The incidence and dynamic risk factors of chronic kidney disease among people with HIV.
We investigate the incidence of chronic kidney disease (CKD) among people with HIV (PWH) and the dynamic risk factors associated with CKD incidence. A population-based cohort study of PWH in South Carolina. Adults (age ≥18 years) PWH diagnosed between 2006 and 2019 who were CKD-free at baseline were included. The associations of HIV-related risk factors and conventional risk factors with the incidence of CKD were investigated during the overall study period and by different follow-up periods (i.e. 5, 10, and 15 years) by multivariate logistic regression. Among 9514 PWH, the incidence of CKD was 12.39 per 1000 person-years. The overall model indicated that conventional risk factors, such as hypertension, dyslipidemia, cardiovascular disease, and diabetes, were significantly associated with a higher risk of developing CKD. HIV-related characteristics, such as high percentage of days with viral suppression, recent CD4 + cell count, and percentage of retention in care, were associated with a lower risk of CKD compared with their counterparts. In the subgroup analysis, the results were similar for the 5-year and 6-10 years follow-up groups. Among patients who did not develop CKD by the 10th year, the risk factors for developing CKD within 11-15 years were dyslipidemia, diabetes, low recent CD4 + cell count, and short duration of retention in care while other predictors vanished. Diabetes, CD4 + cell count, and retention in care were persistently associated with CKD despite of follow-up duration. Closely monitoring diabetes and improving CD4 + cell count and retention in care are important to lower the risk of CKD in PWH.


[Kawasaki disease and innate immunity].
Kawasaki disease (KD) is an acute self-limited systemic vasculitis, and could develop in association with innate immune disorders. An innate immune system appears to play a key role in the development of KD, because pathogen-associated molecular patterns(PAMPs) and damage-associated molecular patterns(DAMPs) are elevated in the sera at acute phase KD, and oral administration of innate immune Nod1 ligand induces KD-like coronary arteritis in mice. PAMPs can be produced massively from microbes in a certain condition. DAMPs are produced from the host cells by the stimulation of PAMPs. We propose a hypothesis that PAMPs and DAMPs activate innate immune system and vascular cells through innate immune pattern recognition receptors(PRR) to release chemokines and cytokines, and induce KD in genetically predisposed individuals.


Management of patients with mildly dysplastic cervical smears.
The management of patients with mild dysplasia on cervical smears remains controversial. Recent studies have shown that many harbor high grade squamous intraepithelial lesions (HSIL) and human papillomavirus (HPV) and warrant further evaluation rather than follow-up. This prospective study dealt with the evaluation of patients with mild dysplastic smears using colposcopy and directed biopsies with view to identifying HSIL/HPV and treating them. Among 100 cases studied, 61% revealed HSIL/HPV; of them, 10% had high grades. Hence, patients with mildly dysplastic lesions should be evaluated further and managed with histopathologic examination of the biopsy specimen. This protocol may be cost effective for evaluating women with mildly dysplastic smears in a referral center, though it may not be so when compared to a policy of treating the infection, repeating the smears and performing colposcopy and biopsy on all those with persistent abnormality.


[Five cases of severe radiation pneumonitis after chemoradiotherapy for esophageal cancer].
Chemoradiotherapy( CRT) for esophageal cancer is a useful modality for both locally advanced and resectable cases. Among adverse events related to CRT, radiation pneumonitis( RP) requires special attention because it has been shown to be occasionally associated with a worse acute prognosis. We report 5 cases of severe RP after CRT. All patients were male, and their mean age was 72 years (range: 66-76 years). The clinical stage of esophageal cancer was I in 1 case, II in 2 cases, and IVa in 2 cases. The mean total radiation dose was 51.8 Gy (range: 43.4-61.4). Initial symptoms and first abnormal findings were a high fever in 4 cases and elevated serum C-reactive protein( CRP) levels in 1 case. No patients presented with respiratory symptoms, including dyspnea and coughing, as initial symptoms. All cases were diagnosed as RP by chest computed tomography examination, an average of 6.8 days after the completion of RT. Four patients required intensive care and were put on ventilator support. All patients received steroid pulse therapy. Two patients recovered from RP; however, 3 died( 1 attributable to multi-organ failure and 2 to respiratory failure). It is important to consider RP caused by CRT when patients present with high fever or elevated CRP levels after the completion of RT for esophageal cancer.


Function and expression study uncovered hepatocyte plasma membrane ecto-ATP synthase as a novel player in liver regeneration.
ATP synthase, canonically mitochondrially located, is reported to be ectopically expressed on the plasma membrane outer face of several cell types. We analysed, for the first time, the expression and catalytic activities of the ecto- and mitochondrial ATP synthase during liver regeneration. Liver regeneration was induced in rats by two-thirds partial hepatectomy. The protein level and the ATP synthase and/or hydrolase activities of the hepatocyte ecto- and mitochondrial ATP synthase were analysed on freshly isolated hepatocytes and mitochondria from control, sham-operated and partial hepatectomized rats. During the priming phase of liver regeneration, 3 h after partial hepatectomy, liver mitochondria showed a marked lowering of the ATP synthase protein level that was reflected in the impairment of both ATP synthesis and hydrolysis. The ecto-ATP synthase level, in 3 h partial hepatectomized hepatocytes, was decreased similarly to the level of the mitochondrial ATP synthase, associated with a lowering of the ecto-ATP hydrolase activity coupled to proton influx. Noteworthily, the ecto-ATP synthase activity coupled to proton efflux was completely inhibited in 3 h partial hepatectomized hepatocytes, even in the presence of a marked intracellular acidification that would sustain it as in control and sham-operated hepatocytes. At the end of the liver regeneration, 7 days after partial hepatectomy, the level and the catalytic activities of the ecto- and mitochondrial ATP synthase reached the control and sham-operated values. The specific modulation of hepatocyte ecto-ATP synthase catalytic activities during liver regeneration priming phase may modulate the extracellular ADP/ATP levels and/or proton influx/efflux trafficking, making hepatocyte ecto-ATP synthase a candidate for a novel player in the liver regeneration process.


Promising Targets and Current Clinical Trials in Metastatic Non-Squamous NSCLC.
Lung adenocarcinoma is the most common subtype of lung cancer today. With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapy, personalized medicine has become a reality for patients with lung adenocarcinoma. Here, we review potential additional targets and novel therapies of interest in lung adenocarcinoma including targets within the cell surface (receptor tyrosine kinases EGFR, human epidermal growth factor receptor 2, RET, ROS1, mesenchymal-epidermal transition, TRK), targets in intracellular signal transduction (ALK, RAS-RAF-MEK, PI3K-AKT-PTEN, WNT), nuclear targets such as poly-ADP ribose polymerase, heat shock protein 90, and histone deacetylase, and selected pathways in the tumor environment. With the evolving ability to identify specific molecular aberrations in patient tumors in routine practice, our ability to further personalize therapy in lung adenocarcinoma is rapidly expanding.


[Lung remodeling in asthma].
Repair is an integral part of every inflammation. Injured cells are replaced by new cells of the same type or by connective tissue. This may result in restitution "ad integrum" or lead to structural changes referred to as remodelling. For many years the importance of this phenomenon for the course of asthma, an undoubtedly chronic inflammatory disease, was underestimated. The presence of only partial reversibility of airflow obstruction in some patients with asthma has significantly changed our view on that problem. The irreversible component of airway obstruction is more prominent in patients with severe disease and persists despite aggressive anti-inflammatory treatment. Recent studies have proved that remodelling in asthma encompasses not only the bronchial tree, but also alveolar tissue. There are many factors supposedly responsible for lung reconstruction characteristic of asthma: mediators, cytokines, and growth factors. Better understanding of these processes should provide a basis for novel, long-term therapeutic strategies in asthma.


Kinetics of Fast Tetramerization of the Huntingtin Exon 1 Protein Probed by Concentration-Dependent On-Resonance R1ρ Measurements.
An approach for the quantitative description of the kinetics of very fast exchange processes (τex < 50-100 μs) associated with transient, reversible protein oligomerization, is presented. We show that on-resonance 15N-R1ρ measurements conducted as a function of protein concentration at several spin-lock radio frequency field strengths are indispensable for unambiguous determination of the rate constants for interconversion between monomeric and higher order oligomeric species. The approach is experimentally demonstrated on the study of fast, reversible tetramerization of the full-length Huntingtin exon 1 protein, httex1, responsible for Huntington's disease. Incorporation of concentration-dependent 15N-R2,eff data, obtained from on-resonance R1ρ measurements performed at three spin-lock field strengths, into analysis of the kinetic scheme describing reversible tetramerization of httex1 allowed us to uniquely determine the rate constants of interconversion between the various species. This approach serves as a valuable complement to the existing array of NMR techniques for studying early, transient oligomerization events in protein aggregation pathways.


Anemia and iron deficiency in school children, adolescents, and adults: a community-based study in rural Amazonia.
We investigated the prevalence and risk factors of anemia and iron deficiency in 389 [corrected] rural Amazonians aged 5-90 years in Acre, Brazil. Anemia and iron deficiency were diagnosed in 16% and 19% of the population, respectively. Anemia was likely to have multiple causes; although nearly half of anemic school children and women had altered iron status indicators, only 19.7% of overall anemia was attributable to iron deficiency. Geo-helminth infection and a recent malaria episode were additional factors affecting iron status indicators in this population.


Online interprofessional learning: the student experience.
Health and social care students in a faculty in the United Kingdom learn together in an interprofessional module through online discussion boards. The module assessment encourages engagement with technology and with group members through peer review. An evaluation of student experience of the module gathered data from 48 students participating in 10 online groups. Analysis of contributions to discussion boards, and transcripts of interviews with 20 students revealed differing levels of participation between individuals and groups. Many students were apprehensive about the technology and there were different views about the advantages and disadvantages of online learning. Students interacted in a supportive manner. Group leadership was seen as associated with maintaining motivation to complete work on time. Students reported benefiting from the peer review process but were uncomfortable with critiquing each other's work. Sensitivity about group process may have inhibited the level of critical debate. Nevertheless the module brought together students from different professions and different sites. Examples of sharing professional knowledge demonstrated successful interprofessional collaboration online.


Mode of action of a new nalidixic acid derivative, AB206.
A new chemotherapeutic agent, AB206, shows potent antibacterial activity against gram-negative bacteria, including most of the nalidixic acid-resistant strains tested. It strongly inhibits deoxyribonucleic acid (DNA) synthesis in Escherichia coli, but only slightly inhibits ribonucleic acid and protein synthesis. Its activity on DNA synthesis in vivo and in vitro is greater than that of nalidixic acid. AB206 also strongly inhibits in vivo DNA synthesis in nalidixic acid-susceptible and -resistant clinical isolates of Proteus and Serratia. AB206 shows high penetrability into E. coli cells, as demonstrated by antibacterial activity with or without ethylenediaminetetraacetic acid, inhibition of in vivo and in vitro DNA synthesis, and uptake of the drug into cells, as compared to nalidixic acid. It appears that the high antibacterial activity of AB206 may be explained both by its potent inhibitory action against DNA synthesis and also by its high penetrability into bacterial cells.


Mechanistic Insights into Cobalt-Catalyzed Regioselective C4-Alkenylation of 3-Acetylindole: A Detailed Theoretical Study.
A detailed mechanistic study of Co(III)-catalyzed C4-alkenylation of 3-acetylindole (1a) was done based on calculations at density functional theory (DFT) and correlated wave function levels. The whole catalytic cycle consists of four steps: C-H activation, olefin insertion, β-hydride elimination, and regeneration of the catalyst. The theoretical results support olefin insertion as the rate-determining step leading to the experimentally observed regioselectivity of the C4 site over the C2 site. By the analysis of three-dimensional (3D) geometries and the NCl plot, the preference for the C4 site over the C2 site could be attributed to the weaker repulsive interaction between the indole moiety and olefin in the transition states of the olefin insertion step for the former. The reliability of the theoretical mechanistic results is further confirmed through the DFT calculation of other related indole derivatives and olefin substrates.


Spontaneous compositional nanopatterning in Li-containing perovskite oxides.
A structure designed to show functionality on the nanometer length scale ideally would spontaneously form periodic nanometer-scale patterns comprising regions with contrasting properties. Here we report the synthesis of three new oxides that spontaneously form a variety of nanostructures with a periodic arrangement of phases with compositional and functional contrast. This is achieved through the partial substitution of Ti by Al, Cr, and Mn in periodically phase-separated (Nd(2/3-x)Li(3x))TiO(3) nanochessboard structures. The generality of this spontaneous compositional nanopatterning is promising for an array of exotic bulk and nanostructural properties.


Whole genome-based genetic insights of blaNDM producing clinical E. coli isolates in hospital settings of Pakistan.
Carbapenem resistance among Enterobacterales has become a global health concern. Clinical Escherichia coli isolates producing the metallo β-lactamase NDM have been isolated from two hospitals in Faisalabad, Pakistan. These E. coli strains were characterized by MALDI-TOF, PCR, antimicrobial susceptibility testing, XbaI and S1 nuclease pulsed-field gel electrophoresis (PFGE), conjugation assay, DNA hybridization, whole genome sequencing, bioinformatic analysis, and Galleria mellonella experiments. Thirty-four blaNDM producing E. coli strains were identified among 52 nonduplicate carbapenem-resistant strains. More than 90% of the isolates were found to be multidrug resistant by antimicrobial susceptibility testing. S1 PFGE confirmed the presence of blaNDM gene on plasmids ranging from 40 kbps to 250 kbps, and conjugation assays demonstrated transfer frequencies of blaNDM harboring plasmids ranging from 1.59 × 10-1 to 6.46 × 10-8 per donor. Whole genome sequencing analysis revealed blaNDM-5 as the prominent NDM subtype with the highest prevalence of blaOXA-1, blaCTX-M-15, aadA2, aac(6')-Ib-cr, and tet(A) associated resistant determinants. E. coli sequence types: ST405, ST361, and ST167 were prominent, and plasmid Inc types: FII, FIA, FIB, FIC, X3, R, and Y, were observed among all isolates. The genetic environment of blaNDM region on IncF plasmids included partial ISAba125, the bleomycin ble gene, and a class I integron. The virulence genes terC, traT, gad, fyuA, irp2, capU, and sitA were frequently observed, and G. mellonella experiments showed that virulence correlated with the number of virulence determinants. A strong infection control management in the hospital is necessary to check the emergence of carbapenem resistance in Gram-negative bacteria.IMPORTANCEWe describe a detailed analysis of highly resistant clinical E. coli isolates from two tertiary care centers in Pakistan including carbapenem resistance as well as common co-resistance mechanisms. South Asia has a huge problem with highly resistant E. coli. However, we find that though these isolates are very difficult to treat they are of low virulence. Thus the Western world has an increasing problem with virulent E. coli that are mostly of low antibiotic resistance, whereas, South Asia has an increasing problem with highly resistant E. coli that are of low virulence potential. These observations allow us to start to devise methodologies to limit both virulence and resistance and combat problems in developing nations as well as the Western world.


Metabolic bone disease in children : etiology and treatment options.
Metabolic bone disease in children includes many hereditary and acquired conditions of diverse etiology that lead to disturbed metabolism of the bone tissue. Some of these processes primarily affect bone; others are secondary to nutritional deficiencies, a variety of chronic disorders, and/or treatment with some drugs. Some of these disorders are rare, but some present public health concerns (for instance, rickets) that have been well known for many years but still persist. The most important clinical consequences of bone metabolic diseases in the pediatric population include reduced linear growth, bone deformations, and non-traumatic fractures leading to bone pain, deterioration of motor development and disability. In this article, we analyze primary and secondary osteoporosis, rickets, osteomalacia (nutritional and hereditary vitamin D-dependent, hypophosphatemic and that due to renal tubular abnormalities), renal osteodystrophy, sclerosing bony disorders, and some genetic bone diseases (hypophosphatasia, fibrous dysplasia, skeletal dysplasia, juvenile Paget disease, familial expansile osteolysis, and osteoporosis pseudoglioma syndrome). Early identification and treatment of potential risk factors is essential for skeletal health in adulthood. In most conditions it is necessary to ensure an appropriate diet, with calcium and vitamin D, and an adequate amount of physical activity as a means of prevention. In secondary bone diseases, treatment of the primary disorder is crucial. Most genetic disorders await prospective gene therapies, while bone marrow transplantation has been attempted in other disorders. At present, affected patients are treated symptomatically, frequently by interdisciplinary teams. The role of exercise and pharmacologic therapy with calcium, vitamin D, phosphate, bisphosphonates, calcitonin, sex hormones, growth hormone, and thiazides is discussed. The perspectives on future therapy with insulin-like growth factor-1, new analogs of vitamin D, strontium, osteoprotegerin, and calcimimetics are presented.


Highly efficient degradation of polyesters and polyethers by decatungstate photocatalysis.
Photocatalytic polymer degradation has been recognized as a promising solution to the global disposal of waste plastics. In this work, we revealed that various polyesters and polyethers were efficiently degraded in the presence of a polyoxometalate photocatalyst, specifically, decatungstate ([W10O32]4-, W10). A catalytic amount of W10 initiated the degradation of various polyesters and polyethers under photo-irradiation with a xenon lamp (λ > 350 nm) using O2 (1 atm) as the oxidant in acetonitrile or water. Moreover, this system can promote polymer degradation even under sunlight. The degradation efficiency, assessed from the degradation rate (Mw0 - Mw)/Mw0 (%) (where Mw0 is the Mw before the reaction), of W10 was notably higher than those of previously reported photocatalysts such as titanium oxide, other polyoxometalates, organometallic compounds, and organic dyes.


Rational Vehicle Design Ensures Targeted Cutaneous Steroid Delivery.
Objective: To design a topical vehicle that provided the optimal balance of betamethasone dipropionate penetration and retention in the skin, with minimal systemic absorption. Design: Six test formulations of betamethasone dipropionate 0.05% in vehicles contained the following penetration enhancers: elaidyl alcohol (Formulation-1), hexanol (Formulation-2), dodecanol (Formulation-3), octadecanol (Formulation-4), docosanol (Formulation-5), or oleyl alcohol (Formulation-6). Test agents were applied to human cadaver skin in static Franz-cell chambers containing receptor fluid. Measurements: Betamethasone absorption into the receptor fluid was measured over 24 hours. The distribution of betamethasone and its metabolites in the stratum corneum, epidermis, and dermis was analyzed using LC-MS/MS. The formulation with the optimal balance of penetration, permeation, retention, and minimal absorption was selected for a similar study comparing its penetration and absorption versus several commercially available betamethasone formulations. Results: Formulation-3 resulted in the highest retention of betamethasone in the skin as well as the highest steroid levels in the receptor fluid at 12 and 24 hours. Formulation-6 had the second highest retention of betamethasone in total skin, with relatively low absorption into the receptor fluid. All other variants had both lower steroid retention in the skin and lower absorption into the receptor fluid, with the exception of Formulation-2 which had higher absorption at 24 hours. Formulation-6/DFD-01 was selected for further development. Comparison of Formulation-6/DFD-01 with commercially available formulations of betamethasone dipropionate showed it had the highest steroid levels in the epidermis and dermis combined, with relatively low levels in the receptor fluid. Conclusion: Formulation-6/DFD-01 had the optimal balance of betamethasone retention in the skin, with low systemic absorption. This designed vehicle ensured retention of the corticosteroid in skin layers to maximize local efficacy while minimizing potential for hypothalamic-pituitary-adrenal suppression.


TET3-mediated demethylation in tomato activates expression of a CETS gene that stimulates vegetative growth.
Expression of the mammalian DNA demethylase enzyme TET3 in plants can be used to induce hypomethylation of DNA. In tomato lines that express a TET3 transgene, we observed distinct phenotypes including an increase in the length and number of leaves of primary shoots. As these changes resemble phenotypes observed in plants with strong expression of SELF PRUNING (SP), a member of the PEBP/CETS family, we investigated in TET3 lines the expression levels of members of the PEBP/CETS gene family, which affect shoot architecture and growth of sympodial units in tomato. We did not detect any changes in SP expression in TET3 lines, but for CEN1.1, a putative family member that has not been functionally characterized, we identified changes in gene expression that corresponded to hypomethylation in the upstream region. In tomato wild type, CEN1.1 is expressed in roots, petals, and shoot apices but not in mature leaves. In contrast, in TET3 transformants, the CEN1.1 gene became hypomethylated and activated in leaves. Ectopic expression of CEN1.1 in tomato caused similar phenotypes to those seen in TET3 transformants. Vegetative growth was increased, resulting both in a delay in inflorescence development and in an instability of the inflorescences, which frequently reverted to a vegetative state. Ectopic expression of CEN1.1 in Arabidopsis thaliana also caused floral repression. Our data suggest that the phenotypes observed in TET3 lines are a consequence of ectopic activation of CEN1.1, which promotes vegetative growth, and that CEN1.1 expression is sensitive to DNA methylation changes.


Changes of glycoconjugate expression in nasal respiratory mucosa of rats exposed to welding fumes.
To investigate the effects of welding fumes on the glycoconjugates in nasal respiratory mucosa, male Sprague-Dawley rats were exposed to manual metal arc stainless steel (MMA-SS) welding fumes at a concentration of 56-76 mg/m(3) total suspended particulate for 2 h/day in an inhalation chamber for 90 days. During the exposure period, the experimental animals were sacrificed after 2 h and 15, 30, 60, and 90 days of exposure; then sections were examined using lectin histochemistry. Some remarkable changes, such as destroyed cilia, desquamation and mucification of epithelial cells, and destruction of nasal septal glands, were seen in the welding fume-exposed groups. Specific changes in the lectin binding patterns were also observed in the welding fume-exposed rats. The Ricinus communis agglutinin-I (RCA-I) staining of the cilia and columnar cells increased slightly when compared with the unexposed rats. The RCA-I and Ulex europaeus agglutinin-I (UEA-I) staining of the goblet cells also increased as the exposure continued. The mucigenous epithelial cells reacted with Bandeiraea simplicifolia lectin-I (BSL-I), RCA-I, and succinylated wheat germ agglutinin A (sWGA) after 15 days of exposure, which was not visible in the control group. The dorsal septal glands exhibited an affinity with peanut agglutinin (PNA), BSL-I, and RCA-I, which was also not visible in the control group. The affinity for Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), PNA, sWGA, BSL-I, and UEA-I in the ventral septal glands of the welding fume-exposed groups tended to increase, whereas the concanavalin A (Con A) reactivity in the dorsal septal glands decreased slightly. In conclusion, it was assumed that the changes in the glycoconjugate residues in the nasal respiratory mucosa of the welding fume-exposed rats represented important components of defense mechanisms against the toxicants in the welding fumes.


Trimethylolpropane phosphate (TMPP) perfusion into the nucleus accumbens of the rat: electroencephalographic, behavioral and neurochemical correlates.
The infusion (0.13 mumol/infusion) of the convulsant trimethylolpropane phosphate (TMPP) into the nucleus accumbens (NA) of adults Sprague-Dawley rats reliably induced subclinical seizures, hyperlocomotor activity, and integrated stereotypies. Observation of these behaviors was temporally correlated with the appearance of EEG paroxysms, as well as with significant decreases in extracellular concentrations of both dopamine (DA) and norepinephrine (NE) in the NA. Repeated perfusion of TMPP revealed significant increases in stereotypic behavior during subsequent pre-drug baseline testing.


Foam soap is not as effective as liquid soap in eliminating hand microbial flora.
Foam soaps are aerosolized liquid soaps dispensed through a special pump mechanism. Currently there are no studies comparing liquid soap with foam soap in regard to efficacy of reducing hand microbial burden. In 3 separate experiments and with 2 different brands of foam soap, it was observed that nonantimicrobial foam soap was not as effective in reducing hand bacterial load as the liquid soap.


Combination Therapy with Isavuconazole and Micafungin for Treatment of Experimental Invasive Pulmonary Aspergillosis.
Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. We hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-d-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole (ISA) and the echinocandin micafungin (MFG) may result in improved outcomes in experimental IPA in persistently neutropenic rabbits. Treatments included ISA at 20 mg/kg of body weight/day (ISA20), 40 mg/kg/day (ISA40), and 60 mg/kg/day (ISA60); MFG at 2 mg/kg/day (MFG2); combinations of ISA20 and MFG2, ISA40 and MFG2, and ISA60 and MFG2; and no treatment (untreated controls [UC]). The galactomannan index (GMI) and (1→3)-β-d-glucan levels in serum were measured. The residual fungal burden (number of CFU per gram) was significantly reduced in ISA20-, ISA40-, ISA60-, ISA20-MFG2-, ISA40-MFG2-, and ISA60-MFG2-treated rabbits compared with that in MFG2-treated or UC rabbits (P < 0.01). Measures of organism-mediated pulmonary injury, lung weights, and pulmonary infarct score were lower in ISA40-MFG2-treated rabbits than in rabbits treated with ISA40 or MFG2 alone (P < 0.01). Survival was prolonged in ISA40-MFG2-treated rabbits in comparison to those treated with ISA40 or MFG2 alone (P < 0.01). These outcome variables correlated directly with significant declines in GMI and serum (1→3)-β-d-glucan levels during therapy. The GMI correlated with measures of organism-mediated pulmonary injury, lung weights (r = 0.764; P < 0.001), and pulmonary infarct score (r = 0.911; P < 0.001). In summary, rabbits receiving combination therapy with isavuconazole and micafungin demonstrated a significant dose-dependent reduction in the residual fungal burden, decreased pulmonary injury, prolonged survival, a lower GMI, and lower serum (1→3)-β-d-glucan levels in comparison to rabbits receiving isavuconazole or micafungin as a single agent.


The estimated cost of "no-shows" in an academic pediatric neurology clinic.
Missed appointments ("no-shows") represent an important source of lost revenue for academic medical centers. The goal of this study was to examine the costs of "no-shows" at an academic pediatric neurology outpatient clinic. This was a retrospective cohort study of patients who missed appointments at an academic pediatric neurology outpatient clinic during 1 academic year. Revenue lost was estimated based on average reimbursement for different insurance types and visit types. The yearly "no-show" rate was 26%. Yearly revenue lost from missed appointments was $257,724.57, and monthly losses ranged from $15,652.33 in October 2013 to $27,042.44 in January 2014. The yearly revenue lost from missed appointments at the academic pediatric neurology clinic represents funds that could have been used to improve patient access and care. Further work is needed to develop strategies to decrease the no-show rate to decrease lost revenue and improve patient care and access.


Detecting subject-specific fatigue-related changes in lifting kinematics using a machine learning approach.
Individual responses to fatigue have been observed in lifting kinematics, suggesting a subject-specific approach is necessary for fatigue identification. One-class support vector machines (OCSVM) may provide an objective method to classify fatigue-related kinematic changes during repetitive lifting. Participants completed a repetitive lifting protocol while motion capture recorded lifting motions. Subject-specific kinematics from participants' first 35% of lifts trained OCSVM decision boundaries. The remaining lifts were separated into test sets and classified against the decision boundary to identify the percentage of outlier lifts within each test set. Spearman's correlation assessed if the test sets' percentage of outlier lifts increased concurrently with participants' rating of perceived exertion (RPE). Significant positive associations were found for participants who demonstrated evidence of fatigue, while no significant associations were found for participants who did not demonstrate evidence of fatigue. These results demonstrate the prospective efficacy of an outlier detection tool for fatigue detection during repetitive lifting.Practitioner Summary: An objective subject-specific fatigue detection method is desired for workplace tasks, such as lifting. An outlier detection machine learning approach was identified when lifting movement patterns changed from baseline throughout a repetitive lifting protocol. Participants who demonstrated an increase in outlier movement patterns had a concurrent increase in self-reported fatigue.


[Thyroid dysfunction in patients with small intestinal bacterial overgrowth].
Small intestinal bacterial overgrowth (SIBO), similarly as thyroid diseases, is characterized by chronic diarrhea or constipation, but it is not known whether there is a causal relationship between these disorders. The aim of the study was to assess thyroid function indices in different clinical forms of SIBO. The study was performed in 34 patients with diarrhea predominant SIBO (group I), 30 with constipation predominant SIBO (group II) and 30 clinically healthy subjects (control group - K). Small intestinal bacterial overgrowth was assessed with lactulose hydrogen breath test (LHBT) using the breath-hydrogen analyzer (Gastrolyser, Bedfont). Serum thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels were determined by immunochemical method (ELFA) and anti-thyroid peroxidase (ATPO) protein level by immunoenzymatic method (ELISA). LHBT value was respectively in groups: K - 8,5 ± 2,9 ppm, I - 66,9 ± 16,9 ppm, II- 62,0 ± 15,5 ppm (p <0,001). The levels of hormones were similar in group K and I, whereas in group II differentiated: FSH 2,5 ± 0,7 vs. 3,8 ± 1,8 mU/L (p <0,05), FT3- 5,1 ± 1,2 vs. 3,7 ± 1,0 mU/L (p <0,05), FT4 - 14,1 ± 2,5 vs. 9,4 mU/L (p <0,01). In both groups of patients the levels of ATPO were statistically significantly higher than in the control group - respectively: K - 6,3 ± 3,1 IU/ml , I - 39,9 ± 23,4 IU/ml (p < 0,001), II - 94,1 ± 56,3 IU/ml (p <0,001). Thyroid function may be impaired in patients with small intestinal bacterial overgrowth which should be taken into account in the diagnostic and therapeutic management of the diseases of these organs.


The role of germ cell loss during primordial follicle assembly: a review of current advances.
In most female mammals, early germline development begins with the appearance of primordial germ cells (PGCs), and develops to form mature oocytes following several vital processes. It remains well accepted that significant germ cell apoptosis and oocyte loss takes place around the time of birth. The transition of the ovarian environment from fetal to neonatal, coincides with the loss of germ cells and the timing of follicle formation. All told it is common to lose approximately two thirds of germ cells during this transition period. The current consensus is that germ cell loss can be attributed, at least in part, to programmed cell death (PCD). Recently, autophagy has been implicated as playing a part in germ cell loss during the time of parturition. In this review, we discuss the major opinions and mechanisms of mammalian ovarian PCD during the process of germ cell loss. We also pay close attention to the function of autophagy in germ cell loss, and speculate that autophagy may also serve as a critical and necessary process during the establishment of primordial follicle pool.


Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States.
To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA). We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non-Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50-71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey. Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%-85.4%), 70.3% of EAC (95% CI: 64.4%-76.2%), 69.3% of GCA (95% CI: 61.0%-77.7%), and 33.6% of GNCA (95% CI: 21.7%-45.5%). These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers.


A right ectopic kidney with bilateral multiple anomalies of the renal vasculature - a case report.
The renal anatomy and its development is complex. This complexity is associated with numerous variations. Each renal variation has its own clinical and surgical importance. There is a good correlation between the ascent of the kidney, the level of its origin and number of the renal arteries. Any anomaly in the renal artery development may be due to a delay in the kidney ascension and it can lead to an ectopic kidney. Ectopic kidneys are more frequent in males and they are observed commonly on the left side. In the present study, we came across a rare case of a unilateral right renal ectopia and bilateral multiple renal arteries, with 5 renal arteries on the right side and 2 on the left side. The renal veins were 3 on the right side and two on the left side, with the retro aortic left renal vein, which were observed during the routine dissection of a male cadaver. This observation would be of immense importance for surgeons, interventional radiologists, nephrologists and vascular surgeons.


Pressure-induced reentrant micellization of amphiphilic block copolymers in dilute aqueous solutions.
The pressure-induced structural changes of a block copolymer, poly(2-ethoxyethoxyethyl vinyl ether)-block-poly(2-hydroxyethyl vinyl ether) (pEOEOVE-b-pHOVE) in aqueous solutions, were studied by means of small-angle neutron scattering (SANS) and dynamic light scattering (DLS) from atmospheric pressure up to 400 MPa. pEOEOVE-b-pHOVE formed a spherical micellar structure above 40 degrees C due to poor solubility of pEOEOVE. Micellization phase diagram was determined by DLS, and a covex-upward pressure-temperature (P-T) phase diagram was obtained having a peak around (P,T)=(150 MPa,48 degrees C). The SANS curves at 50 degrees C were analyzed as a function of P. The micellar core size decreased by pressurizing at low P's (P<or=150 MPa) and then increased by further pressurizing (150 MPa<P<400 MPa). It was confirmed that the water volume fraction in the micellar core was larger at high P's than that at low P's even when the core sizes are the same at both pressure regions. This means that the temperature dependence of hydration is more selective at low pressures than at high pressures, in good accordance with our previous results on concentrated aqueous solutions of block copolymers [Phys. Rev. Lett. 96, 048303 (2006)].


Determinants of performance on the Rey-Osterrieth Complex Figure Test: an analysis, and a new technique for single-case assessment.
The aim of the study was to identify factors determining performance on the Rey - Osterrieth Complex Figure Test in a normal population, in terms of accuracy of initial copy and delayed recall. Both immediate copy and delayed recall were related to age, and especially to the strategy adopted at the initial copy. A regression equation was derived whereby delayed recall could be predicted from the strategy adopted at the initial copy and the subject's age. This should prove useful in the analysis of Rey - Osterrieth performance in individual cases.


Design and synthesis of heterobimetallic Ru(II)-Ln(III) complexes as chemodosimetric ensembles for the detection of biogenic amine odorants.
The detection of neutral biogenic amines plays a crucial role in food safety. Three new heterobimetallic Ru(II)-Ln(III) donor-acceptor complexes, KPrRu, KNdRu, and KSmRu, K{[Ru((II))((t)Bubpy)(CN)4]2-Ln((III))(H2O)4} (where (t)Bubpy = 4,4'-di-tert-butyl-2,2'-bipyridine), have been synthesized and characterized. Their photophysical and X-ray crystallographic data were reported in this study. These complexes were found to be selective for biogenic amine vapors, such as histamine, putrescine, and spermidine, with a detection limit down to the ppb level. The sensitivities of these complexes to the amines were recorded as ~log K = 3.6-5.0. Submicron rods of the complexes, with a nanoscale diameter and microscale length, were obtained through a simple precipitation process. Free-standing polymeric films with different degrees of porosity were fabricated by blending the submicron rods with polystyrene polymer. The polymer with the highest level of porosity exhibited the strongest luminescence enhancement after amine exposure. Real time monitoring of gaseous biogenic amines was applied to real fish samples (Atlantic mackerel) by studying the spectrofluorimetric responses of the Ru(II)-Ln(III) blended polymer film.


Is the sentinel lymph node pathology protocol in breast cancer patients associated with the risk of regional recurrence?
Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse. From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate. In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D.


Analysis of integrated hepatitis B virus DNA and flanking cellular sequences in the hepatocellular carcinoma cell line HCC36.
A hepatocellular carcinoma cell line, HCC36, was established from an adult HBV carrier in Taiwan. From Southern blot analysis, there were at least four sites of integration of HBV DNA, and no viral replicative intermediates were detected. A genomic library was constructed from HCC36 DNA, and two phage clones, designated lambda 36A and lambda 36B, were shown to contain HBV DNA and flanking cellular sequences. In lambda 36A, HBV DNA sequences were quite conserved, and 7.4% base variation was detected. The viral sequences in lambda 36A and lambda 36B differed in only four bases, in addition to the microdeletion and -insertion observed in lambda 36B. The flanking cellular sequences identified in lambda 36A were human Alu sequences and in lambda 36B satellite sequences.


Giant benign solitary fibrous tumor of the pleura: PET/CT findings.
A chest radiograph revealed a large left lower hemithorax mass in a 48-year-old nonsmoker woman with chronic cough and dyspnea. Whole-body contrast-enhanced PET/CT confirmed a large mass with relatively uniform mild FDG uptake (standardized uptake value=1.8). No signs of infiltration, pleural effusion, significant regional lymph nodes, or extrathoracic lesions were seen. A presumptive diagnosis of a probable benign solitary fibrous tumor of the pleura (SFTP) was considered. SFTP was confirmed at surgery. Few reported cases have described the PET/CT findings of SFTPs.


Survival following video-assisted thoracoscopic versus open esophagectomy for esophageal carcinoma.
This study aimed to compare the overall and disease-free survival of patients who underwent video-assisted thoracoscopic esophagectomy (VATE) or open esophagectomy for esophageal carcinoma. Patients who underwent radical esophagectomy via VATE (VATE group, N=89) for esophageal carcinoma between January 2008 and December 2012 were retrospectively enrolled in this study. Patients subjected to open radical esophagectomy (open group) were retrospectively included at a ratio of 1:1, matching the VATE group in sex, age, clinical TNM stage, location of the primary tumor and ASA (American Society of Anesthesiologists) score. All the video-assisted thoracoscopic procedures were successfully completed, without conversion to open procedure. The age, gender, clinical TNM stage, location of the primary tumor and ASA score were similar in the two groups. VATE group was associated with significantly less blood loss and shorter hospital stay. The operative morbidity and mortality were similar between the two groups. The quality of the specimens in terms of resection margin and the number of lymph nodes examined were not inferior in the VATE group. With the median follow-up of 52 months, the 5-year overall survival and disease-free survival were similar between the two groups. The operative approach was not an independent prognostic factor in the overall and disease-free survival in univariate and multivariate analysis. VATE for esophageal carcinoma is associated with more favorable short-term outcomes and comparable long-term prognosis when compared with open esophagectomy.


Updates On Chimeric Antigen Receptor-Mediated Glioblastoma Immunotherapy.
Glioblastoma multiforme (GBM) is the most malignant of the primary central nervous system (CNS) neoplasms, accounting for nearly 80% of all primary brain tumors and is associated with high morbidity and mortality. Immunotherapy is proving to be a fertile ground for next-generation GBM therapy, with large translational research projects and clinical trials currently underway. One particularly promising area is the chimeric antigen receptors (CARs) in the context of lymphocyte adoptive cell therapy (ACT), which has achieved success in the treatment of hematological malignancies. In this review, we will discuss CARs and review current challenges facing their use in GBM therapy. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].


Bis(η-2-tert-butyl-1-trimethyl-silyl-3-phenyl-1-aza-all-yl)nickel(II).
The title compound, [Ni(C(15)H(24)NSi)(2)], is a homoleptic metal-η(3)-aza-allyl centrosymmetric complex containing two aza-allyl ligands bound in an η(3)-manner to an Ni(II) atom located on a center of symmetry. The overall coordination about the Ni(II) atom is square-planar. The C and N atoms of the aza-allyl group are sp(2)-hybridized. The uneven Ni-C and Ni-N distances [2.045 (5)/2.060 (6) and 1.916 (5) Å] are influenced by a steric hindering effect from the nearby benzene ring.


Metaplastic changes in chronic cholecystitis: implications for early diagnosis and surgical intervention to prevent the gallbladder metaplasia-dysplasia-carcinoma sequence.
Metaplastic features of the gallbladder epithelium are considered to be the precursors of gallbladder cancer. Considering the possible role of chronic inflammatory changes in the development of these lesions and the rationale for performing an early prophylactic cholecystectomy, we performed a retrospective study to assess the prevalence of gallbladder metaplasia in patients who underwent cholecystectomy due to underlying cholelithiasis. We reviewed the routine histopathology reports of 86 patients with chronic cholecystitis, who underwent elective cholecystectomy, to assess the prevalence of gallbladder metaplasia in the course of chronic cholecystitis. We further attempted to evaluate the existence of any correlations between the presence of the gallbladder metaplasia and the type of lithiasis, as well as the gallbladder wall thickness. The overall prevalence of metaplastic features in the resected specimens was 25.6%. Dysplastic changes were more frequent in gallbladder specimens with concurrent metaplasia. Moreover, in presence of metaplastic changes, we observed an increase of the average gallbladder wall thickness. Finally, metaplastic and dysplastic changes were associated with the presence of micro-lithiasis rather than macro-lithiasis. Gallbladder metaplastic changes appear to be more frequent in cases of micro-lithiasis and seem to be associated with a chronic thickening of the gallbladder wall. Taking into account the usually sub-clinical course of this group of patients, when compared to patients with macro-lithiasis, further studies are needed to evaluate a possible role of prophylactic cholecystectomy in this population to prevent the long term evolution of these early changes to cancerous lesions.


Comparison of interaction potentials of liquid water with respect to their consistency with neutron diffraction data of pure heavy water.
A number of interaction potential models for liquid water are scrutinized from the point of view of their compatibility with results of neutron diffraction experiments on pure heavy water. For the quantitative assessment a protocol developed recently [L. Pusztai et al., Chem. Phys. Lett. 457, 96 (2008)] using the reverse Monte Carlo method has been applied. The approach combines the experimental total scattering structure factor (tssf) and partial radial distribution functions (prdfs) from molecular dynamics simulations in a single structural model (particle configuration). Goodness-of-fit values to the three (O-O, O-H, and H-H) simulated prdfs and to the experimental tssf provided an unbiased measure characterizing the level of consistency between various interaction potentials and diffraction experiments. Out of the sets of prdfs investigated here, corresponding to SPCE, BJH, ST2, POL3, TIP4P, TIP4P-2005, TTMF3, and ENCS interaction potentials, the ones from the TIP4P-2005 potential proved to be the most consistent with the experimental neutron-weighted tssf of heavy water. More importantly, it is shown that none of the above interaction potentials are seriously inconsistent with the measured structure factor at ambient conditions.


[Immunohistochemical study using a double fluorescent staining on the regional lymph nodes of gastric cancers].
For the purpose to investigate the immunological anti-tumor function of lymphocytes in the regional lymph nodes of gastric cancer, a double staining procedure using several monoclonal antibodies against the surface membranes of T and NK cells with fluorescent antibody technique was conducted. The number of CD11b+ cells out of CD8+ cells was small with almost all being CD11b- belonging to cytotoxic T cells. Leu8+ cells and Leu8- cells out of CD4+ cells were recognized in equal numbers and were reciprocal. The ratio of CD4+ Leu8-/CD4+ demonstrated an increase in the group injected with OK-432. The ratio of OKT9+ or OKIa1+ occupied in CD8+ or CD4+ cells was only several percent, and few in number. An increase for the ratio of CD4+ OKT9+/CD4+ was observed in the group injected with IL-2. Similar increases for the ratio of CD4+ OKIa1+/CD4+ were obtained in the group injected with OK-432 and in the metastatic group, respectively. The Leu7+ CD16+ cells were not observed. The Leu7- CD16+ cells were observed in a part where metastases were focused. These results indicated that lymphocytes in regional lymphocyte of gastric cancer might hold the hidden anti-tumor effect, but did not display the full function without preoperative intratumor injection of BRM such as IL-2 or OK-432.


Naming Speed of Adolescents and Young Adults with Attention Deficit Hyperactivity Disorder: Differences in Alphanumeric Versus Color/Object Naming.
This study investigated the performance of adolescents and young adults with Attention Deficit Hyperactivity Disorder (ADHD), Reading Disorder (RD), and ADHD/RD on measures of alphanumeric and nonalphanumeric naming speed and the relationship between naming speed and academic achievement. The sample (N = 203) included students aged 17-28 years diagnosed with ADHD (n = 83), RD (n = 71), or ADHD/RD (n = 49). Individuals with ADHD performed significantly faster on measures of alphanumeric naming compared with RD and comorbid groups and, within group, demonstrated significantly quicker naming of letters/digits compared with colors/objects. Both alphanumeric rapid naming scores and processing speed scores variably predicted academic achievement scores across groups, whereas nonalphanumeric rapid naming only predicted reading comprehension scores within the ADHD group. Results support findings that older individuals with ADHD show relative weakness in rapid naming of objects and colors. Implications of these findings in regard to assessment of older individuals for ADHD are discussed.


[Use of alpha-lipoic acid and omega-3 in postpartum pain treatment].
Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding.


Local tolerance and activity of MK-927, a novel topical carbonic anhydrase inhibitor.
A three-dose, randomized, double-masked, parallel, placebo-controlled ocular tolerance study was undertaken in 12 healthy, normal volunteers with the water-soluble, topical carbonic anhydrase inhibitor MK-927. To our knowledge, this constitutes the first administration of MK-927 to humans. Ten subjects received three drops of 2% MK-927 ophthalmic solution and two subjects received three drops of placebo (vehicle) in one randomly selected eye. Local tolerance of 2% MK-927 was acceptable and supports further clinical trials in patients. Significant intraocular pressure (IOP)-lowering activity was noted when comparing IOP four hours after first dose with that 20 hours predose in the treated eye of subjects receiving MK-927 (mean percent change in IOP, -29.7%; mean change in IOP, -4.6 mm Hg) as opposed to the same comparison for the contralateral, untreated eye (-7.2% and -1.3 mm Hg, respectively). In the two subjects treated with placebo, IOP-lowering activity was not seen in either the placebo-treated eye (-0.4%) or the contralateral, untreated eye (+3.1%).


Coordination of two opposite flagella allows high-speed swimming and active turning of individual zoospores.
Phytophthora species cause diseases in a large variety of plants and represent a serious agricultural threat, leading, every year, to multibillion dollar losses. Infection occurs when their biflagellated zoospores move across the soil at their characteristic high speed and reach the roots of a host plant. Despite the relevance of zoospore spreading in the epidemics of plant diseases, individual swimming of zoospores have not been fully investigated. It remains unknown about the characteristics of two opposite beating flagella during translation and turning, and the roles of each flagellum on zoospore swimming. Here, combining experiments and modeling, we show how these two flagella contribute to generate thrust when beating together, and identify the mastigonemes-attached anterior flagellum as the main source of thrust. Furthermore, we find that turning involves a complex active process, in which the posterior flagellum temporarily stops, while the anterior flagellum keeps on beating and changes its gait from sinusoidal waves to power and recovery strokes, similar to Chlamydomonas's breaststroke, to reorient its body to a new direction. Our study is a fundamental step toward a better understanding of the spreading of plant pathogens' motile forms, and shows that the motility pattern of these biflagellated zoospores represents a distinct eukaryotic version of the celebrated 'run-and-tumble' motility class exhibited by peritrichous bacteria.


[Clinical experience with reusable and single use flexible ureterorenoscopes].
Flexible ureterorenoscopy (fURS) has become one of the most frequent procedures in urology in recent years. The main problem on the way of the spread of flexible ureterorenoscopy in everyday urological practice all over the world is the fragility of endoscopes. To evaluate the potential use of reusable and single-use ureterorenoscopes for kidney stones. The analysis included 30 patients who underwent of retrograde intrarenal surgery (RIRS) for kidney stones. The patients were divided into two groups. I gr. - RIRS was performed with a reusable flexible ureterorenoscope Flex XC "Karl Storz" (Germany) (n=20), II gr. - a single-use flexible ureterorenoscope PU3022 "Pusen" (China) (n=10) was used. Lithotripsy was performed with a Lumenis Pulse 100H holmium laser (Israel, USA). The age of patients, size and density of stones in I gr. and II gr. were comparable (42.5+/-16.9 vs 50+/-10.07 (years); 8.5+/-2.9 vs 10+/-2.5 (mm); 1248+/-315.3 vs 1376+/-223.3(HU+). Intraoperative complications were noted: in the I gr. - migration of stone fragments and bleeding; in the II gr. - migration of a fragment of stone. The time and efficiency of the operation of I gr. and II gr. were 75+/-39.9 vs 82.5+/-45.7 (min); 18 (90%) vs 9 (90%), respectively. Additional shock wave lithotripsy was required in 2 cases in the I gr., and more frequent usage stent was noted in the II gr. 10 (100%). In I gr. 5 (25%) patients had signs of inflammatory complication and 1 (5%) patient needed a change of antibiotics, after operation. The acute pyelonephritis was indicating in 2 (20%) patients of II gr. in the same period. The use of access sheath was in all patients of II gr. and in 14 (70%) cases of I gr. In 1 case of the II gr. it was not possible extract of a stone fragment from the lower calyx due to the thickness of the intrument. The possibility of bending was higher for the "Karl Storz" ureterorenoscope due to smaller diameter of the instrument. One of the disadvantages of reusable flexible ureterorenoscope is the fragility of the instrument. In our research, the repair of the instrument was required after 12 manipulations. The use of smaller instruments, the use of new digital imaging, the mobility of devices, allows performing interventions simultaneously by two surgeons, achieving the greatest fragmentation or evacuation of fragments of stones with good visualization, as well as using methods of drainage-free lithotripsy ("tubless").


Reassessing the effects of simple carbohydrates on the serum triglyceride responses to fat meals.
The effects of glucose, sucrose, and fructose ingestion on the serum triglyceride responses to meals containing 40 g fat were studied in 21 normolipidemic, nonobese medical students (9 men, 12 women). Mean postprandial lipemia was not significantly lower after meals containing 50 g glucose and 40 g fat than after meals containing 40 g fat alone (2.11 vs 2.42 mmol.L-1.7 h-1, p greater than 0.45) despite a substantial increase in plasma insulin concentrations after the glucose-containing meal. Ingestion of 50 g fructose and 40 g fat (4.23 mmol.L-1.7 h-1, p less than 0.0001) and 100 g sucrose and 40 g fat (3.77 mmol.L-1.7 h-1, p less than 0.001) resulted in significantly greater lipemia than did the ingestion of fat alone. These findings suggest that the ingestion of insulinogenic carbohydrates does not reduce postprandial lipemia in normolipidemic subjects and that the ingestion of fructose and fructose-containing carbohydrates may augment the postprandial lipemia induced by a fat-containing meal.


Prevalence and socioeconomic impact of depressive disorders in India: multisite population-based cross-sectional study.
The National Mental Health Survey (NMHS) of India was undertaken with the objectives of (1) estimating the prevalence and patterns of various mental disorders in representative Indian population and (2) identifying the treatment gap, healthcare utilisation, disabilities and impact of mental disorders. This paper highlights findings pertaining to depressive disorders (DD) from the NMHS. Multisite population-based cross-sectional study. Subjects were selected by multistage stratified random cluster sampling technique with random selection based on probability proportionate to size at each stage. Conducted across 12 states in India (representing varied cultural and geographical diversity), employing uniform, standardised and robust methodology. A total of 34 802 adults (>18 years) were interviewed. Prevalence of depressive disorders (ICD-10 DCR) diagnosed using Mini International Neuropsychiatric Interview V.6.0. The weighted prevalence of lifetime and current DD was 5.25% (95% CI: 5.21% to 5.29%, n=34 802) and 2.68% (95% CI: 2.65% to 2.71%, n=34 802), respectively. Prevalence was highest in the 40-59 age groups (3.6%, n=10 302), among females (3.0%, n=18 217) and those residing in cities with population >1 million (5.2%, n=4244). Age, gender, place of residence, education and household income were found to be significantly associated with current DD. Nearly two-thirds of individuals with DD reported disability of varying severity, and the treatment gap for depression in the study population was 79.1%. On an average, households spent INR1500/month (~US$ 23.0/month) towards care of persons affected with DD. Around 23 million adults would need care for DD in India at any given time. Since productive population is affected most, DD entails considerable socioeconomic impact at individual and family levels. This is a clarion call for all the concerned stakeholders to scale up services under National Mental Health Programme in India along with integrating care for DD with other ongoing national health programmes.


A global view of antibiotic resistance.
Antibiotic resistance is one of the few examples of evolution that can be addressed experimentally. The present review analyses this resistance, focusing on the networks that regulate its acquisition and its effect on bacterial physiology. It is widely accepted that antibiotics and antibiotic resistance genes play fundamental ecological roles - as weapons and shields, respectively - in shaping the structures of microbial communities. Although this Darwinian view of the role of antibiotics is still valid, recent work indicates that antibiotics and resistance mechanisms may play other ecological roles and strongly influence bacterial physiology. The expression of antibiotic resistance determinants must therefore be tightly regulated and their activity forms part of global metabolic networks. In addition, certain bacterial modes of life can trigger transient phenotypic antibiotic resistance under some circumstances. Understanding resistance thus requires the analysis of the regulatory networks controlling bacterial evolvability, the physiological webs affected and the metabolic rewiring it incurs.


Mandatory HMO enrollment in Medicaid: the issue of freedom of choice.
In areas where HMOs have enrolled a small proportion of the general population, physician participation is less in mandatory HMO programs for Medicaid beneficiaries than in fee-for-service Medicaid. But where HMOs have enrolled over one-quarter of the general population, participation rates are indistinguishable under the two systems. In those areas, mandatory enrollment restricts freedom of choice of provider. A plausible reason for this is that individual practice associations, which contract with large numbers of physicians with both fee-for-service and HMO patients, are becoming the lead form of HMO.


Effects of adriamycin on cell differentiation and proliferation in rat testis.
Although adriamycin (ADR) is used to treat many cancers, it can be toxic to healthy organs including the testis. We investigated the effects of ADR on pluripotency in rat testis. Testicular damage was induced by either cumulative or single dose single dose administration of ADR in Wistar albino rats. Rats were divided randomly into three groups: untreated control, cumulative dose ADR group (2 mg/kg ADR every three days for 30 days) and single dose ADR group (15 mg/kg, single dose ADR). Testicular damage was evaluated and seminiferous tubule diameters were measured using light microscopy. Expression levels of Oct4, Sox2, Klf4, c-Myc, Utf1 and Dazl were assessed by immunohistochemistry and real time PCR. Serum testosterone levels were measured using ELISA assay. Histopathologic scores were lower and mean seminiferous tubule diameters were less compared to the ADR groups. Oct4, Sox2, Klf4 and Utf1 expressions were decreased significantly in spermatogenic cells of both cumulative and single dose ADR groups compared to the control group. We found that c-Myc expression in spermatogenic and Leydig cells were increased significantly in both ADR groups compared to the control group. Dazl expression was decreased in the cumulative adriamycin group compared to the control group, but increased in the single dose ADR group compared to both the control and cumulative ADR groups. Serum testosterone levels were decreased in both ADR groups compared to the control group. Our findings suggest that ADR is detrimental to regulation and maintenance of pluripotency in rat testis.


[Adenoid cystic carcinoma or cylindroma of the cervix uteri. Review of the literature apropos of a personal case].
The authors report on a case of cylindroma of the cervix combined with a carcinoma in situ. Reviewing the literature which helped them, they studied the anatomo-pathological characteristics as well as the histogenesis and the therapy for cylindromas, which are more often found in other parts of the body. In particular, they are found in the salivary glands. There the origin is still uncertain and the evolution from the same stage is worse than in epidermoid carcinoma of the cervix.


Network analysis of the MVA and MEP pathways for isoprenoid synthesis.
Isoprenoid biosynthesis is essential for all living organisms, and isoprenoids are also of industrial and agricultural interest. All isoprenoids are derived from prenyl diphosphate (prenyl-PP) precursors. Unlike isoprenoid biosynthesis in other living organisms, prenyl-PP, as the precursor of all isoprenoids in plants, is synthesized by two independent pathways: the mevalonate (MVA) pathway in the cytoplasm and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in plastids. This review focuses on progress in our understanding of how the precursors for isoprenoid biosynthesis are synthesized in the two subcellular compartments, how the underlying pathway gene networks are organized and regulated, and how network perturbations impact each pathway and plant development. Because of the wealth of data on isoprenoid biosynthesis, we emphasize research in Arabidopsis thaliana and compare the synthesis of isoprenoid precursor molecules in this model plant with their synthesis in other prokaryotic and eukaryotic organisms.


[A case of premature emphysema with hereditary alpha-1-antiproteinase deficiency].
A case of alpha-I-antiproteinase (AIPI) hereditary deficiency (serum concentration 34 mg%, determined by NOR-Partigen Assay F-my Behringer) in 41 years old patient with premature emphysema, confirmed by phenotyping (isoelectrofocusing in polyacrylamide gel) phenotype PiZ is presented. Lung function tests showed considerable decrease (FEV1 = 1,2 l., i.e. 34% pred., FEF50% = 0.55 l., i.e. 12% pred., diffusing capacity DLCO = 12.8 ml/min/mmHg, i.e. 43% pred.). Computed tomography revealed huge emphysematous bullae mainly in supradiaphragmatic parts of the lungs. The authors discuss the difficulties in diagnosing homozygotes with A1P1 deficiency. They suggest screening of severe hereditary deficiency in persons with emphysema in age interval 30-55 years. The presented case of premature emphysema and AIPI deficiency (confirmed by phenotyping variant Z) is the first in the polish literature.


Involvement of ribosomal ribonucleic acid operons in Salmonella typhimurium chromosomal rearrangements.
As part of our efforts to understand factors influencing chromosomal organization and rearrangements, we studied a family of Salmonella typhimurium tandum duplication mutants. We found that the duplications were originally generated by unequal recombination between pairs of similarly oriented ribosomal ribonucleic acid operons (rrn). This demonstration involved the physical isolation of the duplicated material as circular deoxyribonucleic acid excised from the duplication. The four rrn operons involved embraced the ilv pur D segment of the chromosome and occurred at positions closely analogous to those previously observed for Escherichia coli. The interval between rrnC and rrnA of S. typhimurium was similar in size to that of E. coli (43 versus 39 kilobases), as was the interval between rrnB and rrnE (94 versus 91 kilobases). The rrnA-to-rrnB interval of S. typhimurium, however, was 155 kilobases, substantially greater than the 126 kilobases observed for E. coli.


The Knee Society system of standardized abbreviations for surgery of the arthritic knee.
A new standardized system of abbreviations has been adopted by the Knee Society to bring clarity and brevity to scientific reports involving the arthritic knee. This system works by using a set of core abbreviations that are modified with prefixes, suffixes, and superscript notations to indicate succinctly the surgical approach, the procedure used, and the type of prosthesis implanted.


Atom-Based Machine Learning Model for Quantitative Property-Structure Relationship of Electronic Properties of Fusenes and Substituted Fusenes.
This study presents the development of machine-learning-based quantitative structure-property relationship (QSPR) models for predicting electron affinity, ionization potential, and band gap of fusenes from different chemical classes. Three variants of the atom-based Weisfeiler-Lehman (WL) graph kernel method and the machine learning model Gaussian process regressor (GPR) were used. The data pool comprises polycyclic aromatic hydrocarbons (PAHs), thienoacenes, cyano-substituted PAHs, and nitro-substituted PAHs computed with density functional theory (DFT) at the B3LYP-D3/6-31+G(d) level of theory. The results demonstrate that the GPR/WL kernel methods can accurately predict the electronic properties of PAHs and their derivatives with root-mean-square deviations of 0.15 eV. Additionally, we also demonstrate the effectiveness of the active learning protocol for the GPR/WL kernel methods pipeline, particularly for data sets with greater diversity. The interpretation of the model for contributions of individual atoms to the predicted electronic properties provides reasons for the success of our previous degree of π-orbital overlap model.


[Surgical and functional results after surgical lung volume reduction in 94 patients with severe emphysema].
Lung volume reduction (LVR) is a new surgical approach designed to relieve shortness of breath and improve exercise tolerance in patients with severe lung emphysema. The aim of this study was to analyse surgical results and changes in the lung function, gas exchange, exercise tolerance and degree of dyspnoea until two years after LVR. From June 1994 to September 1997 ninety-four patients (31 women and 63 men, mean age 64 [35-79] years) with severe emphysema (12 with alpha 1-Pi-deficiency) underwent unilateral (n = 24) or bilateral (n = 70) LVR. 92 from 94 patients were extubated immediately after surgery. 30 days mortality was 2.2% (2/94), 90 days 3.3% (3/94) respectively. Most common postoperative complications were pneumonia (n = 15, 16%) and air leakage longer than 7 days (n = 22, 23.4%). One month after surgery there was a significant increase in forced expiratory vital capacity after one second (FEV1 59%) and significant decrease in total lung capacity (TLC 19%) and residual volume (RV 28%). Also significant changes were observed in paO2, paCO2, 6-minute walking distance, dyspnoea score and respiratory muscle function. Two years after LVR lung function tests in patients with smokers emphysema showed the benefit to be maintained (high responders). Patients with alpha 1-Pi-deficiency showed 6 to 12 months after surgery a remarkable deterioration of functional data (low responders). In selected patients with severe emphysema surgical LVR shows significant improved pulmonary function, gas exchange, dyspnoea and walking distance. The results are better after bilateral operation. Patients selection, rehabilitation program and interdisciplinary care resulted in a low operative morbidity and mortality.


Value of a new pathological classification of lumbar intervertebral disc herniation based on transforaminal endoscopic observations.
Removal of herniated disc materials based on an imaging only method may not relieve symptoms in many patients. Therefore, the aim of the present study was to develop a transforaminal endoscopic method of classifying the pathological type of lumber intervertebral disc herniation and to compare the outcomes of surgery based on the pathological type with those of conventional endoscopic disc removal. The records of patients who received endoscopic transforaminal nucleotomy with foraminoplasty for symptomatic lumbar disc herniation between 2009 and 2013 were retrospectively reviewed. Patients were then divided into two groups: Group A, which consisted of 275 patients who received conventional endoscopic transforaminal nucleotomy with foraminoplasty between 2009 and 2011 and group B, which consisted of 316 patients who received 'targeted' endoscopic transforaminal nucleotomy with foraminoplasty between 2011 and 2013 (based on the pathological type of disc herniation identified at surgery, including fresh, calcified and scar type based on intraoperative observations). The results showed that there were no significant differences in age, gender, body mass index, symptom duration, operated segments or previous invasive therapies between the two groups. Moreover, evaluation of visual analogue scale pain scores and Oswestry disability index scores revealed that the patients in group B had a greater improvement in symptoms than those in group A (P<0.05). In addition, an age >40 years and a longer symptom duration were associated with the calcified type, and previous invasive therapy was associated with the scar type. Therefore, specific surgical treatment based on the transforaminal endoscopic pathological type can result in better outcomes for patients with lumbar disc herniation.


Silica nanoparticles: A review of their safety and current strategies to overcome biological barriers.
Silica nanoparticles (SNP) have gained tremendous attention in the recent decades. They have been used in many different biomedical fields including diagnosis, biosensing and drug delivery. Medical uses of SNP for anti-cancer, anti-microbial and theranostic applications are especially prominent due to their exceptional performance to deliver many different small molecules and recently biologics (mRNA, siRNA, antigens, antibodies, proteins, and peptides) at targeted sites. The physical and chemical properties of SNP such as large specific surface area, tuneable particle size and porosity, excellent biodegradability and biocompatibility make them an ideal drug delivery and diagnostic platform. Based on the available data and the pre-clinical performance of SNP, recent interest has driven these innovative materials towards clinical application with many of the formulations already in Phase I and Phase II trials. Herein, the progress of SNP in biomedical field is reviewed, and their safety aspects are analysed. Importantly, we critically evaluate the key structural characteristics of SNP to overcome different biological barriers including the blood-brain barrier (BBB), skin, tumour barrier and mucosal barrier. Future directions, potential pathways, and target areas towards rapid clinical translation of SNP are also recommended.


Molecular targeted therapies of renal cell carcinoma considering life stage of the patient: Two case reports.
Molecular targeted therapies have markedly improved the prognosis of metastatic renal cell carcinoma (RCC) and patients are able to receive specific treatments depending on their condition. The cases of two patients who presented with large RCC with very different statuses were examined in the current study. One of the patients was elderly with numerous comorbidities, and the other was young and had Case 1 was an elderly female with various comorbidities including a history of cerebral infarction and impaired eyesight. A 7 cm solid mass in the left kidney, pulmonary metastases and a shrunken right kidney were identified. Conservative treatment was selected and the patient underwent treatment with oral sorafenib for 5 years without experiencing disease progression. Case 2 was a middle-aged male in a good general condition who had a 19 cm left renal mass and multiple metastases. Due to the tumor size, the patient was initially treated with oral pazopanib to reduce the renal tumor volume and was able to undergo left radical nephrectomy after 6 months. Molecular targeted therapies were thus used to treat these patients taking into account each patient's life stage; case 1 was treated without surgery for six years and case 2 received treatment as a neoadjuvant.


How VASP enhances actin-based motility.
The function of vasodilator-stimulated phosphoprotein (VASP) in motility is analyzed using a biomimetic motility assay in which ActA-coated microspheres propel themselves in a medium containing actin, the Arp2/3 complex, and three regulatory proteins in the absence or presence of VASP. Propulsion is linked to cycles of filament barbed end attachment-branching-detachment-growth in which the ActA-activated Arp2/3 complex incorporates at the junctions of branched filaments. VASP increases the velocity of beads. VASP increases branch spacing of filaments in the actin tail, as it does in lamellipodia in living cells. The effect of VASP on branch spacing of Arp2/3-induced branched actin arrays is opposed to the effect of capping proteins. However, VASP does not compete with capping proteins for binding barbed ends of actin filaments. VASP enhances branched actin polymerization only when ActA is immobilized on beads or on Listeria. VASP increases the rate of dissociation of the branch junction from immobilized ActA, which is the rate-limiting step in the catalytic cycle of site-directed filament branching.


Alcoholic liver disease.
Alcohol has been implicated in the genesis of liver disease for centuries. Significant progress has been made in our understanding of the pathogenesis of ALD. It is now apparent that both the consumption and the metabolism of alcohol promote the production of inflammatory mediators (cytokines) that result in hepatotoxicity and fibrogenesis. With time, this leads to progressively severe liver injury and, eventually, causes cirrhosis. Unfortunately, effective therapies for most individuals with ALD have not been found. High per capita consumption of alcohol, coupled with the dearth of effective treatments and the failure of most affected individuals to abstain from alcohol, explains why ALD is one of the most prevalent forms of disabling, chronic liver disease in the United States.


Enhanced habit formation in Gilles de la Tourette syndrome.
Tics are sometimes described as voluntary movements performed in an automatic or habitual way. Here, we addressed the question of balance between goal-directed and habitual behavioural control in Gilles de la Tourette syndrome and formally tested the hypothesis of enhanced habit formation in these patients. To this aim, we administered a three-stage instrumental learning paradigm to 17 unmedicated and 17 antipsychotic-medicated patients with Gilles de la Tourette syndrome and matched controls. In the first stage of the task, participants learned stimulus-response-outcome associations. The subsequent outcome devaluation and 'slip-of-action' tests allowed evaluation of the participants' capacity to flexibly adjust their behaviour to changes in action outcome value. In this task, unmedicated patients relied predominantly on habitual, outcome-insensitive behavioural control. Moreover, in these patients, the engagement in habitual responses correlated with more severe tics. Medicated patients performed at an intermediate level between unmedicated patients and controls. Using diffusion tensor imaging on a subset of patients, we also addressed whether the engagement in habitual responding was related to structural connectivity within cortico-striatal networks. We showed that engagement in habitual behaviour in patients with Gilles de la Tourette syndrome correlated with greater structural connectivity within the right motor cortico-striatal network. In unmedicated patients, stronger structural connectivity of the supplementary motor cortex with the sensorimotor putamen predicted more severe tics. Overall, our results indicate enhanced habit formation in unmedicated patients with Gilles de la Tourette syndrome. Aberrant reinforcement signals to the sensorimotor striatum may be fundamental for the formation of stimulus-response associations and may contribute to the habitual behaviour and tics of this syndrome.


Expression of HSP70 mRNA in the embryonic chicken lens: association with differentiation.
The heat shock protein, HSP70 is constitutively expressed in the embryonic chicken lens. The present study investigates the localization of HSP70 mRNA in the lens as a function of developmental age to determine whether the state of proliferation or differentiation of the cells is correlated with expression of this gene. Using reverse transcription and quantitative PCR for HSP70 mRNA in RNA samples derived from microdissected regions of the lens, we have found that the concentration of HSP70 mRNA is highest in the annular pad cells at 6 days of development, and in the annular pad and fiber cells at 14 and 19 days of development, suggesting that expression is associated with fiber cell formation. This association was confirmed by studies of HSP70 transcription and HSP70 mRNA levels in cultured explants of 6 day embryonic chicken lens epithelia differentiating in culture. Nuclear run-on transcription experiments indicated that transcription of HSP70 is elevated after 5 and 24 hr of differentiation in vitro. Other genes whose transcription was monitored, c-myc and delta-crystallin, showed distinct patterns of transcriptional regulation, indicating that the changes in HSP70 transcription are specific. RNA extracted from cultured explants at these same times showed increased levels of a 3.4 kb mRNA which hybridized at high stringency to a chicken HSP70 cDNA probe. These results demonstrate that HSP70 mRNA in the embryonic chicken lens is associated primarily with cells in the early stages of fiber formation, and that increased transcription of this gene is part of the differentiation process.


Computer-assisted learning in medical education.
The advent of cheap and powerful micros has opened the possibility of computer-assisted learning (CAL) in medical education. This article attempts to demonstrate the educational value of CAL, with illustrations of its use. Four styles of CAL are examined, and the danger of trivializing the learning process discussed. The ultimate CAL package which enables students to take charge of their own learning is considered. There are considerable advantages in distance learning, self-assessment, computer-marked examinations and 'audit'. Some of the main problems are considered; these are decisions which must be taken about the choice of hardware and software. The use of various peripheral devices such as slide projectors and videodisc players greatly enhances the value of CAL material, as do alternative input devices. Some thought is given to software style in the presentation of material, and also to the question of the keeping of student records. The use of an author language facilitates program development, and the construction of content-free 'shell' programs enables new material to be added to existing frameworks. Other advantages of CAL include student access to JANET and the possibility of on-line searching of databases. CAL in medical education can help to liberate students from the burden of the rote learning of facts, and enhance the role of reason and imagination in the learning process.


Scoping review of the characteristics assessed by vulnerability indices applied to people experiencing homelessness.
The objectives of this scoping review are to investigate the characteristics assessed by existing vulnerability indices and the health outcomes achieved by applying them to people experiencing homelessness. This review forms part of the development and implementation of a novel tool to prioritise people experiencing homelessness for healthcare based on their need and capacity to access healthcare. Included papers were primary research, published in the English language, participants were experiencing homelessness and aged over 18 years at the time of the study, a vulnerability index was used in the study, sample size was greater than 30, and the study had a health focus. Databases searched were MEDLINE, Embase, CINAHL, Scopus, PubMed and Web of Science, between January-April 2020. The Joanna Briggs Appraisal criteria were used to quality appraise the included studies. Results were synthesised narratively. Six papers were included, a total of 27,509 participants. The reported use of the indices varied; they included screening and profiling homeless populations, comparing homeless populations, and two studies evaluated the predictive capacity, reliability and validity of the indices. One vulnerability index focused on screening for human immunodeficiency virus, one used a 50-item index and four used a nine-item index. No direct health outcomes were reported from applying the vulnerability indices. The studies identified limitations of using vulnerability indices, including the potential bias of relying on self-reported data and two studies highlighted the need for further psychometric testing to ensure validity and reliability of the indices. The sample of included studies was small. Vulnerability indices are reportedly a useful and easily accessible method of gaining valuable data on the health status and health needs of people experiencing homelessness. The variety of characteristics included in the vulnerability indices suggests the importance of tailoring vulnerability indices to the needs of the population to which it is to be applied. Conducting appropriate psychometric testing is critical so that an index can be used to accurately inform decision making and accurately prioritise people experiencing homelessness who are most at risk of mortality and morbidity. A specific tool that prioritises people experiencing homelessness for access to health care is not yet available. The review was funded by a St Vincent's Network Inclusive Health grant.


Remodeling and activation of Escherichia coli RNA polymerase by osmolytes.
The ability of bacteria to survive environmental stresses and colonize the gastrointestinal tract depends on adaptation to high osmolarity. The adaptation involves global reprogramming of gene expression, including inhibition of bulk sigma70 RNA polymerase transcription and activation of bulk sigma38 transcription. The activating signal transduction pathways that originate with osmolytes remain to be established. Experiments here confirm that accumulation of a simple signaling molecule, glutamate, can reprogram RNA polymerase in vitro without the need for specific protein receptors. During osmotic activation, glutamate appears to act as a Hofmeister series osmolyte to facilitate promoter escape. Escape is accompanied by a remodeling of the key interaction between the sigma38 stress protein and the beta-flap of the bacterial core RNA polymerase. This activation event contrasts with the established mechanism of inhibition in which glutamate, by virtue of its electrostatic properties, helps to inhibit binding to ribosomal promoters after osmotic shock. Overall, Escherichia coli survival in natural hosts and reservoirs is expected to rely on the accumulation of simple ions that trigger changes in protein conformation that lead to global changes in transcription.


Highly Efficient Isolation of Circulating Tumor Cells Using a Simple Wedge-Shaped Microfluidic Device.
We have developed a novel simple wedge-shaped microfluidic device for highly efficient isolation of circulating tumor cells (CTCs) from cancer patient blood samples. We used wet chemical etching and thermal bonding technologies to fabricate the wedge-shaped microdevice and performed optimization assays to obtain optimal capture parameters. Cancer cells spiked samples were used to evaluate the capture performance. Clinical assays were performed to isolate and identify CTCs from whole blood samples of patients with liver, breast, lung, and gastric cancer. Outlet height of 5.5 μm and flow rate of 200 μL/min were chosen as the optimal CTC-capture conditions. This method exhibited excellent isolation performance (more than 85% capture efficiency) for four cancer cell lines (HepG2, SKBR3, A549, and BGC823). In clinical assay, the platform identified CTCs 5 in 6 liver (83.3%), 8 in 10 breast (80%), 5 in 8 lung (62.5%), 5 in 9 gastric (55.6%) cancer patients, and only 1 in 25 healthy blood samples (4%). Our wedge-shaped microfluidic device had several advantages, including relatively simple fabrication, high capture efficiency, simple sample processing steps, and easy observation. This method had successfully demonstrated the clinical feasibility of CTC isolation and shown a great potential of clinical usefulness in monitoring tumor prognosis and guiding individualized treatment in the future.


Oleaginous yeasts from Antarctica: Screening and preliminary approach on lipid accumulation.
The capability of 17 Rhodotorula spp. isolated from Antarctica to accumulate intracellular lipids in nitrogen-limited medium was investigated. As results, 10 isolates were selected by Nile red staining, while 12 isolates were selected as oleaginous by analysis of total lipid content (20.4-73%, w/w of dry biomass). The higher lipid production and accumulation was exhibited for six strains belonging to three species of Rhodotorula (Rhodotorula glutinis, Rhodotorula glacialis, and Rhodotorula laryngis). This is the first report where R. laryngis have been identified within oleaginous specie. Lipid accumulation was evaluated comparatively in two nitrogen-limited glucose-based media (MI and MII). MI (low C/N ratio) was more suitable for biomass and lipid production while in MII (high C/N ratio) total lipid content was improved. R. glutinis R4, R. glacialis R15, and R. glutinis R48 showed high lipid concentrations (4.65-6.93 g L-1 ) and they were able to accumulate large amounts of lipids per gram of biomass (47-77%, w/w). A similar profile in fatty acids composition and content of neutral lipids to vegetable oils was observed, indicating that lipids produced by oleaginous Antarctic yeasts can be considered an alternative feedstock for biodiesel production. Antarctica represents an important source of oleaginous yeasts with adaptive capabilities to accumulate considerable amounts of lipids with biotechnological interest at 15 °C and 25 °C.


Parabiotic reinnervation: surgical technic and animal care.
A technic called parabiotic reinnervation was developed to test the hypothesis that a derangement of the trophic function normally exerted by a nerve on a muscle is an element in the pathogenesis of muscular dystrophy in the 129/ReJ dydy mouse. The technic involves the reinnervation of the muscles of the anterior compartment of the hind limb of 1 animal (the recipient) by the peroneal nerve of another animal (the donor). Survival of the parabiosed animals depends on attention to nutrition and cage environment.


Walled-off pancreatic necrosis.
Walled-off pancreatic necrosis (WOPN), formerly known as pancreatic abscess is a late complication of acute pancreatitis. It can be lethal, even though it is rare. This critical review provides an overview of the continually expanding knowledge about WOPN, by review of current data from references identified in Medline and PubMed, to September 2009, using key words, such as WOPN, infected pseudocyst, severe pancreatitis, pancreatic abscess, acute necrotizing pancreatitis (ANP), pancreas, inflammation and alcoholism. WOPN comprises a later and local complication of ANP, occurring more than 4 wk after the initial attack, usually following development of pseudocysts and other pancreatic fluid collections. The mortality rate associated with WOPN is generally less than that of infected pancreatic necrosis. Surgical intervention had been the mainstay of treatment for infected peripancreatic fluid collection and abscesses for decades. Increasingly, percutaneous catheter drainage and endoscopic retrograde cholangiopancreatography have been used, and encouraging results have recently been reported in the medical literature, rendering these techniques invaluable in the treatment of WOPN. Applying the recommended therapeutic strategy, which comprises early treatment with antibiotics combined with restricted surgical intervention, fewer patients with ANP undergo surgery and interventions are ideally performed later in the course of the disease, when necrosis has become well demarcated.


Reference data set for a Norwegian medium voltage power distribution system.
This article describes a reference data set for a representative Norwegian radial, medium voltage (MV) electric power distribution system operated at 22 kV. The data set is developed in the Norwegian research centre CINELDI and will in brief be referred to as the CINELDI MV reference system. Data for a real Norwegian distribution system were provided by a distribution grid company. The data have been anonymized and processed to obtain a simplified but still realistic grid model with 124 nodes. The first part of the data set describes the base version of the reference system that represents the present-day state of the grid, including information on topology, electrical parameters, and existing load points. The data set also comprises a load data set with load demand time series for a year with hourly resolution and scenarios for the possible long-term load development. These data describe an extended version of the reference system with information on possible new load points being added to the system in the future. A third part of the data set is data necessary for carrying out reliability of supply analyses for the system. The base version of the reference system described in this article can be extended to represent other types of distribution grids (e.g., with a ring topology). The reference grid can be used for assessing new methods and principles for distribution system operation and planning, including assessment of flexibility resources, active distribution grid measures, grid reinforcement planning, grid reinvestment planning, reliability of supply analysis, self-healing, etc.


NFκB and AP-1 drive human myometrial IL8 expression.
The uterine expression of the chemokine IL8 increases dramatically with the onset of labour both at term and preterm. The IL8 promoter contains binding sites for the transcription factors nuclear factor-kappa B (NFκB), activator protein-1 (AP-1), and CCAAT/enhancer-binding protein (CEBP). In this study we investigated the roles of these transcription factors in IL1B regulation of the IL8 gene in human myometrium. Using chromatin immune precipitation (ChIP) assay, we showed that each of NFκB, CEBP, and AP-1 binds to the IL8 promoter upon IL1B stimulation. To examine the relative importance of each site in IL8 gene expression, site-directed mutagenesis of each of these sites was performed. We found that the NFκB site was essential for basal and IL1B-stimulated gene expression. Mutation of the AP-1 site reduced both basal and IL1B-stimulated expression but to a lesser extent. Mutation of the CEBP site had no effect upon basal expression but eliminated the IL1B response. Small interfering RNA (siRNA) silencing of NFκB abolished the IL8 response to IL1B significantly; siRNA against AP-1 reduced it to a lesser extent whilst knockdown of CEBP enhanced the response. Our data confirms a central and essential role for NFκB in regulation of IL8 in human myometrium.