CCR1 blockade reduces interstitial inflammation and fibrosis in mice with glomerulosclerosis and nephrotic syndrome.
CC chemokines mediate leukocyte infiltration into inflamed tissue. We have recently shown that blockade of the CC chemokine receptor CCR1 reduces interstitial inflammation and fibrosis in murine obstructive nephropathy. However, it is not known whether CCR 1 blockade is protective in progressive renal injury associated with severe proteinuria. We therefore studied the effect of the small-molecule CCR1 antagonist BX471 in a murine model of adriamycin-induced focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome and progressive interstitial inflammation and fibrosis. Adriamycin nephropathy with persistent proteinuria was induced in male BALB/c mice by two intravenous injections of adriamycin (13 mg/kg) at day 0 and 14. BX471 treatment was started at day 14 when proteinuria and interstitial inflammation had developed. At 6 weeks, renal histology was studied by morphometry and immunohistochemistry. At week 6, adriamycin-treated mice showed FSGS, associated with tubulointerstitial injury consisting of tubular dilation and atrophy, interstitial leukocyte infiltration, and fibrosis. The mRNA expression of CCR1 and CC chemokines, including the CCR1 ligands CCL3 (MIP-1alpha) and CCL5 (RANTES), was up-regulated in diseased kidneys, with a prominent interstitial expression of CCL5. Compared to vehicle-treated controls BX471 significantly reduced the amount of macrophages and T lymphocytes in interstitial lesions by 51% and 22%, respectively. Markers of renal fibrosis such as interstitial fibroblasts (48%) and interstitial volume (23%) were significantly reduced by BX471 treatment. In contrast, the extent of proteinuria and glomerular sclerosis was not affected by BX471 treatment. Blockade of CCR1 substantially reduced interstitial leukocyte accumulation and the subsequent renal fibrosis in a murine model of nephrotic syndrome and FSGS. These findings support a role for CCR1 in interstitial leukocyte recruitment and suggest that CCR1 blockade might be a new therapeutic strategy in progressive nephropathies such as FSGS.


Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies.
To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based neuroimaging studies (morphometric, functional, spectroscopy). We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords (1) psychostimulants or methylphenidate or amphetamine, and (2) neuroimaging or MRI or fMRI, and (3) ADHD or ADD or attention-deficit/hyperactivity disorder or attention deficit hyperactivity disorder. We included only English language articles with new data from case-control or placebo controlled studies that examined attention-deficit/hyperactivity disorder (ADHD) subjects on and off psychostimulants (as well as 5 relevant review articles). We combined details of study design and medication effects in each imaging modality. We found 29 published studies that met our criteria. These included 6 structural MRI, 20 functional MRI studies, and 3 spectroscopy studies. Methods varied widely in terms of design, analytic technique, and regions of the brain investigated. Despite heterogeneity in methods, however, results were consistent. With only a few exceptions, the data on the effect of therapeutic oral doses of stimulant medication suggest attenuation of structural and functional alterations found in unmedicated ADHD subjects relative to findings in controls. Despite the inherent limitations and heterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and controls. These medication-associated brain effects parallel, and may underlie, the well-established clinical benefits.


Effects of triamcinolone acetonide, sodium hyaluronate, amikacin sulfate, and mepivacaine hydrochloride, alone and in combination, on morphology and matrix composition of lipopolysaccharide-challenged and unchallenged equine articular cartilage explants.
To evaluate the effects of triamcinolone acetonide (TA), sodium hyaluronate (HA), amikacin sulfate (AS), and mepivacaine hydrochloride (MC) on articular cartilage morphology and matrix composition in lipopolysaccharide (LPS)-challenged and unchallenged equine articular cartilage explants. 96 articular cartilage explants from 4 femoropatellar joints of 2 adult horses. Articular cartilage explants were challenged with LPS (100 ng/mL) or unchallenged for 48 hours, then treated with TA, HA, AS, and MC alone or in combination for 96 hours or left untreated. Cartilage extracts were analyzed for glycosaminoglycan (GAG) content by dimethyl-methylene blue assay (ng/mg of dry wt). Histomorphometric quantification of total lacunae, empty lacunae, and lacunae with pyknotic nuclei was recorded for superficial, middle, and deep cartilage zones. LPS induced a significant increase in pyknotic nuclei and empty lacunae. Treatment with TA or HA significantly decreased empty lacunae (TA and HA), compared with groups without TA or HA, and significantly decreased empty lacunae of LPS-challenged explants, compared with untreated explants. Treatment with AS or MC significantly increased empty lacunae in unchallenged explants, and these effects were attenuated by TA. Treatment with MC significantly increased empty lacunae and pyknotic nuclei and, in combination with LPS, could not be attenuated by TA. Content of GAG did not differ between unchallenged and LPS-challenged explants or among treatments. Treatment with TA or HA supported chondrocyte morphology in culture and protected chondrocytes from toxic effects exerted by LPS, AS, and MC.


[Detection and prevalence of risk factors to develop chronic noninfectious diseases in the organized population group in West Siberia].
To study prevalence of factors of risk to develop chronic noninfectious diseases (CNID) in the population of railroad men of the West Siberia and these factors association with ischemic heart disease (IHD) and cerebrovascular disorders. A one-stage sample epidemiological survey of CNID risk factors enrolled 10,677 railroad men of West Siberia aged 20-65 years. The risk factors were: arterial hypertension (AH), smoking, hypercholesterolemia (HCE), obesity, low physical activity (LPA), impaired flucose tolerance (IGT). High incidence of AH, HCE, smoking, obesity, LPA, IGT as well as nutritional shift to food rich in fat was found. The results of the regression multivariate analysis show that such factors as AH, HCE and smoking are associated with and contribute much to high risk of IHD; AH, severe HCE and obesity contribute to high risk of cerebral pathology. Further studies are needed of CNID prevalence among railroad men. Measures of primary multifactor prevention should be designed and introduced to correct the above risk factors.


Comparison between gutta-percha and resilon removal using two different techniques in endodontic retreatment.
This study compared the remaining filling material and working time when removing gutta-percha/AH 26 and Resilon/Epiphany from root filled extracted teeth. The root fillings were removed using chloroform and two different rotary systems (K3 and Liberator files). The amount of residual filling material on the canal walls was imaged and measured using image analyzer software. The group filled with Resilon/Epiphany and retreated with K3 files demonstrated the least residual filling material on the walls (p < 0.05). There was no statistically significant difference between the gutta-percha/AH26 and Resilon/Epiphany groups when the Liberator files were used (p > 0.05). In the groups filled with Resilon/Epiphany, the filling was removed faster than groups filled with gutta-percha/AH 26 (p < 0.05). K3 rotary system was faster than Liberator to remove both gutta-percha and Resilon (p < 0.05). Resilon/Epiphany was effectively removed with K3 or Liberator rotary files.


Femoral lengthening in achondroplasia: magnitude of lengthening in relation to patterns of callus, stiffness of adjacent joints and fracture.
Extensive limb lengthening may be indicated in achondroplastic patients who wish to achieve a height within the normal range for their population. However, increasing the magnitude of lengthening is associated with further complications particularly adjacent joint stiffness and fractures. We studied the relationship between the magnitude of femoral lengthening and callus pattern, adjacent joint stiffness and fracture of the regenerate bone in 40 femoral lengthenings in 20 achondroplastic patients. They were divided into two groups; group A had lengthening of less than 50% and group B of more than 50% of their initial femoral length. The patterns of radiological callus formation were classified according to shape, type and features. The incidence of callus features, knee stiffness and regenerate bone fracture were analysed in the two groups. Group B was associated with an increased incidence of concave, lateral and central callus shapes, adjacent joint and stiffness and fracture. Statistically, the incidence of stiffness in adjacent joints and regenerate bone fracture was significantly associated with the magnitude of lengthening. We suggest that careful radiological assessment of the patterns of callus formation is a useful method for the evaluation and monitoring of regenerate bone.


Generalized eruptive keratoacanthomas.
We describe the case of a 71-year-old-woman with a 6-year history of generalized eruptive keratoacanthomas on the extremities. We review the diagnostic clinical and histologic features of the rare Grzybowski variant of generalized eruptive keratoacanthoma. The course of this disease is chronic and often demonstrates a poor response to therapy.


Amino-acid sequence of human alpha 2-antiplasmin.
The amino-acid sequence of human alpha 2-antiplasmin was determined by Edman degradation of peptides purified from CNBr, tryptic and chymotryptic digests. Of the total sequence of 452 amino acids of mature alpha 2-antiplasmin, as deduced from the cDNA sequence [Holmes et al. (1987) J. Biol. Chem. 262, 1659-1664], 444 residues were identified by amino-acid sequencing. Two differences were found between the peptide and cDNA analyses (Gly instead of Leu at position 10 and Gly instead of Ser at position 369). alpha 2-Antiplasmin contains two disulfide bridges (Cys64-Cys104 and Cys31-Cys113) and four glucosamine-based carbohydrate chains attached to Asn87, Asn256, Asn270 and Asn277. alpha 2-Antiplasmin is homologous with 12 other proteins belonging to the serine protease inhibitor (serpin) superfamily.


[Clinical case of tandem translocation between chromosomes 13 and 15].
Cytogenetic and clinical examination of a patient (girl) with tandem translocation between chromosomes 13 and 15 was carried out. Translocation resulted in a partial loss of the genetic material between chromosomes 15 and 13. The problem on karyotype and phenotype relations with the loss of the respective chromosome regions is discussed.


[Treatment of carotid cavernous fistulas].
The diagnosis and treatment of carotid cavernous fistulas (CCF) is an interdisciplinary challenge for both ophthalmologists and interventional neuroradiologists. According to the clinical signs and symptoms the tentative diagnosis is made by the ophthalmologist. It is the task of the neuroradiologist to ascertain this diagnosis by intra-arterial angiography. If a fistula is suspected this invasive diagnostic procedure is indispensable, not only to establish the diagnosis but also to classify those types of fistula with an unfavourable spontaneous course possibly resulting in intracranial haemorrhage. The indication for therapy is based on the clinical symptoms and the angiographic findings. In a number of cases no therapy is required. Since a fistula may change over time, these patients have to be under close ophthalmological surveillance. In many patients a conservative therapeutic approach with manual compression of the carotid artery is sufficient as a fIrst step. Invasive treatment is performed via the endovascular approach in almost all cases. Direct CCF are predominantly treated transarterially with detachable balloons and/or coils. Recently, intracranial stents have been used increasingly. The embolisation of indirect CCF is most effective using the transvenous access with coils. There are several approaches to the cavernous sinus. The interventional occlusion of CCF is nowadays a very effective treatment associated with a comparatively high cure rate and low incidence of complications. By close cooperation between ophthalmologists and neuroradiologists the patients can be protected against visual loss, the development of a secondary glaucoma, and, most importantly, against intracranial haemorrhage.


Review of patients with Strongyloides stercoralis infestation in a tertiary teaching hospital, Kelantan.
Strongyloides stercoralis is an intestinal nematode infecting humans. The actual prevalence of infestation with this parasite in our setting is not well established. Thus, this study was conducted to determine the age, sex and co-morbid conditions among patients with S. stercoralis infestation as well as to study the common manifestations of strongyloidiasis in our patients. Records of patients with positive S. stercoralis larvae from January 2000 to December 2012 in Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan were reviewed. Ten patients were male and two were female. Their ages ranged from 19 to 78 years old. The majority (92%) of cases, presented with intestinal symptoms and 50% with moderate to severe anaemia. Thirty percent of cases had extraintestinal manifestations such as cough, sepsis and pleural effusion. Ninety-two percent of the patients had a comorbid illness. Most patients were immunocompromised, with underlying diabetes mellitus, retroviral disease, lymphoma and steroid therapy contributing to about 58% of cases. Only 58% were treated with anti-helminthic drugs. Strongyloidiasis is present in our local setting, though the prevalence could be underestimated.


Racial and Ethnic Differences in Pediatric Pulmonary Hypertension: An Analysis of the Pediatric Pulmonary Hypertension Network Registry.
To investigate racial and ethnic differences in pulmonary hypertension subtypes and survival differences in a pediatric population. This was a retrospective analysis of a cohort of patients with pulmonary hypertension (aged ≤18 years) enrolled in the Pediatric Pulmonary Hypertension Network registry between 2014 and 2018, comprising patients at eight Pediatric Centers throughout North America (n = 1417). Among children diagnosed after the neonatal period, pulmonary arterial hypertension was more prevalent among Asians (OR, 1.83; 95% CI, 1.21-2.79; P = .0045), lung disease-associated pulmonary hypertension among blacks (OR, 2.09; 95% CI, 1.48-2.95; P < .0001), idiopathic pulmonary arterial hypertension among whites (OR, 1.58; 95% CI, 1.06-2.41; P = .0289), and pulmonary veno-occlusive disease among Hispanics (OR, 6.11; 95% CI, 1.34-31.3; P = .0184). Among neonates, persistent pulmonary hypertension of the newborn (OR, 4.07; 95% CI, 1.54-10.0; P = .0029) and bronchopulmonary dysplasia (OR, 8.11; 95% CI, 3.28-19.8; P < .0001) were more prevalent among blacks, and congenital diaphragmatic hernia was more prevalent among whites (OR, 2.29; 95% CI, 1.25-4.18; P = .0070). An increased mortality risk was observed among blacks (HR, 1.99; 95% CI, 1.03-3.84; P = .0396), driven primarily by the heightened mortality risk among those with lung disease-associated pulmonary hypertension (HR, 2.84; 95% CI, 1.15-7.04; P = .0241). We found significant racial variability in the prevalence of pulmonary hypertension subtypes and survival outcomes among children with pulmonary hypertension. Given the substantial burden of this disease, further studies to validate phenotypic differences and to understand the underlying causes of survival disparities between racial and ethnic groups are warranted.


Insights into the dynamics and control of COVID-19 infection rates.
This work aims to model, simulate and provide insights into the dynamics and control of COVID-19 infection rates. Using an established epidemiological model augmented with a time-varying disease transmission rate allows daily model calibration using COVID-19 case data from countries around the world. This hybrid model provides predictive forecasts of the cumulative number of infected cases. It also reveals the dynamics associated with disease suppression, demonstrating the time to reduce the effective, time-dependent, reproduction number. Model simulations provide insights into the outcomes of disease suppression measures and the predicted duration of the pandemic. Visualisation of reported data provides up-to-date condition monitoring, while daily model calibration allows for a continued and updated forecast of the current state of the pandemic.


Autonomous reinforcement learning with experience replay.
This paper considers the issues of efficiency and autonomy that are required to make reinforcement learning suitable for real-life control tasks. A real-time reinforcement learning algorithm is presented that repeatedly adjusts the control policy with the use of previously collected samples, and autonomously estimates the appropriate step-sizes for the learning updates. The algorithm is based on the actor-critic with experience replay whose step-sizes are determined on-line by an enhanced fixed point algorithm for on-line neural network training. An experimental study with simulated octopus arm and half-cheetah demonstrates the feasibility of the proposed algorithm to solve difficult learning control problems in an autonomous way within reasonably short time.


Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover.
Apart from genetic alterations, development and progression of colorectal cancer has been linked to influences from nutritional intake, hyperalimentation, and cellular metabolic changes that may be the basis for new diagnostic and therapeutic approaches. However, in contrast to genomics and proteomics, comprehensive metabolomic investigations of alterations in malignant tumors have rarely been conducted. In this study we investigated a set of paired samples of normal colon tissue and colorectal cancer tissue with gas-chromatography time-of-flight mass-spectrometry, which resulted in robust detection of a total of 206 metabolites. Metabolic phenotypes of colon cancer and normal tissues were different at a Bonferroni corrected significance level of p=0.00170 and p=0.00005 for the first two components of an unsupervised PCA analysis. Subsequent supervised analysis found 82 metabolites to be significantly different at p<0.01. Metabolites were connected to abnormalities in metabolic pathways by a new approach that calculates the distance of each pair of metabolites in the KEGG database interaction lattice. Intermediates of the TCA cycle and lipids were found down-regulated in cancer, whereas urea cycle metabolites, purines, pyrimidines and amino acids were generally found at higher levels compared to normal colon mucosa. This study demonstrates that metabolic profiling facilitates biochemical phenotyping of normal and neoplastic colon tissue at high significance levels and points to GC-TOF-based metabolomics as a new method for molecular pathology investigations.


Molecular, biological, and in vivo characterization of the guinea pig cytomegalovirus (CMV) homologs of the human CMV matrix proteins pp71 (UL82) and pp65 (UL83).
We recently identified the genes encoding the guinea pig cytomegalovirus (GPCMV) homologs of the upper and lower matrix proteins of human CMV, pp71 (UL82) and pp65 (UL83), which we designated GP82 and GP83, respectively. Transient-expression studies with a GP82 plasmid demonstrated that the encoded protein targets the nucleus and that the infectivity and plaquing efficiency of cotransfected GPCMV viral DNA was enhanced by GP82. The transactivation function of GP82 was not limited to GPCMV, but was also observed for a heterologous virus, herpes simplex virus type 1 (HSV-1). This was confirmed by its ability to complement the growth of an HSV-1 VP16 transactivation-defective mutant virus in an HSV viral DNA cotransfection assay. Study of a GP82 "knockout" virus (and its attendant rescuant), generated on a GPCMV bacterial artificial chromosome construct, confirmed the essential nature of the gene. Conventional homologous recombination was used to generate a GP83 mutant to examine the role of GP83 in the viral life cycle. Comparison of the one-step growth kinetics of the GP83 mutant (vAM409) and wild-type GPCMV indicated that GP83 protein is not required for viral replication in tissue culture. The role of GP83 in vivo was examined by comparing the pathogenesis of wild-type GPCMV, vAM409, and a control virus, vAM403, in guinea pigs. The vAM409 mutant was significantly attenuated for dissemination in immunocompromised strain 2 guinea pigs, suggesting that the GP83 protein is essential for full pathogenicity in vivo.


Sex Differences in the Use of Cardiovascular Drugs: A Survey of Patients in a Single Center.
Patients and medical professionals have a common misconception that cardiovascular diseases (CVD) predominantly affect men, which can lead to less prescribing of cardiovascular drugs to women. This study examined whether there were sex differences in the administration of cardiovascular (CV) drugs in patients admitted to the intensive care unit of the Internal Medicine Clinic of Foča University Hospital (ICFUH). The study comprised 332 patients hospitalized at the ICFUH from January 1st to June 30th, 2019. The following data on leading CVD and risks related to CV drug administration were collected: age, hyperlipidemia (HLD), diabetes mellitus (DM), chronic kidney disease (CKD), liver disease (LD), heart failure (HF), hypertension (HTN), myocardial infarction (MI), and stroke (S). The amount of the CV drugs of interest (statins, antiplatelet drugs, calcium channel blockers, ACE inhibitors, beta blockers, diuretics) administered during hospitalization was expressed as the Defined Daily Dose (DDD)/100 bed-days (BD) for patients of both sexes separately. During hospitalization in the intensive care unit of ICFUH, female patients were less likely to be treated with statins than male patients (30.1 vs. 57.5 DDD/100 BD, P<0.05). There was no difference between sexes regarding the use of antihypertensive drugs. Women were less likely to be treated by antiplatelet therapy, more precisely by acetylsalicylic acid (30.4 vs. 36.9 DDD/100 BD, P<0.05). Our study indicates that there were sex differences in CV drug administration in ICFUH. Presuming that drugs used during hospitalization were at least partially a continuation of the previous therapy prescribed by the family doctor, it is possible that such differences exist in primary care.


Epidermal Cysts: A Clinicopathological Analysis with Emphasis on Unusual Findings.
Epidermoid cysts, one of the common benign intradermal or subcutaneous tumors commonly result from the trauma to the pilosebaceous unit in the hair bearing area. In areas without hair, these cysts are considered implantation and proliferation of squamous epithelium into the dermis due to injury. The aim is to evaluate the clinicopathological details with emphasis on unusual findings related to epidermoid cysts. This is a retrospective cross-sectional study carried out over 2 years. A total of 103 cases of epidermoid cysts were included in the study. The clinical details such as age, gender, sites, and dimensions were noted. The histopathological findings were evaluated and correlated with the clinical findings. The highest incidence was observed in the age group of 21-30 years (23.3%, 24/103) and the most common affected region was the head and neck region (32%, 33/103). The size of cysts ranged from 0.3 to 9 cm in diameter with a mean of 2.1 cm. The unusual sites observed in this study were four at the left sole, two at right sole, two at prepuce, and one each at the right finger, left palm, and oral cavity. Histopathological findings included rupture of epidermoid cysts with giant cell reaction, melanin pigmentation, and association with other pathologies such as keloid and lipoma. Epidermoid cysts are common benign intradermal or subcutaneous tumors, but they can have unusual presentations and histopathological findings. Epidermoid cysts need early diagnosis and treatment as they can cause cosmetic and functional impairment.


Clinical Management of Women with Monogenic Diabetes During Pregnancy.
Monogenic diabetes accounts for 1-2% of all diabetes cases, but is frequently misdiagnosed as type 1, type 2, or gestational diabetes. Accurate genetic diagnosis directs management, such as no pharmacologic treatment for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose sulfonylureas for KATP channel-related diabetes. While diabetes treatment is defined for the most common causes of monogenic diabetes, pregnancy poses a challenge to management. Here, we discuss the key issues in pregnancy affected by monogenic diabetes. General recommendations for pregnancy affected by GCK-MODY determine need for maternal insulin treatment based on fetal mutation status. However, a recent study suggests macrosomia and miscarriage rates may be increased with this strategy. Recent demonstration of transplacental transfer of sulfonylureas also raises questions as to when insulin should be initiated in sulfonylurea-responsive forms of monogenic diabetes. Pregnancy represents a challenge in management of monogenic diabetes, where factors of maternal glycemic control, fetal mutation status, and transplacental transfer of medication must all be taken into consideration. Guidelines for pregnancy affected by monogenic diabetes will benefit from large, prospective studies to better define the need for and timing of initiation of insulin treatment.


A technique for the combination of clearing, staining, and injecting small mammals.
A combined method for clearing soft tissues, staining cartilage and bone, and injecting the vascular system of small mammals was developed using Mus musculus (house mouse). Mammalian muscle tissue remains milky or even opaque after "clearing" by previous techniques due to the relatively high content of intramuscular fat. A method employing chloroform-ethanol successfully renders soft tissues of mammalian specimens translucent without damaging or bleeding color from the latex injected in the circulatory system. Resulting specimens yield an excellent view of the skeletal system and the injected vascular system without obstruction by opaque tissues or disruption by physical removal of connective tissue.


Low rate of microsatellite instability in young patients with adenomas: reassessing the Bethesda guidelines.
Screening adenomas for microsatellite instability (MSI) in patients younger than 40 yr of age has been recommended by the Bethesda Guidelines as a means of identifying patients at risk for hereditary nonpolyposis colorectal cancer (HNPCC). We sought to determine the rate of MSI in adenomas removed from individuals under 40 yr of age over a 5-yr period in a university general gastroenterology practice. We identified patients between 18 and 39 yr of age with endoscopically removed adenomatous colorectal polyps. Patients with polyposis syndromes, inflammatory bowel disease, or colorectal carcinoma were excluded. A three-generation family history was obtained via telephone interview. Endoscopic and histology reports were reviewed. Adenomas were tested for MSI using the BAT26 and BAT40 microsatellite markers, and expression of the MSH2 and MLH1 proteins was assessed by immunostaining. A total of 34 patients had 46 adenomas removed endoscopically. Out of 34 patients, 14 (41%) had a family history of colorectal cancer and 3 were from Amsterdam criteria positive families. A total of 28 of 46 adenomas (61%) were distal to the splenic flexure. Polyps ranged in size from 2 to 20 mm and averaged 6.6 mm. Five polyps (11%) were tubulovillous adenomas, and the remainder were tubular adenomas. None of the polyps were serrated adenomas and none demonstrated high-grade dysplasia. Among the 40 adenomas available for testing, none demonstrated MSI using either BAT26 (0/40) or BAT40 (0/21), nor did any of the polyps tested demonstrate loss of either MSH2 or MLH1 expression (0/16). Screening adenomas from patients younger than 40 yr of age for MSI was ineffective in identifying potentially new cases of HNPCC. New strategies that improve on the current clinical and molecular screening methods should be developed so that at-risk individuals can be identified and referred for germline testing before developing their first cancer.


From pitfall to misdiagnosis and life-threatening treatment.
Sixty-four-section multidetector computed tomography angiography (64-SMCTA) is increasingly used for screening and surgical planning of ruptured intracranial aneurysms due to its high sensitivity and positivity and it is less invasive than digital subtraction angiography (DSA). Combination of both is the best tool when diagnosis is inconclusive. Sometimes the use of 64-SMCTA alone may cause interpretation pitfall and unnecessary life-threatening treatment. This case report is about 64-SMCTA interpretation pitfall, a false positive result that occasioned surgery for clipping an intracranial aneurysm which was not found during surgical procedure. The patient survived the life-threatening surgery and she has been doing well over the last two years. A perceptual error and lack of conspicuity due to some limitations of the scanner to disclose a normal anatomic variant were responsible for this false positive. Whenever 64-SMCTA renders inconspicuous images, this result must be seen as inconclusive and hence a meticulous differential diagnosis and DSA are required before any surgical planning.


Oxidative stress impairs the heat stress response and delays unfolded protein recovery.
Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability. Pretreatment of hydrogen peroxide (H(2)O(2)) specifically and highly sensitized cells to heat stress, and enhanced loss of mitochondrial membrane potential. H(2)O(2) exposure impaired the HSP40/HSP70 induction as heat shock response (HSR) and the unfolded protein recovery, and enhanced eIF2alpha phosphorylation and/or XBP1 splicing, land marks of ER stress. These H(2)O(2)-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells. Importantly, thermal preconditioning blocked H(2)O(2)-mediated inhibitory effects on refolding activity and rescued HSF1 +/+ MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and refolding activity is crucial for H(2)O(2)-mediated enhanced heat sensitivity. H(2)O(2) blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance.


Rare Occurrence of the Left Maxillary Horizontal Third Molar Impaction, the Right Maxillary Third Molar Vertical Impaction and the Left Mandibular Third Molar Vertical Impaction with Inferior Alveolar Nerve Proximity in a 30 Year Old Female: A Case Report.
A combination of horizontal and vertical third molar impaction is a rare occurrence.When the tooth is unable to erupt to its proper position and fail to achieve a normal occlusion, it is known as impacted tooth. In this scientific article, case report of a female patient aged 30 years reported with acombination of horizontally and vertically impacted third molars in the maxilla and mandible has been presented. The treatment included surgical removal of the impacted teeth without any damage to underlying structures. Horizontal impaction of left maxillary third molar, vertical impaction of right maxillary third molar and left mandibular third molar is a rare occurrence. If symptomatic, surgical removal has to be planned as earlier as possible rather than late complications.


Molecular dynamics study of the solvation of an alpha-helical transmembrane peptide by DMSO.
A 10-ns molecular dynamics study of the solvation of a hydrophobic transmembrane helical peptide in dimethyl sulfoxide (DMSO) is presented. The objective is to analyze how this aprotic polar solvent is able to solvate three groups of amino acid residues (i.e., polar, apolar, and charged) that are located in a stable helical region of a transmembrane peptide. The 25-residue peptide (sMTM7) used mimics the cytoplasmic proton hemichannel domain of the seventh transmembrane segment (TM7) from subunit a of H(+)-V-ATPase from Saccharomyces cerevisiae. The three-dimensional structure of peptide sMTM7 in DMSO has been previously solved by NMR spectroscopy. The radial and spatial distributions of the DMSO molecules surrounding the peptide as well as the number of hydrogen bonds between DMSO and the side chains of the amino acid residues involved are extracted from the molecular dynamics simulations. Analysis of the molecular dynamics trajectories shows that the amino acid side chains are fully embedded in DMSO. Polar and positively charged amino acid side chains have dipole-dipole interactions with the oxygen atom of DMSO and form hydrogen bonds. Apolar residues become solvated by DMSO through the formation of a hydrophobic pocket in which the methyl groups of DMSO are pointing toward the hydrophobic side chains of the residues involved. The dual solvation properties of DMSO cause it to be a good membrane-mimicking solvent for transmembrane peptides that do not unfold due to the presence of DMSO.


Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties.
The spectral and metabolic properties of Rhodamine 123, a fluorescent cationic dye used to label mitochondria in living cells, were investigated in suspensions of isolated rat-liver mitochondria. A red shift of Rhodamine 123 absorbance and fluorescence occurred following mitochondrial energization. Fluorescence quenching of as much as 75% also occurred. The red shift and quenching varied linearly with the potassium diffusion potential, but did not respond to delta pH. These energy-linked changes were accompanied by dye uptake into the matrix space. Concentration ratios, in-to-out, approached 4000:1. A large fraction of internalized dye was bound. At concentrations higher than those needed to record these spectral changes, Rhodamine 123 inhibited ADP-stimulated (State 3) respiration of mitochondria (Ki = 12 microM) and ATPase activity of inverted inner membrane vesicles (Ki = 126 microM) and partially purified F1-ATPase (Ki = 177 microM). The smaller Ki for coupled mitochondria was accounted for by energy-dependent Rhodamine 123 uptake into the matrix. Above about 20 nmol/mg protein (10 microM), Rhodamine 123 caused rapid swelling of energized mitochondria. Effects on electron-transfer reactions and coupling were small or negligible even at the highest Rhodamine 123 concentrations employed. delta psi-dependent Rhodamine 123 uptake together with Rhodamine 123 binding account for the intense fluorescent staining of mitochondria in living cells. Inhibition of mitochondria ATPase likely accounts for the cytotoxicity of Rhodamine 123. At concentrations which do not inhibit mitochondrial function, Rhodamine 123 is a sensitive and specific probe of delta psi in isolated mitochondria.


Mechanisms of bradycardia-induced ventricular arrhythmias in myocardial ischemia and infarction.
Experimental and clinical cases have been described in which bradycardia, i.e., heart rates below 60 beats/min or slowing of the heart rate, resulted in lethal ventricular arrhythmias during various stages of myocardial ischemia and infarction. The present study was designed to determine the relationship of lethal ventricular arrhythmias and slow heart rates. In 18 dogs anesthetized with sodium pentobarbital, the left anterior descending (LAD) coronary artery was ligated. Standard ECGs, His bundle electrograms and composite electrograms from intramural and epicardial areas in ischemic and normal zones were recorded during the first 3 hours of ischemia. Vagosympathetic trunk stimulation caused varying degrees of slowing and bradycardia. Of the 18 dogs, slowing of the heart rate or marked bradycardia induced ventricular ectopic beats coupled to the sinus beats in two, sustained ventricular tachycardia in two, and ventricular fibrillation in two. In another group of six dogs studied 17-25 days after LAD ligation, one dog showed sustained ventricular tachycardia in response to vagal-induced bradycardia. In all acute or chronic cases of arrhythmias after LAD ligation, continuous electrical activity was recorded on one or more of the electrograms within or overlying the ischemic or infarcted zones. This bridging electrical activation, which is indicative of slow conduction, provided strong presumptive evidence for reentry as the mechanism of lethal or potentially lethal ventricular arrhythmias triggered by bradycardia in the setting of myocardial infarction.


Spatiotemporal chaos and the dynamics of coupled Langmuir and ion-acoustic waves in plasmas.
A simulation study is performed to investigate the dynamics of coupled Langmuir waves (LWs) and ion-acoustic waves (IAWs) in an unmagnetized plasma. The effects of dispersion due to charge separation and the density nonlinearity associated with the IAWs are considered to modify the properties of Langmuir solitons, as well as to model the dynamics of relatively large amplitude wave envelopes. It is found that the Langmuir wave electric field, indeed, increases by the effect of ion-wave nonlinearity (IWN). Use of a low-dimensional model, based on three Fourier modes, shows that a transition to temporal chaos is possible, when the length scale of the linearly excited modes is larger than that of the most unstable ones. The chaotic behaviors of the unstable modes are identified by the analysis of Lyapunov exponent spectra. The space-time evolution of the coupled LWs and IAWs shows that the IWN can cause the excitation of many unstable harmonic modes and can lead to strong IAW emission. This occurs when the initial wave field is relatively large or the length scale of IAWs is larger than the soliton characteristic size. Numerical simulation also reveals that many solitary patterns can be excited and generated through the modulational instability of unstable harmonic modes. As time goes on, these solitons are seen to appear in the spatially partial coherence state due to the free ion-acoustic radiation as well as in the state of spatiotemporal chaos due to collision and fusion in the stochastic motion. The latter results in the redistribution of initial wave energy into a few modes with small length scales, which may lead to the onset of Langmuir turbulence in laboratory as well as space plasmas.


Testing the psychosis continuum: differential impact of genetic and nongenetic risk factors and comorbid psychopathology across the entire spectrum of psychosis.
A growing number of studies demonstrate high rates of subthreshold psychotic experiences, but there is considerable heterogeneity in rates due to study cohort and design factors, obscuring how prevalent psychotic experiences may or may not relate to rare psychotic disorders. In a representative general population sample (n = 4011) in Izmir, Turkey, the full spectrum of expression of psychosis was categorized across 5 groups representing (1) absence of psychosis, (2) subclinical psychotic experiences, (3) low-impact psychotic symptoms, (4) high-impact psychotic symptoms, and (5) full-blown clinical psychotic disorder and analyzed for continuity and discontinuity in relation to (1) other symptom dimensions associated with psychotic disorder and (2) proxies of genetic and nongenetic etiology. Results were tested for linear and extralinear contrasts between clinical and nonclinical and between disorder and nondisorder expression of psychosis. Demographic variables, indexing premorbid social adjustment and socioeconomic status, impacted mostly linearly; proxy variables of genetic loading (more or more severely affected relatives) impacted in a positive extralinear fashion; environmental risk factors sometimes impacted linearly (urbanicity and childhood adversity) and sometimes extralinearly (cannabis), occasioning a disproportional shift in risk at the clinical disorder end of the spectrum. Affective symptoms were associated with a disproportionally higher risk below the disorder threshold, whereas a disproportionally higher risk above the threshold was associated with psychotic symptom load, negative symptoms, disorganization, and visible signs of mental illness. Liability associated with respectively affective and nonaffective symptom domains, in interaction with environmental risks, may operate by impacting differentially over a quasi-continuous extended psychosis phenotype in the population.


Trends in low birth weight infants and changes in Baltimore's childbearing population, 1972-77.
Linked birth and death records provided the population for a study of trends in low birth weight (LBW) rates in Baltimore between 1972 and 1977 and of the effect of changes in the characteristics of the childbearing population on these trends. The impact of shifts in the birth weight distribution on neonatal mortality rates was also investigated. Trends were analyzed for unstandardized LBW rates as well as for rates standardized on the distributions of maternal age, education, gravidity, prior pregnancy losses, and marital status.Between 1972 and 1977, the 1,500 and 2,000 gm rates rose significantly by approximately 1 infant per 1,000 live births per year among whites and 2 infants per 1,000 live births among nonwhites. Despite declines in rates for most weights, the effect of these increases was a rise in neonatal mortality rates for both races, but especially for nonwhites.The population of women delivering in Baltimore in 1977 became slightly older, slightly more educated, and of higher gravidity than in 1972, but these changes had little impact on yearly fluctuations in LBW rates. In contrast, increases in births to unmarried women and to women with at least one prior pregnancy loss were related to rising LBW rates. For both races, standardization on marital status and prior pregnancy losses diminishes the increase in the LBW rate over the study period, especially when standardization is performed simultaneously for both variables. These findings hold within maternal age, education, and gravidity groups. However, the LBW rates for nonwhite teenage mothers and for nonwhite women with 12 years of less education increased significantly over the study period, regardless of standardization.


Mixture of autoregressive modeling orders and its implication on single trial EEG classification.
Autoregressive (AR) models are of commonly utilized feature types in Electroencephalogram (EEG) studies due to offering better resolution, smoother spectra and being applicable to short segments of data. Identifying correct AR's modeling order is an open challenge. Lower model orders poorly represent the signal while higher orders increase noise. Conventional methods for estimating modeling order includes Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC) and Final Prediction Error (FPE). This article assesses the hypothesis that appropriate mixture of multiple AR orders is likely to better represent the true signal compared to any single order. Better spectral representation of underlying EEG patterns can increase utility of AR features in Brain Computer Interface (BCI) systems by increasing timely & correctly responsiveness of such systems to operator's thoughts. Two mechanisms of Evolutionary-based fusion and Ensemble-based mixture are utilized for identifying such appropriate mixture of modeling orders. The classification performance of the resultant AR-mixtures are assessed against several conventional methods utilized by the community including 1) A well-known set of commonly used orders suggested by the literature, 2) conventional order estimation approaches (e.g., AIC, BIC and FPE), 3) blind mixture of AR features originated from a range of well-known orders. Five datasets from BCI competition III that contain 2, 3 and 4 motor imagery tasks are considered for the assessment. The results indicate superiority of Ensemble-based modeling order mixture and evolutionary-based order fusion methods within all datasets.


Diffusible Factors Essential for Epidermal Cell Redifferentiaion in Catharanthus roseus.
During postgenital tissue fusions, some plant epidermal cells redifferentiate into parenchyma, a different cell type. Diffusible factors cause this response in the fusing gynoecium of the Madagascar periwinkle (Catharanthus roseus). Surgical manipulations of the gynoecium showed that epidermal cells from normally nonfusing surfaces could trasmit and respond to the diffusible factors. Furthermore, the diffusible fators could be trapped in agar-impregnated barriers, as shown by the redifferentiation of carpel epidermal cells from nonfusing regions when the factor-loaded barriers were appressed to them.


Raman spectroscopy coupled with chemometric methods for the discrimination of foreign fats and oils in cream and yogurt.
The adulteration of milk fat in dairy products with cheaper non-milk based fats or oils is frequently encountered in the dairy industry. In this study, Raman spectroscopy with chemometric was used for the discrimination of foreign fats and oils in milk cream and yogurt. Firstly, binary mixtures of cream and oils (corn and sunflower oil), and vegetable fat blends which are potentially or currently used by the dairy industry were prepared. All fat or oil samples and their binary mixtures were examined by using Raman spectroscopy. Then, fat content of skim milk was adjusted to 3% (w/w) by the milk fat, external oils or fats, and binary mixtures, and was used in yogurt production. The lipid fraction of yogurt was extracted and characterized by Raman spectroscopy. The spectral data were then pre-processed and principal component analysis (PCA) was performed. Raman spectral data showed successful discrimination for about the source of the fats or oils. Temperature effect was also studied at six different temperatures (25, 30, 40, 50, 60 and 70 °C) in order to obtain the best spectral information. Raman spectra collected at higher temperatures were more intense. Obtained results showed that the performance of Raman spectroscopy with PCA was very promising and can be expected to provide a simple and quick way for the discrimination of foreign fats and oils in both milk cream and yogurt. Fermentation and yogurt processing affected clustering of fat samples by PCA, probably depending on some lipolysis or production of new products that can affect the Raman scattering. However, those changes did not affect differentiation of samples by Raman spectroscopy.


Periodontal disease progression and glycaemic control among Gullah African Americans with type-2 diabetes.
To evaluate associations between glycaemic control and periodontitis progression among Gullah African Americans with type-2 diabetes mellitus (T2DM). From an ongoing clinical trial among T2DM Gullah, we extracted a cohort previously in a cross-sectional study (N=88). Time from baseline (previous study) to follow-up (trial enrollment, before treatment interventions) ranged 1.93-4.08 years [mean=2.99, standard deviation (SD)=0.36]. We evaluated tooth site-level periodontitis progression [clinical attachment loss (CAL) worsening of > or =2 mm, periodontal probing depth (PPD) increases of > or =2 mm and bleeding on probing (BOP) from none to present] by glycaemic control status (well-controlled=HbA(1c)<7%, poorly-controlled=HbA(1c)> or =7%) using multivariable generalized estimating equations logistic regression, nesting tooth sites/person. Poorly-controlled T2DM (68.18%) was more prevalent than well-controlled T2DM (31.82%). Proportions of tooth sites/person with CAL progression between baseline and follow-up ranged 0.00-0.59 (mean=0.12, SD=0.12), while PPD and BOP progression ranged 0.00-0.44 (mean=0.09, SD=0.11) and 0.00-0.96 (mean=0.24, SD=0.18), respectively. Site-level PPD at baseline was a significant effect modifier of associations between poorly-controlled T2DM and site-level CAL and PPD progression [adjusted odds ratios (OR) according to poorly-controlled T2DM among PPD at baseline=3, 5 and 7 mm, respectively: CAL progression=1.93, 2.64, and 3.62, PPD progression=1.98, 2.76, and 3.84; p<0.05 for all]. Odds of site-level BOP progression were increased (OR=1.24) for poorly-controlled T2DM, yet the results were not significant (p=0.32). These findings from a distinct, homogenous population further support the clinical relevance of identifying patients with poor glycaemic control and periodontitis, particularly among those with disparities for both diseases.


[Evaluation of environmental conditions: air, water and soil in areas of mining activity in Boyacá, Colombia].
Objectives To determine concentrations of PM10, mercury and lead in indoor air of homes, water sources and soil in municipalities near mining operations. Method 6 points were evaluated in areas of influence and 2 in control areas. For measurements of indoor air, we used the NIOSH 600 method (PM10), NIOSH 6009 (mercury) and NIOSH 7300 (lead). For water analysis we used the IDEAM Guide for monitoring discharges. For soil analysis, we used the cold vapor technique (mercury) and atomic absorption (lead). Results In almost all selected households, the average PM10 and mercury concentrations in indoor air exceeded applicable air quality standards. Concentrations of lead were below standard levels. In all water sources, high concentrations of lead were found and in some places within the mining areas, high levels of iron, aluminum and mercury were also found. In soil, mercury concentrations were below the detection level and for lead, differences between the monitored points were observed. Conclusions The results do not establish causal relationships between mining and concentration of these pollutants in the evaluated areas because of the multiplicity of sources in the area. However, such studies provide important information, useful to agents of the environmental health system and researchers. Installation of networks for environmental monitoring to obtain continuous reports is suggested.


Printed multifunctional flexible device with an integrated motion sensor for health care monitoring.
Real-time health care monitoring may enable prediction and prevention of disease or improve treatment by diagnosing illnesses in the early stages. Wearable, comfortable, sensing devices are required to allow continuous monitoring of a person's health; other important considerations for this technology are device flexibility, low-cost components and processing, and multifunctionality. To address these criteria, we present a flexible, multifunctional printed health care sensor equipped with a three-axis acceleration sensor to monitor physical movement and motion. Because the device is designed to be attached directly onto the skin, it has a modular design with two detachable components: One device component is nondisposable, whereas the other one is disposable and designed to be worn in contact with the skin. The design of this disposable sensing sheet takes into account hygiene concerns and low-cost materials and fabrication methods as well as features integrated, printed sensors to monitor for temperature, acceleration, electrocardiograms, and a kirigami structure, which allows for stretching on skin. The reusable component of the device contains more expensive device components, features an ultraviolet light sensor that is controlled by carbon nanotube thin-film transistors, and has a mechanically flexible and stable liquid metal contact for connection to the disposable sensing sheet. After characterizing the electrical properties of the transistors and flexible sensors, we demonstrate a proof-of-concept device that is capable of health care monitoring combined with detection of physical activity, showing that this device provides an excellent platform for the development of commercially viable, wearable health care monitors.


Extragonadal germ cell tumors in Japan.
Extragonadal germ cell tumors (EGCT) represent only 2-5% of adult germ cell malignancies. Some publications from Asia have reported inferior treatment outcomes compared to data from an international study group. To ascertain whether this is generally the case, here we analyze treatment outcomes for 30 Japanese patients with EGCT. The medical records of 30 patients (25 nonseminomas and 4 pure seminomas) treated from 1992 to 2002 were reviewed retrospectively. All patients with seminoma achieved long survival except one who died of chemotherapy-related sepsis. Ten and 11 patients with EGCT presented with mediastinal and retroperitoneal primary sites, respectively. The 5-year overall survival (OS) and progression-free survival (PFS) for nonseminoma was 71% and 42%, respectively. The 5-year OS and PFS was 60% and 44%, respectively, for 10 patients with mediastinal nonseminoma, and 91% and 48%, respectively, for patients with retroperitoneal nonseminoma. Tumor marker values on day 7 were available for 19 patients. Among the 19 patients in whom AFP or beta-HCG were measured on day 7, the values had declined in 12 patients and were transiently elevated in 7 patients compared to pretreatment values. The transient elevations of tumor markers were significantly associated with poor OS (P = 0.02) and PFS (P = 0.008). The treatment outcome of Japanese patients with EGCT seemed to be comparable to that reported from international studies, suggesting no difference between ethnic groups. Transient tumor marker elevations on day 7 predict poor survival in EGCT patients and may be a useful parameter for identifying patients requiring more aggressive treatment.


Discovery of the First Lactate Dehydrogenase Proteolysis Targeting Chimera Degrader for the Treatment of Pancreatic Cancer.
Lactate dehydrogenase (LDH) is a key glycolytic enzyme and biomarker of aggressive cancers. LDHA and LDHB are two main LDH subunits, and both are frequently overexpressed in tumors and essential for tumor growth. A number of LDHA/B small-molecule inhibitors have been developed. Here, we report the discovery of the first LDH proteolysis targeting chimera (PROTAC) degrader, compound 22 (MS6105). 22 potently degraded LDHA in a time- and ubiquitin-proteasome system-dependent manner. Using an unbiased global proteomic study, we confirmed that 22 degraded both LDHA and LDHB significantly. 22 was significantly more potent than the parent LDH inhibitor in suppressing the growth of both quasi-mesenchymal state and epithelial state pancreatic cancer cell lines. Furthermore, 22 was bioavailable in mice through intraperitoneal injection. Overall, 22 could be a valuable chemical tool for the research community to explore pathophysiological functions of LDH in vitro and in vivo.


Summary and frequency of barriers to adoption of CPOE in the U.S.
Medical errors are common, costly, and can potentially be life threatening to patients. Recent studies have established that Computer Provider Order Entry (CPOE) systems reduce medical errors as well as improve safety, quality, and value of patient care. However, research regarding adoption factors associated with CPOE systems is limited. Therefore, the purpose of this review was to determine adoption factors by identifying the frequency of barriers through the analysis of literature and research. A systematic literature review was conducted from EBSCO Host and Google Scholar. The search criteria focused on publication date, keywords, and peer reviewed articles. The final set established for evaluation was ten articles. The authors summarized each article and then identified common barriers. Throughout the ten articles, 31 barriers were identified; 15 of which were unique. The three most frequent barriers identified were: process changes (23%), training (13%), and efficacy (10%). The results of this review identify to policy makers levers to incentivize to encourage adoption. The results also illustrate to vendors the importance of factors to include in both marketing and development. The leadership of healthcare organizations should be encouraged to see such results and know that their concerns are heard. If policy makers and vendors help healthcare organizations overcome barriers to adoption, the organization has a better chance of successful CPOE implementation. If successfully implemented, a CPOE system can improve the process of care, quality of care, and patient outcomes; all of which address issues of Meaningful Use.


Communication approaches to enhance patient motivation and adherence in cardiovascular disease prevention.
Preventive cardiology visits have traditionally focused on educating patients about disease risk factors and the need to avoid and manage them through lifestyle changes and medications. However, long-term patient adherence to the recommended interventions remains a key unmet need. In this review we discuss the rationale and potential benefits of a paradigm shift in the clinician-patient encounter, from focusing on education to explicitly discussing key drivers of individual motivation. This includes the emotional, psychological, and economic mindset that patients bring to their health decisions. Five communication approaches are proposed that progress clinician-patient preventive cardiology conversations, from provision of information to addressing values and priorities such as common health concerns, love for the family, desire of social recognition, financial stressors, and desire to receive personalized advice. Although further research is needed, these approaches may facilitate developing deeper, more effective bonds with patients, enhance adherence to recommendations and ultimately, improve cardiovascular outcomes.


Exploring the Effect of Health App Use on Fruit and Vegetable Consumption.
People may use multiple health apps at the same time or in close sequence, and the effect of health apps may vary across different socioeconomic groups. However, in the context of healthy eating, studies have focused on the effect of using a single health app. This study aims to test the relationship of using multiple health apps with fruit and vegetable consumption, assessing moderation by education level. Employing longitudinal survey data from South Korean adults, we conducted regression analyses to test the lagged association between use of health apps and intake of fruits and vegetables, and whether education moderates the relationship. The results supported the positive lagged relationship of health app use with fruit and vegetable consumption, significant after controlling for confounders and baseline fruit and vegetable consumption. The association was smaller among respondents with higher education. Our findings suggest the positive effect of using multiple health apps on fruit and vegetable consumption, implying the importance of finding the best combination of health apps to maximize their effectiveness in promoting healthy eating. Also, the negative interaction of health app use and education support using mobile communication technology to improve the public health of low socioeconomic status individuals.


Nanoparticle coated emulsions as novel dermal delivery vehicles.
The dermal delivery characteristics of hydrophilic silica nanoparticle coated medium chain triglyceride oil-in-water emulsions are reported and correlated with the physicochemical and interfacial properties of the emulsion based drug carriers. The synergistic drug/stabiliser/nanoparticle interactions are demonstrated to be a function of the charge and concentration of the initial emulsion stabiliser; charge and initial loading phase of nanoparticles and physicochemical properties of the drug molecule. The improved physical stability of the emulsions and the chemical stability of two model lipophilic agents (all-trans-retinol and acridine orange 10-nonyl bromide) confirm that engineered nanoparticle layers can enhance the shelf-life of liable lipophilic agents. Nanoparticle coatings are shown to control the in-vitro release of active agents from emulsions and significantly promote skin retention. The lipophilic agents distributed into the deeper viable skin layers without permeation through full-thickness skin and hence systemic exposure. Nanoparticle-coated submicron oil-in-water emulsions can serve as novel dermal carriers with controlled release kinetics and targeted drug delivery.


Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study.
To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.


Sensory thresholds of normal human feet.
Although several studies in the literature have evaluated the abnormal sensory thresholds of diabetic feet to Semmes-Weinstein monofilament testing, there is very limited data on the sensory thresholds of individuals without diabetes or peripheral neuropathy. The purpose of this study was to assess the dorsal and plantar sensation of the feet from 40 healthy, college-aged volunteers using Semmes-Weinstein monofilaments. Semmes-Weinstein testing is a useful tool in predicting which diabetic patients may be at risk for ulceration of the feet. Several studies have determined 5.07 to be the threshold for protective sensation. Based on the normal values derived in this study, the inability to feel a Semmes-Weinstein monofilament of 5.07 (as in diabetic neuropathy) represents a sensory threshold that is more than 50 times greater than normal. This means that roughly 98% of the sensory ability has been lost. 20 male and 20 female volunteers between the ages of 18 to 22 years old were selected. None had a history of any significant injury or previous surgery to the foot or ankle. There were no known medical conditions associated with decreased foot sensation, (e.g.- diabetes, syphilis, leprosy, myelomeningocele, syringomyelia, or hereditary neuropathy). Volunteers were also questioned regarding participation in athletic activities. The subjects were blindfolded with the leg resting comfortably on a chair as 14 plantar and 5 dorsal locations were tested on each foot. The right foot was always tested first. Each site on the foot had the Semmes-Weinstein monofilaments applied to it first, in an order of increasing stiffness, then repeated in decreasing order, using all twenty monofilaments in the set. A positive threshold response was recorded when the subject could feel the filament and could accurately locate where on the foot the stimulus had been applied. The left foot was then tested in an identical fashion. The mean sensitivity for all sites was 3.63 (0.0075 SEM). There were significant differences between sites, between using increasing or decreasing monofilament stiffness, between subjects, and in some instances, between right foot and left foot values. When testing was performed from the higher to lower monofilament stiffness, subjects were found to have significantly better sensitivity, which indicates the importance of a consistent testing protocol (either all up or all down). Sensation in the lesser toes and the arch were the most sensitive followed by the hallux and the plantar metatarsal heads. The least sensitive site was the heel, with 1/6th the sensitivity of the most sensitive toes.


The necessity of repeat testing for von Willebrand disease in adult patients with mild to moderate bleeding disorders.
In patients with mild-to-moderate bleeding disorders (MBD), von Willebrand disease (VWD) is diagnosed at von Willebrand factor (VWF) levels ≤50 IU/dL. Although VWF levels are unstable, repeated testing for VWD diagnosis is not necessarily advised in recent guidelines. To analyze the relevance of repeated VWF testing to diagnose VWD in patients with MBD. Data of 277 patients with MBD from the Vienna Bleeding Biobank with at least 2 separate assessments of VWF antigen (VWF:Ag) and activity (VWF:Act) were analyzed. In repeated VWF measurements, 36 patients (13.0%) had "changing" VWF levels (≤/>50 IU/dL), 27 (9.7%) had persistent levels ≤50 IU/dL ("pathologic"), and 214 (77.3%) had levels >50 IU/dL ("normal"). Of the 36 changing patients, 22 (61%) were diagnosed with VWD at baseline, whereas the others only met VWD diagnostic criteria at repeated measurements. Using logistic regression, we estimated a probability of change of 26.4% (95% CI, 12.5-47.4) at baseline VWF levels of 30 IU/dL, 50.8% (95% CI, 35.6-65.8) at 50 IU/dL, 18.8% (95% CI, 12.3-27.6) at 60 IU/dL, and 1.2% (95% CI, 0.3-4.9) at 80 IU/dL. Baseline VWF was a strong predictor for changing status (Χ2 = 49.9; P < .001), while age, sex, Vicenza score, and blood type O had limited added value (Χ2 = 5.1; P = .278). Baseline VWF:Ag or VWF:Act cutoffs of 80 IU/dL had negative predictive values of 98.1% and 99.1% for changing status, respectively. Our data emphasize an overlap between patients with VWD and MBD with bleeding disorder of unknown cause and underline the need for repeated VWF testing, especially in patients with VWF levels <80 IU/dL.


Design and analysis of a nonequilibrium cross-coupled network with a detectable similarity measure.
In this paper, a nonequilibrium network which works as a dynamical associative memory is designed. The design is based on a new similarity measure between any stored pattern and a state of the network. Although conventional similarity measures, such as Hamming distance, direction cosine, and so on, are not detectable in a cross-coupled network, the similarity measure proposed in this paper is. The new similarity measure is employed in our design. The network should include the following properties in its output pattern sequence, so that the dynamics of cross-coupled network may be designed: 1) Stored patterns are frequently associated in the dynamical association. 2) The dynamical association is very robust against variation of distributed parameters. Property 1) is achieved by introducing the next two operation modes with inverse N-shaped function into the dynamics of the proposed network. 1) When the state of the network is close enough to a stored pattern at a time step, the state is forced to evolve at the next time step. 2) The state of the network converges to a stored one while it is not close to any stored patterns. By considering these two operation modes, the frequency of associating stored patterns is increased. The authors emphasize the property 2) which is very important for a silicon implementation of the proposed network. In the silicon implementation, parameters of the network must be represented by transistors, resistors, capacitors, and other electric components which exhibit variation in their characteristics. Thus the second property guarantees the easy silicon implementation of the nonequilibrium network proposed in this paper.


Episodic memory in left temporal lobe epilepsy: a functional MRI study.
Left medial temporal lobe epilepsy (MTLE) is associated with verbal memory impairment usually related to hippocampal damage. We used functional MRI (fMRI) to investigate the patterns of functional activity in healthy volunteers and MTLE patients engaged in verbal episodic memory tasks to look for evidence of a reallocation of verbal memory in epileptic patients. fMRI data were collected from seven MTLE patients with left-sided hippocampal sclerosis and 10 healthy right-handed control subjects on a 3T scanner. Subjects were instructed to learn a list of 17 words (encoding) and then to recall them (retrieval) on successive trials. Healthy volunteers and patients both exhibited bilateral activation (right higher than left) of the parahippocampal gyrus during the retrieval. This effect was more marked in the control subjects. In contrast to the control subjects, patients exhibited consistent and extensive left prefrontal activations in all the memory tasks. These findings show that verbal memory tasks did not involve the same functional patterns in patients and healthy volunteers. This may be interpreted as a dysfunctional response due to the epilepsy and left hippocampal sclerosis, and could reflect the early onset and progressive course of the disease.


The relationship between gamma-glutamyltransferase and coronary collateral circulation in patients with chronic total occlusion.
The aim of this study was to evaluate the relation between blood gamma-glutamyltransferase (GGT) levels and coronary collateral circulation in patients with chronic total occlusion (CTO). Two hundred twenty-two patients with chronic stable coronary artery disease (CAD) and CTO were included in this cross-sectional, observational study. Coronary collaterals were graded from 0 to 3 according to the Rentrop method. Patients with grade 0-1 collateral development were regarded as poor collateral group (n=66) while patients with grade 2-3 collateral development were regarded as good collateral group (n=156). Statistical analysis was performed using independent samples t, Mann-Whitney U and Chi-square tests, logistic regression and receiver operator curve analysis. The poor coronary collateral group had significantly higher levels of serum GGT compared to the good collateral group (p<0.001). Multiple logistic regression analysis showed that GGT levels were independent predictors of poor collateral circulation (OR-0.946, 95% CI=0.918-0.9719, p<0.001). The result of ROC curve analysis for GGT was as following: area under the ROC curve (AUC)=0.732, 95% CI: 0.622-0.841, p<0.001. Higher GGT levels are associated with poor coronary collateral circulation in patients with CTO. GGT may be used to predict the grade of coronary collateral circulation in CTO patients with chronic stable CAD.


PSAT-GAN: Efficient Adversarial Attacks Against Holistic Scene Understanding.
Recent advances in deep neural networks (DNNs) have facilitated high-end applications, including holistic scene understanding (HSU), in which many tasks run in parallel with the same visual input. Following this trend, various methods have been proposed to use DNNs to perform multiple vision tasks. However, these methods are task-specific and less effective when considering multiple HSU tasks. End-to-end demonstrations of adversarial examples, which generate one-to-many heterogeneous adversarial examples in parallel from the same input, are scarce. Additionally, one-to-many mapping of adversarial examples for HSU usually requires joint representation learning and flexible constraints on magnitude, which can render the prevalent attack methods ineffective. In this paper, we propose PSAT-GAN, an end-to-end framework that follows the pipeline of HSU. It is based on a mixture of generative models and an adversarial classifier that employs partial weight sharing to learn a one-to-many mapping of adversarial examples in parallel, each of which is effective for its corresponding task in HSU attacks. PSAT-GAN is further enhanced by applying novel adversarial and soft-constraint losses to generate effective perturbations and avoid studying transferability. Experimental results indicate that our method is efficient in generating both universal and image-dependent adversarial examples to fool HSU tasks under either targeted or non-targeted settings.


Heterogeneity of the Type 3 copper in Japanese-lacquer-tree (Rhus vernicifera) laccase.
The two steps of the titration of the Japanese-lacquer-tree (Rhus vernicifera) laccase with N3- [Morpurgo, Rotilio, Finazzi-Agrò & Mondovi (1974) Biochim. Biophys. Acta 336, 324-328; LuBien, Winkler, Thamann, Scott, Co, Hodgson & Solomon (1981) J. Am. Chem. Soc. 103, 7014-7016] were shown to be two distinct reactions, each involving one different portion of the native enzyme molecules. The difference consists in the oxidation state of the Type 3 Cu, which is reduced in the portion with higher affinity for N3- and oxidized in the portion with lower affinity for N3-. The difference is eliminated by treatment with oxidizing (H2O2) or reducing agents, and a single N3- adduct is then formed. The e.p.r. spectra of the H2O2-treated enzyme and of its F- derivatives support this interpretation of the results. The similarity of the spectroscopic properties of the high-affinity N3- adduct to those of the N3- adducts of half-met-haemocyanins and half-met-tyrosinase is discussed.


NRIF is a regulator of neuronal cholesterol biosynthesis genes.
Cholesterol is a critical component of neuronal membranes, required for normal signal transduction. We showed previously that adult hippocampal neurons co-express high levels of cholesterogenic enzymes, and that their expression is under the control of the p75 neurotrophin receptor (p75NTR). Most of the cellular effects of p75NTR are mediated via interacting proteins, including neurotrophin receptor interacting factor (NRIF). In this study, we tested the hypothesis that p75NTR-dependent regulation of cholesterol and lipid biosynthesis genes is mediated by NRIF. We found that in vitro down regulation of NRIF expression decreased the mRNA for two main cholesterogenic enzymes, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr; EC 220.127.116.11) and 7-dehydrocholesterol reductase (Dhcr7; EC 220.127.116.11). Further analyses revealed that NRIF-dependent and Dhcr7-dependent transcriptional changes show a high degree of overlap, and that NRIF reduction resulted in reduced expression of sterol-sensing domain protein SCAP, followed by a decrease in mRNA levels of SRE-motif containing genes (HMGCR, FASN, SREBP2, S1P, and SQS1). Finally, a reduction in cholesterol biosynthesis-related gene expression was also observed in hippocampal tissue of mice with NRIF deletion. Our combined in vitro and in vivo studies suggest that hippocampal neuronal cholesterol biosynthesis is regulated through the p75NTR interacting factor NRIF.


Interventions to increase children's booster seat use: a review.
In children aged 4 to 8 years, booster seats are estimated to reduce by 59% the odds of sustaining clinically significant injuries during a motor vehicle crash, compared to using ordinary vehicle seat belts. Given the safety benefits of booster seats, public health and traffic safety agencies recommend their use for children aged 4 to 8 years traveling in motor vehicles, until the vehicle seat belt can fit them properly. Despite these benefits, booster seat use remains low. Interventions aimed at promoting the use of booster seats for children aged 4 to 8 years have been implemented, but there is little evidence regarding their effects. The Cochrane methodology was used to assess the effects of interventions to increase booster seat use for children aged 4 to 8 years. The reviewers searched online databases, scanned reference lists, hand-searched journals, and contacted relevant agencies and researchers for both randomized controlled trials and controlled before-and-after evaluation studies. The search concluded in 2005 and was not restricted by publication status or language. The search yielded 1350 potential studies. Of these, five studies involving 3070 individuals met the inclusion criteria. Interventions were generally effective in increasing booster seat use among children aged 4 to 8 years. Education paired with incentive or distribution programs produced more consistent results than education-only interventions that targeted parents, children, or both. Incentives or the distribution of free booster seats combined with education increase the use of booster seats.


Treatment options for posttraumatic epilepsy.
Posttraumatic seizures (PTS) and posttraumatic epilepsy (PTE) are common and debilitating consequences of traumatic brain injury (TBI). Early PTS result in secondary brain injury by raising intracranial pressure and worsening cerebral edema and metabolic crisis. PTE is a localization-related epilepsy strongly associated with TBI severity, but risk factors for PTE and epileptogenesis are incompletely understood and are active areas of research. Medical management of PTS in adults and children is reviewed. Surgical options for posttraumatic drug-resistant epilepsy are also discussed. Continuous electroencephalography is indicated for children and adults with TBI and coma because of the high incidence of nonconvulsive seizures, periodic discharges, and associated secondary brain injury in this population. Neuroinflammation is a central component of secondary brain injury and appears to play a key role in epileptogenesis. Levetiracetam is increasingly used for seizure prophylaxis in adults and children, but variability remains. PTS occur commonly after TBI and are associated with secondary brain injury and worse outcomes in adults and children. Current medical and surgical management options for PTS and PTE are reviewed.


Herbivore preference drives plant community composition.
Herbivores are important drivers of plant species coexistence and community assembly. However, detailed mechanistic information on how herbivores affect dominance hierarchies between plant species is scarce. Here, we used data of a multi-site herbivore exclusion experiment in grasslands to assess changes in the cover of 28 plant species in response to aboveground pesticide. application. Moreover, we assessed species-specific values of plant defense of these 28 species measured as the performance of a generalist caterpillar, and the preference of the caterpillar and a slug species in no-choice and choice feeding experiments, respectively. We show that more preferred species in the feeding experiments were those that increased in cover after herbivore exclusion in the field, whereas less preferred ones decreased. Herbivore performance and several measured leaf traits were not related to the change in plant cover in the field in response to herbivore removal. Additionally, the generalist slug and the generalist caterpillar preferred and disliked the same plant species, indicating that they perceive the balance between defense and nutritional value similarly. We conclude that the growth-defense trade-off in grassland species acts via the preference of herbivores and that among-species variation in plant growth and preference to herbivores drives plant community composition.


A cell type-specific cortico-subcortical brain circuit for investigatory and novelty-seeking behavior.
Exploring the physical and social environment is essential for understanding the surrounding world. We do not know how novelty-seeking motivation initiates the complex sequence of actions that make up investigatory behavior. We found in mice that inhibitory neurons in the medial zona incerta (ZIm), a subthalamic brain region, are essential for the decision to investigate an object or a conspecific. These neurons receive excitatory input from the prelimbic cortex to signal the initiation of exploration. This signal is modulated in the ZIm by the level of investigatory motivation. Increased activity in the ZIm instigates deep investigative action by inhibiting the periaqueductal gray region. A subpopulation of inhibitory ZIm neurons expressing tachykinin 1 (TAC1) modulates the investigatory behavior.


Effects of naloxone and neurotensin on excessive grooming behavior of rats induced by bombesin, beta-endorphin and ACTH.
Bombesin, beta-endorphin and ACTH-(1-24) induce excessive grooming behavior in rats. Whereas ACTH increases the frequency of all components of grooming behavior (head washing, bodily grooming and paw licking), the most pronounced element of bombesin- and beta-endorphin-induced excessive grooming is scratching. Naloxone counteracts peptide-induced grooming and in particular excessive scratching is reduced by this opiate antagonist. Also neurotensin suppresses peptide-induced grooming behavior and in particular scratching. It is concluded that the element scratching is the component of grooming behavior which is mainly displayed by activation of opiate receptors and that neurotensin is able to interfere with opiate receptor mediated behavior.


Optometric manpower development and utilization: a look toward the future.
This paper attempts to discuss in detail the rise in demand for optometric services and the manpower problems of the future. A proposal for the rational future development of optometric manpower has been made. Hopefully optometry will be able to consider its future development and scope of practice, and the types of changes to be made as the profession prepares for its increasing role in providing quality vision care to all Americans.


Shared molecular strategies of the malaria parasite P. falciparum and the human virus HIV-1.
We augmented existing computationally predicted and experimentally determined interactions with evolutionarily conserved interactions between proteins of the malaria parasite, P. falciparum, and the human host. In a validation step, we found that conserved interacting host-parasite protein pairs were specifically expressed in host tissues where both the parasite and host proteins are known to be active. We compared host-parasite interactions with experimentally verified interactions between human host proteins and a very different pathogen, HIV-1. Both pathogens were found to use their protein repertoire in a combinatorial manner, providing a broad connection to host cellular processes. Specifically, the two biologically distinct pathogens predominately target central proteins to take control of a human host cell, effectively reaching into diversified cellular host cellular functions. Interacting signaling pathways and a small set of regulatory and signaling proteins were prime targets of both pathogens, suggesting remarkably similar patterns of host-pathogen interactions despite the vast biological differences of both pathogens. Such an identification of shared molecular strategies by the virus HIV-1 and the eukaryotic intracellular pathogen P. falciparum may allow us to illuminate new avenues of disease intervention.


Adverse psychological outcome in women with coronary artery disease.
To investigate gender differences on psychological outcome following cardiac disease, and to identify predictors of psychological distress. In total, 536 consecutive cardiac patients ≤70 years were identified from medical records to participate in the study: 36 of them proved to have died since the index event. The mean time since the index event was one year and seven months. Of the 500 patients, 357 (71%) agreed to attend an interview on biomedical risk factors and fill in a psychological questionnaire. Complete psychological data were available for 287 (80%) patients. Women scored significantly higher on anxiety, depression, vital exhaustion and social inhibition, and lower on wellbeing compared with men. Gender, age, percutaneous transluminal coronary angioplasty, smoking and admission for a recurrent event since the index event were independent predictors of psychological outcome. These results add to current knowledge on gender differences and show that women have an adverse outcome on a range of psychological variables. This has implications for secondary prevention and rehabilitation. Longitudinal studies are needed to assess the implications of adverse psychological outcome in women on prognosis.


Critical review of preclinical approaches to investigate cytochrome p450-mediated therapeutic protein drug-drug interactions and recommendations for best practices: a white paper.
Drug-drug interactions (DDIs) between therapeutic proteins (TPs) and small-molecule drugs have recently drawn the attention of regulatory agencies, the pharmaceutical industry, and academia. TP-DDIs are mainly caused by proinflammatory cytokine or cytokine modulator-mediated effects on the expression of cytochrome P450 enzymes. To build consensus among industry and regulatory agencies on expectations and challenges in this area, a working group was initiated to review the preclinical state of the art. This white paper represents the observations and recommendations of the working group on the value of in vitro human hepatocyte studies for the prediction of clinical TP-DDI. The white paper was developed following a "Workshop on Recent Advances in the Investigation of Therapeutic Protein Drug-Drug Interactions: Preclinical and Clinical Approaches" held at the Food and Drug Administration White Oak Conference Center on June 4 and 5, 2012. Results of a workshop poll, cross-laboratory data comparisons, and the overall recommendations of the in vitro working group are presented herein. The working group observed that evaluation of TP-DDI for anticytokine monoclonal antibodies is currently best accomplished with a clinical study in patients with inflammatory disease. Treatment-induced changes in appropriate biomarkers in phase 2 and 3 studies may indicate the potential for a clinically measurable treatment effect on cytochrome P450 enzymes. Cytokine-mediated DDIs observed with anti-inflammatory TPs cannot currently be predicted using in vitro data. Future success in predicting clinical TP-DDIs will require an understanding of disease biology, physiologically relevant in vitro systems, and more examples of well conducted clinical TP-DDI trials.


Efficient enzymatic degradation process for hydrolysis activity of the Carrageenan from red algae in marine biomass.
Carrageenan is a generic name for a family of polysaccharides obtained from certain species of red algae. New methods to produce useful cost-efficiently materials from red algae are needed to convert enzymatic processes into fermentable sugars. In this study, we constructed chimeric genes cCgkA and cCglA containing the catalytic domain of κ-carrageenase CgkA and λ-carrageenase CglA from Pseudoalteromonas carrageenovora fused with a dockerin domain. Recombinant strains expressing the chimeric carrageenase resulted in a halo formation on the carrageenan plate by alcian blue staining. The recombinant cCgkA and cCglA were assembled with scaffoldin miniCbpA via cohesin and dockerin interaction. Carbohydrate binding module (CBM) in scaffoldin was used as a tag for cellulose affinity purification using cellulose as a support. The hydrolysis process was monitored by the amount of reducing sugar released from carrageenan. Interestingly, these results indicated that miniCbpA, cCgkA and cCglA assembled into a complex and that the dockerin-fused enzymes on the scaffoldin had synergistic activity in the degradation of carrageenan. The observed enhancement of activity by carrageenolytic complex was 3.1-fold-higher compared with the corresponding enzymes alone. Thus, the assemblies of advancement of active enzyme complexes will facilitate the commercial production of useful products from red algae biomass which represents inexpensive and sustainable feed-stocks.


Enhancement of transcription of the SV40 genome in mouse embryo cells by pretreatment with 5-iodo-2'-deoxyuridine.
Treatment of mouse embryo (ME) cells with 5-iodo-2'-deoxyuridine (IdUrd) before infection with SV40 virus, enhances T-antigen (T-Ag) production as detected by immunofluorescence and complement fixation. Cellular DNA and RNA synthesis are inhibited in both SV40 and mock-infected cells after IdUrd treatment. The analogue pretreatment significantly increases the amount of radiolabelled nuclear and cytoplasmic SV40-specific RNA and the RNA polymerase activity of the viral transcriptional complexes of the Sarkosyl supernatants, suggesting that the enhancement of SV40 T-Ag production in infected pretreated ME cells results from an increased synthesis of early virus RNA.


Examining demographic and socio-economic correlates of accurate knowledge about blood donation among African migrants in Australia.
To develop and test a knowledge questionnaire about blood donation in African migrant communities in Australia, which is applicable to other communities, and to assess the relationship between the demographic and socio-economic characteristics and knowledge of the African migrant community. Using a cross-sectional survey of 425 African migrants and refugees living in Victoria and South Australia, we assessed the knowledge questionnaire for readability, item difficulty, point-biserial correlation and reliability. The relationships between demographic and socio-economic factors and knowledge about blood donation were then evaluated using hierarchical multiple regression. The knowledge scale was found to have good psychometric properties and to be reliable: a Flesch reading ease score of 64.7; an average index of item difficulty of 0.42; a point-biserial correlation of 0.38 and a Kuder-Richardson-20 coefficient of 0.78 indicating strong internal consistency. A quarter of respondents (26.1%; 95% CI: 21.9, 30.3) had poor knowledge about issues related to blood donation; 51.1% (95% CI: 46.3, 55.8) had moderate knowledge and 22.8% (95% CI: 18.8, 26.8) were highly knowledgeable. Factors associated with blood donation knowledge were religion, pre-migration area of residence, country of birth, length of stay in Australia, and previous blood donation status. Age, gender, educational attainment, migration and employment status were non-significant. Knowledge and awareness of issues associated with blood donation is important in regard to blood donation decisions, and this article has developed a measure using African migrant communities in Australia that has appropriate psychographic properties. The measure can, therefore, be used by researchers when studying the role of knowledge in relation to blood donation across cultural groups in Australia and other countries. It also identifies that demographic characteristics affect knowledge, which suggests that targeted interventions might be needed, especially when dealing with migrant and refugee communities.


[Current approaches for sampling to study the traces of gunshot residue].
An overview of researches, mainly by foreign specialists, on current available approaches for sampling to study the traces of gunshot residue (GSR) is presented. The comparative characteristics of traditional methods of samples (use of cotton and gauze tampons, blotting paper, textile fabrics, adhesive tapes, adhesives and vacuum samplers), as well as advanced technologies, including special devices and sorbents, are given. The characteristics of samplings from hands, scalp, nostrils, clothes of examined persons as well as procedures, that allow to increase the duration of GSR detection, are described in details. The importance of GSR sustainability over time is noted. On average, the most likely detection periods of particles are less than 1 hour for samples, collected from hands, more than 1 hour for samples from clothes and 2-3 hours for face. It is possible to detect the GSR particles in hair up to 24 h., and in nasal mucus after 6 h. of shot. The methods of identification and determination for analytes of inorganic and organic nature are discussed. The most common methods for determining heavy metal particles are atomic spectrometry, namely atomic absorption with electrothermal atomization and atomic emission. The combination of scanning laser ablation and mass-spectrometry with inductively coupled plasma makes it possible to detect more than 15 analytes in a single sample. Scanning electron microscopy with X-ray detectors is effective for the examination of powder particles. The described methods of sampling complement each other increasing the possibility of evidence base for court proceedings.


U-Net-based approach for automatic lung segmentation in electrical impedance tomography.
Electrical impedance tomography (EIT) is a non-invasive technique that constitutes a promising tool for real-time imaging and long-term monitoring of the ventilation distribution at bedside. However, clinical monitoring and diagnostic evaluations depend on various methods to assess ventilation-dependent parameters useful for ventilation therapy. This study develops an automatic, robust, and rapidly accessible method for lung segmentation that can be used to define appropriate regions-of-interest (ROIs) within EIT images. To date, available methods for patients with defected lungs have the disadvantage of not being able to identify lung regions because of their poor ventilation responses. Furthermore, the challenges related to the identification of lung areas in EIT images are attributed to the low spatial resolution of EIT. In this study, a U-Net-based automatic lung segmentation model is used as a postprocessor to transform the original EIT image to a lung ROI image and refine the inherent conductivity distribution of the original EIT image. The trained U-Net network is capable of performing an automatic segmentation of conductivity changes in EIT images without requiring prior information. The experimental design of this study was based on a finite element method (FEM) phantom used to assess the feasibility and effectiveness of the proposed method, and evaluation of the trained models on the test dataset was performed using the Dice similarity coefficient (DSC) and the mean absolute error (MAE). The FEM experimental results yielded values of 0.0065 for MAE, and values >0.99 for DSC in simulations. The use of a deep-learning-based approach attained automatic and convenient segmentation of lung ROIs into distinguishable images, which represents a direct benefit for regional lung ventilation-dependent parameter extraction and analysis. However, further investigations and validation are warranted in real human datasets with different physiology conditions with CT cross-section dataset to refine the suggested model.


Progression of glaucomatous field defects despite successful filtration.
It is generally assumed that successful filtering surgery, by maintaining intraocular pressure at a low level, will protect a glaucoma patient's remaining visual field. We present three patients with chronic open angle glaucoma and typical visual field changes. In each case, filtering surgery was performed because of progressive loss of visual filed and inadequate pressure control. Despite excellent pressure levels after operation, field loss continued in the operated eye. Certain genetic and systemic factors may contribute to further loss of visual field in the presence of normal intraocular pressures. We stress the importance of careful and continuous examination of the visual fields in all glaucoma patients regardless of the response of pressure to treatment.


The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells.
The neuropeptide substance P is a major mediator of neurogenic inflammation and immunomodulatory activities within the central and peripheral nervous system. In several cell types, substance P induces the expression of proinflammatory cytokines that have been implicated in the pathogenesis of different neuropathologies. Substance P preferentially binds to NK-1, a receptor of the neurokinin family, but how the receptor-elicited signal is translated into inflammatory gene expression is not yet understood. In this work, we describe that in U373 MG astrocytoma cells, nanomolar concentrations of substance P potently triggered activation of NF-kappa B, a transcription factor involved in the control of cytokine expression and apoptosis. Substance P-induced NF-kappa B activation was associated with the increased mRNA expression and secretion of IL-8, an NF-kappa B-controlled target gene. The stimulatory effect of substance P was specific, since an NK-1-selective receptor antagonist completely prevented NF-kappa B activation in response to substance P, but not IL-1 beta. In addition, we show that the activity of substance P required mobilization of intracellular calcium and formation of reactive oxygen intermediates as second messengers. Our results suggest that NF-kappa B may be an important component controlling neurogenic inflammation within the peripheral and central nervous system.