Intrathecal analgesia for labor.
Intrathecal analgesia is a highly effective technique for pain relief in the first stage of labor. It is a technically simple procedure that can be easily learned by family physicians currently performing diagnostic lumbar puncture. Its effectiveness, simplicity, and low incidence of serious complications make it especially applicable to the practices of physicians delivering babies in areas where continuous epidural anesthesia is not available. This article describes the procedure of intrathecal analgesia, and discusses advantages, complications, side effects, and applications.


Genomic Selection in Plant Breeding: Methods, Models, and Perspectives.
Genomic selection (GS) facilitates the rapid selection of superior genotypes and accelerates the breeding cycle. In this review, we discuss the history, principles, and basis of GS and genomic-enabled prediction (GP) as well as the genetics and statistical complexities of GP models, including genomic genotype×environment (G×E) interactions. We also examine the accuracy of GP models and methods for two cereal crops and two legume crops based on random cross-validation. GS applied to maize breeding has shown tangible genetic gains. Based on GP results, we speculate how GS in germplasm enhancement (i.e., prebreeding) programs could accelerate the flow of genes from gene bank accessions to elite lines. Recent advances in hyperspectral image technology could be combined with GS and pedigree-assisted breeding.


Sildenafil citrate: a therapeutic update.
Since its approval by the US Food and Drug Administration in March 1998, sildenafil citrate has been used by millions of men for the treatment of erectile dysfunction. Recent studies and consensus reports have expanded our understanding of its efficacy, safety, contraindications, and drug interactions. This paper reviews recent studies of the efficacy of sildenafil, its adverse effects and drug interactions, and socioeconomic factors involved in its use, with a focus on specific patient populations (prostate cancer, diabetes mellitus, ischemic heart disease, spinal cord injuries, neurologic disorders). Clinical studies, case reports, and commentaries and editorials concerning sildenafil published in the international literature between January 1999 and August 2000 were identified through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical Abstracts, using the terms sildenafil, Viagra, and erectile dysfunction. Sildenafil has demonstrated effectiveness in men with erectile dysfunction associated with prostatectomy, radiation therapy, diabetes mellitus, certain neurologic disorders, and drug therapy (eg, selective serotonin reuptake inhibitors [SSRIs]). It has not been as effective in women with sexual dysfunction, with the exception of SSRI-associated sexual dysfunction. Some disorders unrelated to sexual dysfunction (eg, esophageal motility dysfunction) may also respond to sildenafil. In the general population, sildenafil is considered to have an acceptable tolerability profile; however, patients with moderate to severe cardiovascular disease or those taking nitrate therapy are at increased risk for potentially serious cardiovascular adverse effects with sildenafil therapy. In addition, patients taking drugs that inhibit the cytochrome P450 3A4 isozyme, which metabolizes sildenafil, may experience increased drug concentrations and possible toxicity from normal doses of sildenafil. Sildenafil is an effective first-line therapy for erectile dysfunction in men. The decision to prescribe this agent should include such considerations as the cost-risk-benefit balance, patient access, drug distribution pathways, and prescription drug coverage.


The correlation among gripping volume, insertion torque, and pullout strength of micro-implant.
The fixation stability is the key factor for orthodontic micro-implant to succeed. This study evaluated the mechanical properties of three types of micro-implants by analyzing their structural configurations. Thirty micro-implants of three types (diameter 1.5 mm, Types A, B, C) were assessed. All micro-implants were manually driven into artificial bones at an 8-mm depth. The insertion torque (IT), pullout strength (PS), and gripping volume (GV) of each type were measured. The indexes of mechanical properties denoted as the PS/IT, GV/IT and PS/GV ratios. Intergroup comparisons and intragroup correlation were examined using statistical analysis. Type B had the greatest inner-outer diameter ratio (0.67), and Type A had the smallest (0.53). The IT of Type A (5.26 Ncm) was significantly (p = 0.038) lower than that of Type C (8.8 Ncm). There was no significant difference in the pullout strength. The GV of Type A (9.7 mm3) was significantly greater than Type C (8.4 mm3). Type C was significantly greater than Type B (7.2 mm3). The ratios of mechanical properties (PS/IT, PS/GV, and GV/IT) were found significant in intergroup comparison. The PS/GV ratio was in order: Type B (26.5) > Type A (23.0) > Type C (20.2). Spearman's rho rank correlation test showed that PS of Type B was correlated significantly with GV. The design of thread and gripping volume were the important factors that contributes to the mechanical strengths of micro-implant.


The multifractal structure of contrast changes In natural images: from sharp edges To textures
We present a formalism that leads naturally to a hierarchical description of the different contrast structures in images, providing precise definitions of sharp edges and other texture components. Within this formalism, we achieve a decomposition of pixels of the image in sets, the fractal components of the image, such that each set contains only points characterized by a fixed strength of the singularity of the contrast gradient in its neighborhood. A crucial role in this description of images is played by the behavior of contrast differences under changes in scale. Contrary to naive scaling ideas where the image is thought to have uniform transformation properties (Field, 1987), each of these fractal components has its own transformation law and scaling exponents. A conjecture on their biological relevance is also given.


Cervical pedicle screws: comparative accuracy of two insertion techniques.
Independently assessed radiographic and anatomic comparison of device implantation methods. To compare the relative accuracy of two techniques of inserting cervical pedicle screws. In an attempt to define the anatomic risks of cervical pedicle screw insertion, image-guided stereotactic technology was shown to be superior to some other methods in vitro.- Meanwhile, in vivo experience with Abumi's technique of screw insertion has had few clinically relevant instances of screw malposition. There has been no direct comparison between current image-guided technology and Abumi's fluoroscopically assisted technique. The pedicles (C3-C7) of human cadaveric cervical spines were instrumented with 3.5-mm screws with either of two techniques. Cortical integrity and potential neurovascular injury were independently assessed by computed tomographic (CT) scans and anatomic dissection. A cortical breach was considered "critical" if the screw encroached on any vital structure. If any part of the screw violated the cortex of the pedicle but no vital structure was at risk for injury, the breach was classified as "noncritical." In Group I (StealthStation; Sofamor-Danek, Memphis, TN), 82% of screws were placed in the pedicle, and 18% had a critical breach. In Group II (Abumi technique), 88% of screws were placed in the pedicle, and 12% had a critical breach. No statistically significant differences were demonstrated between each group (P = 0.59). Regarding pedicle dimensions and safety of insertion, a critical pedicle diameter of 4.5 mm was determined to be the size below which a critical breach was likely, but above which there was a significantly greater likelihood for safe screw placement. The most common structure injured in each group was the vertebral artery. The use of a computer-assisted image guidance system did not enhance safety or accuracy in placing pedicle screws compared with Abumi's technique. Both techniques have a noteworthy risk of injuring a critical structure if inserted into the pedicles with a diameter of less than 4.5 mm. Under laboratory conditions, pedicles with a diameter of more than 4.5 mm have a significantly greater likelihood of being safely instrumented by either technique. These data indicate that cervical pedicle screw placement is feasible, but it should be reserved for selected circumstances with clear indications and in the presence of suitable pedicle morphology.


Arrhythmias in patients with hypereosinophilia: a comparison of patients with and without Löffler's endomyocardial disease.
About one third of patients with Löffler's endomyocardial disease have abnormal electrocardiograms and some develop arrhythmias and die suddenly. To assess the significance of these findings, continuous ambulatory ECG monitoring was performed for 48 hr on 6 patients with acute or chronic forms of Löffler's endomyocardial disease, and the types and frequencies of arrhythmias were compared with recordings from 6 other patients with equally high blood eosinophil counts who did not have clinically evident cardiac disease. It was hoped that this would show whether arrhythmias were related to high blood eosinophil counts, cardiac injury or other factors. Three of the patients with endomyocardial disease had multiple ventricular extrasystoles with episodes of ventricular arrhythmias and occasional supraventricular arrhythmias which had not been detected with conventional ECGs. These abnormalities did not occur in 2 of the patients with acute endomyocardial lesions who died, nor were they found in patients who did not have congestive cardiac failure or in the control patients. Rhythm disturbances appeared to be most closely related to the development of cardiac failure and they resolved after successful cardiac surgery. Multiple ventricular extrasystoles and arrhythmias occurring in these patients with Löffler's endomyocardial disease are probably due to metabolic changes in the heart associated with cardiac failure and mechanical changes related to valvular dysfunction rather than a direct effect of the eosinophils themselves on the heart.


Mindfulness and nocturnal rumination are independently associated with symptoms of insomnia and depression during pregnancy.
Insomnia and depression are highly prevalent perinatal complications. Ruminating on stress is etiologically implicated in both disorders, and ruminating while trying to fall asleep has been linked to insomnia and depression during pregnancy. Incompatible with rumination is everyday mindfulness, i.e., living with intentional and nonjudgmental awareness of internal and external experiences in the present moment. Responding to stress mindfully may protect against stress-related perinatal complications such as insomnia and depression. The present study described the association between everyday mindfulness and nocturnal rumination, and examined whether these trait characteristics were independently related to perinatal insomnia and depression. Cross-sectional and secondary analysis of existing data from 65 pregnant women recruited from a multisite hospital in Metro Detroit, MI, USA. Subjects completed online surveys including the Insomnia Severity Index, Edinburgh Postnatal Depression Scale, Presleep Arousal Scale, and the revised Cognitive and Affective Mindfulness Scale. Over half (53.8%) of women screened positive for clinical insomnia and 12.3% screened positive for major depression. Women high in mindfulness, relative to those low in mindfulness, reported less nocturnal rumination (Cohen's d=1.16), insomnia symptoms (Cohen's d=1.24), and depressive symptoms (Cohen's d=1.35). Multivariate linear regression revealed that both mindfulness (β=-.24, p=.03) and rumination (β=.38, p<.01) were independently associated with insomnia. Similarly, a multivariate model showed that mindfulness (β=-.41, p<.001) and rumination (β=.35, p<.01) were independently associated with depression. Ruminating in bed at night is strongly associated with insomnia and depression during pregnancy, whereas mindfulness may potentially protect against these stress-related perinatal complications.


Identification of key genes affecting sperm motility in chicken based on whole-transcriptome sequencing.
Sperm motility is an important index for the evaluation of semen quality. Improving sperm motility is important to improve reproductive performance, promote breeding process, and reduce production cost. However, the molecular mechanisms regulating sperm motility in chickens remain unclear. In this study, histological observation and whole-transcriptome analysis were performed on testicular tissue of chickens with high and low sperm motility. Histological observations showed that roosters with high sperm motility exhibited better semen quality than those with low sperm motility. In addition, the germinal epithelial cells of roosters with low sperm motility were loosely arranged and contained many vacuoles. RNA-seq results revealed the expression of 23,033 mRNAs, 2,893 lncRNAs, and 515 miRNAs in chicken testes. Among them, there were 417 differentially expressed mRNAs (DEmRNAs), 106 differentially expressed lncRNAs (DElncRNAs), and 15 differentially expressed miRNAs (DEmiRNAs) between high and low sperm motility testes. These differentially expressed genes were involved in the G protein-coupled receptor signaling pathway, cilia structure, Wnt signaling, MAPK signaling, GnRH signaling, and mTOR signaling. By integrating the competitive relationships between DEmRNAs, DElncRNAs, and DEmiRNAs, we identified the regulatory pathway of MSTRG.3077.3/MSTRG.9085.1-gga-miR-138-5p-CADM1 and MSTRG.2290.1-gga-miR-142-3p-GNAQ/PPP3CA as crucial in the modulation of chicken sperm motility. This study provides new insights into the function and mechanism of ceRNAs in regulating sperm motility in chicken testes.


Permutation Mutual Information: A Novel Approach for Measuring Neuronal Phase-Amplitude Coupling.
Cross-frequency phase-amplitude coupling (PAC) in neuronal oscillations network plays an important functional role in large scale neuronal communication and neuronal encoding. In the present study, a novel approach named permutation mutual information (PMI) was applied in measuring PAC. It is derived from the permutation entropy based on the mutual information theory, by which the mutual information of permutations of two time series can be evaluated. In order to verify the ability of PMI, a numerical test was performed by using both simulation data and experimental data. The performances of PMI were compared with that of two well-known methods, which were the mean vector length (MVL) and the modulation index (MI). It was found that the performance of PMI was similar to that of MI when measuring PAC intensity, but the coupling sensitivity of PMI was the highest among all these three approaches. Moreover, there was the lowest sensitivity in the MVL measurement, suggesting that MVL was a more conservative approach in detecting the existence of PAC. In addition, an ROC analysis showed that PMI performed better in measuring PAC compared to that of others. Furthermore, the experimental data, obtained from rats' hippocampal CA3 regions, were analyzed by using the three approaches. The result was essentially in line with that of the simulation performances. In a word, the results suggest that PMI is a better choice for assessing PAC under the certain conditions.


Dietary prenatal choline supplementation alters postnatal hippocampal structure and function.
Choline, a compound present in many foods, has recently been classified as an essential nutrient for humans. Studies with animal models indicate that the availability of choline during the prenatal period influences neural and cognitive development. Specifically, prenatal choline supplementation has been shown to enhance working memory and hippocampal long-term potentiation (LTP) in adult offspring. However, the cellular mechanisms underlying these effects remain unclear. Here we report that choline supplementation, during a 6-day gestational period, results in greater excitatory responsiveness, reduced slow afterhyperpolarizations (sAHPs), enhanced afterdepolarizing potentials (ADPs), larger somata, and greater basal dendritic arborization among hippocampal CA1 pyramidal cells studied postnatally in juvenile rats (20-25 days of age). These data indicate that dietary supplementation with a single nutrient, choline, during a brief, critical period of prenatal development, alters the structure and function of hippocampal pyramidal cells.


Seroprevalence of rubella and immunogenicity following rubella vaccination in adolescent girls in India.
Serologic surveys conducted in different countries indicate that rubella is a worldwide infection. Several such sero surveys conducted in India have also confirmed that 6-47% of women are susceptible to rubella infection. The current study was conducted on 1,329 female adolescents in 12 districts of Maharashtra, India, to assess their serological status in terms of rubella exposure. After enrollment, a pre-vaccination blood sample was collected from the participants followed by rubella vaccination (R-vac). Adverse events were monitored for the next 6-8 weeks, at which time a post-vaccination sample was collected. Pre-vaccination rubella immunity was higher in the urban (80.2%) population compared to the rural (73.1%) population. Following R-vac vaccination, out of 1,159 participants who completed the study, all (100%) in the urban and 99.5% of participants in the rural area developed antibodies against rubella. Substantial numbers of women reach childbearing age without immunity against rubella and thus are at a risk of passing the infection to their fetuses, who can then develop subsequent congenital defects leading to congenital rubella syndrome (CRS). An immunization policy recommending vaccination with rubella or rubella containing vaccine is highly desirable to prevent rubella and CRS.


Hyperlocal Spatial Flows in BOLD fMRI Expose Novel Brain-Based Correlates of Schizophrenia.
While analysis of temporal signal fluctuations has long been a fixture of blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) research, the role of spatially localized directional diffusion in both signal propagation and emergent large-scale functional integration remains almost entirely neglected. We are proposing an extensible framework to capture and analyze spatially localized fMRI directional signal flow dynamics. The approach is validated in a large resting-state fMRI schizophrenia study where it uncovers significant and novel relationships between hyperlocal spatial dynamics and subject diagnostic status.


A meta-analysis of drug resistant tuberculosis in Sub-Saharan Africa: how strongly associated with previous treatment and HIV co-infection?
In Sub-Saharan Africa, the fight against tuberculosis (TB) has encountered a great challenge because of the emergence of drug resistant TB strains and the high prevalence of HIV infection. The aim of this meta-analysis was to determine the association of drug-resistant TB with anti-TB drug treatment history and HIV co-infection. After electronic based literature search in the databases of Medline, HINARI, EMBASE and the Cochrane library, article selection and data extraction were carried out. HIV co-infection and previous history of TB treatment were used as predictors for the occurrence of any anti-TB drug resistant or multiple drug resistant TB (MDR-TB). The risk ratios for each included study and for the pooled sample were computed using the random-effects model. Heterogeneity test, sensitivity analyses and funnel plots were also done. The pooled analysis showed that the risk of developing drug-resistant TB to at least one anti-TB drug was about 3 times higher in individuals who had a previous history of anti-TB treatment than new TB cases. The risk of having MDR-TB in previously anti-TB treated TB cases was more than 5-fold higher than that of new TB cases. Resistance to Ethambutol and Rifampicin was more than fivefold higher among the previously treated with anti-TB drugs. However, HIV infection was not associated with drug-resistant TB. There was a strong association of previous anti-TB treatment with MDR-TB. Primary treatment warrants special emphasis, and screening for anti-TB drugs sensitivity has to be strengthened.


Differential inhibition of human placental DNA polymerases delta and alpha by BuPdGTP and BuAdATP.
The p-n-butylphenyl- and p-n-butylanilino- substituted analogs of dGTP and dATP, respectively, were tested as inhibitors of purified human placental DNA polymerases alpha and delta. It was observed that DNA polymerase alpha activity was potently inhibited by these analogs with I0.5 values as low as the nanomolar range, whereas DNA polymerase delta activity was poorly inhibited, with I0.5 values of ca. 100 micromolar. These results argue for a distinct identity of these two enzymes, and demonstrate the usefulness of these analogs as probes of DNA polymerase structures. In addition, these analogs provide a rapid method for the discrimination of the two enzyme activities and a means for the selective assay of DNA polymerase delta. Aphidicolin inhibited both DNA polymerases.


Control of lipolysis by a population of oxytocinergic sympathetic neurons.
Oxytocin (OXT), a nine-amino-acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation and social behaviour1, and has become an intriguing therapeutic target for conditions such as autism and schizophrenia2. Exogenous OXT has also been shown to have effects on body weight, lipid levels and glucose homeostasis1,3, suggesting that it may also have therapeutic potential for metabolic disease1,4. It is unclear, however, whether endogenous OXT participates in metabolic homeostasis. Here we show that OXT is a critical regulator of adipose tissue lipolysis in both mice and humans. In addition, OXT serves to facilitate the ability of β-adrenergic agonists to fully promote lipolysis. Most surprisingly, the relevant source of OXT in these metabolic actions is a previously unidentified subpopulation of tyrosine hydroxylase-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism.


Enantioselective Phytotoxicity and the Relative Mechanism of Current Chiral Herbicides.
Regardless of the achievable of chiral switch, most of the chiral nature agrochemical is still sold as racemate or enantiomer-enriched pesticides. Herbicides, accounted for a large proportion in pesticide market, are of great concern due to the frequent occurrence in environment and the structure selective phyto-biochemical impact on plants. We give a systematic search on the literature database and included approximately 50 papers which were related to the review. We do careful categories for the chiral herbicides according to their structure and listed out the acute phytotoxicity endpoints. The potential mechanism for the enantioselective toxicity was concluded into 5 main points. The enantiomer-specific toxicity on plant growth and flowers are limited on phenoxyalkanoic acid herbicide, aryloxyphenoxypropanoic acid, imidazolinone herbicide, and acetamide pesticide. Data available on the potential mechanism explanation of enantioselective phytotoxicity has been concerned on the genetic transcription, oxidative stress, and photosynthesis disruption, etc. A comparison between the two enantiomers' enantioselective effects identified an organ-specific and species-specific phenomenon for several herbicides. Moreover, a more herbicidal activity enantiomer is also displayed the more toxicity than its antipode. The review elucidated a paucity of information on the enantioselective effect research on various types of plants at the different life stages. It appealed us to conduct a more holistic approach to balance the benefit between herbicidal activity and phytotoxicity when try to develop an enantio-pure herbicide.


Peripheral neuropathy in antineutrophil cytoplasmic antibody-associated vasculitides: Insights from the DCVAS study.
Reported prevalence of vasculitic neuropathy (VN) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is highly variable, and associations with other organ manifestations have not been studied systematically while accounting for diagnostic certainty of VN. Data of all patients with AAV within the Diagnostic and Classification criteria for primary systemic VASculitis study were analyzed cross-sectionally. VN was categorized as definite (histology proven), probable (multiple mononeuropathy or nerve biopsy consistent with vasculitis), or possible (all others). Associations with other organ manifestations were compared in patients with and without VN. Nine hundred fifty-five patients (mean age 57 years, range 18-91 years, 51% female) were identified. Of these, 572 had granulomatosis with polyangiitis (GPA), 218 microscopic polyangiitis (MPA), and 165 eosinophilic granulomatosis with polyangiitis (EGPA). The prevalence of VN was 65% in EGPA, 23% in MPA, and 19% in GPA. Nerve biopsy was performed in 32/269 (12%) patients, demonstrating definite vasculitis in 17/32 (53%) of patients. VN was associated with myeloperoxidase-ANCA positivity (p = 0.004) and skin (p < 0.001), musculoskeletal, (p < 0.001) and cardiovascular (p = 0.005) involvement. Patients with VN were less likely to have renal (p < 0.001), eye (p < 0.001), and gastrointestinal (p = 0.023) involvement. Our study provides comprehensive insights into the prevalence and organ associations of VN in a large, systematically collected AAV cohort. VN is most commonly associated with skin, musculoskeletal, and cardiovascular manifestations. In routine clinical practice, diagnosis of VN is infrequently confirmed by the gold standard of nerve biopsy but rather supported by the clinical setting of active systemic AAV.


OpTrust: An Effective Educational Bundle for Enhancing Faculty-resident Intraoperative Entrustment.
The purpose of this study was to measure the efficacy of a novel faculty and resident educational bundle focused on development of faculty-resident behaviors and entrustment in the operating room. As surgical training environments are orienting to entrustable professional activities (EPAs), successful transitions to this model will require significant faculty and resident development. Identifying an effective educational initiative which prepares faculty and residents for optimizing assessment, teaching, learning, and interacting in this model is critical. From September 2015 to June 2017, an experimental study was conducted in the Department of Surgery at the University of Michigan Health System (UMHS). Case observations took place across general, plastic, thoracic, and vascular surgical specialties. A total of 117 operating room observations were conducted during Phase I of the study and 108 operating room observations were conducted during Phase II following the educational intervention. Entrustment behaviors were rated for 56 faculty and 73 resident participants using OpTrust, a validated intraoperative entrustment instrument. Multiple regression analysis showed a significant increase in faculty entrustment (Phase I = 2.32 vs Phase II = 2.56, P < 0.027) and resident entrustability (Phase I = 2.16 vs Phase II = 2.40, P < 0.029) scores following exposure to the educational intervention. Our study shows improved intraoperative entrustment following implementation of faculty and resident development, indicating the efficacy of this innovative educational bundle. This represents a crucial component in the implementation of a competency-based assessment framework like EPAs.


Not All E-commerce Emits Equally: Systematic Quantitative Review of Online and Store Purchases' Carbon Footprint.
Although it has been studied extensively throughout the past 20 years, the environmental impact of e-commerce can still be considered a controversial subject. Particularly for those wondering whether online shopping constitutes a more environmentally friendly alternative to traditional store-based shopping, evidence can be found that quantitatively supports affirmative as well as opposing claims. Findings differ widely because the contexts and assumptions of the studies from which they are drawn differ widely as well. To advance our understanding of this question and inform actions that can actually reduce the environmental impact of shopping, we carried out a systematic quantitative review of environmental impact assessments that compares the carbon footprint of online and store purchases. Based on over twenty scientific studies, we compiled a dataset of 244 purchases, their estimated carbon footprint and information on the contextual, distribution, behavioral, and geographical conditions on which the calculations are based. We conclude from the reviewed studies that online purchases generally generate a lower carbon footprint than store purchases, but only in the case of car-dependent lifestyles, and possibly only because the studies largely overlook transformations in consumer behavior and in the consumption landscape.


CT features of acute COVID-19 and long-term follow-up.
Since the first few cases of pneumonia attributed to infection with the highly contagious novel coronavirus 2 (SARs-CoV-2) were detected in Wuhan, China, in December 2019, imaging has proven an invaluable diagnostic tool throughout the resulting global pandemic. This review describes the imaging features of severe pulmonary disease caused by SARs-CoV-2, named COVID-19 by the World Health Organization (WHO), particularly focussing on computed tomography (CT). CT plays an important role in understanding the pathology behind the progression of disease, as well as helping to identify the potential complications of COVID-19 pneumonia and recognising possible alternative or concurrent diagnoses. This review also focusses on follow-up imaging of survivors of COVID-19, which continues to contribute substantially to our understanding of the longer-term pulmonary changes in patients who have survived severe COVID-19 pneumonia.


[On the histogenesis of cardiac myxoma].
to investigate the morphological and phenotypic features of cardiac myxoma (CM), to discuss argumentative issues on the sources of its growth. The investigation included 176 sporadic and familial myxomas originating from different cardiac chambers (96% from the atria). The histological, ultrastructural, and immunohistochemical features of the cells and vessels of this tumor were studied. The morphological and phenotypic features of the embryonic endothelium resembling the cells of the primary cardiovascular network were found in the cells and vessels of CM. No signs of other mesenchymal derivatives were detected. The authors anticipate that there is focal cessation of maturation of the embryonic endocardial endothelium and its persistence - hamartia. Postnatal proliferation of embryonic hamartia forms the tumor hamartoma. Differentiated cells may retain the phenotypic (but not morphological) features of closely related cells that have a common precursor. The results of the study have allowed the authors to consider CM to be hamartoma, a monohistioid benign embryonic endocardial endothelioma. Our findings do not exclude the possibility of developing CM from pluripotent mesenchymal cells.


Gold Nanotheranostics: Proof-of-Concept or Clinical Tool?
Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial-nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting, imaging and therapeutics in a single platform, with proven applicability in the management of heterogeneous diseases, such as cancer. In this review, we focus on gold nanoparticle-based theranostics at the lab bench, through pre-clinical and clinical stages. With few products facing clinical trials, much remains to be done to effectively assess the real benefits of nanotheranostics at the clinical level. Hence, we also discuss the efforts currently being made to translate nanotheranostics into the market, as well as their commercial impact.


Porphyrobacter algicida sp. nov., an algalytic bacterium isolated from seawater.
A novel Gram-stain-negative, yellow-pigmented, catalase- and oxidase-positive, non-endospore-forming, flagellated bacterium, designated strain Yeonmyeong 2-22T, was isolated from surface seawater of Geoje Island, Republic of Korea. Strain Yeonmyeong 2-22T showed algalytic activity against the seven strains tested: Cochlodinium polykrikoides, Chattonella marina, Heterosigma akashiwo, Scrippsiella trochoidea, Heterocapsa triquetra, Prorocentrum minimum and Skeletonema costatum. A taxonomic study was carried out based on a polyphasic approach to characterize the exact taxonomic position of strain Yeonmyeong 2-22T. The bacterium was able to grow at 10-40 °C, at salinities from 0 to 9 %, at pH from 4.0 to 9.0 and was not able to degrade gelatin or casein. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain Yeonmyeong 2-22T was considered to represent a novel species of the genus Porphyrobacter, which belongs to the family Erythrobacteraceae, and was related most closely to Porphyrobacter dokdonensis DSW-74T with 97.23 % 16S rRNA gene sequence similarity. The dominant cellular fatty acids of strain Yeonmyeong 2-22T were C18 : 1ω7c (49.7 %), C16 : 0 (12.0 %) and 11-methyl C18 : 1ω7c (11.5 %), and ubiquinone-10 (Q-10) was the predominant respiratory lipoquinone. The genomic DNA G+C content of strain Yeonmyeong 2-22T was calculated to be 63.0 mol%. Phenotypic characteristics of the novel strain also differed from other members of the genus Porphyrobacter. On the basis of polyphasic taxonomic data, strain Yeonmyeong 2-22Trepresents as a novel species of the genus Porphyrobacter, for which the name of Porphyrobacter algicida sp. nov. is proposed. The type strain is Yeonmyeong 2-22T (=KEMB 9005-328T=JCM 31499T).


[Surgical treatment of compression of the parapelvic portion of the ureter by the lower polar renal vessels in children].
Suboperative observations of 73 patients have shown that lower polar renal vessels are often associated with other abnormalities (congenital fibrosis and segmentary hypoplasia of the parapelvic portion of the ureter resulting in the development of hydronephrosis, chronic urethritis, atrophy of the muscle layer and secondary stenosis of the ureter). The operation of choice is resection of the pyeloureteral segment and part of the pelvis followed by antevasal anastomosis.


FVIII inhibitor surveillance in children with hemophilia A in Indonesia: a report from the Indonesian Pediatric Hematology-Oncology Working Group.
Factor VIII (FVIII) inhibitor diagnosis and surveillance in Indonesia are challenging owing to geographic conditions and the lack of laboratory facilities nationwide for inhibitor assays. This study aimed to determine the prevalence of FVIII inhibitors in children diagnosed with hemophilia A (HA) in Indonesia. A cross-sectional study was conducted in 12 hospitals in eight provinces of Indonesia between 2020 and 2021. Factor VIII inhibitor screening was performed in a central hemostasis laboratory for all children with HA (≤18 yr) who had received a minimum of 10 exposure days to clotting factor concentrates. The FVIII inhibitor titer was determined using the Bethesda assay. Children (388) were enrolled in this study, including 219 (56.4%), 131 (33.8%), and 38 (9.4%) with severe, moderate, and mild HA, respectively. The prevalence of children who developed FVIII inhibitors was 37 out of 388 (9.6%). Factor VIII inhibitors were found in 25/219 (11.4%) severe, 11/131 (8.3%) moderate, and 1/38 (2.6%) children with mild HA. Thirteen children had low-titer inhibitors and 24 had high-titer inhibitors, with a median of 9.44 (1.48‒412.0) Bethesda Units. Among 13 children with low-titer inhibitors, eight underwent a confirmation test, of which five tested negative and were classified as transient. A significant difference in annual joint bleeding rate was found between patients with low and high inhibitor titers and those without inhibitors (P<0.001). Factor VIII inhibitor prevalence in Indonesia was relatively low. However, the risk factors that may contribute to FVIII inhibitor development among Indonesian patients require further study.


Potassium ion fluxes in corneal epithelial cells exposed to UVB.
The goal of this study was to investigate the efflux of K(+) from human corneal limbal epithelial cells (HCLE) exposed to ambient levels of UVB, which is known to cause apoptosis, and to examine the effect of K(+) channel blockers on loss of potassium induced by UVB. HCLE cells were exposed to 100-200 mJ/cm(2) UVB, followed by incubation in culture media with 5.5-100 mM K(+), BDS-1, Ba(2+) or ouabain. To measure intracellular cations, cells were washed in 280 mM sucrose and lysed in DI water. K(+) and Na(+) levels in lysates were measured by ion chromatography. HCLE cells showed maximal loss of K(+)(i) 10 min after exposure to UVB and 5.5 mM K(+) media, with recovery of normal K(+) levels after 90 min. Treatment with 1 μM BDS-1 following UVB exposure reduced the loss of K(+) by HCLE cells. Exposure to 0.1-5 mM Ba(2+) inhibited UVB-induced K(+) loss in a time and dose-dependent manner. These results confirm that blocking K(+) channels in HCLE cells exposed to UVB prevents efflux of K(+), confirming that UVB activates K(+) channels in these cells. Electrophysiology data show that K(+) channels remain highly active at least 90 min after UVB exposure. HCLE cells exposed to UVB and incubated in 0.01-1 μM ouabain did not recover from UVB-induced K(+) loss. These data suggest that the Na/K pump may act to restore [K(+)](i) to control levels in HCLE cells following UVB exposure and that the pump is not damaged by exposure to UVB. Incubation of HCLE cells exposed to UVB in medium with 25-100 mM K(+) media prevented K(+) efflux at extracellular concentrations as low as 25 mM (the concentration in tear fluid), maintaining control levels of K(+)(i). In all experiments inward fluxes and intracellular Na(+) levels mirrored K(+) changes, albeit at the expected lower concentrations. The prevention of UVB-induced K(i)(+) loss by 25 mM K(o)(+) is consistent with the possible contribution of the relatively high K(+) concentration in tears to protection of the corneal epithelium from ambient UVB.


Identity-specific coding of future rewards in the human orbitofrontal cortex.
Nervous systems must encode information about the identity of expected outcomes to make adaptive decisions. However, the neural mechanisms underlying identity-specific value signaling remain poorly understood. By manipulating the value and identity of appetizing food odors in a pattern-based imaging paradigm of human classical conditioning, we were able to identify dissociable predictive representations of identity-specific reward in orbitofrontal cortex (OFC) and identity-general reward in ventromedial prefrontal cortex (vmPFC). Reward-related functional coupling between OFC and olfactory (piriform) cortex and between vmPFC and amygdala revealed parallel pathways that support identity-specific and -general predictive signaling. The demonstration of identity-specific value representations in OFC highlights a role for this region in model-based behavior and reveals mechanisms by which appetitive behavior can go awry.


Proposal of Epidemiological Cutoff Values for Apramycin 15 μg and Florfenicol 30 μg Disks Applicable to Staphylococcus aureus.
Apramycin and florfenicol are two antimicrobial agents exclusively used in veterinary medicine. Resistance determinants to these antimicrobial agents have been described in several staphylococci, yet no inhibition zone-based epidemiological cutoff (ECOFF) values are available to detect populations harboring resistance mechanisms. In this study, we propose disk diffusion inhibition zone ECOFF values of Staphylococcus aureus for apramycin and florfenicol. The susceptibility to apramycin and florfenicol was evaluated by disk diffusion of five S. aureus collections, comprising 352 isolates of animal (n = 265) and human (n = 87) origin. The aggregated distributions of inhibition zone diameters were analyzed by the normalized resistance interpretation method to obtain normalized wild-type (WT) population distributions and corresponding ECOFF values. The putative WT populations of S. aureus were characterized by an inhibition zone ≥15 mm (ECOFF = 15 mm) for apramycin and ≥21 mm for florfenicol (ECOFF = 21 mm). Five nonwild-type (NWT) isolates were detected for apramycin, all without inhibition zone and harboring the apmA gene, whereas five NWT isolates were identified for florfenicol, all carrying the fexA gene. The proposed ECOFF values for apramycin and florfenicol may be a valuable tool in future antimicrobial resistance monitoring and surveillance studies to identify S. aureus NWT populations toward these antimicrobial agents.


Effects of Side-Chain Spacing and Length on Hydration States of Poly(2-methoxyethyl acrylate) Analogues: A Molecular Dynamics Study.
Hydration states of polymers are known to directly influence the adsorption of biomolecules. Particularly, intermediate water (IW) has been found able to prevent protein adsorption. Experimental studies have examined the IW content and nonthrombogenicity of poly(2-methoxyethyl acrylate) analogues with different side-chain spacings and lengths, which are HPx (x is the number of backbone carbons in a monomer) and PMCyA (y is the number of carbons in-between ester and ether oxygens of the side-chain) series, respectively. HPx was reported to possess more IW content but lower nonthrombogenicity compared to PMCyA with analogous composition. To understand the reason for the conflict, molecular dynamics simulations were conducted to elucidate the difference in the properties between the HPx and PMCyA. Simulation results showed that the presence of more methylene groups in the side chain more effectively prohibits water penetration in the polymer than those in the polymer backbone, causing a lower IW content in the PMCyA. At a high water content, the methoxy oxygen in the shorter side chain of the HPx cannot effectively bind water compared to that in the PMCyA side chain. HPx side chains may have more room to contact with molecules other than water (e.g., proteins), causing experimentally less nonthrombogenicity of HPx than that of PMCyA. In summary, theoretical simulations successfully explained the difference in the effects of side-chain spacing and length in atomistic scale.


Markers of Hypoxia Correlate with Histologic and Endoscopic Severity of Colitis in Inflammatory Bowel Disease.
Inflammation results in significant shifts in tissue metabolism. Recent studies indicate that inflammation and hypoxia occur concomitantly. We examined whether circulating and tissue markers of hypoxia could serve as surrogate indicators of disease severity in adult and pediatric patients with inflammatory bowel disease (IBD). Serum and colonic biopsies were obtained from pediatric subjects with active IBD colitis and adult subjects with active and inactive ulcerative colitis, along with healthy non-colitis controls of all ages. Disease activity was evaluated by endoscopy and histopathology. Levels of serum hypoxia markers (macrophage inflammatory protein-3α [MIP-3α], vascular endothelial growth factor [VEGF], and erythropoietin [EPO]) were measured. Children with active IBD colitis had higher levels of serum MIP-3α and VEGF compared to non-colitis controls (p<0.01 and p<0.05, respectively). In adult subjects with endoscopically active ulcerative colitis, serum MIP-3α and EPO were significantly elevated compared to non-colitis controls (both p<0.01). In parallel, analysis of colon tissue MIP-3α mRNA and protein in pediatric subjects revealed increased expression in those with IBD colitis compared to controls (p<0.05 and p<0.01 for mRNA and protein, respectively). Serum MIP-3α and VEGF significantly increased with histology grade. Peripheral blood hypoxia markers may be useful indicators of disease activity for pediatric and adult IBD patients.


Molecular dissection of heterosis manifestation during early maize root development.
Heterosis is of paramount agronomic importance and has been successfully exploited in maize hybrid breeding for decades. Nevertheless, the molecular basis of heterosis remains elusive. Heterosis is not only observed in adult traits like yield or plant height, but is already detected during embryo and seedling development. Hence, the maize (Zea mays L.) primary root which is the first organ that emerges after germination is a suitable model to study heterosis manifestation. Various seedling root traits including primary root length and lateral root density display heterosis. Microarray studies suggest organ specific patterns of nonadditive gene expression in maize hybrids. Moreover, such experiments support the notion that global expression trends in maize primary roots are conserved between different hybrids. Furthermore, nonadditive expression patterns of specific genes such as a SUPEROXIDE DISMUTASE 2 might contribute to the early manifestation of heterosis. Proteome profiling experiments of maize hybrid primary roots revealed nonadditive accumulation patterns that were distinct from the corresponding RNA profiles underscoring the importance of posttranscriptional processes such as protein modifications that might be related to heterosis. Finally, analysis of selected metabolites imply that a subtle regulation of particular biochemical pathways such as the phenylpropanoid pathway in hybrids might contribute to the manifestation of heterosis in maize primary roots. In the future, recently developed molecular tools will facilitate the analysis of the molecular principles underlying heterosis in maize roots.


Structural Analysis of Plasmodium falciparum Hexokinase Provides Novel Information about Catalysis Due to a Plasmodium-Specific Insertion.
The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite's strong dependence on this pathway and the significant structural differences of its glycolytic enzymes compared to its human counterpart, glycolysis is considered a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK) containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion that lines the active site. Moreover, we propose that this insertion plays a role in ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both S-glutathionylation and S-nitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.


Molecular quantum similarity analysis of estrogenic activity.
The main objective of this study was to evaluate the capability of 120 aromatic chemicals to bind to the human alpha estrogen receptor (hER alpha) by the use of quantum similarity methods. The experimental data were segregated into two categories, i.e., those compounds with and without estrogenicity activity (active and inactive). To identify potential ligands, semiquantitative structure-activity relationships were developed for the complete set correlating the presence or lack of binding affinity to the estrogen receptor with structural features of the molecules. The structure-activity relationships were based upon molecular similarity indices, which implicitly contain information related to changes in the electron distributions of the molecules, along with indicator variables, accounting for several structural features. In addition, the whole set was split into several chemical classes for modeling purposes. Models were validated by dividing the complete set into several training and test sets to allow for external predictions to be made.


Desmosomal plaque-associated vimentin filaments in human ovarian granulosa cell tumors of various histologic patterns.
Proteins of intermediate-sized filaments and desmosomal plaques (desmoplakins) of four human ovarian granulosa cell tumors were studied by immunofluorescence and immunoelectron microscopy and by two-dimensional gel electrophoresis of microdissected tissue samples. All tumor cells, irrespective of their specific histologic patterns, contained both vimentin and desmoplakins. Cytokeratin-positive structures were absent or very scant in most tumor regions, but more common in trabecular, insular, macro- and microfollicular structures. Biochemical analysis revealed the presence of Cytokeratin Polypeptides 8 and 18. Desmin filaments, neurofilaments, and glial filaments were not detected. Immunoelectron microscopy showed vimentin filaments attached to desmoplakin-positive plaques of desmosomes. These results indicate that granulosa cell tumors contain true desmosomes, which are associated primarily with vimentin filaments. This phenomenon has so far only been described in meningiomas and in blastema cells of nephroblastomas. Our observations suggest that in most neoplastic granulosa cells one epithelial feature, ie, cytokeratin expression, is greatly reduced, whereas desmosomes are still formed in appreciable frequencies. This unusual constellation of cytoskeletal elements in granulosa cell tumors may be useful in the differential diagnosis from other ovarian neoplasms, especially undifferentiated carcinomas. The importance of the use of antibodies specific for exclusively desmosomal proteins in classifying morphologically ill-defined junctional structures (eg, "rudimentary junctions," "primitive junctions," "desmosome-like junctions") is emphasized.


Axial differences in endocytosis along the kidney proximal tubule.
The proximal tubule (PT) reabsorbs filtered proteins via receptor-mediated endocytosis to prevent energetically inefficient wasting in the urine. Recent intravital imaging studies have suggested that protein reabsorption occurs in early (S1) segments, which have a very high capacity. In contrast, uptake of fluid phase substrates also occurs in distal (S2) segments. In this article, we will review these findings and their implications for understanding integrated proximal tubular function, patterns of damage caused by endocytosed toxins, and the origins of proteinuria. We will also discuss whether compensatory downstream increases in protein uptake might occur in disease states, and the environmental factors that could drive these changes.


In-Plane Structure of the Liquid-Vapor Interface of an Alloy: A Grazing Incidence X-ray Diffraction Study of Bismuth:Gallium.
The liquid-vapor interface of a bismuth-gallium mixture (0.2 percent bismuth and 99.8 percent gallium) at 36 degrees C has been studied by grazing incidence x-ray diffraction. The data show, in agreement with thermodynamic arguments, that bismuth is heavily concentrated in the liquid-vapor interface. The x-ray diffraction data are interpreted with the assistance of a simple model that represents the interface as a partial monolayer of bismuth. This analysis leads to the conclusion that the bismuth concentration in the interface is about 80 percent, that there is no significant mixing of gallium and bismuth in the interface, and that the structure function of the interfacial bismuth is like that of supercooled bulk liquid bismuth.


Effects of Home- and Center-Based Exercise Programs on the Strength, Function, and Gait of Prefrail Older Women: A Randomized Control Trial.
The aims of this study were to compare the effects of a multicomponent exercise program provided at a center (CB) versus done part at home and part at a center (H+CB) on frailty status, strength, physical function, and gait of prefrail older women. Twenty-five women were randomly allocated into the CB (n = 14; 69 ± 6 years) and the H+CB (n = 11; 69 ± 7 years) groups. Both groups completed an exercise program including strengthening, balance, and gait exercises. The program was 12 weeks long, done three times per week, for 60 min per session. Frailty, knee and hip muscle strength, spatiotemporal parameters of the usual and maximum speed dual-task gait, and physical function were assessed at baseline and after program completion. The exercise program reversed the prefrail status of most participants independently of the mode of delivery. Strength increased in both groups, but the CB group had more pronounced improvements in gait and physical function. H+CB exercise programs are good options for prefrail older women.


A new strategy for canine visceral leishmaniasis diagnosis based on FTIR spectroscopy and machine learning.
Visceral leishmaniasis is a neglected disease caused by protozoan parasites of the genus Leishmania. The successful control of the disease depends on its accurate and early diagnosis, which is usually made by combining clinical symptoms with laboratory tests such as serological, parasitological, and molecular tests. However, early diagnosis based on serological tests may exhibit low accuracy due to lack of specificity caused by cross-reactivities with other pathogens, and sensitivity issues related, among other reasons, to disease stage, leading to misdiagnosis. In this study was investigated the use of mid-infrared spectroscopy and multivariate analysis to perform a fast, accurate, and easy canine visceral leishmaniasis diagnosis. Canine blood sera of 20 noninfected, 20 Leishmania infantum, and eight Trypanosoma evansi infected dogs were studied. The data demonstrate that principal component analysis with machine learning algorithms achieved an overall accuracy above 85% in the diagnosis.


1-Year Survival of Subjects Discharged From a Long-Term Chronic Ventilator Unit.
Among survivors of intensive care, many remain dependent on mechanical ventilation and are discharged to long-term chronic ventilator units or to skilled nursing facilities. Few long-term outcome data are available on patients transferred from long-term chronic ventilator units. We retrospectively followed subjects discharged from a long-term chronic ventilator unit from 2010-2012. We determined where these subjects went, evaluating whether location of discharge had an effect on mortality. We followed 79 subjects who were 64.9 ± 15.9 y old. Average stay in the long-term chronic ventilator unit was 38.5 ± 20.1 d. Within the first year after discharge, 24 (30.3%) subjects died: 17 in a skilled nursing facility, 7 at home. Of those who survived the first year, 28 had been discharged to a skilled nursing facility and 27 to home. Survivors were younger (62.6 ± 12.4 vs 70.4 ± 13.1 y, P = .03), had shorter intensive care unit lengths of stay (10.4 ± 5.0 vs 16.4 ± 11.5 d, P = .03), and were more likely discharged home from long-term chronic ventilator unit (49.0% vs 29.1%, P = .040). Subjects discharged from an long-term chronic ventilator unit and were alive at 1 y had shorter stays in the ICU and were more likely to be discharged home. Further attention is warranted to assure the survival of critical care patients once they are discharged from intensive care units.


Fast phase randomization via two-folds.
A two-fold is a singular point on the discontinuity surface of a piecewise-smooth vector field, at which the vector field is tangent to the discontinuity surface on both sides. If an orbit passes through an invisible two-fold (also known as a Teixeira singularity) before settling to regular periodic motion, then the phase of that motion cannot be determined from initial conditions, and, in the presence of small noise, the asymptotic phase of a large number of sample solutions is highly random. In this paper, we show how the probability distribution of the asymptotic phase depends on the global nonlinear dynamics. We also show how the phase of a smooth oscillator can be randomized by applying a simple discontinuous control law that generates an invisible two-fold. We propose that such a control law can be used to desynchronize a collection of oscillators, and that this manner of phase randomization is fast compared with existing methods (which use fixed points as phase singularities), because there is no slowing of the dynamics near a two-fold.


Immunogenicity of Salmonella typhi Ty21a vaccine for young children.
An attenuated Salmonella typhi Ty21a vaccine was administered to 18 infants and toddlers (less than or equal to 24 months old) to determine its safety and immunogenicity. The vaccination (10(9) CFU per dose, three doses) was well tolerated. However, after the vaccination there was no evidence of a humoral or cellular immune response to S. typhi. The vaccine used was known to be immunogenic for older children and adults. The results support the view that the immunogenicity of Ty21a is age dependent.


Publication Rate and Consistency of Registered Trials of Motor-Based Stroke Rehabilitation.
To determine the publication rate of motor-rehabilitation trials poststroke and the consistency between registry records and their corresponding main publications in trial design, primary objectives and outcomes, eligibility criteria, and sample size. We searched 18 clinical trial registries to identify randomized controlled trials of motor-based stroke rehabilitation registered after July 2005 and completed before April 2017. Eligible trials included adults with stroke, with at least one outcome measure related to motor function. Information in the registry records was compared with that of their main publications, if any. Three hundred twenty-three trials met our eligibility criteria; we were unable to find a peer-reviewed publication reporting the main findings for 46% (150/323) of these. Of the 169 trials with peer-reviewed articles published in English, 141 (83%) were consistent with the registry record in trial design, 100 (59%) were consistent in primary objectives, 71 (42%) were consistent in primary outcomes, 28 (17%) were consistent in eligibility criteria, and 74 (44%) were consistent in sample size. Approximately half of motor-based stroke rehabilitation trials were not published, even more than 3 years after the end of the trial. When main publications were found, they substantially deviated from information in the registry record. These findings highlight the importance of trial registries for identifying unpublished stroke rehabilitation trials and of searching trial registries when conducting systematic reviews and meta-analysis to help ensure that reviews are unbiased.


[Effect of a short course of physical training on the mental status of post-myocardial infarct patients].
The psychological effect of short exercise on a bicycle trainer (30 sessions over 10 weeks) was assessed in 20 postmyocardial infarction patients, while spontaneous mental changes were assessed in 21 untrained controls. Exercise was started 2 to 2.5 months after the attack. Mental states were assessed by the brief multifactorial personality assessment questionary (the BMPAQ test) and the neuroticism scale (NS). Physical exercise contributed to a more rapid psychological rehabilitation, as evidenced by the BMPAQ and NS testing. The mentality of the control patients improved less rapidly as shown by the BMPAQ test, while their NS parameters remained unchanged. Mental parameters of trained and untrained patients were basically similar within 12 months, after myocardial infarction as evidenced by the BMPAQ test.


Stress, catecholamines, and sleep.
Difficulties in defining stress stem from its subjective nature. Measurements of stress based on its effects on physical and mental morbidity tend to be speculative because of the multifactorial causation of stress-related diseases, and the characteristically long time-lag between stress states and morbidity. In this study catecholamine output was measured in a group of adults Oxfordshire villagers and the observed variations were related to their lifestyles and health perceptions. A marked circadian variation was observed with adrenaline showing the most marked associations with lifestyle. In men it was possible to account for a relatively high proportion of the variation in adrenaline excretion by relating values to certain factors associated with stress. In women there appears to be a similar association between adrenaline output and the social class of the husband. Data were also obtained on sleep characteristics, which were assessed with regard to lifestyle. Very broadly, sleep duration is related to the level of waking activity, while sleep latency and quality are correlated with people's self-perception of health.


A comparison of two selective interrupted suture removal techniques for control of post keratoplasty astigmatism.
Two selective interrupted suture removal techniques were compared to determine which technique resulted in earliest, best visual acuity and least postoperative astigmatism. Sixty-five consecutive optical penetrating keratoplasties were performed using 12 interrupted 10-0 nylon sutures and a 12-bite continuous 10-0 nylon suture, and were alternately assigned to 1 of 2 selective suture removal groups. All patients had refraction, keratometry, and videokeratoscopy postoperatively, starting at 6 weeks. Six weeks postoperatively, Group I underwent simultaneous removal of six alternate sutures, with the first of the 6 sutures removed at the steepest meridian, while Group II had selective sutures removed only at the steepest meridian, if associated with greater than 2 diopters of astigmatism in that meridian. Subsequently, interrupted sutures were then selectively removed until the resultant astigmatism approached 3.0 diopters or less. Measurements of resultant astigmatism are reported prior to selective suture removal, following selective suture removal, at 6 months postoperatively, at the completion of all selective suture removal, and at the final visit. At 6 months, residual astigmatism after the 2 techniques of selective suture removal, as measured by refraction, keratometry, and computer-assisted videokeratoscopy, was 2.8, 3.0 and 3.4 diopters for Group I, and 2.2, 2.6 and 3.7 diopters for Group II. At 1 year, the average final visit, astigmatism was 2.5, 2.4 and 2.7 diopters for Group I, and 2.1, 2.0 and 2.3 diopters for Group II. By the final visit, a best corrected vision of 20/50 or better was achieved in 86% of eyes in Group I and in 65% of eyes in Group II, and there was a significant difference in average keratometry of 47.4 diopters in Group I compared to 46.0 diopters in Group II and, as measured by videokeratoscopy, 47.9 diopters in Group I compared to 45.8 diopters in Group II. Selective suture removal by either technique reduces keratoplasty astigmatism with residual interrupted and continuous sutures in place. The combined use of refraction, keratometry, and videokeratoscopy probably provides more reliable and reproducible quantitative measurements of astigmatism. Minimizing astigmatism by selective suture removal is a major factor in the attempt to achieve excellent and visual function in the majority of patients who have undergone penetrating keratoplasty.


The Sugar Metabolic Model of Aspergillus niger Can Only Be Reliably Transferred to Fungi of Its Phylum.
Fungi play a critical role in the global carbon cycle by degrading plant polysaccharides to small sugars and metabolizing them as carbon and energy sources. We mapped the well-established sugar metabolic network of Aspergillus niger to five taxonomically distant species (Aspergillus nidulans, Penicillium subrubescens, Trichoderma reesei, Phanerochaete chrysosporium and Dichomitus squalens) using an orthology-based approach. The diversity of sugar metabolism correlates well with the taxonomic distance of the fungi. The pathways are highly conserved between the three studied Eurotiomycetes (A. niger, A. nidulans, P. subrubescens). A higher level of diversity was observed between the T. reesei and A. niger, and even more so for the two Basidiomycetes. These results were confirmed by integrative analysis of transcriptome, proteome and metabolome, as well as growth profiles of the fungi growing on the corresponding sugars. In conclusion, the establishment of sugar pathway models in different fungi revealed the diversity of fungal sugar conversion and provided a valuable resource for the community, which would facilitate rational metabolic engineering of these fungi as microbial cell factories.


Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration.
Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Thymoquinone is the main bioactive compound of Nigella sativa. In this study, the preparation, gastroprotective effects, and pharmacokinetic (PK) properties of thymoquinone (TQ)-loaded NLCs (TQNLCs) were evaluated. TQNLCs were prepared using hydrogenated palm oil (Softisan® 154), olive oil, and phosphatidylcholine for the lipid phase and sorbitol, polysorbate 80, thimerosal, and double distilled water for the liquid lipid material. A morphological assessment of TQNLCs was performed using various methods. Analysis of the ulcer index, hydrogen concentration, mucus content, and biochemical and histochemical studies confirmed that the loading of TQ into the NLCs significantly improved the gastroprotective activity of this natural compound against the formation of ethanol-induced ulcers. The safety of TQNLC was tested on WRL68 liver normal cells with cisplatin as a positive control. The average diameter of the TQNLCs was 75 ± 2.4 nm. The particles had negative zeta potential values of -31 ± 0.1 mV and a single melting peak of 55.85°C. Immunohistochemical methods revealed that TQNLCs inhibited the formation of ethanol-induced ulcers through the modulation of heat shock protein-70 (Hsp70). Acute hepatotoxic effects of the TQNLCs were not observed in rats or normal human liver cells (WRL-68). After validation, PK studies in rabbits showed that the PK properties of TQ were improved and indicated that the drug behaves linearly. The Tmax, Cmax, and elimination half-life of TQ were found to be 3.96 ± 0.19 hours, 4811.33 ± 55.52 ng/mL, and 4.4933 ± 0.015 hours, respectively, indicating that TQ is suitable for extravascular administration. NLCs could be a promising vehicle for the oral delivery of TQ and improve its gastroprotective properties.


Recurrent disease or donor cell leukemia?: Brain teaser after allogeneic bone marrow transplantation.
Allogeneic bone marrow transplantation (allo-BMT) is the treatment of choice for many patients with poor prognosis or refractory leukemia. Chimerism and residual tumor load after allo-BMT are widely monitored to detect impending graft rejection and the early phase of relapse. In most cases, the malignant cell population during post-transplant relapse contains host-derived cells, but the leukemic clone can rarely be of donor-cell origin. Various genetic tests with different strategies, targets and sensitivities are available for donor-host discrimination. However, changes in the genomic material of the dominant host cell population as a result of clonal evolution and/or clonal selection can hamper the correct identification of the origin of aberrant cells after allo-BMT, thus confounding the assessment of the chimeric state. Consequently, a good knowledge of the techniques applied in clinical practice and careful interpretation of their results are essential. A lack of host-specific markers at the time of clinical relapse is not adequate for verifying the presence of donor cell leukemia, and unequivocal demonstration of donor-specific markers is also required.


The use of carer perspectives and expert consensus to define key components of a biopsychosocial support intervention for stroke carers.
Objective: To identify the key components of a biopsychosocial support intervention to improve mental wellbeing for informal stroke carers within the first year post-stroke based on the combined perspectives of experts in the field of psychological care after stroke and informal stroke carers themselves. Methods: After reviewing the existing literature a cross-sectional mixed-methods design was adopted comprising 1) focus groups with informal stroke carers about their psychological support needs, and 2) nominal group technique with academic and clinical stroke care experts to reach consensus on intervention priorities. Transcripts were thematically analyzed and combined with the ranked priorities from the nominal group to identify key components for intervention content. Results: Key themes for informal stroke carers were associated with: 1) changes in relationships, roles, and dynamics; 2) emotional impact and acceptance; 3) drawing on inner resources; 4) looking for information, solutions, and explanations; 5) support from others. The expert nominal group placed priority on eight ranked areas: 1) acknowledging "normal" emotions; 2) education about the effects of a stroke; 3) reactions to loss and adjustment; 4) recognizing signs and symptoms of not coping; 5) knowing how and when to access practical and emotional support; 6) strategies for taking care of own health; 7) dealing with difficult emotions; and 8) problem solving skills. Conclusions: Themes from the informal carer focus groups, and ranked priority areas will inform the development of a biopsychosocial support intervention for stroke carers to be tested in a feasibility randomized controlled trial.


Breast cancer statistics, 2017, racial disparity in mortality by state.
In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 252,710 new cases of invasive breast cancer and 40,610 breast cancer deaths are expected to occur among US women in 2017. From 2005 to 2014, overall breast cancer incidence rates increased among Asian/Pacific Islander (1.7% per year), non-Hispanic black (NHB) (0.4% per year), and Hispanic (0.3% per year) women but were stable in non-Hispanic white (NHW) and American Indian/Alaska Native (AI/AN) women. The increasing trends were driven by increases in hormone receptor-positive breast cancer, which increased among all racial/ethnic groups, whereas rates of hormone receptor-negative breast cancers decreased. From 1989 to 2015, breast cancer death rates decreased by 39%, which translates to 322,600 averted breast cancer deaths in the United States. During 2006 to 2015, death rates decreased in all racial/ethnic groups, including AI/ANs. However, NHB women continued to have higher breast cancer death rates than NHW women, with rates 39% higher (mortality rate ratio [MRR], 1.39; 95% confidence interval [CI], 1.35-1.43) in NHB women in 2015, although the disparity has ceased to widen since 2011. By state, excess death rates in black women ranged from 20% in Nevada (MRR, 1.20; 95% CI, 1.01-1.42) to 66% in Louisiana (MRR, 1.66; 95% CI, 1.54, 1.79). Notably, breast cancer death rates were not significantly different in NHB and NHW women in 7 states, perhaps reflecting an elimination of disparities and/or a lack of statistical power. Improving access to care for all populations could eliminate the racial disparity in breast cancer mortality and accelerate the reduction in deaths from this malignancy nationwide. CA Cancer J Clin 2017;67:439-448. © 2017 American Cancer Society.


Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced.
Evaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year. Adults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated. Of 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease. Guselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.


c-Rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells.
The polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation, and tumorigenesis. The mechanism by which Ezh2 expression is regulated is not well defined. In the current study, we report that c-Rel is a critical activator of Ezh2 transcription in lymphoid cells. In activated primary murine B and T cells, plus human leukemia and multiple myeloma cell lines, recruitment of c-Rel to the first intron of the Ezh2 locus promoted Ezh2 mRNA expression. This up-regulation was abolished in activated c-Rel-deficient lymphocytes and by c-Rel knockdown in Jurkat T cells. Treatment of malignant cells with the c-Rel inhibitor pentoxifylline not only reduced c-Rel nuclear translocation and Ezh2 expression, but also enhanced their sensitivity to the Ezh2-specific drug, GSK126 through increased growth inhibition and cell death. In summary, our demonstration that c-Rel regulates Ezh2 expression in lymphocytes and malignant lymphoid cells reveals a novel transcriptional network in transformed lymphoid cells expressing high levels of Ezh2 that provides a molecular justification for combinatorial drug therapy.


Microscopic Analysis of Pre-Insertion Cutting Modalities on Custom, Flexible Iris Prostheses.
To determine the induced edge effects of different clinically utilized device post-manufacture modification styles and modalities on custom iris implants. 1) Academically affiliated multispecialty private practice group, 2) Academic medical Center. Laboratory study. Sample custom iris prostheses were cut using patterns, blades, and surgical instruments described in the literature. The cut edges were evaluated with slit lamp microscopy, light microscopy, and scanning electron microscopy. Disposable blades yielded smoother cuts than scissors. Trephine blade brand significantly impacted the cut surface smoothness of the silicone matrix. Meshwork-embedded prostheses had some irregular sharp edges where the mesh fibers were cut with all modalities, though these were worse with scissors and one tested trephine brand compared to the other. Pseudo-iridectomies and scissor cuts created sharp points and corners in the device periphery. Post-manufacture modifications of iris implants should be minimized. The cut margins of the fiber-free implants have fewer sharp edges and may be preferable for sulcus placement. In-the-bag device placement may mitigate clinical impact of sharp edges and corners. These practices may help to minimize inflammatory sequelae post-implantation.


Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart.
Mitochondrial quality is a crucial determinant of cell viability, and mitochondrial autophagy plays a central role in this control mechanism. Based on studies in yeast, numerous investigations of this process have been conducted, and the framework of mammalian mitochondrial autophagy is progressively appearing. However, many enigmas about the molecular mechanisms involved remain unsolved. Furthermore, the pathological significance of mitochondrial autophagy in the heart remains largely unclear. In this review, we discuss the current understanding of mitochondrial autophagy in mammals with reference to that in yeast. Regarding the process in yeast, some points of uncertainty have arisen. We also summarize recent advances in the research of autophagy and mitochondrial autophagy in the heart. This article is a part of a review series on Autophagy in Health and Disease.


Can citrate efflux from roots improve phosphorus uptake by plants? Testing the hypothesis with near-isogenic lines of wheat.
Phosphorus (P) deficiency in some plant species triggers the release of organic anions such as citrate and malate from roots. These anions are widely suggested to enhance the availability of phosphate for plant uptake by mobilizing sparingly-soluble forms in the soil. Carazinho is an old wheat (Triticum aestivum) cultivar from Brazil, which secretes citrate constitutively from its root apices, and here we show that it also produces relatively more biomass on soils with low P availability than two recent Australian cultivars that lack citrate efflux. To test whether citrate efflux explains this phenotype, we generated two sets of near-isogenic lines that differ in citrate efflux and compared their biomass production in different soil types and with different P treatments in glasshouse experiments and field trials. Citrate efflux improved relative biomass production in two of six glasshouse trials but only at the lowest P treatments where growth was most severely limited by P availability. Furthermore, citrate efflux provided no consistent advantage for biomass production or yield in multiple field trials. Theoretical modeling indicates that the effectiveness of citrate efflux in mobilizing soil P is greater as the volume of soil into which it diffuses increases. As efflux from these wheat plants is restricted to the root apices, the potential for citrate to mobilize sufficient P to increase shoot biomass may be limited. We conclude that Carazinho has other attributes that contribute to its comparatively good performance in low-P soils.


Understanding and treating premenstrual dysphoric disorder: an update for the women's health practitioner.
Up to 7% of women report premenstrual symptoms severe enough to impair daily function, and are said to suffer from premenstrual dysphoric disorder (PMDD). Although PMDD is predominately regarded as a biologically based condition, sociocultural factors, and particularly life stress, past sexual abuse, and cultural socialization, likely interact with hormonal changes. This integrative model has implications for etiology and treatment of PMDD.


Measuring visual function in age-related macular degeneration with frequency-doubling (matrix) perimetry.
To determine the agreement between the Humphrey Matrix perimeter 10-2 test and the 10-2 Humphrey Field Analyzer (HFA) test when assessing visual function in patients with age-related macular degeneration (AMD). Forty-two eyes of 42 subjects with AMD (average 75.0 years, SD=6.2: median visual acuity in logarithm of the minimum angle of resolution of 0.26, range, -0.12 to 1.04) were evaluated with the Matrix and HFA 10-2 visual field tests. Mean deviation (MD), pattern standard deviation, and test time were recorded. We calculated spatial concordance of individual test locations, being the proportion of spatially agreeing locations with identical classification (normal vs. abnormal, p < 5%) on the pattern deviation plot. As multiple HFA stimuli overlapped with some Matrix locations, several criteria for grouping HFA data into locations were investigated. Both MD and pattern standard deviation were significantly correlated for the two devices (r(2)=0.79 and r(2)=0.80, respectively, p<0.0001). Using our standard criterion for abnormal HFA locations (≥50% stimuli abnormal), the median spatial concordance was 0.76, with 95% of tests giving a concordance of ≥0.59. A small, but significant, increase in concordance occurred when a stricter criterion (all stimuli abnormal at a location) was applied. Median fixation loss percentages were 7 and 0% for the HFA and Matrix, respectively. Visual acuity in logarithm of the minimum angle of resolution showed modest correlations with both defect depth (HFA MD: r(2)=0.39, p<0.0001) and size of defect (number of abnormal points on the HFA: r(2)=0.24, p<0.0001). Using a simple metric to calculate spatial concordance, the Matrix 10-2 test quantifies the spatial extent of significant depression of the central visual fields in AMD in a manner similar to the HFA 10-2. The spatial extent and depth of central visual field loss in AMD are only modestly predicted by visual acuity measurements.


A usual presentation of an unusual diagnosis.
Chest pain is one of the most common acute medical emergencies and a significant proportion of cases will manifest in one of the acute coronary syndromes. We report a case in which an intermittent non-specific chest pain led to the detection of primary mediastinal large B-cell lymphoma.


Water structure of a hydrophobic protein at atomic resolution: Pentagon rings of water molecules in crystals of crambin.
The water structure has been analyzed for a model of the protein crambin refined against 0.945-A x-ray diffraction data. Crystals contain 32% solvent by volume, and 77% of the solvent molecules have been located-i.e., 2 ethanol molecules and 64 water molecules with 10-14 alternate positions. Many water oxygen atoms found form chains between polar groups on the surface of the protein. However, a cluster of pentagonal arrays made up of 16 water molecules sits at a hydrophobic, intermolecular cleft and forms a cap around the methyl group of leucine-18. Several waters in the cluster are hydrogen-bonded directly to the protein. Additional closed circular arrays, which include both protein atoms and other water oxygen atoms, form next to the central cluster. This water array stretches in the b lattice direction between groups of three ionic side chains.


New theoretical model to measure pressure produced during impression procedure for complete dentures-Visual inspection of impression material flow.
A theoretical model, based on fluid dynamics, was developed to measure impression pressure. The purpose of this study was to evaluate the validity of this theoretical model by comparing its theoretical analysis against actual pressure measurements conducted using an impression tray and edentulous oral mucosa analog embedded with pressure sensors. In the theoretical model, a hollow tube was mounted onto an impression tray by penetrating through the tray. When force was applied to the tray, pressure was produced which then caused the impression material to flow into the hollow tube. Length of impression material which flowed into tube was denoted as l. In the calculation formula for theoretical model, pressure impulse I was expressed as a function of impression flow length l. For actual pressure measurements, four electric pressure sensors were embedded in an experimental edentulous arch. To visually observe and measure length of impression material flow, four transparent silicon tubes were mounted vertically at different positions on tray. During tray seating, impression material flowed into tubes and pressure which caused material flow movement was measured by the embedded sensor at each tube's position. Based on actual pressure measurements under one experimental condition, regression analysis of pressure data acquired from electric sensors yielded the formula, Y=0.056X²+0.124X. Based on theoretical analysis using a particular viscosity value, the numerical formula yielded was Y=0.057X², which resembled that of the regression formula. Theoretical model presented in this paper augured well for clinical application as an easy and economical means to examine magnitude and distribution of impression pressure by measuring lengths of impression material flow in tubes fixed to impression tray.


Clinical Evidence of Acute Mesoamerican Nephropathy.
Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.


Histone proteins in vivo: cell-cycle-dependent physiological effects of exogenous linker histones incorporated into Physarum polycephalum.
We detail a method which allows biochemical quantities of histone proteins to be introduced into a living eukaryotic cell. This method involves absorption of purified proteins into macroplasmodia of Physarum polycephalum. Further, since Physarum macroplasmodia exist as syncitial culture with completely synchronous nuclei with respect to cell cycle events, proteins may be introduced at specific points during the eukaryotic cell cycle. We show that a linker histone is absorbed whole into these cells and are properly transported to the nuclei of the cell. Furthermore, we also show incorporation of linker histone H5 inhibits the transcriptional activities occurring during the G2 phase in Physarum. This method will make it possible to introduce histones modified with structural probes into chromatin naturally assembled in vivo.


Conditioned medium from MCF-7 cell line induces myofibroblast differentiation, decreased cell proliferation, and increased apoptosis in cultured normal fibroblasts but not in fibroblasts from malignant breast tissue.
We studied the effect of conditioned medium (CM) obtained from cultures of oestrogen-receptor positive breast cancer MCF7 cell line on the differentiation, proliferation and apoptosis patterns of cultured breast fibroblasts from normal interstitial and malignant stromal tissue. Fibroblasts were grown in the presence or absence of CM and examined for the differentiation pattern by immunofluorescence and Western blotting procedures, for proliferation profile by Ki67 expression, and for apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling technique. Monoclonal antibodies specific for non-muscle (NM), smooth muscle (SM) lineage and differentiation markers were applied to these cultures. CM is able to induce a SM-like differentiation in interstitial fibroblasts, i.e., essentially myofibroblast formation. Fibroblasts from tumour stroma showed the presence of a small number of smooth muscle cells (SMC) along with a large number of myofibroblasts. Treatment of these cultures with CM was unable to change this pattern. Only normal fibroblasts were responsive to the proliferation/apoptotic-inhibitory effect of the CM. These data suggest that structural and functional differences exist between stromal fibroblasts from normal breast and breast cancer with respect to the responsiveness to soluble factors present in the CM. We hypothesize that the lack of in vitro sensitivity to CM shown by 'tumour' fibroblasts is the result of an in vivo inherent and stable phenotypic change on the fibroblasts surrounding breast tumour cells occurring via a paracrine mechanism.


Proliferative effect of whey from cows' milk obtained at two different stages of pregnancy measured in MCF-7 cells.
Dietary estrogens may play a role in the etiology of hormone-dependent cancers like breast cancer. Cow's milk contains various endogenous estrogens and feed derived phytoestrogens that potentially contribute to an estrogenic effect of milk in consumers, and therefore we evaluated the effect of milk (whey) in a proliferation assay with estrogen-sensitive MCF-7 human breast cancer cells. Milk samples were obtained from 22 cows representing different stages of pregnancy (first and second half) and whey was produced from the milk. 0·1, 0·25 or 0·5% whey was included in the cell culture medium and after 6 days of treatment cell proliferation was assessed by a colorimetric method with a fluorometer. Whey induced significant (P<0·05) proliferative effects compared with control cells with no added whey at all concentrations tested. There was no difference in the proliferative effect of whey depending on the stage of pregnancy from which the milk was obtained. We did not observe anti-proliferative effects when whey was tested in the presence of 10 pm estradiol in the medium. In conclusion, these results indicate that whey, irrespective of the pregnancy stage from which the milk was obtained induced a significant proliferative response in MCF-7 cells and no anti-proliferative effect, which may be caused, at least in part, by estrogens present in milk. The implications of our findings in relation to for example breast cancer will have to be studied further in other model systems preferentially in vivo.


Hardness and wear resistance of two resin composites cured with equivalent radiant exposure from a low irradiance LED and QTH light-curing units.
To measure and compare three-body wear and Vickers hardness at depths of 0 mm and 2 mm in two composite resin materials cured with either a low irradiance light emitting diode (LED) or a quartz tungsten halogen (QTH) light-curing unit (LCU) in which exposure duration with the LED was increased to deliver equivalent radiant exposure in the 450-490 nm wavelength range. The VIP QTH and Freelight LED LCU's were obtained and the emission spectrum of each was determined using a Spectra Pro 750 spectrograph. Irradiance in the 450-490 nm range for each LCU was determined by calculating the area under the spectral curve. Curing of two composite resins (Z100 and Esthet-X) with equivalent radiant exposure within this prescribed wavelength range was achieved by increasing the irradiation time of the LED 33% from 30-40 seconds to compensate for its lower irradiance (Table 1). The resulting radiant exposure of 8.40 J/cm2 was roughly equivalent to the radiant exposure produced in 30 seconds by the QTH LCU (8.67 J/cm2). The cured specimens were polished with progressively fine wet silicon carbide papers to 600 grit and stored in distilled water at 37 degrees C for 24 hours prior to evaluating hardness and wear. Indentations for Vickers hardness testing were produced by applying a 0.5 kg load with a 15-second dwell time. Equivalent degree of cure was established indirectly through Vickers hardness numbers for the top and bottom surface of 2 mm thick disks of each material cured with each light (N = 3/group). Hardness ratios were computed by dividing mean bottom hardness by mean top hardness within each group. Three-body wear testing (N = 10/group) was performed on similarly fabricated specimens with a mechanical wear device using 44 microm unpolymerized PMMA beads as a simulated food bolus. The composite resin samples opposed spherical, stainless steel styli. A 75 N contact force was applied at 1.2 Hz for 100,000 cycles. Profilometry was used to quantify localized wear of the resin. Multivariate ANOVA and the Tukey-Kramer post hoc test (alpha = 0.05) were used to assess differences in hardness and wear of the materials. With respect to hardness, no difference was noted between top and bottom specimen sides based on material or curing method. Specimens cured using the LED exhibited hardness ratios approaching unity. No significant difference in hardness was found for the main effect of light used, but the main effect of material was highly significant. This was primarily because Z100 cured with the LED demonstrated statistically higher hardness than the other three groups, which were statistically similar. No significant difference in wear was found based on the light used, with the lowest mean wear seen in Z100 cured with the LED. Overall, Z100 exhibited significantly greater surface hardness (P < 0.001) and significantly less wear (P < 0.01) compared to Esthet-X


Exposure to mosquito coil smoke may be a risk factor for lung cancer in Taiwan.
About 50% of lung cancer deaths in Taiwan are not related to cigarette smoking. Environmental exposure may play a role in lung cancer risk. Taiwanese households frequently burn mosquito coil at home to repel mosquitoes. The aim of this hospital-based case-control study was to determine whether exposure to mosquito coil smoke is a risk for lung cancer. Questionnaires were administered to 147 primary lung cancer patients and 400 potential controls to ascertain demographic data, occupation, lifestyle data, indoor environmental exposures (including habits of cigarette smoking, cooking methods, incense burning at home, and exposure to mosquito coil smoke ), as well as family history of cancer and detailed medical history. Mosquito coil smoke exposure was more frequent in lung cancer patients than controls (38.1% vs.17.8%; p<0.01). Risk of lung cancer was significantly higher in frequent burners of mosquito coils (more than 3 times [days] per week) than nonburners (adjusted odds ratio = 3.78; 95% confidence interval: 1.55-6.90). Those who seldom burned mosquito coils (less than 3 times per week) also had a significantly higher risk of lung cancer (adjusted odds ratio = 2.67; 95% confidence interval: 1.60-4.50). Exposure to mosquito coil smoke may be a risk factor for development of lung cancer.


The role of passenger leukocytes in the anomalous survival of neonatal skin grafts in mice.
The anomalous survival of neonatal C3H skin grafts on CBA mice is correlated with the emigration of passenger leukocytes from the graft vasculature. Thus, newborn homografts whose leukocyte populations are eliminated by X-irradiation or by transient sojourn on an intermediate adult C3H host, do not display prolonged survival. Moreover, the continued presence of the newborn grafts is not requisite to the maintenance of the unresponsive state, an observation consonant with the demonstration that CBA mice bearing long-term neonatal C3H skin grafts are leukocyte chimeras. In contrast, neonatal male C57 skin grafts may persist on C57 females after heavy irradiation of the donor, or after passage on an intermediate adult male host. In addition, tolerance is broken by removal of long-persistant newborn grafts from hitherto unresponsive females, and chimerism is not detectable in female C57 mice tolerant of infant male isografts. Finally, leukocytes of neonatal C3H origin, inoculated subcutaneously into CBA males, may occasionally render these animals unresponsive to subsequent adult C3H skin homografts, whereas those taken from infant C57 males usually sensitize their adult female hosts. Thus, passenger leukocytes are implicated in the extended survival of C3H neonatal homografts on CBA recipients, but not in the persistence of H-Y-incompatible neonatal skin isografts on C57 females.