Inotropic and calcium kinetic effects of calcium channel agonist and antagonist in isolated cardiac myocytes from cardiomyopathic hamsters.
The mechanism by which heart cells of cardiomyopathic (CM) hamsters become calcium overloaded is not known. We examined the number of slow calcium channels, calcium uptake via slow calcium channels, calcium pool sizes, and the contractile response to Bay K 8644, verapamil, and nifedipine using isolated cardiac myocytes from 8-9-month-old CM hamsters (BIO 14.6) and age-matched normal controls. The number of dihydropyridine binding sites as assessed by specific binding of [3H]PN200-110 was similar in the two groups (control hearts: Bmax = 333 +/- 89 [mean +/- SD] fmol/mg; CM hearts: Bmax = 357 +/- 75 fmol/mg; n = 5 experiments, p = 0.6). Current density through L-type calcium channels was determined using the whole-cell clamp technique (at -50 mV holding potential and -10 mV test potential) and was the same in CM myocytes (17.8 +/- 1.5 [mean +/- SD] pA/pF) and control myocytes (18.6 +/- 2.1 pA/pF) (n = 5 experiments, p = 0.5). The current-voltage relation (test potentials varied from -40 to +50 mV) was also the same in CM and control cells, as was apparent threshold, peak current, and reversal potential. However, the initial rate of 45Ca influx as well as the size of the rapidly exchangeable calcium pool was significantly greater in myocytes obtained from CM than from normal hamsters. In both myocyte preparations, Bay K 8644 increased the rate of 45Ca uptake by 25% at 60 seconds; verapamil decreased 45Ca uptake at 60 seconds by 16% and 17% in normal and CM hamsters, respectively. A similar inhibitory effect was observed with nifedipine. The amplitude of cell motion in cells driven at 1.5 Hz as assessed by an optical-video system increased progressively with increasing concentrations of extracellular calcium or Bay K 8644 in cardiac myocytes from normal or CM hamsters. However, the concentration-effect curves for the two effectors were shifted to the left in CM cells compared with cells from normal hamsters. Both preparations demonstrated similar contractile responses to verapamil and nifedipine. These findings demonstrate that single enzymatically dissociated cardiac myocytes from CM hamsters have impaired contractile properties analogous to those seen in the intact heart and thus provide a useful experimental system in which to study underlying cellular mechanisms operative in this model of heart failure. Our results further indicate that calcium overload in CM hamster cardiac myocytes may not be due to increased calcium influx via dihydropyridine-sensitive calcium channels, as suggested previously, but rather to abnormalities of intracellular calcium homeostasis.


Comparison of Renal Function and Other Predictors in Lacto-Ovo Vegetarians and Omnivores With Chronic Kidney Disease.
Objective Vegetarian diets have been shown to increase the risk of certain nutritional deficiencies, such as iron. As a number of patients with chronic kidney disease (CKD) in Taiwan are lacto-ovo vegetarians, the aim of this study was to investigate the effects of different proportions and sources of protein in lacto-ovo vegetarian and omnivorous diets, as well as the influence of adequate dietary protein intake, on renal function and nutritional status of Taiwanese patients with stage 3 to stage 5 CKD. Methods This is a cross-sectional study. In total, 100 outpatients with stage 3 to stage 5 CKD were enrolled in this study, including 40 lacto-ovo vegetarians and 60 omnivores. Subjects were divided into the lacto-ovo vegetarian group and omnivorous group based on dietary protein patterns. The indicators of renal function included estimated glomerular filtration rate (eGFR), creatinine, and blood urea nitrogen (BUN). Albumin, hemoglobin (Hb), and red blood cell count (RBC) measurements served as nutritional indicators. The levels of dietary energy and protein, as well as protein sources (plant or animal), were also analyzed. Results The levels of serum phosphate and triglycerides were significantly lower in the lacto-ovo vegetarian group than in the omnivore group, suggesting that lacto-ovo vegetarian diets have both phosphate-lowering and lipid-lowering effects, which could reduce the development of hyperphosphatemia and dyslipidemia. However, since all groups consumed higher than the recommended amounts of protein diet intake, no significant differences were observed in other renal function indices between the two groups. Conclusion Although a larger cohort study is necessary, the findings of this study could help patients with CKD to make healthier food choices and be used to support future medical nutritional therapies.


Effect of UV-C radiation on bioactive compounds of pineapple (Ananas comosus L. Merr.) by-products.
The industrial processing of pineapple generates a high quantity of by-products. To reduce the environmental impact of these by-products and the inherent cost of their treatment, it is important to characterise and valorise these products, converting them into high added value products. Ultra-violet radiation is one of the main sustainable sanitation techniques for fruits. Since this radiation can induce plant stress which can promote the biosynthesis of bioactive compounds, it is important to evaluate its effect in fruits. The amounts of vitamins (C and E) and carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, neoxanthin, violaxanthin and zeaxanthin) in pineapple by-products (core and rind) were analysed before and after treatment with UV radiation. All treated and untreated pineapple by-products contained β-carotene as the main carotenoid (rind, 2537-3225 µg; and core, 960-994 µg 100 g(-1) DW). Pineapple rind also contained lutein (288-297 µg 100 g(-1) DW) and α-carotene (89-126 µg 100 g(-1) DW). The results provide evidence of the potential of pineapple by-products as a source of bioactive compounds with antioxidant activity, which can be used by pharmaceutical, cosmetics and food industries. In addition, UV-C was shown to be a treatment that can add nutritional value to pineapple by-products.


Folding of an Ala-Ala-Ala tripeptide into a beta-turn via hydrophobic encapsulation.
An Ac-Ala-Ala-Ala-NH2 tripeptide was folded into a beta-turn structure even in water through hydrophobic binding by a self-assembled porphyrin cage. The turn conformation of the bound peptide was fully assigned from NOESY measurements and was strongly supported by molecular dynamics simulation. Single mutation experiments and molecular modeling also suggested that CH-pi interactions between methyl groups of Ala residues and porphyrin ligands were important for the stabilization of the turn conformation. Furthermore, we observed the induction of a beta-hairpin structure by encapsulation of a heptapeptide, Ac-Gly-Gly-Ala-Ala-Ala-Gly-Gly-NH2, possessing Ala-Ala-Ala sequence at the middle.


[Nitrogenous metabolism vitamin provision and anthrometric indices by Uzbek young with a different nutrition status].
Nitrogenous metabolism, vitamin provision and anthroponietric indices were inventigated in 1560 Uzbek youths (18-21 years old) with diverse alimentary status. Changes cheatinine in urine, insufficient vitamines content and violations of authropometric indices were revald in patients with protein-calorie deficiency.


An unusual cause of recurrent joint effusions: nonhemophilic hemosiderotic synovitis of the knee.
A 20-year-old female presented with a painful swelling in the right knee and snapping sensation on joint motion that appeared without trauma and recurred several times. She had no history of a bleeding disease or trauma. Physical examination showed no signs of rash or temperature change or systemic or local findings of an infection. The knee was tender and knee motion was painful, with 90 degrees of flexion and full extension. The ballottement test was positive. All laboratory tests including rheumatologic and bleeding parameters were normal. Joint effusion analysis was normal except for its rusty-brown color. Magnetic resonance imaging showed synovial hypertrophy and grade 2 degeneration in the medial meniscus. During diagnostic and surgical arthroscopy, rust-colored synovial hypertrophy was noted in the suprapatellar pouch accompanied by patchy villi and nodules and cystic changes. The gross appearance of the synovium mimicked that of pigmented villonodular synovitis. Biopsy specimens were obtained from different parts of the synovium and a subtotal synovectomy was performed. The histopathologic diagnosis was reported as hemosiderotic synovitis. During a three-year follow-up, she had no pain, snapping sensation, or limitation of motion. There were no recurrent effusions.


The Role of the Oxysterol/EBI2 Pathway in the Immune and Central Nervous Systems.
Oxysterols are pleiotropic messengers interacting with multiple receptor systems. One of the cognate receptors for oxysterols is EBI2, a G protein-coupled receptor highly expressed in the cells of the immune system. Here we discuss the receptor's role in the adapted immunity and inflammation as well as the receptor's expression and function in the CNS with the focus on astrocytes. We also discuss expression and signalling of oxysterol-producing enzymes such as CH25H and CYP7B1 in the CNS and the immune system. These steps will help to elucidate a possible role for this pathway in the physiology of the central and peripheral nervous system and its possible link to human disease.


Low rotational barriers for the most dynamically active methyl groups in the proposed antiviral drugs for treatment of SARS-CoV-2, apilimod and tetrandrine.
A recent screening study highlighted a molecular compound, apilimod, for its efficacy against the SARS-CoV-2 virus, while another compound, tetrandrine, demonstrated a remarkable synergy with the benchmark antiviral drug, remdesivir. Here, we find that because of significantly reduced potential energy barriers, which also give rise to pronounced quantum effects, the rotational dynamics of the most dynamically active methyl groups in apilimod and tetrandrine are much faster than those in remdesivir. Because dynamics of methyl groups are essential for biochemical activity, screening studies based on the computed potential energy profiles may help identify promising candidates within a given class of drugs.


One-leg cycling versus arm cranking: which is most appropriate for physical conditioning after knee surgery?
To compare the cardiorespiratory responses, blood lactate concentration and perceived exertion between 1-leg cycling and arm cranking. Comparison of exercise modalities. Hospital. Fourteen men who had undergone knee surgery were evaluated during rehabilitation. Not applicable. Each patient performed 2 maximal graded tests: 1-leg cycling and arm cranking exercise, with a 7-day interval. Respiratory gas exchange, heart rate, blood lactate concentration, and the ratings of perceived exertion (RPE) were measured. Peak power output, peak minute ventilation, peak oxygen uptake (Vo(2)peak), and peak heart rate did not differ significantly between 1-leg cycling and arm cranking. The first and second ventilatory thresholds occurred at above 40% and 72% of Vo(2)peak, respectively, in both tests. The maximal lactate concentrations and the RPE values were significantly higher during arm cranking (+10%, +12%, respectively, P<.05) compared with corresponding 1-leg cycling values. The maximal cardiorespiratory values were not different between arm cranking and 1-leg cycling. However, the RPE and blood lactate concentration were lower when the exercise was performed with the lower limb. Thus 1-leg cycling may be more easily tolerated than arm cranking by patients participating in aerobic conditioning after knee surgery.


Cell pinball: phenomenon and mechanism of inertia-like cell motion in a microfluidic channel.
An unexpected phenomenon of red blood cells bouncing back and forth between the walls inside a microfluidic channel was observed during experiments, and is presented as "Cell Pinball" in this paper. In general, cells in a microfluidic environment are supposed to move along the streamlines parallel to the channel walls when the Reynolds number is small, and the inertia of the cells becomes negligible. However, the cell pinball presented in this paper does not only move along the streamlines but also moves across the channel with the velocity component perpendicular to the streamlines while the Reynolds number is only 0.74. Furthermore, the motion in the direction perpendicular to the streamlines reverses when the cell pinball hits a wall as it "bounces" at the wall. This phenomenon caught our attention and is investigated with both microbead visualization and confocal microscopy. Consistent patterns of rotation with respect to the direction of motion are observed. A kinematic model is proposed to interpret the phenomenon, and it is believed that the phenomenon is caused by the separation of the centroid of the cell and the contact point. The model successfully interprets the features of cell pinball, and the estimated separation between the centroid and the contact point is presented.


Nonsinusoidal current-phase relationship in Josephson junctions from the 3D topological insulator HgTe.
We use superconducting quantum interference device microscopy to characterize the current-phase relation (CPR) of Josephson junctions from the three-dimensional topological insulator HgTe (3D HgTe). We find clear skewness in the CPRs of HgTe junctions ranging in length from 200 to 600 nm. The skewness indicates that the Josephson current is predominantly carried by Andreev bound states with high transmittance, and the fact that the skewness persists in junctions that are longer than the mean free path suggests that the effect may be related to the helical nature of the Andreev bound states in the surface of HgTe. These experimental results suggest that the topological properties of the normal state can be inherited by the induced superconducting state, and that 3D HgTe is a promising material for realizing the many exciting proposals that require a topological superconductor.


Preparation of β-galacto-oligosaccharides using a novel endo-1,4-β-galactanase from Penicillium oxalicum.
Endo-1,4-β-galactanase is an indispensable tool for preparing prebiotic β-galacto-oligosaccharides (β-GOS) from pectic galactan resources. In the present study, a novel endo-1,4-β-galactanase (PoβGal53) belonging to glycoside hydrolase family 53 from Penicillium oxalicum sp. 68 was cloned and expressed in Pichia pastoris GS115. Upon purification by affinity chromatography, recombinant PoβGal53 exhibited a single band on SDS-PAGE with a molecular weight of 45.0 kDa. Using potato galactan as substrate, PoβGal53 showed optimal reaction conditions of pH 4.0, 40 °C, and was thermostable, retaining >80 % activity after incubating below 45 °C for 12 h. Significantly, PoβGal53 exhibited relatively conserved substrate specificity for (1 → 4)-β-D-galactan with an activity of 6244 ± 282 U/mg. In this regard, the enzyme is in effect the most efficient endo-1,4-β-galactanase identified to date. By using PoβGal53, β-GOS monomers were prepared from potato galactan and separated using medium pressure liquid chromatography. HPAEC-PAD, MALDI-TOF-MS and ESI-MS/MS analyses demonstrated that these β-GOS species ranged from 1,4-β-D-galactobiose to 1,4-β-D-galactooctaose (DP 2-8) with high purity. This work provides not only a highly active tool for enzymatic degradation of pectic galactan, but an efficient protocol for preparing β-GOS.


Genetic tools for studying Capnocytophaga canimorsus.
Capnocytophaga canimorsus, a commensal bacterium from canine oral flora, has been isolated throughout the world from severe human infections caused by dog bites. Due to the low level of evolutionary relationship to Proteobacteria, genetic methods suitable for the genus Capnocytophaga needed to be established. Here, we show that Tn4351, derived from Bacteroides fragilis, could be introduced by conjugation into C. canimorsus and conferred resistance to erythromycin. By mapping and sequencing a naturally occurring plasmid isolated from a clinical isolate of C. canimorsus, we identified a repA gene that allowed us to construct Escherichia coli-Capnocytophaga shuttle vectors. Most commonly used antibiotic markers were not functional in C. canimorsus, but cefoxitin (cfxA), tetracycline (tetQ), and erythromycin (ermF) resistances could be used as markers for plasmid maintenance in C. canimorsus and even in some other Capnocytophaga spp. Shuttle vectors were introduced into C. canimorsus either by conjugation using the origin of transfer (oriT) of RP4 or by electrotransformation. Taking advantage of the promoter of ermF, an expression vector was constructed. Finally, a method that allows site-directed mutagenesis is described. All these genetic tools pave the way, not only for molecular studies of the pathogenesis of C. canimorsus, but also for studies of other oral Capnocytophaga species.


The lipid composition of azole-sensitive and azole-resistant strains of Candida albicans.
The lipid compositions of two azole-sensitive (A and B2630) and two azole-resistant (AD and KB) strains of the opportunistic fungal pathogen Candida albicans were studied by using several lipid extraction procedures: no differences were observed between the lipid content or total phospholipid/neutral lipid ratios of the four strains. All contained phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylserine as major phospholipids, with smaller amounts of phosphatidylglycerol and diphosphatidylglycerol; the relative proportions of these lipids differed between all four strains. The fatty acid composition of each major phospholipid within each strain differed, and there were also interstrain differences. A marked effect of culture growth phase in batch culture on lipid composition was observed. The major neutral lipids in each strain were triacylglycerol, non-esterified sterol and non-esterified fatty acid. The fatty acid compositions of the three fatty-acid-containing neutral lipids were distinct from each other and the phospholipids, and there were also interstrain differences. All strains possessed (lyso)phospholipase activity, which was non-specific. The proportions of triacylglycerol and non-esterified fatty acid did not vary between strains, but the azole-resistant strains AD and KB contained more non-esterified sterol, giving them a phospholipid/sterol ratio approximately half that of azole-sensitive strains. There appeared to be a relationship between the phospholipid/sterol ratio of exponentially growing sensitive strains and their ability to take up azole; this did not extend to the resistant strains, which either did not take up azole (AD and KB) or took it up at a faster rate (Darlington) than sensitive strains.


Dosimetric characterization of a synthetic single crystal diamond detector in clinical radiation therapy small photon beams.
To determine the potentialities of synthetic single crystal diamond Schottky diodes for accurate dose measurements in radiation therapy small photon beams. The dosimetric properties of a diamond-based detector were assessed by comparison with a reference microionization chamber. The diamond device was operated at zero bias voltage under irradiation with high-energy radiotherapic photon beams. The stability of the detector response and its dose and dose rate dependence were measured. Different square field sizes ranging from 1 × 1 cm(2) to 10 × 10 cm(2) were used during comparative dose distribution measurements by means of percentage depth dose curves (PDDs), lateral beam profiles, and output factors. The angular and temperature dependence of the diamond detector response were also studied. The detector response shows a deviation from linearity of less than ±0.5% in the 0.01-7 Gy range and dose rate dependence below ±0.5% in the 1-6 Gy∕min range. PDDs and output factors are in good agreement with those measured by the reference ionization chamber within 1%. No angular dependence is observed by rotating the detector along its axis, while ∼3.5% maximum difference is measured by varying the radiation incidence angle in the polar direction. The temperature dependence was investigated as well and a ±0.2% variation of the detector response is found in the 18-40 °C range. The obtained results indicate the investigated synthetic diamond-based detector as a candidate for small field clinical radiation dosimetry in advanced radiation therapy techniques.


Evaluation of noninvasive tests for the preoperative staging of carcinoma of the esophagus: a prospective study.
A prospective study was undertaken to define the usefulness of conventional full-lung linear tomography, radionuclide liver plus spleen and bone scans, and thoracic and abdominal computed tomography for the preoperative staging of carcinoma of the esophagus. Thirty-three patients with carcinoma of the esophagus were studied. The computed tomographic (CT) scan of the thorax and upper abdomen was the single most accurate noninvasive study. With computed tomography, the relationship of the tumor to the tracheobronchial tree was the feature most useful in predicting local resectability. In all patients with the finding of tracheobronchial compression by the tumor, the tumor could not be resected completely. The predictive value of this CT finding in patients with locally unresectable tumor was high (0.83), indicating its usefulness in assessing unresectability. The CT finding of visible separation between tumor mass and tracheobronchial tree was present in 10 of 14 patients with locally resectable tumor (predictive value, 0.63). However, tumor abutting the tracheobronchial tree without compression was a poor predictor of unresectability (predictive value, 0.36). The radionuclide bone scan was the only other noninvasive study to demonstrate a metastasis not evident by CT scan. The combination of chest and abdominal CT scan, bone scan, and bronchoscopy before operation will accurately stage the majority of patients with esophageal cancer but no noninvasive test is of sufficient reliability to exclude patients from operative resection if otherwise indicated.


The effect of serum immunoglobulin concentration on immune complex detection by polyethylene glycol.
The addition of 4% polyethylene glycol (PEG) to serum and quantitation of immunoglobulins in the dissolved precipitate has been advocated as a simple, reliable method for detecting circulating immune complexes. Because pathological sera, which often yield positive results in this assay, may contain increased concentrations of immunoglobulins compared to normal control sera, we have determined the relationship between total serum immunoglobulin concentration and the quantity of immunoglobulins precipitated by 4% PEG. When IgG was added to normal serum, the quantity and percentage of IgG in the precipitate was directly proportional to total serum IgG concentration. This concentration-dependent precipitation appeared to be unrelated to the presence of aggregates in the IgG preparation, the serum concentration of albumin, or interactions with serum complement. With normal serum, concentrated to yield a wide range of endogenous immunoglobulin concentrations, the percentage of IgG, IgM and IgA in the PEG precipitates was likewise directly proportional to the total serum concentration of these immunoglobulins. In view of these findings, this method is likely to give false-positive results in pathological sera containing increased immunoglobulin concentrations and is probably invalid as a means for detecting circulating immune complexes. However, with a final concentration of 2% PEG, successful discrimination between aggregated immunoglobulin and monomeric IgG may be achieved.


Phase II study of the progesterone antagonist mifepristone in patients with untreated metastatic breast carcinoma: a National Cancer Institute of Canada Clinical Trials Group study.
Mifepristone (RU486) is a progesterone receptor (PgR) antagonist that has been shown to be active in some preclinical hormone-dependent breast cancer tumor models and to produce a few responses in patients with pretreated metastatic disease in two small trials. This trial was designed to assess the response rate and toxic effects of mifepristone in a favorable group of women with PgR-positive recurrent breast cancer who had received no prior therapy. Postmenopausal patients with PgR-positive, bidimensionally measurable disease were eligible provided they had received no other therapy for recurrence. Prior adjuvant hormonal treatment was permitted if a disease-free interval of at least 24 months had been observed. Mifepristone 200 mg was given daily and disease was reassessed every 4 weeks. Standard criteria for tumor response and toxic effects were used. A total of 28 patients were registered in the trial: all were eligible and assessable. Three partial responses were noted for an overall response rate of 10.7% (95% confidence interval [CI], 2% to 28%). Toxic effects were generally mild to moderate and consisted primarily of nausea, lethargy, anorexia, and hot flashes. Mifepristone had minimal activity in this optimal group of patients. While there may be reason to conduct some clinical studies with it in combination with antiestrogens on the basis of some preclinical work, our data do not support its use as a single agent in the management of breast cancer.


[Ecological distribution and spatial niche of pheasants in the Karst mountains of southwest Guangxi Province, China].
The Karst mountain area along the Sino-Vietnam border of southwest Guangxi has been designated a "Global Biodiversity Hotspot" since 2003. We conducted a survey of pheasant species in this area, with seven species recorded, namely Chinese Francolin (Francolinus pintadeanus), Bar-backed Partridge (Arborophila brunneopectus), Mountain Bamboo Partridge (Bambusicola fytchii), Chinese Bamboo Partridge (Bambusicola thoracica), Red Junglefowl (Gallus gallus), Silver Pheasant (Lophura nycthemera) and Common Pheasant (Phasianus colchicus). Analysis and comparison of the distribution and spatial niche of these seven pheasant species revealed that Red Junglefowl had the widest spatial niche, while Chinese Francolin had the narrowest. The spatial niche overlap index was high between Chinese Francolin and the Common Pheasant, Chinese Bamboo Partridge, and Red Junglefowl. With narrow distribution range, small population, and lower ecological adaptability, it is likely that the Bar-backed Partridge is the most vulnerable pheasant species in this area. The results suggest more research and conservation measures are required for pheasant habitat protection in the Karst areas of southwest Guangxi.


How effective is public health policy in Scotland on vitamin D deficiency during pregnancy?
To evaluate the uptake of universal vitamin D supplementation during pregnancy, its effectiveness in preventing vitamin D deficiency and the factors associated with these. The regional public health organisation in Ayrshire, Scotland has a policy of universal provision of vitamin D supplements (10 µg/d) to all pregnant women for the duration of their pregnancy. Pregnant women in this area were recruited at their 12-week antenatal appointment. Blood samples were collected at the 12-week and 34-week appointments. To account for the seasonal variation, women were recruited in two cohorts: summer and winter. Telephone interviews were conducted at 34 weeks to assess the uptake of vitamin D supplements during pregnancy. Other variables were obtained from medical records. The study was conducted in the NHS Ayrshire and Arran Health Board in Scotland. 612 pregnant women (aged 15-44 years) living in Ayrshire (latitude 55°), Scotland. Sixty-six percentage took supplementation as recommended. Consumption of supplementation was significantly associated with a higher median serum 25-hydroxyvitamin D concentrations at 34 weeks. Despite this at 34 weeks, 33 % of the summer cohort had insufficient or deficient vitamin D status, while 15 % of the winter cohort had insufficient or deficient status. In multivariable analysis, only adherence and season were independent predictors of vitamin D status. While supplementation improved and maintained vitamin D status during pregnancy, it was not adequate to ensure all those insufficient at 12 weeks achieved sufficient status at the end of pregnancy.


Characterisation of the nuclear location sequence of Xenopus nucleoplasmin.
Each subunit of the Xenopus nucleoplasmin polypeptide possesses a single nuclear location sequence, the boundaries of which have been determined by deletion analysis. However, the sequence identified in this analysis is unable to locate pyruvate kinase to the cell nucleus. Further investigation revealed that while this sequence element is not sufficient for nuclear localisation, it is a necessary feature of slightly longer sequences which can locate pyruvate kinase to the cell nucleus. This unusual feature of the nucleoplasmin sequence suggests testable models for the interaction of this sequence with the transport mechanism, one of which is discussed here.


Healing following GTR treatment of bone defects distal to mandibular 2nd molars after surgical removal of impacted 3rd molars.
The purpose of this study was to study the healing, following guided tissue regeneration (GTR) treatment, of bone defects distal to mandibular 2nd molars (M2s) after surgical removal of impacted mesioangularly or horizontally inclined third molars (M3s) in patients > or = 25 years. 20 patients with bilateral soft tissue impacted M3s were included in the split-mouth study. The 2 sites to be treated in each patient were randomised before the 1st operation as to which would undergo the test procedure and which would be the control site. After surgical removal of M3 at test sites, a resorbable polylactic acid (PLA) barrier was attached to M2 to cover the post-surgical bone defect. The flap was then replaced and sutured to cover the barrier. Control sites underwent the same procedure, as did the test sites, with the exception that no barrier was placed. The clinical examinations performed were oral hygiene pre- and 12 months postoperatively and probing pocket depth 12 months postoperatively. The alveolar bone level (ABL) at the distal surface of the M2, as determined from radiographs taken at suture removal and 12 months postsurgery, was chosen to be the primary response variable. Most bone defects showed healing up to 10%-20% of the tooth length at both test and control sites. 2 test and 2 control sites showed no improvement in the bone level. The mean values of bone healing registered in mm from the cemento-enamel junction (CEJ) were 2.6 +/- 2.19 SD and 3.0 +/- 2.20 SD for test and control sites, respectively. Different factors affecting the healing result are discussed.


Ticagrelor for Refractory Migraine/Patent Foramen Ovale (TRACTOR): An open-label pilot study.
After finding that the thienopyridines clopidogrel and prasugrel reduced migraine headache (MHA) symptoms in some patients with patent foramen ovale (PFO), this small pilot study was undertaken to determine whether ticagrelor, a nonthienopyridine P2Y12 inhibitor, would have similar MHA effects and might be better suited for a future randomized trial. MHA patients were screened for PFO. Participants with documented right to left shunt (RLS) and ≥6 monthly MHA days received ticagrelor therapy for 28 days. Those with ≥50% reduction in monthly MHA days were deemed responders and completed 2 additional treatment months. The 40 participants had a mean age of 36.2 years and mean MHA frequency of 17.4 d/mo. A total of 39/40 were female. A total of 14/40 met criteria for episodic MHA, 26/40 for chronic MHA, 14/40 had migraine with aura, and 22/40 had a moderate-large RLS (Spencer grade ≥4). Seventeen of 40 participants (43%) were responders. MHA reduction continued through 3 treatment months in all responders. MHA responder rates were not statistically different in participants with episodic or chronic MHA, with or without aura, or with small/larger RLS shunt magnitude. Thirteen (32%) patients had medication side effects, without serious adverse events. P2Y12 inhibition with ticagrelor reduced MHA symptoms similarly to our previous thienopyridine experience, but participants seemed to have a less robust MHA benefit and more frequent side effects than with the thienopyridines, making it an inferior choice for a randomized trial. This study provides Class IV evidence that ticagrelor reduced MHA symptoms in patients with PFO.


30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis.
At its re-birth 30 years ago, the neurodevelopment hypothesis of schizophrenia focussed on aberrant genes and early neural hazards, but then it grew to include ideas concerning aberrant synaptic pruning in adolescence. The hypothesis had its own stormy development and it endured some difficult teenage years when a resurgence of interest in neurodegeneration threatened its survival. In early adult life, it over-reached itself with some reductionists claiming that schizophrenia was simply a neurodevelopmental disease. However, by age 30, the hypothesis has matured sufficiently to incorporated childhood and adult adversity, urban living and migration, as well as heavy cannabis use, as important risk factors. Thus, it morphed into the developmental risk factor model of psychosis and integrated new evidence concerning dysregulated striatal dopamine as the final step on the pathway linking risk factors to psychotic symptoms.


Transventricular aortic valvotomy for critical aortic stenosis in infants.
Ten infants with critical aortic stenosis underwent transventricular valvotomy between November 1983 and September 1984. The ages of the patients ranged from 1 to 38 days (mean 21.2 days). Three patients were less than 1 week of age. One had undergone a previous valvotomy performed with inflow occlusion. Most infants were critically ill when admitted to the hospital, six required inotropic and ventilatory support, and two had peritoneal dialysis before the operation. Transventricular valvotomy was performed through a left thoracotomy with Hegar dilators. Postvalvotomy peak-to-peak gradients ranged from 0 to 35 mm Hg. Three patients died at 2, 3, and 6 weeks after operation. A severe degree of endocardial fibroelastosis was present in one patient, and a second patient died of septicemia caused by wound infection, empyema, and a bronchopleural fistula. Severe left ventricular hypertrophy, with moderate fibroelastosis, was found at autopsy in the third patient. Aortic incompetence was not detected postoperatively. One patient required reoperation 7 months after the transventricular valvotomy. Transventricular valvotomy has proved to be a simple and effective technique to relieve aortic stenosis in sick infants. It permits the correction of associated coarctation of the aorta and avoids a median sternotomy. Results are comparable with the results obtained with either cardiopulmonary bypass or inflow occlusion as seen in both our experience and in the experience of others.


Anterior insula regulates brain network transitions that gate conscious access.
Conscious access to sensory information is likely gated at an intermediate site between primary sensory and transmodal association cortices, but the structure responsible remains unknown. We perform functional neuroimaging to determine the neural correlates of conscious access using a volitional mental imagery task, a report paradigm not confounded by motor behavior. Titrating propofol to loss of behavioral responsiveness in healthy volunteers creates dysfunction of the anterior insular cortex (AIC) in association with an impairment of dynamic transitions of default-mode and dorsal attention networks. Candidate subcortical regions mediating sensory gating or arousal (thalamus, basal forebrain) fail to show this association. The gating role of the AIC is consistent with findings in awake participants, whose conscious access is predicted by pre-stimulus AIC activity near perceptual threshold. These data support the hypothesis that AIC, situated at an intermediate position of the cortical hierarchy, regulates brain network transitions that gate conscious access.


Drugs and Rhabdomyolysis: From Liver to Kidney.
Rhabdomyolysis is a syndrome due to a damage of skeletal muscle and the leakage of intracellular contents into the extracellular fluid and the circulation. Several causes may induce rhabdomyolysis and the major one is the crush syndrome. Most cases of non-traumatic rhabdomyolysis are related to drugs. Many molecules are subject to hepatic metabolism and the concomitant use of drugs, as statins, with other medications acting as substrates of the same isoenzymes can interact and increase the risk of myopathy. Subclinical rise of creatine kinase may be the expression of rhabdomyolysis that can present as a medical emergency such as acute kidney injury (AKI), compartment syndrome, cardiac dysrhythmias and disseminated intravascular coagulopathy. The main pathophysiological mechanisms of myoglobinuric-related AKI are renal vasoconstriction, formation of intraluminal casts and direct cytotoxicity promoted by heme-protein. The aim of this review is to analyze the pathophysiology of myolysis, the causes of rhabdomyolysis and especially the link between the liver and the kidney, which can represent the connecting element for the development of the syndrome.


Associations between visual, hearing, and dual sensory impairments and history of motor vehicle collision involvement of older drivers.
To examine the association between visual and hearing impairment and motor vehicle collision (MVC) involvement in older drivers. Retrospective cohort study. North central Alabama. Population-based sample of 2,000 licensed-drivers aged 70 and older. Visual acuity was measured using the Electronic Visual Acuity test. Contrast sensitivity was measured using the Pelli-Robson chart. Presence of subjective hearing loss and other health conditions were determined using a general health questionnaire. Information regarding MVCs for all participants spanning the 5 years before study enrollment was obtained from the Alabama Department of Public Safety. After adjustment for age, race, sex, number of miles driven, number of medical conditions, general cognitive status, and visual processing speed, older drivers with visual acuity and hearing impairment (rate ratio (RR) = 1.52, 95% confidence interval (CI) = 1.01-2.30), contrast sensitivity impairment alone (RR = 1.42, 95% CI = 1.00-2.02), and contrast sensitivity and hearing impairment (RR = 2.41, 95% CI = 1.62-3.57) had higher MVC rates than drivers with no visual or hearing impairments. Drivers with visual acuity loss alone or hearing loss alone did not have MVC rates that were significantly different from those of the no impairment group after adjustment for multiple variables. Older drivers with dual sensory impairment are at greater MVC risk than those with a visual acuity or hearing deficit alone. A combined screening approach of screening for hearing and visual impairment may be a useful tool to identify older drivers at risk of MVC involvement.


Short-Term Clinical and Oncological Outcome of Prolonging Operation Interval After Neoadjuvant Chemoradiotherapy for Locally Advanced Middle and Low Rectal Cancer.
The purpose of this study is to evaluate the short-term clinical and oncological outcome of prolonging operation interval to 11 weeks after the end of radiotherapy for locally advanced middle and low rectal cancer. A total of 123 patients with stage II/III (cT3/T4 or N+) low and middle rectal cancer who had undergone operation after neoadjuvant chemoradiotherapy were selected. According to the interval time between the last radiotherapy and operation, they were assigned to a short-interval group (SG, <11 weeks, n=66) and long-interval group (LG, ≥11 weeks, n=57). The relations among interval time and short-term clinical outcome and oncological outcome were analyzed. The analysis found that basic information, clinical characteristics, and preoperative treatment between the two groups had no significant difference. There were no differences in operation time, estimated intraoperative blood loss and postoperative complications. The rate of sphincter preservation in the low and middle rectum was 66.7% in the short-interval group and 59.7% in the long-interval group (P=0.42). The incidence of anastomotic leak in the long-interval group was higher than that in the short-interval group (P=0.08). There was no significant difference in the recovery time of intestinal function and median duration of hospitalization between the two groups. The pathological complete remission rate was 17.07%. Multivariate analysis showed interval time had no influence on pathological complete remission. There was no significant difference in 3-year overall survival and 3-year disease-free survival between the two groups. The risk of recurrence and metastasis in patients with positive lymph nodes was higher than those with negative lymph nodes (P<0.05), HR=4.812 (95% CI 2.4-9.648). Prolonging the interval time of operation to 11 weeks after neoadjuvant chemoradiotherapy for middle and low rectal cancer does not improve the pathologic complete remission, morbidity, and mortality. There was no significant effect on oncologic outcome after prolonging the operation interval. Therefore, it is safe to prolong the interval of operation to 11 weeks.


High temperatures and health outcomes: a review of the literature.
To analyse the relationship between high temperatures and population health impacts, in terms of mortality and morbidity. A literature search was conducted using Medline to collect data from studies on heat waves, temperature-health impacts curve, risk factors, and preventive measures. All the data collected was published in English and available up to December 2009. Numerous studies carried out in Europe following the 2003 heat wave, as well as those conducted prior to this date in Europe and North America, showed an increase in heat wave-related excess mortality. Recent studies have demonstrated that a forward shift of deaths may only explain a very limited quantity of the excess mortality observed (up to 15%) during major heat waves. Moreover, the results seem to exclude that ozone acts as a confounding variable, whilst it remains a potential effect modifier. Future research needs to explore the consistency of results in new settings, to quantify the burden of heat-related morbidity and in particular to evaluate the effectiveness of the implemented preventive measures.


Implementation Potential of Moral Reconation Therapy for Criminal Recidivism in Mental Health Residential Programs.
Criminal recidivism is common among patients in mental health residential treatment programs. Moral reconation therapy (MRT) has empirical support for reducing criminal recidivism by modifying antisocial cognitions and behaviors; however, its implementation potential in noncorrectional settings has been rarely studied. This potential was examined in a three-site effectiveness-implementation trial of MRT for justice-involved veterans receiving residential mental health treatment in the U.S. Veterans Health Administration. Semistructured interviews were conducted with 36 veterans who received MRT and 13 residential program staff who were involved in its implementation during the trial. Interviews were guided by the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework and a focus on patient engagement and context. Content analysis was used to identify facilitators of and barriers to MRT implementation in residential mental health treatment. Participants viewed MRT as unique and complementary to usual residential care, with benefits beyond recidivism reduction. However, time intensity of the MRT curriculum, challenges in adapting its content and format, and long-term costs of maintaining MRT were viewed as barriers to implementation. To facilitate implementation, participants suggested streamlining the MRT curriculum, adding motivational components, and establishing partnerships in- and outside the health care system. The findings suggest strategies and modifications to MRT, which, if shown to be effective, may facilitate its wider implementation in mental health residential treatment programs.


Cancer screening by systemic administration of a gene delivery vector encoding tumor-selective secretable biomarker expression.
Cancer biomarkers facilitate screening and early detection but are known for only a few cancer types. We demonstrated the principle of inducing tumors to secrete a serum biomarker using a systemically administered gene delivery vector that targets tumors for selective expression of an engineered cassette. We exploited tumor-selective replication of a conditionally replicative Herpes simplex virus (HSV) combined with a replication-dependent late viral promoter to achieve tumor-selective biomarker expression as an example gene delivery vector. Virus replication, cytotoxicity and biomarker production were low in quiescent normal human foreskin keratinocytes and high in cancer cells in vitro. Following intravenous injection of virus >90% of tumor-bearing mice exhibited higher levels of biomarker than non-tumor-bearing mice and upon necropsy, we detected virus exclusively in tumors. Our strategy of forcing tumors to secrete a serum biomarker could be useful for cancer screening in high-risk patients, and possibly for monitoring response to therapy. In addition, because oncolytic vectors for tumor specific gene delivery are cytotoxic, they may supplement our screening strategy as a "theragnostic" agent. The cancer screening approach presented in this work introduces a paradigm shift in the utility of gene delivery which we foresee being improved by alternative vectors targeting gene delivery and expression to tumors. Refining this approach will usher a new era for clinical cancer screening that may be implemented in the developed and undeveloped world.


Comparison of the "mammal machine" and the "reptile machine": energy production.
Standard metabolism and body composition were measured in Amphibolurus nuchalis and Mus musculus (a reptile and mammal with the same weight and body temperature). The metabolic capacity for energy production was assessed in liver, heart, brain, and kidney in the lizard and mouse by two methods: measurement of mitochondrial enzyme activity (cytochrome oxidase) and measurement of both mitochondrial volume density and membrane surface area. Both methods gave a three- to sixfold greater capacity for energy production in the mammal compared to the lizard which is less than the eightfold difference in their standard metabolisms. The difference in energy production capacity was not due to any single parameter but was a summation of several smaller differences. The mammal had relatively larger internal organs than the reptile, their organs had a greater proportion of mitochondria, and their mitochondria had a greater relative membrane surface area. These differences, it is suggested, may be due in part to different thyroid function in reptiles and mammals.


Eye manifestations of congenital toxoplasmosis.
To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median) and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.


Molecular identification of potential intermediate hosts of Aulonocephalus pennula from the order Orthoptera.
Aulonocephalus pennula is a heteroxenous nematode that commonly infects a declining game bird, the northern bobwhite quail (Colinus virginianus). There is a lack of information on the life cycle of A. pennula and the potential effects of infection on bobwhites. In order to better understand the life cycle of this parasite, various species from the order Orthoptera were collected from a field site in Mitchell County, Texas. Using polymerase chain reaction (PCR), nine potential intermediate hosts were identified from the 35 orthopteran species collected. Later, ten live specimens were collected to identify larvae within the potential intermediate hosts. Larvae were present in three of these and were sent for sequencing. Similarly, the presence of larvae was confirmed from extra tissues of samples identified as positive with PCR. This was the first study to document potential intermediate hosts, but future studies are needed to confirm that these species are capable of transmitting infection to bobwhite. However, this study demonstrates that PCR has increased sensitivity and may be a valuable tool when determining intermediate hosts.


Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure.
Cannabis use has been associated with psychosis and cognitive dysfunction. Some evidence suggests that the acute behavioral and neurocognitive effects of the main active ingredient in cannabis, (-)-trans-Δ9-tetrahydrocannabinol (∆9-THC), might be modulated by previous cannabis exposure. However, this has not been investigated either using a control group of non-users, or following abstinence in modest cannabis users, who represent the majority of recreational users. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ∆9-THC challenge study. Compared to non-users (N=12; <5 lifetime cannabis joints smoked), abstinent modest cannabis users (N=12; 24.5±9 lifetime cannabis joints smoked) showed worse performance and stronger right hemispheric activation during cognitive processing, independent of the acute challenge (all P≤0.047). Acute ∆9-THC administration produced transient anxiety and psychotomimetic symptoms (all P≤0.02), the latter being greater in non-users compared to users (P=0.040). Non-users under placebo (control group) activated specific brain areas to perform the tasks, while deactivating others. An opposite pattern was found under acute (∆9-THC challenge in non-users) as well as residual (cannabis users under placebo) effect of ∆9-THC. Under ∆9-THC, cannabis users showed brain activity patterns intermediate between those in non-users under placebo (control group), and non-users under ∆9-THC (acute effect) and cannabis users under placebo (residual effect). In non-users, the more severe the ∆9-THC-induced psychotomimetic symptoms and cognitive impairments, the more pronounced was the neurophysiological alteration (all P≤0.036). Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis.


Witnessing the formation and relaxation of dressed quasi-particles in a strongly correlated electron system.
The non-equilibrium approach to correlated electron systems is often based on the paradigm that different degrees of freedom interact on different timescales. In this context, photo-excitation is treated as an impulsive injection of electronic energy that is transferred to other degrees of freedom only at later times. Here, by studying the ultrafast dynamics of quasi-particles in an archetypal strongly correlated charge-transfer insulator (La2CuO(4+δ)), we show that the interaction between electrons and bosons manifests itself directly in the photo-excitation processes of a correlated material. With the aid of a general theoretical framework (Hubbard-Holstein Hamiltonian), we reveal that sub-gap excitation pilots the formation of itinerant quasi-particles, which are suddenly dressed by an ultrafast reaction of the bosonic field.


Strategies to improve surgical technical competency: a systematic review.
A cornerstone of surgical residency training is an educational program that produces highly skilled and effective surgeons. Training structures are constantly being revised due to evolving program structures, shifting workforces, and variability in the clinical environment. This has resulted in significant heterogeneity in all surgical resident education, training tools utilized, and measures of training efficacy. We systematically reviewed educational interventions for technical skills in neurosurgery published across PubMed, Embase, and Web of Science over four decades. We extracted general characteristics of each surgical training tool while categorizing educational interventions by modality and neurosurgical application. We identified 626 studies which developed surgical training tools across eight different training modalities: textbooks and literature (11), online resources (53), didactic teaching and one-on-one instruction (7), laboratory courses (50), cadaveric models (63), animal models (47), mixed reality (166), and physical models (229). While publication volume has grown exponentially, a majority of studies were cited with relatively low frequency. Most training programs were published in the development and validation phase with only 2.1% of tools implemented long-term. Each training modality expressed unique strengths and limitations, with limited data reported on the educational impact connected to each training tool. Numerous surgical training tools have been developed and implemented across residency training programs. Though many creative and cutting-edge tools have been devised, evidence supporting educational efficacy and long-term application is lacking. Increased utilization of novel surgical training tools will require validation of metrics used to assess the training outcomes and optimized integration with clinical practice.


Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.
Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidylyltransferase (EPCT) in Leishmania major, which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE. Our results demonstrate that L. major EPCT is a cytosolic protein capable of catalyzing the formation of CDP-ethanolamine from ethanolamine-phosphate and cytidine triphosphate. Genetic manipulation experiments indicate that EPCT is essential in both the promastigote and amastigote stages of L. major as the chromosomal null mutants cannot survive without the episomal expression of EPCT. This differs from our previous findings on the choline branch of the Kennedy pathway (responsible for PC synthesis) which is required only in promastigotes but not amastigotes. While episomal EPCT expression does not affect promastigote proliferation under normal conditions, it leads to reduced production of ethanolamine plasmalogen or plasmenylethanolamine, the dominant PE subtype in Leishmania. In addition, parasites with episomal EPCT exhibit heightened sensitivity to acidic pH and starvation stress, and significant reduction in virulence. In summary, our investigation demonstrates that proper regulation of EPCT expression is crucial for PE synthesis, stress response, and survival of Leishmania parasites throughout their life cycle.


Organic Cation Alloying on Intralayer A and Interlayer A' sites in 2D Hybrid Dion-Jacobson Lead Bromide Perovskites (A')(A)Pb2Br7.
Hybrid layered halide perovskites have achieved impressive performance in optoelectronics. New structural types in the two-dimensional (2D) halide system such as the Dion-Jacobson phases have attracted wide research attention due to the short interlayer distance and unique layer orientation that facilitate better charge-transport and higher stability in optoelectronic devices. Here, we report the first solid solution series incorporating both A and A' cations in the 2D Dion-Jacobson family, with the general formula (A')(A)Pb2Br7 ((A' = 3-(aminomethyl)piperidinium (3AMP) and 4-(aminomethyl)piperidinium) (4AMP); A = methylammonium (MA) and formamidinium (FA)). Mixing the spacing A' cations and perovskitizer A cations generates the new (3AMP)a(4AMP)1-a(FA)b(MA)1-bPb2Br7 perovskites. The crystallographically refined crystal structures using single-crystal X-ray diffraction data reveal that the distortion of the inorganic framework is heavily influenced by the degree of A' and A alloying. A rising fraction of 4AMP in the structure, decreases the Pb-Br-Pb angles, making the framework more distorted. On the contrary, higher FA fractions increase the Pb-Br-Pb angles. This structural evolution fine-tunes the optical properties where the larger the Pb-Br-Pb angle, the narrower the band gap. The photoluminescence emission energy mirrors this trend. Raman spectroscopy reveals a highly dynamical lattice similar to MAPbBr3 and consistent with the local distortion environment of the [Pb2Br7] framework. Density functional theory (DFT) calculations of the electronic structures reveal the same trend as the experimental results where (3AMP)(FA)Pb2Br7 has the smallest band gap while (4AMP)(MA)Pb2Br7 has the largest band gap. The structural effects from solely the organic cations in the 2D system highlight the importance of understanding the high sensitivity of the optoelectronic properties on the structural tuning in this broad class of materials.


Clustering Methods for Vibro-Acoustic Sensing Features as a Potential Approach to Tissue Characterisation in Robot-Assisted Interventions.
This article provides a comprehensive analysis of the feature extraction methods applied to vibro-acoustic signals (VA signals) in the context of robot-assisted interventions. The primary objective is to extract valuable information from these signals to understand tissue behaviour better and build upon prior research. This study is divided into three key stages: feature extraction using the Cepstrum Transform (CT), Mel-Frequency Cepstral Coefficients (MFCCs), and Fast Chirplet Transform (FCT); dimensionality reduction employing techniques such as Principal Component Analysis (PCA), t-Distributed Stochastic Neighbour Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP); and, finally, classification using a nearest neighbours classifier. The results demonstrate that using feature extraction techniques, especially the combination of CT and MFCC with dimensionality reduction algorithms, yields highly efficient outcomes. The classification metrics (Accuracy, Recall, and F1-score) approach 99%, and the clustering metric is 0.61. The performance of the CT-UMAP combination stands out in the evaluation metrics.


A novel approach for mental health disease management: the Air Force Medical Service's interdisciplinary model.
Mental health disorders are one of the most substantial public health problems affecting society today, accounting for roughly 15% of the overall burden of disease from all causes in the United States. Although primary care (PC) has the potential to be the frontline for recognition and management of behavioral health conditions, this has been a challenge historically. In order to more effectively address the broad scope of behavioral health needs, the Air Force Medical Service (AFMS) established a new model of behavioral health care. Through a series of coordinated steps, the AFMS ultimately placed trained behavioral health providers into PC clinics to serve as consultants to PC providers (PCPs). Behavioral Health Consultants (BHCs) provide focused assessments, present healthcare options to patients, and deliver brief collaborative interventions in the PC setting. BHCs see patients at the request of the PCP, in 15-30-min appointments. In the pilot study, patients averaged 1.6 visits to the BHC. Over 70% of patients fell into six categories of presenting problems: situational reactions, depressive disorders, adjustment disorders, anxiety disorders, health promotion, and obesity. Patient data (n = 76) suggest 97% of patients seen were either "satisfied" or "very satisfied" with BHC services, and 100% of the PCPs (n = 23, 68% response rate) were highly satisfied and indicated they would "definitely recommend" others use BHC services for their patients. Both the implications and the limitations of this pilot study are discussed.


Return-sweep saccades during reading in adults and children.
During reading, eye movement patterns differ between children and adults. Children make more fixations that are longer in duration and make shorter saccades. Return-sweeps are saccadic eye movements that move a reader's fixation to a new line of text. Return-sweeps move fixation further than intra-line saccades and often undershoot their target. This necessitates a corrective saccade to bring fixation closer to the start of the line. There have been few empirical investigations of return-sweep saccades in adults, and even fewer in children. In the present study, we examined return-sweeps of 47 adults and 48 children who read identical multiline texts. We found that children launch their return-sweeps closer to the end of the line and target a position closer to the left margin. Therefore, children fixate more extreme positions on the screen when reading for comprehension. Furthermore, children required a corrective saccade following a return-sweep more often than adults. Analysis of the duration of the fixation preceding the corrective saccade indicated that children are as efficient as adults at responding to retinal feedback following a saccade. Rather than consider differences in adult's and children's return-sweep behaviour an artefact of oculomotor control, we believe that these differences represent adult's ability to utilise parafoveal processing to encode text at extreme positions.


Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE): A Cluster-Randomized Pragmatic Trial of a Multifactorial Fall Injury Prevention Strategy: Design and Methods.
Fall injuries are a major cause of morbidity and mortality among older adults. We describe the design of a pragmatic trial to compare the effectiveness of an evidence-based, patient-centered multifactorial fall injury prevention strategy to an enhanced usual care. Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster-randomized, parallel-group, superiority, pragmatic trial being conducted at 86 primary care practices in 10 health care systems across United States. The 86 practices were randomized to intervention or control group using covariate-based constrained randomization, stratified by health care system. Participants are community-living persons, ≥70 years, at increased risk for serious fall injuries. The intervention is a comanagement model in which a nurse Falls Care Manager performs multifactorial risk assessments, develops individualized care plans, which include surveillance, follow-up evaluation, and intervention strategies. Control group receives enhanced usual care, with clinicians and patients receiving evidence-based information on falls prevention. Primary outcome is serious fall injuries, operationalized as those leading to medical attention (nonvertebral fractures, joint dislocation, head injury, lacerations, and other major sequelae). Secondary outcomes include all fall injuries, all falls, and well-being (concern for falling; anxiety and depressive symptoms; physical function and disability). Target sample size was 5,322 participants to provide 90% power to detect 20% reduction in primary outcome rate relative to control. Trial enrolled 5,451 subjects in 20 months. Intervention and follow-up are ongoing. The findings of the STRIDE study will have important clinical and policy implications for the prevention of fall injuries in older adults.


Optimizing primary health care in Burkina Faso: an approach informed by EQUIST
Burkina Faso has made access to primary health care a national priority by including it in the 2021-2030 national health development plan. Our study aimed to analyze the causes of inequalities in access to primary health care, priority interventions and strategies for strengthening primary health care, and their potential impact on reducing maternal and infant mortality. Diarrheal diseases, malaria, and pneumonia are the main causes of inequalities in infant and child deaths in rural areas. As for maternal deaths, abortion and its complications are the main causes of inequalities in deaths associated with hypertensive disorders. The Sahel, Boucle du Mouhoun, Center-North, East, and Cascades regions are the geographical areas where interventions are essential to reduce inequalities in maternal, neonatal, infant and child deaths and malnutrition. The national priorities have included all the high-impact interventions for strengthening primary health care identified in our study. Interventions must prioritize the populations in rural areas, the most affected and high-impact geographical regions. This requires the involvement and empowerment of beneficiary communities and the consideration of the fragile safety context.


Successful participation: the lived experience among children with disabilities.
Children with disabilities are at risk for limited daily occupational participation. This paper presents a phenomenological study describing the meaning of participation in activities outside of school to children with physical and neurological disabilities and their parents. Semi-structured interviews were conducted with eight children and their parents. Nine themes, organized under three categories, describe what successful participation means, and the personal and environmental supports and barriers to participation. Successful participation is defined in terms of being with others and being able to perform tasks independently. This study demonstrates that children with physical and neurological disabilities enjoy the same activities as those children without these disabilities. Activities allowing children to experience enjoyment have the best chance of ensuring children's participation. The role of the parent in providing opportunities for participation, and the importance of environmental and personal resources are particularly important. Finally, implications for occupational therapy and research are discussed.


Functional performance tests, clinical measurements, and patient-reported outcome measures do not correlate as outcomes 1 year after anterior cruciate ligament reconstruction.
The results after anterior cruciate ligament reconstruction (ACLR) are evaluated by laxity measures, functional tests, and patients' perception by patient-reported outcome measures (PROMs). It is not known, if one of these evaluation instruments is representative or if outcome scores from all must be reported to obtain a full evaluation of the condition. The aim was to study the correlations between these three types of outcomes 1 year after primary ACLR. All adult patients (range 18-45 years) who had an ACLR between 1.1.2019 and 31.12.2021 were offered 1-year follow-up by an independent observer. Preoperative information about knee laxity and peroperative information about the condition of menisci and cartilage were registered. At 1-year follow-up clinical and instrumented knee stability and function assessed by four different hop tests were registered. Patients completed four PROMs (the Subjective International Knee Documentation Committee (IKDC) score, the Knee Numeric-Entity Evaluation Score (KNEES-ACL), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Lysholm score) and Tegner activity scale and answered anchor questions regarding satisfaction and willingness to repeat the operation. A total of 190 adults attended the 1-year follow-up and 151 had all assessments. There were only a few positive and weak correlations between performance tests and PROMS and between clinical measurements and PROMS (r = 0.00-0.38), and the majority were of negligible strength. Tegner score had in general the highest correlation (low to moderate). The highest correlation was 0.53 (moderate) between the anchor question about patient satisfaction and Lysholm/IKDC scores. There was no difference in the correlations depending on meniscal condition. In ACLR patients there was no clinically relevant correlation between scores obtained by PROMs, a battery of functional performance tests and instrumented laxity of the knee at 1-year follow-up. Therefore, one type of outcome cannot represent the others. This is an argument for always to include and report all three types of outcomes, and conclusions based on one type of outcome may not be sufficient. II.


Radionuclide scintigraphy of the brain and ultrasound studies in tubercular meningitis.
The present study was undertaken to assess the usefulness of brain scintigraphy and ultrasound evaluation of changes described in tuberculous meningitis. Brain scans were done with Tc-99m DTPA in 127 cases of tuberculous meningitis (TBM) and ultrasound studies in 41 cases with open anterior fontanelles. The data show that 54/127 (42.5%) of cases had abnormal brain scans, of which 33/54 had cerebrovascular infarcts and 14/54 had tuberculomas, while the remaining cases had either subdural effusions or generalized increased activity. The cerebrovascular infarcts were more frequent in patients with acute onset of TBM with associated hemiplegias. The ultrasound studies indicated that 80% of all cases of TBM had a mild to severe dilatation of the ventricles. About 55% of cases had a dilatation of only the lateral ventricles while the remaining cases had a block of aqueduct or beyond the fourth ventricles. Increased intracranial pressure changes were associated with a higher incidence of severe ventricular dilatation. Noninvasive detection methods in the study of TBM are important not only from the point of view of diagnosis but also to understand and evaluate the pathological changes occurring in vivo during the disease process and to judge the progress and response to treatment. A combination of ultrasound and brain scans offers diagnostic accuracy comparable to CT. Apart from cost, the larger radiation doses resulting from CT studies preclude its routine use in pediatric subjects.


Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission.
Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce. Survival was analyzed in 4682 HCT recipients according to disease status: PIF (N = 1440), Rel1 (failing ≥1 reinduction; N = 1256), and CR2 (N = 1986). Patient, disease, and transplantation characteristics were similar, except that patients in CR2 more often had performance scores of 90% to 100%, de novo AML, and longer CR1 duration. Adverse cytogenetics were more common in patients who experienced PIF. The 5-year survival rate adjusted for performance score, cytogenetic risk, and donor type for CR2 was 39% (95% confidence interval [CI], 37%-41%) compared with 18% (95% CI, 16%-20%) for HCT in Rel1 and 21% (95% CI, 19%-23%) in PIF (P < .0001). Although survival is superior for patients who undergo HCT in CR2, transplantation for selected patients in Rel1 or PIF may still be valuable. These data can guide decision making about additional salvage therapy versus prompt HCT for patients not in CR, but they also highlight that AML is intrinsically more treatable in patients who have favorable-risk cytogenetics, those with longer CR1 duration, and younger patients with better performance status. Cancer 2017;123:2025-2034. © 2017 American Cancer Society.


Baseline neurocognitive testing in sports-related concussions: the importance of a prior night's sleep.
The management of sports-related concussions (SRCs) utilizes serial neurocognitive assessments and self-reported symptom inventories to assess recovery and safety for return to play (RTP). Because postconcussive RTP goals include symptom resolution and a return to neurocognitive baseline levels, clinical decisions rest in part on understanding modifiers of this baseline. Several studies have reported age and sex to influence baseline neurocognitive performance, but few have assessed the potential effect of sleep. We chose to investigate the effect of reported sleep duration on baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) performance and the number of patient-reported symptoms. We hypothesized that athletes receiving less sleep before baseline testing would perform worse on neurocognitive metrics and report more symptoms. Cross-sectional study; Level of evidence, 3. We retrospectively reviewed 3686 nonconcussed athletes (2371 male, 1315 female; 3305 high school, 381 college) with baseline symptom and ImPACT neurocognitive scores. Patients were stratified into 3 groups based on self-reported sleep duration the night before testing: (1) short, <7 hours; (2) intermediate, 7-9 hours; and (3) long, ≥9 hours. A multivariate analysis of covariance (MANCOVA) with an α level of .05 was used to assess the influence of sleep duration on baseline ImPACT performance. A univariate ANCOVA was performed to investigate the influence of sleep on total self-reported symptoms. When controlling for age and sex as covariates, the MANCOVA revealed significant group differences on ImPACT reaction time, verbal memory, and visual memory scores but not visual-motor (processing) speed scores. An ANCOVA also revealed significant group differences in total reported symptoms. For baseline symptoms and ImPACT scores, subsequent pairwise comparisons revealed these associations to be most significant when comparing the short and intermediate sleep groups. Our results indicate that athletes sleeping fewer than 7 hours before baseline testing perform worse on 3 of 4 ImPACT scores and report more symptoms. Because SRC management and RTP decisions hinge on the comparison with a reliable baseline evaluation, clinicians should consider sleep duration before baseline neurocognitive testing as a potential factor in the assessment of athletes' recovery.


Progress in the moral reasoning of baccalaureate nursing students between program entry and exit.
Changes in moral reasoning between entry into and exit from a baccalaureate nursing program and the relationship between student characteristics and moral reasoning at entry and exit were explored in this descriptive study. The moral reasoning of four cohorts of students was measured using the Defining Issues Test (DIT). Admission grade point average, prior college credits, and gender accounted for 10% of the variance in DIT P% scores at entry and 14% of the variance at exit from the program. Female students had significantly higher moral reasoning scores than men. Age did not contribute significantly to explaining DIT score variance. DIT P% scores at entry for all four cohorts were within the range of reported norms for college students. Exit scores for all four cohorts were between the normative means for undergraduate students and graduate students. DIT P% score gains between entry and exit were significant for all four cohorts. Students whose entry scores were in the lowest categories had the greatest mean gains.


Testing the accuracy of demographic estimates in countries with generalized epidemics.
To assess the accuracy of demographic estimates that include the effects of HIV/AIDS on adult mortality. To compare estimates of demographic indicators based on UNAIDS/WHO estimates and projections with newly available estimates based on cohort studies, hospital records, national surveys and other sources of data. New information has become available recently from a number of sites in Africa on the ratio of mortality among the HIV-positive and HIV-negative population, the proportion of all adult deaths attributable to AIDS, and the number of orphans. These data are compared with the same indicators calculated from UNAIDS/WHO estimates to assess the accuracy of those estimates. Differences between demographic indicators based on UNAIDS/WHO estimates and study-based estimates are generally within the uncertainty range of the UNAIDS/WHO figures. Demographic estimates based on surveillance data and demographic models are close enough to study-based estimates to be useful for advocacy and medium-term planning. However, significant differences do exist that should be taken into account for short-term planning.


Text classification models for the automatic detection of nonmedical prescription medication use from social media.
Prescription medication (PM) misuse/abuse has emerged as a national crisis in the United States, and social media has been suggested as a potential resource for performing active monitoring. However, automating a social media-based monitoring system is challenging-requiring advanced natural language processing (NLP) and machine learning methods. In this paper, we describe the development and evaluation of automatic text classification models for detecting self-reports of PM abuse from Twitter. We experimented with state-of-the-art bi-directional transformer-based language models, which utilize tweet-level representations that enable transfer learning (e.g., BERT, RoBERTa, XLNet, AlBERT, and DistilBERT), proposed fusion-based approaches, and compared the developed models with several traditional machine learning, including deep learning, approaches. Using a public dataset, we evaluated the performances of the classifiers on their abilities to classify the non-majority "abuse/misuse" class. Our proposed fusion-based model performs significantly better than the best traditional model (F1-score [95% CI]: 0.67 [0.64-0.69] vs. 0.45 [0.42-0.48]). We illustrate, via experimentation using varying training set sizes, that the transformer-based models are more stable and require less annotated data compared to the other models. The significant improvements achieved by our best-performing classification model over past approaches makes it suitable for automated continuous monitoring of nonmedical PM use from Twitter. BERT, BERT-like and fusion-based models outperform traditional machine learning and deep learning models, achieving substantial improvements over many years of past research on the topic of prescription medication misuse/abuse classification from social media, which had been shown to be a complex task due to the unique ways in which information about nonmedical use is presented. Several challenges associated with the lack of context and the nature of social media language need to be overcome to further improve BERT and BERT-like models. These experimental driven challenges are represented as potential future research directions.


Ethnobotanical study of medicinal plants used in the management of diabetes mellitus and hypertension in the Central Region of Togo.
The Tem tribe in the Central Region of Togo is a population with an extensive knowledge of medicinal plants. However, little is known about their medical practices, principally the use of plants in the management of diabetes mellitus (DM) and hypertension (HTN). The present study documented the indigenous medicinal plant utilization for the management of DM and HTN in the Togo Central Region. From March to October 2010, 55 traditional healers were interviewed about their knowledge on the use of plants for DM and HTN treatment. The results revealed that 35/55 (63.64%) healers had treated at least one case of DM and/or HTN. They highlighted the use of 64 species belonging to 31 families in the treatment of DM and/or HTN. The most used plants against diabetes were Psidium guajava L. (Myrtaceae), Khaya senegalensis A. Juss. (Meliaceae), Sarcocephalus latifolius (Sm.) E.A. Bruce (Rubiaceae), Annona muricata L. (Annonaceae), Bridelia ferruginea Benth. (Phyllanthaceae), and Securidaca longepedunculata Fresen. (Polygalacae), while Allium sativum L. (Liliaceae) and Parkia biglobosa Benth. (Fabaceae), followed by Khaya senegalensis A. Juss. (Meliaceae), Gardenia ternifolia Schumach. (Rubiaceae), and Persea americana Mill. (Lauraceae) were the most commonly cited as antihypertensive. The issue revealed that traditional healers of the above mentioned region have basic knowledge regarding herbal medicine for DM and HTN in comparison with previous published reports. Further pharmacological screening of the identified plants should be conducted to ascertain the effectiveness of these plants.


Detection of a 2.6 kb single/low copy DNA sequence on chromosomes of wheat (Triticum aestivum) and rye (Secale cereale) by fluorescence in situ hybridization.
A fluorescence in situ hybridization procedure was developed to detect a 2.6 kb single/low copy DNA sequence on chromosomes of wheat (Triticum aestivum) and rye (Secale cereale). The probe, pTtksuI26, was from the wheat genomic library generated at Kansas State University and was labeled with Bio-11-dUTP by nick translation. The signal was amplified by a protocol of avidin-FITC (fluorescein isothiocyanate), biotinylated goat anti-avidin antibody, avidin-FITC. Two rye chromosomes and several wheat chromosomes showed the hybridization sites. The multiple sites in wheat are probably the result of the homoeologous nature of the three genomes in wheat. The ability to detect the hybridization signal of a small single/low copy DNA sequence is a very important step towards the physical mapping of plant genomes. This procedure might also be useful for studying the genomic relationship among wheat relative species.


Impact of Heart Transplantation on the Functional Status of US Children With End-Stage Heart Failure.
There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT. Organ Procurement and Transplantation Network data were used to identify all US children <21 years of age surviving ≥1 year post-HT from 2005 to 2014 with a functional status score (FSS) available at 3 time points (listing, transplant, ≥1 year post-HT). Logistic regression and generalized estimating equations were used to identify factors associated with abnormal FS (FSS≤8) post-HT. A total of 1633 children met study criteria. At the 1-year assessment, 64% were "fully active/no limitations" (FSS=10), 21% had "minor limitations with strenuous activity" (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7), black race (OR, 1.5; 95% CI, 1.1-2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2-2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0-2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0-2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5-2.7). Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT.


Trefoil peptides: a newly recognized family of epithelial mucin-associated molecules.
Members of the trefoil family of peptides are generally small stable secreted molecules, structurally related by the presence of one, or up to six, compact 6-cysteine motifs. Several trefoil peptides are expressed in mammalian gut and Xenopus gut and skin, often in association with mucins. Chronic ulcerative conditions of the gut, such as Crohn's disease, result in the growth of glandular structures of the ulcer-associated cell lineage (UACL) that secrete epidermal growth factor/urogastrone, transforming growth factor-alpha, and at least three trefoil peptides [pS2, human spasmolytic polypeptide (hSP), and intestinal trefoil factor (hITF/hP1.B)]. Neuroendocrine and goblet cells near the UACL are "recruited" into expressing pS2 and hSP, but the purpose of this concerted expression is unclear. A role in mucosal healing has been proposed. Biological functions of trefoil peptides have been difficult to establish. Pancreatic spasmolytic polypeptide of porcine origin inhibits gastric acid secretion and smooth muscle contraction and is a growth factor for some cultured cells, but pS2, once thought to be breast cancer specific, is not a mitogen. Recombinant trefoil peptides have allowed localization of binding sites and will allow structure-activity relationships to be studied, once the functions are clear.


Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC).
Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, γ-aminobutyric acid GABA(A/C) receptors, and the Gloeobacter violaceus ligand-gated ion channel (GLIC), are receptors that contain multiple allosteric binding sites for a variety of therapeutics, including general anesthetics. Here, we report the x-ray crystal structure of the Erwinia chrysanthemi ligand-gated ion channel (ELIC) in complex with a derivative of chloroform, which reveals important features of anesthetic recognition, involving multiple binding at three different sites. One site is located in the channel pore and equates with a noncompetitive inhibitor site found in many pLGICs. A second transmembrane site is novel and is located in the lower part of the transmembrane domain, at an interface formed between adjacent subunits. A third site is also novel and is located in the extracellular domain in a hydrophobic pocket between the β7-β10 strands. Together, these results extend our understanding of pLGIC modulation and reveal several specific binding interactions that may contribute to modulator recognition, further substantiating a multisite model of allosteric modulation in this family of ion channels.


Therapeutic Potential of Annexin A1 Modulation in Kidney and Cardiovascular Disorders.
Renal and cardiovascular disorders are very prevalent and associated with significant morbidity and mortality. Among diverse pathogenic mechanisms, the dysregulation of immune and inflammatory responses plays an essential role in such disorders. Consequently, the discovery of Annexin A1, as a glucocorticoid-inducible anti-inflammatory protein, has fueled investigation of its role in renal and cardiovascular pathologies. Indeed, with respect to the kidney, its role has been examined in diverse renal pathologies, including acute kidney injury, diabetic nephropathy, immune-mediated nephropathy, drug-induced kidney injury, kidney stone formation, and renal cancer. Regarding the cardiovascular system, major areas of investigation include the role of Annexin A1 in vascular abnormalities, atherosclerosis, and myocardial infarction. Thus, this review briefly describes major structural and functional features of Annexin A1 followed by a review of its role in pathologies of the kidney and the cardiovascular system, as well as the therapeutic potential of its modulation for such disorders.


A H2-evolving photocathode based on direct sensitization of MoS3 with an organic photovoltaic cell.
An organic solar cell based on a poly-3-hexylthiophene (P3HT): phenyl-C61-butyric acid (PCBM) bulk hetero-junction was directly coupled with molybdenum sulfide resulting in the design of a new type of photocathode for the production of hydrogen. Both the light-harvesting system and the catalyst were deposited by low-cost solution-processed methods, i.e. spin coating and spray coating respectively. Spray-coated MoS3 films are catalytically active in strongly acidic aqueous solutions with the best efficiencies for thicknesses of 40 to 90 nm. The photocathodes display photocurrents higher than reference samples, without catalyst or without coupling with a solar cell. Analysis by gas chromatography confirms the light-induced hydrogen evolution. The addition of titanium dioxide in the MoS3 film enhances electron transport and collection within thick films and therefore the performance of the photocathode.


Functional interactions within the parahippocampal region revealed by voltage-sensitive dye imaging in the isolated guinea pig brain.
The massive transfer of information from the neocortex to the entorhinal cortex (and vice versa) is hindered by a powerful inhibitory control generated in the perirhinal cortex. In vivo and in vitro experiments performed in rodents and cats support this conclusion, further extended in the present study to the analysis of the interaction between the entorhinal cortex and other parahippocampal areas, such as the postrhinal and the retrosplenial cortices. The experiments were performed in the in vitro isolated guinea pig brain by a combined approach based on electrophysiological recordings and fast imaging of optical signals generated by voltage-sensitive dyes applied to the entire brain by arterial perfusion. Local stimuli delivered in different portions of the perirhinal, postrhinal, and retrosplenial cortex evoked local responses that did not propagate to the entorhinal cortex. Neither high- and low-frequency-patterned stimulation nor paired associative stimuli facilitated the propagation of activity to the entorhinal region. Similar stimulations performed during cholinergic neuromodulation with carbachol were also ineffective in overcoming the inhibitory network that controls propagation to the entorhinal cortex. The pharmacological inactivation of GABAergic transmission by local application of bicuculline (1 mM) in area 36 of the perirhinal cortex facilitated the longitudinal (rostrocaudal) propagation of activity into the perirhinal/postrhinal cortices but did not cause propagation into the entorhinal cortex. Bicuculline injection in both area 35 and medial entorhinal cortex released the inhibitory control and allowed the propagation of the neural activity to the entorhinal cortex. These results demonstrate that, as for the perirhinal-entorhinal reciprocal interactions, also the connections between the postrhinal/retrosplenial cortices and the entorhinal region are subject to a powerful inhibitory control.


Increased risk of tuberculosis in patients with rheumatoid arthritis.
To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.


Comparison of procedural errors resulting during root canal preparations completed by junior dental students in patients using an '8-step method' versus 'serial step-back technique.'.
To compare procedural errors occurring during preparation of root canals by junior dental students in patients using a new '8-step method' versus traditional 'serial step-back technique. Junior dental students treated 291 root canals of maxillary and mandibular teeth in patients. A new '8-step method' was used to prepare 149 canals, whilst the traditional 'serial step-back technique' was used for 142 root canals. Instrumentation was carried out in both techniques using standardized stainless steel K-files and coronal flaring with Gates-Glidden reamers. In the apical one-third, a filing motion was used in the traditional technique: with the '8-step method,' reaming or filing motions were used in sizes up to 25 and only reaming in sizes larger than 25. All root canals were obturated with gutta-percha points and AH26 using a lateral condensation technique. Pre- and postoperative radiographs were made of each tooth. Procedural errors were recorded and statistically analysed using a binomic test for comparison of proportion. Significantly (P < (1.0001) more root canals maintained their original shape with no deviation (91%) with the'8-step method' compared to the traditional 'serial step-back technique' (61%). The procedural errors detected with the'8-step method' consisted of 10 canals with transportation (5%) and five with root perforations (2%); there were no canal obstructions. With the 'serial step-back technique: significantly (P < 0.0001) more errors occurred: 28 canals were transported (17%), 10 had root perforations (7%), and 16 canals were obstructed (6%). The differences in maintaining the original root canal shape between the two methods were significantly greater in molar versus anterior teeth. The new '8-step method' resulted in fewer procedural errors than the traditional 'serial step-back technique' when junior students prepared root canals in patients.


Intensive optimization and evaluation of global DNA methylation quantification using LC-MS/MS.
DNA methylation is a typical epigenetic phenomenon. Numerous methods for detecting global DNA methylation levels have been developed, among which LC-MS/MS has emerged as an excellent method from the viewpoint of sensitivity, reproducibility, and cost. However, LC-MS/MS methods have limitations due to a lack of the stability and the standardization required for a laboratory assay. The present study aimed to establish a robust assay that guarantees highly accurate measurements of global DNA methylation levels. There are at least three facets of the developed method. The first is discovery of the solvent conditions to minimize sodium adducts. The second is improvement of separation of nucleosides by LC using the columns that had not been used in previous similar studies. The third is success in reduction of the uncertainty of the measurement results, which was achieved by the calibration using the ratio of mdC but not the absolute amount in the presence of internal standards. These facets represent the advantage over methods reported previously. Our developed method enables quantification of DNA methylation with a short time length (8 min) for one analysis as well as with the high reproducibility of measurements that is represented by the inter-day CV% being less than 5%. In addition, data obtained from measuring global DNA methylation levels in cultured cell lines, with or without pharmacological demethylation, support its use for biomedical research. This assay is expected to allow us to conduct initial screening of epigenetic alterations or aberration in a variety of cells.


Case management: creativity in the ambulatory environment.
Case managers, serving as advocates for patients, can provide excellent cost-benefit to medical groups and patients alike. The author describes some of the important aspects of case management initiatives and how medical groups, in particular, can approach their implementation.