Development of theta rhythm in hippocampal formation slices perfused with 5-HT1A antagonist, (S)WAY 100135.
Numerous studies have revealed that median raphe nuclei stimulation induces desynchronization of hippocampal field activity in vivo. Some findings provide evidence for tonic regulation of the theta oscillation of the septo-hippocampal system via the serotonergic system. To date the involvement of serotonergic transmission in theta rhythm generation in hippocampal slices has never been investigated. Thus the aim of the present study was to test whether HPC in vitro preparation is capable of producing theta in the presence of compounds modulating the activity of 5-HT1A receptors. To achieve this a series of experiments designed to determine the effect of different concentrations of the 5-HT1A receptor antagonist (S)WAY 100135 on HPC field activity was carried out. The dominant field potential pattern recorded within HPC slices was epileptiform activity, with a maximum frequency ranging from 0.19 ± 0.06 Hz to 0.69 ± 0.10 Hz. In addition, after the bath application of (S)WAY 100135 in concentrations 3 and 10 µM rhythmic epochs in the theta frequency range were also noted. The highest probability of theta rhythm production was observed after the bath perfusion with a solution of (S) WAY 100135 at a concentration of 10 μM. These theta rhythm epochs were characterized by a higher-than-average amplitude compared to carbachol-induced theta epochs and shorter time duration, with no apparent differences in the average frequency and duration of intervals between theta epochs. These results obtained herein of in vitro studies provide direct evidence for the involvement of serotonergic receptors in the depression of oscillatory activity in the HPC theta band.


Anoxia tolerance of con-familial tiger beetle larvae is associated with differences in energy flow and anaerobiosis.
In this study, we compared survivorship, heat dissipation and biochemical features of anaerobiosis of two tiger beetle species (Coleoptera: Cicindelidae) exposed to anoxia. One species commonly experiences environmental immersion from rainfall and snowmelt (Cicindela togata), and the habitat of the other (Amblycheila cylindriformis) is not prone to flooding. The ancestral genus, A. cylindriformis, survives anoxia for only 2 days at 25 degrees C. In response to anoxia, these larvae immediately lose locomotory abilities, tissue concentrations of ATP fall precipitously within 12 h, and significant amounts of lactate are quickly produced. In contrast, C. togata larvae tolerate anoxia for 5 days. Heat dissipation is downregulated to a greater degree than that seen in A. cylindriformis (3.4% versus 14% of standard normoxic rate, respectively), the ability for locomotion is maintained and normoxic levels of ATP are defended for at least 24 h. Lactate is not accumulated until well into anoxic bout, and significant amounts of alanine are also produced. This study provides evidence that tiger beetles differ in physiological responses to anoxia, and that these differences are correlated with flooding risk and with species distribution.


Genome-wide identification and analysis of glyceraldehyde-3-phosphate dehydrogenase family reveals the role of GmGAPDH14 to improve salt tolerance in soybean (Glycine max L.).
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential key enzyme in the glycolytic pathway and plays an important role in stress responses. Although GAPDH family genes have been found in different plant species, the determination of their gene family analysis and their functional roles in soybean are still unknown. In this study, gene sequence and expression data were obtained using online tools, and systematic evolution, expression profile analysis, and qRT-PCR analysis were conducted. Here a total of 16 GmGAPDH genes were identified on nine chromosomes, which were classified into three clusters. Additionally, all GmGAPDH genes harbor two highly conserved domains, including Gp_dh_N (PF00044) and Gp_dh_C (PF02800). The qRTPCR analysis also showed that most GmGAPDH genes significantly responded to multiple abiotic stresses, including NaHCO3, polyethylene glycol, cold, and salt. Among them, GmGAPDH14 was extraordinarily induced by salt stress. The GmGAPDH14 gene was cloned and overexpressed through soybean hair roots. The overexpressed transgenic soybean plants of the GmGAPDH14 gene have also shown better growth than that of control plants. Moreover, the overexpressed transgenic plants of GmGAPDH14 gene had higher activities of superoxide dismutase but lower malonaldehyde (MDA) content than those of control plants under salt stress. Meanwhile, a total of four haplotypes were found for the GmGAPDH14 gene, and haplotypes 2, 3, and 4 were beneficial for the tolerance of soybean to salt stress. These results suggest that the GmGAPDH14 gene might be involved in the process of soybean tolerance to salt stress. The results of this study will be valuable in understanding the role of GAPDH genes in the abiotic stress response of soybean.


Safety leadership and systems thinking: application and evaluation of a Risk Management Framework in the mining industry.
Safety leadership is an important factor in supporting safety in high-risk industries. This article contends that applying systems-thinking methods to examine safety leadership can support improved learning from incidents. A case study analysis was undertaken of a large-scale mining landslide incident in which no injuries or fatalities were incurred. A multi-method approach was adopted, in which the Critical Decision Method, Rasmussen's Risk Management Framework and Accimap method were applied to examine the safety leadership decisions and actions which enabled the safe outcome. The approach enabled Rasmussen's predictions regarding safety and performance to be examined in the safety leadership context, with findings demonstrating the distribution of safety leadership across leader and system levels, and the presence of vertical integration as key to supporting the successful safety outcome. In doing so, the findings also demonstrate the usefulness of applying systems-thinking methods to examine and learn from incidents in terms of what 'went right'. The implications, including future research directions, are discussed. Practitioner Summary: This paper presents a case study analysis, in which systems-thinking methods are applied to the examination of safety leadership decisions and actions during a large-scale mining landslide incident. The findings establish safety leadership as a systems phenomenon, and furthermore, demonstrate the usefulness of applying systems-thinking methods to learn from incidents in terms of what 'went right'. Implications, including future research directions, are discussed.


Meta-Analysis and Meta-Regression of Risk Factors for Surgical Site Infections in Hepatic and Pancreatic Resection.
The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection. The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework. The primary outcome measure was pooled SSI rates. The secondary outcome measure was risk factor profile determination for SSI. The overall rate of SSI after pancreatic and liver resection was 25.1 and 10.4%, respectively (p < 0.001). 32% of pancreaticoduodenectomies developed SSI vs 23% after distal pancreatectomy (p < 0.001). The rate of incisional SSI in the pancreatic group was 9% and organ/space SSI 16.5%. Biliary resection during liver surgery was a risk factor for SSI (25.0 vs 15.7%, p = 0.002). After liver resection, the incisional SSI rate was 7.6% and the organ space SSI rate was 10.2%. Pancreas-specific SSI risk factors were pre-operative biliary drainage (p < 0.001), chemotherapy (p < 0.001) and radiotherapy (p = 0.007). Liver-specific SSI risk factors were smoking (p = 0.046), low albumin (p < 0.001) and significant blood loss (p < 0.001). The rate of organ/space SSI in patients with POPF was 47.7% and in patients without POPF 7.3% (p < 0.001). Organ/space SSI rate was 43% in patients with bile leak and 10% in those without (p < 0.001). The risk factors for SSI following pancreatic and liver resections are distinct from each other, with higher SSI rates after pancreatic resection. Pancreaticoduodenectomy has increased risk of SSI compared to distal pancreatectomy. Similarly, biliary resections during liver surgery increase the rates of SSI.


Contrast nasopharyngography.
Contrast nasopharyngography was performed in 25 cases of nasopharyngeal lesions, 15 of which were carcinoma, six malignant lymphoma, and four benign lesions including neurofibroma, haemangioma, angiofibroma and tuberculosis. Nasopharyngography was also performed in 22 cases with extranasopharyngeal lesions, including nine of head and neck malignant lymphoma and 13 of tumours originating in adjacent organs. To describe the extent and site of the tumour, the nasopharyngeal walls were labelled segment 1 to 15 on axial and lateral views. The lateral skull films were negative in five of eight small malignancies involving no more than five wall segments, and also negative in six of 10 cases of unilateral involvement. Small lesions involving the unilateral fossa of Rosenmueller and/or the superolateral wall were frequently undetected. Nasopharyngography is indicated in cases where clinical suspicions of a lesion remain after a normal straight film. When malignancies were treated with radiation therapy a pre-irradiation nasopharyngogram clearly depicted the site and extent of the disease, and a post-irradiation study showed a marked shrinkage of the tumour mass and/or markedly improved raggedness of the wall of the nasopharynx. Four benign lesions showed large space-occupying lesions. In the case of tuberculosis, for example, the nasopharyngeal cavity was totally obliterated by the granulomatous tissue. In nine cases of malignant lymphoma involving the neck nodes or the palatine tonsil, the nasopharyngogram was normal.


Biochemical characterization of the β-glucosidase Glu1B from Coptotermes formosanus produced in Pichia pastoris.
β-glucosidases (E.C. 22.214.171.124) are enzymes that hydrolyze β-1,4-glycosidic bonds from non-reducing terminal residues in β-D-glucosides, with the release of glucose. β-glucosidases currently used for the saccharification of lignocellulosic biomass have low efficiency in hydrolyzing cellobiose and are inhibited by glucose, contrary to what would be desirable. In this work, we engineered Pichia pastoris strains to produce the β-glucosidase Glu1B from the termite Coptotermes formosanus, and biochemically characterized the recombinant enzyme. After 36 h of methanol induction in shake flasks, the P. pastoris KM71BGlu strain produced and secreted 4.1 U/mL (approx. 26 mg/L) of N-glycosylated β-glucosidase Glu1B. The recombinant product had an optimum pH of 5.0, optimum temperature of 50 °C, residual activity at 40 °C higher than 80 %, specific activity toward cellobiose of 431-597 U/mg protein, and a Ki for glucose of 166 mM. The protein structure was stabilized by Mn2+ and glycerol. The high specific activity of the recombinant β-glucosidase Glu1B was correlated with the presence of specific residues in the glycone (Gln455) and aglycone (Thr193 and Hys252) binding sites, along with linker residues (Leu192, Ile251, and Phe333) between residues of these two sites. Moreover, the resistance to inhibition by glucose was correlated with the presence of specific gatekeeper residues in the active site (Met204, Gln360, Ala368, Ser369, Ser370, Leu450, and Arg451). Based on its biochemical properties and the possibility of its production in the P. pastoris expression system, the β-glucosidase produced and described in this work could be suitable as a supplement in the enzymatic hydrolysis of cellulose for saccharification of lignocellulosic biomass.


The induction of a multiple wing hair phenocopy by heat shock in mutant heterozygotes.
Phenocopies are developmental defects induced by environmental treatments during differentiation. Because of their resemblance to mutant phenotypes it has been suggested that phenocopies are due to environmental effects on the expression of specific genes during development. In this paper we describe the heat shock (40.8 degrees C) induction of a multiple wing hair phenocopy in the mutant heterozygote (mwh/+). The mwh phenocopy is only induced in heterozygotes of the recessive mutant during a short sensitive period which appears to be the time of expression of the multiple wing hair gene. We suggest that this phenocopy is due to failure of mwh gene expression and that phenocopy sensitive periods may be useful in identifying expression periods for particular genes during development. Furthermore we have been able to demonstrate that a 35 degrees C pretreatment will prevent the induction of the multiple wing hair phenocopy. A similar 35 degrees C pretreatment prevents induction of several different phenocopies by heat in wild-type flies (N. S. Petersen and H. K. Mitchell (1985). In "Comprehensive Insect Physiology, Biochemistry and Pharmacology, Vol. X, Biochemistry." Pergamon, New York). This indicates a common molecular mechanism for both the induction and the prevention of heat-induced phenocopies.


Effect of estrogens on apomorphine-induced circling behavior in the rat.
The effect of administration of estrogens parenterally for 1 week was tested on apomorphine-induced circling in a group of castrated female rats with a lesion of the left entopednucluar nucleus. We observed a significant decrease in the number of turns per minute in estrogen-treated animals as compared with controls. Our tentative explanation is that estrogens decrease the sensitivity of dopamine receptors in the striatum.


Cartilage hair hypoplasia and celiac disease: report of an Indian girl with novel genotype.
Cartilage hair hypoplasia is a genetic disease, characterized by generalized metaphyseal dysplasia mainly affecting the knee joints. Variable extraskeletal features like anemia, malabsorption, impaired spermatogenesis, impaired immunity, and malignancies have been reported. The work up of malabsorption and short stature led to the diagnosis of celiac disease in three previous cases of cartilage hair hypoplasia. Here, we report an Indian girl with a novel genotype, diagnosed as celiac disease with cartilage hair hypoplasia, and review the previous three cases.


Progression of left ventricular diastolic function in the neonate and early childhood from transmitral color M-mode filling analysis.
We implemented sophisticated color M-mode analysis to assess age-dependent progression of left ventricular (LV) diastolic function. Normal infants were prospectively enrolled for serial echocardiograms at 1 week, 1 month, 6 months, 1 year, and 2 years. From color M-mode scans, propagation velocity (VP), strength of filling (VS), and intraventricular pressure difference (IVPD) in 3 segments along apex-to-mitral valve scan line were measured. Age-wise comparisons of diastolic filling from 121 echocardiograms in 31 infants showed VP (cm/s), VS (cm2/s), and E-wave IVPD (mmHg) at 1 week to be 66.2 ± 11.9, 75.3 ± 19.9, and 1.5 ± 0.4, respectively, while VP, VS, and E-wave IVPD at 1 month were 80.3 ± 14.4, 101.2 ± 28.3, and 2.42 ± 1.1, respectively. There were significant differences in VP and segmental IVPD between first week and first month (p < 0.005) and IVPD between the age groups (p < 0.001). Comprehensive analysis of transmitral color M-mode data is feasible in infants, enabling calculation of pressure drop between the LV base and apex and strength of propagation from two distinct slopes. Profound changes very early followed by relatively constant filling mechanics in later infancy indicate significant LV maturation occurring during the first month of life. We implemented sophisticated analytic methods for color M-mode echocardiography in infants to assess age- and dimension-dependent changes in left ventricular diastolic function. Comprehensive characterization of transmitral color M-mode flow was feasible, enabling calculation of pressure drop between left ventricular base and apex and strength of propagation. Left ventricular diastolic filling function has predictable maturational progression, with significant differences in the intraventricular pressure between infants from birth to 2 years. This study forms the basis for future studies to examine alteration of early diastolic filling in congenital heart disease.


The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.
In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.


Extranotochordal chordoma presenting as multiple neck masses: report of a case.
Chordomas are rare tumours which arise from notochordal remnants. A primary cervical chordoma of extranotochordal origin, sparing osseous structures, was excised by a bilateral neck dissection. The patient was disease-free two and a half years later.


The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151.
In vivo tumor cell migration through integrin-dependent pathways is key to the metastatic behavior of malignant cells. Using quantitative in vivo assays and intravital imaging, we assessed the impact of cell migration, regulated by the integrin-associated tetraspanin CD151, on spontaneous human tumor cell metastasis. We demonstrate that promoting immobility through a CD151-specific metastasis blocking mAb prevents tumor cell dissemination by inhibiting intravasation without affecting primary tumor growth, tumor cell arrest, extravasation, or growth at the secondary site. In vivo, this loss of migration is the result of enhanced tumor cell-matrix interactions, promoted by CD151, which prevent dissociation by individual cells and leads to a subsequent inhibition of invasion and intravasation at the site of the primary tumor.


Microscopic cancer cell spread in gastric cancer: whole-section analysis of mesogastrium.
Cancer cells are often found in adipose connective tissue separate from the primary lesion and outside lymph nodes on routine pathologic examination of resected gastric cancer specimens. To identify the anatomical relationship between such cancer cell spread and lymph nodes, we investigated the microscopic cancer cell spread in the mesogastrium (CSM) by the whole-section analysis of the mesogastrium. One thousand five hundred fifty-two sections of the mesogastrium obtained from 37 patients with gastric cancer were subjected. CSM is defined as the existence of cancer cell spread in the mesogastrium separate from the primary lesion. CSM was detected in three (8%) of the 37 patients. CSM was classified into three types. CSM was found in three of the 12 patients with advanced cancer, but not in 25 patients with early cancer. CSM may occur in the mesogastrium separate from metastatic lymph nodes; therefore, we should pay particular attention to the potential existence of CSM in surgery for gastric cancer.


Rat brain myo-inositol 3-phosphate synthase is a phosphoprotein.
The therapeutic effects of lithium in bipolar disorder are poorly understood. Lithium decreases free inositol levels by inhibiting inositol monophosphatase 1 and myo-inositol 3-phosphate synthase (IPS). In this study, we demonstrate for the first time that IPS can be phosphorylated. This was evident when purified rat IPS was dephosphorylated by lambda protein phosphatase and analyzed by phospho-specific ProQ-Diamond staining and Western blot analysis. These techniques demonstrated a mobility shift consistent with IPS being phosphorylated. Mass spectral analysis revealed that Serine-524 (S524), which resides in the hinge region derived from exon 11 of the gene, is the site for phosphorylation. Further, an antibody generated against a synthetic peptide of IPS containing monophosphorylated-S524, was able to discriminate the phosphorylated and non-phosphorylated forms of IPS. The phosphoprotein is found in the brain and testis, but not in the intestine. The intestinal IPS isoform lacks the peptide bearing S524, and hence, cannot be phosphorylated. Evidences suggest that IPS is monophosphorylated at S524 and that the removal of this phosphate does not alter its enzymatic activity. These observations suggest a novel function for IPS in brain and other tissues. Future studies should resolve the functional role of phospho-IPS in brain inositol signaling.


Green synthesis and characterization of iron oxide nanoparticles for the removal of heavy metals (Cd2+ and Ni2+) from aqueous solutions with Antimicrobial Investigation.
Clove and green Coffee (g-Coffee) extracts were used to synthesize green iron oxide nanoparticles, which were then used to sorb Cd2+ and Ni2+ ions out of an aqueous solution. Investigations with x-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, nitrogen adsorption and desorption (BET), Zeta potential, and scanning electron microscopy were performed to know and understand more about the chemical structure and surface morphology of the produced iron oxide nanoparticles. The characterization revealed that the main component of iron nanoparticles was magnetite when the Clove extract was used as a reducing agent for Fe3+, but both magnetite and hematite were included when the g-Coffee extract was used. Sorption capacity for metal ions was studied as a function of sorbent dosage, metal ion concentration, and sorption period. The maximum Cd2+ adsorption capacity was 78 and 74 mg/g, while that of Ni2+ was 64.8 and 80 mg/g for iron nanoparticles prepared using Clove and g-Coffee, respectively. Different isotherm and kinetic adsorption models were used to fit experimental adsorption data. Adsorption of Cd2+ and Ni2+ on the iron oxide surface was found to be heterogeneous, and the mechanism of chemisorption is involved in the stage of determining the rate. The correlation coefficient R2 and error functions like RMSE, MES and MAE were used to evaluate the best fit models to the experimental adsorption data. The adsorption mechanism was explored using FTIR analysis. Antimicrobial study showed broad spectrum antibacterial activity of the tested nanomaterials against both Gram positive (S. aureus) (25923) and Gram negative (E. coli) (25913) bacteria with increased activity against Gram positive bacteria than Gram negative one and more activity for Green iron oxide nanoparticles prepared from Clove than g-Coffee one.


Novel Tropheryma species in a lung biopsy sample from a kidney transplant recipient.
A kidney transplant recipient with recurrent pleuritis underwent an open lung biopsy, the results of which revealed multiple nodular infiltrates. Grocott and periodic acid-Schiff staining were positive. Fungal and Tropheryma whipplei PCR were, however, negative. Further identification was needed. Formalin-fixed, paraffin-embedded (FFPE) extraction was performed using an FFPE extraction kit. T. whipplei was searched for using a real-time PCR targeting the noncoding repeat specific for T. whipplei. Identification of the bacteria in the extract was done using 16S rDNA and 23S rDNA sequencing and BLAST analysis. Internal transcribed spacer PCR was used for fungal DNA identification. The FFPE extract was negative for fungi and T. whipplei. 16S rDNA sequence analysis of a 1375 bp fragment gave T. whipplei as the best match with 26 mismatches, resulting in only 98% agreement. Sequence analysis of the 23S rDNA gene again gave T. whipplei as the best match, but with only 91% agreement. A pan-Tropheryma 16S rDNA real-time PCR was developed, and both the biopsy sample and a respiratory sample of the patient were strongly positive. The patient received antimicrobial treatment targeting T. whipplei with good clinical outcome. 16S and 23S rDNA sequencing gave T. whipplei as the best hit, although with limited agreement. These findings suggest that a novel Tropheryma species that lacks the noncoding repeat, most frequently used for molecular detection of Whipple disease, might be the cause of the pulmonary disease. Adaptation of current PCR protocols is warranted in order to detect all Tropheryma species.


Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal spray: potential effects on clinical safety and efficacy.
Mometasone furoate nasal spray (MFNS) is recommended as a first-line therapy for allergic rhinitis. The purpose of intranasal administration is to deliver maximally effective therapy to the affected nasal tissues while minimizing systemic exposure. This article reviews the pharmacokinetic and pharmacodynamic properties of MFNS, highlighting the potential clinical relevance of data concerning its glucocorticoid receptor binding, bioavailability, and metabolism, and its role in activating and suppressing transcription of steroid-dependent genes. A search of the MEDLINE and EMBASE databases (January 1995-July 2007) was undertaken to identify in vitro, preclinical, and clinical studies and review articles concerning MFNS. Searches were also conducted to identify articles on the pharmacokinetics, pharmacodynamics, and adverse effects of the intranasal corticosteroids discussed in this article. Pertinent abstracts from allergy society meetings and data from the author's research experience were also included. The data reviewed indicate that MFNS has a number of qualities that are important in achieving nasal selectivity with minimal systemic adverse effects. For example, MFNS is stable in nasal tissues and is efficiently metabolized in the liver (AUC for a 400-microg dose: 127 fmol/mL x h). Its systemic bioavailability (0.46%) is one of the lowest among currently available intranasal corticosteroids. Bioactive glucocorticoid metabolites have not been observed in humans. The results of immunologic studies suggest that MFNS may reverse the exaggerated T-helper cell type 2 (Th2)-related cytokine response seen in allergic disease through preferential inhibition of Th2 over the T-helper cell type 1-related cytokine. MFNS is an intranasal corticosteroid with a low potential for systemic adverse effects. The efficacy and safety profiles of MFNS seen in clinical use are consistent with its pharmacokinetic and pharmacodynamic properties.


Co-anaerobic digestion of sawdust and chicken manure with plant herbs: Biogas generation and kinetic study.
Plant herbs specifically serai wangi (SW) and peppermint (PPM) are selected for its insect repellent properties as the use of chicken manure (CM) in anaerobic digestion (AD) potentially attract flies due to the digestate produced. Hence, the addition of SW and PPM in the AD system of CM could deter flies' infestation while producing biogas. Previous work has shown that AD of sawdust (SD) and CM with these plant herbs were able to produce biogas and reduce the flies attraction towards the digestate. However, the combination of SW and PPM for AD of CM has yet to be investigated. This work describes the effect of mixing SW and PPM on the co-AD of SDCM with respect to biogas production, methane yield and kinetic analysis. The mixture of SW and PPM was varied at different concentrations. The composition of methane in biogas was characterized every 10 days by using gas chromatography (GC) equipped with a thermal conductivity detector (TCD). The results suggest that co-AD of 10SW10PPM exhibited the highest biogas production (52.28 mL/gvs) and methane yield (30.89 mL/gvs), which the purity of methane increased by 18.52% as compared to SDCM. However, increasing the concentration of SW and PPM does not significantly improve the overall process. High R2 (0.927-0.999), low RMSE (0.08-0.61) and low prediction error (<10.00%) were displayed by the modified Gompertz, logistic and Cone models. In contrast, Monod and Fitzhugh model is not preferred for the co-AD of SDCM with a mixture of SW and PM, as a high prediction error is obtained throughout the study. Increasing the dosage of PPM decreases the maximum cumulative methane yield, ranging from 31.76 to 7.01 mL/gvs for modified Gompertz and 89.56 to 19.31 mL/gvs for logistic model. The Modified Gompertz obtained a lag phase of 10.01-28.28 days while the logistic model obtained a lag phase of 37.29-52.48 days.


Lower fractional dimension in Alzheimer's disease correlates with reduced locus coeruleus signal intensity.
This study aimed to determine the pattern of fractional dimension (FD) in Alzheimer's disease (AD) patients, and investigate the relationship between FD and the locus coeruleus (LC) signal intensity.A total of 27 patients with AD and 25 healthy controls (HC) were collected to estimate the pattern of fractional dimension (FD) and cortical thickness (CT) using the Computational Anatomy Toolbox (CAT12), and statistically analyze between groups on a vertex level using statistical parametric mapping 12. In addition, they were examined by neuromelanin sensitive MRI(NM-MRI) technique to calculate the locus coeruleus signal contrast ratios (LC-CRs). Additionally, correlations between the pattern of FD and LC-CRs were further examined.Compared to HC, AD patients showed widespread lower CT and FD Furthermore, significant positive correlation was found between local fractional dimension (LFD) of the left rostral middle frontal cortex and LC-CRs. Results suggest lower cortical LFD is associated with LCCRs that may reflect a reduction due to broader neurodegenerative processes. This finding may highlight the potential utility for advanced measures of cortical complexity in assessing brain health and early identification of neurodegenerative processes.


[Therapeutic effect of interferon-alpha on hairy cell leukemia].
Hairy cell leukemia (HCL) is characterized by slow proliferation of special mononuclear cells. Although splenectomy has been evaluated to be the most effective traditional treatment for HCL, the response of patients to splenectomy is not necessarily satisfactory. Recently, the treatment of HCL with Interferon-alpha has been reported to be effective, and we report a female case of HCL who showed marked improvement in her hematological findings with this therapy.


[The Roma birthing wheel: 1 year clinical experience in a specialty hospital].
To test the safety and practicability of spontaneous deliveries with the Roma birthing wheel (RBW). The results of 1 year's clinical experience (1.12.1995-30.11.1996) with the RBW at the Department of Obstetrics and Gynecology, Wilhelminenspital, Vienna, were compared with the results of a group of head-first deliveries before procuring the RBW. Out of 1,555 births, 1,377 (89%) were spontaneous; 209 (15%) women used the RBW. Compared with the figures before the RBW was available, the total duration of labor was reduced by about one third; the birth canal was intact in 44% and the use of painkillers reduced by a range between 8 and 27%. In spontaneous births the use of the RBW definitely has advantages, e.g., shortening of the procedure and acceptance on the part of the women; also, safety for both mother and child remains unchanged.


Restriction endonuclease analysis of the transducing bacteriophage lambda RIF d18.
The lambda rif d 18 bacteriophage carries essential parts of the E. coli genome which can not be mapped by conventional methods. The phage DNA was analysed with four restriction endonucleases (endo R. BamHI, Sall, Hpal and EcoRI) and a physical map was constructed.


The effect of noise variation over time and between populations on the fine spectrotemporal characteristics of different vocalization types.
Noise affects the recognition of acoustic signals by masking information. To compensate for increased noise, individuals often increase the minimum frequency of their vocalization to reduce noise interference. Our goal was to analyze the effect of noise on the characteristics of different bird vocalizations, through a comparative study of vocalizations on the same bird species. We analyzed the effects of noise variation on the fine spectrotemporal characteristics of calls, songs, and duets of White-eared Ground-sparrows (Melozone leucotis) across three populations over a three-year period. We recorded vocalizations and noise levels simultaneously from 41 territories between 2012 and 2014. We measured the duration, minimum, maximum, and maximum amplitude frequency, and counted the number of songs elements for each vocalization recorded. As we predicted, noise influences the minimum frequency of song, but did not have an effect on the fine spectrotemporal characteristics for calls and duets. We did, however, find that low and high frequency of calls and duets increased with noise-population-year interaction. Our results suggest that differences in noise values at each population were inadequate to observe changes in vocalization characteristics. In conclusion, evaluating responses to different noise levels on different vocalization types for the same species expands our understanding of the flexibility of birds to adjust vocalizations in response to anthropogenic noise.


Using the BigMouth repository for periodontal medicine: Breaking the chains?
To achieve the ultimate therapeutic reality of disease prevention, we must first conduct a thorough review of periodontal and peri-implant diseases concomitant with their mechanistic, predisposing, and precipitating factors to address the present oral/systemic needs of our patients. An innovative dental research patient data repository (RPDR) named BigMouth was successfully launched in August 2012 with data on more than 4.5 million patients seen in 11 dental schools (members of the Consortium of Oral Health Research and Informatics, COHRI). Level 1 data access allots researchers with count data that may be used to formulate and test initial hypotheses based on preliminary data trends. Level 2 access gives more detailed, patient-level information with full periodontal charts. Of note, radiographic data were not accessible at the time of writing this manuscript. As we support the use of these innovative "big data" tools for exploratory use, we bring to the forefront the purposeful intention to (1) not overproject unsubstantiated relationships and (2) simultaneously pursue grounding of the mechanistic underpinnings of found associations.


Glycophorins B and C from human erythrocyte membranes. Purification and sequence analysis.
We have developed methods for the preparative purification of two sialoglycoproteins (glycophorins B and C) from human erythrocyte membranes by high-performance ion exchange and gel permeation chromatography in the presence of Triton X-100. Glycophorin B was obtained without any detectable contaminants, and glycophorin C exhibited a purity of about 90-95%. The amino acid sequence of the intramembranous domain (residues 36-71) of glycophorin B was determined and found to be similar to that of the hydrophobic region of the major sialoglycoprotein (glycophorin A). The amino acid sequence of the hydrophobic domain (residues 49-88) of glycophorin C, that was also determined, agreed completely with the structure recently deduced from cDNA sequencing.


Canine parvovirus prevention and prevalence: Veterinarian perceptions and behaviors.
Canine Parvovirus (CPV) causes severe morbidity and mortality in dogs, particularly puppies, worldwide. Although vaccination is highly efficacious in preventing disease, cases continue to occur and vaccination failures are well documented. Maternally derived antibody interference is the leading cause of vaccination failure and age at vaccine administration is a significant risk factor for failure. However, no studies have been performed on practicing veterinarians' usage of and compliance with published vaccination guidelines and label recommendations. Likewise, there are no published studies of veterinarian perceptions on CPV occurrence and mortality and its influence on case outcome. We report a study in which all Australian small companion animal (canine and feline) veterinary hospitals were surveyed, yielding a response rate of 23.5% (534 unique veterinary hospitals). Respondents overall perceived national CPV occurrence ten-times lower (median 2000 cases) than the estimated national caseload (20,000 cases). Respondents from hospitals that did not diagnose CPV perceived national occurrence twenty-times lower (median 1000 cases) than the estimated rate (p < 0.0001). Perceived disease mortality (50%) was 2.74 times higher than that reported (18.2%). In addition, 26.7% of veterinarians reported using serological titer testing to some degree, which some practitioners use in lieu of vaccination if a titer is perceived to reflect sufficient immunity. Based on this study veterinarians appear to be aware of the disease risk in their region but unaware of the burden of CPV disease nationally, and perceive mortality risk higher than it actually is. This might lead to an overestimation of cost to treat, and over-recommendation of euthanasia. Nearly half (48.7%) of respondents recommended final puppy vaccination earlier than guidelines recommend, while 2.8% of respondents recommended a puppy re-vaccination interval longer than supported by vaccine labels and guidelines. Both of these practices may put puppies at risk of CPV infection.


[Influence of smear layer removal and acid etching on the sealing potential of various cavity liners].
Dye penetration experiments were conducted to test the sealing of dentin cavities with cavity liners. Dye penetration was greatest for zinc phosphate cement (Harvard) and smallest for a plastic reinforced calcium hydroxide compound (Care).


Sodium ions, acting at high-affinity extracellular sites, inhibit sodium-ATPase activity of the sodium pump by slowing dephosphorylation.
1. It is known that extracellular Na+ ions, in low concentrations, inhibit Na+-ATPase activity in resealed red cell ghosts and that this inhibition is reversed by high concentrations of extracellular Na+. We have attempted to elucidate these actions of extracellular Na+ by investigating the dependence on Na+ concentration of (a) ATP-ADP exchange and Na+-ATPase activity both in native and in N-ethylmaleimide (NEM)-treated (Na+ + K+)-ATPase from pig kidney, and (b) the rate of hydrolysis of the phosphorylated kidney enzyme in the absence of K+ ions. 2. With the native enzyme, ATP-ADP exchange and Na+-ATPase activity showed similar responses to changes in Na+ concentration: a steep but S-shaped rise between 0 and 2.5 mM, a slight fall (exchange) or a plateau (ATPase) between 2.5 and 10 mM, and a roughly linear rise between 10 and 150 mM. With NEM-treated enzyme, the ATP-ADP exchange, which was greatly accelerated, showed no sign either of inhibition at intermediate Na+ concentrations or of the reversal of that inhibition at higher concentrations. The exchange rate increased with Na+ concentration in a smooth curve and was half-maximal at about 7 mM. 3. The effects, on ATP-ADP exchange, of changing the concentrations of ATP, ADP and Mg have also been investigated. With both native and NEM-treated enzyme, the interactions of ATP, ADP and Mg are complicated; they show that, for the reaction leading to ATP formation, either free ADP rather than MgADP is the substrate, or Mg2+ ions are inhibitory (or both). 4. Since NEM, in the conditions in which we have used it, is believed to act by inhibiting the conversion of an ADP-sensitive form of the phosphoenzyme (E1P) to an ADP-insensitive form (E2P), the absence of Na+ inhibition of ATP-ADP exchange in NEM-treated enzyme, together with the parallel effects of Na+ ions on the ATP-ADP exchange activity and on the Na+-ATPase activity of native enzyme, suggests that the inhibitory effect of external Na+ occurs after the conversion of E1P into E2P. 5. To test whether this inhibitory effect of Na+ reflected inhibition of the hydrolysis of E2P, we measured the rate of loss of incorporated 32P when enzyme, newly phosphorylated by [gamma32P]ATP, was squirted into a large volume of ice-cold solution containing 1,2-cyclohexylenedinitrilotetraacetic aicd (CDTA), unlabelled ATP and 0, 5 or 150 mM-Na+. The rate of loss of radioactivity from the membranes was least at 5 mM-Na+, about twice as great at 150 mM-Na+, and about 5 times as great at 20 microM (final) Na+. 6. An unexpected feature of the results was that the pattern of stimulation of ATP-ADP exchange in intact cells. If Na+ ions are absent externally, a different could be fitted better on the assumption that activation by internal Na+ occurs at two sites with equal affinities, than on the assumptions that activation occurs at a single site or at three sites with equal affinities.


Penicillamine-modified sensor for the voltammetric determination of Cd(II) and Pb(II) ions in natural samples.
A new penicillamine-GCE was developed based on the immobilization of d-penicillamine on aryl diazonium salt monolayers anchored to the glassy carbon electrode (GCE) surface and it was applied for the first time to the simultaneous determination of Cd(II) and Pb(II) ions by stripping voltammetric techniques. The detection and quantification limits at levels of µg L(-1) suggest that the penicillamine-GCE could be fully suitable for the determination of the considered ions in natural samples.


Establishment and characterization of a human renal carcinoma cell line MRT-1, with special reference to the production of serine proteinase inhibitors.
A new human cell line MRT-1 was established from a metastatic lymph node of renal cell carcinoma of a 47 years old Japanese male. The cultured MRT-1 cells exhibit an epithelial appearance and contain lipid vacuoles in their cytoplasm in vitro. The modal chromosome number was 70. Doubling time and plating efficiency were 32.5 h and 5%, respectively (at the 47th passage). Injection of 1X10(6) MRT-1 cells beneath the renal capsule of nude mice resulted in tumor formation resembling the original tumor. Serine proteinase inhibitors produced by the cell line were analyzed. The cultured cells produced alpha 1-antitrypsin (alpha 1-AT) and plasminogen activator inhibitor-1 (PAl-1) into the conditioned medium. Most of the MRT-1 derived alpha 1-AT had lost the affinity to Concanavalin A when compared to the normal plasma alpha 1-AT.


Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring.
To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth. Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.


Kinetics and bioenergetics of Spirulina platensis cultivation by fed-batch addition of urea as nitrogen source.
The cyanobacterium Spirulina platensis was cultivated in bench-scale miniponds on bicarbonate/carbonate solutions using urea as nitrogen source. To minimize limitation and inhibition phenomena, urea was supplied semicontinuously using exponentially increasing feeding rates. The average growth rates obtained alternately varying the total mass of urea added per unit reactor volume (275 < mT < 725 mg/L) and the total feeding time (9 < tT < 15 d) clearly evidenced nitrogen limitation for mT< 500 mg/L and excess nitrogen inhibition above this threshold. The time behavior of the specific growth rate at variable urea feeding patterns allowed estimation of the time-dependent Gibbs energy dissipation for cell growth under the actual depletion conditions of fed-batch cultivations. Comparison of the yield of growth on Gibbs energy obtained using either urea or KNO3 pointed to the preference of S. platensis for the former nitrogen source, likely owing to more favorable bioenergetic conditions.


Periurethral and Intravenous Injections of Adipose-Derived Stem Cells to Promote Local Tissue Recovery in a Rat Model of Stress Urinary Incontinence.
To compare the effects of periurethral and intravenous injection of adipose-derived stem cells (ADSCs) on voiding function and tissue recovery in a stress urinary incontinence (SUI) rat model. Sixty-four postpartum rats were randomly allocated to a normal group and the SUI model was established in 48 rats by vagina balloon dilation and bilateral ovariectomy. The SUI rats were randomized into 3 groups and received urethral injection of PBS (SUI group), periurethral injection of ADSCs (PU group), and intravenous injection of ADSCs (IV group) in 10 days after the ovariectomy. After 1, 7, and 14 days, ADSCs were tracked in urethra specimen. The urinary function of the remaining rats was analyzed at day 28, and urethral tissues were harvested for Western blotting and histochemical analyses. Alpha smooth muscle actin, myosin heavy chain, vascular endothelial growth factor, and neurofilament protein expression was increased in the IV and PU groups. Voiding function was also improved, with no significant differences between the IV and PU groups. The cell retention rate in rat urethral tissues was higher in the PU group than that in the IV group. Compared with the IV group, myosin heavy chain, vascular endothelial growth factor, neurofilament and transforming growth factor-β1 (TGF-β1)/Smad pathway protein expression levels were significantly higher in the PU group, while alpha smooth muscle actin expression was significantly lower (P < .05). Periurethral and intravenous injection of ADSCs induces different degrees of recovery of the urethral sphincter, cytokine secretion levels and cell retention rates in the urethral tissues in SUI rats, however, there was no significant difference in 2 methods.


Infections in Burn Patients.
Infections are the leading cause of mortality in burn patients who survive their initial resuscitation. Burn injury leads to immunosuppression and a dysregulated inflammatory response which can have a prolonged impact. Early surgical excision along with support of the multidisciplinary burn team has improved mortality in burn patients. The authors review diagnostic and therapeutic challenges as well as strategies for management of burn related infections.


Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage.
Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men. To investigate the correlation between vascular endothelial growth factor (VEGF) and cortisol (Cor) and the prognosis of patients with hypertensive cerebral hemorrhage. A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group. Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group. Peripheral venous blood was collected, and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay. A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment (P < 0.05). Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group. Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses. Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage (P < 0.05). Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.


Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system.
Withania somnifera (L.) Dunal, shows several pharmacological properties which are attributed mainly to the withanolides present in the root. The efficacy of medicinally active withanolides constituents depends on the absorption and transportation through the intestinal epithelium. We examined these characteristics by employing the Sino-Veda Madin-Darby canine kidney cells culture system, which under in vitro condition shows the absorption characteristics similar to the human intestinal epithelium. Thus, the aim of the present investigation was to assess the bioavailability of individual withanolides. Withanolides were diluted in Hank's buffered saline at a concentration of 2 μg/ml were tested for permeability studies carried out for 1 h duration. Permeability was measured in terms of efflux pump (P eff) in cm/s. P eff values of withanolide A (WN A), withanone (WNN), 1,2-deoxywithastramonolide (1,2 DWM), withanolide B (WN B), withanoside IV-V (WS IV-V), and withaferin A were 4.05 × 10(-5), 2.06 × 10(-5), 1.97 × 10(-5), 1.80 × 10(-5), 3.19 × 10(-6), 3.03 × 10(-6) and 3.30 × 10(-7) respectively. In conclusion, the nonpolar and low molecular weight compounds (WN A, WNN, 1,2 DWM, and WN B) were highly permeable. As against this, the glycosylated and polar WS IV and WS V showed low permeability. Surprisingly and paradoxically, the highly biologically active withaferin A was completely impermeable, suggesting that further studies possibly using human epithelial colorectal adenocarcinoma (Caco-2) cells may be needed to delineate the absorption characteristics of withanolides, especially withaferin A.


Sustained expression of thrombospondin-1 is associated with the development of glomerular and tubulointerstitial fibrosis in the remnant kidney model.
Transforming growth factor-beta1 (TGF-beta1) has been implicated in the development of progressive nephrosclerosis in the remnant kidney model of chronic renal insufficiency. Thrombospondin-1 (TSP-1) is an extracellular matrix protein which has been recently shown to be capable of converting TGF-beta from its latent to its active form. We studied the expression of TSP-1 mRNA and protein during the development of glomerular and tubulointerstitial nephrosclerosis in the renal ablation model particularly in relation to TGF-beta1 expression. The remnant kidney model in the rat was investigated 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 7.5 weeks and 10 weeks after disease induction. Using single and double immunostaining techniques, renal tissues were examined for TSP-1 protein, TGF-beta1, platelet-derived growth factor BB, extracellular matrix proteins, such as collagens and fibronectin, myofibroblast formation and macrophage influx. TSP-1 mRNA expression was investigated using a radioactive in situ hybridization technique. De novo expression of TSP-1 mRNA and protein occurred in all glomerular cell types as well as in tubular cells, myofibroblasts and some macrophages in areas of tubulointerstitial injury. TSP-1 expression preceded and was sustained during the development of tubulointerstitial and glomerular fibrosis and was frequently localized at sites of increased expression of TGF-beta1, but not of platelet-derived growth factor BB. In the remnant kidney model, the time course and localization of TSP-1 are consistent with its playing a role as a local activator of TGF-beta1, thereby potentially participating in the development of nephrosclerosis.


Arterial spin-labeled perfusion imaging reflects vascular density in nonfunctioning pituitary macroadenomas.
Angiogenesis is very important in clinical features of pituitary adenomas. We investigated the relationship between the blood flow of nonfunctioning pituitary macroadenomas measured by arterial spin-labeled perfusion imaging and the microvessel attenuation of the tissue. Conventional MR imaging with contrast-enhanced T1WI and arterial spin-labeled perfusion imaging were performed before surgery in 11 consecutive patients with nonfunctioning pituitary macroadenomas. ROIs were drawn on the tumors, and the degrees of enhancement were calculated by dividing the signal intensity on the contrast-enhanced T1WI by that on the nonenhanced TIWI. As an index of tumor perfusion, a quantitative analysis was performed by using normalized tumor blood flow values calculated by dividing the mean value of the tumor region of interest by the mean region of interest values in the 2 cerebellar hemispheres. The relative microvessel attenuation was determined as the total microvessel wall area divided by the entire tissue area on CD-31-stained specimens. The degree of enhancement and the normalized tumor blood flow values were compared with relative microvessel attenuation. Additionally, intra- and postoperative tumor hemorrhages were visually graded. The degree of enhancement was not correlated with relative microvessel attenuation. Statistically significant correlations were observed between normalized tumor blood flow values and relative microvessel attenuation (P < .05). At surgery, 3 cases were visually determined to be hypervascular tumors, and 1 of these cases had symptomatic postoperative hemorrhage. A statistically significant difference in normalized tumor blood flow values was observed visually between the intraoperative hypovascular and hypervascular groups (P < .05). Arterial spin-labeled perfusion imaging reflects the vascular density of nonfunctioning pituitary macroadenomas, which may be useful in the preoperative prediction of intra- and postoperative tumor hemorrhage.


The expression in Escherichia coli of recombinant human platelet factor 4, a protein with immunoregulatory activity.
In order to establish more firmly the immunoregulatory effect of platelet factor 4 (PF4) and develop a means to provide material for possible clinical use, the nucleotide sequence for PF4 was synthesized utilizing a ligation strategy of six duplexes ranging from 27 to 43 base pairs in length. The individual oligodeoxynucleotides were synthesized on an automated system. The resultant gene segment (226 base pairs), which incorporated convenient HindIII and BamHI overhangs at the 5' and 3' ends, respectively, was cloned into the pIN-III-ompA-2-expression vector in Escherichia coli, affording a fusion protein of Mr = 8900 with 7 additional amino acids at the amino terminus and 4 at the carboxyl terminus and with aspartic acid rather than asparagine in position 47. The recombinant PF4 (rPF4) was purified by heparin-agarose affinity chromatography and reverse-phase high performance liquid chromatography. It reacted with a monoclonal mouse anti-human PF4 antibody on a Western blot and in an enzyme-linked immunosorbent assay. The rPF4 protein exhibited an immunoregulatory effect like that of human PF4 in its ability to reverse concanavalin A-induced immunosuppression in BALB/c mice.


The surgical management of dislocated traumatic cataracts.
Seven adult patients (six men and one woman, ranging in age from 50 to 83 years) underwent intracapsular cataract surgery for dislocated traumatic cataracts. Six of the seven also had anterior vitrectomies. All seven patients had preoperative visual acuities of counting fingers or worse. There were no serious postoperative complications and five of the patients had postoperative visual acuities of 20/60 or better. Visual acuity improved less in the other two patients because of pre-existing but unrecognized macular disease.


Moral disengagement, self-control and callous-unemotional traits as predictors of cyberbullying: a moderated mediation model.
Cyberbullying has become more prevalent, more difficult to detect, and more harmful to the victims. Whereas considerable prior work has investigated predictors and consequences of cyberbullying, additional research is needed to better understand the mechanisms by which these factors relate to cyberbullying perpetration and victimization. The goal of the present study was to examine the extent to which the link between individual differences in moral disengagement and cyberbullying perpetration is mediated by low self-control and, if so, whether this mediation effect varies by individuals' degree of callous-unemotional traits. To explore these questions, we used cyberbullying, moral disengagement, self-control, and callous-unemotional traits scales and collected online survey data from a sample of 860 Chinese internet users aged 18 years old or older. As hypothesized, a significant positive relation between moral disengagement and cyberbullying emerged that was mediated by individual differences in self-control. Additionally, evidence of moderated mediation was found. That is, the indirect effect varied by degree of callous-unemotional traits, with a significantly stronger mediation effect (and association between self-control and cyberbullying) for individuals who were relatively higher in callous-unemotional traits. We conclude that moral disengagement partially predicts cyberbullying through self-control, while callous-unemotional traits moderate the pathway between self-control and cyberbullying.


A non-adhesive foam dressing for exuding venous leg ulcers and pressure ulcers: six case studies.
Six patients had their wounds dressed with 3M Foam Dressing, a highly absorbent polyurethane foam covered with a breathable layer, for up to four weeks. The dressing was assessed for its effect on the wound and patient comfort, with promising results.


Impact of urban air pollutants and noise levels over daily hospital admissions in children in Madrid: a time series analysis.
The aim of this paper was to analyse the effects of the urban air pollutants and noise levels on daily emergency hospital admissions of children less than 10 years of age in Madrid. Poisson Regression Models were used to quantify the associations. Meteorological variables, influenza epidemics, pollen concentrations and trends and periodicities were used as controlling variables. The main results obtained were the detected relationship (p<0.05) between emergency hospital admissions due to organic diseases and noise levels (AR=2.4%) and for PM(10) concentrations (AR=2.1%). For respiratory diseases statistically significant associations were detected for noise levels (AR=4.7%) and cold temperatures (AR=3.8%). The main association detected for causes of admissions due to bronchitis was for O(3) (AR=36.8%) and for pneumonia was for noise levels (AR=7.7%). The results obtained suggest that noise level particularly is a risk factor for daily emergency hospital admissions for organic and respiratory diseases in children less than 10 years old in Madrid.


Perceptions of pharmacists towards drug shortages in the healthcare system of Pakistan and its impact on patient care: findings from a cross-sectional survey.
This study aimed to explore pharmacists' perceptions on drug shortages and its impingement on the Pakistani healthcare system, in particular on patient care. Online questionnaire survey. Hospital pharmacists from five out of seven regions of Pakistan were approached; including the federal territory (Islamabad) and four provinces (Khyber Pakhtunkhwa, Balochistan, Punjab and Sindh). Prevalence and type of shortages were identified along with strategies to reduce its effect on patient care. A validated questionnaire was distributed through various online platforms to 800 registered hospital pharmacists. A convenience sampling technique was used to obtain information on drug shortages, the reporting system for shortages, the impact on patients and policy solutions for managing drug shortages. Out of 800 hospital pharmacists, 708 completed the questionnaire (response rate: 88.5%). Of these hospital pharmacists, 47% came from hospitals of Punjab, 26% from Khyber Pakhtunkhwa, 13% from Sindh, 11% from Balochistan and 4% from Islamabad; 72% and 28% worked in tertiary and secondary hospitals, respectively. The majority (32%) interacted with shortages daily. The top three drug categories reported in shortage were oncology drugs (54%), cardiovascular drugs (53%) and antimicrobials (42%). 58% of the respondents have seen care delayed as a negative consequence of shortages. 'Creating new communication system' (65%) and 'readjust budget plans' (41%) were the two most frequently indicated recommendations for shortages management at hospital, while 'circulars or alerts from the regulatory authority' (60%) and 'time to time directives from local health statuaries' (48%) were two most widely suggested policy solutions. Drug shortage is a serious concern in Pakistani hospitals, experienced on a daily basis endangering patients' health. Enhanced communication is required, connecting the key stakeholders. Health policies should be reviewed; adequate funds should be allocated to the health sector preventing future shortages.


[IMP-cyclohydrolase/transformylase from ehrlich-ascites carcinoma (author's transl)].
The IMP-cyclohydrolase/transformylase enzyme was purified from Ehrlich ascites tumor cells by ammonium sulfate fractionation and chromatography on Sephadex G-75 and DEAE-Sephadex. The electrophoretically pure enzyme has a molecular weight of about 350000, estimated by a gel filtration, and an isoelectric point of 6.2. It is composed of 8 subunits with a molecular weight of 46000. Every subunit is composed of two different proteins with a molecular weight of 18000 and 28500. Some further characteristics of the enzyme are reported.


The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells along with metastasis in vivo, and to explore the underlying mechanism. RT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual-luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-5p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays. miR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interact with STK32A to promote its expression. Following the validation of the supporting role of STK32A in NSCLC cells and NF-κB p65 phosphorylation, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo. miR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A/NF-κB p65 axis, offering possible targets for the treatment for NSCLC.


Strial dysfunction in mice with cochleo-saccular abnormalities.
Most viable dominant spotting (Wv/Wv) mutant mice, which show cochleo-saccular degeneration, were found to have an endocochlear potential (EP) around zero together with a structurally abnormal stria vascularis. Inner hair cells were well preserved, but outer hair cells in the basal half of the cochlea were degenerating, possibly as a result of primary strial dysfunction. Thresholds for the detection of a compound action potential were raised to around 100 dB SPL in the mutants with no EP, and there was little if any cochlear microphonic at the round window. Of the 20 Wv/Wv mice studied, five partially escaped the effects of the mutation and had measurable positive potentials (15-86 mV) in scala media in the basal turn; responses in these animals were intermediate between control responses and those of mutants with no EP. These findings confirm that the pathological processes in this mutant, with cochleo-saccular abnormalities, are fundamentally different from the pathological processes in animals with neuroepithelial abnormalities reported previously [see Steel and Bock (1983) Arch. Otolaryngol. 109, 22-29, for references].


Work ability in prostate cancer survivors after radical prostatectomy.
The aim of this study was to evaluate work ability (WA) after radical prostatectomy (RP) in prostate cancer survivors, in relation to post-RP urinary leakage (UL) and adjuvant or salvage pelvic radiation therapy (RT) and/or hormone therapy (HT). Patients for this cross-sectional study were selected from two surveys on post-RP adverse effects and WA. All participated in the workforce. Using EPIC-50/26, UL was defined as daily use of at least one pad. Data on RT were obtained from the Cancer Registry of Norway. WA, measured by the Work Ability Score (WAS), was categorized into "excellent", "good" or "moderate/poor". Multinomial logistic regression analyses assessed associations between WA and selected variables. p values below 0.05 were considered statistically significant. Of 563 patients, 18% had received post-RP RT and/or HT. Compared to the "excellent" WAS category, such treatment was significantly associated with belonging to the "good" or "moderate/poor" category. Patients with UL (30%) were more than twice as likely to report a "moderate/poor" WAS than those without UL. Age above 65 years, less than 3 years since RP and co-morbidity were additional factors associated with increased risk of reporting a lower WAS. Half of the patients rated their current WA as "very good" with respect to the physical or mental demands of their work. Increasing age, UL, co-morbidity and time since RP are associated with decreasing post-RP WA. Without specifying the individual therapy, post-RP oncological treatment seems to have an additional negative effect, warranting consideration of patients' work plans when considering post-RP oncological treatment.


A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants.
Caenorhabditis elegans UNC-18 protein, homologous to yeast Sec1p, is important in neurotransmitter release, because the unc-18 mutation leads to severe paralysis and presynaptic acetylcholine (ACh) accumulation. To examine the functional conservation in mammals, we tried to isolate unc-18 isoforms from mouse and human brain cDNA libraries and obtained two classes of isoforms-neural genes and ubiquitous genes. Neural genes were identical to Munc-18 (also known as n-Sec1 or rbSec1), identified in rat and bovine brains as a syntaxin-binding protein. According to "Munc-18" terminology, we call the neural genes Munc-18-1 and the ubiquitous genes Munc-18-3. These mammalian isoforms exhibit 58% (Munc-18-1) and 42-43% (Munc-18-3) amino acid sequence identity with UNC-18. Next, we constructed transgenic unc-18 mutants to test biological activity of mouse Munc-18-1 and Munc-18-3 under the control of C. elegans unc-18 promoter. Munc-18-1 compensates for severe locomotion disability and cholinergic defects, e.g., abnormal sensitivities to cholinesterase inhibitors and cholinergic receptor agonists in unc-18 mutants, but Munc-18-3 fails. These data suggest that Munc-18-1 and C. elegans unc-18 may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals.


Fat Grafting for Facial Rejuvenation: My Preferred Approach.
The author provides his preferred approach to fat grafting for facial rejuvenation. The preferred donor sites include low abdomen and inner thigh. Fat grafts should be harvested with low negative pressure to ensure the integrity and viability of adipocytes. Fat grafts can be processed with proper centrifugation that can reliably produce purified fat with concentrated growth factors and adipose-derived stem cells, all of which are beneficial to improve graft survival. The approach described in this article is supported by the most scientific studies and thus may provide a more predictable long-lasting result if performed properly.


Side-to-side weight-bearing asymmetry in subjects with low back pain.
The purpose of this project was to determine if subjects with low back pain (LBP) exhibit greater side-to-side weight-bearing (WB) asymmetry compared to healthy control subjects without LBP. This study utilized an observational double cohort design and consisted of 35 subjects with LBP and 31 healthy control subjects. Side-to-side WB asymmetry was calculated as the average of the absolute value of the difference between the right and left lower extremity from three trials. The percentage of the average side-to-side WB asymmetry relative to the total body weight was calculated to normalize expected differences in magnitude of asymmetry based on a subject's total body weight. An 11-point numeric pain rating scale was used to represent the subject's current level of pain. Patients with LBP demonstrated significantly greater normalized side-to-side WB asymmetry than healthy control subjects (8.8% vs. 3.6%, respectively, P<0.001). In patients with LBP, higher magnitudes of side-to-side WB asymmetry were significantly associated with increased pain (r=0.39, P=0.021). In conclusion patients with LBP exhibited increased side-to-side WB asymmetry compared to healthy control subjects without LBP. This asymmetry was associated with increased levels of pain. This finding is relevant for planning future studies that will attempt to provide evidence for the construct validity of manipulation by determining if side-to-side WB asymmetry normalizes after a manipulation intervention and if this improvement is associated with improvements in pain and function.


Catastrophic failure of a low profile metal-backed glenoid component after total shoulder arthroplasty.
The longevity of the glenoid component in total shoulder arthroplasty (TSA) continues to be problematic. All polyethylene glenoid components have been most widely used, but loosening rates with time and the need for revision has resulted in high-profile metal-backed components with the potential for a more stable prosthesis bone interface and liner exchange. High revision rates in the high profile metal backed designs led us to evaluate a low profile metal backed component. To examine the rate and mode of failure of a TSA in a single surgeon consecutive series that has been identified by the Australian National Joint Replacement Registry to have a higher than anticipated rate of revision. This is a single surgeon retrospective consecutive series of 51 arthroplasties undertaken in 50 patients (18 males and 32 females) with an average age of 70.4 ears (range 51-90) and mean follow-up of 5.5 years (range 3.7-8.1). We observed a very high (29%) rate of revision of the metal-backed glenoid components in this series. The primary mode of failure was glenoid baseplate nonintegration which with a well-fixed central cage screw led to bone resorption and implant breakage or disassembly. Analysis of the mode of failure of implants identified by robust registries is essential for the development of new prostheses and the pursuit of prosthesis longevity. This low profile metal backed prosthesis has been withdrawn, but without a published mechanism of failure. We feel that any prosthesis withdrawal should be accompanied by appropriate published mechanisms to prevent future component design errors based on similar design problems.


Lipid profiles are associated with lesion formation over 24 months in interferon-β treated patients following the first demyelinating event.
To investigate the associations of serum lipid profile with disease progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were obtained in pretreatment serum from 135 high risk patients with CIS (≥ 2 brain MRI lesions and ≥ 2 oligoclonal bands) enrolled in the Observational Study of Early Interferon β-1a Treatment in High Risk Subjects after CIS study (SET study), which prospectively evaluated the effect of intramuscular interferon β-1a treatment following the first demyelinating event. Thyroid stimulating hormone, free thyroxine, 25-hydroxy vitamin D3, active smoking status and body mass index were also obtained. Clinical and MRI assessments were obtained within 4 months of the initial demyelinating event and at 6, 12 and 24 months. The time to first relapse and number of relapses were not associated with any of the lipid profile variables. Higher LDL-C (p=0.006) and TC (p=0.001) levels were associated with increased cumulative number of new T2 lesions over 2 years. Higher free thyroxine levels were associated with lower cumulative number of contrast-enhancing lesions (p=0.008). Higher TC was associated as a trend with lower baseline whole brain volume (p=0.020). Higher high density lipoprotein was associated with higher deseasonalised 1,25-dihydroxy vitamin D3 (p=0.003) levels and a trend was found for deseasonalised 25-hydroxy vitamin D3 (p=0.014). In early multiple sclerosis, lipid profile variables particularly LDL-C and TC levels are associated with inflammatory MRI activity measures.


Deparaffinization of formalin-fixed paraffin-embedded tissue blocks using hot water instead of xylene.
This study aimed to deparaffinize formalin-fixed paraffin-embedded (FFPE) tissues using hot water instead of xylene and measuring the quantity and quality of the extracted DNA from the respective tissues. To deparaffinize the tissue sections with hot water, small sections were exposed to 90 °C distilled sterile water. After 25 FFPE tissue samples were deparaffinized with the hot water method, DNA was then extracted. The mean of optical density and the ratio of absorbance of the DNA solution were 220.01 ± 36.1 ng/μl and 1.65 ± 0.1, respectively. Polymerase chain reaction (PCR) analysis of the toll-like receptor 4(TLR4) gene showed that the method can be used as a tool for different applications.


Purification of Endo Polygalacturonases from Sclerotinia sclerotiorum: Multiplicity of the Complex Enzyme System
Fourteen forms of endopolygalacturonases were purified from the culture medium of Sclerotinia sclerotiorum with ion exchange chromatographies. Individual forms differ in their isoelectric point but exhibit similar molecular masses. On the basis of the cross-reactions to antibodies raised against a purified acidic endopolygalacturonase, these forms could be divided into two related groups. Polygalacturonase activities constitute a complex enzyme system in which the extensive multiplicity is due to the expression of a large gene family.


Next-generation sequencing reveals unique combination of mutations in cis of CSF3R in atypical chronic myeloid leukemia.
Atypical chronic myeloid leukemia (aCML) is a hematologic disorder characterized by leukocytosis with increased dysplastic neutrophils and their precursors. In CSF3R gene, the activation mutation including T618I is frequently reported in aCML but is rarely accompanied by truncation mutations. Herein, we report a unique aCML patient with two CSF3R mutations (T618I and Y779*) in the same DNA strand. High-coverage next-generation sequencing for 40 genes related with myeloid leukemia was performed. Sanger sequencing was performed to confirm CSF3R mutations. To confirm whether two CSF3R mutations are in cis or not, TA cloning was used. Clinical information and bone marrow pathology were reviewed by two hematopathologists. In the patient diagnosed with aCML in bone marrow study, two CSF3R mutations, (T618I and Y779*) a SETBP1 mutation (G870S) and an U2AF1 mutation (Q157P), were identified by high-coverage next-generation sequencing. The two CSF3R mutations were confirmed to be located in the same DNA strand by TA cloning, indicating that the two mutations are harbored in one malignant clone. The SETBP1 mutation is known to be related with poor prognosis in aCML. Likewise, the patient was refractory to hydroxyurea and showed disease progression. Additionally, we discussed the potential therapeutic targets by reviewing the molecular profile of the patient. We believe that the accurate diagnosis and maximum therapeutic chance could be achieved by profiling the mutations and their characteristics.


Nifedipine attenuates the intraocular pressure response to intubation following succinylcholine.
Forty patients without eye disease, undergoing elective nonophthalmic surgery, were studied to evaluate the efficacy of sublingual nifedipine in attenuating the intraocular pressure response to succinylcholine administration, laryngoscopy and intubation. The patients were randomly given either nifedipine 10 mg or placebo sublingually 20 minutes before induction of anaesthesia. Intraocular pressure (IOP) and systolic blood pressure (SBP) were recorded before and after induction of anaesthesia. The IOP response to succinylcholine administration, laryngoscopy and intubation was significantly less in patients receiving nifedipine (P less than 0.01). The mean maximum rise in IOP above basal level at one minute post-intubation was 7.82 mmHg in the control group compared with 0.15 mmHg in the nifedipine pre-treated group. These results suggest that sublingual nifedipine is effective in attenuating the IOP response after succinylcholine administration, laryngoscopy and intubation.


Mitogen-activated protein kinases: versatile transducers for cell signaling.
Mitogen-activated protein (MAP) kinases are proline-directed serine/threonine protein kinases that are activated via phosphorylation of their own tyrosine residues. Highly conserved during eukaryotic evolution, they serve as common signaling components in distinct transduction pathways initiated by many stimuli. They have been implicated in the control of a broad spectrum of cellular events but are particularly known for their possible roles in cell cycle progression and the control of meiosis.


Vascularized fibular graft for bone defects after wide resection of musculoskeletal tumors.
In reconstruction by vascularized fibular graft (VFG) after wide resection of musculoskeletal tumors, there are problems such as the method of fixing the fibular graft, the period of achieving bone union, and the avoidance of postoperative fractures. We have performed VFG on 19 cases over a 30-year period. We have investigated these problems and now report the results. From 1980 to 2009, we performed VFG on 19 cases to reconstruct the bone defect after resection of a musculoskeletal tumor. The mean age was 19.5 years. Reconstructed bone defects were located in the femur in 10 cases (1 of inlay graft, 1 of individual intercalary graft, 7 of intercalary graft into treated bone, 1 of curettaged bone marrow), the tibia in 3 cases (1 of individual intercalary graft, 2 of intercalary graft into treated bone), the humerus in 3 cases (2 of sling procedure, 1 of individual intercalary graft), the foot in 2 cases individual intercalary graft, and the sacroiliac joint in 1 case of individual intercalary graft. The mean follow-up period after surgery was 7.25 years. We evaluated the success of primary bone union, the period required to achieve bone union, complications, clinical outcome, and the Musculoskeletal Tumor Society (MSTS) score. Successful bone union was achieved for 79% of cases (15/19 patients). The average period required to achieve bone union was 7.8 months. There were 4 cases of non-union and 2 other complications. Clinical outcome status was continuous disease-free in 12 cases and died of disease in 7. The mean MSTS score was 98% (93-100%). Vascularized fibular graft is a useful reconstructive procedure for long-bone defects after wide excision of musculoskeletal tumors. The method of fixation can be selected according to the situation; although times required for bone union are long, it is possible to prevent postoperative fractures by a combined approach with treated bone and/or double barrel fibular grafts.


Comparison of two methods of cervical cerclage by ultrasound cervical measurement.
To compare the effects of cerclage performed with a modified Shirodkar procedure or with McDonald's technique using transvaginal ultrasound measurement of the distance between the external os and the suture. We performed a retrospective study of all patients who underwent a prophylactic cerclage with either the modified Shirodkar procedure or the McDonald's technique over a 3-year period. Physicians chose the cerclage technique according to their own preferences. Transvaginal ultrasound examination of the cervix was performed 2 weeks after the cerclage to measure its functional length and the distance between the external os and the cerclage. During the study period, 14 patients had a cerclage with the modified Shirodkar procedure and 19 patients with the McDonald's technique. Twelve of these 33 patients (36.4%) delivered before 37 weeks. The obstetric characteristics of the patients in both groups were similar. There were no significant differences between the Shirodkar and McDonald groups as to the functional cervical length before (31.3 +/- 8.7 vs. 35.6 +/- 9.7 mm, respectively) or after (37.0 +/- 7.3 vs. 36.1 +/- 7.9 mm) cerclage, the distance between the external os and cerclage (16.7 +/- 3.8 vs. 14.0 +/- 5.2 mm), or the number of deliveries before 32 (0 vs. 2) and 34 (1 vs. 3) weeks. The anterior colpotomy of the Shirodkar procedure increased the distance between the external os and the cerclage by a mean of 2.7 mm. This slight gain does not justify exposing the patient to the risks related to this procedure. When cerclage is necessary, McDonald's technique seems preferable.


Carbon nanoparticles from corn stalk soot and its novel application as stationary phase of hydrophilic interaction chromatography and per aqueous liquid chromatography.
Carbon nanoparticles (CNPs) (6-18 nm in size) were prepared by refluxing corn stalk soot in nitric acid. The obtained acid-oxidized CNPs are soluble in water due to the existence of carboxylic and hydroxyl groups. (13)C NMR measurement shows the CNPs are mainly of sp(2) and sp(3) carbon structure different from CNPs obtained from candle soot and natural gas soot. Furthermore, these CNPs exhibit unique photoluminescence properties. Interestingly, the CNPs might be exploited to immobilize on the surface of porous silica particles as chromatographic stationary phase. The resultant packing material was evaluated by high-performance liquid chromatography, indicating that the new stationary phase could be used in hydrophilic interaction liquid chromatography (HILIC) and per aqueous liquid chromatography (PALC) modes. The separation of five nucleosides, four sulfa compounds and safflower injection was achieved by using the new column in the HILIC and PALC modes, respectively.


Litter size, litter weight, and lamb survivability of Doyogena sheep managed under community-based breeding program in Ethiopia.
Increasing litter size and weight during the marketing time by decreasing mortality among lambs per ewe is the objective of the community-based breeding program (CBBP). This study aims to find out litter size, litter weight per ewe, and preweaning lamb mortality of Doyogena sheep managed under CBBP. The study analyzed the data records of 4530 animals for 8 years from 2013 to 2020. A logistic regression procedure was used to analyze pre-weaning lamb survival rates. Results showed that the overall least-squares means of litter size at birth (LSB), litter size at weaning (LSW), total litter weight at birth (TLWB), and total litter weight at weaning (TLWW) were 1.57 ± 0.02 lambs, 1.50 ± 0.02 lambs, 5.24 ± 0.09 kg, and 24.14 ± 0.69 kg respectively. The incidence of pre-weaning lamb mortality was 4.72%. Year and breeder cooperative vary were observed for pre-weaning lamb losses. Females had lower odds of survival as compared to males. Odds of survival were low for triplets, quadruplets, and low birth weight (≤2 kg) born lambs. The ongoing selection program which aims to improve reproductive and growth performance had a positive influence on the survival rate of lambs. Improvement of the environment in the flock, special care for multiple-born and care for small lambs would lead to further lamb survival improvements.


Deep learning enables ultraviolet photoacoustic microscopy based histological imaging with near real-time virtual staining.
Histological images can reveal rich cellular information of tissue sections, which are widely used by pathologists in disease diagnosis. However, the gold standard for histopathological examination is based on thin sections on slides, which involves inevitable time-consuming and labor-intensive tissue processing steps, hindering the possibility of intraoperative pathological assessment of the precious patient specimens. Here, by incorporating ultraviolet photoacoustic microscopy (UV-PAM) with deep learning, we show a rapid and label-free histological imaging method that can generate virtually stained histological images (termed Deep-PAM) for both thin sections and thick fresh tissue specimens. With the tissue non-destructive nature of UV-PAM, the imaged intact specimens can be reused for other ancillary tests. We demonstrated Deep-PAM on various tissue preparation protocols, including formalin-fixation and paraffin-embedding sections (7-µm thick) and frozen sections (7-µm thick) in traditional histology, and rapid assessment of intact fresh tissue (~ 2-mm thick, within 15 min for a tissue with a surface area of 5 mm × 5 mm). Deep-PAM potentially serves as a comprehensive histological imaging method that can be simultaneously applied in preoperative, intraoperative, and postoperative disease diagnosis.


Naphthalimide intercalators with chiral amino side chains: effects of chirality on DNA binding, photodamage and antitumor cytotoxicity.
Several novel heterocyclic-fused naphthalimides intercalators with chiral amino side chains were investigated. Their side chains' chiral configuration determines DNA binding activities in the order: S-enantiomers > R-enantiomers. And their DNA photodamaging activities were in good agreement with their DNA binding constants, the S-enantiomers could photocleave circular supercoiled pBR322 DNA more efficiently than their R-enantiomers. S-enantiomer B(3) could photodamage DNA at 0.2 microM and cleave supercoiled plasmid DNA from form I to form II completely at 50 microM. Almost all of these intercalators showed effective cytoxicities against human lung cancer cells and murine leukemia cells. S-enantiomers showed different antitumor cytotoxicity by comparison with R-enantiomers. This work may provide additional information for the role of amino side chains on intercalators as antitumor agents.


Hyperlipoproteinemia induced by a transplantable pituitary tumor in the rat.
The MtT-F4 tumor, a transplantable pituitary tumor of rats, induces significant hyperlipidemia in male Fisher 344 rats. The increasive hypercholesterolemia was accompanied by hypertriglyceridemia only in the first month of tumor implantation. Clofibrate feeding inhibited the development of hypercholesterolemia and maintained normal serum triglyceride levels. In contrast to the changes in lipoprotein cholesterol distribution and profile found in experimental hyperlipidemia induced by high fat and cholesterol feeding, the hypercholesterolemic tumor-bearing rats showed no accumulation of cholesterol in the very low density and intermediate density lipoproteins, and no appearance of a new class of lipoprotein, B-VLDL. An HDLc-like lipoprotein appeared as hypercholesterolemia developed. Increased amounts of cholesterol were deposited in the aorta. The effects are attributed to the lipolytic hormones secreted by the tumor and antagonism to their action by clofibrate.


Survival with breast cancer: the importance of estrogen receptor quantity.
The survival of 1184 British Columbian women whose primary breast cancers were diagnosed and assayed for estrogen receptor (ER) between 1975 and 1981 was studied. Median follow-up was 60 months. ER concentrations yielded greater prognostic information than simple positive and negative categories. When ER data were divided into four strata: less than or equal to 1, 2-9, 10-159 and greater than or equal to 160 fmol/mg cytosol protein, the association of higher ER with prolonged survival was highly significant (P less than 0.0001) and independent of TNM stage, nodal status and menopausal status. ER less than or equal to 1 and ER = 2-9 groups were distinct with respect to overall disease-specific survival. Patient age did not predict survival when controlled for ER. Prolonged recurrence-free survival was associated with higher ER (P = 0.0001) for at least 5 years after diagnosis. This significant trend persisted after adjustments for nodal status, TNM stage, menopausal status and the type of systemic adjuvant therapy.


Celastrol enhances AAV1-mediated gene expression in mice adipose tissues.
The transduction of adeno-associated virus (AAV) in adipose tissues was not well characterized and appeared to be insufficient as compared with other targeted tissues in gene therapy. We have found that celastrol, a chemical from a traditional Chinese herb known to inhibit the proteasome activity, was able to enhance the transgene expression mediated by AAV1 in 3T3-L1 preadipocytes both before and after induced differentiation. A synergism of celastrol and nonionic surfactant pluronic F68 cotreatment on AAV1 transduction was observed in the experiments with rat primary preadipocyte cultures and in adipose tissues in vivo. By fluorescent microscopy using Alexa Fluor 647-labeled AAV and quantitative PCR assays, we found that celastrol treatments increased the nuclear distribution of AAV genomic DNAs, but not the total amount of viral cellular uptake in preadipocytes, which was different from the effect of pluronic F68 treatment to significantly promote the AAV internalization. Our data suggested that bioactive monomeric compounds extracted from herbal medicines might be used to facilitate AAV-mediated gene transfer applications.


Hypothalamo-pituitary-adrenal axis in acute myocardial infarction treated by percutaneous transluminal coronary angioplasty: effect of time of presentation.
Acute myocardial infarction (AMI) is associated with a stimulation of cortisol which lasts 24 hours in patients treated by thrombolysis. Percutaneous transluminal coronary angioplasty (PTCA) is an alternative treatment for AMI which reduces the length of myocardial ischemia. Our objective was the determination of the amplitude and duration of cortisol and other hormones of the hypothalamo-pituitary-adrenal (HPA) axis release in patients undergoing PTCA. These responses were also analyzed in relation with the time of onset of AMI. The effect of coronarography with or without angioplasty in patients without AMI was also studied. Plasma ACTH, cortisol, corticotropin-releasing hormone and arginine vasopressin levels were determined during the first 48 hours in 20 patients with first AMI, treated by PTCA and in 10 patients without AMI undergoing coronarography (and angioplasty in five of them). A strong stimulation of the HPA axis was observed in AMI patients, but the duration of cortisol secretion was significantly reduced (less than 8 hours) as compared with previous studies in patients treated with thrombolysis. A clear-cut ACTH-cortisol dissociation was also observed after the third hour. ACTH and cortisol stimulation was higher in patients admitted between 04:00 h and 16:00 h than in patients admitted between 16:00 h and 04:00 h In patients without AMI, coronarography induced a moderate, but significant short-lasting ACTH and cortisol stimulation. In conclusion, our data suggest that the degree of stimulation of the HPA axis may depend upon the type of treatment and the circadian rhythm of this axis.


Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia.
Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg(-1) subcutaneously, or vehicle (control) at 24-36 h of life. At 5-7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia.


Team-based efforts to improve quality of care, the fundamental role of ethics, and the responsibility of health managers: monitoring and management strategies to enhance teamwork.
Highlight the importance of teamwork in health care institutions by performing a review and discussion of the relevant literature. Review paper. A MEDLINE/Pubmed search was performed starting from 1990, and the terms 'team, teamwork, managers, healthcare, and cooperation' were searched in titles, abstracts, keywords, and conclusions; other terms 'patient safety, ethics, audits and quality of care' were specifically searched in abstracts and were used as additional filters criteria to select relevant articles. Thirty-three papers were found relevant; factors affecting the quality of care in health care institutions are multiple and varied, including issues related to individual profile, to administrative structure and to team-based effort. Issues affecting teamwork include mainly self-awareness, work environment, leadership, ethics, cooperation, communication, and competition. Moreover, quality improvement plans aiming to enhance and expand teams are essential in this context. Team monitoring and management are vital to achieve efficient teamwork with all the required qualities for a safer health system. In all cases, health managers' responsibility plays a fundamental role in creating and sustaining a teamwork atmosphere. Teamwork is known to improve outcomes in medicine, whether at the clinical, organizational, or scientific level. Teamwork in health care institutions must increasingly be encouraged, given that individual effort is often insufficient for optimal clinical outcome.