Handwriting Development in Spanish Children With and Without Learning Disabilities: A Graphonomic Approach.
The central purpose of this study was to analyze the dynamics of handwriting movements in real time for Spanish students in early grades with and without learning disabilities. The sample consisted of 120 children from Grades 1 through 3 (primary education), classified into two groups: with learning disabilities and without learning disabilities. The Early Grade Writing Assessment tasks selected for this purpose were writing the alphabet in order from memory, alphabet copying in cursive and manuscript, and allograph selection. The dynamics of these four handwriting tasks were recorded using graphonomic tablets (type Wacom Intuos-4), Intuos Inking pens, and Eye and Pen 2 software. Several events were recorded across four different tasks: velocity, pressure, time invested in pauses, and automaticity. The results demonstrated significant graphonomic variations between groups across grades, depending on the type of task.


Comparative evaluation of two skiing simulators as functional training devices for recreational skiers.
The aims of this study were to examine two ski simulators, Skimagic and Skier's Edge, and to evaluate their efficacy as functional training devices for skiers. Vertical ground reaction forces, knee flexion angle kinematics and muscles activity were recorded on these devices and compared with those measured in similar condition while skiing on snow. Five ski instructors performed three randomized testing sessions (snow, Skimagic and Skier's Edge). During the testing sessions, vertical ground reaction forces were recorded by means of pressure insoles in synchronisation with a portable data logger that collected values of knee flexion-extension and EMG activation of rectus femoris and vastus medialis. EMG activations and ground reaction forces measured while skiing on simulators were lower than on snow. Although less overall EMG activation was present on the simulators, the pattern of EMG activity was closer to real snow on Skimagic than on Skiers' Edge. Results of the present study suggested that the two devices are not effectively applicable for strength training. However, based on the recorded EMG patterns, the Skimagic treadmill is potentially suitable to act as a functional training device for recreational skiers provided that an increase of speed and slope on Skimagic could induce a closer matching of the studied biomechanical parameters with the snow skiing conditions. Key pointsEMG activation and ground reaction forces were lower on both simulators with respect to snow.Both simulators were not able to provide an effective contribution to strength development for skiers.In term of functional training Skier's Edge showed a predominance of concentric action over eccentric which is in contrast with competitive skiing.Skimagic treadmill could be potentially suitable to act as a functional training device for recreational skiers only if an increase of speed and slope will induce a closer matching of the studied biomechanical parameters with the snow skiing conditions.


Best Solutions for Perineal and Pressure Sore Reconstruction.
After studying this article, the participant should be able to: 1. Understand variations of the myocutaneous rectus abdominis muscle flap as it is used for perineal reconstruction and discuss common and alternative options for perineal defect reconstruction. 2. Review primary options and alternatives to pressure sore reconstruction if the primary option is not available and recognize when pressure sore reconstruction is not feasible. 3. Highlight pertinent anatomy and techniques for the flaps described. Perineal reconstruction following tumor resection is often complicated by irradiated tissue and multiple comorbidities, making reconstruction challenging. Management of these conditions can have complication rates as high as 66 percent, which further compounds the costs and implications of managing these wounds. These complication rates can be significantly decreased using flap closure rather than primary closure. Pressure ulcers also occur in patients with poor overall health, multiple comorbidities, and often numerous prior failed reconstruction attempts. Comprehensive management of pressure sores is a significant burden to the health care system, at a cost of $9.1 to $11.6 billion per year. There exists an extensive body of literature describing the pathophysiology and management strategies for these problems. The focus of this article is to discuss best solutions for perineal and pressure ulcer reconstruction, and to explore alternative options for reconstruction.


[Calcium antagonists in chronic renal failure. Undesirable effects on glomerular hemodynamics?].
Seven patients with glomerular proteinuria and hypertension (six with biopsy confirmation of glomerulonephritis, one with proteinuria after unilateral nephrectomy) were randomly given, for 14 days each, a calcium antagonist and then a conversion enzyme inhibitor, or vice versa, following a 14-day pause of all medication. Fractional albuminuria rose significantly during administration of calcium antagonists (P less than 0.05), while it decreased significantly during administration of converting enzyme inhibitor (P less than 0.05). The explanation for this finding may be that calcium antagonists raise glomerular capillary pressure by dilating the afferent arterioles, while converting enzyme inhibitors predominantly cause dilatation of the efferent arterioles.


Sequence of pig 17beta-hydroxysteroid dehydrogenase Type3 cDNA and its expression in mammalian cells.
17beta-Hydroxysteroid dehydrogenase (17beta-HSD) Type3 is an NADPH-dependent membrane-bound enzyme that is specifically expressed in testis and catalyzes the conversion of androstenedione to testosterone. To date, the sequence of Type3 enzymes has been clarified in humans, mice and rats; however, the sequence of the pig enzyme remains unknown. In this study, we determined the cDNA sequence of pig testicular 17beta-HSD Type3. PCR primers for partial pig testicular 17beta-HSD Type3 were designed from rat and human enzyme consensus sequences. Full-length cDNA was obtained by 3'- and 5'-RACE based on partial PCR products. The cDNA coding region was 933 bp in length, which is the same as the human enzyme, and shared 84.7% sequence identity with the human cDNA coding region. The monomer was estimated to have a molecular weight of 34,855 and to contain 310 amino acid residues. The predicted pig amino acid sequence showed 81.9, 75.5 and 72.9% sequence identity with the human, rat and mouse sequences, respectively. To elucidate 17beta-HSD Type3 activity, the expression vector pCMV/pig17beta-HSD3 was established and transfected into human embryo kidney 293 cells. Subsequently, 17beta-HSD activity (androstenedione conversion to testosterone) was strongly detected in cell lysates.


Effect of steaming, blanching, and high temperature/high pressure processing on the amino Acid contents of commonly consumed korean vegetables and pulses.
In the present report, the effects of blanching, steaming, and high temperature/high pressure processing (HTHP) on the amino acid contents of commonly consumed Korean root vegetables, leaf vegetables, and pulses were evaluated using an Automatic Amino Acid Analyzer. The total amino acid content of the samples tested was between 3.38 g/100 g dry weight (DW) and 21.32 g/100 g DW in raw vegetables and between 29.36 g/100 g DW and 30.55 g/100 g DW in raw pulses. With HTHP, we observed significant decreases in the lysine and arginine contents of vegetables and the lysine, arginine, and cysteine contents of pulses. Moreover, the amino acid contents of blanched vegetables and steamed pulses were more similar than the amino acid contents of the HTHP vegetables and HTHP pulses. Interestingly, lysine, arginine, and cysteine were more sensitive to HTHP than the other amino acids. Partial Least Squares-Discriminate Analyses were also performed to discriminate the clusters and patterns of amino acids.


Studies on linear epitopes of Semliki Forest virus in protection studies against lethal challenge virus infection.
Purified reduced and non-reduced glycoproteins E1 and E2 of Semliki Forest Virus (SFV) were used to investigate the protection potency to prevent clinical disease after lethal virus challenge. In parallel synthetic oligopeptides deduced from conserved regions of the nucleotide sequences coding for the glycoproteins E1 and E2 were included. It could be demonstrated that both reduced and non-reduced glycoprotein preparations induced protection against lethal virus challenge, whereas the oligopeptides did not. The role of linear epitopes in immunity and their potential use as synthetic vaccines against Alphaviruses are critically discussed.


Relation Between Renal Function and Coronary Plaque Morphology (from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Virtual Histology-Intravascular Ultrasound Substudy).
We sought to examine the relation between various degrees of renal function and coronary plaque morphology by grayscale and virtual histology intravascular ultrasound (IVUS). ADAPT-DES was a prospective, multicenter registry of 8,582 consecutive patients treated using coronary drug-eluting stents with a prespecified grayscale and virtual histology-IVUS substudy. A lesion-level analysis of study participants was performed by comparing IVUS parameters of culprit and nonculprit lesions across tertiles of estimated creatinine clearance (CrCl). Preintervention IVUS imaging of 762 patients identified 898 culprit and 752 nonculprit native coronary artery lesions. Patients in the lowest CrCl tertile were older, more often women, and more often presented with stable angina. Compared with the middle and upper tertiles, the lowest tertile was significantly associated with culprit lesion smaller mean external elastic membrane cross-sectional area (12.9 vs 14.2 mm3/mm vs 14.9 mm3/mm, p <0.0001), smaller mean lumen cross-sectional area (5.5 mm3/mm vs 5.8 mm3/mm vs 6.1 mm3/mm, p = 0.002), and more dense calcium volume (11.5% vs 10.2% vs 9.7%, p = 0.02). Similar trends were found in the nonculprit lesions. Plaque rupture was least common in patients in the lowest tertile. On multivariable analysis, independent predictors of greater dense calcium volume were lower CrCl, hyperlipidemia, female gender, and presentation without ST-segment elevation myocardial infarction. In conclusion, in the present large-scale IVUS study diminishing renal function was associated with increased coronary calcification and decreased coronary vessel and lumen sizes, with a graded response according to the reduction in CrCl. In addition, these patients were more likely to present with stable angina versus patients with normal renal function who were more likely to present with an acute coronary syndrome.


Use of the SONET Score to Evaluate High Volume Emergency Department Overcrowding: A Prospective Derivation and Validation Study.
Background. The accuracy and utility of current Emergency Department (ED) crowding estimation tools remain uncertain in EDs with high annual volumes. We aimed at deriving a more accurate tool to evaluate overcrowding in a high volume ED setting and determine the association between ED overcrowding and patient care outcomes. Methods. A novel scoring tool (SONET: Severely overcrowded-Overcrowded-Not overcrowded Estimation Tool) was developed and validated in two EDs with both annual volumes exceeding 100,000. Patient care outcomes including the number of left without being seen (LWBS) patients, average length of ED stay, ED 72-hour returns, and mortality were compared under the different crowding statuses. Results. The total number of ED patients, the number of mechanically ventilated patients, and patient acuity levels were independent risk factors affecting ED overcrowding. SONET was derived and found to better differentiate severely overcrowded, overcrowded, and not overcrowded statuses with similar results validated externally. In addition, SONET scores correlated with increased length of ED stay, number of LWBS patients, and ED 72-hour returns. Conclusions. SONET might be a better fit to determine high volume ED overcrowding. ED overcrowding negatively impacts patient care operations and often produces poor patient perceptions of standardized care delivery.


Optical imaging of non-fluorescent nanoparticle probes in live cells.
Precise imaging of cellular and subcellular structures and dynamic processes in live cells is crucial for fundamental research in life sciences and in medical applications. Non-fluorescent nanoparticles are an important type of optical probe used in live-cell imaging due to their photostability, large optical cross-sections, and low toxicity. Here, we provide an overview of recent developments in the optical imaging of non-fluorescent nanoparticle probes in live cells.


Zinc finger protein sall2 is not essential for embryonic and kidney development.
SALL/Sall is a mammalian homolog of the Drosophila region-specific homeotic gene spalt (sal), and heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We earlier reported that mice deficient in Sall1 die in the perinatal period and that kidney agenesis or severe dysgenesis are present. We have now generated mice lacking Sall2, another Sall family gene. Although Sall2 is expressed mostly in an overlapping fashion versus that of Sall1, Sall2-deficient mice show no apparent abnormal phenotypes. Morphology and gene expression patterns of the mutant kidney were not affected. Mice lacking both Sall1 and Sall2 show kidney phenotypes comparable to those of Sall1 knockout, thereby demonstrating the dispensable roles of Sall2 in embryonic and kidney development.


Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan.
Toll-like receptors (TLRs) are pattern-recognition receptors that play an important role in innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR4 recognizes lipopolysaccharides of Gram-negative bacteria. Genetic polymorphisms within the TLR4 gene have been reported to be associated with various inflammatory diseases; therefore, TLR4 appears to be a susceptibility gene for sarcoidosis. Although sarcoidosis has various clinical manifestations, its association with uveitis is more common in Japan than in other countries. The aim of this study was to investigate whether TLR4 polymorphisms were associated with sarcoidosis-related uveitis in a Japanese population. Two hundred twenty-three patients with sarcoidosis and 206 healthy control subjects were recruited at seven sites in Japan. Eight single-nucleotide polymorphisms (SNPs) in TLR4 were genotyped with a TaqMan assay, and allelic and phenotypic diversity were assessed in affected and control subjects. We found no association with susceptibility to sarcoid-related uveitis for any of the SNPs analyzed. Strong linkage disequilibrium was observed among all the SNPs analyzed (D'>/=0.78), which were located in one haplotype block. TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.


Early mineralocorticoid receptor blockade in primary percutaneous coronary intervention for ST-elevation myocardial infarction is associated with a reduction of life-threatening ventricular arrhythmia.
Aldosterone levels are high early after admission for ST elevation myocardial infarction (STEMI) concomitantly with high risk of sudden death and life-threatening ventricular arrhythmia. We assessed the hypothesis that early aldosterone blockade on admission for primary percutaneous coronary intervention (PCI) may be associated with a reduction of life-threatening ventricular arrhythmia in a prospective cohort-nested case (n=159) versus historical control (n=623) study. All cases were treated on admission by 200mg IV bolus of potassium canrenoate, followed by 25mg PO spironolactone daily during the coronary care unit stay. The primary endpoint--in-hospital composite of death, resuscitated cardiac arrest and ventricular tachycardia--was assessed by logistic regression models adjusted on major pre-specified variables and validated by a bootstrap procedure and propensity-score based analyses. Aldosterone blockade was associated with lower risks of the primary endpoint (adjusted ORs 0.26, 95% CI [0.13-0.57]), resuscitated cardiac arrest (adjusted OR 0.39, 95% CI [0.16-0.94]), ventricular tachycardia or fibrillation (adjusted ORs 0.23, 95% CI [0.12-0.45]), as well as ventricular arrhythmia requiring resuscitation or anti-arrhythmic therapy (adjusted OR 0.41, 95% CI [0.19-0.88]). All findings were confirmed by the bootstrap procedure. The benefit on death or resuscitated cardiac arrest seemed sustained at 6month follow-up. Early aldosterone blockade in patients presenting for primary PCI for STEMI is associated with significant reductions in rates of life-threatening arrhythmia and cardiac arrest independent of the initial risk profile, heart failure or hemodynamic status. These findings support the concept of aldosterone blockade early after STEMI, warranting further confirmation by ongoing randomized trials.


Isoflurane-Induced Burst Suppression Is a Thalamus-Modulated, Focal-Onset Rhythm With Persistent Local Asynchrony and Variable Propagation Patterns in Rats.
Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology. Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats. Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within <100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection. Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.


Immunoreactive endothelin in plasma of nonmammalian vertebrates.
Immunoreactive endothelin (ir-ET) was estimated in plasma of nonmammalian vertebrates, using radioimmunoassay (RIA) for endothelin-1 (ET-1). Blood samples were collected from unanesthetized animals. Plasma ET was determined by RIA after extraction. Plasma levels of ir-ET were 0.7 +/- 0.2 pg/ml (n = 6) in the hagfish Eptatretus burgeri, 4.3 +/- 0.9 pg/ml (n = 5) in the banded dogfish Triakis scyllia, 3.6 +/- 0.8 pg/ml (n = 3) in the common Japanese conger Conger myriaster, 9.6 +/- 1.4 pg/ml (n = 7) in the carp Cyprinus carpio, 6.4 +/- 0.8 pg/ml (n = 5) in the bullfrog Rana catesbeiana, 6.7 +/- 0.6 pg/ml (n = 3) in the soft-shelled turtle Trionyx sinensis japonica, and 3.3 +/- 0.6 pg/ml (n = 8) in the Japanese quail Coturnix coturnix japonica. The dilution curves of the plasma extracts from each species almost paralleled the standard curve for ET-1. Analysis of the plasma extracts of the carp by reverse-phase high-performance liquid chromatography revealed that ir-ET consisted of three components, a predominant peak being located at the elution position of synthetic ET-1. The present results demonstrate clearly that an ET-1-like substance circulates in blood of nonmammalian vertebrates, suggesting an endocrine function of the peptide in these species.


CK1BP Reduces α-Synuclein Oligomerization and Aggregation Independent of Serine 129 Phosphorylation.
The pathological accumulation of α-Synuclein (α-Syn) is the hallmark of neurodegenerative α-synucleinopathies, including Parkinsons's disease (PD). In contrast to the mostly non-phosphorylated soluble α-Syn, aggregated α-Syn is usually phosphorylated at serine 129 (S129). Therefore, S129-phosphorylation is suspected to interfere with α-Syn aggregation. Among other kinases, protein kinase CK1 (CK1) is known to phosphorylate α-Syn at S129. We overexpressed CK1 binding protein (CK1BP) to inhibit CK1 kinase activity. Using Bimolecular Fluorescence Complementation (BiFC) in combination with biochemical methods, we monitored the S129 phosphorylation and oligomerization of α-Syn in HEK293T cells. We found that CK1BP reduced the overall protein levels of α-Syn. Moreover, CK1BP concomitantly reduced S129 phosphorylation, oligomerization and the amount of insoluble α-Syn. Analyzing different α-Syn variants including S129 mutations, we show that the effects of CK1BP on α-Syn accumulation were independent of S129 phosphorylation. Further analysis of an aggregating polyglutamine (polyQ) protein confirmed a phosphorylation-independent decrease in aggregation. Our results imply that the inhibition of CK1 activity by CK1BP might exert beneficial effects on NDDs in general. Accordingly, CK1BP represents a promising target for the rational design of therapeutic approaches to cease or at least delay the progression of α-synucleinopathies.


Elevated plasma fibronectin levels associated with venous thromboembolism.
Elevated plasma fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high plasma fibronectin levels are associated with VTE, we compared plasma fibronectin levels in the Scripps Venous Thrombosis Registry for 113 VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean fibronectin concentration compared to controls (127% vs. 103%, p < 0.0001); the difference was greater for idiopathic VTE cases compared to secondary VTE cases (133% vs. 120%, respectively). Using a cut-off of >90% of the control values, the odds ratio (OR) for association of VTE for fibronectin plasma levels above the 90(th) percentile were 9.37 (95% CI 2.73-32.2; p < 0.001) and this OR remained significant after adjustment for sex, age, body mass index (BMI), factor V Leiden and prothrombin nt20210A (OR 7.60, 95% CI 2.14-27.0; p = 0.002). In particular, the OR was statistically significant for idiopathic VTE before and after these statistical adjustments. For the total male cohort, the OR was significant before and after statistical adjustments and was not significant for the total female cohort. In summary, our results suggest that elevated plasma fibronectin levels are associated with VTE especially in males, and extend the potential association between biomarkers and risk factors for arterial atherothrombosis and VTE.


Omitting ALND Is Not Safe for a Cohort of Early-Stage Breast Cancer Patients with 1-2 SLNs Macro-Metastases and Breast-Conserving Therapy: A Single-Center Retrospective Study.
Omitting axillary lymph node dissection (ALND) is recommended for early-stage breast cancer patients with 1-2 sentinel lymph nodes (SLNs) macro-metastases and breast-conserving therapy. However, it is not safe for part of patients, so it is significant to find risk factors and develop a predictive model of non-SLNs metastases in breast cancer patients with 1-2 SLNs macro-metastases and breast-conserving therapy. This retrospective study enrolled 228 breast cancer patients with 1-2 SLNs macro-metastases who underwent ALND and breast-conserving surgery between Jan 2012 and Dec 2017 at Cancer Hospital Chinese Academy of Medical Sciences. Chi-square test and backward stepwise binary logistic regression were used to find factors that influenced non-SLN metastases, then a predictive model was formulated and obtained its area under the curve. Tumor pathologic invasion size, number of positive SLNs and ALN status on imaging was associated with non-SLNs metastases. The predictive model was also formulated based on these three factors to assess and the area under the curve of model was 0.708. We developed a predictive model to assess the high-risk cohort of patients of non-SLNs metastases which can be an auxiliary tool for doctors.


Influence of aprotinin and promazine on survival of isolated pancreatic acinar cells.
Aprotinin, a protease inhibitor, and promazine, an inhibitor of phospholipase A2, were tested for possible inhibition of pancreatic acinar cell (PAC) decline induced by uncoupling of oxidative phosphorylation with 2,4-dinitrophenol (DNP) or by temporary anoxia/reoxygenation. In incubates of acinar cells isolated from rat pancreas the presence of aprotinin did not influence the survival of cells treated with these noxae. This finding excludes that extracellulary acting trypsin, possibly released from damaged cells, contributes to further cell death. While promazine at concentrations of 15 to 20 nmol.(10(6) cells)-1 was well tolerated by untreated PAC, higher concentrations caused a clear reduction of cell viability. At optimum concentration promazine was without influence on DNP-treated cells, but it had a beneficial effect on survival and morphology of anoxia-treated PAC (p less than or equal to 0.05). Therefore, it can be assumed that after anoxia/reoxygenation the membrane phospholipase A2 becomes stimulated and causes phospholipid depletion with final death of the cells. It is suggested that such a mechanism may contribute to the initial cell damage in the pathogenesis of acute pancreatitis, too.


Analytical properties and optimization of time-delayed feedback control.
Time-delayed feedback control is an efficient method for stabilizing unstable periodic orbits of chaotic systems. If the equations governing the system dynamics are known, the success of the method can be predicted by a linear stability analysis of the desired orbit. Unfortunately, the usual procedures for evaluating the Floquet exponents of such systems are rather intricate. We show that the main stability properties of the system controlled by time-delayed feedback can be simply derived from a leading Floquet exponent defining the system behavior under proportional feedback control. Optimal parameters of the delayed feedback controller can be evaluated without an explicit integration of delay-differential equations. The method is valid for low-dimensional systems whose unstable periodic orbits are originated from a period doubling bifurcation and is demonstrated for the Rössler system and the Duffing oscillator.


An experimental setup for high resolution 10.5 eV laser-based angle-resolved photoelectron spectroscopy using a time-of-flight electron analyzer.
We present an experimental setup for laser-based angle-resolved time-of-flight photoemission. Using a picosecond pulsed laser, photons of energy 10.5 eV are generated through higher harmonic generation in xenon. The high repetition rate of the light source, variable between 0.2 and 8 MHz, enables high photoelectron count rates and short acquisition times. By using a time-of-flight analyzer with angle-resolving capabilities, electrons emitted from the sample within a circular cone of up to ±15° can be collected. Hence, simultaneous acquisition of photoemission data for a complete area of the Brillouin zone is possible. The current photon energy enables bulk sensitive measurements, high angular resolution, and the resulting covered momentum space is large enough to enclose the entire Brillouin zone in cuprate high-T(c) superconductors. Fermi edge measurements on polycrystalline Au shows an energy resolution better than 5 meV. Data from a test measurement of the Au(111) surface state are presented along with measurements of the Fermi surface of the high-T(c) superconductor Bi(2)Sr(2)CaCu(2)O(8 + δ) (Bi2212).


Bisanthracene bis(dicarboxylic imide)s as potential photosensitizers in photodynamic therapy: a theoretical investigation.
The electronic structures and spectroscopic properties of four bisanthracene bis(dicarboxylic imide)s (M1-M4) have been investigated theoretically by using density functional theory (DFT) and its time-dependent extension (TDDFT) in view of their potential use as photosensitizers in photodynamic therapy (PDT). The optimized geometries, electronic absorption transitions, singlet-triplet energy gaps, spin-orbit matrix elements, ionization potentials, and electron affinities have been determined in gas phase and in solvent. Both type I and II PDT mechanisms have been considered. In addition, the variation of a series of relevant properties upon heavy atom substitution (Br and I) have been determined and discussed. Results show that only M4 is able to support the type I reaction, and one of its brominated and iodinated derivatives can produce cytotoxic singlet oxygen (type II reaction).


Mental health treatment to reduce HIV transmission risk behavior: a positive prevention model.
Secondary HIV prevention, or "positive prevention," is concerned with reducing HIV transmission risk behavior and optimizing the health and quality of life of people living with HIV/AIDS (PLWHA). The association between mental health and HIV transmission risk (i.e., sexual risk and poor medication adherence) is well established, although most of this evidence is observational. Further, a number of efficacious mental health treatments are available for PLWHA yet few positive prevention interventions integrate mental health treatment. We propose that mental health treatment, including behavioral and pharmacologic interventions, can lead to reductions in HIV transmission risk behavior and should be a core component of secondary HIV prevention. We present a conceptual model and recommendations to guide future research on the effect of mental health treatment on HIV transmission risk behavior among PLWHA.


Phloem loading in squash.
Squash (Cucurbita pepo L. var. melopepo torticalis, Bailey) leaves were supplied with (14)C-sucrose, then specific radioactivities of the glucose and galactose moieties of translocated stachyose were determined. In every case, the specific radioactivity of the galactose moiety was greater than that of the glucose moiety. It is concluded that the stachyose was not synthesized at either the phloem-loading site or subsequent to phloem loading, but rather in cells that were not a part of the translocation system, possibly the mesophyll cells.


[Value of Hounsfield unit on CT in prediction of stone-free rate of upper urinary calculi after extracorporeal shockwave lithotripsy].
To study the value of Hounsfield unit (HU) on CT in prediction of stone-free rate of upper urinary calculi after extracorporeal shockwave lithotripsy (ESWL). Fifty-two patients suffering from solitary stone in the upper urinary tract 0.5 - 1.5 cm in size, 34 males and 18 females, aged 15 - 77, underwent non-contrast helical computerized tomography (NCHCT), and then ESWL. One day, 2 weeks, 4 weeks, and 3 months after the ESWL the patients underwent kidney, ureter, and bladder examination and B mode ultrasonography. The patients with the residual fragments less than 3 mm in size were categorized into the stone-free group. The relationship among the HU, number of shock wave, and the characteristics of the patients were analyzed. Thirty-six of the 52 patients were categorized into the stone-free group (69.2%) and 16 of the 52 were categorized into the residual stone group (30.8%). The CT value of the stone-free group was 579.65 +/- 194.65 HU, significantly lower than that of the residual stone group (1032.18 +/- 270.49 HU, t = 6.842, P < 0.01). The number of shock wave of the stone-free group was 1526.67 +/- 723.01, significantly lower than that of the residual stone group (2612.50 +/- 518.81, t = 5.407, P < 0.01). The OR values for the HU and number of shock wave were 0.993 (95% CI: 0.988 - 0.998) and 0.998 (95% CI: 0.997 - 1.000). The HU value on pretreatment NCHCT of the upper urinary tract stones can be used to predict the stone-free rate after ESWL. ESWL is not indicated to the patients of upper urinary tract stones with high values of HU.


Efficient synthesis of an (aminooxy) acetylated-somatostatin derivative using (aminooxy)acetic acid as a 'carbonyl capture' reagent.
Owing to the high chemoselectivity between an aminooxy function and a carbonyl group, oxime ligation is one of the most preferred procedures for the preparation of peptide conjugates. However, the sensitivity of (aminooxy)acetylated peptides to ketones and aldehydes makes their synthesis and storage difficult. In our study, we established the efficient synthesis of an (aminooxy)acetylated-somatostatin derivative in the presence of free (aminooxy)acetic acid, which was used as a 'carbonyl capture' reagent in the final cleavage step. This (aminooxy)acetylated compound was further used for the chemoselective ligation (oxime bond formation) with daunorubicin and 4-fluorobenzaldehyde leading to the formation of conjugates with potential applications in targeted cancer chemotherapy and positron emission tomography.


CD34-positive cell proportions in peripheral blood correlate with colony-forming capacity.
Blood samples were examined from 25 children with malignancies during hematopoietic recovery following chemotherapy-induced aplasia and from 9 children undergoing tonsillectomy. The proportion of CD34-positive peripheral blood mononuclear cells (PBMNC) evaluated by flow cytometry was compared with the number of colonies (granulocyte-macrophage colony-forming units, CFU-GM; mixed-lineage colony-forming units, CFU-GEMM; and erythroid burst-forming units, BFU-E) grown in methylcellulose medium within 2 weeks. A mean of 1387 myeloid colonies (495-4480) per 10(5) PBMNC seeded developed from 13 samples with detectable CD34 populations (between 0.9% and 5.6%), whereas only 152 (9-386, p = 0.002) and 65 (12-137, p = 0.005) colonies were formed from 12 patient and from 9 control samples in which the percentage of CD34-positive cells was too low for analysis. Linear regression analysis revealed that CD34 positivity correlates with colony-forming capacity (p = 0.0008, r = 0.782). Flow cytometric evaluation of the CD34 proportions can thus predict the in vitro colony-forming capacity of peripheral blood prior to leukapheresis.


Homolytic, Heterolytic, Mesolytic - As You Like It: Steering the Cleavage of a HC(sp3 )-C(sp3 )H Bond in Bis(1H-2,1-benzazaborole) Derivatives.
A set of (3,3')-bis(1-Ph-2-R-1H-2,1-benzazaborole) compounds, in which R=tBu (Bab-tBu)2 , R=Dipp (Bab-Dipp)2 or R=tBu and Dipp (Bab-Dipp)(Bab-tBu), was synthesized and fully characterized using 1 H, 11 B, 13 C, and 15 N NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The central HC(sp3 )-C(sp3 )H bond with restricted rotation at the junction of both 1H-2,1-benzazaborole rings displayed an intriguing reactivity. It was demonstrated that this bond is easily mesolytically cleaved using alkali metals to form the respective aromatic 1Ph-2R-1H-2,1-benzazaborolyl anions M+ (THF)n (Bab-tBu)- (M=Li, Na, K) and K+ (THF)n (Bab-Dipp)- . Furthermore, the central HC(sp3 )-C(sp3 )H bond of bis(1H-2,1-benzazaborole)s is also homolytically cleaved either by heating or photochemical means, giving corresponding 1Ph-2R-1H-2,1-benzazaborolyl radicals (Bab-tBu). and (Bab-Dipp). , which rapidly self-terminate. Nevertheless, their formation was unambiguously established by NMR analysis of the reaction mixtures containing products of the self-termination of the radicals after heating or irradiation. (Bab-Dipp). radical was also characterized using EPR spectroscopy. Importantly, it turned out that the essentially non-polarized HC(sp3 )-C(sp3 )H bond in (Bab-tBu)2 is also cleaved heterolytically with 2 equiv of MeLi, giving the mixture of Li+ (SOL)n (Bab-tBu)- (SOL=THF or Et2 O) and lithium methyl-substituted borate complex Li+ (SOL)n (Bab-tBu-Me)- in a diastereoselective fashion.


Validation of the Lifetime Incidence of Traumatic Events (LITE-S/P) Questionnaires in Children and Adolescents in Slovenia.
Introduction: A traumatic event is an extremely threatening and frightening experience in an individual's life. Children who are exposed to traumatic events are twice as likely to develop a mental disorder. Screening can provide insight into the traumatic experience of children, identifying those eligible for further evaluation, and support. With this aim, we evaluated the psychometric properties of the Lifetime Incidence of Traumatic Events questionnaire (LITE) in Slovene by calculating retest reliabilty, construct validity (cross-informant agreement) and external validity, where we calculated the correlation of the number of differenet traumatic events with psychopathological symptoms. Methods: 280 child-parent pairs (children aged 11.3 ± 2.2 years) from various Slovenian primary schools participated in the study. They were divided into two groups: 180 healthy primary school students and 100 children with Type 1 Diabetes (our study was a part of a larger study The Influence of Psychobiological Adversity on Children and Adolescents with Type 1 Diabetes Study). Two versions of the LITE questionnaire were used. Children completed the child report (LITE-S) and parents the parent report (LITE-P) version. After 4 weeks, 117 children, and 114 parents filled out the LITEs again. External validity was assessed using the Youth Self Report and Child Behaviour Checklist syndrome-oriented scales. Results: Retest reliability for individual scales was r = 0.469-0.639 (ρ = 0.443-0.636; p < 0.001), but higher for individual items (κ = 0.263-0.821; p < 0.001). Correlations between reports from parents and children were r = 0.313-0.345 (ρ = 0.317-0.348; p < 0.001). The number of different events experienced by children correlated significantly with the measured depressive-anxiety, and posttraumatic stress disorder symptoms. Conclusions: Based on our results, the LITE-S and LITE-P "All events" scale have acceptable psychometric properties for use in research and in clinical practise screening. We recommend looking at single items, taking into consideration the responses from both the child and the parent for more precise information. To improve the precision of the psychodiagnostic capacity of the questionnaire, further research on various populations should be performed.


Clinical features of patients with small cell lung cancer and idiopathic pulmonary fibrosis treated with chemotherapy or chemoradiotherapy.
The clinical features of patients with small cell lung cancer (SCLC) and idiopathic pulmonary fibrosis (IPF) have not been fully elucidated. Data on 366 patients with pathologically confirmed SCLC who had been treated with chemotherapy or chemoradiotherapy were retrospectively analyzed to investigate the clinical features of SCLC with IPF. A total of 97 out of the 366 patients were diagnosed with interstitial lung disease (ILD), and 75 of them had IPF. For both the limited disease (LD) and extensive disease (ED) stages, the median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the patients with IPF compared with non-ILD patients. A multivariate analysis showed that poor performance status, ED stage, and the presence of IPF were associated with shorter OS. The response rate to first-line therapy was significantly lower in patients with IPF compared with the non-ILD patients. The rate of patients receiving fewer than three cycles of first-line chemotherapy was higher in patients with IPF, which was a factor of poor survival. In LD-stage patients with IPF, chemoradiotherapy was associated with longer PFS and OS compared with chemotherapy only. In patients with SCLC, the presence of IPF was associated with a lower response rate as well as shorter PFS and shorter OS. There are some cases that are suitable for chemoradiotherapy, even among patients with IPF.The reviews of this paper are available via the supplemental material section.


Ofatumumab Monoclonal Antibody Affinity Maturation Through in silico Modeling
Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements. Validation of the designed antibodies is carried out by docking tools. Increased affinity enhances the biological action of the antibody, which in turn improves the therapeutic effects. Furthermore, the increased antibody affinity can reduce the therapeutic dose of the antibody, resulting in lower toxicity and handling cost. Considering the importance of this issue, using in silico analysis such as docking and molecular dynamics, we aimed to find the important amino acids of the Ofatumumab antibody and then replaced these amino acids with others to improve antibody-binding affinity. Finally, we examined the binding affinity of antibody variants to antigen. Our findings showed that variant 3 mutations have improved the characteristics of antibody binding compared to normal Ofatumumab antibodies. In the present study, the designed anti-CD20 antibodies showed to have potential for improved affinity compared to commercial Ofatumumab.


Some preliminary observations on the mosquitocidal potential of Mesostoma sp. (Turbellaria: Typhloplaniidae).
Observations on the feeding and breeding behaviour of Mesostoma sp. from Delhi are presented. The species is comparable to the M. lingua (a species demonstrated to have high mosquitocidal potential) in predatory potential and may be playing an equally important role here.


Sex Steroids Block the Initiation of Atherosclerosis.
Atherosclerosis is the main cause of death in men and women. This so-called "hardening of the arteries" results from advanced atherogenesis, the accumulation and death of subendothelial fat-laden macrophages (vascular plaque). The macrophages are attracted as the result of signals from injured vessels recruiting and activating cells to quell the injury by inflammation. Among the recruited cells are circulating monocytes that may be captured by the formation of neural cell adhesion molecule (nCAM) tethers between the monocytes and vascular endothelium; the tethers are dependent on electrostatic binding between distal segments of apposed nCAM molecules. The capture of monocytes is followed by their entry into the subendothelial area as macrophages, many of which will remain and become the fat-laden foam cells in vascular plaque. Neural cell adhesion molecules are subject to sialylation that blocks their electrostatic binding. We showed that estradiol-induced nCAM sialylases are present in vascular endothelial cells and tested whether sex steroid pretreatment of human vascular endothelium could inhibit the capture of monocytes. Using in vitro techniques, pretreatment of human arterial endothelial cells with estradiol, testosterone, dehydroepiandrosterone and dihydrotestosterone all induced sialylation of endothelial cells and, in a dose-response manner, reduced the capture of monocytes. Steroid hormones are protective against atherogenesis and its sequellae. Sex steroid depletion is associated with atherosclerosis. Based on this knowledge plus our results using sex steroid pretreatment of endothelial cells, we propose that the blockade of the initial step in atherogenesis by sex steroid-induced nCAM sialylation may be crucial to hormonal prevention of atherosclerosis.


Limb salvage surgery for children and adolescents with malignant bone tumors in a developing country.
To describe the 5-year experience of a multidisciplinary limb salvage program for children and adolescents with malignant bone tumors in Lebanon. Between January 2002 to February 2007, 30 children and adolescents (2 with Ewing sarcoma and 28 with osteosarcoma) underwent Limb Salvage Surgeries (LSS) at the American University of Beirut Medical Center after partnering with the multidisciplinary team at St. Judes Children's Research Hospital (SJCRH). Procedures performed included 12 Repiphysis, noninvasively expandable, prostheses inserted in skeletally immature children, 15 modular prostheses, 2 allografts and 1 rotationplasty. All patients received pre- and postoperative chemotherapy. With a mean follow-up of 31 months, 20 patients are now off therapy, 4 died, and 6 are receiving chemotherapy (3 due to pulmonary recurrence). Complications of surgery included infections in three cases, failure of the expansion mechanism in two, femoral stem fracture in one, prostheses femoral stem loosening in one and wound dehiscence in one. Lengthening of Repiphysis prostheses was achieved by subjecting the limb to an electromagnetic field that would allow controlled release of the Repiphysis expansion mechanism. Ten patients underwent a total of 42 lengthening procedures with an average of 9 mm lengthened per procedure (range 2-15 mm). All patients have good function of the affected limb. Our LSS results are comparable to those reported in the literature. Collaboration with SJCRH and fund raising were critical to the program's success. This endeavor could serve as a model for establishing LSS programs in developing countries.


Rationally Designed Ag@polymer@2-D LDH Nanoflakes for Bifunctional Efficient Electrochemical Sensing of 4-Nitrophenol and Water Oxidation Reaction.
The rational design and demonstration of a facile sequential template-mediated strategy to construct noble-metal-free efficient bifunctional electrocatalysts for efficient oxygen evolution reaction (OER) and electrocatalytic detection of hazardous environmental 4-nitrophenol (4-NP) have continued as a major challenging task. Herein, we construct a novel Ag@polymer/NiAl LDH (designated as APL) nanohybrid as an efficient bifunctional electrocatalyst by a simple hydrolysis method. The well-fabricated APL/GCE exhibited an extensive linear range from 0.1 to 100 μM in optimized conditions. It showed a detection limit (LOD) of 0.0096 μM (9.6 nM) (S/N = 3) for 4-NP in pH 6 by differential pulse voltammetry (DPV). Meanwhile, the newly fabricated APL exhibited outstanding OER activity with a very low overpotential of 259 mV to deliver 10 mA cm-2 current density (J) at a scan rate of 5 mV/s. The Tafel plot value of APL is low (97 mV/dec) compared to that of the benchmark RuO2 due to a fast kinetic reaction. Besides, the durability of the electrocatalyst was assessed by a chronoamperometry test (CA) for 36 h at 1.55 mV vs RHE, and the long-term cycling stability was analyzed by using cyclic voltammetry (CV); after 5000 cycles, the electrocatalyst was highly stable. These demonstrated results could lead to an alternative electrocatalyst construction for the bifunctionally efficient electrochemical sensing of 4-nitrophenol and oxygen evolution reaction.


The role of a new monoclonal antibody assay in the detection of recurrent breast cancer.
The immunoradiometric assay "CA 15-3", recently developed to measure a breast tumor-associated antigen, gave a mean serum value of 13.8 U/ml (S.D. 6.2) for this antigen in 156 non-cancer controls (36 biopsies for a benign breast lesion and 120 healthy controls). Setting a cut-off value of 30 U/ml (specificity 99.3%), only 3 out of 58 primary breast cancer cases were positive. In metastatic breast cancer, 11 out of 33 cases with limited recurrence (33.3%) and 36 out of 56 cases with extensive recurrence (64.3%) gave abnormal values in this assay, above the cut-off point, with an overall sensitivity of 52.8%; the difference between the sensitivity values in the two groups of recurrent cases was statistically significant (P less than 0.01). According to the findings of the present study, CA 15-3 has no role in the detection of primary breast cancer, but its usefulness in disease monitoring can be hypothesized, as circulating levels of the antigen seem to be dependent on the tumor mass.


Acute painless pancreatitis as an unusual presentation of leptospirosis in a low-incidence country.
A healthy, urban-dwelling man presented with lassitude, jaundice without increased liver enzymes or obstructive features on imaging, brief acute kidney injury, leucocytosis with near-normal C reactive protein and markedly increased serum amylase and lipase. Leptospirosis was not considered for 10 days because of the low incidence of the disease in the country, absent animal contact and physicians' low index of suspicion. Presentation without fever and without the commonly associated abdominal pain, myalgia, headache, thrombocytopaenia or elevated serum creatine kinase added to the diagnostic challenge. Once an infectious cause of acute pancreatitis was contemplated, leptospirosis was immediately sought and diagnosed by PCR of urine and microscopic agglutination test, and he fully recovered on ceftriaxone. Physicians in countries with a low incidence of leptospirosis should be more aware of the possibility of the disease even when several key features such as fever or pain are missing and the patient has a rare infectious acute pancreatitis.


Effect of whole-body vibration on the low back. A study of tractor-driving farmers in north India.
A retrospective cohort study of tractor-driving farmers (study group) and non-tractor-driving farmers (control group) matched for age, gender, generic/ethnic group, land-holding, and work routines. To determine, using magnetic resonance imaging and clinical investigations, the effect of whole-body vibrations on the back in tractor-driving farmers. Low back pain and pathologic changes in the lower backs of tractor drivers have been reported. However, no study with a control group matched for work-related risk factors has been reported. Fifty tractor-driving farmers were compared with 50 non-tractor-driving farmers matched for age, gender, ethnic group, land-holding, and work routine. Both groups were interviewed for details of work routine, assets held, family profile, and vibration exposure to assess the influence of these parameters on signs and symptoms of backache. Magnetic resonance imaging was done to assess the effect of exposure on whole-body vibration and degenerative changes in the back. Vibration measurements also were done on tractors to observe the actual severity of the vibrations. Regular work-related backache was more common among tractor-driving farmers (40%) than among non-tractor-driving farmers (18%, P = 0.015). Anthropometric evaluation showed abdominal girth and weight to be significantly higher in tractor-driving farmers (P = 0.006 and 0.046, respectively), whereas while height and arm span were similar between the two groups. Clinical examination for evidence of disc or facet degeneration showed no difference between the two groups. Evaluation of magnetic resonance images of tractor-driving farmers and non-tractor-driving farmers by an orthopedic surgeon, radiologist, and neurosurgeon showed degenerative changes to be similar between the two groups (P > 0.050). Tractor-driving farmers report backache more often than non-tractor-driving farmers, but no significant objective differences on clinical or magnetic resonance imaging evaluation were found between the two groups.


Development of culturally tailored educational brochures on HPV and pap tests for American Indian women.
Participatory formative research guided the creation of a culturally tailored educational brochure about human papillomavirus (HPV) at an American Indian women's clinic. A review of existing educational materials and in-depth interviews were conducted. Nine steps for creating health communications messages that were patterned after National Cancer Institute guidelines guided the brochure development process. Of 95 women tested for HPV, 41% were positive, 32 (34%) agreed to the in-depth interview, and 9 agreed to the pretesting interview. Mean age was 41 years. Interviews revealed key themes concerning emotional reactions to abnormal Pap test results and HPV; need for basic information about HPV, Pap tests, and results; concerns about HPV stigma, sexual transmission, and communication with sexual partner; and the preferred source and format for HPV educational materials. A literature review revealed 12 areas of basic HPV content. A participatory process successfully engaged nursing staff and patients in creating culturally appropriate brochures for clinic use. This article provides specific steps for creating culturally tailored patient education materials.


Hot times in the intensive care unit.
Fever is a common occurrence in the intensive care unit, and pharmacologic approaches are limited, particularly in patients unable to tolerate enteral medications. Although a study by Morris and colleagues in the previous issue of Critical Care suggests that intravenous ibuprofen is safe and effective in critically ill patients, the study is small and the drug was given over only a 24-hour period. Additional studies will need to be performed to demonstrate the safety and efficacy of intravenous ibuprofen in critically ill patients.


Pneumomediastinum in COVID-19 Patients with Acute Respiratory Distress Syndrome.
Pneumomediastinum, an uncommon entity, has been on the rise with increasing cases of COVID-Acute respiratory distress syndrome. It has been unclear whether this entity represents an indicator of poor clinical outcome or not. The aims of this study were to find out the incidence of pneumomediastinum in COVID-Acute respiratory distress syndrome patients, describe their clinical characteristics and try to explain its plausible mechanisms.. A descriptive, cross-sectional study was carried out in the ICU of our hospital among 280 patients admitted with COVID-Acute respiratory distress syndrome over a period of 6 months. Demographics along with various clinical, laboratory, and radiological parameters were analyzed. Relevant statistical analyses were done to summarize our findings. The incidence of pneumomediastinum in COVID-ARDS patients was 2.8%. All patients were male, none had pulmonary co-morbidities and six of them (60%) were on invasive mechanical ventilation. All intubated patients were on lung protective mechanical ventilation. The median PEEP, peak airway pressure and plateau pressure were 10 (IQR: 4), 29 (IQR: 8) and 28 (IQR: 4) respectively. The mean CT severity score was 22.7 (SD: 1.64). Five patients died after 6.8 days (SD: 4.8) of diagnosis. The average hospital stay was of 34 days. Pneumomediastinum is a possible complication of COVID-Acute respiratory distress syndrome which could signify the disease severity and vice versa. Furthermore, it could be an indicator of relatively poor prognosis and therefore requires larger studies to establish the association.


'Essential' hypertension with hypokalemia. Caused by aldosterone-secreting adrenal adenoma.
Primary aldosteronism is a potentially curable cause of hypertension; it occurs in about 1% of hypertensive patients. In the case reported here, persistent hypokalemia developed in a 72-year-old man who had been treated for 13 years for essential hypertension. Investigation revealed elevated aldosterone level and reduced plasma renin activity. Computed tomography and selective angiography showed a tumor in the right adrenal gland. Aldosterone-secreting adenoma of the adrenal gland was diagnosed, and right adrenalectomy was performed. At a six-month follow-up examination, the patient's blood pressure and potassium level were normal.


Melioidosis in a patient from Bangladesh.
A 54 year old Bangladeshi man presented with a history and chest X-ray appearances suggestive of pulmonary tuberculosis. Following deterioration 4 weeks later, he required ventilation. Although a blood culture isolate was subsequently found to be Pseudomonas pseudomallei, it was initially misidentified and dismissed as a contaminant. Further cultures demonstrated the organism, but the patient died, despite treatment with ceftazidime. The case illustrates the importance of taking a detailed travel history and having a high index of suspicion in patients from South East Asia and the Indian sub-continent, including Bangladesh, where the disease has not previously been considered endemic.


Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1.
Rationale: Ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) that is associated with high morbidity and mortality, and for which specific treatments are lacking. In this study, we investigated the protective effect of human urine-derived stem cells (USCs) and their exosomes against IRI-induced AKI to explore the potential of these cells as a new therapeutic strategy. Methods: USCs were derived from fresh human urine. Cell surface marker expression was analyzed by flow cytometry to determine the characteristics of the stem cells. Adult male Sprague-Dawley rats were used to generate a lethal renal IRI model. One dose of USCs (2×106 cells/ml) or exosomes (20 µg/1 ml) in the experimental groups or saline (1 ml) in the control group was administered intravenously immediately after blood reperfusion. Blood was drawn every other day for measurement of serum creatinine (sCr) and blood urea nitrogen (BUN) levels. The kidneys were harvested for RNA and protein extraction to examine the levels of apoptosis and tubule injury. In vitro, the hypoxia-reoxygenation (H/R) model in human kidney cortex/proximal tubule cells (HK2) was used to analyze the protective ability of USC-derived exosomes (USC-Exo). Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), western blotting, superoxide dismutase activity, and malonaldehyde content analyses were used to evaluate oxidative stress in HK2 cells treated with USC-Exo after H/R. Exosomal microRNA sequencing techniques and bioinformatics analysis were used to search for enriched miRNAs in the exosomes and interacting genes. The interaction between miRNAs and the 3' untranslated region of the target gene was detected using a dual luciferase reporting system. The miRNA mimic and inhibitor were used to regulate the miRNA level in HK2 cells. Results: Treatment with USCs led to reductions in the levels of sCr, BUN, and renal tubular cell apoptosis; inhibited the infiltration of inflammatory cells; and protected renal function in the rat IRI model. Additionally, USC-derived exosomes protected against IRI-induced renal damage. miR-146a-5p was the most abundant miRNA in exosomes obtained from the conditioned medium (CM) of USCs. miR-146a-5p targeted and degraded the 3'UTR of interleukin-1 receptor-associated kinase 1 (IRAK1) mRNA, subsequently inhibited the activation of nuclear factor (NF)-κB signaling, and protected HK2 cells from H/R injury. USC transplantation also upregulated miR-146a-5p expression, downregulated IRAK1 expression and inhibited nuclear translocation of NF-κB p65 in the kidney of the rat IRI model. Conclusions: According to our experimental results, USCs could protect against renal IRI via exosomal miR-146a-5p, which could target the 3'UTR of IRAK1 and subsequently inhibit the activation of NF-κB signaling and infiltration of inflammatory cells to protect renal function. As a novel cell source, USCs represent a promising non-invasive approach for the treatment of IRI.


Gastric ulcer healing: a comparison of enprostil versus ranitidine.
Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.


A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1.
Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats.


Pattern formation and dewetting in thin films of liquids showing complete macroscale wetting: from "pancakes"to "swiss cheese".
Based on the complete 3D numerical solutions of the nonlinear thin film equation, we address the problems of surface instability, dynamics, morphological diversity and evolution in unstable thin films of the liquids that display complete macroscale wetting. The twin constraints of complete macroscale wettability and nanoscale instability produce a variety of microscopic morphological phases approximating sharp crystal surfaces with flat tops resembling a mesa or a micro "pancake" or a slice of Swiss cheese. While the maximum thickness of flat regions is found to be independent of the initial film thickness, the precise lateral morphology of microdomains formed depends on the film thickness. As the film thickness is increased, the initial pathway of evolution changes from the formation of small spherical droplets, to long mesas (parapets) and islands, to circular holes, all of which eventually resolve by ripening into a collection of round pancakes at equilibrium. However, beyond a certain transition thickness, a novel metastable honeycombed morphology, resembling a membrane or a slice of Swiss cheese, is uncovered, which is produced by an abrupt "freezing" of the evolution during hole growth. In contrast, the spinodal dewetting in thin films of partially wettable systems always engenders spherical droplets at equilibrium. The equilibrium dewetted area from simulations, as well as from simple mass balance, is shown to decline linearly with the initial film thickness.


Plasma endothelin-1 level in patients with renovascular hypertension - does the kidney with stenosis of the renal artery upregulate production of endthelin-1?
To examine the value of plasma endothelin-1 (ET-1), we measured the level of plasma ET-1 activity of peripheral venous blood and selective renal venous blood in renovascular hypertension patients, and compared that activity with corresponding renin activity and split renal function. ET-1 level, renin activity in selective renal venous blood and peripheral venous blood, and 99mTc-dimercaptosuccinic acid renal uptake as a split renal function test were measured in 11 patients (mean 42.1 years old) with renovascular hypertension (RVH) and 6 patients with both renal cell cancer (RCC) and essential hypertension. 1. In patients with RVH, resting peripheral venous plasma ET-1 ranged from 0.6 to 8.1 (mean 4.07) pg/ml and was higher than the normal level (p <0.01). However, the renal vein ET-1 ratio was nor correlated with the renal vein renin ratio. 2. In patients with RCC, resting peripheral venous plasma ET-1 was not different from the normal level. There was no step-up of plasma ET-1, or renin among renal veins, or the proximal and distal parts of the interior vena cava. 3. Both renal vein renin ratio and renal vein ET-1 ratios were inversely correlated with t99mTC-dimercaptosuccinic acid renal uptake as a split renal function examination in patients with RVH. 4. The peripheral plasma ET-1 level was correlated with the degree of stenosis of the renal artery in patients with RVH of a unilateral lesion, but not bilateral lesions. These results suggest that ET-1 may take part in the hypertensive mechanisms of RVH in addition to the renin-angiotensin system, but its significance in RVH still remains to be examined.


Alcoholic myelopathy without substantial liver disease. A syndrome of progressive dorsal and lateral column dysfunction.
Five well-nourished, alcoholic patients had a progressive myelopathy. Symptoms began with paresthesias of the feet and progressed to a spastic paraparesis with clinical signs of both lateral and dorsal column involvement. Abstinence from alcohol halted progression but did not cause improvement in the myelopathy. The absence of portacaval shunting or notable liver dysfunction in these patients suggests that a direct toxic effect of alcohol must be considered a possible mechanism of spinal cord damage.


Comparative embryotoxicity of different antimalarial peroxides: in vitro study using the rat whole embryo culture model (WEC).
Three groups of compounds: (i) active peroxides (artemisinin and arterolene), (ii) inactive non-peroxidic derivatives (deoxyartemisinin and carbaOZ277) and (iii) inactive peroxide (OZ381) were tested by WEC system to provide insights into the relationship between chemical structure and embryotoxic potential, and to assess the relationship between embryotoxicity and antimalarial activity. Deoxyartemisinin, OZ381 and carbaOZ277 did not affect rat embryonic development. Artemisinin and arterolane affected primarily nucleated red blood cells (RBCs), inducing anemia and subsequent tissue damage in rat embryos, with NOELs for RBC damage at 0.1 and 0.175μg/mL, respectively. These data support the idea that only active antimalarial peroxides are able to interfere with normal embryonic development. In an attempt to establish whether and to what extent activity as antimalarials and embryotoxicity can be divorced, IC(50)s for activity in Plasmodium falciparum strains and the NOELs for RBCs were compared. From this comparison, arterolane showed a better safety margin than artemisinin.


Ammonium nitrate in the culture medium influences regeneration potential of cryopreserved shoot tips of Holostemma annulare.
Influence of NH4NO3 in the pre-freeze and post-freeze culture medium and 2 or 30 day preconditioning in the presence of 0.5 M sucrose on regeneration of shoot tips of Holostemma annulare following cryopreservation using an encapsulation-dehydration protocol was studied. A long preconditioning phase of 30 days significantly reduced tissue water and improved post-freeze recovery of shoot tips. Under the long preconditioning treatment, Murashige & Skoog (MS) medium free of NH4NO3 (MS-3) allowed maximum regeneration (59%) of liquid nitrogen (LN) exposed shoot tips with less frequency of callusing (10.4%) after 45 days of post-freeze culture. Corresponding desiccated control shoot tips showed 85-90% regeneration. A 3.75 mM NH4NO3 concentration (MS-4) favoured 72-89% and 43-47% regeneration after desiccation and LN exposure respectively. The standard MS medium with 20.6 mM NH4NO3 (MS-1) allowed poor regeneration after desiccation (39-53%) as well as LN exposure (8-23%). The study reveals the importance of reducing ammonium nitrate in the culture medium to get maximum recovery of cryopreserved shoot tips of Holostemma annulare.


Social Ties Cut Both Ways: Self-Harm and Adolescent Peer Networks.
Peers play an important role in adolescence, a time when self-harm arises as a major health risk, but little is known about the social networks of adolescents who cut. Peer network positions can affect mental distress related to cutting or provide direct social motivations for self-harm. This study uses PROSPER survey data from U.S. high school students (n = 11,160, 48% male, grades 11 and 12), finding that social networks predict self-cutting net of demographics and depressive symptoms. In final models, bridging peers predicts higher self-cutting, while claiming more friends predicts lower cutting for boys. The findings suggest that researchers and practitioners should consider peer networks both a beneficial resource and source of risk associated with cutting for teens and recognize the sociostructural contexts of self-harm for adolescents more broadly.


Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay.
Transfusion effectiveness of red blood cells (RBCs) has been associated with duration of the storage period. Storage-dependent RBC alterations lead to hemolysis and release of toxic free heme, but the increase of free heme levels over time is largely unknown. In the current study, an apo-horseradish peroxidase (apoHRP)-based assay was applied to measure levels of free heme at regular intervals or periodically in supernatants of RBCs until a maximum storage period of 42 days. Free heme levels increased with linear time-dependent kinetics up to day 21 and accelerated disproportionally after day 28 until day 42, as determined with the apoHRP assay. Individual time courses of free heme in different RBC units exhibited high variability. Notably, levels of free hemoglobin, an established indicator of RBC damage, and those of total heme increased with continuous time-dependent linear kinetics over the entire 42 day storage period, respectively. Supernatants from RBC units with high levels of free heme led to inflammatory activation of human neutrophils. In conclusion, determining free heme in stored RBCs with the applied apoHRP assay may become feasible for testing of RBC storage quality in clinical transfusion medicine.


Transcriptomic Analysis of Laying Hens Revealed the Role of Aging-Related Genes during Forced Molting.
Molting in birds provides us with an ideal genetic model for understanding aging and rejuvenation since birds present younger characteristics for reproduction and appearance after molting. Forced molting (FM) by fasting in chickens causes aging of their reproductive system and then promotes cell redevelopment by providing water and feed again. To reveal the genetic mechanism of rejuvenation, we detected blood hormone indexes and gene expression levels in the hypothalamus and ovary of hens from five different periods during FM. Three hormones were identified as participating in FM. Furthermore, the variation trends of gene expression levels in the hypothalamus and ovary at five different stages were found to be basically similar using transcriptome analysis. Among them, 45 genes were found to regulate cell aging during fasting stress and 12 genes were found to promote cell development during the recovery period in the hypothalamus. In addition, five hub genes (INO80D, HELZ, AGO4, ROCK2, and RFX7) were identified by WGCNA. FM can restart the reproductive function of aged hens by regulating expression levels of genes associated with aging and development. Our study not only enriches the theoretical basis of FM but also provides insights for the study of antiaging in humans and the conception mechanism in elderly women.


Structural Models of Ligand-Bound Sodium Channels.
X-ray and cryo-EM structures of tetrameric and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with drugs and neurotoxins. Such models integrate experimental data, assist in planning new experiments, and may facilitate drug design. This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. Further summarized are sodium channel models with tetrodotoxin, mu-conotoxins, batrachotoxin, scorpion toxins, and insecticides. Possible involvement of sodium ions in the action of some ligands is discussed.


Failure to maintain a suppressed level of serum testosterone during long-acting depot luteinizing hormone-releasing hormone agonist therapy in patients with advanced prostate cancer.
It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.


Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain.
Once bound to methylated CpG sites, methyl-CpG-binding protein 2 (MeCP2) is thought to silence transcription of downstream genes by recruiting a histone deacetylase (HDAC). Mutations within the MeCP2 gene have been found to cause Rett syndrome, a disorder of arrested neuronal development. Using immunohistochemistry, we found that Mecp2, as well as the methyl-CpG-binding protein MBD1, were significantly induced in normal adult rat brain after repeated injections of fluoxetine or cocaine for 10 days (one injection per day). Mecp2 was not induced by repeated injections of 1-(2-bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl)piperazine (GBR-12909) or nortriptyline. Together, the data indicate that the serotonergic system is predominantly involved. Using real-time reverse transcription-polymerase chain reaction experiments, MBD1 mRNA and both Mecp2_e1 and Mecp2_e2 transcripts were found to be induced by fluoxetine. Induction of the methylbinding proteins was accompanied with enhanced HDAC2 labeling intensity and mRNA synthesis in response to fluoxetine. In tandem, acetylated forms of histone H3 were found to be decreased. The effect was characterized in three serotonin projection areas, the caudate-putamen, the frontal cortex, and the dentate gyrus subregion of hippocampus. Our data highlight GABAergic neurons as major target cells expressing Mecp2 in response to the serotonin-elevating agents and suggest that serotonin signaling enhances gene silencing in postmitotic neurons.


Fractional CO2 Laser Resurfacing Complications.
Fractionated CO2 laser technology has allowed physicians to resurface patients with a lower rate of complications than nonfractionated ablative laser treatment. Unfortunately, adverse effects can still occur even with the best technology and physician care. Complication prevention, detection, and treatment are an important part of a physician's ability to provide the best result when treating a patient with fractionated CO2 resurfacing.


Regulation of the Phenylpropanoid Pathway: A Mechanism of Selenium Tolerance in Peanut (Arachis hypogaea L.) Seedlings.
To clarify the mechanisms of selenium (Se) tolerance in peanut seedlings, we grew peanut seedlings with sodium selenite (0, 3, and 6 mg/L), and investigated the phenylpropanoids metabolism in seedling roots. The results showed that selenite up-regulated the expression of genes and related enzyme activities involving in the phenylpropanoids biosynthesis cascade, such as phenylalanine ammonia-lyase, trans-cinnamate-4-hydroxylase, chalcone synthase, chalcone isomerase, and cinnamyl-alcohol dehydrogenase. Selenite significantly increased phenolic acids and flavonoids, which contributed to the alleviation of selenite-induced stress. Moreover, selenite enhanced the formation of endodermis in roots, which may be attributed to the up-regulation of lignin biosynthesis mediated by the selenite-induced changes of H2O2 and NO, which probably regulated the selenite uptake from an external medium. Accumulation of polyphenolic compounds via the phenylpropanoid pathway may be one of the mechanisms of the increasing selenite tolerance in plants, by which peanut seedlings survived in seleniferous soil, accompanied by accumulation of Se.


A noninvasive method for the estimation of increased intracranial pressure in patients with severe traumatic brain injury using optic nerve sheath diameter measured on computed tomography head.
Measurement of optic nerve sheath diameter (ONSD) using ocular ultrasonography has shown a promise in predicting increased intracranial pressure (ICP). However, this method is dependent on operator technique and equipment availability. We propose an alternative method of measuring ONSD and Marshall score grading by utilizing initial computed tomography (CT) head obtained on admission. We believe that such a technique could help predict patients requiring an invasive ICP monitor on admission. Patients were retrospectively selected from the neurosurgery database of a level II trauma center. Control patients originated from a database of nontraumatic brain injury (TBI) patients with a negative CT head and no intracranial pathology. Study subjects included patients aged 18-90 years, who sustained a severe TBI requiring placement of an ICP monitor on admission. All patients had a non-contrast CT head before the placement of an ICP monitor. Patients receiving any intervention for decreasing suspected elevated ICPs and those with any documented orbital fractures before ICP monitor placement were excluded from the study. All measurements were performed by at least of two independent assessors. A total of 242 patients were reviewed, of which 204 (100 control and 104 intervention) met inclusion criteria for this study. T he average age in the control group was 49.1 ± 22.9 years old while the average age of the intervention group was 36.9 ± 15.1 years (P < 0.0001). The average Glasgow Coma Scale was 7 in the intervention group. The average ONSD of the control group was 5.73 ± 0.58 mm compared to 6.76 ± 0.83 mm in the intervention group (P < 0.0001). Linear regression analysis demonstrated a statistically significant correlation between ONSD and opening ICP (r = 0.40, P < 0.001) and peak ICP (r = 0.31, P < 0.0001). An ONSD ≥6.0 mm + Marshall score ≥3 on initial CT head demonstrated a 92.5% sensitivity, 92.6% specificity, and 96.1% positive predictive value for developing an ICP ≥20 mmHg during hospitalization. Utilizing ONSD in combination with Marshall score grading on initial CT head is a strong predictor of elevated ICP. These criteria can be used in future studies to develop more objective criteria to guide ICP monitor placement.


Rapid Classification and Treatment Algorithm of Cardiogenic Shock Complicating Acute Coronary Syndromes: The SAVE ACS Classification.
We aimed to identify the independent "frontline" predictors of 30-day mortality in patients with acute coronary syndromes (ACS) and propose a rapid cardiogenic shock (CS) classification and management pathway. From 2011 to 2019, a total of 11439 incident ACS patients were treated in our institution. Forward conditional logistic regression analysis was performed to determine the "frontline" predictors of 30 day mortality. The C-statistic assessed the discriminatory power of the model. As a validation cohort, we used 431 incident ACS patients admitted from January 1, 2020, to July 20, 2020. Independent predictors of 30-day mortality included age (OR 1.05; 95% CI 1.04 to 1.07, p < 0.001), intubation (OR 7.4; 95% CI 4.3 to 12.74, p < 0.001), LV systolic impairment (OR severe_vs_normal 1.98; 95% CI 1.14 to 3.42, p=0.015, OR moderate_vs_normal 1.84; 95% CI 1.09 to 3.1, p=0.022), serum lactate (OR 1.25; 95% CI 1.12 to 1.41, p < 0.001), base excess (OR 1.1; 95% CI 1.04 to 1.07, p < 0.001), and systolic blood pressure (OR 0.99; 95% CI 0.982 to 0.999, p=0.024). The model discrimination was excellent with an area under the curve (AUC) of 0.879 (0.851 to 0.908) (p < 0.001). Based on these predictors, we created the SAVE (SBP, Arterial blood gas, and left Ventricular Ejection fraction) ACS classification, which showed good discrimination for 30-day AUC 0.814 (0.782 to 0.845) and long-term mortality (p log-rank < 0.001). A similar AUC was demonstrated in the validation cohort (AUC 0.815). In the current study, we introduce a rapid way of classifying CS using frontline parameters. The SAVE ACS classification could allow for future randomized studies to explore the benefit of mechanical circulatory support in different CS stages in ACS patients.


Small RNA-mediated Cry toxin silencing allows Bacillus thuringiensis to evade Caenorhabditis elegans avoidance behavioral defenses.
Pathogen avoidance behavior protects animal hosts against microbial pathogens. Pathogens have evolved specific strategies during coevolution in response to such host defenses. However, these strategies for combatting host avoidance behavioral defenses remain poorly understood. Here, we used Caenorhabditis elegans and its bacterial pathogen Bacillus thuringiensis as a model and determined that small RNA (sRNA)-mediated Cry toxin silencing allowed pathogens to evade host avoidance behavioral defenses. The B. thuringiensis strain YBT-1518, which encodes three nematicidal cry genes, is highly toxic to C. elegans. However, the expression of the most potent toxin, Cry5Ba, was silenced in this strain when YBT-1518 was outside the host. Cry5Ba silencing was due to the sRNA BtsR1, which bound to the RBS site of the cry5Ba transcript via direct base pairing and inhibited Cry5Ba expression. Upon ingestion by C. elegans, Cry5Ba was expressed in vivo by strain YBT-1518. Cry5Ba silencing may allow B. thuringiensis to avoid nematode behavioral defenses and then express toxins once ingested to kill the host and gain a survival advantage. Our work describes a novel model of sRNA-mediated regulation to aid pathogens in combating host avoidance behavioral defenses.


Mutations in Cdh23 cause nonsyndromic hearing loss in waltzer mice.
Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the v(J) allele and a single nucleotide insertion in the v allele are predicted to truncate each protein near the N-terminus and produce a functional null allele. In situ hybridization analysis showed that Cdh23 is expressed in the sensory hair cells of the inner ear, where it has been suggested to be a molecule critical for crosslinking of the stereocilia. In addition, Cdh23 is expressed in the urticulo-saccular foramen,the ductus reuniens, and Reissner's membrane, suggesting that Cdh23 may also be involved in maintaining the ionic composition of the endolymph. Finally, mutations in human CDH23 have recently been described for two loci, DFNB12 and USH1D, which cause nonsyndromic deafness, identifying waltzer as a mouse model for human hearing loss.


A contribution to the Mutillidae (Hymenoptera) of Hong Kong.
A list of 12 species in nine genera occurring in Hong Kong is given. The hitherto unknown male of Bischoffitilla lamellata (Mickel, 1933) is described and illustrated. Six species are newly recorded from Hong Kong. The current number of known mutillid species of Hong Kong is doubled from six to 12.


A field model of left-right asymmetries in the pattern regulation of a cell.
Dynamical models can offer insights into important aspects of patterns that recur throughout the biological world, such as global symmetries, mirror images, and pattern reversals, etc. Building on phenomenological rules of pattern formation (e.g. E. M. Nelsen and J. Frankel, 1986, Dev. Biol. 114, 53), the author developed a mathematical model of a morphogenetic field, expressed as a vector field, which contains the information to specify a pattern. The dynamics of the field arises from the minimization of a nonlinear energy density functional, a quartic polynomial of the field together with field gradient effects. This model was successfully applied in detail to surface patterns observed in right-handed Tetrahymena, where reproducible regions of left- and right-handed domains appear during regulation. Counterpart experiments on left-handed patterned cells suggest an intrinsic asymmetry between right- and left-handed patterning in this biological system, causing left-handed cells to follow different regulation pathways from the right-handed cells. We show that the energy minimization approach can account for this globally different behaviour in a version of the model with small local asymmetry.


Monte Carlo simulation of the water in a channel with charges.
A Monte Carlo simulation of water in a channel with charges suggests the existence of water in immobile, high density, essentially glasslike form near the charges. The channel model has a conical section with an opening through which water molecules can pass, at the narrow end of the cone, and a cylindrical section at the other end. When the charges are placed near the narrow section of the model, the "glass" effectively blocks the channel; with the charges removed, the channel opens. The effect can be determined from the rate of passage of the water molecules through the pore, from the average orientation of the water molecule, and from distortion of the distribution of molecules. In the simulations carried out to date, no external ions have been considered. In addition to the energy, the Helmholtz free energy has been calculated.


Influenza virus host response of C57Bl/6 mice treated with TACI-Ig.
TACI-Ig is a soluble glycoprotein comprised of a human IgG1-Fc fused with the extracellular domain of the human TACI receptor. Chronic exposure to TACI-Ig is associated with reduced circulating B cells in mouse and non-human primates, and a concomitant decrease in circulating immunoglobulin. Because of these activities, TACI-Ig is in clinical evaluation for treatment of various autoimmune diseases and B cell malignancies. In this study, the effect of TACI-Ig treatment on the ability of C57Bl/6 mice to clear influenza virus was evaluated. C57Bl/6 mice were exposed to vehicle (negative control), dexamethasone (positive control), or TACI-Ig (0.05, 0.50, or 5.0 mg/kg, SC, thrice weekly) from within one week prior to viral exposure through 21 days thereafter. Dexamethasone treatment of influenza-infected mice prolonged the infection, and decreased survival, body weight, lymphoid organ weight, influenza-specific IgM and IgG, and viral clearance relative to control animals, consistent with its expected immunosuppressive activity. Animals treated with TACI-Ig (0.05, 0.50, and 5.0 mg/kg) demonstrated a dose-dependent decrease in spleen weight and influenza-specific IgG and IgM in both lung and serum relative to control animals. In addition, flow cytometric analyses showed a decrease in B cells, but not T cells, in peripheral blood in animals treated with TACI-Ig. However, neither viral clearance nor survival was affected by TACI-Ig treatment. These data demonstrate the expected B cell-specific pharmacological effects of TACI-Ig in influenza-challenged C57Bl/6 mice without apparent effect on influenza virus clearance. It is concluded that non-B cell related antiviral competence remains intact during TACI-Ig treatment.


Geographic distribution of cystic fibrosis transmembrane regulator gene mutations in Saudi Arabia.
A descriptive study was undertaken to characterize the cystic fibrosis transmembrane regulator gene mutations (CFTR) in the Saudi Arabian cystic fibrosis (CF) population in relation to clinical presentation and demographic and ethnic origin. During the period October 1992 to September 1997, 70 patients from 46 families were diagnosed as having CF, based on a typical clinical picture and sweat chloride levels > 60 mmol/l and were screened for CFTR mutations. Twelve mutations were identified in 34 families, which constitutes 70% of the CF alleles in the study group. Pancreatic insufficiency (PI) was found in the following mutations: 1548delG in exon 10 (15%) which occurred mainly in native Saudi patients in the central province; 3120 + 1G-->A in intron 16 (10%) and H139L in exon 4 (7%), found mainly in native Saudis from the eastern province; delta F508 mutation (13%) which occurred mainly in expatriates of Middle Eastern origin from different provinces; L117X in exon 19 (2%); G115X in exon 4 (2%); 711 + 1G-->A in intron 5 (2%); N 1303K in exon 21 (2%) and 425del42 in exon 4 (1%); I1234V in exon 19 (13%) with a predominance of nasal polyps and a variable degree of PI and lung disease; R553X in exon 11 (1%), with electrolyte imbalance; and S549R in 11 (2%) with pancreatic sufficiency and minimal pulmonary disease. The clinical picture did not differ significantly between patients of different ethnic origins with the same CFTR mutation.


Hypoglycemia in diabetes: The dark side of diabetes treatment. A patient-centered review.
Hypoglycemia is a frequent occurrence in patients with diabetes who are treated with insulin and insulin secretagogues. Hypoglycemia is the limiting factor that prevents patients from achieving the glycemic control known to reduce the microvascular complications of diabetes. Recurrent episodes of hypoglycemia can lead to impaired awareness of hypoglycemia where the first symptom of a low blood sugar is unconsciousness. The fear of hypoglycemia has a significant effect on the quality of life of patients and their families. In the acute setting, hypoglycemia can kill, and clinical trials have demonstrated that a single episode of severe hypoglycemia increases the risk of subsequent mortality and cardiovascular events. Clinicians must make efforts to recognize and prevent hypoglycemia in order to prevent the adverse events associated with this event. Patient education is central to these efforts. Recent developments in glucose monitoring and drug development have provided more approaches that can be used to reduce the risk of hypoglycemia in patients with diabetes.


Severe hypothyroidism presenting as obstructive sleep apnea.
A 5-year-old child with Down syndrome (DS) diagnosed with mild to moderate obstructive sleep apnea (OSA) and subsequently found to have severe hypothyroidism is presented. Following 3 months of treatment with levothyroxine, she had full resolution of her OSA. This case underscores the importance of routine thyroid function screening in children with DS and demonstrates that OSA in children with DS can be caused by other underlying medical issues that themselves require therapy, such as the hypothyroidism in this child. Although empiric testing of thyroid function is not recommended as part of the routine workup of patients with OSA, when caring for children at higher risk for thyroid dysfunction, such as those with DS, it is important to establish whether or not it is present, as treating it may bring about partial or full resolution of the OSA, as was shown to occur in this patient.


Natural and iatrogenic factors in human immunodeficiency virus transmission.
In the light of the evidence and discussion presented during The Royal Society Discussion Meeting it seems to me that the oral polio vaccine (OPV) hypothesis for the origins of human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome epidemic is less tenable now than one year earlier. The OPV hypothesis does not accord with HIV phylogenetic studies: the geographical correlation has been challenged; the testimony of those directly involved with OPV trial vaccines denies the use of chimpanzees, corroborating tests on the still-available vials of the CHAT vaccines, which contain neither simian immunodeficiency virus nor chimpanzee DNA. Yet one lesson to be learned from considering OPV as a source of HIV is how plausibly it might have happened and how cautious we need to be over introducing medical treatments derived from animal tissues, such as live, attenuated vaccines or xenotransplantation. To cast doubt on the OPV hypothesis is not to dismiss entirely the role of iatrogenic factors in HIV transmission from chimpanzees in the first instance, in HIV adaptation to onward transmission during its early phase in humans, or in the later spread of HIV to patients, for example, with haemophilia. To reduce the argument over the origins of HIV to the 'OPV hypothesis' versus the 'cut-hunter hypothesis' is an oversimplistic and false antithesis. Both natural and iatrogenic transmission of many retroviruses, including HIV, have been thoroughly documented and are not mutually exclusive. Exactly how, when and where the first human(s) became infected with the progenitor of HIV-1 group M, which gave rise to the pandemic strain, is likely, however, to remain a matter of conjecture.


Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms.
Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P < 0.0001) and distant metastasis (P < 0.0001). Colonic NENs had a worse prognosis (P = 0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P = 0.081), but tumor size (P = 0.037) and pathological classification (P = 0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis.


Interleukin-1 modulates protein tyrosine phosphatase activity and permeability of brain endothelial cells.
Interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6), both known to be able to open the blood-brain barrier (BBB), downregulated plasma membrane-associated tyrosine phosphatase activity in primary porcine brain endothelial cells (PBEC). In contrast, transforming growth factor beta (TGF-beta) upregulated PTP activity and tumor necrosis factor alpha (TNF-alpha) had no effect. Plasma membrane-associated PTP activity of PBEC was upregulated at contact inhibited growth arrest. Tightly confluent cells reduced 3H-inulin permeability by 34% compared with just confluent cells indicating the formation of barrier properties. The decrease in permeability temporally correlated with the elevated PTP activity of the cells at growth arrest and was reversed to control by IL-1 alpha. Vanadate, a broad-specificity PTP inhibitor, also enhanced 3H-inulin permeability. These data suggest that IL-1 alpha-induced endothelial permeability could be controlled through lowering PTP activity.


Overexpression and purification of Rhizobium etli glutaminase A by recombinant and conventional procedures.
Rhizobium etli glutaminase A was purified to homogeneity by conventional procedures that included ammonium sulfate differential precipitation, ion-exchange chromatography, hydrophobic interaction chromatography, gel filtration, and dye-ligand chromatography. Alternatively, the structural glsA gene that codifies for glutaminase A was amplified by PCR and cloned in the expression vector pTrcHis. The recombinant protein was purified to homogeneity by affinity chromatography. This protein showed the same kinetic properties as native glutaminase A (K(m) for glutamine of 1.5 mM and V(max) of 80 micromol ammonium min(-1) mg protein(-1)). Physicochemical and biochemical properties of native and recombinant glutaminase were identical. The molecular mass of recombinant glutaminase A (M(r) 106.8 kDa) and the molecular mass of the subunits (M(r) 26.9 kDa) were estimated by mass spectrometry. These results suggest that R. etli glutaminase A is composed of four identical subunits. The high-level production of recombinant glutaminase A elevates the possibilities for determination of its three-dimensional structure through X-ray crystallography.