Monogeneans from Epinephelus chlorostigma (Val.) (Perciformes: Serranidae) off New Caledonia, with the description of three new species of diplectanids.
Gill monogeneans from the brownspotted grouper Epinephelus chlorostigma (Val.) collected in deep water off the coral barrier reef of New Caledonia, South Pacific, comprise seven species. These include the ancyrocephalid Haliotrema sp., the capsalid Allobenedenia cf. epinepheli Yamaguti, 1968, and five diplectanids, namely Pseudorhabdosynochus epinepheli (Yamaguti, 1938), reported in a previous paper, P. cyanopodus Sigura & Justine, 2008 and P. podocyanus Sigura & Justine, 2008, two species originally described from E. cyanopodus Richardson, P. stigmosus n. sp., P. exoticoides n. sp. and Diplectanum femineum n. sp. P. stigmosus is characterised by a sclerotised vagina with a straight primary canal, large ovoid primary chamber and spherical secondary chamber. P. exoticoides is a highly aberrant species, with a thick-walled male quadriloculate organ and a discoid sclerotised vagina with an exceptional structure. Interestingly, P. exoticoides resembles P. exoticus Sigura & Justine, 2008, a species from E. cyanopodus, and P. stigmosus resembles P. cyanopodus and P. podocyanus, also both from E. cyanopodus, suggesting close relationships between the diplectanid faunae of these two fish species. D. femineum belongs to a group of diplectanids, provisionally classified as 'Diplectanum' Diesing, 1858, which all share a small funnel-shaped male copulatory organ. In contrast to other members of this group which have no sclerotised vagina, D. femineum has a sclerotised vagina with the same organisation as those of species of Pseudorhabdosynochus Yamaguti, 1958. This suggests that the species of 'Diplectanum' from groupers are closer to Pseudorhabdosynochus than suggested by the structure of the male organs.


Interaction of phosphatidylcholine liposomes and plasma lipoproteins with sheep erythrocyte membranes. Preferential transfer of phosphatidylcholine containing unsaturated fatty acids.
The interaction of sheep erythrocyte membranes with phosphatidylcholine vesicles (liposomes) or human plasma lipoproteins is described. Isolated sheep red cell membranes were incubated with liposomes containing [14C]phosphatidylcholine or [3H]phosphatidylcholine in the presence of EDTA. A time-dependent uptake of phosphatidylcholine into the membranes could be observed. The content of this phospholipid was increased from 2 to 5%. The rate of transfer was dependent on temperature, the amount of phosphatidylcholine present in the incubation mixture and on the fatty acid composition of the liposomal phosphatidylcholine. A possible adsorption of lipid vesicles to the membranes could be monitored by adding cholesteryl [14C]oleate to the liposomal preparation. As cholesterylesters are not transferred between membranes [1], it was possible to differentiate between transfer of phosphatidylcholine molecules from the liposomes into the membranes and adsorption of liposomes to the membranes. The phosphatidylcholine incorporated in the membranes was isolated, and its fatty acids were analysed by gas chromatography. It could be shown that there was a preferential transfer of phosphatidylcholine molecules containing two unsaturated fatty acids.


[Loss of olfaction with aging: a frequent disorder receiving little attention].
Loss of olfaction in old age is a frequent problem, which occurs at the same frequency as diabetes or severe sensorineural hearing loss. Problems caused by loss of the sense of smell may include weight loss due to loss of appetite, intake of rotten foods, social isolation and depression. Until now the loss of olfactory function has received relatively little attention compared to diabetes or hearing loss. In this article we review the loss of the sense of smell with age. Possible therapies are discussed to improve the quality of life in older people.


Scaling and Root Planing per Quadrant Versus One-Stage Full-Mouth Disinfection: Assessment of the Impact of Chronic Periodontitis Treatment on Quality of Life--A Clinical Randomized, Controlled Trial.
There are few randomized, controlled clinical trials about the effect of non-surgical periodontal treatment on oral health-related quality of life (OHRQL). This study aims to compare the effects of two different forms of non-surgical periodontal therapy, scaling and root planing (SRP) per quadrant and one-stage full-mouth disinfection (FMD), on periodontal clinical parameters and OHRQL of patients with chronic periodontitis. In this randomized, controlled clinical trial, the questionnaires Oral Impacts on Daily Performance (OIDP) and Oral Health and Quality of Life (OHQoL) were given to 90 patients divided into two groups: SRP (n = 45) and FMD (n = 45). Periodontal clinical parameters recorded included probing depth, clinical attachment level, plaque index, and gingival index. For statistical analysis, χ(2) test, Fisher exact test, Mann-Whitney U test, and Wilcoxon test were used. Intention-to-treat analyses were performed at T0 (baseline) for periodontal clinical parameters, T1 (30 days after treatment) for questionnaires, and T2 (180 days after treatment) for both. No significant differences were identified between the SRP and FMD groups in regard to OHQoL and OIDP scores when comparing the data of T1 and T2. Patients treated by both SRP and FMD showed improvement in all periodontal clinical parameters and OHRQL, with no significant differences between treatment groups.


Endodontic retreatment with halothane versus chloroform solvent.
Chloroform has been the most widely used solvent in endodontics, but due to concerns about its safety, alternatives have been sought. The purpose of this study was to compare the effectiveness of gutta-percha removal and time of retreatment between halothane and chloroform used as solvents. Thirty mandibular premolars were prepared, obturated, and stored in a humidor for 14 months, after which they were randomly divided into two groups for retreatment. The teeth were retreated using either halothane or chloroform as the solvent. The time of retreatment was measured to the nearest minute. Retreatment was deemed complete when there was no evidence of gutta-percha or sealer on the files or paper points. Teeth were split longitudinally and photographed. The resulting slides were projected, the canals traced, and the areas of the canal, gutta-percha, and sealer were measured using a sonic digitizer. The results were analyzed statistically by t test. The results showed no significant difference in gutta-percha removal between the two groups. The chloroform group took significantly less time to retreat than halothane (7.7 min. versus 10.8 min, respectively).


Coordinated regulation of vegetative and reproductive branching in rice.
Grasses produce tiller and panicle branching at vegetative and reproductive stages; the branching patterns largely define the diversity of grasses and constitute a major determinant for grain yield of many cereals. Here we show that a spatiotemporally coordinated gene network consisting of the MicroRNA 156 (miR156/)miR529/SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) and miR172/APETALA2 (AP2) pathways regulates tiller and panicle branching in rice. SPL genes negatively control tillering, but positively regulate inflorescence meristem and spikelet transition. Underproduction or overproduction of SPLs reduces panicle branching, but by distinct mechanisms: miR156 and miR529 fine-tune the SPL levels for optimal panicle size. miR172 regulates spikelet transition by targeting AP2-like genes, which does not affect tillering, and the AP2-like proteins play the roles by interacting with TOPLESS-related proteins (TPRs). SPLs modulate panicle branching by directly regulating the miR172/AP2 and PANICLE PHYTOMER2 (PAP2)/Rice TFL1/CEN homolog 1 (RCN1) pathways and also by integrating other regulators, most of which are not involved in tillering regulation. These findings may also have significant implications for understanding branching regulation of other grasses and for application in rice genetic improvement.


Interleukin-2 receptor beta chain as a possible target for low doses of mafosfamide.
The 7-day cytotoxic lymphocytes (CTL) induced in mixed lymphocyte culture express only the chain of the interleukin-2 receptor (IL-2R). In the present study this fact has been confirmed in a murine semi-allogeneic system. The ability of low doses of mafosfamide (Mf) to affect IL-2-induced CTL proliferation has been demonstrated. It was also shown that IL-2 activated resting suppressor cells. The pretreatment of the suppressor cells with either monoclonal antibodies (mAbs) against the p75 chain of IL-2R, or with Mf abolished the suppressive effect of these cells. No restoration of the proliferative response occurred when the anti-IL-2Ralpha mAb had been used. Flow cytometry analysis of 7-day CTL was carried out with mAbs against the alpha and beta chains of IL-2R. CTL treatment with Mf inhibited anti-IL-2Rbeta mAb binding. It may be assumed that the anti-proliferative effects of Mf which have been demonstrated in this paper, were a result of blocking the IL-2R beta chain.


The angiographic ocular choroidal crescent: distortion with intraorbital and remote intracranial pathology.
The ocular choroidal plexus can be identified on virtually all normal internal or common carotid angiograms. Posterior flattening of the choroid is often seen with retrobulbar tumors. This angiographic appearance can also be observed in some patients with papilledema and increased intracranial pressure. In these patients, ampulliform dilatation of the dura and subarachnoid space just posterior to the globe produces a retrobulbar mass effect that can mimic true retrobulbar tumor. Enlargement of the ocular choroid crescent is an unusual angiographic finding and can be seen with intraocular expansile lesions such as unilateral axial high myopia with posterior staphyloma. An abnormally small, shrunken choroidal blush can be seen with microphthalmia, extreme degrees of hyperopia, and in the phthisical eye.


A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage.
We demonstrate that in S. cerevisiae the rate of ongoing S phase is slowed when the DNA is subjected to alkylation. Slowing of replication is dependent on the MEC1 and RAD53 genes, indicating that lesions alone do not slow replication in vivo and that the slowing is an active process. While it has been shown that a MEC1- and RAD53-dependent checkpoint responds to blocked replication or DNA damage by inhibiting the onset of mitosis, we demonstrate that this checkpoint must also have an additional target within S phase that controls replication rate. MEC1 is a homolog of the human ATM gene, which is mutated in ataxia telangiectasia (AT) patients. Like mec1 yeast, AT cells are characterized by damage-resistant DNA synthesis, highlighting the congruence of the yeast and mammalian systems.


Management of infected pancreatic necrosis.
The past two decades have seen major advances in the understanding and clinical management of acute pancreatitis, yet it still lacks a specific treatment, and management is largely supportive and reactive. Surgery is seeing a diminishing role in the early phase of acute pancreatitis but still predominates in the management of infected pancreatic necrosis--the most lethal complication. This review focuses on recent literature but begins with an account of the evolution of infected necrosis management, which serves to place current treatment into context. Although surgeons initially emphasized less invasive approaches to pancreatic necrosis, they now compete with new techniques developed by pioneering physicians, radiologists, and interventional endoscopists. Clinicians adopting the new techniques will need to emulate the dedication and commitment that the current pioneers demonstrate. Although new techniques are still evolving, they should be evaluated against existing standards of treatment.


Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19.
Since the start of the coronavirus disease 2019 (COVID-19) pandemic, important insights have been gained into virus biology and the host factors that modulate the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 displays a highly variable clinical picture that ranges from asymptomatic disease to lethal pneumonia. Apart from well-established general risk factors such as advanced age, male sex and chronic comorbidities, differences in host genetics have been shown to influence the individual predisposition to develop severe manifestations of COVID-19. These differences range from common susceptibility loci to rare genetic variants with strongly predisposing effects, or proven pathogenic variants that lead to known or novel inborn errors of immunity (IEI), which constitute a growing group of heterogeneous Mendelian disorders with increased susceptibility to infectious disease, auto-inflammation, auto-immunity, allergy or malignancies. The current genetic findings point towards a convergence of common and rare genetic variants that impact the interferon signalling pathways in patients with severe or critical COVID-19. Monogenic risk factors that impact IFN-I signalling have an expected prevalence between 1 and 5% in young, previously healthy individuals (<60 years of age) with critical COVID-19. The identification of these IEI such as X-linked TLR7 deficiency indicates a possibility for targeted genetic screening and personalized clinical management. This review aims to provide an overview of our current understanding of the host genetic factors that predispose to severe manifestations of COVID-19 and focuses on rare variants in IFN-I signalling genes and their potential clinical implications.


Structure-based functional analysis of BRCA1 RING domain variants: Concordance of computational mutagenesis, experimental assay, and clinical data.
A significant impediment to the improvement of clinical outcomes in treating breast and ovarian cancers rests with the lack of available interpretations for BRCA1 variants of unknown significance. Two research groups recently implemented large-scale functional assays for quantifying effects of single missense mutations on homology-directed DNA repair activity of BRCA1 variants, which is critical for tumor suppression and strongly correlates with cancer risk, and their results are significantly concordant with each other as well as with known pathogenic and benign variant clinical data. In this work, we implemented an established computational mutagenesis procedure to characterize structural impacts of single residue replacements to the BRCA1 RING domain. The computational data showed similarly strong concordance with known clinical data as well as with experimental data from both functional assays. Predictions made by models trained on our computational data offer a complementary and orthogonal approach for classifying all remaining unexplored BRCA1 RING domain variants.


Crystal structure of methyl parathion hydrolase from Pseudomonas sp. WBC-3.
Methyl parathion hydrolase (MPH, E.C.188.8.131.52), isolated from the soil-dwelling bacterium Pseudomonas sp. WBC-3, is a Zn(II)-containing enzyme that catalyzes the degradation of the organophosphate pesticide methyl parathion. We have determined the structure of MPH from Pseudomonas sp. WBC-3 to 2.4 angstroms resolution. The enzyme is dimeric and each subunit contains a mixed hybrid binuclear zinc center, in which one of the zinc ions is replaced by cadmium. In both subunits, the more solvent-exposed beta-metal ion is substituted for Cd2+ due to high cadmium concentration in the crystallization condition. Both ions are surrounded by ligands in an octahedral arrangement. The ions are separated by 3.5 angstroms and are coordinated by the amino acid residues His147, His149, Asp151, His152, His234 and His302 and a water molecule. Asp255 and a water molecule serve to bridge the zinc ions together. MPH is homologous with other metallo-beta-lactamases but does not show any similarity to phosphotriesterase that can also catalyze the degradation of methyl parathion with lower rate, despite the lack of sequence homology. Trp179, Phe196 and Phe119 form an aromatic cluster at the entrance of the catalytic center. Replacement of these three amino acids by alanine resulted in a significant increase of K(m) and loss of catalytic activity, indicating that the aromatic cluster has an important role to facilitate affinity of enzyme to the methyl parathion substrates.


Histopathologic outcomes and clinical correlations for high-risk patients screened with anal cytology.
Anal cytologic testing is being increasingly used as a preventive screening test in high-risk populations. We document anal cytology results, correlating HIV test results, and histopathologic follow-up outcomes from a large integrated health system which recently implemented anal screening. Anal Pap tests between May 2007 and August 2009 were studied and correlated with HIV test histories and follow-up histopathologic diagnoses. 688 anal cytologic tests were identified with 7.4% reported as unsatisfactory; 72% of anal cytologic tests were abnormal; 91% of patients were HIV positive. The HIV-positive rate and likelihood of high viral load were both significantly greater among patients with abnormal anal cytology than among patients with negative anal cytology, but did not vary significantly among patients with different categories of abnormal anal cytology. For 459 patients with abnormal anal cytology, 198 had anal biopsies. For patients with abnormal anal cytology findings of ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial neoplasia), ASC-H (atypical squamous cells, cannot exclude high-grade squamous lesion), and HSIL (high-grade squamous intraepithelial neoplasia), histopathologic intraepithelial neoplasia (AIN)2/3 or 2/3+ diagnoses were established in 46.5, 56.6, 65, and 80.8%, respectively. Patients with any level of abnormal anal cytology result are at significant risk of the presence of histopathologically verifiable high-grade anal intraepithelial lesions. More specific markers for identifying patients at highest risk of progression to invasive anal carcinoma are needed.


Retzius-Sparing Robot-Assisted Robotic Prostatectomy: Past, Present, and Future.
Radical prostatectomy has undergone many adaptations since its inception, including the Retzius-sparing robotic-assisted radical prostatectomy approach. In this article, we review the origins of radical prostatectomy, the theoretic basis for Retzius-sparing robotic-assisted radical prostatectomy, and outline the key steps of the procedure. To date, there have been 9 studies comparing the outcomes of Retzius-sparing robotic-assisted radical prostatectomy with standard robotic-assisted radical prostatectomy, which have demonstrated improved continence outcomes for Retzius sparing robotic assisted radical prostatectomy within the first year and equivalent oncologic efficacy out to 18 months. Further research is needed to evaluate sexual function outcomes as well as long-term oncologic outcomes.


Structure of distress call: implication for specificity and activation of dopaminergic system.
We conducted a set of playback experiments aimed at understanding whether distress-call structure in the greater short-nosed fruit bat Cynopterus sphinx is specific in encoding information relating to stress that attracts conspecifics. We tested the specificity by playing their distress call and its modified version at a foraging site for free-ranging bats, as well as under captive conditions involving either a small group or individuals. In a separate playback experiment, bats showed a significantly greater response when the natural call as opposed to a modified call was played back to captive as well as free-ranging bats at the foraging site. Under captive conditions, bats showed less of a response to the playback of distress calls when in a group than when alone. We subsequently found that tyrosine hydroxylase (TH) and its transcription factor-nuclear receptor related factor 1 (Nurr-1); and the dopamine transporter (DAT) and its receptor (D1DR) were elevated significantly in the amygdala of bats both emitting and responding to a distress call, but not in the case of bats responding to the modified call. These results suggest that distress-call structure encodes information on the state of stress that is capable of being conveyed to conspecifics.


Quantitative thin-layer chromatographic method for the determination of procainamide and its major metabolite in plasma.
A sensitive and accurate spectrodensitometric method was developed for the determination of procainamide and its major metabolite, N-acetylprocainamide, in plasma. The method involves extraction into organic solvent at alkine pH, separation by thin-layer chromatography and direct measurement of the absorbance of the compounds on the plate at 275 nm. Quantities as low as 10 ng could be measured and a linear relationship was obtained between peak areas and amounts of the compounds in the spots from 10 to 200 ng. The recovery of both drugs from plasma was from 95.4 to 104.8%. The method is sensitive and specific, and procainamide was well separated from N-acetylprocainamide at all investigated concentrations. The method is recommended for clinical assays and pharmacokinetics studies.


Community-engaged research perspectives: then and now.
To fully appreciate the health of an individual, it is necessary to understand the effect of a person's attitudes, beliefs, and behaviors within their social, environmental, and cultural context. The medical model, although extremely useful, has its limitations when it comes to understanding the health of people as they live in the world. Wellness does not happen in the doctor's office alone, akin to the fact that scientific discovery is not limited to a laboratory. In this perspectives article, we posit that by using a community-engaged research approach, we not only allow for the translation of scientific discovery into clinical practice and public health initiatives, but we also create a new way of generating and integrating knowledge to improve health outcomes. In short, community-engaged research is not only a tool for translation, it is unique method for scientific discovery bringing transdisciplinary teams together that study health problems in real-world contexts and consider sustainability at the front end of asking the research question.


Poor Medication Adherence in African Americans Is a Matter of Trust.
The purpose of this paper was to explore the lack of medication adherence in the African American patient community. The paper will address myths that many African American patients believe related to type 2 diabetes, hypertension treatment, and natural remedies. Research has shown that the disparities in the acceptance of healthcare provider advice and prescriptions are a significant concern particularly in African American patients. The acceptance of a provider's diagnosis and subsequent intervention can vary based on several issues including healthcare access, patient preferences, trust of a provider, and treatment recommendations. Patient influences can range from their ability to trust the provider (and what he/she says) to following through with their advice. Several studies have looked at the beliefs and misconceptions some African Americans hold regarding the treatment of hypertension and diabetes with some showing a preference for "natural remedies." This paper will leverage a literature review to seek out myths from African American patients to understand why they are dealing with challenges related to adherence with medication. The searches identified 58 research papers. The study applied an inductive content analysis approach to assess the research papers and identify themes. The barriers identified in this study include disbelief of the diagnosis, distrust for medication, mistrust for physicians and healthcare system, belief in alternative medicine, cultural/generation norms, and access/affordability of care. One of the most prominent factors that crossed all barriers was medical mistrust.


Treatment of groundwater polluted by arsenic compounds by zero valent iron.
Batch experiments were carried out to study the kinetics and efficiency of inorganic arsenic removal by zero valent iron (ZVI) powder, and as well as the effects of pH, anions, and humic material (HM) on this process. Moreover, column experiment was conducted for 31 days to treat arsenate solution of 500 microg As/L using waste iron chippings as filling. Batch experiments showed that both arsenate and arsenite compounds could be removed efficiently from simulated groundwater by ZVI under aerobic and relative anaerobic conditions. Aerobic condition was favorable to arsenic removal especially for arsenate, while arsenite could be removed more rapidly than arsenate in relative anaerobic condition. Oxidation of arsenite to arsenate by iron species in aerobic environment was observed, which is thought to be an important pathway of arsenite removal. In an unsealed system, the removal efficiency of both arsenate and arsenite decreased at higher pH value. In a sealed system, acidic and alkaline condition seemed to be favorable for arsenate and arsenite removal, respectively. Phosphate and low concentration sulfate caused a decrease in arsenate removal, while high concentration sulfate as well as nitrate caused slight increase in arsenate removal. Presence of HM in solution slightly inhibited arsenic removal. Arsenic removal efficiency in column study was influenced by flow rate and work period of the column. More than 98% of arsenate could be removed stably with a hydraulic resident time of 2 h at last, and the effluent meet the drinking water standard.


Resolving intertracer inconsistencies in soil ingestion estimation.
In this article we explore sources and magnitude of positive and negative error in soil ingestion estimates for children on a subject-week and trace element basis. Errors varied among trace elements. Yttrium and zirconium displayed predominantly negative error; titanium and vanadium usually displayed positive error. These factors lead to underestimation of soil ingestion estimates by yttrium and zirconium and a large overestimation by vanadium. The most reliable tracers for soil ingestion estimates were aluminum, silicon, and yttrium. However, the most reliable trace element for a specific subject-day (or week) would be the element with the least error during that time period. The present analysis replaces our previous recommendations that zirconium and titanium are the most reliable trace elements in estimating soil ingestion by children. This report identifies limitations in applying the biostatistical model based on data for adults to data for children. The adult-based model used data less susceptible to negative bias and more susceptible to source error (positive bias) for titanium and vanadium than the data for children. These factors contributed significantly to inconsistencies in model predictions of soil ingestion rates for children. Correction for error at the subject-day level provides a foundation for generation of subject-specific daily soil ingestion distributions and for linking behavior to soil ingestion.


Electrocorticographic correlates of cognitive control in a Stroop task-intracranial recording in epileptic patients.
The human brain executes cognitive control, such as selection of relevant information in the presence of competing irrelevant information, and cognitive control is essential for us to yield a series of optimal behaviors in our daily life. This study assessed electrocorticographic γ-oscillations elicited by cognitive control in the context of the Stroop color-naming paradigm, with a temporal resolution of 10 msec and spatial resolution of 1 cm. Subjects were instructed to overtly read a color word printed in an incongruent color in the reading task, and to overtly name the ink color of a color word printed in an incongruent color in the Stroop color-naming task. The latter task specifically elicited larger γ-augmentations in the dorsolateral-premotor, dorsolateral-prefrontal and supplementary motor areas with considerable inter-subject spatial variability. Such Stroop color-naming-specific γ-augmentations occurred 500 to 200 msec prior to overt responses. Electrical stimulation of the sites showing Stroop color-naming-specific γ-augmentations resulted in temporary naming impairment more frequently than that of the remaining sites. This study has provided direct evidence that a critical process of cognitive control in the context of Stroop color-naming paradigm consists of recruitment of neurons essential for naming located in variable portions of the dorsolateral premotor and prefrontal areas.


LDHk in the retina of diverse vertebrate species: a possible link to the Warburg effect.
LDHk is a cancer-associated lactate dehydrogenase which is also found at high levels in normal mammalian retina. Such retinas share with most cancer tissues a dependence on aerobic glycolysis, leading to high production of lactate. However, retinas of lower vertebrate species are significantly less dependent on aerobic glycolysis. We find that retinas of species less dependent on aerobic glycolysis express significantly lower levels of an LDHk-like activity, less than or equal to the low levels seen in brains. The enzymes from lower species differ from the mammalian retinal enzyme in their pH optima and responsiveness to oxygen; but share a similar degree of inhibition by 5'-5'-dinucleoside tetraphosphates. Therefore, the expression pattern of LDHk in brain and retina of diverse vertebrate species suggests a link with the Warburg effect.


Asymptotic properties of infinite Leslie matrices.
The stable population theory is classically applicable to populations in which there is a maximum age after which individuals die. Demetrius [1972. On an infinite population matrix. Math. Biosci. 13, 133-137] extended this theory to infinite Leslie matrices, in which the longevity of individuals is potentially infinite. However, Demetrius had to assume that the survival probability per time step tends to 0 with age. We generalise here the conditions of application of the stable population theory to infinite Leslie matrix models and apply these results to two examples, including or not senescence.


Spatial organization of chromosomes leads to heterogeneous chromatin motion and drives the liquid- or gel-like dynamical behavior of chromatin.
Chromosome organization and dynamics are involved in regulating many fundamental processes such as gene transcription and DNA repair. Experiments unveiled that chromatin motion is highly heterogeneous inside cell nuclei, ranging from a liquid-like, mobile state to a gel-like, rigid regime. Using polymer modeling, we investigate how these different physical states and dynamical heterogeneities may emerge from the same structural mechanisms. We found that the formation of topologically associating domains (TADs) is a key driver of chromatin motion heterogeneity. In particular, we showed that the local degree of compaction of the TAD regulates the transition from a weakly compact, fluid state of chromatin to a more compact, gel state exhibiting anomalous diffusion and coherent motion. Our work provides a comprehensive study of chromosome dynamics and a unified view of chromatin motion enabling interpretation of the wide variety of dynamical behaviors observed experimentally across different biological conditions, suggesting that the "liquid" or "solid" state of chromatin are in fact two sides of the same coin.


riboviz 2: a flexible and robust ribosome profiling data analysis and visualization workflow.
Ribosome profiling, or Ribo-seq, is the state-of-the-art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses. We present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system for end-to-end processing of Ribo-seq data. riboviz 2 has been extensively tested on diverse species and library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline. riboviz 2 is freely available at github.com/riboviz/riboviz.


In men with rectal chlamydia, 7-d doxycycline increased microbiologic cure at 4 wk vs. 1-dose azithromycin.
Lau A, Kong FYS, Fairley CK, et al. Azithromycin or doxycycline for asymptomatic rectal chlamydia trachomatis. N Engl J Med. 2021;384:2418-27. 34161706.


Phenotypic heterogeneity in the NCI-H125 cell line affects biological activity using the epidermal growth factor receptor as target.
We evaluated the influence of some morphological changes of the NCI-H125 cell line in surface expression of the epidermal growth factor receptor (EGFR) and their impact on some biological activity assays using this molecule as target. Hematoxylin and eosin (H/E) staining, light microscopy immunocytochemistry, flow cytometric antibody-receptor binding test, cell viability determination and cell cycle analysis were performed. Phenotypic changes and inconsistency in EGFR expression were detected in NCI-H125 cell cultures. A significant reduction in the growth rate, mainly characterized by cell cycle arrest in the G0-G1 phase, was also evidenced. Differential distribution of cell viability in NCI-H125 subpopulations and its relationship with the EGFR surface expression were determined. Nuclear alterations observed in NCI- -H125 were not apoptosis related. A lack of control of cell cultures affects the reliability and reproducibility of biomedical and biotechnological research using EGFR as target. Therefore, rigorous control of the above mentioned parameters in these experiments is recommended.


Amino acid substitutions in the membrane-binding domain of cytochrome b5 alter its membrane-binding properties.
The structure-function relationships of the 43-amino-acid membrane-binding domain of cytochrome b5 have been examined in two mutant forms of the protein. In one mutant, two tryptophans in the membrane-binding domain, at positions 108 and 112, were replaced by leucines, and in the second mutant, in addition, aspartic acid 103 was also replaced by leucine. The fluorescence emission spectra of the three proteins and their degree of quenching by brominated lipids indicate that the mutations are not producing major conformational changes or allowing a deeper degree of penetration of the domain into the bilayer. The hydrophobicities of the three proteins were compared, by determining strengths of self-association and membrane affinities, and it was found that the protein with two additional leucines was much less hydrophobic and the one with three additional leucines was much more hydrophobic than the native cytochrome. It appears that small changes in amino acid composition, which produce no gross changes in the structure of the membrane-binding domain, will nevertheless produce very large changes in the strengths of self- and membrane-association. These differences in self-association had profound effects on the times required for membrane-association to reach equilibrium.


Socioeconomic status and health-related quality of life among patients with prostate cancer 6 months after radical prostatectomy: a longitudinal analysis.
To identify the associations between socioeconomic status (SES) and health-related quality of life (HRQOL) and the explanatory contribution of disease, patient and healthcare factors among patients with prostate cancer. Prospective cohort study. In all, 246 patients from 2 hospitals in Hamburg/Germany who underwent radical prostatectomy completed a questionnaire shortly before discharge from hospital and again 6 months later. HRQOL as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C-30 including global quality of life, 5 functional scales and 9 symptom scales/items. Generalised estimating equations were calculated to analyse longitudinal data. Lower SES measured by income, education and occupational status is significantly associated with lower HRQOL 6 months after treatment. This especially holds true for the functional scales. After introducing disease, patient and healthcare factors, associations remain significant in the majority of cases. The explanatory contribution of patient factors such as comorbidity or psychosocial characteristics and of healthcare factors is slightly stronger than that of disease factors. We identified strong social inequalities in HRQOL among patients with prostate cancer 6 months after surgery, in Germany. The underlying causes could not be sufficiently identified, and further research regarding these associations and their explanatory factors is needed.


Lesion-induced mossy fibers to the molecular layer of the rat fascia dentata: identification of postsynaptic granule cells by the Golgi-EM technique.
The axons of the dentate granule cells, the hippocampal mossy fibers, sprout "backward" into the dentate molecular layer when this is heavily denervated. Using the combined Golgi-electron microscopy (EM) technique we now demonstrate that these aberrant supragranular mossy fibers at least in part terminate on granule cell dendrites. Sprouting of mossy fibers into the dentate molecular layer was induced in adult rats by simultaneous surgical removal of the commissural and entorhinal afferents to the fascia dentata. After at least 7 weeks survival, the presence of mossy fiber terminals in the inner part of the dentate molecular layer was demonstrated by light microscopy. In the electron microscope the mossy fiber terminals were identified by their unique structural characteristics, namely, the unusually large size of the terminals, the dense packing of clear synaptic vesicles with a few dense core vesicles intermingled, the presence of asymmetric synaptic contacts with spines and desmosome-like contacts with dendritic shafts, and the continuity with a thin unmyelinated preterminal axon. Golgi-stained granule cells were first identified in the light microscope, and then, after deimpregnation, the same cells were examined in the electron microscope. In ultrathin, serial sections lesion-induced mossy fiber terminals were found in synaptic contact with spines on proximal dendritic segments of such identified Golgi-impregnated granule cells. From this we conclude that the aberrant, supragranular mossy fibers can innervate dendrites of the parent cell group, the dentate granule cells. The results, moreover, provide an example of reactive synaptogenesis where both the sprouted afferents and its postsynaptic element have been identified.


Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus.
High density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma. HDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0±1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir). HOMA-β was lowest, whereas HOMAir was highest in T2DM (P<0.01 and P<0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P<0.05) and cellular cholesterol efflux (P<0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P=0.001) and cellular cholesterol efflux (P=0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β. Pancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.


Antioxidant effects on cell-mediated immunity.
Experiments were performed to determine the effects of dietary selenium and/or vitamin E deficiency on cell-mediated cytotoxicity in the mouse. Natural killer cell-mediated cytotoxicity (NKCC) was depressed after 8 wk on diets deficient in selenium and/or vitamin E. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) was not affected by 8 wk of dietary deficiency of selenium and/or vitamin E. T-lymphocyte-mediated cytotoxicity (TCMC) was found to be depressed by combined selenium-vitamin E deficiency after 7 weeks on diets.


The prevalence and severity of carpal tunnel syndrome during pregnancy.
Carpal tunnel syndrome (CTS) is the most common compression neuropathy of median nerve, which can occur or aggravate during pregnancy and sometimes needs surgery. Since early diagnosis leads to simpler and less risky treatments, this study evaluated the frequency and severity of CTS in pregnancy. In this descriptive cross-sectional study, 100 pregnant women who came to gynecology clinic of university hospitals were randomly selected. At first, they were asked for presence of clinical symptoms, and then clinical tests including Phalen and Tinel were conducted to diagnose CTS. Then, electrodiagnostic studies including sensory and motor distal latencies of median nerve were measured and compared with those of ulnar nerve, and then, nerve conduction velocity of median nerve across wrist was evaluated. Among the studied pregnant women, 19% had CTS, out of whom 47.5% were bilateral and 26.3% had severe CTS. The prevalence in the first, second, and third trimesters were 11%, 26%, and 63%, respectively, and 42% were asymptomatic. Sensitivity and specificity of clinical signs as compared with electrodiagnostic findings were 52% and 23%, respectively. The prevalence of CTS is relatively high in pregnant women. The prevalence and severity of CTS increase and the rate of asymptomatic cases reduces with the age of pregnancy. Clinical examination and history taking could not diagnose all cases, and their sensitivity and specificity are much less than electrodiagnostic tests. Therefore, it is recommended that electrodiagnostic studies be conducted in pregnant women during the third trimester.


Steam explosion processing intensifies the nutritional values of most crop byproducts: Morphological structure, carbohydrate-protein fractions, and rumen fermentation profile.
To investigate the feasibility of steam explosion on the exploitation of ruminant feedstuff, the morphological structure, carbohydrate-protein fractions, and rumen fermentation profile of five typical crop byproducts (corn cob, rice straw, peanut shell, millet stalk, and sugarcane tip) were analyzed before and after steam explosion processing. The results showed that these crop byproducts had different physicochemical properties and rumen fermentation profiles, most of which could be improved by steam explosion processing, i.e., more rough morphological surface, much-broken structure, more digestible carbohydrate fraction (non-NDF +49.92-452.24%), faster gas production rate (c +9.72-68.75%), higher dry matter digestibility (DMD48 +11.38-47.36%), more available energy (ME -3.69-+42.13%, except for peanut shell), along with more unavailable protein fraction (ADICP +27.16-102.70%). It is suggested that steam explosion processing could intensify the feeding value of most crop byproducts for ruminants, but with a caution of heat damage to proteins.


Atypical lymphocytic lobular panniculitis.
Although subcutaneous T-cell lymphoma (SCTCL) is considered an aggressive form of lymphoma, some patients manifest a long waxing and waning phase unaccompanied by constitutional symptoms. Twelve patients were prospectively encountered, presenting with a lymphocytic panniculitis accompanied by lymphoid atypia, although not fulfilling criteria for SCTCL. Clinical, histologic, phenotypic, and genotypic analyses were conducted. There were five men, one boy, and six women; none had symptoms compatible with lupus erythematosus or aggressive SCTCL. All but two had a waxing and waning course of years. Four patients had periodic cytopenias accompanied by fevers. While responding somewhat to prednisone, the lesions relapsed. In one patient, treatment with alemtuzumab (CAMPATH-1) led to complete lesional resolution with no recurrence. Light microscopy showed expansion of the interstices of the fat lobule by mildly atypical lymphocytes of the CD4 subset in 10 biopsies from eight patients; in the other four patients, there was an increase in CD8 lymphocytes. There was diminished expression of CD5 and/or CD7 in the majority of biopsies. Ten of 13 biopsies showed clonal T-cell receptor-gamma rearrangements. We apply the term atypical lymphocytic lobular panniculitis to this distinctive form of lymphocytic panniculitis manifesting this light microscopic, phenotypic, and genotypic profile.


The lysine-rich H1 histones from the slime moulds, Physarum polycephalum and Dictyostelium discoideum lack phosphorylation sites recognised by cyclic AMP-dependent protein kinase in vitro.
Calcium chloride-extracted histones were prepared from nuclei of the slime moulds, Physarum polycephalum and Dictyostelium discoideum, and phosphorylation by purified preparations of cyclic AMP-dependent protein kinase (cAMP-d PK) and growth-associated H1 histone kinase (HKG) examined and compared. Among the major histone fractions and other proteins in the two preparations, the H1 histones from both organisms were found to be effective and exclusive substrates for HKG. cAMP-d PK, which phosphorylates mammalian H1 histone and certain, in particular H2B, of the mammalian core histones, phosphorylated several of the core histones from both slime moulds but did not phosphorylate H1 histone from either. The slime mould H1s remained ineffective substrates for cAMP-d PK even after extensive alkaline phosphatase treatment of the histone preparations. Additional studies demonstrated that the lack of slime mould H1 phosphorylation by cAMP-d PK was not due to competition of the H1 molecules with the core histones for the kinase. Our studies suggest that H1 histones from these organisms, whilst clearly containing sites for phosphorylation by HKG, apparently lack phosphorylation sites recognised by cAMP-d PK. Thus, the mediation of specific nuclear functions by cAMP-dependent phosphorylation of H1 in higher organisms may not occur or be required in these lower eukaryotes.


Misaligned maps lead to predictable errors.
Three experiments were conducted to investigate the ability of subjects to make judgments of direction when using misaligned maps. Two hypotheses were proposed (i) errors would fall into two lawful categories--mirror-image errors and alignment errors; (ii) the effect of map orientation would generalize to a different mode of responding than has been used in previous studies. Support for both hypotheses was obtained. The results are discussed in terms of the mental processes used to align maps to spaces, and the task demands required by different response modes.


Near-infrared light and glucose dual-responsive cascading hydroxyl radical generation for in situ gelation and effective breast cancer treatment.
A general therapeutic strategy to treat breast cancer is attractive as different subtypes of breast cancers often exhibit distinct response to existing cancer therapeutics. To this end, we prepare a catalyst couple of glucose oxidase (GOx) and gallic acid-ferrous (GA-Fe) nanocomplexes, a type of near-infrared (NIR) absorbing Fenton catalyst, to enable NIR-trigger in-situ gelation and enhanced chemodynamic/starvation therapy that appears to be effective for different types of breast cancer cells. In this system, GOx is mixed with GA-Fe in a solution of N,N-dimethylacrylamide (DMAA) and poly (ethylene glycol) double acrylate (PEGDA). Upon intratumoral injection and NIR laser exposure, such GA-Fe show rapid temperature increase, which would simultaneously increase the catalytic efficiencies of GA-Fe and GOx. The cascade production of hydroxyl radicals (•OH) from glucose is then initiated to enable polymerization of DMAA and PEGDA to form a hydrogel at the injection site within the tumor. The continuous production of cytotoxic •OH together with glucose depletion by the intratumorally fixed catalyst couple would further confer effective destruction of breast cancer tumors by such chemodynamic/starvation therapy. Our work presents a hydrogel-based therapeutic strategy for local treatment of solid tumors with high tumor destruction efficacy and low systemic toxicity.


Formylmethanofuran dehydrogenase from methanogenic bacteria, a molybdoenzyme.
Formylmethanofuran dehydrogenase, a key enzyme of methanogenesis, was purified 100-fold from methanol grown Methanosarcina barkeri to apparent homogeneity and a specific activity of 34 mumol.min-1.mg protein-1. Molybdenum was found to co-migrate with the enzyme activity. The molybdenum content of purified preparations was 3-4 nmol per mg protein equal to 0.6-0.8 mol molybdenum per mol enzyme of apparent molecular mass 200 kDa. Evidence is presented that also formylmethanofuran dehydrogenase from H2/CO2 grown Methanobacterium thermoautotrophicum (strain Marburg) is a molybdoenzyme.


The Validity and Reliability of Two Commercially Available Load Sensors for Clinical Strength Assessment.
Handheld dynamometers are common tools for assessing/monitoring muscular strength and endurance. Health/fitness Bluetooth load sensors may provide a cost-effective alternative; however, research is needed to evaluate the validity and reliability of such devices. This study assessed the validity and reliability of two commercially available Bluetooth load sensors (Activ5 by Activbody and Progressor by Tindeq). Four tests were conducted on each device: stepped loading, stress relaxation, simulated exercise, and hysteresis. Each test type was repeated three times using the Instron ElectroPuls mechanical testing device (a gold-standard system). Test-retest reliability was assessed through intraclass correlations. Agreement with the gold standard was assessed with Pearson's correlation, interclass correlation, and Lin's concordance correlation. The Activ5 and Progressor had excellent test-retest reliability across all four tests (ICC(3,1) ≥ 0.999, all p ≤ 0.001). Agreement with the gold standard was excellent for both the Activ5 (ρ ≥ 0.998, ICC(3,1) ≥ 0.971, ρc ≥ 0.971, all p's ≤ 0.001) and Progressor (ρ ≥ 0.999, ICC(3,1) ≥ 0.999, ρc ≥ 0.999, all p's ≤ 0.001). Measurement error increased for both devices as applied load increased. Excellent test-retest reliability was found, suggesting that both devices can be used in a clinical setting to measure patient progress over time; however, the Activ5 consistently had poorer agreement with the gold standard (particularly at higher loads).


[Organisation of bronchitis dispensaries-problems and present situation in the north-eastern region of the GDR (a pilot study of the bronchitis dispensary of the Pediatric Clinic, University of Greifswald) (author's transl)].
The dator on the care of children with CNSLD obtained from pediatricians working at out-patient departments in 15 districts of the Rostock and Neubrandenburg counties (in the north-eastern region of the GDR) are analyzed in a pilot study. This survey shows that there are 6 standard bronchitis dispensaries and on additional dispensary with highly specialized diagnostic equipment (Pediatric Clinic of the University of Greifswald) in 7 of the districts. In the remaining districts care of these children is provided within the framework of general medical outpatient care. 2% of the children having CNSLD only 36% receive medical treatment, which is a rather low percentage. This situation will be improved on the basis of better cooperation with the family doctors and the out-patient departments for lung diseases.


Fifty years of research on antithrombotic therapy: Achievements and disappointments.
The achievements with antithrombotic therapy over the past 50 years have been monumental and the disappointments relatively few. In this review, we will discuss, chronologically, the major developments of the two recognized classes of antithrombotics - anticoagulants and antiplatelet agents.


Urethral prolapse formation after urodynamic testing: a case report.
Urodynamic testing is a widely used modality for evaluation of lower urinary tract symptoms with minimal morbidity to the patient. We report a case of strangulated urethral prolapse in a 74-year-old female that occurred right after urodynamic evaluation. The urethral prolapse was managed conservatively and the patient fully recovered without the need for surgical intervention.


Blockade of endothelin B receptor improves the efficacy of levetiracetam in chronic epileptic rats.
To elucidate the mechanisms that regulate p-glycoprotein (PGP) expression and function in pharmacoresistant epilepsy, we investigated the effect of an ETB receptor antagonist (BQ788) and a p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190) on intractable seizures in chronic epileptic rats. Lithium-pilocarpine-induced chronic epileptic rats were used in the present study. Animals were given levetiracetam (LEV), LEV + SB202190, LEV + BQ788, SB202190 or BQ788 over a 3-day period using an osmotic pump. Seizure activity was recorded by video-EEG monitoring with 2h of recording per day at the same time of day. We also performed western blot after EEG analysis. Compared to control animals, PGP, ETB receptor and p38MAPK expression was increased in the hippocampus of epileptic animals. Neither SB202190 nor BQ788 affected the spontaneous seizure activity in epileptic rats. Three of ten rats were responders and achieved complete seizure control or significant reduction in seizure activity by LEV. In four of ten rats, seizure frequency was unaltered by LEV (non-responders). LEV + SB202190 reduced seizure duration, but not seizure frequency, in both responders and non-responders. LEV + BQ788 alleviated seizure frequency and seizure duration in both responders and non-responders. Compared to responders, PGP and ETB receptor expression was enhanced in the hippocampus of non-responders. To the best of our knowledge, these findings are the first indications of the role of ETB receptor in pharmacoresistant epilepsy. Therefore, the present data suggest that the regulation of the ETB receptor-mediated signaling pathway may be important for identification of new therapeutic strategies for improving antiepileptic drug efficacy.


Web Data Mining: Validity of Data from Google Earth for Food Retail Evaluation.
To overcome the challenge of obtaining accurate data on community food retail, we developed an innovative tool to automatically capture food retail data from Google Earth (GE). The proposed method is relevant to non-commercial use or scholarly purposes. We aimed to test the validity of web sources data for the assessment of community food retail environment by comparison to ground-truth observations (gold standard). A secondary aim was to test whether validity differs by type of food outlet and socioeconomic status (SES). The study area included a sample of 300 census tracts stratified by SES in two of the largest cities in Brazil, Rio de Janeiro and Belo Horizonte. The GE web service was used to develop a tool for automatic acquisition of food retail data through the generation of a regular grid of points. To test its validity, this data was compared with the ground-truth data. Compared to the 856 outlets identified in 285 census tracts by the ground-truth method, the GE interface identified 731 outlets. In both cities, the GE interface scored moderate to excellent compared to the ground-truth data across all of the validity measures: sensitivity, specificity, positive predictive value, negative predictive value and accuracy (ranging from 66.3 to 100%). The validity did not differ by SES strata. Supermarkets, convenience stores and restaurants yielded better results than other store types. To our knowledge, this research is the first to investigate using GE as a tool to capture community food retail data. Our results suggest that the GE interface could be used to measure the community food environment. Validity was satisfactory for different SES areas and types of outlets.


The role of pollination in the population biology of the monocarpic species Cirsium palustre and Cirsium vulgare.
The absence of cross-pollination in Cirsium palustre and Cirsium vulgare resulted in reduced achene production while the achenes produced were heavier than those produced after cross-pollimation. Establishment of plants from non-cross-pollinated achenes is comparatively higher, facilitating the founding of a population from isolated individuals in these wind-dispersed species.If achene weight is the result of a balance between cross-pollination and self-pollination (and/or apomixis), the first causing more and thereby lighter achenes to develop, increasing density of flowering individuals in a population may lower achene weight and consequently seedling survival. This may account for the frequently observed decline of populations of fugitive monocarpic perennials.


Coeliac patients detected during type 1 diabetes surveillance had similar issues to those diagnosed on a clinical basis.
Screening children with type 1 diabetes for coeliac disease is controversial, because they often appear asymptomatic. Our aim was to establish whether active screening should be recommended. This study focused on 22 children whose coeliac disease was detected by serological screening during diabetes surveillance and 498 children diagnosed because of a clinical suspicion. We compared the clinical and histological data at diagnosis and the children's adherence and responses to a gluten-free diet. The serological screening group suffered less from decreased growth (p = 0.016) and clinical symptoms (p < 0.001) at diagnosis than the clinical group. The groups did not differ in terms of age at diagnosis (p = 0.903), gender (p = 0.353), anaemia (p = 0.886), endomysial antibody titres (p = 0.789) and the severity of small-bowel mucosal atrophy (p = 0.104). They also showed equal adherence (p = 0.086) and clinical responses (p = 0.542) to a gluten-free diet after a median follow-up of 13 months. Coeliac patients detected during diabetes surveillance had signs of malabsorption and advanced mucosal damage that was similar to those diagnosed on a clinical basis. They often suffered from unrecognised gluten-dependent symptoms and showed excellent adherence and responses to a gluten-free diet. Our findings support active screening for coeliac disease in patients with type 1 diabetes.


Human chorionic gonadotropin levels in pregnancies with aneuploid fetuses.
Maternal serum human chorionic gonadotropin (hCG) and the free alpha-hCG subunit were evaluated in 249 women from 9 to 11 weeks gestation who subsequently underwent chorionic villus sampling for determination of fetal karyotype and in 20 women of 18 or more weeks gestation who were ascertained to have an aneuploid fetus by genetic amniocentesis. Seven of the first-trimester pregnancies were determined to be aneuploid and six had hCG levels in the normal range (one triploid pregnancy had elevated hCG levels) whereas 12 of the 20 second-trimester cases had abnormal hCG levels and an additional three had elevated levels of alpha-hCG. This study confirms the previous report of abnormal maternal serum hCG levels in women with an aneuploid fetus at greater than or equal to 18 weeks gestation and demonstrates that hCG evaluation is not useful at 9-11 weeks gestation for selecting pregnancies at risk for fetal aneuploidy.


Zinc Protoporphyrin Attenuates White Matter Injury after Intracerebral Hemorrhage.
Intracerebral hemorrhage (ICH)-induced white matter injury has not been well studied. The objective of this study was to examine the effect of zinc protoporphyrin (ZnPP) on white matter injury induced by ICH. This study was divided into two parts. In the first part, rats received either a needle insertion (sham) or 100 μl autologous blood into the right basal ganglia. The rats were euthanized at 1, 3, 7, 14, or 28 days later for myelin basic protein (MBP) measurement. In the second part, rats had intracerebral infusion of 100 μl autologous blood, and an intraperitoneal osmotic mini-pump was implanted immediately after ICH to deliver vehicle or ZnPP (1 nmol/h), a heme oxygenase inhibitor, for up to 14 days. Rats were euthanized at day 28 for MBP staining. The number of MBP-labeled fiber bundles and their area were determined. The time-course showed that the white matter was lost in the ipsilateral basal ganglia from day 1 to day 28 after ICH. The number of MBP-labeled bundles and their area were significantly lower 2 weeks after ICH compared with sham-operated rats (p < 0.05). Systemic treatment with ZnPP attenuated the loss of MBP-labeled bundles (p < 0.01) and area (p < 0.01). In conclusion, marked white matter injury occurs after ICH. ZnPP reduces white matter injury, suggesting a role of heme degradation products in ICH-induced white matter damage.


Anti-CD20 monoclonal antibody (Rituximab) for life-threatening autoimmune haemolytic anaemia in a patient with systemic lupus erythematosus.
Innovative approaches are needed for patients with systemic lupus erythematosus (SLE) who develop autoimmune haemolytic anaemia (AIHA) that does not respond to conventional treatment. Rituximab, a chimaeric anti-CD20 monoclonal antibody, has been demonstrated to be highly effective for in vivo B-cell depletion. We report an 18-year-old-girl with SLE and life-threatening AIHA that did not respond to steroids, intravenous immunoglobulin and cyclosporin A. Rituximab was given weekly at 375 mg/m2 for two doses. The drug was well tolerated and the patient had no adverse effects. Her haemolytic disorder markedly ameliorated, with a progressive increase of haemoglobin levels, starting a few days after therapy. The patient remains disease-free 7 months later.


The origins of bladder cancer.
Bladder cancer, arising from the transitional cells of the mucosal urothelium, may present as a noninvasive, papillary tumor protruding from the mucosal surface, or as a solid, nonpapillary tumor that invades the bladder wall and has a high propensity for metastasis. The nonpapillary tumors originate from in situ dysplasia. The most common environmental risk for bladder cancer is active smoking; occupational exposure to arsenic or other carcinogens is also a risk factor. A possible familial component to bladder cancer has been described. Conventional models of carcinogenesis suppose the existence of successive mutation events within a specific cell clone, enabling its eventual escape from regulation of cell division and maintenance of genomic integrity. Important new information has emerged from whole-organ mapping of the mucosal genome in bladders resected for invasive cancer (Majewski et al, Lab Invest; published online 5 May 2008). Mapping of genetic hits across the entire mucosa demonstrates genetic alterations in six chromosomal regions, not only in mucosal regions of evident dysplasia, but also in morphologically normal mucosa. These clonally expanded regions cover vast expanses of the bladder surface, as a 'first wave' of pre-neoplasia. Target genes in these regions are termed 'forerunner genes' (FR genes), based on the concept that these genes enable the initial clonal expansion of in situ urothelial neoplasia. Extensive further analysis of human populations with urothelial cancer implicates genetic polymorphisms in one of these genes, P2RY5, as being present in a familial cluster of cancers of multiple organs, and as imparting risk for development of bladder cancer in active smokers. P2RY5 is a gene encoded within intron 17 of RB1, a prototypic tumor suppressor gene whose expression is lost at a later stage of bladder carcinogenesis. Alterations of the FR gene status provide a novel opportunity to screen individuals at risk for the earliest stage of bladder pre-neoplasia and represent attractive targets for therapeutic and chemopreventive interventions. These findings support the hypothesis that bladder carcinogenesis is initiated by clonal expansion of genetically altered but histologically normal cells that cover broad expanses of the mucosa. Effort must now be given to identifying the biological function of these novel FR genes.


Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a potential prognostic biomarker in clear cell renal cell carcinoma that correlates with M2 macrophage infiltration and epithelial-mesenchymal.
The six-transmembrane epithelial antigen of the prostate 3 (STEAP3) is a metalloreductase, which is essential for iron uptake. Existing literature has shown that STEAP3 may perform an important role in the onset and progression of tumors. Nonetheless, a complete pan-cancer investigation of the prognostic significance and immune properties of STEAP3 is currently unavailable. As part of our investigation into the possible functions of STEAP3 in malignancies, we conducted a comprehensive analysis to examine the prognostic value and immune features of STEAP3 in human pan-cancer. R and Cytoscape programs were applied to analyze and visualize the data. The expression of STEAP3 in both cell lines and tissues was measured utilizing a variety of approaches. Using the shRNA knockdown technique, we tested the viability of the A498 and 786-O cell lines and validated their functions. Both CCK-8 and transwell assays were conducted to estimate cell proliferation and invasion. The expression of STEAP3 was substantially elevated and was shown to be linked to prognosis in the majority of malignancies, notably in clear cell renal cell carcinoma (ccRCC). In addition, the expression of STEAP3 was shown to have a strong correlation with immune infiltrates, which in turn triggered the recruitment and polarization of M2 macrophages in ccRCC. The protein STEAP3 shows promise as a predictor of responses to immune-checkpoint blockade (ICB) therapy. Positive links between STEAP3 and the epithelial-mesenchymal transition (EMT), the p53 pathway, and the immune-associated pathways were also found in the enrichment analysis. Our results illustrated that the STEAP3 expression level was substantially elevated in ccRCC tissues and suggested that it could stimulate EMT in ccRCC by downregulating CDH1. In a diverse range of cancers, STEAP3 might serve as a biomarker for determining the prognosis as well as a predictor of immunotherapy responsiveness. STEAP3 is a novel biological marker for determining prognosis, and it also performs a remarkable function in the promotion of tumor growth in ccRCC by enhancing invasion and EMT, as well as by triggering the recruitment and polarization of M2 macrophages.


Albumin attenuates neutrophil activation induced by stimulators including antibodies against neutrophil-specific antigens.
As neutrophil activation is related to several adverse transfusion reactions, we studied about the activation induced by anti-neutrophil antibodies and the stabilizing effects of albumin pretreatment by means of flow cytometry. Anti-neutrophil monoclonal antibody (anti-HNA-1a, 1b, 2a) alone induced CD11b expression and shedding of L-selectin, and anti-HNA-1a reinforced reactive oxygen species (ROS) production. Albumin pretreatment significantly reduced CD11b expression and L-selectin shedding induced by fMLP and ROS production induced by PMA, G-CSF combined with PMA or LPS-fMLP, or anti-HNA-1a combined with PMA. These findings suggest that anti-HNA-1a is related to adverse reactions and albumin has a regulating effect on neutrophil activation.


Prediction of organ involvement and survival in systemic sclerosis patients in the first 5 years from diagnosis.
Organ involvement often occurs in early systemic sclerosis and has been related to premature death. Identifying patients at diagnosis at risk of developing early organ involvement would be useful to optimize screening and management strategies. To develop prediction models for the 5-year development of interstitial lung disease, pulmonary arterial hypertension and death. A European multicentre inception cohort was created. For modelling, predefined clinical variables with known predictive value at diagnosis were used. Univariate and multivariate regression analysis were done to select baseline predictors and build the prediction models. The models were tested using the area under the receiver operating characteristic curve comparing observed and expected frequencies. Of 735 patients, 23% developed interstitial lung disease, 8% developed pulmonary arterial hypertension 12% died. The interstitial lung disease model included diffuse cutaneous systemic sclerosis (OR = 1.8), systemic sclerosis disease duration < 3 years (OR = 1.4), puffy fingers (OR = 1.6), and anti-topoisomerase-I-antibodies (OR = 1.8). The pulmonary arterial hypertension model included age > 65 years (OR = 3.2), forced vital capacity < 70% (OR = 2.5) and diffusing capacity of the lung for carbon monoxide < 55% (OR = 1.9). Death was predicted best by age > 65 years (OR = 4.1), male gender (OR = 1.9), no anti-centromere antibodies (OR = 0.5), proteinuria (OR = 1.9), forced vital capacity < 70% (OR = 1.8) and pulmonary arterial hypertension at diagnosis (OR = 10.1). The area under the receiver operating characteristic was 0.66 (95% CI 0.64-0.67), 0.66 (95% CI 0.64-0.68) and 0.70 (95% CI 0.69-0.72), respectively. We have shown that it is possible to predict interstitial lung disease, pulmonary arterial hypertension and death using established variables already available at the moment of systemic sclerosis diagnosis. Discriminatory performance of the models was suboptimal. Further research including new variables is necessary to improve performance.


Natural hybrid of Leishmania infantum/L. donovani: development in Phlebotomus tobbi, P. perniciosus and Lutzomyia longipalpis and comparison with non-hybrid strains differing in tissue tropism.
Infection caused by parasites from L. donovani complex can manifest as a serious visceral disease or a self-healing milder cutaneous form. The different tropism and pathology in humans is caused by the interaction between parasites, host and vector determinants but the mechanisms are not well understood. In Cukurova region in Turkey we previously identified a major focus of cutaneous leishmaniasis caused by L. donovani/infantum hybrids (CUK strain) and isolated this parasite from the locally abundant sand fly, Phlebotomus tobbi. Here, we present the first experimental study with P. tobbi. We tested the susceptibility of this species to various Leishmania under laboratory conditions, characterized glycoproteins in the P. tobbi midgut putatively involved in parasite-vector interaction and compared the development of the CUK strain in the sand fly with one other dermotropic and three viscerotropic strains belonging to the L. donovani complex. Females of laboratory reared P. tobbi, P. perniciosus and Lutzomyia longipalpis were infected using membrane feeding on rabbit blood containing promastigotes of various Leishmania species with different tropisms. The individual guts were checked microscopically for presence and localization of Leishmania parasites; the number of parasites was assessed more precisely by qPCR. In addition, glycosylation of midgut proteins of P. tobbi was studied by lectin blotting of midgut lysate with lectins specific for terminal sugars of N-type and O-type glycans. High infection rates, heavy parasite loads and late-stage infection with colonization of the stomodeal valve were observed in P. tobbi infected by Leishmania major or L. infantum CUK hybrid. In parallel, lectin blotting revealed the presence of O-glycosylated proteins in the P. tobbi midgut. In P. perniciosus and L. longipalpis all five Leishmania strains tested developed well. In both vectors, significantly higher parasite numbers were detected by qPCR for dermotropic L. donovani from Cyprus, however, in all other parameters studied, including localization of infection and colonization of stomodeal valve, dermotropic and viscerotropic strains were not significantly different. We showed high susceptibility of P. tobbi to various Leishmania spp. This, together with the presence of O-glycosylated midgut proteins in their midguts demonstrate that P. tobbi is a permissive vector. Two dermotropic and three viscerotropic strains from the L. donovani complex developed late-stage infections in natural L. infantum vectors, P. perniciosus and L. longipalpis and none of the parameters studied seem to be linked with different tropism of parasites in the vertebrate host.


Lamin B methylation and assembly into the nuclear envelope.
Lamin B is reversibly methyl-esterified and phosphorylated during the mammalian cell cycle. In order to study the role of methylation in lamin B function, we isolated mitotic cells in the presence of the microtubule inhibitor, nocodazole. Following removal of nocodazole, methylation of mitotic lamin B was found to precede its assembly into the nuclear envelope as cells exited mitosis. Very little additional methylation took place on assembled lamins. We were able to slow the rate of lamin B methylation with methylthioadenosine (MTA). A delay in lamin B methylation was accompanied by a corresponding delay in assembly of lamin B into the envelope. The delay was approximately 20-30 min beyond the typical 60-70 min usually required. Assembly of lamins A and C, which are not methylated, was also delayed by MTA, although to a lesser degree, suggesting that an interaction between the lamins is necessary for formation of the nuclear envelope. Chromatin decondensation was also slowed in the presence of MTA. Other inhibitors of methylation which had no inhibitory effect on the methyl esterification of lamin B were tested and found to have no effect on envelope assembly or chromatin decondensation. These results were obtained with Chinese hamster ovary cells as well as with the stem cell line, PC 13. Dephosphorylation of lamin B normally follows a time course similar to that of nuclear envelope assembly. In the presence of MTA, however, lamin B assembly was slowed with little effect on dephosphorylation. This resulted in a large population of dephosphorylated, but unassembled, lamin B protein, demonstrating that dephosphorylation is not sufficient for envelope assembly. The lack of effect on the time course of dephosphorylation also suggests that MTA is not acting upstream of the methylation event.


Simultaneous performance on verbal, nonverbal and motor tasks by right-handed adults.
A series of four dual task experiments was conducted in which different groups of right-handed Ss (N1 = 24; N2 = N3 = N4 = 18) simultaneously performed a repetitive finger tapping task in conjunction with: (a) a verbal fluency task (Experiment I); (b) listening to logical memory stories from the Weschler Memory Scale (Experiment II); (c) reading logical memory stories (Experiment III); and (d) scanning an array of faces (Experiment IV). Results indicated that all three verbal tasks produced significant asymmetrical depression in tapping performance, with the right hand being more disrupted then the left. The visuo-spatial task, however, exerted symmetrical bilateral depression of both hands. Performance on the cognitive tasks (number of words produced in the verbal fluency task; recall of stories either listened to or read, recognition of faces) was unaffected by simultaneous digital tapping.


Crystallographic and Dynamic Aspects of Solid-State NMR Calibration Compounds: Towards ab Initio NMR Crystallography.
The excellent results of dispersion-corrected density functional theory (DFT-D) calculations for static systems have been well established over the past decade. The introduction of dynamics into DFT-D calculations is a target, especially for the field of molecular NMR crystallography. Four (13) C ss-NMR calibration compounds are investigated by single-crystal X-ray diffraction, molecular dynamics and DFT-D calculations. The crystal structure of 3-methylglutaric acid is reported. The rotator phases of adamantane and hexamethylbenzene at room temperature are successfully reproduced in the molecular dynamics simulations. The calculated (13) C chemical shifts of these compounds are in excellent agreement with experiment, with a root-mean-square deviation of 2.0 ppm. It is confirmed that a combination of classical molecular dynamics and DFT-D chemical shift calculation improves the accuracy of calculated chemical shifts.


Patterns of Solidago altissima ramet growth and mortality: the role of below-ground ramet connections.
For the rhizomatous perennial, Solidago altissima, I identified clonal fragments in the field, mapped ramet spatial locations, and documented patterns of ramet recruitment, growth, and mortality. Parent ramet size influenced the size and number of daughter ramets produced, and small ramets had lower survivorship and fecundity than large ramets. Similarly, small rhizomes tended to develop into small ramets, and ramets that survived to produce daughter ramets had longer parent-daughter rhizome connections than ramets that did not survive. In addition, most ramets that died during the growing season were connected to (genetically identical) ramets that persisted. There were large size inequalities among rhizomes, ramets, and clonal fragments. Inequalities in the size of ramets increased during the early part of the growing season, then decreased at the end of the season; similar patterns were observed for the growth of clonal fragments. In both instances, the decrease in size inequality could be attributed to the mortality of small individuals (ramets or clonal fragments). I found little evidence that ramet size hierarchies were structured by intraspecific competition. For example, path analyses and randomization tests indicated that size variation among S. altissima ramets was influenced little by the size of their near neighbors (but was influenced by parent size and rhizome size). In addition, within-season variation for the relative size and growth rate of individual ramets led to poor correlations between early and final ramet size; this result suggests that there was no stable hierarchy of dominant and suppressed ramets. I discuss implications of my results for contrasting interpretations of clonal plant population dynamics.


Dual regulation of hEAG1 channels by phosphatidylinositol 4,5-bisphosphate.
The ether-à-go-go1 (EAG1, Kv10.1) K+ channel is a member of the voltage-gated K+ channel family mainly expressed in the central nervous system and cancer cells. Membrane lipids regulate several voltage-gated K+ channels but their influence on EAG1 channels has been poorly explored. Here we have studied the regulation of hEAG1 channels by phosphatidylinositol 4,5-bisfofate (PIP2) by using different strategies to manipulate the levels of this lipid, and the patch clamp technique. We found that depletion of endogenous PIP2 by activation of the voltage-sensing phosphatase from Danio rerio (Dr-VSP) or the human muscarinic type-1 receptor (hM1R) inhibits hEAG1 currents; however, the application of exogenous PIP2 to increase the level of this lipid on the plasma membrane, also induced an inhibition of hEAG1. In summary, our results indicate that PIP2 have dual effects on hEAG1 channels and its action as activator or inhibitor depends on its initial level on the plasma membrane.


Sustained heparin effect contributes to reduced plasma thrombin generation capacity early after cardiac surgery.
Thrombin is a key component in the coagulation cascade, and impaired thrombin generation has been linked to increased bleeding after surgical procedures. The aim was to evaluate postoperative thrombin generation capacity in plasma after cardiac surgery, and its potential associations to activity of individual coagulation factors and heparin. Forty-eight coronary artery bypass grafting patients were included in a prospective observational cohort study. Thrombin generation capacity was analysed in plasma with calibrated automated thrombogram with tissue factor as activator before (baseline), and 2 h and 24 h after surgery. In addition, plasma activity of coagulation factors II, V, VII, VIII, IX, X, XI, XIII, were determined. Heparin effect was assessed by anti-Xa activity, APTT and thrombin time. Thrombin generation was markedly reduced 2h after surgery compared to baseline. Peak levels decreased with median 74% (interquartile range 52-90), p<0.001, and endogenous thrombin generation potential decreased with 65% (43-86), p<0.001. Postoperative changes in endogenous thrombin generation potential correlated inversely to changes in anti-Xa activity (r=-0.51, p=0.010) and to changes in thrombin time (r=-0.51, p=0.009), but there were no correlations to changes in individual coagulation factor activity. A marked reduction in thrombin generation potential was observed in the early postoperative phase after cardiac surgery. The decrease was independent of reductions in individual coagulation factor activity but correlated to heparin effects. The results indicate that a sustained heparin effect contributes to the postoperative reduction in thrombin generation capacity.


On the use of fluency training in the behavioral treatment of autism: a commentary.
The substantial demand for behavior-analytic treatment of early childhood autism has been associated with rapid dissemination of treatment procedures to practitioners and caregivers. This level of demand could plausibly induce premature dissemination of treatments that do not yet have sufficient empirical support. We argue that this might have happened with the use of fluency training for learners with autism and identify four areas of research that are necessary to ensure that dissemination efforts are better matched to the available empirical support for this instructional strategy.


Estrous cycle staging before mating led to increased efficiency in the production of pseudopregnant recipients without negatively affecting embryo transfer in mice.
The goal was to increase pseudopregnant mice production by estrous cycle staging by visual examination before pairing and to determine the effect of such pseudopregnant recipients on embryo transfer. To compare methods of estrous cycle staging over 14 days, groups consisted of 10 females in proestrus-estrus and 10 vasectomized males; group 1: only daily visual observation; group 2: daily visual observation and cytological examination on day 1; group 3: daily visual observation and daily cytological examination. The average time to first vaginal plug was 1.8 days in group 1, 2.7 days in group 2, and 3.2 days in group 3, whereas the average time between consecutive vaginal plugs was 9.2 days (group 1), 10 days (group 2), and 9.25 days (group 3). The average time between consecutive estrous cycles was 9.7 days (group 1), 11.8 days (group 2), and 9.4 days (group 3). The congruence between visual and cytological examination in determining proestrus-estrus in group 2 was 100% and that for the four stages in group 3 was 79% with a range of 44% to 100%. From 162 plug-positive females originally selected in proestrus-estrus, 49%, 30%, 19%, and 2% were plug-positive on Day 1, Day 2, Day 3, and Day 4, respectively, showing that pseudopregnant mice production was significantly increased on the first 2 days. From 192 plug-positive females originally selected randomly, these values were 31%, 21%, 35%, 10%, and 3% on d1, d2, d3, d4, and d5, respectively. No significant differences were observed between groups with respect to embryo transfers with fresh or cryopreserved embryos although the number of pups born per litter was higher in group A with fresh (7.57 vs. 6.39) and cryopreserved-thawed embryos (5.0 vs. 4.38). Furthermore, the sex ratio and the genotype of the pups were not significantly affected.


Gravitational representation of simultaneously recorded brainstem respiratory neuron spike trains.
Experiments designed to study concurrent processes in neural networks have been hampered by limitations of available analytical methods. A recently described gravitational representation of spike train data was used to evaluate groups of simultaneously monitored medullary respiratory related neurons in anesthetized, vagotomized cats. The results establish that the method can detect and define functional associations among elements of such groups after as few as 20 respiratory cycles.


[Dementia with Lewy bodies].
"Dementia with Lewy bodies (DLB)" was proposed at the first international workshop in 1995. It has received much attention since we had proposed "Lewy body disease" in 1980 and "diffuse Lewy body disease" in 1984. In the CDLB guidelines, which were reported in 1996, the clinical and pathological diagnostic criteria for DLB were shown for the first time. At present, DLB as well as Alzheimer's disease (AD) and vascular dementia (VD) are known as the three major dementing illnesses. The second international workshop was held in 1998, and the third in 2003. One of the authors, K. Kosaka, presented a paper on DLB at each international workshop, based on series of our papers which we had reported since 1976. The revised CDLB guidelines will be reported soon. In addition, the fourth international workshop on DLB will be held by Kosaka in Yokohama in 2007. In this article, we review the history, the clinical, therapeutic, neuropathological, neurochemical and molecular biological issues, based on our previous papers and other important reports on DLB.


Induction of experimental chronic Pseudomonas aeruginosa lung infection with P. aeruginosa entrapped in alginate microspheres.
Alginate-producing, mucoid P. aeruginosa is frequently found in the lungs of patients with cystic fibrosis (CF), where it causes a chronic infection. The importance of alginate in the pathogenesis was demonstrated by the ability to establish chronic P. aeruginosa lung infection in rats if P. aeruginosa entrapped in minute alginate-beads were inoculated transtracheally. Alginate beads containing P. aeruginosa were formed by nebulizing a suspension of seaweed sodium-alginate and P. aeruginosa into a calcium solution. The alginate bead method of establishing infection was compared to an agar-bead method and proved to be quantitatively similar after 4 weeks. The ability of the two methods to induce formation of precipitins, IgA and IgG antibodies against P. aeruginosa antigens, including outer membrane proteins, flagella, exoenzymes and alginate, was assessed by crossed immunoelectrophoresis, enzyme-linked immunosorbent assay and immunoblotting. The two methods of inducing infection were comparable and infected rats had significantly higher antibody response than rats inoculated with sterile beads. We suggest that the alginate bead model closely resembles the later stages of CF-lung infection and that it offers the theoretical advantage of using a substance which is chemically similar to the alginate produced in vivo by P. aeruginosa.


Spread of Neisseria meningitidis serogroup W clone, China.
During February 2011-June 2012, invasive infection with Neisseria meningitidis serogroup W was identified in 11 persons in southeastern China. All isolates tested had matching or near-matching pulsed-field gel electrophoresis patterns and belonged to multilocus sequence type 11. The epidemiologic investigation suggested recent transmission of this clonal complex in southeastern China.


Treatment of local, persistent cutaneous atrophy following corticosteroid injection with normal saline infiltration.
Injections of corticosteroids are commonly used for a variety a dermatologic conditions but may cause local, persistent cutaneous atrophy, with few therapeutic options. To determine the effectiveness of bacteriostatic normal saline infiltration on the improvement of corticosteroid-induced cutaneous atrophy. Four patients with corticosteroid-induced atrophy of the skin, two caused by acneiform cysts and one from intramuscular steroid injection, were treated with weekly injections of normal saline directly into the atrophic site. The patients were seen on weekly follow-up visits, and improvement was documented. All four patients demonstrated complete resolution of skin atrophy and restoration of surface contour within 4 to 8 weeks of initial presentation. Injected volumes of normal saline ranged from 5 to 20 cm(3) per treatment session and three to six weekly treatments. The patients were completely satisfied with these results. Normal saline infiltration offers a safe, tolerable, relatively rapid, and effective treatment for local, persistent corticosteroid-induced atrophy.


Molecular epidemiology of Saccharomyces cerevisiae in an immunocompromised host unit.
Saccharomyces cerevisiae is increasingly recognized clinically, and repeated isolations from patients on a hematology unit in Turku, Finland, led to an epidemiologic investigation. Isolates were recovered from multiple body sites of 23 patients (n = 180) from 1994 to 1995 and from 29 patients (n = 45) from 1997 to 2002; these plus 2 from the hospital kitchen were identified as S. cerevisiae. Isolates were genotyped by restriction fragment length polymorphism (RFLP) of genomic DNA after EcoR1 digestion. Of 108 isolates, 97 (95 patient isolates and 2 from the hospital kitchen) were DNA group B and identical in RFLP pattern. The remaining 11 isolates were DNA group A; 2 patients that shared a room had identical group A isolates, both converted to DNA group B type colonization within 2 months. In almost all patients, S. cerevisiae was first recovered after admission. These data suggest an endemic source of colonizing organisms, possibly from the hospital food preparation area.


Optimization of melanin production by Brevundimonas sp. SGJ using response surface methodology.
Melanins are predominantly indolic polymers which are extensively synthesized in animals, plants and microorganisms. It has wide applications in cosmetics, agriculture and medicine. In the present study, optimization of process parameters influencing melanin production was attempted using the response surface methodology (RSM) from Brevundimonas sp. SGJ. A Plackett-Burman design was used for screening of critical components, while further optimization was carried out using the Box-Behnken design. The optimum conditions observed were pH 5.31, tryptone 1.440 g l-1, L-tyrosine 1.872 g l-1 and CuSO4 0.0366 g l-1. Statistical analysis revealed that the model is significant with model F value 29.03 and R2 value 0.9667. The optimization of process parameters using RSM resulted in a 3.05-fold increase in the yield of melanin. The intermittent addition of L-tyrosine enhanced the melanin yield to 6.811 g l-1. The highest tyrosinase activity observed was 2,471 U mg-1 at the 18th hour of the incubation period with dry cell weight of 0.711 g l-1. The melanin production was confirmed by UV-Visible spectroscopy, FTIR and EPR analysis. Thus, Brevundimonas sp. SGJ has the potential to be a new source for the production of melanin.


Lesions of the posterior septum or of the habenula decrease [3H]hemicholinium-3 binding (as measured by autoradiography) in the interpeduncular nucleus of the rat.
The effects of a bilateral electrolytic lesion of the posterior septum or of the habenula (lateral and medial parts) on [3H]hemicholinium-3 binding sites in the interpeduncular nucleus of the rat were studied through the use of quantitative autoradiography. Lesions of the habenular nuclei or of the posterior septum decreased [3H]hemicholinium-3 binding in the interpeduncular nucleus by 93 and 31%, respectively. These results add further support to the view that the habenula and posterior septum are the major sources of the cholinergic innervation of the interpeduncular nucleus in the rat.


Development and Application of Portable Reflectometric Spectroscopy Combined with Solid-Phase Extraction for Determination of Potassium in Flue-Cured Tobacco Leaves.
Potassium (K) plays important roles in the energy and substance conversion of tobacco metabolism and is also regarded as one of the important indicators of tobacco quality evaluation. However, the K quantitative analytical method shows poor performance in terms of being easy-to-use, cost-effective, and portable. Here, we developed a rapid and simple method for the determination of K content in flue-cured tobacco leaves, including water extraction with 100 °C heating, purification with solid-phase extraction (SPE), and analysis with portable reflectometric spectroscopy based on K test strips. The method development consisted of optimization of the extraction and test strip reaction conditions, screening of SPE sorbent materials, and evaluation of the matrix effect. Under the optimum conditions, good linearity was observed in 0.20-0.90 mg/mL with a correlation coefficient >0.999. The extraction recoveries were found to be in the range of 98.0-99.5% with a repeatability and reproducibility of 1.15-1.98% and 2.04-3.26%, respectively. The sample measured range was calculated to be 0.76-3.68% K. Excellent agreement was found in accuracy between the developed reflectometric spectroscopy method and the standard method. The developed method was applied to analyze the K content in different cultivars, and the content varied greatly among the samples with lowest and highest contents for Y28 and Guiyan 5 cultivars, respectively. This study can provide a reliable approach for K analysis, which may become available on-site in a quick on-farm test.


Examining the effects of adult and peer mediated goal setting and feedback interventions for writing: Two studies.
The current study investigated the effects of goal setting and performance feedback on Curriculum Based Measurement in Written Expression (CBM-WE). This two-study investigation examined the utility of the intervention using two different delivery mechanisms. In Study 1, fourth grade students (n=114) were provided both with (a) feedback from their teachers regarding their performance on CBM-WE probes and (b) new weekly goals or no feedback and goals, once a week for a ten-week intervention period. Study 2 examined the effects of this intervention with a sample of fifth grade students (n=106) when feedback and individual goals were provided by peers within their classrooms twice weekly over the course of eight weeks compared to a practice only control condition. Results in both studies indicated that students receiving the goal setting and feedback intervention performed significantly higher on production-dependent writing indices post-intervention than control groups (ES=.12-.28). Implications regarding the usefulness of goal setting and feedback utilizing CBM procedures are discussed.


Pregnancy Outcomes in Women With Autoimmune Hepatitis - A Nationwide Population-based Cohort Study With Histopathology.
Autoimmune hepatitis (AIH) is a chronic inflammatory liver condition that predominantly affects women. However, pregnancy risks remain unclear. A nationwide population-based cohort study (ESPRESSO) in Sweden from 1992 to 2016 including 309 singleton births in women with AIH and 1532 matched births in women from the general population was performed. AIH was diagnosed as a combination of administrative coding from medical diagnosis of AIH and liver biopsy data from Sweden's 28 pathology departments. Using conditional logistic regression, odds ratios (ORs) for adverse pregnancy outcomes were determined. Among 306 live births to women with AIH, 51 (16.7%) were preterm, compared with 70 of 1524 (4.6%) reference births. This corresponded to an OR of 5.10 for preterm birth (95% confidence interval [CI], 3.29-7.92), with similar odds using sibling comparators. Women with AIH with and without cirrhosis had similar odds for preterm birth. The AIH association was particularly strong with medically indicated preterm birth (OR, 13.01; 95% CI, 5.50-30.79). AIH was associated with low birth weight (OR, 5.31; 95% CI, 2.82-9.99) and low 5-minute Apgar score (OR, 3.46; 95% CI, 1.14-10.49) offspring, but we found no association with congenital malformations (OR, 1.14; 95% CI, 0.68-1.91), small for gestational age (OR, 1.04; 95% CI, 0.38-2.85), stillbirth (OR, 0.59; 95% CI, 0.02-18.88), or neonatal death (OR, 7.42; 95% CI, 0.65-84.25). Maternal AIH was linked to an increased odds of cesarean section (OR, 1.44; 95% CI, 1.04-2.00) and preeclampsia (OR, 3.65; 95% CI, 2.01-6.64), but not to gestational diabetes. Maternal AIH was associated with a 5-fold higher odds of preterm birth, and cirrhosis at diagnosis did not add to the impact of AIH on preterm birth. Future studies are needed to understand how to reduce this risk.