Analysis of changes in farm pond network connectivity in the peri-urban landscape of the Taoyuan area, Taiwan.
The farm pond system for irrigation is the most prominent feature in the Taoyuan area, Taiwan, giving the region a unique landscape and hydrological character. Although this area had more than 3,290 ponds in the 1970s, fewer than 1,800 now remain. This study analyzes changes in irrigation farm ponds and the canal network landscape in the Taoyuan area. The spatial and temporal changes to ponds and the canal network on the Taoyuan plain were examined graphically for each spatial unit (2,765 m × 2,525 m) using aerial photographs for 1979 and 2005. Landscape metrics were calculated to analyze landscape change associated with increased urbanization. Landscape indices of connectivity and circuitry were utilized to describe changes in the configuration of ponds and canal networks. The total length of canals and total number of ponds in the study area decreased significantly during 1979-2005. The average values of connectivity indices (γ- and α-index) also decreased during 1979-2005, reflecting degradation of canal networks due to urban sprawl. A multivariate technique was applied to portion the study area into three zones according to changes to land cover, ponds, and canal networks. The effects of urban sprawl on the spatial pattern of ponds and canal networks are discussed.


Magnetic resonance spectroscopy and analysis of MECP2 in Rett syndrome.
We studied the in vivo cerebral metabolites and documented the presence of MECP2 gene mutations in six Chinese females with Rett syndrome. Magnetic resonance spectroscopy spectra from the frontal lobe (gray and white matter) and deep gray nuclei (basal ganglia and thalamus) of either side were obtained. N-acetylaspartate/total creatine, choline/total creatine, and N-acetylaspartate/choline ratios were analyzed and compared with six healthy age-matched female control subjects. MECP2 gene mutation was identified in four patients; one patient had polymorphism and one patient did not have gene mutation. N-acetylaspartate/total creatine of the frontal lobe of all patients (mean: 2.63, S.D. = 0.33) was decreased compared with age-matched control subjects (mean: 3.15, S.D. = 0.27), and the difference was statistically significant (P = 0.017) with a mean difference of 0.52 (95% CI = 0.68-0.36). The difference in all other metabolite ratios in the frontal lobe and deep gray nuclei were not statistically significant compared with age-matched control subjects. Mild frontal lobe and anterior temporal lobe atrophy was present in three patients. Proton-magnetic resonance spectroscopy is a sensitive method capable of detecting the biochemical changes in Rett syndrome and is able to detect changes before conventional magnetic resonance imaging. Our preliminary results suggest that reduction in N-acetylaspartate/total creatine ratio may not be related to the MECP2 mutation.


Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.
Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.


Adenylosuccinate lyase deficiency.
Adenylosuccinate lyase deficiency is a disease of purine metabolism which affects patients both biochemically and behaviorally. The symptoms are variable and include psychomotor retardation, autistic features, hypotonia, and seizures. Patients also accumulate the substrates of ADSL in body fluids. Both the presence of normal levels of ADSL enzyme activities in some patient tissues and the absence of a clear correlation between mutations, biochemistry, and behavior show that the system has unexplored biochemical and/or genetic complexity. It is unclear whether the pathological mechanisms of this disease result from a deficiency of purines, a toxicity of intermediates, or perturbation of another pathway or system. A patient with autistic features and mild psychomotor delay carries two novel mutations in this gene, E80D and D87E. The creation of a mouse model of this disease will be an important step in elucidating the in vivo mechanisms of the disease. Mice carrying mutations that cause ADSL deficiency in humans will be informative as to the effects of these mutations both during embryogenesis and on the brain, possibly leading to therapies for this disease in the future.


Structural characterization of arabinogalactan extracted from Ixeris chinensis (Thunb.) Nakai and its immunomodulatory effect on RAW264.7 macrophages.
An arabinogalactan (ICPA) was isolated from the water extract of Ixeris chinensis (Thunb.) Nakai. ICPA was mainly composed of galactose and arabinose with minor amount of glucose. The molecular weight of ICPA was 58.1 kDa. Structural analysis by methylation and NMR spectroscopy indicated that ICPA contained α-D-Glcp(1→, →5)-α-L-Araf(1→, β-D-Galf(1→, →3)-β-D-Galf(1→, β-D-Galp(1→, →6)-β-D-Galp(1→, and → 3,6)-β-D-Galp(1→, and that the molar ratio of the sugar residues was about 0.1:1.0:0.1:0.2:1.1:1.0:1.3, respectively. The immunomodulatory activity on RAW264.7 cells was measured in vitro. ICPA stimulated RAW 264.7 cell proliferation at 25-400 μg/mL in a dose-dependent manner. ICPA also enhanced phagocytosis, and the secretion of NO, TNF-α, and IL-6 by the cells. The results suggested the potential utilization of ICPA as an immunomodulatory agent.


Pharmacology of nimodipine. A review.
The major pharmacological findings with nimodipine reviewed in this chapter are summarized in TABLE 3. On the basis of these findings, the following conclusions appear to be justified: 1. Nimodipine is a 1,4-dihydropyridine with Ca2+ channel antagonist properties. It is more lipophilic than nifedipine and its distribution volume in the brain of rats is higher than that of nifedipine. 2. Nimodipine dilates cerebral vessels at considerably lower concentrations than required for dilatation of peripheral blood vessels. It can, therefore, improve cerebral blood flow at doses that do not reduce systemic arterial pressure. 3. Nimodipine inhibits 45Ca uptake into vascular smooth muscle and neuronal cells. 4. Nimodipine antagonized postischemic cerebral hypoperfusion in cats and prolonged life of stroke-prone spontaneously hypertensive (SH) rats at doses that have little if any effect on arterial blood pressure. 5. Nimodipine reduced neurological deficits in dogs and monkeys with global cerebral ischemia. In focal ischemia (MCA occlusion) nimodipine reduced infarct size and neurological deficits and normalized intracellular brain pH. 6. In addition to its cerebral vasodilator effect, nimodipine appears to have a direct neuronal action. The suggested evidence for the neuronal site of action of nimodipine includes: a. Presence of nimodipine binding sites in brain. b. Blockade by nimodipine of Ca2+ channels in single nerve cells and in endocrine cells under conditions of sustained depolarization. c. Interactions with centrally acting drugs. d. Effects on release of various neurotransmitters from neuronal tissue or endocrine cells. e. Demonstration of anticonvulsant action of nimodipine. f. Blockade of behavioral effects of Ca2+ channel agonists by calcium channel antagonists.


Left ventricular-coronary sinus fistula following repeated mitral valve replacements.
After mitral valve replacement, symptomatic deterioration and new murmurs characterstistic of atrioventricular valvular regurgitation are usually the result of periprosthetic leaks or prosthetic dysfunction with or without endocarditis. In the case which we are reporting, an iatrogenic fistula between the left ventricle and coronary sinus was responsible for the murmur and symptoms. This type of shunt has not been previously reported. Thorough debridement of the anulus is necessary during mitral valve replacement; additionally, previously implanted prostheses are occasionally embedded in the endocardial wall and must be excised. Hematoma in the atrioventricular groove and perforations of the posterior left ventricular wall are widely recognized complications of mitral valve replacement. Similar mechanisms of injury can cause other problems such as left ventricular-right atrial communications and the unique anatomic shunt described in this report.


Group B streptococcal infections of the central nervous system in infants with myelomeningocele.
Three cases of group B streptococcal infection of the central nervous system (CNS) occurred among 147 neonates treated for myelomeningocele at The Children's Hospital in Boston from 1970 to 1985. This pathogen was responsible for one third of the nine CNS infections noted in these patients over the 15-year study period. All three children with group B streptococcal CNS infections subsequently required multiple CNS shunting procedures and prolonged hospitalizations. Two children suffered major neurological sequelae. In neonates with myelomeningocele, group B streptococci have direct access to the CNS, perhaps explaining the high incidence of serious meningitis and ventriculitis in this population. Antibiotic prophylaxis for early myelomeningocele repair should be adjusted accordingly.


Effects of clonidine and BS 100-141 on the EEG sleep pattern in rats.
The effects of the peripheral and central alpha-adrenoceptor stimulant and antihypertensive agents clonidine and BS 100-141 (N-amidino-2[2,6-dichlorophenyl]acetamide - HCl) on EEG sleep patterns in rats and on blood pressure in pithed rats have been investigated. Whereas both compounds abolished paradoxical sleep (PS), clonidine, in contrast to BS 100-141, markedly increased the sleeping time. Both drugs caused a dose-dependent increase in the blood pressure of pithed rats. The pressor action was abolished by the alpha-adrenoceptor blocking agent phentolamine, but was not influenced by reserpine, indicating a direct stimulation of vascular alpha-adrenoceptors by both drugs. It is suggested that sedation or sleep induction by adrenergic drugs cannot be explained exclusively by an action on central alpha-adrenoceptors. Rather, the findings suggest that such an action may be involved in the modulation of PS.


Ovicidal effect of chitinase and protease enzymes produced by soil fungi on the camel tick Hyalomma dromedarii eggs (Acari:Ixodidae).
The aim of this study was to evaluate the effect of chitinase and protease enzymes produced by environmentally safe soil Fungi; Aspergillus sp. NRC 4/5H; Mucor sp. NRC 5; Trichoderma sp. NRC 4/56; Aspergillus sojae; Mucor ranosisinus; Aspergillus oryzae on embryo development of the camel tick Hyalomma dromedarii eggs. The experiment was carried out on the 7 day aged eggs. Concentrations of the chitinase and protease crude enzymes [1:1, 1:2, 1:3, 1:4 and 1:5 (v/v)] were prepared from six stock solutions whose concentrations were 5 units/ml each. The prepared chitinase and protease enzymes produced by soil fungi were tested in vitro study for eradication of ticks. Ovicidal effect of the chitin concentrations of extracellular lytic enzymes (chitinase) produced by Aspergillus sp NRC 4/5H, Mucor sp. NRC 5, Trichoderma sp. NRC 4/56 were tested on H. dromedarii eggs. The results showed that the ovicidal effect increased with increasing the chitin concentration in case of Mucor sp. NRC 5. The maximum inhibitory effect which ranged from 95.3 to 100 % was at concentrations ranging from 1:3 to 1:5 ml/ml, respectively. The results of protease enzymes produced by A. sojae, M. ranosisinus and A. oryzae revealed that, it is highly effective in all concentrations on H. dromedarii eggs. It is indicated that the chitinase and protease enzymes produced by fungal species could be used for biological control of the camel tick infestation to avoid the use of carcinogenic chemical.


Uncovering the end uses of the rare earth elements.
The rare earth elements (REE) are a group of fifteen elements with unique properties that make them indispensable for a wide variety of emerging and conventional established technologies. However, quantitative knowledge of REE remains sparse, despite the current heightened interest in future availability of the resources. Mining is heavily concentrated in China, whose monopoly position and potential restriction of exports render primary supply vulnerable to short term disruption. We have drawn upon the published literature and unpublished materials in different languages to derive the first quantitative annual domestic production by end use of individual rare earth elements from 1995 to 2007. The information is illustrated in Sankey diagrams for the years 1995 and 2007. Other years are available in the supporting information. Comparing 1995 and 2007, the production of the rare earth elements in China, Japan, and the US changed dramatically in quantities and structure. The information can provide a solid foundation for industries, academic institutions and governments to make decisions and develop strategies.


Microtubule-driven nuclear rotations promote meiotic chromosome dynamics.
At the onset of meiosis, each chromosome needs to find its homologue and pair to ensure proper segregation. In Drosophila, pairing occurs during the mitotic cycles preceding meiosis. Here we show that germ cell nuclei undergo marked movements during this developmental window. We demonstrate that microtubules and Dynein are driving nuclear rotations and are required for centromere pairing and clustering. We further found that Klaroid (SUN) and Klarsicht (KASH) co-localize with centromeres at the nuclear envelope and are required for proper chromosome motions and pairing. We identified Mud (NuMA in vertebrates) as co-localizing with centromeres, Klarsicht and Klaroid. Mud is also required to maintain the integrity of the nuclear envelope and for the correct assembly of the synaptonemal complex. Our findings reveal a mechanism for chromosome pairing in Drosophila, and indicate that microtubules, centrosomes and associated proteins play a crucial role in the dynamic organization of chromosomes inside the nucleus.


CLIPPERS Responsive to Cladribine as a Durable Steroid-Sparing Agent.
We report a case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) who achieved durable and steroid-free remission after IV cladribine. A 25 year-old man presented with progressively worsening headaches, polydipsia, dysarthria, diplopia and vertigo, and obtundation requiring respiratory support. CSF revealed lymphocytosis, and MRI revealed a perivascular pattern of punctate enhancement involving the pons. An extensive workup for inflammatory, autoimmune, infective, and malignant explanations was unrevealing. He responded dramatically to steroids, compatible with CLIPPERS as a diagnosis of exclusion. Attempts to wean prednisone over the ensuing year resulted in 2 clinical relapses and persistent punctate enhancement. Given significant steroid side effects, steroid-sparing agents were considered. IV cladribine IV (0.0875 mg/kg adjusted body weight daily × 4 days at 0, 4, 8, and 16 months) was selected, given its favorable side effect profile including lower risks of malignancy and infertility and the potential for long-lasting effects. The only side effect was short-term fatigue at the time of infusion. At 20 months after cladribine initiation, he was able to wean-off prednisone altogether. Now at 33 months, he remains in clinical and MRI remission. Cladribine is a rational candidate steroid-sparing treatment for presumed neurologic autoimmune conditions such as CLIPPERS. This study provides Class IV evidence that cladribine is a steroid-sparing treatment consideration in CLIPPERS.


Synthesis of noncollagenous extracellular matrix proteins during development of mineralized nodules by rat periodontal ligament cells in vitro.
To characterize the mineralized nodules produced by rat periodontal ligament (PDL) cells in vitro, we have studied the synthesis and distribution of mineralized tissue proteins at various stages of nodule formation. PDL cells were obtained from coagulum in the socket at 2 days after tooth extraction and cultured in Dulbecco's Modified Eagles Medium (DMEM) containing 10% fetal bovine serum and antibiotics. Confluent cells were grown in the presence of ascorbic acid (50 micrograms/ml), dexamethasone (5 microM), and beta-glycerophosphate (10 mM) for 3 weeks. Four stages showing distinct morphological characteristics during development of mineralized nodules were identified. Protein synthesis and deposition of proteins into the matrix were studied during these stages by metabolic labeling with [35S]methionine for 24 hours. Large quantities of SPARC (secreted protein, acidic and rich in cysteine) were synthesized by confluent cells but decreased during the progress of mineralized nodule formation. Two forms of osteopontin (OPN) (67 kDa and 61 kDa) were synthesized in comparable quantities by confluent cells; OPN and bone sialoprotein (BSP) were induced by dexamethasone and represented the major proteins in the mineralized matrix. The 67 kDa form of OPN was the predominant species in the mineralized matrix. Both OPN and BSP were localized by immunogold electron microscopy on globular as well as fused electron-dense structures at sites of tissue mineralization.


Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.
There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. URL: https://www. gov; Unique identifier: NCT02942407.


Fitness costs associated with chlorantraniliprole resistance in Spodoptera exigua (Lepidoptera: Noctuidae).
The field population of Spodoptera exigua, an intermittently occurring polyphagous pest, has developed resistance to chlorantraniliprole, while whether or not such resistance carries fitness costs remains poorly understood. Here we selected six generations of the Leshan population (LS-P) by two-way selecting method, and obtained a highly resistant strain (CH-RE) and resistant degeneration strain (CH-SE) sharing a similar genetic background. After that fitness costs were evaluated by comparing the life history characteristics of CH-RE, CH-SE and the laboratory susceptible strain (SE-Lab) via the age-stage two-sex life table method. The resistance ratio of CH-RE and CH-SE were 226.69-fold and 3.72-fold, respectively, and the estimated realized heritability (h2 ) of CH-RE was 0.058. Compared with CH-SE, the duration of pre-adult, the longevity of adult, adult preoviposition period (APOP) and average generation time (T) of CH-RE had significantly increased, but the oviposition days, average fecundity, intrinsic growth rate (r), weekly growth rate (λ) and reproductive rate (R0 ) decreased significantly. Moreover, the relative fitness of CH-RE was 0.25, and showed fitness costs. Concurrently, the fecundity of CH-SE was slightly lower than SE-Lab, but there was no significant difference in r, λ and R0 , and the fitness (1) of CH-SE was similar to SE-Lab (1.02), which was no fitness cost. These findings represent that chlorantraniliprole resistance in S. exigua has a fitness cost, and the fitness cost will disappear with the recovery of sensitivity when the insecticide is stopped for field populations, supporting that such resistance would be managed by switching off the selection pressure with rotation with alternate insecticides. © 2020 Society of Chemical Industry.


Synthesis of (3S,4S)-4-aminopyrrolidine-3-ol derivatives and biological evaluation for their BACE1 inhibitory activities.
Synthesis, SAR study and BACE1 inhibitory activity of (3S,4S)-4-aminopyrrolidine-3-ol derivatives (2) were described. The compound 7c exhibited more inhibition activity than 11a (IC50: 0.05μM vs 0.12μM, respectively), but the latter was more effective in cell-based assay (IC50: 1.7μM vs 40% inhibition by 7c @ 10μM) due to the relatively higher cell permeability. Most of the compounds showed high selectivity over BACE2 and cathepsin D. This work will provide useful information for further structural modifications to develop potent BACE1 inhibitors in cell.


Effects of the noradrenergic neurotoxin DSP-4 on the expression of α1-adrenoceptor subtypes after antidepressant treatment.
We have previously reported that chronic imipramine and electroconvulsive treatments increase the α(1A)-adrenoceptor (but not the α(1B) subtype) mRNA level and the receptor density in the rat cerebral cortex. Furthermore, we have also shown that chronic treatment with citalopram does not affect the expression of either the α(1A)- or the α(1B)-adrenoceptor, indicating that the previously observed up-regulation of α(1A)-adrenoceptor may depend on the noradrenergic component of the pharmacological mechanism of action of these antidepressants. Here, we report that previous noradrenergic depletion with DSP-4 (50 mg/kg) (a neurotoxin selective for the noradrenergic nerve terminals) significantly attenuated the increase of α(1A)-adrenoceptor mRNA induced by a 14-day treatment with imipramine (IMI, 20 mg/kg, ip) and abolished the effect of electroconvulsive shock (ECS, 150 mA, 0.5 s) in the prefrontal cortex of the rat brain. The changes in the receptor protein expression (as reflected by its density) that were induced by IMI and ECS treatments were differently modulated by DSP-4 lesioning, and only the ECS-induced increase in α(1A)-adrenoceptor level was abolished. This study provides further evidence corroborating our initial hypothesis that the noradrenergic component of the action of antidepressant agents plays an essential role in the modulation of α(1A)-adrenoceptor in the rat cerebral cortex.


Celebrating the life and research of BNA Past-President Colin Blakemore.
Professor Sir Colin Blakemore was a remarkable neuroscientist, persuasive communicator, and brave advocate for animal research who, sadly, passed away in June 2022 from amyotrophic lateral sclerosis. His work helped establish the concept of neuronal plasticity, which was fundamental to our understanding of the postnatal brain and continues to impact our outlook on neurodegenerative disorders. The BNA2023 Festival of Neuroscience dedicated its last plenary session in his honour, bringing together five prominent neuroscientists whose careers were shaped by Professor Blakemore. Here, we summarise the speakers' reflections on how Colin's support, generosity, and foresight influenced their academic paths, inspired their research, and changed their outlook on life.


A prospective observational study of video laryngoscopy-guided coaching in the pediatric intensive care unit.
There are limited data on the use of video laryngoscopy for pediatric patients outside of the operating room. Our primary aim was to evaluate whether implementation of video laryngoscopy-guided coaching for tracheal intubation is feasible with a high level of compliance and associated with a reduction in adverse tracheal intubation-associated events. This is a pre-post observational study of video laryngoscopy implementation with standardized coaching language for tracheal intubation in a single-center, pediatric intensive care unit. The use of video laryngoscopy as a coaching device with standardized coaching language was implemented as a part of practice improvement. All patients in the pediatric intensive care unit were included between January 2016 and December 2017 who underwent primary tracheal intubation with either video laryngoscopy or direct laryngoscopy. The uptake of the implementation, sustained compliance, tracheal intubation outcomes including all adverse tracheal intubation-associated events, oxygen desaturations (<80% SpO2), and first attempt success were measured. Among 580 tracheal intubations, 284 (49%) were performed during the preimplementation phase, and 296 (51%) postimplementation. Compliance for the use of video laryngoscopy with standardized coaching language was high (74% postimplementation) and sustained. There were no statistically significant differences in adverse tracheal intubation-associated events between the two phases (pre- 9% vs. post- 5%, absolute difference -3%, CI95 : -8% to 1%, p = .11), oxygen desaturations <80% (pre- 13% vs. post- 13%, absolute difference 1%, CI95 : -6% to 5%, p = .75), or first attempt success (pre- 73% vs. post- 76%, absolute difference 4%, CI95 : -3% to 11%, p = .29). Supervisors were more likely to use the standardized coaching language when video laryngoscopy was used for tracheal intubation than with standard direct laryngoscopy (80% vs. 43%, absolute difference 37%, CI95 : 23% to 51%, p < .001). Implementation of video laryngoscopy as a supervising device with standardized coaching language was feasible with high level of adherence, yet not associated with an increased occurrence of any adverse tracheal intubation-associated events and oxygen desaturation.


Repair in normal tissues and the possible relevance to radiotherapy.
Between each fraction in radiotherapy, there is repair and recovery of both normal and neoplastic tissues. Several different types of repair have been identified. Some relate specifically to the effect of changing the number of fractions and others to the overall treatment time. Each will be discussed and particular attention will be paid to slow repair phenomena which have recently been the subject of much interest.


ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro.
Oncogenic drivers such as mutated EGFR are the preferred targets in modern drug development. However, restoring the lost function of tumor suppressor proteins could also be a valid approach to combatting cancer. ITIH5 has been revealed as a potent metastasis suppressor in both breast and pancreatic cancer. Here, we show that ITIH5 overexpression in MDA-MB-231 breast cancer cells can also locally suppress tumor growth by 85%, when transplanted into the mammary fat pad of nude mice. For a potential drug development approach, we further aimed to define downsized ITIH5 polypeptides that still are capable of mediating growth inhibitory effects. By cloning truncated and His-tagged ITIH5 fragments, we synthesized two recombinant N-terminal polypeptides (ITIH5681aa and ITIH5161aa), both covering the ITI heavy chain specific "vault protein inter-alpha-trypsin" (VIT) domain. Truncated ITIH5 variants caused dose-dependent cell growth inhibition by up to 50% when applied to various cancer cell lines (e.g., MDA-MB-231, SCaBER, A549) reflecting breast, bladder and lung cancer in vitro. Thus, our data suggest the substantial role of the ITIH5-specific VIT domain in ITIH5-mediated suppression of tumor cell proliferation. As extracellularly administered ITIH5 peptides mimic the growth-inhibitory effects of the full-length ITIH5 tumor suppressor protein, they may constitute the basis for developing anticancer drugs in the future.


Endoscopic correction of VUR using vantris as a new non-biodegradable tissue augmenting substance: three years of prospective follow-up.
To evaluate the efficacy of Vantris in children with vesicoureteral reflux (VUR) after 3 years of prospective follow-up. Over the last 3 years, 109 children (72 girls and 37 boys) with a mean age of 6.2 ± 3.4 years (mean ± SD) underwent endoscopic correction of reflux using Vantris. VUR was unilateral in 53 and bilateral in 56 patients comprising 165 renal refluxing units (RRUs). Of these, primary VUR was present in 139 RRUs (84.2%) and 26 (15.8%) were complex cases. Ultrasound scan was performed 1 month, 1 year, and 3 years after injection, and voiding cystourethrogram (VCUG) was performed 3 months, 1 year, and 3 years after endoscopic correction. The reflux was corrected in 153 RRUs (92.7%) after a single injection and in 7 RRUs (4.2%) after a second injection. In 5 RRUs (3.1%), VUR downgraded to grade I (3 RRUs) and grade II (2 RRUs) and they were taken off antibiotic prophylaxis. Two patients (1.8%) had afebrile urinary tract infections (UTIs) and 2 patients (1.8%) developed febrile UTI. VCUG was performed in 32 of 71 children (39.1%) who completed 1 year and in 6 of 15 (40%) who completed 3 years of follow-up. None showed VUR recurrence. Ultrasound scan demonstrated normal appearance of kidneys in all but 2 patients (1.8%). One patient required stent insertion because of deterioration of hydronephrosis that resulted in complete resolution of obstruction and another patient required ureteral reimplantation. Our data show that Vantris injection provides a high level of reflux resolution with good clinical outcome during prospective follow-up.


The Relationship Between Quadriceps Femoris Muscle Function and MRI-Derived Water Diffusion and Adipose Tissue Measurements in Young Healthy Males.
Water diffusion and adipose tissue in a muscle can be evaluated by MRI. However, determining which quadriceps femoris muscle (QM) characteristics independently predict peak knee extension torque during maximum voluntary isometric contractions (MVICs), individual muscle activity during MVICs and sit-to-stand transitions is unknown. To determine which QM characteristics predict knee extension muscle strength and individual muscle activity. Prospective, cross-sectional. A total of 20 healthy males (aged 22-40 years) with a physical activity level <1 hour/week. 1.5-T, diffusion-weighted fast spin-echo echo-planar imaging and T1-weighted fast spin-echo sequences. The vastus medialis (VM), vastus lateralis (VL), rectus femoris (RF), and vastus intermedius were segmented in a single axial diffusion-weighted image and T1-weighted image at the right mid-thigh region. λ1-3 and fractional anisotropy (FA), and the percentage of intramuscular adipose tissue (IMAT) were measured. The knee extension peak force during MVICs was measured by a dynamometer, and the torque was calculated at the peak force × length. The ratios of the individual muscle activity to the total muscle (VM, VL, and RF) during MVICs and sit-to-stand transitions were assessed using surface electromyography. Regression analysis was conducted to identify the predictors of peak knee extension torque and of individual muscle activity ratios. A P value < 0.05 was considered statistically significant. The RF λ1 significantly predicted the peak knee extension torque (β = -0.51). The IMAT percentage of the VM significantly predicted the VM muscle activity ratio during the MVIC and sit-to-stand transition (β = -0.82 and β = -0.61, respectively), whereas the ratio of the VM λ1 to the whole QM λ1 significantly predicted the VM muscle activity ratio during the sit-to-stand transitions (β = 0.35 and β = 0.46, respectively). The RF λ1 may allow to estimate peak knee extension muscle torque, and the VM IMAT and λ1 may predict muscle activity in youth. 3. Stage 3.


The significance of carnivory for the fitness of Drosera in its natural habitat : 2. The amount of captured prey and its effect on Drosera intermedia and Drosera rotundifolia.
A field study of two carnivorous plant species, Drosera intermedia and D. rotundifolia, was carried out in a small silting-up bog in Southern Bavaria (FR Germany). Various parameters of undisturbed individuals of both species were measured for a period of two years and subjected to a partial correlation analysis. The importance of prey as a limiting factor for various fitness parameters was confirmed for both species. Other factors may occasionally also be limiting, e.g. assimilation area and water supply. Benefits obtained from the prey are partly transferred to the next year via the winter bud. The importance of the relative demonstrated: Plants of D. rotundifolia showed higher fitness values in higher positions, those of D. intermedia in lower positions. Growth characteristics of both species tended to influence the height of their own position in a corresponding direction: D. intermedia downwards and D. rotundifolia upwards. In both species negative effects of intraspecific neighbourhood were evident, whereas interspecific effects were not detectable. Plants of D. intermedia tend to influence their neighbourhood situation by changing their position by rhizome-like stem growth. In D. intermedia the decision to reproduce by seeds or axillary buds seems to be made at least partially already in the year before. D. rotundifolia was only observed reproducing by seeds. In spite of different catching characteristics (plant shape, plant size, microhabitats, prey spectra), the general catching success, measured as prey biomass per plant biomass, was equal in both species of sundew. This agrees with earlier findings that in this bog both species have the same biomass per ground area.


Selective FL quenching or enhancing of diimine ligands by guanine.
Diimine ligand (DL) 1 significantly exhibited the fluorescence quenching upon binding to guanine. Changing at the para-substituent of the phenyl ring from the hydroxyl to bromo groups reversely enhanced the fluorescence in the presence of guanine. The reverse in the fluorescence selectivity indicated the profound effect of the substituent at the para-position of the phenyl ring. The simple synthesis of DL 1 and DL 2 with good selectivity for guanine offers these DLs as promising compounds for chemosensors of other guanine derivatives.


Expression of stem cell markers as useful complementary factors in the early detection of urinary bladder carcinogens by immunohistochemistry for γ-H2AX.
We previously demonstrated that immunohistochemistry for γ-H2AX, a biomarker of DNA damage, is useful for early detection of urinary bladder carcinogens in rats. In a 28-day repeated-dose study, γ-H2AX was shown to have high sensitivity for detection of bladder carcinogens. However, no reports have evaluated whether a combination of multiple biomarkers may further improve sensitivity. Accordingly, in this study, we aimed to evaluate the applicability of bladder tissue and cancer stem cell markers, including cytokeratin 14 (KRT14), aldehyde dehydrogenase 1A1 (ALDH1A1), and cluster of differentiation 44 (CD44), as complementary markers for early detection of bladder carcinogens. Bladder samples obtained from male F344 rats orally treated with 14 bladder carcinogens and five nonbladder carcinogens for 28 days were used for immunohistochemical analysis of stem cell markers. In the bladder carcinogen-treated rats, increases in KRT14, ALDH1A1, and CD44 expression were observed in 9, 10, and 10 out of 14 groups, respectively, whereas the five nonbladder carcinogens did not cause upregulation of these markers. Although most epithelial cells with KRT14 or ALDH1A1 expression were also positive for CD44, KRT14 and ALDH1A1 expression were mutually exclusive. Twelve bladder carcinogens showed increases in at least one of the three markers, indicating that the combined evaluation showed higher sensitivity than the use of individual markers alone. Importantly, two of three bladder carcinogens that did not induce γ-H2AX immunostaining showed stem cell marker expression. Our results demonstrated that these stem cell markers may be useful as complementary markers for γ-H2AX in evaluation of bladder carcinogens.


Experimental and bioinformatic investigation of the proteolytic degradation of the C-terminal domain of a fungal tyrosinase.
Proteolytic processing is a key step in the production of polyphenol oxidases such as tyrosinases, converting the inactive proenzyme to an active form. In general, the fungal tyrosinase gene codes for a ~60 kDa protein that is, however, isolated as an active enzyme of ~40 kDa, lacking the C-terminal domain. Using the secreted tyrosinase 2 from Trichoderma reesei as a model protein, we performed a mutagenesis study of the residues in proximity of the experimentally determined cleavage site which are possibly involved in the proteolytic process. However, the mutant forms of tyrosinase 2 were not secreted in a full-length form retaining the C-terminal domain, but they were processed to give a ~45 kDa active form. Aiming at explaining this phenomenon, we analysed in silico the properties of the C-terminal domain of tyrosinase 2, of 23 previously retrieved homologous tyrosinase sequences from fungi (C. Gasparetti, G. Faccio, M. Arvas, J. Buchert, M. Saloheimo, K. Kruus, Appl. Microbiol. Biotechnol. 86 (2010) 213-226) and of nine well-characterised polyphenol oxidases. Based on the results of our study, we exclude the key role of specific amino acids at the cleavage site in the proteolytic process and report an overall higher sensitivity to proteolysis of the linker region and of the whole C-terminal domain of fungal tyrosinases.


Hormonal and genetic risk factors for breast cancer in a subset of the Karachi population.
Appraisement of vitamin D receptor (VDR) polymorphisms is thought to be crucial to detect and make approaches targeting groups at risk for breast cancer (BC). Moreover, an understanding of genetic susceptibility can allow us to foresee several risk factors. The objective of our research is to evaluate the T to C base shift within TaqI (rs731236) in exon 9 and the A to G transition within Bsm1 (rs1544410) in intron 8 of the VDR gene as risk factors among BC patients. The study involved 150 BC patients with a definite histological diagnosis. Controls were age-matched. DNA samples of Taq1 and Bsm1 were amplified according to the programmed protocol using a thermal cycler. The amplified PCR products were digested with Taq1 and Bsm1 restriction endonuclease enzymes. RFLP fragments were observed under UV light using 2% agarose gel and 0.5 ug/mL Ethidium bromide. The highest number of BC patients (32.7%) were in the 36 to 45 age group. Ethnicity and parity were found to be statistically significant. TaqI polymorphisms showed the highest genotypic frequency for TC (Tt) at 49 (32.7%), and there were 18 patients (12.0%) and controls with high statistical significance (OD 3.6, CI 2-6.4) and a p-value < 0.0001. However, for the Bsm1 genotype, the A (B) allele may be linked with protection from BC in individuals with the AA (BB) genotype. A positive association was found between VDR genotypes and BC in a collective assay of Taq1 and BsmI. These results need further authentication in large cohort studies prior to applying these SNPs as promising BC markers in the Pakistani populace.


Tumor-like manifestation of endosalpingiosis in uterus: a case report.
We report on a 50-year-old female patient affected by breast cancer and a tumorous lesion located in the subserosal and intramural part of the uterine fundus. It consisted of glandular and cystic forms lined with epithelium of the tubal type. We describe the clinical, macroscopic, and histological features of this rare non-neoplastic lesion, classified as florid endosalpingiosis (ES) and belonging to the spectrum of Müllerian lesions. The discussion focuses on its morphological characteristics, the differential diagnosis, and the potential reasons leading to its origin. To the best of our knowledge, this is the fifth case of florid ES of uterus reported in the English literature.


The Effectiveness of Postoperative Radiotherapy in Patients With Completely Resected Thymoma: A Meta-Analysis.
This meta-analysis aimed to provide a pooled analysis of clinical studies correlating postoperative radiotherapy (PORT) with survival in patients with completely resected thymoma. According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. An electronic search was conducted using online databases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used in this meta-analysis and were calculated from published survival data. A meta-analysis was conducted to assess the impact of PORT in completely resected thymoma on overall survival (OS), disease-free survival (DFS). and disease-specific survival (DSS). We also performed a subgroup analysis for OS of patients with stage II and stage III thymoma. Fourteen studies, which included 3,823 patients (2,096 patients who received PORT and 1,727 patients who did not receive PORT), met the selection criteria. From the available data, the thymoma patients with PORT who did not undergo resection did not have significantly improved OS (HR 0.99; 95% CI 0.87 to 1.13; p = 0.87), DFS (HR 1.21; 95% CI 0.97 to 1.51; p = 0.09), or DSS (HR 0.66; 95% CI 0.39 to 1.13; p = 0.13) compared with the patients who did not undergo PORT. However, our subgroup analysis showed a significant difference in OS in patients with stage II thymoma (HR 0.57; 95% CI 0.41 to 0.80; p = 0.001) and patients with stage III thymoma (HR 0.73; 95% CI 0.59 to 0.90; p = 0.004). Our results showed that for completely resected thymoma, PORT had no advantage in the overall group of patients but increased OS in the patients with stage II and III thymoma after a complete resection. On the basis of this study, PORT is beneficial in patients with stage II and III patients after a complete resection.


Impact of extending direct antiviral agents (DAA) availability in France: an observational cohort study (2015-2019) of data from French administrative healthcare databases (SNDS).
Direct antiviral agents (DAAs) became available in France in 2014 for the treatment of chronic hepatitis C (CHC) in patients with severe fibrosis (prioritized access); in 2017, DAAs became available to all CHC patients (universal access). We evaluated the impact of extending DAA availability on CHC patient care, especially on screening and time to treatment. Adult patients affiliated with the national health insurance system (SNDS) who were screened or treated for CHC between 2015 and 2019 were included. Algorithms were developed to identify at-risk subpopulations. The proportion of screened patients increased by 1% between 2015 and 2019, from 4·6% to 5·6%. The main nonexclusive risk factors for CHC were psychiatric conditions (27%), drug use (21%) and HIV positivity (11%); more than 50% of psychiatric patients had additional risk factors, mainly drug use with a 38% to 52% overlap.The median interval between the last screening test and treatment initiation decreased from 64 days in 2015 to 37 days in 2019.During the study period, 71,466 patients began CHC treatment (median age 55 [48-62]; 59% male), including 46% of "at-risk" patients with an increase in treatment initiation by 44% between 2015 and 2017 and a decrease of 46% between 2017 and 2019. Only 2,212 (3%) patients were treated at least twice.Among treated patients, the proportion of HIV+ patients decreased from 19% to 8% (prioritization consequence), while the proportions increased in the other at-risk subpopulations. we showed that policies extending DAA availability are associated with a screening increase and a decrease in the time to treatment initiation, while universal access led to a surge in treatment initiations in 2017. This study may also contribute to improving the cascade of care in the at-risk subpopulations. For instance, by pointing out their relative importance, especially for the psychiatric subpopulation, it highlights the importance to address them with tailored policies.


[IgA deficiency: clinical and laboratory evaluation of 60 patients from the "Instituto da Criança"].
To evaluate the main clinical findings that suggest DIgA and describe the complications observed. Sixty IgA deficient patients (IgA < 5mg/dl) were included, retrospectively. They were submitted to clinical evaluation and specific laboratorial tests. Their evolution was followed up to 15 years. The main complaints were: recurrent infections (50%), allergies (34%) or autoimmune diseases (10%). The respiratory system was the most affected by infections, and asthma and rhinitis were the most frequent allergic symptoms. No immunological impairment was detected, except for IgA deficiency. IgG and IgM levels were elevated in 50% of the patients. There was improvement of clinical symptoms and some of the patients became asymptomatic during the follow-up. IgA deficiency has a large clinical spectrum and early diagnosis would indicate prophylaxis for infections and allergy.


Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: effects on substance P contents of peripheral and central nervous system tissues.
The effects of s.c. capsaicin treatment on the contents of immunoreactive substance P (ISP) in several peripheral and central nervous system tissues were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Significant differences between vehicle-treated subjects of the WKY and SHR strains were observed in the ISP contents of both superior cervical and celiac sympathetic ganglia. Capsaicin pretreatment significantly reduced the ISP contents of both sympathetic ganglia in both strains. Capsaicin pretreatment significantly elevated the ISP contents of adrenal medullae only in rats of the SHR strain. The effects of s.c. capsaicin administration on the ISP contents of several selected isolated brain nuclei were also examined. No statistically significant strain or treatment differences in the SIP contents of the nucleus tractus solitarii nucleus locus ceruleus and periaqueductal central gray were observed. The ISP contents of the nucleus raphe magnus, periventricular preoptic area, and nucleus amygdaloideus medialis were significantly greater in vehicle-treated SHR rats than in vehicle-treated WKY animals. Capsaicin pretreatment significantly increased the ISP contents of both the periventricular preoptic area and nucleus amygdaloideus medialis in SHR rats. These results indicate that the effects of capsaicin treatment of the ISP contents of nervous systems tissues vary with both the tissues examined and the strain of rat. In addition, the previously reported long-lasting hypotensive effect produced by capsaicin in both the WKY and SHR strains may be related to the significant depletion of the ISP contents in peripheral sympathetic ganglia in both strains.


Neuropeptide Y as a putative modulator of the vagal effects on heart rate.
Neuropeptide Y is stored in sympathetic nerve terminals throughout the heart and has direct and indirect effects on cardiac function. Although neuropeptide Y has been shown to be released upon intense (16-30 Hz) cardiac sympathetic stimulation, we sought to determine whether effective quantities of neuropeptide Y were released from cardiac sympathetic neurons under more natural conditions. We recorded arterial pressure and cardiac cycle length in 29 anesthetized dogs. We assessed neuropeptide Y release by measuring the attenuation of vagally induced increases in cardiac cycle length (10 seconds every 2 minutes) after trains of sympathetic stimulation. We examined the effect of constant-frequency sympathetic stimulation (frequencies of 2, 5, 10, and 15 Hz, applied for train durations of 1, 3, and 5 minutes) on vagally induced chronotropic responses. We also determined the effect of varying the pattern of sympathetic stimulation. Both the magnitude and duration of the inhibition of the vagal effects on cardiac cycle length were augmented significantly by increases in the frequency or duration of sympathetic stimulation. In contrast, the inhibition of the vagally induced chronotropic responses was not significantly affected by changes in the pattern of sympathetic stimulation. We also characterized the role of adrenergic receptors. Phentolamine significantly increased the sympathetically mediated inhibition of the vagal effects on cardiac cycle length, but propranolol had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Incidence of pyometra in Swedish insured cats.
Pyometra is a clinically relevant problem in intact female cats and dogs. The etiology is similar in both animal species, with the disease caused by bacterial infection of a progesterone-sensitized uterus. Here, we studied pyometra in cats with the aim to describe the incidence and probability of developing pyometra based on age and breed. The data used were reimbursed claims for veterinary care insurance or life insurance claims or both in cats insured in a Swedish insurance database from 1999 to 2006. The mean incidence rate (IR) for pyometra was about 17 cats per 10,000 cat years at risk (CYAR). Cats with pyometra were diagnosed at a median age of 4 years and a significant breed effect was observed. The breed with the highest IR (433 cats per 10,000 CYAR) was the Sphynx, and other breeds with IR over 60 cats per 10,000 CYAR were Siberian cat, Ocicat, Korat, Siamese, Ragdoll, Maine coon, and Bengal. Pyometra was more commonly diagnosed with increasing age, with a marked increase in cats older than 7 years. The mean case fatality rate in all cats was 5.7%, which is slightly higher than corresponding reports in dogs of 3% to 4%. Geographical location (urban or rural) did not affect the risk of developing the disease. The present study provides information of incidence and probability of developing pyometra based on age, breed, and urban or rural geographical location. These data may be useful for designing cat breeding programs in high-risk breeds and for future studies of the genetic background of the disease.


Bacterial feeding by the rotifer Brachionus calyciflorus: Clearance and ingestion rates, behavior and population dynamics.
The rotifer Brachionus calyciflorus is capable of collecting and ingesting cells or short chains of a laboratory-grown bacterium Aerobacter aerogenes. Clearance rate, the volume of water effectively processed animal -1h-1, does not vary systematically with bacterial density between 0.01 and 100 μg dry weight ml-1. Consequently, ingestion rates are strongly density-dependent, reaching maximal values at the highest food densities tested. Bacterial feeding rates are consistently lower than those determined with larger food types, except in very dense cell suspensions. A. aerogenes in high concentration (100 μg ml-1) induces Brachionus to orient their pseudotrochal cirri to form screens over the buccal funnel; this behavior is at least four times less frequently observed at low (10 μg ml-1) food density. Despite its occurrence, pseudotrochal screening appears ineffective in regulating bacterial ingestion rate. B. calyciflorus can be cultured xenically for greater than 40 generations fed A. aerogenes alone, with no diminution in net reproductive rate or intrinsic rate of natural increase, and no lengthening in cohort generation time.


Distinct function of monoclonal antibody to TRAIL-R2 as potentiator or inhibitor of the ligand TRAIL-induced apoptosis.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically induces apoptosis in tumor cells but may be toxic to human hepatocytes. Although hepatocytes are susceptible to apoptotic signals mediated by TRAIL-receptor 2 (TRAIL-R2), we previously reported that some anti-TRAIL-R2 monoclonal antibodies (mAbs) produce little hepatocyte toxicity. Those mAbs neutralized the cytotoxic activity of TRAIL by inhibiting receptor-ligand binding. The hepatocyte-toxic mAbs did not compete with TRAIL for binding to TRAIL-R2, and potentiated ligand activity in both cancer cells and hepatocytes. A neutralizing antibody to TRAIL inhibited hepatocyte death by anti-TRAIL-R2 mAbs, suggesting that the toxicity may reflect their ability to potentiate membrane-bound TRAIL on hepatocytes.


Epidemiology of rheumatic diseases in Iran from analysis of four COPCORD studies.
To calculate the epidemiology of Rheumatic Diseases in Iran. The data of Tehran, Zahedan, Sanandaj (urban) and Tuyserkan (rural) stage Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) studies were gathered. The data were adjusted to the population number of the studied areas to represent Iran. The population of Iran is 75 149 669 (71.5% urban areas, males 50.4%) and of the mentioned area were respectively 10 000 000, 580 071, 311 444 and 109 262. The interviewed subjects were 10 291, 1565, 2100 and 5830. Male/female ratio was 0.9/1, 0.8/1, 08/1 and 0.8/1. Musculoskeletal complaints during the past 7 days (people aged ≥ 15 years) were detected in 44.7% of subjects. They were: shoulder 15.6%, wrist 10.4%, hands and fingers 10.2%, hip 8.3%, knee 27.4%, ankle 12.3%, toes 6.2%, cervical spine 14.2% and dorsolumbar spine 23.7%. Osteoarthritis (OA) was detected in 16.9%: knee 15.5%, hands 2.9% and hip 0.32%. Low back pain was found in 15.7%, sciatica in 0.94%, and soft tissue rheumatism in 4.6% (shoulder tenosynovitis 2.5%, frozen shoulder 0.56%, tennis elbow 1.2%, golf elbow 0.48%, de Quervain tenosynovitis 0.24%, trigger finger 0.2%, carpal tunnel syndrome 1.3%). Rheumatoid arthritis was detected in 0.37%, seronegative spondyloarthropathy in 0.24%, ankylosing spondylitis in 0.12%, systemic lupus erythematosus in 0.06%, Behcet's disease in 0.08%, fibromyalgia in 0.79% and gout in 0.13%. Compared to other COPCORD reports (17 countries), Iran gets the following rank: musculoskeletal complaints second, low back pain fourth, osteoarthritis second, knee osteoarthritis third, soft tissue rheumatism sixth, rheumatoid arthritis tenth, seronegative spondyloarthropathies fifth, gout eleventh and fibromyalgia fifth.


Laser treatment of feeder vessels in subfoveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green angiography.
This study aimed to determine whether the indocyanine green angiography (ICGA)-guided laser treatment of feeder vessels (FVs) may be useful in the management of the subfoveal choroidal neovascular membranes (CNVM) in patients with age-related macular degeneration (ARMD). Noncomparative case series. The authors considered a series of 15 patients with subfoveal CNVM in whom feeder vessels could be clearly detected by means of dynamic ICGA but not necessarily with fluorescein angiography (FA). On the basis of the indications of the pilot study, the authors also studied a second series of 16 patients with FVs smaller than 85 microm. Treatment of FV using argon green laser was performed. The ICGA was performed immediately after treatment, after 2, 7, 30 days, and then every 3 months, to assess FV closure. If an FV appeared to be still patent, it was immediately retreated and the follow-up was started again. The follow-up time ranged from 23 to 34 months for the pilot study and from 4 to 12 months for the second series. The obliteration of the membrane and change in visual acuity from baseline were measured. The effect on the treatment of the number and width of the FVs, and the size and location of the membrane, also was evaluated. In the pilot study, the CNVM was obliterated after the first treatment in only one patient, five patients needed more than one treatment, and obliteration failed in nine patients (40% success rate). The rate of success was affected by the width and number of the FVs. The success rate in the second series of 16 patients was higher (75%). The success of the laser treatment of FVs depends on their width, length, and number. Dynamic ICGA, which detects smaller FVs and makes it possible to control the laser effect and initiate immediate retreatment in the case of incomplete FV closure, should be considered mandatory for this type of treatment; a comparable success rate would have been unlikely using the other currently available methods of treating subfoveal CNVMs.


Maladaptive plasticity induced by morphine is mediated by hippocampal astrocytic Connexin-43.
Drug addiction is an aberrant learning process that involves the recruitment of memory systems. We have previously demonstrated that morphine exposure causes maladaptive synaptic plasticity which involved hippocampal glial cells, especially astrocytes. Morphine addiction has been associated with astrocytic connexin 43 (Cx43), which plays a role in synaptic homeostasis. This study aimed to examine the role of hippocampal astrocytic Cx43 in morphine-induced maladaptive plasticity as a mechanism of addiction. Male rats were injected with morphine (10 mg/kg) subcutaneously every 12 h for nine days to induce dependence. Cx43 was inhibited by TAT-Gap19 (1 μl/1 nmol) microinjection in the CA1 region of the hippocampus 30 min before each morning morphine injection. Field potential recordings were used to assess synaptic plasticity. fEPSP was recorded from the CA1 area following CA3 stimulation. Electrophysiological results showed that morphine treatment altered baseline synaptic responses. It also appears that morphine treatment augmented long-term potentiation (LTP) compared with the control group. Hippocampal astrocytic Cx43 inhibition, with the TAT-Gap19, undermines these effects of morphine on baseline synaptic responses and LTP. Despite this, long-term depression (LTD) did not differ significantly between the groups. Additionally, in the morphine-receiving group, inhibition of Cx43 significantly reduced the paired-pulse index at an 80-millisecond inter-pulse interval when assessing short-term plasticity. The results of this study demonstrated that inhibiting Cx43 reduced synaptic plasticity induced by morphine. It can be concluded that hippocampal astrocytes through Cx43 are involved in morphine-induced metaplasticity.


The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub-Saharan Africa.
Orofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa. We carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5' and 3' untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants. We observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175-2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants. This study demonstrates that exons 4 and 7 of IRF6 are mutational 'hotspots' in our cohort and that IRF6 mutants-induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high-risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms.


Novel unsupported and empirically supported therapies: patterns of usage among licensed clinical social workers.
While considerable attention has been focused in recent years on evidence-based practice, less attention has been placed on clinical social workers' choice to use ineffective or harmful interventions, referred to in the present paper as Novel Unsupported Therapies (NUSTs). The present study surveyed 400 Licensed Clinical Social Workers (LCSWs) across the United States in order to determine the extent of their usage of NUSTs, as well as their usage of conventional therapies that lacked support and empirically supported therapies (ESTs). Reasons for selecting interventions were also assessed. While the vast majority (97.5%) reported using some form of EST, 75% of our sample also reported using at least one NUST. Logistic regression analysis revealed that NUST usage was related to female gender and trauma specialization. A split plot ANOVA revealed that respondents rated positive clinical experience higher than published research as a reason for selecting an intervention. LCSWs with a CBT theoretical orientation rated research evidence more highly than those of other theoretical orientations. However, even within the group of LCSWs with a CBT orientation, clinical experience was rated more highly than research evidence. Implications for practice are discussed.


Counting glycans revisited.
We present an algorithm for counting glycan topologies of order n that improves on previously described algorithms by a factor n in both time and space. More generally, we provide such an algorithm for counting rooted or unrooted d-ary trees with labels or masses assigned to the vertices, and we give a "recipe" to estimate the asymptotic growth of the resulting sequences. We provide constants for the asymptotic growth of d-ary trees and labeled quaternary trees (glycan topologies). Finally, we show how a classical result from enumeration theory can be used to count glycan structures where edges are labeled by bond types. Our method also improves time bounds for counting alkanes.


Diagnosis of paediatric HIV infection in a primary health care setting with a clinical algorithm.
To determine the validity of an algorithm used by primary care health workers to identify children with symptomatic human immunodeficiency virus (HIV) infection. This HIV algorithm is being implemented in South Africa as part of the Integrated Management of Childhood Illness (IMCI), a strategy that aims to improve childhood morbidity and mortality by improving care at the primary care level. As AIDS is a leading cause of death in children in southern Africa, diagnosis and management of symptomatic HIV infection was added to the existing IMCI algorithm. In total, 690 children who attended the outpatients department in a district hospital in South Africa were assessed with the HIV algorithm and by a paediatrician. All children were then tested for HIV viral load. The validity of the algorithm in detecting symptomatic HIV was compared with clinical diagnosis by a paediatrician and the result of an HIV test. Detailed clinical data were used to improve the algorithm. Overall, 198 (28.7%) enrolled children were infected with HIV. The paediatrician correctly identified 142 (71.7%) children infected with HIV, whereas the IMCI/HIV algorithm identified 111 (56.1%). Odds ratios were calculated to identify predictors of HIV infection and used to develop an improved HIV algorithm that is 67.2% sensitive and 81.5% specific in clinically detecting HIV infection. Children with symptomatic HIV infection can be identified effectively by primary level health workers through the use of an algorithm. The improved HIV algorithm developed in this study could be used by countries with high prevalences of HIV to enable IMCI practitioners to identify and care for HIV-infected children.


Treatment of comminuted radial head fractures with personalized radial head prosthesis produced with 3-dimensional printing technology.
The radial head is the forearm's pivot point for supination-pronation. Although radial head resection can be performed in comminuted radial head fractures, radial head prosthesis has gained popularity in order to prevent possible complications such as progressive valgus instability in the elbow and secondary ulnocarpal impaction that may develop due to proximal displacement of the radius. As for radial head prostheses, standard prosthetic designs do not provide the same results in everyone, and the alignment of the radial head and radial neck angle cannot be fully achieved. We believe that the radial head must be reconstructed with a complete anatomical implant. We designed and applied personalized prostheses to our patients, and in this study, we wished to share the 2-year results of these patients. In this study, 23 patients who had comminuted radial head fractures had personalized radial head prostheses inserted. Preoperative variables such as type of injury, age, side, additional ligament injury, operation time, number of radial head parts, neck angle of individual prosthesis, stem length, and stem diameter were noted. The mean operating time was 26 ± 9 minutes. One month postoperatively, after physical therapy, elbow range of motion, loss of strength compared to the opposite joint, Mayo elbow scores, QuickDASH scores, and patient satisfaction were evaluated. Patients were evaluated 2 years postoperatively. QuickDASH and Mayo elbow scores were satisfactorily good (mean QuickDASH score: 9.091, mean Mayo score: 91.08). According to the results of the patient satisfaction questionnaire, 16 of the 23 patients reported excellent satisfaction, 5 patients good satisfaction, and 2 patients moderate satisfaction. None of the patients reported poor results. Since personalized radial head prosthesis consists of a single monoblock, its surgical application consists of a single step and has a short operating time. As the applications in the literature increase and more studies are conducted, this subject will be better understood. Our study demonstrated that these patients, whose anatomies were individually replicated, achieved good range of motion and patient satisfaction. In fact, none of the patients reported negative results. In comminuted radial head fractures, surgical implantation of personalized radial head prosthesis is a treatment modality with easy application, short operating time, and good functional results.


Local complications associated with labial salivary gland biopsy for diagnosis of Sjögren's Syndrome: A retrospective cohort study.
To describe local or systemic complications related to the labial salivary glands biopsy (LSGB) used as diagnostic tool for the diagnosis of Sjögren's Syndrome (SS). Clinical databases from a cohort of patients, who underwent LSGB with provisional clinical diagnosis of Sjögren's Syndrome, were retrospectively reviewed. Pain, assessed by registering the intake of analgesic drugs in the first week following the biopsy, and any further relevant clinical information regarding complications after biopsy were recorded. 50 patients received LSGB. 10 of them (9 women and 1 man) showed histopathological findings compatible with SS. Ten patient (20%) receiving labial biopsy developed local complications: three of them (6%) reported a sensory defect at the surgical site that lasted at most few weeks; three patients (6%) reported pain sensation needing the assumption of analgesic drugs, while one patient (2%) described a transient local burning sensation, which resolved in few days. Three patients (6%) showed cutaneous haematoma in the surgical area and two patients (4%) showed mild mucosal inflammation at the biopsy site. LSGB is associated with to few and mild complications and it is a useful tool in the diagnosis of SS. The complications usually resolved in few weeks after the biopsy. Key words:Sjögren's syndrome, labial salivary glands biopsy, adverse events, diagnosis.


Semiochemical delivery systems based on natural polymers to attract sand flies (Diptera: Psychodidae).
The successful use of semiochemicals to attract insects to traps is based on research on the most suitable compounds and their release profiles over time. Based on the group's promising results, matrices with a more adequate release profile and more eco-friendly properties for the release of 1-hexanol were developed. To use a more suitable prototype in the field, the most promising systems were added to a capsule and evaluated in a wind tunnel. Behavioral experiments were performed using the sand fly species, Lutzomyia longipalpis, to evaluate the efficacy of the proposed system. Different delivery systems were developed by varying the polymer (gellan gum and pectin) ratio, crosslinker (aluminum chloride) concentration, and glutaraldehyde removal.The delivery systems were loaded with 1-hexanol, and their release profiles were evaluated using gravimetric analysis under ambient and high-humidity conditions. When the matrix system was placed inside a plastic container, modulations in the active release profile were observed and the system could be reused. Actid attraction behaviors of the sand fly species, Lu. longipalpis, were evaluated in a wind tunnel when exposed to 1-hexanol-loaded release systems at different times. Among the four formulations evaluated, System 2 (gellan gum and pectin in a 1:1 ratio with 5% aluminum chloride) exhibited the most promising release profile, with greater uniformity and longer compound release time. The maximum 1-hexanol release uniformity was achieved over a longer time, mainly every 24 h, under both ambient and high-humidity conditions. System 2 can be reused at least once with the same structure. The wind tunnel trials exhibited efficient activation and attraction of Lu. longipalpis to 1-hexanol after 24, 48, and 72 h in System 2 placed inside the capsules. The polymeric matrix supplemented with 1-hexanol and introduced in plastic capsules showed promising results in attracting sand flies. This system can be used as a solution for other attractive compounds as well as in other applications where their release needs to be controlled or prolonged.


Cytomegalovirus appendicitis in an immunocompetent host.
Cytomegalovirus (CMV) is a common viral pathogen. Asymptomatic infection or a mononucleosis syndrome are the most common manifestations in otherwise healthy individuals. End-organ disease is rare in immunocompetent individuals. Here, we describe a case of CMV appendicitis in a patient without an immune-compromising condition.


Health-related quality of life and disease symptoms in postmenopausal women with HR(+), HER2(-) advanced breast cancer treated with everolimus plus exemestane versus exemestane monotherapy.
Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL. HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30 Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm symptom (BRAS) scales. Between-group differences in change from baseline were assessed using linear mixed models with selected covariates. Sensitivity analysis using pattern-mixture models determined the effect of study discontinuation on/before week 24. Treatment arms were compared using differences of least squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at each timepoint and overall. Clinicaltrials.gov: NCT00863655. Progression-free survival, survival, response rate, safety, and HRQOL. Linear mixed models (primary model) demonstrated no statistically significant overall difference between EVE + EXE and PBO + EXE for QL2 (LSM difference = -1.91; 95% CI = -4.61, 0.78), BRBS (LSM difference = -0.18; 95% CI = -1.98, 1.62), or BRAS (LSM difference = -0.42; 95% CI = -2.94, 2.10). Based on pattern-mixture models, patients who dropped out early had worse QL2 decline on both treatments. In the expanded pattern-mixture model, EVE + EXE-treated patients who did not drop out early had stable BRBS and BRAS relative to PBO + EXE. HRQOL data were not collected after disease progression. These analyses confirm that EVE + EXE provides clinical benefit without adversely impacting HRQOL in patients with HR(+) ABC who recurred/progressed on prior NSAIs versus endocrine therapy alone.


Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.
Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.


Cerebral Hypoperfusion and Other Shared Brain Pathologies in Ischemic Stroke and Alzheimer's Disease.
Newly emerged evidence reveals that ischemic stroke and Alzheimer's disease (AD) share pathophysiological changes in brain tissue including hypoperfusion, oxidative stress, immune exhaustion, and inflammation. A mechanistic link between hypoperfusion and amyloid β accumulation can lead to cell damage as well as to motor and cognitive deficits. This review will discuss decreased cerebral perfusion and other related pathophysiological changes common to both ischemic stroke and AD, such as vascular damages, cerebral blood flow alteration, abnormal expression of amyloid β and tau proteins, as well as behavioral and cognitive deficits. Furthermore, this review highlights current treatment options and potential therapeutic targets that warrant further investigation.


In vitro cytotoxicity to alveolar macrophages of tar from a low-Btu coal gasifier.
The cytotoxicity of fractions, subfractions, and some individual components present in tar from a low-Btu coal gasifier was determined in vitro with cultured dog alveolar macrophages. A subfraction of the tar which contained phenols and neutral nitrogen heterocycles was found to be a major contributor to the cytotoxic activity of the tar. Four compounds present in this subfraction were tested individually. Ranked from the most to the least toxic they were: 9-phenanthrol, 2-fluorenol, phenanthridone, and carbazole.


[Quality of ambulatory medical care in the context of age and care-dependency: Results of a cross-sectional analysis of German health claims data].
Care-dependent community dwelling people are vulnerable to deficits in medical care provided by the German statutory health insurance (GKV). Quality of care indicators (QIs) contribute to the identification of deficits and of potential for the optimization of care. To investigate the discriminatory ability of QIs in a population of elderly people with and without care dependency and different age structures, insights into the feasibility of such QIs based on health claims data are of interest. The aim of this study is an explorative approach to health claims based QIs for the ambulatory medical care of care-dependent elderly which can be used to optimize health care processes. This cross-sectional study used anonymised health claims data of a sample of statutory health insurance members from all German federal states of the year 2016. The sample consisted of 5,934,986 insured persons aged 65 years or older, who were community dwelling with (n = 785,135) or without care-dependency (n = 4,799,369) or who were residents of a nursing home (n = 350,482). 47 QIs focusing on ambulatory care-sensitive conditions such as, asthma, chronic obstructive pulmonary disease, cardiovascular diseases, diabetes mellitus type 2 and depression were calculated on a quarterly basis and are reported descriptively as the arithmetic mean of four quarters stratified by place of residence and age group. The majority of QI values vary between the observed groups with an overarching trend to the disadvantage of older individuals. Even though care-dependent insured persons show higher prevalence rates of the underlying diagnoses of the QIs (except for asthma diagnoses), they score more detrimental QI values than those without care-dependency. This finding holds true after stratification by age group. This study describes differences in the quality of medical care for elderly people. Considering prior empirical evidence of deficits in medical care, factors that act as barriers or facilitators of guideline-oriented medical care need to be investigated. The contribution of patients' preferences, access to medical care or prioritisation by medical and nursing care providers when initiating diagnostic or therapeutic procedures remains unclear. Methodical limitations of this study notably derive from the selection process of the observed groups using two stratification variables. For the further development of QIs other influencing factors on both an individual and a population-related level as well as the providers' ability to influence these factors need to be taken into account and incorporated in a risk-adjusted description of QIs. Measurement of ambulatory medical care of an elderly population based on health claims data is feasible and shows differences in care processes of older and care-dependent individuals if place of residency and level of care-dependency are considered. Further development of the QIs explored should incorporate a thorough methodical foundation, particularly with regard to risk adjustment. In addition, the contribution of individual and contextual factors on QIs remains to be examined with a view to the community-dwelling care-dependent elderly and their ongoing residency in this setting.


Stress survival islet 1 contributes to serotype-specific differences in biofilm formation in Listeria monocytogenes.
Listeria monocytogenes has a significant impact on the food industry by forming biofilms on food-processing equipment. Tandem analysis of whole-genome sequencing data with biofilm data from 166 environmental and food-related L. monocytogenes isolates has revealed serotypic and genetic factors that strongly correlate with adherence and biofilm formation, such as lineage, plasmid harbourage, a three-codon deletion in inlA and the presence of the stress survival islet 1 (SSI-1). Strains from serotype 1/2b, the majority of which contained SSI-1, formed the strongest biofilms, while serotype 4b strains, the majority of which did not contain SSI-1, formed the weakest biofilms. When serotype 1/2a was separated by its SSI-1 genotype, SSI-1-positive 1/2a strains demonstrated significantly higher capacity for biofilm formation after 3 days of growth at 30°C (P < 0·0001). Together, these findings indicate that SSI-1 may contribute to serotype-associated differences in the biofilm-forming capacity in L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: Parallel analysis of whole-genome sequences and serotype-specific data was performed to identify genetic markers that correlate with increased adherence and biofilm formation in L. monocytogenes. The analyses revealed the hitherto unrecognized role of SSI-1 in biofilm formation, contributing to deeper understanding of genetic factors that influence behaviour of the species in the food processing environment..


[Management of disabled patients in private households 1991--empirical analysis with data by the socioeconomic panel].
Domestic care can be provided by relatives, the social net or professional care givers. Even before the new German Care Insurance starts paying, the part of the family in care giving is immense. The readiness for care-giving exists in general, but depends on local and temporal possibilities. This is even clearer by differentiating between care-getting persons in single- and non-single households, irrespective of the degree of illness, are mainly looked after by relatives. The care for people living in single households is mostly provided by professionals.


Properties and sequence of a female-specific, juvenile hormone-induced protein from locust hemolymph.
In the fat body of Locusta migratoria, an RNA transcript of about 800 nucleotides has been detected that is specific to the adult female and dependent on induction by juvenile hormone (JH) or an analog. The corresponding cDNA has been cloned (lambda 21) and a 718-base pair sequence determined. It encodes a 196-amino acid polypeptide, including a signal peptide. An NH2-terminal sequence has 24 out of 28 amino acids identical with those of a previously described 19K locust hemolymph protein, but the remainder of the sequence shows no similarity. From adult female hemolymph, a 21-kDa protein, designated 21K protein, has been purified, with an NH2-terminal sequence exactly matching that deduced from clone lambda 21. This 21K protein is found only in the adult female, is dependent on induction by JH, and is assumed to represent the product of the lambda 21 gene. It shows no immunochemical cross-reaction with locust 19K protein, apolipophorin III, nor with vitellogenin (Vg). Its isoelectric point is pH 5.4; it contains some carbohydrate. 21K protein is synthesized in adult female fat body, accumulates in hemolymph, and is taken up into the developing oocytes in parallel with Vg. In locusts deprived of JH with precocene, production of 21K protein and of lambda 21-hybridizing transcripts is induced by the JH analog, methoprene, in parallel with Vg and its mRNA. Because of its sex-, stage-, and JH-dependent regulation, coordinate with Vg, the 21K protein will be valuable for analysis of gene expression.


Abdominal Pain After Pediatric Inflammatory Bowel Disease Diagnosis: Results From the ImproveCareNow Network.
Although abdominal pain is a hallmark symptom of pediatric inflammatory bowel disease (IBD), limited research has examined pain during the first year after diagnosis. The purpose of the present study is to examine prevalence, predictors, and impact of abdominal pain during the 12 months after pediatric IBD diagnosis using data from the ImproveCareNow (ICN) Network. Participants consisted of 13,875 youth (age 8-18 years, 44% female, 81% Caucasian) with IBD (65% Crohn's disease; 27% ulcerative colitis, 8% indeterminate colitis) enrolled in the ICN Network with data from clinic visits during the first year after diagnosis (1-22 visits; mean = 3.7). Multivariable mixed effects logistic regression models were conducted to analyze the presence versus the absence of abdominal pain, activity limitations, and decrements in well-being. The percentage of youth reporting abdominal pain decreased significantly during the first year after diagnosis and yet a sizeable group reported continued pain at 12 months (55.9% at diagnosis; 34.0% at 12 months). Multivariable analyses revealed that greater time since diagnosis (odds ratio [OR] = 0.98, P < 0.001), higher disease severity (OR = 11.84, P < 0.001), presence of psychosocial risk factors (OR = 2.33, P = 0.036), and female sex (OR = 1.90, P < 0.010) were significant correlates of continuing abdominal pain. Abdominal pain was significantly associated with decrements in well-being (OR = 5.11, P < 0.001) as well as limitations in activity (OR = 9.31, P < 0.001), over and above the influence of disease severity. Abdominal pain is prevalent and impactful, even when controlling for disease activity, during the first year after pediatric IBD diagnosis. Results from the present study can inform screening and tailored pain management intervention efforts in pediatric IBD.


Exudative bronchiolitis after lung transplantation.
After lung transplantation patients frequently develop small airways disease. Exudative bronchiolitis (EB) has not been described previously in this population. We describe a case series of patients who have developed EB after lung transplantation. We reviewed the clinical records and radiologic data of 99 patients who underwent single and bilateral lung transplantation. Data relating to ethnicity, transplant indication, human leukocyte antigen (HLA) status, complications and survival were recorded. The EB cohort, defined by high-resolution computed tomographic (HRCT) evidence of the disease, was compared with a group of patients who had not developed EB. The majority of patients had chronic obstructive pulmonary disease (COPD; n = 51), followed by cystic fibrosis (CF; n = 22), pulmonary fibrosis (n = 8), pulmonary hypertension (n = 7), bronchiectasis (n = 5), lymphangioleiomyomatosis (n = 3) and Eisenmenger's syndrome (n = 3). Thirteen patients were found to have developed EB. EB was more commonly seen in Maori and Pacific Island patients (p < 0.05). EB was significantly associated with early infection post-transplant (p < 0.05) and a history of Aspergillus infection (p < 0.005) or diabetes (p < 0.05). The patients with EB were also significantly more likely to develop bronchiolitis obliterans syndrome (p < 0.0005), bronchiectasis (p < 0.0005) or small airways disease (p < 0.05). Patients with EB had a varied response to treatment, with the majority showing improvement. EB was noted to occur after lung transplantation in a significant proportion of patients, but will not be detected unless HRCT is used routinely. It has been associated with patients' ethnicity, donor haplotype, infection and the development of airways disease. EB may be a prominent indicator of the likelihood of developing BOS.


[Preparation and identification of a monoclonal antibody against recombinant human L-type pyruvate kinase N].
To prepare and identify the monoclonal antibody (mAb) against pyruvate kinase N terminal (PK-N). BALB/C mice were immunized with immunogen PK-N-GST-tag. Then the spleen cells were isolated and fused with SP2/0 cells. After several rounds of detecting and cloning, the hybridoma cell strains secreting anti-PK-N mAb were obtained. Its specificity was evaluated with ELISA and Western blot, and the titer, immunoglobulin subtype and affinity of the mAb were measured. Two cell strains of hybridoma, 2B2E4G and 2C6F5, were obtained. The hybridoma cell strains secreting anti-PK-N mAb belonged to IgG2b subtype, with a mAb titer in ascetic fluid of 1 : 409600 and 1 : 102400, respectively. Their affinity reached 3.54 x 10(8) L/mol and 2.72 x 10(8) L/mol, respectively, as determined by ELISA. Western blot demonstrated that the mAb could specifically recognize the immunogen and the natural cell lysis protein. The cell immunohistochemistry proved that the antibody could recognize human L type pyruvate kinase expressed in the plasma of HL-7702 cell strain and paraffin slice of hepatoma. The success in anti-PK-N mAb preparation provides a foundation for further studies into glycolysis in normal condition and metabolic diseases.


[Hypoplastic left heart syndrome: 10 year experience with staged surgical management].
Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease in 95% of non-treated patients. Surgical staging is the main form of treatment, consisting of a 3-stage approach, beginning with the Norwood operation. Long term survival of treated patients is unknown in our country. 1) To review our experience in the management of all patients seen with HLHS between January 2000 and June 2012. 2) Identify risk factors for mortality. Retrospective analysis of a single institution experience with a cohort of patients with HLHS. Clinical, surgical, and follow-up records were reviewed. Of the 76 patients with HLHS, 9 had a restrictive atrial septal defect (ASD), and 8 had an ascending aorta ≤2mm. Of the 65 out of 76 patients that were treated, 77% had a Norwood operation with pulmonary blood flow supplied by a right ventricle to pulmonary artery conduit, 17% had a Norwood with a Blalock-Taussig shunt, and 6% other surgical procedure. Surgical mortality at the first stage was 23%, and for Norwood operation 21.3%. For the period between 2000-2005, surgical mortality at the first stage was 36%, and between 2005-2010, 15% (P=.05). Actuarial survival was 64% at one year, and 57% at 5years. Using a multivariate analysis, a restrictive ASD and a diminutive aorta were high risk factors for mortality. Our immediate and long term outcome for staged surgical management of HLHS is similar to that reported by large centres. There is an improvement in surgical mortality in the second half of our experience. Risk factors for mortality are also identified.


Differential risk factor profile of diabetes and atherosclerosis in rural, sub-urban and urban regions of South India: The KMCH-Non-communicable disease studies.
South Asia has emerged rapidly as an epicentre of non-communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio-demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub-urban and rural communities of South India. Three communities [Nallampatti (rural), Thadagam (sub-urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH-NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA1c ), non-fasting lipid profile and serum creatinine. Carotid intima-media thickness was measured using B-mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis. A total of 2976 native participants, ≥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub-urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi-urban populations. Association of diabetes with atherosclerosis was observed in urban and semi-urban populations. Hypertension in semi-urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis. Diabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub-urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non-traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non-urbanized communities.


Binding of DNP-specific receptor material of normal thymocytes to DNP-gelatin-coated dishes.
Mouse spleen cells (0.5%) were bound specifically to DNP4-gelatin-coated dishes at 4 degrees C. The DNP-specific spleen cells can be recovered from the dishes by melting the gel at 37 degrees C. In contrast to spleen cells, thymocytes did not bind to DNP-gelatin layers. When dishes were pretreated with large numbers of thymocytes, the binding of splenocytes was reduced in a second adsorption step, depending on the number of thymocytes used for the pretreatment. The reduction of spleen cell binding by pretreatment of dishes with thymocytes could be inhibited by DNP18-rabbit-IgG, but not by ARS13-rabbit-IgG. These data show that, on the release of thymocytes during the incubation with DNP4-gelatin layers, thymocytes leave behind DNP-specific binding material which prevents a second adsorption of DNP-binding spleen cells.


AI-based protein structure databases have the potential to accelerate rare diseases research: AlphaFoldDB and the case of IAHSP/Alsin.
Artificial intelligence (AI)-based protein structure databases are expected to have an impact on drug discovery. Here, we show how AlphaFold could support rare diseases research programs. We focus on Alsin, a protein responsible for rare motor neuron diseases, such as infantile-onset ascending hereditary spastic paralysis (IAHSP) and juvenile primary lateral sclerosis (JPLS), and involved in some cases of amyotrophic lateral sclerosis (ALS). First, we compared the AlphaFoldDB human Alsin model with homology models of Alsin domains. We then evaluated the flexibility profile of Alsin and of experimentally characterized mutants present in patients with IAHSP. Next, we compared preliminary models of dimeric/tetrameric Alsin responsible for its physiological action with hypothetical models reported in the literature. Finally, we suggest the best animal model for drug candidates testing. Overall, we computationally show that drug discovery efforts toward Alsin-involving diseases should be pursued.


Identification of antibodies in anti-CNS and anti-PNS myelin sera by immunoblot, characterization by immunohistochemistry, and their effect in tissue culture.
Immunoblot analysis of antiserum to rat central nervous system (CNS) myelin revealed antibodies to myelin basic protein (MBP), proteolipid protein (PLP), and numerous high molecular weight proteins. In addition, anti-CNS myelin serum exclusively immunostained 4 basic proteins of rat peripheral nervous system (PNS) myelin. Similarly, anti-PNS myelin sera immunostained many high molecular weight proteins in both CNS and PNS myelin in addition to P0 and 4 basic proteins. Purified MBP and PLP were immunostained by anti-CNS myelin sera and MBP and P0 by anti-PNS myelin sera, indicating that antigenic sites are preserved during protein purification. Immunohistochemical localization with antisera was confined to the myelin sheath except that antisera to CNS myelin also stained oligodendrocytes during the active period of myelination. While anti-CNS myelin sera specifically demyelinated centrally myelinated fibers in culture, none of the anti-PNS myelin sera used here demyelinated organotypic spinal cord-dorsal root ganglion cultures.