Caregiver burden in atypical dementias: comparing frontotemporal dementia, Creutzfeldt-Jakob disease, and Alzheimer's disease.
Caregiver burden is a significant issue in the treatment of dementia and a known contributor to institutionalization of patients with dementia. Published data have documented increased caregiver burden in behavioral variant frontotemporal dementia (bvFTD) compared to Alzheimer's disease (AD). Another atypical dementia with high-perceived caregiver burden is sporadic Creutzfeldt-Jakob disease (sCJD), but no formal studies have assessed this perception. The aim of this study was to compare caregiver burden across atypical dementia etiologies. 76 adults with atypical dementia (young-onset AD [YOAD], bvFTD, language variant FTD [lvFTD], and sCJD) were administered an abbreviated version of the Zarit Burden Interview (ZBI), Neuropsychiatric Inventory (NPI-Q), and other assessment instruments during a five-year time period at Johns Hopkins Hospital (JHH). A Cox regression model examined differences between disease categories that impact mean ZBI scores. Mean ZBI scores were significantly different between dementia etiologies, with bvFTD and sCJD having the highest caregiver burden (p = 0.026). Mean NPI-Q caregiver distress scores were highest in bvFTD and sCJD (p = 0.002), with sCJD and bvFTD also having the highest number of endorsed symptom domains (p = 0.012). On regression analyses, an interactive variable combining final diagnosis category and NPI-Q total severity score demonstrated statistically significant differences in mean ZBI scores for sCJD and bvFTD. This study demonstrates that bvFTD and sCJD have increased levels of caregiver burden, NPI-Q caregiver distress, total severity scores, and number of endorsed symptom domains. These results suggest that higher caregiver burden in bvFTD and sCJD are disease specific and possibly related to neuropsychiatric symptoms.


Study on Elastic Mixed Mode Fracture Behavior and II-III Coupling Effect.
Mixed mode fracture is a widely studied topic, while the coupling effects of mixed mode cracking are unclear. In this paper, elastic fracture behaviors and the coupling effects of the mixed mode cracks are studied in detail based on the finite element method, experimental study and linear elastic fracture mechanics. Results show that there always exist II-III coupling effects at the crack tips of mixed mode cracks, which have many effects on the crack tip field and crack propagation behavior. It is found that a mode II component at the tip of a mixed mode crack is the main reason for crack deflection, while the mode III components show no effect. For any mixed mode crack, mode II components at the crack tip can be divided as that by mode II loading which causes plane crack propagation, and by the coupling effect which causes spatial crack propagation. On this basis, a new fracture criterion suitable for any mixed mode crack is proposed, combined with the coupling effect and the linear elastic superposition principle. The research in this paper provides a solution to the problem of an II-III coupling effect in mixed mode fracture research and further promotes the development of fracture mechanics.


Radical graft polymerization of an allyl monomer onto hydrophilic polymers and their antibacterial nanofibrous membranes.
Hydrophilic poly (vinyl alcohol-co-ethylene) (PVA-co-PE) copolymers with 27 mol %, 32 mol % and 44 mol % ethylene were functionalized by melt radical graft copolymerization with 2,4-diamino-6-diallylamino-1,3,5-triazine (NDAM) using reactive extrusion. This functionalization imparts antibacterial properties. The covalent attachments of the NDAM as side chains onto the PVA-co-PE polymer backbones were confirmed. The effects of initiator concentrations and ethylene contents in PVA-co-PE polymers on grafting of NDAM were studied. The chain scissions of PVA-co-PE polymers during reactive extrusion were investigated by monitoring changes in the melt torque and FTIR spectra. The NDAM grafted PVA-co-PE polymers were successfully fabricated into hydrophilic nanofibers and nanofibrous membranes with sufficient surface exposure of the grafted NDAM. The hydrophilicity of the PVA-co-PE polymers and the large specific surface area offered by the nanofiber membranes significantly facilitated the chlorine activation process, enhanced the active chlorine contents of the grafted PVA-co-PE nanofiber membranes, and therefore led to their superior antibacterial properties.


Platinum nanoparticle shape effects on benzene hydrogenation selectivity.
Benzene hydrogenation was investigated in the presence of a surface monolayer consisting of Pt nanoparticles of different shapes (cubic and cuboctahedral) and tetradecyltrimethylammonium bromide (TTAB). Infrared spectroscopy indicated that TTAB binds to the Pt surface through a weak C-H...Pt bond of the alkyl chain. The catalytic selectivity was found to be strongly affected by the nanoparticle shape. Both cyclohexane and cyclohexene product molecules were formed on cuboctahedral nanoparticles, whereas only cyclohexane was produced on cubic nanoparticles. These results are the same as the product selectivities obtained on Pt(111) and Pt(100) single crystals in earlier studies. The apparent activation energy for cyclohexane production on cubic nanoparticles is 10.9 +/- 0.4 kcal/mol, while for cuboctahedral nanoparticles, the apparent activation energies for cyclohexane and cyclohexene production are 8.3 +/- 0.2 and 12.2 +/- 0.4 kcal/mol, respectively. These activation energies are lower, and corresponding turnover rates are three times higher than those obtained with single-crystal Pt surfaces.


Cancer Screening Markers: A Simple Strategy to Substantially Reduce the Sample Size for Validation.
Studies to validate a cancer prediction model based on cancer screening markers collected in stored specimens from asymptomatic persons typically require large specimen collection sample sizes. A standard sample size calculation targets a true-positive rate (TPR) of 0.8 with a 2.5% lower bound of 0.7 at a false-positive rate (FPR) of 0.01 with a 5% upper bound of 0.03. If the probability of developing cancer during the study is P = 0.01, the specimen collection sample size based on the standard calculation is 7600. The strategy to reduce the specimen collection sample size is to decrease both the lower bound of TPR and the upper bound of FPR while keeping a positive lower bound on the anticipated clinical utility. The new sample size calculation targets a TPR of 0.4 with a 2.5% lower bound of 0.10 and an FPR of 0.0 with a 5% upper bound of 0.005. With P = 0.01, the specimen collection sample size based on the new calculation is 1800 instead of 7600. The new sample size calculation requires a minimum benefit/cost ratio (number of false positives traded for a true positive). With P = 0.01, the minimum cost-benefit ratio is 5, which is plausible in many studies. In validation studies for cancer screening markers, the strategy can substantially reduce the specimen collection sample size, substantially reducing costs and making some otherwise infeasible studies now feasible.


Return probabilities and hitting times of random walks on sparse Erdös-Rényi graphs.
We consider random walks on random graphs, focusing on return probabilities and hitting times for sparse Erdös-Rényi graphs. Using the tree approach, which is expected to be exact in the large graph limit, we show how to solve for the distribution of these quantities and we find that these distributions exhibit a form of self-similarity.


Biclustering microarray data by Gibbs sampling.
Gibbs sampling has become a method of choice for the discovery of noisy patterns, known as motifs, in DNA and protein sequences. Because handling noise in microarray data presents similar challenges, we have adapted this strategy to the biclustering of discretized microarray data. In contrast with standard clustering that reveals genes that behave similarly over all the conditions, biclustering groups genes over only a subset of conditions for which those genes have a sharp probability distribution. We have opted for a simple probabilistic model of the biclusters because it has the key advantage of providing a transparent probabilistic interpretation of the biclusters in the form of an easily interpretable fingerprint. Furthermore, Gibbs sampling does not suffer from the problem of local minima that often characterizes Expectation-Maximization. We demonstrate the effectiveness of our approach on two synthetic data sets as well as a data set from leukemia patients.


The Different Functional Distribution of "Not Effector" T Cells (Treg/Tnull) in Colorectal Cancer.
Colorectal cancer (CRC) is the third most common cancer worldwide, ranking as high as the second leading cause of cancer-related deaths in industrialized countries. Consistent with immunosurveillance theory, the immune system is crucial to protect the host from developing tumors, and the major players in tumoral immunity are effector T cells. Anyway, cancer cells develop strategies of immunoevasion influencing the cancer-specific lymphocyte priming, activation, and effector function. Therefore, the T cell subsets that mature during the stages of tumor growth, differently contribute to disease progression and/or regression. In our study, we analyzed the intra-tumoral and peripheral T cell subsets' distribution in 30 patients with CRC, in order to clarify their functional role toward cancer. We found that percentage of infiltrating effector T cells decreased in cancer tissue than in healthy mucosa and that the tumor microenvironment negatively influences the cytolytic activity of T lymphocytes reactive to cancer cells. Moreover, we found that the tumor tissue was infiltrated by a large amount of "not effector" T (neT) cells with a regulatory or an anergic profile, which are unable to kill cancer cells, may be contributing to the CRC promotion. The presence of neT cells was investigated also in the peripheral blood of CRC patients, demonstrating that the peripheral T regulatory cells can inhibit the proliferation of effector T cells, confirming their immunosuppressive properties. Finally, monitoring the changes in circulating neT cells' frequencies after the tumor removal, we confirmed the role of cancer in the modulation of immune system, in particular, in supporting a Tregs-mediated immunosuppression.


Simulated microgravity-mediated reversion of murine lymphoma immune evasion.
No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4+ and CD8+ T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4+ T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4+ T cell response and augmented CD8+ T cell-mediated destruction of the cancer cells in vitro and in vivo. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor's escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth.


A comparative cohort study of totally laparoscopic and open aortobifemoral bypass for the treatment of advanced atherosclerosis.
Totally laparoscopic aortobifemoral bypass (LABF) procedure has been shown to be feasible for the treatment of advanced aortoiliac occlusive disease (AIOD). This study compares the LABF with the open aortobifemoral bypass (OABF) operation. In this prospective comparative cohort study, 50 consecutive patients with type D atherosclerotic lesions in the aortoiliac segment were treated with an LABF operation. The group was compared with 30 patients who were operated on with the OABF procedure for the same disease and time period. We had an explanatory strategy, and our research hypothesis was to compare the two surgical procedures based on a composite event (all-cause mortality, graft occlusion, and systemic morbidity). Stratification analysis was performed by using the Mantel-Haenszel method with the patient-time model. Cox multivariate regression method was used to adjust for confounding effect after considering the proportional hazard assumption. Cox proportional cause-specific hazard regression model was used for competing risk endpoint. There was a higher frequency of comorbidity in the OABF group. A significant reduction of composite event, 82% (hazard ratio 0.18; 95% CI 0.08-0.42, P=0.0001) was found in the LABF group when compared with OABF group, during a median follow-up time period of 4.12 years (range from 1 day to 9.32 years). In addition, less operative bleeding and shorter length of hospital stay were observed in the LABF group when compared with the OABF group. All components of the composite event showed the same positive effect in favor of LABF procedure. LABF for the treatment of AIOD, Trans-Atlantic Inter-Society Consensus II type D lesions, seems to result in a less composite event when compared with the OABF procedure. To conclude, our results need to be replicated by a randomized clinical trial.


Pre-steady-state kinetic analysis of 1-deoxy-D-xylulose-5-phosphate reductoisomerase from Mycobacterium tuberculosis reveals partially rate-limiting product release by parallel pathways.
As part of the non-mevalonate pathway for the biosynthesis of the isoprenoid precursor isopentenyl pyrophosphate, 1-deoxy-D-xylulose-5-phosphate (DXP) reductoisomerase (DXR) catalyzes the conversion of DXP into 2-C-methyl-D-erythritol 4-phosphate (MEP) by consecutive isomerization and NADPH-dependent reduction reactions. Because this pathway is essential to many infectious organisms but is absent in humans, DXR is a target for drug discovery. In an attempt to characterize its kinetic mechanism and identify rate-limiting steps, we present the first complete transient kinetic investigation of DXR. Stopped-flow fluorescence measurements with Mycobacterium tuberculosis DXR (MtDXR) revealed that NADPH and MEP bind to the free enzyme and that the two bind together to generate a nonproductive ternary complex. Unlike the Escherichia coli orthologue, MtDXR exhibited a burst in the oxidation of NADPH during pre-steady-state reactions, indicating a partially rate-limiting step follows chemistry. By monitoring NADPH fluorescence during these experiments, the transient generation of MtDXR·NADPH·MEP was observed. Global kinetic analysis supports a model involving random substrate binding and ordered release of NADP(+) followed by MEP. The partially rate-limiting release of MEP occurs via two pathways--directly from the binary complex and indirectly via the MtDXR·NADPH·MEP complex--the partitioning being dependent on NADPH concentration. Previous mechanistic studies, including kinetic isotope effects and product inhibition, are discussed in light of this kinetic mechanism.


Miliary Tuberculosis in a Crohn's Disease Patient: The Risk beyond the Screening.
Tumor necrosis factor alpha (TNFα) antagonist is recognized as an effective treatment to achieve clinical remission and healing mucosal in patients with moderate to severe active Crohn's disease. Considering that it plays a central role in immune-mediated modulation, there are some obvious concerns about its long-term safety. There is evidence that it may increase the risk of opportunistic infections such as tuberculosis, particularly reactivation of previous latent infection. Due to the global high incidence of tuberculosis and its frequent severity in immunocompromised patients, the exclusion of latent infection is currently part of the screening prior to anti-TNFα therapy. Only a few cases of life-threatening disseminated tuberculosis have been reported in immunocompromised patients probably related to widespread use of higher-accuracy screening tests, such as interferon-γ release assays. However, despite negative screening, the risk of active tuberculosis infection remains during treatment. In that instance, tuberculosis infection becomes considerably more difficult to diagnose due to its altered pattern presentation (extrapulmonary and disseminated infection) and is harder to treat because of the high rate of resistance and its associated relevant morbidity and mortality. We report an enigmatic case of a miliary tuberculosis despite negative latent infection screening, using interferon-γ release assays, in a Crohn's disease patient undergoing treatment with infliximab and azathioprine, focusing on the screening and diagnostic and therapeutic challenge. This case enhances the awareness of anti-TNFα therapy management and the need for strategies to diagnose and treat tuberculosis in this context.


School counselor advocacy for gender minority students.
One-thousand-one-hundred-and-ninety-one school counselors completed an online survey regarding advocacy for and with gender minority students comprising transgender and intersex students (school counselor gender minority advocacy competence). School counselors completed a battery of three competency-based assessments to assess their levels of gender identity counselor competence, intersex counselor competence, and school counselor gender minority advocacy competence. They also completed a demographic form so that competency levels could be examined with demographic variables. Attitudes, school level placement, gender, sexual orientation, gender identity counselor competence, and intersex counselor competence were significantly related to advocacy for and with gender minority students. These findings have implications for the application of identity behavior theory to examine the experiences and behaviors of minoritized individuals and those who advocate for them. These advocates include school counselors and other helping professionals who work with gender minority students.


A mechanism for TAFs in transcriptional activation: activation domain enhancement of TFIID-TFIIA--promoter DNA complex formation.
TATA-binding protein (TBP)-associated factors (TAFs) in TFIID are required for activator proteins to stimulate transcription, but the mechanism by which TAFs function is poorly understood. To study how TAFs participate in transcriptional activation by the Epstein-Barr virus activator Zta, we used agarose gel electrophoresis and DNase I footprinting to compare transcription complex assembly in reactions with either TFIID or TBP in the presence and absence of wild-type Zta or a deletion of Zta lacking its activation domain. A stable complex of promoter DNA with Zta, TFIIA, and TFIID rapidly formed on a template with Zta-binding sites. Zta stimulation of stable complex formation required TAFs as well as the Zta activation domain and TFIIA. The Zta activation domain also induced a TAF-dependent DNA-protein interaction near and downstream of the transcription star site. Stable complexes formed within 1 min supported activated transcription when RNA polymerase II and the remaining general transcription factors were subsequently added. This rapid assembly of a stable Zta-TFIIA-TFIID-promoter complex is probably a significant component of the mechanism by which TAFs and the Zta activation domain cooperate to stimulate transcription.


The use of copper-lowering therapy with tetrathiomolybdate in medicine.
Tetrathiomolybdate (TM), an anticopper drug, has been developed for the neurologic presentation of Wilson's disease. In animal models, lowering copper levels with TM produces antifibrotic, anti-inflammatory, antiautoimmune, and anticancer effects, thought to be due to inhibition of many cytokines that are dependent on available copper for their activity. Clinical testing has been done relatively extensively in Wilson's disease and advanced cancers, but remains in its infancy in other diseases. To review current preclinical and clinical studies done with TM, and our current knowledge of TM efficacy and toxicity. We have reviewed the last 10 years of literature on TM therapy. TM has excellent efficacy and acceptable toxicity for the initial treatment of neurologically presenting Wilson's disease. TM has excellent efficacy in animal models of fibrotic, inflammatory, autoimmune, and neoplastic diseases, as well as Alzheimer's disease models.


Antimicrobial Resistance of Tannin Extract against E. coli Isolates from Sheep.
Plants have been long valuable sources of natural materials that have served to preserve human and animal health; as a result, pharmacological purposes have arisen from the use of plant compounds in most countries, according to a World Health Organization report. The present study aimed to assess the antimicrobial resistance of tannin extract against Escherichia coli (E. coli) isolates in sheep. A total of 100 samples from sheep were used to isolate E. coli and treated with tannin extract (90% purity) to investigate the in vitro effect, as compared to some antibiotics (Clindamycin, Cephalexin, Kanamycin, Tetracycline, and Vancomycin). The bacterial samples were cultured in a selective and differential medium, and Gram staining was used to examine them. The biochemical assays were performed to purify and expose these cultures; moreover, the API 20E system and RapidTM ONE kits were utilized to confirm the bacterial strain. Based on the findings, 50% of the samples showed a positive result for the presence of E. coli. The well diffusion technique was used to investigate the antibacterial activity to confirm the antibacterial action of tannin extract (from pomegranate peel) in different concentrations against E. coli. The highest zone of inhibition for the bacteria ranged from 12±0.5 to 30.3±0.2 at 50% concentrations, proving that tannins extract was significantly effective against E. coli. The presence of E. coli was detected in 50 % of the samples. The well-diffusion technique was used to evaluate the antimicrobial property of tannin extract through various concentrations with the highest zone of inhibition for the bacteria ranging from 12.5 to 30.30.2 at 50%, demonstrating that tannin extract was significantly effective on E. coli.


Exploiting 4-1BB costimulation for enhancing antiviral vaccination.
4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is emerging as an important costimulatory molecule, particularly in the regulation of CD8(+) T cell responses. Costimulation through 4-1BB, such as by utilizing agonistic anti-4-1BB monoclonal antibodies, has been well studied in various tumor models. However, 4-1BB is also an important regulator of antiviral CD8(+) T cell responses. This review summarizes these findings and describes how 4-1BB is beginning to be exploited in terms of boosting antiviral vaccine responses.


Effect of slaughter house pollution on the biochemical composition of Channa orientalis.
The present study deals with the biochemical composition of Channa orientalis from a habitat polluted by slaughter house wastes in comparison to an unpolluted habitat of Mudasarlova stream of Visakhapatnam. The total proteins, carbohydrates and lipids were found to be less in the organisms collected from the polluted habitat. The probable reasons for these variations are discussed in detail.


Synthesis and Functional Characterization of Caffeic Acid Glucoside Using Leuconostoc mesenteroides Dextransucrase.
Caffeic acid was modified via transglucosylation using sucrose and dextransucrase from Leuconostoc mesenteroides B-512FMCM. Following enzymatic modification, a caffeic acid glucoside was isolated by butanol separation, silica gel chromatography, and preparative HPLC. The synthesized caffeic acid glucoside had a molecular mass-to-charge ratio of 365 m/z, and its structure was identified as caffeic acid-3-O-α-d-glucopyranoside. The production of this caffeic acid-3-O-α-d-glucopyranoside at a concentration of 153 mM was optimized using 325 mM caffeic acid, 355 mM sucrose, and 650 mU mL-1 dextransucrase in the synthesis reaction. In comparison with the caffeic acid, the caffeic acid-3-O-α-d-glucopyranoside displayed 3-fold higher water solubility, 1.66-fold higher antilipid peroxidation effect, 15% stronger inhibition of colon cancer cell growth, and 11.5-fold higher browning resistance. These results indicate that this caffeic acid-3-O-α-d-glucopyranoside may be a suitable functional component of food and pharmaceutical products.


Stepwise formation of a SMAD activity gradient during dorsal-ventral patterning of the Drosophila embryo.
Genetic evidence suggests that the Drosophila ectoderm is patterned by a spatial gradient of bone morphogenetic protein (BMP). Here we compare patterns of two related cellular responses, both signal-dependent phosphorylation of the BMP-regulated R-SMAD, MAD, and signal-dependent changes in levels and sub-cellular distribution of the co-SMAD Medea. Our data demonstrate that nuclear accumulation of the co-SMAD Medea requires a BMP signal during blastoderm and gastrula stages. During this period, nuclear co-SMAD responses occur in three distinct patterns. At the end of blastoderm, a broad dorsal domain of weak SMAD response is detected. During early gastrulation, this domain narrows to a thin stripe of strong SMAD response at the dorsal midline. SMAD response levels continue to rise in the dorsal midline region during gastrulation, and flanking plateaus of weak responses are detected in dorsolateral cells. Thus, the thresholds for gene expression responses are implicit in the levels of SMAD responses during gastrulation. Both BMP ligands, DPP and Screw, are required for nuclear co-SMAD responses during these stages. The BMP antagonist Short gastrulation (SOG) is required to elevate peak responses at the dorsal midline as well as to depress responses in dorsolateral cells. The midline SMAD response gradient can form in embryos with reduced dpp gene dosage, but the peak level is reduced. These data support a model in which weak BMP activity during blastoderm defines the boundary between ventral neurogenic ectoderm and dorsal ectoderm. Subsequently, BMP activity creates a step gradient of SMAD responses that patterns the amnioserosa and dorsomedial ectoderm.


Enhanced Na+/H+ exchange activity contributes to the pathogenesis of muscular dystrophy via involvement of P2 receptors.
A subset of muscular dystrophy is caused by genetic defects in dystrophin-associated glycoprotein complex. Using two animal models (BIO14.6 hamsters and mdx mice), we found that Na(+)/H(+) exchanger (NHE) inhibitors prevented muscle degeneration. NHE activity was constitutively enhanced in BIO myotubes, as evidenced by the elevated intracellular pH and enhanced (22)Na(+) influx, with activation of putative upstream kinases ERK42/44. NHE inhibitor significantly reduced the increases in baseline intracellular Ca(2+) as well as Na(+) concentration and stretch-induced damage, suggesting that Na(+)(i)-dependent Ca(2+)overload via the Na(+)/Ca(2+) exchanger may cause muscle damage. Furthermore, ATP was found to be released continuously from BIO myotubes in a manner further stimulated by stretching and that the P2 receptor antagonists reduce the enhanced NHE activity and dystrophic muscle damage. These observations suggest that autocrine ATP release may be primarily involved in genesis of abnormal ionic homeostasis in dystrophic muscles and that Na(+)-dependent ion exchangers play a critical pathological role in muscular dystrophy.


Singlet oxygen-mediated inactivation of acetylcholinesterase: a comparison of purified enzyme in solution and enzyme bound to K562 leukemia cells.
We have compared the singlet oxygen-mediated inactivation of acetylcholinesterase (ACE) in solution with the inactivation of ACE on the surface of K562 leukemia cells. In solution, the actions of the singlet-oxygen quenchers, methionine, azide, disodium [N,N'-ethylenebis (5-sulfosalicylideneimminato)]nickelate(II) (Ni-chelate 1) and disodium [(N,N'-2,3-propionic acid)bis(5-sulfosal-icylideneimminato)] nickelate(II) (Ni-chelate 2) could be explained quantitatively by assuming their only mechanism of action was to quench singlet oxygen. The singlet oxygen quenchers, azide, Ni-chelate 1 and Ni-chelate 2, caused smaller inhibitions in the rate of singlet oxygen-mediated inactivation of ACE on K562 cells than ACE in solution. The effects of these quenchers and of deuterium oxide were interpreted using a mathematical model of singlet-oxygen quenching and diffusion to estimate the lifetime of singlet oxygen near the cell surface. The azide quenching data and the deuterium-oxide data gave lifetimes of 0.9 +/- 0.2 microsecond and 0.45 +/- 0.15 microsecond, respectively. The increases in ACE inactivation lifetime caused by the nickel chelates were anomalously large. The unexpectedly large quenching due to the nickel chelates may have been due to a nonuniform distribution of the chelates in the cytoplasm with a large concentration of the chelate near the cell membrane.


The Gluteus Medius Tendon and Its Insertion Sites: An Anatomical Study with Possible Implications for Gluteus Medius Tears.
Gluteus medius tears are a common hip disorder. Despite this, the etiology of these tears and the anatomical background of the gluteus medius tendon remain unclear. This study aimed to clarify the characteristics of the gluteus medius tendon. We hypothesized that the tendinous portions of the gluteus medius have a nonuniform structure contributing to the tear etiology. Twenty-five hips from 15 Japanese cadavers were analyzed. Twenty-one of the hips were analyzed macroscopically, and the other 4 were analyzed histologically. In all of the specimens, the 3-dimensional (3D) morphology of the greater trochanter was examined using microcomputed tomography (micro-CT). In 10 of the 21 hips analyzed macroscopically, the local thickness of the gluteus medius tendon, detached from the greater trochanter, was measured. The posterior and anterolateral parts of the gluteus medius tendons were roughly distinguished on the basis of the aspects of the iliac origins. The posterior part of the gluteus medius tendon ran in a fan-like shape and converged onto the superoposterior facet of the greater trochanter. The anterolateral part ran posteroinferiorly toward the lateral facet of the greater trochanter. The thickness was greater in the posterior part than in the anterolateral part, and the border between these 2 parts was relatively thin compared with the other parts. The histological study showed that both the posterior and anterolateral parts inserted onto the greater trochanter via fibrocartilage. The gluteus medius tendon consists of thick posterior and thin anterolateral parts, which were identified by the facet or aspect of the bone structures and thinness of their border region. Our findings indicate that, given the nonuniform structure of the gluteus medius tendon, the thin anterolateral part may be more prone to tears than the thick posterior part is and tears may generally be limited to the anterolateral part.


Acute in vivo performance evaluation of the fluorescence affinity sensor in the intravascular and interstitial space in Swine.
We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model. The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6-7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein. Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ± 9.6%] and 23.8% (SD = ± 19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ± 12.5%). The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.


Implementing laparoscopy in Brazil's National Public Health System: the bariatric surgeons' point of view.
Although Brazilian National Public Health System (BNPHS) has presented advances regarding the treatment for obesity in the last years, there is a repressed demand for bariatric surgeries in the country. Despite favorable evidences to laparoscopy, the BNPHS only performs this procedure via laparotomy. 1) Estimate whether bariatric surgeons would support the idea of incorporating laparoscopic surgery in the BNPHS; 2) If there would be an increase in the total number of surgeries performed; 3) As well as how BNPHS would redistribute both procedures. A panel of bariatric surgeons was built. Two rounds to answer the structured Delphi questionnaire were performed. From the 45 bariatric surgeons recruited, 30 (66.7%) participated in the first round. For the second (the last) round, from the 30 surgeons who answered the first round, 22 (48.9%) answered the questionnaire. Considering the possibility that BNPHS incorporated laparoscopic surgery, 95% of surgeons were interested in performing it. Therefore, in case laparoscopic surgery was incorporated by the BNPHS there would be an average increase of 25% in the number of surgeries and they would be distributed as follows: 62.5% via laparoscopy and 37.5% via laparotomy. 1) There was a preference by laparoscopy; 2) would increase the number of operations compared to the current model in which only the laparotomy is available to users of the public system; and 3) the distribution in relation to the type of procedure would be 62.5% and 37.5% for laparoscopy laparotomy.


Bias at the intersection of race and gender: Evidence from preschool-aged children.
There is ample evidence of racial and gender bias in young children, but thus far this evidence comes almost exclusively from children's responses to a single social category (either race or gender). Yet we are each simultaneously members of many social categories (including our race and gender). Among adults, racial and gender biases intersect: negative racial biases are expressed more strongly against males than females. Here, we consider the developmental origin of bias at the intersection of race and gender. Relying on both implicit and explicit measures, we assessed 4-year-old children's responses to target images of children who varied systematically in both race (Black and White) and gender (male and female). Children revealed a strong and consistent pro-White bias. This racial bias was expressed more strongly for males than females: children's responses to Black boys were less positive than to Black girls, White boys or White girls. This outcome, which constitutes the earliest evidence of bias at the intersection of race and gender, underscores the importance of addressing bias in the first years of life.


Growth hormone induced lipolysis during short- and long-term administration in adult Prader-Willi patients.
Prader-Willi syndrome (PWS) is a complex genetic disease, clinically characterised by short stature, abnormal body composition, with more body fat than lean body mass, hyperphagia and obesity. Partial growth hormone (GH) deficiency is common, and GH treatment to PWS children and adults has shown beneficial effects on body composition. In this study, we have evaluated indices of GH's lipolytic effect in 6 PWS adults analysing glycerol, lactate and glucose in dialysate from microdialysis in subcutaneous abdominal adipose tissue. The patients were four men and two women, 19-37 years old; all hypogonadal. BMI was 24.2-49.1, mean 35.9 kg/m(2). All had normal serum insulin levels. They received GH therapy (Genotropin Pfizer) during 12 months and doses were individually titrated to normal serum IGF-I for age. Immediately before treatment start and at 12 months, 30-36 h after the last GH injection, sampling of dialysate was carried out at night (11 p.m. to 7 a.m.), as well as after intravenously injection of a standardised GH dose (0.8 mg). At baseline individual mean night time glycerol and lactate were similar to levels in adults without PWS (160.7-278.1 micromol/L and 0.80-3.99 mmol/L, respectively), and did not change with 12 months GH treatment. Glucose levels were normal, except in a patient with diabetes, and did not change during the study. Compared to baseline the immediate effect of GH injection resulted in a significant increase in glycerol levels after 12 months. In conclusion, night time lipolytic response in this small group of PWS adults seemed normal and did not change after 12 months GH treatment. On the other hand short-term GH induced lipolysis increased, indicating normal lipolytic response in PWS.


Smoking among medical and engineering students.
A cross-sectional survey, using an anonymous self-administered questionnaire, was conducted among 364 medical and engineering students in their first and later years of study. The study compared knowledge, attitudes towards smoking, and smoking practices between the faculties and between the years. The prevalence of current smoking was 24.1%. It was similar in each faculty and in every year, despite greater knowledge on the adverse health effects of smoking among students in the higher years in the faculty of medicine. Greater knowledge of the risks of smoking is not sufficient to bring about a reduction in smoking habits.


Doxycycline as Potential Anti-cancer Agent.
Cancer cells do create hostile microenvironment (deprivation of nutrients, accumulation of acidity, anoxic habitat). Those cells are not only adapted to this sanctuary environment, blunting of immunity but also, grow, migrate to the distal area (metastasis) and communicate with each other in a unique population structure and organization too (clonal expansion). The adaptation requirements push those types of adaptable cells (cancer cells) to be primitive cells. The prevailing pharmacological approach in treating cancer is developing a chemotherapeutic agent that acts on rapidly proliferating cells that are stuck with normally growing epithelium and bone marrow too. The latter approach has been drafted to work on cellular target under the term of "targeted therapy" believing that each target represents Achilles Heels of cancer. In this article, we try to introduce a new concept of cancer pharmacology, by offering new off-label use of Doxycycline, which is characterized by selective toxicity, as potential anticancer agents. This notion is relying on the absence of taxonomic barriers.


Inpatient Unit Leaders' Perspectives on Parent Engagement in Neonatal and Pediatric Intensive Care: A Secondary, Qualitative Analysis.
Hospital unit leaders help set the unit's priorities and are responsible for guiding the unit mission and philosophy of care; however, the perspective of leaders in facilitating parent engagement within intensive care units is limited. The purpose of this study was to explore how medical and nursing unit leaders facilitate parent engagement in intensive care settings. Qualitative secondary analysis of 16 semistructured interviews of unit leadership (medical directors and nurse managers). Directed content analysis explored themes within the interviews using systematic strategies to ensure rigor. Unit leadership described 3 main features of care delivery necessary for supporting parent engagement: (1) culture of care, (2) relationships in care, and (3) environment of care. Communication among providers and parents and timing of decision-making were key areas addressed, along with concerns about physical space limiting parent engagement. Unit leaders discussed how the 3 main features (unit culture, relationships, and physical space) of care delivery were interconnected to optimize parent engagement. Overall, unit leaders recognized the importance of each feature of care delivery in facilitating engagement. Parent engagement is ultimately influenced by the optimization of delivering inclusive care: the physical space, the policies surrounding medical and nursing care, and the overall culture of the unit. Future research needs to explore best practices around relationship building and managing space limitations. Further clarification of the needs and expectations of both parents and providers surrounding parent engagement in intensive care settings is needed.


Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DsrEFH from Allochromatium vinosum.
In purple sulfur bacteria, the proteins encoded by dsr genes play an essential role in the oxidation of intracellular sulfur, which is an obligate intermediate during the oxidation of sulfide and thiosulfate. One such gene product, DsrEFH from Allochromatium vinosum, has been cloned, expressed, purified and crystallized. Synchrotron data were collected to 2.5 A from a crystal of selenomethionine-substituted DsrEFH. The crystal belongs to the primitive monoclinic space group P2(1), with unit-cell parameters a = 56.6, b = 183.1, c = 107.8 A, beta = 99.6 degrees. A full structure determination is under way in order to provide insight into the structure-function relationships of this protein.


Elastic and piezoelectric properties of AlN and LiAlO2 single crystals.
We have successfully grown high-quality AlN piezoelectric single crystal using the sublimation technique. Transparent crack-free boules of approximately 15 mm in diameter and 25 mm in length along the [0001] direction were obtained, with coloring from amber to dark brown depending on growth temperature. Full sets of material parameters of grown AlN and commercially available LiAlO(2) bulk crystals were measured at room temperature. Temperature coefficients of the material parameters of LiAlO(2) were also obtained in a temperature range from -70 to +50 degrees C.


Identifying multivariate disease trajectories and potential phenotypes of early knee osteoarthritis in the CHECK cohort.
To gain better understanding of osteoarthritis (OA) heterogeneity and its predictors for distinguishing OA phenotypes. This could provide the opportunity to tailor prevention and treatment strategies and thus improve care. Ten year follow-up data from CHECK (1002 early-OA subjects with first general practitioner visit for complaints ≤6 months before inclusion) was used. Data were collected on WOMAC (pain, function, stiffness), quantitative radiographic tibiofemoral (TF) OA characteristics, and semi-quantitative radiographic patellofemoral (PF) OA characteristics. Using functional data analysis, distinctive sets of trajectories were identified for WOMAC, TF and PF characteristics, based on model fit and clinical interpretation. The probabilities of knee membership to each trajectory were used in hierarchical cluster analyses to derive knee OA phenotypes. The number and composition of potential phenotypes was selected again based on model fit (silhouette score) and clinical interpretation. Five trajectories representing different constant levels or changing WOMAC scores were identified. For TF and PF OA, eight and six trajectories respectively were identified based on (changes in) joint space narrowing, osteophytes and sclerosis. Combining the probabilities of knees belonging to these different trajectories resulted in six clusters ('phenotypes') of knees with different degrees of functional (WOMAC) and radiographic (PF) parameters; TF parameters were found not to significantly contribute to clustering. Including baseline characteristics as well resulted in eight clusters of knees, dominated by sex, menopausal status and WOMAC scores, with only limited contribution of PF features. Several stable and progressive trajectories of OA symptoms and radiographic features were identified, resulting in phenotypes with relatively independent symptomatic and radiographic features. Sex and menopausal status may be especially important when phenotyping knee OA patients, while radiographic features contributed less. Possible phenotypes were identified that, after validation, could aid personalized treatments and patients selection.


Incidence of atrial fibrillation in elderly patients with type 2 diabetes mellitus.
The incidence of atrial fibrillation (AF), a significant risk factor for cardiovascular disease (CVD), is increasing worldwide. Type 2 diabetes mellitus (T2D) and advanced age are recognized as major risk factors for AF, but herein, we evaluated the incidence of AF in elderly patients with T2D and compared the prognosis between these patients with/without AF. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD2) study is a follow-up cohort study of the JPAD trial, a randomized controlled clinical trial initiated in 2002 in 2535 Japanese patients with T2D, to examine whether low-dose aspirin prevents CVD. After completion of that trial, we followed up the patients until 2019 and evaluated the incidence of AF. We also compared the incidence of cerebral cardiovascular events in elderly patients with T2D with/without AF. During the median follow-up period of 10.9 years, 132 patients developed AF (incidence rate: 5.14/1000 person-years). The adjusted HRs for cerebral cardiovascular events, stroke, coronary artery disease, heart failure, and all-cause death in elderly patients with T2D with versus without AF were 1.65 (95% CI 1.03 to 2.66), 1.54 (95% CI 0.81 to 2.93), 1.96 (95% CI 1.03 to 3.73), 5.17 (95% CI 2.46 to 10.89), and 1.82 (95% CI 1.24 to 2.67), respectively. Annually, 1 in 200 elderly Japanese patients with T2D are estimated to develop AF. Because elderly patients with T2D with AF are at an elevated risk for CVD, careful follow-up of this patient subgroup is necessary. NCT00110448.


Human liver glucuronidation of benzidine.
Although glucuronidation is considered an important pathway in aromatic amine-induced bladder cancer, benzidine glucuronidation has not been assessed in humans. Glucuronidation of benzidine was assessed with human liver microsomes and slices. Emulgen 911-treated microsomes exhibited a Km for benzidine of 0.8 +/- 0.06 mM and a Vmax of 4.2 +/- 0.7 nmol/mg protein/min. A variety of agents were tested for their ability to inhibit benzidine N-glucuronide formation. At 0.25 mM, estriol, 17-epiestriol, bilirubin, hyodeoxycholic acid and cyproheptadine were good inhibitors (< 50% of control). Dose-dependent inhibition studies with estriol, testosterone and 4-aminobiphenyl demonstrated that each agent reached a plateau as its concentration was increased. When these agents were combined at maximal inhibitory concentrations, additive inhibition was observed. These results suggest that more than one UDP-glucuronosyltransferase metabolizes benzidine. The cDNA clones pUDPGTh-1 and -2 encode transferases which metabolize hyodeoxycholic acid and estrogen derivatives, but neither transferase catalyzed benzidine glucuronidation. Slices were used to assess metabolism by intact tissue and converted [3H]benzidine (0.09 mM) to N-acetyl-benzidine. N-Glucuronides of both benzidine and N-acetylbenzidine were observed and represented 14-37% of the total recovered radioactivity. The amount of N-acetylbenzidine N'-glucuronide observed was proportional to the amount of N-acetylbenzidine produced. Thus, N-glucuronidation appears to represent a major pathway for metabolism of benzidine in humans. The extent of N-acetylation affects the proportion of benzidine and N-acetylbenzidine glucuronidated by human liver slices.


Characterization of T cell clones from an athymic mouse.
Although Thy-1+ lymphocytes have been observed in lymphoid tissues of athymic mice, attempts to analyze these cells on the clonal level have previously yielded only populations of CD4-CD8+ cytolytic T cells. Furthermore, studies of responses of these cells to various mitogenic stimuli have demonstrated significant defects in the ability of these cells to proliferate in culture. We report here on the cloning and maintenance in long term culture of T cells from an athymic mouse stimulated in vitro with allogeneic spleen cells. Of 10 Thy-1+ clones, 7 CD4+CD8- and 3 CD4-CD8+ Ag-specific cells were obtained. Among the CD4+ T cells, we observed a variety of specificities, including an autoreactive I-Aq specific clone, a minor lymphocyte stimulating determinant (Mls)-reactive clone, and five allo-I-Ad-specific CD4+ clones; a class II-specific CD4-CD8+ clone was also obtained. In addition, we observed two Thy-1-CD3+ clones (one of which is also CD4+ and expresses V beta 8) which are constitutively responsive to the lymphokines IL-2 and IL-4. Of 11 clones tested, 7 produce IL-2 and/or IL-4 lymphokines after stimulation through the TCR, whereas 4 do not, requiring exogenous lymphokines for optimal responses to Ag. Of 10 clones tested for IL-2R expression, 3 had notably low levels, correlating with low proliferative responses to IL-2. The results reveal the spectrum of T cells available to a mouse which is congenitally athymic and describe the heterogeneity of immune defects expressed in such cells at the clonal level.


Synthesis in vitro of keratin polypeptides directed by mRNA isolated from newborn and adult mouse epidermis.
A method is described which allows the isolation of undegraded total cellular RNA from living epidermis in a one-step procedure. Epidermal tissue is homogenized in 4 M guanidinium thiocyanate/2% sarkosyl buffer and centrifuged through a 5.7 M CsCl cushion. Under appropriate density conditions in the homogenate, large amounts of RNA are sedimented free of DNA and protein to the bottom of the tubes. A prerequisite for the applicability of this method is the preparation of pure epidermis under conditions which efficiently inactivate endogenous RNases. Oligo(dT) affinity chromatography of total RNA yields 3-4% of polyadenylated RNA. Translation of poly(A)-rich fractions from both newborn and adult mouse epidermis in a cell-free reticulocyte system leads to the synthesis of proteins with electrophoretic mobilities identical to those of native keratin polypeptides of the corresponding tissue. Similar to native keratin polypeptides, these proteins are highly insoluble and can selectively be enriched by high-salt extraction of the translation assays. The CNBr cleavage pattern of these purified proteins is identical to that of native keratins. There is no evidence for the synthesis of precursors of these proteins.


[Approach to the patient in the ambulatory surgery unit].
Ambulatory surgery aims to improve the quality of care, provide services in an environment closer to users' normal surroundings, reduce the risk of nosocomial infection and release hospital beds for other uses demanded by the population, thus reducing health costs. Nursing activity in these units should aim to restore health and aid the rapid recovery of patients in their homes. To achieve this, an effective health education program is required. Such programs should be simple and, at the same time, cover the care that these patients will require during the recovery period at home. The unit covers patients in the Virgen de Rocío University Hospital, The Fleming Peripheral Center for Specialties and the Virgen de los Reyes Peripheral Center for Specialties in Seville, Spain and the the specialties included are plastic surgery, otorhinolaryngology, orthopedic surgery, urology, and general surgery. The duration of the education program will be at most 14-17 h.


Investigating psychosocial aspects of participation in early anti-cancer drug trials: towards a choice of methodology.
This paper presents the methodological approach and research methods chosen to explore psychosocial aspects of participation in early anti-cancer drug trials from the perspective of those actually involved. The paper describes how an appropriate methodology, or principles of reasoning behind the choice of research methods, emerged. The choice of methodology was based on three elements: first, an understanding of the competing philosophies about how research can be approached and conducted; second, the author's view of the subject area; and third, a consideration of previous research approaches which have investigated psychosocial aspects of cancer clinical trials. A qualitative methodology situated within an interpretative paradigm was eventually chosen as the most appropriate means of exploring trial participants' experiences and the aim and objectives of the research were developed within this methodological framework.


Cronobacter sakazakii Pyridoxal Kinase PdxY Mediated by TreR and pESA3 Is Essential for Vitamin B6 (PLP) Maintenance and Virulence.
Cronobacter sakazakii is an opportunistic pathogen capable of causing severe infections, particularly in neonates. Despite the bacterium's strong pathogenicity, the pathogenicity of C. sakazakii is not yet well understood. Using a comparative proteomic profiling approach, we successfully identified pdxY, encoding a pyridoxal kinase involved in the recycling of pyridoxal 5'-phosphate (PLP), as a gene essential for the successful pathogenesis of C. sakazakii. Knocking out the pdxY gene resulted in slower growth and reduced virulence. Our study sheds light on the fundamental importance of pyridoxal kinase for the survival and virulence of C. sakazakii. The identification of pdxY as gene essential for successful pathogenesis provides a potential target for the development of new antibiotic treatments. IMPORTANCE The opportunistic pathogen Cronobacter sakazakii is known to cause severe infections, particularly in neonates, and can result in high mortality rates. In this study, we used a comparative proteomic profiling approach to identify genes essential for the successful pathogenesis of C. sakazakii. We successfully identified pdxY, encoding a pyridoxal kinase involved in the salvage pathway of pyridoxal 5'-phosphate (PLP), as a gene essential for the successful pathogenesis of C. sakazakii. Knocking out the pdxY gene resulted in impaired growth and reduced virulence. This study sheds light on the fundamental importance of pyridoxal kinase for the survival and virulence of C. sakazakii, which can be a potential target for the development of new antibiotic treatments. This study highlights the importance of comparative proteomic profiling in identifying virulence factors that can be targeted for the development of new antibiotics.


Cellular and molecular mechanisms in angiogenesis.
Low concentrations of copper sulphate, Dispirin, or Walker carcinoma extract elicit intraocular vascularization when tested by anterior chamber implants in rats. The response is markedly depressed by pre-treatment of animals with methylprednisolone acetate, suggesting that such induced vascularization is mediated by leucocytes. Since many agents inducing vascularization also induce migration of cultured endothelial cells, it raises the problem of how to isolate and study the action of possible leucocyte-derived angiogenic factors. Regardless of the identity of the natural angiogenic factor or factors, it is proposed that during blood vessel formation specialized endothelial cells migrate in response to an angiogenic signal and deposit fibronectin on which other cells can track and subsequently adhere, forming an endothelium.


Enhanced cardiomyogenic induction of mouse pluripotent cells by cyclic mechanical stretch.
The cardiac milieu is mechanically active with spontaneous contraction beginning from early development and persistent through maturation and homeostasis, suggesting that mechanical loading may provide a biomimetic myocardial developmental signal. In this study, we tested the role of cyclic mechanical stretch loading in the cardiomyogenesis of pluripotent murine embryonic (P19) stem cells. A Flexcell tension system was utilized to apply equiaxial stretch (12% strain, 1.25 Hz frequency) to P19 cell-derived embryoid bodies (EBs). Interestingly, while control EBs without any further stimulation did not exhibit cardiomyogenesis, stretch stimulation alone could induce P19-derived EBs to become spontaneously beating cardiomyocytes (CMs). The beating colony number, average contracting area, and beating rate, as quantified by video capturing and framed image analysis, were even increased for stretch alone case relative to those from known biochemical induction with 5-Azacytidine (5-Aza). Key CM differentiation markers, GATA4 and Troponin T, could also be detected for the stretch alone sample at comparable levels as with 5-Aza treatment. Stretch and 5-Aza co-stimulation produced in general synergistic effects in CM developments. Combined data suggest that stretch loading may serve as a potent trigger to induce functional CM development in both beating dynamics and genomic development, which is still a challenge for myocardial regenerative medicine.


MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies.
High throughput gene expression profiling (GEP) is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option.GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported. MAF (MicroArray Facility) is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking), data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF. MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for shared facilities and industry service providers alike.


Transcription and translation in an RNA world.
The RNA world hypothesis requires a ribozyme that was an RNA-directed RNA polymerase (ribopolymerase). If such a replicase makes a reverse complementary copy of any sequence (including itself), in a simple RNA world, there is no mechanism to prevent self-hybridization. It is proposed that this can be avoided through the synthesis of a parallel complementary copy. The logical consequences of this are pursued and developed in a computer simulation, where the behaviour of the parallel copy is compared to the conventional reverse complementary copy. It is found that the parallel copy is more efficient at higher temperatures (up to 90 degrees C). A model for the ribopolymerase, based on the core of the large subunit (LSU) of the ribosome, is described. The geometry of a potential active site for this ribopolymerase suggests that it contained a cavity (now occupied by the aminoacyl-tRNA) and that an amino acid binding in this might have 'poisoned' the ribopolymerase by cross-reacting with the nucleoside-triphosphate before polymerization could occur. Based on a similarity to the active site components of the class-I tRNA synthetase enzymes, it is proposed that the amino acid could become attached to the nascent RNA transcript producing a variety of aminoacylated tRNA-like products. Using base-pairing interactions, some of these molecules might cross-link two ribopolymerases, giving rise to a precursor of the modern ribosome. A hybrid dimer, half polymerase and half proto-ribosome, could account for mRNA translocation before the advent of protein elongation factors.


Clinical studies with treated clotting factor concentrates.
We carried out safety studies in 45 previously untreated patients with congenital coagulatory defects, who needed to be treated with clotting factor concentrates. Non-A, non-B hepatitis developed in patients who received dry heated F VIII preparations with or without chloroform, but not in those who were infused with hot-steam treated F VIII or chromatography treated F IX. Hepatitis B developed in 3 unvaccinated patients who received the same lot of hot steam treated F VIII. None of the 45 patients we have investigated developed HTLV-III/LAV antibody. Thus, dry heating of concentrates does not prevent hepatitis transmission. Hot-steam and hydrophobic interaction chromatography seem to be more effective in preventing hepatitis transmission, but not completely safe. All the above procedures except hot steam seem to protect from hepatitis B. They all seem to prevent HTLV-III/LAV transmission.


ET nurses: on the front line of health care reform.
The most important challenge at the forefront of the national agenda is the need for health care reform. Major concerns of the current system are cost and access to care. This article discusses numerous congressional proposals and strategies for addressing these concerns. ET nurses are in a unique position to influence health care delivery. The Wound Ostomy and Continence Nurses Society has implemented strategies that position ET nurses as part of the solution to the health care crisis. ET nurses must also market themselves in their individual settings as key players in health care reform.


[CHADS₂versus CHA₂DS₂-VASc scoring systems for predicting left atrial thrombus in patients with nonvalvular atrial fibrillation].
To assess the correlation of CHADS₂and CHA₂DS₂-VASc scores for left atrial thrombus in patients with nonvalvular atrial fibrillation and the differences in the results between the two scoring systems. A total of 397 patients with nonvalvular atrial fibrillation were enrolled in this study. The CHADS₂and CHA2DS2-VASc scoring systems were used for evaluating the risk of left atrial thrombus and their differences in the scores and risk stratifications were compared. The correlation of CHADS₂ and CHA₂DS₂-VASc scores with left atrial thrombus was analyzed. The average score of CHA₂DS₂-VASc was significantly higher than that of CHADS₂in these patients (1.37 ± 1.19 vs 0.63 ± 0.78, P<0.001). The proportion of high-risk group was significantly higher (P<0.001) while that of low-risk group significantly lower as stratified by CHA₂DS₂-VASc scores than by CHADS₂scores (P<0.001). Transesophageal echocardiography detected left atrial thrombus in 44 of the total patients. The prevalence of left atrial thrombus increased significantly with a higher risk stratification by CHADS₂or CHA₂DS₂-VASc scores (P<0.05). Univariate analysis showed that female gender, age ≥ 65 years, left atrium diameter ≥ 38 mm, left ventricular ejection fraction ≤ 40%, hypertension, diabetes, coronary heart disease, stroke history, CHADS₂≥ 2, and CHA₂DS₂-VASc ≥ 2 were all correlated with left atrial thrombus, but multivariate logistic analysis identified only CHA₂DS₂-VASc ≥ 2 as the independent risk factor for left atrial thrombus (OR=9.85, 95% CI: 2.178-44.542, P < 0.01). The average score of CHA₂DS₂-VASc is higher than that of CHADS₂and has better predictive ability for left atrial thrombus.


Delayed Thoracodorsal Artery Perforator Free Flap for Calcaneal Degloving Injury Reconstruction.
The thoracodorsal artery perforator (TDAP) flap has a long vascular pedicle that is ideal for lower extremity reconstruction, but it generally relies on the presence of a dominant septocutaneous perforator vessel. Surgical delay optimizes flap survival by creating relative ischemia to augment perforator vessels. In this report, we describe the use of a delayed free TDAP flap in the setting of an absent dominant perforator vessel for the reconstruction of a calcaneal degloving injury. A 22-year-old actively smoking patient with a body mass index of 33.5 presented with a nonhealing left heel wound with overlying necrotic changes after traumatic degloving injury. The entire weight-bearing portion of the calcaneal fat pad and the flanking regions were debrided. The TDAP flap was elevated, revealing three small thoracodorsal artery perforators. Given that a dominant perforator was absent, the flap was surgically delayed. Free-tissue transfer occurred 8 days later. This operation was conducted entirely in left lateral decubitus with simultaneous wound preparation and flap harvest. The flap was elevated on two perforators to elongate the pedicle's length and inset to cover exposed calcaneus and pad the heel. Six months postoperatively, the patient is doing well without flap compromise or ulceration. The TDAP flap is a versatile microsurgical tool, and surgical delay extends the utility of this flap when a dominant septocutaneous perforator is unavailable. Recipient site debridement may occur simultaneously with the TDAP delay procedure. Importantly, only one position is required for flap elevation, microsurgical anastomosis, and insetting, thus obviating intraoperative repositioning.


Extraversion and risk preference in portfolio theory.
One hundred seventy-eight male and female undergraduates completed the Eysenck Personality Inventory and indicated their risk preference assessed under the assumptions of Coombs' portfolio theory. Extraverts preferred higher risk significantly more than did introverts, and also showed significantly greater risk preference change as expected value increased. It was suggested that a theoretically defensible selection of both personality variables and a risk assessment model may lead to greater personality-risk predictability.


Developing Athlete Monitoring Systems in Team Sports: Data Analysis and Visualization.
In professional team sports, the collection and analysis of athlete-monitoring data are common practice, with the aim of assessing fatigue and subsequent adaptation responses, examining performance potential, and minimizing the risk of injury and/or illness. Athlete-monitoring systems should be underpinned by appropriate data analysis and interpretation, to enable the rapid reporting of simple and scientifically valid feedback. Using the correct scientific and statistical approaches can improve the confidence of decisions made from athlete-monitoring data. However, little research has discussed and proposed an outline of the process involved in the planning, development, analysis, and interpretation of athlete-monitoring systems. This review discusses a range of methods often employed to analyze athlete-monitoring data to facilitate and inform decision-making processes. There is a wide range of analytical methods and tools that practitioners may employ in athlete-monitoring systems, as well as several factors that should be considered when collecting these data, methods of determining meaningful changes, and various data-visualization approaches. Underpinning a successful athlete-monitoring system is the ability of practitioners to communicate and present important information to coaches, ultimately resulting in enhanced athletic performance.


Common-path off-axis incoherent Fourier holography with a maximum overlapping interference area.
In this Letter, we present a new method for recording spatially incoherent common-path off-axis Fourier holograms. This method records the three-dimensional (3D) information of an object into a Fourier hologram without the need of any mechanical scanning with incoherent illumination. The proposed setup consists of two gratings to form a common-path configuration, and two customized cells to create a rotational and radial shearing interferometer. While the first grating is placed on the first image plane, the second grating shifts axially from the second image plane to build off-axis geometry. A lens is used to combine two beams to generate the maximum overlapping area at the hologram plane. Proof-of-concept experiments confirm the ability of such a system to achieve the maximum overlapping interference area, stability of the system against the vibration of surrounding environment, numerical reconstruction using only one fast Fourier transform, and 3D capability to capture a 3D object illuminated by an LED light.


A Double Dissociation between Anterior and Posterior Superior Temporal Gyrus for Processing Audiovisual Speech Demonstrated by Electrocorticography.
Human speech can be comprehended using only auditory information from the talker's voice. However, comprehension is improved if the talker's face is visible, especially if the auditory information is degraded as occurs in noisy environments or with hearing loss. We explored the neural substrates of audiovisual speech perception using electrocorticography, direct recording of neural activity using electrodes implanted on the cortical surface. We observed a double dissociation in the responses to audiovisual speech with clear and noisy auditory component within the superior temporal gyrus (STG), a region long known to be important for speech perception. Anterior STG showed greater neural activity to audiovisual speech with clear auditory component, whereas posterior STG showed similar or greater neural activity to audiovisual speech in which the speech was replaced with speech-like noise. A distinct border between the two response patterns was observed, demarcated by a landmark corresponding to the posterior margin of Heschl's gyrus. To further investigate the computational roles of both regions, we considered Bayesian models of multisensory integration, which predict that combining the independent sources of information available from different modalities should reduce variability in the neural responses. We tested this prediction by measuring the variability of the neural responses to single audiovisual words. Posterior STG showed smaller variability than anterior STG during presentation of audiovisual speech with noisy auditory component. Taken together, these results suggest that posterior STG but not anterior STG is important for multisensory integration of noisy auditory and visual speech.


Total synthesis of dysiherbaine.
A convergent total synthesis of the marine natural product dysiherbaine was accomplished. The key steps of the synthesis are an alkylation at the gamma-carbon of a protected glutamate with a highly substituted pyran derived from mannose, which was followed by a ring-contraction cascade reaction, which simultaneously gave the tetrasubstituted carbon and the hexahydrofuro[3,2-b]pyran ring system of the natural product.


Secretory mechanisms and intercellular transfer of microRNAs in living cells.
The existence of circulating microRNAs (miRNAs) in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function of extracellular miRNAs remain unclear. Here, we show that miRNAs are released through a ceramide-dependent secretory machinery and that the secretory miRNAs are transferable and functional in the recipient cells. Ceramide, whose biosynthesis is regulated by neutral sphingomyelinase 2 (nSMase2), triggers secretion of small membrane vesicles called exosomes. The decreased activity of nSMase2 with a chemical inhibitor, GW4869, and a specific small interfering RNA resulted in the reduced secretion of miRNAs. Complementarily, overexpression of nSMase2 increased extracellular amounts of miRNAs. We also revealed that the endosomal sorting complex required for transport system is unnecessary for the release of miRNAs. Furthermore, a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipient cells, thereby leading to cell growth inhibition. Our findings shed a ray of light on the physiological relevance of secretory miRNAs.


A meta-analytic review of the association between pubertal timing and psychopathology in adolescence: Are there sex differences in risk?
Research examining pubertal timing effects on psychopathology has emphasized that a subset of adolescents, particularly females, who experience early pubertal maturation relative to their peers appear to be at increased risk for psychopathology. The aims of the current meta-analysis were (a) to quantify the magnitude of early pubertal timing effects on psychopathology, (b) to examine potential moderators of pubertal timing effects (sex, psychopathology domain, sample composition, measurement method, and mean sample age), and (c) to examine findings in relation to hypotheses in the extant literature explicating differential pubertal timing effects for early versus late youth and males versus females. A systematic literature search was conducted in PubMed and PsycINFO databases and 101 articles met criteria for inclusion. Included studies reported a quantitative association between pubertal timing and higher-order broadband dimensions of psychopathology (i.e., internalizing, externalizing), and/or lower-order subdomains (i.e., distress, fear, antisocial behavior, substance abuse, eating pathology). Using meta-analytic methods, we estimated global effect sizes (Cohen's ds) for the association between pubertal timing and psychopathology. Adolescent sex did not moderate early pubertal timing effects on emotional and behavior problems. However, robust early pubertal timing effects emerged for both males and females across all domains of psychopathology that were small in magnitude (ds∼.20). Measurement method of pubertal timing, but not sample composition or mean sample age, significantly contributed to the heterogeneity of effect sizes across studies. Findings have implications for refinement of theoretical models of pubertal timing effects on psychopathology and highlight the importance of empirical work that can identify pathways which may link offset pubertal timing to psychopathology during adolescence. (PsycINFO Database Record


Subacute thyroiditis following COVID-19 vaccination: Case presentation.
Background: Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19.Purpose: The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine.Research design and study sample: Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal.Data collection and/or Analysis: Data collected during the disease are integral to the medical record.Results: Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.Conclusions: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.


Transitional cell metaplasia of the uterine cervix and vagina: an underrecognized lesion that may be confused with high-grade dysplasia. A report of 59 cases.
Sixty-three examples of transitional cell metaplasia of the cervix or vagina from patients 50 to 84 (average 67.6) years of age are described. Fifty-seven of the 59 patients were postmenopausal and two perimenopausal. Only four patients were documented to have received hormonal therapy. The lesion was an incidental microscopic finding in all patients and was found in 29 hysterectomy specimens, 18 endocervical or endometrial curettage specimens, 11 cervical biopsy or cone biopsy specimens, and five vaginal biopsy specimens. The sites involved by transitional cell metaplasia were the exocervix (n = 14), transformation zone (n = 33), vagina (n = 10), or a combination (n = 4). The cervical and vaginal specimens most commonly showed involvement of the surface epithelium by transitional cell metaplasia. Other transitional cell patterns were isolated stromal nests (n = 9) and invagination of surface epithelium into the underlying stroma (n = 2). The typical appearance of transitional cell metaplasia was a hyperplastic epithelium with lack of maturation, consisting of spindled nuclei with tapered ends and frequent longitudinal nuclear grooves. The nuclei were typically oriented vertically in the deeper layers, and horizontally with a streaming pattern superficially. The cells had low nuclear to cytoplasmic ratios, perinuclear halos, and absent to rare mitotic figures. Mild to moderate atypia was seen in only two cases. Many of the cases could have been confused with squamous dysplasia due to the lack of apparent maturation. However, in most cases, attention to cytologic detail disclosed the typical features of transitional cell metaplasia. This process, usually seen in older women, has not been emphasized and can be overdiagnosed as dysplasia, leading to unnecessary treatment.


[Analysis on geographic distribution of high blood pressure prevalence in children and adolescents aged 7-18 years in China, 2014].
Objective: To understand and evaluate the characteristics of geographic distribution of high blood pressure prevalence in children and adolescents aged 7-18 years in China in 2014, and provide evidence for the prevention of hypertension in children and adolescents. Methods: The data of 2014 Chinese National Surveys on Students Constitution and Health conducting 31 provinces (except Hong Kong, Macao and Taiwan) were collected. A total of 216 299 children and adolescents who had complete blood pressure records were selected as study subjects. The low, middle and high prevalence areas were identified according to their high blood pressure detection rates in the children and adolescents,<4%, 4%-7% and >7%, to analyze the geographic distribution of high blood pressure prevalence in the children and adolescents. The environmental data in the capitals of 31 provinces in 2014 were collected to analyze the correlation between environmental factors and blood pressure Z score in the children and adolescents. Results: The average detection rates of high blood pressure was 6.4% in 31 provinces (1.5%-14.2%). The high prevalence areas were mainly distributed in the eastern China, especially the Circum-Bohai sea area, low prevalence areas were mainly distributed in the central and western areas of China and some provinces in the east. Correlation analysis results showed that the annual average temperature, annual average air humidity and local altitude were negatively correlated with blood pressure Z score, including diastolic and systolic blood pressure, in both boys and girls. The annual average sunshine time, PM(2.5) and PM(10) concentrations, content of SO(2) were positively correlated with blood pressure Z score in both boys and girls. Conclusions: There was a significant difference in high blood pressure of children and adolescents among 31 provinces. More attention should be paid to the children and adolescents living high prevalence area. And it is necessary to understand environmental factors which can affect the blood pressure of children and adolescents.


Multiple single nucleotide polymorphism analysis using penalized regression in nonlinear mixed-effect pharmacokinetic models.
Studies on the influence of single nucleotide polymorphisms (SNPs) on drug pharmacokinetics (PK) have usually been limited to the analysis of observed drug concentration or area under the concentration versus time curve. Nonlinear mixed effects models enable analysis of the entire curve, even for sparse data, but until recently, there has been no systematic method to examine the effects of multiple SNPs on the model parameters. The aim of this study was to assess different penalized regression methods for including SNPs in PK analyses. A total of 200 data sets were simulated under both the null and an alternative hypothesis. In each data set for each of the 300 participants, a PK profile at six sampling times was simulated and 1227 genotypes were generated through haplotypes. After modelling the PK profiles using an expectation maximization algorithm, genetic association with individual parameters was investigated using the following approaches: (i) a classical stepwise approach, (ii) ridge regression modified to include a test, (iii) Lasso and (iv) a generalization of Lasso, the HyperLasso. Penalized regression approaches are often much faster than the stepwise approach. There are significantly fewer true positives for ridge regression than for the stepwise procedure and HyperLasso. The higher number of true positives in the stepwise procedure was accompanied by a higher count of false positives (not significant). We find that all approaches except ridge regression show similar power, but penalized regression can be much less computationally demanding. We conclude that penalized regression should be preferred over stepwise procedures for PK analyses with a large panel of genetic covariates.


The Exchange of Social Support on Online Bariatric Surgery Discussion Forums: A Mixed-Methods Content Analysis.
Bariatric surgery patients often experience physical and psychosocial stressors, and difficulty adjusting to significant lifestyle changes. As a result, social support groups that provide patients with support, coping skills, and nutritional information are valuable components of bariatric care. Support group attendance at bariatric centers is associated with greater post-surgery weight loss; however, several barriers hinder attendance at in-person support groups (e.g., travel distance to bariatric centers). Consequently, online support forums are an increasingly utilized resource for patients both before and after surgery. This study examined and described the type and frequency of social support provided on a large online bariatric surgery forum. A total of 1,412 messages in the pre- (n = 822) and post-surgery (n = 590) sections of the forum were coded using qualitative content analysis according to Cutrona and Suhr's (1992) Social Support Behavior Code model (i.e., including informational, tangible, esteem, network, and emotional support types). The majority of messages provided informational and emotional support regarding: a) factual information about the bariatric procedure and nutrition; b) advice for coping with the surgery preparation process, and physical symptoms; and c) encouragement regarding adherence to surgical guidelines, and weight loss progress. Network, esteem, and tangible support types were less frequent than informational and emotional support types. The results inform healthcare providers about the types of social support available to bariatric patients on online support forums and, thus, encourage appropriate referrals to this resource.


Hydrated vs. freeze-dried human acellular dermal matrix for hernia repair: a comparison in a rabbit model.
Abdominal wall hernias commonly occur following laparotomy. Biologic grafts are used to treat these hernias due to their biocompatibility and their ability to serve as a matrix for tissue regeneration and remodeling. Freeze-dried human acellular dermal matrices (F-HADMs) have been shown to be effective in abdominal wall defect repair. Hydrated human acellular dermal matrices (H-HADMs) have not been previously evaluated. This study evaluates H-HADM and F-HADM in the repair of abdominal wall hernias in the rabbit. Thirty-six 3-4-kg New Zealand white rabbits underwent laparotomy with the creation of a hernia. After defect reperitonealization, the animals underwent hernia repair with H-HADM, F-HADM, or primary repair. Within each group, four animals were survived for 4, 8, and 20 weeks. The outcomes evaluated included recurrences, adhesions, histology, immunohistochemistry, and tensiometry. Thirty-five animals underwent abdominal wall hernia repair. One animal in the F-HADM group developed a recurrent hernia. No significant difference was demonstrated in adhesion scores between the H-HADM (0.75) and F-HADM (0.83) groups. Tensiometry demonstrated no differences in the forces required to disrupt the graft from the native fascia between H-HADM and F-HADM at any time point. H-HADM demonstrated fewer white blood cells (WBC) and eosinophils (EOS) per high-powered field (hpf) than F-HADM at 4 weeks (144 WBC/hpf vs. 534 WBC/hpf, P < 0.05; 87 EOS/hpf vs. 304 EOS/hpf, P < 0.05) and 8 weeks (104 WBC/hpf vs. 314 WBC/hpf, P < 0.05; 41 EOS/hpf vs. 149 EOS/hpf, P < 0.05). At 20 weeks, there was no difference in WBC or EOS (134 WBC/hpf vs. 144 WBC/hpf, P = NS; 86 EOS/hpf vs. 104 EOS/hpf, P = NS). Immunohistochemistry for CD31 demonstrated no difference in vascularity at any time point. H-HADM and F-HADM demonstrate comparable results in abdominal wall hernia treatment in a rabbit model. With both grafts, the weakest area of the repair occurs at the graft and native fascia interface. Hernia repairs with H-HADM and F-HADM demonstrate similar incidences of adhesions and tensile strength characteristics. H-HADM demonstrates a reduced inflammatory response at 4 and 8 weeks compared to F-HADM. Both H-HADM and F-HADM demonstrate similar amounts of vascular ingrowth.


[New Developments in CKD-MBD. Cell Biology of parathyroid in CKD].
Parathyroid monitors the calcium concentration in blood by signals from calcium-sensing receptors, adjusts secretion of parathyroid hormone to keep constant calcium concentration in the body. Although parathyroid parenchymal cells consist of chief cells which secrete PTH, and oxyphil cells which are rich in mitochondria, all hardly perform mitotic proliferation in normal status. However, in CKD, PTH hypersecretion and hyperplasia are started by hyperphosphatemia, hypocalcemia, and activated-vitamin-D deficiency, and the secondary hyperparathyroidism develops. While treatment with cinacalcet hydrochloride salt induced apoptosis into the parathyroid cell, a possibility of promoting the transdifferentiation to oxyphil cells from chief cells was suggested. The specific accumulation to the parathyroid of an oncotropic photosensitizer suggests the possibility of photodynamic diagnosis and treatment of hyperparathyroidism.


The role of emotion in psychotherapeutic change for medically unexplained symptoms.
Evidence of the contribution of emotional processes to the emergence, maintenance, and experience of medically unexplained symptoms (MUS) suggests that clinical approaches which target these processes could be beneficial. In this study, qualitative methods were used to examine patients' perspectives and subjective experiences of emotional processes in the context of a psychotherapy assessment and treatment service for MUS provided in a hospital emergency department (ED). Seven semi-structured interviews were conducted with ED patients presenting with MUS who received a course of intensive short-term dynamic psychotherapy treatment. Interpretative phenomenological analysis was employed with three superordinate themes emerging: Barriers to examining emotional processes; reflections on the therapeutic process; psychological change; and improved well-being. Obstacles to clinical engagement in treatment for MUS were described in relation to patients' and therapists' ability to identify, address, and utilize emotion processes. Specific elements of this work were identified as integral components of the psychotherapy change process for MUS. Directly observing the physical effects of emotional experiencing in MUS provides sensory evidence that can enable patients to make mind-body connections. Psycho-emotional processes warrant further study to explore the applicability to other conceptual models for assessing and treating MUS. Clinical and methodological significance: In this article, we highlight that Medically Unexplained Symptoms (MUS) are a priority area for both physical and mental health care services. We present findings relevant to the effectiveness of a novel psychotherapy innovation within a hospital emergency department (ED). The use of interpretative phenomenological analysis to study the experiences of ED clients with MUS offers an established qualitative method for exploring the processes underlying therapeutic change. The results provide new insights around obstacles to engagement alongside potential solutions when addressing the psychological needs of clients with MUS. Although emotion processes have been described as a potentially important change process for MUS and in psychotherapy more generally, little empirical research has studied these two areas collectively.


Effect of inorganic selenium supplementation on selenosis in postweaning swine.
A total of 72 pigs weaned at 4 wk of age were allotted by litter and weight to nine treatment groups and fed 20% protein cornsoybean meal diets supplemented with various levels of inorganic Se during a 37-d postweaning period. Eight groups were fed diets with 0, 2.5, 5.0, 7.5, 10, 15, 20 or 40 ppm Se provided as sodium selenite, while a ninth was offered the 0- and 40-ppm Se diets in separate feeders. Gains and feed intakes were similar during the trial for the 0- and 2.5-ppm Se diets. Both gain and feed intake declined as dietary Se levels above 5.0 ppm increased. At a dietary Se concentration of 40 ppm, feed consumption ceased within a few days of feeding and subsequent gains were negative. Pigs offered both the 0- and 40-ppm Se diets preferentially selected the basal as compared with the 40-ppm Se diet. When the feeders were switched at 28 d they refused the 40-ppm Se diet within a few hours. After a 17-d period, pigs fed the 20- or 40-ppm Se diet were not able to coordinate their walk, with many exhibiting an inability to stand. Alopecia was demonstrated in pigs fed 15 ppm Se or higher at 17 d, but was evident in the 5.0-ppm group at 37 d. At the termination of the trial, abnormal hoof formation at the coronary band was evident in pigs fed diets containing Se greater than or equal to 5 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)


Proboscis Lateralis : A Rare Bilateral Case in Association with Holoprosencephaly.
Proboscis lateralis is a very rare congenital craniofacial malformation characterized by a trunk like tubular appendage arising commonly from roof of the orbit near medial canthus. It may be seen as an isolated defect with sporadic occurrence or it may be associated with a spectrum of anomalies. It is usually unilateral and very few bilateral cases of proboscis lateralis have been reported in the literature worldwide. Alobar holoprosencephaly is commonly associated with a single central proboscis and cyclopia. Here we report an unusual case of a bilateral proboscis lateralis seen in association with holoprosencephaly.


Silencers and locus control regions: opposite sides of the same coin.
Whether or not genes are in an active or a repressed state in a cell depends on the relative effect of gene silencers and locus control regions (LCRs). Here, we suggest that these elements act as binary switches; the state that prevails (activated or repressed) probably depends on a competition between protein complex formation and the stability of the complexes formed at either of the two elements.


Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.
The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.


Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.
Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response.


Gastric Perforation and Phlegmon Formation by Foreign BodyIngestion.
This is a case report of foreign body ingestion in a suicide attempt resulting in gastric perforation and phlegmon formation during a subsequent 6 month period that eventually required surgical intervention. The patient had a prolonged course because she did not report a history of foreign body ingestion and the initial evaluating physicians had no suspicion about possible foreign body ingestion and may have missed important findings on physical examination. Gastric perforation by a foreign object may have a slow course rather than presenting acute abdomen. The realization of a proper physical examination in the emergency department is key to an accurate diagnosis.