[Effect of starvation on the metabolism of the xenobiotic p-nitroanisole in isolated hepatocytes of rats of both sexes].
Hepatocytes isolated from fed female rats are characterized by the lower contents of cytochrome P-450 and more slowly metabolize the xenobiotic p-nitroanisole (p-NA) than hepatocytes from males. The starvation does not change the cytochrome P-450 contents, but depresses the p-NA biotransformation. The inhibition of p-NA O-demethylation capacity is a result of insufficiently reduced equivalent supply, because the addition of exogenous NADPH to the cells with digitonin-permeabilized plasma membrane increases p-nitrophenol (p-NPh) formation. In the presence of exogenous NADPH hepatocytes from fasting male and female rats produce more p-NPh, than those from fed ones. That suggests the induction of xenobiotic biotransformation system during starvation. Sex differences in response of xenobiotic biotransformation system to starvation manifest themselves in different ratio in contents of free and conjugated p-NPh.


[The experimental and clinical validation of the use of a polikatan preparation in periodontal diseases].
Polycatane, a bischofite-based drug (bischofite is a mineral containing up to 95% dry residue of MgCl2 x 6H2O), exerted antiinflammatory and bacteriostatic effects and stimulated phagocytosis and healing of burn infected ulcer in the buccal mucosa of experimental animals. The drug was effective in the treatment of patients with chronic catarrhal gingivitis and generalized periodontitis of light and medium severity. By its antiinflammatory and wound-healing effects polycatane is superior to polyminerol, the reference drug.


Medications for opioid use disorder in state prisons: Perspectives of formerly incarcerated persons.
Background: Opioid use disorder (OUD) is common among incarcerated persons and risk of overdose and other adverse drug-related consequences is high after release. Recognizing their potential to reduce these risks, some correctional systems are expanding access to medication for opioid use disorder (MOUD). This study explored the experiences and perspectives of formerly incarcerated individuals on MOUD use while incarcerated and after release. Methods: We interviewed 53 individuals with self-reported OUD who were released from New Jersey state prisons. Interviews explored motivations to use MOUD while incarcerated and after release, and experiences with prison-based MOUD and transition to community-based care. We performed cross-case analysis to examine common and divergent perspectives across participants. Results: A common reason for accepting prerelease MOUD was recognition of its effectiveness in preventing drug use, overdose, and other drug-related consequences. Participants who chose not to use MOUD often were focused on being completely medication-free or saw themselves as having relatively low-risk of substance use after a prolonged period without opioid use. A few participants reported challenges related to prison-based MOUD, including logistical barriers, stigma, and once-daily buprenorphine dosing. Most participants effectively transitioned to community-based care, but challenges included insurance lapses and difficulty locating providers. Conclusions: Many formerly incarcerated persons with OUD recognize the value of MOUD in supporting recovery, but some hold negative views of MOUD or underestimate the likelihood that they will return to drug use. Patient education on risks of post-release overdose, the role of MOUD in mitigating risk, and MOUD options available to them could increase engagement. Participants' generally positive experiences with MOUD support the expansion of correctional MOUD programs.


Initial type and abundance of cyanobacteria determine morphotype development of phototrophic ecosystems.
Phototrophic aggregates containing filamentous cyanobacteria occur naturally, for example, as cryoconite on glaciers and microbialites in fresh or marine waters, but their formation is not fully understood. Laboratory models are now available to reproduce aggregation, that is, the formation of different morphotypes like hemispheroids, microbial mats or sphere-like aggregates we call photogranules. In the model, activated sludge as starting matrix is transformed into aggregates enclosed by a phototrophic layer of growing cyanobacteria. These cyanobacteria were either enriched from the matrix or we added them intentionally. We hypothesize that the resulting morphotype depends on the type and concentration of the added cyanobacteria. When cyanobacteria from mature photogranules were added to activated sludge, photogranulation was not observed, but microbial mats were formed. Photogranulation of sludge could be promoted when adding sufficient quantities of cyanobacterial strains that form clumps when grown as isolates. The cyanobacteria putatively responsible for photogranulation were undetectable or only present in low abundance in the final communities of photogranules, which were always dominated by mat-forming cyanobacteria. We suggest that, in a temporal succession, the ecosystem engineer initiating photogranulation eventually disappears, leaving behind its structural legacy. We conclude that understanding phototrophic aggregate formation requires considering the initial succession stages of the ecosystem development.


Cooperative hybridization of oligonucleotides.
Nucleic acids have been demonstrated to be versatile nanoscale engineering materials with the construction of dynamic DNA structures, motors, and circuits. These constructions generally rely on the clever use and integration of relatively few reaction mechanisms and design primitives. Here, cooperative hybridization is introduced as a mechanism in which two oligonucleotides of independent sequence can stoichiometrically, simultaneously, and cooperatively hybridize to a DNA complex. Cooperative hybridization is rigorously characterized and modeled and is shown to implement digital concentration comparison with amplification, as well as digital Boolean logic. These designs, based on cooperative hybridization, excel in being robust to impurities and not requiring oligonucleotide purification.


Pancreatic cystic endocrine tumors: a different morphological entity associated with a less aggressive behavior.
Cystic pancreatic endocrine tumors (CPETs) are rare lesions and their biological features have been scarcely investigated. To compare clinical and pathological features of resected non-functioning sporadic CPETs (NF-CPETs) with solid pancreatic endocrine tumors (SPETs) in a single-institution experience. All patients with a pathologically confirmed diagnosis of sporadic non-functioning pancreatic endocrine tumors who underwent curative resection between 1990 and 2008 were included. A comparison of demographic, clinical and pathological characteristics between CPETs and SPETs was made. Univariate and multivariable analyses were performed to identify preoperative predictors of carcinoma (non-functioning pancreatic endocrine carcinoma). Twenty-one (11.5%) patients with a histological diagnosis of NF-CPET were identified. The median age was 60 years (IQR 46.5-73.5 years) and a diagnosis of carcinoma (non-functioning pancreatic endocrine carcinoma) was made in 3 (14.3%) cases. In the comparison with NF-SPETs, no differences were found in terms of gender (p = 0.75), age (p = 0.81), presenting symptoms (p = 0.43), localization of the tumors (p = 0.46) and type of resection (p = 0.31). The incidence of non-functioning pancreatic endocrine carcinoma was significantly lower in the NF-CPET versus the NF-SPET group (14.3 vs. 40.4%, p = 0.04). By univariate analysis, preoperative predictors of non-functioning pancreatic endocrine carcinoma included the presence of symptoms (OR 3.96, 95% CI 2.06-7.63) and an increase in the absolute value of radiological diameter (OR 1.05, 95% CI 1.03-1.07). A cystic morphology of the lesion turned out to be a negative predictor of carcinoma (OR 0.25, 95% CI 0.70-0.87). These results were confirmed by multivariable analysis. NF-CPETs have a measurable propensity to be benign. In those patients affected by small and asymptomatic NF-CPET a more conservative surgical approach or a follow-up policy could be considered.


30 years after Alma-Ata: has primary health care worked in countries?
We assessed progress for primary health care in countries since Alma-Ata. First we analysed life expectancy relative to national income and HIV prevalence to identify overachieving and underachieving countries. Then we focused on the 30 low-income and middle-income countries with the highest average yearly reduction of mortality among children less than 5 years of age, describing coverage and equity of primary health care as well as non-health sector actions. These 30 countries have scaled up selective primary health care (eg, immunisation, family planning), and 14 have progressed to comprehensive primary health care, marked by high coverage of skilled attendance at birth. Good governance and progress in non-health sectors are seen in almost all of the 14 countries identified with a comprehensive primary health care system. However, these 30 countries include those that are making progress despite very low income per person, political instability, and high HIV/AIDS prevalence. Thailand has the highest average yearly reduction in mortality among children less than 5 years of age (8.5%) and has achieved universal coverage of immunisation and skilled birth attendance, with low inequity. Lessons learned from all these countries include the need for a nationally agreed package of prioritised and phased primary health care that all stakeholders are committed to implementing, attention to district management systems, and consistent investment in primary health-care extension workers linked to the health system. More detailed analysis and evaluation within and across countries would be invaluable in guiding investments for primary health care, and expediting progress towards the Millennium Development Goals and "health for all".


How reliable is an effective orifice area indexed chart?
Patient-prosthesis mismatch (PPM) occurs when a valvular prosthesis is too small relative to the patient's body surface area (BSA). The presence of PPM results in increased transprosthetic gradients and may portend a worse prognosis. It has been shown that reliable effective orifice area (EOA) data can be used to accurately predict PPM, thus preventing its occurrence. The study aim was to assess the predictive abilities of an effective orifice area indexed (EOAI) chart--the Perimount Magna EOAI chart--in the prevention of PPM. A retrospective comparison of projected versus calculated EOA values and the predicted versus actual incidence of PPM was conducted. Forty patients with a Perimount Magna aortic bioprosthesis implanted between 1st January 2006 and 31st March 2009, were identified. The sensitivity, specificity, positive-predictive value (PPV) and negative predictive value (NPV) were each calculated using the Perimount Magna EOAI chart, to assess how well it could predict the incidence of postoperative PPM. The Perimount Magna EOAI chart had a sensitivity of 35% for predicting postoperative PPM, and an NPV of 53%. The projected EOA-values were almost invariably larger than those actually measured; this resulted in a higher proportion of patients than in whom PPM was predicted preoperatively. This EOAI chart proved to be very specific, with specificity of 100% and a PPV of 100%. The Perimount Magna EOAI chart, based on mean EOA data from a small echocardiographic cohort, represents a poor method of predicting and preventing PPM. Rather, EOAI charts should be based on reliable EOA data that reproducibly predict the expected EOA for that prosthesis.


Localized hormone fluxes and early haustorium development in the hemiparasitic plant Triphysaria versicolor.
Perhaps the most obvious phenotypes associated with chemical signaling between plants are manifested by parasitic species of Orobanchaceae. The development of haustoria, invasive root structures that allow hemiparasitic plants to transition from autotrophic to heterotrophic growth, is rapid, highly synchronous, and readily observed in vitro. Haustorium development is initiated in aseptic roots of the facultative parasite Triphysaria versicolor when exposed to phenolic molecules associated with host root exudates and rhizosphere bioactivity. Morphological features of early haustorium ontogeny include rapid cessation of root elongation, expansion, and differentiation of epidermal cells into haustorial hairs, and cortical cell expansion. These developmental processes were stimulated in aseptic T. versicolor seedlings by the application of exogenous phytohormones and inhibited by the application of hormone antagonists. Surgically dissected root tips formed haustoria if the root was exposed to haustorial-inducing factors prior to dissection. In contrast, root tips that were dissected prior to inducing-factor treatment were unable to form haustoria unless supplemented with indole-3-acetic acid. A transient transformation assay demonstrated that auxin and ethylene-responsive promoters were up-regulated when T. versicolor was exposed to either exogenous hormones or purified haustoria-inducing factors. These experiments demonstrate that localized auxin and ethylene accumulation are early events in haustorium development and that parasitic plants recruit established plant developmental mechanisms to realize parasite-specific functions.


Sustained antihypertensive activity of telmisartan compared with valsartan.
Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a missed dose were compared. In two identically designed multinational, randomized, double-blind, forced-titration studies, hypertensive patients (seated diastolic blood pressure (DBP), 95-109 mm Hg, 24 h mean ambulatory DBP, > or = 85 mm Hg) received once-daily telmisartan (40- 80 mg) or valsartan (80-160 mg) for a total of 8 weeks; uptitration occurred after 2 weeks low-dose treatment. After 4 weeks high-dose treatment, patients were given either 1 days double-blind active therapy or placebo (that is, missed dose). Following a further 2 weeks active treatment, a cross-over was performed: patients who had previously received 1 days placebo received active therapy and vice versa. At baseline and after the two active or missed doses, 24 h ambulatory BP monitoring was performed. Data from the studies were pooled, as prospectively planned and analyzed using the intent-to-treat population. After active therapy, last 6 h mean DBP was reduced by 7.6+/-7.9 mm Hg with telmisartan (n=447) compared with 5.8+/-7.8 mm Hg with valsartan (n=430) (P=0.0044). Last 6 h mean systolic blood pressure (SBP) was reduced by 11.1 mm Hg with telmisartan compared with 9.1 mm Hg with valsartan (P=0.0066). After a missed dose, 24 h mean DBP was reduced by 7.2+/-6.5 mm Hg with telmisartan (n=437) compared with 5.5+/-6.2 mm Hg with valsartan (n=431) (P=0.0004). The reduction in 24 h mean SBP after a missed dose was 10.7 mm Hg with telmisartan and 8.7 mm Hg with valsartan (P=0.0024). Absence of treatment-by-study interaction indicated that pooling of studies was appropriate. All 24 hourly mean reductions in DBP and SBP were greater for telmisartan than valsartan. Both treatments were well tolerated. Due to its longer half-life, telmisartan offers more sustained BP control, especially at the end of the dosing period and provides sustained efficacy in poorly compliant patients in the event of a missed dose with a statistical superiority compared with valsartan.


Utility of sequenced genomes for microsatellite marker development in non-model organisms: a case study of functionally important genes in nine-spined sticklebacks (Pungitius pungitius).
Identification of genes involved in adaptation and speciation by targeting specific genes of interest has become a plausible strategy also for non-model organisms. We investigated the potential utility of available sequenced fish genomes to develop microsatellite (cf. simple sequence repeat, SSR) markers for functionally important genes in nine-spined sticklebacks (Pungitius pungitius), as well as cross-species transferability of SSR primers from three-spined (Gasterosteus aculeatus) to nine-spined sticklebacks. In addition, we examined the patterns and degree of SSR conservation between these species using their aligned sequences. Cross-species amplification success was lower for SSR markers located in or around functionally important genes (27 out of 158) than for those randomly derived from genomic (35 out of 101) and cDNA (35 out of 87) libraries. Polymorphism was observed at a large proportion (65%) of the cross-amplified loci independently of SSR type. To develop SSR markers for functionally important genes in nine-spined sticklebacks, SSR locations were surveyed in or around 67 target genes based on the three-spined stickleback genome and these regions were sequenced with primers designed from conserved sequences in sequenced fish genomes. Out of the 81 SSRs identified in the sequenced regions (44,084 bp), 57 exhibited the same motifs at the same locations as in the three-spined stickleback. Di- and trinucleotide SSRs appeared to be highly conserved whereas mononucleotide SSRs were less so. Species-specific primers were designed to amplify 58 SSRs using the sequences of nine-spined sticklebacks. Our results demonstrated that a large proportion of SSRs are conserved in the species that have diverged more than 10 million years ago. Therefore, the three-spined stickleback genome can be used to predict SSR locations in the nine-spined stickleback genome. While cross-species utility of SSR primers is limited due to low amplification success, SSR markers can be developed for target genes and genomic regions using our approach, which should be also applicable to other non-model organisms. The SSR markers developed in this study should be useful for identification of genes responsible for phenotypic variation and adaptive divergence of nine-spined stickleback populations, as well as for constructing comparative gene maps of nine-spined and three-spined sticklebacks.


Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum.
Complexes containing lipopolysaccharide (LPS) and three outer membrane proteins (OMPs) are released by gram-negative bacteria incubated in human serum and into the circulation in an experimental model of sepsis. The same OMPs are bound by immunoglobulin G (IgG) in the cross-protective antiserum raised to Escherichia coli J5 (anti-J5 IgG). This study was performed to identify the three OMPs. The 35-kDa OMP was identified as outer membrane protein A (OmpA) by immunoblotting studies using OmpA-deficient bacteria and recombinant OmpA protein. The 18-kDa OMP was identified as peptidoglycan-associated lipoprotein (PAL) based on peptide sequences from the purified protein and immunoblotting studies using PAL-deficient bacteria. The 5- to 9-kDa OMP was identified as murein lipoprotein (MLP) based on immunoblotting studies using MLP-deficient bacteria. The studies identify the OMPs released into human serum and into the circulation in an experimental model of sepsis as OmpA, PAL, and MLP.


Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription.
Bile acids, steroids, and drugs activate steroid and xenobiotic receptor pregnane X receptor (PXR; NR1I2), which induces human cytochrome P4503A4 (CYP3A4) in drug metabolism and cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis in the liver. Rifampicin, a human PXR agonist, inhibits bile acid synthesis and has been used to treat cholestatic diseases. The objective of this study is to elucidate the mechanism by which PXR inhibits CYP7A1 gene transcription. The mRNA expression levels of CYP7A1 and several nuclear receptors known to regulate the CYP7A1 gene were assayed in human primary hepatocytes by quantitative real-time PCR (Q-PCR). Rifampicin reduced CYP7A1 and small heterodimer partner (SHP; NR02B) mRNA expression suggesting that SHP was not involved in PXR inhibition of CYP7A1. Rifampicin inhibited CYP7A1 reporter activity and a PXR binding site was localized to the bile acid response element-I. Mammalian two-hybrid assays revealed that PXR interacted with hepatic nuclear factor 4 alpha (HNF4 alpha, NR2A1) and rifampicin was required. Coimmunoprecipitation assay confirmed PXR interaction with HNF4 alpha. PXR also interacted with peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha), which interacted with HNF4 alpha and induced CYP7A1 gene transcription. Rifampicin enhanced PXR interaction with HNF4 alpha and reduced PGC-1 alpha interaction with HNF4 alpha. Chromatin immunoprecipitation assay showed that PXR, HNF4 alpha, and PGC-1 alpha bound to CYP7A1 chromatin, and rifampicin dissociated PGC-1 alpha from chromatin. These results suggest that activation of PXR by rifampicin promotes PXR interaction with HNF4 alpha and blocks PGC-1 alpha activation with HNF4 alpha and results in inhibition of CYP7A1 gene transcription. Rifampicin inhibition of bile acid synthesis may be a protective mechanism against drug and bile acid-induced cholestasis.


Bicyclic Imidazolium Inhibitors of Gli Transcription Factor Activity.
Gli transcription factors within the Hedgehog (Hh) signaling pathway direct key events in mammalian development and promote a number of human cancers. Current therapies for Gli-driven tumors target Smoothened (SMO), a G protein-coupled receptor-like protein that functions upstream in the Hh pathway. Although these drugs can have remarkable clinical efficacy, mutations in SMO and downstream Hh pathway components frequently lead to chemoresistance. In principle, therapies that act at the level of Gli proteins, through direct or indirect mechanisms, would be more efficacious. We therefore screened 325 120 compounds for their ability to block the constitutive Gli activity induced by loss of Suppressor of Fused (SUFU), a scaffolding protein that directly inhibits Gli function. Our studies reveal a family of bicyclic imidazolium derivatives that can inhibit Gli-dependent transcription without affecting the ciliary trafficking or proteolytic processing of these transcription factors. We anticipate that these chemical antagonists will be valuable tools for investigating the mechanisms of Gli regulation and developing new strategies for targeting Gli-driven cancers.


Hybrid multi/single layer array transducers for increased signal-to-noise ratio.
In medical ultrasound imaging, two-dimensional (2-D) array transducers are necessary to implement dynamic focusing in two dimensions, phase correction in two dimensions and high speed volumetric imaging. However, the small size of a 2-D array element results in a small clamped capacitance and a large electrical impedance, which decreases the transducer signal-to-noise ratio (SNR). We have previously shown that SNR is improved using transducers made from multi-layer PZT, due to their lower electrical impedance. In this work, we hypothesize that SNR is further increased using a hybrid array configuration: in the transmit mode, a 10 Omega electronic transmitter excites a 10 Omega multi-layer array element; in the receive mode, a single layer element drives a high impedance preamplifier located in the transducer handle. The preamplifier drives the coaxial cable connected to the ultrasound scanner. For comparison, the following control configuration was used: in the transmit mode, a 50 Omega source excites a single layer element, and in the receive mode, a single layer element drives a coaxial cable load. For a 5x102 hybrid array operating at 7.5 MHz, maximum transmit output power was obtained with 9 PZT layers according to the KLM transmission line model. In this case, the simulated pulse-echo SNR was improved by 23.7 dB for the hybrid configuration compared to the control. With such dramatic improvement in pulse-echo SNR, low voltage transmitters can be used. These can be fabricated on integrated circuits and incorporated into the transducer handle.


Uncultured soil bacteria are a reservoir of new antibiotic resistance genes.
Antibiotic resistance genes are typically isolated by cloning from cultured bacteria or by polymerase chain reaction (PCR) amplification from environmental samples. These methods do not access the potential reservoir of undiscovered antibiotic resistance genes harboured by soil bacteria because most soil bacteria are not cultured readily, and PCR detection of antibiotic resistance genes depends on primers that are based on known genes. To explore this reservoir, we isolated DNA directly from soil samples, cloned the DNA and selected for clones that expressed antibiotic resistance in Escherichia coli. We constructed four libraries that collectively contain 4.1 gigabases of cloned soil DNA. From these and two previously reported libraries, we identified nine clones expressing resistance to aminoglycoside antibiotics and one expressing tetracycline resistance. Based on the predicted amino acid sequences of the resistance genes, the resistance mechanisms include efflux of tetracycline and inactivation of aminoglycoside antibiotics by phosphorylation and acetylation. With one exception, all the sequences are considerably different from previously reported sequences. The results indicate that soil bacteria are a reservoir of antibiotic resistance genes with greater genetic diversity than previously accounted for, and that the diversity can be surveyed by a culture-independent method.


microRNA-31 regulates skeletogenesis by direct suppression of Eve and Wnt1.
microRNAs (miRNAs) play a critical role in a variety of biological processes, including embryogenesis and the physiological functions of cells. Evolutionarily conserved microRNA-31 (miR-31) has been found to be involved in cancer, bone formation, and lymphatic development. We previously discovered that, in the sea urchin, miR-31 knockdown (KD) embryos have shortened dorsoventral connecting rods, mispatterned skeletogenic primary mesenchyme cells (PMCs) and shifted and expanded Vegf3 expression domain. Vegf3 itself does not contain miR-31 binding sites; however, we identified its upstream regulators Eve and Wnt1 to be directly suppressed by miR-31. Removal of miR-31's suppression of Eve and Wnt1 resulted in skeletal and PMC patterning defects, similar to miR-31 KD phenotypes. Additionally, removal of miR-31's suppression of Eve and Wnt1 results in an expansion and anterior shift in expression of Veg1 ectodermal genes, including Vegf3 in the blastulae. This indicates that miR-31 indirectly regulates Vegf3 expression through directly suppressing Eve and Wnt1. Furthermore, removing miR-31 suppression of Eve is sufficient to cause skeletogenic defects, revealing a novel regulatory role of Eve in skeletogenesis and PMC patterning. Overall, this study provides a proposed molecular mechanism of miR-31's regulation of skeletogenesis and PMC patterning through its cross-regulation of a Wnt signaling ligand and a transcription factor of the endodermal and ectodermal gene regulatory network.


Protection of Grain Products from Sitophilus oryzae (L.) Contamination by Anti-Insect Pest Repellent Sachet Containing Allyl Mercaptan Microcapsule.
The purpose of this study was to develop an anti-insect pest repellent sachet to prevent Sitophilus oryzae (L.) (Coleoptera: Curculionidae) contamination in grain packaging. The anti-insect pest activities of essential oils (EOs) from garlic (Allium Sativum), ginger (Zingiber Officinalis), black pepper (Piper nigrum), onion (Allium cepa), and fennel (Foeniculum vulgare) as well as major compounds (allyl disulfide, AD; allyl mercaptan, AM) isolated from of garlic and onion (AD and AM) were measured against S. oryzae. The results revealed that garlic EO, onion EO, AD, and AM showed strong fumigant insecticidal activities. Among these, AM showed the highest acetylcholinesterase (AChE) inhibition rate, indicating that the fumigation insecticidal efficacy of AM is related with its AChE inhibition ability. Subsequently, the microcapsules were produced with a high efficiency (80.02%) by using AM as a core material and rice flour as a wall material. Finally, sachet composed of rice flour microcapsule containing 2% AM (RAM) was produced. Repellent assay was performed to measure anti-insect pest ability of the RAM sachet, showed remarkable repelling effect within 48 h both in the presence or absence of attractant. In a release profile of RAM sachet, it was expected to last over 20 mo during the distribution period of brown rice. Moreover, RAM sachet showed no undesirable changes to the sensory properties of the rice both before and after cooking. Taken together, these results suggest that the newly developed RAM sachet could be used as a packaging material to protect grain products from S. oryzae contamination. The rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), causes damages to stored products and its contamination in grain products has become a major problem in cereal market. To preserve brown rice, an anti-insect pest repellent sachet containing 2% allyl mercaptan was newly developed and it showed remarkable repellent abilities against S. oryzae. It could be used as an active food packaging system to protect grain products from insect pest contamination.


Is Colorectal Cancer Screening Appropriate in Nigeria?
The global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria. We used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment. Screening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing. Using the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.


Pharmacokinetics of iododoxorubicin in the rat, dog, and monkey.
The pharmacokinetics of iododoxorubicin (I-DOX) have been studied after single dose administration in the rat (iv and po), dog (iv and po), and monkey (iv). Plasma levels and amounts in urine were monitored by HPLC for both I-DOX and its biologically active metabolite, iododoxorubicinol (I-DOXOL). Plasma levels of I-DOX after iv administration could be described by a three-exponential curve with extremely fast initial phase. Terminal elimination half-lives of I-DOX were similar, 6-7 hr, in all three species. Body weight-normalized clearance (CL) and distribution volumes (Vd) of I-DOX were lower in the dog, but were similar in rat and monkey. The pharmacokinetic parameters also implied metabolic differences between species. Mean I-DOXOL/I-DOX AUC ratios were 0.02, 0.47, and 0.58, respectively, in rat, dog, and monkey, values considerably lower than reported in human studies. I-DOXOL remained slightly longer in the body than I-DOX, as seen both from terminal half-lives (9-11 hr) and mean residence times. In all species, renal excretion was virtually negligible: the amount of I-DOX + I-DOXOL in urine was less than 2% of dose. Mean bioavailabilities of I-DOX were 0.23 and 0.46 in rat and dog, respectively, and, in the latter, about half of I-DOXOL formation occurred during or before the first pass.


Penicillin-binding protein 5 as an inhibitory target of cefozopran in Enterococcus faecalis.
The concentration of cefozopran which inhibits binding of [14C]benzylpenicillin to penicillin-binding protein (PBP) 5 of Enterococcus faecalis TN2OO5 by 50% was 11 mg/L, and its MIC was 12.5 mg/L. Ceftazidime and cefmenoxime, which were inactive at 100 mg/L, showed no affinity for PBP 5 at this concentration. Ampicillin, benzylpenicillin and imipenem showed higher affinity for PBPs 3/4 and PBP 5 than cefozopran, and their MICs were lower than that of cefozopran. No correlation between MICs of the test compounds and the affinity for PBP 1, 2 or 6 was found. These results suggest that cefozopran exhibits antimicrobial activity against E. faecalis TN2OO5 by binding to PBP 5.


Somatic complaints and social competence predict success in childhood overweight treatment.
To determine baseline predictors of treatment success in terms of Body Mass Index-Standard Deviation Scores (BMI-SDS) in a multidisciplinary family-based behavioural lifestyle intervention for overweight and obese children. Overweight and obese children (N = 248; age 8-14 years) and their caregivers participated in a prospective study and attended a lifestyle intervention. Baseline data assessment included anthropometrics, demographics, breakfast behaviour, competence and behavioural problems (Child Behaviour Checklist [CBCL]), family functioning (Family Adaptability and Cohesion Evaluation Scales [FACES] III), and personality (Dutch Personality Questionnaire-Youth [NPV-J]). BMI-SDS was measured at start and after 3, 9, and 12 months of treatment. Mixed modelling was used for analysis. Greater BMI-SDS reductions over the course of one year were found in children with Caucasian parents, with lower baseline BMI-SDS, and higher CBCL-social competence scores. Furthermore, children with non-overweight parents, younger children, and children with lower CBCL-somatic scores were more successful in BMI-SDS reduction. No effects on treatment success were found for the number or position of siblings, having divorced parents or a working mother, educational level of the parents, breakfast behaviour, family functioning, and personality. These results suggest that screening for baseline characteristics in childhood obesity treatment could identify who will benefit most from a paediatric lifestyle intervention. Tailored programs should be developed and the treatment team should focus on children who are less successful in achieving weight reductions. Future research should study by which mechanisms somatic complaints and social competence influence treatment success.


Prevalence and management of anaemia in renal transplant recipients: data from ten European centres.
Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia and also the use of erythropoiesis-stimulating agents were significantly different across the different centres, suggesting substantial practice variations. PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey.


Controlled turnover and 3' trimming of the trans splicing precursor of Trypanosoma brucei.
The maturation of mRNAs in Trypanosoma brucei involves a novel step, in which a short capped sequence is spliced in trans onto the 5' end of nascent mRNAs from a 140-nucleotide precursor. This precursor is called the mini-exon-derived RNA or medRNA. We have used drugs and ultraviolet irradiation as inhibitors to probe the synthesis and processing of medRNA in vivo. Inhibition of RNA synthesis by chloroquine shows that the half-life of medRNA is about 4 minutes. Despite this high turnover, only limited accumulation of medRNA could be achieved following a block in the synthesis of high molecular weight splice acceptor substrates by UV irradiation. This implies that there is a constraint on the steady-state levels of medRNA and that excess medRNA is degraded in the cell. A 3' shortened version of medRNA accumulates upon a block in normal medRNA processing by UV irradiation or upon treatment of the cells with actinomycin D or novobiocin but was shown not to participate in trans splicing, making it a likely candidate for an in vivo degradation intermediate.


Acute Kidney Injury After Radial or Femoral Access for Invasive Acute Coronary Syndrome Management: AKI-MATRIX.
It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).


Analysis of astrovirus serotype 1 RNA, identification of the viral RNA-dependent RNA polymerase motif, and expression of a viral structural protein.
We report the results from sequence analysis and expression studies of the gastroenteritis agent astrovirus serotype 1. We have cloned and sequenced 5,944 nucleotides (nt) of the estimated 7.2-kb RNA genome and have identified three open reading frames (ORFs). ORF-3, at the 3' end, is 2,361 nt in length and is fully encoded in both the genomic and subgenomic viral RNAs. Expression of ORF-3 in vitro yields an 87-kDa protein that is immunoprecipitated with a monoclonal antibody specific for viral capsids. This protein comigrates with an authentic 87-kDa astrovirus protein immunoprecipitated from infected cells, indicating that this region encodes a viral structural protein. The adjacent upstream ORF (ORF-2) is 1,557 nt in length and contains a viral RNA-dependent RNA polymerase motif. The viral RNA-dependent RNA polymerase motifs from four astrovirus serotypes are compared. Partial sequence (2,018 nt) of the most 5' ORF (ORF-1) reveals a 3C-like serine protease motif. The ORF-1 sequence is incomplete. These results indicate that the astrovirus genome is organized with nonstructural proteins encoded at the 5' end and structural proteins at the 3' end. ORF-2 has no start methionine and is in the -1 frame compared with ORF-1. We present sequence evidence for a ribosomal frameshift mechanism for expression of the viral polymerase.


Consistent Healthcare Safety Recommendation System for Preventing Contagious Disease Infections in Human Crowds.
The recent impact of COVID-19, as a contagious disease, led researchers to focus on designing and fabricating personal healthcare devices and systems. With the help of wearable sensors, sensing and communication technologies, and recommendation modules, personal healthcare systems were designed for ease of use. More specifically, personal healthcare systems were designed to provide recommendations for maintaining a safe distance and avoiding contagious disease spread after the COVID-19 pandemic. The personal recommendations are analyzed based on the wearable sensor signals and their consistency in sensing. This consistency varies with human movements or other activities that hike/cease the sensor values abruptly for a short period. Therefore, a consistency-focused recommendation system (CRS) for personal healthcare (PH) was designed in this research. The hardware sensing intervals for the system are calibrated per the conventional specifications from which abrupt changes can be observed. The changes are analyzed for their saturation and fluctuations observed from neighbors within the threshold distance. The saturation and fluctuation classifications are performed using random forest learning to differentiate the above data from the previously sensed healthy data. In this process, the saturated data and consistency data provide safety recommendations for the moving user. The consistency is verified for a series of intervals for the fluctuating sensed data. This alerts the user if the threshold distance for a contagious disease is violated. The proposed system was validated using a prototype model and experimental analysis through false rates, data analysis rates, and fluctuations.


Unlocking short read sequencing for metagenomics.
Different high-throughput nucleic acid sequencing platforms are currently available but a trade-off currently exists between the cost and number of reads that can be generated versus the read length that can be achieved. We describe an experimental and computational pipeline yielding millions of reads that can exceed 200 bp with quality scores approaching that of traditional Sanger sequencing. The method combines an automatable gel-less library construction step with paired-end sequencing on a short-read instrument. With appropriately sized library inserts, mate-pair sequences can overlap, and we describe the SHERA software package that joins them to form a longer composite read. This strategy is broadly applicable to sequencing applications that benefit from low-cost high-throughput sequencing, but require longer read lengths. We demonstrate that our approach enables metagenomic analyses using the Illumina Genome Analyzer, with low error rates, and at a fraction of the cost of pyrosequencing.


A study comparing sexually transmitted infections and HIV among ex-red-light district and non-red-light district sex workers after the demolition of Baina red-light district.
In June 2004, the red-light area of Goa was demolished. We compare HIV and sexually transmitted infections (STIs) between sex workers who had been based in Baina red-light district (ex-RLD-SWs) with sex workers who had never worked in Baina (non-RLD-SWs). Three hundred twenty-six sex workers recruited using respondent-driven sampling, completed interviewer-administered questionnaires, and were tested for Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, and antibodies to HIV. The association between ever working in Baina red-light area and HIV and STIs was examined using multivariate analysis. Non-RLD-SWs made up 55.3% (n = 201) of the sample, 48% of whom had entered sex work since the demolition. Non-RLD-SWs more likely to be less than 20 years old, Goan, have experienced sexual and intimate partner violence, to work part time, from home or the streets, and to have fewer clients. Ex-RLD-SWs were less likely to have curable STIs adjusted odds ratio of 0.27 (95% confidence interval: 0.10 to 0.73) and were more likely to have been exposed to HIV prevention and report consistent condom use with clients. Non-RLD-SWs were more likely to be engaged in high-risk sexual activity. Although partly explained by lack of exposure to HIV prevention and inconsistent condom use, social and professional isolation and greater experience of intimate partner and sexual violence may play a role.


Innovation of natural essential oil-loaded Orabase for local treatment of oral candidiasis.
Oral candidiasis may be manifested in the oral cavity as either mild or severe oral fungal infection. This infection results from the overgrowth of Candida species normally existing in the oral cavity in minute amounts based on many predisposing factors. Several aspects have spurred the search for new strategies in the treatment of oral candidiasis, among which are the limited numbers of new antifungal drugs developed in recent years. Previous studies have shown that thyme and clove oils have antimycotic activities and have suggested their incorporation into pharmaceutical preparations. This study aimed to investigate the possibility of the incorporation and characterization of essential oils or their extracted active ingredients in Orabase formulations. Orabase loaded with clove oil, thyme oil, eugenol, and thymol were prepared and evaluated for their antifungal activities, pH, viscosity, erosion and water uptake characteristics, mechanical properties, in vitro release behavior, and ex vivo mucoadhesion properties. All prepared bases showed considerable antifungal activity and acceptable physical characteristics. The release pattern from loaded bases was considerably slow for all oils and active ingredients. All bases showed appreciable adhesion in the in vitro and ex vivo studies. The incorporation of essential oils in Orabase could help in future drug delivery design, with promising outcomes on patients' well-being.


Photochemical oxazole-nitrile conversion downstream of rhizoxin biosynthesis and its impact on antimitotic activity.
Through metabolic profiling of mutants and wild type of the endofungal bacterium Burkholderia rhizoxinica two novel rhizoxin derivatives with unusual nitrile substitutions were discovered. The nitrile groups result from a photochemical oxidative cleavage of the oxazolyl moiety. In vitro studies revealed that the photooxidation by singlet oxygen also takes place in the absence of a photosensitizer, and that also a thiazolyl-substituted rhizoxin analogue undergoes the same transformation. The resulting nitriles have antimitotic properties but are significantly less active than the parent compounds. These results highlight the impact of photoreactions onto the antiproliferative agent and encourage the introduction of bioisosteric groups that render the compound less susceptible towards photooxidation.


[Treatment of AL-amyloidosis--results from one clinic and review of published experience with new agents (bortezomib, thalidomide and lenalidomide) in AL-amyloidosis].
Fifteen patients with light chain deposits in the form of AL-amyloidosis and 2 patients with light chain deposition as amorphous matter (light chain deposition disease) were treated at our clinic as of 1999. Median age at the diagnosis was 63 (34-77) years. The light chain deposition caused: nephrotic syndrome in 12 (70%) patients, renal insufficiency with reduced filtration in 4 (23%) patients, cardiomyopathy in 4 (23%) patients, hepatosplenomegaly in 2 (12%) patients, manifest coagulopathy in 2 (12%) patients, periorbital hematoma in 2 (12%) patients, visceral and somatic neuropathy in 2 (12%) patients. Treatment with high-dose dexamethasone in combination with adriamycin and vincristine (VAD) or cyclophosphamide (CAD orjust CD) was used in 11 patients. In 4 patients, therapy was completed with high-dose chemotherapy and autologous transplantation; complete haematological and organ treatment response was achieved in all 4 patients with remission lasting 113+, 87+, 50, 45+ months. Of the remaining 7 patients in whom high-dose dexamethasone therapy was not completed with high-dose chemotherapy, 3 achieved complete haematological remission (CR) and very good partial remission (VGPR), with 2 patients achieving complete organ treatment response. Organ response in the third patient cannot be assessed due to the short evaluation period. PR with no organ treatment response was achieved in other 2 patients and 2 patients died during the treatment. Therapy with prednisone and alkylating cytostatics was used in 2 patients with serious organ damage, both patients died after a short period of time due to the disease and thus treatment response cannot be evaluated. Combination of thalidomide, dexamethasone and cyclophosphamide (CTD) was used in 4 patients. Two of these patients did not complete full 2 cycles, one for unmanageable thalidomide-associated constipation, the other died. Two patients underwent a total of 5 and 6 cycles of this treatment with PR effect and plateau after the previous decline of monoclonal immunoglobulin concentrations. Treatment combination of bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) was used in three patients. In one patient (6 completed CTD cycles with the PR result) this combination led to complete haematological remission, complete remission was also achieved in the second patient and the application of 2 CVD cycles led to CR in the third (5 CTD cycles with PR result). Just one of the 3 female patients has been followed up for more than 12 months and so it is possible to evaluate organ treatment response in this patient; nephrotic syndrome ceased, meaning that organ CR has been achieved. Early diagnosis (before severe organ damage occurs) enables administration of aggressive treatment (high-dose chemotherapy and autologous transplantation) with the outlook of complete haematological and organ treatment response. New drugs thalidomide and bortezomib further expand treatment armamentarium; according to our limited experience and published information, bortezomib may be considered as very effective and well tolerated agent suitable, in combination, for patients with the diagnosis of AL-amyloidosis.


HIV-1 envelope proteins and V1/V2 domain scaffolds with mannose-5 to improve the magnitude and quality of protective antibody responses to HIV-1.
Two lines of investigation have highlighted the importance of antibodies to the V1/V2 domain of gp120 in providing protection from HIV-1 infection. First, the recent RV144 HIV-1 vaccine trial documented a correlation between non-neutralizing antibodies to the V2 domain and protection. Second, multiple broadly neutralizing monoclonal antibodies to the V1/V2 domain (e.g. PG9) have been isolated from rare infected individuals, termed elite neutralizers. Interestingly, the binding of both types of antibodies appears to depend on the same cluster of amino acids (positions 167–171) adjacent to the junction of the B and C strands of the four-stranded V1/V2 domain β-sheet structure. However, the broadly neutralizing mAb, PG9, additionally depends on mannose-5 glycans at positions 156 and 160 for binding. Because the gp120 vaccine immunogens used in previous HIV-1 vaccine trials were enriched for complex sialic acid-containing glycans, and lacked the high mannose structures required for the binding of PG9-like mAbs, we wondered if these immunogens could be improved by limiting glycosylation to mannose-5 glycans. Here, we describe the PG9 binding activity of monomeric gp120s from multiple strains of HIV-1 produced with mannose-5 glycans. We also describe the properties of glycopeptide scaffolds from the V1/V2 domain also expressed with mannose-5 glycans. The V1/V2 scaffold from the A244 isolate was able to bind the PG9, CH01, and CH03 mAbs with high affinity provided that the proper glycans were present. We further show that immunization with A244 V1/V2 fragments alone, or in a prime/boost regimen with gp120, enhanced the antibody response to sequences in the V1/V2 domain associated with protection in the RV144 trial.


[Local low pressure in rehabilitation of patients with meningitis].
We studied the validity and effectiveness of interrupted local negative pressure (ILNP) in rehabilitation of patients who had had acute meningitis. ILNP on the lower part of the body was applied in 28 meningitis convalescents having residual manifestations detected at tetrapolar rheography and psychovegetative testing. As the result of the treatment the patients felt better, their psychovegetative status improved, pulse blood filling of cerebral vessels increased while tonicity of microcirculation vessels diminished. Side effects of ILNP were not registered. Thus, ILNP is effective in convalescents after meningitis.


Lung cancer mortality in a site producing hard metals.
To study the mortality from lung cancer from exposures to hard metal dust at an industrial site producing hard metals--pseudoalloys of cobalt and tungsten carbide--and other metallurgical products many of which contain cobalt. A historical cohort was set up of all subjects who had worked for at least 3 months on the site since its opening date in the late 1940s. A full job history could be obtained for 95% of the subjects. The cohort was followed up from January 1968 to December 1992. The exposure was assessed by an industry specific job exposure matrix (JEM) characterising exposure to hard metal dust from 1 to 9 and other possibly carcinogenic exposures as present or absent. Smoking information was obtained by interview of former workers. Standard lifetable methods and Poisson regression were used for the statistical analysis of the data. Mortality from all causes was close to the expected (standardised mortality ratio (SMR) 1.02, 399 deaths) whereas mortality from lung cancer was significantly increased among men (SMR 1.70; 46 deaths, 95% confidence interval (95% CI) 1.24 to 2.26). By workshop, lung cancer mortality was significantly higher than expected in hard metal production before sintering (SMR 2.42; nine deaths; 95%CI 1.10 to 4.59) and among maintenance workers (SMR 2.56; 11 deaths; 95%CI 1.28 to 4.59), whereas after sintering the SMR was lower (SMR 1.28; five deaths; 95%CI 0.41 to 2.98). The SMR for all exposures to hard metal dust at a level >1 in the JEM was in significant excess (SMR 2.02; 26 deaths; 95%CI 1.32 to 2.96). The risks increased with exposure scores, duration of exposure, and cumulative dose reaching significance for duration of exposure to hard metal dust before sintering, after adjustment for smoking and known or suspected carcinogens. Excess mortality from lung cancer was found among hard metal production workers which cannot be attributed to smoking alone. This excess occurred mostly in subjects exposed to unsintered hard metal dust.


[Nitric oxide as a regulator of hemodynamic changes in pregnancy].
Nitric oxide (.NO) produced by the majority of animal cells, has been considered a second messenger, since it is the result of a transduction process induced by a first stimulus. Biochemically, .NO is produced during the conversion of L-arginine to L-citruline by a reaction catalyzed by the enzyme nitric oxide synthetase. Two ixoenzymes have been characterized from this enzyme: a constitutive isoenzyme activated by hormones produced by the endothelial cells and acting on smooth muscle relaxing properties and the other, an inducible isoenzyme whose synthesis is stimulated by cytokines, and produced by macrophages. As pregnancy progresses, the concentrations of .NO, its metabolites, nitrates and nitrites, cGMP and the synthesizing enzyme, nitric oxide synthetase, increase parallelly until reaching a maximum peak before birth. It is considered that .NO is the molecule that maintains the typical vasodilated tone during pregnancy. During preeclampsia, this free radical, as well as its metabolites are found to be significantly decreased, in addition, the administration of .NO donors or of the precursor of L-arginine reverts the vascular abnormalities of this condition. The mechanism of action behind .NO on the vascular endothelium is by its stimulating effect on the enzyme cyclase guanilate, causing an increase in cGMP concentration and the relaxation of the smooth muscle. The nitric oxide generates by macrophages acts as a defense mechanism when linked with other radicals as the superoxide anion (O2).


Synaptonemal complex analysis of mole rats (Spalax ehrenbergi): unusual polymorphisms of chromosome 1.
Two unusual structural polymorphisms in the largest chromosomal pair of the Israeli mole rat, Spalax ehrenbergi, were analyzed from surface-spread and silver-stained preparations of synaptonemal complexes. A C-band negative polymorphism for the length of the 1p arm was visible as axial length differences during late zygonema and early pachynema. This region underwent synaptic adjustment resulting in a fully paired, mid-pachytene synaptonemal complex with equalized axial lengths. The somatically variable and nonargentophilic secondary constriction in the 1q arm was evident as a distinct silver-stained thickening along the synaptonemal complex. Presence of this structure on the synaptonemal complex varied both among individuals and among cells within individuals. The intraindividual variation of this region is hypothesized to represent differential biochemical activity with its cellular visualization being regulated in a manner similar to that of nucleolus organizer regions.


Feeding unsaponifiable compounds from rice bran oil does not alter hepatic mRNA abundance for cholesterol metabolism-related proteins in hypercholesterolemic rats.
The hypocholesterolemic effect of rice bran oil (RBO) is defined in human and animal experiments which indicate the presence of active component(s) in the unsaponifiable fraction, but the detailed mechanism is not known yet. Exogenously hypercholesterolemic (ExHC) rats were fed for 2 weeks on a 0.5% cholesterol diet supplemented with 10% each of RBO, RBO-simulated oil (RBOSO) in its fatty acid composition, or RBOSO plus 0.25% unsaponifiable compounds (UC) from RBO. Rats fed RBO or the UC resulted in lowing serum and liver cholesterol concentration and preventing reduction of high density lipoproteinic-cholesterol. Dietary RBO or the UC led to an elevation of fecal neutral sterol excretion, but no significant change in fecal bile acid excretion or in hepatic abundance of mRNAs for 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol-7alpha-hydroxylase, and low density lipoprotein receptor. Besides, serum and liver alpha-tocopherol concentrations were lowered in RBO or the UC-fed rats. These results show that the UC in RBO leads to a decreased serum cholesterol concentration by interrupting the absorption of intestinal hydrophobic compounds rather than by modifying cholesterol metabolism in the liver.


Intestinal atresia and stenosis: a 25-year experience with 277 cases.
To evaluate the causes, clinical presentation, diagnosis, operative management, postoperative care, and outcome in infants with intestinal atresia. Retrospective case series. Pediatric tertiary care teaching hospital. A population-based sample of 277 neonates with intestinal atresia and stenosis treated from July 1, 1972, through April 30, 1997. The level of obstruction was duodenal in 138 infants, jejunoileal in 128, and colonic in 21. Of the 277 neonates, 10 had obstruction in more than 1 site. Duodenal atresia was associated with prematurity (46%), maternal polyhydramnios (33%), Down syndrome (24%), annular pancreas (33%), and malrotation (28%). Jejunoileal atresia was associated with intrauterine volvulus, (27%), gastroschisis (16%), and meconium ileus (11.7%). Patients with duodenal obstruction were treated by duodenoduodenostomy in 119 (86%), of 138 patients duodenotomy with web excision in 9 (7%), and duodenojejunostomy in 7 (5%) A duodenostomy tube was placed in 3 critically ill neonates. Patients with jejunoileal atresia were treated with resection in 97 (76%) of 128 patients (anastomosis, 45 [46%]; tapering enteroplasty, 23 [24%]; or temporary ostomy, 29 [30%]), ostomy alone in 25 (20%), web excision in 5 (4%), and the Bianchi procedure in 1 (0.8%). Patients with colon atresia were managed with initial ostomy and delayed anastomosis in 18 (86%) of 21 patients and resection with primary anastomosis in 3 (14%). Short-bowel syndrome was noted in 32 neonates. Morbidity and early and late mortality. Operative mortality for neonates with duodenal atresia was 4%, with jejunoileal atresia, 0.8%, and with colonic atresia, 0%. The long-term survival rate for children with duodenal atresia was 86%; with jejunoileal atresia, 84%; and with colon atresia, 100%. The Bianchi procedure (1 patient, 0.8%) and growth hormone, glutamine, and modified diet (4 patients, 1%) reduced total parenteral nutrition dependence. Cardiac anomalies (with duodenal atresia) and ultrashort-bowel syndrome (<40 cm) requiring long-term total parenteral nutrition, which can be complicated by liver disease (with jejunoileal atresia), are the major causes of morbidity and mortality in these patients. Use of growth factors to enhance adaptation and advances in small bowel transplantation may improve long-term outcomes.


Expression and purification of recombinant toxicshock-syndrome toxin I.
Toxic-shock-syndrome toxin I (TSSTI), an exotoxin produced by certain strains of Staphylococcus aureus, has been closely associated with the pathogenesis of toxic shock syndrome. Outside the context of its staphylococcal host, TSSTI may offer therapeutic uses. We report here a strategy for high-level expression and simplified purification of TSSTI. We have subcloned the coding region for TSSTI into a vector containing an inducible T7 promoter sequence and expressed the protein in an Escherichia coli host strain. The recombinant TSSTI protein contained ten sequential histidine residues (Histag) at its N-terminus, which enabled its efficient purification using nickel-agarose-affinity resin. Histag-TSSTI (H-TSSTI) was further purified to homogeneity using a size-exclusion column. By this system, 80 mg of highly purified H-TSSTI can be consistently obtained per litre of culture in under 3 days. H-TSSTI retained biological activity and was unaffected by the presence of the Histag, as measured in lymphocyte proliferation assays.


Isolation of Campylobacter fetus subsp. jejuni from migratory waterfowl.
Since the sources from which humans acquire Campylobacter enteritis are only partially known, we studied the frequency of carriage of Campylobacter fetus subsp. jejuni in migratory waterfowl. Cecal contents of various species of wild ducks were cultured on selective media that contained antibiotics to inhibit normal flora. Thirty-five percent of the 445 ducks cultured harbored C. fetus subsp. jejuni. Migratory waterfowl are yet another reservoir for this enteric pathogen and may be of public health importance for humans in the contamination of water or when used as food.


Strand specific PCR amplification of low copy number DNA.
A method for the amplification of a single DNA strand at low copy number is described. It is a wholly PCR based approach which involves an initial linear amplification of the target using a tagged strand specific primer. This is followed by classical PCR amplification of the progeny using a pair of primers, one specific for the sequence tagged onto the 5' end of the first round primer, the second specific for the target sequence. Given the protocol used the ratio of the two strands in the final amplification product was 50:1.


Resurfacing of atrophic facial acne scars with a high-energy, pulsed carbon dioxide laser.
Treatment of atrophic acne scars has been limited to the use of such traditional treatments as dermabrasion and chemical peels for many years. Recently, the addition of high-energy, pulsed carbon dioxide (CO2) lasers to the treatment armentarium has created renewed enthusiasm for cutaneous resurfacing due to their ability to create specific thermal injury with limited side effects. To determine the effectiveness of a high-energy, pulsed CO2 laser in eliminating atrophic facial scars and to observe for side effects. Fifty patients with skin phototypes I-V and moderate to severe atrophic facial acne scars were included in the study. Each patient received one high-energy, pulsed CO2 laser treatment using identical laser parameters by the same experienced laser surgeon. Baseline and 1-, 4-, 8-, 12-, and 24-week postoperative photographs and clinical assessments were obtained in all patients. Textural analysis of skin before and after laser irradiation were obtained in 10 patients to confirm clinical impressions. Clinical evaluations were conducted independently by two blinded assessors. There was an 81.4% average clinical improvement observed in acne scars following laser treatment. Skin texture measurements of laser-irradiated scars were comparable to those obtained in normal adjacent skin. Side effects were limited to transient hyperpigmentation lasting an average of 3 months in 36% of patients. Prolonged erythema (2 months average) was usual and considered to be a normal healing response. No hypertrophic scarring was observed following laser treatment. High-energy, pulsed CO2 laser treatment can safely and effectively improve or even eliminate atrophic facial scars and provides many benefits over traditional treatment methods.


Practical and Ethical Considerations for Schools Using Social Media to Promote Physical Literacy in Youth.
The rapid development of social media has led to its increased use by children and adolescents for health and well-being purposes. Accordingly, social interactions resulting from social media use can be further integrated into physical and health education pedagogy. Given the relationship between increased physical literacy and positive health outcomes, best practices and lessons learned from social media use in the healthcare industry should be adopted by health and physical educators practicing in schools. Thus, the purpose of this paper is to comment on several practical and ethical challenges and opportunities associated with using social media to improve physical literacy among youth. Specifically, two of the most prominent issues are discussed in depth: (1) integration of social media in physical education settings that educate children and adolescents about the biopsychosocial effects of physical activity, and (2) use of wearable technologies among youth to accrue experiences that enhance physical literacy competencies. In our opinion, health and physical educators who utilize the ALL-ENGAGE Playbook described in this commentary will successfully reach, engage, and impact students with popular social media that adequately promotes physical literacy, including through experiential use of wearable technologies.


ERK-associated changes of AP-1 proteins during fear extinction.
Extensive research has unraveled the molecular basis of learning processes underlying contextual fear conditioning, but the mechanisms of fear extinction remain less known. Contextual fear extinction occurs when an aversive stimulus that initially caused fear is no longer present and depends on the activation of the extracellular signal-regulated kinase (ERK), among other molecules. Here we investigated how ERK signaling triggered by extinction affects its downstream targets belonging to the activator protein-1 (AP-1) transcription factor family. We found that extinction, when compared to conditioning of fear, markedly enhanced the interactions of active, phospho-ERK (pERK ) with c-Jun causing alterations of its phosphorylation state. The AP-1 binding of c-Jun was decreased whereas AP-1 binding of JunD, Jun dimerization protein 2 (JDP2) and ERK were significantly enhanced. The increased AP-1 binding of the inhibitory JunD and JDP2 transcription factors was paralleled by decreased levels of the AP-1 regulated proteins c-Fos and GluR2. These changes were specific for extinction and were MEK-dependent. Overall, fear extinction involves ERK/Jun interactions and a decrease of a subset of AP-1-regulated proteins that are typically required for fear conditioning. Facilitating the formation of inhibitory AP-1 complexes may thus facilitate the reduction of fear.


Cerebral hemodynamic effects of head-up CPR in a porcine model.
To assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. VF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) - ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. MAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. HUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.


Ferulic acid regulates muscle fiber type formation through the Sirt1/AMPK signaling pathway.
Ferulic acid (FA) is a polyphenolic compound of plant cell walls. Several recent studies demonstrated that polyphenolic compounds could regulate muscle fiber type formation. In this study, we investigated the effect of FA on muscle fiber type formation and also explored its molecular mechanism in mouse C2C12 myotubes. Real-time quantitative PCR showed that FA significantly increased the mRNA abundances of myosin heavy chain (MyHC) I, MyHC IIa, sirtuin1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator-1-α (PGC-1α) and myocyte enhancer factor 2C (MEF2C), but decreased the mRNA abundance of MyHC IIb. FA increased succinate dehydrogenase (SDH) activity and decreased lactate dehydrogenase (LDH) activity. Western blot analysis showed that FA significantly increased the protein level of slow-MyHC, but significantly decreased the protein level of fast-MyHC, which were attenuated by AMP-activated protein kinase (AMPK) inhibitor Compound C, AMPKα2 siRNA or Sirt1 inhibitor EX527. We also showed that EX527 attenuated FA-induced increase in the phosphorylation levels of AMPK and liver kinase B1 (LKB1), indicating that AMPK serves as a downstream target of Sirt1. Our present study provides the first in vitro evidence that FA regulates muscle fiber type formation via the Sirt1/AMPK signal pathway.


A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression.
Accurate diagnosis of thyroid tumors is challenging. A particular problem is distinguishing between follicular thyroid carcinoma (FTC) and benign follicular thyroid adenoma (FTA), where histology of fine-needle aspirates is not conclusive. It is often necessary to remove healthy thyroid to rule out carcinoma. In order to find markers to improve diagnosis, we quantified gene transcript expression from FTC, FTA, and normal thyroid, revealing 73 differentially expressed transcripts (P < or = 0.0001). Using an independent set of 23 FTCs, FTAs, and matched normal thyroids, 17 genes with large expression differences were tested by real-time RT-PCR. Four genes (DDIT3, ARG2, ITM1, and C1orf24) differed between the two classes FTC and FTA, and a linear combination of expression levels distinguished FTC from FTA with an estimated predictive accuracy of 0.83. Furthermore, immunohistochemistry for DDIT3 and ARG2 showed consistent staining for carcinoma in an independent set 59 follicular tumors (estimated concordance, 0.76; 95% confidence interval, [0.59, 0.93]). A simple test based on a combination of these markers might improve preoperative diagnosis of thyroid nodules, allowing better treatment decisions and reducing long-term health costs.


Detection of endocervical anti-Chlamydia trachomatis immunoglobulin A in pregnant women by a rapid, 6-minute enzyme-linked immunosorbent assay: comparison with PCR and chlamydial antigen detection methods.
There is a need for a rapid, uncomplicated, and inexpensive test for Chlamydia trachomatis infection in women. We evaluated the ability of a 6-min enzyme-linked immunosorbent assay (ELISA) that requires no laboratory equipment (IgA Rapid SeroTest; Savyon Diagnostics) to detect C. trachomatis immunoglobulin A (IgA) in the endocervices of 167 inner-city pregnant women and compared the results with DNA amplification (Amplicor PCR; Roche Diagnostics) and antigen detection (Chlamydiazyme; Abbott Laboratories) performed on the same women. Anti-C. trachomatis IgA was detected in the cervices of 32 women (19.2%). Samples from 23 women (13.8%) were PCR positive, while chlamydial antigen was present in 20 women (12.0%). There was only 1 sample (4.3%) that was positive by PCR but negative by ELISA; 10 samples were ELISA positive and PCR negative. In contrast, seven samples (30.4%) were PCR positive but Chlamydiazyme negative and four were Chlamydiazyme positive and PCR negative. Compared to PCR, the IgA ELISA had a sensitivity of 95.7%, a specificity of 93.1%, a positive predictive value of 68.8%, and a negative predictive value of 99.3%. The antigen assay had a sensitivity of only 69.6%, a specificity of 97.2%, a positive predictive value of 80.0%, and a negative predictive value of 95.2%. In high-risk groups where laboratory testing is not available, or where the patient might not return to obtain her testing result and be treated, the Rapid IgA SeroTest is a viable alternative for detection of cervical C. trachomatis in pregnant women.


Tail-associated structural protein gp61 of Staphylococcus aureus phage phi MR11 has bifunctional lytic activity.
A tailed bacteriophage, phi MR11 (siphovirus), was selected as a candidate therapeutic phage against Staphylococcus aureus infections. Gene 61, one of the 67 ORFs identified, is located in the morphogenic module. The gene product (gp61) has lytic domains homologous to CHAP (corresponding to an amidase function) at its N-terminus and lysozyme subfamily 2 (LYZ2) at its C-terminus. Each domain of gp61 was purified as a recombinant protein. Both the amidase [amino acids (aa) 1-150] and the lysozyme (aa 401-624) domains but not the linker domain (aa 151-400) caused efficient lysis of S. aureus. Immunoelectron microscopy localized gp61 to the tail tip of the phi MR11 phage. These data strongly suggest that gp61 is a tail-associated lytic factor involved in local cell-wall degradation, allowing the subsequent injection of phi MR11 DNA into the host cytoplasm. Staphylococcus aureus lysogenized with phi MR11 was also lysed by both proteins. Staphylococcus aureus strains on which phi MR11 phage can only produce spots but not plaques were also lysed by each protein, indicating that gp61 may be involved in 'lysis from without'. This is the first report of the presence of a tail-associated virion protein that acts as a lysin, in an S. aureus phage.


When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression.
Late-life depression (LLD) and Alzheimer's Disease (AD) are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging. The aim of the present study was to evaluate in a population of elderly patients affected by depression and dementia the usefulness of CSF AD biomarkers (tau proteins and β-amyloid42-Aβ42) and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (18FFDG-PET) in early differentiating LLD from AD. Two hundred and fifty-six depressed and demented patients, after performing CSF AD biomarkers and 18FFDG-PET, were distributed in two groups on the basis of the current diagnostic guidelines for AD (n = 201) and LLD (n = 55). Patients were then observed for 2 years to verify the early diagnosis. After the 2 year follow-up we compared AD and LLD patients' CSF and 18FFDG-PET data obtained at baseline to a group of age- and sex-matched controls. We found CSF Aβ42 levels significantly higher in LLD compared to AD patients. Remarkably, CSF Aβ42 levels of LLD patients (range between 550 and 1204 pg/mL) did not overlap with those of AD patients (range between 82 and 528 pg/mL). Moreover, we documented no differences in CSF AD biomarkers (Aβ42 and tau proteins) when comparing LLD patients to controls. In addition, AD patients showed the significant reduction of 18FFDG-PET uptake in temporo-parietal regions compared to both controls and LLD. Conversely, LLD and control groups did not differ at 18FFDG-PET analysis, although LLD patients showed heterogeneous patterns of glucose hypometabolism involving cortical and subcortical brain areas. It is noteworthy that at the end of the clinical follow-up, patients owing to AD group showed the expected significant decline of cognitive performances, whereas patients assigned to LLD group improved cognition as depressive symptoms recovered. Hence, in case of co-existence of cognitive impairment and depression in the elderly, we propose CSF AD biomarkers analysis to early differentiate LLD from AD and properly target the patient's therapeutic strategy and clinical follow-up.


The oldest known digestive system consisting of both paired digestive glands and a crop from exceptionally preserved trilobites of the Guanshan Biota (Early Cambrian, China).
The early Cambrian Guanshan biota of eastern Yunnan, China, contains exceptionally preserved animals and algae. Most diverse and abundant are the arthropods, of which there are at least 11 species of trilobites represented by numerous specimens. Many trilobite specimens show soft-body preservation via iron oxide pseudomorphs of pyrite replacement. Here we describe digestive structures from two species of trilobite, Palaeolenus lantenoisi and Redlichia mansuyi. Multiple specimens of both species contain the preserved remains of an expanded stomach region (a "crop") under the glabella, a structure which has not been observed in trilobites this old, despite numerous examples of trilobite gut traces from other Cambrian Lagerstätten. In addition, at least one specimen of Palaeolenus lantenoisi shows the preservation of an unusual combination of digestive structures: a crop and paired digestive glands along the alimentary tract. This combination of digestive structures has also never been observed in trilobites this old, and is rare in general, with prior evidence of it from one juvenile trilobite specimen from the late Cambrian Orsten fauna of Sweden and possibly one adult trilobite specimen from the Early Ordovician Fezouata Lagerstätte. The variation in the fidelity of preservation of digestive structures within and across different Lagerstätten may be due to variation in the type, quality, and point of digestion of food among specimens in addition to differences in mode of preservation. The presence and combination of these digestive features in the Guanshan trilobites contradicts current models of how the trilobite digestive system was structured and evolved over time. Most notably, the crop is not a derived structure as previously proposed, although it is possible that the relative size of the crop increased over the evolutionary history of the clade.


Agraphia for kanji resulting from a left posterior middle temporal gyrus lesion.
To clarify whether agraphia or alexia occurs in lesions of the left posterior middle temporal gyrus. We assessed the reading and writing abilities of two patients with this lesion using kanji (Japanese morphograms) and kana (Japanese syllabograms). Patient 1 first presented with pure alexia more impaired for kana after an infarction in the left middle and inferior occipital gyri and right basal occipital cortex, and after a second infarction in the left posterior middle temporal gyrus adjoining the first lesion he showed alexia with agraphia for kanji and worsened alexia for kana; kanji alexia recovered over the following six to 10 months. Patient 2 presented with alexia with agraphia for kanji following a hemorrhage in the left posterior middle and inferior temporal gyri, which resolved to agraphia for kanji at two months after onset. Kana nonword reading was also slightly impaired, but became normal by six months post-onset. In both patients, kanji agraphia was mostly due to impaired character recall. The present patients demonstrate that damage to the left posterior middle temporal gyrus alone can cause agraphia for kanji. If the adjacent mid fusiform/inferior temporal gyri (Area 37) are spared, the kanji alexia is transient.


High-attenuation mucous plugging in allergic bronchopulmonary aspergillosis.
To assess the prevalence of high-attenuation mucous plugs observed on chest computed tomography (CT) scans in patients with allergic bronchopulmonary aspergillosis. The CT scans of 14 patients with allergic bronchopulmonary aspergillosis, seen between July 1990 and July 1994 at a single tertiary-care institution, were reviewed. The presence and distribution of high-attenuation mucous plugs were recorded in each case. High-attenuation mucous plugs were present in 4 (28%) of the 14 patients. Mucous plugging was unilobar in three of these four patients. Mucous plugging with attenuation similar to that of chest wall muscle was not found in any of the patients with high-attenuation plugging. High-attenuation mucous plugs occur in approximately one quarter of patients with allergic bronchopulmonary aspergillosis and may be more common in patients with unilobar plugging.


A circuit model for nonlinear simulation of radio-frequency filters using bulk acoustic wave resonators.
This paper describes a circuit model for the analysis of nonlinearity in the filters based on radiofrequency (RF) bulk acoustic wave (BAW) resonators. The nonlinear output is expressed by a current source connected parallel to the linear resonator. Amplitude of the nonlinear current source is programmed proportional to the product of linear currents flowing in the resonator. Thus, the nonlinear analysis is performed by the common linear analysis, even for complex device structures. The analysis is applied to a ladder-type RF BAW filter, and frequency dependence of the nonlinear output is discussed. Furthermore, this analysis is verified through comparison with experiments.


A model of a computer file for the intensive neonatal practice "Neonatal Intensive Computer File".
The use of computer methods for processing the databases gathered in a neonatal intensive care unit has more than 20 years experience. During the past years various systems for data management in accordance with the nature of the work have been designed. The aim was to create a method for quick and easy processing of variable clinical material in an uniform format. The method allows the arrangement of the entire primary information into a standardized database suitable for computer processing, following up an unlimited number of parameters, calculating derivative indices, representing and evaluating data by means of graphic trends, surveying current clinical information not only for routine practice, but also for research purposes. We developed a computer file type method. This is a method enabling the systematic and well arranged structuring of the newborn's history, the recordings of the monitoring and life-supporting equipment, the data from clinical, laboratory examinations and all the other implemented diagnostic-therapeutic procedures, family, social and possibly legal background. The proposed method Neonatal Intensive Computer File (NICF) was applied successfully in the management the data of the above mentioned project (Grant L-444, MES-Sofia): organizes the entire information into a form suitable for the everyday clinical practice and for research studies. Neonatal Intensive Computer File (NICF) gives ample possibilities for quick and reliable evaluation of the condition of the newborn infant and the effect of the applied treatment. The introduced panel (complex) of indices with possibilities for its expansion allows early detection of advancing and threatening disturbances, characterizes the type and pinpoints the exact time and location of the disturbances occurring in the system ventilator-patient-physician. The graphic trends visualize the variation of the indices and contributes to the quick evaluation and orientation in them. They are considerably more informative than the single time registered values of any indicator or index. Optimizes the management of the applied ventilation/oxygenation technique and overall treatment, facilitates the timely decision-making process (the change and/or the choice of new therapeutic alternatives) Facilitates the statistical analysis of the total accumulated data or a selected part of it. Allows the use of the same clinical material for the needs of multiple research projects guaranteeing precision and reliability. The accumulated databases (information bank) are important for future prospective and retrospective studies not only in the clinical but also in the social field. The information yielded by Neonatal Intensive Computer File (NICF) can be used for prognostic projections and conclusions in terms of the current condition and outcome as well as ad vitam.


The role of skeletal muscle sphingolipids in the development of insulin resistance.
Insulin resistance is an important risk factor for type 2 diabetes, obesity, cardiovascular disease, polycystic ovary syndrome and other diseases. The most important stage in the development of insulin resistance is impairment of insulin-stimulated skeletal muscle glucose uptake. There is evidence that intramyocellular lipids might be responsible for this process through inhibition of insulin signaling. One of the important intracellular lipid pools is associated with the sphingomyelin signaling pathway. The second messenger in this pathway is ceramide. In vitro data indicate that ceramide inhibits insulin signaling, mainly through inactivation of protein kinase B. In vivo data suggest that ceramide accumulation within muscle cells might be associated with the development of insulin resistance. In this review, we discuss both in vitro and in vivo evidence for the role of muscle ceramide in the impairment of insulin action with particular focus on the question whether findings from animal studies are applicable to humans. We describe problems that are unresolved so far and topics of potential interest for future research.


Integration of tuberculosis and HIV services: Exploring the perspectives of co-infected patients in Ghana.
Scaling up of integrated tuberculosis (TB)-human immunodeficiency virus (HIV) services remains sub-optimal in many resource-limited countries, including Ghana, where the two conditions take a heavy toll on the financial resources of health systems as well as infected persons. Previous studies have documented several implementation challenges towards TB-HIV service integration, but views of patients on integrated service delivery have not received commensurate research attention. This paper explored the experiences of 40 TB-HIV co-infected patients at different stages of treatment in Ghana. Using Normalisation Process Theory as a framework, data were coded using inter-rater coding technique and analysed inductively and deductively with the help of QSR NVivo 10. For several participants, either of the diseases was diagnosed 'accidentally', leading to inconsistencies in co-therapy administration, constraints regarding separate clinic appointment dates for TB and HIV and prolonged TB treatment due to treatment failure. Put differently, there were widespread negative experiences among TB-HIV co-infected patients with regard to treatment and care, especially among patients who were accessing care in separate facilities or separate units in the same facility. Co-infected patients unanimously support full-service integration. However, they felt powerless to request for reforms on a mode of service delivery.


Functional MR imaging of cortical activation of the cerebral hemispheres during motor tasks.
We used functional MR imaging to evaluate cortical activation in the precentral, central, and postcentral regions of the contralateral and ipsilateral cerebral hemispheres during left- and right-handed motor tasks. Ten healthy right-handed volunteers were studied with echo-planner MR imaging (1.5 T) while performing alternating finger apposition tasks with both hands. During the hand tasks, the areas of activated pixels were compared between subregions (precentral, central, and postcentral) of the contralateral and ipsilateral sensorimotor cortex. The activated area of the contralateral sensorimotor cortex was significantly larger than that of the ipsilateral cortex during tasks with either hand, whereas the ipsilateral activated area was significantly larger during the left-handed task than during the right-handed task. Ipsilateral activation was greatest in the precentral region, less in the central region, and least prominent in the postcentral region. Our results confirmed those of previous investigators that ipsilateral activation is more pronounced during left-sided movements than during right-sided movements. The variation in activation of the precentral, central, and postcentral subregions suggests different roles of the ipsilateral and contralateral hemispheres during motor tasks.


Ly-1 B helper cells in autoimmune "viable motheaten" mice.
Previous work has demonstrated that Ly-1 B cells from normal C57BL/6J mice help the response of B cell subsets to the 4-hydroxy-3-nitrophenylacetyl hapten (NP). This regulatory cell population, called BH, preferentially helps the expression of plaque-forming B cells which express a predominant set of serologically related determinants collectively known as the NPb idiotype family. The specificity of BH cell activity in the NP system is a reflection of NPb idiotype-specific BH cell surface receptors. Thus, BH cells recognize autologous (i.e., idiotype) antigens. Given these observations and previous associations of increased Ly-1 B cell frequency in autoimmune mice, it was hypothesized that autoreactive Ly-1 BH cells may be present in high frequencies and in an activated state in autoimmune mice. To test this hypothesis the immunologic activity of BH cells in autoimmune viable motheaten (mev/mev) mice was studied. It was determined that splenic BH cells are approximately 10 times more frequent in viable motheaten than normal mice. The fact that BH cells from viable motheaten mice are activated was suggested by the presence of NPb idiotype-specific BH replacing helper activity in sera or B cell supernatants from these autoimmune mice. The soluble helper activities constitutively produced in mev/mev splenic B cell cultures and detected in mev/mev serum were resolved into two moieties, an NPb idiotype-specific immunoglobulin and a nonimmunoglobulin lymphokine(s) fraction. Purified mev/mev B cell-derived B cell maturation factor could substitute for the lymphokine moiety in the NPb idiotype helper cell assay. These results suggest that at least two signals, anti-idiotype immunoglobulin and a late-acting B cell maturation factor, are required for BH-dependent helper activity. The relationships of these results to current concepts of B cell activation mechanisms and the possible association of Ly-1 BH cells with autoimmunity are discussed.


Composition and some biological activities of the essential oil of Callicarpa americana (L.).
The essential oil profile of Callicarpa americana was examined. Samples were collected from Lafayette county in north central Mississippi, and GC-MS data and retention indices were used to identify 67 oil components. Humulene epoxide II (13.9%), alpha-humulene (10.0%), 7-epi-alpha-eudesmol (9.4%), beta-pinene (8.8%), and 1-octen-3-ol (8.5%) were the major components of the steam-distilled oil. The oil was selectively toxic toward the cyanobacterium Oscillatoria perornata compared to Oscillatoria agardhii and the green alga Selenastrum capricornutum, with complete growth inhibition at 28.5 microgram/mL. The oil was only mildly phytotoxic and antifungal.


High-dimensional immunomonitoring models of HIV-1-specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control.
The development of immunomonitoring models to determine HIV-1 vaccine efficacy is a major challenge. Studies suggest that HIV-1–specific CD8 T cells play a critical role in subjects achieving spontaneous viral control (HIV-1 controllers) and that they will be important in immune interventions. However, no single CD8 T-cell function is uniquely associated with controller status and the heterogeneity of responses targeting different epitopes further complicates the discovery of determinants of protective immunity. In the present study, we describe immunomonitoring models integrating multiple functions of epitope-specific CD8 T cells that distinguish controllers from subjects with treated or untreated progressive infection. Models integrating higher numbers of variables and trained with the least absolute shrinkage and selection operator (LASSO) variant of logistic regression and 10-fold cross-validation produce "diagnostic tests" that display an excellent capacity to delineate subject categories. The test accuracy reaches 75% area under the receiving operating characteristic curve in cohorts matched for prevalence of protective alleles. Linear mixed-effects model analyses show that the proliferative capacity, cytokine production, and kinetics of cytokine secretion are associated with HIV-1 control. Although proliferative capacity is the strongest single discriminant, integrated modeling of different dimensions of data leverages individual associations. This strategy may have important applications in predictive model development and immune monitoring of HIV-1 vaccine trials. Immune monitoring models integrating multiple functions of HIV-1-specific CD8 T cells distinguish controllers from subjects with progressive HIV-1 infection. This strategy may have important applications in predictive model development and immune monitoring of HIV-1 vaccine trials.