Comprehensive outcomes of on- and off-antiviral prophylaxis in hepatitis B patients undergoing cancer chemotherapy: A competing risks analysis.
Although antiviral prophylaxis is essential in hepatitis B patients in the context of cancer chemotherapy, there is little evidence-based consensus regarding the appropriate prevention strategy depending on the underlying type of cancer and viral status. This retrospective study included a comprehensive cohort of 302 hepatitis B surface antigen-positive patients with various cancers undergoing chemotherapy and antiviral prophylaxis. The rates of hepatitis B virus (HBV) reactivation during antiviral therapy (>1 log10 IU/mL increase or positive conversion of serum HBV DNA) and relapse when off antivirals ([re]appearance of HBV DNA >2,000 IU/ml with related alanine aminotransferase elevation) were evaluated, together with the associated risk factors, in a competing risks analysis where cancer death was considered as the competing event. During antiviral prophylaxis, HBV was reactivated in six patients (1.9%), who had leukemia (n = 4) or lymphoma (n = 2) and were treated with lamivudine (n = 4) or entecavir (n = 2). The incidence rate of HBV relapse in 127 off-prophylaxis patients was 21.3% during a median post-antiviral period of 11.7 months. Lymphoma, pre-prophylactic HBV DNA ≥2,000 IU/ml, and age ≥50 years were independent predictors of off-treatment HBV relapse (adjusted hazard ratios 5.25, 3.07, and 0.34, respectively; Ps < 0.05). Antiviral and anticancer drugs, duration of consolidation on antiviral prophylaxis, and HBeAg positivity were not independent predictors. In conclusion, hepatitis B flare-ups are not rare in patients receiving cancer chemotherapy during and after anti-HBV prophylaxis, even when potent antivirals are used. Patients with hematopoietic or lymphoid neoplasms or high viral burdens should receive prolonged and powerful HBV prophylaxis. J. Med. Virol. 88:1576-1586, 2016. © 2016 Wiley Periodicals, Inc.


Quantitative assessment of condyle positional changes before and after orthognathic surgery based on fused 3D images from cone beam computed tomography.
To establish one method that can be used to quantitatively evaluate the condyle positional changes with 3D images in postoperative mandibular prognathism patients. This is a retrospective observational study. Twenty-one patients who underwent bilateral sagittal split ramus osteotomy (BSSRO) were scanned with cone beam computed tomography (CBCT) for temporomandibular joints (TMJs) at 1 week preoperatively (T0), 1 to 2 weeks (T1), 3 months (T2), 6 months (T3), and 12 months (T4) postoperatively. The data were then grouped into T0T1, T1T2, T2T3, T3T4 and T0T1, T0T2, T0T3, and T0T4. Semi-automatic registration was conducted, and the condyle positional changes were measured in segmented 3D models. Inter- and intra-observer variability and the repeatability of registration were analyzed with paired t test; the repeated measurement analysis of variance was used for analyzing the repeatability of the marked points; the consistency of segmentation was analyzed with nonparametric test of multiple paired samples (Friedman test) and the independent-sample t test was applied to comparing changes between different periods of time. Differences were considered to be statistically significant when P < 0.05. In T0T1 and T1T2, the condylar position was changed greatly. In T2T3, the mean condylar translations were less than 0.2 mm in all directions, the mean rotational changes of condyle were less than 0.2 mm; in the period of T3T4, the mean condylar translations in all directions were less than 0.02 mm. For series 2, the condyle translational changes in axial, coronal, and sagittal views were within 0.10 mm, and the rotation direction of condyle in all three views was the same within 1 year after operation. Fused three-dimensional images can be used to qualitatively and quantitatively evaluate condyle positional changes. The condylar position might be stable at 3 months postoperatively. The condyles of most of patients did not fully return to their preoperative position within 1 year after the operation. One method for fusing images has been established to detect the condylar positional changes. This method may be applied to estimate the bony changes of condyle, even bony changes in other part of dentomaxillofacial region. Meanwhile, the data of condyle positional changes from asymptomatic patients after the surgery within 1 year can be used as a reference for further exploration of the relationship between orthognathic surgery and the occurrence of osteoarthritis postoperatively in the future. • By fused 3D images, the change of condylar position after bilateral sagittal split ramus osteotomy can be observed intuitively. • For the patients with mandibular prognathism, the condylar position would be stable at 3 months postoperatively. • The condyles of most mandibular prognathism patients did not fully return to their preoperative position within 1 year after operation.


Transversal craniofacial growth evaluated on children dry skulls using V2 and V 3 canal openings as references.
The aim of this study was to investigate the transversal relationships between two cephalometric landmarks and lines on the face using ovale, rotundum, greater palatine and infra-orbital foramina as references. Thirty-four children dry skulls, 19 males and 15 females aged 0-6 years, were examined by computed tomography scanning by using constructed tomographic axial and frontal planes. The cephalometric transversal dimensions of the face skull were measured between the right and left landmarks from the orbital lateral wall and from the zygomatic arch. The cephalometric transversal dimensions of the base skull were measured between the right and left ovale, rotundum, greater palatine and infra-orbital foramina. Statistical analysis using partial correlations, regardless of the age, showed strong relationships (p < 0.05) among transversal measurements with nerve canal openings and transversal distances of skull face. We showed that the cranial base transversal growth was very strongly related to facial transversal growth from the postnatal period up to 6 years of age.


Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach.
Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.


An innovative approach of urban noise monitoring using cycle in Nagpur, India.
Noise is one of the most significant sources of environmental pollution in metro cities. Traffic noise plays an important role to contribute to ambient noise pollution. Noise pollution monitoring was carried out using sound level meter mounted on the cycle with the help of mould fixed on it. Cycle is a noiseless mode of transport and therefore, it was used for noise monitoring over 700 locations in Nagpur City. Noise levels were recorded at each location for 5 min during peak rush hours of traffic in the morning and in the evening at an interval of 1 s leading to around 300 readings each. Noise indices like Leq, L90, L10, Lmax and Lmin were calculated for noise level data analysis. TNI was also determined for analysis of traffic noise on intersections of roads. Equivalent noise levels were transferred into the Geographic Information System (GIS) and spatial analysis tool was used to create spatial and strategic noise maps. Based on the maps, it is revealed that noise levels are exceeded all over the city with respect to ambient noise standards. It was experienced that intersections of roads during peak rush time are very noisy due to honking. The study recommends the noise monitoring through cycle-mounted sound level meter since it covers unapproachable sites, more coverage in the city that helps in identifying hotspot area of concern for noise abatement strategies and planning.


White finger millet starch: Hydrothermal and microwave modification and its characterisation.
White finger millet (WFM) starch was modified by hydrothermal (HS) and microwave (MS) methods. Modification methods had a significant change in the b* value observed in the HS sample, and it caused the higher chroma (∆C) value. The treatments have not significantly changed the chemical composition and water activity (aw) of native starch (NS) but reduced the pH value. The gel hydration properties of modified starch enhanced significantly, especially in the HS sample. The least NS gelation concentration (LGC) of 13.63 % increased to 17.74 % in HS and 16.41 % in MS. The pasting temperature of the NS got reduced during the modification process and altered the setback viscosity. The starch samples exhibit the shear thinning behavior and reduce starch molecules' consistency index (K). FTIR results exhibit that the modification process highly altered the short-range order of starch molecules more than the double helix structure. A significant reduction in relative crystallinity was observed in the XRD diffractogram, and the DSC thermogram depicts the significant change in the hydrogen bonding of starch granules. It can be inferred that the HS and MS modification method significantly alters the properties of starch, which can increase the food applications of WFM starch.


Commentary: Cultural Issues in Decisionmaking.
This case presents several fundamental ethical issues. The first issue is the patient's refusal of treatment (a nasogastric tube [NGT] insertion). Second, the patient's refusal of a seemingly beneficial treatment, combined with her medical history, ultimately necessitates an assessment of her decisionmaking capacity. Third, the sister's reluctance to participate in decisionmaking requires a discussion of appropriate surrogate decisionmakers. Finally, the main ethical component to this case is a cultural one, which should be addressed appropriately.


Petechial exanthem in "bathing trunk" distribution caused by parvovirus B19 infection.
We report a 13-year-old boy with a petechial rash on the genital area, in which primary infection by Parvovirus B19 was demonstrated by seroconversion. To our knowledge this is the first instance of an exanthem arising from Parvovirus B19 with an exclusive genital distribution without typical acral involvement.


Monoclonal antibodies to lampbrush chromosome antigens of Pleurodeles waltlii.
Germinal vesicles of oocytes from Pleurodeles waltlii were used for immunization of BALB/c mice to obtain hybridomas secreting monoclonal antibodies. The hybridomas were screened for reactivity of their antibodies against lampbrush chromosomes of oocytes, as revealed by indirect immunostaining. Antibodies labelling the lampbrush chromosomes were also tested on histological sections of oocytes, embryos, and larvae of Pleurodeles. Characterization of the antigens was accomplished through immunoblotting of two-dimensional electrophoretic gels of germinal vesicle proteins. The ten monoclonal antibodies giving a positive reaction were classed into five groups. Group 1, exemplified by antibody A33, recognizes all the lampbrush chromosome transcribing sites (loops). Moreover, it differentially labels the cell nuclei during embryonic and larval development. Group 2, antibody B71, also stains all the loops of the lampbrush chromosomes, but does not react with cell nuclei of embryos and larvae. Group 3, antibody A1, labels specific loops, some of which are heterozygous in the strain of P. waltlii used. These heterozygosities have allowed us to localize and to characterize a chromosomal segment on bivalent IV which is heteromorphic in the two partners of the bivalent. We suggest that this heteromorphism represents a morphological distinction between Z and W heterochromosomes. Moreover, this antibody reacts with only one transcription unit along a loop that contains several units. Group 4, antibody B24, stains the only two structures in the lampbrush chromosomes of P. waltlii that do not have a loop organization, the mass "M" and the spheres. Group 5, antibody A35, reacts with the chromomeres. The antigens corresponding to antibodies A33 and B24 have been identified as proteins, which have apparent molecular weights of 80 and 104 kilodaltons, respectively. They correspond to proteins abundant in the germinal vesicles. All the antibodies described here cross-react with the lampbrush chromosomes of five other species of Urodeles.


A randomized controlled trial of Vitamin D supplementation in Iranian patients with schizophrenia: Effects on serum levels of glycogen synthase kinase-3β and symptom severity.
Growing evidence has shown that hypovitaminosis D is a risk factor for developing schizophrenia and comorbid conditions. Therefore, this study aimed to examine the effect of vitamin D supplementation on serum levels of vitamin D, metabolic factors related to insulin resistance (IR) and the severity of the disorder in patients with schizophrenia. Forty-eight chronic male patients with schizophrenia with vitamin D deficiency (≤20 ng/mL= (≤50 nmol/l) were selected and randomly assigned to vitamin D treatment and placebo groups. Subjects were supplemented for 8 weeks with vitamin D (2000 IU/day) or placebo. Within-group comparison revealed that the vitamin D group had a significant reduction in waist circumference, Positive and Negative Syndrome Scale - total score (PANSS-TS), and glycogen synthase kinase 3 beta (GSK-3β) levels (P = .022, P = <.001 and P = .013, respectively). On the other hand, the placebo group showed a significant increase in the level of fasting serum insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (P = .003 and P = .003). The between-group comparison showed a significant difference in terms of PANSS-TS, GSK-3β, fasting serum insulin (FSI), and HOMA-IR (P = .022, P = .048, P = .013 and P = .014 respectively). Among vitamin D deficient patients with schizophrenia, vitamin D supplementation may affect GSK-3 β, an important biomarker in schizophrenia and insulin resistance. In addition, vitamin D supplementation in such patients may reduce the disorder's symptom severity.


High yielding alkylations of unactivated sp3 and sp2 centres with alkyl-9-BBN reagents using an NHC-based catalyst: Pd-PEPPSI-IPrf.
High yielding, room temperature cross couplings of unactivated alkyl bromides and aryl bromides/chlorides with alkyl-9-BBN reagents has been achieved using an NHC-based catalyst (Pd-PEPPSI-IPr) via a general, functional-group tolerant and easily implemented protocol.


Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: a study in WBN/Kob rats.
The effects of various vasorelaxant agents on aortas from control and genetically diabetic rats were examined. The concentration-response curves for the isoproterenol (ISO)-induced relaxation of both aortic strips with and without endothelium are shifted to the right in diabetic rats. The relaxation responses of diabetic aorta to forskolin and vasoactive intestinal peptide did not differ from those of controls. The relaxation responses of diabetic aorta to cromakalim and nicorandil did not differ from those of controls. These results indirectly indicate that ISO-induced relaxation responses of the aortic strips from genetically diabetic rats decreased, and that this decreased relaxation response of the strips to ISO may be due to decreased density or affinity of beta adrenoceptors on the endothelium and vascular smooth muscle.


Drug Addiction Stigma in the Context of Methadone Maintenance Therapy: An Investigation into Understudied Sources of Stigma.
Experiences of stigma from others among people with a history of drug addiction are understudied in comparison to the strength of stigma associated with drug addiction. Work that has studied these experiences has primarily focused on stigma experienced from healthcare workers specifically even though stigma is often experienced from other sources as well. Because stigma has important implications for the mental health and recovery efforts of people in treatment, it is critical to better understand these experiences of stigma. Therefore, we characterize drug addiction stigma from multiple sources using qualitative methodology to advance understandings of how drug addiction stigma is experienced among methadone maintenance therapy patients and from whom. Results demonstrate that methadone maintenance therapy patients experience prejudice, stereotypes, and discrimination from friends and family, coworkers and employers, healthcare workers, and others. Discussion highlights similarities and differences in stigma experienced from these sources.


Predicting solvent effects on the structure of porous organic molecules.
A computational approach for the prediction of the open, metastable, conformations of porous organic molecules in the presence of solvent is developed.


Complications of Catheter Drainage for Amoebic Liver Abscess.
Per-cutaneously inserted catheter drainage is an accepted treatment modality for a large amoebic liver abscess. Complications that can arise are; secondary infection, bleeding into the abscess cavity, inadvertent catheter misplacement into the IVC and rupture of abscess with spillage into the peritoneal cavity. We report a case of a large amoebic liver abscess that presented with complications related to per-cutaneously inserted catheter drainage.


Influence of light on pectic enzymes in root exudates of Trifolium alexandrinum inoculated with Rhizobium trifolii.
An in vitro experiment was conduced under bacteriologically controlled conditions to examine the effect of light on the production of pectin methyl esterase (PME) and pectin polygalacturonase (PG) in the root exudates of Trifolium alexandrinum inoculated with an efficient strain of Rhizobium trifolii. The results revealed that PME and PG increased with an increase in the duration of light to which plants were exposed. However, both the enzymes were detected in the root exudates of nonphotosynthesizing plants.


In vitro remodelling of plasma lipoproteins in whole plasma by lipoprotein lipase in primary and secondary hypertriglyceridaemia.
In patients with familial lipoprotein lipase deficiency (FLPL-d) and glycogen storage disease type I (GSD-I), hypertriglyceridaemia (1445 +/- 247 and 1082 +/- 312 mg dl-1, n = 5 per group) was associated primarily with reduced extrahepatic lipoprotein lipase (LPL) activity (0.33 +/- 0.33 and 1.69 +/- 0.38 mumol FFA ml-1 h-1) when compared with controls (4.83 +/- 0.90). Hypercholesterolaemia was characterized by elevated LDL cholesterol (191 +/- 30 and 344 +/- 34 vs. 115 +/- 5 mg dl-1 in controls P less than 0.01) and low HDL cholesterol (12 +/- 2 and 22 +/- 2 vs. 56 +/- 3 in controls, P less than 0.001). In order to ascertain the role of LPL in the interconversion and remodelling of lipoproteins in these disorders, we analysed lipid and lipoprotein profiles before and following in vitro incubation of patient plasma with purified milk LPL (EC 188.8.131.52) for 6 h at 37 degrees C. The efficiency of exogenous LPL in vitro was demonstrated by the extent of hydrolysis of chylomicrons and of VLDL-TG in both groups. Concomitant with the disappearance of TG-rich lipoprotein particles, a consistent per cent increment of IDL (99.2 +/- 30.8 and 43.9 +/- 70.5), LDL (152.8 +/- 36.2 and 137.0 +/- 36.1) and of HDL2 (144.8 +/- 29.4 and 99.8 +/- 18.7) was observed in both groups of patients. The enhancement of the latter fractions contrasted with the decline of HDL3 mass concentration (25.4 +/- 7.7 and 51.4 +/- 5.8%), suggesting that a major shift of HDL3----HDL2 occurs following in vitro lipolysis by LDL. Simultaneous compositional and morphological changes of individual lipoprotein particles were noted, confirming the dynamic movement and exchange of neutral lipids and proteins. Specificity of LPL results was demonstrated by experiments in which incubation of the whole plasma at 37 degrees C without exogenous lipolytic enzyme did not cause any substantial changes. The present study, therefore, demonstrates a correction of the major lipoprotein abnormalities associated with FLPL-d and GSD-I by exogenous LPL. No substantial difference was noted between primary (FLPL-d) and secondary (GSD-I) hyperlipidaemias. These studies allow us to conclude that a simple in vitro system, utilizing an exogenous source of LPL and plasma from patients, may serve as a suitable model for the study of the metabolic relationships of lipoproteins. However, in view of the fact that the extent of lipolysis achieved in vitro did not differ between FLPL-d and GSD-I, it may not be able to separate primary from secondary hyperlipaemias.


The structural basis of β2 integrin intra-cellular multi-protein complexes.
In multicellular organisms, cell adhesion is a pivotal physiological process which is essential for cell-cell communications, cell migration, and interactions with extracellular matrix. Integrins, a family of large hetero-dimeric type I membrane proteins, are known for driving cell adhesion functions. Among 24 different integrins, four β2 integrins, αL β2, αM β2, αX β2 and αD β2, are specific for cell adhesion and migration of leukocytes. Many cytosolic proteins interact with short cytosolic tails (CTs) of β2 and other integrins which are essential in bi-directional signaling processes. Further, phosphorylation of CTs of integrins regulates binding of intra-cellular proteins and signaling systems. In this review, recent advances in structures and interactions of multi-protein complexes of integrin tails, with a focus on β2 integrin, and cytosolic proteins are discussed along with a proposed future direction.


[The study of dendritic cells derived from acute myeloid leukemia cells].
To induce dendritic cells (DCs) from primary acute myeloid leukemia (AML) cells with cytokines, so as to provide a new approach for immunotherapy of leukemia. Bone marrow MNCs were isolated from 12 AML patients and 6 healthy donors, and co-cultured with rhGM-CSF 1000 U/ml, rhIL-4500 U/ml and TNF-alpha 50 U/ml for 10 days. The morphologic features were observed by Wright's staining, inverted microscope and electron microscope. CD(80), CD(86), CD(83), CD(1a), HLA-DR expression were assayed by flow cytometry, cytogenetic analysis was performed by fluorescence in-situ hybridization (FISH), the function of antigen presenting were tested by mixed lymphocyte reaction (MLR). After cultured with cytokines, typical dendritic appearance with delicate membrane projections could be founded, the CD(80), CD(86), CD(83), CD(1a) markers and capacity of stimulating allogeneic T cells were upregulated significantly. The cultured DCs were confirmed to generate from malignant origin. There have no difference in morphology and immunophenotype expression between the DCs from AML patients and those from normal individuals. However, DCs derived from AML patients displayed decreased activity when tested in MLR. Primary AML cells could be induced into AML-DCs with cytokines. The study suggests that it may be used efficiently in immunotherapy of AML.


Ischemic stroke in COVID-19 patients: a cross-sectional study from an Indonesian COVID-19 referral hospital.
COVID-19 increases the risk of acute ischemic stroke. The objective of this study is to identify the risk factors, comorbidities, and outcomes in COVID-19 patients with acute ischemic stroke at University of Indonesia Hospital. The clinical condition of COVID-19 patients with ischemic stroke is more severe for patients older than 55 years (p < 0.05), patients at the critical COVID-19 clinical stage, and patients with atrial fibrillation (p < 0.05). The level of C-reactive protein (CRP) more than 60 mg/L correlated with the outcome of the patient as well. The study concluded that, age, COVID-19 clinical degree, and atrial fibrillation significantly affect the outcome in COVID-19 patients with stroke.


Amplification of satellite III DNA in an unusually large chromosome 14p+ variant.
A phenotypically normal male (WSm) was found to have an unusually large short arm of chromosome 14. Increase in the size of this variant chromosome [Wsm-var(14)] was estimated to be approximately 30% that of a normal chromosome 14 by G-banding using trypsin and staining with Leishman. The extra chromosomal material was positive in CBG staining (C-banding using BaOH and staining with Giemsa), suggesting the presence of repetitive DNA. In situ hybridisation using repetitive probes demonstrated this material to be strongly positive for satellite III DNA, and negative for Y-specific heterochromatic DNA. Hybridisation with an alpha DNA probe specific for human acrocentric chromosomes indicated the retention of the centromere, and the absence of alpha DNA in the extra chromosomal material. We propose the origin of the extra chromosomal material in WSm-var(14) to be a result of amplification of contiguous satellite III DNA that is normally present in the short arm of chromosome 14. This variant chromosome does not appear to be associated with the abnormal phenotype in WSm's daughter who is mentally retarded and carries a t(1;?)(q41;?) translocation of chromosome 1.


A general synthesis for PEDOT-coated nonconductive materials and PEDOT hollow particles by aqueous chemical polymerization.
A method for coating functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) on nonconductive substrates in aqueous solution allows the deposition of PEDOT thin layers on various substrates, including silica and polystyrene (PS) nanoparticles, siliceous mesocellular foam, and chitosan-alginate fibers. The surface property is tuned by controlling the monomer composition in the aqueous solutions. Using appropriate organic solvents to remove the PS cores of PEDOT-coated PS nanoparticles, hollow PEDOT particles with single holes and PEDOT capsules can be formed.


A literature review of different pressure ulcer models from 1942-2005 and the development of an ideal animal model.
The literature from 1942-2005 was reviewed in order to determine an inexpensive animal model which can closely mimic pressure ulcers seen in humans of varying ages, without the need for surgical procedures. Two animal models for producing pressure ulcers were found to be inexpensive: pigs to mimic pressure ulcers in young humans due to their fixed skin, and rats to mimic pressure ulcers in the elderly due to their loose skin. The methods which were found to be inexpensive, reproducible, non-invasive and easy to carry out without the need of a surgeon or specialist were the use of magnets for rat models and the use of a cast placed over a bony prominence for pig models.


Comparison of treatment potential of electrocoagulation of distillery effluent with and without activated Areca catechu nut carbon.
Physico-chemical characteristics of distillery effluent samples have been determined. The water quality parameters (WQPs) measured are colour, pH, electrical conductivity, turbidity, total dissolved solids (TDS), chloride, total hardness (THA), calcium, iron, bio-chemical oxygen demand (BOD) and chemical oxygen demand (COD). Almost all the values of WQPs of the distillery effluents have been found to be very high and well above the permissible limit suggested by Bureau of Indian Standards (BIS). Electrocoagulation (EC) technique is employed to treat the distillery effluents. Removal efficiency of WQPs is compared by adopting EC technique with and without the addition of indigenously prepared activated areca nut [botanical name: Areca catechu; kotta pakku, in (vernacular)] carbon (AAC). About 99% of turbidity has been removed in both the cases. The experimental results also revealed that the WQPs like EC, TDS, etc. of the effluents could be reduced. Loss of weight of sacrificial electrode (anode) is also ascertained. EC with AAC is found to be more effective than EC without AAC.


Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy.
Numerous resting-state fMRI studies have demonstrated altered functional connectivity within canonical intrinsic connectivity networks (ICNs) in patients with idiopathic generalized epilepsy (IGE). It is possible that the widespread ICN abnormalities on electroencephalography in IGE derive from abnormal functional interactions between ICNs. To test this possibility, we explored the functional connectivity between the subnetworks of the default mode network (DMN), attention network (ATN), and frontoparietal control network (FPN) using independent component analysis of resting-state fMRI data collected from 27 patients with IGE characterized by generalized tonic-clonic seizures (GTCS) and 29 matched healthy controls. It was observed that the left FPN exhibited increased connectivity with the anterior DMN and ventral ATN, while the right FPN exhibited increased connectivity with the anterior and posterior DMNs in the patients with IGE-GTCS. Furthermore, the functional connectivity between the anterior DMN and ventral ATN was negative in healthy controls but positive in the patients with IGE-GTCS. In addition, the anterior DMN exhibited increased intranetwork functional connectivity in the right frontal pole in IGE-GTCS. These findings suggest that IGE-GTCS is likely associated with a disrupted brain organization probably derived from abnormal functional interactions among ICNs. Furthermore, the alterations in the functional architecture of the ICNs may be related to deficits in mentation and attention in IGE-GTCS, providing informative evidence for the understanding of the pathophysiology of IGE-GTCS.


Fisetin overcomes non-targetability of mutated KRAS induced YB-1 signaling in colorectal cancer cells and improves radiosensitivity by blocking repair of radiation-induced DNA double-strand breaks.
KRAS is frequently mutated, and the Y-box binding protein 1 (YB-1) is overexpressed in colorectal cancer (CRC). Mutant KRAS (KRASmut) stimulates YB-1 through MAPK/RSK and PI3K/AKT, independent of epidermal growth factor receptor (EGFR). The p21-activated kinase (PAK) family is a switch-site upstream of AKT and RSK. The flavonoid compound fisetin inhibits RSK-mediated YB-1 signaling. We sought the most effective molecular targeting approach that interferes with DNA double strand break (DSB) repair and induces radiosensitivity of CRC cells, independent of KRAS mutation status. KRAS activity and KRAS mutation were analyzed by Ras-GTP assay and NGS. Effect of dual targeting of RSK and AKT (DT), the effect of fisetin as well as targeting PAK by FRAX486 and EGFR by erlotinib on YB-1 activity was tested by Western blotting after irradiation in vitro and ex vivo. Additionally, the effect of DT and FRAX486 on DSB repair pathways was tested in cells expressing reporter constructs for the DSB repair pathways by flow cytometry analysis. Residual DSBs and clonogenicity were examined by γH2AX- and clonogenic assays, respectively. Erlotinib neither blocked DSB repair nor inhibited YB-1 phosphorylation under KRAS mutation condition in vitro and ex vivo. DT and FRAX486 effectively inhibited YB-1 phosphorylation independent of KRAS mutation status and diminished homologous recombination (HR) and alternative non-homologous end joining (NHEJ) repair. DT and FRAX486 inhibited DSB repair in CaCo2 but not in isogenic KRASG12V cells. Fisetin inhibited YB-1 phosphorylation, blocked DSB repair and increased radiosensitivity, independent of KRAS mutation status. Combination of fisetin with radiotherapy may improve CRC radiation response, regardless of KRASmut status.


Improved techniques using Giemsa stained glycol methacrylate tissue sections to quantitate basophils and other leukocytes in inflammatory skin lesions.
Improved techniques were developed for processing inflammatory skin lesions in glycol methacrylate (JB-4, Polysciences, Inc.) and for quantitating their leukocyte infiltrates by light microscopy: (1) fixation of entire pelts from rabbits, guinea pigs, rats and mice bearing multiple lesions eliminated artifacts due to biopsy and produced uniformly oriented skin sections; (2) adding dimethylsulfoxide and hydrogen peroxide to the Karnovsky-type fixative increased the rate and effectiveness of fixation; (3) the presence of glycerol in the infiltrating methacrylate and the polymerized plastic block improved the sectionability of skin and other tissues; (4) coating slides with JB-4 Solution A prevented detachment of specimens; (5) Giemsa staining at a carefully selected pH provided optimal differentiation of leukocytes from the several species examined, including man. These techniques, which allowed an accurate histologic assessment of inflammatory skin lesions, were especially valuable for quantitating basophils.


The efferent projections of the nucleus accumbens in the rat.
The efferent projections of the nucleus accumbens have been examined in the rat. This has been achieved by mapping the distribution of degenerating axons and terminals following the placement of small electrolytic lesions within the accumbens. Quantitatively, the majority of accumbens efferent fibres appear to terminate in the diencephalon, while there are also projections to cortical and brain stem structures. The evidence suggests that the nucleus accumbens sends efferent fibres to the cingulum, lateral hypothalamus, globus pallidus, thalamus (including the reuniens, gelatinosus, parataenial, medial and anteromedial nuclei) and the substantia nigra.


Comparisons of paired orthotopic cardiac transplant donor and recipient electrocardiograms.
Electrocardiograms of 20 consecutive donor and paired recipient orthotopic heart transplant patients were compared. Recipients were markedly older than donors; all patients were males, and both groups had similar body weight. The heart rate was faster, QRS was longer, QT was shorter, QRS axis was more shift to the left, and precordial voltage was decreased in the recipient ECGs in the first 72 hours after transplant. These changes persisted during late follow-up (12 +/- 6 months after transplant). Seventy percent and 60% of recipients within the first 72 hours after transplant and during late follow-up, respectively, had a new RBBB delay compared to their paired donor ECG. There was a trend toward less clockwise rotation in the ECGs of patients who had a new incomplete RBBB in the late follow-up compared to patients who did not. Thus new RBBB delays, QT shortening, QRS axis left shift, and decrease in precordial voltage are commonly seen on ECGs after orthotopic cardiac transplantation. A new heart position and recipient's weight do not seem to account for the development of a new RBBB delay and decrease in precordial voltage. Other factors, such as mechanical or thermal injury and change in donor-to-recipient age, may be involved.


Biomedical informatics methods in pharmacogenomics.
Pharmacogenomics is the study of the genetic basis of individual variation in response to therapeutic agents. Pharmacogenomics may potentially affect on every step of health care and every drug treatment protocol. The optimal approach to pharmacogenomics in hypertension requires the integration of different disciplines, in which biomedical informatics plays an essential role. This chapter describes biomedical informatics methods used in dealing with key issues in pharmacogenomics. These key issues include the association between structure and function, the interaction between gene and drug, and the correlation between genotype and phenotype. Heterogeneous resources, including web sites, databases, and software analysis tools, are selected, organized, and integrated in practical methods to support these studies. Bioinformatics methods described in this chapter include genetic sequence searching, comparison, structural modeling, functional analysis, and systems biology studies, with emphasis on single-nucleotide polymorphism (SNP) analysis. Medical informatics methods such as disease and drug information and clinical terminology are also embraced in this chapter. This combination of both biological and medical informatics provides comprehensive methodologies to resolve complex problems in pharmacogenomics.


Purification and partial characterization of the plasma clotting protein from the pink shrimp Farfantepenaeus paulensis.
A clotting protein (CP) was purified from the plasma of the pink shrimp Farfantepenaeus paulensis by sequential anion-exchange chromatography. The shrimp CP was able to form stable clots in vitro in the presence of hemocyte lysate and Ca2+, suggesting that the clotting reaction is catalyzed by a Ca2+-dependent transglutaminase present in shrimp hemocytes. Dansylcadaverine was incorporated into the shrimp CP in the presence of endogenous transglutaminase (hemocyte lysate), confirming that the shrimp purified CP is the substrate for the transglutaminase enzyme. The molecular mass of the CP was determined by gel filtration to be 341 kDa and 170 kDa by SDS-PAGE under reducing conditions. These results suggest that the shrimp CP consists of two identical subunits, covalently linked by disulphide bonds. The amino acid sequence at the N-terminus was 100% identical to that of the penaeids Litopenaeus vannamei and Penaeus monodon and 66% to 80% identical to the CPs of other decapods. This is the first report of a CP characterization in an Atlantic penaeid species. Further studies, including a molecular cloning approach would enable to detect which tissues express the gene of the clotting protein. It would be also useful to understand the mechanism by which the coagulation time is delayed in shrimps under stress conditions.


[The anti-arrhythmic effect of the electrophoresis of a natural shirsal preparation in the 2nd-stage rehabilitation of myocardial infarct patients].
Experimental and clinical trials of antiarrhythmic effect of shirsal (natural salt of lake Shira mineral water) have shown that rehabilitation complex including shirsal electrophoresis is beneficial for MI patients with arrhythmia. Shirsal electrophoresis extends indications for sanatorium treatment of MI patients with stable angina of effort (functional class III-IV), grade I-IV arrhythmia, chronic circulatory insufficiency.


Rapeseed plant: biostimulation effects of plant growth-promoting Actinobacteria on metabolites and antioxidant defense system under elevated CO2 conditions.
The present study set out to evaluate the potential of plant growth-promoting Actinobacteria (PGPB) in improving some physiological and molecular parameters of rapeseed (Brassica napus L.) plants under ambient and elevated CO2 conditions by assessing some nitrogen- and sulfur-containing metabolites, antioxidant defense system and antimicrobial activity. With this aim, a pot experiment was conducted where the rapeseed plants were treated with Actinobacterium sp. strain NCO2 (OQ451136) and were grown under two levels of air CO2 concentrations: ambient CO2 (aCO2 , 410 μmol CO2 mol-1 ); and elevated CO2 (eCO2 , 710 μmol CO2 mol-1 ). There was an increase in the photosynthetic pigments (+35-80%) and photosynthesis rate (+20-34%) in PGPB-treated plants under eCO2 compared to control plants, resulting in further growth and biomass production (+53-294%). These results were associated with an enhancement in the content of total antioxidant capacity (+15-128%), polyphenols (+21-126%) and α-tocopherols (+20-138%) under both eCO2 and PGPB application (in combination or individual application), while only the combined treatment (eCO2 + PGPB) led to a significantly higher accumulation of antioxidant enzymes (+88-197%), β-tocopherols (+177%) and flavonoids (+155%). Moreover, nitrogen- and sulfur-containing metabolites (glucosinolates and amino acids) were improved by PGPB treatment and/or CO2 levels, in which PGPB increased the amino acid-derived glucosinolate induction by eCO2 with low levels of effective sulforaphane. Therefore, the interaction effects of beneficial Actinobacteria and eCO2 are expected to boost the level of antioxidant molecules and to have a helpful role in improving plant biomass and adaptability to complicated climate changes in the future. © 2023 Society of Chemical Industry.


Utilizing SENSE to achieve lower station sub-millimeter isotropic resolution and minimal venous enhancement in peripheral MR angiography.
To use the parallel imaging technique, sensitivity encoding (SENSE), to increase spatial resolution and decrease venous contamination in peripheral magnetic resonance angiography (MRA). Moving table, single-bolus peripheral contrast-enhanced (CE) -MRA was performed on nine patients. Manual table movement combined with SENSE in the upper station allowed for more rapid overall scan coverage such that acquisition of the lower station began 34 seconds after aortic contrast arrival. True sub- millimeter isotropic resolution was achieved in the lower station. Diagnostic MR angiograms of all three stations were obtained in all nine patients. Venous enhancement did not confound interpretation in any case. Sub-millimeter lower station resolution provided excellent vascular detail. Decreased delay time between upper and lower station acquisition in single bolus peripheral MR angiograms, now possible using parallel imaging techniques, combined with lower station sub-millimeter resolution may decrease venous contamination and increase overall interpretability, thus increasing clinical acceptance of peripheral MRA.


Upregulation of the pro-opiomelanocortin gene in motoneurones after acrylamide administration in mice.
Immunocytochemistry was used to demonstrate the presence of beta-endorphin and alpha-MSH, and in situ hybridisation was used to study the presence of pro-opiomelanocortin (POMC) mRNA, in spinal motoneurones, up to 8 days following the administration of a single dose of acrylamide in mice. The proportions of POMC-mRNA positive neurones, beta-endorphin-immunoreactive neurones and alpha-MSH-immunoreactive neurones were significantly increased in the treated animals compared to controls. It seems likely that upregulation of the POMC gene precedes acrylamide-induced neuropathy.


Himatanthus bracteatus stem extracts present anti-flavivirus activity while an isolated sesquiterpene glucoside present only anti-Zika virus activity in vitro.
The hexane and ethanol extracts from Himatanthus bracteatus (Apocynaceae) stems were evaluated for antiviral activity against Zika virus, yellow fever virus and dengue virus 2 and for cytotoxicity in Vero cells by MTT assay. The ethanol extract showed good antiviral activity against the three viruses with selective indexes (SI) > 10 and its fractionation led to the isolation of the known plumieride that was active only against Zika virus (SI of 15.97).


Tibetan Plateau increases the snowfall in southern China.
The role of the Tibetan Plateau (TP) in Asian hydrological climate is crucial, yet there is a lack of quantitative estimates regarding its impact on snowfall in China. Some opinions suggest that the TP functions as a large barrier that obstructs cold outbreaks, protecting southern China from severe snowstorms. Through topography experiments with and without the TP, our study suggests that the TP's presence results in a 60% decrease in snowfall in northern China by significantly reducing moisture. In contrast, it promotes a 1500% increase in snowfall in southern China, particularly from November to March, by drawing cold air from the north and moisture from the south to southern China. The presence of TP significantly enhances winter relative humidity in southern China, causing discomfort for humans. This research refutes some trending views and improves our understanding of the TP's role in China's winter climate.


Tuning the degree of CO2 activation by carbon doping Cun- (n = 3-10) clusters: an IR spectroscopic study.
Copper clusters on carbide surfaces have shown a high catalytic activity towards methanol formation. To understand the interaction between CO2 and the catalytically active sites during this process and the role that carbon atoms could play in this, they are modeled by copper clusters, with carbon atoms incorporated. The formed clusters CunCm- (n = 3-10, m = 1-2) are reacted with CO2 and investigated by IR multiple-photon dissociation (IR-MPD) spectroscopy to probe the degree of CO2 activation. IR spectra for the reaction products [CunC·CO2]-, (n = 6-10), and [CunC2·CO2]-, (n = 3-8) are compared to reference spectra recorded for products formed when reacting the same cluster sizes with CO, and with density functional theory (DFT) calculated spectra. The results reveal a size- and carbon load-dependent activation and dissociation of CO2. The complexes [CunC·CO2]- with n = 6 and 10 show predominantly molecular activation of CO2, while those with n = 7-9 show only dissociative adsorption. The addition of the second carbon to the cluster leads to the exclusive molecular activation of the CO2 on all measured cluster sizes, except for Cu5C2- where CO2 dissociates. Combining these findings with DFT calculations leads us to speculate that at lower carbon-to-metal ratios (CMRs), the C can act as an oxygen anchor facilitating the OCO bond rupture, whereas at higher CMRs the carbon atoms increasingly attract negative charge, reducing the Cu cluster's ability to donate electron density to CO2, and consequently its ability to activate CO2.


Acute coronary syndrome and its treatment outcomes in Ethiopia: a systematic review and meta-analysis.
Acute coronary syndrome (ACS) is the principal cause of death in developing countries including Ethiopia. No study reports the overall patterns of risk factors and burden of in-hospital mortality in Ethiopia. This study, therefore, aimed to assess the magnitude of risk factors, management, and in-hospital mortality of ACS in Ethiopia. Electronic searching of articles was conducted using PubMed, Science Direct, EMBASE, Scopus, Hinari, and Google Scholar to access articles conducted in Ethiopia. The Preferred Reporting Items for Systematic Reviews checklist was used for identification, eligibility screening, and selection of articles. Data were extracted with an abstraction form prepared with Microsoft Excel and exported to STATA for analysis. Funnel plot, Begg's test, and Egger's test were used to determine publication bias. Heterogeneity between the studies was checked by I2 statistic. The pooled prevalence of risk factors and in-hospital mortality of ACS were estimated using a random-effects meta-analysis model. Most (59.367%) of the patients had ST-segment elevation myocardial infarction (STEMI). Hypertension (54.814%) was the leading risk factor for ACS followed by diabetes mellitus (38.549%). Aspirin (56.903%) and clopidogrel (55.266%) were most frequently used in patients with STEMI ACS, respectively. The pooled proportion of in-hospital mortality of ACS was 14.82% which was higher in patients with STEMI (16.116%). The rate of in-hospital mortality is still high which was higher in patients with STEMI. Initiation of treatment must consider the heterogeneity of each patient's risk factor and reperfusion therapy should be implemented in our setting.


A Rare Spinal Injury: Gunshot Wound to The Odontoid Process.
Case report. We present a 18-year-old male patient with gunshot injury through right scapular region with the bullet ending up and causing a fracture in the odontoid process. Odontoid fracture owing to gunshot wound is an extremely rare injury. An 18-year-old male patient was brought to the emergency department with gunshot injury. x-Ray imaging showed retained bullet in the odontoid process. Computed tomography scan showed fracture of the odontoid and body of scapula consistent with the trajectory of the bullet. Owing to a normal neurological examination, conservative follow-up was decided and given a Philadelphia collar. At 2 years' follow-up, patient demonstrated limited axial rotation and flexion/extension. However, no pain and neurologic problem were observed. Odontoid fracture owing to gunshot wound can be treated conservatively; emergency or elective surgical intervention was not necessary. In the follow-up, patient did not demonstrate any signs of neurological impairment or infection. 5.


Effectiveness of Transarterial Embolization in Treatment of Symptomatic Hepatic Hemangiomas: Systematic Review and Meta-analysis.
To evaluate the current evidence for the effectiveness of transarterial embolization (TAE) in treatment of symptomatic hepatic hemangiomas. A systematic literature review was conducted in PubMed, CINAHL and Scopus databases to identify studies of hepatic hemangiomas treated with transarterial embolization. Main outcome was defined as the mean difference between pre- and post-TAE hemangioma diameters. Treatment agents were categorized as Lipiodol based [bleomycin (L + BE), pingyangmycin (L + PYG) or ethanol (L + ethanol)] and non-Lipiodol based (polyvinyl-alcohol-only). Conventional random-effect meta-analysis technique was applied to analyze data. Of 3080 initially inspected publications, 21 studies were included in the meta-analysis comprising of 1450 patients with total of 1871 hemangiomas (36.2% male, mean age: 46.3 ± 3.6 years). One hundred and twenty-six, 1666, 41 and 38 lesions were treated with L + BE, L + PYG, L + ethanol and PVA, respectively. Median follow-up time after embolization was 12 months. Lipiodol-based treatments showed significant effect in reducing hemangioma size after TAE compared to PVA (P < 0.001). Pooled diameter reduction (cm) (95% confidence interval) was - 4.37( - 5.32, - 3.42), - 4.70( - 5.70, - 3.71), - 0.93( - 2.02, 0.16) for overall TAE treatment, Lipiodol-based and non-Lipiodol-based treatments, respectively. Main complications included post-embolization syndrome and transient liver enzyme elevation (pooled incidence for Lipiodol-based and non-Lipiodol-based techniques: 36% and 33%; and 37% and 0, respectively). No fatal complications were reported. Symptomatic improvement was reported in 63.3%-100% of the cases with majority of studies (15/21) reporting improvement in all cases (pooled response rate: 98%). Transarterial embolization with bleomycin, pingyangmycin or ethanol in combination with Lipiodol is safe and associated with reduced size of hemangiomas resulting in symptoms alleviation.


Local radiotherapy versus nonradiotherapy to distant lesions for metastatic nasopharyngeal carcinoma: Retrospective cohort study.
To evaluate the efficiency of local radiotherapy to metastatic lesions in patients with metastatic nasopharyngeal carcinoma (mNPC). The overall survival was observed and compared for mNPC patients who received local radiotherapy versus nonradiotherapy to metastatic lesions by using the Kaplan-Meier method and Cox analysis. One hundred and nine patients with NPC were involved in this study, with 61 (56.0%) received radiotherapy to metastatic sites and 48 (44.0%) did not receive radiotherapy to metastatic sites. The 2- and 5-year OS for patients who received local radiotherapy to metastatic lesions were 65.8% and 35.7%, and for patients who did not receive radiotherapy to metastatic lesions were 45.3% and 26.2%. The multivariable adjusted hazard radios for local radiotherapy versus nonradiotherapy to metastatic lesions were 0.482 (95% confidence interval is 0.278-0.834, p = 0.009). Local radiotherapy to metastatic lesions might be a protective factor for patients with mNPC.


Synthesis of 4-aryl-1H-1,2,3-triazoles through TBAF-catalyzed [3 + 2] cycloaddition of 2-aryl-1-nitroethenes with TMSN3 under solvent-free conditions.
TBAF-catalyzed [3 + 2] cycloaddition reactions of 2-aryl-1-cyano- or 2-aryl-1-carbethoxy-1-nitroethenes 1 with TMSN3 under SFC allow the corresponding 4-aryl-5-cyano- or 4-aryl-5-carbethoxy-1H-1,2,3-triazoles 2 to be prepared under mild reaction conditions and with good to excellent yields (70-90%). The proposed protocol does not require dried glassware or inert atmosphere.


Brazilian red propolis exhibits antiparasitic properties in vitro and reduces worm burden and egg production in an mouse model harboring either early or chronic Schistosoma mansoni infection.
Propolis has been used in folk medicine for thousands of years and, in the past few decades, it has attracted renewed interest. Although propolis has been traditionally used in many communities worldwide against parasitic diseases, its effect against Schistosoma mansoni infection remains unclear. To demonstrate the effects of Brazilian red propolis on Schistosoma mansoni ex vivo and in an animal model of schistosomiasis. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the crude extract of propolis on pairing and egg production. In a mouse infected with either immature (early infection) or adult (chronic infection) worms, propolis was administered by oral gavage and we studied the influence of this natural product on worm burden and egg production. Propolis 25 μg/mL reduced motility and caused 100% mortality of adult parasites ex vivo. Further analysis revealed a pronounced reduction in oviposition after exposure to propolis at sub-lethal concentrations. In addition, scanning electron microscopy showed morphological alterations in the tegument of schistosomes. In the animal model, propolis markedly reduced worm burden and egg production in both early and chronic S. mansoni infection when compared to untreated control animals. The efficacy of Brazilian red propolis in both in vitro and in vivo studies suggests its potential anthelmintic properties against S. mansoni infection.


Dural Arteriovenous Fistula Formation Complicated Cerebral Venous Sinus Stenosis After Venous Sinus Stenting.
Venous stenting has become a promising treatment for venous sinus stenosis. However, it is not without its own set of risks. We reported de novo formation of dural arteriovenous fistula poststenting for venous sinus stenosis in a patient with pseudotumor cerebri. Multiple factors, including subclinical thrombus formation, sinus wall injury by stent placement, and up-regulated inflammatory factors, may contribute to its pathogenesis. This case indicates that physicians may need to be aware of this rare complication, which can be managed without resumption of pseudotumor cerebri symptoms.


Heart and Brain: Complex Relationships for Left Ventricular Dysfunction.
This review summarizes the evidence for the established vascular/hypoperfusion model and explores the new hypothesis that configures the heart/brain axis as an organ system where similar pathogenic mechanisms exploit physiological and pathological changes. Although associated by common risk factors, similar epidemiological stratification and common triggers (including inflammation, oxidative stress, and hypoxia), heart failure and Alzheimer's disease have been, for long time, viewed as pathogenically separate illnesses. The silos began to be broken down with the awareness that vascular dysfunction, and loss of cardiac perfusion pump power, trigger biochemical changes, contributing to the typical hallmark of Alzheimer's disease (AD)-the accumulation of Aβ plaques and hyperphosphorylated Tau tangles. Compromised blood flow to the brain becomes the paradigm for the "heart-to-head" connection. Compelling evidence of common genetic variants, biochemical characteristics, and the accumulation of Aβ outside the brain suggests a common pathogenesis for heart failure (HF) and AD. These new findings represent just the beginning of the understanding the complex connection between AD and HF requiring further studies and interdisciplinary approaches. Altogether, the current evidence briefly summarized in this review, highlight a closer and complex relationship between heart failure and Alzheimer's that goes beyond the vascular/perfusion hypothesis. Genetic and biochemical evidence begin to suggest common pathogenic mechanisms between the two diseases involving a systemic defect in the folding of protein or a seeding at distance of the misfolded proteins from one organ to the other.


Epidemiological research on rare diseases using large-scale online search queries and reported case data.
Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China's national database of rare diseases during the same period. A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories. Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies.


The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus.
Recent research has shown that neurons in the ventrolateral preoptic nucleus are crucial for sleep by inhibiting wake-promoting systems, but the process that triggers their activation at sleep onset remains to be established. Since evidence indicates that sleep induced by adenosine, an endogenous sleep-promoting substance, requires activation of brain A(2A) receptors, we examined the hypothesis that adenosine could activate ventrolateral preoptic nucleus sleep neurons via A(2A) adenosine receptors in rat brain slices. Following on from our initial in vitro identification of these neurons as uniformly inhibited by noradrenaline and acetylcholine arousal transmitters, we established that the ventrolateral preoptic nucleus comprises two intermingled subtypes of sleep neurons, differing in their firing responses to serotonin, inducing either an inhibition (Type-1 cells) or an excitation (Type-2 cells). Since both cell types contained galanin and expressed glutamic acid decarboxylase-65/67 mRNAs, they potentially correspond to the sleep promoting neurons inhibiting arousal systems. Our pharmacological investigations using A(1) and A(2A) adenosine receptors agonists and antagonists further revealed that only Type-2 neurons were excited by adenosine via a postsynaptic activation of A(2A) adenosine receptors. Hence, the present study is the first demonstration of a direct activation of the sleep neurons by adenosine. Our results further support the cellular and functional heterogeneity of the sleep neurons, which could enable their differential contribution to the regulation of sleep. Adenosine and serotonin progressively accumulate during arousal. We propose that Type-2 neurons, which respond to these homeostatic signals by increasing their firing are involved in sleep induction. In contrast, Type-1 neurons would likely play a role in the consolidation of sleep.


A comparative study of interfacial thermal conductance between metal and semiconductor.
To understand and control thermal conductance of interface between metal and semiconductor has now become a crucial task for the thermal design and management of nano-electronic and micro-electronic devices. The interfacial alignments and electronic characteristics of the interfaces between metal and semiconductor are studied using a first-principles calculation based on hybrid density functional theory. The thermal conductance of interfaces between metal and semiconductor were calculated and analyzed using diffuse mismatch model, acoustic mismatch model and nonequilibrium molecular dynamics methods. Especially, according to nonequilibrium molecular dynamics, the values of thermal conductance were obtained to be 32.55 MW m-2 K-1 and 341.87 MW m-2 K-1 at C-Cu and Si-Cu interfaces, respectively. These results of theoretical simulation calculations are basically consistent with the current experimental data, which indicates that phonon-phonon interaction play a more important role than electron-phonon interaction during heat transport. It may be effective way to improve the interfacial thermal conductance through enhancing the interface coupling strength at the metal-semiconductor interface because the strong interfacial scattering plays a role in suppressing in the weaker interface coupling heterostructure, leading to the lower thermal conductance of interfaces. This could provide a beneficial reference for the design of the Schottky diode and thermal management at the interfaces between metal and semiconductor.


Coronary flow reserve and diastolic dysfunction in hypertrophic cardiomyopathy.
We studied 14 patients with hypertrophic cardiomyopathy during and after atrial pacing by simultaneous registration of left ventricular high fidelity pressure measurements and M-mode echocardiography together with great cardiac vein flow measured by thermodilution. Heart rate rose from 75 +/- 18 to 142 +/- 14 beats/minute with an increase of 93 +/- 30 to 127 +/- 46 milliliters/minute of great cardiac vein flow (increase of flow/beat: 0.8 versus 1.5 milliliters/beat in normal individuals; P less than 0.05). In addition, diastolic hemodynamic parameters (such as left ventricular end-diastolic pressure, T1 (time constant of relaxation) (of first 40 milliseconds) and T2 (of second 40 milliseconds) and LVdP/dt-) changed from, respectively, 27.4 +/- 7.1 to 24.0 +/- 10.3 mm Hg; (NS), 67.3 +/- 16.1 to 65.7 +/- 22.2 liters/second; (NS) 68.6 +/- 36.9 to 52.9 +/- 19.4 (P less than 0.05), and 1592 +/- 75 to 1302 +/- 48 mm Hg/sec; P less than 0.05. Left ventricular end-diastolic dimensions decreased whereas end-diastolic wall thickness increased from, respectively, 37 +/- 3 to 34 +/- 4 millimeters; (P less than 0.05) and 14 +/- 2 to 17 +/- 1 millimeters (P less than 0.05). Eleven of the 14 patients experienced angina pectoris concomitant with ST-T depression of 1 millimeter or more on the electro-cardiogram. No correlations were found between great cardiac venous flow and hemodynamically or ultrasonically derived diastolic parameters of left ventricular function.


Contribution of social support to home-quarantined Chinese college students' well-being during the COVID-19 pandemic: the mediating role of online learning self-efficacy and moderating role of anxiety.
Due to the outbreak of the COVID-19 pandemic, the implementation of quarantine policy led to an unprecedented home-quarantined living and online learning context for Chinese college students. This study aimed to investigate whether and how social support contributed to home-quarantined Chinese college students' well-being during the COVID-19 pandemic. In particular, this study examined the mediating role of online learning self-efficacy in explaining how social support contributed to home-quarantined Chinese college students' well-being. The study also examined the moderating effect of anxiety, which may buffer the effectiveness of social support and online learning self-efficacy in home-quarantined online learning contexts. Data include 2481 responses to an online questionnaire survey from home-quarantined Chinese college undergraduates. Data were analyzed by performing Partial Least Squares regression. Results showed that social support associated positively with home-quarantined Chinese college students' online learning self-efficacy and well-being. The results revealed a partial mediating effect of online-learning self-efficacy on the positive effect of social support on well-being. The moderating effect analysis found that the positive association of online learning self-efficacy with social support and well-being was stronger in home-quarantined Chinese college students who perceived no anxiety.


Analgesic efficacy and safety of a novel injectable formulation of diclofenac compared with intravenous ketorolac and placebo after orthopedic surgery: a multicenter, randomized, double-blinded, multiple-dose trial.
A novel injectable formulation of diclofenac, Dyloject, utilizes hydroxypropyl-β-cyclodextrin (HPβCD) as a solubilizing agent, allowing dosing as a small-volume intravenous bolus for postoperative pain. In this test of the efficacy and safety of HPβCD diclofenac, we hypothesized that HPβCD diclofenac would relieve moderate and severe pain after orthopedic surgery. Adults 18 to 85 years old with moderate and severe pain within 6 hours after surgery were randomized to HPβCD diclofenac, ketorolac tromethamine, or placebo, and stratified by risk cohort. The HPβCD diclofenac non-high-risk cohort dose was 37.5 mg, the high-risk cohort received 18.75 mg, and patients ≥95 kg received 50 mg. The ketorolac dose was 30 mg in the non-high-risk and high-weight cohorts and 15 mg in the high-risk cohort. Rescue intravenous morphine was given for pain as needed. Efficacy was measured by the sum of pain intensity differences (SPID). Mean SPID scores of 277 patients were significantly better with HPβCD diclofenac and ketorolac than with placebo (P<0.0001), across all risk cohorts (P<0.05). HPβCD diclofenac was associated with better SPID scores, faster onset of analgesia, and significantly lower opioid requirement (P<0.008) than ketorolac. In patients more than or equal to 65 years, HPβCD diclofenac was associated with significantly better analgesic efficacy (P=0.05), and lower opioid requirement versus ketorolac. The incidence of treatment-related adverse events was similar across groups. HPβCD diclofenac is safe and efficacious for acute moderate and severe pain after orthopedic surgery and significantly spares morphine use.


Risk factors for coronary heart disease among Jerusalem schoolchildren: preliminary findings.
The presence of risk factors for cardiovascular diseases were investigated in 7- and 11-year-old schoolchildren (808 subjects). Data analysis was performed according to sex, age, and country of origin of the father. The following variables were investigated: weight, height, total plasma cholesterol (TCH), high density lipoprotein cholesterol (HDL), plasma triglycerides, and systolic and diastolic blood pressure. Significant differences were found between sex, age, and origin groups for most variables. The prevalence of hypercholesterolemia (greater than 180 mg/dl) varied between 9.6 and 14.1%, in the different sex and age groups, and that of low HDL cholesterol (less than 40 mg/dl), 6.8-12.1%. Elevated systolic blood pressure (greater than 130 mm Hg) was found in 4.4-6.7% of the 7-year-old children, and in 13,4-18.6% of the 11 year-olds. Elevated diastolic blood pressure (greater than 85 mm Hg) was found predominantly in the 11-year-old children, 6.2-9.1%. These findings demonstrate the necessity to initiate health programs related to prevention of cardiovascular diseases in childhood.


SONOGRAPHY : A VALUABLE MODALITY IN EVALUATION OF CHRONIC NON-TRAUMATIC DISORDERS OF THE SHOULDER JOINT.
Chronic non-traumatic shoulder pain may be due to arthralgia, shoulder myalgia, glenohumeral synovitis, adhesive capsulitis, or degenerative joint disease. Clinical skills and routine radiography may not be adequate to establish the diagnosis. This study was designed to assess the role of sonography in such a setting. Twenty-six consecutive patients attending the clinical immunology outpatient department for chronic shoulder pain were evaluated. Based on our findings, we have described 4 distinct sonographic patterns. Pattern 1 consisted of the normal sonographic appearance with semicircular smooth humeral head profile parallel to which was an echo-free synovial space measuring 1-2 mm. This pattern indicated shoulder arthralgia or myalgia without intrinsic shoulder joint disease. Pattern 2 consisted of reduction in the echo-free space indicative of adhesive capsulitis. Pattern 3 consisted of uniform increase in this space, thus indicating active synovial inflammation with effusion. Pattern 4 showed irregularity of the humeral head with reduction in the gleno-humeral joint space and loss of parallelism between the humeral head and the surrounding gleno-humeral synovial space. This last pattern indicated advanced deformed inflammatory or degenerative arthritis. It is concluded that these 4 sonographic patterns will be of considerable help in pinpointing the diagnosis in cases of chronic non-trumatic shoulder pain.


Purification and characterization of DNA-relaxing enzyme from Haemophilus gallinarium.
A DNA-relaxing enzyme capable of concerted nicking and closing of DNA backbone bonds has been purified from Haemophilus gallinarum by two chromatographic steps and gel filtration. The enzyme efficiently catalyzes the removal of superhelical turns from a negatively twisted DNA and requires Mg2+ for this activity. Slight removal of superhelical turns from a positively twisted DNA generated by binding of ethidium bromide is found, but only at high enzyme concentrations. The DNA-relaxing activity is inhibited markedly with heat-denatured DNA, whereas native DNA and RNA have almost no affect on this activity.


Variations of SCE frequencies in peripheral lymphocytes of ex-smokers.
We measured SCE frequencies over a period of 8 months in 14 smokers who stopped smoking at the start of the study. In a first group of 10 subjects, who did not resume smoking during the period of cytogenetic follow-up, a lowering of SCE frequencies was already evident after 18 days and this became statistically significant after 78 days. SCE decrease was related to the logarithm of the period (in days) for which smoking was interrupted (r = 0.98; p less than 0.001). In a second group of 4 subjects, who at various times resumed smoking, the decrease of SCE followed the same pattern as in the first group during the period of nonsmoking, but SCE frequencies rose even higher once smoking was resumed. Our study indicates that the decrease of SCE in ex-smokers is rather rapid during the first 78 days after stopping smoking, and much slower from the 78th to the 233rd day.


Protein phosphatase 2A affects myofilament contractility in non-failing but not in failing human myocardium.
Protein phosphatase (PP) type 2A is a multifunctional serine/threonine phosphatase that is involved in cardiac excitation-contraction coupling. The PP2A core enzyme is a dimer, consisting of a catalytic C and a scaffolding A subunit, which is targeted to several cardiac proteins by a regulatory B subunit. At present, it is controversial whether PP2A and its subunits play a critical role in end-stage human heart failure. Here we report that the application of purified PP2AC significantly increased the Ca2+-sensitivity (ΔpCa50=0.05±0.01) of the contractile apparatus in isolated skinned myocytes of non-failing (NF) hearts. A higher phosphorylation of troponin I (cTnI) was found at protein kinase A sites (Ser23/24) in NF compared to failing myocardium. The basal Ca2+-responsiveness of myofilaments was enhanced in myocytes of ischemic (ICM, ΔpCa50=0.10±0.03) and dilated (DCM, ΔpCa50=0.06±0.04) cardiomyopathy compared to NF. However, in contrast to NF myocytes the treatment with PP2AC did not shift force-pCa relationships in failing myocytes. The higher basal Ca2+-sensitivity in failing myocytes coincided with a reduced protein expression of PP2AC in left ventricular tissue from patients suffering from ICM and DCM (by 50 and 56% compared to NF, respectively). However, PP2A activity was unchanged in failing hearts despite an increase of both total PP and PP1 activity. The expression of PP2AB56α was also decreased by 51 and 62% in ICM and DCM compared to NF, respectively. The phosphorylation of cTnI at Ser23/24 was reduced by 66 and 49% in ICM and DCM compared to NF hearts, respectively. Our results demonstrate that PP2A increases myofilament Ca2+-sensitivity in NF human hearts, most likely via cTnI dephosphorylation. This effect is not present in failing hearts, probably due to the lower baseline cTnI phosphorylation in failing compared to non-failing hearts.


Transmission of an expanding donor-derived del(20q) clone through allogeneic hematopoietic stem cell transplantation without the development of a hematologic neoplasm.
Donor cell leukemia is a rare complication of allogeneic hematopoietic stem cell transplantation (HSCT), which may result from the development of a new malignancy in previously healthy donor cells after transplant into the recipient, or it may derive from the transmission of an occult leukemia from donor to recipient. We report a case of donor derived 20q11.2 deletion in a male patient who received an allogeneic HSCT from his HLA-identical sister for the treatment of his chronic lymphocytic leukemia. Bone marrow cells from the donor were found to contain the 20q deletion that expanded over time, but which was absent in her peripheral blood cells. Although cases of donor cell leukemia after HSCT have been reported, in this case there has been no evidence of an associated hematologic neoplasm in either the donor or recipient. Pre-transplant donor bone marrow evaluations are not practical or warranted, however the finding of new cytogenetic abnormalities after transplant mandates a thorough evaluation of the donor.


Two new JK silencing alleles identified by single molecule sequencing with 20-Kb long-reads.
The Kidd blood group gene SLC14A1 (JK) accounts for approximately 20 Kb from initiation codon to stop codon in the genome. In genomic DNA analysis using Sanger sequencing or short-read-based next generation sequencing, it is difficult to determine the cis or trans positions of single nucleotide variations (SNVs), which are occasionally more than 1 Kb away from each other. We aimed to determine the complete nucleotide sequence of a 20-Kb genomic DNA amplicon to characterize the JK allelic variants associated with Kidd antigen silencing in a blood donor. The Jk(a-b-) phenotype was identified in this donor by standard serological typing. A DNA sample obtained from whole blood was amplified by long-range PCR to obtain a 20-Kb fragment of the SLC14A1 gene, including the initiation and stop codons. The fragment was then analyzed by Sanger sequencing and single-molecule sequencing. Transfection and expression studies were performed in CHO cells using the expression vector construct of JK alleles. Sanger sequencing and single-molecule sequencing revealed that the donor was heterozygous with JK*01 having c.276G>A (rs763262711, p.Trp92Ter) and JK*02 having c.499A>G (rs2298719, p.Met167Val), c.588A>G (rs2298718, p.Pro196Pro), and c.743C>A (p.Ala248Asp). The two JK alleles identified have not been previously described. Transfection and expression studies indicated that the CHO cells transfected with JK*02 having c.743C>A did not express the Jkb and Jk3 antigens. We identified new JK silencing alleles and their critical SNVs by single-molecule sequencing and the findings were confirmed by transfection and expression studies.


Pneumomediastinum during spontaneous vaginal delivery.
We report two rare cases of spontaneous pneumomediastinum that presented shortly after childbirth and resolved without treatment. Spontaneous pneumomediastinum has been described in a wide range of seemingly unrelated but recurrent clinical scenarios. We highlight their common etiologic factors and provide the anatomic and physiologic bases for the radiologic signs that are common in all these conditions.


Pediatric tuberculosis pyramid and its fate with and without chemotherapy/chemoprophylaxis.
The latest available information on total and infectious cases of tuberculosis in the country and also large number of sputum positive cases being detected annually, particularly after the involvement of multipurpose workers in the primary health care programme for the control of tuberculosis, is presented. The consequences of the large pool of infectious cases in the population lead to spread of bacilli to children with development of primary infection in them. These children with primary infection, specially high risk group in infancy and early childhood, get serious complications of the disease. It may be emphasized that BCG vaccination cannot prevent the lodgement of tubercle bacilli in the lung but can only contain or restrict haematogenous spread. Inspite of increasing coverage of infants with BCG vaccination there are an increasing number of cases of intrathoracic tuberculosis, particularly various groups of mediastinal nodes. However, to a lesser extent haematogenous complications do occur in malnourished children, as BCG has a limited value in preventing serious complications in children with malnutrition. The clinical pattern of pediatric tuberculosis has also changed in vaccinated and partly or inadequately drug treated children. Hence, chemoprophylaxis/chemotherapy to prevent complications of primary infection has been tried. Even relatively privileged children in developed countries are reported to have complications of primary infection to an extent of 10 to 15%, as per the studies all over world. So preventive chemoprophylaxis, preferably with two bactericidal drugs, should be considered as the main strategy for controlling primary infection. Chemoprophylaxis with two drugs should be used as incidence of isoniazid resistant bacilli has increased. All concerned with child health should consider the strategy of treatment of primary infection in high risk children by chemoprophylaxis by starting a large multicentric trial both in urban and rural areas, as a part and parcel of primary health care intervention already in practice for cases of sputum positive pulmonary tuberculosis.


[Microsurgical ventral surgery in cervical intervertebral disk displacement].
The author deals with his microsurgical method for the removal of cervical intervertebral disk prolapses. Almost the whole intervertebral space is cleared and subsequently stabilised with bones of the patient's iliac crest.


Syntheses of carbon-11 labeled piperidine esters as potential in vivo substrates for acetylcholinesterase.
A series of carbon-11 labeled N-methylpiperidinyl esters were prepared as potential in vivo substrates for acetylcholinesterase (AChE). Target compounds were designed based on the structure of N-[11C]methylpiperidin-4-yl propionate, an ester currently used to measure AChE enzymatic activity in the human brain, to examine the structure-activity relationship for in vivo enzymatic hydrolysis. Changes in steric bulk and in the ester order ("reverse" esters) were made. Addition of methyl groups was made to both the acid side chain (synthesis of N-[11C]methylmethylpiperidin-4-yl isobutyrate) and to the piperidine ring (syntheses of N-[11C]methyl-4-methylpiperidin-4-yl propionate, N-[11C]methyl-4-methylpiperidin-4-yl acetate, and N-[11C]methyl-3-methylpiperidin-4-yl propionate). Alterations of the order of the ester heteroatoms was accomplished through syntheses of the N-[11C]methyl-2,3- and 4-piperidinecarboxylic acid ethyl esters. Finally, an additional piperidine-based ester (N-[11C]methylpiperidin-2-yl)methyl propionate was also prepared. All carbon-11-labeled esters were prepared by N-[11C]methylation reactions, using the desmethyl precursors and no-carrier-added [11C]methyltriflate, and were obtained in decay-corrected yields (not optimized) of 10-40% and high specific activities.


Interventional pharmacoeconomics for immune checkpoint inhibitors through alternative dosing strategies.
Immune checkpoint inhibitors (ICIs) are approved for the treatment of a variety of cancer types. The doses of these drugs, though approved by the Food and Drug Administration (FDA), have never been optimised, likely leading to significantly higher doses than required for optimal efficacy. Dose optimisation would hypothetically decrease the risk, severity, and duration of immune-related adverse events, as well as provide an opportunity to reduce costs through interventional pharmacoeconomic strategies such as off-label dose reductions or less frequent dosing. We summarise existing evidence for ICI dose optimisation to advocate for the role of interventional pharmacoeconomics.


Intermittent coronary artery occlusion caused by a floating thrombus in the left coronary sinus of valsalva of a patient with a normal aorta and protein C deficiency.
A floating thrombus in the ascending aorta is an uncommon source of embolism. We report a case in which a floating mass in the left coronary sinus of Valsalva caused intermittent left main coronary trunk occlusion, leading to myocardial ischemia and cardiogenic shock. The mass was surgically resected. Macroscopically, the aortic wall and leaflets were normal. On histologic examination the mass was found to be a thrombus. This patient had a low level of protein C; therefore, it was presumed that the thrombus was due to protein C deficiency.


Desiccation in oil protects bacteria in thermal processing.
Edible oils have long been considered to have a protective effect on bacteria from thermal inactivation, but the mechanism for this effect remains unclear. Our recent study suggests that the water activity (aw) of oil decreases exponentially with increasing temperature. Therefore, in thermal processing, the aw of the bacteria inside oil may also decrease making the bacteria more resistant to heat. To validate this hypothesis, the equilibrium aw of bacteria (Enterococcus faecium NRRL B2354, or E. faecium) in peanut oil samples, with different initial aw (0.93, 0.75, 0.52 & 0.33) at room temperature, were measured at elevated temperatures up to 80 °C. Meanwhile, the thermal resistances of E. faecium in these samples were also tested at 80 °C. Results indicate that the aw of the bacteria-in-oil systems changed in the same manner as that of pure peanut oil; it decreased exponentially with temperature from 0.93, 0.75, 0.52 & 0.33 (at ~23 °C) to 0.36, 0.30, 0.21 & 0.13 (at 80 °C), respectively. This confirmed that bacterial cells experienced desiccation in oil during the thermal treatments. The thermal death rates of E. faecium in peanut oil samples followed first-order kinetics. The D80 value (time needed to achieve 1-log reduction at 80 °C) increased exponentially with the reduced aw at 80 °C, from 87 min at aw 0.36 to 1539 min at aw 0.13. A graphical comparison (logD80 vs. high-temperature aw) showed a similarity between the thermal resistance of E. faecium in oil and that in dry air, which supports the hypothesis that oil protects bacteria from thermal treatments through desiccation.


The effectiveness of exercise programmes in patients with multiple myeloma: A literature review.
A limited number of clinical studies have investigated the effectiveness of participation in exercise training programmes for patients with multiple myeloma (MM), exploring the different biomedical, physical, psychological and quality of life. The aim of this literature review is to evaluate current quantitative and qualitative evidence concerning the effectiveness of participation in exercise programmes for patients with MM in improving physiological and/or psychological status. A literature search encompassing studies published between January 1998 and July 2013 was conducted through ten electronic databases. This search was further expanded through citation chaining, manual grey literature searches, and peer review consultation. In total, seven interventional studies were identified and appraised using Critical Appraisal Skill Programme (CASP) or Centre for Evidence-Based Management of Amsterdam (CEBMa). Though the majority of the studies presented encouraging data, however, three studies that implemented individualized exercise interventions for patients at different stages of MM and myeloablative treatment showed mixed results. In conclusion, the effectiveness of participation in exercise programmes remains unclear for patients with MM, as the studies reviewed were flawed by relatively weak methodological approaches.


Occurrence of aflatoxin B1 and ochratoxin A in Lebanese cultivated wheat.
An extensive survey of filamentous fungi isolated from wheat grown and consumed in Lebanon and their capacity to produce aflatoxin B1 (AFB1) and ochratoxin A (OTA) was conducted to assess fungi potential for producing these toxins in wheat. From the 468 samples of wheat kernel, collected at preharvest stage from different locations during 2008 and 2009 cultivation seasons, 3,260 fungi strains were isolated with 49.4% belonging to Penicillium spp. and 31.2% belonging to Aspergillus spp. Penicillium spp. was detected on wheat samples with a high amount of P. verrucosum (37.0%). Among the different Aspergillus spp. isolated, A. niger aggregate was predominant and constituted 37.3%. whereas the isolation rate of A. flavus and A. ochraceus was 32.2 and 25.6%, respectively. The ability to produce OTA and AFB1 by isolates belonging to Aspergillus spp. and Penicillium spp. was analyzed by high performance liquid chromatography with fluorescence detector (HPLC-FLD). It was found that 57.0% of Penicillium spp. and 80% of A. ochraceus isolates tested produced OTA, respectively, at maximum concentrations of 53 and 65 μg/g CYA. As for the aflatoxinogenic ability, 45.3% of A. flavus produced AFB1, with maximum concentration of 40 μg/g CYA. A total of 156 wheat samples were analyzed for the levels of OTA and AFB1 by HPLC-FLD. The results showed that 23.7% were contaminated with OTA, at a concentration higher than 3 μg/kg and 35.2% of these samples were contaminated with AFB1 at concentration higher than 2 μg/kg. The risks originating from toxin levels in wheat produced in Lebanon should be monitored to prevent their harmful effects on public health.


Oral-facial-digital syndrome II. Transitional type between Mohr and Majewski syndrome: report of a new case with congenital stenosis of the trachea.
We present a female patient with laryngeal anomalies, tracheostenosis and pre- and postaxial polydactyly. Bilateral duplication of the hallux, polydactyly of hands, growth retardation and conductive hearing defect are consistent with oral-facial-digital (OFD) type II syndrome. Three similar cases of OFD syndrome with hypoplasia of the larynx, epiglottis and/or trachea without tibial dysplasia have been previously reported by Silengo and Temtamy and McKusick. The present patient adds one more case to this group of variants of OFD syndrome. We believe that those cases may be considered to form a separate subentity of OFD syndromes although overlapping features within the different subtypes make a precise classification very difficult.


Ovarian cancers arising from endometriosis: a microenvironmental biomarker study including ER, HNF1ß, p53, PTEN, BAF250a, and COX-2.
The microenvironmental biomarkers of different subtypes of ovarian cancers arising from endometriosis have not been studied in Taiwan. Their expression can help in understanding the carcinogenic mechanism. Our study used immunohistochemistry to compare the expression of estrogen receptor (ER), hepatocyte nuclear factor-1 beta (HNF1ß), p53, phosphatase and tensin homolog (PTEN), BAF250a, and cyclooxygenase-2 (COX-2) among 79 cases of endometriosis-associated ovarian cancers, including 40 (50%) clear cell carcinomas (CCCs), 33 (41%) endometrioid (EM) adenocarcinomas, four (5%) serous carcinomas, one adenosquamous carcinoma, and one adenosarcoma. Positive stainings for ER, HNF1ß, p53, and COX-2 were identified in 34 (43%), 30 (38%), 10 (13%), and 44 (56%) cases. Loss of PTEN and BAF250a were noted in 29 (37%) and 37 (47%) cases. The expression of ER was reversely correlated with that of HNF1ß (rho = -0.417, p < 0.001) and correlated with p53 (rho = 0.284, p = 0.011). ER positivity was commonly identified in EM adenocarcinomas (91%), and rarely in CCCs (8%) and serous carcinoma (0%; p < 0.001). By contrast, HNF1ß expression was frequently noted in CCCs (65%) and serous carcinomas (50%), but less in EM adenocarcinoma (6%; p < 0.001). All staining results were similar between atypical endometriosis glandular epithelium and contiguous malignant parts. Only nine cases showed 10 minor differences (10/474, 2%) in ER, HNF1ß, and BAF250a. For the staining patterns of p53, COX-2, and PTEN, there was no difference between the invasive and precursor parts. Our results supported the suggestion that estrogen-dependent ovarian cancer arising from endometriosis is substantially more associated with EM adenocarcinoma than CCCs. The positive HNF1ß staining was a frequent finding in CCCs, but not in EM adenocarcinoma. The similar staining patterns of atypical endometriosis glandular cells with the invasive parts confirmed their precursor status.


Small leucine-rich proteoglycans (SLRPs): characteristics and function in the intervertebral disc.
The intervertebral disc (IVD) is responsible for normal spinal motion and load distribution. However, degeneration may occur due to age- and non-age-related processes and is primarily characterized by a reduction in the number of chondrocyte-like cells and abnormal extracellular matrix (ECM) structure in the nucleus pulposus. Although IVD progenitor cells have been identified, the local microenvironment components regulating the behaviour of these progenitor cell populations remain unknown. Small leucine-rich proteoglycans (SLRPs) are bioactive components of the ECM associated with fibrillogenesis, cellular growth and apoptosis and tissue remodelling. SLRPs support the survival of IVD progenitor cells under hypoxic conditions via the activation of specific hypoxia-inducible factors. Additionally, SLRPs deficiency (biglycan) in knockout mice is sufficient to accelerate the IVD degenerative process. These data suggest that SLRPs play an important role in the homeostasis of IVD. Given their specific properties and physiological functions, we propose a role of SLRPs in IVD degeneration and potential application in its regeneration. Copyright © 2015 John Wiley & Sons, Ltd.


Modulation of circadian clock by crude drug extracts used in Japanese Kampo medicine.
Circadian rhythm is an approximately 24 h endogenous biological rhythm. Chronic disruption of the circadian clock leads to an increased risk of diabetes, cardiovascular disease, and cancer. Hence, it is important to develop circadian clock modulators. Natural organisms are a good source of several medicines currently in use. Crude drugs used in Japanese traditional Kampo medicine or folk medicines are an excellent source for drug discovery. Furthermore, identifying new functions for existing drugs, known as the drug repositioning approach, is a popular and powerful tool. In this study, we screened 137 crude drug extracts to act as circadian clock modulators in human U2OS cells stably expressing the clock reporter Bmal1-dLuc, and approximately 12% of these modulated the circadian rhythm. We further examined the effects of several crude drugs in Rat-1 fibroblasts stably expressing Per2-luc, explant culture of lung from Per2::Luciferase knockin mice, and zebrafish larvae in vivo. Notably, more than half of the major ingredients of these crude drugs were reported to target AKT and its relevant signaling pathways. As expected, analysis of the major ingredients targeting AKT signaling confirmed the circadian clock-modulating effects. Furthermore, activator and inhibitor of AKT, and triple knockdown of AKT isoforms by siRNA also modulated the circadian rhythm. This study, by employing the drug repositioning approach, shows that Kampo medicines are a useful source for the identification of underlying mechanisms of circadian clock modulators and could potentially be used in the treatment of circadian clock disruption.


Two cases of nasolacrimal duct obstruction operated by endoscopic dacryocystorhinostomy after orbital fracture reconstruction with an implant.
To report two cases of nasolacrimal duct obstruction (NLDO) caused by orbital fracture reconstruction with an implant successfully treated with endoscopic dacryocystorhinostomy (EnDCR). Two patients presented with NLDO after orbital fracture reconstruction with an implant. Case 1 was a 67-year-old female. She became aware of epiphora in her left eye after undergoing orbital fracture reconstruction with an implant for a left orbital floor fracture 14 years previously. Dacryocystitis was diagnosed based on a lacrimal syringing test because of pus reflux. Computed tomography (CT) showed that the implant was inserted on the left orbital floor, crossing into the lacrimal sac; dacryoendoscopy showed that the implant blocked the nasolacrimal duct. EnDCR was performed without implant removal. The symptoms resolved postoperatively. Case 2 involved a 6-year-old male who had been aware of epiphora in his left eye since undergoing orbital fracture reconstruction with an implant for a left orbital floor fracture one month prior. Dacryocystitis was diagnosed based on a lacrimal syringing test because of pus reflux. CT showed an unclear implant location, but dacryoendoscopy showed that the implant blocked the nasolacrimal duct. The implant was removed. However, EnDCR was performed because there was no improvement in NLDO. The symptoms resolved after EnDCR. One previous report of NLDO after orbital floor fracture reconstruction was performed with external dacryocystorhinostomy with implant removal. Dacryoendoscopy and CT are useful for confirming the location of the implant and obstruction. Depending on the implant's location, it may be possible to perform EnDCR without removing the implant.


An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans.
The fungal pathogen Candida albicans is able to utilize haemin and haemoglobin as iron sources. Haem-iron utilization is facilitated by Rbt5, an extracellular, glycosylphophatidylinositol (GPI)-anchored, haemin- and haemoglobin-binding protein. Here, we show that Rbt5 and its close homologue Rbt51 are short-lived plasma membrane proteins, degradation of which depends on vacuolar activity. Rbt5 facilitates the rapid endocytosis of haemoglobin into the C. albicans vacuole. We relied on recapitulation of the Rbt51-dependent haem-iron utilization in Saccharomyces cerevisiae to identify mutants defective in haemoglobin utilization. Homologues of representative mutants in S. cerevisiae were deleted in C. albicans and tested for haemoglobin-iron utilization and haemoglobin uptake. These mutants define a novel endocytosis-mediated haemoglobin utilization mechanism that depends on acidification of the lumen of the late secretory pathway, on a type I myosin and on the activity of the ESCRT pathway.


Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons.
D-serine, which is synthesized by the enzyme serine racemase (SR), is a co-agonist at the N-methyl-D-aspartate receptor (NMDAR). Crucial to an understanding of the signaling functions of D-serine is defining the sites responsible for its synthesis and release. In order to quantify the contributions of astrocytes and neurons to SR and D-serine localization, we used recombinant DNA techniques to effect cell type selective suppression of SR expression in astrocytes (aSRCKO) and in forebrain glutamatergic neurons (nSRCKO). The majority of SR is expressed in neurons: SR expression was reduced by ~65% in nSRCKO cerebral cortex and hippocampus, but only ~15% in aSRCKO as quantified by western blots. In contrast, nSRCKO is associated with only modest decreases in D-serine levels as quantified by HPLC, whereas D-serine levels were unaffected in aSRCKO mice. Liver expression of SR was increased by 35% in the nSRCKO, suggesting a role for peripheral SR in the maintenance of brain D-serine. Electrophysiologic studies of long-term potentiation (LTP) at the Schaffer collateral-CA1 pyramidal neuron synapse revealed no alterations in the aSRCKO mice versus wild-type. LTP induced by a single tetanic stimulus was reduced by nearly 70% in the nSRCKO mice. Furthermore, the mini-excitatory post-synaptic currents mediated by NMDA receptors but not by AMPA receptors were significantly reduced in nSRCKO mice. Our findings indicate that in forebrain, where D-serine appears to be the endogenous co-agonist at NMDA receptors, SR is predominantly expressed in glutamatergic neurons, and co-release of glutamate and D-serine is required for optimal activation of post-synaptic NMDA receptors.