Exercise physiology. An overview.
Through the study of equine exercise physiology, one can learn more about what happens to the body of the performance horse during all forms of exercise. Better understanding of skeletal, joint, tendon, and ligament adaptations to loading and stress may allow adjustments to be made in training techniques to reduce the incidence of injury. The information obtained from exercise research may also facilitate the investigation of questions such as the following: What makes one horse perform better than another? How can one bring out the optimal performance in each horse? How can one tell when a horse has arrived at its peak performance capability? What are the factors that actually limit performance?


Prostaglandin and histamine release from stimulated rat peritoneal mast cells.
The production of five prostanoids (PGD2, PGE2, PGF2 alpha, 6-oxo-PGF1 alpha, and TxB2) was examined after mast cell activation. Prostaglandin D2 (PGD2) was the major prostanoid produced after stimulation of rat peritoneal mast cells with the calcium ionophore A 23187, compound 48/80 or anti-rat IgE. The amount of PGD2 generated was not dependent on the quantity of histamine released. The time course of PGD2 production paralleled the release of histamine following activation with A 23187 or anti-rat IgE but with compound 48/80 release of histamine reached a maximum within 15 sec, whereas production of PGD2 was apparent only after 5 min and was still increasing at 30 min.


Functional relevance of ceruloplasmin mutations in Parkinson's disease.
Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo-ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)-linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo-ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.


Multimodal therapy for the treatment of severe ischemic stroke combining GPIIb/IIIa antagonists and angioplasty after failure of thrombolysis.
Intraarterial and intravenous thrombolysis are often ineffective for the treatment of acute ischemic stroke and are associated with a significant risk of intracranial hemorrhage (ICH). Multimodal rescue therapy combining mechanical disruption and platelet GPIIb/IIIa receptor antagonists may improve recanalization. Patients who did not recanalize with thrombolysis were treated with GPIIb/IIIa antagonists, angioplasty, or an embolectomy device. Treatment was individualized based on vascular anatomy, stroke mechanism, patient status, and symptom duration. Twelve patients were treated within 3.8+/-2.2 hours. The mean National Institutes of Health Stroke Scale (NIHSS) score was 19.4+/-4.1. Six patients had carotid terminus occlusion, whereas 5 had middle cerebral artery and 1 had basilar artery occlusion. The average doses of intraarterial tPA and reteplase were 17.1+/-8.6 mg and 2+/-0.6 units, respectively. All patients received either an intravenous or intraarterial abciximab bolus (mean 11.8+/-5.8 mg) and heparin (mean 3278+/-1716U). Eleven were treated with angioplasty and 4 had mechanical embolectomy or stenting. Complete (8) or partial (3) recanalization was achieved in 11 cases. There was only one (8.3%) symptomatic hemorrhage. Patients had a favorable outcome at discharge (mean NIHSS 8.9+/-8.7) and 6 (50%) had an NIHSS < or =4 at discharge. Multimodal rescue therapy was effective at recanalizing occluded cerebral vessels that failed thrombolysis without an excess risk of ICH.


Lymphocyte proliferation response in patients with delayed hypersensitivity reactions to heparins.
Heparins can induce delayed-type hypersensitivity (DTH) reactions mediated by specific T lymphocytes. However, the interaction between heparins and lymphocytes has not been sufficiently studied. To analyse the lymphocyte response to heparins using different types of antigen-presenting cells in patients with DTH reactions to these drugs. We studied seven patients with DTH reactions to heparins diagnosed by delayed reading of intradermal skin testing (n = 5) or drug provocation test (n = 2) and nine tolerant controls. Biopsies were obtained from intradermal testing or during the acute reaction. Peripheral blood mononuclear cells were used to obtain T and B lymphocytes, monocytes and monocyte-derived dendritic cells (DC). T-lymphocyte proliferation was assayed by means of (3)H-thymidine incorporation. Skin testing showed a high degree of cross-reactivity within low molecular weight heparins with good tolerance to sodium heparin, fondaparinux and lepirudin in most cases. The proliferative response was positive in six patients to most of the heparins tested with both monocytes and B cells (the classical lymphocyte transformation test) or immature DC as antigen-presenting cells, giving a higher response with DC. At a second evaluation 1 year later, the proliferative response was found only with DC, and mainly to the culprit drug. A model using DC in the lymphocyte proliferation test is a more appropriate way to assess the immunological response in DTH to heparins; additionally, it can detect a response over a longer time. These findings may be useful for the diagnostic evaluation of drug reactions.


Regulation of N-myristoyltransferase by novel inhibitor proteins.
N-myristoylation ensures the proper function and intracellular trafficking of proteins. Many proteins involved in a wide variety of signaling, including cellular transformation and oncogenesis, are myristoylated. The myristoylation of proteins is catalyzed by the ubiquitously distributed eukaryotic enzyme N-myristoyltransferase (NMT). Previously, we reported that NMT activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that the increase in NMT activity appears at an early stage in colonic carcinogenesis. Furthermore, we observed that NMT expression is elevated in colorectal and gallbladder carcinoma. In our laboratory, an endogenous NMT inhibitor protein (NIP71) was discovered from bovine brain that inhibited NMT activity in rat colonic tumors. Very recently we have demonstrated that the protein NIP71, which is a potential inhibitor of NMT, is homologous to heat-shock cognate protein (HSC70). In addition, we have discovered that enolase is a potent inhibitor of NMT. Further work may elucidate the role of HSC70 and/or enolase in the regulation of NMT, which may lead to the development of a gene-based therapy of colorectal cancer. The interaction of oncoproteomic and oncogenomic data sets through powerful bioinformatics will yield a comprehensive database of protein properties, which will serve as an invaluable tool for cancer researchers to understand the progress of tumorigenesis.


Expression of the mouse lactate dehydrogenase-A promoter fused with the bacterial gpt gene in Chinese hamster ovary cells.
The promoter region of the cloned mouse lactate dehydrogenase-A gene was fused with the gpt gene of Escherichia coli, and this fusion gene was shown to express in Chinese hamster ovary cells. This result demonstrates that the cloned LDH-A promoter is indeed functional.


Endovascular vs Medical Management for Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis of CLEAR and RESCUE-Japan.
Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO. We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days). Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR. In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management. This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.


[Method for preoperative localization of non-palpable microcalcifications within the mammary gland (spherical marking) (author's transl)].
A method for preoperative localization of non-palpable suspected microcalcifications within the mammary gland is described. This procedure is superior to the conventional methods with methylenblue.


The Eighth Human Leucocyte Differentiation Antigen (HLDA8) Workshop: natural killer cell section report.
Monoclonal antibodies submitted to the natural killer (NK) cell section of the Eighth International Workshop on Human Leucocyte Differentiation Antigens (HLDA8) comprised those to known clusters of differentiation (CD), those to well-characterised molecules without a CD nomenclature, and those to unknown molecules. From the HLDA8 workshop, the seven well-characterised molecules in the NK cell panel were assigned a CD classification. These were NKG2D (CD314), LAIR-1 (CD305), NKp46 (CD335), NKp44 (CD336), NKp30 (CD337), CRACC (CD319), and NKG2C (CD159c).


Extraocular muscle insertion positions and outcomes of strabismus surgery: correlation analysis and anatomical comparison of Western and Chinese populations.
To compare the insertion locations of extraocular muscles between Taiwanese (Han Chinese) and Western populations and to determine whether anatomical differences warrant different surgical guidelines. Insertion locations were compared between a Taiwanese population of subjects who had received surgical treatment for strabismus and a control group who had not. Insertion locations and surgical outcomes in the strabismus group were also compared with those reported in other countries. In Taiwanese subjects, extraocular muscle insertion locations were not significantly different between strabismus subjects and controls. However, the distances from the insertion location to the limbus of the inferior rectus, lateral rectus and superior rectus were significantly shorter in the Taiwanese subjects than in Western populations. Extraocular muscle insertion locations for the Taiwanese population in this study significantly differed from those reported in studies of Western populations. Therefore, surgical guidelines for performing lateral rectus recession to treat exotropia in Western populations may be inappropriate for Taiwanese and other Asian populations.


Very Low Vitamin D Levels are a Strong Independent Predictor of Mortality in Hospitalized Patients with Severe COVID-19.
There is controversy regarding the association between hypovitaminosis D and COVID-19 outcomes. We assessed the association between 25-hydroxyvitamin D levels and COVID-19 outcomes in hospitalized subjects with severe SARS-CoV-2 infection. Retrospective cohort study. Serum 25-hydroxyvitamin D levels of subjects with severe COVID-19 pneumonia were measured at hospital admission, between March 17th, 2020, and March 1st, 2021. Out of 2,908 patients, 571 (19.6%) had vitamin D deficiency (defined as a serum 25-hydroxyvitamin D level <12.5 ng/mL [<31.25 nmol/L]), and 1069 (36.7%) had levels between 12.5 ng/mL (31.25 nmol/L) and 20 ng/mL 850 nmol/L). Compared to subjects without vitamin D deficiency, those with 25-hydroxyvitamin D level <12.5 ng/mL had higher rates of in-hospital mortality at 30 d (28.0 vs. 17.3%; p <0.001), global mortality (31.9 vs. 20.8%; p <0.001), mechanical ventilation requirement (23.8 vs. 17.2%; p <0.001), and significantly longer hospital stay (median [interquartile range] of 9 [6-17 d] vs. 7 [5-12 d], p <0.001). In the unadjusted analysis, the risk of in-hospital death was greater for patients with vitamin D deficiency (HR 1.43; 95% CI, 1.20-1.70; p <0.001). After adjusting for confounders, the risk of in-hospital death within 30 d remained significantly greater in patients with vitamin D deficiency (HR 1.46; 95% CI, 1.21-1.76; p <0.001). The risk was reduced but remained significant with 25-hydroxyvitamin D levels between 12.5 ng/mL and 20 ng/mL (HR 1.31; 95% CI 1.10-1.55, p = 0.02). In comparison with other clinical biomarkers, vitamin D deficiency was an independent predictive marker of in-hospital mortality after adjusting for confounders. Very low 25-hydroxyvitamin D levels measured at hospital admission were significantly associated with in-hospital mortality and are a useful prognostic biomarker in severe COVID-19 patients.


Unsettling Place(s) at the end of life.
Critical considerations of space and place at the end of life have been limited in the social science literature. To address this gap, we draw on empirical data from two interrelated but separate qualitative Australian data sets to critically examine dying in relation to considerations of space, place and affect. These studies share the primary aim to better understand and articulate end-of-life experiences, with one using video reflexive ethnography and the other semi-structured interviews with patients. Challenging the broader valorisation of particular places of dying and death (e.g. home, hospice, hospital), we critically explore the meanings and affects of space and place and how they are rooted in normative expectations. Drawing on participant accounts we interrogate simplistic concepts of home versus hospice, or hospital versus community, developing a critical social science of the intersections of space and place at the end of life.


Parotid Duct Repair by Facial Vein Graft versus Gore-Tex, A Sialographic Evaluation.
The most common method for parotid duct anastomosis is suturing. A ductal defect of greater than 1cm may prevent a direct anastomosis. The goal of this study was a sialographic evaluation to compare repairing a parotid duct with facial vein graft versus Gore-Tex tub in 19 dogs. Nineteen dogs were studied in this experimental trial. Extra oral transverse incisions were made in buccal regions bilaterally to expose parotid ducts and a defect (2 cm) was performed in similar areas (right and left). The right resected duct was repaired with facial vein graft and the left anastomosis was performed by using the Gore-Tex tube microscopically. Sialography was used to evaluate the ductal leakage. Statistical analysis was performed, using SPSS software and McNemar's test. Based on the sialography evaluation; the ductal leakage was seen in five cases (26.31%) on the right side and in seven cases (36.84%) in the left side. Statistical analysis using McNemar's test suggested no statistically significant difference between ductal leakages in right and left parotid ducts (p> 0.05). The results of this study suggest that the efficacies of Gore-Tex tube and vein graft in parotid duct anastomosis are similar, but the use of Gore-Tex tube had a number of advantages, including reduced morbidity of the graft and short operation time.


Identification and subcellular localization of a novel Cu,Zn superoxide dismutase of Mycobacterium tuberculosis.
Periplasmic copper, zinc superoxide dismutases (Cu,ZnSOD) of several Gram-negative pathogens have been shown to play an important role in protection against exogenous superoxide radicals and in determining virulence of the pathogens. Here we report the cloning and characterization of the sodC gene, encoding Cu,ZnSOD, from the Gram-positive Mycobacterium tuberculosis. The predicted protein sequence contains 240 amino acids with a putative signal peptide at the N-terminus and shows approximately 25% identity to other bacterial sodC. Recombinant proteins of a full-length sodC and a truncated form lacking the putative signal peptide were overexpressed in Escherichia coli and affinity purified. Renatured recombinant M. tuberculosis sodC protein possessed characteristics of a Cu,ZnSOD. Immunoblotting with an antiserum against the recombinant M. tuberculosis Cu,ZnSOD allowed detection of a single polypeptide in the lysate of M. tuberculosis. This polypeptide has a similar size as the recombinant protein without the putative signal peptide indicating that the endogenous Cu,ZnSOD in M. tuberculosis might be processed and secreted. Furthermore, immunogold electron microscopic image showed that Cu,ZnSOD is located in the periphery of M. tuberculosis. The enzymatic activity and subcellular localization of this novel Cu,ZnSOD suggest that it may play a role in determining virulence of M. tuberculosis.


Improving the differentiation potential of pluripotent stem cells by optimizing culture conditions.
Embryoid cells and induced pluripotent stem cells (iPSCs) are pluripotent stem cells (PSCs). They retain differentiation and self-renewal potential. However, the differentiation potential of PSCs can be changed by the culture medium. PSCs retain their differentiation potential when cultured with medium that supports the glycolytic pathway, showing high expression of chromodomain-helicase-DNA-binding protein 7 (CHD7), but lose their differentiation potential with medium that supports mitochondrial function, showing reduced levels of CHD7. Labeling cells by their copy number variant profile revealed that genetically different PSC populations can be cultured by medium selection. Another factor that defines the self-renewal potential of PSCs is culture condition. PSCs form colonies as they grow, and spontaneous differentiation inevitably occurs along the rim of these colonies in areas that lack cell-to-cell contact; because of this, undifferentiated cell populations would diminish if differentiated cells are not removed properly. Seeding cells on a less potent cell-binding material may minimize the inclusion of differentiated cells, exploiting the reduced adhesive properties of differentiated cells. Culturing cells with medium that supports the glycolytic pathway, using CHD7 as a biomarker for differentiation potential, and culturing cells on less sticky material can improve the differentiation potential of already established PSC clones.


A gas chromatographic/mass spectrometric screening, confirmation, and quantification method for estrogenic compounds.
A method is described for the screening, quantification and confirmation of a variety of estronenic substances in animal tissues. A solid-phase extraction technique combined with a liquid/liquid extraction allows for rapid sample preparation and high throughput for the following compounds in bovine liver, muscle and kidney: diethylstilbestrol, dienestrol, hexestrol, zeranol, taleranol, zearalanone, zearalenone, zearalenol, estradiol and estriol. Gas chromatography/mass spectrometry and selected ion monitoring is used for the determination with detection limits ranging from 50 to 150 ppt.


Obstacles to bottom-up implementation of marine ecosystem management.
Ecosystem management (EM) offers a means to address multiple threats to marine resources. Despite recognition of the importance of stakeholder involvement, most efforts to implement EM in marine systems are the product of top-down regulatory control. We describe a rare, stakeholder-driven attempt to implement EM from the bottom up in San Juan County, Washington (U.S.A.). A citizens advisory group led a 2-year, highly participatory effort to develop an ecosystem-based management plan, guided by a preexisting conservation-planning framework. A key innovation was to incorporate social dimensions by designating both sociocultural and biodiversity targets in the planning process. Multiple obstacles hindered implementation of EM in this setting. Despite using a surrogate scheme, the information-related transaction costs of planning were substantial: information deficits prevented assessment of some biodiversity targets and insufficient resources combined with information deficits prevented scientific assessment of the sociocultural targets. Substantial uncertainty, practical constraints to stakeholder involvement, and the existence of multiple, potentially conflicting, objectives increased negotiation-related costs. Although information deficits and uncertainty, coupled with underinvestment in the transaction costs of planning, could reduce the long-term effectiveness of the plan itself, the social capital and momentum developed through the planning process could yield unforeseeable future gains in protection of marine resources. The obstacles we identified here will require early and sustained attention in efforts to implement ecosystem management in other grassroots settings.


Uveitis: effect of vitrectomy combined with lensectomy.
Combined lensectomy-vitrectomy was performed on 25 eyes in 20 patients with cataracta complicata associated with uveitis from various etiologies. Postoperative follow-up averaged 15 months, with visual improvement in 24 of the 25 eyes. Primary cause of postoperative decreased vision was cystoid macular edema. Operative complications included retinal detachment and choroidal ischemia. The technique employed and the effect of lensectomy-vitrectomy on decreasing the number and severity of recurrent attacks of uveitis are discussed.


Benefits and harms of mammography screening.
Mammography screening for breast cancer is widely available in many countries. Initially praised as a universal achievement to improve women's health and to reduce the burden of breast cancer, the benefits and harms of mammography screening have been debated heatedly in the past years. This review discusses the benefits and harms of mammography screening in light of findings from randomized trials and from more recent observational studies performed in the era of modern diagnostics and treatment. The main benefit of mammography screening is reduction of breast-cancer related death. Relative reductions vary from about 15 to 25% in randomized trials to more recent estimates of 13 to 17% in meta-analyses of observational studies. Using UK population data of 2007, for 1,000 women invited to biennial mammography screening for 20 years from age 50, 2 to 3 women are prevented from dying of breast cancer. All-cause mortality is unchanged. Overdiagnosis of breast cancer is the main harm of mammography screening. Based on recent estimates from the United States, the relative amount of overdiagnosis (including ductal carcinoma in situ and invasive cancer) is 31%. This results in 15 women overdiagnosed for every 1,000 women invited to biennial mammography screening for 20 years from age 50. Women should be unpassionately informed about the benefits and harms of mammography screening using absolute effect sizes in a comprehensible fashion. In an era of limited health care resources, screening services need to be scrutinized and compared with each other with regard to effectiveness, cost-effectiveness and harms.


De novo analysis of transcriptome reveals genes associated with leaf abscission in sugarcane (Saccharum officinarum L.).
Sugarcane (Saccharum officinarum L.) is an important sugar crop which belongs to the grass family and can be used for fuel ethanol production. The growing demands for sugar and biofuel is asking for breeding a sugarcane variety that can shed their leaves during the maturity time due to the increasing cost on sugarcane harvest. To determine leaf abscission related genes in sugarcane, we generated 524,328,950 paired reads with RNA-Seq and profiled the transcriptome of new born leaves of leaf abscission sugarcane varieties (Q1 and T) and leaf packaging sugarcane varieties (Q2 and B). Initially, 275,018 transcripts were assembled with N50 of 1,177 bp. Next, the transcriptome was annotated by mapping them to NR, UniProtKB/Swiss-Prot, Gene Ontology and KEGG pathway databases. Further, we used TransDecoder and Trinotate to obtain the likely proteins and annotate them in terms of known proteins, protein domains, signal peptides, transmembrane regions and rRNA transcripts. Different expression analysis showed 1,202 transcripts were up regulated in leaf abscission sugarcane varieties, relatively to the leaf packaging sugarcane varieties. Functional analysis told us 62, 38 and 10 upregulated transcripts were involved in plant-pathogen interaction, response to stress and abscisic acid associated pathways, respectively. The upregulation of transcripts encoding 4 disease resistance proteins (RPM1, RPP13, RGA2, and RGA4), 6 ABC transporter G family members and 16 transcription factors including WRK33 and heat stress transcription factors indicate they may be used as candidate genes for sugarcane breeding. The expression levels of transcripts were validated by qRT-PCR. In addition, we characterized 3,722 SNPs between leaf abscission and leaf packaging sugarcane plants. Our results showed leaf abscission associated genes in sugarcane during the maturity period. The output of this study provides a valuable resource for future genetic and genomic studies in sugarcane.


[Tissue specific uncoupler of mitochondrial oxidative phosphorylation].
The influence of endogenous uncoupling agent from the rat liver on oxidative phosphorylation of the liver, kidney, heart, lungs, and brain mitochondria was studied; the tissue-specificity of its action was demonstrated. The selective action of the uncoupler on the mitochondrial membrane is more obviously expressed within the range of pH 6.9--6.3 approaching such of the hepatocyte cytoplasm. The tissue-specificity was independent of the original state of mitochondria and could be eliminated only by heat injury of the oxidative phosphorylation. The activity of the tissue-specific uncoupling factor failed to diminish when the ribosomes and microsomes were removed by centrifugation. Addition of bovine albumin to the incubation medium had no influence of the value of the tissue-specific uncoupling. Participation of the uncoupler in the intratissue proliferation control is discussed.


MRI background parenchymal enhancement, fibroglandular tissue, and mammographic breast density in patients with invasive lobular breast cancer on adjuvant endocrine hormonal treatment: associations with survival.
To investigate if baseline and/or changes in contralateral background parenchymal enhancement (BPE) and fibroglandular tissue (FGT) measured on magnetic resonance imaging (MRI) and mammographic breast density (MD) can be used as imaging biomarkers for overall and recurrence-free survival in patients with invasive lobular carcinomas (ILCs) undergoing adjuvant endocrine treatment. Women who fulfilled the following inclusion criteria were included in this retrospective HIPAA-compliant IRB-approved study: unilateral ILC, pre-treatment breast MRI and/or mammography from 2000 to 2010, adjuvant endocrine treatment, follow-up MRI, and/or mammography 1-2 years after treatment onset. BPE, FGT, and mammographic MD of the contralateral breast were independently graded by four dedicated breast radiologists according to BI-RADS. Associations between the baseline levels and change in levels of BPE, FGT, and MD with overall survival and recurrence-free survival were assessed using Kaplan-Meier survival curves and Cox regression analysis. Two hundred ninety-eight patients (average age = 54.1 years, range = 31-79) fulfilled the inclusion criteria. The average follow-up duration was 11.8 years (range = 2-19). Baseline and change in levels of BPE, FGT, and MD were not significantly associated with recurrence-free or overall survival. Recurrence-free and overall survival were affected by histological subtype (p < 0.0001), number of metastatic axillary lymph nodes (p < 0.0001), age (p = 0.01), and adjuvant endocrine treatment duration (p < 0.001). Qualitative evaluation of BPE, FGT, and mammographic MD changes cannot predict which patients are more likely to benefit from adjuvant endocrine treatment.


Spectral analysis of Doppler ultrasonic decompression data.
Several aspects of spectral analysis of bubble transients in Doppler ultrasonic decompression data are discussed. The computation of energy density spectra, using fast Fourier transform techniques for analyzing bubble transients, is described. Spectral analysis of data from probes implanted within animals, using a conventional Fourier analyzer, provided good visual indications of bubble events and interesting changes in spectral structure. A new transient spectral analysis technique that is suitable for quantitative real-time monitoring of small decompression bubbles is described. In a feasibility study using data from an implanted probe, an increase of 900% in bubble signal/noise ratio was observed.


Female sexual hormones influence motor behaviour in rats after lesion of the entopeduncular nucleus.
In rats bearing a unilateral lesion of the entopeduncular nucleus, female sexual hormones administered daily for fifteen days can decrease the rate of circling and the motility counts recorded after an injection of apomorphine 0.5 mg/kg, s.c. This suggests that female hormones can decrease the response to dopaminergic agonists in the basal ganglia possibly by affecting the sensitivity of the receptors. This may have interesting clinical applications especially in Parkinson's disease and tardive dyskinesias.


A novel two-component system found in Mycobacterium tuberculosis.
We report the identification of a novel two-component system in Mycobacterium tuberculosis. We show that the putative histidine kinase with the genomic locus tag Rv3220c is able to self-phosphorylate in the presence of Mg2+/ATP and subsequently transfer the phosphoryl group to a novel response regulator PdtaR. This creates a biochemical link between the two proteins and establishes a newly identified two component system, which acts at the level of transcriptional antitermination. We also suggest that this system has potential for the development of lead compounds for inhibition of phosphotransfer.


Hormone-sensitive magnesium transport in murine S49 lymphoma cells: characterization and specificity for magnesium.
1. The hormone-sensitive transport of Mg(2+) into murine S49 lymphoma cells and its relationship to other divalent cation transport systems have been investigated.2. Mg(2+) influx, measured with (28)Mg(2+), is saturable with an apparent extracellular ion concentration at half-maximal influx (K(in)) for Mg(2+) of 330 muM and a maximal influx rate of 360 p-mole/min.10(7) cells (2.9 n-mole/min.mg cell protein or a flux rate of about 0.12 p-mole/sec.cm(2)). Efflux of Mg(2+) is biphasic with half-times of 55 and 240 min at 37 degrees C and is temperature-sensitive.3. beta-Adrenergic agonists inhibit influx but not efflux of Mg(2+) in S49 cells. Efflux of Mg(2+) is also unaffected by extracellular [Mg(2+)] or [Ca(2+)]. These results imply that the mechanism of the transport system does not involve Mg-Mg exchange.4. Mn(2+) is a non-competitive inhibitor of Mg(2+) influx with an inhibition constant, K(i), of about 200 muM. The weak inhibition exhibited by Ca(2+) (K(i) > 5 mM) is also non-competitive. La(3+) inhibits Mg(2+) transport half-maximally at about 100 muM; Ni(2+), Zn(2+), Co(2+) and Sc(3+) are all less effective than La(3+). The Ca(2+)-channel blockers cis-diltiazem, verapamil, and nifedipine and the monovalent cations Na(+) and K(+) also have no effect on Mg(2+) influx. However, increasing the extracellular pH stimulates Mg(2+) influx.5. Total cellular Mg(2+) is about 85 n-mole/10(7) cells; however, at apparent isotopic equilibrium with (28)Mg(2+) less than 3% of total cellular Mg(2+) has been exchanged. This indicates that cellular Mg(2+) is highly compartmented and that recently transported Mg(2+) exchanges very slowly with bulk intracellular Mg(2+).6. Ca(2+) influx has a K(in) of 80 muM and is much slower than Mg(2+) influx. V(max) varied in different experiments from 3 to 15 p-mole/min.10(7) cells (25-125 p-mole/min.mg cell protein). Efflux of Ca(2+) is biphasic with half-times of 22 and 200 min and is temperature-sensitive. Hormonal stimulation has no effect on either influx or efflux of Ca(2+). Mg(2+) is a competitive inhibitor of Ca(2+) influx (K(i) = 3 mM).7. Two kinetic components of Mn(2+) influx are present with apparent K(in)s of 4 muM and 100 muM. Maximal influx rates are 5 and 60 p-mole/min.10(7) cells (40 and 480 p-mole/min.mg cell protein), respectively. Influx of Mn(2+) is not altered by beta-adrenergic agonist.8. Uptake of Na(+) or K(+) is unaltered by beta-adrenergic stimulation. These data in the S49 lymphoma cell indicate that (a) Mg(2+) is translocated by a transport system independent of those that transport other divalent cations, (b) hormonal inhibition of divalent ion transport is specific for Mg(2+) and (c) cellular Mg(2+) is highly compartmented.


Optimisation and critical evaluation of a collision cell technology ICP-MS system for the determination of arsenic in foodstuffs of animal origin.
The determination of arsenic (75As) was studied using an ICP-MS equipped with collision cell technology (CCT). Different mixtures of gases (He and H2) were tested using HCl conditions and a He flow rate of 4 mL min(-1) was found to be suitable for the removal of the poly-atomic spectral interference [40Ar35Cl]+. Trueness of the optimised method has been evaluated in both standard and CCT modes on six certified reference materials in foodstuffs of animal origin and on three external proficiency testing schemes (FAPAS). The results obtained generally coincided with the certified values, except for CCT mode in some categories of samples (meat, mussels and milk powder), for which a positive bias on results was observed due to the formation of poly-atomic interferences within the collision cell. The main interferences were studied and their contributions estimated. [58Fe16O1H]+ and [74Ge1H]+ were the most significant interferences formed in the cell. Finally, different parameters (e.g. hexapole and quadrupole bias voltage, nebuliser gas flow) were optimised to try to attenuate these interferences.


Clinical research nurse utilisation and role in the conduct of decentralised clinical trials: a literature review.
The decentralised clinical trial (DCT) model has been popularised given its remote or virtual design, permitting expanded participant enrolment into community settings. Clinical research nurses (CRNs) are specially trained in the management of clinical trials; however, the utilisation of the research nurse role relating to decentralised trial conduct is not well-established. A literature review was conducted to describe the role of the research nurse in the conduct of DCTs and the current utilisation of this nurse specialty for decentralised trial management. Use of keywords 'DCT' or 'virtual trial' and 'nursing' were used to identify full-text, peer-reviewed literature in the English language and published within the last 10 years that described the clinical research nursing role. Of the 102 pre-screened articles identified across five databases, 11 articles were eligible for full-text analysis. Thematic groupings of common discussion elements included Variance in Decentralised Clinical Trial Model Implementation, CRN Involvement in Decentralised Trial Conduct and Reporting and Shared Challenges of Decentralised Trial Implementation Affecting the CRN Role. Implications of this literature review include expanded trial sponsor awareness of the support requirements to facilitate research nurse utilisation and optimal decentralised trial conduct.


Predictive value of the shock index (SI) compared to the age-adjusted pediatric shock index (SIPA) for identifying children that needed the highest-level trauma activation based on the presence of consensus criteria.
In previous studies, SIPA was shown to be better than the SI in identifying children who have an elevated ISS, required transfusion, or were at a high risk of death. No comparison has been made to the consensus-based criteria that identify patients requiring the highest-level trauma activation. The objective of this study was to determine if the SIPA was more accurate than the SI in identifying children with increased need for trauma team activation as defined by the criterion standard definition, and secondly the sensitivity and specificity of the SI and SIPA. Retrospective review of prospectively collected trauma based data. Children aged 1-17 years admitted to a pediatric level 1 trauma center between 1/1/16 and 12/31/17 and met the prehospital criteria for level 1 or 2 trauma activation were included. We evaluated the ability of SI > 0.9 at ED presentation and elevated SIPA to predict need for trauma activation based on consensus criteria. SIPA cutoffs were > 1.22 (age 4-6), >1.0 (age 7-12), and > 0.9 (age 13-17). Among 3378 children, 1486 (44%) had an elevated SI and 590 (18%) had an elevated SIPA. There were 160 (5%) patients who met at least one consensus criterion. Broadly, sensitivity and specificity analyses reveal poor sensitivity for both SI and SIPA (59.4% versus 43.1% respectively) measures but a moderate specificity for SIPA (83.8%). Both SI and SIPA have a poor PPV (6.4% versus 11.7%) but high NPV (96.6% versus 96.7%). Overall, SIPA has higher accuracy than SI in predicting consensus criteria 82% versus 57%). SIPA is more accurate than the SI in identifying children who meet a consensus criterion defining the need for highest-level trauma activation. The low PPV and sensitivity suggest that SIPA alone, while somewhat less likely to lead to overtriage than SI is not ideal for ruling in the need for level one resources as defined by the consensus criteria. Prognosis study, retrospective. Level II.


Structure of novel enzyme in mannan biodegradation process 4-O-β-D-mannosyl-D-glucose phosphorylase MGP.
The crystal structure of a novel component of the mannan biodegradation system, 4-O-β-D-mannosyl-D-glucose phosphorylase (MGP), was determined to a 1.68-Å resolution. The structure of the enzyme revealed a unique homohexameric structure, which was formed by using two helices attached to the N-terminus and C-terminus as a tab for sticking between subunits. The structures of MGP complexes with genuine substrates, 4-O-β-D-mannosyl-D-glucose and phosphate, and the product D-mannose-1-phosphate were also determined. The complex structures revealed that the invariant residue Asp131, which is supposed to be the general acid/base, did not exist close to the glycosidic Glc-O4 atom, which should be protonated in the catalytic reaction. Also, no solvent molecule that might mediate a proton transfer from Asp131 was observed in the substrate complex structure, suggesting that the catalytic mechanism of MGP is different from those of known disaccharide phosphorylases.


Protective effect of polyethylene glycol-superoxide dismutase on leukocyte dynamics in rat retinal microcirculation under lipid hydroperoxide-induced oxidative stress.
The levels of lipid hydroperoxide (LHPs) in vitreous are elevated in a variety of retinal disorders. Recently, we have shown that increased levels of LHPs in the vitreous enhanced leukocyte-endothelium interaction in the retina, which should contribute to the initial disturbance of the retinal microcirculation. Based upon the previous work, the purpose of the present study was to investigate the effect of polyethylene glycol-superoxide dismutase (PEG-SOD), one of the important enzyme antioxidants, on leukocyte-endothelial interaction in the retinal microcirculation under LHP-induced oxidative stress. Male Brown-Norway rats weighing approximately 250 g were used. LHP(18:2) was made from linoleic acid (LA) with lipoxygenase and 10 microg of LHP dissolved in 5 microl of sodium borate buffer (SBB, 0.02 m) was slowly injected into the vitreous using a 33-gauge needle. PEG-SOD (5000 units/kg) was given intravenously 5 min before LHP injection. At 2, 4, 6, 12, 24 and 48 hr after the vitreous injections, we evaluated the number of rolling leukocytes along the major retinal veins and the number of leukocytes that accumulated in the retinal microvasculature with acridine orange digital fluorography. In LHP-treated rats, leukocyte rolling along the major retinal veins was maximal at 6 hr after LHP injection. The number of rolling leukocytes in the PEG-SOD-treated rats was decreased to 5.5% of those in the LHP-treated rats at 6 hr after LHP injection (P<0.01). No rolling leukocytes were observed in either control or vehicle-treated eyes. The number of accumulated leukocytes in LHP-treated eyes started to increase at 12 hr, and peaked at 24 hr which was significantly higher than in both control and vehicle-treated eyes (P<0.01). The number of accumulated leukocytes in the PEG-SOD-treated rats was reduced by 88.0% at 24 hr (P<0.01). Intravenous injection of PEG-SOD significantly inhibited the leukocyte rolling and its accumulation under LHP-induced oxidative stress. These results suggest that PEG-SOD might attenuate various retinal microcirculatory disorders associated with LHP.


Preferential relocation of the N-methyl-D-aspartate receptor NR1 subunit in nucleus accumbens neurons that contain dopamine D1 receptors in rats showing an apomorphine-induced sensorimotor gating deficit.
Sensorimotor gating as measured by prepulse inhibition (PPI) to startle-evoking auditory stimulation (AS) is disrupted in schizophrenia and in rodents receiving systemic administration of apomorphine, a dopamine D1/D2 receptor agonist, or MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. The functional analogies and our prior results showing apomorphine- and AS-induced relocation of the dopamine D1 receptor (D1R) in the nucleus accumbens (Acb) shell suggest that apomorphine and AS may affect the subcellular distribution of the NMDA receptor NR1 subunit, a protein that forms protein-protein interactions with the D1R. We quantitatively compared the electron microscopic immunogold labeling for NR1 in dendritic profiles distinguished with respect to presence of D1R immunoreactivity and location in the Acb shell or core of rats receiving a single s.c. injection of vehicle (VEH) or apomorphine (APO) alone, or combined with AS (VEH+AS, APO+AS). The rats in the APO+AS group were previously shown to have PPI deficits, whereas the rats in the VEH+AS group had normal PPI. A significantly higher percentage of plasmalemmal and a lower percentage of cytoplasmic NR1 immunogold particles were seen in D1R-labeled dendritic spines in the Acb shell of the APO+AS group compared with all other groups. D1R-containing small dendrites in the Acb shell of the APO+AS group also showed a significantly higher density of plasmalemmal and a lower density of cytoplasmic NR1 immunogold particles compared with VEH or APO groups. In the Acb core, the APO+AS group had significantly fewer dendritic spines co-expressing NR1 and D1R compared with VEH or VEH+AS groups. These results, together with our earlier findings, suggest that NMDA receptors are preferentially mobilized in D1R-containing Acb neurons of rats showing apomorphine-induced disruption of PPI in a paradigm using acoustic stimulation.


Statins inhibited erythropoietin-induced proliferation of rat vascular smooth muscle cells.
Erythropoietin (EPO) directly stimulates the proliferation of vascular smooth muscle cells, and this is believed to be one of the mechanisms of vascular access failure of hemodialysis patients. However, precise mechanisms of the EPO-induced proliferation of vascular smooth muscle cells are not certain. HMG-CoA reductase inhibitors (statins) are primarily used to reduce cholesterol levels, but also exert other effects, including reno-protective effects. We evaluated the effect of several statins with various hydrophilicities on the EPO-induced proliferation of primary cultured rat vascular smooth muscle cells (VSMCs) in vitro. EPO significantly and concentration-dependently increased DNA synthesis as assessed by [³H]thymidine incorporation, cell proliferation as assessed by WST-1 assay, and activation of the p44/42MAPK pathway. Therapeutic doses of statins (pravastatin, simvastatin, atorvastatin and fluvastatin) in patients with hypercholesterolemia almost completely suppressed all of the EPO-induced effects in a concentration-dependent manner. Co-addition of mevalonic acid almost completely reversed the effects of statins. Statin alone did not affect the basal proliferation capacity of the cells. The effects were almost similar among the statins. We concluded that statins inhibited EPO-induced proliferation in rat VSMCs at least partly through their inhibition of HMG-CoA reductase activity. In the future, statins might prove useful for the treatment of EPO-induced hyperplasia of vascular access. Because the statins all showed comparable effects irrespective of their hydrophilicities, these effects might be a class effect.


Manual wheelchair propulsion by people with hemiplegia: within-participant comparisons of forward versus backward techniques.
To test the hypotheses that people with hemiplegia using arms and legs to propel their wheelchairs perform better backward than forward and prefer the backward direction. Within-participant cross-sectional design. Manual wheelchair users (N=18) with hemiplegia caused by stroke, a sample of convenience. Rehabilitation center. Participants each performed 9 skills from the Wheelchair Skills Test (WST 4.1)-4 low-rolling-resistance skills (rolls 10m, turns 90° while moving, rolls 2m across 5° side slope, descends 5cm level change) and 5 high-rolling-resistance skills (ascends 5° incline, rolls 2m on soft surface, gets over 15-cm pothole, gets over 2-cm threshold, ascends 5cm level change)-in both the forward and backward directions, in random order. Total percentage capacity scores from the modified WST 4.1, success rates for individual skills, and responses from an orally administered questionnaire regarding direction preferences. The mean ± SD total WST 4.1 capacity scores were 53%±26% in the forward direction and 76%±30% in the backward direction (P<.001). For the 4 low-rolling-resistance skills, there were no clinically significant differences (≥20%) between forward and backward success rates. For the 5 high-rolling-resistance skills, the success rates were 33% to 50% higher in the backward direction. Participants preferred the forward direction for low-rolling-resistance skills and the backward direction for high-rolling-resistance skills. Wheelchair skills that involve high rolling resistance are performed more successfully in the backward than the forward direction, and participants prefer the backward direction for such skills. These findings have implications for wheelchair selection and skills training.


Gender differences in associations between body mass index and DSM-IV mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions.
The purpose of this study is to examine gender differences in associations between body mass index (BMI) and affective disorders. We used logistic regression to examine the effects of BMI and gender on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mood and anxiety disorders in a sample of 40,790 adults. Obesity (BMI >30.0) was associated with increased risk for any mood disorder, major depressive disorder, and dysthymic disorder, in both men and women (odds ratios [ORs], 1.35-1.88). Risk of bipolar I and II disorders was elevated in obese women (ORs, 1.70-2.41) but not men. Overweight (BMI = 25.0-29.9) predicted increased risk for any mood disorder and bipolar I disorder in women but not in men (ORs, 1.16-1.44). Obesity was associated with increased odds of any anxiety disorder and specific phobia in men and women (ORs, 1.35-1.79). Obese women were additionally at increased risk for social phobia. Overweight predicted increased risk of social phobia and specific phobia for women but not for men (ORs, 1.27-1.37). Obese individuals of both genders are at increased risk for a range of mood and anxiety disorders, but women who are even moderately overweight experience increased risks for some disorders as well.


Delay in treatment of invasive cervical cancer due to intimate partner violence.
Intimate partner violence (IPV) is underreported and creates a complex psychosocial medium that adversely affects the health of its victims. We present the first case report in the literature, though likely not the first time, in which a patient delayed her cancer treatment due to domestic abuse and her disease progressed. A 41-year-old female with vaginal bleeding was diagnosed with cervical cancer. After several years of declining recommendations for treatment, she was questioned separate from her partner and she revealed a long-standing history of abuse. Physicians must be aware of the signs of spousal abuse to lessen negative impact on the treatment of their patients. Once domestic violence is discovered, there are many resources available to help patients with their needs.


Developing a Mobile App for Patients to Monitor Medical Record Changes Using Blockchain.
According to recent revisions to medical laws in Korea, changes to electronic medical records are to be documented. To do so, however, a transparent system with which to store original documents and changes thereto is needed. The transparency and immutability of blockchain records are the key characters of blockchain technology. Employing these characteristics, we developed an application with which to monitor changes of medical records using blockchain.


Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction.
In patients with ST-elevation acute myocardial infarction (STEMI), reperfusion therapy limits infarct size, but can directly evoke myocardial reperfusion injury. Activation of the Na(+)/H(+) exchanger (NHE) plays an important role in reperfusion injury. TY-51924, a novel NHE inhibitor, significantly reduced infarct size in animal studies and was well tolerated in early-phase clinical trials. This study aim was to evaluate the efficacy and safety of TY-51924 in patients with STEMI. In this multicenter, randomized, double-blind, placebo-controlled Phase II trial, 105 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (pPCI) were randomly assigned to receive an intravenous infusion of either TY-51924 or placebo. Primary endpoints were myocardial salvage index (MSI) as determined by single photon emission computed tomography (SPECT) 3-5 days after pPCI and safety up to 7 days. Baseline characteristics were similar in the two groups. MSI 3-5 days after pPCI (0.200 vs. 0.290, p=0.56), 3 months after pPCI (0.470 vs. 0.500, p=0.76), and the incidences of side effects did not differ between the two groups as a whole. However, on post hoc analysis of 52 patients with a large area at risk (AAR) (≥38%) and no antegrade coronary flow, MSI by SPECT at 3 months after pPCI was significantly higher in TY-51924 group (0.450 vs. 0.320, p=0.03). TY-51924 did not adversely influence hemodynamics. TY-51924 did not improve MSI or increase side effects as a whole. However, TY-51924 is potentially cardioprotective in the presence of a large AAR and no antegrade coronary flow.


Corneal Response to Scleral Contact Lens Wear in Keratoconus.
To verify corneal alterations in patients with keratoconus who wear scleral contact lenses (ScCLs), focusing on corneal endothelial assessment. Scleral contact lenses were fitted in 22 patients with keratoconus. During a 90-day follow-up, patients were assessed in three visits: at baseline, after 30 days, and after 90 days. Patients underwent visual acuity measurement, slitlamp biomicroscopy of the anterior segment, specular microscopy of the corneal endothelium, corneal pachymetry, measurement of the clearance between the cornea and the lens, and follow-up of ectasia. Variables related to endothelial morphology and pachymetry values did not change significantly over time. Central clearance measurements decreased in the 90-day period. No progression of corneal ectasia was observed, neither were infectious or inflammatory processes in the same period. Daily wear of ScCLs in patients with keratoconus was not associated with adverse effects on the cornea or endothelium over a period of 90 days nor was there evidence of disease progression. Central clearance values diminished over that period, but the significance of this observation remains unclear.


Which children would benefit most from tympanostomy tubes (grommets)? A personal evidence-based review.
Otitis media with effusion (OME) is a common condition in young children. OME causes some hearing loss, and can cause permanent changes in the tympanic membrane as well as other symptoms. In most cases OME is of short duration. As long-lasting bilateral OME for decades has been associated with delayed cognitive and language development, parents and ENT specialists have a positive attitude towards treatment with tympanostomy tubes (TT). This personal evidence-based review is build on own observations and research combined with newer studies and guidelines. The review argues for a relatively restrictive treatment policy concerning the use of TT in children with OME without signs or symptoms of impaired social or linguistic function. Six months with bilateral OME and significant hearing loss should be present before treatment with TT in otherwise healthy children. At the moment we have no evidence for the subgroups of children excluded from the RCTs, i.e. children with speech/language delays, behaviour and learning problems, or syndromes. Clinicians will need to make their own decisions regarding treatment of such children. The situation just now is that some children are over-treated and some are under-treated. There is an urgent need for prospective cohort studies and randomised studies on children with long-lasting OME in an attempt to characterise the children who would benefit most from TT.


Influence of pH on the detection of low- and high-avidity anti-dsDNA.
In 2 radioimmunoassays in use to detect antibodies to dsDNA, the Farr assay and the PEG assay, we observed inhibitory effects of normal human serum (NHS) on the DNA binding by SLE sera. This was found to be due by the fact that, during incubation at 37 degrees C, CO2, introduced in the incubation mixture by the serum, evaporates from the mixture. This results in increase in pH to values well above pH 8.0, which in turn leads to a decreased DNA binding by antibody. When SLE sera are tested at low dilution, this phenomenon may lead to false negative results. Proper pH control, by the use of buffers with a greater buffering capacity than PBS, completely prevented the observed inhibitory effects. However, under these conditions NHS bound significant amounts of DNA in both assays. The non-specific DNA binding by NHS was found to be heat-stable, but could be eliminated either by aerosil treatment of the sera or by addition of dextran sulphate to the incubation mixture. Lipoproteins and, to a lesser extent, the complement component C1q appear responsible for this non-specific binding. To avoid false negative results with SLE sera as well as non-specific binding by NHS, we propose the use of stronger buffers in combination with added dextran sulphate to the incubation mixture in both the Farr assay and the PEG assay.


Hemopexin-mediated heme transport to the liver. Evidence for a heme-binding protein in liver plasma membranes.
Isolated liver plasma membranes interact with heme-hemopexin and effect the removal of heme from the complex. This heme is rapidly accumulated by a previously undescribed heme-binding membrane component (HBC). This intrinsic membrane component can be solubilized from the membrane with Triton X-100 in a form that retains the ability to bind heme. Solubilized HBC was shown to be distinct from hemopexin itself, free heme, ligandin, globin, heme oxygenase, cytochrome P-450, and albumin. Since formation of the heme-HBC complex is effected by the interaction of heme-hemopexin with its receptor, HBC may either be a subunit of the heme-hemopexin receptor or a separate protein that interacts with the receptor. HBC can also bind heme (Kd apparent 200 nM) that is presented to it in a nonprotein bound form, showing true heme-binding activity. HBC is proteinaceous since treatment with proteases, heat, and disulfide bond reducing agents diminishes its ability to bind heme. HBC and any associated detergent elutes from Sephacryl S-200 with an apparent molecular weight of 115,000 and Stokes radius of 7.5 nm. This component, which may comprise 0.5% of liver plasma membrane protein, appears to have an acidic pI since it adsorbs to DEAE-cellulose at pH 7.4 but not to CM-cellulose at pH 6.4. In sucrose gradients, HBC migrates with S values of 1.69 and 4.02, suggesting that it has subunits or that it forms multimers under these conditions.


Fetal window of vulnerability to airborne polycyclic aromatic hydrocarbons on proportional intrauterine growth restriction.
Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters. In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn. One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (-3%, 95% Confidence Interval (CI), -5 to -0%), birthweight (-105 g, 95% CI, -188 to -22 g), and birth length (-0.78 cm, 95% CI, -1.30 to -0.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 μm/g, 95% CI, 1 to 5 μm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort. PAH exposure appears to exert the greatest adverse effect on fetal growth during the first trimester. The present data support the need for the protection of pregnant women and the embryo/fetus, particularly during the earliest stage of pregnancy.


Clinical implications of BRAF mutation in thyroid carcinoma.
Significant progress has recently been made in the clinical management of papillary thyroid carcinoma. The accuracy of diagnosis and prognostic stratification of this type of carcinoma are high but still fall below 100%. Lack of effective treatments for advanced stage papillary thyroid carcinoma leads to death in some patients. Approximately half of all such carcinomas harbor mutations in the gene encoding the serine/threonine-kinase B-type Raf kinase (BRAF), resulting in constitutive activation of the mitogen-activated protein kinase-extracellular-signal-regulated kinases signal transduction pathway. There is intriguing evidence that BRAF mutation testing of papillary thyroid carcinoma might improve the diagnosis, prognostic stratification and treatment of these tumors but large, prospective trials are needed to define the actual clinical impact of these approaches.


Characterizing bourbon whiskey via the combination of LC-MS and GC-MS based molecular fingerprinting.
To discover molecular fingerprints that vary by bourbon's age or color, 121 commercial bourbon samples were analyzed using both gas chromatography and liquid chromatography combined with mass spectrometry. In total, 81 non-volatile compounds and 102 volatile compounds were identified. A subset of samples containing age information was divided into training (n = 70) and testing (n = 12) groups to build and validate the Partial Least Square - Discriminant Analysis models for age-based classification. After internal and external validation, our models showed that 8 molecular markers unitedly provided up to 100% accuracy of prediction in distinguishing unaged (0 years), younger (0-4 years), and older (>4 years) bourbons. Additional efforts were also made to detect molecular signatures that contributed to the color differences in bourbon. Overall, our study provided a powerful strategy for the confident identification of high-quality products and robust evaluation of their commercial values.


Immune-related microRNA signature for predicting prognosis and the immune microenvironment in hepatocellular carcinoma.
As vital regulators of post-transcription gene expression, microRNAs are involved in the initiation and progression of hepatocellular carcinoma (HCC), including antitumor immune responses. We aimed to identify an immune-related microRNA signature and explore the influence of this signature on the prognosis and immunity of HCC. Differentially expressed immune-related microRNAs were identified between high- and low-immunity groups in the TCGA-HCC dataset. Then, Cox regression models were used to construct an immune-related microRNA signature. We assessed the prognostic value and clinical relevance of this signature. Furthermore, we analyzed the effect of the immune-related microRNA signature on immune cells and immune checkpoints. We screened 41 differentially expressed immune-related microRNAs, of which 7 microRNAs were used to construct the immune signature. Survival analysis showed that high-risk patients had a shorter survival. The immune-related microRNA signature was an independent prognostic marker and was associated with the clinical stage. To understand the functional mechanism of the seven-microRNA signature, we predicted target genes of microRNAs. Enrichment analysis indicated that these target genes participated in immune responses. Moreover, we found that the microRNA signature was related to tumor-infiltrating immune cells. In high-risk patients, there was a higher expression of inhibitory immune checkpoints. On the contrary, the expression of stimulatory immune checkpoints was lower in high-risk patients. We successfully identified an immune-related microRNA signature that was strongly correlated with the prognosis and immune microenvironment of HCC. The immune-related microRNAs signature might have important implications for improving the clinical outcomes of HCC patients.


Pathological changes of peripheral nerve and muscle of patients with hemiatrophy.
Peripheral nerve and muscle of patients with hemiatrophy were biopsied and examined by means of light and electron microscope. The unmyelinated nerve fibers decreased in number and remaining fibers were atrophic with irregular shape and high electron density, while myelinated nerve fibers slightly decreased in number. The Schwann cells enveloping nerve fibers were also atrophic with high electron density. The muscles contained numerous glycogen granules in the myofilaments and between the myofilaments. The mitochondria in the muscles showed atrophy with high electron density. Some parts of severe atrophy showed honeycomb-like structure forming large vacuoles in the muscle fibers. From the findings mentioned above, it is speculated that primary change was nerve fibers, especially unmyelinated nerve fibers.


Enzyme replacement therapy with idursulfase in patients with mucopolysaccharidosis type II.
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase. This leads to the progressive accumulation of glycosaminoglycans in tissues throughout the body. As a result, patients may suffer from severe airway obstruction, skeletal deformities, cardiomyopathy and, in severely affected patients, there may be progressive neurological decline. Despite the early onset of signs and symptoms, diagnosis is often delayed. Until recently, treatment for MPS II has been largely palliative; however, enzyme replacement therapy with recombinant iduronate-2-sulphatase, which is produced in a human cell line and targets the underlying cause of the disease, has now been approved. This short review provides an overview of the natural history of MPS II and current experience of enzyme replacement therapy with idursulfase.


A new genus of fossil Mymaridae (Hymenoptera) from Cretaceous amber and key to Cretaceous mymarid genera.
Myanmymar aresconoidesgen n., sp. n. is described from one female in Burmese amber, dated as about 100 my. It is similar to Arescon on wing features but is unique among Mymaridae in having distinctly segmented palpi. It is the fifth mymarid genus definitely referable to the Cretaceous period. A key to Cretaceous mymarid genera is presented and the features of Myanmymar are compared with the other Cretaceous and extant mymarid genera.


Interactions between the coccid, Icerya seychellarum (Westw.) and its host tree species on Aldabra Atoll : II. Scaevola taccada (Gaertn.) Roxb.
(i) In an area of coastal scrub on Aldabra Atoll the growth and phenology of 120 bushes of Scaevola taccada was measured along three transects stretching 200 m inland from the sea, between May 1977 and November 1978. Correlations between bush parameters, the infestation by the coccid Icerya seychellarum and prevailing saline conditions were measured. Considerable death (up to 50% of labelled clusters) of S. taccada occurred in 1977-78. Leaf infestation ranged from 0 to 1.6 mg dry weight of coccids cm-2 total leaf area per cluster. (ii) Coccids fed predominantly on senescing leaves and seasonal differences in leaf infestation were closely associated with changes in leaf phenology. Under experimental conditions coccids could utilize green leaves. (iii) Infestation increased with distance away from the sea whilst the influence of salt, and its effect in increasing leaf succulence, decreased inland. Infestation was strongly negatively correlated with leaf succulence. (iv) Two experiments with S. taccada showed that coccids significantly reduced the growth of leaves and roots and increased the rate of leaf senescence. 0.5 mg cm-2 of coccids reduced leaf production by 39%. (v) In May 1977 the proportion of dead clusters was significantly positively correlated with coccid infestation and in 1978, when mean cluster death doubled, death near the coast (0-100 m) was positively correlated with leaf succulence, whilst inland (101-200 m) death significantly increased with increasing infestation. (vi) It was concluded that coccids could account for the reductions in leaf production in the field and that they contributed to much of the bush death. (vii) The effects of coccids on the leaf production of S. taccada and Euphorbia pyrifolia (Part I) closely agreed. It was estimated that 1.25 mg cm-2 of coccids can completely check leaf production.


Sellar Metastases: Diagnosis and Management.
Sellar metastases account for 0.87% of all intracranial metastases. They are usually asymptomatic and can be the first manifestations of some occult malignancy. The diagnosis is made mainly during the screening of patients with known primary lesions or can present with neurologic or hormonal changes related to compression or invasion of surrounding structures. Differentiating these lesions from other more common lesions such as pituitary adenoma maybe difficult. Management is mainly aimed at the primary lesion and is palliative to improve quality of life or for pathologic confirmation.


Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept).
Purpose The present study evaluated the platelet distribution pattern and growth factor release (VEGF, TGF-β1 and EGF) within three PRF (platelet-rich-fibrin) matrices (PRF, A-PRF and A-PRF+) that were prepared using different relative centrifugation forces (RCF) and centrifugation times. Materials and methods immunohistochemistry was conducted to assess the platelet distribution pattern within three PRF matrices. The growth factor release was measured over 10 days using ELISA. Results The VEGF protein content showed the highest release on day 7; A-PRF+ showed a significantly higher rate than A-PRF and PRF. The accumulated release on day 10 was significantly higher in A-PRF+ compared with A-PRF and PRF. TGF-β1 release in A-PRF and A-PRF+ showed significantly higher values on days 7 and 10 compared with PRF. EGF release revealed a maximum at 24 h in all groups. Toward the end of the study, A-PRF+ demonstrated significantly higher EGF release than PRF. The accumulated growth factor releases of TGF-β1 and EGF on day 10 were significantly higher in A-PRF+ and A-PRF than in PRF. Moreover, platelets were located homogenously throughout the matrix in the A-PRF and A-PRF+ groups, whereas platelets in PRF were primarily observed within the lower portion. Discussion the present results show an increase growthfactor release by decreased RCF. However, further studies must be conducted to examine the extent to which enhancing the amount and the rate of released growth factors influence wound healing and biomaterial-based tissue regeneration. Conclusion These outcomes accentuate the fact that with a reduction of RCF according to the previously LSCC (described low speed centrifugation concept), growth factor release can be increased in leukocytes and platelets within the solid PRF matrices.


Hydrochemical investigation of groundwater in a trans-Himalayan region of Ladakh, India, using geochemical modelling and entropy technique.
Evaluating the hydrogeochemistry and groundwater quality status is vital to understand the sources and extent of groundwater contamination. Chemometric analysis, geochemical modelling and entropy technique were explored to delineate the hydrogeochemistry of groundwater in the trans-Himalayan region. Analysis of hydrochemical facies revealed that 57.14, 39.29, and 3.57% of samples were Ca-Mg-HCO3-, Ca-Mg-Cl- and Mg-HCO3- water types, respectively. Gibbs diagrams illustrate the effects of the dissolution of carbonates and silicates during weathering on groundwater hydrogeochemistry. The PHREEQC modelling depicted that most of the secondary minerals are supersaturated except for halite, sylvite, and magnetite which are undersaturated and in equilibrium with nature. Multivariate statistical techniques, including principal component analysis, were applied for source apportionment indicating that the hydrochemistry of the groundwater was mainly controlled by geogenic sources (rock-water interaction) along with secondary pollution through increased anthropogenic sources. Heavy metal accumulation in groundwater depicted the order of Cd > Cr > Mn > Fe > Cu > Ni > Zn. EWQI analysis revealed that none of the samples fell into excellent and good categories. In total, 92.86% of groundwater samples were in an average category while the rest of the samples (7.14%) were unfit for drinking. This study will provide baseline data and a scientific framework which can be used in source apportionment studies, predictive modelling and efficient management of water resources.


Validation of a computerized technique for detection of the gas exchange anaerobic threshold in cardiac disease.
Respiratory gas exchange data were collected from 77 men greater than 6 months after acute myocardial infarction. Maximal exercise was performed on an ergometer cycle programmed for a ramp protocol of 15 W/min. The gas exchange anaerobic threshold (ATge) was determined by analysis of the carbon dioxide elimination (VCO2) vs oxygen consumption (VO2) curve below a respiratory exchange ratio of 1.00 using a computerized algorithm. This value was estimated at the inflection of VCO2 from a line with a slope of 1 which intersects the VCO2 vs VO2 curve. The relation of the ATge to the lactate acidosis threshold was studied in 29 patients. The reproducibility of the ATge method was studied in 77 patients. Mean (+/- standard deviation) VO2 for the ATge was 905 +/- 220 vs 866 +/- 299 ml/min for the lactate acidosis threshold (r = 0.86, p less than 0.001). Mean VO2 at the ATge for test 1 was 968 +/- 225 vs 952 +/- 217 ml/min for test 2 (r = 0.71, p less than 0.001). Mean peak VO2 was 1,392 +/- 379 vs 912 +/- 202 ml/min at the ATge (r = 0.76, p less than 0.001). Results demonstrate that this ATge method correlates well with the lactate acidosis threshold, is reproducible, and should be useful as an objective measure of submaximal exercise performance.


Antimicrobial and antioxidant activity on Pakistan origin Launaea nudicaulis (L.) Hook f.: A promising halophyte.
Facultative type of Halophytes is those which can easily grow on both saline and non-saline soil conditions Launaea nudicaulis (L.) Hook f. belongs to family compositae [Asteraceae] is facultative halophyte with great medicinal values. The main objective of this study is to explore anti-oxidant and anti-bacterial potential on different morphological parts of Launaea nudicaulis (L.) Hook f. The results of the antibacterial activity of methanolic extracts of leaves stem and roots of Launaea nudicaulis (L.) Hook f. showed that the potent antibacterial activity observed in all three morphological parts against Staphylococcus aureus. DPPH scavenging activity of extracts of root, stem, leaves against standard i.e., ascorbic acid at different concentrations of 20, 40, 60, 80 and 100 showed that root extract have more significant activity when compared to the ascorbic acid. Documented potentials of halophytes are elevating its prominence which motivates scientist to further explore with extensive research.


Arthroscopic Posterior HAGL Repair Using a Direct Transaxillary Portal.
Humeral avulsion of the glenohumeral ligament (HAGL lesion) is a challenging problem in surgery for shoulder instability. Open and arthroscopic approaches and techniques have been described to address this issue. Especially posterior HAGL lesions increase the surgical complexity, as open anterior approaches provide limited visibility and access for successful repair. This article describes an alternative technique using an arthroscopic transaxillary approach to deploy the suture anchor with a perpendicular angle to the humeral bone, thus, improving the ability to perfectly position the anchor at the anatomic insertion of the inferior humeral ligament.


The utility of bronchoalveolar lavage findings in the diagnosis of eosinophilic esophagitis in children.
Bronchoalveolar lavage (BAL)-nucleated cell counts and the lipid-laden alveolar macrophage index (LLMI) have been investigated in predicting chronic aspiration as well as reflux esophagitis with variable results. To date, BAL neutrophil percentages and the LLMI have not been described in patients with eosinophilic esophagitis (EoE). To evaluate BAL neutrophil percentages and LLMI levels in patients with EoE and compare these levels in patients with aerodigestive concerns without biopsy-proven EoE. Retrospective review of patients referred to an aerodigestive evaluation team for overlapping aerodigestive complaints (dysphagia, stridor, subglottic stenosis, feeding intolerance, and chronic aspiration). Patients underwent microlaryngoscopy, esophagogastroduodenoscopy with biopsy, and bronchoscopy and BAL were indicated by symptoms. BAL neutrophil percentages, LLMI levels, esophageal biopsy results, and esophageal dual-probe pH/impedance were recorded and compared. Fifty-one patients were included in the study that underwent comprehensive workup for aerodigestive complaints. Patients were subdivided into two groups: (1) negative esophageal biopsy (for EoE) and (2) positive esophageal biopsy. There were no significant differences between the groups in percentage neutrophils (p=0.55, unpaired t-test) or LLMI levels (p=0.14, unpaired t-test). BAL neutrophil percentages and the LLMI are unreliable in identifying patients with silent aspiration and gastroesophageal reflux. To date, there is no report of the utility of BAL neutrophil percentages and the LLMI in diagnosing patients with EoE. Our series indicates no correlation in neutrophil percentages or LLMI in patients with EoE versus patients without EoE that are referred to tertiary centers with aerodigestive concerns. BAL neutrophil percentages and LLMI levels are not a reliable predictor of eosinophilic esophagitis in children with complex aerodigestive concerns. Esophageal biopsy remains the gold standard for diagnosis of EoE and the challenge remains to find other markers that raise suspicion for EoE for the non-gastroenterologist or that stage the extent of disease beyond the esophagus.


Do viruses play an etiologic role in ankylosing spondylitis or psoriatic arthritis?
High venous blood levels of 2-5A, an adenylic acid polymer synthesized in the presence of double-stranded RNA and considered as a viral replication indicator, have been found in blood samples from ankylosing spondylitis and psoriatic arthritis patients, but not from patients with seropositive rheumatoid arthritis or acute chondrocalcinosis. These findings suggest the possibility that ankylosing spondylitis and psoriatic arthritis might be virus-induced diseases.


Bioprosthetic Valve Fracture After TAVR Complicated by Balloon Rupture: Bail-Out TAVR in TAVR in SAVR.
Transcatheter aortic valve replacement in surgical aortic valve is a safe and effective procedure to treat patients with failed bioprosthetic surgical valves at high risk for reoperation. Performing bioprosthetic valve fracture has been shown to improve postprocedural hemodynamics of TAVR in surgical aortic valve replacement. However, specific complications related to valve fracture are becoming more common. (Level of Difficulty: Advanced.).


A febrile occlusion revealing a biliary ileus.
Biliary ileus is a consequence of the migration of a gallstone from the gallbladder to the digestive tract, most often via a biliodigestive fistula that causes a bowel obstruction. The clinic is atypical and capricious, including bowel obstruction and signs of cholecystitis, causing a delay in diagnosis. The therapeutic objective is to remove the intestinal obstacle by an enterotomy with stone extraction, with or without treatment of the biliary pathology (cholecystectomy and biliary fistula cure). The surgery remains the treatment of choice; laparoscopy and endoscopy present a less invasive alternative and are beginning to prove their effectiveness. The morbi-mortality remains high for biliary ileus, this is principally caused by the delay in diagnosis.


Heterophile antibodies. Part III. Evidence for linkage of high responder activity to sheep red blood cells and the formation of specific antibodies to HBsAg.
Group A, B and O subjects who produce immune antibodies to group A1 or B red blood cells also produce high titer antibodies to sheep red blood cells. Sheep red blood cells appear to possess AB-like as well as non-AB determinants on their surface membranes, each capable of producing and reacting with antibodies of their respective specificities. The antibodies against AB-like determinants preferentially agglutinate A or B cells whereas non-AB-like determinants preferentially stimulate hemolytic antibodies. Human antibodies reacting with these two kinds of determinants on sheep red blood cells may be produced in response to microorganisms possessing very similar factors on their membranes. Individuals who possess AB-like determinants in their secretions, similar to the determinants present on sheep red blood cells (or microorganisms), often make weaker antibodies to these red blood cells. Subjects lacking corresponding anti-sheep inhibitors in their secretions generally produce stronger sheep red blood cell antibodies. There is a positive correlation between the formation of antibodies to HBsAg and strong agglutinating antibodies to sheep red blood cells, indicating that similar determinants may be found on HBsAg virus and on sheep red blood cells. No such correlation was found for anti-tetanus antibodies.


Peripheral neuropathy and myopathy. An experimental study of rats on alcohol and variable dietary thiamine.
The effects of variable dietary thiamine concentrations (deficient, normal, surplus) on the development of alcoholic neuromyopathy in rats exposed for 36 weeks to 10-25% (v/v) ethanol or water (control group) as the sole drinking fluid were studied by histological and electrophysiological methods. Abnormalities in the structure of the sciatic nerve (phagocytosis, myelin abnormalities, increase in nonspecific cholinesterase activity) and tibial muscles (angular atrophic fibers, group atrophy, fibre necrosis) developed more frequently in animals on diets deficient in thiamine than in animals on diets with normal or surplus thiamine, and more frequently in animals drinking alcohol and water than in those drinking water alone. No differences were observed between the different groups in the number of perivascular sympathetic nerves, in the motor nerve conduction velocities and in the muscle fibrillation potentials. Thus, thiamine deficiency, established as a significant reduction of red blood cell transketolase activity, seems to have a deleterious effect on the peripheral nerves and muscles. The effect is enhanced by the simultaneous consumption of ethyl alcohol.


[Psychotherapy in patients with fibromyalgia syndrome].
A guideline for the treatment and diagnostic procedures in fibromyalgia syndrome (FMS) was developed in cooperation with 10 German medical and psychological associations and 2 patient self-help groups. A systematic literature search including all controlled studies of evaluated multicomponent therapy was performed in the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-12/2006), PsychInfo (1966-12/2006) and Scopus (1980-12/ 2006). Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strengths of recommendations was done according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. Cognitive and operant behavioral therapy is strongly recommended (grade A). Guided imagery/hypnotherapy and written emotional disclosure are recommended (grade B). Psychotherapeutic programs tailored to FMS subgroups should be developed and tested.


Eicosapentaenoic acid enhanced apoptotic and oxidant effects of cisplatin via activation of TRPM2 channel in brain tumor cells.
Cisplatin (CiSP) induced-overload Ca2+ entry results in the increase of mitochondrial oxidative stress and apoptosis in the cancer cell. TRPM2 cation channel is gated by the cytosolic ADP-ribose (ADPR) and reactive oxygen species (ROS). The high content of polyunsaturated fatty acid (PUFA) in the brain is a main target of ROS. Eicosapentaenoic acid (EPA) induces oxidant action via the enhance of PUFA content in the glioblastoma (DBTRG) cells. We hypothesized that a combination of CiSP and EPA may offer a potential therapy in the DBTRG cell by exerting the antitumor, oxidant, and apoptotic actions and stimulating Ca2+ influx and TRPM2 activity. In the DBTRG cells, we induced four groups as control, EPA (30 μM for 24 h), CiSP (25 μM for 24 h), and CiSP + EPA. The CiSP-induced intracellular Ca2+ responses to the TRPM2 activation were increased in the DBTRG cells from coming H2O2 and ADPR. The responses were decreased in the cells by the inhibitions of TRPM2 (ACA and 2/APB) and PARP/1 (DPQ and PJ34). The incubation of EPA further increased the intracellular Ca2+ responses, mitochondria function, and the generation of ROS in the DBTRGs. After the treatment of EPA, lipid peroxidation, apoptosis, cell death, caspase -3, -8, and -9 levels were further increased in the DBTRG, although the levels of glutathione, glutathione peroxidase, cell numbers, and cell viability were further decreased in the cells. In summary, anticancer, apoptotic, and oxidant actions of CiSP were further increased via the activation of TRPM2 channel in the DBTRGs by the treatment of EPA. Hence, TRPM2 stimulation via EPA could be used as an effective agent in the treatment of glioblastoma tumors with CiSP.


Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review.
Symptomatic venous thromboembolism (VTE) after total or partial knee arthroplasty (TPKA) and after total or partial hip arthroplasty (TPHA) are proposed patient safety indicators, but its incidence prior to discharge is not defined. To establish a literature-based estimate of symptomatic VTE event rates prior to hospital discharge in patients undergoing TPHA or TPKA. Search of MEDLINE, EMBASE, and the Cochrane Library (1996 to 2011), supplemented by relevant articles. Reports of incidence of symptomatic postoperative pulmonary embolism or deep vein thrombosis (DVT) before hospital discharge in patients who received VTE prophylaxis with either a low-molecular-weight heparin or a subcutaneous factor Xa inhibitor or oral direct inhibitor of factors Xa or IIa. Meta-analysis of randomized clinical trials and observational studies that reported rates of postoperative symptomatic VTE in patients who received recommended VTE prophylaxis after undergoing TPHA or TPKA. Data were independently extracted by 2 analysts, and pooled incidence rates of VTE, DVT, and pulmonary embolism were estimated using random-effects models. The analysis included 44,844 cases provided by 47 studies. The pooled rates of symptomatic postoperative VTE before hospital discharge were 1.09% (95% CI, 0.85%-1.33%) for patients undergoing TPKA and 0.53% (95% CI, 0.35%-0.70%) for those undergoing TPHA. The pooled rates of symptomatic DVT were 0.63% (95% CI, 0.47%-0.78%) for knee arthroplasty and 0.26% (95% CI, 0.14%-0.37%) for hip arthroplasty. The pooled rates for pulmonary embolism were 0.27% (95% CI, 0.16%-0.38%) for knee arthroplasty and 0.14% (95% CI, 0.07%-0.21%) for hip arthroplasty. There was significant heterogeneity for the pooled incidence rates of symptomatic postoperative VTE in TPKA studies but less heterogeneity for DVT and pulmonary embolism in TPKA studies and for VTE, DVT, and pulmonary embolism in TPHA studies. Using current VTE prophylaxis, approximately 1 in 100 patients undergoing TPKA and approximately 1 in 200 patients undergoing TPHA develops symptomatic VTE prior to hospital discharge.


The effect of gender equality on happiness: Statistical modeling and analysis.
In this article, the researcher presents linear regression models that describe how five gender-equality indexes affect individuals' perceptions of well-being and happiness, controlling for their economic income and weighed by the population of the countries that contribute to the models. The logical premise of this study is that gender equality is not only favorable for women, but it is also conducive to fostering the greatest level of happiness for all people. The researcher believes that most findings confirmed this assumption and the opinion of John Stuart Mill regarding gender equality, while two exceptions are explained by social quality theory and the male breadwinner model.


Isolation of Compounds.
Plants are the storehouse of many chemical compounds that possess various biological activities. Identification of these compounds becomes critical in understanding the exact mechanism behind the therapeutic potential of these plants. Screening and isolation of compounds from plants important to human health involves various methods that need careful handling and attention. A detailed method of isolation using thin layer chromatography (TLC) and column is explained.


Breastfeeding and neurological outcome at 42 months.
This study investigated the effect of early feeding mode on the neurological condition at 42 months. For this purpose, healthy pregnant women were recruited in Groningen and Rotterdam, The Netherlands. Children were healthy and born at term. At 42 months, the children were neurologically examined by means of the Touwen/Hempel technique. In addition to the clinical diagnosis, the neurological findings were interpreted in terms of optimality. Special attention was paid to the quality of movements in terms of fluency. In total, 200 (51%) exclusively breastfed(for > or = 6 weeks) and 194 (49%) formula-fed children were studied. Twelve (3%) 42-month-old children were considered to be neurologically mildly abnormal and 1 child was diagnosed as abnormal. No effect of the type of feeding was found on the clinical diagnosis or the neurological optimality. After adjustments for study centre and social, obstetric, perinatal and neonatal neurological differences, a beneficial effect of breastfeeding on the fluency of movements was found (odds ratio for non-optimal fluency 0.56; 95% confidence interval 0.37-0.85). The prolongation of full breastfeeding beyond 6 weeks did not influence the quality of movements. In conclusion, among Dutch preschool children, there was a small advantageous effect of full breastfeeding during the first 6 weeks of life on the fluency of movements.


Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids.
To improve the properties of cytotoxic triterpenoid acids 1-5, a large set of hydrophilic esters was synthesized. We choose betulinic acid (1), dihydrobetulinic acid (2), 21-oxoacid 3 along with highly active des-E lupane acids 4 and 5 as a model set of compounds for esterification of which the properties needed to be improved. As ester moieties were used - methoxyethanol and 2-(2-methoxyethoxy)ethanol and glycolic unit (type a-d), pyrrolidinoethanol, piperidinoethanol and morpholinoethanol (type f-h), and monosaccharide groups (type i-l). As a result, 56 triterpenic esters (49 new compounds) were obtained and their cytotoxicity on four cancer cell lines and normal human fibroblasts was tested. All new compounds were fully soluble at all tested concentrations, which used to be a problem of the parent compounds 1 and 2. 16 compounds had IC50 < 10 μM on at least one cancer cell line, 12 compounds had cytotoxicity of <10 μM against at least three of four tested cancer cell lines. The highest activity was found for compound 3c (1.8 μM on MCF7, 2.8 μM on HeLa, and 1.6 μM on G-361 cells) which also had no toxicity on non-cancerous BJ fibroblasts at the highest tested concentration (50 μM). High selective cytotoxicity was also found in compounds 1k, 2k, 3c, and 3i that are ideal candidates for drug development. Therefore, more studies to identify the mechanism of action were performed in case of 1k, 3c, and 3g such as effects on cell cycle and apoptosis. It was found that compounds 3c and 3g can induce apoptosis via caspase-3 activation and modulation of protein Bcl-2 in G-361 cells. In conclusion, compounds 1k, 3c, and 3g show high and selective cytotoxicity, therefore they are significantly better candidates for anti-cancer drug development than the parent acids 1-5.


Stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1.
The stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1 has been determined. 3H-Labeled TF1 was allowed to bind to a 32P-labeled DNA fragment containing a TF1 binding site. Multiple TF1-DNA complexes were resolved from each other and from unbound DNA by native gel electrophoresis. DNA-protein complexes were cut from polyacrylamide gels, and the amounts of 3H and 32P contained in each slice were measured. A ratio of 1.12 +/- 0.06 TF1 dimer/DNA molecule was calculated for the fastest-migrating TF1-DNA complex. We conclude that TF1 has a DNA-binding unit of one dimer. More slowly migrating complexes are apparently formed by serial addition of single TF1 dimers.


Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment.
A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM. This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival. A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1-0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009). A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM.


Application of Schrödinger equation in quantum well of Cu2ZnSnS4 quaternary semiconductor alloy.
An approximate solution of the radial Schrödinger equation is obtained with a generalized group of potentials in the presence of both magnetic field and potential effect using supersymmetric quantum mechanics and shape invariance methodology. The energy bandgap of the generalized group of potentials was calculated for s - wave cases at the ground state. By varying the numerical values of the potential strengths, the energy band gap of Hellmann's potential and Coulomb-Hulthẻn potential respectively were obtained. It is noted that the inclusion of the potential effect greatly affects the accuracy of the results. Our calculated results are in agreement and better than the existing calculated results. The present results approximately coincide with the standard bandgap of Cu2ZnSnS4 (CZTS).


High-performance carboxymethyl cellulose-based hydrogel film for food packaging and preservation system.
Most traditional food packaging and preservation films suffer from limited stretchability and relatively simple functionality, which severely restricts their practical application. In this study, a highly stretchable and versatile sodium carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA)/poly(ethylene imine) (PEI)/tannic acid (TA) hydrogel film was elaborately designed and demonstrated as an efficient food packaging and preservation system. The dynamic reversible non-covalent within three-dimensional (3D) network structures served as sacrificial bonds to dissipate the loaded energy and endowed the hydrogel film with excellent elongation ~400 %, which is much larger than that of conventional food packaging films (<50 %). Furthermore, the optimized CMC/PVA/PEI/TA3 hydrogel film delivers versatile performances, including self-healing, whole UV-blocking (<400 nm), strong adhesive strength (234.08 KPa), antioxidation virtues, oxygen barrier (32.64 cm3*μm/(m2*d*KPa)) and water vapor barrier (642.92 g/(m2*24 h)). Notably, the shelf life of fresh strawberries, mangoes, and cherries was prolonged by at least one week under ambient conditions when the packaging box was covered by the fabricated CMC/PVA/PEI/TA3 film. Thus, our work not only provides a highly stretchable and versatile hydrogel film but also boosts the in-depth comprehension and rational design of robust food packaging and preservation films.