genetic structure (IS5-bla NDM-5-ble MBL-trpF-dsbD-IS26-ISKox3) and was located on highly related conjugative IncX3 plasmids. The colistin resistance gene mcr-8.1 was carried by three CRKP and located on self-transmissible IncFII(K)/IncFIA(HI1) and IncFII(pKP91)/IncFIA(HI1) plasmids. The genetic context of mcr-8.1 consisted of IS903-orf-mcr-8.1-copR-baeS-dgkA-orf-IS903 in three strains. Single nucleotide polymorphism (SNP) analysis confirmed the clonal spread of CRKP carrying-bla NDM-5 and mcr-8.1 between two human workers in the same chicken farm. Additionally, the SNP analysis showed clonal expansion of CRKP and CRKQ strains from well water in different farms, and the clonal CRKP was clonally related to isolates from animal farms and a wastewater treatment plant collected in other studies in the same province. These findings suggest that CRKP and CRKQ are capable of disseminating via horizontal gene transfer and clonal expansion and may pose a significant threat to public health unless preventative measures are taken.


Nyctanthes arbor-tristis positively affects immunopathology of malaria-infected mice prolonging its survival.
In order to search for new products that display antimalarial and immunomodulatory mechanisms that complement direct antiparasitic activity, a set of in vitro and in vivo experiments were designed to evaluate the effect of Nyctanthes arbor-tristis in Plasmodium berghei infected mice. Three extracts of N. arbor-tristis leaves from varying concentrations of alcohol and water were considered for their potential to suppress expression of pro-inflammatory mediators from macrophages primed with lipopolysaccharide. The ethanolic extract, which lowered the pro-inflammatory mediators [tumour necrosis factor (TNF), 13.52-55.83 %; interleukin-6 (IL-6), 0-17.29 %; and NO, 39.37-81.63 %], was selected to be examined in malaria (P. berghei) infected mice. Corroborating the in vitro results, it was observed that the extract could normalise the TNF (78 %) and IL-6 (70.35 %) optimally at 1 g/kg, thus retarding the pathological process in infected mice and increasing the mean survival time from 10.6 to 15.6 days. There were no signs of toxicity in the acute oral toxicity test up to 2 g/kg. (1)H NMR of the biologically active extract was obtained to ensure the presence of the compound of interest, i.e., iridoid glycoside. The quality and the reproducibility of results were ensured by means of achieving characteristic high-performance liquid chromatography fingerprint of the extract.


Local anesthesia in hair transplantation.
Safe and effective use of local anesthesia is essential in hair transplantation. To review the agents and techniques of local anesthesia as applied to hair transplantation. Information was retrieved from texts, journal articles found by MEDLINE searches, and related references. Agents, vasoconstrictors, maximum dosages, toxicity, and techniques are discussed. Effective local anesthesia can be maintained throughout hair transplantation. Care must be exercised to minimize discomfort through proper technique and to minimize toxicity through judicious use of vasoconstrictors and nerve blocks and by monitoring total dosage. Constant monitoring for toxicity is required, as is early intervention in the unlikely event that warning signs should appear.


Intracardiac tumour and brain lesions in tuberous sclerosis. A case report of antenatal diagnosis by ultrasonography.
A case of antenatal tuberous sclerosis was diagnosed by ultrasonography. Intracardiac tumour (highly suspected rhabdomyoma) with transitory heart failure and multiple brain lesions were observed. After delivery, echocardiography, spiral CT and MR imaging diagnosis of tuberous sclerosis was confirmed by typical skin lesions (depigmented macules) and development of seizures.


Financial reimbursement - irrelevant for GPs' readiness to implement brief intervention to reduce alcohol consumption? A cross-sectional vignette study.
General Practitioners' (GPs) readiness to implement screening and brief intervention (SBI) to treat patients with excessive alcohol consumption is low. Several studies identified crucial barriers such as insufficient financial reimbursement. In contrast to the barriers-account, we assume that low implementation readiness of GPs may be less attributed to external barriers but rather more so to inherent characteristics of SBI. To test our assumption, we conducted a vignette study assessing the GPs' readiness to implement SBI in comparison to a pharmacological intervention also designed for the treatment of excessive drinkers in relation to standard or above-standard financial reimbursement. According to our hypothesis GPs should be less ready to implement SBI regardless of financial reimbursement. A convenience sample of GPs was recruited to answer the questionnaire. To assess the GPs' implementation readiness a 4-item 6-point Likert scale was developed and pretested. One hundred forty GPs completed the questionnaire. GPs were more ready to implement the pharmacological intervention than SBI, F(1,132) = 27.58, p > .001 (main effect). We found no effect for financial reimbursement, F(1,132) = 3.60, ns, and no interaction effect, F(1,132) = 2.20, ns. Further research should investigate more thoroughly the crucial characteristics of SBI to initiate a modification process finally leading to more effective primary care dependency prevention.


Erythrodermic pityriasis rubra pilaris treatment: Two case reports and literature review.
Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis characterized by hyperkeratotic follicular papules and erythematous-desquamative plaques that tend to progressively evolve into erythroderma. Treatment is challenging given that international guidelines are not available and large-scale trials do not exist. Traditionally, many topical and systemic drugs had been used as consolidated agents; recently, biologicals are gaining increasing importance, promisingly dominating the therapeutic scenario ahead. Herein, we present a case series showing the "past" and the "future" therapeutic approaches to erythrodermic PRP, one case treated with acitretin and nb-UVB phototherapy combination, while the other with ustekinumab, performing also a throughout literature review.


Visceral Leishmaniasis/HIV co-infection in northeast Brazil: evaluation of outcome.
Since the beginning of the HIV burden, Visceral Leishmaniasis (VL)/HIV co-infection has been diagnosed not only in areas where VL is endemic (Latin America, India, Asia, Southern Europe), but also in North America, were it is considered an opportunistic disease. Clinical presentation, diagnostic tests sensitivity and treatment response in this population differs from VL alone. To evaluate factors related to an unfavorable outcome in patients with VL/HIV diagnosis in a reference center in northeast Brazil. Co-infected patients, diagnosed from 2010 to 2012, were included. Data from medical records were collected until one year after VL treatment completion. Forty-two HIV-infected patients were included in the study. Anemia, leukopenia, and thrombocytopenia were present in 95%, 70.7%, and 63.4%, respectively. Mean T CD4+ (LTCD4) lymphocyte count was 183 cells/dL. Highly active antiretroviral therapy (HAART) was being used by 54.7% of cases. A favorable outcome was seen in 71.4% of cases. Recurrence of VL occurred in nine patients and deaths were secondary to infectious complications (3/42 patients). Very low LTCD4 count (<100 cells/dL) was the only independent variable associated with an unfavorable outcome in multivariate analysis (p=0.03). Low LTCD4 count at presentation was associated with unfavorable outcome in VL/HIV patients.


Spontaneous Subclavian Artery Dissection Causing Ischemia of the Medulla Oblongata and Cerebellum.
Spontaneous subclavian artery dissection is a rare etiology. Spontaneous artery dissection causing brain ischemia is rare in all ischemic strokes. However, in young to middle-aged patients with brain ischemia, spontaneous carotid or vertebral artery dissection causing ischemic stroke accounts for 10-25%. A 58-year-old man with a history of hypertension presented to the Emergency Department with a sudden onset of left-arm paresthesia and numbness followed by symptoms of vertigo and vomiting. A neurological examination showed left-arm paresthesia, horizontal-rotational nystagmus, and left-side dysmetria according to a finger-to-nose test. Contrast-enhanced computed tomography showed left subclavian artery dissection. Diffusion-weighted imaging demonstrated hyperintensity in the left medulla oblongata and inferior part of the cerebellum. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Spontaneous artery dissection is an important etiology of ischemic stroke among young patients. Cervical magnetic resonance angiography is the gold standard for the diagnosis of arterial dissection. Cervical disc disease is a common etiology in a patient with neck and shoulder pain without cause or neurologic symptoms, when cervical MRI is negative, however, spontaneous subclavian artery dissection should be considered in the differential diagnosis when a patient, especially in a case of younger patient, presents with acute new-onset neck and shoulder pain followed by the onset of neurological symptoms.


Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors.
A series of new heterocycles-linked chalcone conjugates has been designed and synthesized by varying different alkane spacers. These conjugates were tested for their in vitro cytotoxic potential against a panel of selected human cancer cell lines namely, lung (A549 and NCI-H460), prostate (DU-145 and PC-3), colon (HCT-15 and HCT-116), and brain (U-87 glioblastoma) by MTT assay. Notably, among all the tested compounds, 4a exhibited potent cytotoxicity on NCI-H460 (lung cancer) cells with IC50 of 1.48±0.19µM. The compound 4a showed significant inhibition of tubulin polymerization and disruption of the formation of microtubules (IC50 of 9.66±0.06μM). Moreover, phase contrast microscopy and DAPI staining studies indicated that compound 4a can induce apoptosis in NCI-H460 cells. Further, the flow-cytometry analysis revealed that compound 4a arrests NCI-H460 cells in the G2/M phase of the cell cycle. In addition, molecular docking studies of the most active compounds 4a and 4b into the colchicine site of the tubulin, revealed the possible mode of interaction by these new conjugates.


A proposed method for approximate estimates of the ion-activity products of calcium oxalate and calcium phosphate in spot-urine samples or in urine samples collected during less well defined periods of time.
The purpose of this study is to derive approximate estimates of ion-activity products of CaOx (APCaOx) and CaP (APCaP) useful for spot urine or other less well defined short-term urine collections. In accordance with previously applied and described principles for estimating ion-activity products, the intention was to derive simplified estimates of AP(CaOx)CONC and AP(CaP)CONC by using urine concentrations of the most important determinants of APCaOx and APCaP. A comparison thus was made between estimates derived in that manner and AP(CaOx) index and AP(CaP) index obtained from calculations based on analysis of 24 h urine samples. The best fit between estimates of AP(CaOx) index in 24 h urine and AP(CaOx) indexCONC was obtained with the following formula (r = 0.99; p = 0.0000): [Formula in text] The corresponding formula for AP (CaP) indexCONC was derived from comparison with the corresponding calculations of AP(CaP) index in 24 h urine (r = 0.91; p = 0.0000): [Formula in text] The proposed simplified formulas enable calculation of approximate estimates of APCaOx and APCaP in spot-urine samples or any kind of urine collection for which duration of the collection period is less well known and by using the concentrations (c) of the variables in mmol/L in the two formulas.


Primary repair of flexor tendons in the hand with early passive mobilization.
Flexor tendon injuries in zones I-III in the hand were treated by meticulous suture of the tendons and peritendinous structures, followed by early passive mobilization of the injured fingers, the remaining fingers being kept extended by a plaster splint. This method was used in 51 cut tendons in 38 patients. The functional recovery approached normal in 72%, and only 8% were poor.


Rare-earth elements in the NBS standard reference materials spinach, orchard leaves, pine needles and bovine liver.
A highly sensitive radiochemical neutron activation method for the determination of all rare-earth elements (REE) in NBS biological reference materials is described. The materials are irradiated, dissolved in HF/HCl solutions, mixed with scandium and REE carriers (except La, Pr, Nd, Dy, Er), and the resulting solutions evaporated to dryness. The residues are dissolved in HCl and the REE precipitated as fluorides on addition of HF/NH4F solutions. The REE fluorides were collected, dissolved in a nitric/boric acid solution and the radioactivity of the resulting solutions determined by gamma spectrometry. The concentrations of REE in the NBS SRM Spinach, Orchard Leaves, Pine Needles, and Bovine Liver were found to be in the ng/g to microgram/g range. The relative standard deviations are approximately 8%. The results agreed, within experimental errors, with literature values. The distribution patterns of REE in the NBS materials relative to chondritic meteorites resemble the patterns for geological materials.


Carbohydrate profiling of bacteria by gas chromatography-mass spectrometry: chemical derivatization and analytical pyrolysis.
Carbohydrate profiling by gas chromatography-mass spectrometry is a powerful tool for the identification and detection of bacteria. Its increasing applicability in the microbiology laboratory is illustrated by three examples. In the first, differentiation of legionellae by their sugar composition was determined with alditol acetate derivatization followed by selected- ion monitoring. In the second example, a carbohydrate pyrolysis product from Streptococcus agalactiae was used to differentiate group B streptococci from other Lancefield groups after direct sampling from culture plates. The third example employed the carbohydrates rhamnose and muramic acid as chemical markers for the direct detection of bacterial cell wall degradation products in mammalian tissues. The analysis of carbohydrate markers for bacteria by gas chromatography-mass spectrometry has great potential for use in clinical identification of isolated bacteria as well as in the rapid diagnosis of bacterial infections without prior culture.


Clinical results after cardiac valve replacement with the Sorin prosthesis. A 6-year experience.
The mechanical valve produced by Sorin is a modified tilting disc device. Between March 1979 and November 1985, 763 Sorin prostheses were implanted in 710 patients. The study has been restricted to 504 isolated mitral or aortic valves. There were 238 females and 266 males whose ages ranged from 2 to 71 years (mean 43.8). Follow-up is 99.23% and covers 1045 patient-years. No structural failure has been observed. In the aortic position, 282 Sorin prostheses were implanted with the large orifice orientated towards the right coronary sinus. Hospital mortality was 5% (14/282). Actuarial survival at 78 months was 94.68% +/- 1.6% with a linearized mortality rate of 1.7% patient-years. There were 11 late deaths (9 valve-related and 2 non valve-related). The linearized rate of occurrence of embolic events was 0.32 patient-years (2/268). Actuarial survival complication-free at 78 months was 90.88% +/- 2.83%. Preoperatively, 19.8% patients were in NYHA class II, 68.5% in III and 11.7% in IV; postoperatively, 79.3% patients were in NYHA class I, 19.5% in II and 1.2% in III. In the mitral position, 222 Sorin prostheses were implanted with the large orifice orientated anteriorly in 46 patients (group 1) and posteriorly-in 176 patients (group 2). Hospital mortality was 4.5% (10/222). Actuarial survival at 66 months was 93.25% +/- 2.1% with a linearized mortality rate of 2.8 patient-years. There were 12 late deaths (9 valve-related and 3 non valve-related). The 66-month actuarial freedom from embolic events was 95.8% +/- 1.89% with a linearized rate of occurrence of 1.44 patient-years.(ABSTRACT TRUNCATED AT 250 WORDS)


Collaborative Work or Individual Chores: The Role of Family Social Organization in Children's Learning to Collaborate and Develop Initiative.
In many communities, children learn about family and community endeavors as they collaborate and become involved in community activities. This chapter analyzes how parents promote collaboration and learning to collaborate at home in an Indigenous and in a non-Indigenous Mexican community. We examine variation among parents with different extent of experience with schooling and concepts regarding child development and relate these to patterns of child collaboration at home among Mexican Indigenous and urban families. Drawing on interviews with 34 mothers in the P'urhépecha community of Cherán, Michoacán, and 18 interviews in the cosmopolitan city of Guadalajara, Mexico, we argue that the social nature of participation may be a key feature of learning to collaborate and pitch in in families and communities where school has not been a central institution of childhood over generations.


Effect of a novel extracorporeal cytokine apheresis method on endocan, copeptin And interleukin-6 levels in sepsis: An observational prospective study.
There is still an evident need for useful biomarkers and effective therapeutic approaches regarding the challenging management of sepsis. The aim of the study is to evaluate the effect of each Cytosorb hemoadsorption therapy course on blood levels of inflammatory biomarkers of sepsis including endocan, copeptin, interleukin-6, procalcitonin, C-reactive protein. There were a total of 178 samples belonging to 34 patients that were diagnosed with sepsis and undergone Cytosorb therapy during the study period. Patient demographics were recorded. Arterial blood samples were obtained both before and and after each Cytosorb course. Levels of copeptin, interleukin-6, procalcitonin, C-reactive protein, erythrocyte sedimentation rate, white blood cell count, and creatinine were assessed both before and after each Cytosorb treatment. Levels of endocan, copeptin, interleukin-6, procalcitonin, C-reactive protein, and erythrocyte sedimentation rate were all significantly decreased after the Cytosorb course when compared with levels before therapy (p = 0.039, 0.001, 0.010, 0.001, 0.002 and 0.001, respectively). There was no significant difference between white blood cell count and creatinine levels before and after Cytosorb courses (p = 0.204 and 0.277). Cytosorb courses achieved significant decreases in endocan, copeptin, interleukin-6, procalcitonin and C-reactive protein levels. Decreasing plasma levels of inflammatory cytokines may help alleviate the cytokine storm and may have a role in improve outcomes. Further prospective randomized controlled studies with larger sample size are needed concerning the long-term effects of this decrease in cytokine levels on outcome and mortality.


Human Genetic Variation and HIV/AIDS in Papua New Guinea: Time to Connect the Dots.
Human genetic polymorphisms known to influence HIV acquisition and disease progression occur in Papua New Guinea (PNG). However, no genetic association study has been reported so far. In this article, we review research findings, with a view to stimulate genotype-to-phenotype research. PNG, a country in Oceania, has a high prevalence of HIV and many sexually transmitted infections. While limited data is available from this country regarding the distribution of human genetic polymorphisms known to influence clinical outcomes of HIV/AIDS, genetic association studies are lacking. Our studies, in the past decade, have revealed that polymorphisms in chemokine receptor-ligand (CCR2-CCR5, CXCL12), innate immune (Toll-like receptor, β-defensin), and antiretroviral drug-metabolism enzyme (CYP2B6, UGT2B7) genes are prevalent in PNG. Although our results need to be validated in further studies, it is urgent to pursue large-scale, comprehensive genetic association studies that include these as well as additional genetic polymorphisms.


Sexual Dimorphism: How Female Cells Win the Race.
Sexual dimorphisms are established by sex determination pathways and are maintained during regeneration of adult tissues. Two recent studies in Drosophila elucidate the contribution of cell-autonomous and endocrine mechanisms to the establishment and maintenance of growth dimorphism in larvae and the adult intestine.


Comparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: study protocol for a systematic review and network meta-analysis.
Depressive disorders are among the most common psychiatric disorders in children and adolescents, and have adverse effects on their psychosocial functioning. Questions concerning the efficacy and safety of antidepressant medications in the treatment of depression in children and adolescents, led us to integrate the direct and indirect evidence using network meta-analysis to create hierarchies of these drugs. Seven databases with PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to December 2013 (updated to May, 2015). There are no restrictions on language or type of publication. Randomised clinical trials assessing first-generation and newer-generation antidepressant medications against active comparator or placebo as acute treatment for depressive disorders in children and adolescents (under 18 years of age) will be included. The primary outcome for efficacy will be mean improvement in depressive symptoms, as measured by the mean change score of a depression rating scale from baseline to post-treatment. The tolerability of treatment will be defined as side effect discontinuation, as defined by the proportion of patients who discontinued treatment due to adverse events during the trial. We will also assess the secondary outcome for efficacy (response rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We will perform the Bayesian network meta-analyses for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. The network meta-analysis will provide useful information on antidepressant treatment for child and adolescent depression. The results will be disseminated through peer-reviewed publication or conference presentations. PROSPERO CRD42015016023.


Estimation of volatile N-nitrosamines in rubber nipples for babies' bottles.
A method is described for the estimation of volatile N-nitrosamines in the rubber nipples of babies' bottles. In a study of rubber nipples from one manufacturer, N-nitrosodimethylamine, N-nitrosodiethylamine and N-nitrosopiperidine were determined by gas chromatography, using a thermal energy analyser, and their presence was confirmed by mass spectrometry with average levels of individual nitrosamines ranging from 22 to 281 ppb. When the nipples were sterilized in a conventional sterilizer together with milk or infant formula the three nitrosamines migrated into the milk or formula. Storing a bottle of milk with a rubber nipple inverted in it for 2 hr at room temperature or overnight in a refrigerator after sterilization resulted in an 8-13% average increase in the nitrosamine levels migrating into the milk. On repeated sterilization of a single nipple, the quantities of nitrosamines migrating into milk from rubber nipples declined steadily, but after seven sterilizations, nitrosamines were still readily detectable in the milk. Nitrosamine levels were higher in rubber nipples after sterilization, indicating the presence of nitrosamine precursors in the nipples. No nitrosamines were found in raw, uncured rubber. Chemical accelerators and stabilizers added during the vulcanization process are the source of the amine precursors in rubber nipples.


[Surgical treatment of metastatic penile cancer - what is the scientific rationale?]
The treatment of metastases of penile cancer is confined to lymphatic metastases. Limited lymph node metastasis in penile cancer can be cured by radical lymph node surgery if complete removal of all lymph nodes of the region is achieved. Adjuvant chemotherapy is recommended. This approach applies to the regional lymph nodes of the inguinal and pelvic regions. Applying this concept to retroperitoneal lymph node metastases may also be reasonable in selected cases. The individual prognosis depends on the extent of lymphatic spread.


Event-related potentials to auditory stimuli following transient shifts of spatial attention in a Go/Nogo task.
The effects of spatial attention on the human auditory event-related potential (ERP) were examined, while attention was oriented on a trial-by-trial basis. Additionally, it was investigated whether the ERP modulation to Nogo stimuli depends on attention. In four experiments, Go and Nogo stimuli were delivered 13.3 degrees from the left or right of fixation. In Experiments 1 and 2, subjects had to press a button whenever a Go stimulus was presented at the location previously indicated by a visual precue. In Experiments 3 and 4, the cue indicated the likely location of the upcoming stimulus but a button-press was required to Go stimuli at either location. Attended (correctly cued) as compared with unattended (incorrectly cued) stimuli elicited a bimodal negative deflection in the ERPs with a parietally distributed first and a frontocentrally distributed second part. Further, Nogo stimuli evoked differential ERP modulations in the N2 and in the P3 range. The former were dependent and the latter were independent of spatial attention.


Identification of a new C-23 oxidation pathway of metabolism for 1,25-dihydroxyvitamin D3 present in intestine and kidney.
Evidence is presented for the existence of a new C-23 oxidation pathway for the metabolism of the hormonally active form of vitamin D3, namely 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). Homogenates of intestinal mucosa or kidney, but not liver, from rats and chicks convert 1,25(OH)2[26,27-3H]D3 into two new metabolites, 1 alpha,25-dihydroxy-23-oxo-vitamin D3 (1,25(OH)2-23-oxo-D3) and 1 alpha,25,26-trihydroxy-23-oxo-vitamin D3 (1,25,26(OH)3-23-oxo-D3), and an unknown metabolite(s) which has been possibly subjected to side chain modification/cleavage so that the tritium of the substrate has been converted into a form which is volatile. The isolation and chemical characterization of 1,25(OH)2-23-oxo-D3 and 1,25,26(OH)3-23-oxo-D3 from homogenates of chick intestinal mucosa has recently been described (Ohnuma, N., Kruse, J., Popjak, G., and Norman, A. W. (1982) J. Biol. Chem. 257, 5097-5102). Based on kinetic studies with chick intestinal homogenates, the proposed C-23 oxidation pathway is: 1,25(OH)2D3 leads to 1,25(OH)2-23-oxo-D3 leads to 1,25,26(OH)3-23-oxo-D3 leads to unknown metabolite with altered side chain. The relative enzyme activities of the C-23 pathway in tissues from vitamin D-replete chicks are: intestine, kidney liver, 18:3:less than 1. The activity of the C-23 pathway in homogenates of chick intestinal mucosa can be enhanced 10 x by prior priming of the birds with a single intravenous dose of 500 ng (1.3 nmol) of 1,25(OH)2D3; the induction of the enzyme activity is maximal by 3-6 h and returns to basal levels by 12 h. A comparison was made in chick and rat intestinal homogenates of this C-23 pathway and the previously known C-24 oxidation pathway, which converts 1,25(OH)2D3 into 1,24,25-trihydroxyvitamin D3 (1,24,25(OH)3D3); it was calculated that under these conditions 72% of the 1,25(OH)2D3 was metabolized by the C-23 oxidation pathway, 13% by the C-24 pathway, and only 14% by other as yet unspecified pathways. It is proposed that the newly discovered C-23 pathway for metabolism of 1,25(OH)2D3 by the target intestinal mucosa and kidney may play a prominent role under physiological conditions of controlling the tissue levels of this hormonally active form of vitamin D3.


Prognostic value of Beclin 1, EGFR and ALK in non-squamous non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The study was carried out to investigate the prognostic value of Beclin 1, EGFR and ALK for this cancer. Patients diagnosed with non-squamous NSCLC and admitted to our hospital from January 2011 to September 2016 were analyzed. Expression of Beclin 1 and mutation of EGFR and ALK were assessed using polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) and analyzed for their relationship with demographic and clinical characteristics of the patients. Multivariate Cox regression models were applied to analyze the risk factors associated with survival and receiver response curves (ROC) were plotted to determine the prognostic value of Beclin 1, EGFR and ALK for patients with non-squamous NSCLC. Compared with adjacent normal tissue, Beclin 1 expression was elevated in the cancer tissue significantly; assessments of EGFR and ALK mutations showed that out of the 480 patients, 233 (48.5%) and 75 (12.6%) patients had EGFR and ALK mutations. Univariate analysis revealed that Beclin 1 level, EGFR and ALK mutations were associated with lymph node metastasis, TNM stage, tumor differentiation and prognosis, but not with gender, age and smoking status. The Kaplan-Meier survival analysis indicated that low Beclin 1 expression and positive EGFR and ALK rearrangements were associated with higher survival rate and longer progress-free survival (PFS). Multivariate Cox regression analysis showed that Beclin 1, EGFR, ALK mutations, tumor differentiation grade, TNM stage and lymph node metastasis were independently associated with PFS. ROC analysis showed that Beclin 1, EGFR and ALK were significant predictors for PFS; the areas under curve (AUC) for Beclin 1, EGFR and ALK were 0.812 (P = 0.018, cut-off value: 1.2), 0.781 (P = 0.011, cut-off value: 15%) and 0.722 (P = 0.010, cut-off value: 11%), respectively, suggesting that they have significant prognostic value for lung cancer patients. Our data indicate that Beclin 1, EGFR and ALK genes are associated with the prognosis of patients with non-squamous NSCLC. High Beclin 1 expression and negative EGFR and ALK mutations predict a poor prognosis with PFS.


In search of work/life balance: trainee perspectives on part-time obstetrics and gynaecology specialist training.
Part-time training (PTT) is accessed by approximately 10% of Australian obstetrics and gynaecology trainees, a small but increasing minority which reflects the growing demand for improved work/life balance amongst the Australian medical workforce. This survey reports the attitudes and experiences of both full-time and part-time trainees to PTT. An email-based anonymous survey was sent to all Australian obstetrics and gynaecology trainees in April 2009, collecting demographic and training status data, data on personal experiences of PTT and/or trainees, and attitudes towards PTT. 105 responses were received (20% response rate). These indicated strong support (90%) from both full-time (FT) and part-time (PT) trainees for the availability of PTT. PT trainees were significantly more likely than FT trainees to be female with children. Improved morale was seen as a particular advantage of PTT; decreased continuity of care as a disadvantage. Although limited by poor response rate, both PT and FT Australian obstetric trainees were supportive of part-time training. Both groups recognised important advantages and disadvantages of this mode of training. Currently, part-time training is accessed primarily by female trainees with family responsibilities, with many more trainees considering part-time training than the number that access it.


Functional mapping of the Yersinia enterocolitica adhesin YadA. Identification Of eight NSVAIG - S motifs in the amino-terminal half of the protein involved in collagen binding.
The virulence plasmid-encoded YadA of Yersinia enterocolitica serotype O:3 is a 430-amino-acid outer membrane protein, synthesized with a 25-amino-acid signal peptide. YadA forms homotrimeric surface structures that function as adhesin between bacteria and collagen as well as other host proteins. The structure-function relationships of YadA were studied, and the collagen-binding determinants of YadA were located to its amino-terminal half. Collagen did not bind to any of the overlapping 16-mer YadA peptides, indicating that the collagen binding site of YadA is conformational. Epitope mapping of YadA identified 12 linear antigenic epitopes altogether. Seven epitopes were uniquely recognized by an anti-YadA antiserum able to inhibit collagen binding. Four of these epitopes shared a motif NSVAIG-S that is repeated eight times within the N-terminal half of YadA. Site-directed mutagenesis showed that these motifs are absolutely required for YadA-mediated collagen binding, revealing a novel type of collagen-binding mechanism.


Acid tolerance of an acid mine drainage bioremediation system based on biological sulfate reduction.
The acid tolerance response of an AMD bioremediation system based on sulfate reduction was investigated. Efficient sulfate reduction was observed with a maximum sulfate reduction rate of 12.3±0.8 mg L(-1) d(-1) and easily available organic carbon was released during high acid treatment with an initial pH of 2.0. The rapid increase in sulfate reduction was observed when the extreme acid treatment with an initial pH of 1.0 was stopped. Column experiment on acid shock showed that efficient sulfate reduction was maintained while precipitation of Cu or Zn still occurred during extreme or high acid shock. More than 98% of Cu and 85% of Zn were removed in the high acid column experiment with influent pH of 2.0. The majority bacteria in the remediation system used for high acid drainage belonged to genera Clostridiaceae, Eubacterium, Pseudobutyrivibrio, and Clostridium. These findings showed high acid tolerance of the straw remediation system.


Survey of cancer control attitudes among Missouri state legislators.
A number of cancer control efforts, while proven to be effective, require significant support from state and local lawmakers in order to be successful. This survey of state legislators' attitudes toward health risks and risk reduction measures that could be undertaken shows a favorable outlook for cancer control programs in Missouri.


Diminished plasma free fatty acid clearance in obese subjects.
Obese subjects were compared with lean subjects to define the previously reported disturbance of plasma free fatty acid (FFA) kinetics in terms of altered net transport (lipolysis) or clearance (esterification). These measurements were made during prolonged constant infusions of 1--14C-palmitate toward the end of sustained glucose ingestion and again 6-8 hr after stopping glucose. Net transport of FFA was suppressed to equally low levels in obese and lean subjects, though at the expense of higher insulin concentrations in the obese. Whereas in the lean subjects the clearance of FFA was significantly stimulated with glucose, the obese subjects showed low clearance rates both during and after stopping glucose. When glucose was stopped, net transport rose more rapidly and to a greater extent in some obese than in the lean subjects. The increased influx of FFA led to a rise in the plasma triglyceride level only in the lean subjects. These studies suggest that clearance of plasma FFA, probably denoting esterification in tissues such as muscle and adipose tissue, is impaired in obesity and cannot be readily stimulated with glucose and insulin. Lipolysis, measured as net transport of FFA, however, is suppressible with glucose and insulin in the obese, though this might be achieved only at insulin levels that are higher than those in lean subjects.


Engineering human ventricular heart muscles based on a highly efficient system for purification of human pluripotent stem cell-derived ventricular cardiomyocytes.
Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish. The purification system used TALEN-mediated genomic editing techniques to insert the neomycin or EGFP selection marker directly after the myosin light chain 2 (MYL2) locus in human pluripotent stem cells. Purified early ventricular cardiomyocytes were estimated by immunofluorescence, fluorescence-activated cell sorting, quantitative PCR, microelectrode array, and patch clamp. In subsequent experiments, the mixture of mature MYL2-positive ventricular cardiomyocytes and mesenchymal cells were cocultured with decellularized natural heart matrix. Histological and electrophysiology analyses of the formed tissues were performed 2 weeks later. Human ventricular cardiomyocytes were efficiently isolated based on the purification system using G418 or flow cytometry selection. When combined with the decellularized natural heart matrix as the scaffold, functional human ventricular heart muscles were prepared in a dish. These engineered human ventricular muscles can be great tools for regenerative therapy of human ventricular damage as well as drug screening and ventricular-specific disease modeling in the future.


Evaluating the sorption of organophosphate esters to different sourced humic acids and its effects on the toxicity to Daphnia magna.
Because of large usage as flame retardants and additives, organophosphate esters (OPEs) are widely detected in the environment and regarded as emerging contaminants. However, the sorption of OPEs to organic matter and its effects have scarcely been studied. In the present study, the sorption of 9 commonly used OPEs to 4 representative humic acids--Elliott Soil humic acid, Suwannee River humic acid, Aldrich humic acid, and Acros humic acid--in the range of 0 mg/L to 50 mg/L dissolved organic carbon (DOC), was evaluated with negligible-depletion solid-phase microextraction and verified by its impacts on the toxicity to the aquatic invertebrate Daphnia magna. Whereas OPEs with a high octanol/water partition coefficient (log K(OW)=4.51-6.64) were associated with humic acids mainly by hydrophobic interaction with DOC partition coefficient (K(DOC)) in the range of 10²·²² to 10⁵·³¹, the sorption of low-K(OW) OPEs (log K(OW)=-0.65 to 2.59) to humic acids was not hydrophobic interaction-dominant, with K(DOC) in the range of 10³·⁴⁷ to 10⁴·²⁹. These results were corroborated by the effects of humic acids on the acute toxicity of 3 high-K(OW) OPEs to D. magna. The sorption of OPEs to Suwannee River humic acid was weak and had negligible effects on the toxicity of high-K(OW) OPEs; the presence of terrestrial Acros humic acid (50 mg/L DOC), however, significantly decreased the toxicity by 53% to 60%. The results indicated that the strong sorption between high-K(OW) OPEs and terrestrial humic acid might affect their transportation and bioavailability.


Age- and sex-based recovery curves to track functional outcomes in older adults with total knee arthroplasty.
older adults with total knee arthroplasty (TKA) frequently undergo rehabilitation to address limited knee flexion range-of-motion, quadriceps weakness and gait speed limitations. This study aimed to develop age- and sex-specific recovery curves of knee flexion range-of-motion, quadriceps strength and fast gait speed post-TKA. a population-based sample of 2,987 patients undergoing primary TKA participated, of whom 2015 (68%) were 65 years of age or older. At 4, 8 and 12 weeks post surgery, knee flexion range-of-motion, quadriceps strength and fast gait speed were quantified. Quantile regression was used to determine the percentiles of the knee and gait measures. the various knee and gait measures improved nonlinearly over time, with substantial improvements observed in the 1st 8-10 weeks post surgery. Age-specific, sex-specific recovery curves were developed to show the recovery patterns at multiple percentile levels. A web interface was created to facilitate easy computation of the percentile rank for a given outcome value. we have provided reference percentile values for knee flexion range-of-motion, quadriceps strength and gait speed recovery post-TKA. Such information may assist rehabilitation professionals in interpreting outcomes and quantifying deviations from the expected recovery pattern.


Chronic dopamine D1, dopamine D2 and combined dopamine D1 and D2 antagonist treatment in Cebus apella monkeys: antiamphetamine effects and extrapyramidal side effects.
To determine: (1) whether the apparent lack of efficacy of dopamine D1 (D1) antagonists in the clinic might be attributable to development of tolerance to antipsychotic effects; and (2) whether combined D1 and D2 antagonism might contribute to clozapine's clinical profile, eight Cebus apella monkeys were chronically treated with a D1 antagonist (NNC 756) ((+)-8-chloro-7-hydroxy-3-methyl-5-(7-(2,3- dihydrobenzofuranyl)-2,3,4,5-tetrahydro-1H-3-benzazepine), a D2 antagonist (raclopride) or a combination of the two antagonists. Prior neuroleptic exposure had resulted in oral dyskinesia in seven monkeys and sensitization to dystonia in all, yielding a model for acute and chronic extrapyramidal side effects (EPS). Dextroamphetamine-induced motoric unrest and stereotypies were used as a psychosis model. We found tolerance toward dystonic symptoms during D1 and D1 + D2 treatments but not during D2 treatment. D2 but not D1 or D1 + D2 antagonism caused exacerbation of dyskinesia. Both D1 and D1 + D2 antagonism were superior to D2 antagonism alone in counteracting the amphetamine-induced behaviors, with no tolerance to antiamphetamine effects. These findings suggest: (1) reasons other than tolerance (e.g., differences among antagonists) may explain the lack of efficacy in clinical trials with D1 antagonists; and (2) that D1 antagonism alone or combined and modest D1 and D2 antagonism offers the potential of antipsychotic efficacy with a lower risk of EPS than traditional D2 antagonism. Further clinical trials with D1 or combined D1 and D2 antagonists are, therefore, recommended.


Streamflow modeling and contribution of snow and glacier melt runoff in glacierized Upper Indus Basin.
The Upper Indus Basin has a large concentration of glaciers and mainly fed by snow and glacier melt. These melt runoffs are the primary driver of discharge and significantly contribute to Indus flows. Therefore, the present study was undertaken in the Upper Indus Basin (UIB) up to the Besham Quila site. This study focuses on quantifying runoff's contribution from different sources, including snow and glacier melt, and evaluates model performance in the glacierized Himalayan basin. The model was calibrated (1981-2000) and validated (2001-2007) daily and monthly using 27 years of measured discharge data at the Besham Quila station. A statistical indicator shows a "good" relationship between simulated and observed discharge on a daily and "very good" on a monthly timestamp. In this study, the annual contribution from snow/ice melt in the basin was quantified and found to be 51% of the total runoff. Apart from this, around 30% of water comes from direct runoff generated through liquid precipitation and 3.8% from groundwater. The remaining (~15%) is contributed by interflows sourced from the rainfall and snow/ice melt. The basin receives 61% contribution from snow and glacier melt during monsoon (July-Sept) and 38% during summer (April-June) seasons, while negligible in other seasons. A decreasing trend is observed in modelled total runoff and melt runoff of about 1.11 × 109 m3 a-1 and 0.73 × 109 m3 a-1, respectively.


Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood.
Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.


Controlled release of sulfasalazine release from "smart" pectin gel microspheres under physiological simulated fluids.
Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255 min in simulated gastric fluid (pH = 1.2), simulated intestinal fluid (pH = 6.8), and phosphate buffer (pH = 7.4) were 15.0%, 47.0%, and 52.2%, respectively.


Noninvasive prediction of pulmonary hemodynamics in chronic thromboembolic pulmonary hypertension by electrocardiogram-gated computed tomography.
The aim of the study was to investigate the potential of electrocardiogram (ECG)-gated computed tomography pulmonary angiography (CTPA) as a predictor of disease severity in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Forty-five CTEPH patients with a mean age of 63.8 years±12.7 y (±standard deviation) who had undergone ECG-gated CTPA and right heart catheterization (RHC) were included in the study. Right ventricular to left ventricular volume ratio (RVV/LVV), diameter ratio on 4-chamber view (RVD4CH/LVD4CH), pulmonary trunk (PT) diameter, PT to aortic diameter ratio (PT/A), and septal angle were correlated to mean pulmonary artery pressure (mPAP). Moreover, RVV/LVV and RVD4CH/LVD4CH were adjusted to pulmonary diameter index (PADi) and PT/A index. Areas under the curve (AUC) for predicting mPAP above 40 mmHg, 35 mmHg, and 30 mmHg were calculated. RVD4CH/LVD4CH revealed the strongest correlation to mPAP before (r = 0.6507) and after (r = 0.7650; p < 0.0001) PT/A adjustment. The AUCs for predicting pH with mPAP over 40 mmHg and 30 mmHg were 0.9229 and 0.864, respectively. A cutoff value of 1.298 enabled prediction of pH with mPAP over 40 mmHg with a sensitivity, specificity, positive predictive, and negative predictive value of 80.00 %, 95.83 %, 88.46 %, and 94.12 %, respectively. Intra- and interobserver variability were excellent for all parameters. Combining different and easily evaluable ECG-gated CTPA parameters enables excellent prediction of pulmonary hemodynamics in CTEPH patients. Ventricular diameter ratio on 4-chamber view adjusted by the PT/A ratio yielded the best correlation to mPAP.


Interactions after death: plant litter controls priority effects in a successional plant community.
We performed a field experiment to test whether the presence of litter produced by the dominant species in the first successional year affects the plant community structure in the following year. We removed the litter of Setaria faberii (the first-year dominant) in midfall, early spring, mid-spring, or late spring. Both the fall and early spring removal increased the biomass of Erigeron annuus, which became dominant, and reduced the biomass of S. faberii. In the fall-removal treatment more plants of E. annuus flowered, while early spring removal increased the biomass of rosettes (non-flowering individuals) at the end of the growing season. In the other treatments and in the control S. faberii retained dominance, but its biomass was the highest in mid-spring removal plots. The removal of litter of S. faberii in the fall and in early spring allowed E. annuus to pre-empt the site and dominate the community. When litter was not removed, it strongly hindered the growth of E. annuus, favoring S. faberii. These results highlight the importance of litter as a historical factor linking interactions across successive generations, and controlling the community structure.


Pre-transplant Panel Reactive Antibody and Survival in Adult Cystic Fibrosis Patients After Lung Transplantation.
Survival implications of pre-transplant antibodies to human leukocyte antigens prior to lung transplantation (LTx) in adult cystic fibrosis (CF) patients are unknown. Data from the United Network for Organ Sharing Registry (1987-2013) were used to compare survival differences in adult CF patients with pre-transplant class I and II panel reactive antibody (PRA) levels ≤10 versus >10 %. Of 3149 CF LTx recipients, 1526 and 1399 were included in univariate survival analyses of class I and II PRA, respectively, while 1106 and 1001 were included in multivariate Cox analyses for class I and class II, respectively. Kaplan-Meier survival functions failed to demonstrate significant differences in survival with PRA >10 % for class I (Log-rank test: χ (2) (df = 1): 1.11, p = 0.293) or class II (Log-rank test: χ (2) (df = 1): 0.99, p = 0.320). Adjusting for covariates, multivariate Cox models demonstrated that class II PRA >10 % was associated with a significant increase in mortality hazard (HR 1.918; 95 % CI 1.128, 3.261; p = 0.016), whereas class I PRA >10 % was uncorrelated with this outcome. Pre-transplant PRA class II >10 % in adult CF patients is associated with elevated mortality hazard after LTx.


Intraocular endoscopy in the management of ocular trauma: clinical settings and treatment outcomes at a tertiary eye care centre.
To report the application of endoscopy in the management of ocular trauma, describe the clinical settings and the treatment outcomes. Retrospective, consecutive, non-comparative case series at a tertiary eye care centre. Data recorded included aetiology of trauma, presenting vision, corneal condition at presentation, per-operative clinical findings during endoscopy, prognostication of the cases on table, final visual and anatomic outcome. Odds ratios for a favourable outcome were computed for various surgical indications. The study included 58 eyes of 58 patients. Males constituted 82% of all cases. Mean age at presentation was 35.55 ± 18.9 years, median 31.5 years. Commonest corneal condition causing opaque media was corneal oedema (44.8%) followed by corneal laceration in 25.8%, repaired corneal laceration in 13.7% and scarred cornea in 12%. Commonest indication for surgery was retinal detachment (36.2%) followed by vitreous haemorrhage (29.3%), retained foreign body (13.7%) and combined detachment with haemorrhage in 10.3%. Of the 58 eyes, 17 eyes were deemed inoperable on endoscopic examination and 11 eyes were deemed to have poor prognosis. Of the fair prognosis (n = 30), 60% had final vision of 20/400 (p = 0.0001) compared to 10% before surgery and 13.33% had final vision of 20/40 (p = 0.03) as compared to nil in the pre-operative period. Odds ratio for a favourable visual outcome was best for the indication of vitreous haemorrhage (OR = 9, p = 0.0006). Endoscopy in ocular trauma with opaque media provides adequate visualisation and allows for prognostication. In cases deemed to have prognosis, suitable intervention leads to globe and vision salvage.


Tracking longitudinal biomarkers in burn patients with sepsis and acute kidney injury: an unsupervised clustering approach.
Sepsis is a grave medical disorder characterized by a systemic inflammatory response to infection. Furthermore, it is a leading cause of morbidity and mortality, especially in hospitalized patients. Acute kidney injury (AKI) is a common complication of sepsis and is associated with increased morbidity and mortality. Patients with burns are particularly vulnerable to developing sepsis and AKI due to the extensive tissue damage and immune suppression resulting from burn injury. In this study, unsupervised clustering algorithms were used to track longitudinal biomarkers in patients with burns and assess their impact on mortality. This retrospective study included adult patients with burns aged ≥ 18 years, who were admitted to the burn intensive care unit of Hallym University and Hangang Sacred Heart Hospital between July 2010 and December 2021. The patients were divided into two subgroups: those with sepsis (538 patients) and those without sepsis (826 patients). The longitudinal biomarkers were grouped into three clusters using the k-means clustering algorithm. Each cluster was assigned a letter from A to C according to its mortality rate. The odds ratio (OR) of pH was 9.992 in the positive group and 31.745 in the negative group in cluster C. The OR for lactate dehydrogenase (LD) was 3.704 in the positive group and 6.631 in the negative group in cluster C. The OR for creatinine was 2.784 in the positive group and 8.796 in the negative group in cluster C. The OR for blood urea nitrogen (BUN) in the negative group was 0.348, indicating a negative predictor of mortality. Regarding the application of Continuous Renal Replacement Therapy (CRRT) and ventilation, ventilation was significant in both groups. In contrast, CRRT application was not significant in the sepsis-positive group. Furthermore, it was not selected as a variable in the negative group. The pH, LD, and creatinine were significant in both groups, while lactate and platelets were significant in the sepsis-positive group. In addition, albumin, glucose, and BUN were significant in the sepsis-negative group. Continuous renal replacement therapy was not significant in either group. However, the use of a ventilator was associated with poor prognosis.


Outpatient parenteral antimicrobial therapy technology.
Health care costs are continuing to spiral upward despite government and public insistence on cost containment. To meet the challenge, medical professionals and organizations are seeking opportunities for cost reduction and alternatives for delivery health care. This article discusses the tools that allow the effective delivery of care using the outpatient parenteral antimicrobial therapy (OPAT) model.


Drug discovery from natural products - Old problems and novel solutions for the treatment of neurodegenerative diseases.
The use of natural products has been shown to be a fruitful approach in the discovery of novel pharmaceuticals. In fact, many currently approved drugs originated from compounds that were first identified in nature. Chemical diversity of natural compounds cannot be matched by man-made libraries of chemically synthesized molecules. Many natural compounds interact with and modulate regulatory protein targets and can be considered evolutionarily-optimized drug-like molecules. Despite this, many pharmaceutical companies have reduced or eliminated their natural product discovery programs in the last two decades. Screening natural products for pharmacologically active compounds is a challenging task that requires high resource commitment. Novel approaches at the early stage of the drug discovery pipeline are needed to allow for rapid screening and identification of the most promising molecules. Here, we review the possible evolutionary roots for drug-like characteristics of numerous natural compounds. Since many of these compounds target evolutionarily conserved cellular signaling pathways, we propose novel, early-stage drug discovery approaches to identify drug candidates that can be used for the potential prevention and treatment of neurodegenerative diseases. Invertebrate in vivo animal models of neurodegenerative diseases and innovative tools used within these models are proposed here as a screening funnel to identify new drug candidates and to shuttle these hits into further stages of the drug discovery pipeline.