Behavioral Study of 3- and 5-Halocytisine Derivatives in Zebrafish Using the Novel Tank Diving Test (NTT).
Anxiety is a serious mental disorder, and recent statistics have determined that 35.12% of the global population had an anxiety disorder during the COVID-19 pandemic. A mechanism associated with anxiolytic effects is related to nicotinic acetylcholine receptor (nAChR) agonists, principally acting on the α4β2 nAChR subtype. nAChRs are present in different animal models, including murine and teleosteos ones. Zebrafish has become an ideal animal model due to its high human genetic similarities (70%), giving it high versatility in different areas of study, among them in behavioral studies related to anxiety. The novel tank diving test (NTT) is one of the many paradigms used for studies on new drugs related to their anxiolytic effect. In this work, an adult zebrafish was used to determine the behavioral effects of 3- and 5-halocytisine derivatives, using the NTT at different doses. Our results show that substitution at position 3 by chlorine or bromine decreases the time spent by the fish at the bottom compared to the control. However, the 3-chloro derivative at higher doses increases the bottom dwelling time. In contrast, substitution at the 5 position increases bottom dwelling at all concentrations showing no anxiolytic effects in this model. Unexpected results were observed with the 5-chlorocytisine derivative, which at a concentration of 10 mg/L produced a significant decrease in bottom dwelling and showed high times of freezing. In conclusion, the 3-chloro and 3-bromo derivatives show an anxiolytic effect, the 3-chlorocytisine derivative being more potent than the 3-bromo derivative, with the lowest time at the bottom of the tank at 1mg/L. On the other hand, chlorine, and bromine at position 5 produce an opposite effect.


Type 2 Valvular Heart Disease Affects Decision Making for Anticoagulation in Patients with Atrial Fibrillation: The UMBRIA-Fibrillazione Atriale Prospective Study.
Background Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Aim We investigated whether type 2 VHD (other than moderate-severe rheumatic mitral stenosis or mechanical heart valve) influences the prescription of anticoagulants in AF. Methods Umbria-Fibrillazione Atriale is a prospective multicenter registry in patients with AF. For the purpose of this study, type 2 VHD patients were propensity matched with non-VHD counterparts in a 1:1 ratio. Patients with type 1 VHD (moderate-severe mitral stenosis or mechanical heart valve) were excluded. Results We identified 2,212 patients with AF and excluded 46 because data on VHD were unavailable. Type 2 VHD was present in 426 patients (19.7%). Before registry entry visit, 77.1% of type 2 VHD and 66.8% of non-VHD patients were on anticoagulants. At discharge, 90.8 and 85.2% of patients, respectively, were on anticoagulants. After propensity-score matching, 386 patient-pairs were created. In the matched sample, the likelihood of being on anticoagulants before (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.02-2.01, p = 0.036) and after (1.63, 95% CI: 1.04-2.57, p = 0.034) the entry visit was higher in type 2 VHD than in non-VHD patients. Patients with type 2 VHD were 70% more likely to receive vitamin K antagonists (VKAs) (OR: 1.70, 95% CI: 1.28-2.27, p < 0.001), and 32% less likely to receive non-vitamin K oral anticoagulants (NOACs; OR: 0.68, 95% CI: 049-0.94, p = 0.011) than non-VHD patients. Conclusion VKAs consistently outperformed NOACs as preferred treatment option in patients with type 2 VHD. This could potentially deny to these patients the well-established benefits of NOACs observed in phase III trials.


Performance consistency in picture naming: a study of the rehabilitation effect on two aphasic patients.
We describe the effect of language rehabilitation on the naming deficits of 2 patients affected by longstanding amnestic aphasia. In particular, our aim was to study the evolution of the rate of inconsistent naming (i.e., performance with stimuli that were named sometimes correctly and sometimes incorrectly when the test was repeated at close intervals) by means of a stochastic model based on Markov chains (Faglioni & Botti, 1993). From a quantitative point of view, both patients showed a significant improvement that was still present several months after treatment. However, at baseline these patients showed different degrees of consistency which revealed a basic difference in the way their language functions. One case presented with low consistency, delayed responses, and self-corrections: A clear effect of rehabilitation was improvement in consistency and reduction of delays. In the other case, at baseline consistency was greater, but naming of pictures did not improve even after delay or self-correction; after rehabilitation more stimuli were named correctly, but only after delay and self-correction. The relevance of consistency and its relationship with delayed naming and self-corrections is discussed. It is suggested that consistency analysis based on stochastic models would make a useful contribution to the description and interpretation of naming deficits in aphasic patients.


5-Substituted-furan-2(3H)-ones in [8 + 2]-Cycloaddition with 8,8-Dicyanoheptafulvene.
This study demonstrates the use of organocatalytic Brønsted base activation of 5-substituted-furan-2(3H)-ones to generate 2π-components for the diastereoselective [8 + 2]-cycloaddition involving 8,8-dicyanoheptafulvene as an 8π-component. The use of dienolates in a higher-order cycloaddition reaction leads to the formation of biologically relevant polycyclic products bearing a γ-butyrolactone structural motif, thus broadening the synthetic potential of Brønsted base activated higher-order cycloadditions.


A Biliary Tract-Specific Near-Infrared Fluorescent Dye for Image-Guided Hepatobiliary Surgery.
Despite advances, visual inspection, palpation, and intraoperative ultrasound remain the most utilized tools during surgery today. A particularly challenging issue is the identification of the biliary system due to its complex architecture partially embedded within the liver. Fluorescence guided surgical interventions, particularly using near-infrared (NIR) wavelengths, are an emerging approach for the real-time assessment of the hepatobiliary system. However, existing fluorophores, such as the FDA-approved indocyanine green (ICG), have significant limitations for rapid and selective visualization of bile duct anatomy. Here we report a novel NIR fluorophore, BL (Bile Label)-760, which is exclusively metabolized by the liver providing high signal in the biliary system shortly after intravenous administration. This molecule was identified by first screening a small set of known heptamethine cyanines including clinically utilized agents. After finding that none of these were well-suited, we then designed and tested a small series of novel dyes within a prescribed polarity range. We validated the molecule that emerged from these efforts, BL-760, through animal studies using both rodent and swine models employing a clinically applicable imaging system. In contrast to ICG, BL-760 fluorescence revealed a high target-to-background ratio (TBR) of the cystic duct relative to liver parenchyma 5 min after intravenous injection. During hepatic resection surgery, intrahepatic ducts were clearly highlighted, and bile leakage was easily detected. In conclusion, BL-760 has highly promising properties for intraoperative navigation during hepatobiliary surgery.


Introducing Platelet-Rich Stroma: Platelet-Rich Plasma (PRP) and Stromal Vascular Fraction (SVF) Combined for the Treatment of Androgenetic Alopecia.
Androgenetic alopecia (AGA) is characterized by miniaturization of the hair follicles gradually causing conversion of terminal hairs into vellus hairs, leading to progressive reduction of the density of hair on the scalp. Approved therapeutic options are limited and show side effects. To evaluate injections of stromal vascular fraction (SVF), which is rich in adipose-derived stromal cells (ASCs) in combination with platelet-rich plasma (PRP) in the upper scalp as a new autologous treatment option for AGA. Ten male patients (age range, 25-72 years), suffering from AGA at stage II to III according to the Norwood-Hamilton scale, have been treated with a single injection of autologous PRS (ACPSVF: combination of PRP and SVF) in the upper scalp. Preinjection and 6 and 12 weeks postinjection changes in hair density were assessed using ultra high-resolution photography (Fotofinder). Hair density was significantly increased after 6 weeks and 12 weeks postinjection (P = 0.013 and P < 0.001). In hair-to-hair matching analyses, new hair grew from active follicles. Furhtermore nonfunctioning hair follicles filled with hyperkeartotic plugs, up to today assumed incapable of forming new hair, proved to grow new hair. No side effects were noted after treatment. A single treatment of platelet-rich stroma injected in the scalp of patients with AGA significantly increased hair density within 6 to 12 weeks. Further research is required to determine the optimal treatment regimen. Preferred options to our opinion include the repetition of PRS or additional treatments with PRP.


LACTATE DEHYDROGENASE ISOZYMES: LABILITY AT LOW TEMPERATURE.
A change in the lactate dehydrogenase isozyme pattern can arise when human tissue homogenates are kept at -20 degrees C. This change is most pronounced in a homogenate with a pH of about 7.9 in barbital buffer and is not seen when nicotinamide adeninedinucleotide is added to the homogenates before freezing, nor when the homogenates are kept at room temperature, nor when the tissue alone is kept at -20 degrees C.


Hepatic preneoplasia in hepatitis B virus transgenic mice.
Hepatocarcinogenesis in hepatitis B virus transgenic mice was studied by means of a correlative cytomorphological and cytochemical approach at different time points in animals from 1 to 34 mo old. HBsAg-positive ground-glass hepatocytes emerged throughout the liver parenchyma in nearly all transgenic mice during the first 4 mo after birth. The panlobular expression of HBsAg persisted until foci of altered hepatocytes appeared (6 to 9 mo of age). Three different types of foci of altered hepatocytes-namely, glycogen-storage foci, mixed cell foci and glycogen-poor foci-developed. Hepatocellular adenomas and carcinomas appeared after 11 mo. Orcein staining revealed frequent transitions between ground-glass hepatocytes extensively expressing HBsAg and glycogen-storage (predominantly clear-cell) foci containing HBsAg-positive cytoplasmic components. Similar transitions between ground-glass hepatocytes and glycogenotic (clear) cells were often found in diffuse parenchymal glycogenosis at 11 or 12 mo. Remnants of HBsAg-positive material were also detected in mixed cell foci, glycogen-poor diffusely basophilic cell foci, hepatic adenoma and hepatocellular carcinoma. These findings suggest that ground-glass hepatocytes are the direct precursor of foci of altered hepatocytes and their neoplastic descendants. The extensive expression of HBsAg is gradually down-regulated during neoplastic transformation, just as the morphological the biochemical phenotypes of foci of altered hepatocytes, hepatic adenoma and hepatocellular carcinoma in transgenic mice resemble those described in chemical hepatocarcinogenesis. The predominant sequence of cellular changes leading from glycogen-storage (predominantly clear cell) foci to mixed cell foci, hepatic adenoma and hepatocellular carcinoma is characterized by a gradual decrease in the activities of glycogen synthase, phosphorylase, glucose-6-phosphatase and adenylate cyclase, whereas glucose-6-phosphate dehydrogenase and pyruvate kinase activities increase. These alterations indicate a shift from the glycogenotic state toward an increase in the pentose phosphate pathway and glycolysis.


Monosodium Urate Crystals Generate Nuclease-Resistant Neutrophil Extracellular Traps via a Distinct Molecular Pathway.
Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent with NETs is present in fluid from acutely inflamed joints of gout patients. NETs also coat the crystals found in uninflamed tophi of chronic gout patients. We developed a quantitative, live cell imaging assay, which measures the key features of NETosis, namely, cell death and chromatin decondensation. We show that MSU and other physiologically relevant crystals induce NETosis through a molecular pathway that is distinct from PMA and Candida hyphae. Crystals interact with lysosomes to induce NADPH oxidase-independent cell death, with postmortem chromatin decondensation mediated by neutrophil elastase. The resulting MSU-induced NETs are enriched for actin and are resistant to serum and DNase degradation. These findings demonstrate a distinct physiological NETosis pathway in response to MSU crystals, which coats MSU crystals in DNA that persists in tissues as gouty tophi.


Laboratory study of iron isotope fractionation during dissolution of mineral dust and industrial ash in simulated cloud water.
Atmospheric deposition is a key mode of iron (Fe) input to ocean regions where low concentrations of this micronutrient limit marine primary production. Various natural particles (e.g., mineral dust, volcanic ash) and anthropogenic particles (e.g., from industrial processes, biomass burning) can deliver Fe to the ocean, and assessment of their relative importance in supplying Fe to seawater requires knowledge of both their deposition flux and their Fe solubility (a proxy for Fe bioavailability). Iron isotope (54Fe, 56Fe, 57Fe, 58Fe) analysis is a potential tool for tracing natural and anthropogenic Fe inputs to the ocean. However, it remains uncertain how the distinct Fe isotopic signatures (δ56Fe) of these particles may be modified by physicochemical processes (e.g., acidification, photochemistry, condensation-evaporation cycles) that are known to enhance Fe solubility during atmospheric transport. In this experimental study, we measure changes over time in both Fe solubility and δ56Fe of a Tunisian soil dust and an Fe-Mn alloy factory industrial ash exposed under irradiation to a pH 2 solution containing oxalic acid, the most widespread organic complexing agent in cloud- and rainwater. The Fe released per unit surface area of the ash (∼1460 μg Fe m-2) is ∼40 times higher than that released by the dust after 60 min in solution. Isotopic fractionation is also observed, to a greater extent in the dust than the ash, in parallel with dissolution of the solid particles and driven by preferential release of 54Fe into solution. After the initial release of 54Fe, the re-adsorption of A-type Fe-oxalate ternary complexes on the most stable surface sites of the solid particles seems to impair the release of the heavier Fe isotopes, maintaining a relative enrichment in the light Fe isotope in solution over time. These findings provide new insights on Fe mobilisation and isotopic fractionation in mineral dust and industrial ash during atmospheric processing, with potential implications for ultimately improving the tracing of natural versus anthropogenic contributions of soluble Fe to the ocean.


Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons.
Studies on the expression and cellular function of sigma receptors in autonomic neurons were conducted in neonatal rat intracardiac and superior cervical (SCG) ganglia. Individual neurons from SCG and intracardiac ganglia were shown to express transcripts encoding the sigma-1 receptor using single-cell RT-PCR techniques. The relationship between sigma receptors and calcium channels was studied in isolated neurons of these ganglia under voltage-clamp mode using the perforated-patch configuration of the whole cell patch-clamp recording technique. Bath application of sigma receptor agonists was shown to rapidly depress peak calcium channel currents in a reversible manner in both SCG and intracardiac ganglion neurons. The inhibition of barium (I(Ba)) currents was dose-dependent, and half-maximal inhibitory concentration (IC50) values for haloperidol, ibogaine, (+)-pentazocine, and 1,3-Di-O-tolylguanidin (DTG) were 6, 31, 61, and 133 microM, respectively. The rank order potency of haloperidol > ibogaine > (+)-pentazocine > DTG is consistent with the effects on calcium channels being mediated by a sigma-2 receptor. Preincubation of neurons with the irreversible sigma receptor antagonist, metaphit, blocked DTG-mediated inhibition of Ca2+ channel currents. Maximum inhibition of calcium channel currents was > or =95%, suggesting that sigma receptors block all calcium channel subtypes found on the cell body of these neurons, which includes N-, L-, P/Q-, and R-type calcium channels. In addition to depressing peak Ca2+ channel current, sigma receptors altered the biophysical properties of these channels. Following sigma receptor activation, Ca2+ channel inactivation rate was accelerated, and the voltage dependence of both steady-state inactivation and activation shifted toward more negative potentials. Experiments on the signal transduction cascade coupling sigma receptors and Ca2+ channels demonstrated that neither cell dialysis nor intracellular application of 100 microM guanosine 5'-O-(2-thiodiphosphate) trilithium salt (GDP-beta-S) abolished the modulation of I(Ba) by sigma receptor agonists. These data suggest that neither a diffusible cytosolic second messenger nor a G protein is involved in this pathway. Activation of sigma receptors on sympathetic and parasympathetic neurons is likely to modulate cell-to-cell signaling in autonomic ganglia and thus the regulation of cardiac function by the peripheral nervous system.


Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis.
JAK-STAT is a rational drug target in myelofibrosis (MF) given its association with JAK2/MPL mutations and aberrant inflammatory cytokine expression. We conducted a Phase 1/2 trial of CYT387, a potent JAK1/2 inhibitor, in patients with high- or intermediate-risk primary or post-polycythemia vera/essential thrombocythemia MF. Pre-planned safety and efficacy analysis has been completed for the initial 60 patients. In the dose-escalation phase (n=21), the maximum-tolerated dose was 300 mg/day based on reversible grade 3 headache and asymptomatic hyperlipasemia. Twenty-one and 18 additional patients were accrued at two biologically effective doses, 300 mg/day and 150 mg/day, respectively. Anemia and spleen responses, per International Working Group criteria, were 59% and 48%, respectively. Among 33 patients who were red cell-transfused in the month prior to study entry, 70% achieved a minimum 12-week period without transfusions (range 4.7->18.3 months). Most patients experienced constitutional symptoms improvement. Grade 3/4 adverse reactions included thrombocytopenia (32%), hyperlipasemia (5%), elevated liver transaminases (3%) and headache (3%). New-onset treatment-related peripheral neuropathy was observed in 22% of patients (sensory symptoms, grade 1). CYT387 is well tolerated and produces significant anemia, spleen and symptom responses in MF patients. Plasma cytokine and gene expression studies suggested a broad anticytokine drug effect.


Half Z-plasty, band release, and cavity filling for correction of inverted nipple.
The aim of this study was to describe another technique using a half Z-plasty, band release, and cavity filling to correct challenging inverted nipples. In five nipples of three adult Korean female cadavers, the tensile strength of the lactiferous duct was measured. A half Z-plasty was designed below the nipple on the areola using a vertical long axis of 30°, 45°, and 60° for one flap and another of 90° with 15 silicone-made nipple protectors. In six inverted nipples of three women, a half Z-plasty, band release, and cavity filling was performed. The mean breaking strength of each lactiferous was 4.7 ± 2.3 N. The sum of the forces to break three ducts was 14.1 ± 6.5 N. The mean angle change of the nipple projection of the silicone model was 7.2° ± 0.3°, 9.4° ± 0.5°, and 13.4° ± 0.5°, respectively, in the 30°, 45°, and 60° flap. In all three nipples operated on, sufficient eversion of the nipples was satisfactorily obtained postoperatively. Releasing the inverted nipple was performed by severing the underlying tight fibrous tissue bands and canaliculi. The support of the nipple was maintained by propping and obliterating the dead space. This procedure was carried out through a half Z-plasty incision below the nipple on the areola.


Nonlinear droop compensation for current waveforms in MRI gradient systems.
Providing accurate gradient currents is challenging due to the gradient chain nonlinearities, arising from gradient power amplifiers and power supply stages. This work introduces a new characterization approach that takes the amplifier and power supply into account, resulting in a nonlinear model that compensates for the current droop. The gradient power amplifier and power supply stage were characterized by a modified state-space averaging technique. The resulting nonlinear model was inverted and used in feedforward to control the gradient coil current. A custom-built two-channel z-gradient coil was driven by high-switching (1 MHz), low-cost amplifiers (<$200) using linear and nonlinear controllers. High-resolution (<80 ps) pulse-width-modulation signals were used to drive the amplifiers. MRI experiments were performed to validate the nonlinear controller's effectiveness. The simulation results validated the functionality of the state-space averaging method in characterizing the gradient system. The performance of linear and nonlinear controllers in generating a trapezoidal current waveform was compared in simulations and experiments. The integral errors between the desired waveform and waveforms generated by linear and nonlinear controllers were 1.9% and 0.13%, respectively, confirming the capability of the nonlinear controller to compensate for the current droop. Phantom images validated the nonlinear controller's ability to correct droop-induced distortions. Benchtop measurements and MRI experiments demonstrated that the proposed nonlinear characterization and digitally implemented feedforward controller could drive gradient coils with droop-free current waveforms (without a feedback loop). In experiments, the nonlinear controller outperformed the linear controller by a 14-fold reduction in the integral error of a test waveform.


Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses.
beta-Carotene and its metabolites exert a broad range of effects, in part by regulating transcriptional responses through specific nuclear receptor activation. Symmetric cleavage of beta-carotene can yield 9-cis retinoic acid (9-cisRA), the natural ligand for the nuclear receptor RXR, the obligate heterodimeric partner for numerous nuclear receptor family members. A significant portion of beta-carotene can also undergo asymmetric cleavage to yield apocarotenals, a series of poorly understood naturally occurring molecules whose biologic role, including their transcriptional effects, remains essentially unknown. We show here that beta-apo-14'-carotenal (apo14), but not other structurally related apocarotenals, represses peroxisome proliferator-activated receptors (PPAR) and RXR activation and biologic responses induced by their respective agonists both in vitro and in vivo. During adipocyte differentiation, apo14 inhibited PPARgamma target gene expression and adipogenesis, even in the presence of the potent PPARgamma agonist BRL49653. Apo14 also suppressed known PPARalpha responses, including target gene expression and its known antiinflammatory effects, but not if PPARalpha agonist stimulation occurred before apo14 exposure and not in PPARalpha-deficient cells or mice. Other apocarotenals tested had none of these effects. These data extend current views of beta-carotene metabolism to include specific apocarotenals as possible biologically active mediators and identify apo14 as a possible template for designing PPAR and RXR modulators and better understanding modulation of nuclear receptor activation. These results also suggest a novel model of molecular endocrinology in which metabolism of a parent compound, beta-carotene, may alternatively activate (9-cisRA) or inhibit (apo14) specific nuclear receptor responses.


Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia.
Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.


The role of the Sunda shelf biogeographic barrier in the cryptic differentiation of Conus litteratus (Gastropoda: Conidae) across the Indo-Pacific region.
Geographical and oceanographic processes have influenced the speciation of marine organisms. Cone snails are marine mollusks that show high levels of endemism and a wide distributional range across the Indian and Pacific Oceans. Discontinuities in distributions caused by biogeographic barriers can affect genetic connectivity. Here we analysed the connectivity within Conus litteratus using samples from the Lakshadweep archipelago (Arabian Sea, Indian Ocean) and from the Pacific Ocean. Maximum likelihood analyses based on the mitochondrial cytochrome C oxidase subunit I (COI) and on the non-coding 16S ribosomal RNA (16S rRNA) genes revealed cryptic diversity within C. literatus occupying distinct oceanographic regions. The intraspecific genetic distances between the two distinct clades of C. literatus from the Arabian Sea and the Pacific Ocean ranged from 7.4% to 7.6% for COI and from 2.4% to 2.8% for 16S rRNA genes, which is larger than the threshold limit for interspecific differentiation. The haplotype network analysis also corroborated the existence of two different lineages within C. litteratus. The detected genetic discontinuities reflect the effect of the Sunda shelf biogeographic barrier on the allopatric divergence of C. litteratus.


The effect of indefinite pretrial incarceration on the anxiety level of an urban jail population.
This study investigated the effect of indefinite incarceration on the anxiety levels of males (N = 60) held in a large metropolitan county jail. The IPAT Anxiety Scale Questionnaire (Self Analysis Form) was administered to 60 male Ss (18 to 26 years of age) at intervals of 1 weeks and 8 weeks after incarceration. An analysis of variance, one-way with repeated measures, on the matching IPAT Anxiety Scale scores revealed a highly significant increase in anxiety (p less than .001) from 1 week to 8 weeks. A Newman-Keuls posttest comparison also indicated that anxiety levels rose significantly (p less than .001). The results suggested that indefinite pretrail incarceration can increase anxiety to a level of psychological morbidity. The possible effect of this finding upon the guarantee of a right to speedy trial was discussed.


Antenatal care attendance and uptake of skilled delivery, Lokitaung Sub-County Hospital, Turkana County, Kenya.
Globally, nearly 500,000 women die annually from pregnancy- and childbirth-related complications. Antenatal care (ANC) is one of the most important factors in preventing maternal and infant mortality. This study investigated whether ANC attendance and sociodemographic characteristics of pregnant women influence uptake of skilled delivery at Lokitaung Sub-County Hospital, Turkana County, Kenya.


Performance of technical trading rules: evidence from Southeast Asian stock markets.
This paper examines the profitability of technical trading rules in the five Southeast Asian stock markets. The data cover a period of 14 years from January 2000 to December 2013. The instruments investigated are five Southeast Asian stock market indices: SET index (Thailand), FTSE Bursa Malaysia KLC index (Malaysia), FTSE Straits Times index (Singapore), JSX Composite index (Indonesia), and PSE composite index (the Philippines). Trading strategies investigated include Relative Strength Index, Stochastic oscillator, Moving Average Convergence-Divergence, Directional Movement Indicator and On Balance Volume. Performances are compared to a simple Buy-and-Hold. Statistical tests are also performed. Our empirical results show a strong performance of technical trading rules in an emerging stock market of Thailand but not in a more mature stock market of Singapore. The technical trading rules also generate statistical significant returns in the Malaysian, Indonesian and the Philippine markets. However, after taking transaction costs into account, most technical trading rules do not generate net returns. This fact suggests different levels of market efficiency among Southeast Asian stock markets. This paper finds three new insights. Firstly, technical indicators does not help much in terms of market timing. Basically, traders cannot expect to buy at a relative low price and sell at a relative high price by just using technical trading rules. Secondly, technical trading rules can be beneficial to individual investors as they help them to counter the behavioral bias called disposition effects which is the tendency to sell winning stocks too soon and holding on to losing stocks too long. Thirdly, even profitable strategies could not reliably predict subsequent market directions. They make money from having a higher average profit from profitable trades than an average loss from unprofitable ones.


Capsule formation by nonropy starter cultures affects the viscoelastic properties of yogurt during structure formation.
The aim of this work was to study the structure formation of yogurt made with cultures containing ropy Lactobacillus delbrueckii ssp. bulgaricus (R), capsule-forming nonropy Streptococcus thermophilus (CNR), and noncapsule-forming nonropy cultures (NCNR). Similar gelation profiles were shown for milk fermented by ropy and nonropy lactic cultures. The gelation point occurred at lower pH values in milk fermented with R or NCNR compared to that of milk fermented with CNR culture. Differences between capsule forming ropy and nonropy cultures were observed in the aggregation behavior of the caseins. Gels made with R culture had the highest maximum in loss tangent (tan delta). However, this maximum occurred at the highest pH value when CNR culture was used. The earlier gelation of milk fermented by the encapsulated nonropy strain of Strep. thermophilus resulted in increased structure rearrangement as the pH dropped, interfering with the formation of a more compact structure.


Linking rhizosphere microbiome composition of wild and domesticated Phaseolus vulgaris to genotypic and root phenotypic traits.
Plant domestication was a pivotal accomplishment in human history, but also led to a reduction in genetic diversity of crop species compared to their wild ancestors. How this reduced genetic diversity affected plant-microbe interactions belowground is largely unknown. Here, we investigated the genetic relatedness, root phenotypic traits and rhizobacterial community composition of modern and wild accessions of common bean (Phaseolus vulgaris) grown in agricultural soil from the highlands of Colombia, one of the centers of common bean diversification. Diversity Array Technology-based genotyping and phenotyping of local common bean accessions showed significant genetic and root architectural differences between wild and modern accessions, with a higher specific root length for the wild accessions. Canonical Correspondence Analysis indicated that the divergence in rhizobacterial community composition between wild and modern bean accessions is associated with differences in specific root length. Along the bean genotypic trajectory, going from wild to modern, we observed a gradual decrease in relative abundance of Bacteroidetes, mainly Chitinophagaceae and Cytophagaceae, and an increase in relative abundance of Actinobacteria and Proteobacteria, in particular Nocardioidaceae and Rhizobiaceae, respectively. Collectively, these results establish a link between common bean domestication, specific root morphological traits and rhizobacterial community assembly.


An Optimized Artificial Intelligence System Using IoT Biosensors Networking for Healthcare Problems.
In today's environment, electronics technology is growing rapidly because of the availability of the numerous and latest devices which can be deployed for monitoring and controlling the various healthcare systems. Due to the limitations of such devices, there is a dire need to optimize the utilization of the devices. In healthcare systems, Internet of things (IoT) based biosensors networking has minimal energy during transmission and collecting data. This paper proposes an optimized artificial intelligence system using IoT biosensors networking for healthcare problems for efficient data collection from the deployed sensor nodes. Here, an optimized tunicate swarm algorithm is used for optimizing the route for data collection and transmission among the patient and doctor. The fitness function of the optimized tunicate swarm algorithm used the distance, proximity, residual, and average energy of nodes parameters. The proposed method is attributed to the optimal CH chosen under TSA operation having a lower energy consumption. The performance of the proposed method is compared to the existing methods in terms of various metrics like stability period, lifetime, throughput, and clusters per round.


A review of the use of complementary and alternative medicines by children with inflammatory bowel disease.
The Inflammatory Bowel Diseases (IBDs) are diagnosed more commonly in children and adolescents. Following diagnosis, the key objectives are to achieve and then maintain remission. Although some therapies are able to effectively modify and modulate inflammatory events, none of the available interventions cure these conditions. Consequently, children and their parents face uncertainty and may look to alternative management options as ways to help their child, which may include various complementary and alternative medicines (CAMs). A number of studies have shown that many children with IBD receive or are given CAM agents. This article reviews the rates and patterns of CAM use in children with IBD, and emphasizes the increasing importance of these aspects of the management of children with IBD.


Renal Hypoxia in CKD; Pathophysiology and Detecting Methods.
Chronic kidney disease (CKD) is a major public health problem. Accumulating evidence suggests that CKD aggravates renal hypoxia, and in turn, renal hypoxia accelerates CKD progression. To eliminate this vicious cycle, hypoxia-related therapies, such as hypoxia-inducible factor (HIF) activation (prolyl hydroxylase domain inhibition) or NF-E2-related factor 2 activation, are currently under investigation. Clinical studies have revealed heterogeneity in renal oxygenation; therefore, the detection of patients with more hypoxic kidneys can be used to identify likely responders to hypoxia-oriented therapies. In this review, we provide a detailed description of current hypoxia detection methods. HIF degradation correlates with the intracellular oxygen concentration; thus, methods that can detect intracellular oxygen tension changes are desirable. The use of a microelectrode is a classical technique that is superior in quantitative performance; however, its high invasiveness and the fact that it reflects the extracellular oxygen tension are disadvantages. Pimonidazole protein adduct immunohistochemistry and HIF activation detection reflect intracellular oxygen tension, but these techniques yield qualitative data. Blood oxygen level-dependent magnetic resonance imaging has the advantage of low invasiveness, high quantitative performance, and application in clinical use, but its biggest disadvantage is that it measures only deoxyhemoglobin concentrations. Phosphorescence lifetime measurement is a relatively novel in vivo oxygen sensing technique that has the advantage of being quantitative; however, it has several disadvantages, such as toxicity of the phosphorescent dye and the inability to assess deeper tissues. Understanding the advantages and disadvantages of these hypoxia detection methods will help researchers precisely assess renal hypoxia and develop new therapeutics against renal hypoxia-associated CKD.


The success rate of external dacryocystorhinostomy.
To compare the success rate of external dacryocystorhinostomy with and without silicone intubation. This study included 129 patients with lacrimal drainage system disorders who underwent the external dacryocystorhinostomy and divided in two groups depending on whether silicone intubation was used during the surgery or not. Forty one DCR's were performed with intubation and 88 without. The data was analysed using the average, standard deviation, variation coefficient, and the statistical significance was determined using t-test. The mean age of the patients was 38.0 +/- 14.6SD years, including 97 females and 32 males. The mean duration of tubes was 5.2 +/- 0.8SD months. The mean time of follow-up was 14.7 +/- 3.5SD months. Intraoperative complications were present more frequently in the group without intubation 19.3% compared to 12.2% in the group with intubation (p > 0.05). The postoperative complication was closure of the anastomosis, less frequent in the group with intubation 4.9% compared to 12.5% in the group without intubation (p > 0.05). The success rate was evaluated by lacrimal patency to irrigation and relief of epiphora. Patency was achieved in 89.9% of cases, whereas epiphora recurred in 10.1% of cases. By groups, patency in the group with intubation was higher 95.1% compared to 87.5% in the group without intubation (p > 0.05). Our findings suggest that success rate was higher in dacryocystorhinostomy with silicone intubation, although results were not statistically significant. Prospective studies involving larger patient numbers are required to confirm this beneficial effect of silicone intubation.


Chondroid lipoma associated with osteoclast-like multinucleated giant cells - a case report.
Chondroid lipoma is a rare soft tissue neoplasm. We report case of chondroid lipoma associated with osteoclast-like multinucleated giant cells. To the best of our knowledge, the presence of these giant cells has not been previously described in the English literature. The recognition of these cells is important and their occurrence in this rare neoplasm should not mislead the pathologist to misdiagnose this entity.


Retinal Detachment Due to Retinal Dialysis: Surgical Outcome After Scleral Buckling.
The aim of this study was to determine the efficacy and safety of scleral buckling surgery in retinal detachment due to retinal dialysis. This study was a prospective, interventional case series. A total of 48 eyes of 48 consecutive patients were included after obtaining informed written consent. Besides taking a thorough history, all eyes were examined by a retinal surgeon. The macula status, site, and extent of retinal dialysis and rhegmatogenous retinal detachment (RRD) were particularly noted. Proliferative vitreoretinopathy grading was done. Buckling was performed by a single surgeon. At every follow-up, visual acuity, intraocular pressure, retina status, and buckle position were noted. Any complication found was recorded. Follow-up was done for at least 6 months. SPSS version 16 was used for data analysis. We included 48 cases of RRD due to retinal dialysis. The mean ± SD age of the patients was 26.85 ± 15.1 years. The macula was detached in 85.4% of the cases, and proliferative vitreoretinopathy grade C was found in 25% of the cases. A surgical reattachment rate of 95.8% was attained after a single primary buckling procedure. Final Snellen best-corrected visual acuity of 6/18 or better was attained in 12.5% of the cases. However, 62.5% of the cases had best-corrected visual acuity in the range of 6/24 to 6/60. Subretinal hemorrhage occurred in 8.3% of cases intraoperatively after subretinal fluid drainage. We conclude that scleral buckling has a definite role in the management of RRD due to retinal dialysis.


Acute Coronary Syndrome After Inactivated SARS-COV-2 Vaccine.
CoronaVac is an inactivated coronavirus disease (COVID-19) vaccine that was granted an emergency authorization by the World Health Organization in June 2021. We present the two cases of patients presenting with chest pain, abnormal electrocardiography, and elevated troponin consistent with non-ST-elevation myocardial infarction within 24 hours after receiving the CoronaVac COVID-19 vaccine.


The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS.
Meninges that surround the CNS consist of an outer fibrous sheet of dura mater (pachymeninx) that is also the inner periosteum of the skull. Underlying the dura are the arachnoid and pia mater (leptomeninges) that form the boundaries of the subarachnoid space. In this review we (1) examine the development of leptomeninges and their role as barriers and facilitators in the foetal CNS. There are two separate CSF systems during early foetal life, inner CSF in the ventricles and outer CSF in the subarachnoid space. As the foramina of Magendi and Luschka develop, one continuous CSF system evolves. Due to the lack of arachnoid granulations during foetal life, it is most likely that CSF is eliminated by lymphatic drainage pathways passing through the cribriform plate and nasal submucosa. (2) We then review the fine structure of the adult human and rodent leptomeninges to establish their roles as barriers and facilitators for the movement of fluid, cells and pathogens. Leptomeningeal cells line CSF spaces, including arachnoid granulations and lymphatic drainage pathways, and separate elements of extracellular matrix from the CSF. The leptomeningeal lining facilitates the traffic of inflammatory cells within CSF but also allows attachment of bacteria such as Neisseria meningitidis and of tumour cells as CSF metastases. Single layers of leptomeningeal cells extend into the brain closely associated with the walls of arteries so that there are no perivascular spaces around arteries in the cerebral cortex. Perivascular spaces surrounding arteries in the white matter and basal ganglia relate to their two encompassing layers of leptomeninges. (3) Finally we examine the roles of ligands expressed by leptomeningeal cells for the attachment of inflammatory cells, bacteria and tumour cells as understanding these roles may aid the design of therapeutic strategies to manage developmental, autoimmune, infectious and neoplastic diseases relating to the CSF, the leptomeninges and the associated CNS.


Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene.
The acetylation polymorphism may affect rates of activation or detoxification of common carcinogens, thereby influencing cancer risk. Our aim was to define the ethnic distribution of the major slow acetylator mutations in the polymorphic N-acetyltransferase gene, in order to provide background data for epidemiological studies. Our results contain new analyses on 803 individuals, including 365 new specimens and 438 specimens that had been partly characterized in an earlier study. Tests were done to establish the specificity and reproducibility (98%) of our PCR assays. The recognized slow acetylator mutations, 191A, 481T, 590A, and 857A (which correspond to alleles M4 and M4b; M1 and r3; M2/r2; and M3 and S3, respectively), accounted for nearly all slow acetylator alleles among blacks, whites, Asian Indians, Hispanics, Koreans, Japanese, Hong Kong Chinese, Taiwanese, Filipinos and Samoans. The ethnic distribution supports an interpretation that the acetylation polymorphism existed before Paleolithic splitting of human populations from Africa. We identified two additional NAT2 mutations, suggesting that other rare alleles are likely to be found.


The APO E4 allele and cognition in New Mexico Hispanic elderly.
To determine if the apolipoprotein E E4 (APO E4) allele is associated with cognitive performance in New Mexico Hispanic elderly. We performed a cross-sectional survey of 105 community volunteers, aged 60 years and older, born in New Mexico, with both parents of Hispanic descent. Subjects were excluded for medical conditions that could influence cognitive performance. We also performed a longitudinal analysis on 18 participants who were re-tested over a 3-year interval. The main outcome measures for both the cross-sectional and longitudinal analysis were scores on 5 cognitive tests comparing subjects with the E4 allele to those without the E4 allele. The mean age was 69 years, with a range of 60 to 91. For the cross-sectional analysis, there were no significant differences between the 2 groups on the cognitive tests, although subjects with an E4 allele did not perform as well on color trails A (P=.09). In the longitudinal analysis we found that the variability of cognitive test scores tended to be higher in the E4 group on most cognitive measures. The time needed to complete color trails A (indicating slower performance) was significantly greater (P<.05) in the E4 group. For the total recall portion of the Fuld Object Memory test, the E4 group did not perform as well on follow-up (P=.08). We found no significant cross-sectional association between the APO E4 allele and cognitive performance. In our longitudinal analysis, the time needed to complete color trails A was significantly greater in the E4 group, and the E4 group did not perform as well on total recall.


[Virus-induced opsoclonus-myoclonus syndrome during pregnancy].
Opsoclonus-myoclonus syndrome (OMS) is a very rare condition with various etiologies (paraneoplastic, parainfectious, toxic, idiopathic, etc.) with an autoimmune pathogenetic mechanism of development. The authors describe the case of OMS in a 41-year-old woman at 37 weeks of gestation, who developed opsoclonus, myoclonus, severe trunk ataxia, tremor and bilateral pyramidal symptoms, inability to sit, stand and walk without support. Differential diagnosis was conducted between virus-induced OMS, rotavirus encephalitis, paraneoplastic syndrome, and demyelinating diseases of the central nervous system. Routine laboratory tests of blood and urine, serological tests of blood and cerebrospinal fluid (CSF) revealed no pathology. Only small lymphocytic pleocytosis and a slight increase in protein were observed in CSF. No pathology was detected during magnetic resonance imaging. On the 40th week of pregnancy (20th day of illness), the patient gave birth to a healthy full-term baby through the birth canal. In view of the most likely autoimmune process triggered by rotavirus infection, intravenous immunosuppressive therapy with methylprednisolone (1000 mg/day №3) was performed, followed by switching to prednisolone per os (60 mg/kg/day), as well as neuroprotective and neurometabolic therapy with cytoflavin. On day 42 of the illness (and on day 20 of the immunosuppressive therapy), a significant positive trend was noted. The patient was discharged on day 56 with light residual elements of opsoclonus and ataxia, and could walk independently without support. Thus, in case of suspected OMS, it is necessary to conduct a mandatory full diagnostic search, especially aimed at exclusion of the paraneoplastic process. And also, given the possibility of recurrence, further outpatient monitoring of these patients should be carried out.


The use of platelet-rich fibrin to enhance the outcomes of implant therapy: A systematic review.
To assess the impact of platelet-rich fibrin (PRF) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and radiographic outcomes of PRF administration for bone regeneration and implant therapy? A systematic literature search comprised three databases: MEDLINE, EMBASE, and Cochrane followed by a hand search of relevant scientific journals. Human studies using PRF for bone regeneration and implant therapy were considered and articles published up to December 31, 2017 were included. Eligible studies were selected based on the inclusion criteria. Randomized controlled trials (RCT) and controlled clinical trials (CCT) were included. In total, 5,963 titles were identified with the search terms and by hand search. A total of 12 randomized controlled trials (RCT) met the inclusion criteria and were chosen for data extraction. Included studies focused on alveolar ridge preservation after tooth extraction, osseointegration process, soft tissue management, bone augmentation, bone regeneration after sinus floor elevation and surgical peri-implantitis treatment. Overall, the risk of bias was moderate or unclear. Nine studies showed superior outcomes for PRF for any of the evaluated variables, such as ridge dimension, bone regeneration, osseointegration process, soft tissue healing. Three studies failed to show any beneficial effects of PRF. No meta-analysis could be performed due to the heterogeneity of study designs. There is moderate evidence supporting the clinical benefit of PRF on ridge preservation and in the early phase of osseointegration. It remains unclear whether PRF can reduce pain and improve soft tissue healing. More research support is necessary to comment on the role of PRF to improve other implant therapy outcomes.


Fidgetin interacting with microtubule end binding protein EB3 affects axonal regrowth in spinal cord injury.
Fidgetin, a microtubule-severing enzyme, regulates neurite outgrowth, axonal regeneration, and cell migration by trimming off the labile domain of microtubule polymers. Because maintenance of the microtubule labile domain is essential for axon initiation, elongation, and navigation, it is of interest to determine whether augmenting the microtubule labile domain via depletion of fidgetin serves as a therapeutic approach to promote axonal regrowth in spinal cord injury. In this study, we constructed rat models of spinal cord injury and sciatic nerve injury. Compared with spinal cord injury, we found that expression level of tyrosinated microtubules in the labile portion of microtubules continuously increased, whereas fidgetin decreased after peripheral nerve injury. Depletion of fidgetin enhanced axon regeneration after spinal cord injury, whereas expression level of end binding protein 3 (EB3) markedly increased. Next, we performed RNA interference to knockdown EB3 or fidgetin. We found that deletion of EB3 did not change fidgetin expression. Conversely, deletion of fidgetin markedly increased expression of tyrosinated microtubules and EB3. Deletion of fidgetin increased the amount of EB3 at the end of neurites and thereby increased the level of tyrosinated microtubules. Finally, we deleted EB3 and overexpressed fidgetin. We found that fidgetin trimmed tyrosinated tubulins by interacting with EB3. When fidgetin was deleted, the labile portion of microtubules was elongated, and as a result the length of axons and number of axon branches were increased. These findings suggest that fidgetin can be used as a novel therapeutic target to promote axonal regeneration after spinal cord injury. Furthermore, they reveal an innovative mechanism by which fidgetin preferentially severs labile microtubules.


Intramuscular Fat in the Medial Gastrocnemius Muscle of People Who Have Had a Stroke.
Objective: To compare intramuscular fat fraction in people who have ankle contractures following stroke with the intramuscular fat fraction in control participants. Design: mDixon MRI images were used to quantify intramuscular fat fractions in the medial gastrocnemius muscles of people who had experienced a hemiparetic stroke (n = 14, mean age 60 ± 13 years) and control participants (n = 18, mean age 66 ± 12 years). Results: Intramuscular fat fractions were similar in the paretic and non-paretic sides of stroke patients (mean on paretic side 14.5%, non-paretic side 12.8%, difference 1.6%, 95% confidence interval -0.7 to 4.1%). The intramuscular fat fraction on the paretic side was higher than in the control group (mean intramuscular fat fraction in control muscles 7.6%; difference 7.8%, 95% confidence interval 4.6-10.9%). The difference between intramuscular fat fractions in non-paretic and control legs increased with age. Body mass index was similar in stroke patients and controls. There was no association between medial gastrocnemius intramuscular fat fraction and dorsiflexion range. Conclusion: Muscles of stroke patients had elevated intramuscular fat fractions compared to muscles from control participants which were not explained by differences in body mass index. There is no clear relationship between intramuscular fat in the medial gastrocnemius muscle and dorsiflexion range of motion.


A 40 kd protein binds specifically to the 5'-untranslated regions of yeast mitochondrial mRNAs.
Using a gel mobility shift assay we show that a 40 kd protein (p40), present in extracts of yeast mitochondria, binds specifically to the 5'-untranslated leader of cytochrome c oxidase subunit II mRNA. Binding of p40 to coxII RNA protects an 8-10 nucleotide segment from diethylpyocarbonate modification, indicating that the protein interacts with only a restricted region of the 5'-leader. This segment is located at position -12 with respect to the initiation AUG. Deletion of 10 nucleotides encompassing this site completely abolishes protein binding. Nevertheless, Bal31 deletion analysis within the coxII leader shows that a major part of the leader is essential for p40 binding, suggesting that binding of the protein is also dependent on secondary structural features. p40 binds to other mitochondrial leader mRNAs including those for coxI, coxIII and cyt b. p40 is present in a cytoplasmic (rho0) petite mutant lacking mitochondrial protein synthesis. It is therefore presumably nuclear encoded. The possible biological function of the protein is discussed.


[Use of chemical war gases at the Russian-German front during the First World War].
The First World War was notable for the widespread use of machine military hardware and absolutely new type of weapon--chemical weapon. As a result of the first gas attack by chlorine undertaken by the German army against the Russian armies on May, 31st, 1915, heavy poisonings have received 9100 people, 6000 of them died. Chemical attack of Germany against Russia was limited by the use chemical gases of suffocating action: chlorine, bromine,phosgene and diphosgene. It is not known exactly, how many times Germany attacked Russian positions with use of chemical gases. On available data, in the First World War from application by German of the chemical weapon Russia has suffered more, than any other of the at war countries: from five hundred thousand poisoned have died nearby 66,000 people. In turn, having received in the order the chemical weapon of own manufacture, Russian army itself tried to attack in the German armies. It is authentically known only about several cases of application dy Russian of fighting poison gases, and in all cases of loss of germen were insignificant.


A pragmatic bottom-up approach to harmonize the units of clinical chemistry tests among Belgian clinical laboratories, focusing on immunoassays.
Harmonization of units is an important step to improve the comparability of clinical chemistry results, but few examples exist of successful harmonization efforts. We present the results of a pragmatic approach that was implemented in Belgium from 2012. After a large consultation and information of stakeholders, preferred units were proposed for 140 assays, including the 23 immunoassays discussed in more detail here. The change occurred in two phases, first involving assays for which there was no change in the numerical result, then changes involving a change in numerical results. Laboratories were invited to participate in this harmonization on a voluntary basis. The project was based on a bottom-up approach, large consultation and the pragmatic choice of the proposed units, including conventional and SI units. The large heterogeneity of units was drastically reduced; adoption of the preferred units increased from 3% (insulin) - 45% (HCG) to 70% (insulin) - 96% (LH and FSH). Adoption of the preferred units was higher if it involved no change in numerical values (90%) than when there was a change (76%). We believe that the harmonization effort has reached its goals. Without aiming at implementing SI units for all parameters, our strategy was successful with a large majority of the laboratories switching to the proposed units. Moreover, the harmonization program is still progressing, with additional laboratories converting to the consensus units.


Changes in Quantity Measures of Various Forms of Cannabis Consumption among Emerging Adults in Canada in Relation to Policy and Public Health Developments.
Limited research examines changes in quantities of various forms of smoked/vaped cannabis among regular consumers, including emerging adults (EAs; 18 to 29) in Canada. This information is particularly relevant in the current context of emerging cannabis behaviors among EAs related to political amendments (legalization of cannabis), vaping-related lung illnesses (EVALI), and unprecedented pandemics (COVID-19). This study investigated the impact of legalizing recreational cannabis use in Canada, the EVALI epidemic, and the COVID-19 pandemic on the quantity of smoked/vaped forms of cannabis in relation to gender differences. EAs retrospectively self-reported the quantity of herb, hash, concentrates, joint size, and the number of joints and vaping cartridges in relation to three consecutive developments: pre-legalization, post-legalization; pre-EVALI, post-EVALI, pre-COVID-19, and during COVID-19. The quantity of herb use significantly increased among heavy users, and vaping quantity significantly increased among light users. Overall, an increasing incremental trend was observed in the average quantity of cannabis forms used over time. Males consumed higher quantities of all cannabis forms than females. More males than females reported using concentrates (p < 0.05). These findings reveal unique aspects of the amount of various cannabis forms smoked/vaped in relation to gender and provides preliminary evidence of cannabis consumption behaviors in relation to changing social and cultural contexts.


Development and gamma scintigraphy evaluation of gastro retentive calcium ion-based oral formulation: an innovative approach for the management of gastro-esophageal reflux disease (GERD).
Calcium chloride is an essential calcium channel agonist which plays an important role in the contraction of muscles by triggering calcium channel. First time hypothesized about its role in the treatment of GER (gastro-esophageal reflux) and vomiting disorder due to its local action. There are two objectives covered in this study as first, the development and optimization of floating formulation of calcium chloride and another objective was to evaluate optimized formulation through gamma scintigraphy in human subjects. Gastro retentive formulation of calcium chloride was prepared by direct compression method. Thirteen tablet formulations were designed with the help of sodium chloride, HPMC-K4M, and carbopol-934 along with effervescing agent sodium bicarbonate and citric acid. Formulation (F8) fitted best for Korsmeyer-Peppas equation with an R2 value of 0.993. The optimized formulation was radiolabelled with 99mTc-99 m pertechnetate for its evaluation by gamma scintigraphy. Gastric retention (6 h) was evaluated by gamma scintigraphy in healthy human subjects and efficacy of present formulation confirmed in GER positive human subjects. Gamma scintigraphy results indicated its usefulness in order to manage GERD. Stability studies of the developed formulation were carried out as per ICH guidelines for region IV and found out to be stable for 24 months.


Malignant melanoma of the cervix uteri.
Primary malignant melanoma of the uterine cervix in a 70-year-old Negro female is reported. Only 9 other cases have been reported in the literature. The diagnosis, prognosis, and modern trends in therapy for this lesion are discussed.


Paperless medical records: reinventing the patient experience.
At North Shore Magnetic Imaging Center, the patient paper medical record system was becoming very cumbersome, and it served as a source of frustration for everyone involved: patients, technologists, radiologists, and staff members. The center's mapping of a typical patient experience indicated that, from the initial phone call scheduling an exam to a completed visit (claim processed and payment received), a record could be handled by as many as 20 sets of hands! In June 2002, the center's growth and a concern that patients were losing a one-on-one experience with the medical staff led to an evaluation of workflow processes existing at that time. The evaluation began with a survey of staff members, center management, radiologists, and referring physicians. Their responses indicated 3 common themes: stress, overload, and frustration over systems in place. Comments from the survey were grouped into 3 areas: Continue to Do, Stop Doing, and Start Doing. The Start Doing responses provided solid objectives. The center set out to establish a breakthrough project that included all stakeholders--patients, staff, management, and radiologists. The Reinvention Project had 2 primary goals: move to a paperless environment and increase the level of patient care. The project was divided into internal and external teams. The internal team, called the Reinvention Team, was responsible for the actual hands-on aspects of the process. There were numerous external teams; each had defined roles and specific outcomes for achievement. The external teams' responsibilities included implementing an Internet protocol telephone system; researching voice recognition; restructuring job descriptions, training manuals, and performance evaluations; and conducting a patient-centered focus group.


Investigation of the expression of irisin and some cachectic factors in mice with experimentally induced gastric cancer.
The purpose of this study was to determine whether irisin is secreted by gastric tumor cells experimentally induced in mice, and also if it has any effect on cancer cachexia. 12 out of 60 BALB/c mice were used as a control group, while N-nitroso-N-methylurea (MNU) was administered orally to the remaining 48. After 150 days, the surviving mice were sacrificed by decapitation, blood and stomach, skeletal muscle, brown and white adipose tissue specimens were collected. Following histopathological evaluation of the stomach tissues, it was decided to create four groups, one control group and three consisting of mice administered MNU, no cancer, pre-cancer and cancer. Gene expression analyses of fibronectin type III domain containing protein 5 (FNDC5) and some cachexia-related proteins were performed in tissue samples, while levels of irisin, and various inflammatory and tumor markers together with cachectic factors were determined in serum samples. The levels of inflammatory, tumor markers and cachectic factors in serum samples were significantly higher in the cancer group compared with the control group. No expression of FNDC5 or zinc-α-2 glycoprotein, a cachectic factor, was observed in gastric tissues from the control and MNU groups, whereas significantly increased FNDC5 expression was determined in the both white and brown adipose tissues from the cancer group. Increased FNDC5 expression in white and brown adipose tissues may have a cachectic effect in mice with induced cancer. However, it is not possible to explain the mechanism of the relationship between irisin and gastric cancer development on the basis of the results of this study.


Primary papillary carcinoma of the thyroid arising in a branchial cyst: case report and review of the literature.
We report a case of papillary carcinoma of the thyroid that arose in a branchial cyst. The patient, a 45-year-old woman, presented with a left lateral neck mass of 3 months' duration. The cyst was removed intact. Because we could not rule out the possibility that a small primary malignancy was present within the gland, we performed a total thyroidectomy; however, no occult primary tumor of the thyroid was found. The patient was placed on thyroid hormone replacement therapy, and she was well at 2 years of follow-up. We briefly review the literature regarding the possible embryologic origin of such a phenomenon and the role of fine-needle aspiration cytology in differentiating a branchial cyst from a metastatic lymph node. To the best of our knowledge, this is only the 11th reported case of a thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst, and the second such report from India.


A Qualitative Study of Barriers to Care for People With Co-Occurring Disorders.
The present qualitative study used face-to-face and telephone interviews with service providers in the Tampere area in Finland to describe the provider viewpoint on barriers to care for people with co-occurring disorders. The core barrier concerns the definition and understanding of the problems: client and professional perspectives often differ, and both can be out of step with what the care system actually proposes. Professionals need to take into account contexts with potentially multiple barriers to care. Providers in each local area should examine possible barriers and find solutions together, integrating the client perspective at each step in the process.


Iron-Based Superconducting Nanowires: Electric Transport and Voltage-Noise Properties.
The discovery of iron-based superconductors paved the way for advanced possible applications, mostly in high magnetic fields, but also in electronics. Among superconductive devices, nanowire detectors have raised a large interest in recent years, due to their ability to detect a single photon in the visible and infrared (IR) spectral region. Although not yet optimal for single-photon detection, iron-based superconducting nanowire detectors would bring clear advantages due to their high operating temperature, also possibly profiting of other peculiar material properties. However, there are several challenges yet to be overcome, regarding mainly: fabrication of ultra-thin films, appropriate passivation techniques, optimization of nano-patterning, and high-quality electrical contacts. Test nanowire structures, made by ultra-thin films of Co-doped BaFe2As2, have been fabricated and characterized in their transport and intrinsic noise properties. The results on the realized nanostructures show good properties in terms of material resistivity and critical current. Details on the fabrication and low temperature characterization of the realized nanodevices are presented, together with a study of possible degradation phenomena induced by ageing effects.


Role of serum leptin level as a marker of severity of pre eclampsia.
To explore the possibility of serum leptin being a marker of severity of pre-eclampsia, so that risk of imminent eclampsia and eclampsia can be reduced. This observational study was conducted at a private hospital of Hyderabad from 31st July to 1st December 2007. Forty primipara with same age, body mass indices and gestational age were included in this study. Twenty women had raised blood pressure in third trimester of pregnancy and 20 women with a normal blood pressure in third trimester of pregnancy. The exclusion criteria included history of diabetes, twin pregnancy, chronic hypertension, liver or renal disease. After counselling and affordability of laboratory testing their blood sample was taken for serum leptin, uric acid, serum creatinine and urine for albumin. The serum leptin level was measured by radio-immunoassay (RIA) kits. All data was filled in a pre-designed proforma after taking detailed history and examination. Statistical analysis was performed on SPSS. Student's t-test was applied where applicable. Mean systolic and diastolic blood pressure between pre-eclamptic and control group showed a marked difference (p < 0.001) ranging from 149.50 +/- 3.44 and 104.40 +/- 3.03 as compared to control 107 +/- 1.56 and 74.50 +/- 1.49 respectively, similarly proteinuria was present in 20 (100%) cases of pre-eclampsia and 07 (35%) of normotensive women. Mean serum leptin level was significantly high in pre-eclampstic (79.380 +/- 3.287), when compared with a control group (27.825 +/- 1.050). Mean serum uric acid in pre-eclamptic (5.040 +/- 0.147) showed significant changes than control (3.600 +/- 0.141), while serum creatinine level was insignificant in both groups. It has been observed that Mean +/- SEM value of serum leptin level was much higher in severe pre-eclamptics (76.418 +/- 5.056) than in women with mild pre-eclampsia (40.856 +/- 2.807). All the parameters correlated positively and significantly with increased blood pressure. Elevated plasma leptin concentration appears to be a marker of pre-eclampsia independently or along with other parameters of pre-eclampsia could be used to reduce the severity of pre-eclampsia thus avoiding risk effects of pre-eclampsia to mother and foetus. This study still needs more research work to prove our results.


Pediatric craniocerebral gunshot injuries: A National Trauma Database study.
We aimed to determine the outcomes and prognostic factors in pediatric craniocerebral gunshot injury (CGI) patients. Pediatric patients may have significantly different physiology, neuroplasticity, and clinical outcomes in CGI than adults. There is limited literature on this topic, mainly case reports and small case series. We queried the National Trauma Data Bank for all pediatric CGI between 2014 and 2017. Patients were identified using International Classification of Diseases, Ninth Revision, codes. Demographic, emergency department, and clinical data were analyzed. Subgroup analysis was attempted for groups with Glasgow Coma Scale (GCS) scores of 9 to 15 and ages 0 to 8 years. In a 3-year period, there were 209 pediatric patients (aged 0-18 years) presenting to American hospitals with signs of life. The overall mortality rate was 53.11%. A linear relationship was demonstrated showing a mortality rate of 79% by initial GCS in GCS score of 3, 56% in GCS scores of 4 to 8, 22% in GCS scores of 9 to 12, and 5% in GCS scores of 13 to 15. The youngest patients, aged 0 to 8 years, had dramatically better initial GCS and subsequently lower mortality rates. Regression analysis showed mortality benefit in the total population for intracranial pressure monitoring (odds ratio, 0.267) and craniotomy (odds ratio, 0.232). This study uses the National Trauma Data Bank to quantify the prevalence of pediatric intracranial gunshot wounds, with the goal to determine risk factors for prognosis in this patient population. Significant effects on mortality for invasive interventions including intracranial pressure monitoring and craniotomy for all patients suggest low threshold for use of these procedures if there is any clinical concern. The presence of a 79% mortality rate in patients with GCS score of 3 on presentation suggests that as long as there is not a declared neurologic death, intracranial pressure monitoring and treatment measures including craniotomy should be considered by the consulting clinician. Prognostic and epidemiological, level III.


Clinical study of duloxetine hydrochloride combined with doxazosin for the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome: An observational study.
To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker (alpha-blocker) doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).In all, 150 patients were enrolled and 126 patients completed the study (41 patients in the doxazosin group, 41 patients in the sertraline group, and 44 patients in the duloxetine group). This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ± 1.29, 2.66 ± 1.57, and 3.24 ± 1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ± 2.17, 4 ± 2.11, and 4.90 ± 2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63.41% after 1, 3, and 6 months, respectively. The SF-MPQ score in the sertraline group decreased to 1.76 ± 1.28, 3.07 ± 2, and 3.93 ± 2.53 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the sertraline group decreased to 3.56 ± 4.11, 5.73 ± 5.26, and 7.27 ± 6.50 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the duloxetine group was 36.36%, 88.64%, and 88.64% after 1, 3, and 6 months, respectively. The SF-MPQ score in the duloxetine group decreased to 3.61 ± 2.54, 6.05 ± 3.66, and 7.41 ± 4.26 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the duloxetine group decreased to 3.14 ± 3.28, 6.93 ± 3.90, and 9.43 ± 4.67 after 1, 3, and 6 months, respectively (P < 0.05). There were significant differences in the reduction of the NIH-CPSI score and the SF-MPQ score between the duloxetine group and the sertraline group and between the duloxetine group and the doxazosin group (P < 0.01). There were significant differences in the reduction of the HAD score at 3 months between the duloxetine group and the doxazosin group, and there were significant differences in the reduction of the HAD score at 6 months among the groups (P < 0.05). The incidence rates of adverse reactions in the duloxetine group, the sertraline group, and the duloxetine group were 29.5%, 17%, and 7.3%, respectively, with adverse events ranging from mild to moderate.There was a clear relationship between the extent of pain and mental factors in CP/CPPS with the main symptom of pain. Doxazosin combined with duloxetine exhibited good safety and efficacy in the treatment of pain disorder in CP/CPPS.


Characteristics of maternal heart rate patterns during labor and delivery.
To find patterns characteristic of maternal heart rates recorded by an electronic fetal monitor and compare them with concomitant fetal heart rate (FHR) patterns. Maternal heart rates and FHRs during active labor and delivery were simultaneously recorded in 26 parturients with singleton pregnancies in vertex presentation. The FHRs were obtained by an external ultrasound transducer or via a spiral scalp electrode and maternal heart rates by a triple-wire cable with electrocardiographic electrodes attached to the chest. Representative tracings of 30-60 minutes duration were selected from all stages of labor and after delivery of the placenta. Quantitative assessments were carried out under guidelines from the National Institute of Child Health and Human Development after blinding the source of these tracings. Patterns were compared by appropriate statistical analyses. Baseline maternal heart rates were significantly lower and their variability significantly higher than FHRs during all stages of labor. Maternal heart rates showed no decelerations; the proportion of tracings with accelerations increased as labor advanced, most of them coinciding with uterine contractions or bearing down efforts. The FHRs had both decelerations and accelerations. However, tracings with only accelerations (and no decelerations) were observed in decreasing frequency as labor advanced. Maternal accelerations had higher amplitudes and longer durations than fetal accelerations, especially in the second stage of labor. Maternal heart rate patterns recorded by electronic fetal monitors closely resemble fetal patterns. Baseline "fetal bradycardia," the absence of decelerations in the second stage of labor, and marked accelerations coinciding with uterine contractions may suggest a maternal heart rate rather than an FHR recording.


A Non-canonical BRCT-Phosphopeptide Recognition Mechanism Underlies RhoA Activation in Cytokinesis.
Cytokinesis partitions the cell contents to complete mitosis. During cytokinesis, polo-like kinase 1 (PLK1) activates the small GTPase RhoA to assemble a contractile actomyosin ring. PLK1 is proposed to pattern RhoA activation by creating a docking site on the central spindle that concentrates the RhoA guanine nucleotide exchange factor ECT2. However, ECT2 targeting to the central spindle is dispensable for cytokinesis, indicating that how PLK1 controls RhoA activation remains unresolved. To address this question, we employed an unbiased approach targeting ∼100 predicted PLK1 sites in two RhoA regulators: ECT2 and the centralspindlin complex, composed of CYK4 and kinesin-6. This comprehensive approach suggested that the only functionally critical PLK1 target sites are in a single cluster in the CYK4 N terminus. Phosphorylation of this cluster promoted direct interaction of CYK4 with the BRCT repeat module of ECT2. However, mutational analysis in vitro and in vivo led to the surprising finding that the interaction was independent of the conserved "canonical" residues in ECT2's BRCT repeat module that, based on structurally characterized BRCT-phosphopeptide interactions, were presumed critical for binding. Instead, we show that the ECT2 BRCT module binds phosphorylated CYK4 via a distinct conserved basic surface. Basic surface mutations mimic the effects on cytokinesis of loss of CYK4 cluster phosphorylation or inhibition of PLK1 activity. Together with evidence for ECT2 autoinhibition limiting interaction with CYK4 in the cytoplasm, these results suggest that a spatial gradient of phosphorylated CYK4 around the central spindle patterns RhoA activation by interacting with ECT2 on the adjacent plasma membrane.


[Relationship between protein binding and antimicrobial activities of antibiotics against Streptococcus pneumoniae and Haemophilus influenzae].
Fifty isolates of Streptococcus pneumoniae and 42 isolates of Haemophilus influenzae were isolated from the blood of children admitted to pediatric wards of hospitals in subprefucture between January 1998 and December 2005. The susceptibilities were measured by a microbroth dilution method using a standard broth and a broth containing 4.5% albumin. Against S. pneumoniae, penicillin G, ampicillin, cefotaxime, ceftriaxone, panipenem, meropenem, vancomycin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used and against H. influenzae, ampicillin, piperacillin, cefotaxime, ceftriaxone, panipenem, meropenem, clavulanic acid/ amoxicillin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used. Against S. pneumoniae, tebipenem was the highest antimicrobial activity in oral antibiotics (MIC90; < or = 0.06 microg/ml) and panipenem showed the highest activity for intravenous antibiotics (MIC90; < or = 0.12 microg/ml). Against H. influenzae, cefditoren was the highest activity for oral antibiotics (MIC90; < or = 0.06 microg/ml) and meropenem showed the highest activity for intravenous antibiotics (MIC90; < or = 50.06 microg/ml). The MIC90s measured by albumin containing broth were higher than those measured by standard broth. Protein binding rates of ceftriaxone, cefditoren, and faropenem were greater than 90%, and the MIC90 of these antibiotics measured by albumin addition methods were over 4-fold higher than those measured by standard methods.


[In vivo study of degradation of poly-(D,L-) lactide and poly-(L-lactide-co-glycolide) osteosynthesis material].
Comparison of the degradation of poly(D,L)lactide (Resorb X) or poly(lactide-co-glycolide) (LactoSorb) in vivo. LactoSorb and Resorb X osteosynthesis plates were fixed at the lateral aspect of the femora of 26 Chinchilla rabbits using the respective osteosynthesis screws. After intraperitoneal injection of fluorochromes the screw plate bone blocks were resected after 1, 6, 12, 14, 16, 21, 26 months and radiologic, histologic as well as fluorescence microscopic examinations were carried out. Newly formed bone was detectable above and beneath the polymers 1 month after the implantation. The implants were totally covered by newly formed bone after 6 months. While the LactoSorb screws were found to be as birefringent as after 1 month, in the Resorb X screws a continuous resorption by phagocytizing marrow cells starting from the periphery was detectable. Resorb X was totally resorbed in histologic slides 12 months after implantation, while total resorption of LactoSorb lasted 14 months; both polymers were replaced by marrow cells. Bone remodeling was not finished 26 months after implantation in both polymers. Resorption of Resorb X was finished earlier than the resorption of LactoSorb. Both materials were found by fluorescence microscope to be completely resorbed after 12 or 14 months, but bone remodeling of the screw holes was not yet finished 26 months after implantation.


Profile of Articles Published in AJR From 2014 to 2018 and Potential Association With Bibliometric Parameters.
OBJECTIVE. The purpose of this study was to assess the profile of articles published in the American Journal of Roentgenology (AJR) and potential associations with bibliometric indexes over a 5-year period. MATERIALS AND METHODS. Citable documents published from 2014 to 2018 were retrieved from the Journal Citation Reports database. Six bibliometric indexes were assessed. The following article parameters were retrieved: type, subspecialty (17 topics covered by AJR), origin, and title. Differences between groups were assessed by t test, ANOVA, Kruskal-Wallis test, or chi-square test. Citability was assessed by regression analysis. RESULTS. After exclusions, 2210 articles were considered citable and included in the analyses. Most of the metrics improved slightly, except for the Eigenfactor score and article influence score, which decreased. Original articles were preponderant; AJR published significantly more review articles than did three other general radiology journals. The mean number of citations per year of original articles (2.03 ± 2.18) was significantly larger than that of review articles (2.06 ± 2.47) (p = .02). The mean number of citations per year was significantly higher for articles with mixed-origin authorship (3.12 ± 3.19) than for articles with American (2.02 ± 2.17) or non-American (1.93 ± 2.26) authors only (p < .001). The distributions of mean number of citations per year among subspecialties differed significantly (p = .001). Articles on abdominal, musculoskeletal, pediatric, and women's imaging were more frequently cited. Multivariate regression analysis showed that subspecialty and presence of acronyms or initialisms in the title were the only independent predictors of citability (both, p = .001). CONCLUSION. The main AJR bibliometric indexes increased slightly from 2014 to 2018, except for those from the Eigenfactor Project. The presence of acronyms or initialisms in the title and subspecialty were the only independent predictors of citability.


VITRECTOMY FOR PHACOANAPHYLACTIC GLAUCOMA SECONDARY TO POSTERIOR CAPSULAR RUPTURE IN AN ADULT WITH PERSISTENT HYPERPLASTIC PRIMARY VITREOUS.
Persistent hyperplastic primary vitreous (PHPV) is a developmental anomaly in which the normal regression of the primary vitreous and hyaloid vasculature does not occur. In the literature, there are a few cases of PHPV in adulthood. We report the novel presentation of phacoanaphylactic glaucoma secondary to posterior capsular rupture in an adult with PHPV. We discuss the best management of this condition with a review of the literature on this topic. Case report and literature review. Medical management was unsuccessful in this case and vitrectomy and fragmatome lensectomy improved vision from PL to counting fingers. This case is unusual in the age of the patient in question as PHPV usually presents in childhood, as such there are few accounts in the literature to guide optimum management of adult PHPV. We suggest that surgical management of late-presenting PHPV should be considered to improve functional outcome.


Clinicopathologic Features of the Non-CNS Primary Ewing Sarcoma Family of Tumors in the Head and Neck Region.
Ewing sarcoma family of tumor (ESFT) is a group of malignant neoplasms that affect children and young adults. Primary ESFT does not commonly arise from the head and neck region. This study aimed to elucidate the clinicopathologic characteristics of ESFT of the head and neck region except for central nervous system primitive neuroectodermal tumors. Among the 207 cases of ESFT of the bone and soft tissue, diagnosed at Asan Medical Center during a 20-year period, 25 (12.1%) involved the head and neck region. Of those, 21 were available for histologic, immunohistochemical, and molecular studies. EWSR1 rearrangement was detected in 19 cases by reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. Primary sites included the cranial area (6 cases, 31.6%), sinonasal tract (6 cases, 31.6%), paraspinal space (4 cases, 21.0%), and other spaces (3 cases, 15.8%). The 5-year overall survival and disease-free survival rates for all cases were 69.7% and 33.6%, respectively. A large tumor size (>5 cm) correlated significantly with overall survival (P=0.009), but not with disease-free survival (P=0.210). Microscopically, 8 cases (42.1%) showed nested growth pattern. Clear and/or eosinophilic cytoplasm was observed in 68.4% cases. Immunopositivity for CD99, Friend leukaemia integration-1 (FLI-1), CD57, and caveloin-1 were detected in 100%, 88.9%, 83.3%, and 50% cases, respectively. ESFT in the head and neck region had a favorable prognosis and frequent atypical and epithelioid features. An awareness of these histologic and immunophenotypic characteristics will improve the diagnostic accuracy for head and neck round cell malignancies.


Fabrication of concave microlens arrays by local fictive temperature modification of fused silica.
A simple and convenient means of fabricating concave microlens arrays direct on silica glass by using the local fictive temperature modification of fused silica is presented. This method is based on the fact that an increased fictive temperature results in a much higher HF acid etching rate of fused silica. Combining the abrupt local fictive temperature enhancement by the CO2 laser pulse and the subsequent etching by the HF acid solution, concave microlens arrays with high fill factors, excellent smoothness, and optical performance are generated on fused silica.


Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans.
Although the underlying mechanisms of longevity are not fully understood, it is known that mutation in genes that share similarities with those in humans involved in the insulin/insulin-like growth factor I (IGF-I) signal response pathway can significantly extend life span in diverse species, including yeast, worms, fruit flies, and rodents. Intriguingly, the long-lived mutants, ranging from yeast to mice, share some important phenotypic characteristics, including reduced insulin signaling, enhanced sensitivity to insulin, and reduced IGF-I plasma levels. Such genetic homologies and phenotypic similarities between insulin/IGF-I pathway mutants raise the possibility that the fundamental mechanism of aging may be evolutionarily conserved from yeast to mammals. Very recent findings also provide novel and intriguing evidence for the involvement of insulin and IGF-I in the control of aging and longevity in humans. In this study, we focus on how the insulin/IGF-I pathway controls yeast, nematode, fruit fly, and rodent life spans and how it is related to the aging process in humans to outline the prospect of a unifying mechanism in the genetics of longevity.


Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate.
Treatment with PTH (parathyroid hormone) or a high-P(i) diet causes internalization of the type IIa sodium-dependent phosphate (Na/P(i) IIa) co-transporter from the apical membrane and its degradation in the lysosome. A dibasic amino acid motif (KR) in the third intracellular loop of the co-transporter is essential for protein's PTH-induced retrieval. To elucidate the mechanism of internalization of Na/P(i) IIa, we identified the interacting protein for the endocytic motif by yeast two-hybrid screening. We found a strong interaction of the Na/P(i) IIa co-transporter with a small protein known as the PEX19 (human peroxisomal farnesylated protein; PxF, Pex19p). PEX19 can bind to the KR motif, but not to a mutant with this motif replaced with NI residues. PEX19 is highly expressed in mouse and rat kidney. Western blot analysis indicates that PEX19 is located in the cytosolic and brush-border membrane fractions (microvilli and the subapical component). Overexpression of PEX19 stimulated the endocytosis of the Na/P(i) IIa co-transporter in opossum kidney cells in the absence of PTH. In conclusion, the present study indicates that PEX19 may be actively involved in controlling the internalization and trafficking of the Na/P(i) IIa co-transporter.


The Effect of a Traditional Preparation Containing Piper nigrum L. and Bunium persicum (Boiss.) B.Fedtsch. on Immobility Stress-Induced Memory Loss in Mice.
Alzheimer's disease is a progressive, age-related, and neurodegenerative disease characterized by mental decline. The exact cause of Alzheimer's disease is unclear, but cholinergic dysfunction, protein accumulation, and oxidative stress are among the most important hypotheses. The main purpose of our study was to investigate the effects of aqueous and hydroalcoholic extract combination of these two medicinal plants, black pepper and cumin (as a related formulation in traditional Persian medicine), on memory and learning of an immobilized stress animal model. In this study, hydroalcoholic and aqueous extracts of cumin and black pepper fruits were prepared. Six groups of mice were treated orally for 2 weeks: control group, immobility stress, and stress-induced immobility mice received different doses of the hydroalcoholic extract (100 and 200 mg/kg) and aqueous extract (100 and 200 mg/kg). The shuttle box, novel object detection, and rotarod test were used to evaluate memory and learning. The activities of acetylcholinesterase, catalase (CAT), and superoxide dismutase (SOD) and the level of reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the brain tissue. Immobility stress significantly reduced learning and motor coordination. Furthermore, MDA levels and acetylcholinesterase activity were significantly increased, while CAT and SOD activities were significantly reduced in the brain of immobility-induced stress mice. Other findings indicated that hydroalcoholic and aqueous extracts (100 and 200 mg/kg) of cumin and black pepper fruits have an improving effect on animal motor coordination and learning ability, GSH content, and CAT, SOD, and acetylcholinesterase enzyme function in comparison with stress groups (p < 0.05). The hydroalcoholic and aqueous extracts of cumin and black pepper fruits have protective effects against stress-induced memory deficit and oxidative stress and may have beneficial therapeutic effect in the treatment of neurodegenerative diseases.


Inhibitory effect of NBL1 on PDGF-BB-induced human PASMC proliferation through blockade of PDGFβ-p38MAPK pathway.
Pulmonary artery remodelling is a key feature in the pathological progress of pulmonary arterial hypertension (PAH). Moreover, excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a critical role in the pathogenesis of pulmonary artery remodelling. Neuroblastoma suppressor of tumorigenicity 1 (NBL1) has been previously shown to induce growth inhibition in tumour cells. However, the effect of NBL1 in the regulation of human PASMC proliferation remains unclear. In cultured human PASMCs, we observed a dose-dependent inhibitory effect of NBL1 on platelet derived growth factor (PDGF)-BB-induced cell growth, DNA synthesis and proliferating cell nuclear antigen (PCNA) expression, as measured by MTS assay, 5-ethynil-2-deoxyuridine (EdU) analysis and western blots respectively. We also detected the expression and activities of cell-cycle positive regulators (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and negative regulators (p21 and p27) in human PASMCs by western blots and co-immuoprecipitation (IP). Our results show that NBL1-induced growth suppression is associated with the decreased activity of cyclin D1-CDK4 and the decreased phosphorylation of p27 in PDGF-BB-treated human PASMCs. By western blots using the phosphor-specific antibodies, we further demonstrated that NBL1 induced growth suppression is mediated by blockade of the up-stream PDGF-receptor β (PDGFRβ)-p38 mitogen-activated protein kinase (MAPK). In conclusion, our results suggest that NBL1 could inhibit PDGF-BB-induced human PASMC proliferation, and the underlying mechanism is associated with the decreased cyclin D1-CDK4 activity and up-regulated p27 by decreasing the phosphorylation of p27 via blockade of PDGFRβ-p38MAPK signal cascade. Our findings may provide a potential therapeutic target for PAH.


A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas.
Herstatin (HST) is an alternatively spliced HER2 product with growth-inhibitory properties in experimental cancer systems. The role of HST in adult human tissues and disease remains unexplored. Here, we investigated HST expression at the mRNA and protein (immunohistochemistry [IHC]) level in parallel with parameters reflecting HER activation in 187 breast carcinomas and matched noncancerous breast tissues (NCBT). Noncancerous breast tissues demonstrated the highest HST/HER2 transcript ratios corresponding to a few positive epithelial and stromal cells by IHC. Although HST/HER2 transcript ratios in tumors were inversely associated with HER2 IHC grading (P = .0048 for HER2 IHC-1+ and P = .0006 for HER2 IHC-2+ vs HER2-negative tumors), relative HST expression within the same tumor/NCBT system remained constant. HST/HER2 ratios did not predict the presence of HST protein, which was found in 46 (25%) of 187 tumors. A subgroup of HER2 IHC-3+ tumors exhibited high HST/HER2 transcript ratios, strong HST protein positivity, and cytoplasmic phospho-Akt/PKB and p21(CIP1/WAF1) localization. In conclusion, HST may act as a paracrine factor in the adult breast. Because HST is described as an endogenous pan-HER inhibitor, the presence of this protein in breast carcinomas may portent the inefficiency of exogenous efforts to block HER2 dimerization, whereas its absence may justify such interventions.