Structural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide.
The islet amyloid polypeptide (IAPP) is the main constituent of the amyloid fibrils found in the pancreas of type 2 diabetes patients. The aggregation of IAPP is known to cause cell death, where the cell membrane plays a dual role: being a catalyst of IAPP aggregation and being the target of IAPP toxicity. Using ATR-FTIR spectroscopy, transmission electron microscopy, and molecular dynamics simulations we investigate the very first molecular steps following IAPP binding to a lipid membrane. In particular, we assess the combined effects of the charge state of amino-acid residue 18 and the IAPP-membrane interactions on the structures of monomeric and aggregated IAPP. Distinct IAPP-membrane interaction modes for the various IAPP variants are revealed. Membrane binding causes IAPP to fold into an amphipathic α-helix, which in the case of H18K-, and H18R-IAPP readily moves beyond the headgroup region. For all IAPP variants but H18E-IAPP, the membrane-bound helix is an intermediate on the way to amyloid aggregation, while H18E-IAPP remains in a stable helical conformation. The fibrillar aggregates of wild-type IAPP and H18K-IAPP are dominated by an antiparallel β-sheet conformation, while H18R- and H18A-IAPP exhibit both antiparallel and parallel β-sheets as well as amorphous aggregates. Our results emphasize the decisive role of residue 18 for the structure and membrane interaction of IAPP. This residue is thus a good therapeutic target for destabilizing membrane-bound IAPP fibrils to inhibit their toxic actions.


Hyalurondiase: both a tumor promoter and suppressor.
Originally termed as the "spreading factor", hyaluronidases (HAases) are present in a variety of toxins and venoms. For example, HAase is the virulent factor of beta-hemolytic Streptococci and it is also present in the venoms of snake, bee, wasp, scorpion, etc, where it aids in the spread of these venoms in the body. In mammals, testicular HAase present in the sperm acrosome is necessary for the fertilization of the ovum. Despite a lot of work on bacterial, invertebrate and testicular HAases, a connection between HAase and cancer was unequivocally established just over a decade ago and the functional significance of HAases in cancer was demonstrated just about a year ago. In this part of the review, we will focus on the recent advances in our understanding of the role of HAases in cancer.


Polygenic expression of somatostatin in orange-spotted grouper (Epinephelus coioides): molecular cloning and distribution of the mRNAs encoding three somatostatin precursors.
In the present study, three preprosomatostatin (PSS) cDNAs were characterized from hypothalamus of orange-spotted grouper Epinephelus coioides. The first cDNA encodes a 123-amino acid protein (PSSI) that contains the SS14 sequence at its C-terminal extremity and that is identical to that of PSSI of human and other vertebrates. The second cDNA encodes a 127-amino acid protein (PSSII) that contains the SS28 sequence with [Tyr7, Gly10]-SS14 at its C-terminus. The third cDNA encodes a 110-amino acid protein (PSSIII) that contains the somatostatin variant [Pro2]-SS14 at its C-terminal extremity. All these three PSS mRNAs were expressed in brain and pituitary with different mRNA levels. In peripheral tissues, PSSII was more widely distributed than PSSI and PSSIII. High mRNA levels of PSS were found in stomach, intestine and ovary. PSS mRNAs were detected throughout embryogeny and early larval development. Its levels increased with the embryonic development and maintained a higher level during larva developing. The mRNA distribution suggests that the three grouper PSS products play important physiological functions in adult fish as well as in cell growth and organ differentiation in embryo and larva development.


A comparison of 131I-labeled antibodies, 2-deoxy-2-[18F]fluoro-D-glucose and 68Ga-EDTA in the imaging of human tumor xenografts in nude mice.
Three different biological properties--glucose metabolism, gallium imaging and antigen-antibody interaction--have been targeted to image human tumor xenografts implanted in nude mice. Seventy-two experiments were performed in 25 nude mice. Two types of human tumors were used: colorectal carcinoma SW 1116 and melanoma WM 9. Immunoscintigraphic studies produced the highest tumor sampling and confirmed earlier findings that F(ab')2 fragments generate better tumor images than whole antibodies.


Photorhabdus temperata subsp. stackebrandtii subsp. nov. (Enterobacteriales: Enterobacteriaceae).
The bacterial symbiont of the entomopathogenic nematode Heterorhabditis bacteriophora strain GPS11 was characterized by 16S rRNA gene sequence and physiological traits. The phylogenetic tree built upon 16S rRNA gene sequences clustered the GPS11 bacterial isolate with Photorhabdus temperata strains which have been previously isolated from Heterorhabditis species. The phylogenetic tree further identified four subgroups in P. temperata, and the relationships among these subgroups were confirmed by gyrase subunit B (gyrB) gene sequence analysis. The subgroup containing the GPS11 bacterial isolate differs from other subgroups in sequences of 16S rRNA and gyrB gene, physiological traits, nematode host species, and geographic origin. Therefore, the subgroup comprising the GPS11 bacterial isolate is proposed here as a new subspecies: Photorhabdus temperata subsp. stackebrandtii subsp. nov. (type strain GPS11). The type strain has been deposited in ATCC and DSMZ collections.


Reduction in selective under-ascertainment bias in population-based estimates of cancer patient survival by age adjustment.
Selective under-ascertainment of cancer patients by cancer registries may bias population-based estimates of cancer patient survival. As prognosis is strongly age related for many forms of cancer, age adjustment of cancer survival rates, which is primarily used to enhance the validity of comparative analyses between cancer populations, might also effectively reduce this type of bias. We empirically assessed this potential "side-effect" of age adjustment using data from the Finnish Cancer Registry. Analyses of five-year absolute and relative survival for patients diagnosed in 1990-1994, and age adjustment to the age structure of patients diagnosed in 1985-1989, were used as examples. Various patterns of selective under-ascertainment were simulated, and the bias in crude and age adjusted five-year survival rates was compared. Age adjusted estimates were less biased in most scenarios, which may be an additional argument for application of age adjustment in the analysis and reporting of population-based cancer survival rates.


Environmental Risk Factors for Osteoarthritis: The Impact on Individuals with Knee Joint Injury.
Osteoarthritis is a debilitating chronic condition involving joint degeneration, impacting over 300 million people worldwide. This places a high social and economic burden on society. The knee is the most common joint impacted by osteoarthritis. A common cause of osteoarthritis is traumatic joint injury, specifically injury to the anterior cruciate ligament. The purpose of this review is to detail the non-modifiable and modifiable risk factors for osteoarthritis with particular focus on individuals after anterior cruciate ligament injury. After reading this, health care providers will better comprehend the wide variety of factors linked to osteoarthritis.


AMDIS Case Conference: Implementing Electronic Health Records in a Small Subspecialty Practice.
Electronic health record adoption has failed to achieve critical mass in small private practices in no small part due to lack of leadership; the challenge of cultural change; and the difficulty of adapting to new automated workflows. We present one small practice that successfully navigated these obstacles, and examine its accomplishments through the lens of organizational psychology.


Development and pilot-testing of a health-related quality of life chronic generic module for children and adolescents with chronic health conditions: a European perspective.
Health-related quality of life (HRQOL) assessment in children and adolescents with chronic health conditions is increasingly considered as a relevant topic. The aim of the EU-funded DISABKIDS project is to develop, test, and implement European instruments for the assessment of HRQOL of children and adolescents with disabilities and their families. The current paper describes the development and pilot testing of a chronic generic HRQOL measure. Using literature searches, expert consulting and focus groups with children/adolescents and their families, items of the instruments were developed and translated into the respective languages. A pilot test with 360 children and adolescents was conducted. Children and adolescents (8-12, 13-16 years) with different chronic health conditions (asthma, epilepsy, diabetes, arthritis, atopic dermatitis, cerebral palsy, and cystic fibrosis) as well as their families were included. Data were analysed according to predefined psychometric and content criteria. Psychometric analyses resulted in a 56-item chronic generic HRQOL questionnaire with six domains ('Medication', 'Physical', 'Emotion', 'Independence', 'Social Inclusion', 'Social Exclusion') with acceptable internal consistency.


IGFBP-3 sensitizes prostate cancer cells to interferon-gamma-induced apoptosis.
Insulin-like growth factor binding protein-3 (IGFBP-3) has been shown to exhibit diverse biological actions, including IGF-independent effects on cell growth and cell death. Here we report that IGFBP-3 sensitizes prostate cancer cells to interferon-gamma (IFN-gamma)-induced apoptosis and inhibition of cell proliferation. The cell growth or cell death of prostate cells in response to the treatments of IGFBPs and/or IFN-gamma was measured, and the signaling pathways mediating these actions assessed. Cell proliferation was minimally affected when M12 prostate cancer cells were treated with exogenous IGFBP-3 (1-5 microg/ml), IGFBP-1 (1-5 microg/ml) or IFN-gamma (20 U/ml). However, strong inhibition of cell growth and significant apoptosis were observed when M12 cells were co-treated with IGFBP-3 and IFN-gamma, but not with IGFBP-1 and IFN-gamma. These effects were IGF-independent and appear not to require intracellular localization of IGFBP-3, as similar results were obtained with mutants of IGFBP-3 that either could not bind IGF or has impaired ability to be internalized. Further analyses revealed that IGFBP-3, but not IGFBP-1, could significantly enhance the weak tyrosine phosphorylation of STAT1 induced by IFN-gamma (20 U/ml) alone. The IGFBP-3-promoted apoptosis in the presence of IFN-gamma could also be abrogated by blockade of the mTOR pathway with its pharmacological inhibitors, LY294002 or rapamycin. These results demonstrated that in a cancer cell line not responsive to exogenous IGFBP-3 alone, IGFBP-3 sensitized the cells to the anti-proliferative, proapoptotic actions of IFN-gamma through an IGF-independent, STAT1- and mTOR-dependent mechanism.


Optimal prediction of bone mineral density with ultrasonic measurements in excised human femur.
Bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) techniques is the current gold standard for osteoporotic fracture risk prediction. Quantitative ultrasound (QUS) techniques in transmission measurements are, however, increasingly recognized as an alternative approach. It is feasible to select different QUS methods, one type being optimized to assess microarchitectural properties of bone structure and another to assess BMD. Broadband ultrasonic attenuation (BUA) and ultrasonic velocity (UV) measured on the proximal human femur have been shown to be both significantly correlated with BMD. However, a great diversity of algorithms has been reported to measure the time-of-flight used to derive UV values. The purpose of this study was to determine which procedure results in the optimal BMD prediction at the proximal femur from ultrasound measurements. Thirty-eight excised human femurs were measured in transmission with a pair of focused 0.5-MHz central frequency transducers. Two-dimensional scans were performed and radiofrequency (RF) signals were recorded digitally at each scan position. BUA was estimated and eight different signal processing techniques were performed to estimate UV. For each signal-processing technique UV was compared to BMD. We show that the best prediction of BMD was obtained with signal-processing techniques taking into account only the first part of the transmitted signal (r2BMD-SOS = 0.86). Moreover, we show that a linear multiple regression using both BUA and speed of sound (SOS) and applied to site-matched regions of interest improved the accuracy of BMD predictions (r2BMD-SOS/BUA = 0.95). Our results demonstrate that selecting specific signal-processing methods for QUS variables allows optimal assessment of BMD. Correlation is sufficiently high that this specific QUS method can be considered as a good surrogate of BMD.


Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit.
The corpus cavernosum is the erectile tissue in the penis and clitoris. Although nitrergic neurotransmission has been characterized in detail in the penile corpus cavernosum, functional studies on the inhibitory non-adrenergic non-cholinergic (NANC) transmission in the clitoral corpus cavernosum have been lacking. Here we demonstrate that electrical field stimulation (EFS) induces NANC relaxation responses in the clitoral corpus cavernosum of the rabbit. These responses were inhibited by NG-nitro-L-arginine methylester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) or tetrodotoxin. The inhibitory effect of L-NAME was partially reversed by L-arginine but not by D-arginine. EFS-induced relaxations were enhanced by an inhibitor of type V cyclic GMP phosphodiesterase, zaprinast. These results suggest that nitrergic neurotransmission is responsible for the NANC relaxation responses in the clitoral corpus cavernosum of the rabbit.


Nonablative laser surgery for pigmented skin.
Nonablative laser surgery has been proven to improve early photodamaged skin and acne scars. These techniques include treatments with lasers, light sources, and/or radiofrequency devices. To review the history of nonablative technology and its applicability to darker skin types and to provide an objective look at the various published studies documenting the efficacy of nonablative technology. Nonablative laser surgery can improve skin quality and acne scars in all skin types. Complications are rare but can occur. Future studies are required to compare the efficacy of the various nonablative technologies.


Management of acute and chronic disorders of the trachea and subglottis.
During a 14 year period, 22 patients with stricture, acute laryngeal injury, and cancer were treated. Nine patients had postintubation tracheal stenosis and underwent tracheal resection with good to excellent results. Six patients had strictures after tracheostomy. In one patient, stenosis occurred after repair and repeated dilatation was necessary. He subsequently had to undergo repeat tracheostomy, but the tube was later removed and his symptoms disappeared. Our current preference for suture is either 3-0 polypropylene or polyglycolic acid. Acute separation of the trachea can occur with trauma to the neck, either by garrotting or direct blunt force. The diagnosis is suspected when endotracheal intubation is impossible and a step off below the larynx and crepitation exists. Emergency tracheostomy is necessary, however, and primary repair can be delayed for up to 24 hours if other conditions require attention. Tracheal resection for squamous cell carcinoma is possible, but only a small group of patients may be surgical candidates.


An early report: a modified porphyrin-linked metronidazole targeting intracellular Porphyromonas gingivalis in cultured oral epithelial cells.
Porphyromonas gingivalis (P. gingivalis) has a strong association with the pathogenesis of periodontal disease. Recurrence of periodontal disease following therapy is attributed to numerous factors, and of growing interest is the potential problem of intracellular bacteria that are able to persist and multiply within the host cell, thereby facilitating relapse of infection. The effect of antibiotic therapy in controlling P. gingivalis is questionable. Accordingly, while metronidazole is very effective against anaerobic extracellular P. gingivalis by disrupting the DNA of anaerobic microbial cells, this antibiotic does not effectively penetrate into mammalian cells to inhibit intracellular bacteria. Therefore in the present study, a modified porphyrin-linked metronidazole adducts, developed in our laboratory, was used to kill intracellular P. gingivalis. A series of experiments were performed, including cytotoxicity assays and cellular uptake of adducts by flow cytometry coupled with live cell imaging analysis, P. gingivalis invasion and elimination assays, and the analysis of colocalization of P. gingivalis and porphyrin-linked metronidazole by confocal laser scanning microscopy. Findings indicated that P. gingivalis and porphyrin-linked metronidazole were colocalized in the cytoplasm, and this compound was able to kill P. gingivalis intracellular with a sufficient culture time. This is a novel antimicrobial approach in the elimination of P. gingivalis from the oral cavity.


Krameria, free fatty acids and oil-collecting bees.
Vogel's report of the production of glycerides rather than nectar as rewards gathered by bees described an association involving several genera of insects and numerous plant families. We report here that members of the Krameriaceae produce floral lips more unusual than those described by Vogel. Our data also provide evidence that the oils of Krameria are collected by bees of only one genus, Centris (Anthophoridae), and used, mixed with pollen, as larval food.


Results of an enhanced clinic handoff and resident education on resident patient ownership and patient safety.
Although internal medicine resident clinic handoffs present risks for patients, few interventions exist. The authors evaluated an enhanced handoff. In 2011, the authors formalized a handoff protocol including a standardized sign-out process, resident education, improved scheduling, and time to establish care through telephone visits. The authors surveyed 25 residents in 2011 and 19 in 2010 regarding their perceptions and performed chart audits to examine patient outcomes. Compared with 2010, residents in 2011 reported longer handoffs (>20 minutes, 52% versus 6%, P<.01), more verbal handoffs (80% versus 38%, P<.01), more patients aware of the handoff (100% versus 74%, P=.01), less discomfort with paperwork for patients not yet seen (40% versus 74%, P=.03), and more ownership of patients before the first visit (56% versus 26%, P=.05). In 2011, more patients saw their correct primary care provider (82% versus 44%, P<.01), and more tests were followed up appropriately (67% versus 46%, P=.02). The authors detected in 2011 a trend for patients to be seen the month their physician intended (40% versus 33%, P=.06) and a trend toward fewer acute (hospital and emergency department) visits three months post handoff (20% versus 26%, P=.06). Enhancing clinic handoffs can improve the handoff process, increase the likelihood of patients seeing the correct primary care provider within the target time frame, reduce missed tests, and possibly reduce acute visits.


Development of an improved real time PCR for the detection of bovine leukaemia provirus nucleic acid and its use in the clarification of inconclusive serological test results.
With the aim to erradicate Enzootic Bovine Leukosis from Poland, a more sensitive real-time polymerase chain reaction was required and developed to detect proviral Bovine leukaemia virus (BLV) DNA, the causative agent of Enzootic Bovine Leukosis (EBL). This new method proved more sensitive for our needs, than the current protocols available in the public domain. DNA was extracted from peripheral blood leukocytes of 51 cattle, which had given rise to doubtful serological test results by ELISA, and from mesenteric lymph nodes of six cattle that were slaughtered as EBL suspect cases. Additionally, fourteen DNA samples were obtained from animals with a strong BLV antibody response by ELISA. All real-time data were compared to results obtained from three different nested PCR methods. All 14 strongly positive ELISA samples were positive in all PCR tests. The real-time assay in comparison to the conventional PCR methods detected 7.8% (4/51) more specimens positive for BLV nucleic acid and showed a detection limit down to one copy. These observations represent the first report in the value of using a real-time method to help elucidate the disease status of animals when inconclusive ELISA results are obtained in the diagnostic laboratory. Thus, this method should be recommended for use in countries which have implemented an EBL-eradication programme, where a low level of BLV infection is evident.


Ecological resistance to the invasion of a freshwater clam, Corbicula fluminea: fish predation effects.
Fish predation is shown to have a twenty nine fold effect on the abundance of the invasive freshwater clam, Corbicula fluminea, in a Texas reservoir. This predation has prevented the clam from establishing the high densities commonly reported for it elsewhere. The high magnitude of the fish effect is attributed to Corbicula being an invader to this reservoir and not being able to cope well with the mix of resident fish species. In the absence of fish, colonization of the reservoir by Corbicula is spatially patchy. When fish interact with these clams, they remove sufficient numbers of individuals from dense patches to create the appearance of a spatially uniform distribution.


Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents.
The widespread use of antineoplastic drugs in cancer treatment increased concern about possible hazard to workers involved in the preparation and administration of these drugs. In the present study, the effects of commercial antioxidative drug Oligogal Se on genome protection were analyzed in 15 nurses handling the antineoplastic drugs at the Oncology Department in comparison to twenty healthy volunteers. The nurses took antioxidant mixture Oligogal Se, consisting of vitamins C, E, A and selenium, one capsule per day, over a period of 6 months. Genome damage was measured in peripheral blood lymphocytes by usage of sister chromatid exchange test and the cytokinesis-block micronuclei test. The frequency of sister chromatid exchange (SCE) and micronuclei (MN) in the exposed group was significantly higher when compared to the control group (SCE, p<0.05; MN, p<0.01 respectively). After antioxidant supplementation, the frequency of sister chromatid exchange and micronuclei decreased (p<0.05) when compared with the values from the beginning of the study, but were still above the values of the control group. The effects of confounding factors such as cigarette smoking and cytostatics exposure time were also evaluated. The data indicated that Oligogal Se contributed to the decreasing of genome damages in workers handling the cytostatics.


Experimental murine cryptococcal infection results in contamination of bedding with Cryptococcus neoformans.
Cryptococcus neoformans is a fungal pathogen that survives in diverse environments. To determine whether cages of mice infected with C. neoformans posed an infection risk to animal caregivers, we investigated whether the fungus could be isolated from the bedding or stool of mice infected by intratracheal (i.t.), intravenous (i.v.), or intraperitoneal (i.p.) routes. The bedding of mice infected i.t. was contaminated with C. neoformans. In contrast, no contamination of bedding with C. neoformans was detected in cages of mice infected i.v. or i.p. C. neoformans was not isolated from murine feces. The C. neoformans strain recovered from bedding material was indistinguishable from the infecting strain by biochemical and molecular techniques. This result suggests that precautions may be warranted when disposing bedding from cages that housed mice with pulmonary C. neoformans infection.


Clinico-bacteriological profile and outcome of empyema.
Empyema thoracis is a common cause of morbidity in children. We conducted a prospective observational study in 50 children (age 0-15 y) diagnosed with empyema to study its clinico-bacteriological profile and outcome in a referral hospital. Staphylococcus aureus was the most common causative organism, most of them being MRSA, followed by Pneumococcus and Pseudomonas. Primary video-assisted thoracoscopy appeared to be a good mode of management with lesser duration of hospital stay. However, the number of children undergoing this procedure was very less, to come to any conclusion.


Temporal changes in body surface peak R isochrone maps and left ventricular function in patients with myocardial infarction.
Body surface peak R isochrone mapping and radionuclide ventriculography were performed twice in 22 patients with myocardial infarction. Eighty-seven unipolar electrocardiograms distributed over the anterior chest and the back were recorded simultaneously. For each lead, the time from the onset of QRS to the peak of the R wave was measured. From this data for 87 leads an isochrone map was constructed. The lead points where R waves were not observed were designated the no R-wave area (No-R area), which was postulated to correspond to the unexcited regional myocardium. Other abnormal findings, i.e., delay of peak R time near the No-R area (peri-No-R area delay), crowding of isochrone lines, and an island-like zone of delayed peak R times were postulated to indicate slow conduction in the partially excited regional myocardium. In three patients, abnormal patterns in the peak R isochrone maps during the acute phase (within a month from the onset of myocardial infarction) improved in the chronic phase with a significant increase in left ventricular ejection fraction. In two patients, the No-R area decreased after the left ventricular aneurysmectomy. In other patients, abnormal patterns of the isochrone maps and the ejection fraction remained unchanged during the chronic phase of myocardial infarction. We conclude that the comparison of peak R isochrone map patterns between the acute and chronic phase may be useful in evaluating the balance of reversible and irreversible regional damage in myocardial infarction.


Computer-assisted morphometric study on the postnatal growth of axon size and myelin thickness in the ventral and dorsal roots of the rabbit.
The morphometric analysis of the myelinated fibers is of great value in developmental, experimental, and pathological studies. The present study was performed on the ventral and dorsal spinal roots (L7) of new-born, 10-, 15-, 20-, 30-, 60-, 120- and 240-day-old rabbits. Semi-thin cross-sections were investigated by OLYMPUS Video image analyser. The average axonal diameter was measured as an average length of Feret's diameters and the specific width of the myelin sheaths as a total width of the myelin sheath. In the ventral roots, the increase of the axon size is more intensive than the increase of the myelin thickness. In adult rabbits, the mean axonal diameter for the ventral root is approximately 15% greater than the mean axonal diameter for the dorsal root, whereas the mean myelin thickness values are practically equal for both roots. For the period newborn-adult (240-day-old) rabbits, a full correlation was found in respect to the increase of the dorsal root mean axonal diameter and mean myelin thickness (380% and 380%). In the ventral roots, the mean axonal diameter increased 420% whereas the mean myelin thickness increased 350%. It is intriguing whether the greater axonal size of the ventral roots might compensate their relatively thin myelin sheaths in comparison to the dorsal roots. Our findings of essential increase (16%) of the mean myelin thickness in the last (120-240 days) period in both, ventral and dorsal roots, points to a protracted period of myelinization in the rabbit.


Draft Genomic Resources for the Brown Rot Fungal Pathogen Monilinia laxa.
Monilinia laxa is the causal agent of brown rot on stone fruit, and it can cause heavy yield losses during field production and postharvest storage. This article reports the draft genome assembly of the M. laxa Mlax316 strain, obtained using a hybrid genome assembly with both Illumina short-reads and PacBio long-reads sequencing technologies. The complete draft genome consists of 49 scaffolds with total size of 42.81 Mb, and scaffold N50 of 2,449.4 kb. Annotation of the M. laxa assembly identified 11,163 genes and 12,424 proteins which were functionally annotated. This new genome draft improves current genomic resources available for M. laxa and represents a useful tool for further research into its interactions with host plants and into evolution in the Monilinia genus.


Effect of carrier gas change during sewage sludge or sewage sludge and willow pyrolysis on ecotoxicity of biochar-amended soil.
Different pyrolysis conditions determine the properties of the biochar. The properties of biochar may affect directly or indirectly their influence on living organisms. The aim of this study was to determine the toxicity of biochar obtained under different conditions (temperature: 500 or 700 °C, carrier gas: N2 or CO2, feedstock: sewage sludge or sewage sludge/biomass mixture) after adding to the soil in long-term pot experiment (180 days). Biochars were added to the podzolic loamy sand at a 2% (w/w) dose. Samples were collected at the beginning of the experiment and after 30, 90 and 180 days. The bacteria Aliivibrio fischeri (luminescence inhibition - Microtox), the plant Lepidium sativum (root growth and germination inhibition test - Phytotoxkit F), and the invertebrate Folsomia candida (mortality and reproduction inhibition test - Collembolan test) were used as the test organisms. In the long-term perspective for most tests, changing the carrier gas from N2 to CO2 resulted in reduced toxicity of the biochar. A particularly beneficial effect of changing the gas to CO2 was observed for the solid-phase test with L. sativum. The CO2 during pyrolysis had the least beneficial effect on toxicity towards A. fischeri.


The "Inverted Bonds" Revisited: Analysis of "In Silico" Models and of [1.1.1]Propellane by Using Orbital Forces.
This article dwells on the nature of "inverted bonds", which refer to the σ interaction between two sp hybrids by their smaller lobes, and their presence in [1.1.1]propellane. Firstly, we study H3 C-C models of C-C bonds with frozen H-C-C angles reproducing the constraints of various degrees of "inversion". Secondly, the molecular orbital (MO) properties of [1.1.1]propellane and [1.1.1]bicyclopentane are analyzed with the help of orbital forces as a criterion of bonding/antibonding character and as a basis to evaluate bond energies. Triplet and cationic states of [1.1.1]propellane species are also considered to confirm the bonding/antibonding character of MOs in the parent molecule. These approaches show an essentially non-bonding character of the σ central C-C interaction in propellane. Within the MO theory, this bonding is thus only due to π-type MOs (also called "banana" MOs or "bridge" MOs) and its total energy is evaluated to approximately 50 kcal mol-1 . In bicyclopentane, despite a strong σ-type repulsion, a weak bonding (15-20 kcal mol-1 ) exists between both central C-C bonds, also due to π-type interactions, though no bond is present in the Lewis structure. Overall, the so-called "inverted" bond, as resulting from a σ overlap of the two sp hybrids by their smaller lobes, appears highly questionable.


Effects of phosphorylation on the kinetic properties of rat liver ATP-citrate lyase.
Homogeneous rat liver ATP-citrate lyase (EC 22.214.171.124) was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. In agreement with other workers, the maximum level of phosphorylation that we observed was approx. 2 mol/mol of tetramer. Phosphorylated and non-phosphorylated forms of ATP-citrate lyase were prepared. Their kinetic properties were examined using an assay system in which the concentrations of Mg.ATP, magnesium.citrate and CoA were varied systematically at a constant concentration of Mg2+. The phosphorylated form had a two-fold higher Km for Mg.ATP than did the non-phosphorylated form, but no other kinetic differences between the two forms were detected. When ATP-citrate lyase was assayed at a concentration of Mg.ATP well below Km, it was found that phosphorylation of the enzyme correlated well with a decrease of approx. 50% in its activity. This is the first demonstration that phosphorylation can affect the activity of ATP-citrate lyase.


A review of Chifengiinae (Insecta: Orthoptera: Prophalangopsidae) with description of new Jurassic material from the northwestern Junggar Basin, China.
A complete and well-preserved forewing assigned to the orthopteran insect Parahagla cheni Xu, Fang and Zhang, 2023 is described from the Lower Jurassic Badaowan Formation of the northwestern Junggar Basin (Karamay, Xinjiang, northwestern China), based on which the species is diagnostically revised. It represents the earliest record of the subfamily Chifengiinae under the family Prophalangopsidae. The subfamily Chifengiinae is reviewed and a key to its genera and species is provided in the discussion. A further discuss of the palaeobiogeographic distribution of Chifengiinae shows that the subfamily probably first appeared in the Palaeoarctic in the earliest Jurassic, and later quickly migrated and occupied most areas of eastern Palaeoarctic from the Middle Jurassic to the Early Cretaceous.


An empirical taxometric alternative to traditional classification of temporomandibular disorders.
A number of investigators have suggested that the generic classification temporomandibular disorders (TMD) may consist of several subsets of patients. Two primary factors are to be significant in discriminating subgroups, namely, presence or absence of TM joint abnormalities and psychological characteristics such as traits, maladaptive behavioral patterns, and gross psychopathology. Few attempts, however, have been made to integrate psychosocial and behavioral parameters in order to identify a taxonomy of TMD patients and, subsequently, to examine the differentiation of subgroups on oral dysfunction/structural abnormalities (OD/SA). The primary purpose of this paper was to develop and cross-validate an empirically derived classification system of TMD patients. The first study identified three unique subgroups of TMD patients, labeled 'dysfunctional,' 'interpersonally distressed,' and 'adaptative copers.' A second study cross-validated and confirmed the uniqueness and accuracy of the taxonomy. Subsequent analyses were performed that demonstrated that these groups were not distinguishable on the basis of any measures of OD/SA. The taxonomy identified is compared and contrasted with other reported subgroups of TMD patients and the implications of this classification system for treatment of TMD patients are discussed.


Disparities in ACL Reconstruction: the Influence of Gender and Race on Incidence, Treatment, and Outcomes.
Anterior cruciate ligament (ACL) rupture is a common injury that has important clinical and economic implications. We aimed to review the literature to identify gender, racial and ethnic disparities in incidence, treatment, and outcomes of ACL injury. Females are at increased risk for ACL injury compared to males. Intrinsic differences such as increased quadriceps angle and increased posterior tibial slope may be contributing factors. Despite lower rates of injury, males undergo ACL reconstruction (ACLR) more frequently. There is conflicting evidence regarding gender differences in graft failure and ACL revision rates, but males demonstrate higher return to sport (RTS) rates. Females report worse functional outcome scores and have worse biomechanical metrics following ACLR. Direct evidence of racial and ethnic disparities is limited, but present. White athletes have greater risk of ACL injury compared to Black athletes. Non-White and Spanish-speaking patients are less likely to undergo ACLR after ACL tear. Black and Hispanic youth have greater surgical delay to ACLR, increased risk for loss to clinical follow-up, and less physical therapy sessions, thereby leading to greater deficits in knee extensor strength during rehabilitation. Hispanic and Black patients also have greater risk for hospital admission after ACLR, though this disparity is improving. Females have higher rates of ACL injury with inconclusive evidence on anatomic predisposition and ACL failure rate differences between genders. Recent literature has suggested inferior RTS and functional outcomes following ACLR in females. Though there is limited and mixed data on incidence and outcome differences between races and ethnic groups, recent studies suggest there may be disparities in those who undergo ACLR and time to treatment.


Muscle ultrasound in hereditary muscle disease.
In this review we summarise the key techniques of muscle ultrasound as they apply to hereditary muscle disease. We review the diagnostic utility of muscle ultrasound including its role in guiding electromyography and muscle biopsy sampling. We summarize the different patterns of sonographic muscle involvement in the major categories of genetic muscle disorders and discuss the limitations of the technique. We hope to encourage others to adopt ultrasound in their care for patients with hereditary muscle diseases.


Rapid autonomic tone regulation of atrioventricular nodal conduction in man.
The changes in P-P intervals and atrioventricular nodal (AVN) conduction during the Valsalva maneuver were studied in 17 patients. In spite of a significant decrease in the sinus P-P interval during phase II of the maneuver (733 +/- 143 to 520 +/- 86 msec, p less than 0.005) and prolongation during phase IV (884 +/- 171 msec, p less than 0.01), there was no change in the AH interval (control: 78 +/- 15: phase II: 76 +/- 15: phase IV: 72 +/- 14 msec, N.S.). In six patients consecutive P-P intervals during phase II were recorded in solid-state memory and were used to trigger pacing of the high right atrium at rest. This showed a significant increase in the AH interval (75 +/- 10 to 123 +/- 45 msec, p less than 0.05). Valsalva maneuver during constant rate atrial pacing resulted in a significant decrease in the AH interval during phase II (115 +/- 36 to 80 +/- 15 msec, p less than 0.001). During phase IV there was prolongation of the AH interval (156 +/- 58 msec) but in 11 patients (61%) a variable degree of Wenckebach periodicity appeared. Thus autonomic tone modulates the changes in AVN conduction induced during physiologic heart rate variation, resulting in maintenance of adequate 1:1 AVN conduction.


Effectiveness of hepatic arterial embolization on radiofrequency ablation volume in a swine model: relationship to portal venous flow and liver parenchymal pressure.
To evaluate the effectiveness of transcatheter arterial embolization (TAE) on radiofrequency (RF) ablation volume and compare portal vein (PV) flow and liver parenchymal pressure before and after treatment. Eight healthy female swine were divided into four groups to be treated with RF ablation alone (RF-only group), RF ablation after TAE with gelatin sponge particles (GSPs; RF/TAE group), RF ablation after TAE with Lipiodol plus GSPs (RF/TAE/Lipiodol group), and PV embolization (PVE) with GSPs after TAE with Lipiodol plus GSPs (RF/TAE/Lipiodol/PVE group). Five ablations were created in each swine, with 10 ablations per group. A 2-cm expandable LeVeen needle electrode was used for RF ablation. The greatest ablation volume (18,410.1 mm(3) +/- 3,986.4) was observed in the RF/TAE/Lipiodol/PVE group. Of the RF-only, RF/TAE, and RF/TAE/Lipiodol groups, the RF/TAE/Lipiodol group (14,835.5 mm(3) +/- 2,743.2) had a significantly larger ablation volume than the RF-only (8,002.6 mm(3) +/- 2,788.3) and RF/TAE groups (10,398.5 mm(3) +/- 2965.8; P < .05/3). PV pressures increased significantly after TAE (P < .01) compared with the pressure before TAE in the RF/TAE/Lipiodol and RF/TAE/Lipiodol/PVE groups, but not in the RF/TAE group. A marked increase in liver parenchymal pressure was seen during RF ablation; however, there were no significant differences among groups. Accumulation of Lipiodol was noted in the sinusoids in the RF/TAE/Lipiodol and RF/TAE/Lipiodol/PVE groups. TAE with blockade of PV flow before RF ablation was associated with greater ablation volumes. Liver parenchymal pressure showed no correlation with increased ablation volume.


De Novo Genome Assembly of a Plant-Associated Rhodococcus qingshengii Strain (RL1) Isolated from Eruca sativa Mill. and Showing Plant Growth-Promoting Properties.
Rhodococcus qingshengii RL1 was isolated from surface-sterilized leaves of Eruca sativa Mill. and shows plant growth-promoting (PGP) properties. The de novo genome assembly consists of one chromosome with 6,253,838 bp and two plasmids with 144,038 bp and 448,745 bp. Many genes could be identified reflecting its PGP potential.


Synthesis and characterization of bis nitrato[4-hydroxyacetophenonesemicarbazone) nickel(II) complex as ionophore for thiocyanate-selective electrode.
The PVC based-ion selective electrode viz., bis nitrato[4-hydroxyacetophenone semicarbazone] nickel(II) as an ionophore was prepared for the determination of thiocyanate ion. The ionophore was characterized by FT-IR, UV-vis, XRD, magnetic moment and elemental analysis (CHN). On the basis of spectral studies an octahedral geometry has been assigned. The best performance was obtained with a membrane composition of 31% PVC, 63% 2-nitrophenyl octylether, 4.0% ionophore and 2.0% trioctylmethyl ammonium chloride. The electrode exhibited an excellent Nernstian response to SCN(-) ion ranging from 1.0 × 10(-7) to 1.0 × 10(-1)M with a detection limit of 8.6 × 10(-8)M and a slope of -59.4 ± 0.2 mV/decade over a wide pH range (1.8-10.7) with a fast response time (6s) at 25 °C. The proposed electrode showed high selectivity for thiocyanate ion over a number of common inorganic and organic anions. It was successfully applied to direct determination of thiocyanate in biological (urine and saliva) samples in order to distinguish between smokers and non-smokers, environmental samples and as an indicator electrode for titration of thiocyanate ions with AgNO3 solution.


DELE1 oligomerization promotes integrated stress response activation.
Mitochondria are dynamic organelles that continually respond to cellular stress. Recent studies have demonstrated that mitochondrial stress is relayed from mitochondria to the cytosol by the release of a proteolytic fragment of DELE1 that binds to the eIF2α kinase HRI to initiate integrated stress response (ISR) signaling. We report the cryo-electron microscopy structure of the C-terminal cleavage product of human DELE1, which assembles into a high-order oligomer. The oligomer consists of eight DELE1 monomers that assemble with D4 symmetry via two sets of hydrophobic inter-subunit interactions. We identified the key residues involved in DELE1 oligomerization, and confirmed their role in stabilizing the octamer in vitro and in cells using mutagenesis. We further show that assembly-impaired DELE1 mutants are compromised in their ability to induce HRI-dependent ISR activation in cell culture models. Together, our findings provide molecular insights into the activity of DELE1 and how it signals to promote ISR activity following mitochondrial insult.


Malignant testicular unclassified sex cord stromal tumor: a case report.
Most testicular tumors are germ cell tumors; sex cord stromal tumors are infrequent, accounting for only 3-5% of testicular tumors. Unclassified sex cord stromal tumors are extremely rare. Generally, 10% of sex cord stromal tumors are malignant. We report a case of malignant unclassified sex cord stromal tumor with retroperitoneal lymph node metastasis at first visit and a corresponding literature review. A 72-year-old Japanese man visited our department primarily for indolent right scrotum enlargement in September 2020. Blood biochemistry examination, urinalysis, and tumor markers (alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) showed no abnormal findings. Contrast-enhanced computed tomography showed enlarged para-aortic lymph node (18 × 16 and 10 × 102 mm); a 50 × 452 mm mass with uneven contents was found in the right testicle. The patient underwent inguinal orchiectomy in September 2020. As per immunohistochemistry, the tumor cells were diffusely positive for SF-1 and Ki-67, partially positive for inhibin, and negative for CAM5.2, CK7, CK20, C-KIT, CD30, LCA, GATA-3, TTF-1, and PAX8. Calretinin was expressed in approximately 5% of tumor cells; thus, sex cord/gonadal stroma components were considered to be involved. The final pathological diagnosis was unclassified malignant sex cord stromal tumor. The patient was diagnosed with pT1, N1, M0, S0, and tumor-node-metastasis stage IIA disease. The patient received postoperative chemotherapy with four courses of etoposide and cisplatin therapy from November 2020. Post-chemotherapeutic computed tomography showed new metastatic lesions including lung, liver, pancreas, and para-aortic lymphadenopathy, which increased in size. Disease progression was observed. Cancer genome research was performed using the OncoGuide National Cancer Center oncopanel system; however, no gene mutation for which the drug could be expected to be effective was found. The patient opted for best supportive care at a nearby hospital and died from cancer progression in January 2022. We encountered a case of malignant testicular unclassified sex cord stromal tumor pathologically diagnosed as testicular tumor with retroperitoneal lymph node metastasis in a patient who underwent inguinal orchiectomy. Future data collection is necessary to establish multimodality therapy for malignant testicular unclassified sex cord stromal tumor.


Survey of intracellular recording in the cochlear nucleus of the cat.
Intracellular recordings were made in the cochlear nucleus of anesthetized cats. In anterior passes, one never obtained sustained depolarizations from 'primary-like' units. For 'chopper' units, however, it was possible to record sustained depolarizations accompaneid by spikes that lasted as long as the tone burst. 'Pauser, 'buildup' and 'on' units also had spike responses that could be accompanied by sustained depolarizations. For 'pauser', 'buildup' and 'on' units, hyperpolarization was not seen during the times when no spike discharges appeared so long as the tone bursts were at the characteristic frequency of the units.


A model approach to the population dynamics of the rotifer Brachionus rubens in two-stage chemostat culture.
A model, based on energy-flow considerations, is presented which describes the population dynamics of Brachionus rubens in the second stage of a two-stage algalrotifer chemostat. The rotifers are foodlimited with substrate-inhibition occurring at high algal densities. The model shows two stable states: steady state with constant density of rotifers and washout of the animals. Which one of the stable states is reached depends on the initial conditions.Empirical data are in general agreement with the model. Deviations may be explained by the fact that the data underlying the model calculations are based on a different food alga (Chlorella vulgaris) than the one used in the experiments (Monoraphidium minutum).The observed population growth rate reaches a maximum value of 0.84 (1/day) at algal densities of 3-4. 106 cells/ml. It decreases at higher algal densities. The egg ratio is related linearily to algal density without being reduced at high algal densities.


The experiences of nurses and midwives regarding nursing education in Ghana: A qualitative content analysis.
The nursing education in Ghana has only witnessed minimal advancement though one of the earliest in Africa. This study aimed to explore nursing education in Ghana at the bachelor degree level in terms of the program's strengths, weaknesses, opportunities, and threats from the perspectives of nurses and midwives. A qualitative design based on the content analysis approach was used in this study. We purposefully sampled and interviewed thirty-five nurses and midwives at the Tamale Teaching in Ghana from September 2018 to May 2019. The data analysis revealed five main categories; professionally developed, diverse implementation, insufficient resources, applied opportunities, and threatening policies. The findings highlight the strengths, weaknesses, opportunities, and threats of nursing education at the bachelor degree level in Ghana. The nursing education in Ghana has some internal capabilities in the form of strengths and weaknesses, such as the program being professionally regulated and operates on a well-developed curriculum, yet challenged with insufficient faculty and resources. The external opportunities and threats present as global recognition and career opportunities, amidst the proliferation of adjunct nursing programs. Recommendations have been highlighted.


An effect of cell-culture passage on ultraviolet-enhanced viral reactivation by mammalian cells.
The ability of ultraviolet-irradiated African green monkey kidney cells to reactivate UV-damaged herpes simplex virus was tested over a range of 57 passages (24-81). Several types of controls were employed to minimize daily variations. The results indicate that in this system cells demonstrate an increasing efficiency to reactivate UV-damaged virus until approx. passage 60, followed by a decrease in this ability beyond this passage. Chromosome counts at selected passages revealed no significant change in chromosome number as a function of passage. The mechanism(s) or factor(s) causing this effect are unknown.


[Delirium in stroke: systematic review and meta-analysis].
Due to the complexity of the symptoms, delirium detection poses a challenge in stroke patients. A large body of literature has established that neurospecific challenges can have a considerable impact on diagnosis and are underrepresented in screening. An analysis of current scientific literature on delirium screening tests and their applicability in stroke patients, acknowledging neurospecific challenges and evaluating diagnostic test accuracy. A systematic literature search was conducted in PubMed, CINAHL, and Cochrane Library databases. Studies published between 2018 and 2021 were evaluated and the study quality was assessed according to the Institute for Clinical Systems Improvement. Furthermore, the specificity and sensitivity of delirium screening tests were pooled RESULTS: The systematic literature review found a total of 2636 articles, following a review of the inclusion and exclusion criteria. Thus, 18 moderate-quality studies with a total of 3320 patients and 9 distinct delirium screenings were identified. Within those 18 studies, the prevalence of delirium was 34.2%. However, the delirium prevalence was significantly lower in 6 studies that included patients with neurologic impairments (26.5 vs. 32.1%, p = 0.0004). Pooled sensitivity and specificity for the 4AT (Rapid assessment test for delirium ) were 82 and 77%, while these values were 72 and 93% for the CAM-ICU (Confusion Assessment Method for Intensive Care Units) and 79 and 72% for the ICDSC (Intensive Care Delirium Screening Checklist). Neurological impairments may influence the test quality of delirium screening in stroke patients. The CAM-ICU can be recommended for nonaphasic patients. The ICDSC can be used in all stroke patients on stoke units with an adjusted cut-off value of > 5 points.


Participation in Negative Capacitance of Diffusion-Controlled Voltammograms of Hemin.
Hemin in dimethyl sulfoxide solution has exhibited voltammograms controlled by diffusion at glassy carbon electrodes for slow scan rates, although it is adsorbed slightly. In contrast, voltammograms for high scan rates, v > 1 V s-1, were governed by some kinds of kinetics judging from the scan rate dependence of peaks. The kinetics is close to that of a ferrocenyl derivative, in which the currents include the capacitive component with negative values. The capacitive one can be identified with the proportionality to the scan rates. The variation of the peak currents with v yielded -200 μF cm-2. This negative value, being associated with the charge transfer reaction, makes cyclic voltammograms deviated downward from the diffusion-controlled behavior, resembling an irreversible reaction of the Butler-Volmer kinetics. Double layer capacitances are generally formed so that the applied electric field may be relaxed. The reduction of hemin forms a dipole coupled with a cation of the salt. The dipole orients from the electrode to the bulk, whereas the solvent dipoles orients in the opposite direction. Therefore, the capacitance is observed negatively. The capacitance determined by ac impedance took also negative values when the applied dc potential was only in the potential domain for the charge transfer. These complications can be avoided in electrocatalysis by use of such slow voltammetry as scan rates of 0.1 V s-1 and ac frequency of 0.2 Hz.


Report of the Tunisian Registry of Primary Immunodeficiencies: 25-Years of Experience (1988-2012).
Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to not only recurrent infections but also autoimmune diseases and malignancies. The aim of this study was to describe and analyze the distribution, clinical features and eventual outcome of PID among Tunisian patients. We reviewed the record of 710 patients diagnosed with Primary Immunodeficiency Diseases (PIDs) from the registry of the Tunisian Referral Centre for PIDs over a 25-year period. The male-to-female ratio was 1.4. The median age at the onset of symptoms was 6 months and at the time of diagnosis 2 years. The estimated prevalence was 4.3 per 100,000 populations. The consanguinity rate was found in 58.2 % of families. According to the International Union of Immunological Societies classification, spectrums of PIDs were as follows: combined T-cell and B-cell immunodeficiency disorders account for the most common category (28.6 %), followed by congenital defects of phagocyte (25.4 %), other well-defined immunodeficiency syndromes (22.7 %), predominant antibody deficiency diseases (17.7 %), diseases of immune dysregulation (4.8 %), defect of innate immunity (0.4 %) and complement deficiencies (0.4 %). Recurrent infections, particularly lower airway infections (62.3 %), presented the most common manifestation of PID patients. The overall mortality rate was 34.5 %, mainly observed with combined immunodeficiencies. The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of Combined Immunodeficiencies and phagocyte defects in number and/or function. More is needed to improve PID diagnosis and treatment in our country.


Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.
Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.


Solution conformation of peptides by the intramolecular nuclear Overhauser effect experiment. Study of valinomycin-K+.
This study demonstrates how the intramolecular nuclear Overhauser effect (NOE) experiment can be employed quantitatively to select from a set of possible conformations for a peptide or a protein the particular conformation (or a group of conformations) most consistent with the data. This procedure is demonstrated on a model depsipeptide system--valinomycin K+ in CDCl3--for which the solution conformation has been inferred by other methods. The NOE enhancements are very sensitive to the conformations assumed by this antibiotic. It is shown that the set of conformations, collectively labeled as A2 (including the X-ray crystallographic structure) gives a very good description of the NOE enhancements. The structure proposed by Bystrov et al. (1977. Eur. J. Biochem. 78:63) for the uncomplexed valinomycin in nonpolar solvents is also consistent with the experimental data on the potassium complex. Using statistical hypothesis testing involving the Hamilton R-factor ratio criterion, all the other models have been rejected as inconsistent with the experimental data. A general formalism is presented for describing the NOE effects in isotropically reorienting molecules. The formalism is not restricted to the extreme narrowing limit of the rotational correlation times and hence applies to both small and large molecules. Some of the factors that can influence the NOE measurements, viz. anisotropic rotational diffusion, conformational averaging, and nuclear spin diffusion, have been considered in this study.


Flavobacterium buctense sp. nov., isolated from freshwater.
A gram-negative, non-gliding motile, aerobic bacterium, designated as strain T7(T), was isolated from freshwater of Chishui River flowing through Maotai town, Guizhou Province, southwest of China. Based on the 16S rRNA gene sequence analysis, the isolate was identified as a member of the genus Flavobacterium and that shared less than 97 % sequence similarities with recognized Flavobacterium species. Its closest phylogenetic relative was Flavobacterium dankookense (96.9 %), followed by Flavobacterium cheonhonense (96.8 %) and Flavobacterium macrobrachii (96.7 %). The strain formed smooth yellow colonies on R2A plates, and cells were observed to be short rods. Strain T7(T) was found to be able to grow at 15-30 °C (optimum 25 °C), at NaCl concentration of 0-0.5 % (optimum 0 %) and at pH 6.5-9.5 (optimum pH 7.5). Catalase and oxidase tests were positive. Polar lipids of strain T7(T) included phosphatidylethanolamine, four unidentified polar lipids, one unidentified phospholipid and one unidentified aminolipid. Chemotaxonomic analysis revealed menaquinone-6 as the dominant respiratory quinone and C(15:0), iso-C(15:0) and iso-C(15:1) as the major fatty acids. The DNA G+C content of strain T7(T) was determined to be 38.2 mol%. On the basis of phylogenetic, phenotypic and genetic data obtained in this study, strain T7(T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium buctense sp. nov. is proposed. The type strain is T7(T) (=JCM 30750=CGMCC 1.15216).


[Current evaluation of beta-adrenergic agents in the treatment of bronchial spasm].
The current status of beta-adrenergics in the treatment of bronchospasm is discussed. Personal experience is reviewed with special attention being paid to associations of the drugs on aminophylline, atropine and bechlomethasone dipropionate.


Fluoroalcohols as novel buffer components for basic buffer solutions for liquid chromatography electrospray ionization mass spectrometry: retention mechanisms.
Two fluoroalcohols--1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 1,1,1,3,3,3-hexafluoro-2-methyl-2-propanol (HFTB)--were evaluated as volatile buffer acids in basic mobile phases for LC-ESI-MS determination of acidic and basic compounds. HFIP and HFTB as acidic buffer components offer interesting possibilities to adjust retention behavior of different analytes and expand the currently rather limited range of ESI-compatible buffer systems for basic mobile phases. Comparing with commonly used basic buffer components the fluoroalcohols did not suppress the ionization of the analytes, for several analytes ionization enhancement was observed. RP chromatographic retention mechanisms were evaluated and compared to traditional buffer system. All trends in retention of the acidic and basic analytes can be interpreted by the following model: the neutral fluoroalcohols are quite strongly retained by the stationary phase whereas their anions are less retained, thus their amount on the stationary phase is dependent on mobile phase pH; the anions of the fluoroalcohols form ion pairs in the mobile phase with the basic analytes; the fluoroalcohols on the stationary phase surface compete with acidic analytes thereby hindering their retention; the fluoroalcohols on the stationary phase bind basic analytes thereby favoring their retention.


Measuring morbidity: disease counts, binary variables, and statistical power.
This study compares the use of the binary disease variables with counts of the same conditions in models of self-rated health to better understand the advantages and disadvantages of each approach. In particular, the analysis seeks to determine if statistical power is adequate for the binary variable approach. Morbidity measures from adults in 2 large national surveys were used in both cross-sectional and longitudinal analyses. Although differences across the approaches are modest, the binary variable approach offers greater explanatory power and slightly higher R2 values. Despite these advantages, statistical power is insufficient in some cases, especially for conditions that are relatively rare and/or that manifest modest differences on the outcome variable. Statistical power estimates are advisable when using the binary variable approach, especially if the list of diseases and health conditions is extensive. Although a simple count of diseases may be useful in some research applications, separate counts for serious and nonserious conditions should be more useful in many research projects while avoiding the risk of inadequate statistical power.


Dissimilar behavioral and spatial avoidance responses by shrimps from tropical and temperate environments exposed to copper.
Behavioral changes associated with exposure to pollutants represent the earliest response for organisms confronted by perceivable chemical signals. This study was carried out with the objective of evaluating behavioral responses associated with different scenarios of exposure to pollutants (non-forced vs forced) in two shrimp species (Penaeus vannamei and Palaemon varians), representative of different latitudes and using copper as a model contaminant. The effects on locomotion were evaluated by exposing the shrimps to a range of copper concentrations (0, 0.5, 5, 50, and 250 µg/L) in the forced scenario. After exposure, the movement patterns for each shrimp were recorded and used to estimate changes in the shrimps' locomotion. For the non-forced scenario, the avoidance response was assessed by placing shrimps in a multi-compartment system where they were able to move freely along a gradient of copper (0, 0.5, 5, 50, and 250 µg/L). In terms of locomotion, an opposite trend was observed between the species: movements were significantly reduced in P. varians with concentrations above 50 µg/L, while hyperactivity was observed for P. vannamei. When exposed to a gradient of copper in the multi-compartment system, both species significantly avoided the highest concentrations of copper, although the repellence of copper was stronger for P. vannamei. In summary, both species of shrimps were able to recognize and avoid copper; however, in terms of locomotion, they showed an opposite behavioral reaction. These results show that a contamination event can have different behavioral outcomes depending on the species and complementing forced and non-forced exposure with species-specific information can be helpful to characterize and predict the effects of contaminants at higher biological levels.


Skin nontuberculous mycobacterial infection in systemic lupus erythematosus: an unusual skin infection mimicking lupus vasculitis.
To report 2 cases of skin nontuberculous mycobacteria (NTM) occurring in lupus patients and to systematically review the medical literature addressing skin NTM in lupus. We reported 2 cases of skin NTM in lupus patients followed at the Toronto Lupus Clinic. We conducted a systematic review of the literature on NTM in lupus patients. Ovid Medline (1946 to March 12, 2012) and Embase (1980 to March 12, 2012) were searched for relevant publications. Of the 1356 retrieved abstracts, 19 publications were identified and 25 cases of skin NTM were extracted. Skin presentations in this review ranged from papules, plaques, and nodules to ulcerative lesions and abscesses. Skin lesions occurred in the setting of active and inactive lupus and while patients were maintained on steroids and sometimes immunosuppressants. The pathogen species included Mycobacterium chelonae, Mycobacterium haemophilum, Mycobacterium kansasii, Mycobacterium avium, Mycobacterium scrofulaceum, Mycobacterium fortuitum, Mycobacterium marinatum, and Mycobacterium szulgai. The duration of antimycobacterial drugs ranged from 3 to 12 months. Skin excision, drainage, and debridement might be required in some cases. Empirical monotherapy was used initially, and the final choice of antibiotics was based on the susceptibility determined in culture. Overall, the outcomes of the skin lesions resulted in either complete recovery or improvement. A high index of suspicion in lupus patients is required to diagnose NTM, as the initial presentation of NTM can mimic lupus skin manifestations.


Barriers and Challenges of Cancer Patients and Their Experience with Patient Navigators in the Rural US/Mexico Border Region.
Patient navigation is a widely used approach to minimize health disparities among socioeconomically marginalized cancer patients. Although patient navigation is widely used, there is a dearth of studies exploring patient experience with navigators among rural cancer patients. This qualitative study explores the challenges and barriers to cancer care faced by cancer patients living in a US/Mexico border region in Southern California. We individually interviewed 22 cancer patients, most of whom were Latino. Data were analyzed using constant comparison with a reiterative analysis method. The main themes relating to barriers to care and experiences with patient navigators include the following: (1) removing financial barriers, (2) coordinating services, and (3) providing therapeutic interventions. The cancer patients highly valued the navigators for their knowledge about community resources, support, and advocacy. This study suggests that it is imperative that navigators know the regional and binational health care utilization issues that impact patients' access to cancer care.


Transcriptional activation of the heme oxygenase gene by TPA in mouse M1 cells during their differentiation to macrophage.
The activation of the heme oxygenase (HO), fos, and AP-1 genes was determined at intervals after treatment of M1 cells (derived from mouse myeloleukemia) with heme or 12-O-tetradecanoylphorbol 13-acetate (TPA). On treatment with heme, M1 cells did not differentiate into macrophage but their HO gene was activated and showed maximum transcriptional activity after treatment with heme for 2 h. In contrast, on treatment with TPA, these cells adhered to the culture flasks within 5 h and differentiated into macrophage-like cells. Moreover, the sequential activation of the fos, AP-1, and HO genes was observed during this period, with the maximal transcriptional activities after TPA treatment for 0.5, 1, and 1.5 h, respectively. Thus, the HO gene was activated by treatment with either heme or TPA, and the latter activation was associated with activations of the fos and AP-1 genes. As the rat HO gene is known to have a TPA-sensitive element in its promoter region, this gene was suggested to be activated by a fos-AP-1 complex protein.


Inhibitory effect of a standardized pomegranate fruit extract on Wnt signalling in 1, 2-dimethylhydrazine induced rat colon carcinogenesis.
De-regulation of Wnt signalling is increasingly being implicated in both experimental and human carcinogenesis including colon cancer. Our goal was to identify possible dietary agents that block Wnt signalling as a step toward investigating new strategies for suppression of colon cancer. Pomegranate extract has emerged as an intriguing candidate due to its polyphenolic content. We used a 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis model to investigate the expression pattern of the main key players in Wnt signalling by reverse transcription polymerase chain reaction (RT-PCR) analysis. Our results showed that many Wnt-target genes, e.g., Wnt5a, frizzled receptor (FRZ)-8, β-catenin, T cell factor/lymphoid enhancer binding protein (Tcf4/Lef1), c-myc and cyclin D1, were up-regulated whereas adenomatous polyposis coli (APC) and axin1 exhibited down-regulation in colonic tissues of our DMH-colon cancer group compared with the normal group. Standardized pomegranate extract minimised all the aberrant alterations observed in the studied Wnt genes in colonic tissues of the DMH+pomegranate group as compared with the DMH-induced colon cancer group. This effect was also confirmed by the normalization of survival rate, inhibition of tumour incidence and a reduction of serum tumour marker carcinoembryonic antigen (CEA) level. Histopathological observations provided supportive evidence for the biochemical and molecular analyses. Standardized pomegranate extract holds great promise in the field of colon cancer prevention by dietary agents.


Non-random distribution of Alu-family repeats in human chromosomes.
A phage lambda recombinant clone containing at least 8 Alu-family repeats (AFRs) has been isolated from a human genomic library, and DNA from the phage was used as a probe for in situ hybridization on G-banded human metaphase chromosomes of healthy donors and leukemic patients. Some chromosome bands show prominent clusters of silver grains in all individuals examined: 1p34, 1q23, 2q21-22, 10p14, 11p14, 10q21 and 11q14. The data suggest non-random distribution of AFRs in the human genome.


Smoking-related interstitial lung diseases.
Cigarette smoke, a toxic collection of thousands of chemicals generated from combustion of tobacco, is recognized as the primary causative agent of certain diffuse interstitial and bronchiolar lung diseases. Most patients afflicted with these disorders are cigarette smokers, and smoking cessation has been shown to be capable of inducing disease remission and should occupy a pivotal role in the management of all smokers with these diffuse lung diseases. The role of pharmacotherapy with corticosteroids or other immunomodulating agents is not well established but may be considered in patients with progressive forms of smoking-related interstitial lung diseases.


A practical approach to difficult urinary catheterizations.
Routine placement of transurethral catheters can be challenging in some situations, such as urethral strictures, severe phimosis and false passages. Intravaginal retraction of the urethral meatus can complicate Foley placement in postmenopausal females. In men, blind urethral procedures with mechanical or metal sounds without visual guidance or guidewire assistance are now discouraged due to the increased risk of urethral trauma and false passages. Newer techniques of urethral catheterization including guidewires, directed hydrophilic mechanical dilators, urethral balloon dilation, and direct vision endoscopic catheter systems are discussed, along with the new standardized protocol for difficult transurethral catheter insertions. Suprapubic catheter placement techniques, including percutaneous trocars and the use of the curved Lowsley tractor for initial suprapubic catheter insertion, are reviewed. Prevention and management of common catheter-related problems such as encrustation, leakage, Foley malposition, balloon cuffing and frequent blockages are discussed.


Texture analysis of T2-weighted MRI predicts SDH mutation in paraganglioma.
Texture analysis can quantify sophisticated imaging characteristics. We hypothesized that 2D textures computed with T2-weighted and post-contrast T1-weighted MRI can predict succinate dehydrogenase (SDH) mutation status in head and neck paragangliomas. Our retrospective study included 21 patients (1 to 4 tumors/patient) with 24 pathologically proven paragangliomas in the head and neck. Fourteen lesions (58%) were SDH mutation-positive. All patients underwent T2-weighted and post-contrast T1-weighted MRI sequences. Three 2D texture features of dependence non-uniformity normalized (DNN), small dependence high gray level emphasis (SDHGLE), and small dependence low gray level emphasis (SDLGLE) were calculated. Computed textures between SDH mutants and non-mutants were compared using Mann-Whitney U test. Area under the receiver operating characteristic (AUROC) curve was used to quantify the predictive power of each texture. Only T2-based SDLGLE was statistically significant (p = 0.048), and AUROC was 0.71. Diagnostic accuracy was 70.8%. 2D texture parameter of T2-based SDLGLE predicts SDH mutation in head and neck paragangliomas. This noninvasive technique can potentially facilitate further genetic workup.


Revealing the metabolic mechanism of dandelion extract against A549 cells using UPLC-QTOF MS.
Dandelion extract exhibits potential anticancer activity and is expected to be a new type of natural anticancer drug. However, the effect mechanism of dandelion extract to lung cancer cells is still unclear. Here, untargeted metabolomics approach based on LC-MS was used to characterize the metabolic responses of A549 cells to dandelion extract exposure and to provide new clues for the antitumor mechanism of dandelion extract from the metabolomics perspective. A total of 16 differentially expressed and time-related metabolites were identified between dandelion extract exposure and control groups. The perturbed metabolic pathways of A549 cells after dandelion extract exposure mainly include the glycerophospholipid metabolism and purine metabolism. These results concluded that dandelion extract may exert anticancer activity by affecting malignant proliferation, disturbing the stability of cell membrane structure, reducing the adhesion of tumor cells to extracellular matrix and fibronectin, and finally inducing tumor cell death.


Extranodal NK/T-Cell Lymphoma With Widespread Cutaneous and Subcutaneous Involvement on 18 F-FDG PET/CT.
Nasal-type extranodal natural killer/T-cell lymphoma is an aggressive rare type of lymphoma that mostly affects the nasal cavity and adjacent areas. However, some patients can present with distant nodal or extranodal involvement including the Waldeyer ring, gastrointestinal tract, genitourinary organs, lung, thyroid, skin, or adrenal glands. Herein, we present a unique case of extranodal natural killer/T-cell lymphoma with widespread cutaneous and subcutaneous involvement on 18 F-FDG PET/CT.


Attentional bias to pain-related information: a meta-analysis.
This meta-analysis investigated whether attentional bias, that is, the preferential allocation of attention to information that is related to pain, is a ubiquitous phenomenon. We also investigated whether attentional bias effects are related to the methodological quality of the study, to procedural differences in their measurement, or to individual differences in pain severity, pain-related fear, anxiety, and depression. Results indicated that individuals who experience chronic pain (n=1023) display an attentional bias towards pain-related words or pictures, but this bias was of a small effect size (d=0.134), and did not differ from that in control groups (d=0.082; n=1398). No evidence was found for an attentional bias towards pain-related words and pictures for acute pain (d=0.049), procedural pain (d=0.142), and experimental pain (d=0.069). However, research in which attentional bias towards signals of impending experimental pain in healthy volunteers was investigated, revealed an attentional bias of medium effect size (d=0.676). Moderator analyses in the chronic pain group identified important procedural variables that affected the presence and magnitude of an attentional bias towards pain-related words and pictures, that is, type and exposure time of pain-related information. None of the individual difference variables affected the magnitude of the attentional bias. Implications of current findings and future directions are discussed.


Profiles in altered metabolism. II.--Accumulation of homogentisic acid in serum and urine following acetylsalicylic acid ingestion.
Homogentisic acid elevations have been found in urine and serum of patients on long term heavy salicylate therapy and those acutely intoxicated with acetylsalicylic acid. Loading of two normal volunteers with single oral acetylsalicylate doses produced transient elevations in urinary homogentisic acid excretion. These findings suggest that heavy salicylate use results in the partial inhibition of homogentisic acid oxidase in vivo.


The anticholinesterase activity of mefloquine.
The characteristics of the inhibition of electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by the antimalarial agents mefloquine, chloroquine, amodiaquine and amopyroquine were determined. The antimalarials were found to be non-competitive inhibitors of both AChE and BChE. In both enzyme systems, inhibitory potencies were in the order amodiaquine greater than amopyroquine greater than chloroquine greater than mefloquine. The low inhibitory potency of mefloquine may account in part for the appearance of gastrointestinal and central nervous system disturbances only at high doses of the drug.


The gene for human complement C9 is on chromosome 5.
By hybridizing a cloned cDNA coding for human complement factor C9 to hybrid cells containing subsets of human chromosomes on a rodent background, we have determined that the human gene for C9 is localized on chromosome 5.


A case of endoscopic full-thickness resection for gastric gastrointestinal stromal tumor in the submucosal tunnel.
The patient was a 49-year-old female with a submucosal tumor (12×12 mm) located in the lesser curvature side of the stomach. The diagnosis by endoscopic ultrasound fine-needle aspiration was of a gastrointestinal stromal tumor. Computed tomography and endoscopic ultrasound showed gastrointestinal stromal tumor with an intra-luminal growth type. Endoscopic full-thickness resection was then performed. To achieve good counter traction, enough safety margin, and minimal defect of muscle, full-thickness resection via creating a submucosal tunnel was performed as a new technique. The final histological diagnosis was gastrointestinal stromal tumor with R0 resection.


Slow interaction of 5'-adenylyl-beta,gamma-imidodiphosphate with Escherichia coli DNA gyrase. Evidence for cooperativity in nucleotide binding.
We have examined the kinetics of interaction between Escherichia coli DNA gyrase and the nonhydrolyzable ATP analog 5'-adenylyl-beta,gamma-imidodiphosphate (ADPNP) in the presence and absence of ATP. In the absence of ATP, [alpha-32P]ADPNP binds extremely slowly to gyrase, with an apparent second-order rate constant (k1) of 120 M-1 min-1. Similarly, the limited negative supercoiling of closed-circular DNA caused by ADPNP binding is slow, requiring at least 2 h to reach completion in the presence of 100 microM ADPNP. A very slow but detectable rate of dissociation of ADPNP from gyrase was measured, with a rate constant of 3.5 x 10(-4) min-1. The calculated dissociation constant for ADPNP is thus 2.9 microM. ADPNP is a potent competitive inhibitor of ATP-dependent DNA supercoiling. Inhibition is established much more rapidly than can be accounted for by the slow rate of ADPNP binding in the absence of ATP. We have found that ATP can accelerate the rate of [32P]ADPNP binding by more than 15-fold (k1 = 1,850 M-1 min-1). The ATP-promoted rate enhancement requires the presence of DNA; in the absence of DNA, ATP has no effect on the rate of binding. Relaxed closed-circular, nicked-circular, and linear pBR322 DNA are all equally effective cofactors for ATP-stimulated binding of ADPNP. After a short lag, the presence of ATP also greatly speeds up ADPNP dissociation from gyrase bound initially to closed-circular DNA, with the restoration of DNA supercoiling activity. This effect is not observed in the presence of nicked-circular or linear DNA, suggesting that ADPNP dissociates more rapidly from gyrase bound to supercoiled DNA. The results of ADPNP binding provide evidence for cooperative interactions between the nucleotide binding sites. To account for these data, a model is proposed for the interaction of nucleotides at the two ATP binding sites on DNA gyrase.


Six year follow-up after catheter ablation of atrial fibrillation: a palliation more than a true cure.
Long-term outcomes after pulmonary vein isolation for atrial fibrillation (AF) remain uncertain. In particular, the influence of rigorous arrhythmia monitoring on outcomes is not yet clear. In this study, 103 patients with symptomatic AF who underwent catheter ablation at a single academic medical center from 2002 to 2006 were evaluated, with a median follow-up time of 6 years. The primary end point was the success rate of catheter ablation, defined as the absence of any atrial arrhythmia recurrence lasting >10 seconds at the clinical visit and electrocardiographic or long-term cardiac rhythm recording after a single procedure and after the last procedure. In all, 153 procedures were performed, with a median of 1 (interquartile range 1 to 2) per patient as follows: 61 had 1, 35 had 2, 6 had 3, and 1 had 4 catheter ablations. Freedom from all atrial arrhythmias was present in 23% of patients at 6 years after a single procedure and in 39% of patients after the last procedure. No clinical predictors of AF recurrence were recognized after a single procedure, whereas after the last procedure, in univariate and multivariate Cox regression analysis, only nonparoxysmal AF (hazard ratio 1.92, 95% confidence interval 1.07 to 3.47, p = 0.02) was a predictor of recurrence. In conclusion, AF recurrence at 6-year follow-up after catheter ablation in a selected group of patients with symptomatic drug-refractory AF was relatively high, with 2/3 of AF relapses occurring in the first year of follow-up. Strict clinical surveillance after catheter ablation should be considered to help guide clinical decisions.


Characterization of three digital signal processor systems used in gamma ray spectrometry.
Various manufacturers have recently introduced digital signal processing systems that allow data acquisition in gamma spectrometry at high-input counting rates (several thousand pulses per second). In these systems, the signal digitization is performed immediately following the preamplification stage. This allows digital shaping and filtering of the signal which increases the number of possible combinations in signal shaping and as a consequence, optimizes the resolution as a function of the detector characteristics and the counting rate. Basic characteristic parameters of three digital signal processors that were recently introduced in the market have been studied and compared to those of an analog system. This study is carried out using a hyper-pure coaxial type germanium detector and 57Co, 60Co and 137Cs radioactive sources. Performance parameters such as energy resolution, system throughput, and counting losses that are due to dead time and pile-up effects are presented and discussed.


Development of a laboratory robotic system for automated bioanalytical methods--II. A robot computer program for guarding totally automated bioanalytical methods.
The application of fully automated, unattended sample preparation performed by a laboratory robot for the analysis of drugs in biological samples requires the prevention of system failures which may arise in the on-line coupled chromatographic system or in other components of the robotic system. A computer program has been developed which can help to detect such problems. The control program for the robotic sample preparation contains a number of safety measures to intercept robotic or human errors. A routine is implemented, guarding for chromatographic malfunctions and errors in dispensing liquids by the robot. After detection of trouble, sample preparation is interrupted.


Predatory functional responses under increasing temperatures of two life stages of an invasive gecko.
The direct effects of temperature increases and differences among life-history might affect the impacts of native and invasive predators on recipient communities. Comparisons of functional responses can improve our understanding of underlying processes involved in altering species interaction strengths and may predict the effect of species invading new communities. Therefore, we investigated the functional responses of the mourning gecko Lepidodactylus lugubris (Duméril & Bibron, 1836) to explore how temperature, body-size and prey density alter gecko predatory impacts in ecosystems. We quantified the functional responses of juvenile and adult geckos in single-predator experiments at 20, 23 and 26 °C. Both displayed saturating Type-II functional responses, but juvenile functional responses and the novel Functional Response Ratio were positively affected by temperature as juvenile attack rates (a) increased as a function of increased temperature. Handling times (h) tended to shorten at higher temperature for both predator stages. We demonstrate that the effects of temperature on functional responses of geckos differ across ontogeny, perhaps reflecting life-history stages prioritising growth and maturation or body maintenance. This indicates that temperature-dependent gecko predatory impacts will be mediated by population demographics. We advocate further comparisons of functional responses to understand the invasiveness and future predatory impacts of geckos, and other invasive species globally, as temperatures change.


Laminar and areal differences in the origin of the subcortical projection neurons of the rat somatosensory cortex.
Fluorescent retrograde tracing techniques were employed in a double-labelling paradigm to determine the distribution of corticospinal, corticotectal, and corticotrigeminal projection neurons in layer Vb of the adult and neonatal rat somatosensory cortex. The double-labelling paradigm allowed a direct comparison of the cortical distribution of neurons projecting to each target and identification of neurons projecting to more than one target. In the adult rat, each population of projection neurons was found to have a unique laminar and/or areal distribution. Corticospinal projection neurons were located throughout the width of layer Vb in the medial granular portion of somatosensory cortex, while corticotrigeminal projection neurons were distributed throughout the width of layer Vb in the more laterally located dysgranular portion of somatosensory cortex. Corticotectal projection neurons were located more superficially in layer Vb than either corticospinal or corticotrigeminal projection neurons and found scattered throughout both dysgranular and granular somatosensory cortex. Each combination of subcortical injections also resulted in double labelling a small percentage of uniquely distributed neurons. These distribution differences coupled with measurements of cell size allowed us to identify the parent population of the dual projection neurons. Subpopulations of corticotectal neurons also project to the brainstem trigeminal complex and to the spinal cord. Subpopulations of corticotrigeminal neurons also project to the spinal cord, and a proportion of corticotrigeminal neurons projects to at least two targets within the brainstem trigeminal complex (nucleus principalis and subnucleus interpolaris). In the adult rat, corticospinal neurons (as defined by either laminar position or somal size) did not appear to give off collaterals to either the superior colliculus or brainstem trigeminal complex. In the neonatal rat, double-labelled neurons which project to both the spinal cord and the tectum are distributed throughout the full width of layer Vb, rather than restricted to the superficial portion of the layer as in the adult rat. Further, it appears as if the ontogenetic change in the laminar distribution of corticospinal and tectal projection neurons is achieved by mechanisms of selective process elimination rather than cell death. These results are discussed in terms of both the developmental factor which may contribute to the discrete distribution of cortical projection neurons found in the adult and the functional significance of bifurcating projection neurons.


The tabletting machine as an analytical instrument: qualification of the measurement devices for punch forces and validation of the calibration procedures.
The quality of force measurement in an eccentric tabletting machine equipped with piezo-electric load washers mounted under pre-stress at the upper and lower punches, and the reliability of their calibration in situ and under working conditions were carefully investigated, since this tabletting machine is used as an 'analytical instrument' for the evaluation of the compression behaviour of pharmaceutical materials. For a quasistatic calibration procedure the repeatability under standard conditions and the robustness against variations in machine settings, installation conditions, equipment and handling were evaluated. Two differently constructed reference load cells equipped with strain gauges were used for the calibration of the upper punch sensor. The lower punch sensor was calibrated against the upper one. Except for a mechanical hysteresis, owing to uneven stress distribution over the piezo-electric sensors, the results of the quasistatic measurements are assessed to be satisfactory. In addition, dynamic calibrations were performed. One of the strain-gauged load cells was used in addition to two piezo-electric load washers installed without pre-stress. The dynamic behaviour of all the transducers used is deficient. While for the piezo-electric sensors a significant change in the slope of the calibration function with respect to the quasistatic behaviour was observed, for the strain-gauged load cell a pronounced hysteresis must be noted. Comparing the dynamic behaviour at different profiles of rates of force development generated by variations in machine speed and by maximum force setting, the variability in the sensitivity of the upper and lower punch piezo-electric load washers is comparatively small.


Cytophotometric analyses of thalamic neuronal RNA in soman intoxicated rats.
Quantitative azure B-RNA cytophotometry was used to monitor metabolic responses of individual neurons within the ventrobasal nuclear complex (VBC) and nucleus reticularis (NR) of the rat thalamus following administration of soman (0.5, 0.9 or 1.5 LD50, sc). A dose-dependent depression in brain acetylcholinesterase (AChE) was evidenced. With respect to thalamic RNA responses, a complex pattern of RNA alterations was evidenced, with these two regions generally exhibiting opposite patterns of dose-related RNA changes. With sub-lethal dosages of soman, RNA accumulation was evidenced in the acetylcholine (ACh) mediated excitatory VBC region and RNA depletion in the ACh mediated inhibitory NR neurons. With a lethal dose, an opposite RNA response pattern was observed in both thalamic regions. It is postulated that the observed RNA response pattern with sub-lethal dosages of soman is what one would anticipate with cholinergic brainstem reticular formation activation. The absence of such a response with lethal doses strongly suggests some disruption of functional excitatory cholinergic activity and perhaps also an impairment of inhibitory cholinergic synaptic activity.


Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors.
In a case-control study of 495 breast cancer patients and 785 controls between 20 and 56 years of age, the risk of breast cancer associated with a family history of breast cancer was studied according to age and reproductive factors. The familial risk of breast cancer was not significantly modified by age at onset, age at menarche, number of children, age at first full-term pregnancy, menstrual cycle length or age at menopause. However, the familial risk significantly increased with the number of abortions (p < 0.05) and seemed to decrease after a natural menopause (p = 0.08). These results suggest that a familial predisposition to breast cancer exerts the same influence during the first six decades of life, except maybe when there are isolated or repeated events such as abortions or artificially imposed menopause, in which case the risk is apparently greater.


Proximal ear hole injury heals by limited regeneration during the early postnatal phase in mice.
Ear pinna is a particular feature of mammals that shows several repair responses depending on age. Two millimeter hole made in the pinna of middle-aged female mice heals due to partial reconstitution of new tissues (limited regeneration), whereas a hole punched in the ear of young mice forms a scar tissue. In these studies, the injury is made in the center of the ear pinna, but little is known about the type of reparative response along the proximodistal polarity of the ear. This study evaluated the effect of pinna polarity, age, and sex in the ear hole-repairing response in Balb/c mice. Proximal injuries were repaired more efficiently by limited regeneration than wounds made in the middle region. Non-injured ear histological analysis revealed a higher presence of muscle, adipose tissue, cartilage, and larger blood vessels in the proximal ear area, which could influence ear hole closure by limited regeneration. To evaluate the healing response during ear growth, we punched a standard hole in the proximal area of the ear on postnatal day 21 and 8-month-old mice (adults). Thirty-five days after the wound, both groups reached the same wound closure, despite the greater proportional size of holes made in the younger mice. Ear growth also improved ear hole closure in male mice. These results suggest that ear growth accelerates hole closure, providing an example of enhanced regenerative abilities in growing structures. Finally, hole closure kinetics in the growing ear indicated an early re-differentiation phase exhibited at 14 days post-wound. In conclusion, ear topography and growth positively influenced the healing response to ear holes, making it a tractable model to study in mammals.


Ocular complications of systemic cancer chemotherapy.
Cancer chemotherapy has changed rapidly in recent years. New agents are constantly being developed. Established agents are being used with increased frequency, in new combinations, at higher dosages, and via new routes of administration. Enhanced survival, as well as increased drug toxicity, has resulted. Ocular toxicity is not uncommon and can greatly impact on quality of life. Practitioners in all fields are increasingly caring for patients who are receiving cancer chemotherapy. The recognition of eye disease resulting from chemotherapy is essential to appropriate patient management. We provide a review of the rapidly growing body of literature on the ocular toxicity of systemic cancer chemotherapy with particular attention to context, clinical course, mechanism, prevention and treatment.


The increased functional connectivity between the locus coeruleus and supramarginal gyrus in insomnia disorder with acupuncture modulation.
Insomnia disorder (ID) seriously affects the quality of people's daily life, and acupuncture is an effective therapy for it. As an essential component of the upward activation system, the locus coeruleus (LC) plays a crucial role in sleep-wake regulation, its aberrant functional connectivity (FC) is found to be involved in ID. The purpose of this study was to explore the modulation effect of acupuncture on the resting state FC of LC in ID patients. 60 ID patients were recruited and randomly assigned to real acupuncture (RA) or sham acupuncture (SA) treatment. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. With LC as the region of interest, the FC method was adopted to examine acupuncture-related modulation of intrinsic connectivity in ID patients. The Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy were used to assess sleep quality and cortical hyperarousal states. Associations between clinical outcomes and FC features were calculated using Pearson's correlation analysis. The improvement in sleep quality and hyperarousal in the RA group was greater than that in the SA group. After treatment, the FC between the LC and left inferior frontal gyrus (IFG) decreased in the RA group. The FC between the LC and left insula and supramarginal gyrus (SMG) was higher in the RA group. The change of LC FC values with the SMG was negatively associated with the change in PSQI scores. Acupuncture can modulate FC between the LC and IFG, insular gyrus, and SMG. This may imply the potential mechanism of acupuncture treatment for insomnia.


CREPE: a Shiny app for transcription factor cataloguing.
Transcription factors (TFs) are proteins that directly interpret the genome to regulate gene expression and determine cellular phenotypes. TF identification is a common first step in unraveling gene regulatory networks. We present CREPE, an R Shiny app to catalogue and annotate TFs. CREPE was benchmarked against curated human TF datasets. Next, we use CREPE to explore the TF repertoires of Heliconius erato and Heliconius melpomene butterflies. CREPE is available as a Shiny app package available at GitHub (github.com/dirostri/CREPE). Supplementary data are available at Bioinformatics Advances online.