A rapid assay for evaluation of iron-chelating agents in rats.
The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hepatocytes. The isotope was maximally available to chelators during the first 6 hr after its injection, nearly all the excretion being in the bile. The bile 59Fe/total iron ratio was independent of both the chelator and its dose. However, in iron-loaded rats, the ratio was reduced, and the isotope excretion was a less sensitive measure of intrahepatic chelation. In the proposed assay, test chelators were given to normal rats 2 hr after an intravenous injection of 59Fe-ferritin. Four hours later, the radioiron in the liver and in the gut gave a sensitive measure of the mobilization of hepatic iron to the bile. In addition, chemical iron determinations identified a small alternative source of urinary chelate with agents known to promote urine excretion in man. The assay gave a rapid and precise screen for chelators given by parenteral and oral routes.


Comparing age-related macular degeneration phenotype in probands from singleton and multiplex families.
To compare age-related macular degeneration (AMD) phenotype between probands in singleton and multiplex families to determine whether data from these two groups may be combined for consolidated genetic analyses. Retrospective case-control study. Individuals 55 years of age or older with AMD were identified. Complete histories and examinations were recorded, 35-mm fundus photographs obtained, and macular findings graded. Detailed information was recorded, including the presence of extramacular and peripheral drusen, peripheral reticular pigmentary change, posterior vitreous detachment, and iris color. Comparisons were performed between probands from singleton and multiplex families. There was no statistically significant difference in grade between the 411 singleton and 125 multiplex probands (P = .52), and the distribution of grades was similar between the two groups. No statistically significant difference was found between proband groups with respect to the presence or extent of small (P = .48), intermediate (P = .72), and large drusen (P = .74) and retinal pigment epithelium hyper- (P = .76) and hypopigmentation (P = .55); in the presence or grade of peripheral reticular pigment change; the presence of geographic atrophy in exudative disease, extramacular drusen, or posterior vitreous detachment; lens status; iris color; visual acuity; intraocular pressure; optic nerve cupping; and body mass index. A statistically significant difference between the two groups was noted in the presence of peripheral drusen (P = .0001). Singleton and multiplex AMD probands share a similar phenotype. This suggests that multiplex and singleton data can be combined for consolidated genetic analyses.


Vibrio areninigrae sp. nov., a marine bacterium isolated from black sand.
A Gram-negative, facultatively anaerobic, motile, slightly curved rod-shaped bacterial strain was isolated from black sand collected from Soesoggak, Jeju island, Korea. The strain, designated J74T, was able to grow in the presence of 1-7.5 % NaCl, at temperatures of 4-45 degrees C and at pH 5-10. Strain J74T was oxidase- and catalase-positive, arginine dihydrolase-negative and sensitive to the vibriostatic agent O/129. Strain J74T was characterized based on physiology, morphology, biochemical features and 16S rRNA gene sequence analysis. The isolate required sodium ions for growth and utilized a wide range of compounds as sole sources of carbon and energy. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain J74T belongs to the class Gammaproteobacteria. It was found to be associated with the genus Vibrio and was phylogenetically related most closely to the type strain of Vibrio hispanicus (98.7 % 16S rRNA gene sequence similarity). However, DNA-DNA hybridization experiments between strain J74T and V. hispanicus KCTC 12827T revealed a level of relatedness of 37.7 %. Thus, phenotypic and phylogenetic data suggested that J74T should be placed in the genus Vibrio as representing a novel species, for which the name Vibrio areninigrae sp. nov. is proposed. The type strain is J74T (=KCTC 22122T =JCM 14949T).


Actin microfilaments control the MHC class II antigen presentation pathway in B cells.
Newly synthesised major histocompatibility complex class II molecules associate with invariant chains (Ii) to form nonameric complexes. These complexes are transported to endosomes, where proteolytic enzymes generate alphabeta class II dimers associated with nested Ii-derived peptides. These peptides are then exchanged with antigen peptide, and mature class II molecules reach the cell surface. The role of the actin cytoskeleton in the transport and maturation of class II molecules has not been studied. We show here that upon treatment with cytochalasin D (cyto D), the rate of Ii degradation is drastically reduced in B cells. Cyto D treatment also leads to a delayed appearance of stable forms of class II molecules, and a reduced presentation efficiency of antigen determinants requiring newly synthesised class II molecules. Under such conditions, we found that invariant chain fragments and class II molecules are accumulated in early and late endosomal compartments, whereas the leupeptin protease inhibitor induces their accumulation in lysosomal compartments. The addition of cyto D to leupeptin blocks the delivery of class II/invariant chain complexes to lysosomes, and further inhibits degradation of Ii. The dynamics of the actin cytoskeleton can therefore control the meeting point between newly synthesised class II molecules and lysosomal proteases, involved in Ii degradation and antigen peptide loading.


Genotype X diet interactions in mice predisposed to mammary cancer. I. Body weight and fat.
High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F(2) population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity.


A study of therapeutic effect of the growth of children with hypothyroidism.
This study was done to see the therapeutic effect of the growth of children who was diagnosed as hypothyroidism. Thirty-four children with primary hypothyroidism were included in this study. Height, weight and head circumference were measured at initial diagnosis and at every follow up visit. Thyroid function was done. The value was interpreted as abnormal if the range was above or below the normal (T3=70-200 u/L, T4=4-13 u/L, TSH=0.3-6 u/L). X-ray to see the bone age for the chronological age was performed. The value was interpreted as abnormal if the ossification center for the chronological age in inappropriate. Treatment was started with Eltroxine from the day of diagnosis. Dose was adjusted according to the response to the medicine. T3, T4 and TSH level was taken as the guideline to adjust the dose of the drug. X-ray was considered in the follow up where it was indicated. Marked improvement in the anthropometry was seen in comparison to the initial assessment which was well correlated with the normalization of the TSH level and the x-ray of the bone. Serial follow up of these patients was necessary in order to assess the growth in height, weight and head circumference along with the repeated thyroid function to correlate the response of the drug.


Heightened sensitivity to somatosensory stimuli in anorexia nervosa: an exploratory study with the SASTCA scale.
To analyse the presence of heightened sensory sensitivity in patients with anorexia nervosa, which seems similar but not identical to that described in patients with unexplained somatic symptoms or body dysmorphic disorder. We developed a sensory sensitivity scale in eating disorders (SASTCA), which measures the intensity of the response to specific somatosensory stimuli. The scale was completed by 48 patients with anorexia and a control group of 31 participants matched in age, sex and social and educational level. The results were compared with those obtained with the Barsky Somatosensory Amplification Scale (SSAS). The reliability (Cronbach's/alpha, 0.946; Guttman/ split-half, 0.936) and validity (ROC, 0.933) of the SASTCA scale are indicative of its high sensitivity and specificity. The anorexia group had a significantly higher mean score on the SASTCA scale than the control group (p<.001). Similarly, the patients with anorexia had a significantly higher mean value on the SSAS than the participants in the control group (p<.01), although the difference was less extreme. The 2 scales correlated positively (r=.634). These preliminary results suggest the presence in Anorexia of heightened sensory sensitivity which differs from the sensitivity of the control group. This sensitivity has a significant relationship with that described in patients with somatic complaints about health (SSD) or appearance (BDD). Could this heightened sensory sensitivity help us to explain the process of forming the distorted body self-concept (I'm fat, sick, ugly) in all these patients? Once its presence has been confirmed in other patients with anorexia, their relatives and other patients with somatic disorders this heightened sensitivity could constitute the somatic endophenotype of anorexia?


Randomized, Double-Masked, Placebo-Controlled Dose Escalation Study of TAK-639 Topical Ophthalmic Solution in Subjects with Ocular Hypertension or Primary Open-Angle Glaucoma.
TAK-639 is a topical, nine-amino acid, synthetic, C-type natriuretic peptide analog in Phase 1 development for the treatment of ocular hypertension (OHT) and primary open-angle glaucoma (POAG). TAK-639 is postulated to lower intraocular pressure (IOP) through a novel mechanism of action (MOA) that increases trabecular meshwork outflow. We investigated the safety and tolerability of TAK-639 in subjects with OHT or POAG. This was a phase 1, multicenter, randomized, double-masked, placebo-controlled, single- and multiple-dose escalation study. Subjects (aged 18-90 years) with OHT or POAG were randomized 5:2 to TAK-639 or placebo. Three dose levels were planned (0.1%, 0.3%, 0.6% TAK-639), each with four dosing regimens (QD, BID, TID, QID). Safety measures included treatment-emergent adverse events (TEAEs) and ophthalmologic examinations. Pharmacokinetics and pharmacodynamics (reduction of IOP) were also evaluated. In total, 63 subjects were randomized and received 0.1%, 0.3% and 0.6% TAK-639, as single dose, QD, or BID, and 0.1% and 0.3% TID. The study was terminated before 0.6% TID or QID dosing cohorts were studied; instead, 0.6% BID was repeated in a new cohort. TEAEs were instillation related and of mild-to-moderate intensity. There were no TEAEs leading to premature discontinuation, and no serious TEAEs. The most common treatment-related TEAEs were instillation site pain and transient corneal staining with fluorescein. There were no clinically significant concerns across dose groups for all other safety measures, including drop comfort, best corrected visual acuity, slit-lamp biomicroscopy, and corneal epithelial integrity. Little or no systemic exposure was observed. There was a marginal reduction in IOP in one cohort at the highest dose (0.6%) and regimen (BID) tested, suggesting biological plausibility of targeting the trabecular meshwork through this mechanism. TAK-639 was generally well tolerated up to 0.6% BID. Further non-clinical studies will improve understanding of the MOA and the penetration of TAK-639 to the anterior chamber.


Desensitization of skate photoreceptors by bleaching and background light.
Through extracellular measurements of photoreceptor responses to flashed stimuli, we examined how the bleaching of rhodopsin affects increment receptor threshold in the isolated retina of the skate (Raja oscellata and R. erinacea). Both initially unbleached and previously bleached photoreceptors, when exposed to full-field luminous backgrounds of fixed intensity, attain approximately stable levels of increment threshold that vary with the intensity of the background light. Values of stabilized increment thresholds measured after various extents of bleaching (less than approximately 50%), when plotted against background intensity in log-log coordinates, tend to converge with increasing intensity of the background; this relationship of the increment threshold functions resembles that which Blakemore and Rushton (1965b) found to describe the transient effect of bleaching on psychophysical increment threshold for the human rod mechanism. Our data are consistent with the possibility that related photochemical processes govern the stabilized levels of receptor sensitivity exhibited by the isolated retina (a) during steady illumination and (b) long after substantial bleaching.


Dyspnea in the patient with cardiopulmonary disease.
Dyspnea in the patient with cardiopulmonary disease has been defined and discussed, emphasizing those conditions which increase the work of breathing: increased elastic resistance; increased airway obstruction; and deformities of the chest wall, lung, and pleura. Methods of assessing the cardiopulmonary status of the patient as it relates to each condition were presented. Determining and understanding such clinical signs as patterns of breathing, cough and secretions, râles, rhonchi, wheezes, diminished or augmented breath sounds, poor or unequal expansion of the rib cage, and dullness or hyperresonance on percusion is extremely important for the nurse in order to accurately and comprehensively make a nursing assessment. Such an assessment can provide the information necessary to plan more effectively for the care of the patient with cardiopulmonary disease.


Lessons in de novo peptide sequencing by tandem mass spectrometry.
Mass spectrometry has become the method of choice for the qualitative and quantitative characterization of protein mixtures isolated from all kinds of living organisms. The raw data in these studies are MS/MS spectra, usually of peptides produced by proteolytic digestion of a protein. These spectra are "translated" into peptide sequences, normally with the help of various search engines. Data acquisition and interpretation have both been automated, and most researchers look only at the summary of the identifications without ever viewing the underlying raw data used for assignments. Automated analysis of data is essential due to the volume produced. However, being familiar with the finer intricacies of peptide fragmentation processes, and experiencing the difficulties of manual data interpretation allow a researcher to be able to more critically evaluate key results, particularly because there are many known rules of peptide fragmentation that are not incorporated into search engine scoring. Since the most commonly used MS/MS activation method is collision-induced dissociation (CID), in this article we present a brief review of the history of peptide CID analysis. Next, we provide a detailed tutorial on how to determine peptide sequences from CID data. Although the focus of the tutorial is de novo sequencing, the lessons learned and resources supplied are useful for data interpretation in general.


Plamsa leptin response to acute fasting and refeeding in untreated women with bulimia nervosa.
Leptin is known to regulate body weight, energy balance, and reproduction. Therefore, investigation of its physiology is of obvious interest in bulimia nervosa (BN), an eating disorder characterized by body weight-related psychopathology, acute changes in the energy balance, and reproductive alterations. To date, the few studies that have assessed leptin production in BN have had several limitations, including the measurement of blood leptin levels in treated patients and the lack of normal weight healthy controls, so that the information they provide is not conclusive. As the investigation of leptin dynamics is likely to be more informative, we decided to assess leptin response to acute fasting and refeeding in both untreated patients with BN and healthy controls. Twelve women meeting the diagnostic criteria for BN of the Diagnostic and Statistical Manual of Mental Disorders, and 10 healthy women of the same age range participated in a 3-day study. At 1800 h on day 1, they received a meal of 1088 Cal, with 53% carbohydrates, 17% protein, and 30% fat. Then, they fasted until 1800 h on day 2, when they received the same meal. On day 3, they received a standard hospital diet of 2600 Cal, divided into 3 meals, with the same percentages of nutrients as described above. Blood samples were collected at different time points for plasma leptin, glucose, and insulin measurements. In bulimic patients, plasma leptin values were significantly lower than in healthy women (P < 0.0001) and were positively related to body weight, expressed as body mass index (r = 0.86; P < 0.0001). The leptin response to the fasting/refeeding paradigm significantly differed between patients and controls (time x group interaction, P < 0.0001). In fact, in healthy subjects, acute fasting induced a 58% decline in the plasma leptin concentration, whereas such a decrease was only 7% in bulimic women (P < 0.001). After acute refeeding, plasma leptin increased in both groups, although in the patients it did not reach the absolute values observed in normal controls. No significant difference was observed between bulimics and controls in plasma insulin response to the fasting/refeeding paradigm, whereas an abnormal increase in blood glucose levels was observed in the patients after the first meal following acute fasting. We conclude that in untreated women with BN, leptin, despite its very low plasma values, still holds its function as a sensor of body weight changes, but loses its role of signaling acute changes in energy balance.


Surgery is not indicated for the treatment of premature ejaculation.
Premature ejaculation (PE) is considered the most common male sexual disorder, affecting up to 75% of men at some point in their lives. While medical management is the mainstay of therapy, surgical options such as dorsal nerve neurectomy (DNN), hyaluronic acid (HA) gel glans penis augmentation, and circumcision have been studied as alternative forms of treatment. Preliminary studies have suggested that DNN and HA gel glans penis augmentation are relatively safe and effective, but due to a lack of large, multicenter, randomized-control trials with long-term follow-up, the International Society of Sexual Medicine (ISSM) has been unable to endorse DNN or HA gel glans penis augmentation as options in the treatment of PE. Conflicting data regarding the efficacy and safety of circumcision has similarly led to its exclusion from ISSM recommendations for the treatment of PE. Ethical concerns, particularly the fundamental concept of non-maleficence, are also barriers to the implementation of surgery for PE.


Incidence of stroke and myocardial infarction in women of reproductive age.
Information on the incidence of vascular disease in women of reproductive age has been limited. These disease are rare in this age group, and a large population base is required for reliable estimation of incidence. For a case-control study of vascular disease and low-dose oral contraceptive use, we used emergency department logs and hospital admission and discharge records to ascertain fatal and nonfatal cases of first-ever stroke and myocardial infarction (MI) in women 15 to 44 years of age who were-members of a large California HMO. Incidence rates of stroke and MI were calculated on the basis of these data. The incidence of MI not associated with pregnancy was 5.0 per 100,000 women-years. The incidence of stroke not associated with pregnancy was 10.7 per 100,000 women-years. MI was very rare until age 35 years. At every age, about half of hemorrhagic strokes were due to subarachnoid hemorrhage. The incidence rates of stroke and MI are low in women of reproductive age in the United States.


Proteases of Plasmodium falciparum as potential drug targets and inhibitors thereof.
Malaria, caused by protozoa of the genus Plasmodium, remains one of the most dreadful infectious diseases worldwide killing more than 1 million people per year. The emergence of multidrug-resistant parasites highly demands a steadfast and continuous search not only for new targets but also for new anti-infectives addressing the known ones. As proteases in general have been proven to be excellent drug targets and the development of inhibitors has frequently resulted in approved drugs, this review will only focus on the proteases of Plasmodium falciparum as drug targets. The completion of the sequencing of the Plasmodium falciparum genome in 2002 lead to the discovery of nearly 100 putative proteases encoded therein. Within this review, only those proteases and inhibitors thereof will be discussed in more detail, in which their biological function has been determined undoubtedly or in those cases, in which the development of specific inhibitors has significantly contributed to the understanding of the underlying biological role of the respective protease thus validating the role as promising drug target.


EZH2 inhibition stimulates repetitive element expression and viral mimicry in resting splenic B cells.
Mammalian cells repress expression of repetitive genomic sequences by forming heterochromatin. However, the consequences of ectopic repeat expression remain unclear. Here we demonstrate that inhibitors of EZH2, the catalytic subunit of the Polycomb repressive complex 2 (PRC2), stimulate repeat misexpression and cell death in resting splenic B cells. B cells are uniquely sensitive to these agents because they exhibit high levels of histone H3 lysine 27 trimethylation (H3K27me3) and correspondingly low DNA methylation at repeat elements. We generated a pattern recognition receptor loss-of-function mouse model, called RIC, with mutations in Rigi (encoding for RIG-I), Ifih1 (MDA5), and Cgas. In both wildtype and RIC mutant B cells, EZH2 inhibition caused loss of H3K27me3 at repetitive elements and upregulated their expression. However, NF-κB-dependent expression of inflammatory chemokines and subsequent cell death was suppressed by the RIC mutations. We further show that inhibition of EZH2 in cancer cells requires the same pattern recognition receptors to activate an interferon response. Together, the results reveal chemokine expression induced by EZH2 inhibitors in B cells as a novel inflammatory response to genomic repeat expression. Given the overlap of genes induced by EZH2 inhibitors and Epstein-Barr virus infection, this response can be described as a form of viral mimicry.


The composition and stability of the vaginal microbiome of healthy women.
Our knowledge of the composition of the vaginal environment in healthy women stands greatly improved. An imbalance in microbial communities is associated with a number of different diseases, disorders and other adverse health outcomes. Cultivation-independent studies have been published indicating that each woman has unique vaginal microbiota. The vaginal microbiome in pregnant women is more stable and associated with high level of Lactobacillus, particularly, Lactobacillus crispatus and low bacterial diversity. The current review was planned to provide a more complete picture of the abundance of various bacteria species in the vagina and how they impact women's reproductive health and pregnancy outcomes. This should provide a better understanding of what is considered a "healthy" or "unhealthy" vaginal microbiome and how the dysibiosis of the vagina affects the women. Additionally, it was planned to identify factors that influence the structure and / or composition of the microbial community.


Rose geranium essential oil as a source of new and safe anti-inflammatory drugs.
Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.


In vivo comparison of the optical clearing efficacy of optical clearing agents in human skin by quantifying permeability using optical coherence tomography.
The objective of this work is to quantify and compare the optical clearing efficacy of glucose, propylene glycol, glycerol solutions through the human skin tissue in vivo by calculating permeability coefficient of three solutions. Currently, the permeability coefficient of agent in tissues was extracted from optical coherence tomography (OCT) amplitude data mainly through the OCT signal slope and the OCT amplitude methods. In this study, we report the OCT attenuation coefficient method which is a relatively novel and rarely reported methodology to measure the permeability coefficient during the optical skin clearing procedure. The permeability coefficients for 40% propylene glycol, glucose and glycerol were (2.74 ± 0.05) × 10(-6) cm s(-1), (1.78 ± 0.04) × 10(-6) cm s(-1) and (1.67 ± 0.04) × 10(-6) cm s(-1), respectively. It could be clearly seen that the permeability coefficient of the 40% propylene glycol solution is higher than that of 40% glucose solution, and the permeability coefficient of the 40% glucose solution is higher than that of the 40% glycerol solution. These indicate 40% propylene glycol solution is more effective than others in the human skin in vivo. We then compare and prove consistency of optical clearing efficacy figured out by three different methods.


Receptor-mediated binding, endocytosis and cellular processing of macromolecules conjugated with colloidal gold.
Receptor-mediated expression of cellular functions assures biological specificity, regulation, and control of nutritive and metabolic requirements. The study of receptor-ligand interactions is a central theme in many published reports employing colloidal gold labeling. With the ligand directly conjugated with colloidal gold, the investigator is afforded the opportunity to observe all phases of cellular binding, endocytosis, lysosomal delivery and catabolism. Reviewed are published studies employing direct ligand conjugation with colloidal gold, the relative merits and disadvantages of this type of procedure and data from recent studies investigating endothelial receptor binding of proteins in the coagulation and fibrinolysis cascades.


Efficacy of antitumor chemotherapy in C3H mice enhanced by the antiangiogenesis steroid, cortisone acetate.
The effect of "antiangiogenesis" therapy using cortisone acetate (CA) with or without heparin on tumor growth as well as in combination with chemotherapy was investigated. C3H mice were implanted intradermally with N-[4-(5-nitro-2-furyl)-thiazolyl]formamide induced undifferentiated transitional cell carcinoma, MBT-2, in the right flank. The treatment was initiated 9 to 10 days after tumor inoculation. Daily injections of CA (250 mg/kg s.c.) suppressed tumor growth significantly in a dose dependent fashion. Administration of heparin (Elkins-Sinn) at the concentration of 200, 400, or 1000 units/ml in drinking water for 3 to 6 days was neither additive nor detrimental to the effect of CA. Chemotherapy was combined with CA; 3 days of administration of 250 mg/kg of CA in tapering doses was used. The chemotherapeutic agent was injected once 24 h before the initial CA. Combinations of chemotherapy (Adriamycin, 2.5-7.5 mg/kg i.v; cisplatin, 3-9 mg/kg i.p.; cyclophosphamide, 50-150 mg/kg i.p.; cis-(diammino)(1,1-cyclobutanedicarboxylate)platinum(II) (JM-8), 60-150 mg/kg i.p.; mitomycin C, 3-4.5 mg/kg i.p.) with CA showed additive suppression of tumor growth. Mice tolerated chemotherapy alone, CA alone, and both in combination. CA combined with JM-8 was not tolerated. Mice tolerated 100 to 150 mg/kg of JM-8, whereas the addition of CA to JM-8 resulted in a 66% (6 of 9) to 89% (8 of 9) mortality rate. CA at a concentration of 5 and 25 micrograms/ml showed no direct cytotoxic activity against MBT-2 cells in vitro. However, 3 days of administration of 250 mg/kg of CA inhibited tumor angiogenesis generated by MBT-2 cells in C3H mice using a dorsal air sac assay. The data suggest that CA alone inhibits tumor angiogenesis in C3H mice and that antiangiogenesis therapy enhances the antitumor efficacy of chemotherapeutic agents without increasing host toxicity (except for JM-8).


Aetiology and clinical features of facial cellulitis: a prospective study.
In the early 20th century, the face was the predominant site of cellulitis. Despite a relative decrease in the incidence of facial cellulitis, it is still common. There are few studies on this condition during the last decades. The aim of this study was to describe contemporary aetiological and clinical characteristics of patients admitted to hospital with non-suppurative facial cellulitis. Patients were included prospectively. Clinical details, comorbidities and biochemistry results were recorded. Investigations included cultures of skin swab and blood and tests for streptococcal antibodies during the acute and convalescent stages. Sixty-five patients were included. Serology, cultures and response to penicillin monotherapy identified probable or confirmed β-haemolytic streptococci (BHS) aetiology in 75% (49/65) of cases. Significant comorbidities were present in 54% (35/65). Fever, chills or rigors before or at admission was noted in 91% (59/65). Patients presented most often with sharply demarcated erythema and raised borders (54/64). Penicillin or penicillinase-resistant penicillin alone or in combination cured 68% (44/65) of the patients. Supplementary clindamycin was used in 28% (18/65), most often only for 1-3 days. Only four patients needed a second course of antibiotics. Clinical failure was more often seen in patients with non-BHS aetiology (p = .037). Few complications were noted; 14.5% (9/62) experienced transient diarrhoea, and only one had confirmed Clostridium difficile infection. No patients developed cerebral venous sinus thrombosis, and there were no fatalities. Our findings indicate that BHS are the leading cause of facial cellulitis. Most patients exhibit sharply demarcated lesions and systemic symptoms. Narrow-spectrum β-lactam antibiotics and short hospital stay appear sufficient. Few complications and low recurrence rates were seen.


Cytogenetics in the management of myelodysplastic neoplasms (myelodysplastic syndromes, MDS): Guidelines from the groupe francophone de cytogénétique hématologique (GFCH).
Myelodysplastic neoplasms (MDS) are clonal hematopoietic neoplasms. Chromosomal abnormalities (CAs) are detected in 40-45% of de novo MDS and up to 80% of post-cytotoxic therapy MDS (MDS-pCT). Lately, several changes appeared in World Health Organization (WHO) classification and International Consensus Classification (ICC). The novel 'biallelic TP53 inactivation' (also called 'multi-hit TP53') MDS entity requires systematic investigation of TP53 locus (17p13.1). The ICC maintains CA allowing the diagnosis of MDS without dysplasia (del(5q), del(7q), -7 and complex karyotype). Deletion 5q is the only CA, still representing a low blast class of its own, if isolated or associated with one additional CA other than -7 or del(7q) and without multi-hit TP53. It represents one of the most frequent aberrations in adults' MDS, with chromosome 7 aberrations, and trisomy 8. Conversely, translocations are rarer in MDS. In children, del(5q) is very rare while -7 and del(7q) are predominant. Identification of a germline predisposition is key in childhood MDS. Aberrations of chromosomes 5, 7 and 17 are the most frequent in MDS-pCT, grouped in complex karyotypes. Despite the ever-increasing importance of molecular features, cytogenetics remains a major part of diagnosis and prognosis. In 2022, a molecular international prognostic score (IPSS-M) was proposed, combining the prognostic value of mutated genes to the previous scoring parameters (IPSS-R) including cytogenetics, still essential. A karyotype on bone marrow remains mandatory at diagnosis of MDS with complementary molecular analyses now required. Analyses with FISH or other technologies providing similar information can be necessary to complete and help in case of karyotype failure, for doubtful CA, for clonality assessment, and for detection of TP53 deletion to assess TP53 biallelic alterations.


Lectin from red algae Amansia multifida Lamouroux: Extraction, characterization and anti-inflammatory activity.
Seaweed lectins are very promising biotechnological tools that also gain prominence when applied to the pharmacology field. The purpose of the present work was to isolate and characterize lectin from the red algae Amansia multifida and subsequently test it in general inflammation models. The lectin was purified by ion exchange chromatography, characterized with two-dimensional electrophoresis, automated analysis of amino acid sequences and circular dichroism spectroscopy. The pharmacological tests performed were paw edema induced by carrageenan or rapid inflammatory mediators, peritonitis induced by carrageenan and myeloperoxidase leukocyte count assays, glutathione and cytokine concentration. Our results have identified a 30 KDa molecular weight protein that presents a major secondary structure arranged in β-strand elements (~43%). A fragment of 20 amino acid residues was sequenced and presented low identity to the known classes of lectins from marine alga. This lectin was able to modulate inflammatory parameters such as paw edema, leukocyte migration, oxidative stress and proinflammatory cytokines. Thus, the lectin from the seaweed Amansia multifida has evident anti-inflammatory properties because it acts by reducing the formation of edema by modulating the effect of vascular mediators, migration of neutrophils, proinflammatory cytokines and oxidative stress control.


Epitaxial Growth of Two-Dimensional Insulator Monolayer Honeycomb BeO.
The emergence of two-dimensional (2D) materials launched a fascinating frontier of flatland electronics. Most crystalline atomic layer materials are based on layered van der Waals materials with weak interlayer bonding, which naturally leads to thermodynamically stable monolayers. We report the synthesis of a 2D insulator composed of a single atomic sheet of honeycomb structure BeO (h-BeO), although its bulk counterpart has a wurtzite structure. The h-BeO is grown by molecular beam epitaxy (MBE) on Ag(111) thin films that are also epitaxially grown on Si(111) wafers. Using scanning tunneling microscopy and spectroscopy (STM/S), the honeycomb BeO lattice constant is determined to be 2.65 Å with an insulating band gap of 6 eV. Our low-energy electron diffraction measurements indicate that the h-BeO forms a continuous layer with good crystallinity at the millimeter scale. Moiré pattern analysis shows the BeO honeycomb structure maintains long-range phase coherence in atomic registry even across Ag steps. We find that the interaction between the h-BeO layer and the Ag(111) substrate is weak by using STS and complementary density functional theory calculations. We not only demonstrate the feasibility of growing h-BeO monolayers by MBE, but also illustrate that the large-scale growth, weak substrate interactions, and long-range crystallinity make h-BeO an attractive candidate for future technological applications. More significantly, the ability to create a stable single-crystalline atomic sheet without a bulk layered counterpart is an intriguing approach to tailoring 2D electronic materials.


Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review.
Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses.


Sexual behaviors and associated factors among antiretroviral treatment attendees in Ethiopia.
Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome is one of the major public health problems throughout the world. Nowadays, antiretroviral treatment (ART) is available in health institutions and HIV-positive individuals who are eligible for ART are taking it. But studies show reinfection of HIV is occurring in them for unknown reasons. This study aimed to assess risky sexual practice and associated factors among HIV-positive ART attendees. An institution-based cross-sectional study was employed in ten randomly selected health centers in Addis Ababa, between October 05 and November 05, 2013. Simple random sampling technique was employed to select 376 respondents for face-to-face interviews from ART registration book. After the data collection process, data were entered and analyzed using the SPSS version 20 statistical package. Then the effect of each variable was observed by regression analysis to identify the predictors for risky sexual practice at a significant level of P<0.05. A total of 376 respondents were included in the study, with 100% response rate. The mean age of the total respondents was 35.28±8.94 (standard deviation). Of the 376 respondents, 30.4% had a history of risky sexual practice, which was inconsistent condom use in the last 3 months prior to the study period. Factors associated with risky sexual practice included alcohol consumption (adjusted odds ratio [AOR] =2.01, 95% CI: 1.07, 3.77), being single (AOR =0.29, 95% CI: 0.15, 0.59) and widowed (AOR =0.32, 95% CI: 0.13, 0.77) respondents, and the gender of the respondents, with an AOR of 1.55 (95% CI: 1.01, 2.33), shows a significant relationship with risky sexual behavior. Generally, a significant number (30%) of the respondents engaged in risky sexual behavior; so health providers should encourage, support, and allow clients to effectively use condoms during their sexual practice.


Inner-city clinics enable a ministry to continue. A Minnesota congregation expands its acute care ministry in order to serve the poor.
In 1991 the St. Paul Province of the Sisters of St. Joseph of Carondelet formed Carondelet LifeCare Ministries (CLM) to ensure that the poor and underserved in the Minneapolis-St. Paul area have access to affordable healthcare. The sisters decided that they could best serve this population by going directly to them, opening health clinics in neighborhoods throughout the metropolitan area. The first of CLM's St. Mary's Health Clinics began operations in January 1992. Since then, 10 clinics have opened to persons in poor and medically underserved neighborhoods, and CLM plans to establish a network of 15 to 20 health clinics within the next year. The clinics, which are staffed primarily by volunteers, offer primary, basic, intervention care. Patients are referred, when necessary, to specialty and subspecialty physicians. Clinics are initially open for one-half day per week, and hours are expanded as need dictates. The clinics served 2,689 patients in 1993, two-thirds of whom were women and children. Patient ethnic mix is representative of the demographics of the metropolitan area. Clinic volunteers work a minimum of four hours a month. A core paid staff--consisting of a director of nursing, a staff nurse, and a clinic coordinator--recruit volunteers and oversee daily operations. St. Mary's Health Clinics provide a variety of educational programs to prepare volunteers for their work.


Lichen planopilaris with significant post-inflammatory pigmentary alteration.
Lichen planopilaris is an uncommon dermatological manifestation of lichen planus of the scalp and results in cicatricial alopecia. We present a patient with lichen planopilaris and significant post-inflammatory pigmentary alteration, confirmed by histopathology. The patient's case represents a clinically important variation from an expected typical pattern of dyschromia at periphery of alopecic zones in lichen planopilaris.


Non-avalanche single photon detection without carrier transit-time delay through quantum capacitive coupling.
Searching for innovative approaches to detect single photons remains at the center of science and technology for decades. This paper proposes a zero transit-time, non-avalanche quantum capacitive photodetector to register single photons. In this detector, the absorption of a single photon changes the wave function of a single electron trapped in a quantum dot (QD), leading to a charge density redistribution nearby. This redistribution translates into a voltage signal through capacitive coupling between the QD and the measurement probe. Using InAs QD/AlAs barrier as a model system, the simulation shows that the output signal reaches ~4 mV per absorbed photon, promising for high-sensitivity, ps single-photon detection.


Enhanced visual processing contributes to matrix reasoning in autism.
Recent behavioral investigations have revealed that autistics perform more proficiently on Raven's Standard Progressive Matrices (RSPM) than would be predicted by their Wechsler intelligence scores. A widely-used test of fluid reasoning and intelligence, the RSPM assays abilities to flexibly infer rules, manage goal hierarchies, and perform high-level abstractions. The neural substrates for these abilities are known to encompass a large frontoparietal network, with different processing models placing variable emphasis on the specific roles of the prefrontal or posterior regions. We used functional magnetic resonance imaging to explore the neural bases of autistics' RSPM problem solving. Fifteen autistic and eighteen non-autistic participants, matched on age, sex, manual preference and Wechsler IQ, completed 60 self-paced randomly-ordered RSPM items along with a visually similar 60-item pattern matching comparison task. Accuracy and response times did not differ between groups in the pattern matching task. In the RSPM task, autistics performed with similar accuracy, but with shorter response times, compared to their non-autistic controls. In both the entire sample and a subsample of participants additionally matched on RSPM performance to control for potential response time confounds, neural activity was similar in both groups for the pattern matching task. However, for the RSPM task, autistics displayed relatively increased task-related activity in extrastriate areas (BA18), and decreased activity in the lateral prefrontal cortex (BA9) and the medial posterior parietal cortex (BA7). Visual processing mechanisms may therefore play a more prominent role in reasoning in autistics.


Mycobacterium microti Interferes with Bovine Tuberculosis Surveillance.
Mycobacterium microti, a member of the Mycobacterium tuberculosis complex, was originally described as the cause of tuberculosis in wild rodents. However, in the last few years, an increasing number of cases have been reported in wildlife (wild boars and badgers) and livestock (goat and cattle) in the frame of bovine tuberculosis (bTB) surveillance program, demonstrating the risk of interference with bTB diagnosis in France. In 2019, we detected four cattle infected with M.microti, from three different herds in three different distant regions. For all these cases, ante-mortem diagnosis by the skin test (single intradermal comparative cervical tuberculin (SICCT)) was positive. Confirmation of M.microti infection was based on molecular tests, i.e., specific real-time PCR and spoligotyping. These results highlight a non-negligible risk of interference in the bTB diagnosis system and raise concern about the reliability of diagnostic tests used for bTB surveillance. The use of highly specific tests, like the interferon gamma test (IFN-γ) employed in France or new synthetic specific tuberculins for skin testing could alternatively be used to accurately identify M.bovis (or Mycobacterium caprae) infection at ante-mortem examination. At post-mortem diagnosis, the use of specific molecular tools should be considered to accurately distinguish pathogens within the MTBC and to avoid misleading bTB diagnosis.


Metabolomic evolution of the postpartum dairy cow uterus.
High rates of early pregnancy loss are a critical issue in dairy herds, particularly in seasonal, grazing systems. Components of the uterine luminal fluid (ULF), on which the early embryo depends for sustenance and growth, partly determine early pregnancy losses. Here, changes in ULF from early to mid-postpartum in crossbred dairy cows were explored, linking them with divergent embryo development. For this, the uteri of 87 cows at Day 7 of pregnancy at first and third estrus postpartum were flushed to collect ULF. Eighteen metabolites (chiefly organic acids and sugars) significantly varied in abundance across postpartum, indicating a molecular signature of physiological recovery consistent of the upregulation of pyrimidine metabolism and glycerophospholipid metabolism, and downregulation of pentose phosphate and taurine metabolism pathways. Joint pathway analysis of metabolomics data and a previously generated proteomics data set on the same ULF samples suggests key links between postpartum recovery and subsequent successful embryo development. These include upregulation of VEGFA and downregulation of metabolism, NRF2, T-cell receptor, which appear to improve the ULF's capacity of sustaining normal embryo development, and a putative osmo-protectant role of beta-alanine. These relationships should be further investigated to develop tools to detect and reduce early pregnancy loss in dairy cows.


Glucose starvation induces a drastic reduction in the rates of both transcription and degradation of mRNA in yeast.
Gradual depletion of essential nutrients in yeast cultures induces a complex physiological response, leading initially to induction of pathways required for the utilization of alternative nutrients and, when such sources are depleted, to entry into stationary phase. Abrupt removal of sugar does not allow the proper establishment of stationary phase. Here we report that abrupt removal of glucose from the growth medium elicits a coordinated response in yeast cells that resembles, in some aspects, the gradual passage to stationary phase. Phosphorylation of RNA polymerase II at a subset of sites in the COOH-terminal domain (CTD) is decreased. Transcription by RNA polymerases I and II is shut down almost completely, whereas transcription by RNA polymerase III continues. In parallel, the rate of mRNA degradation is drastically reduced, at a stage preceding poly(A) shortening. This response is suited for conservation of scarce resources while preserving the ability of cells to recover when nutrients become available.


[Committee for Immunization Programme and Registry and changes in the National Immunization Programme in Spain].
The Committee for Immunization Programme and Registry (Ponencia de Programa y Registro de Vacunaciones) was created in 1991 to advise the Interterritorial Council of the National Health System on the situation of vaccine preventable diseases and the establishment and evaluation of measures for their prevention and control. Among other functions, this Committee evaluates the immunization programmes taking into account the scientific evidence and the epidemiological situation. In this way the Committee advises decision makers on the Public Health Commission of the Interterritorial Council. Any change in the National Immunization Programme, since the first one published in 1996 by the Interterritorial Council to the current Immunization Programme throughout life, has been advised from the technical and scientific point of view by this Committee. Taking into account both the work developed and the methodology used for developing the technical advice, the Committee for Immunization Programme and Registry is considered the National Immunization Technical Advisory Group for Spain. This paper reviews the functions and work developed by the Committee for Immunization Programme and Registry, the changes conducted in the National Immunization Programme under its advice and the current challenges.


Relationship between clinical severity of respiratory syncytial virus infection and subtype.
The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV infection or diagnosed in the outpatient department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.


FiGS: a filter-based gene selection workbench for microarray data.
The selection of genes that discriminate disease classes from microarray data is widely used for the identification of diagnostic biomarkers. Although various gene selection methods are currently available and some of them have shown excellent performance, no single method can retain the best performance for all types of microarray datasets. It is desirable to use a comparative approach to find the best gene selection result after rigorous test of different methodological strategies for a given microarray dataset. FiGS is a web-based workbench that automatically compares various gene selection procedures and provides the optimal gene selection result for an input microarray dataset. FiGS builds up diverse gene selection procedures by aligning different feature selection techniques and classifiers. In addition to the highly reputed techniques, FiGS diversifies the gene selection procedures by incorporating gene clustering options in the feature selection step and different data pre-processing options in classifier training step. All candidate gene selection procedures are evaluated by the .632+ bootstrap errors and listed with their classification accuracies and selected gene sets. FiGS runs on parallelized computing nodes that capacitate heavy computations. FiGS is freely accessible at http://gexp.kaist.ac.kr/figs. FiGS is an web-based application that automates an extensive search for the optimized gene selection analysis for a microarray dataset in a parallel computing environment. FiGS will provide both an efficient and comprehensive means of acquiring optimal gene sets that discriminate disease states from microarray datasets.


Diabetes and Insulin Therapy, but Not Metformin, Are Related to Hepatocellular Cancer Risk.
Introduction. Metabolic conditions, including type 2 diabetes, have been related to hepatocellular carcinoma (HCC) risk. We have further analyzed the role of diabetes and antidiabetic treatments on HCC. Methods. Data derived from a hospital-based case-control study (Italy, 2005-2012) on 224 HCC patients and 389 controls. Odds ratios (ORs) were estimated using multiple logistic regression models. Results. Sixty-nine (30.9%) cases versus 52 (13.5%) controls reported a diabetes diagnosis, corresponding to a multivariate OR of 2.25 (95% confidence interval, CI = 1.42-3.56). A stronger excess risk emerged for a longer time since diabetes diagnosis (OR = 2.96 for <10 years and 5.33 for ≥10 years). Oral therapies were inversely, though not significantly, related to HCC risk, OR being 0.44 for metformin and 0.88 for sulfonylureas; conversely, insulin was nonsignificantly directly associated (OR = 1.90). Compared to nondiabetic subjects who were never smokers, those who were diabetics and ever smokers had an OR of 6.61 (95% CI 3.31-13.25). Conclusion. Our study confirms an over 2-fold excess HCC risk in diabetics, with a stronger excess risk in diabetic subjects who are also tobacco smokers. Metformin may decrease the risk of HCC, whereas insulin may increase the risk.


Efficient multiple-trait association and estimation of genetic correlation using the matrix-variate linear mixed model.
Multiple-trait association mapping, in which multiple traits are used simultaneously in the identification of genetic variants affecting those traits, has recently attracted interest. One class of approaches for this problem builds on classical variance component methodology, utilizing a multitrait version of a linear mixed model. These approaches both increase power and provide insights into the genetic architecture of multiple traits. In particular, it is possible to estimate the genetic correlation, which is a measure of the portion of the total correlation between traits that is due to additive genetic effects. Unfortunately, the practical utility of these methods is limited since they are computationally intractable for large sample sizes. In this article, we introduce a reformulation of the multiple-trait association mapping approach by defining the matrix-variate linear mixed model. Our approach reduces the computational time necessary to perform maximum-likelihood inference in a multiple-trait model by utilizing a data transformation. By utilizing a well-studied human cohort, we show that our approach provides more than a 10-fold speedup, making multiple-trait association feasible in a large population cohort on the genome-wide scale. We take advantage of the efficiency of our approach to analyze gene expression data. By decomposing gene coexpression into a genetic and environmental component, we show that our method provides fundamental insights into the nature of coexpressed genes. An implementation of this method is available at http://genetics.cs.ucla.edu/mvLMM.


Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.
Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs). We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden. Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.


Neonatal diabetes mellitus.
Neonatal diabetes mellitus is a rare form of insulin dependent diabetes mellitus that present within the first month of life, lasting at least two weeks and requiring insulin therapy. Intrauterine growth restriction, failure to thrive, fever, dehydration, hyperglycemia and acidosis with or without ketonuria are the clinical features of the disease. We report four cases of neonatal diabetes mellitus; two of them had a transient course.


Vitamin A supplementation and human immunodeficiency virus load in injection drug users.
The use of vitamin A therapy during human immunodeficiency virus (HIV) infection is under clinical investigation, and vitamin A could potentially modulate HIV replication because the virus genome contains a retinoic acid response element. A randomized, double-masked, placebo-controlled clinical trial was conducted to determine the impact of single high-dose vitamin A supplementation, 60-mg retinol equivalent (200,000 IU), on HIV load and CD4 lymphocyte count. HIV-infected injection drug users (120) were randomly allocated to receive vitamin A or placebo. Plasma vitamin A level, CD4 lymphocyte count, and HIV load were measured at baseline and 2 and 4 weeks after treatment. Vitamin A supplementation had no significant impact on HIV load or CD4 lymphocyte count at 2 and 4 weeks after treatment. This study suggests that high-dose vitamin A supplementation does not influence HIV load.


Posterior composite Class II restorations: in vitro comparison of preparation designs and restoration techniques.
The aim of this study was to evaluate conservative preparation designs for the restoration of Class II lesions with posterior resin composite. Fourteen primary and 14 permanent molars were obtained. Conservative modified MO and DO preparations were placed in half the teeth; conventional MO and DO preparations were placed in the remaining teeth. Randomly, a glass-ionomer liner was placed over the exposed dentin in one preparation of each tooth, a calcium hydroxide liner was placed in the remaining preparations. Posterior resin composite was placed in all teeth, and the teeth were loaded with a 17-kg force. Teeth were thermocycled, stored in 37 degrees C water, then immersed in 50% silver nitrate solution and placed in developer. The teeth were sectioned and photographed. Microleakage was calculated according to the depth of dye penetration, on a 6-degree scale. Results demonstrated the conservative modified restorations and conventional restorations, when glass-ionomer liner was used, to have less marginal microleakage, in both primary and permanent teeth, than their calcium hydroxide counterparts.


Kinetic and temporospatial parameters in male and female cats walking over a pressure sensing walkway.
Several factors may influence kinetic data measurements, including body conformation and body mass. In addition, gender differences in gait pattern have been observed in healthy humans. Therefore, the aim of this study was to compare the kinetic and temporospatial parameters in clinically healthy male and female cats using a pressure-sensitive walkway. Eighteen crossbreed adult cats were divided into two groups: G1 had ten male cats (nine neutered) aged from 1 to 4 years and body mass 3.1-6.8 kg; G2 had eight spayed female cats, aged from 1 to 6 years and body mass 3.3-4.75 kg. The data from the first five valid trials were collected for each cat. A trial was considered valid if the cat maintained a velocity between 0.54-0.74 m/s and acceleration from -0.20 to 0.20 m/s2. The peak vertical force (PVF), vertical impulse (VI), gait cycle time, stance time, swing time, stride length, and percentage body weight distribution among the four limbs were determined. In addition, the lengths of each forelimb and each hind limb were measured using a tape with the animal standing. No significant differences were observed in each group in either the forelimbs or the hind limbs or between the left and right sides for any of the variables. For both groups, the PVF (%BW), the VI, and the percentage body weight distribution were higher at the forelimbs than the hind limbs. The stride length was larger for males; however, the other kinetic and temporospatial variables did not show any statistically significant differences between the groups. The lengths of the forelimbs and hind limbs were larger in the male cats. There was a significant moderate positive correlation between the stride length and the length of the limbs. In conclusion, the only difference observed between male and female cats was the stride length, and this was due to the greater body size of male cats. This difference did not affect other temporospatial or kinetics variables.


Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model.
Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancreatic cancer model including surgical tumour induction and subsequent chemotherapeutic treatment via repeated intraperitoneal injections. Cancer cell injection into the pancreas was performed during a laparotomy under general anaesthesia. After a four-day recovery phase, mice received either drug treatment (galloflavin and metformin) or the respective vehicle substances via daily intraperitoneal injections. In addition to clinical scoring, an automated home-cage monitoring system was used to assess voluntary wheel running (VWR) behaviour as an indicator of impaired well-being. After surgery, slightly elevated clinical scores and minimal body weight reductions, but significantly decreased VWR behaviour were observed. During therapy, body weight declined in response to chemotherapy, but not after vehicle substance injection, while VWR activity was decreased in both cases. VWR behaviour differed between treatment groups and revealed altered nightly activity patterns. In summary, by monitoring VWR a high impact of repeated injections on the well-being of mice was revealed and substance effects on well-being were distinguishable. However, no differences in tumour growth between treatment groups were observed. This might be due to the severity of the procedures uncovered in this study, as exaggerated stress responses are potentially confounding factors in preclinical studies. Finally, VWR was a more sensitive indicator of impairment than clinical scoring in this model.


Flow patterns in the ductus arteriosus during open fetal myelomeningocele repair.
The objective of this study is to perform a longitudinal evaluation of blood flow patterns in the ductus arteriosus (DA) during the perioperative period in fetal myelomeningocele (MMC) surgical patients. Serial fetal echocardiograms were reviewed in 10 MMC cases where mothers received indomethacin and intravenous and inhaled anesthesia. One-way analysis of variance was utilized to evaluate for differences in peak systolic velocity, end-diastolic velocity (EDV), time-averaged mean velocity (TAMV), and Pulsatility Index (PI) throughout the monitoring period. Regression analysis was performed to evaluate the relationship between PI and maternal hemodynamics and medications. The DA TAMV and EDV increased between baseline and inhaled anesthesia and decreased between inhaled anesthesia and postoperative day 2. PI decreased to a nadir during inhaled anesthesia and then increased through postoperative day 2. Three distinct ductal flow patterns, characterizing degree of ductal constriction, were observed. Two fetuses exhibited a severely constricted ductal flow pattern with concurrent moderate tricuspid insufficiency and right ventricular dysfunction during inhaled anesthesia. Abnormal DA flow patterns culminating in significant DA constriction occurred during fetal MMC repair. Limiting maternal exposure to indomethacin, supplemental oxygen, and inhaled anesthesia may reduce the incidence and severity of DA constriction and perhaps reduce fetal cardiac dysfunction during open fetal surgery.


"Just Bring Us the Real Ones": The Role of Forensic Crime Laboratories in Guarding the Gateway to Justice for Sexual Assault Victims.
Throughout the United States, hundreds of thousands of sexual assault kits (SAKs; also termed "rape kits") have never been submitted by law enforcement personnel to a crime laboratory for forensic DNA testing. Prior research indicates that negative stereotypes about victims influence police decisions to submit kits for testing, but forensic crime laboratory personnel may also be involved in SAK submission decisions. The purpose of the current study was to explore the communication and collaboration between police and crime lab personnel regarding SAK submissions within a community with large numbers of unsubmitted rape kits. Drawing from 3 years of ethnographic observations and longitudinal qualitative interviews, we found that the police department's crime lab did not have sufficient resources to test all rape kits in police custody, which is a problem forensic laboratories are facing throughout the United States. However, we also found that access to this limited resource was controlled by crime lab personnel and their rape myth beliefs about which victims and which cases were considered worthy of the time, effort, and attention of the criminal justice system. Lab personnel emphasized that police should only submit "real" cases for forensic DNA testing, which they typically defined as physically violent stranger-perpetrated sexual assaults; "shady" cases did not merit testing, which they defined as known-offender assaults, reports made by adolescent victims, and cases in which the victim may have been engaged in sex work. We noted marked similarities in police and lab personnel's rape myth acceptance, and stakeholders readily agreed that they did have a common understanding about which victims were not credible and therefore which SAKs did not merit testing. We discuss these findings in light of recommendations from the National Academy of Sciences for the independence and autonomy of the forensic sciences from law enforcement.


The role of autophagy in corpus luteum regression in the rat.
Autophagy is associated with luteal cells death during regression of the corpus luteum (CL) in some species. However, the involvement of autophagy or the association between autophagy and apoptosis in CL regression are largely unknown. Therefore, we investigated the role of autophagy in CL regression and its association with apoptosis. Ovaries were obtained from pseudopregnant rats at Days 2 (early), 7 (mid-), and 14 and 20 (late-luteal stage) of the pseudopregnancy; autophagy-associated protein (microtuble-associated protein light chain 3 [LC3]) was immunolocalized and its expression level was measured. Luteal cell apoptosis was evaluated by measuring cleaved caspase 3 expression. LC3 expression increased slightly from early to mid-luteal stage, with maximal levels detected at the late-luteal stage in steroidogenic luteal cells. The expression level of the membrane form of LC3 (LC3-II) also increased during luteal stage progression, and reached a maximum at the end point of late-luteal stage (Day 20). This pattern coincided with cleaved caspase 3 expression. Furthermore, LC3-II expression increased, as did levels of cleaved caspase 3 in luteal cells cultured with prostaglandin F(2alpha) known to induce CL regression. These findings suggest that luteal cell autophagy is directly involved in CL regression, and is correlated with increased apoptosis. In addition, autophagic processes were inhibited using 3-methyladenine or bafilomycin A1 to evaluate the role of autophagy in apoptosis induction. Inhibition of autophagosome degradation by fusion with lysosomes (bafilomycin A1) increased apoptosis and cell death. Furthermore, inhibition of autophagosome formation (3-methyladenine) decreased apoptosis and cell death, suggesting that the accumulation of autophagosomes induces luteal cell apoptosis. In conclusion, these results indicate that autophagy is involved in rat luteal cell death through apoptosis, and is most prominent during CL regression.


Light activates Ube3a, an Angelman syndrome-associated gene, by mediating the chromatin structures during postnatal development of mouse retina.
Angelman syndrome, a severe neurodevelopmental disorder, is primarily caused by mutations or deletions of maternally inherited ubiquitin protein ligase E3A (UBE3A). Activation of the silenced paternal copy of UBE3A can occur with pharmacological perturbation; however, an environmental approach has not been examined. Here, we found Ube3a is highly expressed in embryonic and early neonatal mouse retina and is maternally-, but not paternally-, expressed in ganglion cells, amacrine cells, and horizontal cells. Moreover, we analyzed UBE3A expression in the retina and visual cortex of postnatal day 28 mice (P28) following exposure to light emissions from white compact-fluorescent bulbs or blue light-emitting diodes from postnatal day 0 (P0) to 28 (P28), encompassing a crucial phase of visual system development. We found higher levels of Ube3a RNA and protein in the retina, but not visual cortex compared with tissues from P28 mice exposure to typical lighting (controls). Levels of both paternal- and maternal-UBE3A protein in mouse retina were higher than controls in P28 mice exposed to white or blue light. Moreover, levels of open and repressive chromatin structures, indicated by histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), respectively, were increased in the Ube3a promoter from mouse retina exposed to white or blue light. Our findings strongly suggest that extended exposure to white or blue light constitutes a substantial environmental factor that can effectively promote UBE3A expression within the central nervous system.


[Syphilis in a patient with the primary diagnosis of infectious mononucleosis, cytomegalovirus and herpes infection].
The paper reports a case of fresh secondary syphilis affecting oral cavity and lips in a 25 year old woman. The primary diagnosis of infectious mononucleosis, cytomegalovirus and herpes infection proved erroneous. Retrospective differential diagnostics of infectious mononucleosis, cytomegalovirus and herpes infection from fresh secondary syphilis was performed This case suggests the absence of vigilance with respect to venereal diseases in the medical personnel.


How to fit in: The learning principles of cell differentiation.
Cell differentiation in multicellular organisms requires cells to respond to complex combinations of extracellular cues, such as morphogen concentrations. Some models of phenotypic plasticity conceptualise the response as a relatively simple function of a single environmental cues (e.g. a linear function of one cue), which facilitates rigorous analysis. Conversely, more mechanistic models such those implementing GRNs allows for a more general class of response functions but makes analysis more difficult. Therefore, a general theory describing how cells integrate multi-dimensional signals is lacking. In this work, we propose a theoretical framework for understanding the relationships between environmental cues (inputs) and phenotypic responses (outputs) underlying cell plasticity. We describe the relationship between environment and cell phenotype using logical functions, making the evolution of cell plasticity equivalent to a simple categorisation learning task. This abstraction allows us to apply principles derived from learning theory to understand the evolution of multi-dimensional plasticity. Our results show that natural selection is capable of discovering adaptive forms of cell plasticity associated with complex logical functions. However, developmental dynamics cause simpler functions to evolve more readily than complex ones. By using conceptual tools derived from learning theory we show that this developmental bias can be interpreted as a learning bias in the acquisition of plasticity functions. Because of that bias, the evolution of plasticity enables cells, under some circumstances, to display appropriate plastic responses to environmental conditions that they have not experienced in their evolutionary past. This is possible when the selective environment mirrors the bias of the developmental dynamics favouring the acquisition of simple plasticity functions-an example of the necessary conditions for generalisation in learning systems. These results illustrate the functional parallelisms between learning in neural networks and the action of natural selection on environmentally sensitive gene regulatory networks. This offers a theoretical framework for the evolution of plastic responses that integrate information from multiple cues, a phenomenon that underpins the evolution of multicellularity and developmental robustness.


The impact of a standardized disease management program on race/ethnicity and gender disparities in care and mortality.
Data on racial and gender differences in mortality in patients followed in a standardized heart failure disease management program (HFDMP) are scarce. Survival was calculated by race/ethnicity and gender for 837 patients enrolled in a HFDMP. (The patients studied were indigent African American and White outpatients [39% African American, 36% female] enrolled into at Leonard J. Chabert Medical Center in Houma, Louisiana.) The hazard ratio associated with demographic and clinical characteristic individually and as a whole, was estimated for the four groups. White males had the highest mortality (African American female: HR=0.64, African American male: HR=0.65, White female: HR=0.67, p<.05). Age (HR=1.04, p<.001), ejection fraction (HR=0.97, p<.001), New York Heart Association (NYHA) (HR=1.57, p<.001), systolic blood pressure (HR=0.99, p<.05), hematocrit (HR=0.96, p<.01), diabetes (HR=0.98, p<.05), and body mass index (HR=0.98, p<.05) were significant predictors of mortality in the univariate model. Age (HR=1.04, p<.001), NYHA (HR=1.40, p<.001), diabetes (HR=2.52, p<.001), and White female (HR=.44, p<.01) were significant predictors of mortality in the multivariate model. With the exception of White females, who demonstrated lower mortality, amongst African American males and females and White males who participated in a HFDMP no difference in survival was observed.


Treatment of temporomandibular disorders among adolescents: a comparison between occlusal appliance, relaxation training, and brief information.
In a randomized trial the effects of occlusal appliance and relaxation therapy, each combined with brief information, were compared with brief information only, in adolescents with temporomandibular disorder (TMD) pain. One-hundred-and-twenty-two adolescents (93 F and 29 M aged 12-18 years) were randomly assigned to one of the following 3 groups: brief information + occlusal appliance (BI + OA), brief information + relaxation therapy (BI + RT), or brief information (BI). Included were subjects reporting pain once a week or more often, in addition to receiving a diagnosis of TMD according to the Research Diagnostic Criteria (RDC/TMD). They were evaluated before and after treatment and at a 6-month follow-up by means of self-reports and clinical assessment. The result revealed a significantly higher reduction in frequency of pain, in pain intensity (visual analog scale [VAS]), and in a composite pain index (intensity x frequency) for patients treated with BI + OA compared with those treated with BI alone. In the BI + OA group, 60% of the patients attained a clinically significant improvement (at least 50% or more) on the pain index, a significantly higher proportion compared to that obtained in the other 2 treatment groups. Analgesic consumption was also significantly more reduced in the BI + OA group compared to the BI group. However, no significant differences were found between the treatment groups in jaw opening or in muscle and TMJ tenderness scores. Occlusal appliance was found to be superior to both relaxation therapy and brief information regarding pain reduction and can therefore be recommended when treating adolescents with TMD pain.


Reversible cardiac dysfunction associated with hypocalcemia: a systematic review and meta-analysis of individual patient data.
Case reports have documented reversible cardiac dysfunction in the setting of severely depressed extracellular calcium concentrations. The present systematic review and meta-analyses of individual patient data were conducted to further characterize the cardiac dysfunction associated with low serum calcium levels in the clinical setting. We searched Ovid MEDLINE, Embase, PubMed databases and the Cochrane Library and the Registry of Clinical Trials from 1948 through August 2011. Studies that evaluated low serum calcium and cardiac dysfunction were identified and included for review. A total of 43 studies comprised of 47 individual cases met inclusion criteria. Univariate linear regression analysis showed a statistically significant correlation between corrected QT interval (QTc) length and corrected total serum calcium level (B = -23.19, SE = 8.04, P = 0.01), left ventricular ejection fraction and corrected total serum calcium (B = 5.16, SE = 1.29, P < 0.01) and ionized serum calcium (B = 5.48, SE = 2.04, P = 0.03). Hypocalcemia may be associated with reversible cardiac dysfunction including QTc interval prolongation and depressed left ventricular systolic function. The available evidence is very limited and does not provide a rationale for a certain threshold or a recommendation for calcium replacement. Future research is needed in this important and common metabolic disorder.


Investigation into mechanical, absorption and swelling behaviour of hemp/sisal fibre reinforced bioepoxy hybrid composites: Effects of stacking sequences.
This work focuses on the fabrication of hybrid bio-composites using green epoxy as the matrix material, hemp (H) and sisal (S) fibre mats as the reinforcements. The hybrid composite with sisal/hemp fibres were fabricated by cost effective hand lay-up technique, followed by hot press with different stacking sequences. Static properties of the composites such as tensile, compressive, inter-laminar shear strengths (ILSS) and hardness were examined. The physical properties such as density, void content, water absorption and thickness swelling were also analyzed. The experimental results indicate that hybrid composites exhibited minor variation in tensile strength when the stacking sequence was altered. The hybrid composite with the intercalated arrangement (HSHS) exhibited the highest tensile modulus when compared with the other hybrid counterparts. Hybrid composites (SHHS and HSSH) offered 40% higher values of compressive strength than the other layering arrangements. HHHH sample exhibited the highest ILSS value of 4.08 MPa. Typical failure characteristics of the short beam test such as inter-laminar shear cracks in the transverse direction, micro-buckling and fibre rupture were also observed.


Variation in body composition in professional soccer players: interseasonal and intraseasonal changes and the effects of exposure time and player position.
The aim of this study was to examine variations in measures of body composition in elite soccer players. Skinfolds and measures of body mass (BM) recorded on a monthly basis across an entire competitive season in a group of senior professional players (n = 26) were used to estimate percentage body fat (%BF) and provide fat-free body mass (FFBM) values. Mean values in players were compared between 6 specific positional roles (goalkeepers, central and lateral defenders/midfielders and center-forwards). In-season variations in measures were studied by comparing values at 5 separate points across the season. The effects of positional group (goalkeepers, defenders, midfielders, and forwards) and exposure time to play (participation time in training and matches) in relation to in-season variations were also examined. To investigate interseasonal changes, repeated measures were taken in players (n = 9) over 3 consecutive seasons. In relation to positional role, a difference in average %BF and BM values was observed (p < 0.001), with substantial differences observed in goalkeepers, lateral midfielders, and forwards. Across all players, there were significant in-season variations in %BF (between start- and mid-season and mid- and end-season, p < 0.001) and FFBM (between start- and mid-season and start- and end-season, p < 0.001), whereas BM remained unchanged. Further analysis of these fluctuations in %BF and FFBM at different points of the season showed that variations differed across the positional groups (p < 0.01), especially in defenders and midfielders. In contrast, no association was observed between measures and exposure time and no differences were reported across seasons. Practitioners should consider individual positional role when interpreting mean body composition data. They should also take into account positional groups when in-season variations in body composition are identified.


Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis.
We investigated whether plasma and synovial fluid (SF) samples from patients with rheumatoid arthritis (RA) contained extracellular mitochondrial DNA (mtDNA) or the oxidatively damaged DNA adduct 8-hydroxy-2'-deoxyguanosine (8-oxodG). Moreover, we correlated the laboratory findings of the patients with RA with their levels of mtDNA and 8-oxodG. SF and plasma samples from 54 patients with RA, SF from 30 non-arthritic control subjects, and plasma from 22 healthy volunteers were collected. The samples were subjected to polymerase chain reaction (PCR) using mitochondrial genomic primers, and the products were analyzed by SDS-polyacrylamide-gel electrophoresis. The intensities of the PCR-amplified bands were quantified and normalized to a reference sample. Furthermore, the SF samples were assayed by enzyme-linked immunosorbent assay for 8-oxodG. Extracellular PCR-amplifiable mtDNA was detected in the SF of 38 of 54 (70%) patients with RA, but not in any of the SF controls. PCR-amplifiable mtDNA was detected in the plasma of 30 of 54 (56%) of patients with RA and in 6 of 22 (27%) of the healthy volunteers. The levels of mtDNA in the plasma and SF samples of patients with RA were significantly higher (P < 0.0001) than in the respective control samples. The presence of both mtDNA and 8-oxodG in SF was significantly correlated with the presence of rheumatoid factor in the patients with RA. Extracellular mtDNA and oxidized DNA were detected in the SF of the great majority of patients with RA, but were absent or present at low levels in the control SF. These findings indicate that endogenous nucleic acid compounds might participate in joint inflammation by activating immune cells in the joints to produce proinflammatory cytokines.


[Combined effect of adenosine and papaverine on the metabolism of adenine nucleotides in rat thymocytes].
It is shown that in [14C]adenine-labelled thymocytes adenosine increases the content of adenine nucleotides and simultaneously accelerates their catabolism. Papaverine induces acceleration of splitting and a decrease of the specific ATP radioactivity but increases the AMP content and its specific radioactivity. The both effectors intensify considerably the outlet of total radioactive label from cells. If the papaverine effect in the extracellular medium results in accumulation mainly of hypoxanthine in the extracellular medium then the adenosine presence causes accumulation of inosine and hypoxanthine approximately in equal amounts. The release of labelled adenosine from thymocytes in all cases is an insignificant part of extracellular radioactivity. A conclusion is drawn that under conditions of the combined action of the substances under study papaverine removes the adenosine effect caused by its under study papaverine removes the adenosine effect caused by its phosphorylation with the formation of ATP and exerts the dose-depended action on adenine nucleotide metabolism in thymocytes.


Hemothorax associated with telangiectatic osteosarcoma in a dog.
Hemothorax in a dog was attributed to bleeding from an intrathoracic mass attached to the sixth through the tenth ribs. The mass contained numerous cavernous, blood-filled spaces as well as bands of osteoid and occasional foci of osseous tissue. The diagnosis was telangiectatic osteosarcoma. Telangiectatic osteosarcoma is an uncommon variant of osteosarcoma. Cavernous, blood-filled spaces and paucity of bone are important histologic features. Metastasis was described in one of the seven telangiectatic osteosarcomas reported in dogs, and none was found in this case.


Fabrication and Characterization of Human Serum Albumin Particles Loaded with Non-Sericin Extract Obtained from Silk Cocoon as a Carrier System for Hydrophobic Substances.
Non-sericin (NS) extract was produced from the ethanolic extract of Bombyx mori silk cocoons. This extract is composed of both carotenoids and flavonoids. Many of these compounds are composed of substances of poor aqueous solubility. Thus, this study focused on the development of a carrier system created from biocompatible and biodegradable materials to improve the biological activity of NS extracts. Accordingly, NS was incorporated into human serum albumin template particles with MnCO3 (NS-HSA MPs) by loading NS into the preformed HAS-MnCO3 microparticles using the coprecipitation crosslinking dissolution technique (CCD-technique). After crosslinking and template dissolution steps, the NS loaded HSA particles are negatively charged, have a size ranging from 0.8 to 0.9 µm, and are peanut shaped. The degree of encapsulation efficiency ranged from 7% to 57% depending on the initial NS concentration and the steps of adsorption. In addition, NS-HSA MPs were taken up by human lung adenocarcinoma (A549 cell) for 24 h. The promotion of cellular uptake was evaluated by flow cytometry and the results produced 99% fluorescent stained cells. Moreover, the results from CLSM and 3D fluorescence imaging confirmed particle localization in the cells. Interestingly, NS-HSA MPs could not induce inflammation through nitric oxide production from macrophage RAW264.7 cells. This is the first study involving the loading of non-sericin extracts into HSA MPs by CCD technique to enhance the bioavailability and biological effects of NS. Therefore, HSA MPs could be utilized as a carrier system for hydrophobic substances targeting cells with albumin receptors.


Condition and fate of logged forests in the Brazilian Amazon.
The long-term viability of a forest industry in the Amazon region of Brazil depends on the maintenance of adequate timber volume and growth in healthy forests. Using extensive high-resolution satellite analyses, we studied the forest damage caused by recent logging operations and the likelihood that logged forests would be cleared within 4 years after timber harvest. Across 2,030,637 km2 of the Brazilian Amazon from 1999 to 2004, at least 76% of all harvest practices resulted in high levels of canopy damage sufficient to leave forests susceptible to drought and fire. We found that 16+/-1% of selectively logged areas were deforested within 1 year of logging, with a subsequent annual deforestation rate of 5.4% for 4 years after timber harvests. Nearly all logging occurred within 25 km of main roads, and within that area, the probability of deforestation for a logged forest was up to four times greater than for unlogged forests. In combination, our results show that logging in the Brazilian Amazon is dominated by highly damaging operations, often followed rapidly by deforestation decades before forests can recover sufficiently to produce timber for a second harvest. Under the management regimes in effect at the time of our study in the Brazilian Amazon, selective logging would not be sustained.


Comparing the transcriptional profile of mesenchymal cells to cardiac and skeletal muscle cells.
Marrow-derived stroma cells (MSCs) can differentiate into multiple lineages including myogenic cells. However, the molecular mechanisms that direct MSCs to each differentiation pathway are poorly understood. Our study was designed to gain insights into the potential regulatory pathways that may assist in defining MSC commitment and differentiation properties. This will delineate the similarities or differences in the expression of genes between several cell types of mesenchymal origin. In this study, we established in vitro models, which allow following the discrete stages of differentiation of cardio- and myogenic-cells compared with MSC. Gene expression of each cell type at several stages of their differentiation path was evaluated by means of Affymetrix Gene Chips. Bioinformatic clustering of genes confirmed that with time in culture the myogenic cells ceased proliferating and commenced with differentiation. The expression profile analysis revealed the similarity and differences between myogenic cells and MSCs. This research compared at the molecular levels snapshots of gene expression patterns and elaborated on the overlap or differences between the analyzed cellular systems. Our results shed light on gene profiles of cells throughout their differentiation pathways. Establishing the gene signature of the differentiation process of cells that belong to several mesenchymal lineages may contribute to the understanding of molecular pathways that underlay mesenchymal tissue remodeling.


Physically Triggered Morphology Changes in a Novel Acremonium Isolate Cultivated in Precisely Engineered Microfabricated Environments.
Fungi are strongly affected by their physical environment. Microfabrication offers the possibility of creating new culture environments and ecosystems with defined characteristics. Here, we report the isolation of a novel member of the fungal genus Acremonium using a microengineered cultivation chip. This isolate was unusual in that it organizes into macroscopic structures when initially cultivated within microwells with a porous aluminum oxide (PAO) base. These "templated mycelial bundles" (TMB) were formed from masses of parallel hyphae with side branching suppressed. TMB were highly hydrated, facilitating the passive movement of solutes along the bundle. By using a range of culture chips, it was deduced that the critical factors in triggering the TMB were growth in microwells from 50 to 300 μm in diameter with a PAO base. Cultivation experiments, using spores and pigments as tracking agents, indicate that bulk growth of the TMB occurs at the base. TMB morphology is highly coherent and is maintained after growing out of the microwells. TMB can explore their environment by developing unbundled lateral hyphae; TMB only followed if nutrients were available. Because of the ease of fabricating numerous microstructures, we suggest this is a productive approach for exploring morphology and growth in multicellular microorganisms and microbial communities.


TGF-β Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPβ Pathways.
Lung epithelial cells play critical roles in idiopathic pulmonary fibrosis. In the present study, we investigated whether transforming growth factor-β (TGF-β)-induced expression of connective tissue growth factor (CTGF) was regulated by the extracellular signal-regulated kinase (ERK)/a disintegrin and metalloproteinase 17 (ADAM17)/ribosomal S6 kinases 1 (RSK1)/CCAAT/enhancer-binding protein β (C/EBPβ) signaling pathway in human lung epithelial cells (A549). Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. TGF-β-induced ERK phosphorylation as well as ADAM17 phosphorylation was attenuated by U0126. The TGF-β-induced increase in RSK1 phosphorylation was inhibited by TAPI-0 and U0126. TGF-β-induced C/EBPβ phosphorylation was weakened by U0126, ADAM17 siRNA, and RSK1 siRNA. In addition, TGF-β increased the recruitment of C/EBPβ to the CTGF promoter. Furthermore, TGF-β enhanced fibronectin (FN), an epithelial-mesenchymal transition (EMT) marker, and CTGF mRNA levels and reduced E-cadherin mRNA levels. Moreover, TGF-β-stimulated FN protein expression was reduced by ADAM17 siRNA and CTGF siRNA. The results suggested that TGF-β induces CTGF expression through the ERK/ADAM17/RSK1/C/EBPβ signaling pathway. Moreover, ADAM17 and CTGF participate in TGF-β-induced FN expression in human lung epithelial cells.


Average intensity and spreading of an elliptical gaussian beam propagating in a turbulent atmosphere.
An analytical formula for the average intensity of an elliptical Gaussian beam (EGB) propagating in a turbulent atmosphere is derived. The spreading properties of an EGB in a turbulent atmosphere are studied. It is found that an EGB will eventually become a circular Gaussian beam in a turbulent atmosphere. This interesting phenomenon is quite different from the propagation of an EGB in free space. The evolution properties are closely related to the parameters of the beam and the turbulent atmosphere.