Hypotonia-induced cell swelling enhances ultrasound-induced mechanical damage to cancer cells.
It has been shown that killing of suspended cells by low-intensity ultrasound (0.08-0.11 W/cm(2)) can be enhanced by a mild non-lethal hypotonic (146 mOsm) medium. In this study we wished to determine whether hypotonia-induced cell swelling of suspension cells was directly related to enhancement of ultrasound-mediated cell killing, and to verify whether similar effects could be observed on circulating and attached cells. U937 cells under mild hypotonia were exposed to ultrasound for different times with real-time monitoring of cell size using a particle-size-distribution analyzer. To study the effect on attached cells, HeLa cells were exposed to ultrasound while under hypotonia in an in vivo-simulated set-up. The result showed that the enhanced cell killing (up to more than twice) was directly proportional to hypotonia-induced cell swelling. Similar membrane damage based on PI staining could be observed on HeLa cells treated with hypotonia. An in vivo-simulated circulating system also showed similar findings for hypotonia-enhanced ultrasound cell killing. These findings showed that mild hypotonia can be used to augment the effect of ultrasound in the treatment of cancers, particularly leukemia. The results showing that such enhancement is related to cell swelling could guide us toward proper timing of sonication while under hypotonic treatment.


Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation.
While external ionizing radiation has been used for treating non-small cell lung cancer (NSCLC), improved efficacy of this modality would be an important advance. Ectopic expression of the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes in NSCLC cells facilitated concentration of iodide in NSCLC cells, which markedly induced apoptosis in vitro and in vivo. Pre-incubation of the NIS/TPO-modified NSCLC cells in iodide followed by ionizing radiation generates bystander tumoricidal effects and potently enhances tumor cell killing. This iodide-induced bystander effect is associated with enhanced gap junction intercellular communication (GJIC) activity and increased connexin-43 (Cx43) expression. Thus, iodide may serve as an enhancer to markedly improve the efficacy of radiation therapy in combined therapeutic modalities.


Up-regulation of IL-33 expression in various types of murine cells by IL-3 and IL-4.
The crucial roles of the novel cytokine IL-33 in allergic, inflammatory, infectious and autoimmune diseases are becoming characterized. However, the cytokines which regulate IL-33 expression and secretion are still largely unknown. In this study, IL-3 and IL-4 were found to up-regulate IL-33 mRNA expression in mouse peritoneal exudate cells by a two-color DNA microarray and further confirmed by real time PCR and ELISA. IL-3 and IL-4 synergistically promote IL-33 mRNA expression and IL-33 intracrine in the heterogeneous cell populations as peritoneal exudates cells, bone marrow cells and splenic cells. IL-3 and IL-4 also induced IL-33 introcrine in the peritoneal exudate cells from the macrophage-deficient op/op mice, suggesting that macrophage is not the only target of IL-3 and IL-4 in the heterogeneous peritoneal exudate cells. Furthermore, IL-3 and IL-4 were verified to promote the IL-33 intracrine in the homogeneous cell population as fibroblasts and mast cells. These results indicate that up-regulation of IL-33 expression by IL-3 and IL-4 is not a feature particular to a specific type of cells. Up to 100 cytokines were screened, but none of them stimulated the secretion or release of IL-33 in the culture system. In summary, we confirm for the first time that IL-3 and IL-4 are critical for IL-33 intracrine in murine cells of various types, indicating that IL-3 and IL-4 may play an important role in the constitutive expression of IL-33 in vivo.


Training needs of nurses and social workers in the end-of-life care for people with intellectual disabilities: a national survey.
Nurses and social workers caring for people with intellectual disabilities are increasingly confronted with clients in need of end-of-life care. Previous studies, however, suggest that professionals in intellectual disability care services lack knowledge and experience concerning end-of-life care. Moreover, the proportion of nurses within the staff of intellectual disability services has declined in recent years, while the proportion of social workers has increased, which may have consequences for the quality of end-of-life care. To gain insight into the quality of end-of-life care, past vocational training, training needs and expert consultation opportunities of nurses and social workers working in intellectual disability care services. Survey questionnaire study conducted in the Netherlands. Intellectual disability care services. The study sample was recruited from an existing nationally representative research panel of care professionals. In 2011, all 181 nurses and social workers in the research panel who worked in intellectual disability care services were sent our survey questionnaire. Postal survey addressing education, views and needs regarding end-of-life care. The response was 71.8%. Respondents positively evaluated the quality of end-of-life care. However, most respondents felt inadequately trained in end-of-life care issues. Nurses had received more training in end-of-life care and had fewer training needs than social workers. Respondents wished for additional training, especially in supporting clients in dealing with the impending death and farewell process. Half of the respondents were unaware of the availability of external consultation facilities. This study shows that although nurses and social workers positively appraise the quality of end-of-life care for people with intellectual disabilities, the majority feel inadequately trained to provide good end-of-life care. As the number of people with intellectual disability in need of end-of-life care grows, organizations need to offer additional relevant training and must give information about the availability of external expert consultation for nurses and social workers.


Electrophoretic characterization of pyrimidine 5'-nucleotidase of human erythrocytes and its distinction from acid phosphatase.
Electrophoresis of red cell pyrimidine 5'-nucleotidase was carried out on cellulose acetate strips. One major band of activity was found in preparations from human erythrocytes. This enzyme showed a specificity for the pyrimidine nucleotides UMP and CMP. No activity was detected with AMP. Pyrimidine 5'-nucleotidase activity could be separated from that of acid phosphatase with the use of alpha-glycerophosphate. This method may be useful in the study of pyrimidine 5'-nucleotidase deficiency in red cells.


Treatment of scleroderma skin ulcers with a hydrocolloid membrane.
The purpose of this study was to determine the usefulness of hydrocolloid membrane dressings in the treatment of finger and hand ulcers of scleroderma (progressive systemic sclerosis). Ten pairs of ulcers occurring in seven patients were studied. The ulcers in each patient were treated in a paired comparison trial: one ulcer in each pair was treated with a hydrocolloid membrane; the other was a control. Treatment was continued until at least one ulcer of each pair was healed. The rate of healing of the hydrocolloid membrane-treated ulcers was significantly faster than that of the control ulcers. Pain was rapidly and dramatically reduced in all hydrocolloid membrane-treated ulcers. An infection caused by Pseudomonas aeruginosa occurred in a hydrocolloid membrane-treated ulcer but rapidly responded to topical therapy. Hydrocolloid membrane treatment of sclerodermatous hand ulcers appears to be an effective method of accelerating healing and reducing pain.


Yeast mitochondrial leucyl-tRNA synthetase CP1 domain has functionally diverged to accommodate RNA splicing at expense of hydrolytic editing.
The yeast mitochondrial leucyl-tRNA synthetase (ymLeuRS) performs dual essential roles in group I intron splicing and protein synthesis. A specific LeuRS domain called CP1 is responsible for clearing noncognate amino acids that are misactivated during aminoacylation. The ymLeuRS CP1 domain also plays a critical role in splicing. Herein, the ymLeuRS CP1 domain was isolated from the full-length enzyme and was active in RNA splicing in vitro. Unlike its Escherichia coli LeuRS CP1 domain counterpart, it failed to significantly hydrolyze misaminoacylated tRNA(Leu). In addition and in stark contrast to the yeast domain, the editing-active E. coli LeuRS CP1 domain failed to recapitulate the splicing activity of the full-length E. coli enzyme. Although LeuRS-dependent splicing activity is rooted in an ancient adaptation for its aminoacylation activity, these results suggest that the ymLeuRS has functionally diverged to confer a robust splicing activity. This adaptation could have come at some expense to the protein's housekeeping role in aminoacylation and editing.


Structural analysis of a water insoluble polysaccharide from pearl millet and evaluating its prebiotic activity.
Epidemiological studies have shown an inverse correlation between dietary intake of prebiotics and the risk of chronic diseases. Pearl millet is a potential economic source to develop a new class of prebiotics in the form of its polysaccharide. In the present study, the chemical structure of a water insoluble homopolysaccharide (PMG), and its prebiotic properties were investigated. The structure of PMG was elucidated on the basis of total hydrolysis, methylation analysis, and 1D/2D NMR (1H, 13C, DEPT-135, HSQC, DQF-COSY, NOESY and ROESY) experiments. The results indicated that PMG was a glucan with an average molecular weight ~ 361 kDa having a backbone of (1 → 3) α-d-glucopyranosyl residues. Hydrolysis of PMG by salivary and pancreatic α amylase was 1.75 % ± 0.34 and 1.99 % ± 0.18 respectively. A positive prebiotic score of PMG with both L. acidophilus and L. brevis (0.446 ± 0.031 & 0.427 ± 0.016) hints towards its prebiotic potential. These observations suggest that PMG might be used as a potential prebiotic component in the food and pharmaceutical applications.


Lung afferent activity: implications for respiratory sensation.
Stimuli within the lung can cause the sensations of pain, ache, irritation and urge-to-cough. In general these are abolished or inhibited by vagal section or vagal anaesthesia, or local anaesthesia within the airways. They are present in patients with functional high cervical spinal cord transaction and after general neuromuscular paralysis. There are at least nine sensors in the bronchopulmonary system, studied almost entirely in animals. It is at present impossible to link any one sensor with any one pattern of sensation. It is reasonable to suppose that urge-to-cough arises from sensors what mediate cough, but there are at least five sensors involved in this reflex, and how they relate to unpleasant sensation is unknown. The problem is that sensation can almost only be studied in humans, and the vagal neural mechanisms almost only in other species. Vagal sensors can also ameliorate the sensation of air hunger, and this is probably due to the action of slowly adapting pulmonary stretch receptors (SARs). The same sensors may give rise to the awareness of lung volume and its changes. Many sensors in the lungs can be sensitized or desensitized by natural or imposed conditions, and this could underlie the sensitization and desensitization of dyspnoeic sensations that have been described.


[Analysis of immune microenvironment by multiplex immunohistochemistry in locally advanced non-small cell lung cancer: Principles and perspectives].
Recent therapeutic advances in non-small cell lung cancer allow a better understanding of the interactions between the tumour and its direct immune environment. The identification of new immune biomarkers integrating both cell subpopulations and their interactions is a real issue in oncology. New techniques of tissue analysis, particularly multiplex immunohistochemistry, consisting of a labelling of several antigens of interest by immunofluorescence on the same slide, provide a better understanding of the tumour environment. Integration of these modalities of analysis to the therapeutic decision is promising, because it allows an increased characterization of each tumour, particularly interesting with radiotherapy and immunotherapy. This article describes the potential of these assays in locally advanced non-small cell lung cancer.


The human leucocyte sodium pump in adrenocortical insufficiency.
In view of the known effects of cortisol and related compounds on sodium balance, we examined leucocyte 22Na+ efflux in patients with adrenocortical insufficiency. The ouabain-sensitive 22Na+ efflux rate constant, which reflects sodium pump activity, was lowered in secondary hypoadrenalism (mean 1.95 +/- SD 0.25 vs 2.33 +/- 0.45 h-1, P less than 0.002, n = 6). Patients with hypoadrenalism also had higher intracellular sodium content (mean 34.9 +/- SD 3.5 vs 27.8 +/- 9.5 mmol/kg dry weight, P less than 0.008) and lower intracellular potassium to sodium ratios (mean 9.7 +/- SD 0.7 vs 12.9 +/- 3.6, P less than 0.001). These defects in cellular sodium balance were corrected following replacement therapy with cortisol, prednisolone or dexamethasone. In-vitro incubation of normal leucocytes with 5-20 nmol/l dexamethasone led to an increase in the Na+/K+-ATPase activity. The effect of cortisol and related compounds on the distribution of sodium between intra- and extra-cellular fluid may be mediated by their action on the sodium pump.


The relationship between perceived mutuality and bulimic symptoms, depression, and therapeutic change in group.
This pilot study examined (a) the effectiveness of short-term group relational therapy (RT) in comparison to short-term group cognitive-behavioral therapy (CBT), and (b) the relationship between perceived mutuality (PM) in relationships and severity of bulimic and depressive symptoms in women with bulimia nervosa (BN). Fifteen women ages 20-54 diagnosed with BN (n=11) or binge-eating disorder (BED, n=4) were randomly assigned to a 16-week manualized RT or CBT group. The following measures were administered at baseline, at 8 and 16 weeks, and at 6th- and 12th-month follow-ups: Eating Disorders Inventory-2 (EDI-2), Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), and the Mutual Psychological Development Questionnaire (MPDQ). A series of mixed design analyses of variance (ANOVA) were computed to examine group therapy effectiveness and outcomes related to PM and symptom severity. Both group RT and CBT treatment conditions showed significant improvement in reducing binge eating, vomiting, and depression at end of treatment and across follow-up assessment times. Low levels of PM with father at baseline were associated with high levels of bulimic and depressive symptoms across assessment times, whereas low PM with mother was only associated with high levels of depression. Pilot study findings supported the idea that group work focused primarily on PM and relational factors can be effective in treating women with bulimic and depressive symptoms. Findings also suggest that relationships with fathers play an important role in recovery.


Bilateral V-Y flap for a perianal basal cell carcinoma: A case report.
Basal cell carcinomas are rare in non-sun-exposed skin, and are even rarer in the perianal region. Alertness to the unusual occurrence of this tumor at perianal site, with understanding of its clinical course, can prevent delay in its diagnosis and morbid aggressiveness in the management of the disease. A 93 year old female, referred to our hospital because of a three month bleeding ulcerative lesion, with a diameter approximately of 4.5×3.2cm, located in the perianal region. Tumors of the anus and perianal are infrequent neoplasms of the digestive tract. There are many diseases that can be confused with this diagnosis and it is commonly delayed because the tumor is rarely thought of in this particular cutaneous topography. Suspicion and early diagnosis, give the opportunity for a timely and appropriate treatment and also prevent tumor extension. Treatment modalities include early wide local excision to clear margins, ensuring further local recurrence and distant metastasis. The use of local V-Y advancement fasciocutaneous flaps may be another valid option for the reconstruction of perianal skin defects, with less morbidity than other flaps described in the literature.


Rifampicin in periprosthetic joint infections: where do we stand and where are we headed?
A periprosthetic joint infection (PJI) is a major complication of arthroplasty. Treatment of PJI consists of surgical debridement with or without the exchange of the implant and long-term antimicrobial treatment. Rifampicin is regarded as one of the cornerstones of antimicrobial treatment for staphylococcal PJI, but the exact role of rifampicin for PJI in different clinical scenarios remains to be elucidated. In this perspective article, an overview is provided of in vitro, in vivo and clinical studies that were the basis of the current guidelines and recommendations for rifampicin use in daily practice for PJI. Controversial issues on indication, dosing, timing, duration, and antibiotic drug interactions will be addressed. Finally, the most urgent clinical questions on rifampicin use that need answering in the nearby future will be formulated. Many inquiries remain concerning the exact indications and clinical use of rifampicin in PJI. Randomized controlled trials are needed to answer these questions.


Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast.
Nuclear retention of pre-mRNAs is tightly regulated by several security mechanisms that prevent pre-mRNA export into the cytoplasm. Recently, spliceostatin A, a methylated derivative of a potent antitumor microbial metabolite FR901464, was found to cause pre-mRNA accumulation and translation in mammalian cells. Here we report that spliceostatin A also inhibits splicing and nuclear retention of pre-mRNA in a fission yeast strain that lacks the multidrug resistance protein Pmd1. As observed in mammalian cells, spliceostatin A is bound to components of the SF3b complex in the spliceosome. Furthermore, overexpression of nup211, a homolog of Saccharomyces cerevisiae MLP1, suppresses translation of pre-mRNAs accumulated by spliceostatin A. These results suggest that the SF3b complex has a conserved role in pre-mRNA retention, which is independent of the Mlp1 function.


Effect of tourism and trade on intestinal parasitic infections in Guatemala.
A survey was performed to determine if infection with gastrointestinal parasites differs between the rural and urban poor inhabitants of Guatemala. A total of 317 stool samples from children in two towns, one rural and one urban, were examined using the formalin-ether concentration method. The overall prevalence of parasites in infected children was 67%, 20%, 30%, and 22%, respectively for Ascaris lumbricoides, Trichuris trichiura, Giardia duodenalis and Entamoeba histolytica in the rural town of La Mano de Leon and 49%, 14%, 15%, and 21%, respectively in the urban town of Santa Maria de Jesus. Two sub-studies were carried out to determine the effects of (1) gender and (2) age on the rate of parasitic infections. Female children in the 1-to 6-year-olds age group in Santa Maria de Jesus had more infections with A. lumbricoides and T. trichiura when compared to La Mano de Leon. A. lumbricoides was most prevalent in Santa Maria de Jesus. These results propose that accessibility to tourism and trade decreases the risk for the establishment of parasitic diseases in children of Guatemala possibly due to improvements in basic nutrition and availability of health care.


The injected-charge contrast mechanism in scanned imaging of doped semiconductors by very slow electrons.
A new contrast mechanism is reported that visualizes doped areas in semiconductors in very low-energy electron micrographs. The method is based on the use of the cathode lens principle in a scanning electron microscope, in order to form a primary beam of energy in units of electron volts. Below about 3eV the doped areas exhibited a strong contrast, the explanation of which is based on the injection and recombination of electrons and on the ability of the small negative surface charge thereby created to decrease the very low landing energy of incident electrons near enough to conditions of total reflection. This imaging method enables one to study the charge injection effects in semiconductors, and in view of its high contrast the mode may offer fast image acquisition, while the extremely low-electron energy ensures operation free of any radiation damage to the specimen.


Solution-phase combinatorial synthesis of ureas using nitrophenylcarbamates.
Nitrophenylcarbamates were reacted with various amines to yield ureas. A high throughput purification of these crude products was achieved by using polymer bound scavengers.


Transcriptome Analysis of Neuroendocrine Regulation of Ovine Hypothalamus-Pituitary-Ovary Axis during Ovine Anestrus and the Breeding Season.
Most sheep are seasonal estrus, and they breed in autumn when the days get shorter. Seasonal estrus is an important factor that affects the productivity and fertility of sheep. The key point to solve this problem is to explore the regulation mechanism of estrus in sheep. Therefore, in this study, transcriptomic sequencing technology was used to identify differentially expressed mRNAs in the hypothalamus, pituitary and ovary of Small Tail Han sheep (year-round estrus) and tan sheep (seasonal estrus) among luteal, proestrus and estrus stages. There were 256,923,304,156 mRNAs being identified in the hypothalamus, pituitary and ovary, respectively. Functional analysis showed that the photosensor, leucine and isoleucine biosynthesis pathways were enriched significantly. It is speculated that photoperiod may initiate estrus by stimulating the corresponding pathways in hypothalamus. ODC1, PRLH, CRYBB2, SMAD5, OPN1SW, TPH1 are believed to be key genes involved in the estrogen process. In conclusion, this study expanded the database of indigenous sheep breeds, and also provided new candidate genes for future genetic and molecular studies on the seasonal estrus trait in sheep.


Establishment of mouse model of MYH9 disorders: heterozygous R702C mutation provokes macrothrombocytopenia with leukocyte inclusion bodies, renal glomerulosclerosis and hearing disability.
Nonmuscle myosin heavy chain IIA (NMMHCIIA) encoded by MYH9 is associated with autosomal dominantly inherited diseases called MYH9 disorders. MYH9 disorders are characterized by macrothrombocytopenia and very characteristic inclusion bodies in granulocytes. MYH9 disorders frequently cause nephritis, sensorineural hearing disability and cataracts. One of the most common and deleterious mutations causing these disorders is the R702C missense mutation. We generated knock-in mice expressing the Myh9 R702C mutation. R702C knock-in hetero mice (R702C+/- mice) showed macrothrombocytopenia. We studied megakaryopoiesis of cultured fetal liver cells of R702C+/- mice and found that proplatelet formation was impaired: the number of proplatelet tips was decreased, proplatelet size was increased, and proplatelet shafts were short and enlarged. Although granulocyte inclusion bodies were not visible by May-Grünwald Giemsa staining, immunofluorescence analysis indicated that NMMHCIIA proteins aggregated and accumulated in the granulocyte cytoplasm. In other organs, R702C+/- mice displayed albuminuria which increased with age. Renal pathology examination revealed glomerulosclerosis. Sensory hearing loss was indicated by lowered auditory brainstem response. These findings indicate that Myh9 R702C knock-in mice mirror features of human MYH9 disorders arising from the R702C mutation.


The case for polyvalent cancer vaccines that induce antibodies.
Antibodies are ideally suited for eradicating pathogens from the bloodstream and early tissue invasion. With regard to cancer cells, passively administered and vaccine induced antibodies have accomplished this, eliminating circulating tumor cells and systemic or intraperitoneal micrometastases in a variety of preclinical models. A series of cancer cell-surface differentiation antigens have now been identified and synthesized. Antibodies against each can be induced in most vaccinated patients using keyhole limpet hemocyanin conjugate vaccines with a potent immunological adjuvant. Polyvalent vaccines may be required due to tumor cell heterogenely, heterogeneity of the human immune response and the correlation between overall antibody titer against tumor cells and antibody effector mechanisms. Trials testing the clinical impact of these polyvalent vaccines in the adjuvant setting are planned for the near future.


Autocrine motility factor and its receptor: role in cell locomotion and metastasis.
The ability to locomote and migrate is fundamental to the acquisition of invasive and metastatic properties by tumor cells. Autocrine motility factor (AMF) is a 55 kD cytokine produced by various tumor cells which stimulates their in vitro motility and in vivo lung colonizing ability. AMF stimulates cell motility via a receptor-mediated signalling pathway. Signal transduction following binding of AMF to its receptor, a cell surface glycoprotein of 78 kD (gp78) homologous to p53, is mediated by a pertussis toxin sensitive G protein, inositol phosphate production and the phosphorylation of gp78. Cell surface gp78 is localized to the leading and trailing edges of motile cells but following cell permeabilization is found within an extended network of intracellular tubulovesicles. Gp78 tubulovesicles colocalize with microtubules and extension of the tubulovesicular network to the cell periphery is dependent on the presence of intact microtubules. Gp78 labeled vesicles can be induced to translocate between the cell center and periphery by altering intracellular pH as previously described for tubulovesicles labeled by fluid phase uptake. Anti-gp78 mAb added to viable motile cells is localized to large multivesicular bodies which, with time, relocate to the leading edge. Binding of AMF to its receptor induces signal transduction, similar to chemotactic stimulation of neutrophil mobility, as well as the internalization and transport of its receptor to the leading edge stimulating pseudopodial protrusion and cell motility.


Inflammatory degeneration of joint tissue in adjuvant arthritis after intraarticular treatment with the mixture of silver drug and nicotinic acid.
Combination intraarticular administration of Poviargol (0.5 mg/kg) and nicotinic acid (1.0 mg/kg) reduced symptoms of local and general inflammation in rats with adjuvant arthritis. We revealed a decrease in morphological signs of inflammatory degeneration of joint tissue and reduction of metabolic disorders.


Hexahydrocarbon effects on intermediate filament organization in human fibroblasts.
We reported previously that 2,5-hexanedione (2,5-HD), the neurotoxic metabolite of methyl-n-butylketone (MnBK) and n-hexane, induced aggregation of intermediate filaments of the vimentin type in cultured fibroblasts. To determine if these findings have relevance to the mechanism by which these hexacarbons induce their filamentous axonopathy, it was necessary to show that only those hexacarbon analogues that induce focal accumulation of neurofilaments in nerve fibers do aggregate intermediate filaments in fibroblasts. We report here that the nonneurotoxic hexacarbons, 1,6-hexanediol and 2,4-hexanedione (2,4-HD), had no primary effect on intermediate filament distribution in fibroblasts, although the profound, nonspecific cytotoxicity of the latter controverted comparisons with equimolar, effective concentrations of 2,5-HD. Fibroblasts did not metabolize MnBK to 2,5-HD sufficiently to induce reproducible aggregation of intermediate filaments in these cells in culture.


Effect of low-molecular-weight heparin in women undergoing frozen-thawed embryo transfer cycles: a retrospective cohort study.
Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) during in vitro fertilization (IVF) treatment are still tough problems without effective treatments; thus, they are important research topics. There is controversy on whether low molecular weight heparin (LMWH) improves pregnancy outcomes in women with unexplained RPL and RIF. Moreover, currently, there is a paucity of reports on the role of LMWH in the entire population undergoing frozen-thawed embryo transfer (FET) cycles. This study aimed to estimate the effects of LMWH on pregnancy outcomes in women undergoing FET cycles. There were 1881 female patients included in the study. Of the 1881 patients, 107 underwent preimplantation genetic diagnosis cycles, which were analyzed individually. The patients were divided into two groups: the LMWH group received injections of 4100 IU/d LMWH from the day of transfer until 14 ± 2 days posttransplant, the control group was the comparison group (without LMWH use). The baseline characteristics and reproductive outcomes of the patients were reviewed. Of the 1774 women with normal FET cycles, no significant differences were found in the number of embryos implanted (1.31 ± 0.02 vs. 1.28 ± 0.02), embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, late abortion rate, and ectopic pregnancy rate between the two groups. The LMWH group had a higher early abortion (17.8% [76/427] vs. 12.5% [55/439], p = 0.030). In the sub-group analysis, among the patients who underwent more than four transfers, the LMWH group had a lower late abortion rate (1.7% [1/60] vs. 13.2% [7/53], p = 0.043). Similarly, of the 107 women who underwent preimplantation genetic diagnosis cycles, the reproductive outcomes were comparable between the two groups. In the general population and PGD patients, LMWH did not improve pregnancy outcomes. Therefore, the routine use of LMWH is not recommended for early treatment.


Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis.
Aberrant fetal growth remains a leading cause of perinatal morbidity and mortality and is associated with a risk of developing non-communicable diseases later in life. We performed a systematic review and meta-analysis combining human and animal studies to assess whether prenatal amino acid (AA) supplementation could be a promising approach to promote healthy fetal growth. PubMed, Embase and Cochrane libraries were searched to identify studies orally supplementing the following AA groups during gestation: (1) arginine family; (2) branched chain (BCAA); (3) methyl donors. Primary outcome was fetal/birth weight. 22 human and 89 animal studies were included in the systematic review. The arginine family, and especially arginine itself, was studied most. Our meta-analysis showed beneficial effects of arginine and (N-Carbamyl) glutamate (NCG), but not aspartic acid and citrulline on fetal/birth weight. However, no effects were reported when isonitrogenous control diet was included. BCAA and methyl donor supplementation did not affect fetal/birth weight. Arginine family supplementation, in particular arginine and NCG, improves fetal growth in complicated pregnancies. BCAA and methyl donor supplementation do not seem to be as promising to target fetal growth. Well controlled research in complicated pregnancies is needed before ruling out AA supplements or preferring arginine above other AAs.


Proportion of night eating syndrome in Arab population of Oman.
Globally obesity has reached epidemic proportions with alarming rates in the Arabian Gulf countries. The impact of behavioral eating habits and in particular night eating syndrome (NES) have not been emphasized in the region. This study assessed the proportion of NES in an Omani Arab adult population sample. A night eating syndrome questionnaire (NEQ) was distributed to Omani adults above the age of 20. Out of the 454 respondents, 26.4 % endorsed evening hyperphagia while nocturnal ingestion was present in 4.7 % of the respondents. In addition, 1.5 % of the respondents met the NES criteria. The proportion of NES in Omani adult population is similar to the reported rates in general world populations. In conclusion, night eating syndrome is present in the Omani Arab adults and should be taken into account in national management for increased obesity trends in the region.


N-Caffeoyl serotonin as selective COX-2 inhibitor.
The inhibitory effects of the synthetic serotonin analogues (1-8) on COX (1 and 2) were evaluated. Two serotonin derivatives (4 and 8) showed inhibitory effect of COX (1 and 2). Especially, 4 exhibited excellent inhibitions on COX-2 with extremely high potency (IC(50)=42.5 μM). The inhibitory activities of cinnamic acid derivatives and serotonin were evaluated to clarify whether inhibitory activities of compound 4 and 8 are due to cinnamic acid moiety or serotonin moiety. Caffeic acid and N-caffeoyl serotonin (4) exhibited selective inhibition of COX-2 compared to aspirin. Comparison caffeic acid with 4 suggested that the linkage of caffeic acid and serotonin enhance COX-2 inhibition. Comparison of structures of caffeic acid and sinapic acid implied that catechol moiety of cinnamic acid derivatives is a major contributing factor for selective inhibition of COX-2. The selective COX-2 inhibitory activity of compound 4 is significant and could be employed as drugs against inflammatory and allergy.


[Hormonal contraception as a risk factor for developing cervical cancer: biological, epidemiological and immunological evidence].
Cervical cancer has been extensively studied, as well as the various risk factors for that cancer. One such factor is the prolonged use of hormonal contraceptives. To report the biological, immunological and epidemiological findings arising from the use of oral contraceptives and their relation to cervical cancer. Retrospective study based on information published in national and international literature. Controversy persists between the epidemiological data and experimental biological association between hormonal contraceptives and cancer induced by HPV. It is important to consider the biological findings because in Mexico the use of hormonal contraceptives is very broad and the number of cases of cervical cancer and only extensive epidemiological studies will clarify this controversy.


cis-β-Bromostyrene derivatives from cinnamic acids via a tandem substitutive bromination-decarboxylation sequence.
cis-β-Bromostyrene derivatives were synthesized stereospecifically from cinnamic acids through β-lactone intermediates. The synthetic sequence did not require the purification of the β-lactone intermediates although they were found to be stable and readily purified in most cases.


Aqueous phase hydrogenolysis of glycerol to bio-propylene glycol over Pt-Sn catalysts.
PtSn supported on SiO(2) obtained via surface organometallic chemistry techniques catalyzes hydrogenolysis of glycerol to obtain bio-propylene glycol (PG). Bimetallic catalysts with Sn contents between 0.1% and 1% wt were carefully prepared by selective hydrogenolysis of Sn(n-C(4)H(9))(4) on Pt. TEM, TPR, H(2) and CO chemisorptions, and XPS studies have shown that tin selective deposition on the metallic phase is obtained. At 200°C under N(2) or H(2) pressure, the presence of tin increases drastically: both the selectivity and the activity of the glycerol conversion into PG. During 2h batch runs; it could be observed that PtSn catalysts with Sn/Pt ratio=0.2 showed the best performance (PG selectivity=59% and 83% under N(2) and H(2) pressure respectively). The increase in activity and selectivity could be explained by the presence of Sn(+n) species "acid Lewis sites" which would facilitate the C-OH adsorption and its subsequent C-O cleavage favoring the propylene glycol production.


Expression profiles and potential corneal epithelial wound healing regulation targets of high-mobility group box 1 in diabetic mice.
As a damage-associated molecular pattern molecule, high-mobility group box 1 protein (HMGB1) is involved in diabetes and its complications. However, the role of HMGB1 in diabetic keratopathy is not yet understood. The purpose of this study was to investigate the potential roles of HMGB1 in the development of diabetic keratopathy as well as potential strategies to block HMGB1 in order to prompt epithelial wound healing and nerve regeneration in diabetic corneas. The results demonstrated that diabetic keratopathy developed in mice over the duration of the diabetic condition with typical symptoms, including damaged ocular surfaces and corneal nerves. The diabetic corneas had significantly increased protein expression levels of HMGB1 and its receptors-the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4)-compared to the age-matched normal corneas (P < 0.05). Corneal HMGB1 levels significantly increased during the corneal wound healing process of the diabetic mice, peaking on the first day after the wound was created and then decreasing to the unwounded level on the seventh day. Exogenous HMGB1 peptide significantly retarded wound and nerve healing, while glycyrrhizin (an HMGB1 inhibitor) significantly prompted wound and nerve healing. Further, the western blot results confirmed that RAGE and TLR4 were also involved in corneal wound and nerve healing. In conclusion, these data showed that HMGB1 and its related receptors are highly involved in the development of diabetic keratopathy. This finding indicates that the blockage of HMGB1 might serve as a strategy to prompt diabetic corneal and nerve wound healing.


A Single Institution Cadaveric Study on Anatomical Variation of the Sublingual Gland Duct.
The purpose of this study was to conduct a cadaveric dissection study on the anatomical variation of the sublingual (SLG) excretory ducts and dictate an improved understanding of the anatomical communication between the SLG duct and submandibular (SMG) ducts. This study is carried out by standardized dissection of anterior floor of mouth in 6 formalin-fixed adult cadavers in Silent Mentor Workshop University Malaya in August 2020. The cadavers had no trace of scars, adhesions, signs of trauma or operation. SMG duct opening was identified lateral to the lingual frenulum through a papilla in the floor of mouth behind the lower incisor tooth. A horizontal incision line was done over floor of mouth just lateral to the opening. SMG duct and SLG was traced and skeletonized. Any presence of major duct arising from the SLG and its communication with SMG duct were investigated. We found there are 3 patterns of SLG excretory duct variants; (1) One major (Bartholin's) duct which open independently at its own orifice adjacent to the orifice of the Wharton's duct of SMG. (2) One major (Bartholin's) duct which joined into the Wharton's duct of SMG. (3) Absent of a major duct arising from SLG. The overall mean diameter of SLG ducts were 1.3 ± 0.41 and the mean length of SLG ducts were 18.5 ± 6.55. The overall mean diameter of SMG ducts was 2.6 ± 0.74 and the mean length of SMG ducts were 46.5 ± 6.57. Excretory ductal system of SLG showed great variations, not only between the different cadavers but also within the different sides of the same cadaver. Awareness of potential anatomical variations can aid in the accurate diagnosis and treatment of patients with salivary gland pathology as well as help surgeons reveal potential risk factor and avoid complications during surgical procedures in the floor of mouth.


Practice-education synergy: a research focus on continuity of care.
In this article we have described one focus of an ongoing partnership between a VHA medical center and a university-based school of nursing: to improve patient outcomes through a research program focused on patient-centered continuity of care. A nursing effectiveness and patient outcomes matrix was introduced as a framework to guide variable identification, including nursing-specific outcomes. Opportunities and challenges inherent in developing this program of research were discussed. The synergy of a successful practice-education collaboration not only strengthens the links between practice and education but may also directly affect patient-centered outcomes of nursing care.


Quantifying creatinine and urea in human urine through Raman spectroscopy aiming at diagnosis of kidney disease.
Due to their importance in the regulation of metabolites, the kidneys need continuous monitoring to check for correct functioning, mainly by urea and creatinine urinalysis. This study aimed to develop a model to estimate the concentrations of urea and creatinine in urine by means of Raman spectroscopy (RS) that could be used to diagnose kidney disease. Midstream urine samples were obtained from 54 volunteers with no kidney complaints. Samples were subjected to a standard colorimetric assay of urea and creatinine and submitted to spectroscopic analysis by means of a dispersive Raman spectrometer (830 nm, 350 mW, 30 s). The Raman spectra of urine showed peaks related mainly to urea and creatinine. Partial least squares models were developed using selected Raman bands related to urea and creatinine and the biochemical concentrations in urine measured by the colorimetric method, resulting in r = 0.90 and 0.91 for urea and creatinine, respectively, with root mean square error of cross-validation (RMSEcv) of 312 and 25.2 mg/dL, respectively. RS may become a technique for rapid urinalysis, with concentration errors suitable for population screening aimed at the prevention of renal diseases.


Novel functionalized pyrido[2,3-g]quinoxalinones as antibacterial, antifungal and anticancer agents.
A series of twelve novel pyrido[2,3-g]quinoxalinones (3-14), variously substituted at the C-3 position, was synthesized, structurally determined and submitted to a preliminary in vitro evaluation for antibacterial, anticandida and anticancer activities. Results of the antimicrobial screening showed that all compounds, with the exception of 6, 11 and 12, exhibited interesting activity against all strains tested; while compound 10 was found to have encouraging in vitro anticancer activity at a concentration of l0(-4) M.


C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm.
Ruptured abdominal aortic aneurysm (RAAA) is associated with a systemic inflammatory response syndrome and multiple organ dysfunction. The potential role of a novel C5 complement inhibitor in attenuation of pathological complement activation and tissue injury was explored in a model of RAAA. Anaesthetized rats were randomized to sham (control) or shock and clamp (SC) groups. Animals in the SC group underwent 1 h of haemorrhagic shock (mean arterial pressure 50 mmHg or less), 45 min of supramesenteric aortic clamping and 2 h of reperfusion. They were randomized to receive an intravenous bolus of a functionally blocking anti-C5 monoclonal antibody (C5 inhibitor), at a dose of 20 mg/kg, or saline. Lung injury was assessed by permeability to 125I-labelled albumin, tissue myeloperoxidase (MPO) activity, and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNAs encoding tumour necrosis factor (TNF) alpha and interleukin (IL) 6. The lung permeability index was significantly increased in the SC compared with the sham group (P = 0.032); this was prevented by the C5 inhibitor (P = 0.015). Lung MPO activity was significantly increased in the SC compared with the sham group (P < 0.001), and this increase was attenuated by treatment with the C5 inhibitor (P < 0.001). Semiquantitative RT-PCR in SC group demonstrated downregulation of TNF-alpha mRNA (P = 0.050) and upregulation of IL-6 mRNA (P < 0.001), which were both prevented by the C5 inhibitor (P = 0.014 and P < 0.001 respectively). These results indicated that C5 complement inhibition can reduce shock and acute lung injury in an experimental model of RAAA.


Stabilization of the reduced halocarbon-cytochrome P-450 complex of halothane by N-alkanes.
Under anaerobic conditions, various halogenated compounds, when metabolized by cytochrome P-450, form complexes which are spectrally detectable. Previous studies have shown that halothane forms such a complex with cytochrome P-450, and the result is a strong absorption at 470 nm. Stabilization of this proposed intermediate carbanion complex has never been demonstrated in a biological system. Data are presented which show that several organic solvents (C5-C7N-alkanes) will stabilize the complex formed between halothane and cytochrome P-450. Stabilization allowed the decay of the complex to be studied, and it is demonstrated that the product of decay was chlorodifluoroethylene, which substantiates the hypothesis that the complex is a two electron-reduced carbanion. Carbon tetrachloride and benzyl bromide, which also produce spectrally visible intermediate complexes, were not stabilized by this treatment. Stabilization of the halothane complex in a biological system may facilitate studies to identify precisely the halothane-cytochrome P-450 complex and to clarify the mechanisms of halothane reduction by cytochrome P-450.


Adsorption of histones on natural polysaccharides: The potential as agent for multiple organ failure in sepsis.
Histones are intracellular proteins that are structural elements of nuclear chromatin and regulate gene transcription. However, the extracellular histones released in response to bacterial challenges have been identified as mediators contributing to endothelial dysfunction, organ failure, and death during sepsis. In the present study, the adsorption of histones as well as plasma proteins (α1-acid glycoprotein (AGP), albumin, and γ-globulin) on alginic acid, pectin, dextran, and chitosan was examined in order to evaluate the potential of natural polysaccharides as therapeutic agents for multiple organ failure in sepsis. Alginic acid and pectin strongly adsorbed histones, whereas the adsorption abilities of dextran and chitosan toward histones were very low or negligible. Among the natural polysaccharides examined, only alginic acid did not adsorb any of the plasma proteins. These results demonstrated that alginic acid strongly adsorbed histones, but not plasma proteins; therefore, it has potential as a candidate drug for the treatment of multiple organ failure in sepsis.


Ultrasound imaging for risk assessment in atherosclerosis.
Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall;


Fat-lowering effects of isorhamnetin are via NHR-49-dependent pathway in Caenorhabditis elegans.
Isorhamnetin (3-O-methylquercetin), a flavonol found in dill weed, sea buckthorn berries, kale and onions, has been suggested to have anti-obesity effects, but there is limited evidence of its mechanisms of action on lipid metabolism. The goal of this study was to investigate the effects of isorhamnetin on lipid metabolism using Caenorhabditis elegans as an animal model. Isorhamnetin reduced fat accumulation without affecting food intake or energy expenditure in C. elegans. The isorhamnetin's fat-lowering effects were dependent on nhr-49, a homolog of the human peroxisome proliferator-activated receptor alpha (PPARα). Isorhamnetin upregulated an enoyl-CoA hydratase (ech-1.1, involved in fatty acid β-oxidation) and adipose triglyceride lipase (atgl-1, involved in lipolysis) via NHR-49-dependent pathway at transcriptional levels. Isorhamnetin also upregulated the C. elegans AMP-activated protein kinase (AMPK) subunits homologs (aak-1 and aak-2), involved in energy homeostasis. These results suggest that isorhamnetin reduces body fat by increasing fat oxidation in part via NHR-49/PPARα-dependent pathway.


Comparative distribution of two antidepressant drugs (imipramine and indalpine) in the rat as determined by analog computer simulation.
A ten-compartment analog computer model is presented to determine the precise distribution and excretion of two antidepressant drugs, LM 5008 AND Imipramine. Eight patterns were simulated using experimental data and drug distribution in the two undetermined compartments were obtained by the analog model. Close agreement with existing experimental data lends confidence in the model as a valuable tool for predictions in a variety of therapeutic situations.


Trypanosoma brucei: Miniature anion-exchange centrifugation technique for detection of low parasitaemias: Adaptation for field use.
The miniature anion-exchange/centrifugation (AEC) method, originally developed for the detection of submicroscopic trypanosomaemias in laboratory rodents, has been adapted for the diagnosis of trypanosomiasis in man in the field using blood samples obtained by finger-prick. It has been tested in a survey in The Gambia. The method is shown to be highly sensitive and to fulfil the first essential criteria for exploitation in the field, namely, that it can be operated in the open air under tropical conditions, and that an adequate number of subjects can be examined in a normal working day at an acceptable cost. The method also offers two advantages over the other highly sensitive method applicable to small blood samples, the microhaematocrit buffy-coat microscopy (MBCM) method, namely, that it minimized the requirements for highly critical microscopy and provides, in the same operation, samples of diluted plasma which can be used for serological study.


Effect of patient information on the quality of pharmacists' drug use review decisions.
To evaluate the effect of incremental increases in patient information on the quality of pharmacists' clinical decisions related to legally mandated prospective drug utilization review (DUR) responsibilities. Unblinded comparison of two groups. 28 community pharmacists in Indiana (group 1) and 32 Public Health Service pharmacists employed in the Indian Health Service (IHS) (group 2). Clinical cases involving prescribing problems were developed from patient charts. Each case contained four levels of increasing patient information: Level 1 included only information required for a legal prescription in Indiana; Level 2 added the patient's current medication profile, age, and allergies; Level 3 added the diagnosis or reason for use of the prescribed medication; and Level 4 added the physician's progress note. Pharmacists were asked to evaluate the prescribed drug therapy at each level of each case and complete a Dispensing Appropriateness Index (DAI) report, which included all prospective DUR criteria required by the Omnibus Budget Reconciliation Act of 1990. The quality of pharmacists' DUR decisions at each level of patient information was evaluated by comparing pharmacists' responses on the DAI reports with the consensus judgment of two clinical experts. The quality of both community and IHS pharmacists' DUR decisions improved significantly at each incremental level of patient information. Pharmacists in this study made better decisions when they had access to more complete patient information on which to base their decisions.


Pressure hyperalgesia in hind limb suspended rats.
Spaceflight and simulated microgravity often associate with pain and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not simulated microgravity induced by hind limb suspension (HLS) in rats lead to insulinopenia and pressure hyperalgesia. Adult male rats were divided into HLS (N = 20) and control, non-suspended (N = 16) groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after HLS. Bodyweights and PPT of control and HLS animals measured on the day of suspension were not different. During the experiment, control rats gained 61 +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26 +/- 3 g of weight during the same time period and their PPT declined from 105 +/- 6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area were affected by HLS. However, the random plasma insulin of HLS rats was significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng ml(-1)). The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rat's sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.


Diabetes mellitus is associated with increased elastin fiber loss in ligamentum flavum of patients with lumbar spinal canal stenosis: results of a pilot histological study.
Lumbar spinal canal stenosis (LSCS) is associated with fibrosis, decreased elastin-to-collagen ratio, and hypertrophy of the ligamentum flavum (LF). Diabetes mellitus (DM) is known to cause metabolic disturbances within the extracellular matrix in multiple tissues. These alterations may play a major role in the severity of clinical symptoms of LSCS affecting diabetic patients. We aimed to examine the hypothesis that DM may contribute to the LF changes seen in patients with LSCS. The study cohort included 29 patients: 23 with LSCS (10 with DM vs. 13 without DM) as well as six patients with lumbar disc herniation (LDH). Surgical LF specimens were retrieved for histological assessment. Morphologic quantification of confocal microscopy images using fast Fourier transform analysis allowed us to compare anisotropy and elastin fiber orientation between groups. There was a significant positive correlation between fasting plasma glucose values and degree of elastin degradation (r = 0.36, p = 0.043). The diabetic patients with LSCS showed a significantly greater loss of elastic fibers (2.3 ± 0.9 vs. 1.5 ± 0.55, p = 0.009), although fibrosis was shown to be similar (1.44 ± 0.7 vs. 1.43 ± 0.88, p = 0.98). There was no significant difference in the degree of calcification in the LSCS group between patients with and without diabetes (1.71 vs. 2.05%, p = 0.653). Fiber orientation was found to be less homogenous in the LSCS compared with the LDH group, although not significantly affected by DM. The present study points to a significant contribution of DM to the loss of elastin fibers that occurs in the LF of patients with LSCS.


Cognitive Emotion Regulation as a Mediator between Posttraumatic Stress Symptoms and Hypomanic Personality within a Non-Clinical Population.
There is a high prevalence of traumatic life events within individuals diagnosed with bipolar disorder. However, currently there is limited theoretical understanding of this relationship. To explore whether non-clinical symptoms of posttraumatic stress have a direct effect on the non-clinical symptoms of bipolar disorder, or whether this relationship is mediated by cognitive emotion regulation strategies. A cross-sectional design within non-clinical participants completing an online survey including the Impact of Events Scale, Cognitive Emotion Regulation Questionnaire and the Hypomanic Personality Scale. Posttraumatic stress symptoms were associated with hypomanic personality. Intrusive memories contributed a small but significant proportion of the variance between these two measures. Rumination of negative emotions mediated the relationship between posttraumatic stress and hypomanic personality. The relationship between traumatic events and an increased prevalence of bipolar disorder remains poorly understood. Further research should explore rumination as a potential target for treatment within those suffering from both posttraumatic stress and bipolar disorder.


Microbiome reengineering by four environmental factors for the rapid biodegradation of trichloroethylene.
Trichloroethylene (TCE) was once a widely applied industrial solvent, but is now an infamous contaminant in groundwater. Although anaerobic reductive dechlorination is considered a greener remediation approach, the accumulation of toxic intermediates, such as vinyl chloride (VC), and a longer remediation period are highly concerning. Biostimulation and bioaugmentation have been developed to solve these problems. The former method may not be effective, and the latter may introduce foreign genes. Here, we propose a new approach by applying environmental stresses to reshape the indigenous microbiome. In this study, by using the Taguchi method, the effects of heating, pH, salinity, and desiccation were systematically examined. The optimum conditions were defined as 50 °C, pH 9, 3.50% salinity (w/v), and 21% volumetric water content (θW). The top performing group, G7, can complete the conversion of 11.81 mg/L TCE into ethene in 3.0 days with a 1.23% abundance of Dehalococcoides mccartyi 195 (Dhc 195). Redundancy analysis confirmed that temperature and salinity were the predominant factors in reorganizing the microbiomes. The microbiome structure and its effectiveness can last for at least 90 d. The repetitive selection conditions and sustainable degradation capability strongly supported that microbiome reengineering is feasible for the rapid bioremediation of TCE-contaminated environmental matrices.


A Survey of Knowledge, Attitudes, and Practices of Providers and Staff at Al-Zahraa University Hospital Regarding the Baby-Friendly Hospital Initiative and the International Code of Marketing Breast Milk Substitutes.
Four hundred eight providers and staff members who care for breastfeeding mothers and babies at Al-Zahraa University Hospital, Cairo, Egypt were randomly selected to assess their knowledge, attitudes, and practices regarding the Baby-Friendly Hospital Initiative. The majority of the participants scored above 50% on the knowledge and attitude questions, however, on the practice questions only 45.3% scored above 50%, similar to the result obtained 10 years prior. The results indicate that most attention should be focused on developing practice guidelines and monitoring outcomes since knowledge and attitude were found to be adequate. We would recommend self-appraisal of staff as a first step to others whose hospitals are in the process of implementing the Baby-Friendly Hospital Initiative.


Assessing Fungal Diversity and Abundance in the Black Soldier Fly and its Environment.
Detritivorous insects that flourish in decaying environments encounter microorganisms throughout their life cycle. However, it is not clear whether the microbial composition of the decaying environment affects the microbial composition of the insect gut, or whether the opposite is true, with the microorganisms that are adapted to the insect's digestive system being dispersed by the insects to new habitats, thereby becoming more and more common in the environment. To test these questions the fungal composition of the black soldier fly (BSF) (Stratiomyidae; Hermetia illucens Linnaeus) larval gut and its surrounding decaying environment (household compost bins) were analyzed using amplicon sequencing. Constancy in the dominance of the genus Candida (Debaryomycetaceae) in most of the environments and larval guts was found. This finding may suggest a 'core' structure to the fungal community of the BSF. In locations where nutrient composition of the environment had higher fiber content, the Candida was not dominant and the most common fungi were the genus Gibberella (Nectriaceae) and the family Dipodascaceae. The later was dominant also in the larval gut and the former was replaced with Meyerozyma (Debaryomycetaceae), which may suggest a selection process by the insect's gut. Little is known about the ecological interactions of insects with eukaryotic microorganisms, such as yeast-like fungi. As their metabolic complexity and ability is intense, they have the potential to dramatically affect the physiological condition of the insect.


Effects of kainic acid lesions in rat ventral lateral geniculate nucleus upon field potentials of the superior colliculus: correlation between morphological and physiological observations.
Morphological and physiological effects of kainic acid (KA) lesions in rat ventral lateral geniculate nucleus (LGV) were studied 1.5 and 6 h after KA injection. Morphological changes were examined mainly by electron micrographs. At 1.5 h after KA injection dendrites were dilated and some vacuolations occurred in both dendrites and perikarya including geniculotectal relay neurons while axons were completely intact and cell organelles almost remained intact. Six h after KA injection dendrites and cell bodies were massively dilated with degeneration of cell organelles accompanied by sparse cytoplasm and deformed chromatin in the nucleus. However, almost all presynaptic axons, mainly retinogeniculate fibers, still remained intact. The electron micrographs demonstrate that destruction occurred first in dendrites, next in cell bodies and finally axons were likely to be affected. These morphological changes induced by KA are compatible with physiological effects which were assessed by the field response of the superior colliculus (SC) evoked by stimulation of the optic chiasm. During 1.5-2 h after KA injection all components of the SC response, the presynaptic and postsynaptic negative-positive waves were enhanced. The enhancement of the SC response may be correlated with morphological changes in terms of excitatory action of KA resulting in facilitation of geniculotectal transmission. Six h after KA injection postsynaptic negative-positive waves gradually declined in amplitude while the presynaptic wave returned to control level. The late suppression of postsynaptic components of the SC response may be attributable to a marked loss of geniculotectal transmission resulting from destruction of geniculotectal relay neurons by KA.


Leupeptin's effect on organ weight, RNA, DNA, and protein content after long bone fracture in the rat.
Long bone fracture in the rat is accompanied by enhanced urinary nitrogen loss reflecting changes in protein synthesis and breakdown. The effects of leupeptin, an inhibitor of lysosomal proteases, were assessed on organ weights, RNA, DNA, and protein content after injury in the rat. Two groups of 8-week-old rats were studied: The first group received left femoral fracture. Half of these received leupeptin (25 mumole ip/day), and the remainder received saline. The second group served as uninjured pair-fed controls, with half receiving leupeptin and half receiving saline. On Days 0, 1, 2, 4, and 7 after injury, animals were sacrificed and organs were removed for determination of weight, RNA, DNA, and protein content. All injured rats lost weight, with maximum loss occurring on Day 4. Food intake was also reduced. Pair-fed rats lost the same amount of weight as injured ones, and leupeptin could not prevent whole body weight loss. Expressed as percentage of total body weight, livers from leupeptin-treated injured rats weighed 10% greater than saline-treated ones on Days 2, 4, and 7 after injury (P less than 0.05). No differences occurred in RNA, DNA, or protein contents. Diaphragms similarly weighed 10, 20, and 30% greater on Days 2, 4, and 7 after injury, respectively, in leupeptin-treated rats (P less than 0.05). In addition, the RNA and DNA contents of diaphragms were 96 and 88% greater, respectively, in treated rats than in controls (P less than 0.05) on Day 4. It is concluded that leupeptin causes a relative increase in the weights of livers and diaphragms after injury, and causes a marked increase in the RNA and DNA contents of diaphragms.


The role of CTLA-4 and PD-1 in anti-tumor immune response and their potential efficacy against osteosarcoma.
Immunotherapy is proved to be a promising therapeutic strategy against human malignancies. Evasion of immune surveillance is considered to be a major factor of malignant progression. Inhibitory receptors, especially CTLA-4 and PD-1, are found to play critical roles in the mediation of anti-tumor immune efficacy. Thus, antibodies targeting these immune checkpoints have emerged as the attractive treatment approaches to those patients with cancer. Osteosarcoma is highly malignant and current treatment remains a challenge, especially for those patients with metastasis. Despite some achievements, the effect of immunotherapy against osteosarcoma is still unsatisfactory. The present review attempts to show the role and mechanism of CTLA-4 and PD-1 in immune response and summarize the recent findings related to the effect of inhibitory receptor antibodies on the immune response against tumors, especially osteosarcoma, and the correlation between PD-1 or/and CTLA-4 expression and outcome of osteosarcoma patients. We further discuss the utilization of the combination therapy against osteosarcoma.


Evolution of the melanocortin-1 receptor gene (MC1R) in chamois (Rupicapra spp.).
The taxonomy of chamois and the effects of historical and evolutionary events on its diversification are still under discussion given that different morphological and genetic features presented partially discordant views. One of the morphological features that differentiate the two currently considered species, Rupicapra pyrenaica (southern chamois) and R. rupicapra (northern chamois) is coat color pattern. The melanocortin-1 receptor gene (MC1R) is related with differences in coloration in different mammals and was analyzed here in a sample of 25 chamois covering the 10 subspecies recognized, three in R. pyrenaica, (parva, pyrenaica and ornata) and seven in R. rupicapra (cartusiana, rupicapra, tatrica, carpatica, balcanica, asiatica and caucasica). Comparison with other caprinae showed that the MC1R gene has evolved under strong purifying selection. Three well differentiated haplotypes were identified: one shared by the seven subspecies of R. rupicapra, other common to the two Iberian chamois, both of the species R. pyrenaica, and a third haplotype, basal in the phylogenetic tree, unique to the subspecies from the Apennines, R. pyrenaica ornata. This pattern of variation, with three conspicuous clades, concurs with previous findings on microsatellites and mtDNA and argues in favor of the old classifications that distinguished the species R. ornata.


Adrenocorticotropin hormone response to diazepam in healthy young men.
The effects of diazepam (DZ) infusions on changes in adrenocorticotropin hormone (ACTH) are a source of debate. In this study, 66 healthy young adult men were evaluated for changes in plasma ACTH after intravenous infusions with placebo, 0.12 mg/kg and 0.20 mg/kg of DZ. After the higher DZ dose, 85% of the subjects demonstrated a decrease in ACTH of 20% or more, with the nadir occurring between 30 and 60 min postinfusion and values returning to baseline levels by 180 min. These results support the conclusion that at the clinically relevant doses used here, DZ infusions are associated with a significant decrease in ACTH.


Investigation of interpolation techniques for the reconstruction of the first dimension of comprehensive two-dimensional liquid chromatography-diode array detector data.
Simulated and experimental data were used to measure the effectiveness of common interpolation techniques during chromatographic alignment of comprehensive two-dimensional liquid chromatography-diode array detector (LC×LC-DAD) data. Interpolation was used to generate a sufficient number of data points in the sampled first chromatographic dimension to allow for alignment of retention times from different injections. Five different interpolation methods, linear interpolation followed by cross correlation, piecewise cubic Hermite interpolating polynomial, cubic spline, Fourier zero-filling, and Gaussian fitting, were investigated. The fully aligned chromatograms, in both the first and second chromatographic dimensions, were analyzed by parallel factor analysis to determine the relative area for each peak in each injection. A calibration curve was generated for the simulated data set. The standard error of prediction and percent relative standard deviation were calculated for the simulated peak for each technique. The Gaussian fitting interpolation technique resulted in the lowest standard error of prediction and average relative standard deviation for the simulated data. However, upon applying the interpolation techniques to the experimental data, most of the interpolation methods were not found to produce statistically different relative peak areas from each other. While most of the techniques were not statistically different, the performance was improved relative to the PARAFAC results obtained when analyzing the unaligned data.


Comparative analysis of protein synthesis, transcription and cytoplasmic polyadenylation of mRNA during maturation of bovine oocytes in vitro.
In many species, large numbers of macromolecules are accumulated during oocyte growth. The messenger and ribosomal RNAs produced in these cells are far in excess of those necessary to support protein synthesis. Thus, the aim of this study was to elucidate the processes of translational regulation during meiotic maturation. The relationship between transcription, translation and polyadenylation of mRNA during in-vitro maturation (IVM) of bovine oocytes was investigated. The results presented here show that overall protein synthesis is stimulated during meiotic maturation (approximately three times) concomitantly with the onset of germinal vesicle breakdown after 6 to 10 h of IVM. However, in metaphase II, the incorporation of [35S]methionine into proteins showed only basal levels, as in the germinal vesicle (GV) stage. Furthermore, in the course of IVM, de-novo transcription strongly declines as determined by measuring the incorporation of [3H]uridine into RNA. In contrast to this finding, the incorporation of [3H]adenosine increased and showed a peak during the time interval from 6 to 10 h of IVM, parallel with the onset of germinal vesicle breakdown (GVBD) and translation. In the further course of maturation, only a moderate decrease of [3H]adenosine incorporation was observed. These results indicate that (i) translation increased at the time of GVBD; (ii) these processes were accompanied by polyadenylation of mRNA; and (iii) although transcription declines, polyadenylated mRNA is accumulated until metaphase II (as shown by poly(U)-hybridization), in which protein synthesis is low. The correlation of these processes is discussed here. A detailed knowledge of the biochemical and molecular processes which occur during oocyte maturation can be useful for the improvement of IVM conditions.


Intercity variability and local factors influencing the level of pesticide residues in marketed fruits and vegetables of China.
Controlling pesticide residues in marketed fruits and vegetables is an essential issue for food safety and public health. Local governments improve local conditions, like policymaking and implementation, economic structure and development level, and agricultural practices, to control pesticide residues. However, the level of influence and relative importance of these local factors are not analyzed quantitatively. Here we present the food safety level across 42 Chinese cities as measured by the level of pesticide residues (LPR) in fresh fruits and vegetables, and explore how local socio-economic and policy factors influence its intercity variability. A total of 12,070 sample measurements were used in this study. The relationships between LPR and local socio-economic-policy factors were tested by using Pearson correlation analysis, two-sided independent t-test, and stepwise multivariable linear regression. Our analysis shows that: (1) the pesticide residues in 97.1% of the samples were within legal limits, but the LPR had a considerable cross-city disparity and (2) eight socio-economic-policy variables were found to be significantly correlated with LPR at the city level. Six policy-related variables, namely the number of pesticide-related policies, the number of food safety-related policies, the number of food safety-related news reports, the supermarket revolution, the administrative level of the city and the transparency of supervision of food safety, could explain 32.8% of the intercity variability of LPR. This was followed by the gross domestic product (GDP) per capita from the tertiary sector (15.6%) and the pesticide usage per cultivated area in local agriculture (13.4%). After eliminating the collinearity of these variables, local socio-economic-policy factors collectively could explain around 40% of the intercity variability of LPR. This indicates that local-level policy may have a larger impact on local food safety in terms of LPR than economic factors or local agricultural practice, underscoring the critical role of local government in ensuring food safety.


Higher reinfection rate after two-stage revision arthroplasty in patients with refractory diabetes mellitus: a retrospective analysis with a minimum ten-year follow up.
Treatment protocols for two-stage revision arthroplasty with diabetes mellitus (DM) have not yet been established. The control of glycated hemoglobin (HbA1c) in two-stage revision arthroplasty is still debated. This study aimed to clarify the importance of preoperative HbA1c levels before each stage of revision arthroplasty and to analyze the risk factors for reinfection. Five hundred eighty-eight patients suffered from first-time PJI and was treated in our institute from January 1994 to December 2010 were reviewed. The mean follow-up time was 13.8 (range, 10.2-24.8) years. Patients underwent two-stage revision arthroplasty with DM at presentation were included. The endpoint of the study was reinfection of the revision arthroplasty. Demographic, survivorship, and surgical variables were also analyzed. Eighty-eight patients were identified and grouped by HbA1c level before the first stage surgery: Groups 1 and 2 had HbA1c levels < 7% and ≥ 7%, respectively. Reinfection was identified in 4.55% (2/44) and 18.18% (8/44) of the patients in Groups 1 and 2, respectively. Survivorship analysis revealed correction of the HbA1c before the final stage of revision arthroplasty as an independent factor (p < 0.001). The identified risks for reinfection were HbA1c levels ≥ 7% before final-stage surgery, ≥ 3 stages of revision arthroplasty, and extended-spectrum beta-lactamase (ESBL)-Escherichia coli PJI. The HbA1c level before the final stage of revision arthroplasty could affect staged revision arthroplasty outcomes. Therefore, the necessity of postponing the elective final-stage revision arthroplasty procedure for HbA1c control should be further investigated in the future.


The extent of the psychological impairment of prosthodontic outpatients at a German University Hospital.
Psychological factors are not only important in patients with temporomandibular disorders (TMDs), but also in patients suffering from tooth loss and/or in those awaiting prosthodontic care with fixed or removable dentures as several authors emphasize. The purpose of the present prospective observational study was to compare prosthodontic outpatients of the Department of Prosthodontics at the University of Duesseldorf and patients seeking care at the TMD/Orofacial Pain Outpatient Clinic (TMD/OFPOC) at the same university with respect to sociodemographic data, self-reported somatic complaints, and psychological impairment. A total of 234 patients received two self-administered questionnaires including the Symptom-Check-List. Complete data have been obtained from 65 prosthodontic outpatients and 60 patients of the TMD/OFPOC. Results indicated statistically significant group differences regarding sociodemographic data and somatic complaints. Concerning the latter, in 11 of the 21 items, groups differed significantly and confirmed the absence of any mixing between the two outpatient clinics. Although the evaluation of psychological impairment revealed no significant group differences, in 21.9% of the prosthodontic outpatients and in 22.0% of the patients from the TMD/OFPOC, the extent of the determined psychological impairment was similar to that of psychotherapeutic outpatients; in 9.4% and 8.5% it was similar to that of psychotherapeutic inpatients, respectively. Within the limitations of this study, in approximately one third of the evaluated patients of both the prosthodontic outpatient clinic and the TMD/OFPOC the psychological impairment reached values comparable to those of psychotherapeutic outpatients and psychotherapeutic inpatients. Therefore, the present findings emphasize the need to intensify the integration of psychosomatic aspects into dentistry and, in particular, to add psychological considerations to future German education plans.


Cell membrane coated nanocarriers - an efficient biomimetic platform for targeted therapy.
Targeted therapy approaches have become the core of modern translational science and as an intriguing field, it is the solution of the conventional drug delivery problems that were once unanswered. Traditional methods of delivering drugs and therapeutics faced issues of solubility, sustained release, not enough amount getting through the diseased site, for e.g a tumor. Various formulations of liposomes, polymers, dendrimers, etc have succeeded and made their way for clinical trials trying to enhance the pharmacokinetic and biodistribution of the drug. Many stealth coatings that include hydrophilic polymers (PEG, chitosan, polyacrylamides, etc) can act as a covering around the nanoparticle that can shield the surface from aggregation, opsonization and evade immune system, thus considered in Generally Recognized as Safe (GRAS) category. Several other polymers such as poly-2-oxazoline, polyethylene oxide, PEG-based surfactant (polysorbate-80), and zwitterionic phospholipids have also been tested for their antifouling properties. However, the polymer coating approach requires labor-intensive procedures and conjugation chemistries that often fail in mice model. Besides, due to immunogenicity and allergic reactions evoked by the PEG-coated nanoparticles, there was an urge to find biomimicking materials that can prove better as shielding agents which paved the way for cell membrane coated nanoparticles (CMCNPs) to come into the limelight. CMCNPs consist of a nanoparticle inner core covered by cell membrane that can be implicated in targeted drug delivery approaches, photothermal therapy, diagnosis or imaging making it a powerful theranostic tool. In this review, mode of preparation of CMCNPs, different sources of cell membranes (RBCs, WBCs, platelets, cancer cells, stem cells with some other unconventional sources) and nanoparticle cores that are employed have been thoroughly emphasized. In addition to this, advancements and limitations with respect to this newly emerging field have been focussed.


Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg.
Palmar hyperlinearity is a typical clinical feature of Filaggrin gene (FLG) null mutations. There are reports of FLG mutations and allergic sensitization; however, reports on the relationship between palmar hyperlinearity to sensitization are limited. This study aimed to examine the association between palmar hyperlinearity and sensitization in atopic dermatitis (AD) children. This cross-sectional, case-control study included children ˂ 6 years old with moderate-severe AD whose parents consented for mutation analysis and photographic documentation. Each child underwent genotyping to detect the eight most prevalent FLG mutations in the Japanese population: R501X, 3321delA, S1695X, Q1701X, S2554X, S2889X, S3296X, and K4022X. Clinical features and parameters including egg-specific IgE were examined, and palm photographs were evaluated by 12 trained dermatologists blinded to genotyping results. Of the 57 patients (age range, 2 months to 5 years; median, 22 months), 16 were heterozygotes and three were compound heterozygotes. Palmar hyperlinearity, as recognized by more than two-thirds of dermatologists, was significantly associated with FLG mutation (P = 0.002, OR = 6.98, 95% CI = 2.1-23.7), and this association was observed especially in children over 2 years. Cross-shaped crease of the thenar eminence, as known in previous reports, also demonstrated significant correlation with FLG mutation. When the children were divided according to the presence or absence of palmar hyperlinearity, the egg white-specific IgE was significantly higher in the hyperlinearity group (55.9 vs 18.3 IU/mL, P < 0.05). Palmar hyperlinearity indicates possible inherited barrier abnormalities of the skin in early childhood. Its identification may help to predict a more accurate prognosis, such as sensitization.


[Acute heart failure and preserved systolic function: can we explain all only by the diastolic dysfunction? A prospective study on 145 patients hospitalized for acute pulmonary edema].
Heart failure with conserved systolic function is frequent and attributed to the diastolic dysfunction. The diagnosis of diastolic heart failure requires the association of clinical signs of heart failure, a conserved left ventricular systolic function and a diastolic dysfunction. To determine the proportion of cases of isolated diastolic heart failure among patients hospitalized for acute pulmonary edema. The left ventricular ejection fraction (LVEF), the diastolic function and levels of NT-proBNP have been assessed at admission of 145 patients hospitalized for acute pulmonary edema. 49% of patients included were older than 80 years (mean age 78.6 + 0.9 years). Among the 83 patients with conserved LVEF, 25% had an ischemic heart disease, 24% a severe valvular disease, 22% an atrial fibrillation, 5% a severe bradycardia, 2% a severe hypertrophic obstructive cardiomyopathy. Only 15 patients presented an isolated diastolic heart failure. The level of NT-proBNP was correlated to LVEF but was not able to identify those with isolated diastolic heart failure in the group with "conserved systolic function". Among patients hospitalized for acute pulmonary edema, the prevalence of heart failure with conserved systolic function is high, but only 10% of them presented an isolated diastolic heart failure. The NT-proBNP levels do not permit to identify them.


Microstructural and physiological responses to cadmium stress under different nitrogen levels in Populus cathayana females and males.
Although increasing attention has been paid to the relationships between heavy metal and nitrogen (N) availability, the mechanism underlying adaptation to cadmium (Cd) stress in dioecious plants has been largely overlooked. This study examined Cd accumulation, translocation and allocation among tissues and cellular compartments in Populus cathayana Rehder females and males. Both leaf Cd accumulation and root-to-shoot Cd translocation were significantly greater in females than in males under a normal N supply, but they were reduced in females and enhanced in males under N deficiency. The genes related to Cd uptake and translocation, HMA2, YSL2 and ZIP2, were strongly induced by Cd stress in female roots and in males under a normal N supply. Cadmium largely accumulated in the leaf blades of females and in the leaf veins of males under a normal N supply, while the contrary was true under N deficiency. Furthermore, Cd was mainly distributed in the leaf epidermis and spongy tissues of males, and in the leaf palisade tissues of females. Nitrogen deficiency increased Cd allocation to the spongy tissues of female leaves and to the palisade tissues of males. In roots, Cd was preferentially distributed to the epidermis and cortices in both sexes, and also to the vascular tissues of females under a normal N supply but not under N deficiency. These results suggested that males possess better Cd tolerance compared with females, even under N deficiency, which is associated with their reduced root-to-shoot Cd translocation, specific Cd distribution in organic and/or cellular compartments, and enhanced antioxidation and ion homeostasis. Our study also provides new insights into engineering woody plants for phytoremediation.


Electrodiagnostic evaluation of lower extremity mononeuropathies.
This article discusses the anatomy of lower limb mononeuropathies and reviews the general approach to evaluating patients in the electrodiagnostic laboratory with suspected mononeuropathies of the lower limb. Through illustrative cases of patients presenting with a floppy foot, buckling knee, or painful foot, the approaches using nerve conduction studies and needle electromyography are reviewed, and the pattern of findings of peroneal, tibial, sciatic, femoral, and obturator neuropathies is shown.


Observational learning promotes hippocampal remote awake replay toward future reward locations.
The neural circuit mechanisms underlying observational learning, learning through observing the behavior of others, are poorly understood. Hippocampal place cells are important for spatial learning, and awake replay of place cell patterns is involved in spatial decisions. Here we show that, in observer rats learning to run a maze by watching a demonstrator's spatial trajectories from a separate nearby observation box, place cell patterns during self-running in the maze are replayed remotely in the box. The contents of the remote awake replay preferentially target the maze's reward sites from both forward and reverse replay directions and reflect the observer's future correct trajectories in the maze. In contrast, under control conditions without a demonstrator, the remote replay is significantly reduced, and the preferences for reward sites and future trajectories disappear. Our results suggest that social observation directs the contents of remote awake replay to guide spatial decisions in observational learning.


Quantification of fetal heart rate variability by magnetocardiography and direct electrocardiography.
A computer method for quantification of fetal heart rate (FHR) variability from fetal magnetocardiography during pregnancy and from direct fetal electrocardiography during labor is presented. It is based on statistical analysis of the QRS interval sequences. Beat-to-beat variation is characterized by a differential index (DI) and long-term variation by an interval index (II). The effect of the sample time on the DI is minimal, and hence the DI can be calculated from rather short samples. The II is more sensitive to FHR trends and should be calculated from longer samples, but between the periodic changes, accelerations, and decelerations. Variable amounts of detection pulses are lost in both methods. The DI is sensitive to the missing intervals; no analysis result should be accepted if the number of lost intervals exceeds 10 per cent. The II is less sensitive to the number of missing intervals. The means and standard deviations of the variability indices for eight fetuses during pregnancy and for five fetuses during labor are presented.


Analysis of mono- and disaccharides by high-performance liquid chromatography of the benzyloxime-perbenzoyl derivatives.
A group of biologically important mono- and disaccharides are separated by high-performance liquid chromatography of the benzyloxime-perbenzoyl derivatives on a normal-phase microparticulate column with a hexane-dioxane mixture as the eluting solvent. A single, quantifiable derivative of each sugar is formed easily. These derivatives are detected by UV absorption at either 230 or 254 nm, with a sensitivity in the picomole range at the former wavelength. The sugars in the residues from the evaporation of small aliquots of biologic fluids (10-100 microliter) are derivatized without prior isolation and are determined quantitatively by the use of appropriate internal standards. The analyses could be performed routinely with a simple, inexpensive instrument.


Is intracytoplasmic membrane structure a generic criterion? It does not coincide with phylogenetic interrelationships among phototrophic purple nonsulfur bacteria.
The 16S rRNA or rRNA gene sequences of the type strains of 5 species of Rhodobacter, Rhodopseudomonas blastica and Paracoccus denitrificans were determined. The sequence analysis revealed that Rhodobacter species, whose intracytoplasmic membrane systems were characteristically vesicular, composed a sole cluster. Rhodopseudomonas blastica, whose intracytoplasmic membrane system was lamellar, was included in the cluster of Rhodobacter. The phylogenetic co-clustering of these bacteria conformed to their possessing of the identical types of carotenoids. Paracoccus denitrificans, which is nonphototrophic, is a right member of the Rhodobacter cluster. Rhodobacter species, Rhodopseudomonas blastica and Paracoccus denitrificans are apart from the other phototrophic bacteria and have the common deletions of 21 bases at the positions 1258 to 1278 (Escherichia coli numbering system). It was demonstrated that the morphological character "intracytoplasmic membrane structure", that has been regarded as a generic criterion does not reflect the phylogeny in the phototrophic bacteria. The transfer of Rhodopseudomonas blastica to the genus Rhodobacter is proposed.


Alterations in Mc1r gene expression are associated with regressive pigmentation in Astyanax cavefish.
Diverse changes in coloration across distant taxa are mediated through alterations in certain highly conserved pigmentation genes. Among these genes, Mc1r is a frequent target for mutation, and many documented alterations involve coding sequence changes. We investigated whether regulatory mutations in Mc1r may also contribute to pigmentation loss in the blind Mexican cavefish, Astyanax mexicanus. This species comprises multiple independent cave populations that have evolved reduced (or absent) melanic pigmentation as a consequence of living in darkness for millions of generations. Among the most salient cave-associated traits, complete absence (albinism) or reduced levels of pigmentation (brown) have long been the focus of degenerative pigmentation research in Astyanax. These two Mendelian traits have been linked to specific coding mutations in Oca2 (albinism) and Mc1r (brown). However, four of the seven caves harboring the brown phenotype exhibit unaffected coding sequences compared to surface fish. Thus, diverse genetic changes involving the same genes likely impact reduced pigmentation among cavefish populations. Using both sequence and expression analyses, we show that certain cave-dwelling populations harboring the brown mutation have substantial alterations to the putative Mc1r cis-regulatory region. Several of these sequence mutations in the Mc1r 5' region were present across multiple, independent cave populations. This study suggests that pigmentation reduction in Astyanax cavefish evolves through a combination of both coding and cis-regulatory mutations. Moreover, this study represents one of the first attempts to identify regulatory alterations linked to regressive changes in cave-dwelling populations of A. mexicanus.


A prospective study of antimicrobial-related adverse drug reactions in hospitalized patients.
No previous systematic evaluation of antimicrobial-related adverse drug reactions (ADRs) in Taiwanese patients has been reported. The present study aimed to assess the incidence, risk factors, clinical manifestations, and causative agents of antimicrobial-ADRs in hospitalized patients. 299 patients who received antimicrobial treatment during hospitalization in the infection ward of a tertiary hospital for at least two days from October 1, 1999 to February 29, 2000 were prospectively enrolled. Data of patients with parenteral antimicrobial-related ADRs were retrieved for further analysis. The incidence of antimicrobial-related ADRs (93.1% type B) was 24.1%. Compared with patients without ADRs, patients with antimicrobial-related ADRs were more likely to have a previous history of drug allergy (27.8% vs 16.2%, p=0.035) and had longer duration of hospitalization (28.3 +/- 21.0 vs 12.6 +/- 9.4 days, p<0.001). The incidence of parenteral antimicrobial-related ADRs in terms of total courses was 16.3% (78/480). Carbapenems (53.8%), amphotericin B (52.9%), and glycopeptides (37.0%) had the highest incidence of associated ADRs. Blood dyscrasias (32.1%), dermatomucosal effects (23.1%), and febrile reactions (17.9%) were the three most common manifestations of ADRs. Antimicrobial-related ADRs occurred frequently in Taiwanese hospitalized patients.


Thermal adaptation and heat shock response of Tilapia ovary cells.
The growth of tissue culture TO-2 cells derived from the warm water fish Tilapia, the induction of thermotolerance, and protein synthesis profiles of these cells in response to temperature changes were examined. TO-2 cells can grow between 15 to 34 degrees, with an optimal growth temperature of 31 degrees. There is no apparent killing of the cells when the temperature is lowered to 4 degrees for up to 3 days. Survival of TO-2 cells at 43 degrees was studied after various preheat treatments: 1) acute heating at 40 degrees for 15 min followed by 31 degrees incubation, 2) chronic exposure at 37 degrees for several hr, or 3) long-term thermal adaptation at 34 degrees. The cells acquire thermotolerance from pre-exposure to 37 degrees for as short as 6 hr. Preheating at 40 degrees followed by incubation at 31 degrees also induces thermotolerance against a subsequent 43 degrees heat challenge. In addition, 34 degrees thermal adapted cells are resistant to 43 degrees heating. One- and two-dimensional gel electrophoresis of proteins after heat treatments show that three major heat shock proteins with molecular weights around 87, 70, and 27 kD are preferentially synthesized. The synthesis of two additional proteins with an isoelectric point of 6.9 and molecular weights of 60 and 44 kD are significantly enhanced in 34 degrees thermal-adapted and 37 degrees chronic heated cells, but not in cells subjected to an acute heat shock at either 40 degrees or 43 degrees. On the other hand, the 27 kD heat shock proteins are mainly present in the 43 degrees, 40 degrees, and 37 degrees heat-shocked cells, but not in the 34 degrees thermal-adapted cells.


Recovery of lignin peroxidase from submerged liquid fermentation of Amauroderma rugosum (Blume & T. Nees) Torrend using polyethylene glycol/salt aqueous two-phase system.
Amauroderma rugosum is a wild mushroom species widely distributed in tropics and is classified under the class of Basidiomycetes. Basidiomycetes are well-known for their abilities of producing lignocellulolytic enzymes such as lignin peroxidase (LiP), laccase (Lac) and manganese peroxidase (MnP). Different factors such as nutrient sources, incubation period and agitation affect the production of lignocellulolytic enzymes. The A. rugosum produced LiP in the medium supplemented with potato dextrose broth (PDB), 0.5% yeast and 1.0% saw dust at 26.70±3.31 U/mL. However, the LiP activity was increased to 106.32±5.32 U/mL when supplemented with 150 μm of copper (CuSO4). The aqueous two-phase system (ATPS) is a simple, rapid and low cost method for primary extraction and recovery of LiP. A total of 25 systems made from five different molecular weights of polyethylene glycol (PEG)/dipotassium hydrogen phosphate (K2HPO4) were tested. PEG 600 produced the highest top phase purification factor (PFT) of 1.33±0.62 with yield of 72.18±8.50%. The optimization of the ATPS parameters, such as volume ratio VR, pH and crude enzyme loading are the factors controlling the phase partition. Our results showed that significant improvement (PFT of 6.26±2.87 with yield of 87.31±3.14%) of LiP recovery can be achieved by optimized the parameters.


Methyl cinnamate derivatives enhance UV-induced mutagenesis due to the inhibition of DNA excision repair in Escherichia coli B/r.
UV-induced mutagenesis in Escherichia coli B/r WP2 was enhanced by certain derivatives of methyl cinnamate which themselves were not mutagenic. Methyl ferulate, methyl isoferulate and methyl sinapate showed this effect markedly. Such an enhancement effect was absent with the derivatives of cinnamic acid and ethyl cinnamate and was not observed in Escherichia coli WP2s uvrA. Methyl sinapate also enhanced 4NQO-induced mutation and suppressed liquid-holding recovery in the above repair-proficient strain. The presence of methyl sinapate in plating agar medium decreased the survival of UV-irradiated cells of a recombination-repair-deficient strain, CM571 recA. However, the effect was not observed with those of WP2s uvrA. In an in vitro experiment in which the removal rate of thymine dimers was measured, methyl sinapate clearly inhibited this repair event. From these results, we conclude that methyl sinapate inhibits DNA excision repair, thus enhancing UV mutagenicity.


Determinants of Latina obesity in the United States: the role of selective acculturation.
Obesity has reached epidemic proportions in the United States. Hispanic American women in particular have higher rates of obesity than their non-Hispanic White counterparts. In this article, the authors review the existing literature on acculturation as it relates to obesity and health behaviors among U.S. Hispanic women. In addition, a conceptual framework is proposed to examine factors contributing to obesity through "selective acculturation." This concept challenges traditionally held unilateral assumptions that underscore Hispanic women's unhealthful behavioral patterns by explaining a process whereby Hispanic women both maintain some older health-related behaviors and acquire new ones once they settle in a new culture.