Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM‑MSCs in liver cirrhosis in vitro. Human BM‑MSCs and hepatic stellate cells (HSCs) were cultured using a vertical double cell co‑culture system. Groups were divided into HSCs alone (control group) and the co‑culture system of BM‑MSCs with HSCs (experimental group). HSC morphology was observed by inverted phase contrast microscopy. The proliferative capacity of HSCs was measured with the MTT assay and flow cytometry. Hoechst staining was performed to examine the apoptosis of HSCs. Transforming growth factor (TGF)‑β1 and Smad7 mRNA expression were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. BM‑MSCs did not inhibit the proliferation of HSCs at 24 h, however significantly inhibited the proliferation of HSCs at 48 and 72 h. BM‑MSCs additionally induced the apoptosis of HSCs at 48 h. The concentration of TGF‑β1 in the supernatant at 24 h and 48 h in the co‑cultured system was observed to be significantly lower than in the control group (P<0.05). The level of TGF‑β1 mRNA in the experimental group at 48 h was significantly lower than the control group, however Smad7 mRNA levels were significantly greater than in the control group. Additionally, TGF‑β1 protein levels were significantly lower than in the control group, however levels of Smad7 were greater than the control group. It was concluded that BM‑MSCs are able to inhibit the proliferation and promote the apoptosis of HSCs. In addition, the mechanism may be associated with inhibition of the TGF-β1/Smad pathway in HSCs.


A computational peptide model induces cancer cells' apoptosis by docking Kringle 5 to GRP78.
Cells can die through a process called apoptosis in both pathological and healthy conditions. Cancer development and progression may result from abnormal apoptosis. The 78-kDa glucose-regulated protein (GRP78) is increased on the surface of cancer cells. Kringle 5, a cell apoptosis agent, is bound to GRP78 to induce cancer cell apoptosis. Kringle 5 was docked to GRP78 using ClusPro 2.0. The interaction between Kringle 5 and GRP78 was investigated. The interacting amino acids were found to be localized in three areas of Kringle 5. The proposed peptide is made up of secondary structure amino acids that contain Kringle 5 interaction residues. The 3D structure of the peptide model amino acids was created using the PEP-FOLD3 web tool. The proposed peptide completely binds to the GRP78 binding site on the Kringle 5, signaling that it might be effective in the apoptosis of cancer cells.


The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature.
Endothelial cells actively maintain an anti-thrombotic environment; loss of this protective function may lead to thrombosis and systemic coagulopathy. The transcription factor ERG is essential to maintain endothelial homeostasis. Here, we show that inducible endothelial ERG deletion (ErgiEC-KO) in mice is associated with spontaneous thrombosis, hemorrhages and systemic coagulopathy. We find that ERG drives transcription of the anticoagulant thrombomodulin (TM), as shown by reporter assays and chromatin immunoprecipitation. TM expression is regulated by shear stress (SS) via Krüppel-like factor 2 (KLF2). In vitro, ERG regulates TM expression under low SS conditions, by facilitating KLF2 binding to the TM promoter. However, ERG is dispensable for TM expression in high SS conditions. In ErgiEC-KO mice, TM expression is decreased in liver and lung microvasculature exposed to low SS but not in blood vessels exposed to high SS. Our study identifies an endogenous, vascular bed-specific anticoagulant pathway in microvasculature exposed to low SS.


A case of bacteremia and pneumonia caused by Streptococcus equi subspecies equi infection in a 70-year-old female following horse exposure in rural Wyoming.
The occurrence of zoonotic infections following an animal exposure continues to be an important consideration for all patients, especially those within agricultural communities. Streptococcus equi subspecies equi (S. equi subsp. equi) is a bacteria known to cause a common infection called 'Strangles' in horses. This article highlights a new case of pneumonia and bacteremia in a patient caused by S. equi subsp. equi following strangles exposure in a horse. Rarely has there been reported horse to human transmission of subsp. equi. A 70-year-old woman attended a rural emergency department with complaints of dry heaving, fever, chills, shakes, and nausea and presented with a cough. She had undergone a screening colonoscopy two days prior with no other significant medical history. The patient had computed tomography (CT) evidence of a pneumonia and positive blood cultures growing S. equi subsp. equi consistent with bacteremia. The patient later disclosed the recent passing of her horse following its sudden illness six days prior to her emergency department presentation. She had cuddled and kissed the horse prior to its death. The patient was treated with IV lactated ringers during the initial evaluation and admission and also received IV piperacillin-tazobactam 4.5 g every eight hours intravenously during her hospital stay. She was transitioned to an oral antibiotic on discharge. Subsequent blood cultures drawn the day after discharge were negative for S. equi subsp. equi, indicating successful treatment of her bacteremia. This report discusses an atypical presentation of S. equi subsp. equi infection in an otherwise healthy individual, manifesting as early sepsis, pneumonia, and bacteremia. The patient likely developed this infection following direct contact exposure to her horse who had died from presumed strangles a few days prior to her symptom onset. This case highlights the importance of investigating potential exposures to S. equi subsp. equi in rural areas, areas where farming and ranching are prevalent, particularly among individuals working with horses. It is especially important to acknowledge high risk populations such as immunocompromised individuals with signs and symptoms of meningitis or bacteremia.


Mental Health, Material Possessions, and Social Capital During COVID-19: A Study of the United States Urban Working-Age Population.
This study evaluates the associations between the urban working-age population's mental health, material possession, and social capital during the COVID-19 pandemic. The specific stressors examined in this empirical analysis are income level, food insecurity, and virtual psychological support. This paper further examines the differences across the employed and unemployed population groups. We obtained data from the COVID-19 Household Impact Survey and constructed four measures of mental health conditions: Nervous, Depressed, Lonely, and Hopeless. Our empirical analyses use an ordinal regression model that takes both time and regional factors into consideration to control for potential time effects and time-invariant confounders that only vary between regions. For the employed group, the main results suggest that lower income and food insecurity is correlated with a higher frequency of mental health symptoms, while virtual psychological support predicts a better mental health status. For the unemployed group, food insecurity is negatively associated with mental health, and virtual psychological might help alleviate nervousness and depression.


Gut architecture, digestive constraints and feeding ecology of deposit-feeding and carnivorous polychaetes.
We analyze gut architectures of 42 species of marine polychaetes in terms of their anatomically distinct compartments, and quantify differences among guts in terms of ratios of body volume to gut volume, relative compartmental volumes, total gut aspect ratios and compartmental aspect ratios. We use multivariate techniques to classify these polychaetes into 4 groups: carnivores with tubular guts; deposit feeders with tubular guts; deposit feeders with 3 gut compartments; and deposit feeders with 4 or 5 gut compartments. Tubular guts, morphological expressions of plug flow, are common among deposit feeders and may allow relatively rapid ingestion rates and short throughput times. Median gut volume per unit of body volume in deposit feeders (31%) is twice that of carnivores (15%) and ranges up to 83% in one deep-sea species. Deep-sea deposit feeders tend to have relatively larger and longer guts than closely-related nearshore and shelf species. Guts of a number of deep-sea deposit feeders and nearshore and shelf deposit feeders from muddy environments are relatively longer and narrower as body size increases, suggesting that digestive diffusion limitations may be important. Gut volume scales as (body volume)1 while ingestion rate scales as (body volume)0.7. If diet and the chemical kinetics of digestion do not change appreciably, throughput time and thus the extent of digestion of given dietary components therefore must increase as a deposit feeder grows. Digestive processing constrainst may be most important in juveniles of species (especially those species with plug-flow guts) that are deposit feeders as adults.


Draft Genome Sequence of Bacillus subtilis ALBA01, a Strain with Antagonistic Activity against the Soilborne Fungal Pathogen of Onion Setophoma terrestris.
Bacillus subtilis is a nonpathogenic bacterium that lives in soil and has long been used as biological control agent in agriculture. Here, we report the genome sequence of a B. subtilis strain isolated from rhizosphere of onion that shows strong biological activity against the soilborne fungal pathogen Setophoma terrestris.


Assessing short- and long-term modifications of steady-state water infiltration rate in an extensive Mediterranean green roof.
Green roof detention capacity is related to the steady-state infiltration rate, is, of the growing medium. With the aim to investigate short- and long-term modifications of the detention capacity of an extensive Mediterranean green roof, three mini-disk infiltrometer (MDI) measurement campaigns were conducted at construction, after one season and after five years of operation. A laboratory experiment was designed to separately measure is in the upper and the lower part of the substrate profile. During the first operating season, field is increased by a factor of 2.4 and 1.9 for near-saturated (applied pressure head, h0 = -30 mm) and quasi-saturated conditions (h0 = -5 mm), respectively. Similar rainfall height did not induce significant modifications in the upper layer of the laboratory columns, even if contribution of small pores to water infiltration tended to increase. Differently, is significantly decreased by a factor of 3.4-5.3 in the lower layer. After the simulated rainfall, the upper layer was less packed (mean bulk density, ρb = 1.083 kg m-3) and the lower layer was more packed (ρb = 1.218 kg m-3) as compared with the initial density (ρb = 1.131 kg m-3) and the lower part enriched in small particles. Short-term modifications in the experimental plot were thus attributed to fine particles washing-off and bulk density decrease in the upper layer, yielding an overall more conductive porous medium. After five years of green roof operation, field is did not further increase thus showing that the washing/clogging mechanism was complete after one season or it was masked by counteracting processes, like root development and hydrophobicity.


Darwin, malthus, süssmilch, and euler: the ultimate origin of the motivation for the theory of natural selection.
It is fairly well known that Darwin was inspired to formulate his theory of natural selection by reading Thomas Malthus's Essay on the Principle of Population. In fact, by reading Darwin's notebooks, we can even locate one particular sentence which started Darwin thinking about population and selection. What has not been done before is to explain exactly where this sentence - essentially Malthus's ideas about geometric population growth - came from. In this essay we show that eighteenth century mathematician Leonhard Euler is responsible for this sentence, and in fact forms the beginning of the logical chain which leads to the creation of the theory of natural selection. We shall examine the fascinating path taken by a mathematical calculation, the many different lenses through which it was viewed, and the path through which it eventually influenced Darwin.


Are Circulating microRNAs Involved in Tumor Surveillance?
By studying literature data and having performed an in silico analysis, the circulating microRNA expression profiles of healthy individuals appear to show an abundance of microRNAs with predominant tumor suppressor activity. We hypothesize that circulating tumor suppressor microRNAs might constitute a sort of continuous tumor surveillance, whereby circulating microRNAs delivering gene expression modulating epigenetic information might halt cell transformation and tumorigenesis. This mechanism might complement the well-known cancer immune surveillance. A further hypothesis is also discussed, supposing that the tissue specific action of microRNAs might represent a putative defense mechanism against the potential tumor-promoting actions of secreted miRNA.


Clinical efficacy and safety of intravenous itraconazole in the management of invasive candidiasis in patients of surgery and critical care.
Although itraconazole exhibits potent activity against Candida species, there have been few studies examining the use of intravenous itraconazole in the treatment of invasive candidiasis. A nationwide multicenter clinical study was conducted to evaluate the efficacy and safety of intravenous itraconazole in the management of invasive candidiasis, including non-albicans Candida species, in non-neutropenic patients undergoing surgery and critical care. Between September 2007 and August 2009, patients with proven and presumed candidiasis were enrolled at 22 participating institutions. Patients with presumed candidiasis had a deep-body temperature of 37.8°C or higher and were positive for serum β-D: -glucan or two or more colonization sites of Candida species. The main exclusion criterion was severe renal impairment (creatinine clearance <30 ml/min). The primary efficacy analysis was based on clinical and microbiological responses 5-10 days after the end of treatment, assessed by an independent data review committee. Of the 60 patients enrolled, 49 were included in the modified intention-to-treat population; 31 patients received a definitive diagnosis and 18 patients a presumed diagnosis. Intravenous itraconazole was used as first-line therapy to treat 39 patients and as second-line therapy for 10 patients. The isolated species included Candida albicans (25 strains with definitive diagnosis and 17 with presumed diagnosis) and non-albicans species (16 and 10, respectively). Treatment was successful in 61.5% patients (65.5% in first-line and 50.0% in second-line therapy); 60% of proven invasive candidiasis (IC) patients were judged as successful compared with 63.2% of presumed candidiasis patients. Eradication rate was 63.6% for C. albicans and 71.4% for C. glabrata. Adverse effects occurred in 9 of 60 patients (15.0%), commonly impaired liver function. The clinical efficacy and safety of intravenous itraconazole were suggested in the management of proven and presumed candidiasis including C. glabrata in non-neutropenic patients. The status of intravenous itraconazole in the Japanese guideline warrants reconsideration.


Secreted type of amyloid precursor protein induces glial differentiation by stimulating the BMP/Smad signaling pathway.
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Although cytotoxicity of amyloid β peptides has been intensively studied within pathophysiology of AD, the physiological function of amyloid precursor protein (APP) still remains unclarified. We have shown previously that secreted APPα (sAPPα) is associated with glial differentiation of neural stem cells. To elucidate specific mechanisms underlying sAPPα-induced gliogenesis, we examined the potential involvement of bone morphogenic proteins (BMPs). BMPs are one of the factors involved in glial differentiation of neural progenitor cells. When expressions of BMP-2, -4, and -7 were examined, upregulation of BMP-4 expression was solely observed as a result of treatment with sAPPα in a time and dose-dependent manner. Furthermore, the treatment of sAPPα promoted phosphorylation of Smad1/5/8, a downstream signaling mediator of BMP receptors. Interestingly, N-terminal domain of APP (1-205) was sufficient to elevate BMP4 expression, resulting in an increase of glial fibrillary acidic protein (GFAP) expression and phosphorylation of Smad1/5/8. However, the application of APP neutralizing antibody and anti-BMP4 antibody significantly suppressed expression of BMP-4 as well as phosphorylation of Smad1/5/8. Thus, our results indicate that sAPPα-induced gliogenesis is in part mediated by the BMP-4 signaling pathway. We also observed upregulation of BMP-4 and phosphorylation of Smad1/5/8 in APP transgenic mice. It is imperative to unravel the mechanisms underlying the role of BMP-4 during APPα-induced glial differentiation in hope of providing novel prevention or treatment for AD.


Goniometric measurements of the forelimb and hindlimb joints in sheep.
The aim of this study was to evaluate angle-of-motion values for the forelimb and hindlimb in clinically healthy adult Santa Ines sheep by means of a standard goniometer. Twenty female Santa Ines sheep, ranging in age between three- to six-years-old, and weighing 32-45 kg (mean ± standard deviation [SD]: 30.4 ± 3.7) were used. A standard transparent plastic goniometer was used to measure passive maximum flexion, maximum extension, and range-of-motion (ROM) of the shoulder, elbow, carpal, hip, stifle, and tarsal joints in the right and left limbs. The goniometric measurements were done with the sheep awake and in a standing position. The measurements were made in triplicate by two independent investigators. In all evaluated joints, there was no significant difference either between the means of the two sides or between measurements performed by the two investigators. The mean ± SD values of the measurements (degrees) were as follows: 20 ± 1 (flexion), 170 ± 2 (extension), and 150 ± 2 (ROM) for the carpal joint; 34 ± 4 (flexion), 145 ± 6 (extension), and 110 ± 4 (ROM) for the elbow joint; 88 ± 2 (flexion), 144 ± 6 (extension), and 56 ± 5 (ROM) for shoulder joint; 35 ± 4 (flexion), 163 ± 3 (extension), and 129 ± 4 (ROM) for tarsal joint; 46 ± 4 (flexion), 146 ± 6 (extension), and 100 ± 4 (ROM) for the stifle joint; 54 ± 3 (flexion), 143 ± 7 (extension), and 89 ± 5 (ROM) for the hip joint. The data obtained provide useful and objective information on the joints. More studies are necessary using other sheep breeds.


Effect of apparent depth cues on accommodation in a Badal optometer.
The aim was to analyse the effect of peripheral depth cues on accommodation in Badal optometers. Monocular refractions at 0.17 and 5.00 D of accommodative stimulus were measured with the PowerRef II autorefractor (Plusoptix Inc., Atlanta, Georgia, USA). Subjects looked (randomly) at four different scenes, one real scene comprising familiar objects at different depth planes (Real) and three virtual scenes comprising different two-dimensional pictures seen through a Badal lens. The first image consisted of a photograph of the real scene taken in conditions that closely mimic a healthy standard human eye performance (out-of-focus [OoF] blur); the second image was the same photograph rendered with a depth of focus to infinity (OoF sharpness); and finally the third image consisted of a fixation target and a even white surrounding (White). In all cases the field of view was 25.0° and the fixation target was a Maltese cross subtending to two degrees. Twenty-eight right eyes from healthy young subjects were measured. The achieved statistical power was 0.9. At 5.00 D of accommodative stimulus, the repeated measures analysis of variance was statistically significant (p < 0.05) and the corresponding Bonferroni post hoc tests showed the following mean accommodative response differences and standard deviation (p-value) between the real and the virtual scenes: real-white =-0.66 ± 0.92 D (p < 0.01); real-OoF sharpness = -0.43 ± 0.88 D (p = 0.07); real-OoF blur =-0.25 ± 0.93 D (p = 0.89). A stimulus poor in depth cues inaccurately stimulates accommodation in Badal optometers; however, accommodation can be significantly improved in the same Badal optometer, when displaying a realistic image rich in peripheral depth cues, even though these peripheral cues (also referred to as retinal blur cues) are shown in the same plane as the fixation target. These results have important implications in stereoscopic virtual reality systems that fail to represent appropriately retinal blur.


The Surgeon's Role in Gastric Electrical Stimulation Therapy for Gastroparesis.
Gastroparesis, which can be viewed as a syndrome featuring nausea, vomiting, and abdominal pain, and associated other symptoms and findings, is increasingly seen by surgeons. Gastroparesis is associated with a number of gastrointestinal anatomic and physiologic findings. This article reviews the use of bioelectric therapy of neuromodulation, via gastric electrical stimulation, for patients with drug refractory gastroparesis syndromes including surgical aspects of device placement and subsequent management. In addition to an overall approach to the placement and subsequent management of gastric electrical stimulation devices, several newer concepts are discussed. The role of pyloric dysfunction in gastroparesis is also discussed including how stimulation devices and pyloric therapies may be used in concert. The additions of full-thickness gastrointestinal biopsies along with other physiologic, including GI electrophysiology, as well as some serologic measures, are also discussed. In addition, evolving approaches and emerging technologies for bioelectric neuromodulation of the gastrointestinal tract are introduced. Gastroparesis syndromes can be approached in a systematic manner based on known pathophysiology and when indicated can be helped with surgical therapies including neuromodulation.


Effect of Cytotoxic Compounds on Activity of Antioxidant Enzyme System in MCF-7 and H1299 Cells.
We studied the function of the antioxidant system in tumor cell lines MCF-7 and H1299 that differ by the state of tumor suppressor gene p53. Exposure to different classes of cytotoxic compounds induced several types of antioxidant system responses that depend on the type of cell line. The effects of platinum(II) and platinum(IV) complexes on activity of antioxidant enzymes vary, which can be explained by differences in their accumulation and biotransformation in tumor cells. Triazole and oxazolidinone derivatives had little effect on activity of superoxide dismutase and catalase in H1299 cells, but increased superoxide dismutase activity in MCF-7 cells.


Staff activities and behaviour are the source of many feelings: relatives' interactions and relationships with staff in nursing homes.
Family members do not give up their involvement in the life of their older relatives when they move to an institution. Relatives feel that it is they who take the initiative to establish a working relationship with the staff at the nursing home. Relatives want more spontaneous information from staff, particularly about residents' daily lives, and there is a need for relatives to have opportunities to talk with staff under relaxed conditions. Staff behaviour and activities towards residents and relatives are a source of many feelings for relatives. Relatives' understandings of the challenges faced by staff are not communicated to staff, nor are positive or negative experiences explicitly passed on to staff.


Detection of microRNAs by the combination of Exonuclease-III assisted target recycling amplification and repeated-fishing strategy.
A simple but effective method for the detection of miRNAs was proposed by integrating exonuclease-III assisted target recycling amplification and repeated-fishing strategy. In the proposed method, exonuclease-III assisted target recycling amplification reaction is adopted to produce a large amount of DNA fragments with fluorescence group at its 5' end in the presence of the target miRNA, which are then repeatedly fished out from the reaction mixture by a gold foil modified with a capture probe and transferred into a so-called 'product tube'. The amount of the target miRNA can then be determined from the fluorescence measurement of the solution in the 'product tube'. Application to the detection of miRNA-155 in samples of KH-2 and BRSA-2B cells revealed that the proposed method could achieve sensitive and accurate quantification of the target miRNA with a limit of detection of 36 fM and recovery rates in the range from 96.2% to 105%. Its simplicity, sensitivity and resistance to possible fluorescence interferences in complex biological samples make the proposed method a potentially competitive alternative for miRNAs detection in complex biological samples.


Cytochrome P450-derived eicosanoids and vascular dysfunction in coronary artery disease patients.
Accumulating preclinical and epidemiologic evidence has emerged to suggest that modulation of cytochrome P450 (CYP)-mediated eicosanoid metabolism may be a viable vascular protective therapeutic strategy for the secondary prevention of coronary artery disease (CAD). The functional relationship between CYP-derived eicosanoid metabolite levels and vascular dysfunction in humans with established CAD, however, has not been evaluated. Therefore, we characterized the relationship between inter-individual variation in soluble epoxide hydrolase (sEH) and CYP ω-hydroxylase metabolism and established vascular function phenotypes predictive of prognosis in a cohort of patients with atherosclerotic cardiovascular disease. Plasma epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHET), and 20-hydroxyeicosatetraenoic acid (20-HETE) levels were quantified by HPLC-MS/MS in 106 patients with stable, angiographically-confirmed CAD. Relationships between biomarkers of CYP-mediated eicosanoid metabolism and vascular function phenotypes were evaluated by Pearson's correlation. A significant inverse association was observed between 20-HETE levels (a biomarker of CYP ω-hydroxylase metabolism) and brachial artery flow-mediated dilation (r = -0.255, p = 0.010). An inverse association was also observed between 14,15-EET:DHET ratios (a biomarker of sEH metabolism) and both monocyte chemoattractant protein-1 levels (r = -0.252, p = 0.009) and a consolidated cellular adhesion molecule 'score' reflecting the levels of E-selectin and P-selectin (r = -0.216, p = 0.027). No associations with C-reactive protein or epithelial neutrophil-activating protein-78 levels were observed. Collectively, these findings demonstrate that enhanced CYP ω-hydroxylase and sEH metabolic function are associated with more advanced endothelial dysfunction and vascular inflammation, respectively, in patients with established atherosclerotic cardiovascular disease. These findings lay the foundation for future clinical research in this area.


The ventilation of multiple-bed hospital wards: review and analysis.
Although the merits of ventilating operating theatres and isolation rooms are well known, the clinical benefits derived from ventilating hospital wards and patient rooms are unclear. This is because relatively little research work has been done in the ventilation of these areas compared with that done in operating theatres and isolation rooms. Consequently, there is a paucity of good quality data from which to make important decisions regarding hospital infrastructure. This review evaluates the role of general ward ventilation to assess whether or not it affects the transmission of infection. A critical review was undertaken of guidelines in the United Kingdom and United States governing the design of ventilation systems for hospital wards and other multibed rooms. In addition, an analytical computational fluid dynamics (CFD) study was performed to evaluate the effectiveness of various ventilation strategies in removing airborne pathogens from ward spaces. The CFD simulation showed the bioaerosol concentration in the study room to be substantially lower (2467 cfu/m(3)) when air was supplied and extracted through the ceiling compared with other simulated ventilations strategies, which achieved bioaerosol concentrations of 12487 and 10601 cfu/m(3), respectively. There is a growing body of evidence that the aerial dispersion of some nosocomial pathogens can seed widespread environmental contamination, and that this may be contributing to the spread infection in hospital wards. Acinetobacter spp in particular appear to conform to this model, with numerous outbreaks attributed to aerial dissemination. This suggests that the clinical role of general ward ventilation may have been underestimated and that through improved ward ventilation, it may be possible to reduce environmental contamination and thus reduce nosocomial infection rates.


Defining effective clinician roles in end-of-life care.
Our goal was to determine primary care clinician perceptions of what is important to the provision of quality end-of-life care. We used ethnography, a qualitative research method involving the use of open-ended semistructured interviews. We included 38 family practice residency faculty from 9 community residency programs of the Affiliated Family Practice Residency Network, Department of Family Medicine, University of Washington School of Medicine. The roles described by interviewees when discussing their best practices while delivering end-of-life care were compiled. Primary care clinicians organize their delivery of quality end-of-life care predominantly through their relationships with patients and families. They play 3 roles when providing end-of-life care. As consultants, clinicians provide expert medical advice and treatment. As collaborators, they seek to understand the patient and family experience. Seasoned clinicians act as guides, using their personal intuitive knowledge of patient and family to facilitate everyone's growth when providing end-of-life care. Shifting clinician focus from skills and knowledge toward relationship, meaning, and roles provides new opportunities to improve end-of-life care for patients, families, and clinicians.


Molecular cloning of cDNAs encoding human GLEPP1, a membrane protein tyrosine phosphatase: characterization of the GLEPP1 protein distribution in human kidney and assignment of the GLEPP1 gene to human chromosome 12p12-p13.
Human glomerular epithelial protein 1 (GLEPP1), a receptor-like membrane protein tyrosine phosphatase (PTPase), was cloned and sequenced from a human renal cortical cDNA library. The human nucleotide and derived amino acid sequences were, respectively, 90 and 97% identical to those of rabbit. Human GLEPP1 is predicted to contain 1188 amino acids. The predicted mature protein is 1159 amino acids long and contains a large extracellular domain, a single transmembrane domain, and a single intracellular PTPase domain. Monoclonal and polyclonal antibodies raised against a human GLEPP1 fusion protein recognized a protein with distribution restricted to the glomerulus in human kidney and with an apparent molecular weight of approximately 200 kDa. The GLEPP1 gene was assigned to human chromosome 12p12-p13 by fluorescence in situ hybridization.


Ca2+ -activated Cl- channels (TMEM16A) underlie spontaneous electrical activity in isolated mouse corpus cavernosum smooth muscle cells.
Penile detumescence is maintained by tonic contraction of corpus cavernosum smooth muscle cells (CCSMC), but the underlying mechanisms have not been fully elucidated. The purpose of this study was to characterize the mechanisms underlying activation of TMEM16A Ca2+ -activated Cl- channels in freshly isolated murine CCSMC. Male C57BL/6 mice aged 10-18 weeks were euthanized via intraperitoneal injection of sodium pentobarbital (100 mg.kg-1 ). Whole-cell patch clamp, pharmacological, and immunocytochemical experiments were performed on isolated CCSM. Tension measurements were performed in whole tissue. TMEM16A expression in murine corpus cavernosum was confirmed using immunocytochemistry. Isolated CCSMC developed spontaneous transient inward currents (STICs) under voltage clamp and spontaneous transient depolarizations (STDs) in current clamp mode of the whole cell, perforated patch clamp technique. STICs reversed close to the predicted Cl- equilibrium potential and both STICs and STDs were blocked by the TMEM16A channel blockers, Ani9 and CaCC(inh)-A01. These events were also blocked by GSK7975A (ORAI inhibitor), cyclopiazonic acid (CPA, sarcoplasmic reticulum [SR] Ca2+- ATPase blocker), tetracaine (RyR blocker), and 2APB (IP3 R blocker), suggesting that they were dependent on Ca2+ release from intracellular Ca2+ stores. Nifedipine (L-type Ca2+ channel blocker) did not affect STICs, but reduced the duration of STDs. Phenylephrine induced transient depolarizations and transient inward currents which were blocked by Ani9. Similarly, phenylephrine induced phasic contractions of intact corpus cavernosum muscle strips and these events were also inhibited by Ani9. This study suggests that contraction of CCSM is regulated by activation of TMEM16A channels and therefore inhibition of these channels could lead to penile erection.


Quantitation of human shoulder anatomy for prosthetic arm control--I. Surface modelling.
Anatomical data and models for the human shoulder musculo-skeletal system are developed with the intent of quantifying physiological subcomponents of a model-based multi-axis prosthetic limb control scheme which has heretofore been implemented empirically. Part I presents the controller formulation, the surface descriptions of the muscles (and bones), and the centroidal trajectory data of the muscles. The data partially quantify the muscle modelling components of the controller, and set the stage for the analysis of the force-to-moment anatomical conversion factors of Part II.


Cardiac nuclear medicine, present status, future hopes as seen from the view of a cardiologist.
The present techniques of nuclear medicine that are used in cardiology are critically evaluated. They are used mainly for the assessment of coronary circulation (measurement of regional flow and perfusion), on the determination of left ventricular muscle function (radionuclear ventriculography) and on the study of cardiac metabolism. The last-mentioned technique is unique insofar as (except for magnetic resonance imaging) there is no other method available to analyse myocardial metabolism noninvasively in living man. Of immense practical importance is the diagnosis and quantitation of the abnormal coronary flow and perfusion, as coronary artery disease is one of the major diseases of the Western world. Finally, the value of nuclear imaging techniques is compared with that of other nonnuclear methods. In present-day medicine, with its increasingly high costs, the value of nuclear techniques must be assessed very carefully.


Intragastric Balloon for Overweight Patients.
Current treatments for overweight adults include reduced-calorie diet, exercise, behavior modification, and selective use of medications. Many achieve suboptimal results with these measures and progress to obesity. Whether the intragastric balloon (IGB), a reversible device approved for treatment of obesity, is a safe and effective option in overweight adults is less well studied. We conducted a study to prospectively analyze the safety and effectiveness of IGB in overweight adults, to compare the results to a simultaneously studied cohort of obese patients, and to share procedural tips for safe IGB placement and removal. One hundred thirty-nine patients were evaluated in this prospective, nonrandomized study. Twenty-six overweight [body mass index (BMI), 26-30)] and 113 obese (BMI > 30) patients underwent outpatient, endoscopic IGB placement under intravenous sedation. The IGB was filled with a 550-900 mL (average, 640 mL) solution of saline, radiological contrast, and methylene blue, with an approximate final proportion of 65:2:1. The patients were followed up at 1-2 weeks and then monthly for 6 months. At 6 months, they underwent IGB removal via an esophageal overtube to optimize safety, and then they were observed for 6 more months. IGB time was 190 ± 36 d in the overweight patients and 192 ± 43 d in the obese patients. Symptoms of IGB intolerance included nausea and pain, which were transiently present in 50-95% of patients for several days, and necessitated early IGB removal in 6% of patients. There were no procedure-related complications and no IGB-related esophagitis, erosion, perforation, or obstruction. The percentage of excess weight loss (EWL%) was 96 ± 54% in the overweight group and 41 ± 26% in the obese group (P < 0.001). In overweight adults failing standard treatments, IGB placement for 6 months had an acceptable safety profile and excellent weight loss.


Binding patterns of lectins to human retinoblastoma cells: preliminary findings.
Lectin binding patterns of cultivated retinoblastoma cell lines Y-79 and Mac-7 and freshly isolated tumor tissue revealed membrane-associated sugar residues NAcD-Gal, D-Gal, mannose, and D-GlcNAc. Compared to normal retinal pigment epithelium, LCA positively bound to retinoblastoma cells. Similarities in the glycoconjugate patterns with LV-B-1 cells are shown.


Learning the ABCs of melanoma-initiating cells.
Tumor stem or initiating cells have been proposed to exist for melanoma. Stem-like cells have been propagated from melanoma cell lines and specimens. Additionally, classical stem cell markers, including ABCG2 and CD133, have been identified in clinical melanomas. However, definitive markers for the purification and further characterization of melanoma-initiating cells remained elusive. Recently, Schatton et al. provided solid evidence that the doxorubicin-resistant ATP-binding cassette transporter ABCB5 marks primitive cells capable of recapitulating melanomas in xenotransplantation models. The identification of melanoma-initiating cells has far-reaching implications, as new therapeutic strategies can be envisioned that specifically target these cells.


Interferon: a candidate as the endogenous substance preventing tolerance and dependence to brain opioids.
It has been suggested that protein synthesis and immunological factors play a role in the development of tolerance and dependence to opiates. Interferon (IFN) is known to influence protein synthesis and the immune system. Our and other data suggest that IFN may be an agent that prevents the development of tolerance and the physical dependence to endogenous opioids.


Impact of high-fat diet on liver genes expression profiles in mice model of nonalcoholic fatty liver disease.
Evidences have shown that NAFLD influences expression of some drug metabolic enzyme genes. This study aims to investigate the role of HFD-induced NAFLD in regulating the transcription of genes, particularly the drug metabolizing genes variation. Transcriptome analysis demonstrated that HFD feeding caused the 150 genes expression to change, most genes associated with lipid metabolism, inflammatory, oxidative stress and oxidoreductase activity up-regulated, whereas most genes involved in nucleic acid metabolism repressed. The genes involved in drug metabolism had 16 down-regulated and 21 up-regulated in NAFLD. The over-4-fold change genes included the down-regulation of Cyp8b1, Cyp7a1, Sult3a1, Sult1e1, Cyp17a1, Cyp3a41a, Gstt3, Cyp51, Cyp2c54 and Cyp4f14, and the up-regulation of Asns, Past1, Cyp2c55, Gstm2, Cyp2e1 and Gstaα1. In conclusion, significant alterations in the expression of drug metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions or drug toxicity in nonalcoholic fatty liver disease.


Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.
The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.


Bendamustin-Rituximab Combination Is a Safe and Effective, Ambulatory Treatment for Elderly Patients with Chronic Lymphocytic Leukemia: Retrospective Real-world Analysis by Age from a German Registry and Review of the Literature.
Treatment recommendations in chronic lymphocytic leukemia (CLL) are based upon selected, otherwise healthy study populations mostly under 72 years of age. The Project group Internistic Oncology (PIO) embarked on an analysis of the 'real-world' safety and efficacy of bendamustine with and without rituximab in unselected outpatients. A multicenter, open-label, prospectively stratified, retrospective study was conducted to determine routine feasibility, toxicity, and response rates obtained by bendamustine with and without rituximab in a random population of mostly elderly patients with CLL. Records were obtained from 775 patients with CLL from 60 private medical oncology practices. Informed consent was obtained prior to study participation. The median observation time was 28 months. Patients were stratified according to age, and treatment. Response criteria and statistics followed international guidelines adopted by the "German Chronic Lymphocytic Leukemia Study Group". Overall, 57.5% of patients were over 70 (range=36-95) years old. Eastern Cooperative Oncology Group performance status and age influenced the total dose given, decreasing by 20% between ECOG 0 and 3, and by 15% above 80 years old. Response rates did not differ between the ages of 60 to 80 years, with an overall remission rate for bendamustine of 83%, and for the combination therapy of 89%, decreasing above the age of 80 years. Febrile neutropenia occurred in 25% of 775 patients, and grade 3 or 4 non-hematological adverse events in 9.55% (n=74), not interfering with the treatment. Bendamustine with and without rituximab was associated with high activity and tolerability, irrespective of age and risk factors. The median overall survival was 64 months with a 3-year survival rate of 72%; progression-free survival was 30.6 months, and the 3 year PFS was 43%. The good tolerability and feasibility of bendamustine with and without rituximab, in particular for the elderly population with CLL argues for it being a safe outpatient treatment.


Prevention and management of peritonitis in horses.
Peritonitis and adhesions in the horse are best managed through prevention. Perioperative antimicrobial therapy, nonsteroidal anti-inflammatory therapy, experienced personnel, and good surgical techniques should minimize complications after surgery. Despite preventative measures, some horses still develop peritonitis after surgery. Immediate, intensive treatment is necessary to enhance their chances for survival.


Fractalkine-Dependent Microglial Pruning of Viable Oligodendrocyte Progenitor Cells Regulates Myelination.
Oligodendrogenesis occurs during early postnatal development, coincident with neurogenesis and synaptogenesis, raising the possibility that microglia-dependent pruning mechanisms that modulate neurons regulate myelin sheath formation. Here we show a population of ameboid microglia migrating from the ventricular zone into the corpus callosum during early postnatal development, termed "the fountain of microglia," phagocytosing viable oligodendrocyte progenitor cells (OPCs) before onset of myelination. Fractalkine receptor-deficient mice exhibit a reduction in microglial engulfment of viable OPCs, increased numbers of oligodendrocytes, and reduced myelin thickness but no change in axon number. These data provide evidence that microglia phagocytose OPCs as a homeostatic mechanism for proper myelination. A hallmark of hypomyelinating developmental disorders such as periventricular leukomalacia and of adult demyelinating diseases such as multiple sclerosis is increased numbers of oligodendrocytes but failure to myelinate, suggesting that microglial pruning of OPCs may be impaired in pathological states and hinder myelination.


Novel Insight into Utilization of Flavonoid Glycosides and Biological Properties of Saffron (Crocus sativus L.) Flower Byproducts.
Saffron (Crocus sativus L.) byproducts are considered as a cheap source of bioactive polyphenolics endowed with potential antioxidant effects. The saffron biowaste is utilized for extraction of flavonoid glycosides and their potential biological properties. The total amount of polyphenolics and polysaccharides was found to be higher in the tepal than in the stamen. The bioactive compounds quercetin-3-O-sophoroside (Q-3-sop) and kaempferol-3-O-sophoroside (K-3-sop) were analyzed using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA) and identified by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). The antioxidant effects were studied using 2,2 diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), ferric ion reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC); Q-3-sop showed stronger antioxidant effects compared to K-3-sop, crocin-I, and crocin-II. Furthermore, Q-3-sop also inhibited cell apoptosis caused by H2O2 by reducing the levels of cellular reactive oxygen species (ROS). In terms of cytogenetic effects, Q-3-sop revealed no cytogenic effects on onion root meristem cells but chromosomal aberration was observed at the highest dose (200 ppm). Thus, saffron byproducts and its flavonoids could be utilized as natural antioxidant agents with no cytogenetic effects.


Effect of fibrin-targeting on clot lysis with urokinase-type plasminogen activator.
The effect of fibrin-targeting of urokinase-type plasminogen activator (u-PA) on its fibrinolytic potency was studied using recombinant fusion proteins of u-PA with the NH2-terminal region of tissue-type plasminogen activator (t-PA/u-PA) and chemical complexes of u-PA with F(ab')2 fragments of a fibrin specific monoclonal antibody (u-PA/MA-15C5-F(ab')2). Two chain derivatives of a low Mr variant of u-PA comprising amino acids Leu144-Leu411 (tcu-PA-32k), obtained by cleavage of recombinant single-chain u-PA (rscu-PA-32k) with thrombin (rtcu-PA-32k/T) or plasmin (rtcu-PA-32k/P) were investigated. The plasmin-derived two chain u-PA moieties, rtcu-PA-32k/P, rt-PA/tcu-PA-32k/P and rtcu-PA-32k/MA-15C5-F(ab')2/P had high specific activities in amidolytic and fibrin plate assays (130,000 and 150,000 IU/mg u-PA, 43,000 and 71,000 IU/mg u-PA and 32,000 and 56,000 IU/mg u-PA respectively). The thrombin-derived two chain u-PA moieties had a very low amidolytic activity, corresponding to less than or equal to 1 percent of that of their plasmin-derived counterparts. On fibrin plates, however, rtcu-PA-32k/T had a negligible activity, whereas rt-PA/tcu-PA-32k/T and rtcu-PA-32k/MA-15C5-F(ab')2/T had specific activities of 12,000 and 25,000 IU/mg u-PA respectively. The catalytic efficiency for plasminogen activation of rtcu-PA-32k/MA-15C5-F(ab')2/T is 4,000-fold lower than that of rtcu-PA-32k/MA-15C5-F(ab')2/P, but its concentration required for 50 percent lysis in 2 hours of a 125I-fibrin labeled plasma clot in human plasma (C50) is only 25-fold higher. The catalytic efficiency of rt-PA/tcu-PA-32k/T is 1,600-fold lower and the C50 100-fold higher than that of rt-PA/tcu-PA-32k/P. The catalytic efficiency and the fibrinolytic potential of rtcu-PA-32k/T are negligible as compared to that of rtcu-PA-32k/P. These observations may be explained by conversion of the thrombin derived two chain u-PA moieties to their plasmin-derived analogues at the fibrin surface. This conversion appears to be most efficient for the antibody conjugate which has a high fibrin-affinity, less efficient for the t-PA/u-PA chimera which has only moderate fibrin-affinity, and negligible for the unconjugated u-PA moiety which has no fibrin-affinity. These findings illustrate the importance of plasmin-mediated positive feedback mechanisms in u-PA mediated clot lysis.


Determination of residual solvents in pharmaceutical products by gas chromatography coupled to a head-space injection system and using an external standard.
A method of determination of residual solvents in powders using gas chromatography with an head-space injection system has been developed. The chromatographic conditions and parameters of the injection system were optimized to enable the quantification by external standardization of most common solvents in concentrations ranging from a few ppm to a few per cent.


Complications of Vascular Disease.
Vascular diseases and their sequelae increase perioperative risk for noncardiac surgical patients. In this review, the authors discuss vascular diseases, their epidemiology and pathophysiology, risk stratification, and management strategies to reduce adverse perioperative outcomes.


Some factors governing the efficacy of positional pseudoaccommodative intraocular lenses.
To examine the effects of ametropia (spherocylindrical), corneal curvature, target anterior chamber depth (ACD), misplacement, and some design features on the performance of positional pseudoaccommodative intraocular lenses (PPAIOLs). Theoretical investigation based on computer models to determine the practical limitations of PPAIOLs. Using a suitable model eye featuring gradient index optics within the cornea, the PPAIOL curvatures were calculated for axial ametropia ranging from -10 diopters (D) to +10 D, where the IOL was located at an ACD of 4.05 mm. The change in refraction (y) of the hypothetical pseudophakic eye was calculated for each millimeter of forward movement (x) of the PPAIOL up to 1 mm from the pole of the corneal back surface. The computations were repeated for a range of hypothetical PPAIOL refractive indices (1.49-1.70), ACDs, equiconvex and meniscus (back surface radius, -10 mm and -25 mm), corneal astigmatism (-1 D to -5 D), and radii (after corneal refractive surgery). Diopter/millimeter values represent the gradient of the relationship between x and y. Mathematical models describe the association between the diopter/millimeter gradient and key clinical dependent variables. (1) For a polymethyl methacrylate (refractive index, 1.49) PPAIOL of equiconvex design and 4.05-mm ACD, the predicted diopter/millimeter value is a function of ametropia (a), where diopter/millimeter = 1.666+0.136a+0.0018a2. (2) For 6-mm ACD and a refractive index of 1.7, diopter/millimeter = 1.836+0.159a+0.0027a2. (3) The equiconvex design benefits hyperopic but not myopic eyes. (4) For PPAIOLs correcting >4 D of astigmatism, more than 0.5 D of residual astigmatism is present at near after 1 mm of IOL displacement. (5) In emmetropic cases, the predicted diopter/millimeter value is a function of the corneal radius (r) where diopter/millimeter = 7.376-1.162r+0.0545r2. (6) Positional pseudoaccommodative IOL misplacement does not significantly affect the accommodative ability. (1) Hyperopic eyes with relatively steep corneas should benefit more from the PPAIOL than myopic eyes with relatively flat corneas. (2) A full, binocular, near refraction should be performed to correct any residual spheroastigmatism in anisometropia and cases in which the PPAIOL is toric.


Intestinal obstruction from appendiceal abscess in a newborn infant.
Perforated appendix in the newborn period is rare, its symptoms are occult and its outcome is disastrous. Associated mechanical small bowel obstruction as part of the clinical picture is rare indeed. We have treated a premature infant who presented with prolonged intermittent vomiting. Factors contributing to difficulty in diagnosis and to eventual succussful management are discussed.


The relationship between TLR4 rs4986790 and rs4986791 gene polymorphisms and Helicobacter pylori infection in children with gastritis.
TLR4 is involved in H. pylori lipopolysaccharide recognition and its SNPs might be related to increased risk of developing premalignant conditions and gastric cancer. The objectives of the study were to evaluate the associations between both TLR4 rs4986790 and rs4986791 gene polymorphisms and H. pylori infection in children with gastritis. We performed a cross-sectional study on 150 children admitted in a Tertiary Centre from Romania, between March 2016 and July 2018 in order to evaluate them regarding demographic, endoscopic, histopathological and TLR4 gene polymorphisms. Our final sample consisted of 50 children with H.pylori associated gastritis (group 1-Ghp group) and 97 children with gastritis without H.pylori infection (group 2). Poor socioeconomic status was a significant risk factor for H.pylori infection. We found no significant differences regarding the clinical symptoms and laboratory parameters between the two groups. Concordant results were found between the histopathological exam and rapid urease test. Variant genotypes of TLR4rs4986790 and TLR4rs4986791 gene polymorphisms acted as protective factors against H. pylori infection, without statistical significance. The variant genotype of the TLR4 gene polymorphisms might be protective factors for H.pylori infection, while socioeconomic status is an risk factor for H. pylori infection. Urease test is a usefull diagnostic tool for H. pylori infection.


Kenya.
The Kenya coast is bathed by the northward-flowing warm waters of the East Africa Coastal Current, located between latitudes 1 and 5 degrees S. With a narrow continental shelf, the coastal marine environments are dominated by coral reefs, seagrass beds and mangroves, with large expanses of sandy substrates where river inputs from Kenya's two largest rivers, the Tana and Athi rivers, prevent the growth of coral reefs. The northern part of the coast is seasonally influenced by upwelling waters of the Somali Current, resulting in lower water temperatures for part of the year. The coast is made up of raised Pleistocene reefs on coastal plains and hills of sedimentary origin, which support native habitats dominated by scrub bush and remnant pockets of the forests that used to cover East Africa and the Congo basin. The marine environment is characterized by warm tropical conditions varying at the surface between 25 degrees C and 31 degrees C during the year, stable salinity regimes, and moderately high nutrient levels from terrestrial runoff and groundwater. The semi-diurnal tidal regime varies from 1.5 to 4 m amplitude from neap to spring tides, creating extensive intertidal platform and rocky-shore communities exposed twice-daily during low tides. Fringing reef crests dominate the whole southern coast and parts of the northern coast towards Somalia, forming a natural barrier to the wave energy from the ocean. Coral reefs form the dominant ecosystem along the majority of the Kenya coast, creating habitats for seagrasses and mangroves in the lagoons and creeks protected by the reef crests. Kenya's marine environment faces a number of threats from the growing coastal human population estimated at just under three million in 2000. Extraction of fish and other resources from the narrow continental shelf, coral reef and mangrove ecosystems increases each year with inadequate monitoring and management structures to protect the resource bases. Coastal development in urban and tourist centers proceeds with little regard for environmental and social impacts. With a faltering economy, industrial development in Mombasa proceeds with few checks on pollution and other impacts. In 1998 Kenya's coral reefs suffered 50-80% mortality from the El Niño-related coral bleaching event that affected the entire Indian Ocean. The institutional, human resource and legal infrastructure for managing the coastal environment has in the past been low, however these are rapidly improving with the revitalization of national institutions and the passing in 1999 of an Environment Act. Marine Protected Areas are the key tool currently used in management of marine ecosystems, and focus principally on coral reefs and biodiversity protection. New initiatives are underway to improve application of fisheries regulations, and to use Integrated Coastal Area Management (ICAM) as a framework for protecting marine and coastal environments.


LncRNA H19 Regulates Lipopolysaccharide (LPS)-Induced Apoptosis and Inflammation of BV2 Microglia Cells Through Targeting miR-325-3p/NEUROD4 Axis.
Spinal cord injury (SCI) is a devastating traumatic event worldwide. Work from the past decade has highlighted the key involvement of long non-coding RNAs (lncRNAs) in SCI. Nevertheless, the molecular action of lncRNA H19 in SCI is still not fully understood. The levels of H19, microRNA (miR)-325-3p, and neuronal differentiation 4 (NEUROD4) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Flow cytometry was performed to assess cell apoptosis. The levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and IL-6 were detected using the enzyme-linked immunosorbent assay (ELISA). Targeted relationships among H19, miR-325-3p, and NEUROD4 were confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP), or RNA pull-down assays. Our data showed that H19 level was overexpressed in lipopolysaccharide (LPS)-treated BV2 cells. H19 silencing alleviated LPS-evoked cell apoptosis and inflammation. Mechanistically, H19 in BV2 cells directly targeted miR-325-3p, and NEUROD4 was a direct target of miR-325-3p. Moreover, miR-325-3p was a functional target of H19 in regulating cell apoptosis and inflammation induced by LPS. Enforced expression of miR-325-3p relieved LPS-evoked cell apoptosis and inflammation through reducing NEUROD4. Furthermore, H19 in BV2 cells regulated NEUROD4 expression through targeting miR-325-3p. Our results identified that the silencing of H19 attenuated LPS-evoked microglia cell apoptosis and inflammation after SCI at least partially through targeting the miR-325-3p/NEUROD4 axis, highlighting a novel approach for SCI management.


Unraveling the Stretch-Induced Microstructural Evolution and Morphology-Stretchability Relationships of High-Performance Ternary Organic Photovoltaic Blends.
The stretchability and stretch-induced structural evolution of organic solar cells (OSCs) are pivotal for their collapsible, portable, and wearable applications, and they are mainly affected by the complex morphology of active layers. Herein, a highly ductile conjugated polymer P(NDI2OD-T2) is incorporated into the active layers of high-efficiency OSCs based on nonfullerene small molecule acceptors to simultaneously investigate the morphological, mechanical, and photovoltaic properties and structural evolution under stretching of ternary blend films with various acceptor contents. The structural robustness of the blend films is indicated by their stretch-induced structural evolution, which is monitored in real-time by a combination of in situ wide/small angle X-ray scattering. It is found that adding the soft P(NDI2OD-T2) can enhance the stretchability and structural robustness of ternary blend films by more entangled chains and tie chains to dissipate strain. Furthermore, the stretchability of the ternary blends can be superbly predicted by a 3D equivalent box model. This work provides instructive insight and guidance for designing stretchable electronics and predicting the stretchability of multicomponent blends.


The Role of Matricellular Proteins in Brain Edema after Subarachnoid Hemorrhage.
Accumulated evidence suggests that blood-brain barrier disruption or brain edema is an important pathologic manifestation for poor outcome after aneurysmal subarachnoid hemorrhage. Many molecules may be involved, acting simultaneously or at different stages during blood-brain barrier disruption via multiple independent or interconnected signaling pathways. Matricellular protein is a class of nonstructural, secreted, and multifunctional extracellular matrix proteins, which potentially mediates brain edema formation. This study reviews the role of osteopontin and tenascin-C, representatives of matricellular proteins, in the context of brain edema formation after subarachnoid hemorrhage in both clinical and experimental settings.


Hemodynamic monitoring in childhood.
Hemodynamic monitoring is indicated in children with impending or manifest cardiocirculatory failure. Since cardiocirculatory failure is characterized by an imbalance between oxygen delivery and oxygen demand due to perfusion failure, the parameters monitored should aid in the assessment of these oxygen variables. Oxygen delivery depends on oxygen content and cardiac output. Cardiac output is determined by heart rate and stroke volume; stroke volume by preload, afterload and contractility. Since the direct measurement of oxygen consumption routinely is almost impossible, global oxygen utilization represented by mixed venous oxygen saturation may be used to quantify the relationship between oxygen delivery and oxygen consumption. Justification of invasive hemodynamic monitoring depends among other things on an optimal balance between usefulness of information and complications associated with the techniques used. In future, the development of further noninvasive techniques and the scientific evaluation of recommended monitoring techniques are prospects in cardiovascular monitoring in childhood.


Correlative light and scanning electron microscopy (CLSEM) for analysis of bacterial infection of polarized epithelial cells.
Infection of mammalian host cells by bacterial pathogens is a highly dynamic process and microscopy is instrumental to reveal the cellular and molecular details of host-pathogen interactions. Correlative light and electron microscopy (CLEM) combines the advantages of three-dimensional live cell imaging with ultrastructural analysis. The analyses of adhesion to, and invasion of polarized epithelial cells by pathogens often deploys scanning electron microscopy (SEM), since surface structures of the apical brush border can be analyzed in detail. Most available CLEM approaches focus on relocalization of separated single cells in different imaging modalities, but are not readily applicable to polarized epithelial cell monolayers, since orientation marks on substrate are overgrown during differentiation. To address this problem, we developed a simple and convenient workflow for correlative light and scanning electron microscopy (CLSEM), using gold mesh grids as carrier for growth of epithelial cell monolayers, and for imaging infection. The approach allows fast live cell imaging of bacterial infection of polarized cells with subsequent analyses by SEM. As examples for CLSEM applications, we investigated trigger invasion by Salmonella enterica, zipper invasion by Listeria monocytogenes, and the enterocyte attachment and effacement phenotype of enteropathogenic Escherichia coli. Our study demonstrates the versatile use of gold mesh grids for CLSEM of the interaction of bacterial pathogens with the apical side of polarized epithelial cells.


Influence of symptomatic periodontal disease on changes in skeletal bone density during medication therapy for osteoporosis in postmenopausal women: the Japanese Osteoporosis Intervention Trial (JOINT)-04 and JOINT-05.
Japanese postmenopausal women with symptomatic periodontal disease had a significantly smaller increase in the T-score for total hip bone density than those without periodontal disease during medication therapy for osteoporosis. Intervention to treat symptomatic periodontal disease before and/or during osteoporosis therapy could maintain the effect of osteoporosis medications. Women with periodontal disease may be more likely to develop osteoporosis. We evaluated whether the presence of symptomatic periodontal disease can influence changes in skeletal bone mineral density (BMD) during medication therapy for osteoporosis in Japanese postmenopausal women. A total of 4,258 postmenopausal women participated in the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04 trial) and number 5 (JOINT-05 trial), which were multi-center, open-label, randomized controlled trials in Japan. Of these, 3,670 non-edentulous subjects participated in the study. Subjects who had self-reported symptoms of periodontal disease at baseline were defined as having periodontal disease. The study outcome was the difference in BMD changes during the study between subjects with and without periodontal disease. Mixed models for repeated measures after adjusting for covariates were used to investigate the difference in the BMD changes during the study between subjects with and without periodontal disease. Subjects with periodontal disease had significantly lower T-scores for total hip (p = 0.035) and metacarpal (p = 0.048) BMD than those without periodontal disease at baseline. During medication therapy for osteoporosis, subjects with periodontal disease had a significantly smaller increase in T-score for total hip BMD than those without periodontal disease (p = 0.021), although no significant differences were observed in the changes in T-scores for other skeletal BMD measurements between subjects with and without periodontal disease. The presence of self-reported symptoms of periodontal disease may be associated with a decrease in the effect of osteoporosis medications in Japanese postmenopausal women.


Translunate, palmar perilunate fracture-subluxation of the wrist.
Three cases of palmar perilunate subluxation associated with a fracture of the palmar pole of the lunate are described. Wrist hyperflexion with a longitudinal loading force transmitted through the capitate probably accounts for this injury.


'Sum of activities' as dependent parameter: a new CoMFA-based approach for the design of pan PPAR agonists.
A 'sum-model' (3D QSAR - CoMFA) has been developed to design PPAR(alpha/gamma/delta) (peroxisome proliferator activated receptor) pan agonists by using the sum of activities (EC(50)) of compounds against individual subtypes as a dependent parameter. In addition, the three subtype specific CoMFA models were also generated using the identical training set molecules (N=28). All four models were validated using the popular 'leave-one-out' (LOO) method and with a test set of 9 molecules. The generated models were found to be statistically significant with r(cv)(2)>0.5 and r(ncv)(2)>0.9 and the lower values of standard error of estimation (SEE) ranging from 0.097 to 0.160. From the contour map analyses the 'sum-model' was found to represent the three subtype specific models and also predicted the sum of activities of the training set molecules with reasonable accuracy. The new molecules were designed based on the 'sum-model' and were found to dock well in the PPARgamma active site. This approach may find wider applications in the research related to other classes of 'designed multiple ligands'.


Screening and assessing ideas and delusions of reference using a semi-structured interview scale: a validation study of the Ideas of Reference Interview Scale (IRIS) in early psychosis patients.
Ideas and delusions of reference (IOR/DOR) are an important but underrecognized research target. Difficulty in their reliable assessment has been a barrier. A screening and assessment tool incorporating a self-information processing framework, the Ideas of Reference Interview Scale (IRIS), was developed and validated in patients with early psychosis. Comprehensive review of IOR/DOR phenomena in the literature and pilot interviews were conducted for scale item development. Self-referential themes were summarized into 15 items. A consecutive sample of 137 outpatients with early psychosis was interviewed using IRIS. Their IOR/DOR experiences were also rated independently by clinicians on the Scale for the Assessment of Positive Symptoms (SAPS) and self-rated using the IOR subscale on the Schizotypal Personality Questionnaire (SPQ). Inter-rater reliability of IRIS was examined in a subsample of 15 participants. IRIS demonstrated good internal consistency (Cronbach's alpha 0.80), inter-rater reliability (intraclass correlation coefficient 0.95), and divergent validity with other symptoms. IRIS correlated satisfactorily with the IOR/DOR item or subscale on SAPS and SPQ (Spearman's rho = 0.71 and 0.47, respectively). IRIS provided a reliable high-resolution tool for progressing single-symptom research into IOR/DOR, a potential target feature of schizophrenia. The scale allows future investigation into self-referential processing and detailed phenomenological comparison in different clinical, subclinical, and healthy populations.


Female frequencies and fitness components between sex phenotypes among gynodioecious populations of the colonizing species Trifolium hirtum All. in California.
Male sterility has been recently discovered in Californian populations of rose clover (Trifolium hirtum). This study describes the frequency distribution of male sterility in Turkish and Californian populations, and compares fitness components of hermaphrodites and females. As male-steriles were found in Turkey, it is likely that they were introduced to California during the 1940's with the original material derived from Turkey. The spread of male-sterile genotypes in California has given rise to an asymmetrical frequency distribution of male sterility with positive skewness. The frequency of females has not exceeded fifty percent and it appears to be temporally stable in most of the Californian populations. The hypothesis that female frequencies and fitness differences between phenotypes are correlated was tested by comparing sex phenotypes in seven populations with contrasting levels of male sterility. The analysis of those populations showed no evidence for such a correlation as no significant differences were found between sex phenotypes for fecundity and seed germination. The hypothesis that females are maintained due to fitness differences in the progeny of hermaphrodites and females was experimentally tested in the population with maximum frequency of male-steriles. The results showed no significant differences in the demographic performance of the progenies of hermaphrodites and females. The present results are discussed in terms of the possible mechanism of maintenance of gynodioecy in rose clover.


The role of the Src family kinase Lyn in the immunomodulatory activities of cathelicidin peptide LL-37 on monocytic cells.
Cathelicidin LL-37 is a multifunctional, immunomodulatory and antimicrobial host-defense peptide of the human immune system. Here, we identified the role of SFKs in mediating the chemokine induction activity of LL-37 in monocytic cells. LL-37 induced SFK phosphorylation; and chemical inhibitors of SFKs suppressed chemokine production in response to LL-37 stimulation. SFKs were required for the downstream activation of AKT, but Ca(2+)-flux and MAPK induction were SFK-independent. Through systematic siRNA knockdown of SFK members, a requirement for Lyn in mediating LL-37 activity was identified. The involvement of Lyn in cathelicidin activities was further confirmed using Lyn-knockout mouse BMDMs. The role of SFKs and Lyn was also demonstrated in the activities of the synthetic cationic IDR peptides, developed as novel, immunomodulatory therapeutics. These findings elucidate the common molecular mechanisms mediating the chemokine induction activity of natural and synthetic cationic peptides in monocytic cells and identify SFKs as a potential target for modulating peptide responses.


Synthesis, characterization and biological activity of some 1, 3, 4-thiadiazol derivatives.
Thiadiazoles are their derivatives exhibit a wide variety of pharmacological activities such as Antibacterial and anti-inflammatory. In the present study we have synthesized derivatives some 2,5 substituted 1,3,4- thiadiazoles. The structures of these synthesized compounds were confirmed by IR, NMR, and MASS spectra data. These compounds were evaluated for varies biological activities such as antibacterial and anti-inflammatory activity.


Bilateral transpopliteal approach for treatment of complex SFA and iliac occlusions.
We present a successful case of percutaneous intentional extraluminal recanalization (PIER) of bilateral long superficial femoral artery (SFA) occlusions and a long iliac artery occlusion through ultrasound-guided retrograde popliteal artery punctures. To our knowledge, PIER of SFA occlusions via popliteal approach has been reported in only three cases, and subintimal recanalization of combined SFA and iliac occlusions has not been reported.


Analysis of cutaneous and internal gill gas exchange morphology in early larval amphibians, Pseudophryne bibronii and Crinia georgiana.
This study uses stereological techniques to examine body, internal gill and cardiovascular morphology of two larval amphibians, Pseudophryne bibronii and Crinia georgiana, to evaluate the roles of diffusive and convective gas exchange. Gosner stage 27 specimens were prepared for light microscopy and six parallel sections of equal distance taken through the body as well as a further six through the heart and internal gills. Body, internal gill and heart volume as well as body and internal gill surface areas were determined. The harmonic mean distance across the internal gills was also measured and used to estimate oxygen diffusive conductance, DO₂. The species were of similar body size and surface area, but the heart and internal gills were larger in P. bibronii, which may represent precursors for greater growth of the species beyond stage 27. The much larger surface area of the skin compared to the internal gills in both species suggests it is the main site for gas exchange, with the gills supplementing oxygen uptake. The sparse cutaneous capillary network suggests diffusion is the main oxygen transport mechanism across the skin and directly into deeper tissues. A numerical model that simplifies larval shape, and has an internal (axial vessels) and external oxygen source, confirms that diffusion is able to maintain tissue oxygen with limited convective input.


Expression of genes involved in the salicylic acid pathway in type h1 thioredoxin transiently silenced pepper plants during a begomovirus compatible interaction.
The type-h thioredoxins (TRXs) play a fundamental role in oxidative stress tolerance and defense responses against pathogens. In pepper plants, type-h TRXs participate in the defense mechanism against Cucumber mosaic virus. The goal of this study was to analyze the role of the CaTRXh1-cicy gene in pepper plants during compatible interaction with a DNA virus, the Euphorbia mosaic virus-Yucatan Peninsula (EuMV-YP). The effects of a transient silencing of the CaTRXh1-cicy gene in pepper plants wëre evaluated by observing the accumulation of viral DNA and the visible symptoms of pepper plants under different treatments. The accumulation of salicylic acid (SA) and the relative expression of the defense genes NPR1 and PR10 were also evaluated. Results showed that viral DNA accumulation was higher in transiently CaTRXh1-cicy silenced plants that were also infected with EuMV-YP. Symptoms in these plants were more severe compared to the non-silenced plants infected with EuMV-YP. The SA levels in the EuMV-YP-infected plants were rapidly induced at 1 h post infection (hpi) in comparison to the non-silenced plants inoculated with EuMV-YP. Additionally, in pepper plants infected with EuMV-YP, the expression of NPR1 decreased by up to 41 and 58 % at 28 days post infection (dpi) compared to the non-silenced pepper plants infected with only EuMV-YP and healthy non-inoculated pepper plants, respectively. PR10 gene expression decreased by up to 70 % at 28 dpi. Overall, the results indicate that the CaTRXh1-cicy gene participates in defense mechanisms during the compatible interaction of pepper plants with the EuMV-YP DNA virus.


Interfacial deformation between an impacting water drop and a silicone-oil surface.
Detailed observations have been conducted on the interfacial deformation of a silicone oil surface and a water drop falling on it. Eleven kinds of silicone oils with wide variations of kinematic viscosity, nu(T)=1-10(5) mm(2)/s, have been tested. The oil surface is disturbed by a water drop with a diameter d(L)=3.1 mm, which falls freely on it from a height of 100-1000 mm. Special attention has been directed to the maximum depth of the cavity formed on the oil surface D(M) and to the maximum diameter of the water drop spreading on the oil surface d(M). We have categorized the configurations of the oil cavity into seven patterns, and those of the water drop at the oil-water interface into five patterns. The maximum cavity depth D(M)/d(L) can be well correlated by a dimensionless group Re(TL)We(TL), where Re(TL) is Reynolds number based on d(L) and nu(T) and We(TL) is Weber number with the water density and surface tension of oil. The maximum diameter of the impacting water drop d(M)/d(L) can be correlated by the Reynolds number with a viscosity of water (Re(L)) and the Ohnesorge number (Oh). Moreover, the condition under which the impacting water drop is smashed into pieces has been also examined based on Re(L) and Oh.


Release of cAMP gating by the alpha6beta4 integrin stimulates lamellae formation and the chemotactic migration of invasive carcinoma cells.
The alpha6beta4 integrin promotes carcinoma in-vasion by its activation of a phosphoinositide 3-OH (PI3-K) signaling pathway (Shaw, L.M., I. Rabinovitz, H.H.-F. Wang, A. Toker, and A.M. Mercurio. Cell. 91: 949-960). We demonstrate here using MDA-MB-435 breast carcinoma cells that alpha6beta4 stimulates chemotactic migration, a key component of invasion, but that it has no influence on haptotaxis. Stimulation of chemotaxis by alpha6beta4 expression was observed in response to either lysophosphatidic acid (LPA) or fibroblast conditioned medium. Moreover, the LPA-dependent formation of lamellae in these cells is dependent upon alpha6beta4 expression. Both lamellae formation and chemotactic migration are inhibited or "gated" by cAMP and our results reveal that a critical function of alpha6beta4 is to suppress the intracellular cAMP concentration by increasing the activity of a rolipram-sensitive, cAMP-specific phosphodiesterase (PDE). This PDE activity is essential for lamellae formation, chemotactic migration and invasion based on data obtained with PDE inhibitors. Although PI3-K and cAMP-specific PDE activities are both required to promote lamellae formation and chemotactic migration, our data indicate that they are components of distinct signaling pathways. The essence of our findings is that alpha6beta4 stimulates the chemotactic migration of carcinoma cells through its ability to influence key signaling events that underlie this critical component of carcinoma invasion.


Intestinal lymphangiectasia, a disease characterized by selective loss of naive CD45RA+ lymphocytes into the gastrointestinal tract.
Intestinal lymphangiectasia (InL) is a disease characterized by hypoproteinemia and lymphocytopenia resulting from blocked intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract. This leads to immunologic abnormalities including hypogammaglobulinemia, skin anergy and impaired allograft rejection. In the present study, we evaluated whether the above immunologic abnormalities are secondary to a quantitative or qualitative disorder of T cells. In initial studies we demonstrated that adult InL patients' peripheral blood contain strikingly (and significantly) reduced numbers of CD4+/CD45RA+ T cells, whereas the numbers of CD4+/CD45RO+ T cells were only moderately (and not significantly) reduced. In addition, the CD4+/CD45RO+ T cell population contained an increased percentage of highly differentiated and previously sensitized cells, as demonstrated by decreased CD27 and CD31 expression and increased HLA-DR and CD69 expression. In subsequent functional studies, we showed that the InL CD4+/CD45RO+ T cells, when stimulated in vitro, proliferate fivefold less than control CD4+/CD45RO+ T cells and produce fourfold more IL-4 and threefold less IFN-gamma and IL-2. Thus, this cytokine production profile also reflects the highly differentiated nature of the residual cell population. Overall, these studies provide new information on the trafficking of naive/mature and Th1/Th2 T cell populations in this disease model.


Concerted action of berberine in the porcine intestinal epithelial model IPEC-J2: Effects on tight junctions and apoptosis.
The plant alkaloid berberine has been shown to have many beneficial effects on human health. This has led to its use as a treatment for various cancer types, obesity, and diabetes. Moreover, a described barrier-strengthening effect in human cancer cell lines indicates that it might be useful for the treatment of inflammatory bowel disease. Detailed information regarding its effects on intestinal epithelium remains limited. In our current study, we describe the impact of berberine on a non-transformed porcine small intestinal epithelial cell model, IPEC-J2. Incubation of IPEC-J2 monolayers with berberine revealed dose- and time-dependent effects on barrier properties. A viability assay confirmed the specific effect of berberine on the apoptotic pathway, paralleled by the internalization of the sealing tight-junction (TJ) proteins claudin-1, claudin-3, and occludin within 6 h. Hence, the barrier function of the cells was reduced, as shown by the reduced transepithelial electrical resistance and the increased [3 H]-D-Mannitol flux. A decrease of claudin-1, claudin-3, and occludin expression was also observed after 24 h, whereas ZO-1 expression was not significantly changed. These data indicate an early effect on both cell viability and barrier integrity, followed by a general effect on TJ architecture. The intracellular co-localization of claudin-1 and occludin or claudin-3 and occludin points to an initial induction of apoptosis accompanied by the internalization of sealing TJ proteins. Although barrier strengthening has been reported in cancerogenic epithelial models, our results show a barrier-weakening action, which represents a new aspect of the effect of berberine on epithelia. These results agree with the known toxic potential of plant alkaloids in general and show that berberine is also capable of exerting adverse effects in the intestinal epithelium.


Evaluation of Tetrofosmin Cold Kit Fractionation Using Alternative New Method of Quality Control for Testing Radiochemical Purity.
Objective The aim of this study is to establish a method for the fractionation of tetrofosmin cold kit under different storage conditions and to optimize an alternate chromatography method from the reference method to test radiochemical purity (RCP). Materials and Methods Tetrofosmin cold kit vial was fractionated aseptically in six equal fractions and stored in vials and syringes. To test the stability of the reconstituted solution for a longer duration, the mother vials and syringes were stored at two different temperatures, that is, at 4°C and at -20°C till further used. Radiolabeling of fractionated tetrofosmin was performed as per the standard labeling protocol. Radionuclide purity, radioassay, and pH were tested. Radiolabeling efficiency and RCP were determined by paper chromatography. Results Radionuclide purity of eluate was greater than 99.9%. The pH of technetium-99m (Tc-99m) eluate and Tc-99m tetrofosmin was between 4.5-7.5 and 7.5-9.5, respectively. The deviation in the radioactivity during all measurements was less than 1%. The kits fractioned in glass vials resulted in higher radiolabeling yield and RCP as compared with kits fractionated in syringes. The RCP of glass vial versus syringe was observed to be greater than 95 versus 90% and 95 versus 80% at -20°C and 4°C, respectively. Conclusion Tetrofosmin kit can be used in a cost-effective manner by fractionation. One tetrofosmin vial can be used in six fractions for up to 15 days when stored at -20°C and 4°C freezer temperature. The alternative method to check the RCP of Tc-99m tetrofosmin is safer and less time consuming as compared with the reference method.


Metabolism and binding of benzo[a]pyrene in randomly-proliferating, confluent and S-phase human skin fibroblasts.
The metabolism of benzo[a]pyrene in randomly proliferating and confluent cultures of human skin fibroblast cells was compared with cell cultures in early S phase of the cell cycle after a G1 block. When each cell population was exposed to [G-3H]benzo[a]pyrene for 24 hours and the organic soluble metabolites in the extracellular medium and intracellular components were analyzed by HPLC, a quantitative increase in metabolism was observed in the confluent cell populations. The amount of organic soluble metabolites in the extracellular medium of the confluent dense cultures was 2.7 times the amount found in randomly proliferating cultures and 1.5 times that of the synchronized cultures. The trans-7,8- and 9,10 dihydrodiols and 3-hydroxy benzo[a]pyrene were the major metabolites formed. Small amounts of the sulphate conjugate, 9-hydroxy-benzo[a]pyrene and the tetrols were also detected. Cytoplasmic as well as nuclear extracts from the confluent cell cultures also contained higher amounts of metabolites compared to those from the randomly proliferating and S-phase cells. The levels of DNA modification by metabolically activated benzo[a]pyrene did not differ among the randomly proliferating, confluent and S-phase cells. However, the S-phase cells exhibited approximately 50-fold increase in the frequency of transformation compared to the randomly proliferating cells. Confluent cells were not transformed by benzo[a]pyrene. These data suggest that factors other than random modification of DNA by the carcinogen might have a significant role in the expression of a transformed phenotype and that metabolism and transformation are not directly related. Furthermore, confluent dense cultures with a heightened capability for metabolism of benzo[a]pyrene were more active in the detoxification of benzo[a]pyrene than in the production of the metabolites associated with cellular transformation.


Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.
Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II.


Does an increase of low income families affect child health inequalities? A Swedish case study.
Reduction of health inequalities is a primary public health target in many countries. A change of proportion of low income families might affect child health inequalities. Yet, the importance of family incomes in high income welfare states is not well established. The aim of this study was to investigate the effect of increased percentage of low income families on child health inequalities during an economic recession in Sweden, 1991-1996. Health inequalities for six health indicators were assessed during the period 1991-1996 and during adjacent periods. Relative inequality indices were estimated according to Pamuk and Mackenback. Appraisal of a child's socioeconomic situation was based on social data for the child's residency area. The total population of children and adolescents 0-<19 years old living in Stockholm County, Sweden, was studied. Each one year cohort comprised 20 470-25 420 people. Mortality; rate of low birth weight; days of hospital care for infections, asthma/allergic disorders, and unintentional injuries; and rate of abortions. Mortality decreased annually by 6.9%. The average relative inequality index for mortality before the recession was 1.40 and was lower during the recession, 1.14. The remaining five health indicators, and the relative inequality index for these indicators, did not differ significantly between the recession years (1991-1996) and adjacent periods. Relative health inequalities did not change, or decreased, during the recession years. The findings indicate that the connection was weak between child health inequalities and family incomes, within the frame of time and the range of income changes that occurred during the study period.


Factors Associated with HPV Vaccine Adherence among Latino/a Adolescents in a Rural, Texas-Mexico Border County.
Completion of human papillomavirus (HPV) vaccine series among Texas Hispanic adolescents is low compared to national data. We examined the association between HPV vaccine initiation and completion among Hispanic adolescents in a rural, Texas-Mexico border county and specific individual and neighborhood-level characteristics. Cross-sectional analysis of data from a broader cancer prevention program. Underserved colonias communities in a Texas-Mexico border county. Hispanic mothers or caregivers (n=712) and adolescents aged 11-17 years (n=1120) linked to publicly available data about their neighborhood. HPV vaccine adherence (ie, initiation and completion) as reported in either the Texas Immunization Registry or adolescents' electronic medical records, measured at the end of the cancer prevention program. Logit and multi-level mixed-effects logistic regression of individual- and neighborhood-level data. Factors associated with HPV vaccine initiation and completion were female gender (P<.01), adolescent insurance status (P<.001), and receipt of required vaccines (P<.001). After controlling for neighborhood-level characteristics, only receipt of required vaccines remained significant. Findings indicate a relationship between Hispanic adolescents' receiving the required vaccine series for school admission and HPV vaccine initiation and completion. In resource-limited settings like federally qualified health centers, further efforts should focus on implementing best practices at both the provider level (eg, education on bundled vaccine recommendation) and practice-level (eg, outreach and support by trained immunization navigators).


Spatial prediction of landslide susceptibility using hybrid support vector regression (SVR) and the adaptive neuro-fuzzy inference system (ANFIS) with various metaheuristic algorithms.
Landslides are natural and sometimes quasi-natural hazards that are destructive to natural resources and cause loss of human life every year. Hence, preparing susceptibility maps for landslide monitoring is essential to minimizing their negative effects. The main aim of the current research was to develop landslide susceptibility maps for Icheon Township, South Korea, using hybrid Machin learning and metaheuristic algorithms, that is, the bee algorithm (Bee), the adaptive neuro-fuzzy inference system (ANFIS), support vector regression (SVR), and the grey wolf optimizer (GWO), and to compare their predictive accuracy. Based on identified landslide locations, an inventory map was prepared and divided into training and validation data sets (70%/30%). the predicated model outcomes were validated with root mean square error (RMSE), and area under receiver operating characteristic curve (AUC), and pairwise comparison values for the ANFIS, ANFIS-Bee, ANFIS-GWO, SVR, SVR-Bee, and SVR-GWO models were obtained. The area under the curve was obtained with the training and validation data sets. Based on the training data sets, AUC of 80%, 83%, 83%, 69%, 81%, and 80% were obtained for the SVR, SVR-GWO, SVR-Bee, ANFIS, ANFIS-GWO, and ANFIS-Bee models, respectively. For the validation data sets, values of 79%, 82%, 82%, 68%, 79%, and 79%, respectively, were obtained. The SVR-GWO and SVR-Bee models were the most predictive models in terms of constructing the exceptionally focused landslide susceptibility map, with little spatial variation in the highly susceptible classes. Furthermore, the MSE, RMSE, and pairwise comparisons indicated that the SVR-GWO and SVR-Bee models were superior models for this study township. In addition, ANFIS individually was not superior to the ensembles of ANFIS-GWO and ANFIS-Bee for landslide assessment. These landslide susceptibility maps provide a platform for land use planning with an eye toward sustainable development of infrastructure and damage reduction for Icheon Township.


Concealed primary aortic sarcoma induced hypertensive encephalopathy resulting from a thoracic aortic occlusion: a case report.
Primary aortic sarcoma is a rare condition that is frequently associated with distal embolization. In addition, growth characteristics of primary aortic sarcoma lead to the narrowing of the involved aortic lumen. A 72-year-old Korean male with primary aortic sarcoma showed progressive unexplained blood pressure elevation that didn't improve with additional antihypertensive drug therapy. Because follow-up measures were not taken, the patient ultimately developed hypertensive encephalopathy with concurrent embolic dissemination. Although we successfully performed open transcatheter embolectomy in both legs, the patient died because of multiple organ failure 3 days after surgery. Given the ominous prognosis for this condition, this case report highlights the fact that the value of early detection and prompt evaluation of altered vital signs should not be overemphasized. We describe a rare case of primary aortic sarcoma that showed hypertensive encephalopathy caused by thoracic aortic occlusion and also had embolic metastases to the lower extremities.


Prominent isovolumic relaxation flow in a patient with cardiac tamponade.
We present herein the case of a 72-year-old man who presented with orthopnea and was diagnosed with cardiac tamponade due to carcinomatous pericarditis. Pulsed Doppler echocardiogram showed prominent isovolumic relaxation flow (IVRF) directed from the cardiac base toward the apex. Such flow is rare in pericardial effusion and may be due to enhanced early diastolic untwisting, sphericalization of apex, and restriction of wall motion by epicardial fibrous tissue. We describe herein a rare case of prominent IVRF with interesting underlying mechanisms.