Dynamics of cytokines predicts risk of hepatocellular carcinoma among chronic hepatitis C patients after viral eradication.
Chronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development. To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy. One hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment. HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively. Downregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.


Incidents of bee poisoning with pesticides in the United Kingdom, 1994-2003.
For over 20 years, the UK Agriculture Departments have monitored the direct effects of pesticides on beneficial insects, mainly honeybees (Apis mellifera, L.) and bumblebees (Bombus terrestris, L.), as part of the Wildlife Incident Investigation Scheme (WIIS). The Central Science Laboratory (CSL) has contributed to WIIS by providing the required laboratory skills for the determination of bee diseases and the expert analytical experience necessary to determine low-level pesticide residues and interpret these results. The results from WIIS form part of the pesticide regulatory process coordinated by the Pesticides Safety Directorate (PSD) and are published each year. This paper has reviewed the data from WIIS over the 10 year period from 1994 to 2003. The overall trend is that suspected poisoning incidents, reported by beekeepers and the general public, have declined from 56 incidents per year to 23 incidents per year. The number of these incidents that have been attributed to pesticide poisoning has also declined, from 25 incidents to five incidents per year. The possible reasons for these changes and the circumstances involved in the bee poisoning incidents are discussed. However, the source of the pesticide in bee poisoning incidents is often uncertain and the likely cause of these incidents and any trends over time are also discussed.


Nuclear tRNA export in trypanosomes: a journey full of twists and turns guided by tRNA modifications.
Transfer RNAs play a key role in protein synthesis. Following transcription, tRNAs are extensively processed prior to their departure from the nucleus to become fully functional during translation. This includes removal of 5′ leaders and 3′ trailers by a specific endo- and/or exonuclease, 3′ CCA tail addition, posttranscriptional modifications and in some cases intron removal. In this minireview, the critical factors of nuclear tRNA trafficking are described based on studies in classical models such as yeast and human cell lines. In addition, recent findings and identification of novel regulatory loops of nuclear tRNA trafficking in trypanosomes are discussed with emphasis on tRNA modifications. The comparison between the representatives of opisthokonts and excavates serves here to understand the evolutionary conservation and diversity of nuclear tRNA export mechanisms.


New developments in the treatment of gastric carcinoma.
The recent successes being achieved with combination chemotherapy regimens strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remission (CRs). The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease free. The expected survival of patients with unresectable LAD is approximately 4-6 months without any treatment and 6-9 months with standard chemotherapy. Compared with the latter results, the preoperative use of etoposide, adriamycin, and platinum (EAP) seems to improve the prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stage IIIa or IIIb). However, partly because of the severe toxicities (myelo-suppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens. Considering the predominantly palliative treatment intentions in far-advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53%, including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. The high remission rate and long medical survival time achieved with ELF, plus its good tolerability, make this combination a valuable alternative to anthracycline-containing regimens. In addition to developing new treatment plans and strategies, it is also desirable to predict treatment outcome with an acceptable degree of certainty. Combinations of variable defined patient subgroups with significantly different probabilities for achieving objective response and for survival. The results of this analysis may contribute to a more patient-oriented and risk-adapted chemotherapy and to better comparability of future studies.


Polylactosaminoglycan glycomics: enhancing the detection of high-molecular-weight N-glycans in matrix-assisted laser desorption ionization time-of-flight profiles by matched filtering.
For over 30 years, protocols based on the mass spectrometry (MS) of permethylated derivatives, complemented by enzymatic degradations, have underpinned glycomic experiments aimed at defining the structures of individual glycans present in the complex mixtures that are characteristic of biological samples. Both MS instrumentation and sample handling have improved markedly in recent years, enabling greater sensitivity and better signal-to-noise ratios, thereby facilitating the detection of glycans at much higher masses than could be achieved in the past. The latter is especially important for the characterization of the biologically important class of N-glycans that carry polylactosaminoglycan chains. Such advances in data acquisition heighten the need for informatics tools to assist in glycan structure assignment. Here, utilizing mouse lung tissue as a model system, we present evidence of polylactosaminoglycan-containing N-glycans with permethylated molecular weights exceeding 13 kDa. We show that antennae branching patterns and lengths can be successfully determined at these high masses via MS/MS experiments, even when MS ion counts are very low. We also describe the development and application of a matched filtering algorithm for assisting high-molecular-weight glycan detection and structure assignment.


Precision Cardio-Oncology.
Modern oncologic therapies and care have resulted in a growing population of cancer survivors with comorbid, chronic health conditions. As an example, many survivors have an increased risk of cardiovascular complications secondary to cardiotoxic systemic and radiation therapies. In response, the field of cardio-oncology has emerged as an integral component of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, as current clinical management of cancer therapy-related cardiovascular disease remains limited by a lack of phenotypic data, implementation of precision medicine approaches has become a focal point for deep phenotyping strategies. In particular, -omics approaches (a field of study in biology ending in -omic, such as genomics, proteomics, or metabolomics) have shown enormous potential in identifying sensitive biomarkers of cardiovascular disease, applying sophisticated, pattern-revealing technologies to growing databases of biologic molecules. Moreover, the use of -omics to inform radiologic strategies may add a dimension to future clinical practices. In this review, we present a paradigm for a precision medicine approach to the care of cardiotoxin-exposed cancer patients. We discuss the role of current imaging techniques; demonstrate how -omics can advance our understanding of disease phenotypes; and describe how molecular imaging can be integrated to personalize surveillance and therapeutics, ultimately reducing cardiovascular morbidity and mortality in cancer patients and survivors.


Gonadal function in men with the Martin-Bell (fragile-X) syndrome.
We evaluated testicular function in 15 men with the Martin-Bell (fragile-X) mental retardation syndrome. Macro-orchidism was present in all subjects. Their mean serum LH and FSH levels and plasma testosterone and dihydrotestosterone levels were normal. The mean plasma levels of androstenedione, 17-hydroxyprogesterone, and progesterone were slightly elevated above the normal range, whereas the plasma levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate were normal. The response in the levels of plasma testosterone following a 5 day period of hCG stimulation was normal in 8 subjects and there was no abnormal accumulation of androgen precursors. The level of 5 alpha-reductase activity and androgen receptor binding was normal in genital skin fibroblasts derived from 3 of these patients. The response of gonadotropin secretion to GnRH stimulation was normal in the 8 men who were tested. Therefore, our data are consistent with the hypothesis that testicular enlargement in men with the Martin-Bell syndrome is not mediated by hormonal factors.


Spatial disorientation: decades of pilot fatalities.
Spatial disorientation (SD) has been a contributing factor in aviation mishaps for decades and efforts to mitigate SD have not been proportionate to the danger it poses to pilots. We argue that SD contributes to nearly 33% of all mishaps with a fatality rate of almost 100%. However, SD has not garnered the respect and awareness it requires from leadership and pilots because of historically inaccurate reporting within accident investigations and under-reporting of SD data in research. Over 30 research studies and 10 mishap case studies are presented to portray SD's role in aviation accidents since 1913. Research and training are recommended to improve pilot respect and awareness for SD-inducing scenarios that would include pilot recognition and successful recovery using SD-specific simulators. Consequently, funding is needed to further SD research, to fund SD training, as well as amend the current mishap investigation process to better articulate SD contributions in aviation accidents.


Clinical courses of hypochondriac-cenesthopathic symptoms in schizophrenia.
The systematic detailed clinical studies regarding bodily complaints in schizophrenics are relatively few. This paper focuses on the longitudinal courses of hypochondriac-cenesthopathic (H-C) symptoms in schizophrenia. From a group of 183 subjects meeting DSM-III-R criteria for schizophrenia, who were observed for at least 5 years, 81 patients with H-C symptoms were selected. The pattern of the appearance of their H-C symptoms was investigated. There was a near equality in the incidence of acute type and chronic type H-C symptoms. This was also the case for the early and tardive types. On the other hand, the complex type was more frequent than the simple type. When the H-C symptoms occurred in the acute stage, there existed accompanying symptoms as a rule. Among the six clinical courses (subtypes) of H-C symptoms, the most frequent was the acute-complex-early type, the least frequent was the chronic-simple-early type.


Masculine ideology, norms, and HIV prevention among young Black men.
This study examines the relationship between masculine ideology, adherence to norms, and HIV prevention among young Black heterosexual and gay men on the campus of a historically Black college/university. The data from four focus groups and nine individual interviews (N = 35) were aggregated and two recurring themes emerged: sexual communication, and mate availability. Additional themes related to HIV prevention were stigma, protection, and testing. The importance of investigating masculinity with young men is highlighted and implications for professionals working with college students to prevent the transmission of HIV are included.


[Dental fluorosis prevalence in Mexican localities of 27 states and the D.F.: six years after the publication of the Salt Fluoridation Mexican Official Regulation].
To identify the prevalence and severity of dental fluorosis in communities located in 28 states of Mexico. The National Dental Caries Survey 2001 (NDCS2001) data base was analyzed. The information of 26,893 students, ages 12 and 15 years old, of 27 states and the Federal District was examined. Dean's dental fluorosis index was applied by standardized examiners. The fluorosis prevalence and the Community Fluorosis Index (FCI) were calculated. The fluorosis prevalence was 27.9% (95% CI 24.4, 28.5). A statistical significance difference in the fluorosis prevalence was observed among the states studied (p < 0.0001). The lowest prevalence was detected in Morelos (3.2%) and the highest in Durango (88.8%). In 18 (64.3%) of the states included more than 90% of the participants showed very mild or lower levels of the dental fluorosis index. A low level of the FCI was found in the localities belonging to 19 (67.9%) of the states studied (FCI < 0.4). The lowest FCI was found in Colima, Yucatán and Morelos. The highest FCI were found in Durango, Zacatecas, Aguascalientes and San Luis Potosí (1 ≤ ICF). This information indicates that in these states dental fluorosis is a public health problem. Two-thirds of the states had localities with low prevalence of dental fluorosis; however, approximately, one-third of the states investigated the fluorosis levels showed the need of a reduction in fluoride exposure among the young population.


Pharmacology of Parkinson's disease.
The approach to treatment of Parkinson's disease depends on the severity of symptoms at presentation and the response to previous therapy. The pharmacotherapy of Parkinson's disease is discussed with respect to management of cardinal symptoms, management of associated features, and future directions for therapy.


Moderate-to-heavy alcohol intake is associated with differences in synchronization of brain activity during rest and mental rehearsal.
In alcohol-dependent individuals, synchronization of brain activity is different from that in non-alcohol-dependent individuals as reflected by EEG differences at alpha and beta frequencies (8-30 Hz). These EEG differences may not only be related to long-term alcohol intake but also to genetic factors that are associated with alcohol dependence. Thus, it is not known what the pure effect of long-term alcohol intake on synchronization of brain activity is. Therefore, we investigated whether EEG synchronization differs between light (0.5-6 drinks per week), moderate (7-20 drinks per week), and heavy (21-53 drinks per week) drinkers. All participants (49 males and 47 females) were free of a personal and family history of alcohol dependence. Eyes-closed EEG was recorded at rest and during mental rehearsal of pictures. EEG synchronization was determined by computing Synchronization Likelihood for six frequency bands (0.5-4 Hz, 4-8 Hz, 8-12 Hz, 12-20 Hz, 20-30 Hz, 30-45 Hz). Both male and female heavy drinkers displayed a loss of lateralization in alpha (8-12 Hz) and slow-beta (12-20 Hz) synchronization. In addition, moderately and heavily drinking males had lower fast-beta (20-30 Hz) synchronization than lightly drinking males. It is concluded that both male and female drinkers who drink 21 alcoholic drinks per week or more have impaired synchronization of brain activity during rest and mental rehearsal at alpha and beta frequencies as compared to individuals who drink less. As individuals with a personal or family history of alcohol dependence were excluded, the confounding effects of genetic factors related to alcohol dependence on synchronization of brain activity were minimized.


Preparation of bioactive and surface functional oligomannosyl neoglycoprotein using extracellular pH-sensitive glycosylation of mutant lysozyme having N-linked signal sequence in yeast.
Bioactive oligomannosyl lysozyme with improved surface functionalities was successfully prepared by using an extracellular pH-sensitive glycosylation system for heterogeneous protein in yeast cell. A recombinant Saccharomyces cerevisiae carrying a mutant lysozyme gene encoding the signal sequence of an N-linked glycosylation site at position 49 was cultivated in various pH conditions to investigate the effects of extracellular pH on the glycosylation patterns and the expression of the protein. A large polymannose (Man(310)GlcNAc(2)) chain-linked lysozyme was predominantly expressed accompanied by small amounts of a core-type oligomannose chain (Man(14)GlcNAc(2))-linked lysozyme in the yeast medium where the extracellular pH was kept at 3.5 or above, while an oligomannose chain lysozyme was preferentially expressed in the yeast medium where the pH was less than 3. The lytic activities of the oligomannosyl and the polymannosyl lysozymes were found to be 70.4 and 5.1%, respectively, of the wild-type lysozyme when Micrococcus lysodeikticus cells were used as the substrate. The enzymatic activity of the oligomannosyl lysozyme was totally conserved for the glycolysis assay with a soluble substrate, glycol chitin, whereas that of the polymannosyl lysozyme was not. After heating the sample up to 95 degrees C at pH 7.0 where no visible protein coagulation was observed, thermostability of the enzymatic activity of the oligomannosyl lysozyme was drastically improved with more than 60% of residual lytic activity. Emulsifying properties of the protein also were highly improved by the oligomannosylation, in which the emulsifying activity was 3.2 times higher than that of the wild-type protein. Corresponding to the increase of the surface functionalities, the surface tension of the oligomannosyl protein exhibited a significantly (p < 0.05) lower value compared to that of the wild-type. By using the lower pH medium at 3.0, it was revealed that a substantial amount (0.31 mg/L) of the oligomannosyl lysozyme was successfully obtained in the culture medium. Therefore, the extracellular pH-sensitive glycosylation system can be used to obtain bioactive and surface functional neoglycoproteins.


A ratiometric imaging method for mapping ion flux densities.
A heterogeneous distribution of ion channels on the cell surface is a prerequisite for several cellular functions. Thus, there has been considerable interest in methods allowing the mapping of ion channel distributions. Here we report on a novel ratiometric imaging technique appropriate to measure spatially resolved ion flux signals by using ion sensitive dyes. However, given that certain relevant cell properties like the surface to volume ratio may exhibit significant spatial heterogeneities, the local influx signal cannot be interpreted as a measure of the local open channel concentration or flux density. To overcome this problem, we suggest an internal normalization procedure, which, in analogy to, but clearly distinct from, well-established ratioing techniques, eliminates effects which would otherwise obscure the desired result. Ratioing is performed on flux signals from a given cell, triggered by two different, subsequent stimuli. If the two stimuli address different ion channels, the flux density distribution caused by two channel types can be determined relative to each other. In cases where one of the stimuli triggers a spatially homogeneous flux signal, ratioing yields an ion flux density map for a given channel type. Thus distribution patterns of ion channels active during a given stimulus may be derived.


Confidentiality and the rape victim: ethical intent versus political reality.
... The clinician who works with the victim of rape, either in hospital emergency departments, community mental health settings, college environments, or private practice, should consider ways that would effect the many overdue reforms for which this specialty cries out. The need for sensitivity in the area of record keeping, particularly as to how such records might be used, can hardly be debated. Beyond this, there is the role of patient advocate, calling upon the clinician to serve an educative function with reference to the members of his profession and of the larger society. Confidentiality of patient records can be preserved only to the extent that the cultural context in which they exist values such privacy.


Maternal morbidity and mortality associated with delivery after intrauterine fetal death.
To determine the maternal morbidity and mortality associated with delivery after intrauterine fetal death (IUFD) and to find out the place of fetal destructive procedures and cesarean section. Cross-sectional study. Labour Room, Nishtar Hospital, Multan from January to December 2003. All women were included in the present study who presented before the onset of labour pains, after intrauterine fetal death at 26 weeks or onward with singleton pregnancy. Assessment of maternal demographic characteristics, gestational age at fetal demise, delivery-IUFD interval, mode of delivery; vaginal with or without fetal destructive procedures/cesarean section and maternal complications were the main outcome measures. There were 1834 live birth and 63 deliveries with intrauterine fetal death. Mode of delivery was vaginal in 87.4% and cesarean section in 12.6% of the cases. Twelve (21%) of the vaginal deliveries were complicated by lower urogenital tract injuries in certain cases, whereas 75% (6/8) of patients delivered by cesarean section developed major postoperative complications like postpartum haemorrhage, shock, endometritis, peritonitis and wound dehiscence. No maternal death was identified. Rate of delivery with intrauterine fetal death was 34.3/1000 live-birth deliveries. Maternal morbidity like perineal tear, urinary tract infection, menstrual disorder and even secondary infertility may follow after vaginal mode of delivery by forceps and destructive procedures. The frequency and severity of complications after cesarean delivery are quite higher and may rarely lead to even maternal death.


Therapeutic value of glycosaminoglycans in cancer.
Glycosaminoglycans are unbranched polysaccharides composed of repeating units of alternating uronic acids and amino sugars. Most glycosaminoglycans are covalently attached to core proteins to form proteoglycans. Posttranslational modifications result in specific motifs that bind to a large variety of ligands, thus regulating growth factor signaling, cellular behavior, inflammation, angiogenesis, and the proteolytic environment. Dysregulated expression of glycosaminoglycans is present in cancer and reported to correlate with clinical prognosis in several malignant neoplasms. Recent knowledge on the biological roles of these molecules in cancer biology, tumor angiogenesis, and metastasis has promoted the development of drugs targeting them. Pharmaceutical approaches include the use of chemically modified heparins and glycosaminoglycans with defined structures, combination of inhibitors of glycosaminoglycan biosynthesis and polyamine depletion, and biologically active glycosaminoglycan-binding peptides. In addition, glycosaminoglycans are used as tumor-specific delivery and targeting vehicles for toxins and chemotherapeutics. Encouraging results in animal studies and clinical trials show the clinical relevance of glycosaminoglycan-based drugs and the use of glycosaminoglycans as therapeutic targets.


Dysbiotic events in gut microbiota: impact on human health.
The human body is colonized by a large number of microbes coexisting peacefully with their host. The most colonized site is the gastrointestinal tract (GIT). More than 70% of all the microbes in the human body are in the colon. The microorganism population is 10 times larger of the total number of our somatic and germ cells. Two bacterial phyla, accounting for more than 90% of the bacterial cells, dominate the healthy adult intestine: Firmicutes and Bacteroidetes. Considerable variability in the microbiota compositions between people is found when we look at the taxonomic level of species, and strains within species. It is possible to assert that the human microbiota could be compared to a fingerprint. The microbiota acts as a barrier from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis), has been linked to important human diseases such as inflammation related disorders. The present review summarizes our knowledge on the gut microbiota in a healthy context, and examines intestinal dysbiosis in inflammatory bowel disease (IBD) patients; the most frequently reported disease proven to be associated with changes in the gut microbiota.


Fatal case of Naegleria fowleri meningo-encephalitis in an infant: case report.
Primary amoebic meningo-encephalitis (PAM) is extremely rare and is caused by Naegleria fowleri. It is ?commonly seen in older children who swim in water contaminated with Naegleria species. It is very rare to contract the illness by any other means. We report a case of PAM in an infant aged 6 months. To the best of our knowledge, only one other case of PAM in an infant has been reported from India. A high index of suspicion is required in infants who manifest similarly to pyogenic meningitis but whose CSF shows no bacterial organisms so that a wet mount of a CSF sample can be done for early detection of Naegleria fowleri infection and appropriate intervention.


Salivary and fecal microbiota: potential new biomarkers for early screening of colorectal polyps.
Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls. In this case-control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC). In comparison to the HC group, the CP group's microbial diversity increased in saliva and decreased in feces (p < 0.05), but there was no significantly difference in microbiota richness (p > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified Porphyromonas gingivalis, Fusobacterium nucleatum, Leptotrichia wadei, Prevotella intermedia, and Megasphaera micronuciformis as the major contributors to the salivary microbiota, and Ruminococcus gnavus, Bacteroides ovatus, Parabacteroides distasonis, Citrobacter freundii, and Clostridium symbiosum to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined. The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.


Surface structures, haemagglutination and cell surface hydrophobicity of Bacteroides fragilis strains.
Nineteen strains of Bacteroides fragilis were examined by negative staining for surface structures. One strain (ATCC 23745) possessed peritrichous fibrils, 16 strains carried peritrichous fimbriae and two strains carried no surface structures. The fimbriae had a diameter of 2.1 +/- 0.25 nm and appeared to be 'curly'. Only a small proportion (4 to 41%, depending on the strain) of cells in a population carried fimbriae or fibrils. Strain A312 Showed phase variation of fimbriae as expression of fimbriae was repressed at 20 degrees C and in early exponential phase at 37 degrees C. The fibrils on strain ATCC 23745 did not exhibit phase variation in response to changes in incubation temperature, growth phase or growth in two different media. Capsules were demonstrated by the Indian ink method on 18 of the 19 strains, varying in size from strain to strain and within the same population. Cultures often contained both capsulate and noncapsulate cells. All strains possessed an electron dense ruthenium red staining layer between 7.9 and 23.9 nm in width attached to the outer membrane. Cell surface hydrophobicity quantified by the hexadecane partition assay gave low values ranging from 6.6 to 52.1%. Only a few strains were able to haemagglutinate and these were only weakly active. There was no correlation between cell surface hydrophobicity, haemagglutinating activity and surface structures.


Identification of Six Autophagy-Related-lncRNA Prognostic Biomarkers in Uveal Melanoma.
Currently, no autophagy-related long noncoding RNA (lncRNA) has been reported to predict the prognosis of uveal melanoma patients. Our study screened for autophagy-related lncRNAs in 80 samples downloaded from The Cancer Genome Atlas (TCGA) database through lncRNA-mRNA coexpression. We used univariate Cox to further filter the lncRNAs. Multivariate Cox regression and LASSO regression were applied to construct an autophagy-associated lncRNA predictive model and calculate the risk score. Clinical risk factors were validated using Cox regression to determine whether they were independent prognostic indicators. Functional enrichment was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The model was built with six predictive autophagy-associated lncRNAs and clustered uveal melanoma patients into high- and low-risk groups. The risk score of our model was a significant independent prognostic factor (hazard ratio = 1.0; p < 0.001). Moreover, these six lncRNAs were significantly concentrated in the biological pathways of cytoplasmic component recycling, energy metabolism, and apoptosis. Thus, the six autophagy-associated lncRNAs are potential molecular biomarkers and treatment targets for uveal melanoma patients.


Renal clearance of theophylline in man.
The renal clearance of theophylline was determined in 12 experiments with six healthy human adult volunteers and was found to decrease from 8.50+/-2.20 to 276.+/-1.13 ml/min/m2 during 8 hours after oral administration of a single dose of theophylline, 200 mg/m2. There was a strong and highly statistically significant positive correlation between the renal clearance of theophylline and the urine flow rate for each subject, but there was no consistent correlation between renal clearance and plasma concentrations of theophylline.


Increased complications and morbidity in children with hemophagocytic lymphohistiocytosis undergoing hematopoietic stem cell transplantation.
Hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with primary hemophagocytic lymphohistiocytosis (HLH) and for patients with secondary HLH who fail to respond to therapy. Retrospective study of HSCT for HLH with focus on complications and outcome. Eighteen children (10 males), with a median age of 1.2 yr (5 months-16 yr), received HSCT for HLH. Fourteen children had primary HLH. Four children underwent transplant while not in remission. Sixteen received myeloablative and two received reduced intensity conditioning regimen. A high incidence of complications was found: 13 (72%) children had 22 episodes of culture-proven infections; seven (38%) had hepatic veno-occlusive disease; nine (50%) developed respiratory complications; and nine (50%) required intensive care unit admission. Eight children had acute graft-versus-host disease (GVHD), and three developed chronic GVHD. Three patients died from multi-organ failure before day +100, and another patient died from pulmonary hemorrhage after day 100. Three patients failed to engraft (two developed recurrent HLH and died from complications after a second HSCT). Three of four children not in remission at the time of transplantation died. Actuarial survival at three yr was 61%. HSCT for HLH carries significant risks with high infection, organ dysfunction, and ICU admissions rates.


Activation of mitogen-activated protein kinase pathways by Mycoplasma fermentans membrane lipoproteins in murine macrophages: involvement in cytokine synthesis.
Stimulation of monocytes and resident macrophages by mycoplasmas induces production of numerous cytokines. We have previously reported that membrane lipoproteins derived from Mycoplasma fermentans are responsible for the induction of proinflammatory cytokines by monocytic cells and that triggering protein tyrosine kinase activation is an essential requirement for this biologic effect. In the present study, we have investigated the effect of M. fermentans-derived membrane lipoproteins (LAMPf) on mitogen-activated protein kinase (MAPK) cascades in the murine macrophage cell line RAW 264.7 and have analyzed the contribution of these pathways to the cytokine induction mediated by this agent. Treatment of murine macrophages with LAMPf resulted in significant activation of MAPK family members extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and p38. Unlike LPS, these effects were demonstrated to be independent of the presence of serum. The activation of MAPKs paralleled the tyrosine kinase activation and peaked at 30 min after stimulation. The specific p38 inhibitor SB203580 abrogated the mycoplasma-induced IL-6, IL-1beta, and TNF-alpha synthesis. The selective MAPK/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD-98059 blocked both IL-1beta and TNF-alpha but not IL-6 production by RAW 264.7 cells in response to LAMPf. Additionally, transfection of murine macrophages with a JNK dominant negative mutant significantly reduced only IL-6 production. These data underscore the role of MAPKs as signal transduction molecules controlling the expression of cytokines upon mycoplasma stimulation.


Rare-earth-doped biological composites as in vivo shortwave infrared reporters.
The extension of in vivo optical imaging for disease screening and image-guided surgical interventions requires brightly emitting, tissue-specific materials that optically transmit through living tissue and can be imaged with portable systems that display data in real-time. Recent work suggests that a new window across the short-wavelength infrared region can improve in vivo imaging sensitivity over near infrared light. Here we report on the first evidence of multispectral, real-time short-wavelength infrared imaging offering anatomical resolution using brightly emitting rare-earth nanomaterials and demonstrate their applicability toward disease-targeted imaging. Inorganic-protein nanocomposites of rare-earth nanomaterials with human serum albumin facilitated systemic biodistribution of the rare-earth nanomaterials resulting in the increased accumulation and retention in tumour tissue that was visualized by the localized enhancement of infrared signal intensity. Our findings lay the groundwork for a new generation of versatile, biomedical nanomaterials that can advance disease monitoring based on a pioneering infrared imaging technique.


MDMA: a social drug in a social context.
The drug ±3,4-methylenedioxymethamphetamine (MDMA, "ecstasy," "molly") is thought to produce prosocial effects and enhance social interaction. However, in most laboratory studies to date, the participants have been tested under nonsocial conditions, which may not simulate the effects the drug produces in more naturalistic social settings. Healthy experienced MDMA users participated in three laboratory sessions in which they received MDMA (0.5 or 1.0 mg/kg or placebo, double blind). They were randomly assigned to one of three social conditions, in which they were tested alone (solitary (SOL); N = 10), in the presence of a research assistant (research assistant present (RAP); N = 11) or in the presence of another participant who also received the drug (other participant present (OPP); N = 11). As expected, MDMA increased heart rate and blood pressure and produced positive subjective effects in all the three groups. It also increased ratings of attractiveness of another person and increased social interaction in RAP and OPP. The social context affected certain responses to the drug. The effects of MDMA were greater in the OPP condition, compared to the SOL or RAP conditions, on measures of "feel drug," "dizzy," and on cardiovascular. But responses to the drug on other measures, including social behavior, did not differ across the conditions. These findings provide some support for the idea that drugs produce greater effects when they are used in the presence of other drug users. However, the influence of the social context was modest, and it remains to be determined whether other variables related to social context would substantially alter the effects of MDMA or other drugs.


Effect of bilateral blockade of the pharyngeal branch of the vagus nerve on soft palate function in horses.
To determine the effect of bilateral blockade of the pharyngeal branch of the vagus nerve on soft palate function in horses. 5 Standardbreds. Peak tracheal inspiratory and expiratory pressures and airflow were measured while horses exercised at the speeds corresponding to 75 and 100% of the speed that resulted in maximal heart rate, with and without pharyngeal branch of the vagus nerve blockade. Respiratory frequency-to-stride frequency coupling ratio was measured by correlating foot fall measurements with respiratory frequency. The pharyngeal branch of the vagus nerve was blocked bilaterally as the nerve coursed through the auditory tube diverticulum (guttural pouch) across the longus capitus muscle. Persistent, reversible dorsal displacement of the soft palate (DDSP) occurred in all horses after nerve blockade, and lasted from 1 to 3 hours; normal nasopharyngeal function returned within 3 hours. Compared with control values, peak expiratory tracheal pressure increased (P = 0.001), expiratory impedance increased (P = 0.007), and minute ventilation decreased (P = 0.04). Respiratory frequency-to-stride frequency coupling ratio decreased (P = 0.009) so that horses took 1 breath/stride without the nerve block and, approximately, 1 breath/2 strides with the block. DDSP creates flow-limiting expiratory obstruction and may be caused by neuromuscular dysfunction involving the pharyngeal branch of the vagus nerve. It may alter performance by causing expiratory obstruction and by altering breathing strategy in horses. A repeatable, reversible model of DDSP exists that allows further study of the disease. Dysfunction of the neuromuscular group, pharyngeal branch of the vagus nerve and palatinus and palatopharyngeus muscles, may be implicated in the pathogenesis of clinical DDSP.


Aplastic anemia: analysis of stromal cell function in long-term marrow cultures.
Marrow samples from 89 patients with aplastic anemia (AA) were evaluated for their ability to grow stromal layers in standard long-term marrow cultures (LTMCs). Results were highly variable: 6.8% failed to grow any stromal cells (group I); 42.5% either failed to grow to confluency or appeared to have a decreased number of adipocytes and/or macrophages (group II); and 52.8% appeared as normal confluent cultures with fibroblasts, adipocytes, and macrophages (group III). Analyses of patient data suggested that group I patients had a longer disease duration and poorer survival (P = .07). Enzyme-linked immunosorbent assay analysis of cytokine production was performed on 20 of the normal-appearing AA LTMCs and 12 LTMCs established from normal donors. Significant differences between the AA and control groups were apparent for macrophage inflammatory protein-1 alpha (MIP-1 alpha), interleukin-1 receptor antagonist (IL-1ra), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and leukemia-inhibitory factor (LIF). The most dramatic differences observed were elevated levels of MIP-1 alpha and GM-CSF and decreased levels of IL-1ra, particularly after IL-1 alpha stimulation. In contrast, IL-1 alpha stimulation of AA LTMCs produced levels of IL-6, LIF, and G-CSF comparable with those of controls. These data suggest that defects exist within the microenvironment of some AA marrows. Whether the majority of these defects are the cause or consequence of aplasia is not clear. However, we speculate that some of these abnormalities may contribute to the maintenance of the hypoplastic state and, in extreme cases, prevent engraftment of donor marrow.


[Ablation by radiofrequency in the treatment of atrial arrhythmia].
Atrial arrhythmias resistant to medical therapy are still a common indication for ablation of the normal atrioventricular conduction pathway (Tawara node and His Bundle). However, the development of catheter techniques of intra-atrial ablation to destroy arrhythmogenic myocardial zones enables radical cure of the arrhythmias with the respect of the nodo-hisian pathway. With respect to common flutter, a number of series, including our own, show a 50 to 75% long-term success rate. We believe that a very high success rate in the ablation of flutter will probably be achieved in a reproducible manner but this will require a more accurate understanding of the tachycardia circuit and technological developments allowing controlled radio-frequency destruction of bigger atrial myocardial zone. Experience of radio-frequency ablation atrial of atrial extrasystoles is more limited than that of flutter and there are fewer published series. Globally, catheter ablation of atrial tachycardia remains a more difficult and a less well codified procedure than that of accessory pathways or of intra-nodal reentry. Radio-frequency ablation in this indication is not without danger in view of the thinness of the atrial wall. We believe that radio-frequency catheter ablation for atrial arrhythmias should, for the moment, be reserved for centres specialised in the techniques of electro-physiological investigation and ablation.


Identification of an isoschizomer of the HhaI DNA methyltransferase in Mycoplasma arthritidis.
The genome of Mycoplasma arthritidis strain 158 has modified cytosine residues at AGCT sequences that render the DNA resistant to digestion with the AluI restriction endonuclease. The DNA methyltransferase responsible for the base modification has previously been designated MarI. From the complete genome sequence of M. arthritidis, we identify Marth_orf138 as a candidate marI gene. Marth_orf138 was cloned in Escherichia coli and its TGA codons converted to TGG. DNA isolated from E. coli cells expressing the modified Marth_orf138 gene was degraded by the AluI nuclease, indicating that Marth_orf138 does not code for MarI. However, the DNA from E. coli was found to have acquired resistance to the restriction endonuclease HhaI. Genomic DNA from M. arthritidis was also found to be resistant to HhaI (recognizes GCGC). The M. arthritidis isoschizomer of the HhaI DNA methyltransferase, coded by Marth_orf138, is designated MarII. Transformation of M. arthritidis was not significantly affected by modification of plasmid at HhaI sites, indicating that the mycoplasma lacks a restriction endonuclease that recognizes GCGC sites.


Penicillin biosynthesis: energy requirement for tripeptide precursor formation by delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Acremonium chrysogenum.
In nonribosomal peptide formation by multifunctional enzymes, peptide synthetases catalyze the activation and directed condensation of amino acids. The peptide synthetase involved in penicillin biosynthesis (ACV synthetase) forms the tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine from the respective L-amino acids and ATP. So far, the energy requirements for the nonribosomal process have not been clearly established. For ACV synthetase we show that ATP consumption depends on the reaction conditions employed. By simultaneously estimating peptide and AMP production by employing fluorescence detection and UV spectroscopy, respectively, we have determined the energy consumption with high accuracy. Under unfavorable reaction conditions more than 20 mol of ATP are consumed/mol of tripeptide formed, while optimal conditions permit the expected energy requirement of one ATP for each carboxyl group activation, corresponding to three ATP for tripeptide formation. The third ATP is required for the activation of L-valine to maintain the valyl-thioester stage for epimerization and peptide bond formation, and this high-energy bond is sacrificed by hydrolytic removal of the product. No extra energy is required for the directed transport in peptide elongation. Additional energy consumed has been traced to hydrolytic loss of activated intermediates, as has been shown by the analysis of incomplete reaction mixtures.


Is there an association between maternal carbamazepine use during pregnancy and eye malformations in the child?
To check for an association between carbamazepine (CBZ) use by the mother during pregnancy and congenital eye malformations (i.e., anophthalmia, microphthalmia, and coloboma) in the child, as suggested by Sutcliffe et al. (1998), who reported four cases. We checked all the cases with these eye malformations for CBZ use by the mother in the EUROCAT Northern Netherlands dataset, which registers infants with congenital malformations and records possible teratogenic exposures (including medication taken by the mother). We also reviewed 13 studies in the literature. The EUROCAT dataset recorded 77 cases of anophthalmia, microphthalmia, or coloboma, but none with prenatal exposure to CBZ. Prenatal CBZ exposure was recorded in seven other cases without congenital eye malformation. Large studies in the literature on the teratogenic effects of CBZ (and other antiepileptic drugs), including data from the MADRE database, revealed no association between these congenital eye malformations and prenatal CBZ exposure. One case reported bilateral anophthalmia and other congenital anomalies after prenatal exposure to CBZ in combination with vigabatrin and dexamethasone. Our data do not support Sutcliffe's suggestion that prenatal CBZ exposure may result in congenital eye malformations. However, despite the large population represented, both the low birth prevalence of these congenital eye malformations and the low prevalence of CBZ exposure during pregnancy make it difficult to exclude an increased relative risk. The many large prospective and retrospective studies in the literature seem to agree with our findings, although there is still uncertainty about the teratogenic effect of CBZ in polytherapy.


Evaluation of a bioglass-coated Al2O3 total hip prosthesis in sheep.
A bioglass-coated fully dense alumina total hip was evaluated in sheep without using polymer bone "cement." After 3 months following surgery, both the acetabular cup and femoral stem component were firmly attached to bone. Histologic and radiographic analysis of the bone-implant interface showed regions of woven and even lamellar bone formation where high load transmission occurred. In regions of low loading or poor fit, a pseudosynovial fibrous lining was present.


Reduced Contraction of Blood Clots in Venous Thromboembolism Is a Potential Thrombogenic and Embologenic Mechanism.
Contraction (retraction) of the blood clot is a part of the clotting process driven by activated platelets attached to fibrin that can potentially modulate the obstructiveness and integrity of thrombi. The aim of this work was to reveal the pathogenic importance of contraction of clots and thrombi in venous thromboembolism (VTE). We investigated the kinetics of clot contraction in the blood of 55 patients with VTE. In addition, we studied the ultrastructure of ex vivo venous thrombi as well as the morphology and functionality of isolated platelets. Thrombi from VTE patients contained compressed polyhedral erythrocytes, a marker for clot contraction in vivo. The extent and rate of contraction were reduced by twofold in clots from the blood of VTE patients compared with healthy controls. The contraction of clots from the blood of patients with pulmonary embolism was significantly impaired compared with that of those with isolated venous thrombosis, suggesting that less compacted thrombi are prone to embolization. The reduced ability of clots to contract correlated with continuous platelet activation followed by their partial refractoriness. Morphologically, 75% of platelets from VTE patients were spontaneously activated (with filopodia) compared with only 21% from healthy controls. At the same time, platelets from VTE patients showed a 1.4-fold reduction in activation markers expressed in response to chemical activation when compared with healthy individuals. The results obtained suggest that the impaired contraction of thrombi is an underappreciated pathogenic mechanism in VTE that may regulate the obstructiveness and embologenicity of venous thrombi.


Local unitary equivalence of multipartite pure states.
Necessary and sufficient conditions for the equivalence of arbitrary n-qubit pure quantum states under local unitary (LU) operations are derived. First, an easily computable standard form for multipartite states is introduced. Two generic states are shown to be LU equivalent iff their standard forms coincide. The LU-equivalence problem for nongeneric states is solved by presenting a systematic method to determine the LU operators (if they exist) which interconvert the two states.


Off-axis four-mirror telescope with a wide field of view and a long focal length using double integrated mirrors.
An off-axis four-mirror optical system has the advantages of a wide field of view (FOV) and a small telephoto ratio. However, it will bring difficulties in assembly and detection. Here we report an off-axis four-mirror free-form telescope with a long focal length and a wide field of view based on two integration mirrors. The initial structure of a coaxial four-mirror optical system is established based on the Seidel aberration theory. A Zernike Fringe free-form surface is introduced to correct aberrations. By gradually increasing the entrance pupil diameter and the FOV, we finally obtain an off-axis four-mirror telescope with a FOV of 0.4∘×20∘, an F-number of 11.5, a long focal length of 2000 mm, and a volume of 360×400×600m m 3. In addition, four mirrors remain coaxially aligned, remarkably facilitating detection and adjustment. The proposed off-axis four-mirror telescope, with double integration mirrors, holds great potential for application in aerospace remote sensing observations.


De facto diagnosis specialties: Recognition and discovery.
A medical specialty indicates the skills needed by health care providers to conduct key procedures or make critical judgments. However, documentation about specialties may be lacking or inaccurately specified in a health care institution. Thus, we propose to leverage diagnosis histories to recognize medical specialties that exist in practice. Such specialties that are highly recognizable through diagnosis histories are de facto diagnosis specialties. We aim to recognize de facto diagnosis specialties that are listed in the Health Care Provider Taxonomy Code Set (HPTCS) and discover those that are unlisted. First, to recognize the former, we use similarity and supervised learning models. Next, to discover de facto diagnosis specialties unlisted in the HPTCS, we introduce a general discovery-evaluation framework. In this framework, we use a semi-supervised learning model and an unsupervised learning model, from which the discovered specialties are subsequently evaluated by the similarity and supervised learning models used in recognition. To illustrate the potential for these approaches, we collect 2 data sets of 1 year of diagnosis histories from a large academic medical center: One is a subset of the other except for additional information useful for network analysis. The results indicate that 12 core de facto diagnosis specialties listed in the HPTCS are highly recognizable. Additionally, the semi-supervised learning model discovers a specialty for breast cancer on the smaller data set based on network analysis, while the unsupervised learning model confirms this discovery and suggests an additional specialty for Obesity on the larger data set. The potential correctness of these 2 specialties is reinforced by the evaluation results that they are highly recognizable by similarity and supervised learning models in comparison with 12 core de facto diagnosis specialties listed in the HPTCS.


The evolution of antifungal peptides in Drosophila.
An essential component of the immune system of animals is the production of antimicrobial peptides (AMPs). In vertebrates and termites the protein sequence of some AMPs evolves rapidly under positive selection, suggesting that they may be coevolving with pathogens. However, antibacterial peptides in Drosophila tend to be highly conserved. We have inferred the selection pressures acting on Drosophila antifungal peptides (drosomycins) from both the divergence of drosomycin genes within and between five species of Drosophila and polymorphism data from Drosophila simulans and D. melanogaster. In common with Drosophila antibacterial peptides, there is no evidence of adaptive protein evolution in any of the drosomycin genes, suggesting that they do not coevolve with pathogens. It is possible that this reflects a lack of specific fungal and bacterial parasites in Drosophila populations. The polymorphism data from both species differed from neutrality at one locus, but this was not associated with changes in the protein sequence. The synonymous site diversity was greater in D. simulans than in D. melanogaster, but the diversity both upstream of the genes and at nonsynonymous sites was similar. This can be explained if both upstream and nonsynonymous mutations are slightly deleterious and are removed more effectively from D. simulans due to its larger effective population size.


My week: Marc Armour.
Marc Armour, is a fourth-year vet student at the Royal Veterinary College. Now on rotations, he chose to spend a week doing EMS with the BVA's journals, which are published by BMJ. Here's how he got on.


Plasmon enhanced solar-to-fuel energy conversion.
Future generations of photoelectrodes for solar fuel generation must employ inexpensive, earth-abundant absorber materials in order to provide a large-scale source of clean energy. These materials tend to have poor electrical transport properties and exhibit carrier diffusion lengths which are significantly shorter than the absorption depth of light. As a result, many photoexcited carriers are generated too far from a reactive surface and recombine instead of participating in solar-to-fuel conversion. We demonstrate that plasmonic resonances in metallic nanostructures and multilayer interference effects can be engineered to strongly concentrate sunlight close to the electrode/liquid interface, precisely where the relevant reactions take place. On comparison of spectral features in the enhanced photocurrent spectra to full-field electromagnetic simulations, the contribution of surface plasmon excitations is verified. These results open the door to the optimization of a wide variety of photochemical processes by leveraging the rapid advances in the field of plasmonics.


In vivo effects of a single dose of norepinephrine and epinephrine on tissue respiration of hibernating and non-hibernating species of frogs.
In vivo effects of a single dose of norepinephrine (NE) and epinephrine (EP) were studied on the rate of tissue (liver and skeletal muscle) respiration in Rana limnocharis (hibernating Sp.) and Rana cyanophlyctis (non-hibernating Sp.) during winter and summer months after 10 and 30 min, 1, 6, 12 and 24 hr of administration. During winter both NE and EP induced significant increase in the rate of tissues respiration only after 30 min after their administration in both the species and the stimulatory effect lasted up to 6 hr. During summer, however, NE and EP stimulated respiratory rate of tissues comparatively after a shorter lag period (10 to 30 min) in R. limnocharis than that of R. cyanophlyctis (30 min to 6 hr). These findings seem to suggest that NE and EP can stimulate tissue respiration very quickly, and, therefore, might be suitable as emergency hormones for instant/faster stimulation of energy metabolism in amphibians.


Cancer cell death induced by the intracellular self-assembly of an enzyme-responsive supramolecular gelator.
We report cancer cell death initiated by the intracellular molecular self-assembly of a peptide lipid, which was derived from a gelator precursor. The gelator precursor was designed to form nanofibers via molecular self-assembly, after cleavage by a cancer-related enzyme (matrix metalloproteinase-7, MMP-7), leading to hydrogelation. The gelator precursor exhibited remarkable cytotoxicity to five different cancer cell lines, while the precursor exhibited low cytotoxicity to normal cells. Cancer cells secrete excessive amounts of MMP-7, which converted the precursor into a supramolecular gelator prior to its uptake by the cells. Once inside the cells, the supramolecular gelator formed a gel via molecular self-assembly, exerting vital stress on the cancer cells. The present study thus describes a new drug where molecular self-assembly acts as the mechanism of cytotoxicity.


Morphine and cocaine exert common chronic actions on tyrosine hydroxylase in dopaminergic brain reward regions.
We studied levels of tyrosine hydroxylase immunoreactivity and phosphorylation state in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in an effort to understand better the mechanisms by which these brain reward regions are influenced by opiates and cocaine. In the VTA, chronic, but not acute, administration of either morphine or cocaine increased levels of tyrosine hydroxylase immunoreactivity by 30-40%, with no change observed in the relative phosphorylation state of the enzyme. In the NAc, chronic, but not acute, morphine and cocaine treatments decreased the phosphorylation state of tyrosine hydroxylase, without a change in its total amount. In contrast, morphine and cocaine did not regulate tyrosine hydroxylase in the substantia nigra or caudate/putamen, brain regions generally not implicated in drug reward. Morphine and cocaine regulation of tyrosine hydroxylase could represent part of a common biochemical basis of morphine and cocaine addiction and craving.


The search for life on Mars.
Mars appears to have no life on its surface today. However, the presence of fluvial features provides evidence that liquid water was once present on the martian surface. By analogy with Earth, life may have originated on Mars early in its history, possibly during the end of the late heavy bombardment. Analysis of the one meteorite from Mars which dates to this early time appears to contain evidence of this early environment and possibly life. As the climate cooled and liquid water became unavailable, life would have eventually died out. The cold deserts of Antarctica provide a glimpse of what martian ecosystems might have been like as conditions worsened. The search for fossil evidence of past life on Mars may provide the first direct indication of life beyond Earth.


[Hepatocellular carcinoma without cirrhosis in a patient with nonalcoholic steatohepatitis].
All cases of hepatocellular carcinoma reported thus for in patients with nonalcoholic steatohepatitis have occurred on preexisting cirrhosis. We report the case of a 68-Year-old male patient with nonalcoholic steatohepatitis who developed hepatocellular carcinoma in the absence of cirrhosis. This observation suggests a possible relationship between nonalcoholic steatohepatitis and/or excess body weight, and hepatocellular carcinoma independent of cirrhosis. Further epidemiological studies are needed to evaluate the incidence of this association.


Nursing's Critical Role in Driving Toward Health Equity: One Organization's Experience.
In the last decade, there has been active discourse within nursing communities regarding healthcare disparities associated with racism. To address this critical problem, a multidisciplinary team at a pediatric healthcare setting identified 33 projects across 4 key drivers of health equity. The drivers of health equity include: 1) developing a diverse nursing workforce; 2) creating a nursing culture with a strong sense of belonging; 3) providing learning and growth opportunities; and 4) providing equitable nursing care. This article describes 1 organization's approach to addressing healthcare disparities associated with racism through a nursing program to address equity, diversity, inclusion, and antiracism.


Dispersive Micro-Solid Phase Extraction for Sensitive Determination of Methotrexate from Human Saliva Followed by Spectrophotometric Method.
For biological assessing of hospital personnel occupationally exposed to antineoplastic drugs, highly sensitive and accurate methods are required. Methotrexate (MTX) is an anticancer agent that is widely used in a variety of human cancers. For the first time, dispersive-micro solid phase extraction (D-µ-SPE) has been applied for determination of low levels of MTX in saliva samples. The method is based on rapid extraction of MTX using graphene oxide adsorbent. The sample preparation time is decreased by the fact that the adsorbent dispersed in the sample solution and extraction equilibrium can be reached very fast. This significant feature which obtained with this method is of key interest for routine trace laboratory analysis. The influence of different variables on D-µ-SPE was investigated. Under optimum conditions, the calibration graph was linear over the range of 10-1000 ng/ml. The relative standard deviations are better than 9.0%. The proposed method was successfully applied for the determination of MTX in patient samples.


Diversity and population dynamics of pests and predators in irrigated rice fields with treated and untreated pesticide.
The monitoring of rice pests and their predators in pesticide untreated and treated rice fields was conducted at the southern of Thailand. Twenty-two species in 15 families and 6 orders of rice pests were sampled from untreated rice field. For treated rice field, 22 species in 14 families and 5 orders of rice pest were collected. Regardless of treatment type, dominant species and individual number of rice pest varied to physiological stage of rice. Lepidopteran pests had highest infestation during the vegetative stage of rice growth, while hemipteran pests composed of hopper species (Hemipetra: Auchenorrhyncha) and heteropteran species (Hemiptera: Heteroptera) were dominant groups during the reproductive stage and grain formation and ripening stage of rice growth. In contrast, dominant species of predator did not change throughout rice growing season. There were 35 species in 25 families and seven orders and 40 species in 29 families and seven orders of predators collected from untreated and treated rice field, respectively. Major predators of both rice fields were Micraspis discolor (Fabricius) (Coleoptera: Coccinellidae), Tetragnatha sp. (Araneae: Tetragnathidae) and Agriocnemis pygmaea Rambur (Odonata: Agrionidae). The population dynamic of predators were not related with rice pest population in both treatments. However, the fluctuation of population pattern of rice pests in the untreated treatment were more distinctly synchronized with their predators than that of the treated treatment. There were no significant differences in the total number of rice pest and predator between two treatments at vegetative and reproductive stages of rice growth. Untreated rice field had a higher population number of predator and a lower population number of rice pest than that of treated rice field during grain formation and ripening stages. These results indicated the ago-ecosystem balance in rice fields could be produced through minimal pesticide application, in order to allow the natural balance between pests and their predators to be restored and maintained.


High Costs of Dialysis Transportation in the United States: Exploring Approaches to a More Cost-effective Delivery System.
Background: The costs of transporting end-stage renal disease (ESRD) patients to dialysis centers are high and growing rapidly. Research has suggested that substantial cost savings could be achieved if medically appropriate transport was made available and covered by Medicare. Objectives: To estimate US dialysis transportation costs from a purchaser's perspective, and to estimate cost savings that could be achieved if less expensive means of transport were utilized. Methods: Costs were estimated using an actuarial model. Travel distance estimates were calculated using GIS software from patient ZIP codes and dialysis facility addresses. Cost and utilization estimates were derived from fee schedules, government reports, transportation websites and peer-reviewed literature. Results: The estimated annual cost of dialysis transportation in the United States is $3.0 billion, half of which is for ambulances. Most other costs are due to transport via ambulettes, wheelchair vans and taxis. Approximately 5% of costs incurred are for private vehicle or public transportation use. If ambulance use dropped to 1% of trips from the current 5%, costs could be reduced by one-third. Conclusions: Decision-makers should consider policies to reduce ambulance use, while providing appropriate levels of care.


Differential Diagnosis of Popliteal Artery Entrapment Syndrome in Light of an Atypical Clinical Manifestation.
Popliteal artery entrapment syndrome (PAES) is a type of arterial obstruction seen in athletic and young patients with no cardiovascular risk factors. It is caused by aberrant anatomy affecting the position of the popliteal artery or gastrocnemius muscle or functional obstruction resulting from a hypertrophied gastrocnemius muscle. Rich's classification has been used to define the various entities. PAES presents as unilateral claudication exacerbated by physical exertion. However, such a clinical presentation is shared amongst not only vascular diseases but also musculoskeletal diseases. Therefore, a wide array of differential diagnoses must be considered when popliteal artery entrapment-induced claudication is suspected.


Suffering, sovereignty, and the purposes of God: Christian convictions and medical killing.
Despite a variety of "non-ecumenical" features in Christian arguments about suicide, assisted suicide, and euthanasia, there are obvious "ecumenical" aspects to be found in the general Christian prohibition of these practices. A fair reading of the Christian tradition requires that we acknowledge both the differences that distinguish particular perspectives and the fundamental themes that allow an identifiably Christian position to emerge in stark contrast to the secular discussion of these issues. Central to Christian interpretations of dying and death are an acknowledgment of God's sovereignty over human life, an understanding of suffering that stresses identification with Christ as the source of Christian hope, and the recognition that God's creative and redemptive purposes are generally (or always) at odds with the deliberate choice of assisted suicide or euthanasia.


The formation of the study of Shushu and its development in the Middle Ages: a tentative study of a field of scientific study peculiar to East Asia.
Natural science in East Asia formed a unique field of study called the study of shushu, which consisted of various fields of natural science and divinations derived from the Yijing [Chinese characters: see text]. Though the study of shushu is a field peculiar to East Asia where people want to evaluate the essence of the scientific culture of East Asia properly, it seems indispensable to grasp its structure and historical development. In this paper, the process of transformation of fangshu [Chinese characters: see text] in the pre-Qin period into shushu caused by the great thought revolution occurring in the period of Han period and its development in the Middle Ages are discussed. In particular, the origin of the theory of yinyang [Chinese characters: see text] and the five phases that is the theoretical basis of the study of shushu is studied using materials excavated recently in China. Using the texts preserved in Japan seen in the Wuxing Dayi [Chinese characters: see text] and the Ishinpŏ [Chinese characters: see text] the development of the theory of yinyang and five phases in the Middle Ages and its theoretical characteristics are discussed.


Steroid Efficacy on Audiologic Recovery in Patients With Sudden Sensorineural Hearing Loss and Vestibular Schwannoma: A Retrospective Review.
The objectives of this study are to (i) estimate the incidence of vestibular schwannoma (VS) among patients in an integrated healthcare system who present for evaluation of sudden sensorineural hearing loss (SSNHL) and (ii) evaluate the efficacy of empiric steroid therapy on audiologic recovery among SSNHL patients ultimately diagnosed with VS. A retrospective chart review was performed on patients presenting with SSNHL in 2021 at a multicenter integrated healthcare system serving over 4 million members. Patient demographics, audiometric data, VS diagnosis, therapeutic steroid intervention, and data regarding treatment response were recorded. A clinically significant audiometric improvement was defined as (i) an increase of 15% in word recognition score, (ii) a decrease of 15 dB in four-frequency pure-tone average (PTA) using frequencies of 500, 1000, 2000, and 4000 Hz, or (iii) a PTA of <20 dB on follow-up audiogram. Six hundred fifty-eight patients were reviewed, of which 309 (56.0% male; mean, 57.5 years) met the inclusion criteria with audiometric data and magnetic resonance imaging data. Ten patients (70.0% male; mean, 51.3 years) were found to have VS. Of these, five patients received oral steroid therapy alone, and five had combination therapy (oral + intratympanic steroid injections). No patients received intratympanic steroid therapy alone. Median PTA improvement with steroid therapy was 3.1-dB hearing loss, and median word recognition score improvement was 16.5%. Six of 10 patients demonstrated clinically significant audiometric improvement with steroid therapy. This study represents the largest US-based study showcasing the prevalence of VS in patients originally presenting with SSNHL. It also reinforces previous findings that VS does not preclude trials of steroid therapy.


Anti-signal recognition particle autoantibody ELISA validation and clinical associations.
The aim of this study was to develop and validate a quantitative anti-signal recognition particle (SRP) autoantibody serum ELISA in patients with myositis and longitudinal association with myositis disease activity. We developed a serum ELISA using recombinant purified full-length human SRP coated on ELISA plates and a secondary antibody that bound human IgG to detect anti-SRP binding. Protein immunoprecipitation was used as the gold standard for the presence of anti-SRP. Serum samples from three groups were analysed: SRP(+) myositis subjects by immunoprecipitation, SRP(-) myositis subjects by immunoprecipitation and non-myositis controls. The ELISA's sensitivity, specificity, positive predictive value and negative predictive value were evaluated. Percentage agreement and test-retest reliability were assessed. Serial samples from seven SRP immunoprecipitation-positive subjects were also tested, along with serum muscle enzymes and manual muscle testing. Using immunoprecipitation, we identified 26 SRP(+) myositis patients and 77 SRP(-) controls (including 38 patients with necrotizing myopathy). Non-myositis control patients included SLE (n = 4) and SSc (n = 7) patients. Anti-SRP positivity by ELISA showed strong agreement (97.1%) with immunoprecipitation (κ = 0.94). The sensitivity, specificity, positive predictive value, and negative predictive value of the anti-SRP ELISA were 88, 100, 100 and 96, respectively. The area under the curve was 0.94, and test-retest reliability was strong (r = 0.91, P < 0.001). Serial samples showed that anti-SRP levels paralleled changes in muscle enzymes and manual muscle testing. We developed a quantitative ELISA for detecting serum anti-SRP autoantibodies and validated the assay in myositis. Longitudinal assessment of SRP levels by ELISA may be a useful biomarker for disease activity.


Glutathione and K(+) channel remodeling in postinfarction rat heart.
Electrical remodeling of the diseased ventricle is characterized by downregulation of K(+) channels that control action potential repolarization. Recent studies suggest that this shift in electrophysiological phenotype involves oxidative stress and changes in intracellular glutathione (GSH), a key regulator of redox-sensitive cell functions. This study examined the role of GSH in regulating K(+) currents in ventricular myocytes from rat hearts 8 wk after myocardial infarction (MI). Colorimetric analysis of tissue extracts showed that endogenous GSH levels were significantly less in post-MI hearts compared with controls, which is indicative of oxidative stress. This change in GSH status correlated with significant decreases in activities of glutathione reductase and gamma-glutamylcysteine synthetase. Voltage-clamp studies of isolated myocytes from post-MI hearts demonstrated that downregulation of the transient outward K(+) current (I(to)) could be reversed by pretreatment with exogenous GSH or N-acetylcysteine, a precursor of GSH. Upregulation of I(to) was also elicited by dichloroacetate, which increases glycolytic flux through the GSH-related pentose pathway. This metabolic effect was blocked by inhibitors of glutathione reductase and the pentose pathway. These data indicate that oxidative stress-induced alteration in the GSH redox state plays an important role in I(to) channel remodeling and that GSH homeostasis is influenced by pathways of glucose metabolism.


Symmetry-induced fluctuation relations in open quantum systems.
We derive a general scheme to obtain quantum fluctuation relations for dynamical observables in open quantum systems. For concreteness, we consider Markovian nonunitary dynamics that is unraveled in terms of quantum jump trajectories and exploit techniques from the theory of large deviations like the tilted ensemble and the Doob transform. Our results here generalize to open quantum system fluctuation relations previously obtained for classical Markovian systems and add to the vast literature on fluctuation relations in the quantum domain, but without resorting to the standard two-point measurement scheme. We illustrate our findings with three examples to highlight and discuss the main features of our general result.


Disappearance rates of plasma growth hormone after intravenous somatostatin in renal and liver disease.
Plasma immunoreactive growth hormone (hGH) was measured before, during and after the administration of intravenous somatostatin to 3 patients with chronic renal failure and 4 with severe liver disease who had elevation of basal hGH. During somatostatin infusion, the hGH levels declined acutely in a linear fashion when log hGH was plotted against time. Rather surprisingly, the plasma hGH half disappearance time (t 1/2) was 27 min and 18 min in liver and renal disease respectively. These values do not differ from data obtained on normal subjects using exogenous hGH, labelled or unlabelled. Control data on normal subjects using this technique are not available as it was not possible to measure subnormal levels of plasma hGH with the required precision. It is possible that our findings of plasma hGH T 1/2 in liver and renal disease within the normal range reported using exogenous hGH might suggest that high levels of plasma hGH found in these two diseases are primarily caused by hypersecretion rather than impaired clearance.


Immune reactions in mucous membranes. IV. Histochemistry of intestinal mast cells during helminth expulsion in the rat.
The histochemistry of intestinal (IMC) and connective tissue mast cells (CTMC) in the normal rat is compared. Acid mucopolysaccharide appears to be less strongly sulfated and the granule content of monoamines is lower in IMC. After infection with the intestinal helminth, Nippostrongylus brasiliensis, the mucosal content of IMC is altered. During the early phase of immunologic expulsion of this parasite (self-cure) the IMC proliferate and differentiate; the histochemical properties of the granules appear to reflect this process. Very large numbers of mature IMC are found in the mucosa during the later, rapid phase of worm expulsion. Both acid mucopolysaccharide and monoamines are depleted from the granules of these cells; this is consistent with previous studies suggesting that IMC discharge occurs at this stage. These findings lend further support to the hypothesis that the biogenic products of IMC discharge are responsible for the increase in mucosal permeability which occurs during self-cure and which may facilitate the rapid translocation of antiworm antibody into the intestinal lumen.


HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis.
Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium stibogluconate is a drug of choice for the treatment of leishmaniasis. Because sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV-1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory-adapted and clinical strains of HIV-1, we report that sodium stibogluconate induces an increase in HIV-1 transcription and virus replication in primary CD4(+) T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor- kappa B and activator protein 1, as well as the Syk, Jun, and mitogen-activated protein kinase/extracellular signal-related kinase signal-transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV-1-infected patients.


Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank imaging data.
Previous reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n = 1157) and white matter integrity (n = 1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments. Whilst we found no significant differences in subcortical volumes, significant reductions were found in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) (β = -0.182, p = 0.005). We also found reductions in FA in association/commissural fibres (β = -0.184, pcorrected = 0.010) and thalamic radiations (β = -0.159, pcorrected = 0.020). Tract-specific FA reductions were also found in the left superior longitudinal fasciculus (β = -0.194, pcorrected = 0.025), superior thalamic radiation (β = -0.224, pcorrected = 0.009) and forceps major (β = -0.193, pcorrected = 0.025) in depression (all betas standardised). Our findings provide further evidence for disrupted white matter integrity in MDD.


Health systems research training as a tool for more effective Hansen's disease control programmes in Brazil.
In Brazil, Hansen's disease (HD) is still a public health problem. Although much progress has been made in Hansen's disease control (HDC) at all levels of government over the past 20 years, efforts have been hampered by information gaps related to specific areas of the disease, exacerbated by an absence of appropriate evaluation instruments and routine systematic analysis. Health Systems Research (HSR) aims to collect the necessary data to provide the most relevant information to policy makers and health managers to take more informed decisions. In Brazil, four HSR courses on HDC were organized by two non-governmental organizations (NGOs), Netherlands Leprosy Relief (NLR) and the British Leprosy Relief Association (LEPRA) between 2001 and 2005. Key personnel working in HDC from various states were invited to participate in the courses. The research proposals were developed during an HSR workshop and carried out in the field. The research topics of the projects included the following: the integration of HDC programmes into the primary health care system; the high percentage of the new patients diagnosed and treated at state referral centres; the psychological and social impact of surgical rehabilitation; the efficacy of neurolysis; the quality of the national health information system and the effectiveness of new case detection and health education campaigns. Following the completion of the field work, the data were analysed and a research report written. The results and recommendations were later presented to key stakeholders and policy makers in the states. Practical outcomes of the HSR courses include the drafting of new HDC guidelines; improvement of health information system databases and the revision of epidemiological data. These results have been presented at national and international congresses and published in peer-reviewed jornals. HSR has had a positive impact on the working routines of trainees through the process of learning the research methodology, collecting relevant data and implementing the recommendatons that originate from the findings. We conclude that HSR is an important vehicle for human resource development and a practical tool to improve the effectiveness of HDC programmes, primarily at the state and municipal levels. HSR also is an example of a successful cooperation between NGOs and governmental organizations working in HDC.


Enhancement of lipid accumulation in microalgae by metabolic engineering.
Microalgal lipids have drawn great attention as a promising sustainable resource for biodiesel or food supplement production. The development of high-performance strains of microalgae by metabolic engineering is invaluable for increasing the quantity or quality of desired lipids. The synthesis routes of lipids used as biodiesel in microalgae are based on fatty acid synthase (FAS) and triacylglycerols (TAG) biosynthesis pathway. Polyunsaturated fatty acids (PUFAs), including ω-6 and ω-3 fatty acids, are essential nutrients for humans. Notably, microalgae possess two distinct pathways for polyunsaturated fatty acids (PUFAs) biosynthesis, including the desaturase/elongase pathway and the polyketide synthase (PKS) pathway. Thus, it is necessary to identify which biosynthetic pathways are responsible for PUFA synthesis in particular microalgae species. In recent years, various key enzymes and functional domains involved in fatty acid and TAG biosynthesis pathway were identified and potentially regulated by genetic engineering approaches to elevate specific lipids content. In addition, other studies have reported the implementation of strategies to increase lipid accumulation based on increasing acetyl-CoA/NADPH supply, enhancing photosynthetic efficiency, or blocking competing pathways. Furthermore, other efforts have used transcription factor engineering to simultaneously regulate multiple genes related to lipid accumulation. This review summarizes recent research about a variety of microalgae lipid biosynthesis pathways, and discusses multiple gene manipulation strategies that have been employed for specific lipid overproduction in industrial microalgae.


Dual-specificity phosphatase 3 deficiency or inhibition limits platelet activation and arterial thrombosis.
A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. A better understanding of the molecular mechanisms leading to platelet activation is important for the development of improved therapies. Recently, protein tyrosine phosphatases have emerged as critical regulators of platelet function. This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated by the collagen receptor glycoprotein VI and the C-type lectin-like receptor 2. DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism compared with wild-type mice and showed severely impaired thrombus formation on ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of phospholipase Cγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen- and C-type lectin-like receptor 2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. DUSP3 plays a selective and essential role in collagen- and C-type lectin-like receptor 2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a protein tyrosine phosphatase, implicated in platelet signaling, has been targeted with a small-molecule drug.


Characterization of matrix metalloproteinases in denervated muscle.
In a nerve crush model of denervation, we examined muscle matrix metalloproteinase (MMP) expression, localization and activity. In normal muscle, MMP mRNA levels were low, and immunohistochemically MMPs were distributed around the muscle fibre with MMPs-3, -7 and -9 also staining at the neuromuscular junction. Seven days after nerve crush, muscle MMP immunoreactivity, especially MMP-12 and MMP-14, became irregularly distributed. At 20 days reinnervation of the muscle was observed, and some restitution of the normal pattern of immunoreactivity was noted concomitant with a higher level of MMP mRNA expression. In situ zymography showed that MMP activity was very weak in normal muscle whereas it was increased up to 40 days following denervation. Our results suggest that MMPs in muscle are involved in the tissue changes following denervation. Further experiments are required to test the hypothesis that MMP inhibition may be beneficial in protecting muscle from excessive remodelling following denervation and therefore improve reinnervation.


Synthesis, characterization and bioevaluation of technetium-99m labeled N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose as a tumor imaging agent.
N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose (NHADG) was synthesized by conjugation of salicylaldehyde to glucosamine. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m ((99m)Tc) in pertechnetate form ((99m)Tc O4-) was carried out via chelation reaction in the presence of stannous chloride dihydrate. Maximum radiochemical yield of (99m)Tc-NHADG complex (99%) was obtained by using 1 mg NHADG, 200 μg SnCl2.2H2O, at pH 9.5 and reaction time of 15 min. The radiochemical purity of the (99m)Tc-NHADG complex was measured by instant thin layer chromatography (ITLC) and paper chromatography (PC), without any notable decomposition at room temperature over a period of 4h. The biological evaluation results show that the (99m)Tc labeled NHADG conjugate is able to specifically target mammary carcinoma in mice models, thus highlighting its potential as an effective (99m)Tc labeled glucose-derived agent for tumor imaging.


DEPRESSION AND ANXIETY IN PARENTS OF CHILDREN WHO ARE CANDIDATES FOR LIVER TRANSPLANTATION.
The primary stress factor for families in the pre-transplant period is reported as the waiting time for suitable organs, leading to anxiety, despair, and distress. We investigated the psychosocial factors, anxiety and depression, in the parents of children who are candidates for liver transplantation. Thirty-five pediatric liver transplantation candidates and their 38 parents, from February to August 2014, were included. Participants were evaluated using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression Scale (CGI). We found that a significant number of parents (n=25, 65.7%) were diagnosed with clinical psychiatric disease: 18.4% (n=7) with depression and 47.3% (n=18) with anxiety disorders. There was a significant difference in the examination scores of parents between genders (P <0.05). There was also a significant difference in CGI and HAM-D scores of parents relative to the history and presence of liver disease (P <0.05). The rate of these disorders was high in relation to the prevalence of depression and anxiety disorders in the community reported in the literature. Therefore, it is necessary to evaluate psychosocial factors of parents of all transplant candidate children as a part of routine care so that the high-risk to family members and to enable early intervention.


HIV positive sero-status disclosure and its determinants among people living with HIV /AIDS following ART clinic in Jimma University Specialized Hospital, Southwest Ethiopia: a facility- based cross-sectional study.
Even though, the disclosure of HIV sero- status to sexual partners, friends or relatives is the main tool for prevention and care strategies, most of the HIV/AIDS patients do not inform their close friends. The most common reasons for not disclosure of their status to the community were majorly fear of social rejection and discriminations. Therefore, this study assessed the HIV positive sero-status disclosure and its determinants among People Living with HIV /AIDS (PLWH/A) followed by the Antiretroviral therapy (ART) Clinic in Jimma University Specialized Hospital, Southwest Ethiopia. A facility based cross-sectional study design was used among 351 ART patients that selected by systematic random sampling from ART clinic of Jimma University Specialized Hospital in March-2014. Data were collected through interviewer-administered questionnaires and analyzed using SPSS version 20.0 software. In a descriptive analysis frequency, mean and percentage were calculated. Bivariate and multivariate analyses were used to identify associated factors and the association between the explanatory and dependent variables was estimated. Only 37.6% (n = 132) were revealed their HIV positive status to anyone. Disclosure was done towards the sexual partners (88.6%), close family (72.7%) and a larger population (18.2%). Age ≤ 39 years (AOR = 0.014 [95%, CI = 0.005, 0.037]),Male sex (AOR = 3.039, [95% CI = 1.164, 7.935]), WHO stage III - IV at ART start(AOR = 2.766, [95%, CI = 1.321, 5.791]), presence of comorbidity (AOR = 2.500, [95%, CI = 1.483, 4.214]), having any clinical symptoms for HIV(AOR = 2.98, [95%, CI = 1.724, 5.152]),Low physical domain related quality of life (AOR = 3.83, [95%, CI = 2.008, 7.315]) and high social domain related quality of life (AOR = 0.053, [95%, CI = 0.022, 0.125]) were statistically significant association with their HIV sero-status disclosure. Findings of this study indicated, the disclosure of HIV status is very low. Discloser is more likely when the patient is older, male, and has a higher level of education. Clinical determinants for disclosure was the WHO stage III-IV, treatment duration of ≥2 years, comorbidity, presence of clinical symptoms for HIV, low physical domain related quality of life, low social domain related quality of life and low overall quality of life.


Eating disorder training and attitudes among primary care residents.
The ability to diagnose eating disorders (ED) is important and difficult for primary care physicians (PCPs). Previous reports suggest that PCPs feel their training is inadequate. To explore residents' interest and comfort diagnosing and treating ED. An internet survey was sent to primary care residencies. Logistic regression models were fitted to identify factors correlated with residents' interest and comfort in diagnosing and treating ED. Family Medicine and Internal Medicine residents had higher interest in ED than Pediatric residents, as did female residents and residents exposed to teenagers with unexplained weight loss. Residents in programs with an ED program and faculty interested in ED were more comfortable diagnosing ED. Interest in, and comfort diagnosing and treating ED are associated with specialty type, presence of an ED program, presence of faculty interested in ED, and resident exposure to ED outpatients and teenagers with unexplained weight loss.


Detection of early glaucomatous structural damage with confocal scanning laser tomography.
The authors determine which optic disc topographic parameters obtained by the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany) are most useful in detecting individuals with early glaucomatous visual field loss. Ninety-nine eyes of 49 healthy individuals and 50 age-matched individuals with early glaucomatous visual field loss were included. Three images were obtained and the mean topography image was created and used in the analyses. The HRT discriminant analysis function (software version 2.01) was applied and compared to the Fisher linear discriminant function developed in this population. Analysis was repeated after stratifying by disc area (< 2 mm2 or 2-3 mm2). There were statistically significant differences between the healthy and glaucomatous groups for all optic disc topographic parameters (p < 0.05) measured. These differences remained after the analysis was repeated controlling for disc size, except for height variation contour. Applying the HRT discriminant function to this study population resulted in sensitivity and specificity of 62% and 94%, respectively. The sensitivity was 83% while specificity remained high (91%) for larger disc sizes. Using this data, additional discriminant functions that differentiated similarly between the two groups were found. The best formula used cup-shape measure (third moment), rim area, height variation contour, and retinal nerve fiber layer thickness and had a sensitivity and specificity of 78% and 88%, respectively. Several different discriminant analysis formulas are capable of detecting early glaucomatous visual field loss in a comparable manner. The characteristics of the study population are likely to influence the discriminating power of these various formulas.