Celecoxib attenuates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced cirrhotic rats.
Endoplasmic reticulum (ER) stress is an important mechanism in the progression of chronic and acute liver diseases, especially in the progression and recovery of liver fibrosis. Excessive and long-term ER stress induces apoptosis. ER stress-induced apoptosis is considered to be an important pathway in the development of liver fibrosis. Cyclooxygenase-2 (COX-2) induction is also closely related to ER stress. In our previous studies, we showed that celecoxib, a COX-2 inhibitor, improves liver fibrosis and portal hypertension. However, the role and mechanism of celecoxib in alleviating liver fibrosis remain unclear. To investigate whether celecoxib alleviates liver fibrosis by inhibiting hepatocyte apoptosis via the ER stress response. Cirrhosis was induced by intraperitoneal injections of thioacetamide (TAA) for 16 wk (injection dose is 200 mg/kg per 3 d for the first 8 wk and 100 mg /kg per 3 d after 8 wk). Thirty-six male Sprague-Dawley rats were randomly divided into three groups, namely, control group, TAA group, and TAA + celecoxib group. In the last 8 wk, TAA-induced cirrhotic rats received celecoxib (20 mg/kg/day) or the vehicle by gastric gavage. After 16 wk, the rats were sacrificed, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were detected. The hepatic fibrosis areas were evaluated by Sirius red staining and the degree of fibrosis was assessed by measuring the level of hydroxyproline. ER stress levels were evaluated by detecting the marker proteins glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), PKR-like ER protein kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1α). Apoptosis levels were evaluated by detecting caspase-12 and caspase-3. The serum ALT and AST levels in the liver were significantly reduced by celecoxib; however, the serum ALB had no significant changes. Celecoxib significantly reduced the degree of liver fibrosis and the levels of hydroxyproline (-38% and -25.7%, respectively, P < 0.01). Celecoxib ameliorated ER stress by reducing the level of GRP78 compared to the TAA group (P < 0.05). Consistently, after celecoxib administration, the upregulation of TAA-induced hepatic apoptosis markers (caspase-12 and caspase-3) and CHOP were significantly inhibited. In addition, after celecoxib treatment, the expression of key molecules associated with ER stress (PERK, ATF6, and IRE1) was decreased (P < 0.05). Therapeutic administration of celecoxib effectively reduces hepatic apoptosis in TAA-induced cirrhotic rats. The mechanism of action may be attributed to the suppression of CHOP expression, which subsequently inhibits ER stress.


Multidisciplinary approach to community engagement in global public health research.
Recently, there has been a renewed interest in the role of community engagement in knowledge production and ethical issues such as 'helicopter research', indicating exploitative research activities of some researchers as well as short-term relationships with research communities especially in low- and middle-income countries. This approach is detrimental to both communities and the larger scientific community as this may breed mistrust. Major institutions such as the National Institute of Health and Care Research in the United Kingdom have highlighted the importance of community engagement as a tool to improve the reach, quality, and impact of the research by incorporating the voices and concerns of marginalized communities. Similarly, in its 2022 guidance, the American Society for Human Genetics (ASGH) highlights the need to address underrepresentation in genomics research through community engagement. Establishing ethical and meaningful long-term relationships can be challenging especially for researchers who are not members of the community or those from other countries. This article describes how 'community-engaged research' can address some ethical challenges in global public health in different cultural settings.


Proposed alternative terminology and subclassification of so called "dysplastic naevi".
The term "dysplastic" melanocytic naevus has recently been used to describe pigmented naevi with unusual histological and clinical features. There is currently no clear clinical or pathological definition of the term, and this has led to a lack of comparability of material described in reports on these lesions. As a result of careful histological study and a clinicopathological correlation of 100 naevi, we suggest that three distinct groups of histopathological features distinguish so called dysplastic naevi from banal melanocytic naevi. These are architectural atypia, cytological atypia, and a host response. Description of each of these features in routine reports and in published series in place of the loose use of the term "dysplastic" would enable comparisons to be made between series of melanocytic lesions reported from different centres. In the course of this study we observed a considerably increased incidence of naevus type giant cells in the dermal portion of the atypical naevi. These giant cells should not be confused with possibly premalignant cytological atypia.


The Schizosaccharomyces pombe cdt2(+) gene, a target of G1-S phase-specific transcription factor complex DSC1, is required for mitotic and premeiotic DNA replication.
We have defined five sev genes by genetic analysis of Schizosaccharomyces pombe mutants, which are defective in both proliferation and sporulation. sev1(+)/cdt2(+) was transcribed during the G1-S phase of the mitotic cell cycle, as well as during the premeiotic S phase. The mitotic expression of cdt2(+) was regulated by the MCB-DSC1 system. A mutant of a component of DSC1 affected cdt2(+) expression in vivo, and a cdt2(+) promoter fragment containing MCB motifs bound DSC1 in vitro. Cdt2 protein also accumulated in S phase and localized to the nucleus. cdt2 null mutants grew slowly at 30 degrees and were unable to grow at 19 degrees. These cdt2 mutants were also medially sensitive to hydroxyurea, camptothecin, and 4-nitroquinoline-1-oxide and were synthetically lethal in combination with DNA replication checkpoint mutations. Flow cytometry analysis and pulsed-field gel electrophoresis revealed that S-phase progression was severely retarded in cdt2 mutants, especially at low temperatures. Under sporulation conditions, premeiotic DNA replication was impaired with meiosis I blocked. Furthermore, overexpression of suc22(+), a ribonucleotide reductase gene, fully complemented the sporulation defect of cdt2 mutants and alleviated their growth defect at 19 degrees. These observations suggest that cdt2(+) plays an important role in DNA replication in both the mitotic and the meiotic life cycles of fission yeast.


Cyclic nucleotide phosphodiesterase activities in Neurospora crassa.
Cyclic nucleotide phosphodiesterase activities in soluble Neurospora crassa mycelial extracts were resolved into two peaks, phosphodiesterase I and II, by chromatography on DEAE-cellulose columns. Phosphodiesterase I hydrolysed cyclic AMP and cyclic GMP equally well. Phosphodiesterase II was active on cyclic GMP but scarcely active on cyclic AMP. Phosphodiesterase I was resolved by gel filtration and sucrose-density-gradient centrifugation into three peaks having molecular weights of about 57 000, 125 000 and 225 000. This suggests that this enzyme activity has at least three aggregation forms, tentatively defined as monomeric, dimeric and tetrameric. Similarly, phosphodiesterase II was resolved into two forms, having molecular weights of about 170 000 and 320 000. Evidence on the interconversion between phosphodiesterase I forms was obtained.


Neuroscience, ethics, and national security: the state of the art.
National security organizations in the United States, including the armed services and the intelligence community, have developed a close relationship with the scientific establishment. The latest technology often fuels warfighting and counter-intelligence capacities, providing the tactical advantages thought necessary to maintain geopolitical dominance and national security. Neuroscience has emerged as a prominent focus within this milieu, annually receiving hundreds of millions of Department of Defense dollars. Its role in national security operations raises ethical issues that need to be addressed to ensure the pragmatic synthesis of ethical accountability and national security.


Disruption of layers 3 and 4 during development results in altered thalamocortical projections in ferret somatosensory cortex.
The precision of projections from dorsal thalamus to neocortex are key toward understanding overall cortical organization and function. To identify the significance of layer 4 cells in receiving the bulk of thalamic projections in somatosensory cortex, we disrupted layer 4 genesis and studied the effect on thalamic terminations in ferrets. Second, we ascertained the result of layer 4 disruption on functional responses and topographic organization. Methylazoxy methanol (MAM) was injected into pregnant ferrets on embryonic day 33 (E33), when most layer 4 neurons of somatosensory cortex are generated. This treatment resulted in dramatic reduction in the thickness of targeted layer 4. E38 MAM treatment was used as a control, when layer 2-3 neurons are generated. The projections of ventrobasal thalamus into somatosensory cortex were studied using DiI injections. We found only subtle differences between groups (normal, E33, or E38 MAM-treated) in the thalamic afferent pattern on postnatal day 1 (P1) and P7. On P14, thalamic terminations distribute almost equally throughout the remaining cortical layers in the E33 MAM-treated group compared with normal and E38 MAM-treated animals, in which the ventrobasal thalamus projects primarily to central layers. Electrophysiological recordings conducted on mature ferrets treated with MAM on E33 demonstrated that somatotopic organization and receptive field size are normal. These findings emphasize the importance of layer 4 in determining the normal laminar pattern of thalamic termination and suggest that, although its absence is likely to impact on complex neocortical functional responses, topographic organization does not arise from the influence of layer 4.


The impact of reduction of pain after lumbar spine surgery: the relationship between changes in pain and physical function and disability.
Prospective cohort study. To examine the relationship between improvement in pain intensity and subsequent improvement in physical function and disability during the first 12 months after lumbar spine surgery. Little is known about how reduction of pain intensity after surgery may predict improvements in physical function and disability. We prospectively enrolled 260 individuals undergoing elective surgery for degenerative lumbar spine conditions from August 2005 through August 2011. Preoperative and postoperative (3, 6, and 12 mo) assessment tools were numeric pain rating scale, Short Form 12 version 2 physical component score (physical function), and Oswestry Disability Index (disability). Changes were defined using minimum clinically important differences. The association between improvement in pain intensity and subsequent improvement in physical function and disability during the first 12 postoperative months was assessed using standard regression methods. Significance was set at a P value less than 0.05. Preoperatively, mean pain intensity was 5.2 (standard deviation, 2.4), physical function was 27.9 (standard deviation, 9.2), and disability was 40.1% (standard deviation, 16.8%). Pain intensity had improved in 164 (63.1%) patients by 3 and 6 months and in 184 (70.8%) by 12 months. Patients with improvement in pain postoperatively were more likely to have subsequent improvement in physical function (odds ratio, 2.11; 95% confidence interval, 1.10-3.16) during the course of 12 postoperative months. The association between postoperative pain reduction and reduced disability was similar (odds ratio, 1.61; confidence interval, 1.12-2.33). Most patients experienced clinically important postsurgical reductions in pain intensity by 3 months after surgery. Those patients were more likely to have clinically important improvement in physical function and reduction in disability during the first postoperative year. 1.


Chromatographic evidence for the existence of multiple forms of cathepsin B1.
Preparations of ox spleen cathepsin B1 have been found to give multiple peaks of activity upon chromatography on DEAE-cellulose in NaCl gradients or by equilibrium chromatography in 0.05m-NaCl. CM-cellulose gradient chromatography also shows several cathepsin B1 peaks. This evidence indicates that ox spleen cathepsin B1 can exist in at least three to five forms. All forms have the same molecular weight, are thiol-activated and are inhibited by typical thiol inhibitors. The possible sources of this multiplicity of activity are discussed and a possible physiological role for cathepsin B2 is suggested.


Considerations for successful cancer immunotherapy in aged hosts.
Improvements in understanding cancer immunopathogenesis have now led to unprecedented successes in immunotherapy to treat numerous cancers. Although aging is the most important risk factor for cancer, most pre-clinical cancer immunotherapy studies are undertaken in young hosts. This review covers age-related immune changes as they affect cancer immune surveillance, immunopathogenesis and immune therapy responses. Declining T cell function with age can impede efficacy of age-related cancer immunotherapies, but examples of successful approaches to breach this barrier have been reported. It is further recognized now that immune functions with age do not simply decline, but that they change in potentially detrimental ways. For example, detrimental immune cell populations can become predominant during aging (notably pro-inflammatory cells), the prevalence or function of suppressive cells can increase (notably myeloid derived suppressor cells), drugs can have age-specific effects on immune cells, and attributes of the aged microenvironment can impede or subvert immunity. Key advances in these and related areas will be reviewed as they pertain to cancer immunotherapy in the aged, and areas requiring additional study and some speculations on future research directions will be addressed. We prefer the term Age Related Immune Dysfunction (ARID) as most encompassing the totality of age-associated immune changes.


Long-term patterns of drug use among an urban African-American cohort: the role of gender and family.
Cross-sectional analyses and the little existing longitudinal analyses on substance use over the life course have been integral in providing information about the epidemiology of substance use in the United States. However, it is unclear whether these estimates provide an accurate portrayal of long-term substance use patterns among African-American men and women who have grown up in an inner city environment. The current study uses longitudinal data from a community cohort of African-American inner-city males and females followed from first grade through mid-adulthood. It identifies the substance use patterns through mid-adulthood, including lifetime prevalence, age of onset and termination, and sequencing of substance classes, as well as the risk of initiation of substance use changes over the life course using survival analysis. It also investigates whether early family structure and process play a role in drug use initiation throughout the life course, and whether the relationship between family factors and drug initiation differs by gender. Overall, among the general trends of use, we find a considerable amount of abstention with over 40% of the participants never using illegal drugs by mid-adulthood, over 70% never using cocaine, and over 90% never using heroin. With respect to onset, we find a long-term influence of early family factors on substance use, particularly for females. Family discipline in childhood and family cohesion and parental rule setting during adolescence seem to be key factors in predicting later substance use for females. The implications of these findings for future research and policy are discussed.


Socio-demographic correlates of attitude towards corneal donation among health science students and academic staff of Jimma University.
Diseases affecting the cornea are a major cause of blindness worldwide, and affect mainly the young and those of middle age resulting in blindness during the normally productive years and beyond Cornea transplants can cure corneal blindness; however, the number of corneas available in Ethiopia is small. To assess the socio-demographic factors influencing the attitude of academic staff and students towards corneal donation. A cross-sectional study was conducted in Jimma University in January 2009 on a total of 403 students and academic staff Data was analyzed using SPSS version 13.0. Independent-samples t-test, ANOVA, and descriptive statistics were done as necessary. Level of significance was taken at 5%. The respondents were in the age group of 18-43 years with mean 22.1 (SD +/- 3.3), and 324 (81.6%) of them were males. Among the respondents, 327 (81.8%) had heard about cornea donation. Respondents who had awareness about corneal donation, age above 66th percentile, educational level of year four and above had a more positive attitude towards corneal donation (p < 0.05). But those with church attending habit, and Muslims had unfavorable attitude (p > 0.05). Level of awareness and religion play a significant role in influencing attitude towards corneal donation. Religious leaders should therefore, play an active role to change people's attitude.


Growth and luminescence of the bacterium Xenorhabdus luminescens from a human wound.
Xenorhabdus luminescens, a newly isolated luminous bacterium collected from a human wound, was characterized. The effects of ionic strength, temperature, oxygen, and iron on growth and development of the bioluminescent system were studied. The bacteria grew and emitted light best at 33 degrees C in a medium with low salt, and the medium after growth of cells to a high density was found to have antibiotic activity. The emission spectrum peaked at 482 nm in vivo and at 490 nm in vitro. Both growth and the development of luminescence in X. luminescens required oxygen and iron. The isolated luciferase itself exhibited a temperature optimum at about 40 degrees C; after purification by affinity chromatography, it showed two bands (52 and 41 kilodaltons) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicative of an alpha and beta subunit structure. Reduced flavin mononucleotide (Km of 1.4 microM) and tetradecanal (Km of 2.1 microM) were the best substrates for the luciferase, and the first-order decay constant under these conditions at 37 degrees C was 0.79 s-1.


Comparative hypoglycemic and nephroprotective effects of tocotrienol rich fraction (TRF) from palm oil and rice bran oil against hyperglycemia induced nephropathy in type 1 diabetic rats.
Diabetic nephropathy (DN) is a serious complication confronted by patients with diabetes. Available data indicate that the development of DN is linked to hyperglycemia. Tocotrienol rich fraction (TRF) from palm oil (PO) and rice bran oil (RBO) has been shown to lower the blood glucose level in patients and preclinical animal models. This study was designed to investigate if TRF from PO and RBO could improve the renal function in DN by the virtue of their hypoglycemic and antioxidant activities. Male Wistar rats having an average body weight (bw) 250g were divided into four groups of six each .The first group served as diabetic control [injected with 55mg/kg bw of streptozotocin (STZ), intraperitoneally], while the second and third group received PO-TRF and RBO-TRF, respectively, by gavage at a dose of 200mg/kg bw/day, over a period of 8 weeks post-induction of diabetes. The fourth group comprised of age-matched male Wistar rats that received single intraperitoneal injection of normal saline only and served as control. After 8 weeks of STZ injection and TRF treatment, 24h urine was collected and animals were sacrificed. Fasting blood glucose, glycosylated hemoglobin, biochemical markers of renal function and oxidative stress were evaluated in serum, urine and kidney tissue. The results show that treatment with PO-TRF as well as RBO-TRF significantly improved the glycemic status and renal function in type 1 diabetic rats but PO-TRF afforded greater efficiency at similar dose as compared to RBO-TRF. In conclusion, PO-TRF was found to be more effective hypoglycemic and nephroprotective agent in DN than RBO-TRF.


Etiology and Outcomes of Acquired Pediatric Sixth Nerve Palsies.
Acquired sixth nerve (CN6) palsies in children may be benign or associated with an underlying neurologic condition. In children who presented with isolated (no associated neurologic or ophthalmic symptoms or signs) CN6 palsies, the rate of newly diagnosed neurologic disorders (such as tumors) is unclear. Moreover, the factors associated with spontaneous resolution and amblyopia in children with acquired CN6 palsies are unknown. We retrospectively reviewed the charts of all children younger than 18 years diagnosed with CN6 palsy at our institution from 2010 to 2020. We recorded ophthalmologic and neurologic history and examination findings, neuroimaging results, etiology of CN6 palsy, and outcomes including spontaneous resolution and amblyopia. We assessed etiologies of isolated and nonisolated CN6 palsies as well as frequency and factors associated with spontaneous resolution and amblyopia (in children ≤7 years). One hundred seventy-two children met inclusion criteria. Twenty CN6 palsies (12%) were isolated at presentation. Most isolated cases were presumed postviral or postvaccination (50%) or idiopathic (30%), but 2 cases (10%) were associated with newly diagnosed tumors. Spontaneous resolution occurred in 59% of CN6 palsies at a median of 12.3 weeks and was associated with older age (P = 0.03) and nontumor etiology (P = 0.006). Amblyopia developed in 18% of children at risk, exclusively in those with anisometropia, pre-existing strabismus, or younger than 12 months. Our findings and chart reviews suggest that approximately 10% of isolated acquired pediatric CN6 palsies are associated with a newly diagnosed brain tumor. This risk must be discussed with parents when considering immediate vs delayed neuroimaging. In addition, infants and children ≤7 years with secondary amblyogenic risk factors (anisometropia or pre-existing strabismus) require close follow-up to monitor and treat amblyopia.


Pharmacological effects of rosa damascena.
Rosa damascena mill L., known as Gole Mohammadi in is one of the most important species of Rosaceae family flowers. R. damascena is an ornamental plant and beside perfuming effect, several pharmacological properties including anti-HIV, antibacterial, antioxidant, antitussive, hypnotic, antidiabetic, and relaxant effect on tracheal chains have been reported for this plant. This article is a comprehensive review on pharmacological effects of R. damascena. Online literature searches were performed using Medline, medex, Scopus, and Google Scholar websites backed to 1972 to identify researches about R. damascena. Searches also were done by going through the author's files and the bibliographies of all located papers.


Tandem repeats in plant mitochondrial genomes: application to the analysis of population differentiation in the conifer Norway spruce.
Mitochondrial DNA, widely applied in studies of population differentiation in animals, is rarely used in plants because of its slow rate of sequence evolution and its complex genomic organization. We demonstrate the utility of two polymorphic mitochondrial tandem repeats located in the second intron of the nad1 gene of Norway spruce. Most of the size variants showed pronounced population differentiation and a distinct geographical distribution. A GenBank search revealed that mitochondrial tandem repeats occur in a broad range of plant species and may serve as a novel molecular marker for unravelling population processes in plants.


Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1.
Delta(9)-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines. To assess the sensitivity of CxCa cells to AEA, we selected three cell lines that were exposed to increasing doses of AEA with or without antagonists to receptors to AEA. DNA fragmentation and caspase-7 activity were used as apoptosis markers. The expression of receptors to AEA were analyzed in CxCa cell lines as well as CxCa biopsies. The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CB1 and CB2 cannabinoid receptors mediated a protective effect. Furthermore, unexpectedly, a strong expression of the three forms of AEA receptors was observed in ex vivo CxCa biopsies. Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs.


[Interaction of nonelectrolytes, the derivatives of 5-hydroxybenzimidazole, with erythrocyte membrane].
The method of spin probe and scanning electron microscopy were used to study the effects of some new synthetic antioxidants and bioregulators, the derivatives of 5-hydroxybenzimidazole, on the membrane structure and morphology of erythrocytes. Analysis of EPR spectra and electron micrographs revealed that the derivatives with various side substituents affect the membrane structure and shape of erythrocytes in a concentration-dependent manner, the effect correlating with the hydrophobic properties of the side derivatives. It was shown that all the compounds in the concentration range 1.10(-7) - 1.10(-3) M exhibit the echinocytogenic action, the most profound effect being found in the compound with benzyl- and ethoxygroup in sites 2 and 5, respectively. Our data suggest that nonelectrolytes, the derivatives of 5-hydroxybenzimidazole, are located in the outer monolayer of erythrocyte membrane.


Diversity of phlebotomine sand flies (Diptera: Psychodidae) in Ibitipoca State Park, Minas Gerais, Brazil.
Leishmaniasis is a complex of zoonotic diseases that are endemic to many Brazilian states. They are transmitted to the vertebrates by the bite of the hematophagous female sand fly (Diptera: Psychodidae) vectors. Despite the increasing occurrence of visceral and cutaneous leishmaniasis cases in large urban centers, their transmission continues to occur primarily in a wild environment and may be associated with professional activities, ecotourism activities, or both. This study investigates the ecological parameters of the sand flies present in Ibitipoca State Park, Minas Gerais, Brazil. During 2009, systematic collections of sand flies were made monthly using HP light traps installed at five sites, including three natural settings (a cave, riparian vegetation, and a rain forest), the tourist and researchers' accommodations, and a surrounding domestic livestock area. In total, 161 sand flies (seven species) were collected, the most abundant, particularly in the surrounding domestic livestock area, being Lutzomyia (Psychodopygus) lloydi (Antunes, 1937). Furthermore, a previously unidentified Lutzomyia (Sciopemyia) sp. was prevalent in the cave environment. There are no existing records of the occurrence of leishmaniasis in Ibitipoca State Park; however, the some species of the subgenus Psychodopygus are known vectors of Leishmania spp in Brazil. Hence, the presence of a species of this genus in areas surrounding the park may represent a risk to ecotourism and the local inhabitants. Our study shows the importance of regular monitoring of the various areas used by humans to determine the distribution and spread of sand fly vectors for preventive management to forestall potential risk to health and consequent effect on ecotourists.


A genomic region required for phototrophic thiosulfate oxidation in the green sulfur bacterium Chlorobium tepidum (syn. Chlorobaculum tepidum).
The specific enzymes employed by Chlorobium tepidum for the anaerobic oxidation of thiosulfate, sulfide and elemental sulfur during anoxygenic photosynthesis are not well defined. In particular, it is unclear how C. tepidum completely oxidizes thiosulfate. A C. tepidum genomic region, encoding a putative quinone-interacting membrane-bound oxidoreductase (Qmo) complex (CT0866-0868), hypothetical proteins (CT0869-0875) and a sulfide : quinone oxidoreductase (SQR) homologue (CT0876), was analysed for its role in anaerobic sulfur oxidation. Transcripts of genes encoding the Qmo complex, which is similar to archaeal heterodisulfide reductases, were detected by RT-PCR only while sulfide or elemental sulfur were being oxidized, whereas the SQR homologue and CT0872 were expressed during thiosulfate oxidation and into early stationary phase. A mutant of C. tepidum was obtained in which the region between CT0868 and CT0876 was replaced by a transposon insertion resulting in the truncation or deletion of nine genes. This strain, C5, was completely defective for growth on thiosulfate as the sole electron donor in C. tepidum, but only slightly defective for growth on sulfide or thiosulfate plus sulfide. Strain C5 did not oxidize thiosulfate and also displayed a defect in acetate assimilation under all growth conditions. A gene of unknown function, CT0872, deleted in strain C5 that is conserved in chemolithotrophic sulfur-oxidizing bacteria and archaea is the most likely candidate for the thiosulfate oxidation phenotype observed in this strain. The defect in acetate assimilation may be explained by deletion of CT0874, which encodes a homologue of 3-oxoacyl acyl carrier protein synthase.


The hunting of targets: challenge in miRNA research.
MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of around 60% of the human protein-coding genes. In the past decade, deregulation of miRNAs (by expression and/or function) has been associated with the pathogenesis, progression and prognosis of different diseases, including leukemia. The number of discovered genes encoding miRNAs has risen exponentially in this period, but the numbers of miRNA-target genes discovered and validated lag far behind. Scientists have gained more in-depth knowledge of the basic mechanism of action of miRNAs, but the main challenge still remaining is the identification of direct targets of these important 'micro-players', to understand how they fine-tune so many biological processes in both healthy and diseased tissue. Many technologies have been developed in the past few years, some with more potential than others, but all with their own pros and cons. Here, we review the most common and most potent computational and experimental approaches for miRNA-target gene discovery and discuss how the hunting of targets is challenging but possible by taking the experimental limitations in consideration and choosing the correct cellular context for identifying relevant target genes.


The tobacco industry, state politics, and tobacco education in California.
Proposition 99 added 25 cents to the California state cigarette tax and mandated that 20% of the new revenues be spent on tobacco education and prevention programs. This paper examines the implementation of these programs and the tobacco industry's response to Proposition 99. Political expenditure data for twelve tobacco firms and associations were gathered from California's Fair Political Practices Commission and secretary of state's Political Reform Division. Tobacco education expenditure data were collected from Governor's Budgets and the Department of Finance. Since Proposition 99 passed, tobacco industry political expenditures in California have risen 10-fold, from $790,050 in the 1985-1986 election to $7,615,091 in the 1991-1992 election. The tobacco industry is contributing more heavily to the California legislature than to Congress. A statistical analysis of data on campaign contributions indicates that California legislators' policy-making is influenced by campaign contributions from the tobacco industry. Since fiscal year 1989-1990, the state has ignored the voters' mandate and spent only 14.7% of the new revenues to tobacco education. Medical care programs received more money than permitted by the voters. The tobacco industry has become politically active in California following the passage of Proposition 99. One result may be that the state has underfunded tobacco education by $174.7 million through the 1993-1994 fiscal year. The estimated redirection of funds to medical care would essentially eliminate the tobacco education campaign by the year 2000.


The diverse roles of protein kinase C in pancreatic beta-cell function.
Members of the serine/threonine PKC (protein kinase C) family perform diverse functions in multiple cell types. All members of the family are activated in signalling cascades triggered by occupation of cell surface receptors, but the cPKC (conventional PKC) and nPKC (novel PKC) isoforms are also responsive to fatty acid metabolites. PKC isoforms are involved in various aspects of pancreatic beta-cell function, including cell proliferation, differentiation and death, as well as regulation of secretion in response to glucose and muscarinic receptor agonists. Recently, the nPKC isoform, PKCepsilon, has also been implicated in the loss of insulin secretory responsiveness that underpins the development of Type 2 diabetes.


Associations between the 11-bp deletion in the myostatin gene and carcass quality in Angus-sired cattle.
An 11-bp deletion in the bovine myostatin (MSTN) gene was identified as the causative mutation for the double-muscling phenotype in Belgian Blue and Asturiana cattle. More recently, this mutation was also identified in the South Devon breed of cattle, in which it has been found to be associated with a general increase in muscle mass. The present study found that the mutant allele was also segregating in a commercial population of Scottish Aberdeen Angus beef cattle. The mutation was found at a low frequency (0.04) with no animals homozygous for the mutation in the sample population (536 animals). The effects of this mutation on various carcass traits of economic interest were then tested. We found that the mutation significantly increased carcass weight, sirloin weight, hindquarter weight, muscle conformation score and eye muscle area, but had no effect on the fat traits.


Measurement of cyclosporine in plasma from patients with various transplants: HPLC radioimmunoassay with a specific monoclonal antibody compared.
This study compares cyclosporin A (CsA) concentrations in plasma from patients receiving various transplants, as measured by HPLC and RIA with a monoclonal antibody for CsA and an 125I-labeled ligand. The RIA was restandardized with in-house standards because it overestimated CsA by an average of 23%. The RIA was sensitive to 2 micrograms/L, the standard curve was linear from 20 to 500 micrograms of CsA per liter, analytical recovery was 98%, and CVs were less than 8% for intra- and interassay precision. RIA (y) vs HPLC (x) for 283 plasma samples from 145 patients gave a slope = 1.1256, r = 0.979. When the results were segregated according to transplant type, CsA in liver and heart recipients was overestimated by RIA as compared with HPLC: slope = 1.202, r = 0.973 and slope = 1.1477, r = 0.983, respectively. Adult and pediatric CsA values were acceptable when RIA and HPLC were compared: slope = 1.0755, r = 0.977 and slope = 1.0563, r = 0.980, respectively. For six samples (four heart, two liver recipients) where HPLC and RIA values demonstrated wide discrepancies, repeat HPLC and analysis of eluate fractions gave CsA concentrations nearer values by the initial HPLC assay. We conclude that this RIA cannot be substituted for HPLC in the case of heart and liver recipients. The need for each laboratory to standardize the RIA is obvious.


Differences in the activity and distribution of peroxidases from three different portions of germinating Brassica oleracea seeds.
Peroxidase (POD, EC 18.104.22.168) activity, cellular localization and isozyme patterns were investigated in the seed integument, cotyledon and embryo axis of Brassica oleracea cv. Cappuccio during pregermination and seedling growth. Seeds started to germinate after 24 h of imbibition. POD activity was localized in the pigmented layer of the integument and in procambial strands of the cotyledon and embryo axis in the first 24 h of imbibition. It was localized in the integumental cells of palisade, pigmented and aleurone layers and in epidermal, meristematic, procambial cells and xylem elements of the root and hypocotyl after 48 h of imbibition. POD activity increased during germination and early seedling growth: in the integument, it reached a maximum value after 72 h of imbibition, in the embryo axis and cotyledons, it increased up to 144 h of imbibition. The increase in peroxidase activity was accompanied by the appearance of new isozymes correlated with the development of seedling tissues. The isozyme profile was characterized by nine peroxidases: isoperoxidase of 50 kDa peculiar to integuments, that of 150 kDa to cotyledons and that of 82 kDa to the embryo axis. During pregerminative phase isozymes of 84 kDa were detected in the integument and cotyledons, of 48.5 kDa in the embryo axis. After germination, peroxidase activity and the complexity of the isozyme pattern increased, suggesting that they play a relevant role after rupture of the integument.


[Prophylactic migraine treatment with topiramate].
Migraine is a very common disorder characterized by the combination of typical headache with associated autonomic symptoms and ranked by the WHO as number 19 among all diseases worldwide causing disability. Considerable progresses have been made in recent years to understand the pathophysiology of migraine, which has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. When headaches are frequent or particularly severe, prophylactic therapy should be considered, however preventive treatment is often insufficient to decrease migraine frequency substantially or is not well tolerated. The present paper summaries the possible drug treatment options which have the A level of evidence for effective preventive therapy of migraine. Summarises the evidences for the prophylactic migraine treatment, specially the role of the newly approved topiramate in the prophylaxis.


Histone acetylation regulates ORMDL3 expression-mediated NLRP3 inflammasome overexpression during RSV-allergic exacerbation mice.
Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1-like protein 3 (ORMDL3) and lead to NOD-like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV-induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV-bronchiolitis follow-up. In BEAS-2B, ORMDL3-induced NLRP3 inflammasome expression. BEAS-2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3-small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.


Optical quasi logic gates based on polarization-dependent four-wave mixing in subwavelength metallic waveguides.
All-optical quasi logic gates are demonstrated by means of polarization-dependent four-wave mixing (FWM) in metal-insulator-metal (MIM) waveguides filled with a Kerr nonlinear medium. By using finite-difference-time-domain (FDTD) methods, we perform a quantitative comparison of the FWM efficiency associated with different pump polarization states. By manipulating the core thickness and the polarization properties of the pump and signals, all-optical NOT, NAND, NOR, and NXOR logical functions are obtained.


Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients.
Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.


WITHDRAWN: Dynamic exercise therapy for treating rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the musculoskeletal system. Inflammation of the joints and tendons results in pain, swelling and restricted movement, eventually leading to radiological changes and deformities. Exercise therapy is considered to be an important cornerstone of the treatment of RA in all stages of the disease. To assess the effects of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. We searched the Cochrane Musculoskeletal trials register, the Cochrane Controlled trials Register, MEDLINE, EMBASE and SCISEARCH databases up to May 1997 in order to controlled trials on the effect of exercise therapy. Randomized trials on the effect of dynamic exercise therapy in RA patients with an exercise program fulfilling the following criteria: a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 minutes, b) exercise frequency of two sessions per week, and c) duration of intervention of greater than six weeks Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled at least seven out of 10 methodological criteria. Due to heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective at increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. The results suggest that dynamic exercise therapy is effective at increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. Dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.


Combined Pulmonary Fibrosis and Emphysema.
Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the combination of upper lobe emphysema and lower lobe fibrosis, the latter owing to various interstitial lung diseases. These patients have a characteristic lung function profile, with relatively preserved dynamic and static lung volumes, contrasting with a significant reduction of carbon monoxide transfer. The pathogenic mechanisms leading to the coexistence of emphysema with fibrosis remain unclear and different theories have been proposed. CPFE is frequently complicated by pulmonary hypertension, acute exacerbations, and lung cancer leading to poor natural history and prognosis. The syndrome of CPFE represents a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases. Currently, there are no established recommendations regarding the management of patients with CPFE. We provide a review on the existing knowledge of CPFE regarding the epidemiology, pathogenesis, clinical manifestations, radiologic appearance, complications, prognosis, and possible treatment options.


Polychlorinated dibenzo-dioxins and -furans detoxification of soil promoted by K-polyethylene glycol technology.
The detoxification of soil and sludge from polychlorinated dibenzo-dioxins (PCDD) and -furans (PCDF) has been achieved by means of the K-PEG technology based on the in situ formation of the complex between polyethylene glycol (PEG) and KOH. Dechlorination of the pollutants was promoted by heating the samples up to 250 degrees C, above the PEG thermal degradation onset (>140 degrees C). As a consequence, a bursting evolution of hydrogen was observed which gave a reductive character to the reaction media and atmosphere. PCDD and PCDF chlorine atoms were progressively eliminated by a hydrodehalogenation reaction. After optimisation of the experimental parameters, the toxicity index was lowered more than 98%. In order to gain insight on the mechanism of the reaction, PEG thermal degradation chemistry was studied in some detail. The analytical results (mainly by mass and IR spectroscopy) suggest that PEG has an essential role on promoting the dehalogenation reaction by acting as a phase transfer agent as well as a source of hydride.


Campylobacter in Africa - A specific viewpoint.
Campylobacter infections and campylobacteriosis-associated post-infectious sequelae are a significant global health burden that needs to be addressed from a specific African perspective. We conducted a comprehensive literature search on NCBI PubMed to compile a comprehensive narrative review article on Campylobacter infections in Africa, focusing on key aspects in human and veterinary medicine as well as food hygiene. We specifically focused on the epidemiology of enteropathogenic Campylobacter spp. in sub-Saharan and North Africa considering antimicrobial susceptibility. The most significant sequela resulting from molecular mimicry to Campylobacter surface structures is the Guillain-Barré syndrome, which was mainly examined in the context of limited studies conducted in African populations. A dedicated subsection is allocated to the limited research on the veterinary medically important species Campylobacter fetus. There are significant differences in the composition of the gut microbiome, especially in rural areas, which affect the colonization with Campylobacter spp. and the manifestation of campylobacteriosis. There may be a problem of overdiagnosis due to asymptomatic colonization, particularly in the detection of Campylobacter using molecular biological techniques. To reduce the colonization and infection rate of Campylobacter, we propose implementing several control measures and urge further research to improve the current understanding of the peculiarities of campylobacteriosis in Africa.


Optimization of a triple etalon interferometer.
The High Resolution Doppler Imager (HRDI) is a triple etalon Fabry-Perot interferometer designed to measure Doppler shifts of rotational lines in the O(2) atmospheric system from the Upper Atmosphere Research Satellite. These shifts are used to determine wind vectors in the stratosphere and mesosphere. This paper presents the techniques used to determine the gap thicknesses and reflectivities of the three etalons of the HRDI instrument. The spacings are found to be 1.000, 0.186, and 0.025 cm. These spacings are independent of the reflectivity of the etalons. The reflectivities of the three etalons should be nearly equal to minimize the errors in the wind measurement caused by mistuning of the etalons. The choice of the reflectivity does not strongly influence the statistical error in the wind error when the values are less than ~0.90.


Accumulation of Domain-Specific Physical Inactivity and Presence of Hypertension in Brazilian Public Healthcare System.
Hypertension is one of the most common noncommunicable diseases worldwide, and physical inactivity is a risk factor predisposing to its occurrence and complications. However, it is still unclear the association between physical inactivity domains and hypertension, especially in public healthcare systems. Thus, this study aimed to investigate the association between physical inactivity aggregation in different domains and prevalence of hypertension among users of Brazilian public health system. 963 participants composed the sample. Subjects were divided into quartiles groups according to 3 different domains of physical activity (occupational; physical exercises; and leisure-time and transportation). Hypertension was based on physician diagnosis. Physical inactivity in occupational domain was significantly associated with higher prevalence of hypertension (OR = 1.52 [1.05 to 2.21]). The same pattern occurred for physical inactivity in leisure-time (OR = 1.63 [1.11 to 2.39]) and aggregation of physical inactivity in 3 domains (OR = 2.46 [1.14 to 5.32]). However, the multivariate-adjusted model showed significant association between hypertension and physical inactivity in 3 domains (OR = 2.57 [1.14 to 5.79]). The results suggest an unequal prevalence of hypertension according to physical inactivity across different domains and increasing the promotion of physical activity in the healthcare system is needed.


Performance, nutrient utilization, and energy partitioning in broiler chickens offered high canola meal diets supplemented with multicomponent carbohydrase and mono-component protease.
Two broiler chicken experiments were conducted to investigate the effects of canola meal (CM) replacing soybean meal (SBM) in diets supplemented with carbohydrase and protease on performance and partitioning of energy. First, a 2 × 2 × 2 factorial arrangement of treatments was employed to evaluate: protein meals (CM vs. SBM), carbohydrase (none or 300 mg/kg), protease (none or 200 mg/kg), and their interactions. Each treatment was fed to 6 replicated pens of 16 male broilers (Ross 308) from d 10 to 35. In the second experiment, 32 broiler chicks were used in a 2 × 2 factorial arrangement to investigate CM and carbohydrase effects on energy partitioning. Birds were transferred into 16 closed-circuit calorimeter chambers (4 chambers/diet; 2 birds/chamber) to measure heat production (HP), metabolizable and net energy (NE) by gaseous exchange, and total excreta collection from d 25 to 28. There were no 3-way interactions among experimental factors for any of the performance parameters measured. Birds given CM diets consumed less feed, had lower BW, and exhibited higher FCR compared to the control birds (P < 0.01). Both enzymes, alone or in combination, improved final BW and FCR (P < 0.05). There was an interaction between carbohydrase and protease for FCR over the grower period (P < 0.01), in which the combination of the enzymes resulted in further improvement of FCR. Energy, DM, and crude protein digestibility values were higher in control birds (P < 0.05). There was an interaction of protein meal and carbohydrase for HP, respiratory quotient (P < 0.05), and NE:ME ratio of the diets (P = 0.06). Inclusion of CM without carbohydrase increased HP and decreased NE and NE:ME ratio of the diets (P < 0.05). Carbohydrase decreased HP and increased retained energy (P = 0.06) and NE and NE:ME ratio (P < 0.05). In conclusion, high CM in the diet negatively affects growth performance through reduction in feed consumption, nutrient digestibility, and NE of the diet, which could partly be restored by enzyme supplementation.


Distress and quality of life characteristics associated with seeking surgical treatment for stress urinary incontinence.
Current research focuses on three variables in evaluating the impact of stress urinary incontinence (SUI) on daily living: severity of incontinence, distress or bother resulting from incontinence, and effect on health related quality of life (HRQoL). Understanding the impact of these variables is important as they are the driving force behind women seeking surgical treatment. Given the importance of HRQoL in determining need for treatment, as well as evaluating treatment success, this review provides an assessment of the degree to which HRQoL is impaired in women seeking surgical treatment. PubMed searches for the terms "quality of life and distress and urinary incontinence" and "quality of life and bother and urinary incontinence" were performed with limits of English, human and female subjects through May 2008. All studies using validated instruments were included. No time limit was placed on the search. Of 178 articles retrieved, 21 met the inclusion criteria, and 17 reported methods of scoring. The studies used the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ). Wide ranges of mean and individual levels of severity of symptoms, UDI and IIQ scores were seen among women seeking surgical treatment. Fourteen studies reported baseline and post-surgical treatment distress and QoL data. Statistically significant improvements between baseline and post-surgical UDI and IIQ scores were reported in 12 studies. Reported cure rates ranged from 46% to 97%. Satisfaction with the procedure was reported in 4 studies and ranged from 84% to 91%. A minority of studies reported the relationship between reduction in symptoms and change in HRQoL. HRQoL is the main reason women seek surgical treatment for incontinence and surgical treatment leads to a significant improvement in mean HRQoL scores. Assessment of HRQoL has proved less useful in identifying why individual women seek treatment for incontinence. Preliminary work has begun to characterize the interaction between severity of symptoms, distress or bother resulting from these urinary symptoms, impact on HRQoL, and treatment seeking behavior, but further research is needed. Greater standardization in the reporting of results of distress or bother and HRQoL would allow for comparison across studies.


All-trans and 9-cis retinoid acids inhibit proliferation, migration, and synthesis of extracellular matrix of human vascular smooth muscle cells by inducing differentiation in vitro.
The aim of this study was to evaluate the effects of 9-cis retinoid acid (9-cis RA) and all-trans RA (ATRA) on proliferation, migratory ability, synthesis of extracellular matrix, intracellular signal transduction, and differentiation of human aortic smooth muscle cells (haSMCs) in vitro. Changes of cell proliferation following incubation with RAs in different doses (10-6 M, 10-7 M, and 10-8 M) were determined directly by proliferation kinetics and indirectly by bromodeoxyuridine enzyme-linked immuno sorbant assays and colony-formation assays. The migratory ability of haSMCs was examined with the help of migration assays. The production of the extracellular matrix protein tenascin was explored by immunostaining. The amounts of total p44/p42 mitogen-activated protein kinases (MAPKs) and their phosphorylated forms were detected with the help of Western blots. To judge the state of differentiation of haSMCs, cell cycle distribution and the pattern of alpha-actin were analyzed. Both RAs clearly inhibited the proliferation of haSMCs in a dose-dependent manner. 9-cis RA had a tendency to be more effective than ATRA. After treatment with RAs, the migratory ability was especially reduced during stimulation with platelet-derived growth factor (PDGF) and the synthesis of tenascin decreased. Although the total p44/p42 MAPKs were downregulated, the amounts of activated forms increased markedly in the cells incubated with RAs and particularly stimulated with PDGF. The cell-cycle analysis demonstrated an increased G1-phase, complemented by a stronger expression of alpha-actin after treatment. 9-cis RA especially has the potential to inhibit the proliferation, migration, and synthesis of extracellular matrix of haSMCs by inducing differentiation in vitro.


A comparison of the pitfall trap, Winkler extractor and Berlese funnel for sampling ground-dwelling arthropods in tropical montane cloud forests.
Little is known about the ground-dwelling arthropod diversity in tropical montane cloud forests (TMCF). Due to unique habitat conditions in TMCFs with continuously wet substrates and a waterlogged forest floor along with the innate biases of the pitfall trap, Berlese funnel and Winkler extractor are certain to make it difficult to choose the most appropriate method to sample the ground-dwelling arthropods in TMCFs. Among the three methods, the Winkler extractor was the most efficient method for quantitative data and pitfall trapping for qualitative data for most groups. Inclusion of floatation method as a complementary method along with the Winkler extractor would enable a comprehensive quantitative survey of ground-dwelling arthropods. Pitfall trapping is essential for both quantitative and qualitative sampling of Diplopoda, Opiliones, Orthoptera, and Diptera. The Winkler extractor was the best quantitative method for Psocoptera, Araneae, Isopoda, and Formicidae; and the Berlese funnel was best for Collembola and Chilopoda. For larval forms of different insect orders and the Acari, all the three methods were equally effective.


The medical visit context of treatment decision-making and the therapeutic relationship.
The ascendance of the autonomy paradigm in treatment decision-making has evolved over the past several decades to the point where few bioethicists would question that it is the guiding value driving health-care provider behaviour. In achieving quasi-legal status, decision-making has come to be regarded as a formality largely removed from the broader context of medical communication and the therapeutic relationship within which care is delivered. Moreover, disregard for individual patient preference, resistance, reluctance, or incompetence has at times produced pro forma and useless autonomy rituals. Failures of this kind, have been largely attributed to the psychological dynamics of the patients, physicians, illnesses, and contexts that characterize the medical decision. There has been little attempt to provide a framework for accommodating or understanding the larger social context and social influences that contribute to this variation. Applying Paulo Freire's participatory social orientation model to the context of the medical visit suggests a framework for viewing the impact of physicians' communication behaviours on patients' capacity for treatment decision-making. Physicians' use of communication strategies can act to reinforce an experience of patient dependence or self-reliance in regard to the patient-physician relationship generally and treatment decision-making, in particular. Certain communications enhance patient participation in the medical visit's dialogue, contribute to patient engagement in problem posing and problem-solving, and finally, facilitate patient confidence and competence to undertake autonomous action. The purpose of this essay is to place treatment decision-making within the broader context of the therapeutic relationship, and to describe ways in which routine medical visit communication can accommodate individual patient preferences and help develop and further patient capacity for autonomous decision-making.


[Efficacy of frequency-neurofeedback and Cogmed JM-working memory training in children with ADHD].
The need for and the interest in non-pharmacological treatments for children with ADHD are increasing. The treatments include electro-encephalogram (EEG) frequency-neurofeedback and Cogmed working memory training. To investigate the efficacy of frequency-neurofeedback and Cogmed working memory training in children with ADHD. Forty-one children with ADHD (aged 8-15 years) were assigned to frequency-neurofeedback or to placebo-neurofeedback in a randomized double-blind trial. We took measurements to find out whether frequency-neurofeedback had reduced the severity of the ADHD-symptoms, and/or had improved neurocognitive ability and global clinical functioning. Fifty-one children with ADHD (aged 5-7 years) were assigned to the active Cogmed JM-working memory training or to the placebo working memory training in a randomised double-blind trial. We took measurements to find out whether Cogmed JM-working memory training had reduced the ADHD symptoms, and/or had improved neurocognitive ability, daily performance and global clinical functioning. The ADHD symptoms and global clinical functioning of the children in both neurofeedback groups improved. However, frequency-neurofeedback did nor produce any significantly better treatment results than did the placebo neurofeedback. At the neurocognitive level, frequency-neurofeedback did not yield any measurements that were significantly superior to those achieved with placebo feedback. Various outcome measurements improved in both groups with memory training. However, the active working memory training was not found to have produced significantly better results than the placebo training with regards to the ADHD symptoms, neurocognitive ability and daily and global functioning. Children from the active working memory training group showed improvements in trained working memory tasks but not on untrained tasks. Neither study produced any conclusive evidence for the efficacy of the investigated treatments in children with ADHD. However, both types of treatments can be further improved. Furthermore, the controlled designs may have restricted the embedding of the treatments. Because of possible improvements in the treatments in the future and because of the design restrictions affecting the treatments in their present form, it is still too early to draw any definitive conclusions about the validity and advantages of the two treatment methods.


Developing Best Practice Guidance for Discharge Planning Using the RAND/UCLA Appropriateness Method.
Background: Discharge from acute mental health inpatient units is often a vulnerable period for patients. Multiple professionals and agencies are involved and processes and procedures are not standardized, often resulting in communication delays and co-ordination failures. Early and appropriate discharge planning and standardization of procedures could make inpatient care safer. Aim: To inform the development of a multi-component best practice guidance for discharge planning (including the 6 component SAFER patient flow bundle) to support safer patient transition from mental health hospitals to the community. Methods: Using the RAND/UCLA Appropriateness method, a panel of 10 professional stakeholders (psychiatrists, psychiatric nurses, clinical psychologists, pharmacists, academics, and policy makers) rated evidence-based statements. Six hundred and sixty-eight statements corresponding to 10 potential components of discharge planning best practice were rated on a 9-point integer scale for clarity, appropriateness and feasibility (median ≥ 7-9) using an online questionnaire then remote online face-to-face meetings. Results: Five of the six "SAFER" patient flow bundle components were appropriate and feasible for inpatient mental health. One component, "Early Flow," was rated inappropriate as mental health settings require more flexibility. Overall, 285 statements were rated as appropriate and feasible. Forty-four statements were considered appropriate but not feasible to implement. Discussion: This consensus study has identified components of a best practice guidance/intervention for discharge planning for UK mental health settings. Although some components describe processes that already happen in everyday clinical interactions (i.e., review by a senior clinician), standardizing such processes could have important safety benefits alongside a tailored and timely approach to post-discharge care.


Novel insights on acute myocarditis in pediatric patients.
Acute myocarditis (AM) is an inflammatory affliction of the heart muscle characterized by recent onset with a broad spectrum of clinical manifestations that globally affect millions of individuals, notably children and young adults. The absence of distinct patterns of onset or predictable progression poses a significant threat to survival, potentially leading to advanced heart failure and malignant arrhythmias. Myocardial fibrosis, a hallmark of myocardial remodeling, is increasingly recognized as a contributor to adverse outcomes in acute myocarditis cases. Advances in molecular and immunological techniques have highlighted the intricate interplay between viral infections, dysregulated immune responses, and genetic susceptibility. Currently, there is no clear consensus for diagnosis or ongoing follow-up in pediatric patients. The conventional diagnostic tool, endomyocardial biopsy (EMB), considered the gold standard, has been complemented by the effectiveness of cardiac magnetic resonance imaging (CMRI) techniques. Given the procedural complexities and associated complications, there is a pressing need to explore non-invasive alternatives. In this context, biomarkers emerge as promising contenders by evaluating both the inflammatory processes and cardiac remodeling, providing valuable observations into disease severity, progression, and treatment response. Therapeutic strategies in these cases, focusing on the specific pathways or immune components associated with the etiologies, have exhibited promise for better outcomes. Acute myocarditis in children remains a multifaceted clinical challenge, necessitating a comprehensive understanding of its pathophysiology, diagnosis, and management. This review aims to delve into novel insights surrounding the pathophysiology, diagnosis, and management of acute myocarditis in pediatric patients.


Efficacy of 3 commonly used hearing aid circuits: A crossover trial. NIDCD/VA Hearing Aid Clinical Trial Group.
Numerous studies have demonstrated that hearing aids provide significant benefit for a wide range of sensorineural hearing loss, but no carefully controlled, multicenter clinical trials comparing hearing aid efficacy have been conducted. To compare the benefits provided to patients with sensorineural hearing loss by 3 commonly used hearing aid circuits. Double-blind, 3-period, 3-treatment crossover trial conducted from May 1996 to February 1998. Eight audiology laboratories at Department of Veterans Affairs medical centers across the United States. A sample of 360 patients with bilateral sensorineural hearing loss (mean age, 67.2 years; 57% male; 78.6% white). Patients were randomly assigned to 1 of 6 sequences of linear peak clipper (PC), compression limiter (CL), and wide dynamic range compressor (WDRC) hearing aid circuits. All patients wore each of the 3 hearing aids, which were installed in identical casements, for 3 months. Results of tests of speech recognition, sound quality, and subjective hearing aid benefit, administered at baseline and after each 3-month intervention with and without a hearing aid. At the end of the experiment, patients ranked the 3 hearing aid circuits. Each circuit markedly improved speech recognition, with greater improvement observed for soft and conversationally loud speech (all 52-dB and 62-dB conditions, P</=.001). All 3 circuits significantly reduced the frequency of problems encountered in verbal communication. Some test results suggested that CL and WDRC circuits provided a significantly better listening experience than PC circuits in word recognition (P =.002), loudness (P =.003), overall liking (P =.001), aversiveness of environmental sounds (P =.02), and distortion (P =.02). In the rank-order ratings, patients preferred the CL hearing aid circuits more frequently (41.6%) than the WDRC (29.8%) and the PC (28.6%) (P =.001 for CL vs both WDRC and PC). Each circuit provided significant benefit in quiet and noisy listening situations. The CL and WDRC circuits appeared to provide superior benefits compared with the PC, although the differences between them were much less than the differences between the aided vs unaided conditions. JAMA. 2000;284:1806-1813.


[Familial progressive external opthalmoplegia, parkinsonism and polyneuropathy associated with POLG1 mutation].
Multiple mitochondrial DNA (mtDNA) deletions usually occur secondarily to a mutation in one of the enzymes involved in mtDNA maintenance, such as polymerase γ, which is encoded by the nuclear polymerase γ1 gene (POLG1) and POLG2. Patients with multiple mtDNA deletion disorders show clinical heterogeneity of symptoms, in addition to usually seen progressive external ophthalmoplegia (PEO). We conducted clinical, histological and genetic analyses of two affected sisters in a family with the autosomal dominant inheritance pattern of PEO. A 73-year-old woman (patient 1) with congenital hypogonadism and PEO developed L-dopa responsive parkinsonism about the age of 60. Neurological examination revealed mild proximal muscle weakness and polyneuropathy too. Her 69-year-old sister (patient 2) also showed PEO, parkinsonism and polyneuropathy. Histopathological studies of biopsied muscle specimens from patient 1 revealed numerous ragged red fibers as well as fibers with increased succinate dehydrogenase activity and decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected, both by Southern blot and long-range PCR assays of total DNA from the biopsied muscle specimens. A systemic mutational analysis in both sisters revealed a heterozygous p.Y955C (c.2864A>G) mutation in POLG1. This is the first Japanese family identified with this mutation. We reviewed cases with this mutation highlighting a wide phenotypic spectrum of this disorder.


Photographic review of results from a clinical study comparing benzoyl peroxide 5%/clindamycin 1% topical gel with vehicle in the treatment of rosacea.
A photographic analysis was conducted of results from a randomized, double-blind, vehicle-controlled, 12-week study that assessed the efficacy of topical benzoyl peroxide 5%/clindamycin 1% (BP/C) gel (BenzaClin) versus vehicle in the treatment of rosacea. The objective was to compare the baseline and end-of-treatment photographs of patients treated with BP/C versus those treated with vehicle. Patients were randomized to receive once-daily treatment with BP/C or vehicle for 12 weeks. Three blinded, independent reviewers evaluated papule and pustule severity at baseline and at week 12 for each patient. An Overall Global Improvement (OGI) scale was used to assess efficacy. Fifty patients (BP/C, 26; vehicle, 24) were evaluated. At end of treatment, significant (P < .001) improvements were seen in the number of papules and pustules based on the OGI scale for patients receiving BP/C. At week 12, 7. 7% of patients treated with BP/C were rated as "clear/nearly clear" from baseline compared with a change of 0% in patients receiving vehicle. An additional 15.4% of patients were rated as having a "marked improvement" from baseline compared with a change of 4.2% in patients receiving vehicle. Interrater reliability was high, based on intraclass correlation coefficient (ICC) of 0.647 (BP/C) and 0.722 (vehicle) on the OGI scale (P < .001). These results showed that BP/C was significantly more effective than vehicle in improving papules and pustules associated with rosacea.


Optical characterization of electron-phonon interactions at the saddle point in graphene.
The role of many-body interactions is experimentally and theoretically investigated near the saddle point absorption peak of graphene. The time and energy-resolved differential optical transmission measurements reveal the dominant role played by electron-acoustic phonon coupling in band structure renormalization. Using a Born approximation for electron-phonon coupling and experimental estimates of the dynamic lattice temperature, we compute the differential transmission line shape. Comparing the numerical and experimental line shapes, we deduce the effective acoustic deformation potential to be Deff(ac)≃5 eV. This value is in accord with recent theoretical predictions but differs from those extracted using electrical transport measurements.


'Being politically active does not have to be difficult.' A content analysis of tobacco industry-sponsored advocacy websites.
To characterise the thematic content of tobacco industry-sponsored advocacy websites in the USA and to compare these sites to identify differences in products, target audience, policies or themes. In 2017, US-based Google and purposive searches identified six US tobacco industry-sponsored advocacy websites. A coding guide based on existing literature, tobacco policy issues and iterative review of the websites was developed and, descriptive analyses of themes on individual websites and overall were conducted. We identified 18 themes; the most common of these were: tobacco taxes (13.9%), providing advocacy resources (10.6%) and pleas for action (10.3%). Related themes were aggregated into four broad categories: advocacy (36.7%), taxes (31.4%), legislation is excessive or unnecessary (21%), and support for weaker tobacco control policies (10.9%). Websites targeting consumers provided more resources to facilitate advocacy than websites targeting retailers. Websites promoting protobacco advocacy are an important and evolving strategy for the tobacco industry. Websites are particularly well suited to leverage marketing activities (eg, building relationships with retailers and consumers) to achieve policy objectives. Monitoring these tactics may allow advocates to counter and anticipate industry opposition to tobacco policy.


If SMBG Accuracy Is Critical to Patient Safety, Why Are Inaccurate Meters Still on the Market?
In this issue of Journal of Diabetes Science and Technology, Christiansen and colleagues report results from two studies, laboratory and clinical, that assessed the accuracy of a new blood glucose monitoring system, the Contour®Next ONE (Ascensia Diabetes Care, Parsippany, NJ, USA). The new system comprises a blood glucose meter that can link (via Bluetooth®) to the Contour™ Diabetes app, which operates on a smartphone or tablet. Results from both studies showed that the system exceeded the accuracy standards defined by the International Organization for Standardization (ISO) 15197:2013. It is worrisome, however, that many FDA-cleared (and marketed) blood glucose monitoring systems do not meet ISO accuracy criteria. Significant improvements in regulatory oversight and enforcement are needed.


Urinary incontinence and life-space activity/mobility additively increase the risk of incident disability among older adults.
To examine the associations of a combination of urinary incontinence (UI) and life-space activity/mobility with the risk of incident disability among community-dwelling older adults. The participants were 12,808 older adults for the cross-sectional study and 12,516 older adults who completed the follow-up assessment. UI was assessed using a questionnaire. Life-space activity/mobility was evaluated using total, physical, and social scores on the Active Mobility Index (AMI). Participants were classified into four groups (high AMI total score + no UI; high AMI total score + UI; low AMI total score + no UI; low AMI total score + UI). Incident disability was extracted from the Japanese Long-Term Care System. During the 24-month follow-up, 562 participants (4.5 %) developed disability. Those with a low AMI score + no UI (hazard ratio, 1.35; 95 % confidence interval, 1.07-1.71) and those with a low AMI score + UI (hazard ratio, 2.00; 95 % confidence interval, 1.56-2.56) had a higher risk of incident disability than those with a high AMI score + no UI in the follow-up analysis. A combination of UI and low AMI score was associated with an increased risk of incident disability, whereas having UI but a high AMI score was not associated with an increased risk of incident disability. Our findings may help identify older adults at high risk of developing disabilities.


Two-staged biliary reconstruction with temporary complete external biliary drainage as a bailout procedure in a pediatric patient after difficult living donor liver retransplantation.
Biliary leakage at the site of the hepaticojejunostomy after liver transplantation is a life-threatening complication. We herein present the case of a 7-year-old girl who underwent complete external biliary drainage during difficult living donor liver retransplantation as a bailout procedure. The patient had undergone duct-to-duct biliary reconstruction in the initial living donor liver transplantation. In the retransplantation, Roux-en-Y (RY) reconstruction was planned but abandoned due to the critical condition in the operation. As an alternative procedure, the patient underwent complete external drainage using a 6Fr drainage tube with cuff. Five months after retransplantation when the nutrition status and physical strength of a patient recovered fully, RY hepaticojejunostomy was successfully performed. This is a case report of two-staged biliary reconstruction with temporary complete external biliary drainage used in pediatric liver retransplantation, which was performed after some months not a few days. It is a safe and feasible alternative when primary anastomosis is deemed to carry a high risk of bile leakage in cases of difficult liver transplantation in critically ill patients.


Drug-resistant epilepsy: Drug target hypothesis and beyond the receptors.
Epilepsy is a chronic neurological disorder that affects more than 50 million people worldwide. Despite a recent introduction of antiseizure drugs for the treatment of epileptic seizures, one-third of these patients suffer from drug-resistant epilepsy (DRE). The therapeutic target hypothesis is a cited theory to explain DRE. According to the target hypothesis, the failure to achieve seizure freedom leads to alteration of the structure and/or function of the antiseizure medication (ASM) target. However, this hypothesis fails to explain why patients with DRE do not respond to antiseizure medications of different targets. This review presents different conditions, such as epigenetic mechanisms and protein-protein interactions that may result in alterations of diverse drug targets using different mechanisms. These novel conditions represent new targets to control DRE.


The restorative role of annexin A1 at the blood-brain barrier.
Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood-brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood-brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood-brain barrier damage in disease and aging.


Heart failure-associated changes in RNA splicing of sarcomere genes.
Alternative mRNA splicing is an important mechanism for regulation of gene expression. Altered mRNA splicing occurs in association with several types of cancer, and a small number of disease-associated changes in splicing have been reported in heart disease. However, genome-wide approaches have not been used to study splicing changes in heart disease. We hypothesized that mRNA splicing is different in diseased hearts compared with control hearts. We used the Affymetrix Exon array to globally evaluate mRNA splicing in left ventricular myocardial RNA from controls (n=15) and patients with ischemic cardiomyopathy (n=15). We observed a broad and significant decrease in mRNA splicing efficiency in heart failure, which affected some introns to a greater extent than others. The profile of mRNA splicing separately clustered ischemic cardiomyopathy and control samples, suggesting distinct changes in mRNA splicing between groups. Reverse transcription-polymerase chain reaction validated 9 previously unreported alternative splicing events. Furthermore, we demonstrated that splicing of 4 key sarcomere genes, cardiac troponin T (TNNT2), cardiac troponin I (TNNI3), myosin heavy chain 7 (MYH7), and filamin C, gamma (FLNC), was significantly altered in ischemic cardiomyopathy and in dilated cardiomyopathy and aortic stenosis. In aortic stenosis samples, these differences preceded the onset of heart failure. Remarkably, the ratio of minor to major splice variants of TNNT2, MYH7, and FLNC classified independent test samples as control or disease with >98% accuracy. Our data indicate that mRNA splicing is broadly altered in human heart disease and that patterns of aberrant RNA splicing accurately assign samples to control or disease classes.


Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial.
Abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application results in high local drug concentrations and may be more effective than a standard intravenous bolus. Patients undergoing primary PCI were randomized to either intracoronary (n=77) or intravenous (n=77) bolus abciximab administration with subsequent 12-hour intravenous infusion. The primary end point was infarct size and extent of microvascular obstruction as assessed by delayed enhancement magnetic resonance. Secondary end points were ST-segment resolution at 90 minutes, Thrombolysis in Myocardial Infarction flow and perfusion grades after PCI, and the occurrence of major adverse cardiac events within 30 days. The median infarct size was 15.1% (interquartile range, 6.1% to 25.2%) in the intracoronary versus 23.4% (interquartile range, 13.6% to 33.2%) in the intravenous group (P=0.01). Similarly, the extent of microvascular obstruction was significantly smaller in intracoronary compared with intravenous abciximab patients (P=0.01). Myocardial perfusion measured as early ST-segment resolution was significantly improved in intracoronary patients with an absolute ST-segment resolution of 77.8% (interquartile range, 66.7% to 100.0%) versus 70.0% (interquartile range, 45.2% to 83.5%; P=0.006). The Thrombolysis in Myocardial Infarction flow after PCI was not different between treatment groups (P=0.51), but there was a trend toward an improved perfusion grade (P=0.09). There also was a trend toward a lower major adverse cardiac event rate after intracoronary versus intravenous abciximab application (5.2% versus 15.6%; P=0.06; relative risk, 0.33; 95% CI, 0.09 to 1.05). Intracoronary bolus administration of abciximab in primary PCI is superior to standard intravenous treatment with respect to infarct size, extent of microvascular obstruction, and perfusion.


Abdominal neurenteric cyst.
Neurenteric cysts are extremely rare congenital anomalies, often presenting in the first 5 years of life, and are caused by an incomplete separation of the notochord from the foregut during the third week of embryogenesis. They are frequently accompanied with spinal or gastrointestinal abnormalities, but the latter may be absent in adults. Although usually located in the thorax, neurenteric cysts may be found along the entire spine. We present a 24-year-old woman admitted for epigastric pain, nausea, vomiting, low grade fever and leucocytosis. She underwent cystgastrostomy for a loculated cyst of the distal pancreas at the age of 4 years, which recurred when she was at the age of 11 years. Ultrasound and computer tomograghy (CT) scan revealed a 16 cm multiply 15 cm cystic mass in the body and tail of pancreas, with a 6-7 mm thickened wall. Laboratory data and chest X-ray were normal and spinal radiographs did not show any structural abnormalities. The patient underwent a complete cyst excision, and after an uneventful recovery, remained symptom-free without recurrence during the 5-year follow-up. The cyst was found to contain 1200 mL of pale viscous fluid. It was covered by a primitive single-layered cuboidal epithelium, along with specialized antral glandular parenchyma and hypoplastic primitive gastric mucosa. Focal glandular groups resembling those of the body of the stomach were also seen. In addition, ciliary respiratory epithelium, foci of squamous metaplasia and mucinous glands were present. The wall of the cyst contained a muscular layer, neuroglial tissue with plexogenic nerve fascicles, Paccini corpuscle-like structures, hyperplastic neuroganglionar elements and occasional psammomatous bodies, as well as fibroblast-like areas of surrounding stroma. Cartilagenous tissue was not found in any part of the cyst. Immunohistochemistry confirmed the presence of neurogenic elements marked by S-100, GFAP, NF and NSE. The gastric epithelium showed mostly CK7 and EMA immunoexpression, and the respiratory epithelium revealed a CK8 and CK18 immunoprofile without CK 10/13 positive elements, though neither CEA or AFP positive cells were found. To our knowledge, this is the first reported case of an abdominally located neurenteric cyst with no associated spinal anomalies.


"Listening Between the Lines": Soundscapes in Yusef Komunyakaa's Poetry.
Yusef Komunyakaa's poetry is widely acclaimed for its sui generis soundscapes, which shows the poet's highly sensitive auditory perception in his literary creations. Soundscapes, in his poetry, play a pivotal role in revealing social malaise-racial inequalities and gender-biased black relations-in the multiracial US. This article thus explores race- and gender-related societal problems mirrored in Komunyakaa's poetry through the prism of soundscapes. It first aims to examine how soundscapes are presented between poetic lines as a culture carrier, and then investigates the disciplinary power and oppositional function of soundscapes. Combining textual close reading with interdisciplinary research methodology, this article brings to light the complexity and specificity of soundscapes in Komunyakaa's poetry. For one thing, the soundscape constructed by the privileged serves as an oppressive force to discipline the disempowered groups; for another, the soundscape the underprivileged produce is utilized as an instrument of resistance and healing, offering them a sonic weapon to deconstruct the oppressive sound imperialism as well as construct the affective community of African Americans. This study not only adds to the research on Komunyakaa's poetry by offering a renewed viewpoint of excavating this poet and his political proposition of equality and equity, but also attracts academic attention to the role of literary soundscape in Afro-American literature in revealing the long-standing societal problems in the US.


Evolution of modular conidiophore development in the aspergilli.
Conidiophores are reproductive structures that enable filamentous fungi to produce and disseminate large numbers of asexual spores. The diversity in conidiophore morphology is sufficiently large to serve as a basis for fungal systematics. Aspergillus and Penicillium species are members of the family Trichocomaceae that form conidiophores with characteristic architecture. Whereas the Penicillium conidiophore appears to be a modified branched hyphal structure, the Aspergillus conidiophore is seemingly more complex and includes additional cell types. Here, it is proposed that the "aspergillioid" conidiophore may have evolved from a "penicillioid" ancestor via changes in expression of key regulators of the cell cycle and the GTPase Cdc42. Because the transcriptional regulatory network that controls conidiophore development in Aspergillus is well characterized, further study of how this network links to regulators of the cell cycle and Cdc42 should provide fundamental insight into the evolution of developmental morphogenesis in fungi (i.e., fungal evo-devo).


Interactions between thyroid hormone and tryptophan transport in rat liver are modulated by thyroid status.
We have identified both N-ethylmaleimide (NEM)-resistant (system T) and NEM-sensitive (system L1) L-[3H]tryptophan transporters in sinusoidal membrane vesicles (SMVs) from euthyroid, hypothyroid (propylthiouracil-treated), and hyperthyroid [L-3,5,3'-triiodothyronine (L-T3)-injected] rats. L-[125I]T3 associates with SMVs largely by surface binding. Kinetic characteristics of tryptophan uptake and T3 binding (transporter or receptor abundance and substrate affinity) are not significantly affected by thyroid status. T3 and thyroxine (T4) inhibit NEM-resistant tryptophan uptake in SMVs to an extent dependent on the thyroid status of the donor rat, increasing in the order hypothyroid < euthyroid < hyperthyroid; the inhibitor constant for this inhibition (0.3 microM T3) is equal to the dissociation constant for T3 binding. Both T3 binding and T3 inhibition of tryptophan transport in SMVs are markedly reduced by treatments (Triton X-100 or trypsin) that do not significantly affect vesicle integrity or transport of tryptophan and glucose. T3 and/or T4 transport at the liver-plasma interface may be facilitated by direct interactions between hormone receptors and system T transporter proteins. Modulation of such interactions may be important for control of hepatic T4 and/or T3 turnover and aromatic amino acid metabolism during altered thyroid status.


Effects of metformin on endometrial cancer cell growth in vivo: a preoperative prospective trial.
Metformin, an antidiabetic drug, decreases the incidence of various cancers in diabetic patients. Metformin-induced inhibition of cancer cell proliferation has been confirmed in vitro but not in humans. Because endometrial cancer is associated with insulin resistance, the authors investigated whether a diabetes-therapeutic metformin dose inhibits cancer cell growth in patients with endometrial cancer. A dose of metaformin was administered (1500-2250 mg/day) to 31 patients with endometrial cancer preoperatively for 4 to 6 weeks. Cell proliferation was assessed in patient tissues using immunohistochemical and Western blot analyses and DNA synthesis was measured in serum using a thymidine uptake assay. All statistical tests were 2-sided. P values of < .05 were considered statistically significant. Preoperative metformin treatment decreased DNA synthesis in sera and significantly reduced the Ki-67 (mean proportional decrease, 44.2%; 95% confidence interval [95% CI], 35.4-53.0 [P < .001]) and topoisomerase IIα (mean proportional decrease, 36.4%; 95% CI, 26.7-46.0 [P < .001]) labeling indices. Levels of phospho-ribosomal protein S6 and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) were found to be significantly decreased and phospho-adenosine monophosphate-activated protein kinase and p27 levels were significantly increased. Preoperative metformin use caused significant decreases in circulating factors, including insulin, glucose, insulin-like growth factor 1, and leptin. DNA synthesis-stimulating activity in patient sera was significantly decreased during metformin administration. An antidiabetic dose of metformin inhibited endometrial cancer cell growth in vivo, an effect likely due to its effect on humoral factor(s). This translational study provides considerable rationale to initiate large clinical trials.


Polarity effect in commercial ionization chambers used in photon beams with small fields.
Ionization chambers are the instruments of choice for use in photon dosimetry. Ionization chambers together with radiographic films represent the best detectors for measurement of dose distribution for a quality assurance (QA) program in intensity-modulated radiotheraphy (IMRT). The polarity effect was investigated for seven different commercially available ionization chambers. This study concentrated on measuring the dependence of the polarity effect at various energies, and for various field size, ionization chamber, and electrometer combinations. Of the seven chambers, CC01, PTW23323, and PTW31006 had the largest polarity effect for small field sizes. The materials of the central electrode of these three chambers were steel or air-equivalent plastic C-552. The magnitude of the polarity effect was shown to be strongly dependent on the material of the collecting electrode. This polarity effect dependence was observed for the ionization chambers and small field sizes studied.


Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells.
Research dealing with early diagnosis and efficient treatment in colon cancer to improve patient's survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non-specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated form (CL-SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti-cancer activity against colon cancer cells.


The role of substance P in the human urinary bladder.
Detrusor muscle from human bladder contracted to field stimulation after atropine. It also responded to exogenous substance P by an atropine-insensitive mechanism. We tested whether substance P might mediate noncholinergic excitation. Tachyphylaxis to substance P did not effect noncholinergic responses to field stimulation. A substance P antagonist was ineffective in blocking responses to field stimulation or to exogenous substance P. Capsaicin had only nonspecific depressant effects on field stimulated contraction in high (10(-4) M) concentrations. These data do not support the hypothesis that substance P is the mediator of noncholinergic, field stimulated contractions of human detrusor muscle.