The anti-plaque efficacy of a chlorhexidine mouthrinse used in combination with toothbrushing with dentifrice.
Although the efficacy of chlorhexidine (CHX) chemically can be affected by the presence of a sodium lauryl sulphate (SLS)-containing dentifrice in the oral cavity, previous data, collected without supervision, showed that the level of plaque inhibition offered by a 0.2% CHX post-brushing rinse in one jaw is not reduced under the influence of toothbrushing with a 1.5% SLS-containing dentifrice in the opposite jaw. The aim of the present study was to investigate, during a 4-day supervised study period, the anti-plaque efficacy of a 0.2% CHX pre-brushing rinse in one jaw, under the influence of toothbrushing in the opposite jaw, either with a SLS-containing dentifrice or with a SLS-free dentifrice. Three different dentifrices were tested. Two of them contained SLS (Colgate Total & Aquafresh Natural Whitening), the other (Zendium) did not. The study was an examiner blind, randomised 4-cell, crossover design. It used a 4-day plaque accumulation model to compare under supervision 4 different oral hygiene regimens with a washout period of at least one week. Thirty-five healthy volunteers were enrolled in the study and were randomly assigned to a sequence according to a 4 x 4 Latin square design. At the beginning of each 4-day test period, they received a thorough dental prophylaxis. Plaque was scored in one randomly assigned (upper or lower) jaw, called the study jaw. At the end of the 4-day period the study jaw was used to study the effect of the four regimens on the level of plaque accumulation. The opposite jaw was assigned as the dentifrice jaw and served only to introduce the effect of brushing with a dentifrice in the study model. Four oral hygiene regimens were designed. During the randomly assigned test periods, rinsing with 0.2% CHX and then brushing the dentifrice jaw was performed twice daily. In regimen 1, 2, and 3 the subjects used a dentifrice in the assigned dentifrice jaw being either a dentifrice with SLS (Colgate Total and Aquafresh Natural Whitening) or a SLS-free dentifrice (Zendium). Regimen 4 served as a control during witch subjects only rinsed with 0.2% CHX. No other oral hygiene methods were allowed. After 4 days of undisturbed plaque accumulation, the amount of plaque was evaluated (Lobene et al. 1982, Quigley & Hein 1962, Turesky et al. 1970 modifications). The overall plaque index for regimen 1, 2 and 3 was, respectively, 1.8, 1.8 and 1.9. For regimen 4, the overall plaque index was 1.9. There was no significant difference in plaque accumulation between the four regimens. Within the present study design, it can be concluded that the anti-plaque efficacy of a pre-brushing 0.2% CHX mouthrinse does not seem to be reduced under the influence of a normal toothbrushing exercise with a dentifrice after rinsing, whether the dentifrice contains SLS or not.


Effects of rapid mannitol infusion on cerebral blood volume. A positron emission tomographic study in dogs and man.
Positron emission tomography was used to study the effect of a rapid infusion of mannitol on cerebral blood volume (CBV) in five dogs and in three human subjects. The ability of mannitol to reduce intracranial pressure (ICP) has always been attributed to its osmotic dehydrating effect. The effects of mannitol infusion include increased osmolality, total blood volume, central venous pressure (CVP), and cerebral blood flow, and decreased hematocrit, hemoglobin concentration, serum sodium level, and viscosity. Mannitol's ability to dilate the cerebral vasculature, either directly or indirectly, and thus to transiently increase ICP, is a subject of controversy. By in vivo labeling of red cells with carbon-11, the authors were able to demonstrate an early increase in CBV in dogs of 20%, 27%, and 23% (mean increase, p less than 0.05) at 1, 2, and 3 minutes, respectively, after an infusion of 20% mannitol (2 gm/kg over a 3-minute period). The animals' muscle blood volume increased by 27% (mean increase, p less than 0.05) 2 minutes after infusion. In the human subjects, lower doses and a longer duration of infusion (1 gm/kg over 4 minutes) resulted in an increase in CBV of 8%, 14% (p less than 0.05), and 10% at 1, 2, and 3 minutes, respectively, after infusion. In dogs, ICP increased by 4 mm Hg (mean increase, p less than 0.05) 1 minute after the infusion, before decreasing sharply. The ICP was not measured in the human subjects. Hematocrit, hemoglobin, sodium, potassium, osmolality, heart rate, mean arterial pressure (MAP), and CVP were measured serially. Results of these measurements, as well as the significant decrease in MAP that occurred after mannitol infusion, are discussed. This study demonstrated that rapid mannitol infusion increases CBV and ICP. The increase in muscle blood volume, in the presence of a decreased MAP and an adequate CVP, suggests that mannitol may have caused vasodilation in these experiments.


Purification and characterization of membrane-bound malate dehydrogenase from Acetobacter sp. SKU 14.
Membrane-bound NAD(P)-independent malate dehydrogenase (EC 188.8.131.52) was purified to homogeneity from the membrane of thermotolerant Acetobacter sp. SKU 14, an isolate from Thailand. The enzyme was solubilized from the membrane fraction of glycerol-grown cells with 1% Triton X-100 in the presence of 0.1 M KCl, and purified to homogeneity through steps of column chromatographies on DEAE-Sephadex A-50 and DEAE-Toyopearl in the presence of 0.1% Triton X-100. The purified enzyme showed a single protein band in both native-PAGE and SDS-PAGE. The enzyme was a homodimer with a molecular mass of 60 kDa subunit and had noncovalently bound FAD as the cofactor. The enzyme was stable over pH 5 and had its maximum activity at pH 11.0 when ferricyanide was used as an electron acceptor. The enzyme activity was elevated by the addition of ammonium ions. The substrate specificity was very strict to only L-malate, of which the apparent Km was 10 mM and over 20 compounds involving D-malate were not oxidized by the enzyme.


Thermophilic and alkaliphilic Actinobacteria: biology and potential applications.
Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally, and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications.


A QUANTITATIVE-GENETIC ANALYSIS OF LARVAL LIFE-HISTORY TRAITS IN HYLA CRUCIFER.
We used a half-sib design to examine the genetic components of phenotypic variance in several life-history traits in Hyla crucifer. Egg viability, hatchling size, larval growth rate, length of larval period, and size at metamorphosis play critical roles in determining survivorship and are subject to persistent selection. Egg viability varied among families considerably, with most embryo mortality occurring between gastrulation and neurulation. Hatchling size was the only trait in which maternal effects were influential. Dominance genetic variance played the predominant role in determining phenotypic variance in hatchling size, growth rate, and length of larval period, accounting for, respectively, 70, 63, and 47% of the total variance. Size at metamorphosis displayed little dominance genetic variance and, unlike the other traits, displayed a high heritability. All additive genetic correlations between traits were positive. The directions of environmental correlations were the same as the directions of changes that have been induced in previous experimental work. The correlations due to dominance effects described a principal axis that independent ecological studies indicate to be directly correlated with fitness. These results agree with theoretical expectations for traits under consistent directional selection.


Feasibility of a birth cohort study dedicated to assessing acute infections using symptom diaries and parental collection of biomaterials.
A birth cohort dedicated to studying infections in early childhood may be assisted by parental recording of symptoms on a daily basis and a collection of biomaterials. We aimed at testing the feasibility of this approach for use in a long-term study focusing on infections in children in Germany. Parents of 1- to 3-year-old children (n = 75) were recruited in nursery schools. They were asked to complete a symptom diary on a daily basis and to take monthly and symptom-triggered nasal swabs and stool samples from their child over the study period of three months. Feasibility was measured by means of the return proportions of symptom diaries and bio samples; acceptance was assessed by a questionnaire delivered to participants at the end of the study. The majority of the participants filled in the symptom diary during the three months study for 75 or more days (77.3%), and provided the monthly nasal swabs (62.7%) and stool samples (65.3%). The time needed for the tasks was acceptable for most participants (symptom diary: 92.3%, nasal swabs: 98.5%, stool samples: 100.0%). In 64.3% of the symptom-triggered nasal swabs, respiratory viruses were found compared to 55.5% in throat swabs taken by health-care professionals within the "ARE surveillance Lower Saxony", a special project by the Governmental Institute of Public Health of Lower Saxony to investigate causal pathogens for acute respiratory infections in children. The parental assessment of symptoms and collection of biomaterials in a birth cohort dedicated to studying infections appears feasible in a middle class German population. The success of the study will depend on the ability to maintain these activities over a long time period.


In situ observation of the on-surface thermal dehydrogenation of n-octane on Pt(111).
The catalytic dehydrogenation of alkanes constitutes a key step for the industrial conversion of these inert sp3-bonded carbon chains into other valuable unsaturated chemicals. To this end, platinum-based materials are among the most widely used catalysts. In this work, we characterize the thermal dehydrogenation of n-octane (n-C8H18) on Pt(111) under ultra-high vacuum using synchrotron-radiation X-ray photoelectron spectroscopy, temperature-programmed desorption and scanning tunneling microscopy, combined with ab initio calculations. At low activation temperatures, two different dehydrogenation stages are observed. At 330 K, n-C8H18 effectively undergoes a 100% regioselective single C-H bond cleavage at one methyl end. At 600 K, the chemisorbed molecules undergo a double dehydrogenation, yielding double bonds in their carbon skeletons. Diffusion of the dehydrogenated species leads to the formation of carbon molecular clusters, which represents the first step towards poisoning of the catalyst. Our results reveal the chemical mechanisms behind the first stages of alkane dehydrogenation on a platinum model surface at the atomic scale, paving the way for designing more efficient dehydrogenation catalysts.


Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS): A Rare Treatable Neuroradiological Spectrum.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare CNS inflammatory disorder involving the pons and other parts of the brainstem. It is characterised by a combination of brainstem symptoms and classical magnetic resonance imaging (MRI) features of bilateral, symmetrical punctate, perivascular enhancement of pontine lesions. Another hallmark feature of this rare disease is the responsiveness to corticosteroid treatment. As the corticosteroid treatment is tapered, the symptoms exacerbate and worsen the clinical outcome. Clinicians and radiologists should be aware of this infrequent inflammatory disorder and should always be considered as a differential diagnosis. Herein, we report the case of a 17-year-old female with a similar clinicoradiological spectrum as CLIPPERS.


Cross-cultural adaptation and psychometric properties of the Indonesian version for quality of life among breast cancer patients.
Breast cancer is one of the most important health problems worldwide. Quality of life (QoL) is an important indicator to evaluate symptoms in cancer patients, including those with breast cancer. Culturally suitable, valid, reliable, and appropriate instruments to measure the QoL of breast cancer patients are needed, which is still rare in Indonesia. This study aimed to translate the EORTC QLQ-BR45 instrument into Indonesian and evaluate its psychometrics. A cross-sectional study was performed on 635 patients conveniently selected from the oncology department in referral hospital. The first phase of this study involved translation of the existing EORTC QLQ-BR45 into Indonesian, and in the second phase, we evaluated its psychometric properties. Construct validity was evaluated using confirmatory factor analysis (CFA). Criterion validity was examined according to the association between disease stage and Karnofsky Performance Scale (KPS). A total of 635 (99.00%) completed the EORTC QLQ-BR45 successfully. The instrument indicated good readability and high content validity. All Cronbach's alpha coefficients were satisfactory (overall value, 0.87). For construct validity, patients with KPS ≥80% did better than those with KPS ≤70% as did two multi-item scales in functional scales (body image and breast satisfaction) and five multi-item scales in symptom scales (systemic therapy side effects, endocrine therapy, and arm, breast, and endocrine sexual symptoms). Body image score of late-stage patients was significantly higher. CFA indicated that the nine-factor structure of the Indonesian EORTC QLQ-BR45 was a good fit for the data. The Indonesian EORTC QLQ-BR45 questionnaire is reliable and valid with good psychometric properties, thus can be used for breast cancer patients in Indonesia.


CRISPR-engineered genome editing for the next generation neurological disease modeling.
Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate impact of mutated genes on these neurological diseases, a feasible but flexible genome editing tool had remained to be developed. An advance of genome editing technology using the clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR-associated protein (Cas) offers us a tremendous potential to create a variety of mutations in the cell, leading to "next generation" disease models carrying disease-associated mutations. We will here review recent progress of CRISPR-based brain disease modeling studies and discuss future requirement to tackle current difficulties in usage of these technologies.


Clinical outcomes and risk stratification for papillary thyroid carcinoma presenting with distant metastasis before the era of tyrosine kinase inhibitors.
Radioactive iodine (RAI) therapy has been the mainstay of treatment for papillary thyroid carcinoma (PTC) patients with distant metastasis (DM). Although tyrosine kinase inhibitors (TKIs) were introduced for the treatment of RAI refractory metastatic thyroid carcinoma several years ago, clinical outcomes for PTC patients with DM treated using RAI therapy remain unclear. We retrospectively examined 64 PTC patients (9 men, 55 women) with DM at diagnosis treated using RAI therapy without administration of any kind of chemotherapy or TKIs. Median age of patients was 58 years. Site of DM was the lungs (n = 59), bone (n = 3), and pleural dissemination (n = 2). No patients showed multiple-organ metastases at diagnosis. By the end of the study period, 21 patients had died of PTC. Cause-specific survival rates at 10, 15, and 20 years after initial surgery were 68.2%, 63.6% and 61.1%, respectively. Uni- and multivariate analyses identified age ≥55 years (HR 3.1, p = 0.023), site of DM other than the lungs (HR 13.4, p < 0.0001), and DM with no RAI avidity (HR 5.1, p = 0.0098) as factors independently associated with disease-related death. When analyses were restricted to patients with lung metastasis (n = 59), surgical non-curability was another independent risk factor (HR 5.2, p = 0.0047) in addition to age and RAI avidity. According to risk stratification analysis based on these risk factors, patients with site of DM other than the lungs or with lung metastasis showing ≥2 risk factors among age ≥55 years, DM with no RAI avidity, and surgical non-curability are expected to show higher mortality rates.


Thrombin promotes matrix metalloproteinase-13 expression through the PKCδ c-Src/EGFR/PI3K/Akt/AP-1 signaling pathway in human chondrocytes.
Thrombin is a key mediator of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis and osteoarthritis. Matrix metalloproteinase-13 (MMP-13) may contribute to the breakdown of articular cartilage during arthritis. However, the role of thrombin in MMP-13 production in chondrocytes is unknown. In this study, we investigated the intracellular signaling pathways involved in thrombin-induced MMP-13 expression in human chondrocytes. We found that stimulation with thrombin led to increased secretion of MMP-13 in cultured human chondrocytes. Further, this thrombin-induced MMP-13 production was reduced after transfection with siRNAs against protease activated receptors 1 and 3 (PAR1 and PAR3), but not with PAR4 siRNA. Treatment with specific inhibitors for PKCδ, c-Src, EGFR, PI3K, Akt, or AP-1 or with the corresponding siRNAs against these signaling proteins also abolished the thrombin-mediated increase in MMP-13 production in chondrocytes. Our results provide evidence that thrombin acts through the PAR1/PAR3 receptors and activates PKCδ and c-Src, resulting in EGFR transactivation and activation of PI3K, Akt, and finally AP-1 on the MMP-13 promoter, thereby contributing to cartilage destruction during arthritis.


Meaningful improvement thresholds in measures of pain and quality of life in oral lichen planus.
To evaluate the responsiveness of measures of pain and oral health-related quality of life (OH-QoL) in patients with oral lichen planus (OLP) and to determine thresholds for minimal important change (MIC) and minimal important difference (MID) for use in this patient population. Data from baseline and 4-month follow-up including Visual Analog Scale (VAS), Numerical Rating Scale (NRS), 14-item Oral Health Impact Profile (OHIP-14), 15-item and 26-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-15; COMDQ-26) were collected from 157 patients with OLP. Responsiveness was assessed by testing hypotheses and calculating the area under the curve. MIC and MID were established based on triangulation of distribution-based and anchor-based estimates. The results supported adequate responsiveness of VAS, NRS, COMDQ-15 and COMDQ-26 for use in OLP, while the OHIP-14 demonstrated relatively low sensitivity to detect improvement in the OLP status. Recommended meaningful improvement thresholds were as follows: VAS (MIC 16 mm; MID 18 mm), NRS (MIC/MID 2 points), OHIP-14 (MIC/MID 5 points), COMDQ-15 (MIC 5 points; MID 6 points) and COMDQ-26 (MIC/MID 9 points). This study provides some evidence of responsiveness as well as establishing meaningful improvement thresholds in scores of pain and OH-QoL measures in OLP.


The Effectiveness of Zinc Supplementation in Taste Disorder Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Food taste and flavour affect food choice and acceptance, which are essential to maintain good health and quality of life. Reduced circulating zinc levels have been shown to adversely affect the taste, but the efficacy of zinc supplementation to treat disorders of taste remains unclear. In this systematic review and meta-analysis, we aimed to examine the efficacy of zinc supplementation in the treatment of taste disorders. We searched four electronic bibliographical databases: Ovid MEDLINE, Ovid Embase, Ovid AMAD, and PubMed. Article bibliographies were also searched, which yielded additional relevant studies. There were no restrictions on the publication date to facilitate the collection and identification of all available and relevant articles published before 7 February 2021. We performed a systematic review and meta-analysis according to the PRISMA Statement. This review was registered at PROSPERO and given the identification number CRD42021228461. In total, we included 12 randomized controlled trials with 938 subjects. The intervention includes zinc (sulfate, gluconate, picolinate, polaprezinc, and acetate), and the pooled results of the meta-analysis of subjects with idiopathic and zinc-deficient taste disorder indicate that improvements in taste disorder occurred more frequently in the experimental group compared to the control group (RR = 1.38; 95% CI: 1.16, 1.64, p=0.0002). Zinc supplementation appears to confer a greater improvement in taste perception amongst those with chronic renal disease using zinc acetate (overall RR = 26.69, 95% CI = 5.52-129.06, p < 0.0001). The doses are equivalent to 17 mg-86.7 mg of elemental zinc for three to six months. Zinc supplementation is an effective treatment for taste disorders in patients with zinc deficiency, idiopathic taste disorders, and in patients with taste disorders induced by chronic renal failure when given in high doses ranging from 68 to 86.7 mg/d for up to six months.


Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (P < 0.05, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all P < 0.05). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS.


Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma.
Previous studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC). Based on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments. This study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration. PANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.


[The startle reaction in emotion research].
The human startle response is modulated by affective states. The startle response is facilitated in unpleasant, aversive context, such as fear, and reduced during pleasure. This association can be explored by simple technical methods. The modulation of startle is found also in animal. It offers the opportunity to investigate human emotional processes by a biologically based, language free paradigm.


Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway.
Vitamin K4 (VK4) is a synthetic hydrophilic menadione compound, which is clinically used as hemostasis medicine. It has been reported that several vitamin Ks had inhibitory effects on various cancer cells. However, there is no report about VK4s anticancer activity. The goal of this study was to investigate the inhibitory effect of VK4 on human prostate PC-3 cells and the mechanisms involved. We found that VK4 dose-dependently inhibited cell proliferation in PC-3 cells with an IC50 value of about 20.94 microM. Hoechst 33258 Staining results showed that VK4 caused DNA fragmentation in PC-3 cells. PI staining results indicated that VK4-induced PC-3 cell cycle arrest at the S phase. Further mechanistic studies revealed that VK4-mediated induction of apoptosis in PC-3 cell is associated with disruption of mitochondrial membrane potential, down-regulation of Bcl-2, and up-regulation of Bax, release of cytochrome c from mitochondria, and activation of caspase-3 and PARR Thus, VK4 might be useful in prostate cancer chemotherapy.


Particles on curved surfaces: a dynamic approach by a phase-field-crystal model.
We present a dynamic model to study ordering of particles on arbitrary curved surfaces. Thereby the particles are represented as maxima in a density field and a surface partial differential equation for the density field is solved to the minimal energy configuration. We study annihilation of dislocations within the ordered system and premelting along grain-boundary scars. The obtained minimal energy configurations on a sphere are compared with existing results and scaling laws are computed for the number of excess dislocations as a function of system size.


Early amniocentesis for prenatal cytogenetic evaluation.
Early amniocentesis at 11-14 weeks gestation was evaluated in 100 consecutive patients to see how this technique compares with later amniocentesis. There were no complications as a consequence of the procedure or related pregnancy losses of chromosomally normal fetuses. Samples obtained from three (3%) patients showed insufficient cell growth; two of these patients elected a repeat procedure, which yielded a normal karyotype in each case. There were five abnormal karyotypes, one of which was a culture artifact; in the latter case, repeat amniocentesis at 15 weeks yielded a normal result. Of the 95 pregnancies with normal karyotypes, 94 were progressing normally at follow-up, and one patient elected pregnancy termination because of maternal indications. It appears that early amniocentesis may be an attractive alternative to traditional amniocentesis, in that it provides results at an earlier gestational age and may avoid certain disadvantages of chorionic villus sampling.


Quantification of DDX3Y, RBMY1, DAZ and TSPY mRNAs in testes of patients with severe impairment of spermatogenesis.
Y chromosome microdeletion is the most important genetic cause of impairment of spermatogenesis. Nevertheless, a significant proportion of patients with spermatogenic failure do not have this condition. This study investigated the expression level of AZF genes, DDX3Y (DBY), RBMY1, DAZ and TSPY in testicular tissues of 42 subjects with impaired spermatogenesis compared with 33 with normal spermatogenesis. Histopathological evaluation was performed in all subjects and tissues were classified according to Johnsen Score. Transcript amounts were determined by quantitative-competitive RT-PCR. Patients with complete Sertoli cell-only syndrome (SCOS) did not exhibit RBMY1, DAZ and TSPY gene expression, however, we detected very low expression of DDX3Y transcript. Tissue samples with focal SCOS showed significantly decreased expression of all genes (P < 0.001). Maturation arrest and hypospermatogenesis tissues expressed significantly low levels of DDX3Y testicular transcript (P < 0.001), while the mRNA levels of the other genes were similar to that in tissues from the normal spermatogenesis group. Negative or diminished gene expression of DDX3Y, RBMY1, DAZ and TSPY in tissues samples with SCOS or focal SCOS reflects the absence or the lower number of germ cells, respectively. The finding that the testicular transcript of DDX3Y is significantly decreased in patients with severe spermatogenenic failure, especially in those presenting maturation arrest, suggests an important role of DDX3Y during spermatogenesis.


Fatty acid transfer across the myocardial capillary wall.
Interstitial transudate of isolated isometrically working perfused rat hearts was analyzed to investigate fatty acid (FA) release and transfer across the capillary wall. Unsaturated FA were released under certain conditions. Lowering medium FA (16:0) with constant or varying FA/A-ratio (A: albumin) decreased interstitial FA-concentration down to 17% of arterial FA-concentration. This was accompanied by reduced uptake-rate. Transcapillary diffusion-resistance, unless markedly altering, cannot be responsible for this observation. Calculated diffusion-rates of FA and FA* protein-complexes in the endothelial cytoplasm and interstitium indicate that FA-transfer takes place almost exclusively bound to carrier-proteins. The apparent permeability surface-area-values of FA for transendothelial FA-transfer are three orders of magnitude higher than those for sucrose; diffusion-coefficients for FA across the endothelium are close to those in water, excluding substantial diffusion-barrier of the capillary wall. Dissociation-rate-constants calculated from experimental data are in the range of those reported for FA* albumin-complexes in vitro. Thus the observed transcapillary FA-gradients are apparently due to the limited dissociation-rate of the FA*albumin-complex in the intravascular space.


Ovarian endometriotic cysts. An analysis of cytologic atypia and DNA ploidy patterns.
Cytologic atypia may be seen in the glandular epithelium that lines ovarian endometriotic cysts. The significance of this atypia has not been fully elucidated. The authors studied the morphologic appearance and DNA ploidy of the glandular epithelium from 36 ovarian endometriotic cysts by image analysis on formalin-fixed paraffin-embedded tissue sections. In 29 of the cases the corresponding endometrium proper also was studied. The DNA content was diploid in all eutopic endometrium and in the lining epithelium of all endometriotic cysts without atypia or with only mild cytologic atypia. DNA aneuploidy was observed in 3 of 6 endometriotic cysts with severe atypia. Our findings indicate that mild cytologic atypia in the glandular epithelium of endometriotic cysts is associated with normal DNA ploidy patterns, whereas severe atypia may be associated with aneuploidy. These findings support the hypothesis that cytologic atypia represents the precursor lesion for the invasive epithelial malignancy that may arise in ovarian endometriotic cysts.


Rhodium-catalyzed reaction of terminal alkynes with allylamine leading to (E)-3-alkylidene N-heterocycles.
Terminal alkynes react with allylamine in the presence of a RhCl(PPh3)3 catalyst to give (E)-3-alkylidene-3,4-dihydro-2H-pyrroles. The products consist of two molecules of alkyne and one molecule of allylamine. Although dimers, trimers, and oligomers of alkynes are also obtained as byproducts, the addition of various ammonium salts to the reaction suppresses such oligomerization, resulting in an increase in product.


[Evaluation of electrophysiologic properties of the heart atrium in patients with electrically induced atrial fibrillation].
Paroxysmal palpitation is a frequent non-specific symptom observed in clinical practice. It is not always possible to identify the arrhythmogenic cause of this complaint. The induction of paroxysmal atrial fibrillation (PAF) during transoesophageal pacing (TEP) was found to be particularly useful when arrhythmia paroxysms were not evidenced by standard electrocardiography or by 24-hour Holter monitoring. The objective of the present study was a comparative assessment of the electrophysiological parameters obtained from a patient group with PAF induced during TEP and from a patient group with no arrhythmia, in order to determine the hazard of spontaneous PAF occurrence. The study included 116 patients complaining of palpitations who underwent TEP. Of these, 53 were selected (34 males and 19 females; mean age, 47.6 +/- 13.1) in whom a sustained PAF episode (> 30 sec) had been induced during TEP. These patients are referred to Group I. Group II (control) comprised the remaining 63 patients (38 males and 25 females; mean age 45.5 +/- 8.5) in whom no PAF episode had been induced during TEP. All patients (Group I and Group II) underwent echocardiography, 24-hour Holter monitoring, exercise test and TEP. During TEP the following parameters were evaluated: left atrial effective refractory period (AERP), sinoatrial conduction time (SACT), maximal and corrected sinus node recovery time (SNRT and CNRT), Wenckebach periodicity (WP) and mean cycle duration (CD). Thus, the AERP value amounted to 299.8 +/- 42.4 msec and 259.5 +/- 54.9 msec (p < 0.001) for Group I and Group II, respectively. The SACT and SNRT values totalled 132.3 +/- 45.1 msec and 1011.1 +/- 165.6 msec in Group I, and 103.2 +/- 29.9 msec and 838.3 +/- 172.7 msec in Group II, respectively (p < 0.001). Compared to the control (235 +/- 95.7 msec; 200.3 +/- 64.9 msec, respectively), the group of patients with electrically-induced PAF (Group I) showed significantly longer CNRT (383.4 +/- 172.5 msec, p < 0.001) and WP (350.8 +/- 59.3 msec, p < 0.001). The study had led to the following finding: patients with electrically-induced PAF had significantly longer left effective refractory periods, sinoatrial conduction times, maximal and corrected sinus node recovery times and Wenckebach periodicities.


Thyrotoxicosis. Results and risks of current therapy.
Effective therapy for thyrotoxicosis hinges on prompt recognition of the syndrome. When the diagnosis is suspected clinically but is not certain, the free thyroxine index is the most cost-effective test to order initially. The thyroidal radioactive iodine (123I) uptake is measured to differentiate Graves' disease from thyroiditis and other forms of thyrotoxicosis. Definitive therapy includes antithyroid drugs, iodine 131, and surgery. Patient preference has a large role in the final therapeutic choice.


pH changes during in vitro adherence of Escherichia coli to HeLa cells.
Escherichia coli-induced acidic pH conditions were observed during the in vitro adherence of E. coli to HeLa cells. No pH changes occurred in the absence of adherence. This suggests that adherence affects the function or interaction of HeLa cells and E. coli.


Erythrasma - A Red Herring in the Ongoing Epidemic of Tinea.
We describe the presentation of five adults with erythrasma, misdiagnosed as tinea and prescribed antifungal treatment which resulted in incomplete clearance. The lesions were restricted to axillary and/or inguinal folds. They were dry, brown macules with fine scaling. Except for one with moderate pruritus, they were asymptomatic. No fungal elements could be demonstrated in any of the patients in 10% KOH preparation. Gram stain revealed short gram-positive rods in varying proportions. All the patients showed a pink fluorescence on Wood's lamp examination. After treatment with topical clindamycin singly or in combination with oral azithromycin, there was complete clearance of the lesions leaving normal-appearing skin in three and residual hyperpigmentation in one. The overdiagnosis of tinea in the ongoing epidemic of dermatophytosis is a potential concern. Wood's lamp examination is very useful to confirm or exclude erythrasma.


[The treatment of zoster neuralgia].
Neuralgic pain during or following herpes zoster infection is a common problem in pain therapy. The current management of neuralgias due to zoster is discussed with reference to patients in a chronic pain clinic within an anesthesiology department. The courses of 80 patients followed up for at least 3 months from the pain clinic at the University Hospital in Kiel were analyzed. The mean age was 69 years. The predominant locations for zoster lesions were the thoracic segments (65%) and the first branch of the trigeminal nerve (19%). Diabetes mellitus was present in 20% of the patients and malignant disease in 18%. In 2 patients recurrent postherpetic neuralgia was the first symptom of HIV infection. Despite pretreatment, the mean initial pain score was 8 on an analog scale (range 0-10). Acute herpes zoster pain during the infection was treated with virustatic agents, corticosteroids and sympathetic blocks. Postherpetic neuralgias required a more sophisticated approach, depending on the stage of the disease and the type of pain involved: sympathetic blockade with local anesthetic agents or injections of very low dose opioids to sympathetic ganglia, transcutaneous electrical nerve stimulation, and antidepressants or anticonvulsants. The success of the therapy is correlated with the duration of pain. If the history of zoster pain was less than 1 month, the majority of patients showed good or excellent results. On the other hand, only one-third of patients with a history longer than 6 months had adequate pain relief. Therefore, early and appropriate treatment is desirable for patients suffering from zoster neuralgias.


Personality and mood correlates of avoidant personality disorder.
Avoidant personality disorder (APD) has been recognized as prevalent and clinically important; however, it is not clear how APD maps onto established personality and mood dimensions. In this cross-sectional survey study, 365 college students completed questionnaires assessing APD features and theoretically relevant personality and mood dimensions. Based on these self-report data, 6.6% may meet DSM-IV criteria for APD. Hierarchical regression analyses showed that APD features were associated with introversion, neuroticism, low self-esteem, and pessimistic expectancies. Additionally, APD features were linked with self-reports of elevated emotional responsiveness to threats and reduced emotional responsiveness to incentives (the behavioral inhibition system and behavioral activation system scales). After controlling for the effects of other personality, temperament, and cognitive measures, affective distress (i.e., anger, anxiety, and depression) was no longer related to APD. Results are consistent with APD models that emphasize the joint influences of emotional vulnerability and social-cognitive triggering and sustaining factors.


Longitudinal study of institutional downsizing: effects on individuals who remain in the institution.
In a 4-year study we examined the longitudinal effects of deinstitutionalization programs on those who remain in institutions being downsized. Individual outcomes investigated were community access, social activities, community inclusion, family relationships, and choice. Effects of residential relocation on individual outcomes such as adaptive behavior were evaluated and total daily per-person expenditure on institutional services for participants was determined. Downsizing was associated with decreased community integration but no change in most other outcomes. Availability of therapy services fell over time, and individuals experienced many residential and day program moves within the institution. Per person expenditure on services increased substantially. Finally, no significant changes in adaptive behavior were associated with intrainstitutional moves.


A Biologically Plausible Action Selection System for Cognitive Architectures: Implications of Basal Ganglia Anatomy for Learning and Decision-Making Models.
Several attempts have been made previously to provide a biological grounding for cognitive architectures by relating their components to the computations of specific brain circuits. Often, the architecture's action selection system is identified with the basal ganglia. However, this identification overlooks one of the most important features of the basal ganglia-the existence of a direct and an indirect pathway that compete against each other. This characteristic has important consequences in decision-making tasks, which are brought to light by Parkinson's disease as well as genetic differences in dopamine receptors. This paper shows that a standard model of action selection in a cognitive architecture (ACT-R) cannot replicate any of these findings, details an alternative solution that reconciles action selection in the architecture with the physiology of the basal ganglia, and extends the domain of application of cognitive architectures. The implication of this solution for other architectures and existing models are discussed.


Degradation of 2,3,4,6-tetrachlorophenol at low temperature and low dioxygen concentrations by phylogenetically different groundwater and bioreactor bacteria.
Effects of low temperature and low oxygen partial pressure on the occurrence and activity of 2,3,4,6-tetrachlorophenol degrading bacteria in a boreal chlorophenol contaminated groundwater and a full-scale fluidized-bed bioreactor were studied using four polychlorophenol degrading bacterial isolates of different phylogenetic backgrounds. These included an alpha-proteobacterial Sphingomonas sp. strain MT1 isolated from the full-scale bioreactor and three isolates from the contaminated groundwater which were identified as beta-proteobacterial Herbaspirillum sp. K1, a Gram-positive bacterium with high G + C content Nocardioides sp. K44 and an alpha-proteobacterial Sphingomonas sp. K74. The Sphingomonas strains K74 and MT1 and Nocardioides sp. K44 degraded 2,4,6-trichlorophenol and 2,3,4,6-tetrachlorophenol as the sole carbon and energy sources. Close to stoichiometric inorganic chloride release with the 2,3,4,6-tetrachlorophenol removal and the absence of methylation products indicated mineralization. Tetrachlorophenol degradation by the Herbaspirillum sp. K1 was enhanced by yeast extract, malate, glutamate, pyruvate, peptone and casitone. At 8 degrees C, Sphingomonas sp. K74 had the highest specific degradation rate (mu(max) = 4.9 x 10(-2) mg h(-1) cell(-1)) for 2,3,4,6-tetrachlorophenol. The Nocardioides strain K44 had the highest affinity (K(s) = 0.46 mg l(-1)) fortetrachlorophenol. K1 and MT1 grew microaerophilically in semisolid glucose medium. Furthermore, the growth of MT1 was inhibited in liquid glucose medium at high oxygen partial pressure indicating sensitivity to accumulating toxic oxygen species. On the other hand, trichlorophenol degradation was not affected by oxygen concentration (2-21%). The isolates K44, K74 and MT1, with optimum growth temperatures between 23 and 25 degrees C, degraded tetrachlorophenol faster at 8 degrees C than at room temperature indicating distinctly different temperature optima for chlorophenol degradation and growth on complex media. These results show efficient polychlorophenol degradation by the isolates at the boreal groundwater conditions, i.e., at low temperature and low oxygen concentrations. Differences in chlorophenol degradation and sensitivities to chlorophenols and oxygen among the isolates indicate that the phylogenetically different chlorophenol degraders have found different niches in the contaminated groundwater and thus potential for contaminant degradation under a variety of saturated subsurface conditions.


Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells.
The objective of this study was to determine whether cyclic strain could promote human umbilical vein endothelial cells (HUVECs) to express markers in common with the mature smooth muscle cell (SMC) phenotype, suggesting endothelial cell to SMC transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch and 60 cycles/min for 24-96 hr, and demonstrated elongation with enhanced and organized F-actin distribution. By using real-time polymerase chain reaction analysis, the mRNA levels of five specific SMC markers, SM22-alpha, alpha-smooth muscle actin (alpha-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC), and calponin-1 were significantly increased in cyclic strain-treated HUVECs as compared with those in static control cells. Protein levels of SM22-alpha and alpha-SMA were also substantially increased by Western blot and immunofluorescence staining. In addition, two specific endothelial markers, von Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR-2), showed a reduction in mRNA expression. In addition, cyclic strain-induced increase of SM22-alpha and alpha-SMA expression were reversible when cells were cultured back to the static condition. These results demonstrate a possible endothelial cell to SMC transdifferentiation in response to cyclic strain. Hemodynamic forces in modulating endothelial phenotype may play an important role in the vascular system.


Computational design and biosensor applications of small molecule-sensing allosteric ribozymes.
Here I describe accurate and time-efficient computational methods for designing small molecule-sensing allosteric ribozymes that serve as logic gates with NOT or YES Boolean logic functions. Theophylline-sensing ribozymes are engineered to have a high cleavage rate of 1.3 min(-1) under physiologically relevant conditions. They are highly specific to theophylline and do not respond to caffeine, which differs in a single methyl group. These ribozymes are designed by fusing a theophylline aptamer with an extended version of the hammerhead ribozyme by modeling secondary structures. Purine-sensing ribozymes are designed by fusing the minimal version of the hammerhead ribozyme with bacterial guanine or adenine aptamers by modeling 3D interactions. I have developed high-throughput compatible arrays based on purine RNA sensors that can be used for antibacterial drug discovery. The ribozymes can be employed as molecular sensors in various applications, including exogenous control of gene expression, high-throughput screening arrays, and molecular computing.


Analysis of Interior-Point Paths.
Infeasible-interior-point paths are the main tools in interior-point methods for solving many kinds of optimization problems. These paths are usually parametrized by a penalty-parameter r ↓ 0 and further parameters describing their off-centrality and infeasiblilty. Starting with an early result of C. Witzgall et al. [12] in linear programming, this paper gives an overview on results concerning the existence of these paths, their analyticity and the limiting behavior of their derivatives as r ↓ 0, and this also for degenerate problems in the areas of linear programming, linear complementarity problems, and semi-definte programming.


Surveillance culture for multidrug-resistant gram-negative bacteria: Performance in liver transplant recipients.
The prevalence of infection with multidrug-resistant gram-negative bacteria (MDR-GNB) after solid-organ transplantation is increasing. Surveillance culture (SC) seems to be an important tool for MDR-GNB control. The goal of this study was to analyze the performance of SC for MDR-GNB among liver transplant (LT) recipients. This was a prospective cohort study involving patients who underwent LT between November 2009 and November 2011. We screened patients for extended spectrum β-lactamase-producing Escherichia coli, extended spectrum β-lactamase-producing Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB). We collected SC samples immediately before LT and weekly thereafter, until hospital discharge. Samples were collected from the inguinal-rectal area, axilla, and throat. The performance of SC was evaluated through analysis of its sensitivity, negative predictive value, and accuracy. During the study period, 181 patients were evaluated and 4,110 SC samples were collected. The GNB most often identified was CRAB, in 45.9% of patients, followed by CRKP in 40.3%. For all microorganisms, the positivity rate was highest among the inguinal-rectal samples. If only samples collected from this area were considered, the SC would fail to identify 34.9% of the cases of CRAB colonization. The sensitivity of SC for CRKP was 92.5%. The performance of SC was poorest for CRAB (sensitivity, 80.6%). Our data indicate that SC is a sensitive tool to identify LT recipients colonized by MDR-GNB.


Evaluation of reference genes at different developmental stages for quantitative real-time PCR in Aedes aegypti.
The mosquito Aedes aegypti (Ae. aegypti) is the most notorious vector of illness-causing viruses such as Dengue, Chikugunya, and Zika. Although numerous genetic expression studies utilizing quantitative real-time PCR (qPCR) have been conducted with regards to Ae. aegypti, a panel of genes to be used suitably as references for the purpose of expression-level normalization within this epidemiologically important insect is presently lacking. Here, the usability of seven widely-utilized reference genes i.e. actin (ACT), eukaryotic elongation factor 1 alpha (eEF1α), alpha tubulin (α-tubulin), ribosomal proteins L8, L32 and S17 (RPL8, RPL32 and RPS17), and glyceraldeyde 3-phosphate dehydrogenase (GAPDH) were investigated. Expression patterns of the reference genes were observed in sixteen pre-determined developmental stages and in cell culture. Gene stability was inferred from qPCR data through three freely available algorithms i.e. BestKeeper, geNorm, and NormFinder. The consensus rankings generated from stability values provided by these programs suggest a combination of at least two genes for normalization. ACT and RPS17 are the most dependably expressed reference genes and therefore, we propose an ACT/RPS17 combination for normalization in all Ae. aegypti derived samples. GAPDH performed least desirably, and is thus not a recommended reference gene. This study emphasizes the importance of validating reference genes in Ae. aegypti for qPCR based research.


Activins are critical modulators of growth and survival.
Activins betaA and betaB (encoded by Inhba and Inhbb genes, respectively) are related members of the TGF-beta superfamily. Previously, we generated mice with an Inhba knock-in allele (InhbaBK) that directs the expression of activin betaB protein in the spatiotemporal pattern of activin betaA. These mice were small and had shortened life spans, both influenced by the dose of the hypomorphic InhbaBK allele. To understand the mechanism(s) underlying these abnormalities, we now examine growth plates, liver, and kidney and analyze IGF-I, GH, and major urinary proteins. Our studies show that activins modulate the biological effects of IGF-I without substantial effects on GH, and that activin signaling deficiency also has modest effects on hepatic and renal function. To assess the relative influences of activin betaA and activin betaB, we produced mice that express activin betaB from the InhbaBK allele, and not from its endogenous Inhbb locus. InhbaBK/BK, Inhbb-/- mice have failure of eyelid fusion at birth and demonstrate more severe effects on somatic growth and survival than either of the corresponding single homozygous mutants, showing that somatic growth and life span are supported by both activins betaA and betaB, although activin betaA plays a more substantial role.


Prognostic significance of the FLT3 ITD mutation in patients with normal-karyotype acute myeloid leukemia in relapse.
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutation is related to poor prognosis in normal-karyotype acute myeloid leukemia (AML). However, the prognostic significance of the mutation at relapse has not been adequately investigated. We investigated the prognostic significance of the FLT3 ITD mutation at relapse in normal-karyotype AML patients. We analyzed 69 normal-karyotype AML patients, in whom paired bone marrow samples taken at initial diagnosis and subsequent relapse were analyzed for the FLT3 ITD mutation at the Asan Medical Center between 1995 and 2009. Forty patients showed a persistent wild-type genotype, 11 showed the FLT3 ITD mutation at diagnosis and relapse, and 9 lost and another 9 acquired the mutation at relapse. The mutation status at relapse affected the overall survival (OS), with the mutation group showing shorter OS and survival after relapse than the wild-type group did (P<0.001 and P<0.001, respectively), despite having received more frequent stem cell transplantation after relapse than the wild-type group did. However, no difference was detected in the OS and survival after relapse with regard to the mutation status at diagnosis. The patients with FLT3 ITD mutation at relapse showed poorer prognoses than those without the mutation. However, mutation status at diagnosis did not affect the outcome. These results suggest that, in normal-karyotype AML patients with relapse, the prognostic significance of FLT3 ITD mutation at relapse is greater than that of the mutation status at diagnosis.


EVOLUTION OF DIFFERENT GALL TYPES IN WILLOW-FEEDING SAWFLIES (HYMENOPTERA: TENTHREDINIDAE).
The sawflies that feed on the plant family Salicaceae can be divided into eight informal groups based on larval feeding habit or gall type: (1) species with free-living larvae; (2) leaf folders; (3) leaf blade gallers; (4) apical leaf gallers; (5) basal leaf gallers; (6) midrib and petiole gallers; (7) stem gallers; and (8) bud gallers. It has been proposed that the galling habit evolved from free-living larvae via leaf folders, and that the different gall types evolved gradually in the sequence mentioned above. Thus, the galling site would have "wandered" from the leaf margin toward the stem as a result of gradual changes in oviposition site preference. Allozyme data from eight informative loci were used to reconstruct the phylogeny of 18 representative sawfly species. The results suggest that indeed leaf folders seem to be a basal group; leaf blade gallers evolved independently of the other true gallers; apical and basal leaf gallers are not the ancestors of petiole and bud gallers, but they may share a common galling ancestor; bud gallers evolved from midrib/petiole gallers; and stem gallers are polyphyletic. The cause for the observed wandering of the galling site could be intraspecific competition due to a possible "nutrient shading effect" of galls situated closer to the host plant's main vascular system.


Endovascular Management of Post-Irradiated Carotid Blowout Syndrome.
To retrospectively evaluate the clinical and technical factors related to the outcomes of endovascular management in patients with head-and-neck cancers associated with post-irradiated carotid blowout syndrome (PCBS). Between 2000 and 2013, 96 patients with PCBS underwent endovascular management. The 40 patients with the pathological lesions located in the external carotid artery were classified as group 1 and were treated with embolization. The other 56 patients with the pathological lesions located in the trunk of the carotid artery were divided into 2 groups as follows: group 2A comprised the 38 patients treated with embolization, and group 2B comprised the 18 patients treated with stent-graft placement. Fisher's exact test was used to examine endovascular methods, clinical severities, and postprocedural clinical diseases as predictors of outcomes. Technical success and immediate hemostasis were achieved in all patients. The results according to endovascular methods (group 1 vs 2A vs 2B) were as follows: technical complication (1/40[2.5%] vs 9/38[23.7%] vs 9/18[50.0%], P = 0.0001); rebleeding (14/40[35.0%] vs 5/38[13.2%] vs 7/18[38.9%]), P = 0.0435). The results according to clinical severity (acute vs ongoing PCBS) were as follows: technical complication (15/47[31.9%] vs 4/49[8.2%], P = 0.0035); rebleeding (18/47[38.3%] vs 8/49[16.3%], P = 0.0155). The results according to post-procedural clinical disease (regressive vs progressive change) were as follows: alive (14/21[66.7%] vs 8/75[10.7%], P<0.0001); survival time (34.1±30.6[0.3-110] vs 3.6±4.0[0.07-22] months, P<0.0001). The outcomes of endovascular management of PCBS can be improved by taking embolization as a prior way of treatment, performing endovascular intervention in slight clinical severity and aggressive management of the post-procedural clinical disease.


Immunology of HIV infection, I: Biology of the interferons.
Interferons (IFN) are the prototypic biologic response modifiers. They comprise a multigene family of regulatory proteins and glycoproteins that affect a variety of cellular functions, including normal and neoplastic cell growth, immune reactivity, and host-parasite interactions. Their importance to basic cell biology and cellular immune defense, and their interactions with human immunodeficiency viruses (HIV) on the molecular and cellular levels, form the basis for this review.


Transient deterioration of albumin-bilirubin scores in early post-dose period of molecular targeted therapies in advanced hepatocellular carcinoma with 50% or higher liver occupation: A STROBE-compliant retrospective observational study.
Real-world clinical cases of molecularly targeted agent (MTA) administration to patients with advanced hepatocellular carcinoma (HCC) with ≥50% liver occupation have been reported, but treatment outcomes have rarely been described. We have encountered several cases in which albumin-bilirubin (ALBI) scores deteriorated markedly and C-reactive protein (CRP) levels elevated in the early post-dose period. The present study therefore investigated early clinical changes in ALBI score and CRP levels after initiating MTA in advanced HCC patients with ≥50% liver occupation, focusing on antitumor response at 6 weeks.This retrospective study included 46 HCC patients with liver occupation ≥50% and 191 patients with <50%, Child-Pugh score ≤7, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1, who were treated with sorafenib or lenvatinib as first-line systemic therapy at our hospital between June 2011 and January 2020. We analyzed their medical records up to March 2020 and investigated the outcomes and changes in CRP and ALBI scores classified according to antitumor response at 6 weeks.Overall survival was significantly longer in patients with partial response (PR) + stable disease (SD) (13.7 months) than in patients with progressive disease (PD) (1.7 months, P < .001) in the ≥50% group. Patients with antitumor response of PR + SD at 6 weeks in the ≥50% group showed more marked deterioration of ALBI score at 2 weeks than those in the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. Focusing on patients with PD at 6 weeks, ALBI score deteriorated over time in both groups. Regarding CRP, on 6-week PR + SD patients, a significant increase in CRP levels at 1 and 2 weeks was evident in the >50% group compared to the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. In PD patients, no difference between groups in CRP elevation occurred at 1 and 2 weeks.In MTA treatment for patients with ≥50% liver occupation, to obtain an antitumor response of PR + SD, adequate management might be important considering transient deteriorated ALBI scores and elevated CRP levels.


Long-term results of transpedicle body augmenter in treating burst fractures.
Short-segment fixation alone to treat thoracolumbar burst fractures is common but it has a 20-50% incidence of implant failure and rekyphosis. A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture. This article is to evaluate the longterm results of short-segment fixation with TpBA for treatment of thoracolumbar burst fractures. Patients included in the study had a single-level burst fracture involving T11-L2 and no distraction or rotation element with limited neurological deficit. Patients in the control group (n = 42) were treated with short-segment posterior instrumentation alone, whereas patients in the augmented group (n = 90) were treated with a titanium spacer designed for transpedicle body reconstruction. The followup was 48-101 months. The radiographic and clinical results were evaluated and compared by Student's t test and Fisher's exact test. The blood loss, operation time and hospitalization were similar in both the groups. The immediate postoperative anterior vertebral restoration rate of the augmented group was similar to that of the control group (97.6% ± 2.4% vs. 96.6% ± 3.2%). The final anterior vertebral restoration was greater in the augmented group than in the control group (93.3% ± 3.4% vs. 62.5% ± 11.2%). Immediate postoperative kyphotic angles were not significantly different between the groups (3.0° ± 1.8° vs. 5.1° ± 2.3°). The final kyphotic angles were less in the augmented group than the control group (7.3° ± 3.5° vs. 20.1° ± 5.4°). The augmented group had less (P < 0.001) implant failure [0% (n=0) vs. 23.8% (n=10)] for the control group) and more patients (P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group [90.0% (n=81) vs. 66.7% (n=28)]. All patients in the augmented group and 39 (92.8%) patients in the control group experienced neurological recovery to Frankel Grade E. Three patients in the control group had improvement to Frankel Grade D from Frankel Grade C, but later had deterioration to Frankel Grade C because of loosening and dislodgement of the implant. Posterior body reconstruction with TpBA can maintain kyphosis correction and vertebral restoration, prevent implant failure and lead to better clinical results.


[Phosphorus Fractions and Quantitative Identification of Pollution Sources in Nanhai Wetland, Baotou].
In this study, total phosphorus (TP) and the phosphorus (P) fractions in the water and surface sediments of the Baotou Nanhai wetland in China were determined using molybdenum blue/ascorbic acid spectrophotometry and continuous extraction methods. An APCS-MLR receptor model was combined with correlation analysis (CA) and principal component analysis (PCA) to identify and quantify the pollution sources. The results showed ① differences in the pollution level of phosphorus between the surface sediments and water. The contribution of dissolved inorganic phosphorus (DIP) to TP in the water (WTP) was the lowest, while the contribution of calcium-bound phosphorus (HCl-P) to TP in the surface sediments (STP) was the largest in the study area. The surface sediments of the Nanhai Lake (L area) and the wetland plant area (P area) exhibited high bioavailability and the potential for releasing phosphorus into the water, which could result in eutrophication and is therefore of concern. ② The APCS-MLR receptor model indicated that the main pollution sources of phosphorus were industrial wastewater and domestic sewage (29.07%), and pesticides and fertilizers (29.00%). In addition, the degradation of animal and plant residues (18.49%) also contributed to pollution in the study area.


A Coarse Alignment Method Based on Digital Filters and Reconstructed Observation Vectors.
In this paper, a coarse alignment method based on apparent gravitational motion is proposed. Due to the interference of the complex situations, the true observation vectors, which are calculated by the apparent gravity, are contaminated. The sources of the interference are analyzed in detail, and then a low-pass digital filter is designed in this paper for eliminating the high-frequency noise of the measurement observation vectors. To extract the effective observation vectors from the inertial sensors' outputs, a parameter recognition and vector reconstruction method are designed, where an adaptive Kalman filter is employed to estimate the unknown parameters. Furthermore, a robust filter, which is based on Huber's M-estimation theory, is developed for addressing the outliers of the measurement observation vectors due to the maneuver of the vehicle. A comprehensive experiment, which contains a simulation test and physical test, is designed to verify the performance of the proposed method, and the results show that the proposed method is equivalent to the popular apparent velocity method in swaying mode, but it is superior to the current methods while in moving mode when the strapdown inertial navigation system (SINS) is under entirely self-contained conditions.


Annexin XXI (ANX21) of Giardia lamblia has sequence motifs uniquely sdhared by giardial annexins and is specifically localized in the flagella.
We have identified a novel annexin, ANX21, in trophozoites of Giardia lamblia. The nucleotide sequence encoding this protein deviated from a published sequence in predicting an additional endonexin fold in the fourth annexin domain. In addition, several motifs exclusively shared by other annexins of G. lamblia in their predicted fourth repeat and predicted to be localized on the opposite (concave) surface of the molecule became apparent. Western blots of trophozoite fractions probed with antiserum against the recombinant protein indicated that this annexin, like the other giardial annexins ANX19 and ANX20, associates with phospholipids in the presence of Ca(2+). Finally, confocal laser scanning of trophozoites showed that the protein, apart from the median body, was exclusively localized in the eight flagella. Together, these data suggest that ANX21 may function as a Ca(2+)-regulated structural element linking phospholipid bilayer and underlying axoneme.


Outcomes of arteriovenous fistula creation: A Jordanian experience.
The arteriovenous fistula is considered the preferred hemodialysis access due to its lower complication rate and longer patency. The aim of this study is to report the outcomes of arteriovenous fistula creation and to study the predictive factors for these outcomes. This is a retrospective study of all patients who underwent autogenous arteriovenous fistula creation procedure by a single surgeon during the period from October 2011 till December 2017. All the procedures were performed at an academic referral center by a single surgeon. All patients who underwent arteriovenous fistula creation in the upper limb during the study period were included. All patients were diagnosed with end-stage renal disease and referred for arteriovenous fistula creation either before or after initiating hemodialysis. Data were collected from the patients' charts. The primary outcomes were the primary failure and secondary patency rates. Secondary outcome was to find the factors associated with decreased patency. The Kaplan-Meier curve with the log-rank test was used to describe the patency while univariate and multivariate analyses were done to the factors considered relevant to the patency. The total number of procedures was 291; of which, 18 were lost to follow-up. The primary failure rate was 12%. Secondary patency rate at 1 and 5 years was 79% and 53%, respectively. Diabetes mellitus and fistulae placed on right side were associated with decreased patency. The primary failure rate was relatively low in this study but the long-term functionality of the arteriovenous fistulae needs to be improved.


Apolipoprotein E isoform dependently affects Tat-mediated HIV-1 LTR transactivation.
Apolipoprotein E (ApoE) is the major carrier protein that mediates the transport and delivery of cholesterol and other lipids in the brain. Three isoforms of ApoE (ApoE2, ApoE3, ApoE4) exist in humans, and their relative expression levels impact HIV-1 infection, HIV-1/AIDS disease progression, and cognitive decline associated with HIV-1-associated neurocognitive disorder. Because HIV-1 Tat, a viral protein essential for HIV-1 replication, can bind to low-density lipoprotein receptor-related protein 1 (LRP1) that controls ApoE uptake in the brain, we determined the extent to which different isoforms of ApoE affected Tat-mediated HIV-1 LTR transactivation. Using U87MG glioblastoma cells expressing LTR-driven luciferase, we determined the extent to which LRP1 as well as ApoE2, ApoE3, and ApoE4 affected Tat-mediated HIV-1 LTR transactivation. A specific LRP1 antagonist and siRNA knockdown of LRP1 both restricted significantly Tat-mediated LTR transactivation. Of the three ApoEs, ApoE4 was the least potent and effective at preventing HIV-1 Tat internalization and at decreasing Tat-mediated HIV-1 LTR transactivation. Further, Tat-mediated LTR transactivation was attenuated by an ApoE mimetic peptide, and ApoE4-induced restriction of Tat-mediated LTR transactivation was potentiated by an ApoE4 structure modulator that changes ApoE4 into an ApoE3-like phenotype. These findings help explain observed differential effects of ApoEs on HIV-1 infectivity and the prevalence of HAND in people living with HIV-1 infection and suggest that ApoE mimetic peptides and ApoE4 structure modulator might be used as a therapeutic strategy against HIV-1 infection and associated neurocognitive disorders.


Riboflavin mediates m6A modification targeted by miR408, promoting early somatic embryogenesis in longan.
Plant somatic embryogenesis (SE) is an in vitro biological process wherein bipolar structures are induced to form somatic cells and regenerate into whole plants. MicroRNA (miRNA) is an essential player in plant SE. However, the mechanism of microRNA408 (miR408) in SE remains elusive. Here, we used stable transgenic technology in longan (Dimocarpus longan) embryogenic calli to verify the mechanism by which miR408 promotes cell division and differentiation of longan early SE. dlo-miR408-3p regulated riboflavin biosynthesis by targeting nudix hydrolase 23 (DlNUDT23), a previously unidentified gene mediating N6-methyladenosine (m6A) modification and influencing RNA homeostasis and cell cycle gene expression during longan early SE. We showed that DlMIR408 overexpression (DlMIR408-OE) promoted 21-nt miRNA biosynthesis. In DlMIR408-OE cell lines, dlo-miR408-3p targeted and downregulated DlNUDT23, promoted riboflavin biosynthesis, decreased flavin mononucleotide (FMN) accumulation, promoted m6A level, and influenced miRNA homeostasis. DNA replication, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, the pentose phosphate pathway, and taurine and hypotaurine metabolism were also closely associated with riboflavin metabolism. In a riboflavin feeding assay, dlo-miR408-3p and pre-miR408 were upregulated and DlNUDT23 was downregulated, increasing the m6A level and cell division and differentiation in longan globular embryos. When riboflavin biosynthesis was inhibited, dlo-miR408-3p was downregulated and DlNUDT23 was upregulated, which decreased m6A modification and inhibited cell division but did not inhibit cell differentiation. FMN artificial demethylated m6A modification affected the homeostasis of precursor miRNA and miRNA. Our results revealed a mechanism underlying dlo-miR408-3p-activated riboflavin biosynthesis in which DlNUDT23 is targeted, m6A modification is dynamically mediated, and cell division is affected, promoting early SE in plants.


Cloning and sequence analysis of cDNA encoding endopolygalacturonase I from Stereum purpureum.
Endopolygalacturonase (endoPG) I was obtained from Stereum purpureum by an improved easier purification procedure. It was found that EndoPG I consisted of three glycosilated proteins with the same isoelectric point and different molecular masses, 42, 45, and 48 kDa, respectively. However, the enzymatic deglycosilation product of endoPG I gave a single band at the position corresponding to 39kDa on SDS-PAGE. Furthermore, the N-terminal amino acid sequences of three endoPGs were identical one another up to 20 residues. A cDNA library was constructed and positive cDNA clones encoding endoPG I were isolated by using antibody raised against the purified endoPG I. Nucleotide sequence analysis of the cDNA disclosed a 1212-bp open reading frame that encoded 403 amino acid residues. The N-terminal amino acid sequence (residues 1-20) of endoPG I coincided with the deduced amino acid sequence starting from the 25th residue. Therefore, the sequence of the first 24 residues represented a signal peptide and the remaining sequence, consisting of 379 residues, was the mature protein with molecular mass of 39.1 kDa. The deduced sequence of endoPG I showed 30-45% similarity in comparison with those of bacterial and fungal endoPGs, and the sequence of putative active site residues reported for the endoPGs was highly conserved in the sequence of endoPG I.


Structural insight into the antagonistic action of diarylheptanoid on human estrogen receptor alpha.
Estrogen receptor α (ER α) is an important therapeutic target in the regulation of ligand dependent signaling in breast cancer. The current study investigates the anti-estrogenic potential of the Diarylheptanoid, 5-hydroxy-7-(4-hydroxy-3 methoxyphenyl)-1-phenyl-3-heptanone (DAH) in silico. Rigid Docking analysis of DAH at the ligand binding domain (LBD) of ER α showed hydrogen bond interactions with Arg394 and Glu353 at the active site, similar to the positive controls 4-Hydroxy Tamoxifen (4-OHT) and Fulvestrant (FUL). The protein and the protein-DAH complexes were further analyzed using molecular dynamics simulations for a time scale of 50 ns using GROMACS. Root mean square fluctuation (RMSF) analysis showed large fluctuations at the N-terminal region of Helices (H) 3, 9 and at the C-terminal region of H11, which could be involved in the antagonistic conformational change. Interestingly, H12 appeared to move away from the ligand binding pocket and occupy the co-activator binding groove at the LBD of ER α. Secondary structure analysis of the protein upon binding of DAH and CUR showed structural change from α-helix to Turn conformation at H4. We hypothesize that this structural change at H4, similar to the positive control, could hinder the activity of AF-2 by blocking the binding of co-activator. These conformational changes in ER α indicate an anti-estrogenic and therapeutic potential of the DAH.


Identification of aero-allergen sensitization in children seeking treatment for bronchial asthma at a tertiary care hospital for children in Sri Lanka.
Despite a significant rise in asthma globally as well as in Sri Lanka, data regarding allergen sensitization patterns and other risk factors for asthma are not available. Therefore, we set out to determine the allergen sensitization patterns in children with asthma in Sri Lanka. Skin prick testing for common indoor aeroallergens (cockroach, cat, dog, house dust mite, moulds) were carried out in 156 children with bronchial asthma at Lady Ridgeway Hospital for Children. 49.1% of the patients were sensitized to at least one allergen and 6.4% were sensitized to three or more allergens. Of the children 37.8% tested positive to house dust mite, 23.7% to cockroach, 5.8% to indoor moulds, 12.2% to cats and 8.9% to dogs. Allergen sensitization was significantly less in children aged four years or younger than in older children (p<0.0001). A family history of asthma or allergic rhinitis (AR) was a significant risk factor (p<0.0001) for allergen sensitization (OR 10.9, 95% CI 3.9 to 30.1). Frequency of symptoms was significantly higher in those who used firewood alone compared to those who used other fuels (OR 2.5, 95% CI 1.1 to 5.8). Sensitization to aero-allergens was seen in a majority of children with asthma. Sensitization was significantly more in children above 4 years of age. Patients with more frequent symptoms and with AR were more likely to be sensitized to allergens.


Marizomib, a potent second generation proteasome inhibitor from natural origin.
The malignance of cancers reinforces the need to find potent antineoplastic agents. In the past decades, proteasome has been witnessed as a potential target to fulfil this purpose, as evidenced by the fact that the first-in-class proteasome inhibitor Bortezomib was marketed in 2003. Marizomib (Salinosporamide A, NPI-0052), as a marine natural product, promises to be of high efficacy against multiple myeloma (MM), relapsed/refractory MM and other types of solid tumours. Compared with Bortezomib, it arguably has fewer severe side effects. Marizomib has been termed as orphan drug against multiple myeloma by US Food and Drug Administration (FDA) in 2013 and by European Medicines Agency (EMA) in 2014. As one of the second generation proteasome inhibitors (PIs), Marizomib is expected to bring about a sustained and complete therapeutic to extend cancer patients' life span. In this article, we intended to briefly review the historical developments, mechanisms, pharmacology, biosynthesis and side effects of this agent, aiming to provide concise coverage for a broad readership. In the end, we proposed our perspective for its futuristic applications.


Limb allografts in rats immunosuppressed with cyclosporine: as a whole-joint allograft.
We performed limb allografts in three inbred rat strains immunosuppressed with cyclosporine. As controls, 10 autografts and 10 isografts exhibited an excellent result. In minor-mismatched allografts (Lewis to Fischer, n = 45), with the use of cyclosporine, the grafted limbs survived and the articular cartilage retained normal architecture and cell viability 52 weeks after grafting, but without cyclosporine treatment severe degeneration and destruction of articular cartilage were shown by 16 weeks after operation. In major-mismatched allografts (Brown Norway to Fischer, n = 35), the articular cartilage of cyclosporine-treated animals maintained normal architecture and cell viability 52 weeks after operation despite the gross appearance of skin rejection, while that of non-cyclosporine-treated animals was degenerated and destroyed by 6 weeks. These results suggest the possibility of whole-joint allografts in humans with the use of cyclosporine, as well as other organ transplantations.


Quantifying adherence to treatment and its relationship to quality of life in a well-characterized haemophilia population.
It is known that chronically ill patients adhere to medical treatment plans only 50% of the time. Adherence to treatment with factor infusion therapy in haemophilia patients is essential to stop bleeding. It also prevents both acute and chronic life and limb threatening complications. This study, performed in a well-described haemophilia population, was completed in an effort to understand the critical issue of adherence in patients with haemophilia. A major component of the methodology of this study was the development of a unique scoring system to quantify adherence. Adherence scores in patients on On-Demand treatment strategies were then compared to those on High Intensity treatment strategies. Quality of life (QoL) studies were also performed on the study population to assess the association of treatment regimen and adherence scores to QoL measures. Results of this study demonstrated that adherence to On-Demand therapy was significantly greater than adherence to High Intensity treatment regimens and in children, High Intensity treatment regimens, which included prophylaxis, correlated with better QoL scores in body pain. It is envisioned that the development of an objective scoring system for adherence will prove useful in future studies of adherence as well as in the development of intervention strategies that can overcome barriers to adherence in haemophilia patients.


Quantitative studies on the transplantability of murine and human tumors into the brain and subcutaneous tissues of NCr/Sed nude mice.
The transplantability of experimental tumors into the brain (i.c.) and s.c. tissues of C3Hf/Sed and athymic NCr/Sed nude mice was examined using quantitative cell transplantation assays. Studies using the immune-competent C3H animals showed that brain is a more favorable site for the transplantation of syngeneic tumor than s.c. tissue and that this is true for nonimmunogenic as well as immunogenic tumors. The capacity of the brain to act as an immunological sanctuary can be overwhelmed by a strong, systemic, secondary immune response such as that evoked by the methylcholanthrene-induced sarcoma FSal. In studies performed using NCr/Sed nude mice, the allogeneic tumor MCaIV was found not to be demonstrably immunogenic. The cell dose required to transplant the tumor into 50% of recipients (TD50) could neither be increased by immunization procedures nor decreased by six Gy whole-body irradiation (WBI) prior to transplantation. Delayed-type hypersensitivity to this tumor was not expressed by nude mice after rechallenge with tumor antigen. The TD50 was again lower for i.c. than s.c. transplantation and the ratio s.c./i.c. was comparable to that found in syngeneic C3Hf/Sed hosts. Three human tumors have been similarly tested. They were: FaDu, a pharyngeal squamous carcinoma; HFSal, a fibrosarcoma; and U87, a malignant glioma. s.c. TD50 values were in all cases significantly higher than those obtained i.c. The ratios TD50 s.c./i.c. ranged from 6.4 to greater than 50 in five studies, substantially higher than those found for transplantation of murine tumors into either the syngeneic or the allogeneic recipients. Six Gy WBI reduced the s.c. TD50 for these tumors, but in each case the value remained significantly higher than that obtained i.c. 19.4 Gy WBI given in 10 equal fractions and followed by i.v. bone marrow rescue reduced further the s.c. TD50 for FaDu. NCr/Sed nude mice demonstrated cross-reacting delayed-type hypersensitivity against FaDu and HFSal. A small proportion of FaDu tumors (less than 2%) displayed a spontaneous halt in growth or even regression. When the host cell infiltrate of these tumors was analyzed, an increase was seen in the proportion of Thy 1.2 and asialo-GM1-positive cells as compared with progressively growing tumors. These data strongly suggest that a residual low level of immune reactivity exists in nude mice against xenotransplanted human tumors. This resistance to s.c. transplantation may be diminished by WBI and is less for intracerebral implantation.


[Study of administration of buprenorphine suppository for postoperative pain relief following transvaginal hysterectomy].
Buprenorphine suppository (BSP) has been available as an analgesic agent in Japan since 1990. It has gained considerable popularity in various clinical situations; however, its usefulness for postoperative pain relief has been controversial. The present study is addressed to postoperative pain in fifty-seven women who underwent transvaginal hysterectomy under spinal anesthesia with tetracaine and phenylephrine. We examined the analgesic effects of buprenorphine (0.4 mg) suppository. Patients were divided into four groups according to the timing of buprenorphine suppository administration: group A1, preoperative administration of BSP, n = 12; group A2, postoperative administration of BSP, n = 17; group A3, intravenous injection of 0.1 mg of buprenorphine during surgery and postoperative administration of BSP, n = 14; group C, control group, n = 14. All the patients in group C complained of pain within 24 hr. The onset time of pain after surgery was significantly longer in patients in group A1 (372 +/- 220 min) and A3 (481 +/- 161 min) than in control group C (282 +/- 97 min). The percentage of patients who did not complain of pain within 24 hr was the largest in group A3 (36%). However there were no significant differences in age, body weight, effective analgesic time, analgesic level or operation time among the four groups. Nausea and vomiting were observed in all groups: C (36%), A1 (41%), A2 (18%), and A3 (29%). From these results, we conclude that preoperative or intraoperative administration of buprenorphine is useful for control of postoperative pain; the method of administration of buprenorphine suppository needs further study.


Diabetic cataract formation: potential role of glycosylation of lens crystallins.
A high glucose concentration in vivo or an increased glucose of glucose 6-phosphate concentration in vitro has been found to lead to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins. In vitro, this glycosylation imparts an increased susceptibility of the crystallins to sulfhydryl oxidation. Disulfide crosslinks result in the formation of high molecular weight aggregates and an opalescence in the crystallin solutions. The addition of reducing agents prevents as well as reverses the formation of high molecular weight aggregates and the opalescence of the crystallins. These phenomena suggest a new interpretation of previous results on cataract formation and a new approach for development of drugs to prevent cataracts.


Renal failure associated with the use of dextran-40.
A typical case of dextran-40 associated acute renal failure is presented. In this patient a single plasma exchange was successful in considerably lowering the plasma dextran concentration. At the same time the elevated plasma oncotic pressure was reduced to normal values. Diuresis returned within 12 h. Several possible explanations of the mechanism of renal failure associated with the use of dextran-40 are discussed. While the mechanism of dextran-associated renal failure remains unsolved, plasma exchange seems to be effective therapy.


In vitro approaches to assess bioavailability and human gastrointestinal mobilization of food-borne polychlorinated biphenyls (PCBs).
This study reports on the potential for gastrointestinal (GI) mobilization and bioavailability of food-borne PCBs in humans. The development and validation of a GI simulator and operational protocols, developed in compliance with the requirements of German DIN 19738 risk assessment test procedure, are presented. Food, naturally contaminated with PCBs, was homogenized with simulated saliva fluid and shaken in the GI simulator with simulated gastric fluids (containing pepsin, mucine) for 2 h at 37 degrees C. Afterwards, the simulated intestinal fluids (containing pepsin, mucine, trypsin, pancreatin, bile) were added and the mixture shaken for a further 6 h prior to centrifugation and filtration using Buchner funnels to separate the undigested GI residues from GI fluids. PCBs were recovered from GI residues and fluids by Soxhlet and liquid-liquid extraction respectively, cleaned up using silica-SFE, and analyzed by gas chromatography mass spectrometry detection (GC-MSD). Detailed studies with fish indicate variations in mobilization and bioavailability of Sigma PCBs (28, 52, 101, 118, 153, 138 and 180). For example, the bioavailable fractions (fractions mobilized) in mackerel, salmon, crab and prawn were 0.77, 0.60, 0.54, and 0.72 respectively of the Sigma PCBs initially present in these food samples. The bioavailable fraction was dependent on the physicochemical characteristics of the PCBs. In mackerel bioavailable fractions for individual PCB congeners ranged from 0.47-0.82, from 0.30-0.70 in salmon, 0.44-0.64 in crab and in prawn from 0.47-0.77. Future studies will focus on understanding better, the variability in bioavailable fractions to be expected for different foodstuffs, in addition to tissue culture techniques using human gut cell lines to investigate a simultaneous mobilization and absorption of food-borne PCBs.


JC virus load in progressive multifocal leukoencephalopathy: analysis of the correlation between the viral burden in cerebrospinal fluid, patient survival, and the volume of neurological lesions.
JC virus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a demyelinating central nervous system infection that mainly affects patients with acquired immunodeficiency syndrome. The diagnostic value of the detection of JCV DNA in cerebrospinal fluid (CSF) has been proved. A correlation between the JCV burden in CSF and the PML prognosis has been proposed. To our knowledge, the present study is the first to examine JCV burden in CSF in relation to the magnitude of neurological damage. An in-house quantitative polymerase chain reaction assay was used for measurement of the JCV burden in CSF samples from 12 patients with PML. A wide variation in JCV load (6.4 log) was found among the patient CSF samples, a finding that makes JCV load measurements worthwhile. Virus load values of >4.68 log were associated with shorter patient survival time. No correlation was found between the virus load values and the global volume of brain tissue damaged. Our data suggest that factors other than the volume of neurological lesions influence the shedding of JCV in the CSF.


Identification of immune biomarkers associated with basement membranes in idiopathic pulmonary fibrosis and their pan-cancer analysis.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown etiology, characterized by diffuse alveolitis and alveolar structural damage. Due to the short median survival time and poor prognosis of IPF, it is particularly urgent to find new IPF biomarkers. Previous studies have shown that basement membranes (BMs) are associated with the development of IPF and tumor metastasis. However, there is still a lack of research on BMs-related genes in IPF. Therefore, we investigated the expression level of BMs genes in IPF and control groups, and explored their potential as biomarkers for IPF diagnosis. In this study, the GSE32537 and GSE53845 datasets were used as training sets, while the GSE24206, GSE10667 and GSE101286 datasets were used as validation sets. In the training set, seven immune biomarkers related to BMs were selected by differential expression analysis, machine learning algorithm (LASSO, SVM-RFE, Randomforest) and ssGSEA analysis. Further ROC analysis confirmed that seven BMs-related genes played an important role in IPF. Finally, four immune-related Hub genes (COL14A1, COL17A1, ITGA10, MMP7) were screened out. Then we created a logistic regression model of immune-related hub genes (IHGs) and used a nomogram to predict IPF risk. The nomogram model was evaluated to have good reliability and validity, and ROC analysis showed that the AUC value of IHGs was 0.941 in the training set and 0.917 in the validation set. Pan-cancer analysis showed that IHGs were associated with prognosis, immune cell infiltration, TME, and drug sensitivity in 33 cancers, suggesting that IHGs may be potential targets for intervention in human diseases including IPF and cancer.


Commercially available prostaglandin analogs for the reduction of intraocular pressure: similarities and differences.
Over the last 12 years, the pharmacological management of glaucoma and ocular hypertension has significantly changed with the introduction of the prostaglandin analogs, specifically, latanoprost, bimatoprost, and travoprost. Their ability to effectively reduce intraocular pressure with once-per-day dosing, their comparable ocular tolerability with timolol, and their general lack of systemic side effects have made them the mainstay of pharmacological therapy for glaucoma and ocular hypertension in most parts of the world. A review of their pharmacology reveals that they are all prodrugs that are converted to their respective free acids within the eye to activate the prostanoid FP receptor and to reduce intraocular pressure by enhancing the uveoscleral and the trabecular meshwork outflow pathways. A review of numerous prospective, randomized comparative studies indicates that no clinically significant differences exist among these agents regarding their ability to lower intraocular pressure.


Bovine milk intake and xanthine oxidase activity in blood serum.
Xanthine oxidase activity in blood serum was measured by a sensitive radio-enzymatic assay. Pigs receiving 7.6 liters of milk daily for 100 days did not show any detectable enzymatic activity in their blood Xanthine oxidase activity in blood serum of 25 human volunteers had an average of 6.7 milliunits per liter with a range of 0 to 34.6 milliunits per liter. Neither a causal nor statistically significant relationship existed between xanthine oxidase activity in blood and average daily milk consumption, age, or sex.


Further resolution of porcine phylogeny in Southeast Asia by Thai mtDNA haplotypes.
The mtDNA control region of 72 Thai native pigs and 11 Thai wild boars indigenous to Northern Thailand was comparatively sequenced. In total, 36 nucleotide variations that accounted for 24 haplotypes have been described (TNH01 to TNH20 and TWH01 to TWH04). These haplotypes and further publicly available mtDNA haplotypes were used to assess phylogenetic relationships. Twenty-three of the 24 haplotypes became integrated into the Asian clade of the phylogenetic tree and eight of them recapitulated another major cluster of haplotypes within this clade (Thai haplogroup, THG). Only haplotype TNH01 fit in with the European clade of the phylogenetic tree. An additional analysis using 510 bp of the mtDNA incorporated the THG haplotypes in to clade MTSEA (mountainous and Southeast Asian distribution) to form haplogroup MTSEA-THG. Recently, MTSEA was renamed in MC3. MC3 contains only signatures of pigs scattered across the Indo-Burma Biodiversity Hotspot (IBBH), a region including Thailand to the Kra Isthmus. Here we propose a putative independent porcine domestication event in South-east Asia (SEA). All haplotypes of haplogroup MTSEA-THG have revealed unique and previously unknown nucleotide signatures at positions 24 (nucleotide A) and at positions 183 (nucleotide C) that differentiate them from all other porcine mtDNA haplotypes.


Construction of a copper nanocluster/MnO2 nanosheet-based fluorescent platform for butyrylcholinesterase activity detection and anti-Alzheimer's drug screening.
An abnormal level of butyrylcholinesterase (BChE) activity is highly connected with hepatic damage and Alzheimer's disease. Herein, a facile and efficient method was proposed for BChE detection by incorporating polyethyleneimine-capped copper nanoclusters (PEI-CuNCs) with manganese dioxide (MnO2) nanosheets. The emission of PEI-CuNCs can be significantly quenched by MnO2 nanosheets via the inner filter effect. With the addition of BChE, the hydrolysis of butyrylthiocholine iodide produces thiocholine which can reduce MnO2 nanosheets to Mn2+, thus resulting in the fluorescence recovery of PEI-CuNCs. Based on that, a fluorescence "turn-on" sensing platform for BChE activity determination was constructed with a detection limit of 2.26 U L-1. This sensing method is able to detect BChE in human serum samples and identify the serums of normal persons and cirrhotic patients effectively, indicating its great potential in the clinical diagnosis of liver diseases. Furthermore, the approach can also be used to screen BChE inhibitors, which are promising medications to alleviate the symptoms of Alzheimer's disease.


Incorporating evolutionary measures into conservation prioritization.
Conservation prioritization is dominated by the threat status of candidate species. However, species differ markedly in the shared genetic information they embody, and this information is not taken into account if species are prioritized by threat status alone. We developed a system of prioritization that incorporates both threat status and genetic information and applied it to 9546 species of birds worldwide. We devised a simple measure of a species' genetic value that takes into account the shape of the entire taxonomic tree of birds. This measure approximates the evolutionary history that each species embodies and sums to the phylogenetic diversity of the entire taxonomic tree. We then combined this genetic value with each species' probability of extinction to create a species-specific measure of expected loss of genetic information. The application of our methods to the world's avifauna showed that ranking species by expected loss of genetic information may help preserve bird evolutionary history by upgrading those threatened species with fewer close relatives. We recommend developing a mechanism to incorporate a species' genetic value into the prioritization framework.