Female Adults with Patellofemoral Pain Are Characterized by Widespread Hyperalgesia, Which Is Not Affected Immediately by Patellofemoral Joint Loading.
Compare pressure pain thresholds (PPTs) at the knee and a site remote to the knee in female adults with patellofemoral pain (PFP) to pain-free controls before and after a patellofemoral joint (PFJ) loading protocol designed to aggravate symptoms. Cross-sectional study SETTING: Participants were recruited via advertisements in fitness centers, public places for physical activity and universities. Thirty-eight females with patellofemoral pain, and 33 female pain-free controls. All participant performed a novel PFJ loading protocol involving stair negotiation with an extra load equivalent 35% of body mass. PPTs and current knee pain (measured on a visual analogue scale) was assessed before and after the loading protocol. PPTs were measured at four sites around the knee and one remote site on the upper contralateral limb. Females with PFP demonstrated significantly lower PPTs locally and remote to the knee, both before and after the PFJ loading protocol when compared to control group. Following the loading protocol, PPTs at knee were significantly reduced by 0.54 kgf (95%CI = 0.33; 0.74) for quadriceps tendon, 0.38 kgf (95%CI = 0.14; 0.63) for medial patella, and 0.44 kgf (95%CI = 0.18; 0.69) for lateral patella. No significant change in PPT remote to the knee was observed - 0.10 kgf (95%CI = -0.04; 0.24). Female adults with PFP have local and widespread hyperalgesia compared to pain free controls. A novel loading protocol designed to aggravate symptoms, lowers the PPTs locally at the knee but has no effect on PPT on the upper contralateral limb. This suggests widespread hyperalgesia is not affected by acute symptom aggravation.


Alternative fate of glyoxylate during acetate and hexadecane metabolism in Acinetobacter oleivorans DR1.
The glyoxylate shunt (GS), involving isocitrate lyase (encoded by aceA) and malate synthase G (encoded by glcB), is known to play important roles under several conditions including oxidative stress, antibiotic defense, or certain carbon source metabolism (acetate and fatty acids). Comparative growth analyses of wild type (WT), aceA, and glcB null-strains revealed that aceA, but not glcB, is essential for cells to grow on either acetate (1%) or hexadecane (1%) in Acinetobacter oleivorans DR1. Interestingly. the aceA knockout strain was able to grow slower in 0.1% acetate than the parent strain. Northern Blot analysis showed that the expression of aceA was dependent on the concentration of acetate or H2O2, while glcB was constitutively expressed. Up-regulation of stress response-related genes and down-regulation of main carbon metabolism-participating genes in a ΔaceA mutant, compared to that in the parent strain, suggested that an ΔaceA mutant is susceptible to acetate toxicity, but grows slowly in 0.1% acetate. However, a ΔglcB mutant showed no growth defect in acetate or hexadecane and no susceptibility to H2O2, suggesting the presence of an alternative pathway to eliminate glyoxylate toxicity. A lactate dehydrogenase (LDH, encoded by a ldh) could possibly mediate the conversion from glyoxylate to oxalate based on our RNA-seq profiles. Oxalate production during hexadecane degradation and impaired growth of a ΔldhΔglcB double mutant in both acetate and hexadecane-supplemented media suggested that LDH is a potential detoxifying enzyme for glyoxylate. Our constructed LDH-overexpressing Escherichia coli strain also showed an important role of LDH under lactate, acetate, and glyoxylate metabolisms. The LDH-overexpressing E. coli strain, but not wild type strain, produced oxalate under glyoxylate condition. In conclusion, the GS is a main player, but alternative glyoxylate pathways exist during acetate and hexadecane metabolism in A. oleivorans DR1.


Association between the Preoperative C-Reactive Protein-to-Albumin Ratio and the Risk for Postoperative Pancreatic Fistula following Distal Pancreatectomy for Pancreatic Cancer.
Postoperative pancreatic fistula (POPF) are major postoperative complications (POCs) following distal pancreatectomy (DP). Notably, POPF may worsen the prognosis of patients with pancreatic cancer. Previously reported risks for POCs include body mass index, pancreatic texture, and albumin levels. Moreover, the C-reactive protein-to-albumin ratio (CAR) is a valuable parameter for prognostication. On the other hand, POCs sometimes lead to a worse prognosis in several cancer types. Thus, we assumed that CAR could be a risk factor for POPFs. This study investigated whether CAR can predict POPF risk in patients with pancreatic cancer following DP. This retrospective study included 72 patients who underwent DP for pancreatic cancer at Ehime University between January 2009 and August 2022. All patients underwent preoperative CAR screening. Risk factors for POPF were analyzed. POPF were observed in 17 of 72 (23.6%) patients. POPF were significantly associated with a higher CAR (p = 0.001). The receiver operating characteristic curve analysis determined the cutoff value for CAR to be 0.05 (sensitivity: 76.5%, specificity: 88.9%, likelihood ratio: 6.88), indicating an increased POPF risk. Univariate and multivariate analysis revealed that CAR ≥ 0.05 was a statistically independent factor for POPF (p < 0.001, p = 0.013). Therefore, CAR has the potential to predict POPF following DP.


Direct coupling of a gas-liquid separator to an ion mobility spectrometer for the classification of different white wines using chemometrics tools.
The potential of a vanguard technique as is the ion mobility spectrometry with ultraviolet ionization (UV-IMS) coupled to a continuous flow system (CFS) have been demonstrated in this work using a gas phase separator (GPS). This vanguard system (CFS-GPS-UV-IMS) has been used for the analysis of different types of white wines to obtain a characteristic profile for each type of wine and their posterior classification using different chemometric tools. Precision of the method was 3.1% expressed as relative standard deviation. A deep chemometric study was carried out for the classification of the four types of wines selected. The best classification performance was obtained by first reducing the data dimensionality by principal component analysis (PCA) followed by linear discriminant analysis (LDA) and finally using a k-nearest neighbour (kNN) classifier. The classification rate in an independent validation set was 92.0% classification rate value with confidence interval [89.0%, 95.0%] at 95% confidence level. The same white wines analyzed using CFS-GPS-UV-IMS were analyzed using gas chromatography with a flame detector (GC-FID) as conventional technique. The chromatographic method used for the determination of superior alcohols in wine samples shown in the Regulation CEE 1238/1992 was selected to carry out the analysis of the same samples set and later the classification using appropriate chemometrics tools. In this case, strategies PCA-LDA and kNN classifier were also used for the correct classification of the wine samples. This combination showed similar results to the ones obtained with the proposed method.


Effects of the phage P1 restriction system on coliphage phi W: degradation and complex formation of phage phi W DNA.
Growth of phages phi W and T7 was restricted in Escherichia coli lysogenic for phage P1. Only a fraction of the infected cells gave burst of phages. Cells permitting phage growth gave normal burst size. Host strains carrying P1 mutants with defective endonuclease gave no restriction of phages T7 and phi 3, the latter a host-range mutant of phi W. Degradation but not modification of parental phage DNA could be demonstrated. Although no DNA, RNA or protein was synthesized in phi W infected P1 lysogenic cells, the parental phage DNA was found in increasingly larger complexes during the course of infection. At early times after infection, parental phage DNA was found to sediment about twice as fast as mature phage DNA. At later times during the infection the parental phage DNA was recovered as a very rapidly sedimenting material. Such material was also found in alkaline sucrose gradient centrifugation after treatment of the cell extract with sodium dodecyl sulphate, pronase digestion and phenol extractions.


Impacts of an anti-androgen and an androgen/anti-androgen mixture on the metabolite profile of male fathead minnow urine.
Male and female fathead minnows (Pimephales promelas, FHM) were exposed via water to 20 or 200 microg/L of cyproterone acetate (CA), a model androgen receptor (AR) antagonist. FHM were also exposed to 500 ng/L of 17beta-trenbolone (TB), a model AR agonist, and to mixtures of TB with both concentrations of CA. The urine metabolite profile (as measured by 1H NMR spectroscopy) of male FHM exposed to the high concentration of CA was markedly different from that of controls, and this difference was less for males coexposed to the associated TB+CA mixture. The exposure to TB alone had almost no impact on the male urine profile. These results suggest that male FHM urinary metabolite profiling may be useful for directly detecting effects of anti-androgens. In contrast, the urinary profile of male FHM exposed to the lower concentration of CA was not very different from that of controls, but, unexpectedly, this difference was increased when coexposed to the associated TB+CA mixture. This suggests that TB with CA at the lower concentration impacts male FHM through an interactive effect possibly unrelated, or in addition, to AR antagonism. The relative occurrence of male-like nuptial tubercles in female FHM exposed to TB and to the mixtures of TB and CA supported the metabolomics data.


Triple helix-forming oligonucleotides conjugated to new inhibitors of topoisomerase II: synthesis and binding properties.
Triplex-forming oligonucleotides (TFOs) are among the most specific DNA ligands and represent an important tool for specific regulation of gene expression. TFOs have also been used to target DNA-modifying molecules to obtain irreversible modifications on a specific site of the genome. A number of molecules have been recognized to target topoisomerase II and stabilize double-stranded cleavage mediated by this enzyme thus determining permanent DNA damage. Among these poisons, etoposide (VP16), a 4'-demethylepipodophyllotoxin derivative, is widely used in cancer chemotherapy. In the aim to design DNA site-specific molecules, three analogues of VP16 (1, 2, and 3), recently described (Duca et al. J. Med. Chem. 2005, 48, 596-603), were attached to TFOs, together with a fourth one, of which the synthesis is reported here. Two different oligonucleotides, differing by the length (a 16-mer and a 20-mer), and two different linker arms between the oligonucleotide and the drug were used. The coupling reaction between the drug and the TFO was further improved. For the first time, we also report the synthesis of TFO conjugates bearing two molecules of inhibitor linked to the same oligonucleotide end. In total, 16 new conjugates were synthesized and evaluated for their ability to form triple helices. The loss in triplex stability due to the conjugation of the TFO to compounds that do not interact with DNA is compensated by the presence of the ethylene glycol linker arm. This stabilization effect is more pronounced at the 3' end than at the 5' end. All conjugates form a stable triplex selectively on the DNA target at 37 degrees C and pH 7.2.


Evaluation and validation of a PulseNet standardized pulsed-field gel electrophoresis protocol for subtyping Vibrio parahaemolyticus: an international multicenter collaborative study.
The pandemic spread of Vibrio parahaemolyticus is an international public health issue. Because of the outbreak potential of the organism, it is critical to establish an internationally recognized molecular subtyping protocol for V. parahaemolyticus that is both rapid and robust as a means to monitor its further spread and to guide control measures in combination with epidemiologic data. Here we describe the results of a multicenter, multicountry validation of a new PulseNet International standardized V. parahaemolyticus pulsed-field gel electrophoresis (PFGE) protocol. The results are from a composite analysis of 36 well-characterized V. parahaemolyticus isolates from six participating laboratories, and the isolates represent predominant serotypes and various genotypes isolated from different geographic regions and time periods. The discriminatory power is very high, as 34 out of 36 sporadic V. parahaemolyticus strains tested fell into 34 distinguishable PFGE groups when the data obtained with two restriction enzymes (SfiI and NotI) were combined. PFGE was further able to cluster members of known pandemic serogroups. The study also identified quality measures which may affect the performance of the protocol. Nonadherence to the recommended procedure may lead to high background in the PFGE gel patterns, partial digestion, and poor fragment resolution. When these quality measures were implemented, the PulseNet V. parahaemolyticus protocol was found to be both robust and reproducible among the collaborating laboratories.


Effect of field pea replacement level on intake and digestion in beef steers fed by-product-based medium-concentrate diets.
Four ruminally and duodenally cannulated steers (703.4 +/- 41 kg initial BW) were used in a 4 x 4 Latin square to evaluate the effects of field pea inclusion level on intake and site of digestion in beef steers fed medium-concentrate diets. Steers were offered feed ad libitum at 0700 and 1900 daily and were allowed free access to water. Diets consisted of 45% grass hay and 55% by-products based concentrate mixture and were formulated to contain a minimum of 12% CP (DM basis). Treatments consisted of (DM basis) 1) control, no pea; 2) 15% pea; 3) 30% pea; and 4) 45% pea in the total diet, with pea replacing wheat middlings, soybean hulls, and barley malt sprouts in the concentrate mixture. Experimental periods consisted of a 9-d dietary adjustment period followed by a 5-d collection period. Grass hay was incubated in situ, beginning on d 10, for 0, 2, 5, 9, 14, 24, 36, 72, and 98 h; and field pea and soybean hulls for 0, 2, 5, 9, 14, 24, 36, 48, and 72 h. Total DMI (15.0, 13.5, 14.1, 13.5 +/- 0.65 kg/d) and OM intake (13.4, 12.0, 12.6, 12.0 +/- 0.58 kg/d) decreased linearly (P = 0.10) with field pea inclusion. Apparent ruminal (17.5, 12.0, 0.6, 6.5 +/- 4.31%) and true ruminal CP digestibility (53.5, 48.7, 37.8, 46.2 +/- 3.83) decreased linearly (P < 0.10) with increasing field pea. Neutral detergent fiber intake (8.9, 7.9, 7.8, 7.0 +/- 0.3 kg/d) and fecal NDF output (3.1, 2.9, 2.6, 2.3 +/- 0.2 k/d) decreased linearly (P < 0.03) with increasing field pea. No effects were observed for microbial efficiency or total-tract digestibility of OM, CP, NDF, and ADF (P > or = 0.16). In situ DM and NDF disappearance rates of grass hay and soybean hulls decreased linearly (P < 0.05) with increasing field pea. Field pea in situ DM disappearance rate responded quadratically (P < 0.01; 5.9, 8.4, 5.5, and 4.9 +/- 0.52%/h, for 0, 15, 30, and 45% field pea level, respectively). Rate of in situ CP disappearance of grass hay decreased linearly (P < 0.01) with increasing field pea level. Field pea is a suitable ingredient for beef cattle consuming medium-concentrate diets, and the inclusion of up to 45% pea in by-products-based medium-concentrate growing diets decreased DMI, increased dietary UIP, and did not alter OM, NDF, or ADF digestibility.


Identification and characterization of a novel chloroplast/mitochondria co-localized glutathione reductase 3 involved in salt stress response in rice.
Glutathione reductases (GRs) are important components of the antioxidant machinery that plants use to respond against abiotic stresses. In rice, one cytosolic and two chloroplastic GR isoforms have been identified. In this work, we describe the cloning and characterization of the full-length cDNA encoding OsGR3, a chloroplast-localized GR that up to now was considered as a non-functional enzyme because of assumed lack of N-terminal conserved domains. The expression of OsGR3 in E. coli validated that it can be translated as a protein with GR activity. OsGR3 shows 76 and 53 % identity with OsGR1 (chloroplastic) and OsGR2 (cytosolic), respectively. Phylogenetic analysis revealed 2 chloroplastic GRs in Poaceae species, including rice, sorghum and brachypodium, but only one chloroplastic GR in dicots. A plastid transit peptide is located at the N terminus of OsGR3, and genetic transformation of rice with a GR3-GFP fusion construct further confirmed its localization in chloroplasts. Furthermore, OsGR1 and OsGR3 are also targeted to mitochondria, which suggest a combined antioxidant mechanism in both chloroplasts and mitochondria. However, both isoforms showed a distinct response to salinity: the expression of OsGR3 but not OsGR1 was induced by salt stress. In addition, the transcript level of OsGR3 was greatly increased with salicylic acid treatment but was not significantly affected by methyl jasmonate, dehydration or heat shock stress. Our results provide new clues about the possible roles of functional OsGR3 in salt stress and biotic stress tolerance.


Genetics of adult body mass and maintenance of adult body mass in captive baboons (Papio hamadryas subspecies).
Adult body mass and changes in mass during an individual's life are important indicators of general health and reproductive fitness. Therefore, characterization of the factors that influence normal variation in body mass has important implications for colony management and husbandry. The main objective of this study was to quantify the genetic contribution to adult body mass and its maintenance in baboons. Intra-individual mean and variance in body mass were calculated from multiple weight measures available for each of 1,614 animals at least 10 years of age. Heritabilities were estimated using maximum likelihood methods. Mean adult body mass had a significant heritability (50%) as did variance in adult body mass (12%). The sexes differed in several respects: on average females were smaller than males and had greater variability in adult body mass; mean and variance in body mass increased with age in females only; and number of offspring showed a significant positive relationship with body mass in females only. There were significant differences between subspecies in body mass as well as ability to maintain body mass. These results indicate that there is a significant genetic influence on body mass and its maintenance, and suggest that different factors influence changes in body mass with age as well as body mass maintenance in male and female baboons.


Measles, mumps, and rubella vaccine in genital warts: A case report of two patients.
Genital warts have a big psychological impact on the affected individuals, as the treatment requires time and multiple sessions at a time. They can also increase the chances of acquiring other sexually transmitted diseases. Various treatment options are available including the topical application of imiquimod, podophyllin, trichloroacetic acid application, cryotherapy, and radiofrequency cautery. However, all of these require multiple sessions, and chances of recurrences are high. Some of them also have multiple local side effects as burning, irritation, erythema, and swelling. Overall genital warts represent a frustrating challenge for both patients and physicians. Intralesional immunotherapy has shown promising efficacy in the treatment of warts including the following: Bacille Calmette-Guerin vaccine, candida antigen, Mw vaccine, and measles, mumps, and rubella (MMR) vaccine. We report the two cases of genital warts, who had an excellent response with intralesional MMR vaccine.


Enhancement of insulin-mediated rat muscle glucose uptake and microvascular perfusion by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside.
Insulin-induced microvascular recruitment is important for optimal muscle glucose uptake. 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, an activator of AMP-activated protein kinase), can also induce microvascular recruitment, at doses that do not acutely activate glucose transport in rat muscle. Whether low doses of AICAR can augment physiologic insulin action is unknown. In the present study we used the euglycemic hyperinsulinemic clamp to assess whether insulin action is augmented by low dose AICAR. Anesthetized rats were studied during saline infusion or euglycemic insulin (3 mU/kg/min) clamp for 2 h in the absence or presence of AICAR for the last hour (5 mg bolus followed by 3.75 mg/kg/min). Muscle glucose uptake (R'g) was determined radioisotopically with (14)C-2-deoxyglucose and muscle microvascular perfusion by contrast-enhanced ultrasound with microbubbles. AICAR did not affect blood glucose, or lower leg R'g, although it significantly (p < 0.05) increased blood lactate levels and augmented muscle microvascular blood volume via a nitric oxide synthase dependent pathway. Insulin increased femoral blood flow, whole body glucose infusion rate (GIR), R'g, hindleg glucose uptake, and microvascular blood volume. Addition of AICAR during insulin infusion increased lactate production, further increased R'g in Type IIA (fast twitch oxidative) and IIB (fast twitch glycolytic) fiber containing muscles, and hindleg glucose uptake, but decreased R'g in the Type I (slow twitch oxidative) fiber muscle. AICAR also decreased GIR due to inhibition of insulin-mediated suppression of hepatic glucose output. AICAR augmented insulin-mediated microvascular perfusion. AICAR, at levels that have no direct effect on muscle glucose uptake, augments insulin-mediated microvascular blood flow and glucose uptake in white fiber type muscles. Agents targeted to endothelial AMPK activation are promising insulin sensitizers, however, the decrease in GIR and the propensity to increase blood lactate cautions against AICAR as an acute insulin sensitizer.


[Detection of antibodies against Anaplasma sp. in small ruminants from the semi-arid region against Pernambuco State, Brazil].
This paper reports the detection of antibodies against Anaplasma sp. in goats and sheep from the semi-arid region from Pernambuco State, Brazil, using an enzyme-linked immunosorbent assay with recombinant MSP5 of Anaplasma marginale. Sera from 243 goats and 68 sheep from Ibimirim municipality were analyzed and frequencies of antibodies of 11.93% (29/243) and 16.17% (11/68) were found for goats and sheep, respectively. The epidemiological relevance of the findings was discussed.


Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly.
Limited data exist regarding metabolic risk factors for deaths from hepatocellular carcinoma (HCC) in aging individuals. We investigated the association between diabetes, dyslipidemia, and HCC mortality in those aged 40 years or more (middle-aged and elderly). In this prospective cohort study based on nationwide health screening units, we consecutively followed middle-aged and elderly participants who had no chronic hepatitis B or C virus infection and received health screening from January 1 1998 to December 31 2008. There were 235 deaths from HCC among 50,080 individuals, ascertained by validated death certificates and the national death registry. Diabetes (adjusted hazard ratio [HR], 3.38; 95% confidence interval [CI], 2.35 to 4.86) was positively associated with deaths from HCC. However, hypertriglyceridemia (HR, 0.38; 95% CI, 0.26 to 0.55) and hypercholesterolemia (HR, 0.50; 95% CI, 0.37 to 0.67) were inversely associated with HCC mortality. The above significant associations remained in the lag time analyses, applied to check for reverse causation. Metabolic syndrome, as defined by the American Heart Association / National Heart Lung Blood Institute criteria (HR, 0.63; 95% CI, 0.46 to 0.86) or by the International Diabetes Federation criteria (HR, 0.62; 95% CI, 0.43 to 0.89), was inversely associated with deaths from HCC, especially in men. Middle-aged and elderly individuals, once having diabetes, deserve HCC surveillance to reduce HCC mortality. More research is needed to elucidate why having baseline dyslipidemia relates to lower future HCC mortality.


Biotechnology in europe.
The countries of the European Economic Community have recently mounted considerable efforts to commercialize biotechnology. Together, these efforts approach the same number of companies and level of government spending as those in the United States. In Europe there is more government emphasis on support for industry-university collaborations and industrial projects than in the United States, where basic research is emphasized. European efforts are often not easily delineated from those in the United States; many European companies have extensive U.S. operations and many U.S. companies have involvement in Europe. Strategies and efforts in European biotechnology are examined and compared to those in the United States.


Detection of NTRK gene fusions in solid tumors: recommendations from a Latin American group of oncologists and pathologists.
NTRK gene fusions have been detected in more than 25 types of tumors and their prevalence is approximately 0.3% in solid tumors. This low prevalence makes identifying patients who could benefit from TRK inhibitors a considerable challenge. Furthermore, while numerous papers on the evaluation of NTRK fusion genes are available, not all countries have guidelines that are suitable for their setting, as is the case with Latin America. Therefore, a group of oncologists and pathologists from several countries in Latin America (Argentina, Chile, Ecuador, Mexico, Peru and Uruguay) met to discuss and reach consensus on how to identify patients with NTRK gene fusions in solid tumors. To do so, they developed a practical algorithm, considering their specific situation and limitations.


Identification of the Key Immune-Related Genes in Chronic Obstructive Pulmonary Disease Based on Immune Infiltration Analysis.
Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity worldwide. A better understanding of new biomarkers for COPD patients and their complex mechanisms in the progression of COPD are needed. An algorithm was conducted to reveal the proportions of 22 subsets of immune cells in COPD samples. Differentially expressed immune-related genes (DE-IRGs) were obtained based on the differentially expressed genes (DEGs) of the GSE57148 dataset, and 1509 immune-related genes (IRGs) were downloaded from the ImmPort database. Functional enrichment analyses of DE-IRGs were conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Ingenuity Pathway Analysis (IPA). We defined the DE-IRGs that had correlations with immune cells as hub genes. The potential interactions among the hub genes were explored by a protein-protein interaction (PPI) network. The CIBERSORT results showed that lung tissue of COPD patients contained a greater number of resting NK cells, activated dendritic cells, and neutrophils than normal samples. However, the fractions of follicular helper T cells and resting dendritic cells were relatively lower. Thirty-eight DE-IRGs were obtained for further analysis. Functional enrichment analysis revealed that these DE-IRGs were significantly enriched in several immune-related biological processes and pathways. Notably, we also observed that DE-IRGs were associated with the coronavirus disease COVID-19 in the progression of COPD. After correlation analysis, six DE-IRGs associated with immune cells were considered hub genes, including AHNAK, SLIT2 TNFRRSF10C, CXCR1, CXCR2, and FCGR3B. In the present study, we investigated immune-related genes as novel diagnostic biomarkers and explored the potential mechanism for COPD based on CIBERSORT analysis, providing a new understanding for COPD treatment.


Detection of RNA viruses from influenza and HIV to Ebola and SARS-CoV-2: a review.
RNA-based viruses likely make up the highest pandemic threat among all known pathogens in about the last 100 years, since the Spanish Flu of 1918 with 50 M deaths up to COVID-19. Nowadays, an efficient and affordable testing strategy for such viruses have become the paramount target for the fields of virology and bioanalytical chemistry. The detection of the viruses (influenza, hepatitis, HIV, Zika, SARS, Ebola, SARS-CoV-2, etc.) and human antibodies to these viruses is described and tabulated in terms of the reported methods of detection, time to results, accuracy and specificity, if they are reported. The review is focused, but not limited to publications in the last decade. Finally, the limits of detection for each representative publication are tabulated by detection methods and discussed. These methods include PCR, lateral flow immunoassays, LAMP-based methods, ELISA, electrochemical methods (e.g., amperometry, voltammetry), fluorescence spectroscopy, AFM, SPR and SERS spectroscopy, silver staining and CRISPR-Cas based methods, bio-barcode detection, and resonance light scattering. The review is likely to be interesting for various scientists, and particularly helpful with information for establishing interdisciplinary research.


Properties of a tobacco DNA methyltransferase, NtMET1 and its involvement in chromatin movement during cell division.
Plants possess three types of DNA methyltransferase, among which methyltransferase type 1 (MET1) is considered to play a major role by maintaining the CpG methylation patterns. However, little information is available as to its enzymatic activity, interacting proteins and spatial and temporal behaviours during DNA replication. In the present study, one example, NtMET1 from tobacco plants, was selected and an analysis was made of its biochemical properties and cellular localization. NtMET1 was expressed in Sf9 insect cells, and a purified sample was subjected to a standard in vitro methylation assay. Intramolecular interaction was examined by the yeast two-hybrid and pull-down assays. Transgenic tobacco plants (Nicotiana tabacum) over-expressing NtMET1 were constructed via Agrobacterium-mediated transformation. Cellular localization was examined by fluorescence protein fusion, which was expressed in tobacco bright yellow 2 cells. In vitro assays showed no detectable methylation activity when both hemimethylated and unmethylated DNA samples were used as the substrate. In planta assays with over-expressing transgenic lines showed no hypermethylation but rather hypomethylation of genomc DNA. The inability of methylation was conceivably due to a tight intramolecular interaction between the N- and C-terminal regions with the catalytic domain residing on the C-terminus being completely masked. Cellular localization analyses indicated that NtMET1 localized to the nucleus in the resting stage and migrates to the cytoplasm during mitosis, particularly at metaphase. The pattern observed resembled that of Ran GTPase, and in vitro pull-down assays showed a clear interaction between NtMET1 and AtRAN3, an Arabidopsis orthologue of tobacco Ran GTPase, NtRan-A1. The results suggest that enzymatic activity of NtMET1 is well adjusted by its own intra/intermolecular interaction and perhaps by interactions with other proteins, one of which was found to be Ran GTPase. Results also revealed that NtMET1 becomes localized to the vicinity of chromatin with the aid of Ran GTPase during cell division, and may play an important role in progress through mitosis independently of methylation activity.


Development and evaluation of a biomedical search engine using a predicate-based vector space model.
Although biomedical information available in articles and patents is increasing exponentially, we continue to rely on the same information retrieval methods and use very few keywords to search millions of documents. We are developing a fundamentally different approach for finding much more precise and complete information with a single query using predicates instead of keywords for both query and document representation. Predicates are triples that are more complex datastructures than keywords and contain more structured information. To make optimal use of them, we developed a new predicate-based vector space model and query-document similarity function with adjusted tf-idf and boost function. Using a test bed of 107,367 PubMed abstracts, we evaluated the first essential function: retrieving information. Cancer researchers provided 20 realistic queries, for which the top 15 abstracts were retrieved using a predicate-based (new) and keyword-based (baseline) approach. Each abstract was evaluated, double-blind, by cancer researchers on a 0-5 point scale to calculate precision (0 versus higher) and relevance (0-5 score). Precision was significantly higher (p<.001) for the predicate-based (80%) than for the keyword-based (71%) approach. Relevance was almost doubled with the predicate-based approach-2.1 versus 1.6 without rank order adjustment (p<.001) and 1.34 versus 0.98 with rank order adjustment (p<.001) for predicate--versus keyword-based approach respectively. Predicates can support more precise searching than keywords, laying the foundation for rich and sophisticated information search.


Keratin intermediate filament dynamics in cell heterokaryons reveals diverse behaviour of different keratins.
To study the dynamics of keratin intermediate filaments, we fused two different types of epithelial cells (PtK2 and BMGE+H) and studied how the keratins from the parental cells recombine and copolymerize to form the heterokaryon cytoskeleton. The behaviour of the keratins during this process was followed by immunofluorescence using specific antibodies. After fusion, the parental cytoskeletons undergo a depolymerization process most apparent in the region adjacent to the fusion area. The depolymerized subunits spread throughout the heterokaryon and copolymerize into a new hybrid cytoskeleton. The complete process is very rapid, occurring in 3-4 hours, thus demonstrating the highly dynamic nature of the keratin cytoskeleton. Although newly synthesised subunits contribute to the formation of the hybrid cytoskeleton, the process takes place with similar kinetics in the absence of protein synthesis, showing the dynamic nature of the keratins from pre-existing cytoskeletons. During this process, specific keratins behave differently. Keratins K8, K18, K5 and K10 are mobilised from the parental cytoskeletons and reassemble rapidly into the hybrid cytoskeleton (3-6 hours), whereas K14 requires a substantially longer period (9-24 hours). Thus, different keratins, even when they form part of the same heterodimeric/tetrameric complexes, as is the case for K5 and K14, exhibit different dynamics. This suggests that individual polypeptides or homopolymeric complexes rather than exclusively heterodimeric/ tetrameric subunits, as is currently thought, can also take part in keratin intermediate filament assembly and dynamics. Biochemical analysis performed in the absence of protein synthesis revealed greater amounts of K5 than of K14 in the soluble pool of BMGE+H cells. Crosslinking and immunoprecipitation experiments indicated an excess of monomeric K5, as well as of K5/K14 heterodimers and K5 homodimers in the soluble pool. These results are in agreement with the different dynamic behaviour of these keratins observed in immunofluorescence. On the contrary, the phosphorylation levels of K5 and K14 are similar in both the soluble pool and the polymerized fraction, suggesting that phosphorylation does not play an important role in the different dynamics displayed by these two proteins. In summary, our results demonstrate that, following fusion, the keratin intermediate filament network reshapes rather rapidly and that keratins are highly dynamic proteins, although this mobility depends on each particular polypeptide.


Erlotinib inhibits growth of a patient-derived chordoma xenograft.
Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease.


Market Women's Perspectives on Coronavirus Disease 2019 (COVID-19): The Case of Ghana and South Africa.
Globally, countries are still battling health challenges and the negative economic stress on the citizenry caused by COVID-19. This study explored the perspectives of market women in Ghana and South Africa on COVID-19. Data collection was executed in both Ghana and South Africa between March 2021 and December 2021. Employing semi-structured questionnaires, face-to-face interviews were conducted. Most of the market women in Ghana described COVID-19 as a global pandemic, while market women in South Africa described the disease as the deadly flu. There were similarities in the perceived signs and symptoms of COVID-19. Market women in both countries specifically observed that not adhering to the safety protocols was the major mode of transmission. Lemon, garlic and ginger were the most common foodstuffs used by the market women to fight COVID-19. To prevent COVID-19 at their places of work, market women stressed the importance of observing the safety protocols. An overwhelming majority of market women in both countries bemoaned the negative impact of COVID-19 on their businesses and suggested the need for financial assistance from their respective governments. The findings are intended to assist policymakers in both Ghana and South Africa to implement interventional projects to assist women whom the literature suggests are the most vulnerable during pandemics such as COVID-19.


Monitoring a nuclear factor-κB signature of drug resistance in multiple myeloma.
The emergence of acquired drug resistance results from multiple compensatory mechanisms acting to prevent cell death. Simultaneous monitoring of proteins involved in drug resistance is a major challenge for both elucidation of the underlying biology and development of candidate biomarkers for assessment of personalized cancer therapy. Here, we have utilized an integrated analytical platform based on SDS-PAGE protein fractionation prior to liquid chromatography coupled to multiple reaction monitoring mass spectrometry, a versatile and powerful tool for targeted quantification of proteins in complex matrices, to evaluate a well-characterized model system of melphalan resistance in multiple myeloma (MM). Quantitative assays were developed to measure protein expression related to signaling events and biological processes relevant to melphalan resistance in multiple myeloma, specifically: nuclear factor-κB subunits, members of the Bcl-2 family of apoptosis-regulating proteins, and Fanconi Anemia DNA repair components. SDS-PAGE protein fractionation prior to liquid chromatography coupled to multiple reaction monitoring methods were developed for quantification of these selected target proteins in amounts of material compatible with direct translation to clinical specimens (i.e. less than 50,000 cells). As proof of principle, both relative and absolute quantification were performed on cell line models of MM to compare protein expression before and after drug treatment in naïve cells and in drug resistant cells; these liquid chromatography-multiple reaction monitoring results are compared with existing literature and Western blots. The initial stage of a systems biology platform for examining drug resistance in MM has been implemented in cell line models and has been translated to MM cells isolated from a patient. The ultimate application of this platform could assist in clinical decision-making for individualized patient treatment. Although these specific assays have been developed to monitor MM, these techniques are expected to have broad applicability in cancer and other types of disease.


[Ion permeability of cerebroside and sphingomyelin bilayer membranes].
Ionic conductivity of bilayer membranes formed of cerebrosides and sphingomeylins isolated from bovine brains and its dependence on medium pH were studied. It was found that conductivity of the membranes from cerebrosides in KC1, CaCl2 solutions is 2-3 orders, and from sphingomyelin 1-2 orders higher than that of bilayers from lecithin and phospholipids. Both in cerebroside and sphingomyelin membranes the conductivity depended on medium pH, unlike the bilayer membranes of the brain and liver phospholipids.


Make science evolve into a One Health approach to improve health and security: a white paper.
The World One Health Congresses are biennial gatherings of approximately 1500 professionals from relevant international organisations, OIE, FAO, WHO, World Bank, leading scientific experts and researchers in the field of One Health, animal production and trade, food safety, animal health, human health and environmentology/ecology, government representatives in public health, human health, food safety, environmental health and global health security. The Congress is organized by the One Health Platform. This white paper summarizes highlights of the 5th International One Health Congress in Saskatoon, Canada, June 2018 and serves as a roadmap for the future, detailing several concrete action points to be carried out in the run-up to the 6th World One Health Congress in Edinburgh, Scotland, June 2020.


Reactive thrombocytosis and risk of subsequent venous thromboembolism: a cohort study.
It is uncertain whether reactive thrombocytosis is associated with an increased risk of venous thromboembolism. This study assessed the incidence of reactive thrombocytosis, defined as platelet count ≥ 500 × 10(9) L(-1) , at intensive care unit discharge and its association with subsequent venous thromboembolism. This cohort study involved linkage of routinely collected intensive care unit, laboratory, radiology and death registry data of critically ill patients admitted to the intensive care unit between January 2009 and March 2010. The census date for survival and radiologically confirmed venous thromboembolism was 31 October 2011. Of the 1446 patients who survived to intensive care unit discharge, 139 patients had reactive thrombocytosis (9.6%, 95% confidence interval [CI] 8.2-11.2%). Twenty-nine patients developed venous thromboembolism after discharge (2%, 95% CI 1.4-2.9%; 67 per 100 person-years, 95% CI 45-97) and the median time to develop venous thromboembolism was 25 days (interquartile range 8-148). Reactive thrombocytosis was associated with an increased risk of subsequent venous thromboembolism (hazard ratio 5.3, 95% CI 1.7-16.4), after adjusting for other covariates. Platelet counts explained about 34% of the variability in the risk of venous thromboembolism and had a relatively linear relationship with the risk of venous thromboembolism when the platelet counts were > 400 × 10(9) L(-1) . Venous thromboembolism after intensive care unit discharge was associated with an increased risk of mortality (hazard ratio 2.0, 95% CI 1.1-3.9), after adjusting for reactive thrombocytosis. Reactive thrombocytosis during the recovery phase of critical illness was associated with an increased risk of subsequent venous thromboembolism.


A practical guide to cancer subclonal reconstruction from DNA sequencing.
Subclonal reconstruction from bulk tumor DNA sequencing has become a pillar of cancer evolution studies, providing insight into the clonality and relative ordering of mutations and mutational processes. We provide an outline of the complex computational approaches used for subclonal reconstruction from single and multiple tumor samples. We identify the underlying assumptions and uncertainties in each step and suggest best practices for analysis and quality assessment. This guide provides a pragmatic resource for the growing user community of subclonal reconstruction methods.


Therapeutic Opportunities for Targeting microRNAs in Cancer.
MicroRNAs (miRNAs) are small noncoding RNAs that can function as either powerful tumor promoters or suppressors in numerous types of cancer. The ability of miRs to target multiple genes and biological signaling pathways has created intense interest in their potential clinical utility as predictive and diagnostic biomarkers, and as innovative therapeutic agents. Recently, accumulating preclinical studies have illustrated the feasibility of slowing tumor progression by either overexpressing tumor suppressive miRNAs, or by neutralizing the activities of oncogenic miRNAs in cell- and animal-based models of cancer. Here we highlight prominent miRNAs that may represent potential therapeutic targets in human malignancies, as well as review current technologies available for inactivating or restoring miRNA activity in clinical settings.


A comparison of 4D time-resolved MRA with keyhole and 3D time-of-flight MRA at 3.0 T for the evaluation of cerebral aneurysms.
A subarachnoid hemorrhage (SAH) due to the rupture of a cerebral aneurysm (CA) is a devastating event associated with high rates of mortality. Magnetic resonance angiography (MRA), as a noninvasive technique, is typically used initially. The object of our study is to evaluate the feasibility of 4D time-resolved MRA with keyhole (4D-TRAK) for the diagnostic accuracy and reliability of the detection and characterization of cerebral aneurysms (CAs), with a comparison of 3D time-of-flight MRA (3D-TOF-MRA) by using DSA as a reference. 3D-TOF-MRA, 4D-TRAK and 3D-DSA were performed sequentially in 52 patients with suspected CAs. 4D-TRAK was acquired using a combination of sensitivity encoding (SENSE) and CE timing robust angiography (CENTRA) k-space sampling techniques at a contrast dose of 10 ml at 3 T. Accuracy, sensitivity, specificity of 4D-TRAK and 3D-TOF-MRA were calculated and compared for the detection of CAs on patient-based and aneurysm-based evaluation using 3D-DSA as a reference. The overall image quality of 4D-TRAK with a contrast dose of 10 ml was in the diagnostic range but still cannot be compared with that of 3D-TOF-MRA. In 52 patients with suspected CAs, fifty-eight CAs were confirmed on 3D-DSA finally. Fifty-one (with 2 false-positives and 9 false-negatives) and 58 (with 1 false-positive and 1 false-negative) CAs were visualized on 4D-TRAK and 3D-TOF-MRA, respectively. Accuracy, sensitivity and specificity on patient-based evaluation of 4D-TRAK and 3D-TOF-MRA were 92.31%, 93.33%, 85.71% and 98.08%, 100%, 85.71%, respectively, and 74.07%, 75.00%, 66.67% and 96.30%, 95.83%, 100% on aneurysm-based evaluation in patients with multiple CAs, respectively. Subgroup analysis revealed that for 19 very small CAs (maximal diameter <3 mm, measured on 3D-DSA), 9 were missed on 4D-TRAK and 1 on 3D-TOF-MRA (P = 0.008). However, for 39 CAs with maximal diameter ≥ 3 mm, the diagnostic accuracy is equally (39 on 4D-TRAK vs. 39 on 3D-TOF-MRA) (P = 1). In four larger CAs with maximal diameter ≥ 10 mm, 4D-TRAK provided a better characterization of morphology than 3D-TOF-MRA. 4D-TRAK at a lower contrast dose of 10 ml with a combination of SENSE and CENTRA at 3 T could provide similar diagnostic accuracy rate for CAs with maximal diameter ≥ 3 mm, and a better characterization of morphology for larger CAs with maximal diameter ≥ 10 mm compared to 3D-TOF-MRA. However, further study is still needed to improve the "vascular edge" artifact and the compromise in spatial resolution in depiction of CAs with maximal diameter<3 mm.


A New Activated Sludge Model with Membrane Separation-Implications for Sewage and Textile Effluent.
A new model for the activated sludge process with membrane separation is presented, based on the effective filtration size. A new size threshold is imposed by the membrane module. The model structure requires a modified fractionation of the chemical oxygen demand and includes chemical oxygen demand fractions entrapped in the reactor or in the flocs as model components. This way, it offers an accurate mechanistic interpretation of microbial mechanisms taking place in membrane activated sludge systems. Denim processing wastewater was selected for model implementation, which emphasized the significance of entrapped fractions of soluble hydrolysable and soluble inert chemical oxygen demand responsible for better effluent quality, while underlining the shortcomings of existing activated sludge models prescribed for systems with conventional gravity settling. The model also introduced particle size distribution analysis as a new experimental instrument complementing respirometric assessments, for an accurate description of chemical oxygen demand fractions with different biodegradation characteristics in related model evaluations.


Experimental removal of introduced slider turtles offers new insight into competition with a native, threatened turtle.
The red-eared slider turtle (Trachemys scripta elegans; RES) is often considered one of the world's most invasive species. Results from laboratory and mesocosm experiments suggest that introduced RES outcompete native turtles for key ecological resources, but such experiments can overestimate the strength of competition. We report on the first field experiment with a wild turtle community, involving introduced RES and a declining native species of conservation concern, the western pond turtle (Emys marmorata; WPT). Using a before/after experimental design, we show that after removing most of an introduced RES population, the remaining RES dramatically shifted their spatial basking distribution in a manner consistent with strong intraspecific competition. WPT also altered their spatial basking distribution after the RES removal, but in ways inconsistent with strong interspecific competition. However, we documented reduced levels of WPT basking post-removal, which may reflect a behavioral shift attributable to the lower density of the turtle community. WPT body condition also increased after we removed RES, consistent with either indirect or direct competition between WPT and RES and providing the first evidence that RES can compete with a native turtle in the wild. We conclude that the negative impacts on WPT basking by RES in natural contexts are more limited than suggested by experiments with captive turtles, although wild WPT do appear to compete for food with introduced RES. Our results highlight the importance of manipulative field experiments when studying biological invasions, and the potential value of RES removal as a management strategy for WPT.


Evaluation of promotion of iron-rich foods for the prevention of nutritional anemia in India.
Nutritional anemia due to iron deficiency is the most common cause of anemia in India. The average diet in India is low in iron and mostly of vegetable origin. This can be improved by increasing awareness of foodstuffs that are rich in iron and ensuring their availability. The objective of the study was to assess the quality of information available on iron-rich foods and to assess their production and consumption in India. This was a review of common textbooks for medical, nursing, and home science students; related policy and program documents; and government publications on production and consumption of various foodstuffs in India. Details of specific foods that are rich in iron have not been provided. Instead, food groups such as pulses, cereals, nuts, and green leafy vegetables (GLVs) have been mentioned that are good sources of non-heme iron. This is in spite of the fact that all the foodstuffs in these groups are not uniformly iron rich. Among cereals and pulses, rice and red gram dal (arhar) are the most commonly produced and consumed, though they have the lowest iron content. Spinach and mustard leaves believed to be iron rich and commonly consumed are among those GLVs having lowest iron content. Details of 5-10 foodstuffs which have the highest iron content within each food group should be available in relevant books and documents meant for education, production, and consumption data.


The impact of income definitions on mortality inequalities.
Income is a strong predictor of adult mortality. Measuring income is not as simple as it may sound. It can be conceptualized at the individual or the household level, with the former better reflecting an individual's earning ability, and the latter better capturing living standards. Furthermore, respondents are often grouped into income categories based on their positions in the income distribution, and this operationalization can be done on the basis of age-specific or total population income distributions. In this study, we look at how four combinations of different conceptualizations (individual vs. household) and operationalizations (age-specific vs. total population) of income can affect mortality inequality estimates. Using Finnish registry data, we constructed period life tables for ages 25+ from 1996 to 2017 by gender and for four income definitions. The results indicated that the slope index of inequality for life expectancy varied by 1.1-5.7 years between income definitions, with larger differences observed for women than for men. The overall age patterns of relative index of inequality for mortality rates yielded by the four definitions were similar, but the levels differed. The period trends across income definitions were consistent for men, but not for women. We conclude that researchers should pay particular attention to the choice of the income definitions when analyzing the association between income and mortality, and when comparing the magnitude of inequality across studies and over time.


A case report of a tongue ulcer presented as the first sign of occult tuberculosis.
Tuberculosis (TB) is a serious infectious disease with considerable fatality, typically affecting the pulmonary system and, rarely, other body organs including the oral cavity. Due to the rarity of oral TB, it is frequently overlooked in differential diagnosis of oral lesions. Despite a declining trend in TB incidence in recent years, it is still a major public health problem with high contagiousness, thereby requiring the early diagnosis and prompt treatment. A 57-year-old male patient presented with chief complaint of painful ulcer on tip of his tongue. He reported that the ulcer developed without any remarkable event such as mechanical trauma, vesicle formation or systemic illness. His past medical history revealed the TB over 40 years ago, which had reportedly healed after pharmacological treatments. As the ulceration persisted after topical steroid application and careful education about avoiding possible mechanical stimuli, biopsy was performed and histological finding showed typical findings of oral tuberculosis including intense granulomatous inflammatory features with small red rods of mycobacterial organisms as well as epithelioid cells and Langhans giant cells. After suitable antituberculosis treatments, oral tuberculosis ulcer was almost completely healed. We present a case of oral TB affecting tip of the tongue in a patient with a history of pulmonary TB and emphasize the understanding of intraoral manifestations for early diagnosis and prompt treatment of TB. The present case represented the importance of understanding oral tuberculosis manifestations for dental clinicians who might be frequently the first health care professionals to encounter various oral lesions.


Evaluation of polylactic acid nanoparticles safety using Drosophila model.
Cytotoxicity of nanoparticles and their sub-lethal effect on cell behavior and cell fate are a high topic of studies in the nanomaterial field. With an explosion of nanoparticle types (size, shape, polarity, stiffness, composition, etc.), Drosophila has become an attractive animal model for high throughput analysis of these nanocarriers in the drug delivery field with applications in cancer therapy, or simply to generate a fast and complete cytotoxic study of a peculiar nanoparticle. In respect to that, we have conducted an in cellulo study of poly(lactic acid) (PLA) nanoparticle cytotoxicity, and determined that near lethal nanoparticle doses, oxidative stress as well as P53 and ATP pathways may lead to cell cycle arrest at G1, and ultimately to cell death. Neither viability nor the development of Drosophila larvae are affected by the ingestion of PLA nanoparticles at sub-lethal concentrations. Drosophila will be a useful model to study PLA and PLA-modified nanoparticle toxicity, and nanoparticle fate after ingestion.


Extraordinary case presentations in pediatric pituitary adenoma: report of 6 cases.
Pediatric pituitary adenomas (PPAs) are rare neoplasms with a propensity for unusual presentations and an aggressive clinical course. Here, the authors describe 6 highly atypical PPAs to highlight this tendency and discuss unexpected management challenges.A 14-year-old girl presented with acute hemiparesis and aphasia. MRI revealed a pituitary macroadenoma causing internal carotid artery invasion/obliteration without acute apoplexy, which was treated via emergent transsphenoidal resection (TSR). Another 14-year-old girl developed precocious galactorrhea due to macroprolactinoma, which was medically managed. Several years later, she re-presented with acute, severe, bitemporal hemianopia during her third trimester of pregnancy, requiring emergent induction of labor followed by TSR. A 13-year-old boy was incidentally diagnosed with a prolactinoma after routine orthodontic radiographs captured a subtly abnormal sella. An 18-year-old male self-diagnosed pituitary gigantism through a school report on pituitary disease. A 17-year-old boy was diagnosed with Cushing disease by his basketball coach, a former endocrinologist. A 12-year-old girl with growth arrest and weight gain was diagnosed with Cushing disease, which was initially treated via TSR but subsequently recurred and ultimately required 12 operations, 5 radiation treatments involving 3 modalities, bilateral adrenalectomy, and chemotherapy. Despite these efforts, she ultimately died from pituitary carcinoma.


National health care 'by-passing' in Bangladesh: a comparative study.
Using data from a survey of urban residents of Dhaka, Bangladesh, the phenomenon of by-passing national health care resources in favor of foreign ones has been analyzed. The results clearly suggest that the incidence of national health care by-passing is relatively widespread, particularly among the wealthy residents of Dhaka. The findings of this study show that the health care system in Bangladesh is costly, some specialized care is not available, and the quality of services obtained in foreign countries is perceived as better than what is available nationally. While complete prevention of national health care by-passing is not possible, improvement in health care services available within Bangladesh will help in decreasing the incidence of by-passing.


Targeting Calcium Signaling Induces Epigenetic Reactivation of Tumor Suppressor Genes in Cancer.
Targeting epigenetic pathways is a promising approach for cancer therapy. Here, we report on the unexpected finding that targeting calcium signaling can reverse epigenetic silencing of tumor suppressor genes (TSG). In a screen for drugs that reactivate silenced gene expression in colon cancer cells, we found three classical epigenetic targeted drugs (DNA methylation and histone deacetylase inhibitors) and 11 other drugs that induced methylated and silenced CpG island promoters driving a reporter gene (GFP) as well as endogenous TSGs in multiple cancer cell lines. These newly identified drugs, most prominently cardiac glycosides, did not change DNA methylation locally or histone modifications globally. Instead, all 11 drugs altered calcium signaling and triggered calcium-calmodulin kinase (CamK) activity, leading to MeCP2 nuclear exclusion. Blocking CamK activity abolished gene reactivation and cancer cell killing by these drugs, showing that triggering calcium fluxes is an essential component of their epigenetic mechanism of action. Our data identify calcium signaling as a new pathway that can be targeted to reactivate TSGs in cancer.


Cord blood and breast-milk antibodies in neonatal rotavirus infection.
Studies were carried out during an outbreak of rotavirus type 2 infection in a neonatal nursery to determine the protective role of antibodies in cord blood and breast milk. The range, distribution, and geometric mean titres of rotavirus-specific antibody in the cord blood were similar among rotavirus-positive and rotavirus-negative neonates, and the amount of virus excreted did not correlate with antibody levels. Despite the protective effect of breast feeding, the pattern of rotavirus-specific IgA and IgG antibodies in the expressed breast milk of mothers of babies who were rotavirus excreters and non-excreters was similar. Nevertheless, a higher proportion of expressed breast milk samples contained rotavirus-specific IgA group 2 (92%) and type 2 (97%) specific antibodies than type I (67%) antibodies, and the geometric mean titres of group 2 and type 2 specific antibodies were tenfold higher than type I antibodies. Among breast-fed babies who excreted rotavirus there was no correlation between type 2 rotavirus-specific IgA antibodies in expressed breast milk and the amount of neonatal virus excretion. These studies suggest that factors other than the rotavirus antibodies in expressed breast milk are of importance in preventing rotavirus infection in newborn infants.


Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia.
Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM) pretreatment (24 h) significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2 mg/kg i.p. once a day for 7 days) ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-γ coactivator 1alpha (PGC-1α) and nuclear respiratory factor 1 (NRF1), two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II), markers for autophagy. These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis.


Primary hemiarthroplasty for treatment of proximal humeral fractures.
Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery. A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury. The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p < 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically. Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.


Pannexin1 Channels Are Required for Chemokine-Mediated Migration of CD4+ T Lymphocytes: Role in Inflammation and Experimental Autoimmune Encephalomyelitis.
Pannexin1 (Panx1) channels are large high conductance channels found in all vertebrates that can be activated under several physiological and pathological conditions. Our published data indicate that HIV infection results in the extended opening of Panx1 channels (5-60 min), allowing for the secretion of ATP through the channel pore with subsequent activation of purinergic receptors, which facilitates HIV entry and replication. In this article, we demonstrate that chemokines, which bind CCR5 and CXCR4, especially SDF-1α/CXCL12, result in a transient opening (peak at 5 min) of Panx1 channels found on CD4(+) T lymphocytes, which induces ATP secretion, focal adhesion kinase phosphorylation, cell polarization, and subsequent migration. Increased migration of immune cells is key for the pathogenesis of several inflammatory diseases including multiple sclerosis (MS). In this study, we show that genetic deletion of Panx1 reduces the number of the CD4(+) T lymphocytes migrating into the spinal cord of mice subjected to experimental autoimmune encephalomyelitis, an animal model of MS. Our results indicate that opening of Panx1 channels in response to chemokines is required for CD4(+) T lymphocyte migration, and we propose that targeting Panx1 channels could provide new potential therapeutic approaches to decrease the devastating effects of MS and other inflammatory diseases.


Amyotrophic lateral sclerosis immunoglobulins increase intracellular calcium in a motoneuron cell line.
A hybrid motoneuron cell line (VSC4.1) was used as a model system to study the relationship between alterations in intracellular calcium and subsequent cell death induced by immunoglobulin fractions purified from sera of patients with ALS. Using fluo-3 fluorescence imaging, immunoglobulins from 8 of 10 patients with ALS were found to induce transient increases in intracellular calcium ([Ca2+]i) in differentiated VSC4.1 cells. These transient [Ca2+]i increases required extracellular calcium entry through voltage-gated calcium channels sensitive to synthetic FTX and to high concentrations (>1 microM) of omega-agatoxin IVa. The incidence of transient [Ca2+]i increases induced by ALS immunoglobulins correlated with the extent of cytotoxicity induced by the same ALS immunoglobulins in parallel cultures of VSC4.1 cells. Furthermore, manipulations which blocked transient [Ca2+]i increases (addition of synthetic FTX or omega-agatoxin IVa) also inhibited the cytotoxic effects of ALS immunoglobulins. No transient calcium increases were observed in VSC4.1 cells following addition of immunoglobulins from 7 neurologic disease control patients. However, transient [Ca2+]i increases were observed following addition of immunoglobulins from 4 of 5 patients with myasthenia gravis (MG). The [Ca2+]i changes induced by MG immunoglobulins were not blocked by s-FTX, suggesting that they result from a different mechanism than those induced by ALS immunoglobulins. These results suggest that immunoglobulins from patients with ALS can induce transient increases in intracellular calcium in a motoneuron cell line, which may represent early events in the cascade of processes leading to injury and death of susceptible cells.


Interaction of human monocytes, macrophages, and polymorphonuclear leukocytes with zymosan in vitro. Role of type 3 complement receptors and macrophage-derived complement.
Macrophages take up zymosan in the absence of exogenous complement via receptors for iC3b (type 3 complement receptors) acting with or without lectin-like receptors for mannosyl-fucosyl-terminated glycoconjugates. We previously provided evidence that macrophages themselves secrete complement-alternative pathway components able to opsonize zymosan locally (Ezekowitz et al., J. Exp. Med. 1984. 159:244-260). We show here that covalently bound C3 cleavage products C3b and iC3b can be eluted from zymosan particles cultivated with 36-h adherent human monocytes in the absence of serum. The ligand binding site of type 3 complement receptors is involved in macrophage-zymosan interactions as shown by inhibition studies of zymosan binding and uptake with Fab fragments of anti-C3 antibodies and monoclonal antireceptor antibodies M01 and OKM10. In contrast, antibody IB4, which binds to a receptor epitope distinct from the binding site, does not inhibit zymosan uptake. Selective modulation of macrophage receptors onto anticomplement receptor antibody and mannose-rich yeast mannan, respectively, confirms that the complement and lectin-like receptors are distinct. Human polymorphonuclear leukocytes, which express receptors for complement, but are not known to secrete complement proteins, bind and ingest only exogenously opsonized zymosan. Unopsonized zymosan is a poor trigger of respiratory burst activity in neutrophils or 7-d adherent human macrophages, but induces cell aggregation and secretion of large amounts of superoxide anion when these cells are co-cultivated in serum-free medium and challenged with zymosan. Our studies indicate that complement and/or other products synthesized by macrophages at extravascular sites could play an important role in opsonization and lysis of pathogens able to activate the alternative pathway and mediate macrophage-neutrophil collaboration in first-line host defence.


A vertical microfluidic probe.
Performing localized chemical events on surfaces is critical for numerous applications. We earlier invented the microfluidic probe (MFP), which circumvented the need to process samples in closed microchannels by hydrodynamically confining liquids that performed chemistries on surfaces (Juncker et al. Nat. Mater. 2005, 4, 622-628). Here we present a new and versatile probe, the vertical MFP (vMFP), which operates in the scanning mode while overcoming earlier challenges that limited the practical implementation of the MFP technology. The key component of the vMFP is the head, a microfluidic device (∼1 cm(2) in area) consisting of glass and Si and having microfluidic features fabricated in-plane in the Si layer. The base configuration of the head has two micrometer-size channels that inject/aspirate liquids and terminate at the apex which is ∼1 mm(2). In scanning mode, the head is oriented vertically with the apex parallel to the surface with typical spacing of 1-30 μm. Such length scales and using flow rates from nanoliters/second to microliters/second allow chemical events to be performed on surfaces with tens of picoliter quantities of reagents. Before scanning, the head is clipped on a holder for leak-free, low dead volume interface assembly, providing a simple world-to-chip interface. Surfaces are scanned by mounting the holder on a computer-controlled stage having ∼0.1 μm resolution in positioning. We present detailed steps to fabricate vMFP heads having channels with dimensions from 1 μm × 1 μm to 50 μm × 50 μm for liquid localization over areas of 10-10,000 μm(2). Additionally, advanced design strategies are described to achieve high yield in fabrication and to support a broad range of applications. These include particulate filters, redundant aperture architectures, inclined flow-paths that service apertures, and multiple channels to enable symmetric flow confinement. We also present a method to characterize flow confinement and estimate the distance between the head and the surface by monitoring the evolution of a solution of fluorescently labeled antibody on an activated glass surface. This flow characterization reveals regimes of operation suitable for different surface topographies. We further integrate the dispensing of immersion liquid to the vMFP head for processing surfaces for extended periods of time (∼60 min). The versatility of the vMFP is exemplified by patterning fluorescently labeled proteins, inactivation of cells using sodium hypochlorite, and staining living NIH fibroblasts with Cellomics. These applications are enabled by the compact design of the head, which provides easy access to the surface, simplifies alignment, and enables processing surfaces having dimensions from the micrometer to the centimeter scale and with large topographical variations. We therefore believe that ease-of-operation, reconfigurability, and conservative use of chemicals by the vMFP will lead to its widespread use by microtechnologists and the chemical and biomedical communities.


[Metabolic capacity of skeletal muscles and health].
The metabolic capacity of skeletal muscle plays a significant role for insulin sensitivity and the blood lipid profile. The metabolic capacity of the muscle is a function of the individual's physical activity level. This is also true for the content of type IIx muscle fibres, which is reduced and the number of capillaries, which is elevated with muscle usage. Several of these skeletal muscle features are risk factors for or linked with life style-induced diseases such as type II diabetes, hypertension, hyperlipidaemia and obesity. This central role of the skeletal muscle and its functional metabolic capacity for life style diseases highlights the importance of people maintaining daily physical activity. This article focuses on the link between the metabolic capacity of skeletal muscle and the metabolic syndrome and briefly discusses possible metabolic explanations for this relationship. An important aspect is that when skeletal muscle has a high capacity for lipid oxidation more saturated fatty acids are oxidized and more unsaturated fatty acids are built into the phospholipid fraction of the plasma membrane, giving it more fluidity and improved insulin sensitivity. Moreover, the article points at the role of these fatty acids in activating genes via the PPAR-receptor system essential for enzyme and transport proteins in the lipid metabolism.


Alteration of plasma proteins at metamorphosis in the lamprey (Petromyzon marinus dosatus).
Coincident with metamorphosis in the lamprey (Petromyzon marinus dosatus), a new, more rapidly moving plasma protein component appears. In the mature lamprey this new component is of major quantitative importance. With paper electrophoretic mobility as the sole criterion, the new component is considered to be an alpha globulin rather than albumin.


Using VARK Approach for Assessing Preferred Learning Styles of First Year Medical Sciences Students: A Survey from Iran.
Preferred learning styles of learners are different, which depend on tastes, mentality preparedness, as well as physical condition, in terms of sensory modalities. Identifying and employing appropriate learning styles could play an important role in selecting teaching styles, which can improve education ultimately. The present study aimed to assess the diversity of learning styles amongst medical students of a medical sciences university which was located west of Iran, in 2010. A cross-sectional study which employed VARK learning style's questionnaire was done on 141 first year medical sciences students at Ilam University of Medical Sciences in 2010. Data was collected with use of VARK questionnaire. The validity of the questionnaire was assessed on basis of experts' views and its reliability was calculated by using Cronbach's alpha coefficients (α=0.86). Data were analysed by using SPSS software and Chi-square test. Overall, 41.6% of the samples preferred to use a single learning style (Uni-modal). Of these, 17.7% preferred the Aural style, 17% preferred Reading and Writing, 6.4% preferred Kinesthetic style and 0.7% preferred Visual styles. Among the rest of the 82 students who preferred more than one style (multimodal), 17% chose two modes (bimodal), 13.5% chose three modes (tri-modal), and 27.6% chose four modes (quad-modal). There was a significant difference between educational levels and majors on one hand and choice of quad modal of VARK styles on the other hand (p=0.008). A significant association was also found between participants' genders and selection of visual and reading/writing styles (p=0.03). The preferred learning styles of medical students in the present study were aural and reading/writing. It is suggested that all medical students must be tested to determine their desired learning styles by using VARK questionnaire, also to choose appropriate teaching methods and to improve educational goals.


Regulating DNA Self-Assembly Dynamics with Controlled Nucleation.
Controlling the nucleation step of a self-assembly system is essential for engineering structural complexity and dynamic behaviors. Here, we design a "frame-filling" model system that comprises one type of self-complementary DNA tile and a hosting DNA origami frame to investigate the inherent dynamics of three general nucleation modes in nucleated self-assembly: unseeded, facet, and seeded nucleation. Guided by kinetic simulation, which suggested an optimal temperature range to differentiate the individual nucleation modes, and complemented by single-molecule observations, the transition of tiles from a metastable, monomeric state to a stable, polymerized state through the three nucleation pathways was monitored by Mg2+-triggered kinetic measurements. The temperature-dependent kinetics for all three nucleation modes were correlated by a "nucleation-growth" model, which quantified the tendency of nucleation using an empirical nucleation number. Moreover, taking advantage of the temperature dependence of nucleation, tile assembly can be regulated externally by the hosting frame. An ultraviolet (UV)-responsive trigger was integrated into the frame to simultaneously control "when" and "where" nucleation started. Our results reveal the dynamic mechanisms of the distinct nucleation modes in DNA tile-based self-assembly and provide a general strategy for controlling the self-assembly process.


LUBAC Formation Is Impaired in the Livers of Mice with MCD-Dependent Nonalcoholic Steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is a disorder characterized by hepatic lipid accumulation followed by the inflammation-induced death of hepatocytes and fibrosis. In this process, oxidative stress contributes to the induction of several inflammatory cytokines including TNF-α andIL-1β in macrophages, while, in hepatocytes, NF-κB reportedly induces the expressions of cell survival genes for protection from apoptosis. Recently, it was reported that the new ubiquitin ligase complex termed linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on NF-κB essential modulator (NEMO) and thereby induces NF-κB pathway activation. In this study, we demonstrated the formation of LUBAC to be impaired in the livers of NASH rodent models produced by methionine and choline deficient (MCD) diet feeding, first by either gel filtration or Blue Native-PAGE, with subsequent confirmation by western blotting. The reduction of LUBAC is likely to be attributable to markedly reduced expression of SHARPIN, one of its components. Thus, impaired LUBAC formation, which would result in insufficient NF-κB activation, may be one of the molecular mechanisms underlying the enhanced apoptotic response of hepatocytes in MCD diet-induced NASH livers.


Post-discharge health education for patients with enterostomy: A nationwide interventional study.
After discharge, patients with enterostomy face problems with poor self-nursing ability and low levels of psychological and social adjustment, which, without timely intervention, seriously affect their quality of life. We delivered health education to discharged enterostomy patients based on a WeChat health management program and evaluated its impact on their ostomy self-care ability and psychosocial adaptation level. Based on the WeChat health management program, we conducted continuous health education in the first, third, seventh, 11th, and 23rd weeks after discharge of enterostomy patients/before temporary enterostomy restoration to observe its impact on their self-care ability and psychosocial adaptation levels, as evaluated by an ostomy self-care ability questionnaire and ostomy adjustment inventory-20 checklist. We included 4201 patients with enterostomy. Our findings showed that the self-care score of patients with enterostomy at discharge (baseline) (mean = 15.23, standard deviation (SD) = 5.22) was lower than that after intervention (mean = 17.71, SD = 1.28) (P < 0.05). The enterostomy psychosocial adaptation score of the enterostomy patients at discharge (baseline) (mean = 44.59, SD = 9.82) was lower than that after intervention (mean = 50.25, SD = 12.97) (P < 0.05). Health education for enterostomy patients after discharge can improve their self-care ability and psychological adaptation. Future studies could further explore the views and attitudes of this population toward health education based on the WeChat health management program.


Isolation and characterization of the 5' region of the human mismatch repair gene hPMS1.
The hPMS1 gene encodes a mutL homolog that is implicated in DNA mismatch repair and was found to be mutated in the germline of a patient with hereditary nonpolyposis colorectal cancer (HNPCC). To understand transcriptional regulation and to perform mutational analysis in the promoter region, we cloned and characterized the genomic sequence of the 5' region of the gene. hPMS1 has an intron upstream of the initiation codon. There were several transcripts with alternative splicing sites and multiple transcriptional start sites. The cloned 1.4-kbp fragment of the 5' region contains a CpG island but no TATA-boxes, typical for promoters of housekeeping genes. The promoter activity of the fragment was almost equal to that of the SV40 early promoter. Deletion analysis showed that about a 300-bp region was sufficient to initiate transcription. Although we searched for mutations in the hPMS1 promoter region in HNPCC kindreds, neither germline nor somatic mutations were detected. However, we found a highly informative polymorphism in the first exon that is useful for searching allelic losses because no polymorphic changes in hPMS1 have been reported previously.


A Local Planner for Accurate Positioning for a Multiple Steer-and-Drive Unit Vehicle Using Non-Linear Optimization.
This paper presents a local planning approach that is targeted for pseudo-omnidirectional vehicles: that is, vehicles that can drive sideways and rotate on the spot. This local planner-MSDU-is based on optimal control and formulates a non-linear optimization problem formulation that exploits the omni-motion capabilities of the vehicle to drive the vehicle to the goal in a smooth and efficient manner while avoiding obstacles and singularities. MSDU is designed for a real platform for mobile manipulation where one key function is the capability to drive in narrow and confined areas. The real-world evaluations show that MSDU planned paths that were smoother and more accurate than a comparable local path planner Timed Elastic Band (TEB), with a mean (translational, angular) error for MSDU of (0.0028 m, 0.0010 rad) compared to (0.0033 m, 0.0038 rad) for TEB. MSDU also generated paths that were consistently shorter than TEB, with a mean (translational, angular) distance traveled of (0.6026 m, 1.6130 rad) for MSDU compared to (0.7346 m, 3.7598 rad) for TEB.


Background parenchymal enhancement at breast MR imaging: normal patterns, diagnostic challenges, and potential for false-positive and false-negative interpretation.
At magnetic resonance (MR) imaging, both normal and abnormal breast tissue enhances after contrast material administration. The morphology and temporal degree of enhancement of pathologic breast tissue relative to normal breast tissue form the basis of MR imaging's diagnostic accuracy in the detection and diagnosis of breast disease. Normal parenchymal enhancement at breast MR imaging is termed background parenchymal enhancement (BPE). BPE may vary in degree and distribution in different patients as well as in the same patient over time. Typically BPE is minimal or mild in overall degree, with a bilateral, symmetric, diffuse distribution and slow early and persistent delayed kinetic features. However, BPE may sometimes be moderate or marked in degree, with an asymmetric or nondiffuse distribution and rapid early and plateau or washout delayed kinetic features. These patterns cause diagnostic difficulty because these features can be seen with malignancy. This article reviews typical and atypical patterns of BPE seen at breast MR imaging. The anatomic and physiologic influences on BPE in women undergoing diagnostic and screening breast MR imaging are reviewed. The potential for false-positive and false-negative interpretations due to BPE are discussed. Radiologists can improve their interpretive accuracy by increasing their understanding of various BPE patterns, influences on BPE, and the potential effects of BPE on MR imaging interpretation.


[Thermography in assessing the microcirculation of patients with acute and chronic viral hepatitis].
The important role is emphasized of microcirculatory disorders in the pathogenesis of viral hepatitis and the necessity of their early diagnosis. For this purpose the method of infrared thermography of the upper extremities (hands) was used that allowed to reveal pronounced disorders of the peripheral hemodynamics in a significant number of patients with acute and chronic viral hepatitis, in particular, hepatitis B that promoted a more severe, progressive course of the disease. It is concluded that for instituting pathogenetically substantiated treatment, prognosis and prevention of unfavourable outcomes it is necessary to supplement clinico-laboratory data by instrumental examination of the terminal blood flow, in particular, thermography of the extremities.


Diversity and biogeography of a species-rich ant fauna of the Australian seasonal tropics.
Although ants are an ecologically dominant and extensively studied faunal group throughout the tropics, there is a poor understanding of tropical ant diversity and distribution at large spatial scales. Here we use a collection developed from 3 decades of ant surveys to present the first analysis of ant diversity and biogeography of a large tropical region. Our objective was to document the species richness, composition, and biogeographic distributions of the ant fauna of the 400 000 km2 "Top End" of Australia's Northern Territory. The known Top End ant fauna comprises 901 native species from 59 genera. The richest genera are Pheidole (90 species), Melophorus (83), Monomorium (83), Camponotus (71), Meranoplus (63), Polyrhachis (57), Rhytidoponera (50), Tetramorium (43), Cerapachys (32), and Iridomyrmex (31). The fauna is the center of diverse radiations within species-groups of genera such as Meranoplus, Rhytidoponera, and Leptogenys. It also includes IndoMalayan species that have likely bypassed the normal dispersal route into Australia through Cape York Peninsula in North Queensland. Faunistic similarity with other regions of far northern Australia is associated more with rainfall than with geographic proximity. Most (60%) of Top End ant species have not been recorded elsewhere, and, despite uncertainties relating to species delimitation and sampling intensity, this appears to be a credible estimate of the level of endemism. Such exceptionally high endemism can be attributed to the Top End's geographic isolation from other regions of northern Australia with comparably high rainfall.


Current management of Hodgkin's disease.
The accepted management of Hodgkin's disease has changed markedly in the past two decades. It should be considered a tumor of unifocal origin and potentially one of the most curable cancers, given early diagnosis, careful evaluation, meticulously accurate staging and aggressive, radical treatment. This requires a team effort, is tedious and expensive, and morbidity and mortality remain significant, but the high yield of long remissions and apparent cures justifies this approach to the problem.


Validation of 11 kGy as a radiation sterilization dose for frozen bone allografts.
A radiation sterilization dose (RSD) of 25 kGy is deleterious to bone allografts. This study aimed to establish a lower RSD for bone allografts using method 1 of International Standard Organisation 11137.2:2006. This provides a database to select an RSD corresponding to an allograft's bioburden, given that the bioburden's gamma resistance is equal to or less than the standard. This can be verified by irradiating 100 allografts at a dose selected to provide a sterility assurance level of 10(-2). The bioburden of our allografts was 0, which prescribed a verification dose of 1.3 kGy. After irradiating 100 allografts, sterility tests returned no positive cultures. We therefore validated an RSD of 11 kGy for allografts with that bioburden. According to the standard, this RSD provides a sterility assurance level of 10(-6) for bone allografts.


On the complexity of chloroplast RNA metabolism: psaA trans-splicing can be bypassed in chlamydomonas.
In the chloroplast, the posttranscriptional steps of gene expression are remarkably complex. RNA maturation and translation rely on a large cohort of nucleus-encoded proteins that act specifically on a single target transcript or a small set of targets. For example in the chloroplast of Chlamydomonas, trans-splicing of the two split introns of psaA requires at least 14 nucleus-encoded proteins. To investigate the functional significance of this complex trans-splicing pathway, we have introduced an intron-less copy of psaA in the chloroplast genomes of three mutants deficient in trans-splicing and of the wild type. We find that the intron-less psaA gene rescues the mutant phenotypes. The growth of strains with the intron-less psaA is indistinguishable from the wild type under the set of different experimental conditions that were investigated. Thus, the trans-splicing factors do not appear to have any other essential function and trans-splicing of psaA can be bypassed. We discuss how these observations support the hypothesis that complex RNA metabolism in the chloroplast may in part be the result of a nonadaptive evolutionary ratchet. Genetic drift may lead to the accumulation of chloroplast mutations and the recruitment of compensatory nuclear suppressors from large preexisting pools of genes encoding RNA-binding proteins.


Behavioral and Neural Fusion of Expectation with Sensation.
Humans perceive expected stimuli faster and more accurately. However, the mechanism behind the integration of expectations with sensory information during perception remains unclear. We investigated the hypothesis that such integration depends on "fusion"-the weighted averaging of different cues informative about stimulus identity. We first trained participants to map a range of tones onto faces spanning a male-female continuum via associative learning. These two features served as expectation and sensory cues to sex, respectively. We then tested specific predictions about the consequences of fusion by manipulating the congruence of these cues in psychophysical and fMRI experiments. Behavioral judgments and patterns of neural activity in auditory association regions revealed fusion of sensory and expectation cues, providing evidence for a precise computational account of how expectations influence perception.


Self-reported urinary continence outcomes for repeat midurethral synthetic sling placement.
To evaluate our experience with tension-free transvaginal tape (TVT) placement for the management of stress urinary incontinence (SUI) in women who had previously undergone a failed midurethral synthetic sling (MUS) procedure. Ten women underwent retropubic TVT insertion for continued or recurrent SUI following a prior MUS procedure. No attempt was made to remove the previously placed sling at the time of surgery. A retrospective chart review was performed to obtain perioperative and follow-up patient information. Post-operatively, each patient completed a mailed incontinence questionnaire to assess self-reported urinary continence outcomes. All 10 women were available for follow-up at a mean period of 16 months (range 6 to 33). Four of the 10 patients achieved complete continence, and another three patients reported significantly improved continence and quality of life. Three women stated that their continence did not improve. TVT placement may be a viable option for the management of women with persistent or recurrent SUI following an initial MUS procedure.


Changes in the contents of oleoresin and pungent bioactive principles of Jamaican ginger (Zingiber officinale Roscoe.) during maturation.
Changes in the yields of the oleoresin and content of pungent bioactive principles: [6], [8], [10] gingerols and [6] shogaol of Jamaican ginger ( Zingiber officinale) were investigated during different stages of maturity (7-9 months). Ethanolic oleoresin extracts were prepared (95%, w/w) by cold maceration of dried ginger powder, and their percentage yields were calculated (w/w). The pungent bioactive principles in the ginger oleoresin were extracted with methanol and quantitatively analyzed by high performance liquid chromatography (HPLC). Ginger harvested at 8 months from Bourbon, Portland had the highest oleoresin yield (8.46 +/- 0.46%). [6] Gingerol was found to be the most abundant pungent bioactive principle in all the oleoresin samples investigated, with the 9 months sample from Bourbon, Portland containing the highest level (28.94 +/- 0.39%). The content of [6] gingerols was also found to be consistently high (7-9 months) in oleoresin samples from Johnson Mountain, St. Thomas (15.12 +/- 0.39 to 16.02 +/- 0.95%). The results suggest that Bourbon in Portland may be the most ideal location for cultivating ginger for high yields and quality, however, Johnson Mountain in St. Thomas could prove to be the least restrictive location, allowing for harvesting of good quality material throughout the maturity period (7-9 months).


Psychiatric diagnosis as a risk marker for victimization in a national sample of children.
Research examining childhood abuse has shown an association between victimization and psychiatric diagnoses (e.g., posttraumatic stress disorder, depression). Historically, psychiatric diagnoses have been emphasized as a consequence of victimization, with less research examining if it also functions as a risk factor for further victimization, perhaps making diagnoses a general victimization risk marker. In addition, much of this research has emphasized particular types of victimization such as childhood physical or sexual abuse. Researchers have given less attention to other forms of victimization (e.g., peer victimization, witnessed violence) or a diverse victimization history. Using the Juvenile Victimization Questionnaire (JVQ) we surveyed parents and children between the ages of 2 and 17 using a random digit dial (RDD) methodology. We examined the relationship between a number of different forms of victimization (termed poly-victimization ) in the preceding year and parent-reported lifetime psychiatric diagnosis. Results show that children with a psychiatric diagnosis have significantly higher rates of victimization than children without a psychiatric diagnosis. In addition, using logistic regression models, we find that psychiatric diagnosis was associated with increased risk for poly-victimization, conventional crime victimization, maltreatment, peer or sibling victimization, and witnessing violence, but not sexual abuse. The results highlight the need to consider psychiatric diagnoses as a risk marker for past and possible future victimization. In addition, the importance of obtaining a comprehensive and more diverse victimization history when working with children is highlighted.