Microvascular circulation of the ascending colon in horses.
Microvascular circulation of the ascending colon in healthy horses was studied using microangiography, light microscopy, and scanning electron microscopy. The pelvic flexure with 30 cm of ventral and dorsal colon attached was removed from 14 adult horses immediately after horses were euthanatized. The lumen was flushed with warm water, and this section of the ascending colon was placed in a 37-C bath of isotonic NaCl. In sections from 8 horses, colic vessels were perfused with a radio-opaque medium for microangiography. After angiographic evaluation, tissue sections were prepared for light microscopic observation, using standard histologic methods. In sections from 6 horses, injection replicas were made by perfusing the vessels with 2 types of plastics. The results of microangiography, light microscopy, and scanning electron microscopy of vascular replicas were correlated, providing a comprehensive documentation of the microvasculature of the ascending colon at the pelvic flexure. Arteries branched from mesenteric colic vessels approximately every 2 cm toward the colonic tissue. Immediately after branching, arterial vessels formed an anastomotic plexus, the colonic rete. However, each branch from the colic vessel eventually continued into the colonic tissue. A second set of vessels originated from the colonic tissue. A second set of vessels originated from the colonic rete and supplied the mesenteric lymph nodes. Arterial vessels penetrated the tunica muscularis into the submucosa 3 to 4 cm toward the antimesenteric border forming a submucosal vascular network. From the submucosal arterioles, branching took place at right angles to supply the mucosal capillaries. Capillaries surrounded the colonic glands and anastomosed at the luminal surface, forming a superficial luminal honeycomb-appearing vascular plexus.(ABSTRACT TRUNCATED AT 250 WORDS)


Depressive Symptoms and Conversational Self-Focus in Adolescents' Friendships.
This multi-method, longitudinal study considered the interplay among depressive symptoms, aversive interpersonal behavior, and interpersonal rejection in early and middle adolescents' friendships. In particular, the study examined a newly identified interpersonal process, conversational self-focus (i.e., the tendency to redirect conversations about problems to focus on the self). Traditional interpersonal theories of depression suggest that individuals with depressive symptoms engage in aversive behaviors (such as conversational self-focus) and are rejected by others. However, in the current study, not all adolescents with depressive symptoms engaged in conversational self-focus and were rejected by friends. Instead, conversational self-focus moderated prospective relations of depressive symptoms and later friendship problems such that only adolescents with depressive symptoms who engaged in conversational self-focus were rejected by friends. These findings are consistent with current conceptualizations of the development of psychopathology that highlight heterogeneity among youth who share similar symptoms and the possibility of multifinality of outcomes.


Considering Dogs as Complementary Targets of Chagas Disease Control.
This review describes the role that dogs play in Latin American countries where Chagas disease is endemic. Multiple studies determined the high frequency with which canine populations are infected with Trypanosoma cruzi. The infection prevalence of dogs is greater than that of humans and the presence of infected dogs in households is associated with a higher risk of human infection. Dog infectiousness to triatomine vectors is several-fold higher than that of humans, thereby underscoring their major role in the domestic transmission of T. cruzi. Insecticide spraying of houses is in most cases efficacious but the lack of sustainability hinders this vector-focused strategy. Multi-pronged approaches have been adopted to improve control measures but dog intervention was never included. Experimental evaluation of systemic insecticides or deltamethrin-impregnated collars suggested that dog intervention leading to triatomine killing could curb domestic transmission of T. cruzi. Larger field studies are required to determine its applicability and efficacy. However, the implementation of dog intervention could complement other control measures currently in place, mostly in periods when vector spraying has been interrupted.


Adjuvant chemotherapy decision-making in stage II colon adenocarcinoma associated with patients' age and high-risk factors.
To clarify whether the combination of age and high-risk factors (HRFs) was preferable for adjuvant chemotherapy (AC) decision-making in patients with stage II colon adenocarcinoma. We conducted a retrospective study analyzing eligible colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. A nomogram was used to predict patient prognosis. Decision curve analysis (DCA) predicted model clinical benefit. Restricted cubic spline calculated the optimal cut-off value. A total of 8570 patients with stage II colon adenocarcinoma were included in this study; 25.2% received AC. A nomogram predicting the prognosis of patients with stage II colon adenocarcinoma was constructed with age and HRFs, and scores were assigned to the relevant variables. DCA showed that age combined with HRFs was superior to treatment decision-making based on HRFs alone. Patients were grouped according to their total score with the cut-off value of 100. AC did not significantly improve overall survival (OS) in low-score group (hazard ratios (HRs) 1.01, 95% confidence intervals (CIs) 0.86-1.18, p = 0.918). In high-score group, AC improved 5-year OS by about 7.6% (HR 0.73, 95% CI 0.61-0.88, p = 0.001). And high-score group mainly included patients aged < 50 years with two or more HRFs and patients aged ≥ 50 years with at least one HRF. Age and HRFs could be preferable for determining the group of stage II colon adenocarcinoma patients who would benefit from AC. Patients aged < 50 years with two or more HRFs might be a potential benefit population for AC.


Plasmid-mediated factors conferring diffuse and localized adherence of enteropathogenic Escherichia coli.
Histopathological evidence suggests that the adherence of enteropathogenic Escherichia coli (EPEC) to the mucosa of the small bowel is an important step in pathogenesis. Several reports have shown that many EPEC isolates adhere to HEp-2 and HeLa cells in tissue cultures. In the HeLa cell assay, there are at least two distinct patterns of adherence: localized adherence, which is characterized by the formation of bacterial microcolonies, and diffuse adherence, in which bacteria cover the cell uniformly. We have found that these two patterns can be demonstrated in HEp-2 cells as well as in HeLa cells and that the results of the two assays are closely correlated. Using a DNA probe which is sensitive and specific for localized adherence to HEp-2 cells, we provide evidence that localized adherence and diffuse adherence by EPEC are due to at least two genetically distinct adhesions which confer phenotypic differences in both the morphology of HEp-2 cell adherence and in surface hydrophobicity. The two factors are each encoded on plasmids which vary in size from 55 to 70 megadaltons; one strain exhibiting localized adherence carried these genes on the chromosome.


Determinants of selectivity in Xer site-specific recombination.
A remarkable property of some DNA-binding proteins that can interact with and pair distant DNA segments is that they mediate their biological function only when their binding sites are arranged in a specific configuration. Xer site-specific recombination at natural plasmid recombination sites (e.g., cer in ColE1) is preferentially intramolecular, converting dimers to monomers. In contrast, Xer recombination at the Escherichia coli chromosomal site dif can occur intermolecularly and intramolecularly. Recombination at both types of site requires the cooperative interactions of two related recombinases, XerC and XerD, with a 30-bp recombination core site. The dif core site is sufficient for recombination when XerC and XerD are present, whereas recombination at plasmid sites requires approximately 200 bp of adjacent accessory sequences and accessory proteins. These accessory factors ensure that recombination is intramolecular. Here we use a model system to show that selectivity for intramolecular recombination, and the consequent requirement for accessory factors, can arise by increasing the spacing between XerC- and XerD-binding sites from 6 to 8 bp. This reduces the affinity of the recombinases for the core site and changes the geometry of the recombinase/DNA complex. These changes are correlated with altered interactions of the recombinases with the core site and a reduced efficiency of XerC-mediated cleavage. We propose that the accessory sequences and proteins compensate for these changes and provide a nucleoprotein structure of fixed geometry that can only form and function effectively on circular molecules containing directly repeated sites.


Multiple sclerosis symptom recrudescence at the end of the natalizumab dosing cycle.
This study was undertaken to determine how frequently patients receiving natalizumab for multiple sclerosis (MS) experience recrudescence of their MS symptoms at the end of the dosing cycle. One hundred consecutive MS patients receiving natalizumab completed a survey evaluating changes in symptoms during the natalizumab dosing cycle. Ninety-one patients also completed questionnaires at two time points: the first week after natalizumab infusion and the last week of the dosing cycle. These included the Multiple Sclerosis Quality of Life-54 (MSQOL-54), Fatigue Visual Analog Scale (VAS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-II (BDI-II). End of dosing interval (EDI) symptoms were reported as currently being experienced by 57% of respondents. An additional 10% reported that they previously experienced that phenomenon, but not currently, and 33% reported never experiencing this. In those with EDI symptoms, they began to occur a median of 21 days after infusion and improved again a median of 1 day after infusion. The most common symptoms reported were fatigue, weakness, walking impairment, and cognitive difficulties. No specific demographic or disease characteristics were associated with this phenomenon. In the subgroup with EDI symptoms, the MSQOL-54, Fatigue VAS, FSS, and BDI-II scores were all significantly worse in the last week of the dosing cycle when compared with the first week. No difference was seen in these scores between first and last week in the subgroup not experiencing symptom recrudescence. Recrudescence of fatigue, weakness, walking impairment, or cognitive difficulties at the end of the dosing cycle occurs in about two-thirds of MS patients receiving natalizumab.


A randomized controlled clinical trial of a nurse-led structured psychosocial intervention program for people with first-onset mental illness in psychiatric outpatient clinics.
This study aimed to test the effectiveness of a nurse-led structured psychosocial intervention program in Chinese patients with first-onset mental illness. A single-blind, parallel group, randomized controlled trial design was used. The study involved 180 participants with mild to moderate-severe symptoms of psychotic or mood disorders who were newly referred to two psychiatric outpatient clinics in Hong Kong. Patients were randomly assigned to either an eight-session nurse-led psychosocial intervention program (plus usual care) or usual psychiatric outpatient care (both n=90). The primary outcome was psychiatric symptoms. Outcomes were measured at recruitment, one week and 12 months post-intervention. Patients in the psychosocial intervention group reported statistically significant improvements in symptoms compared to treatment as usual. There were also significant improvements in illness insight and perceived quality of life and reduction in length of re-hospitalizations over the 12-month follow-up. The findings provide evidence that the nurse-led psychosocial intervention program resulted in improved health outcomes in Chinese patients with first-onset mental illness.


Localization and developmental expression of the activin signal transduction proteins Smads 2, 3, and 4 in the baboon fetal ovary.
We recently demonstrated that the reduction in the number of primordial follicles in ovaries of near-term baboon fetuses deprived of estrogen in utero was associated with increased expression of alpha-inhibin, but not activin betaA and betaB or the activin receptors. Therefore, we proposed that estrogen regulates fetal ovarian follicular development by controlling the intraovarian inhibin:activin ratio. As a prelude to conducting experiments to test this hypothesis, in the current study we determined whether the primate fetal ovary expressed Smads 2/3 and 4 and whether expression of these activin-signaling proteins was altered in fetal ovaries of baboons in which estrogen production was suppressed. Western blot analyses demonstrated that the 59 kDa Smad 2, 54 kDa Smad 3, and 64 kDa Smad 4 proteins were expressed in fetal ovaries of untreated baboons at both mid and late gestation and that the level of expression was not significantly altered in late gestation by in vivo treatment with CGS 20267 or CGS 20267 and estrogen. Immunocytochemistry localized Smads 2/3 and 4 to cytoplasm of oocytes and pregranulosa cells at midgestation and oocytes and granulosa cells of primordial follicles in late gestation. Smad 4 was also detected in granulosa cell nuclei in late gestation, and nuclear expression appeared to be decreased in fetal ovaries of baboons deprived of estrogen. The site of localization of Smads correlated with localization of the activin receptors IA and IIB, which we previously showed were abundantly expressed in oocytes and (pre)granulosa cells at both mid and late gestation and unaltered by estrogen deprivation. In summary, the results of the current study are the first to show that the intracellular signaling molecules required to transduce an activin signal are expressed in the baboon fetal ovary and that expression was not altered by estrogen deprivation in utero. These findings, coupled with our previous observations showing that estrogen deprivation reduced follicle numbers and upregulated/induced expression of inhibin but not activin or the activin receptors, lend further support to the hypothesis that estrogen regulates fetal ovarian folliculogenesis by controlling the intraovarian activin:inhibin ratio.


Cross-linking of horseradish peroxidase adsorbed on polycationic films: utilization for direct dye degradation.
Horseradish peroxidase (HRP) was immobilized on the polyaniline (PANI) grafted polyacrylonitrile (PAN) films. The maximum HRP immobilization capacity of the PAN-g-PANI-3 film was 221 μg/cm(2). The HRP-immobilized PAN-g-PANI-3 film retained 79 % of the activity of the same quantity free enzyme. The HRP-immobilized PAN-g-PANI-3 film was operated for the decolorization of two different benzidine-based dyes in the presence of hydrogen peroxide. The maximum decolorization grade was obtained at pH 6.0 for both dyes. The HRP-immobilized PAN-g-PANI-3 film was very effective for removal of Direct Blue-53 compared to Direct Black-38 from aqueous solutions. The immobilized HRP exhibited high resistance to proteolysis by trypsin compared to the free counterpart. Immobilized HRP preserved 83 % of its original activity even after 8 weeks of storage at 4 °C, while the free enzyme lost its initial activity after 3 weeks of storage period.


Age of Migration Life Expectancy with Functional Limitations and Morbidity in Mexican Americans.
The U.S. Mexican American population enjoys longer life expectancies relative to other racial/ethnic groups but is disproportionately affected by chronic conditions and functional limitations. Studying the impact of heterogeneity in age, time and other characteristics of migration among older Mexican Americans can inform our understanding of health disparities and healthcare needs in later-life. This research used 20 years of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly to assess the proportion of life spent with functional limitations and one or more morbidity (according to age of migration and sex) in the U.S. Mexican-American population. The results indicate that early-life and late-life migrant women spend more years with Performance-Oriented Mobility Assessment limitations than U.S.-born women. Conversely, midlife migrant women were not statistically different from U.S.-born women in years spent disabled. In men, midlife migrants had longer life expectancies and had more disability-free years than U.S.-born men. For morbidity, late-life migrant women spent a significantly smaller proportion of their elderly years with morbidity than U.S.-born women, but late-life migrant men spent more years with morbidity than U.S.-born men. These findings illustrate that older Mexican Americans in the United States are heterogeneous in nativity and health outcomes. More years spent disabled or unhealthy may result in greater burden on family members and greater dependence on public resources. These findings have implications for the development of social and health policies to appropriately target the medical conditions and disabilities of older Mexican Americans entering late life.


A Salmonella typhimurium genetic locus which confers copper tolerance on copper-sensitive mutants of Escherichia coli.
Three distinct clones from a Salmonella typhimurium genomic library were identified which suppressed the copper-sensitive (Cu(s)) phenotype of cutF mutants of Escherichia coli. One of these clones, pCUTFS2, also increased the copper tolerance of cutA, -C, and -E mutants, as well as that of a lipoprotein diacylglyceryl transferase (lgt) mutant of E. coli. Characterization of pCUTFS2 revealed that the genes responsible for suppression of copper sensitivity (scs) reside on a 4.36-kb DNA fragment located near 25.4 min on the S. typhimurium genome. Sequence analysis of this fragment revealed four open reading frames (ORF120, ORF627, ORF207, and ORF168) that were organized into two operons. One operon consisted of a single gene, scsA (ORF120), whereas the other operon contained the genes scsB (ORF627), scsC (ORF207), and scsD (ORF168). Comparison of the deduced amino acid sequences of the predicted gene products showed that ScsB, ScsC, and ScsD have significant homology to thiol-disulfide interchange proteins (CutA2, DipZ, CycZ, and DsbD) from E. coli and Haemophilus influenzae, to an outer membrane protein (Com1) from Coxiella burnetii, and to thioredoxin and thioredoxin-like proteins, respectively. The two operons were subcloned on compatible plasmids, and complementation analyses indicated that all four proteins are required for the increased copper tolerance of E. coli mutants. In addition, the scs locus also restored lipoprotein modification in lgt mutants of E. coli. Sequence analyses of the S. typhimurium scs genes and adjacent DNAs revealed that the scs locus is flanked by genes with high homology to the cbpA (predicted curved DNA-binding protein) and agp (acid glucose phosphatase) genes of E. coli located at 22.90 min (1,062.07 kb) and 22.95 min (1,064.8 kb) of the E. coli chromosome, respectively. However, examination of the E. coli chromosome revealed that these genes are absent at this locus and no evidence has thus been obtained for the occurrence of the scs locus elsewhere on the genome.


Epidemiological study of cauda equina syndrome.
: The primary purpose of this study was to determine the characteristics and outcomes of the patients admitted at our clinics diagnosed with cauda equina syndrome (CES). Secondarily, this study will serve as a basis for other comparative studies aiming at a better understanding of this condition and its epidemiology. : We conducted a retrospective study by reviewing the medical records of patients diagnosed with CES and neurogenic bladder between 2005 and 2011. The following variables were analyzed: gender, age, etiology, topographic level of the lesion, time between disease onset and diagnosis, presence of neurogenic bladder, time between diagnosis and surgery, neurological damage and neurogenic bladder persistence. : Considering that CES is a rare condition, we were not able to establish statistic correlation between the analyzed variables and the outcomes of the disease. However, this study brought to light the inadequacy of our public health system in treating that kind of patient. : The study shows that despite the well-defined basis for managing CES, we noted a greater number of patients with sequels caused by this condition, than is seen in the literature. The delayed diagnosis and, consequently, delayed treatment, were the main causes for the results observed. Level of Evidence IV, Case Series .


Detection of hyperacute subarachnoid hemorrhage of the brain by using magnetic resonance imaging.
The purpose of this study was to determine the diagnostic accuracy of high-field (1.5-tesla) magnetic resonance (MR) imaging in the assessment of hyperacute (< 12 hours after onset of symptoms) subarachnoid hemorrhage (SAH). This investigation included 13 patients who were examined 2 to 12 hours posthemorrhage by using an MR imaging protocol consisting of T2-weighted and proton-density (PD)-weighted images, T1-weighted images, fast echoplanar-diffusion-weighted (EP-DW) images, and fluid-attenuated inversion-recovery (FLAIR) images. Subarachnoid hemorrhage had been diagnosed using computerized tomography (CT) scanning in all cases. In all 13 cases, SAH was reliably detected on both PD-weighted and FLAIR images. In contrast with FLAIR studies, the PD-weighted images were free of cerebrospinal fluid flow artifacts. The SAH was detected on T1-weighted images in only two cases and could not be detected on any T2-weighted or EP-DW images. Even hyperacute SAH can be diagnosed reliably from high-field MR images obtained using PD-weighted or FLAIR sequences. Use of these sequences in an emergency MR protocol may preclude the need for additional CT studies to rule out SAH.


Complex and reticulate origin of edible roses (Rosa, Rosaceae) in China.
While roses are today among the most popular ornamental plants, the petals and fruits of some cultivars have flavored foods for millennia. The genetic origins of these edible cultivars remain poorly investigated. We collected the major varieties of edible roses available in China, assembled their plastome sequences, and phased the haplotypes for internal transcribed spacers (ITS1/ITS2) of the 18S-5.8S-26S nuclear ribosomal cistron. Our phylogenetic reconstruction using 88 plastid genomes, of primarily maternal origin, uncovered well-supported genetic relationships within Rosa, including all sections and all subgenera. We phased the ITS sequences to identify potential donor species ancestral to the development of known edible cultivars. The tri-parental Middle-Eastern origin of R. × damascena, the species most widely used in perfume products and food additives, was confirmed as a descendent of past hybridizations among R. moschata, R. gallica, and R. majalis/R. fedtschenkoana/R. davurica. In contrast, R. chinensis, R. rugosa, and R. gallica, in association with six other wild species, were the main donors for fifteen varieties of edible roses. The domesticated R. rugosa 'Plena' was shown to be a hybrid between R. rugosa and R. davurica, sharing a common origin with R. 'Fenghua'. Only R. 'Jinbian' and R. 'Crimson Glory' featured continuous flowering. All remaining cultivars of edible roses bloomed only once a year. Our study provides important resources for clarifying the origin of edible roses and suggests a future for breeding new cultivars with unique traits, such as continuous flowering.


[The specific features of coronary artery lesion in patients with signs of high cardiac risk in non-ST segment elevation acute coronary syndrome].
The paper covers risk stratification for cardiac events in patients with non-ST segment elevation acute coronary syndrome. It defines an association between risk factors, the specific features of coronary artery lesions, and the outcomes of the disease in relation to the used treatment policy. Particular emphasis is laid on the factors that are a handicap to the detection of a symptom-associated coronary artery in this category of patients.


A new staging system for idiopathic retinal periphlebitis.
To develop and standardize a universally acceptable new staging system for idiopathic retinal periphlebitis (Eales disease). A new staging system was established and standardized based on standard terminology and features. Idiopathic retinal periphlebitis was classified as peripheral and central types. Peripheral disease consisted of four stages. Stage 1 is periphlebitis of small (1a) and large (1b) caliber vessels with superficial retinal hemorrhages. Stage 2a denotes capillary nonperfusion and 2b neovascularization elsewhere/of the disc. Stage 3a is classified as fibrovascular proliferation and 3b vitreous hemorrhage. Stage 4a is traction/combined rhegmatogenous retinal detachment whereas 4b is rubeosis iridis, neovascular glaucoma, complicated cataract, and optic atrophy. A total of 253 cases of idiopathic retinal periphlebitis (mean age, 24.7 +/- 4.7 years, all male) presenting at this tertiary care center were classified prospectively according to the new staging system, by two independent observers (interobserver correlation = 0.7). The new staging system was consistent, simple, and easy to recall. Peripheral and central types of idiopathic retinal periphlebitis were found in 94.07% and 5.93% of cases, respectively. The new staging system also defined the severity of the disease. Vitreous hemorrhage was found to be the commonest presenting feature (51.68%), whereas traction/combined rhegmatogenous detachment was found in 5.88% of cases. The new staging system is useful in classifying and assessing the severity of disease. Management strategy can also be defined according to the stage of the disease. It is designed to promote the use of standard assessment with applications to clinical management and research.


Changes in Triathletes' Performance and Body Composition During a Specific Training Period for a Half-Ironman Race.
The number of recreational athletes completing a Half-Ironman triathlon has increased exponentially in recent years. However, there is a lack of research on how to train for this kind of an event. The purpose of this study was thus to analyse triathletes' changes in performance and body composition following a triathlon-specific training period. Fourteen male amateur triathletes completed a 7-week period of general training and a 13-week period of specific training for a Half-Ironman triathlon. Anthropometric measures and performance tests were carried out to assess the effects of the specific training program. Results showed that the pre-test value of VO2max for cycling was inversely correlated not only with the percentage of change in cycling performance, but also with the percentage change in several variables of running performance. In swimming, inverse correlations were observed between the time of the first 800 m test and the time percentage change for this test, but not with the percentage change in the performance of other segments of the race. Moreover, the somatotype component of endomorphy and the fat mass percentage of the first anthropometry were highly correlated with the percentage change in VO2max in the run segment. These results highlight the importance of providing individualised training, considering that the same training program had a different impact on recreational triathletes belonging to the same group. Amateur athletes with higher initial performance levels probably need a greater amount of training to achieve improved adaptation.


Synthesis of Breitfussin B by Late-Stage Bromination.
The breitfussins are halogenated natural products whose structures were determined with the assistance of atomic-force microscopy. The site selectivity of N-bromosuccinimide-mediated bromination of a model breitfussin core was found to be strongly dependent on solvent selection; use of acetone led to oxazole bromination, and use of a pyridine-containing mixture led to pyrrole bromination. This tunable site-selective bromination was used in a protecting-group-free synthesis of breitfussin B that proceeded in 9.2% yield over 12 reactions and five chromatographic separations. A bromooxazole analogue of breitfussin A was also prepared by late-stage bromination but isomerized on silica gel to form breitfussin B. This isomerization appeared to proceed through a unimolecular pathway.


Association of HScore Parameters with Severe COVID-19: A Systematic Review and Meta-Analysis.
Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients. A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05. Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051). Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters' roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.A preprint of this study was published at https://www.researchsquare.com/article/rs-54490/v2.


Identification of antigenic Brugia adult worm proteins by peptide mass fingerprinting.
With the recent completion of the Brugia malayi genome, proteomics offers a new resource for a deeper understanding of the biology of filarial parasites. We employed 2-dimensional (2D) gel electrophoresis followed by peptide mass fingerprinting on a matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometer to identify Brugia adult worm proteins and then determined which proteins were recognized by the host humoral immune response. We identified 18 unique proteins, several of which were determined to be antigenic by immunoblot. The proteins identified here may contribute to future studies to analyze the transmission and pathogenesis of lymphatic filariasis.


Structure determination of an unstable macromolecular complex enabled by nanobody-peptide bridging.
Structure determination of macromolecular complexes is challenging if subunits can dissociate during crystallization or preparation of electron microscopy grids. We present an approach where a labile complex is stabilized by linking subunits though introduction of a peptide tag in one subunit that is recognized by a nanobody tethered to a second subunit. This allowed crystal structure determination at 3.9 Å resolution of the highly non-globular 320 kDa proconvertase formed by complement components C3b, factor B, and properdin. Whereas the binding mode of properdin to C3b is preserved, an internal rearrangement occurs in the zymogen factor B von Willebrand domain type A domain compared to the proconvertase not bound to properdin. The structure emphasizes the role of two noncanonical loops in thrombospondin repeats 5 and 6 of properdin in augmenting the activity of the C3 convertase. We suggest that linking of subunits through peptide specific tethered nanobodies represents a simple alternative to approaches like affinity maturation and chemical cross-linking for the stabilization of large macromolecular complexes. Besides applications for structural biology, nanobody bridging may become a new tool for biochemical analysis of unstable macromolecular complexes and in vitro selection of highly specific binders for such complexes.


Beta2-microglobulin amyloidosis in hemodialysis and peritoneal dialysis patients.
Beta(2)-microglobulin (beta(2)-M) amyloidosis is an important cause of morbidity in patients on dialysis. In this cross-sectional study, we evaluated supraspinatus tendon thickness (as a measure of shoulder involvement from beta(2)-M amyloidosis) in patients who are on hemodialysis (HD) compared with those on continuous ambulatory peritoneal dialysis (CAPD). In 27 patients on HD who were treated with high-flux dialyzers, 31 patients on CAPD, and 31 healthy volunteers, we performed bilateral shoulder magnetic resonance imaging and measured the supraspinatus tendon thickness using electronic calipers. There were no statistically significant differences in age or dialysis duration between the HD and CAPD patients. Each patient was asked about the presence or absence of shoulder pain. The supraspinatus tendon thickness in HD patients (mean thickness 6.6 +/- 1.3 mm, range 3.20-8.80 mm, N = 53) and CAPD patients (6.8 +/- 0.9 mm, range 4.9-8.8 mm, N = 61) was not significantly different (P = 0.289); however, the mean thickness in either group was higher than in the healthy controls (5.5 +/- 0.6 mm, range 4.3-6.8 mm, N = 61) (HD patients vs. controls: P = 0.000; CAPD patients vs. controls: P = 0.000). Patients with shoulder pain had higher mean supraspinatus tendon thickness measurements than patients without shoulder pain (P = 0.042). The thickness of supraspinatus tendons is not significantly different between patients on CAPD and HD. An association exists between shoulder pain and mean supraspinatus tendon thickness. This hidden complication of ESRD should be further studied in larger populations of dialysis patients.


Repression of transforming growth factor-beta receptor type I promoter expression by Sp1 deficiency.
In this report, we describe the mechanism of TGF-beta receptor type I (RI) repression in the GEO human colon carcinoma cells. Treatment of GEO cells with the DNA methyltransferase inhibitor, 5 azacytidine induced RI expression and restored TGF-beta response. A stably transfected RI promoter-reporter construct (RI-Luc) expressed higher activity in the 5 aza C treated GEO cells, suggesting the activation of a transactivator for RI transcription. Gel shift analysis indicated enhanced binding of proteins from the 5 aza C treated nuclear extracts to radiolabeled Sp1 oligonucleotides specifically contained in the RI promoter. Protein stability studies after cyclohexamide treatment suggested an increase in the Sp1 protein stability from the 5 aza C treated GEO cells. Further, transfection of Sp1 cDNA into untreated GEO control cells increased RI promoter activity and thus induced RI expression. 5 aza C mediated Sp1 expression in Sp1 deficient GEO colon and MCF-7 breast cancer cells also enhanced the activity of several other Sp1 dependent promoters such as TGF-beta receptor type II (RII), Cyclin A and p21/waf1/cip1. These results indicate that restoration of Sp1 in several different types of Sp1 deficient cells leads to enhanced activation of a wide range of Sp1 dependent promoters.


Dapagliflozin attenuates early markers of diabetic nephropathy in fructose-streptozotocin-induced diabetes in rats.
Early detection and clinical interference are major challenges for the prevention of diabetic nephropathy (DN) progression. This study investigated the effects of dapagliflozin, a sodium glucose co-transporter 2 inhibitor, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetes in rats. Fr-STZ rats were treated with either dapagliflozin (1 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Fr-STZ rats displayed marked early tubular renal damage and glomerular podocyte injury as evidenced by renal KIM-1, NGAL, cystatin C, and vanin-1 mRNA, as well as urinary NAG elevation and nephrin mRNA suppression, associated with the development of marked renal interstitial fibrosis and glomerulosclerosis despite the presence of normoalbuminuria. Propagation of oxidative, inflammatory, fibrotic, and apoptotic reactions was obvious in the setting of renal glucose overload. Dapagliflozin significantly attenuated the renal tubular injury makers namely KIM-1, NGAL, vanin-1 and urinary NAG. In addition, it restored glomerular nephrin expression and reversed renal histopathological changes. Oxidative, inflammatory, and fibrotic processes were also alleviated. This study suggests that dapagliflozin exerts a renoprotective effect against early features of DN in rats presumably by inhibition of diabetes-induced renal tubular and glomerular injury thereby modulating oxidative, inflammatory, and fibrotic as well as apoptotic mechanisms elicited during hyperglycemia.


The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort.
There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very limited. The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development. Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5 μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out. Thirty-six statistically significant associations considering multiple testing (p < 2.19 × 10-4) were observed. Among the novel associations we observed that individuals living farther from the coast had a higher risk of developing prostate cancer (OR = 1.13, CI95% = 1.06-1.20, P = 1.98 × 10-4). This association was partially mediated by physical activity (indirect effect (IE) = -8.48 × 10-7) and the time spent outdoor (IE = 9.07 × 10-6). All PGSs showed statistically significant associations. Finally, genome-environment interaction analysis showed that local environment and genetic variability affect cancer risk independently. Living close to the coast and air pollution were associated with a decreased risk of prostate cancer and skin melanoma, respectively. These findings from the UKBB support the role of the local environment on cancer development, which is independent from genetics and may be mediated by several lifestyle factors.


TUP1, CPH1 and EFG1 make independent contributions to filamentation in candida albicans.
The common fungal pathogen, Candida albicans, can grow either as single cells or as filaments (hyphae), depending on environmental conditions. Several transcriptional regulators have been identified as having key roles in controlling filamentous growth, including the products of the TUP1, CPH1, and EFG1 genes. We show, through a set of single, double, and triple mutants, that these genes act in an additive fashion to control filamentous growth, suggesting that each gene represents a separate pathway of control. We also show that environmentally induced filamentous growth can occur even in the absence of all three of these genes, providing evidence for a fourth regulatory pathway. Expression of a collection of structural genes associated with filamentous growth, including HYR1, ECE1, HWP1, ALS1, and CHS2, was monitored in strains lacking each combination of TUP1, EFG1, and CPH1. Different patterns of expression were observed among these target genes, supporting the hypothesis that these three regulatory proteins engage in a network of individual connections to downstream genes and arguing against a model whereby the target genes are regulated through a central filamentous growth pathway. The results suggest the existence of several distinct types of filamentous forms of C. albicans, each dependent on a particular set of environmental conditions and each expressing a unique set of surface proteins.


Hospice Use in Patients With Cancer: A Comprehensive Clinical Literature Review.
Patients with cancer, particularly those with aggressive types of cancer, can benefit from hospice care at the end of life. Providers require more information about patients with cancer who do not use hospice care. With this information, oncology nurses can provide individualized informed care to improve quality of life for patients with advanced or aggressive cancers. This review aims to provide an overview of research outcomes of hospice use in the United States and answer the following question: "What are the differences in hospice use among patients with cancer?" ProQuest Central, PubMed®, Scopus®, and CINAHL® databases were searched for articles published from 2017 to 2023. Seventeen studies were included. Despite increased use over time, hospice services are underutilized among patients with cancer in general. Disparities in hospice use were noted across different types of cancer and individuals of different races or ethnicities, among other considerations. Based on findings from this review, oncology nurses can advocate for patients to receive hospice services that provide quality end-of-life care.


Liquid|liquid|electrode triple-phase boundary photovoltammetry of pentoxyresorufin in 4-(3-phenylpropyl)pyridine.
Voltammetric responses of pentoxyresorufin in 4-(3-phenylpropyl)-pyridine (PPP) microdroplets immersed in aqueous electrolyte are investigated in the absence and in the presence of light. The reduction of pentoxyresorufin to leuco-pentoxyresorufin in the dark is shown to occur in a two-electron, two-proton process sensitive to the aqueous pH and the PPP|aqueous electrolyte interfacial tension. No significant net photoelectrochemical current responses are observed, although transient responses indicative of distinct electron and hole charge carriers are seen in the presence of pentoxyresorufin. EPR evidence confirms the formation of radical intermediates upon illumination. As a coreactant, duroquinone in the PPP microdroplet phase is investigated and also shown to undergo two-electron, two-proton reduction (to duroquinol) without significant photoelectrochemical activity. When investigated in combination, pentoxyresorufin acts as a photocatalyst for the oxidation of duroquinol to duroquinone. Wavelength-resolved photovoltammetry experiments clearly implicate pentoxyresorufin as the primary photoexcited intermediate. The photoelectrochemical mechanism is explained on the basis of the presence of a long-lived (possibly charge-separated) photoexcited intermediate in the PPP microphase. Implications for light-energy harvesting are discussed.


Implications of Pubertal Timing for Romantic Relationship Quality Among Heterosexual and Sexual Minority Young Adults.
Relative to on-time or late-maturing peers, girls who begin puberty early typically begin romantic and sexual experiences earlier; however, advanced pubertal status does not necessarily coincide with commensurate interpersonal skills necessary for healthy romantic relationships. Research is limited on the long-term implications of early puberty for relationship quality, and virtually nothing is known about the social implications of early timing for sexual minority females. Using linear regression, we examine longitudinal associations between two measures of girls' pubertal timing (self-perceived timing and menarcheal age) and romantic relationship quality in young adulthood, stratified by sexual orientation, among 5,568 females in waves I and IV of the National Longitudinal Study of Adolescent to Adult Health. We also examine whether identified associations are mediated by parent-adolescent relationship quality. Among sexual minorities, early self-perceived pubertal timing was associated with lower adult romantic relationship quality compared with on-time maturers (β = -2.32; standard error = 1.44; p = .05); this association was mediated by parent-adolescent relationship quality. Among heterosexuals, girls experiencing menarche before age 12 (early maturers) reported lower adult relationship quality compared to on-time maturers (β = -.43; standard error = .22; p = .03); parent-adolescent relationship quality did not mediate this association. Early maturation is associated with lower romantic relationship quality in young adulthood. However, evidence of the association varies by measure of pubertal timing, and the processes by which pubertal timing is linked to later relationship quality may be different for sexual minority and heterosexual females. Potential explanations and public health implications are discussed.


Primary HIV infection in infants: impact of highly active antiretroviral therapy on the natural course.
In the absence of any antiretroviral therapy, about one-third of infants with perinatally acquired HIV infection develop AIDS within the first months of life, while the remainder show slower disease progression. As the rate of viral replication during the first 3 months of life is strictly correlated with and predictive of disease outcome, any treatment that keeps the virus at low levels during primary infection might substantially modify the natural history of infection. Emerging data show that some infants treated early with highly active antiretroviral therapy have persistenty undetectable levels of HIV, and lack an HIV-specific immune response, despite preservation of immune functions. These findings strongly suggest that early therapeutic intervention might lead to a long-term suppression of viral replication.


The morphometric analysis of the central retinal artery.
In this study, we aimed to investigate some features of the central retinal artery (CRA), which supplies the internal aspect of the retina. The CRA is the main vessel supplying blood to the retina. The origin, course and penetration point of the optic nerve by the CRA were studied in 30 human orbits. We compared the right sides to the left sides on the basis of gender in order to statistically analyse the relation between them. The CRA arose directly from the ophthalmic artery in 28 specimens. In two specimens, however, it arose in common with the medial posterior ciliary artery. When we observed the penetration point (site) of the CRA into the optic nerve, in 28 of 30 (93.3%) cases, the artery entered the nerve from the lower medial aspect and in two (6.7%) cases from the upper lateral aspect. The CRA penetrated the optic nerve between 6.4 and 15.2 mm behind the eyeball and reached the eyeball through the centre of the optic nerve. Because of the small diameter of the artery, it has a high risk of getting damaged during a surgical approach to the orbit. Therefore the anatomical relationships of this artery must be well known.


Quantification of photoinduced order increase in liquid crystals with naphthopyran guests.
Photoinduced order-increasing phase transitions can occur in dye-liquid crystal mixtures when the photoproduct of the excitation of the dye molecules is more compatible with the liquid crystalline medium than the initial dye species. A detailed investigation of the photoinduced changes of the phase behavior and optical properties of mixtures of liquid crystals with naphthopyran guests upon exposure to light at 365 nm is presented here. In these guest-host systems, the nematic-to-isotropic phase transition temperature is increased upon irradiation. We show that the nematic range can be extended up to 2.9 °C by illumination in 5CB (4-n-pentyl-4'-cyanobiphenyl) liquid crystal mixtures. The order parameter is significantly increased by illumination at all temperatures within the nematic range and the changes are larger at higher concentrations of the guests. In particular, the illuminated guest-host mixtures exhibit order parameters close to those of the neat liquid crystal host at the same temperature relative to the clearing point. An improved understanding of the photophysical processes taking place at the molecular level in these material systems can inform the design of photoresponsive materials and enhance their potential utility in optical or photonic devices.


Polymorphism of heat-shock protein gene HSP70-2 in Crohn disease: possible genetic marker for two forms of Crohn disease.
Previous reports have shown that heat-shock protein 70 (HSP70) may be associated with Crohn disease. However, genetic analysis of the HSP70 gene in Crohn disease has not been done. The aim of this study is to investigate whether HSP70-2 gene polymorphism is involved in susceptibility to Crohn disease in the Japanese population and whether it correlates with clinical manifestation of the disease. A total of 108 genetically unrelated patients with Crohn disease and 108 healthy controls were typed for HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis (alleles A and B). Patients with Crohn disease were classified into two types: either perforating or non-perforating. Genotype and allele frequency did not differ between patients and controls. In patients with Crohn disease, allele A frequency was significantly higher in the non-perforating than in the perforating type (P = 0.02). When patients with Crohn disease of more than 6.7 years' duration were assessed, the differences in genotype and allele frequency between the two groups became more significant (P < 0.001 and P < 0.001, respectively). These data suggest that HSP70-2 gene polymorphic allele A is a possible genetic marker of less severe clinical phenotype in Japanese patients with Crohn disease.


Diagnostic yield of the Japan NBI Expert Team (JNET) classification for endoscopic diagnosis of superficial colorectal neoplasms in a large-scale clinical practice database.
Magnifying Narrow Band Imaging (NBI) during colonoscopy is a reliable method for differential and depth diagnoses of colorectal lesions. This study examined the diagnostic yield of magnifying NBI based on the Japan NBI Expert Team (JNET) classification in a clinical setting using a large-scale clinical practice database. Types 1, 2A, 2B and 3 correspond to the histopathological classifications of hyperplastic polyp/sessile-serrated polyp, low-grade intramucosal neoplasia, high-grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively. The prospective records of colonoscopy reports and pathological data of 1558 consecutive superficial colorectal lesions removed by colonoscopy were retrospectively analysed. After excluding 156 lesions, the documented JNET classifications of the remaining 1402 colorectal lesions were analysed. Diagnostic yield was analysed and also compared between expert endoscopists and nonexpert endoscopists. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were respectively 75%, 96%, 74%, 96% and 93% for type 1; 91%, 70%, 92%, 67% and 87% for type 2A; 42%, 95%, 26%, 98% and 93% for type 2B; and 35%, 100%, 93%, 98% and 98% for type 3. Nonexpert and expert endoscopists alike had specificity, NPV and accuracy >90% for types 1, 2B and 3, and a sensitivity and PPV >90% for type 2A. Type 2B had a low sensitivity of 42% because it included various histological features. The JNET classification proved useful in a clinical setting both for expert and nonexpert endoscopists, as was expected from the original JNET definition, but type 2B requires further investigation using pit pattern diagnosis.


The euglycemic hyperinsulinemic clamp examination: variability and reproducibility.
The aim was to examine the reproducibility of the euglycemic hyperinsulinemic clamp method. From a random population sample of 60-year-old clinically healthy men, 32 subjects with varying degrees of insulin sensitivity were recruited. Conventional 2-h clamp examinations were carried out at an interval of 2 weeks. Insulin was infused intravenously (priming for 10 min and thereafter 1.0 mU/kg body wt/min). Glucose was infused concomitantly aiming at a whole blood glucose of 5 mmol/L. The glucose infusion rate (GIR) was adjusted for body weight or fat free mass (FFM), the latter measured with dual-energy X-ray absorptiometry. During the final hour of each examination (60-120 min) the mean whole blood glucose concentrations were 5.06+/-0.15 and 5.09+/-0.17 mmol/L, respectively. Of the different time intervals studied, the glucose infusion rate during the final hour (GIR60-120) showed the highest correlation and lowest coefficient of variation (GIR60-120 adjusted by FFM: r=0.70, coefficient of variation=14.7%). Adjustment of GIR for weight instead of FFM underestimated insulin sensitivity in obese men. GIR60-120 adjusted for FFM tended to increase during the second examination. The measurement error was constant across all GIR. In summary, the euglycemic hyperinsulinemic clamp method has a coefficient of variation around 15%. The glucose infusion rate should be adjusted for fat free mass.


Intravitreous Delivery of Αb-Crystallin Ameliorates N-Methyl-N-Nitrosourea Induced Photoreceptor Degeneration in Mice: An in vivo and ex vivo Study.
αB -crystallin (αBC) belongs to the family of small heat shock proteins that are necessary for maintaining oxygen homeostasis. This study was designed to explore the possible effects of αBC on N-methyl- N-nitrosourea (MNU) induced retinal degeneration and the underlying mechanisms. The αBC was injected into the vitreous bodies of MNU administered mice. The retinal morphology and visual function of experimental animals were analyzed by electroretinography (ERG), Spectral domain optical coherence tomography (SD-OCT), fundus photographs, optokinetic testing and immunohistochemistry assay. Optokinetic behavioural tests and ERG examination suggested that the visual impairments of the MNU administered mice were ameliorated effectively by αBC treatment. OCT analysis showed that the major retinal architecture of the MNU administered mice was efficiently rescued by αBC treatment. Fundus examination suggested that the lesion size of the MNU administered mice was decreased by αBC treatment. MNU induced photoreceptor loss was also mitigated by αBC treatment as shown by hematoxylin and eosin staining. In particular, the immunostaining study suggested that M-cone photoreceptors, rather than the S-cone photoreceptors, were preferentially rescued, indicating that the photoreceptor populations have different sensitivities to αBC. The mechanism study suggested that the anti-apoptotic, anti-oxidative and neurotrophic function of αBC collectively contributed to these therapeutic effects. Intravitreal delivery of αBC could alleviate MNU induced photoreceptor degeneration and visual impairment. Further refinement of the αBC induced protection would afford a novel therapeutic strategy for retinitis pigmentosa.


Morphologic alterations in ovine placenta and fetal liver following induced severe placental insufficiency.
Umbilical-placental embolization with microspheres has been used as a model of placental insufficiency and intrauterine growth restriction (IUGR). However, the effects of embolization on placental structure and organ morphology of the resulting IUGR fetus are relatively unexplored. In this study using ovine fetuses, we determined the location and distribution of microspheres within the placenta and explored the extent of placental and fetal organ morphologic changes induced by placental embolization. We hypothesized that microspheres administered into the umbilical circulation over 4 days would cause placental damage without significant morphologic alterations in fetal kidney or liver. Eleven pregnant sheep at 118 +/- 1 (SE) days' gestation were studied. In six fetuses, embolization was induced by injections of 15-microm diameter microspheres on 4 successive days into the fetal descending aorta proximal to the umbilical arteries. Five fetuses served as time controls. In embolized fetuses, microspheres were detected in the placenta embedded in the fetal cytotrophoblastic layer or maternal parenchyma adjacent to villous cytotrophoblasts. Fetal cytotrophoblasts appeared normal except for loss of distinct separation between fetal and maternal cell layers. Microspheres were also detected in the fetal membranes within capillaries. The body weights of embolized fetuses were lower than controls, as were the body weight-normalized liver but not kidney weights. In the liver of the embolized fetuses, the number of hematopoietic cell clusters was markedly reduced, whereas the fetal kidneys appeared normal. We conclude that after 4 days of umbilical-placental embolization, microspheres were concentrated at the fetal villi proximal to the apical maternal-fetal interface and in the fetal membranes. There were noticeable morphologic changes in the embolized placentas, with no apparent gross damage to the placenta. The reduction in fetal liver weight and liver extramedullary hematopoietic cell abundance associated with embolization may predispose the fetus to alterations in liver function that could persist after birth.


Vegetative traits can predict flowering quality in Phalaenopsis orchids despite large genotypic variation in response to light and temperature.
Phalaenopsis is an economically important horticultural ornamental, but its growth is slow and costly. The vegetative cultivation phase is long and required to ensure sufficient plant size. This is needed to develop high quality flowering plants. We studied the effects of temperature (27 or 31 °C) and light intensity (60 or 140 μmol m-2 s-1) on plant growth and development during the vegetative cultivation phase in two experiments, with respectively 19 and 14 genotypes. Furthermore, the after-effects of treatments applied during vegetative growth on flowering traits were determined. Increasing light intensity in the vegetative phase accelerated both vegetative plant growth and development. Increasing temperature accelerated vegetative leaf appearance rate, but strongly reduced plant and root biomass accumulation when temperatures were too high. Flowering was greatly affected by treatments applied during vegetative growth, and increased light and temperature increased number of flower spikes, and number of flowers and buds. Genotypic variation was large in Phalaenopsis, especially in traits related to flowering, thus care is needed when generalising results based on a limited number of cultivars. Plant biomass and number of leaves during vegetative growth were positively correlated with flowering quality. These traits can be used as an early predictor for flowering capacity and quality of the final product. Additionally, this knowledge can be used to improve selection of new cultivars.


Seizures and quinolone antibiotics in children: a systematic review of adverse events.
Quinolone antibiotics have a broad spectrum of activity including against Gram-negative organisms (especially Pseudomonas), but their use has been associated with the development of seizures. Our objective was to evaluate the association between the administration of quinolones and seizures for three groups of children: those with epilepsy; those with other CNS disorders; and those without any CNS disorder. We conducted a systematic review of the MEDLINE, EMBASE and CENTRAL databases. Any studies reporting the administration of quinolones to children and including a methodology for identifying or reporting adverse events were identified by two authors who worked independently. Data relating to study characteristics (including population, intervention, comparison and outcome data) and study quality (including the quality of adverse event reporting) were extracted. We identified 140 studies involving 21 884 children. No studies reported involving children with epilepsy and 21 studies reported the involvement of 317 children with CNS disorders. 2/317 (0.63%) children with CNS disorders developed seizures and at least 4/21 567 (0.023%) children without CNS pathology were reported to have developed seizures. The quality of adverse event reporting in included studies was low. Only 8/140 (5.71%) included studies provided details of a methodology for actively identifying adverse neurological events. Even for children with CNS disorders the risk of developing seizures in association with the use of quinolones seems to be low. Further evaluations of quinolone use in children should include methodologies for actively identifying and reporting adverse neurological events.


Diiron azadithiolates as models for the [FeFe]-hydrogenase active site and paradigm for the role of the second coordination sphere.
The [FeFe] hydrogenases (H2ases) catalyze the redox reaction that interconverts protons and H2. This area of biocatalysis has attracted attention because the metal-based chemistry is unusual, and the reactions have practical implications. The active site consists of a [4Fe-4S] cluster bridged to a [Fe2(μ-dithiolate)(CN)2(CO)3](z) center (z = 1- and 2-). The dithiolate cofactor is [HN(CH2S)2](2-), called the azadithiolate ([adt(H)](2-)). Although many derivatives of Fe2(SR)2(CO)6-xLx are electrocatalysts for the hydrogen evolution reaction (HER), most operate by slow nonbiomimetic pathways. Biomimetic hydrogenogenesis is thought to involve intermediates, wherein the hydride substrate is adjacent to the amine of the adt(H), being bonded to only one Fe center. Formation of terminal hydride complexes is favored when the diiron carbonyl models contain azadithiolate. Although unstable in the free state, the adt cofactor is stable once it is affixed to the Fe2 center. It can be prepared by alkylation of Fe2(SH)2(CO)6 with formaldehyde in the presence of ammonia (to give adt(H) derivatives) or amines (to give adt(R) derivatives). Weak acids protonate Fe2(adt(R))(CO)2(PR3)4 to give terminal hydrido (term-H) complexes. In contrast, protonation of the related 1,3-propanedithiolate (pdt(2-)) complexes Fe2(pdt)(CO)2(PR3)4 requires strong acids. The amine in the azadithiolate is a kinetically fast base, relaying protons to and from the iron, which is a kinetically slow base. The crystal structure of the doubly protonated model [(term-H)Fe2(Hadt(H))(CO)2(dppv)2](2+) confirms the presence of both ammonium and terminal hydrido centers, which interact through a dihydrogen bond (dppv = cis-C2H2(PPh2)2). DFT calculations indicate that this H---H interaction is sensitive to the counterions and is strengthened upon reduction of the diiron center. For the monoprotonated models, the hydride [(term-H)Fe2(adt(H))(CO)2(dppv)2](+) exists in equilibrium with the ammonium tautomer [Fe2(Hadt(H))(CO)2(dppv)2](+). Both [(term-H)Fe2(Hadt(H))(CO)2(dppv)2](2+) and [(term-H)Fe2(adt(H))(CO)2(dppv)2](+) are highly active electrocatalysts for HER. Catalysis is initiated by reduction of the diferrous center, which induces coupling of the protic ammonium center and the hydride ligand. In contrast, the propanedithiolate [(term-H)Fe2(pdt)(CO)2(dppv)2](+) is a poor electrocatalyst for HER. Oxidation of H2 has been demonstrated, starting with models for the oxidized state ("Hox"), for example, [Fe2(adt(H))(CO)3(dppv)(PMe3)](+). Featuring a distorted Fe(II)Fe(I) center, this Hox model reacts slowly with high pressures of H2 to give [(μ-H)Fe2(adt(H))(CO)3(dppv)(PMe3)](+). Highlighting the role of the proton relay, the propanedithiolate [Fe2(pdt)(CO)3(dppv)(PMe3)](+) is unreactive toward H2. The Hox-model + H2 reaction is accelerated in the presence of ferrocenium salts, which simulate the role of the attached [4Fe-4S] cluster. The redox-complemented complex [Fe2(adt(Bn))(CO)3(dppv)(FcP*)](n+) catalyzes both proton reduction and hydrogen oxidation (FcP* = (C5Me5)Fe(C5Me4CH2PEt2)).


The spectrum of segmental colitis associated with diverticulosis.
Segmental colitis associated with diverticulosis (SCAD) has been defined as chronic colonic inflammation surrounding diverticula with rectal sparing. Distinguishing this condition from inflammatory bowel disease may be difficult. Our aim was to evaluate the epidemiological and clinical characteristics of SCAD in our area. Retrospective case identification with prospective follow-up was done. Patients with endoscopic findings suggestive of SCAD were enrolled. The epidemiological, clinical, and histological characteristics of these patients were analyzed. Out of 605 patients with diverticulosis, 23 cases of SCAD were identified (3.8%). Four patients had histological characteristics suggestive of ulcerative colitis, in 1 case the histology was suggestive of ischemic colitis, 6 patients had histology compatible with SCAD, and the remaining patients had either transitional mucosa or minimal lesions. Four cases were refractory to conservative treatment (mesalamine and antibiotics) and surgery was required. No cases of extension of colonic inflammation in diverticula-free areas were found. Segmental colitis associated with diverticulosis is not a rare disorder. It may occur with a spectrum of clinical and histologic features and may be confused with ulcerative colitis. The majority of the cases respond to medical therapy with antibiotics and/or mesalamine, whereas few cases are refractory and need surgery. No evolution to inflammatory bowel disease was observed.


[Mechanism of action of a novel antitumor preparation of chlofiden. Effect on RNA synthesis].
Study of the influence of the antitumor preparation chlofiden on RNA synthesis by sarcoma 45 and liver cells was carried out using 14C-orotic acid. Chlofiden was shown to activate RNA transport from the nucleus to the cytoplasm, and to reduce label incorporation into the nuclear and cytoplasmic RNA. Chlofiden increased the rate of RNA processes, which promoted some increase of label incorporation into low molecular RNA fraction of the nucleus and the cytoplasm. High and stable antitumor activity of chlofiden on sarcoma 45 was established.


[Effect of buried bound water in protein-ligand association processes].
The role of water molecules on the protein-ligand interface during macromolecular association has been determined. The free energy of association of insulin has been calculated by the molecular mechanics method using the continuum Poisson-Boltzman models. The previously developed scheme of the decomposition of association free energy onto contributions from individual interactions has been used to calculate intermolecular interactions, the solvation free energy, and the entropies of the process of macromolecular association. An analysis of the calculated oscillation spectra indicated that the presence of water molecules on the protein-protein interface promotes an increase in the contribution of vibration entropy to the free energy of association due to the enhancement of the flexibility of the complex. It was shown that water molecules involved in the formation of protein-water-ligand hydrogen bond change the balance of forces in the system.


Promoters for synthesis of the pre-C and pregenomic mRNAs of human hepatitis B virus are genetically distinct and differentially regulated.
Two similar, yet functionally distinct genomic RNAs are transcribed from the DNA genome of the human hepatitis B virus. The pre-C RNAs encode the precore protein which is proteolytically processed to yield e antigen. The pregenomic RNAs encode both the nucleocapsid protein and reverse transcriptase and serve as the templates for viral DNA replication. To determine whether synthesis of these two RNAs is directed from a single or a closely spaced pair of promoters, we introduced point and insertion mutations into the basal elements of the promoter that directs their synthesis. Transcription from these mutants was examined both in cell-free transcription systems derived from hepatoma (HepG2) and nonliver (HeLa) cell lines and by transient transfection of hepatoma cell lines (Huh7 and HepG2). The data from these experiments indicated that synthesis of the pre-C and pregenomic RNAs is directed by two distinct promoters and that the basal elements of these two promoters partially overlap, yet are genetically separable, with each consisting of its own transcriptional initiator and a TATA box-like sequence situated approximately 25 to 30 bp upstream of its sites of initiation. A 15-bp insertion was found to be sufficient to physically separate these two promoters. Furthermore, these two promoters can be differentially regulated, with the transcriptional activator Sp1 specifically activating transcription from the pregenomic promoter and the hepatocyte nuclear factor 4 specifically repressing transcription from the pre-C promoter. Thus, we conclude that the promoters used in synthesis of the pre-C and pregenomic mRNAs are genetically distinct and separately regulated.


2H/1H variation in microbial lipids is controlled by NADPH metabolism.
The hydrogen-isotopic compositions (2H/1H ratios) of lipids in microbial heterotrophs are known to vary enormously, by at least 40% (400‰) relative. This is particularly surprising, given that most C-bound H in their lipids appear to derive from the growth medium water, rather than from organic substrates, implying that the isotopic fractionation between lipids and water is itself highly variable. Changes in the lipid/water fractionation are also strongly correlated with the type of energy metabolism operating in the host. Because lipids are well preserved in the geologic record, there is thus significant potential for using lipid 2H/1H ratios to decipher the metabolism of uncultured microorganisms in both modern and ancient ecosystems. But despite over a decade of research, the precise mechanisms underlying this isotopic variability remain unclear. Differences in the kinetic isotope effects (KIEs) accompanying NADP+ reduction by dehydrogenases and transhydrogenases have been hypothesized as a plausible mechanism. However, this relationship has been difficult to prove because multiple oxidoreductases affect the NADPH pool simultaneously. Here, we cultured five diverse aerobic heterotrophs, plus five Escherichia coli mutants, and used metabolic flux analysis to show that 2H/1H fractionations are highly correlated with fluxes through NADP+-reducing and NADPH-balancing reactions. Mass-balance calculations indicate that the full range of 2H/1H variability in the investigated organisms can be quantitatively explained by varying fluxes, i.e., with constant KIEs for each involved oxidoreductase across all species. This proves that lipid 2H/1H ratios of heterotrophic microbes are quantitatively related to central metabolism and provides a foundation for interpreting 2H/1H ratios of environmental lipids and sedimentary hydrocarbons.


Acquired myasthenia gravis in a poodle.
An 11-year-old, spayed female, teacup poodle was evaluated for a chronic cough, lethargy, hindlimb weakness, and reluctance to exercise. Thoracic radiographs revealed megaesophagus and aspiration pneumonia. Serum antibodies against acetylcholine receptors confirmed the diagnosis of myasthenia gravis. The unusual clinical history and case outcome are discussed.


T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats.
The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the V beta 8.5-J beta 2.3 gene combination, with extensive N region additions to both D beta 1 and D beta 2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different V beta 8 subfamily member (V beta 8.5) than the V beta 8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.


Cortisol increases growth hormone-receptor expression in human osteoblast-like cells.
It is well known that high levels of glucocorticoids cause osteoporosis and that physiologic levels of growth hormone (GH) are required for normal bone remodeling. It has been suggested that glucocorticoids regulate GH-responses via the regulation of GH-receptor expression. The aim of the present study was to investigate whether cortisol plays a role in the regulation of GH-receptor expression in cultured human osteoblasts. The effect of serum starvation and cortisol on GH-receptor expression was tested in human osteoblast (hOB)-like cells. Serum starvation for 24 h resulted in an increase in GH-receptor mRNA levels (90 +/- 1% over control culture). Cortisol increased GH-receptor mRNA levels in a dose-dependent manner with a maximal effect at 10(-6)M. The stimulating effect of cortisol on GH-receptor mRNA levels was time-dependent, reaching a peak 12 h after the addition of cortisol (126 +/- 29% over control culture) and remaining up to 12 h later. The increase in GH-receptor mRNA levels was accompanied by an increase in 125I-GH binding which reached a maximum at 24 h (196 +/- 87% over control culture). In conclusion, glucocorticoids increase GH-receptor expression in hOB-like cells. Further studies are needed to clarify whether glucocorticoid-induced regulation of the GH-receptor is important in human bone physiology.


Adaptive fuzzy neural network control design via a T-S fuzzy model for a robot manipulator including actuator dynamics.
This paper focuses on the development of adaptive fuzzy neural network control (AFNNC), including indirect and direct frameworks for an n-link robot manipulator, to achieve high-precision position tracking. In general, it is difficult to adopt a model-based design to achieve this control objective due to the uncertainties in practical applications, such as friction forces, external disturbances, and parameter variations. In order to cope with this problem, an indirect AFNNC (IAFNNC) scheme and a direct AFNNC (DAFNNC) strategy are investigated without the requirement of prior system information. In these model-free control topologies, a continuous-time Takagi-Sugeno (T-S) dynamic fuzzy model with online learning ability is constructed to represent the system dynamics of an n-link robot manipulator. In the IAFNNC, an FNN estimator is designed to tune the nonlinear dynamic function vector in fuzzy local models, and then, the estimative vector is used to indirectly develop a stable IAFNNC law. In the DAFNNC, an FNN controller is directly designed to imitate a predetermined model-based stabilizing control law, and then, the stable control performance can be achieved by only using joint position information. All the IAFNNC and DAFNNC laws and the corresponding adaptive tuning algorithms for FNN weights are established in the sense of Lyapunov stability analyses to ensure the stable control performance. Numerical simulations and experimental results of a two-link robot manipulator actuated by dc servomotors are given to verify the effectiveness and robustness of the proposed methodologies. In addition, the superiority of the proposed control schemes is indicated in comparison with proportional-differential control, fuzzy-model-based control, T-S-type FNN control, and robust neural fuzzy network control systems.


Establishing the existence of the active stomach point in the auricle utilizing radial artery tonometry.
One component of Oriental medicine diagnosis utilizes the palpation of the radial pulse both for internal medicine and also to help clinicians accurately choose body acupuncture treatment points. In the mid-1980s, an attempt was made to capture diagnostic information with three pressure transducers positioned bilaterally over the radial arteries in such a fashion as to simulate classical Chinese pulse diagnosis (Yoon and Ikezono, 1986 and 1987). The results of this pilot study were subsequently difficult to replicate. In the early 1950s, Paul Nogier in Lyon, France introduced a different pulse diagnostic technique (Nogier, 1976). By touching an acupuncture needle on an active auricular acupuncture point, the radial artery wall over the styloid process changes in tone more prominently than when inactive points on the acuricle are touched. This dermal/cardiovascular reflex of pulse diagnostic technique helps, then to localize salient auricular points to treat regarding a patient's illness. Objective digitalized measurements of the Nogier radial arterial pulse wave were performed by computerized tonometry. This demonstrated that when an active stomach point in the auricle (n = 11) was detected utilizing an imperceptible electric current, the initial upstroke of the pressure wave, the pulse pressure and the peak-to-peak interval of the radial artery pulse wave all increased significantly compared to placebo point electronic detection. Thus, the existence of an active auricular point on the auricle was verified by radial artery tonometry.


Body temperature as a mouse pharmacodynamic response to bombesin receptor subtype-3 agonists and other potential obesity treatments.
Treatment of rodents with a bombesin receptor subtype-3 (BRS-3) agonist reduces food intake and increases fasting metabolic rate, causing weight loss with continued treatment. In small mammals, core body temperature (T(b)) is regulated in part by nutritional status, with a reduced T(b) during fasting. We report that fed Brs3 knockout mice have a lower T(b), which is discordant with their nutritional status. Treatment of wild-type mice with a BRS-3 agonist increased T(b), more so when the baseline T(b) was reduced such as by fasting or during the inactive phase of the light cycle. With repeated BRS-3 agonist dosing, the T(b) increase attenuated despite continued weight loss efficacy. The increase in T(b) was not prevented by inhibitors of prostaglandin E (PGE) production but was partially reduced by a β-adrenergic blocker. These results demonstrate that BRS-3 has a role in body temperature regulation, presumably secondary to its effect on energy metabolism, including effects on sympathetic tone. By making use of this phenomenon, the reversal of the fasting T(b) reduction was developed into a sensitive single-dose pharmacodynamic assay for BRS-3 agonism and other antiobesity compounds acting by various mechanisms, including sibutramine, cannabinoid-1, and melanin-concentrating hormone-1 receptor blockers, and melanocortin, β₃-adrenergic, and cholecystokinin-1 receptor agonists. These drugs increased both the fasted T(b) and the fasted, resting metabolic rates. The T(b) assay is a robust, information-rich assay that is simpler and has a greater throughput than measuring metabolic rate and is a practical, effective tool for drug discovery.


Mechanism of Cu,Zn-superoxide dismutase activation by the human metallochaperone hCCS.
The mechanism for copper loading of the antioxidant enzyme copper, zinc superoxide dismutase (SOD1) by its partner metallochaperone protein is not well understood. Here we show the human copper chaperone for Cu,Zn-SOD1 (hCCS) activates either human or yeast enzymes in vitro by direct protein to protein transfer of the copper cofactor. Interestingly, when denatured with organic solvents, the apo-form of human SOD1 cannot be reactivated by added copper ion alone, suggesting an additional function of hCCS such as facilitation of an active folded state of the enzyme. While hCCS can bind several copper ions, metal binding studies in the presence of excess copper scavengers that mimic the intracellular chelation capacity indicate a limiting stoichiometry of one copper and one zinc per hCCS monomer. This protein is active and unlike the yeast protein, is a homodimer regardless of copper occupancy. Matrix-assisted laser desorption ionization-mass spectrometry and metal binding studies suggest that Cu(I) is bound by residues from the first and third domains and no bound copper is detected for the second domain of hCCS in either the full-length or truncated forms of the protein. Copper-induced conformational changes in the essential C-terminal peptide of hCCS are consistent with a "pivot, insert, and release" mechanism that is similar to one proposed for the well characterized metal handling enzyme, mercuric ion reductase.


Knowledge and Attitudes of Women towards Human Papilloma Virus and HPV Vaccine in Thulamela Municipality of Vhembe District in Limpopo Province, South Africa.
Human papillomavirus (HPV) is the most common sexually transmitted viral infection. HPV can cause cervical cancer and other cancers of the genitals, neck and throat. Two HPV vaccines are available, Cervarix and Gardasil, which are the first vaccines directed at the prevention of cervical cancer. The purpose of the study was to assess the knowledge of human papilloma virus and HPV vaccine among rural women in Vhembe district in Limpopo Province. A quantitative descriptive approach was adopted. The quantitative design enabled the discovery of more information by means of direct questioning of a sample of women 30years and older. A convenience sampling was used to select 1546 respondents. Data was analysed using the Statistical Package for Social Sciences. The findings revealed that (97.8%) of women lacked knowledge about Human Papilloma Virus and HPV vaccine and were also not aware of the transmission methods of HPV virus. Furthermore (94.3%) were not aware who was eligible for HPV vaccine and the age range for vaccination and (92.1%) displayed negative attitudes to the use of vaccines if given a pamphlet to let their daughters be immunized. The awareness on human papilloma virus and HPV vaccine among women in Vhembe district is limited. There is a need to educate and promote awareness on cervical cancer screening methods among women to reduce the burden of morbidity and mortality.


Recovery from the 'locked-in' syndrome.
Four patients made substantial recovery following the locked-in syndrome of vascular origin. Clinical and radiologic features supported the presence of ventral pontine infarction secondary to basilar artery occlusion. Quadriplegia and mutism persisted for one to 12 weeks before recovery of motor function began. Improvement continued over several years. All patients regained functional though dysarthric speech. Three of the four patients are ambulatory, one without assistance. As a few patients make a notable recovery from the locked-in syndrome resulting from ventral pontine infarction, aggressive supportive therapy should be considered in the early months of the syndrome.


Delivery of anticancer drugs using polymeric micelles stabilized by hydrogen-bonding urea groups.
Polymeric micelles comprising a hydrogen-bonding core were formed from block copolymers with pendant urea groups and explored as drug delivery vehicles. The amphiphilic block copolymers were synthesized by organocatalytic ring opening polymerization (ROP) of urea-functionalized cyclic carbonates from a poly(ethylene glycol) macroinitiator. The urea functionality was incorporated because its ability to increase the hydrophobic core's affinity toward polar organic compounds through intermolecular hydrogen bonding. Doxorubicin (DOX), a lipophilic anticancer drug with hydrogen-bonding functionalities, was systematically incorporated into the micelle's hydrophobic interior via hydrogen bonding to the functionalized monomers. Micelles employing urea groups were found to more efficiently interact with DOX thus allowing increased drug loading capacity while maintaining a desirable micellular size. More importantly, while DOX-loaded micelles were shown to kill HepG2 human liver carcinoma cell lines efficiently, all of the polymers were non-cytotoxic.


Enzyme-Linked Phage Receptor Binding Protein Assays (ELPRA) Enable Identification of Bacillus anthracis Colonies.
Bacteriophage receptor binding proteins (RBPs) are employed by viruses to recognize specific surface structures on bacterial host cells. Recombinant RBPs have been utilized for detection of several pathogens, typically as fusions with reporter enzymes or fluorescent proteins. Identification of Bacillus anthracis, the etiological agent of anthrax, can be difficult because of the bacterium's close relationship with other species of the Bacillus cereussensu lato group. Here, we facilitated the identification of B. anthracis using two implementations of enzyme-linked phage receptor binding protein assays (ELPRA). We developed a single-tube centrifugation assay simplifying the rapid analysis of suspect colonies. A second assay enables identification of suspect colonies from mixed overgrown solid (agar) media derived from the complex matrix soil. Thus, these tests identified vegetative cells of B. anthracis with little processing time and may support or confirm pathogen detection by molecular methods such as polymerase chain reaction.


Ceria-Based Nanozymes in Point-of-Care Diagnosis: An Emerging Futuristic Approach for Biosensing.
In recent years, there has been a notable increase in interest surrounding nanozymes due to their ability to imitate the functions and address the limitations of natural enzymes. The scientific community has been greatly intrigued by the study of nanoceria, primarily because of their distinctive physicochemical characteristics, which include a variety of enzyme-like activities, affordability, exceptional stability, and the ability to easily modify their surfaces. Consequently, nanoceria have found extensive use in various biosensing applications. However, the impact of its redox activity on the enzymatic catalytic mechanism remains a subject of debate, as conflicting findings in the literature have presented both pro-oxidant and antioxidant effects. Herein, we creatively propose a seesaw model to clarify the regulatory mechanism on redox balance and survey possible mechanisms of multienzyme mimetic properties of nanoceria. In addition, this review aims to showcase the latest advancements in this field by systematically discussing over 180 research articles elucidating the significance of ceria-based nanozymes in enhancing, downsizing, and enhancing the efficacy of point-of-care (POC) diagnostics. These advancements align with the ASSURED criteria established by the World Health Organization (WHO). Furthermore, this review also examines potential constraints in order to offer readers a concise overview of the emerging role of nanoceria in the advancement of POC diagnostic systems for future biosensing applications.


Clinical characteristics of acute fatty liver of pregnancy in a tertiary Indonesian hospital.
Acute fatty liver of pregnancy (AFLP) is a rare, often autosomal recessive disorder with a major risk for maternal and perinatal mortality and morbidity. In order to achieve a more favorable outcome, awareness of its clinical signs and symptoms and early recognition are of pivotal importance. Over a 5-year period 18 patients were diagnosed with AFLP (one twin, 19 babies). The most common sign and symptoms were jaundice, hypoglycemia, nausea and vomiting, encephalopathy, and hypertension. Abnormal laboratory test results included: elevated total/ conjugated (direct) bilirubin, AST, ALT, PT, APTT, creatinine, leukocyte count, and hypoalbuminemia. Maternal and fetal mortality rate was high: 66.7% resulted in a maternal death and 57.9% in an intrauterine fetal demise (IUFD). The number of complications was found to correlate with maternal death (p = 0.042). Surviving AFLP patients had ≤ 3 complications, while patients with > 3 complications on presentation had a high risk of maternal death (OR = 5.0; 95% CI: 0.55-45.4). The presence of hypertension significantly increased the risk of maternal death (OR: 24.5; 95% CI: 1.1-542.8; p = 0.01). The risk of IUFD was primarily related to gestational age at delivery and birth weight. The high rate of jaundice as presenting symptom of AFLP suggests that Indonesian primary maternity care providers may often miss its important earlier signs and symptoms, in particular de-novo onset of nausea and vomiting in late pregnancy.


Primary extranodal diffuse large B-cell lymphoma of the uterine cervix.
Small bowel volvulus is defined as the torsion of the small intestine, potentially leading to bowel obstruction, gangrene and perforation. It is a rare condition, especially in adults. A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection. Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.


Item reduction and psychometric validation of the Oily Skin Self Assessment Scale (OSSAS) and the Oily Skin Impact Scale (OSIS).
Developed using focus groups, the Oily Skin Self Assessment Scale (OSSAS) and Oily Skin Impact Scale (OSIS) are patient-reported outcome measures of oily facial skin. The aim of this study was to finalize the item-scale structure of the instruments and perform psychometric validation in adults with self-reported oily facial skin. The OSSAS and OSIS were administered to 202 adult subjects with oily facial skin in the United States. A subgroup of 152 subjects returned, 4 to 10 days later, for test–retest reliability evaluation. Of the 202 participants, 72.8% were female; 64.4% had self-reported nonsevere acne. Item reduction resulted in a 14-item OSSAS with Sensation (five items), Tactile (four items) and Visual (four items) domains, a single blotting item, and an overall oiliness item. The OSIS was reduced to two three-item domains assessing Annoyance and Self-Image. Confirmatory factor analysis supported the construct validity of the final item-scale structures. The OSSAS and OSIS scales had acceptable item convergent validity (item-scale correlations >0.40) and floor and ceiling effects (<20%). Cronbach's alpha coefficients ranged from 0.83 to 0.89 for the OSSAS and 0.82 to 0.87 for the OSIS, demonstrating excellent internal consistency. The a priori test–retest reliability criterion (intraclass correlation [ICC] ≥0.7) was met for one of the three OSSAS domains and one of the two OSIS domains. OSSAS and OSIS domains distinguished among groups that differed in patient-reported facial oily skin severity (P < 0.0001), and bother associated with oily skin (P < 0.0001). The OSSAS and OSIS versions tested in this study have been found to have strong psychometric properties in this patient sample (adults with self-reported oily facial skin), as assessments of self-reported oily facial skin severity and its emotional impact, respectively.


[Autoimmune hepatitis in pediatric patients].
Autoimmune hepatitis (AIH) is an inflammatory disease of unknown origin that is responsible for progressive liver necrosis and ultimately cirrhosis. Our aim was to evaluate the characteristics of autoimmune hepatitis presenting in the pediatric age. We conducted a retrospective study of all patients diagnosed with AIH in our hospital department during the last 10 years. Variables analyzed included age, sex, clinical presentation, hepatic function, immunoglobulins, autoimmunity markers, histology, treatment, need for transplant, and clinical evolution. According to the positive level of auto-antibodies, AIH patients were classified as type I AIH (ANA and/or smooth-muscle antibodies) and type II (anti-LKM-1). Seven patients were diagnosed in this period -5 girls (71.5%) and 2 boys (28.5%). Five patients presented with type-I serological markers, and two with type-II markers. Age range at diagnosis was from 21 months to 12 years. In the type-I group, 3 patients presented with acute hepatitis while 2 other patients were diagnosed from laboratory findings while asymptomatic. Elevated aminotransferase (10 times the normal level) was observed in 71.5%, and 85% had elevated immunoglobulins. Treatment with azathioprine and prednisone was started after diagnosis with an average time to remission of 14 months. Two patients relapsed following steroid withdrawal. AIH can have different forms of clinical presentation, and is sometimes indistinguishable from viral hepatitis. AIH must be ruled out in patients presenting with concomitant elevation of aminotransferases and immunoglobulins. The commonly accepted treatment is a combination of azathioprine and corticosteroids. A high percentage of patients experience a relapse of disease after steroids are withdrawn. Therefore, some patients will need to stay on combined therapy with minimal doses of steroids.


Variation of breeding system, floral rewards, and reproductive success in clonal Calystegia species (Convolvulaceae).
The reproductive biology of four Japanese Calystegia species (Convolvulaceae) was studied to examine the effects of clonality and population structure on reproductive success. Calystegia soldanella, C. hederacea, and C. japonica are self-incompatible, while C. sepium is self-compatible but needs pollinator services for self-pollination. The showy, bisexual flowers of Calystegia offer pollen and nectar that attract many kinds of insects such as bees and syrphid flies. Clones of C. soldanella often formed mats just above the high tide line on beaches and produced a great number of seeds. Calystegia hederacea and C. japonica were distributed as patches of separate clones and often failed to transfer pollen grains among clones. Fruit and seed sets in C. hederacea and C. japonica were not limited by pollinators but by the number of compatible pollen grains. Although C. sepium clones were also distributed in patches, high and stable fecundity was achieved by self-compatibility and pollinator attraction. We suggest that self-compatibility in C. sepium has evolved under fertilization limitation caused by geitonogamy or facilitated selfing.


Hydrophobicity of Self-Assembled Monolayers of Alkanes: Fluorination, Density, Roughness, and Lennard-Jones Cutoffs.
The interplay of fluorination and structure of alkane self-assembled monolayers and how these affect hydrophobicity are explored via molecular dynamics simulations, contact angle goniometry, and surface-enhanced infrared absorption spectroscopy. Wetting coefficients are found to grow linearly in the monolayer density for both alkane and perfluoroalkane monolayers. The larger contact angles of monolayers of perfluorinated alkanes are shown to be primarily caused by their larger molecular volume, which leads to a larger nearest-neighbor grafting distance and smaller tilt angle. Increasing the Lennard-Jones force cutoff in simulations is found to increase hydrophilicity. Specifically, wetting coefficients scale like the inverse square of the cutoff, and when extrapolated to the infinite cutoff limit, they yield contact angles that compare favorably to experimental values. Nanoscale roughness is also found to reliably increase monolayer hydrophobicity, mostly via the reduction of the entropic part of the work of adhesion. Analysis of depletion lengths shows that droplets on nanorough surfaces partially penetrate the surface, intermediate between Wenzel and Cassie-Baxter states.