The Application of Quality Identification in Honey by Photoacoustic Spectroscopy.
The photoacoustic spectrum of glucose, sucrose and honey solutions in the visible range are measured by using the single-light photoacoustic spectrometer, and are compared with the spectra from spedtrophotometry method. The spectral characteristics of the above solutions show that the spectral background intensity and spectral profile have some differences for different kinds of solutions. The spectra of the three kinds of solutions all have strong peak value at 485 and 655 nm, but the intensity ratios between the two peaks are different. Besides, there are characteristic peak at 475, 576 and 630 nm for glucose, and the sucrose has apparent characteristic peak at 632 nm, these characteristic peaks can be used for detecting whether the natural honey has been added glucose or sucrose. By comparing two kinds of spectrum of the same solution, the intensity of photoacoustic spectrum is more responsive to the wavelength, indicating photoacoustic spectrometry has a higher sensitivity in the test of material composition.


Creation and detection of Skyrmions in a Bose-Einstein condensate.
We present the first experimental realization and characterization of two-dimensional Skyrmions and half-Skyrmions in a spin-2 Bose-Einstein condensate. The continuous rotation of the local spin of the Skyrmion through an angle of pi (and half-Skyrmion through an angle of pi/2) across the cloud is confirmed by the spatial distribution of the three spin states as parametrized by the bending angle of the l vector. The winding number w = (0,1,2) of the internal spin states comprising the Skyrmions is confirmed through matter-wave interference.


Neural ECM molecules in synaptic plasticity, learning, and memory.
Neural extracellular matrix (ECM) molecules derived from neurons and glial cells accumulate in the extracellular space and regulate synaptic plasticity through modulation of perisomal GABAergic inhibition, intrinsic neuronal excitability, integrin signaling, and activities of L-type Ca(2+) channels, NMDA receptors, and Rho-associated kinase. Genetic or enzymatic targeting of ECM molecules proved to bidirectionally modulate acquisition of memories, depending on experimental conditions, and to promote cognitive flexibility and extinction of fear and drug memories. Furthermore, evidence is accumulating that dysregulation of ECM is linked to major psychiatric and neurodegenerative diseases and that targeting ECM molecules may rescue cognitive deficits in animal models of these diseases. Thus, the ECM emerged as a key component of synaptic plasticity, learning, and memory and as an attractive target for developing new generation of synapse plasticizing drugs.


Role of MSC-derived small extracellular vesicles in tissue repair and regeneration.
Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and repair, secreting vesicles to the extracellular environment. Isolated exosomes were shown to affect angiogenesis, immunomodulation and tissue regeneration. Numerous efforts have been dedicated to describe the mechanism of action of these extracellular vesicles (EVs) and guarantee their safety, since the final aim is their therapeutic application in the clinic. The major advantage of applying MSC-derived EVs is their low or inexistent immunogenicity, prompting their use as drug delivery or therapeutic agents, as well as wound healing, different cancer types, and inflammatory processes in the neurological and cardiovascular systems. MSC-derived EVs display no vascular obstruction effects or apparent adverse effects. Their nano-size ensures their passage through the blood-brain barrier, demonstrating no cytotoxic or immunogenic effects. Several in vitro tests have been conducted with EVs obtained from different sources to understand their biology, molecular content, signaling pathways, and mechanisms of action. Application of EVs to human therapies has recently become a reality, with clinical trials being conducted to treat Alzheimer's disease, retina degeneration, and COVID-19 patients. Herein, we describe and compare the different extracellular vesicles isolation methods and therapeutic applications regarding the tissue repair and regeneration process, presenting the latest clinical trial reports.


The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity.
Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome.


Effects of Chain Parameters on Kinetics of Photochromism in Acrylic-Spiropyran Copolymer Nanoparticles and Their Reversible Optical Data Storage.
Chemical bonding between photochromic compounds and polymer matrices will induce several consitions such as photostability, photoreversibility, elimination of dye aggregation, and undesirable negative photochromism. In such polymeric systems, the switching rate and photoisomerization are closely dependent on several parameters like chain flexibility, steric restrictions, polarity, and even proticity of the surrounding medium. Here, copolymerization of a synthesized spiropyran-based monomer with butyl acrylate (BA) and methyl methacrylate (MMA) comonomers was carried out with various compositions of MMA and BA through emulsion polymerization, and the corresponding photoisomerization kinetics were studied. Particle sizes and their distributions were analyzed by dynamic light scattering, and morphologies were investigated by scanning and transmission electron microscopic analyses. The results showed the particles are spherical with diameter 62-82 nm. Differential scanning calorimetric thermograms were employed to determine Tg of the prepared copolymers, which ranged from -23 to 93 °C. The kinetics of photoisomerization was then studied by UV-vis spectroscopy. Finally, a latex containing spiropyran/acrylic copolymer with Tg of about 0 °C and optimum rate of coloration and decoloration was considered in reversible optical data storage studies due to its fast photochromism and good film-formation properties.


First Record of Triatoma maculata (Erichson, 1848) (Hemiptera: Reduviidae: Triatomini) in the Municipality of Riohacha, La Guajira - Colombia.
Knowledge of vector insect species, their habitat, and geographical distribution is crucial for determining the risk of transmission of the etiological agents that cause disease in humans, which allows defining strategies for prevention, surveillance, and control in line with the characteristics of each area. To determine the presence and public health importance of vectors of Chagas disease in the indigenous settlements of Marbacella and El Horno of the Wayúu ethnic group in the municipality of Riohacha, La Guajira, Colombia. From active search, installation and inspection of biosensors, and occasional catches, Hemiptera: Reduviidae: Triatomini were collected intra and in the peridomicile housing of the indigenous settlements of El Horno and Marbacella of the Wayúu ethnic group. Indices of intra and peridomestic infestation, colonization, density, dispersion, and natural infection with Trypanosoma cruzi Chagas, 1909 were calculated. 79.6% (n = 90) of the specimens were collected in the peridomicile and 20.3% (n = 23) in the intradomicile, all corresponding to Triatoma maculata (Erichson, 1848). The natural infection indices with T. cruzi accounted for 43.5% for Marbacella and 36% for El Horno. This is the first reported capture of individuals of T. maculata, considered a secondary vector of Chagas disease in Colombia, naturally infected with T. cruzi in the municipality of Riohacha expanding the geographical distribution of the species in the department of La Guajira.


Exhaled nitric oxide as biomarker of acute lung injury: an unfulfilled promise?
The discovery of nitric oxide (NO) as a signalling and regulatory molecule and its subsequent detection in the exhaled breath has not only yielded new mechanistic insights but also diagnostic opportunities and therapeutic targets in several important medical conditions. In diseases involving chronic pulmonary inflammation such as asthma that affects millions worldwide, exhaled NO has achieved spectacular successes with patients currently owning handheld devices and monitoring inflammatory aspects of their conditions in their own homes. This has been facilitated by recognition by regulatory bodies, scientific and clinical societies and insurance companies. While characteristic changes in exhaled NO have also been observed in acute lung injury (ALI), the promise of exhaled NO as a surrogate biomarker of this life-threatening disease has not been achieved. In this work, we have analysed factors contributing to successes of exhaled NO in the asthma field and contrasted these on the ALI field. We provide a snapshot of current status of exhaled NO field in ALI and propose a framework for definite evaluation of exhaled NO as a clinically useful biomarker.


Heterogeneous dynamics, ageing, and rejuvenating in van der Waals liquids.
It has been shown over the past ten years that the dynamics close to the glass transition is strongly heterogeneous: fast domains coexist with domains three or four decades slower, the size of these regions being about 3 nm at T(g). The authors extend here a model that has been proposed recently for the glass transition in van der Waals liquids. The authors describe in more details the mechanisms of the alpha relaxation in such liquids. It allows then to interpret physical ageing in van der Waals liquids as the evolution of the density fluctuation distribution towards the equilibrium one. The authors derive the expression of macroscopic quantities (volume, compliance, etc.). Numerical results are compared with experimental data (shape, times to reach equilibrium) for simple thermal histories (quenches, annealings). The authors explain the existence of a "Kovacs memory effect" and the temporal asymmetry between down jump and up jump temperatures experiments, even for systems for which there is no energy barriers. Their model allows also for calculating the evolution of small probe diffusion coefficients during ageing.


[Diagnostic value of the clinical probability score of deep venous thrombosis in the elderly].
There is a lack of scientific data concerning the incidence, clinical signs, risk factors and diagnostic management of deep vein thrombosis (DVT) in the elderly. We carried out a prospective case-control study in a geriatric setting. We included one in-patient without clinical signs of deep vein thrombosis for each hospitalised patient with clinically suspected DVT. Clinical signs, risk factors of DVT and a compression ultrasonography of the proximal and distal leg veins were performed in all patients at admission. Also, the clinical probability was assessed by means of the clinical score model described by Wells. There were 102 patients aged over 85 included during the 5 months period of the study. Fifty-one patients have had a clinical suspicion of DVT and 51 patients were clinically asymptomatic. There were 43% symptomatic DVT and 12% asymptomatic DVT. Clinical signs and symptoms of DVT were neither sensitive nor specific. Risk factors associated most frequently with DVT were: immobilisation (prevalence 64%), paralysis of the legs (22%), varicose veins (25%), deshydratation (28,5%), infections (18%). A significant relationship between a risk factor and DVT was found only for immobilisation (P<0,05) and deshydratation (P<0,02). The prevalence of DVT increased with the clinical probability score: 11.4% for the low score, 27.6% for the moderate score and 55% for the high score. Incidence of DVT is high among hospitalised elderly patients, especially for the asymptomatic ones. Clinical signs alone do not reliably predict DVT. Clinical probability score could be useful to improve diagnostic management of DVT in this population.


First Reusable Catalyst for the Reductive Coupling Reaction of Organohalides with Aldehydes.
In this study, we simulate the reductive coupling (Barbier-Grignard-type) reaction of organohalides with aldehydes using a new reusable catalyst. In this regard, bimetallic alloys of NiCo encapsulated in melamine-based dendrimers (MBD) immobilized on magnetic nanoparticles symbolized as γ-Fe2O3-MBD/NiCo were designed and synthesized. The structure and properties of the catalyst were studied by a variety of techniques such as Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), energy-dispersive spectrometry (EDS) mapping, and inductively coupled plasma (ICP). The presence of NiCo nanoalloys was confirmed by XRD and XPS analysis, TEM images, and EDS mapping. Various secondary alcohols were produced in good to high yields by reductive coupling of different types of aldehydes and organohalides in the presence of HCO2K as a nonmetallic reducing agent in aqueous media catalyzed by γ-Fe2O3-MBD/NiCo. In these reactions, the high catalytic performance of γ-Fe2O3-MBD/NiCo was achieved in comparison to monometallic counterparts due to the synergistic cooperative effect of Co and Ni in the NiCo nanoalloys. Magnetic and hydrophilic properties of the catalyst facilitate the catalyst recyclability for seven runs. The reusability of γ-Fe2O3-MBD/NiCo, use of water as an environmentally friendly solvent, ease of processing, and absence of metal additives make this process an excellent choice for the reductive coupling reaction to produce secondary alcohols from aldehydes. This is the first report on these kinds of reactions using a reusable catalyst.


The Antitumor Effect of Topotecan Loaded Thiolated Chitosan-Dextran Nanoparticles for Intravitreal Chemotherapy: A Xenograft Retinoblastoma Model.
This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model. The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested in vitro by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration. NPs had a mean diameter, polydispersity index, and zeta potential of 30 ± 4 nm, 0.24 ± 0.03 and +10 ± 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, P = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 ± 2%) and vitreous seeds (89 ± 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPH-CMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection (P = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH (P > 0.05). This investigation revealed definitive antitumor efficacy of TPH-CMD-TCS-NPs by intravitreal administration in the rabbit xenograft retinoblastoma model.


Conformation-Restricted Partially and Fully Fused BODIPY Dimers as Highly Stable Near-Infrared Fluorescent Dyes.
A set of highly stable conformation-restricted partially and fully fused BODIPY dimers (α,β-cyclohexadiene-fused and α,β-benzene-fused dimers) were synthesized from a one-pot condensation of 2-formylpyrroles with α,β-cyclohexadiene-fused bipyrrole 3. Effective expansion of π-conjugation over these fused BODIPY dimers was observed by X-ray analysis, density functional theory (DFT) calculations, and electrochemical and optical measurements, as demonstrated by their strong absorption and emissions in the near-infrared (NIR) range (650 to 820 nm).


Metabolic evaluation in patients with nephrolithiasis: A report from Isfahan, Iran.
Nephrolithiasis is a major public health problem worldwide. In recent years, growing evidence suggest that this disease may originate from underlying metabolic disorders. This is the first study that reports the frequency of different metabolic abnormalities among patients with nephrolithiasis in Isfahan, a large central province of Iran. From the time period between March 2009 and August 2010, 437 nephrolithiasis patients in Isfahan province enrolled in this study. Metabolic evaluation was performed by obtaining a 24-hours urine sample and fasting venous blood draw. We analyzed urine samples for volume, creatinine, calcium, citrate, oxalate, uric acid, sodium, and cystine. Fasting blood samples were assessed for serum calcium, phosphorus, sodium, potassium, uric acid, albumin, creatinine and blood urea nitrogen. The mean age was 46 ± 13.8 years (rang: 18-87). Nearly 50% were first time stone formers. The most common metabolic abnormalities were hypocitraturia (40.5%) and hypernatriuria (31.8%) that was followed by hyperoxaluria (28.8%). Hypercalciuria was detected only in 9.2% of the cases. Although, high calcium excretion was the most frequent metabolic derangement in several similar studies, in our province with considerably high prevalence of vitamin D deficiency, it is not frequent among nephrolithiasis patients. Instead, other metabolic risk factors were in higher frequencies.


Environmental applications of three-dimensional graphene-based macrostructures: adsorption, transformation, and detection.
Just as graphene triggered a new gold rush, three-dimensional graphene-based macrostructures (3D GBM) have been recognized as one of the most promising strategies for bottom-up nanotechnology and become one of the most active research fields during the last four years. In general, the basic structural features of 3D GBM, including its large surface area, which enhances the opportunity to contact pollutants, and its well-defined porous structure, which facilitates the diffusion of pollutant molecules into the 3D structure, enable 3D GBM to be an ideal material for pollutant management due to its excellent capabilities and easy recyclability. This review aims to describe the environmental applications and mechanisms of 3D GBM and provide perspective. Thus, the excellent performance of 3D GBM in environmental pollutant adsorption, transformation and detection are reviewed. Based on the structures and properties of 3D GBM, the removal mechanisms for dyes, oils, organic solvents, heavy metals, and gas pollutants are highlighted. We attempt to establish "structure-property-application" relationships for environmental pollution management using 3D GBM. Approaches involving tunable synthesis and decoration to regulate the micro-, meso-, and macro-structure and the active sites are also reviewed. The high selectivity, fast rate, convenient management, device applications and recycling utilization of 3D GBM are also emphasized.


Promethean Evolution: A Comparison of the Immune and Neural Systems.
In contrast to normal Darwinian evolution involving adaptation to past challenges, it has been suggested that evolution has devised two unique biological mechanisms to permit the host to anticipate future challenges: the adaptive immune response and neural memory functions. Certain phenomenological similarities, some sharing of names, and the participation in both systems of a group of physiologically active molecules suggested to many that the two might be intimately related. This article compares the two systems in terms of the familiar parlance of immunology-specificity, repertoire, degeneracy, memory, mediators, pathways, and genetics-to show that they differ in most respects, except insofar as they may utilize some of the same agents, many of which participate in the normal functions of other tissues and systems of the body. Indeed, this very difference provides a further demonstration of the wonders of the evolutionary process.


Patient selection for cytoreductive surgery and HIPEC for the treatment of peritoneal metastases from colorectal cancer.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a viable option for selected patients with peritoneal metastases (PM) from colorectal origin, resulting in long-term survival and even cure in some cases. However, adequate patient selection for this treatment is currently one of the major challenges. The aim of this review is to provide a comprehensive overview of clinically relevant factors associated with overall survival. This may help to guide clinicians through the complex interplay of patient, tumor, and treatment characteristics to adequately select patients who benefit the most from this extensive surgical treatment. First, basic principles of colorectal PM and the CRS and HIPEC treatment will be discussed. According to available literature, especially extent of peritoneal disease, completeness of cytoreduction, and signet ring cell histology have great influence on the outcome after CRS and HIPEC. Other factors that seem to have a negative prognostic value are the presence of liver metastases and the absence of treatment with neo-adjuvant systemic therapy. Prognostic models combining the above-mentioned factors, such as the Colorectal Peritoneal Metastases Prognostic Surgical Score nomogram, may provide clinically relevant tools to use in everyday practice.


tRNAscan-SE 2.0: improved detection and functional classification of transfer RNA genes.
tRNAscan-SE has been widely used for transfer RNA (tRNA) gene prediction for over twenty years, developed just as the first genomes were decoded. With the massive increase in quantity and phylogenetic diversity of genomes, the accurate detection and functional prediction of tRNAs has become more challenging. Utilizing a vastly larger training set, we created nearly one hundred specialized isotype- and clade-specific models, greatly improving tRNAscan-SE's ability to identify and classify both typical and atypical tRNAs. We employ a new comparative multi-model strategy where predicted tRNAs are scored against a full set of isotype-specific covariance models, allowing functional prediction based on both the anticodon and the highest-scoring isotype model. Comparative model scoring has also enhanced the program's ability to detect tRNA-derived SINEs and other likely pseudogenes. For the first time, tRNAscan-SE also includes fast and highly accurate detection of mitochondrial tRNAs using newly developed models. Overall, tRNA detection sensitivity and specificity is improved for all isotypes, particularly those utilizing specialized models for selenocysteine and the three subtypes of tRNA genes encoding a CAU anticodon. These enhancements will provide researchers with more accurate and detailed tRNA annotation for a wider variety of tRNAs, and may direct attention to tRNAs with novel traits.


VisRD--visual recombination detection.
VisRD, a program for visual recombination detection in a sequence alignment is presented. VisRD is written in Java and is designed to complement the multi-purpose phylogenetic software package SplitsTree4. The software is freely available from http://www.lcb.uu.se/~vmoulton/software/visrd/


Intramedullary versus extramedullary fixation for the treatment of intertrochanteric hip fractures.
One hundred thirty-one patients (135 fractures) who sustained an intertrochanteric fracture were assigned randomly to treatment with either a sliding hip screw or an intramedullary hip screw and followed up prospectively. In patients with unstable intertrochanteric fractures, the intramedullary device was associated with 23% less surgical time and 44% less blood loss; however, use of the intramedullary hip screw in patients who had a stable fracture pattern required 70% greater fluoroscopic time. Intraoperative complications occurred exclusively in patients in the intramedullary hip screw group. There were no differences in the rates of functional recovery between the two fixation groups.


Ab initio treatment of time-resolved x-ray scattering: application to the photoisomerization of stilbene.
In this work we present a general theoretical outline for calculating time-dependent x-ray scattering signal changes from first principles. We derive a formalism for the description of atom-atom correlation functions as Fourier transforms of quantum-chemically calculated electron densities and show their proportionality to the molecular form factor. The formalism derived in this work is applied to the photoisomerization of stilbene. We can demonstrate that wide-angle x-ray scattering offers a possibility to study the changes in electron densities in nonperiodic complex systems, which renders it a suitable technique for the investigation of (bio)organic systems.


Osimertinib Administration as the Primary Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy for Brain Metastasis of De Novo T790M-positive Lung Cancer.
A 69-year-old woman underwent left upper lobectomy for left upper lobe lung adenocarcinoma. She later perceived a left visual field defect, and a brain metastasis was detected on head magnetic resonance imaging (MRI). Epidermal growth factor receptor (EGFR) testing identified two separate EGFR mutations: an L858R mutation in exon 21 and a de novo T790M mutation in exon 20. Treatment with osimertinib was started. After one month, head MRI showed that the brain metastasis had shrunk, and the visual field defect had also improved. In this case, first-line osimertinib was effective for treating brain metastasis of de novo T790M-positive lung cancer.


Cancer cryotherapy: evolution and biology.
Since the inception of cryosurgery in the 1850s, landmark advances in chemistry, physics, materials science, and biology have culminated in the sophisticated cryosurgical devices currently in use. Effective cryosurgical tissue injury depends on four criteria: 1) excellent monitoring of the process; 2) fast cooling to a lethal temperature; 3) slow thawing; and 4) repetition of the freeze-thaw cycle. Meeting these criteria depends on understanding the imaging technology used to visualize the iceball, the type of cryogen used, the size of the probe, and probe arrangement. Third-generation cryosurgical equipment offers advantages over previous designs. These machines rely on argon for freezing but also use helium to warm probes and accelerate the treatment process, and they offer additional safety by being able to rapidly arrest iceball formation. Metallurgic advances have led to the development of thinner probes, which have been easily adapted to perineal templates similar to those used for prostate brachytherapy.


Histological Changes and Ghrelin, P-Selectin, and Leptin Parameter in Patients with Hepatic Hydatidosis in Iraq.
Humans and animals are affected by hydatid cyst disease as a worldwide zoonotic disease, which is caused by the metacestode stage of Echinococcus spp. This study was performed to evaluate the histological change of liver and blood concentrations of biomarkers, such as ghrelin, p-selectin, and leptin, in humans infected with hydatid cyst. A total of 30 surgical specimens of liver and blood of infected humans and 30 healthy individuals as a control group were evaluated. Liver tissue sections in cases infected with hydatid cyst and control group, histological abnormalities in the liver, including fibrosis, increased inflammatory cells, dystrophic areas, and necrosis were compared in this study. In addition, serum leptin levels were significantly lower in patients with hydatid cyst disease QUOTE <0.05) than in the control group (P-value<0.05), whereas p-selectin and ghrelin levels significantly decreased in patients (P-value<0.05). The results of this research can be effective in improving and promoting the treatment programs of hydatidosis.


Catalytic activity of human guanylate-binding protein 1 coupled to the release of structural restraints imposed by the C-terminal domain.
Human guanylate-binding protein 1 (hGBP-1) shows a dimer-induced acceleration of the GTPase activity yielding GDP as well as GMP. While the head-to-head dimerization of the large GTPase (LG) domain is well understood, the role of the rest of the protein, particularly of the GTPase effector domain (GED), in dimerization and GTP hydrolysis is still obscure. In this study, with truncations and point mutations on hGBP-1 and by means of biochemical and biophysical methods, we demonstrate that the intramolecular communication between the LG domain and the GED (LG:GED) is crucial for protein dimerization and dimer-stimulated GTP hydrolysis. In the course of GTP binding and γ-phosphate cleavage, conformational changes within hGBP-1 are controlled by a chain of amino acids ranging from the region near the nucleotide-binding pocket to the distant LG:GED interface and lead to the release of the GED from the LG domain. This opening of the structure allows the protein to form GED:GED contacts within the dimer, in addition to the established LG:LG interface. After releasing the cleaved γ-phosphate, the dimer either dissociates yielding GDP as the final product or it stays dimeric to further cleave the β-phosphate yielding GMP. The second phosphate cleavage step, that is, the formation of GMP, is even more strongly coupled to structural changes and thus more sensitive to structural restraints imposed by the GED. Altogether, we depict a comprehensive mechanism of GTP hydrolysis catalyzed by hGBP-1, which provides a detailed molecular understanding of the enzymatic activity connected to large structural rearrangements of the protein. DATABASE: Structural data are available in RCSB Protein Data Bank under the accession numbers: 1F5N, 1DG3, 2B92.


A nonanuclear triangular macrocycle and a linear heptanuclear heterometallic complex based on a 2-substituted imidazole-4,5-dicarboxylate ligand.
A Cp*Rh-based nonanuclear triangular macrocycle complex [(Cp*Rh)9L3(NO3)4.5(MeOH)](OTf)4.5 (1), a Cp*Ir-based trinuclear complex [(Cp*Ir)3L(MeCN)4](OTf)3 (2) and a linear heptanuclear heterometallic complex [(Cp*Ir)6ZnL2(MeCN)8(MeOH)2](OTf)8 (3) (Cp* = η(5)-pentamethylcyclopentadienyl) have been synthesized from a 2-(4-(pyridin-4-yl)phenyl)-1H-imidazole-4,5-dicarboxylic acid proligand. These complexes were further characterized by X-ray crystallography, (1)H NMR, DOSY NMR, IR spectroscopy, and elemental analyses.


Yeast glucan in the cyst wall of Pneumocystis carinii.
Ultrastructurally, the cyst wall of Pneumocystis carinii consists of an electron-dense outer layer, an electron-lucent middle layer, and an innermost plasmalemma. This is similar in appearance to the cell wall of some yeasts, e.g. Saccharomyces cerevisiae, which consists of an outer dense layer of mannan, a middle lucent layer of beta-1,3-glucan (yeast glucan) and an innermost plasmalemma. The cyst wall of P. carinii, as well as the cell wall of S. cerevisiae, can be labeled by a variety of methods which stain polysaccharides, such as Gomori's methenamine silver (GMS) and by Aniline blue, a dye which selectively stains beta-1,3-glucan. The treatment of P. carinii cysts with Zymolyase, which the key enzyme is beta-1,3-glucan laminaripentaohydrolase, results in lysis of the outer 2 layers of the cyst wall and the loss of positive staining by both GMS and Aniline blue. The lysis of elements of the cyst wall of P. carinii is achieved under the same conditions and concentration at which Zymolyase lyses the outer 2 layers of the cell wall of viable cells of S. cerevisiae. These observations indicate that a major component of the cyst wall of P. carinii is beta-1,3-glucan.


Evaluating tilt table testing in syncope 2: management options.
This is a two-part unit on syncope and the value of tilt table testing. Part 1 discussed the physiology of syncope, the procedure of tilt table testing, and indications and contraindications for it. This second part outlines the four common non-cardiac causes of syncope, treatment and management options.


Two new components from Gnetum pendulum.
Two new compounds, 3-O-(13-hydroxy-9Z,11E,15E-octadecatrienoyl) cycloeucalenol (1) and 24'-hydroxy-tetracosyl ferulate (2), together with one known compound, tetracosyl ferulate (3), were isolated from the dried stems of Gnetum pendulum. The two new compounds were structurally elucidated by spectroscopic and chemical methods.


Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss.
The genetic predispositions to venous thrombosis such as factor V Leiden (FVL) mutation (Arg 506 Gln), prothrombin (FII) gene mutation (G20210A), and mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) have been reported to be associated with recurrent pregnancy loss. This paper examines the prevalence of markers for genetic thrombophilias in women with recurrent miscarriage. The prevalence of FVL, FII G20210A and MTHFR C677T was compared in 108 women with three or more pregnancy losses either exclusively in the first trimester, or mixed first and second trimester losses, with the prevalence found in 82 fertile parous control women without miscarriages. Markers for the thrombophilias were assessed by PCR analysis. Twenty-three of the 108 patients (21.3%), had thrombophilia markers, which was similar to the proportion of patients in the control group (20.7%) with these markers. The prevalences of FVL and FII G20210A were lower in the study group than in the control group (3.7 versus 6.1% for FVL and 4.6 versus 6.1% for FII respectively); however, the difference was not statistically significant. In contrast, the prevalence of MTHFR C677T was higher in the study group than the control population (13 versus 8.5% respectively), but this difference was not statistically significant. There was no statistically significant prevalence of any particular thrombophilia in patients with previous first and second trimester pregnancy losses compared with patients with first trimester losses alone. Thrombophilia was not found to be associated with recurrent pregnancy loss.


Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.
Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.


Immunological Involvement of MicroRNAs in the Key Events of Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is an archetype autoimmune disease characterized by a myriad of immunoregulatory abnormalities that drives injury to multiple tissues and organs. Due to the involvement of various immune cells, inflammatory cytokines, and related signaling pathways, researchers have spent a great deal of effort to clarify the complex etiology and pathogenesis of SLE. Nevertheless, current understanding of the pathogenesis of SLE is still in the early stages, and available nonspecific treatment options for SLE patients remain unsatisfactory. First discovered in 1993, microRNAs (miRNAs) are small RNA molecules that control the expression of 1/3 of human genes at the post-transcriptional level and play various roles in gene regulation. The aberrant expression of miRNAs in SLE patients has been intensively studied, and further studies have suggested that these miRNAs may be potentially relevant to abnormal immune responses and disease progression in SLE. The aim of this review was to summarize the specific miRNAs that have been observed aberrantly expressed in several important pathogenetic processes in SLE, such as DCs abnormalities, overactivation and autoantibody production of B cells, aberrant activation of CD4+ T cells, breakdown of immune tolerance, and abnormally increased production of inflammatory cytokines. Our summary highlights a novel perspective on the intricate regulatory network of SLE, which helps to enrich our understanding of this disorder and ignite future interest in evaluating the molecular regulation of miRNAs in autoimmunity SLE.


Potential applications of optical coherence tomography in posterior segment trauma.
To describe potential clinical applications of optical coherence tomography (OCT) in diagnosis and surgical timing in eyes with posterior segment trauma. In a noncomparative study, 7 consecutive patients who had open-globe or closed-globe injury and were found to have posterior abnormality that could also be detected by OCT are described. All patients had documented OCT abnormalities in the posterior segment. In one patient with a penetrating injury, two metal foreign bodies were located in the posterior segment, one in the vitreous compartment coupled with inflammatory reaction and localized posterior vitreous detachment and the other embedded in the retina. In a second patient with a penetrating injury, OCT revealed the appearance of posterior vitreous detachment 5 days after injury. A closed-globe injury in one patient resulted in anterior optic neuropathy, manifested as disc edema and thickening of the circumpapillary retinal nerve fiber layer. The other patients had received blunt trauma and were found to have either full-thickness macular holes (2 patients), retinal pigment epithelium detachment at the papillomacular bundle site (1 patient), or macular edema (1 patient). OCT may serve as an important adjunct imaging device in evaluation of injuries to the posterior segment, qualitatively and quantitatively. It has potential in diagnosing subtle key abnormalities and in follow-up of these injuries.


Mouse models of Mdm2 and Mdm4 and their clinical implications.
Mdm2 and Mdm4 are two key negative regulators of the tumor suppressor p53. Deletion of either Mdm2 or Mdm4 induces p53-dependent early embryonic lethality in knockout mouse models. The tissue-specific deletion of Mdm2 induces p53-dependent apoptosis, whereas the deletion of Mdm4 induces both p53-dependent apoptosis and cell cycle arrest. Compared to Mdm4 deletion, Mdm2 deletion causes more severe phenotypic defects. Disrupting the Mdm2 and Mdm4 interaction using knockin mice models causes embryonic lethality that can be completely rescued by the concomitant loss of p53, suggesting that Mdm2 and Mdm4 heterodimerization is critical to inhibit p53 activity during embryogenesis. Overexpression of Mdm2 and Mdm4 in mice induces spontaneous tumorigenesis, which clearly indicates that Mdm2 and Mdm4 are bona fide oncogenes. Studies from these mouse models strongly suggest that blocking Mdm2- and Mdm4-mediated p53 inhibition is an appealing therapeutic strategy for cancer patients with wild-type p53 alleles.


Near-infrared fluorescence guided laparoscopic cholecystectomy in the spectrum of complicated gallstone disease.
ICG fluorescence (ICGF) guidance during laparoscopic cholecystectomy (LC) is gaining wider acceptance. While the accruing data largely addresses ICGF guidance during LC in patients with uncomplicated gallstone disease (UGS) and acute cholecystitis, there is a paucity of data related for complicated gall stone disease (CGS) such as choledocholithiasis, bilio-enteric fistula, remnant gall bladder, etc. The purpose of this study was to evaluate the role of ICGF during LC in the spectrum of CGS with state of the art 4 chip camera system. Retrospective review from a prospectively maintained database of all patients who underwent ICGF guided LC during the period June 1st, 2019 till December 30th, 2021 formed part of the study. Clinical profile and findings on ICGF during LC for CGS were studied. The data was studied to evaluate the potential roles of ICGF during LC for CGS. Of 68 patients, there were 29 males and 39 females. Among them were 32 and 36 in the uncomplicated and complicated gallstone disease groups, respectively. ICGF showed CBD visualization in 67(98.5%) and cystic duct in 62(91%). ICGF guidance helped in management of CGS, prior to, during and after completion of LC. It had novel application in patients undergoing CBD exploration. In our small series of patients with CGS, ICGF guidance enabled a LC and laparoscopic subtotal cholecystectomy in 94% and 6% of patients respectively. The study highlights potential roles and advantages with ICGF guided laparoscopic management for CBD stones, bilioenteric fistula, completion cholecystectomy and cystic duct stones. Large scale multicenter prospective studies are required to clarify the role of ICGF in the wide spectrum of CGS.


Deconstructing hierarchies: Service users as co-teachers in occupational therapy education.
While occupational therapy currently tends to view itself as operating based on a client-centered, collaborative approach, studies often reflect a gap between rhetoric and practice. This work presents a new pedagogic standard which moves away from the medical model and toward a collaborative, client-centred approach. It functions to support a practice which embraces the respect for, and partnership with, people receiving services and replaces historic patterns which may strengthen the legitimacy of the professional and sustain clients' dependence. This pedagogy develops a therapeutic dialogue which draws from partnerships created in the classroom, where occupational therapy students engage in courses with a co-teacher service user, and examines how the collaboration with service users contributes to the training of occupational therapy students. Students and co-teachers can participate in the challenging experience of integrating theoretical knowledge with lived experience, thereby augmenting the development of a new and inclusive knowledge base.


[Expression and characterization of juvenile hormone binding protein Bmtol gene in silkworm, Bombyx mori].
The head of the silkworm is a nerve center and a sense organ, contains antennaes and sensory hair, feels the outside signal, and responds to the external signal delivered to the brain. Juvenile hormone is mainly synthesized and secreted by corpora allata, and it needs to be played with the aid of the hormone binding protein, because the juvenile hormone binding protein is the carrier of juvenile hormone transport and plays a functional in vivo, they have an extremely important function in insects. The objective of this study is to screened and identify a novel BmTOL proteins that it has a conserved structure of the juvenile hormone binding protein family by SilkDB and NCBI database. Its coding gene number is BGIBMGA003404 (GenBank Accession No. KY681053). We also expressed the recombinant protein using the prokaryotic expression system, and then successfully purified the recombinant protein by Ni-NTA chromatography column to generate the polyclonal antibodies. The expression patterns analysis in various tissues showed that both in transcriptional and protein levels Bmtol was higher expressed in head. Furthermore, the expression level of Bmtol gene was higher in newly exuviated silkworm, and expression level of Bmtol gene was lower from at 3 days 5th instar to 7 days pupa, began to increase after the moth. Immunohistochemistry showed that BmTOL protein was localized in the cortex, antennaes and brain of the head, It may be related to the information transmission of the head, and provides an important source of information for the growth and development of silkworm.


Dermatologic care of sexual and gender minority/LGBTQIA youth, Part 2: Recognition and management of the unique dermatologic needs of SGM adolescents.
Sexual and gender minority (SGM) individuals, including lesbian, gay, bisexual, transgender/gender diverse, questioning/queer, intersex, and asexual (LGBTQIA) persons, represent a historically underserved population within the field of medicine, though their unique health needs are increasingly recognized. Part 2 of this two-part review will address unique concerns regarding acne, tanning behavior, sexually transmitted infections, and other health disparities among SGM adolescents. A more comprehensive understanding of the dermatologic needs of SGM youth will better allow pediatric dermatologists to actively and compassionately care for this health disparity population.


Functional limitation in later-life: the impact of sips, socialization, and sadness.
Findings on the health impact of moderate alcohol use in later-life have been discrepant. Unaddressed mechanisms of action and validity concerns may contribute to contrasting results. Several studies have demonstrated a beneficial relationship between moderate alcohol use and functional ability. Research is needed to identify mechanisms of action that explain this relationship, while employing methods to reduce common validity concerns in alcohol use research. This study examines social interaction and depressive symptoms as serial mediators in the relationship between moderate alcohol use and functional limitation in later-life. HRS data from 2012-2016 were utilized (n = 1,474); heavy drinkers, adults younger than 65, and respondents with inconsistent alcohol use from 2008 to 2016 were excluded. Hypotheses were evaluated using a longitudinal serial mediation model with bias-corrected bootstrapping. Results indicated that, in the context of demographic variables, medical burden, and previous functional limitation, the relationship between 2012 moderate alcohol use and 2016 reduced functional limitation is only present when considering the mediating effect of 2014 depressive symptoms as a single mediator, and 2012 social interaction and 2014 depressive symptoms as serial mediators, respectively (total effect model R2=.167). Data indicate that relationships between moderate drinking and reduced functional limitation are explained through increased social interaction and subsequent reduced depressive symptoms. Results identify social interaction as an accessible treatment target to address depressive symptoms and functional limitation, and support increased assessment of IADLs in adults experiencing depressive symptoms (and vice versa) to facilitate early treatment/prevention of functional and emotional decline.


Birthweight-for-gestational-age z-scores are associated with early childhood cardiometabolic health in the Peri/Postnatal Epigenetic Twin Study.
Birthweight has been consistently related to risk of cardiometabolic disorders in later life. Twins are at higher risk of low birthweight than singletons, so understanding the links between birthweight and cardiometabolic health may be particularly important for twins. However, evidence for the association of birthweight with childhood markers of cardiometabolic health in twins is currently lacking. Previous studies have often failed to appropriately adjust for gestational age or fully implement twin regression models. Therefore, we aimed to evaluate the association of birthweight-for-gestational-age z-scores with childhood cardiometabolic health in twins, using within-between regression models. The Peri/Postnatal Epigenetic Twins Study is a Melbourne-based prospective cohort study of 250 twin pairs. Birthweight was recorded at delivery, and childhood anthropometric measures were taken at 18-month and 6-year follow-up visits. Associations of birthweight with markers of cardiometabolic health were assessed at the individual, between- and within-pair level using linear regression with generalised estimating equations. Birthweight-for-gestational-age z-scores were associated with height, weight and BMI at 18 months and 6 years, but not with blood pressure (twins-as-individual SBP: β = 0.15, 95% CI: -0.81, 1.11; twins-as-individual DBP: β = 0.22, 95% CI: -0.34, 0.77). We found little evidence to indicate that the within-between models improved on the twins-as-individuals models. Birthweight was associated with childhood anthropometric measures, but not blood pressure, after appropriately adjusting for gestational age. These associations were consistent across the within-between and twins-as-individuals models. After adjusting for gestational age, results from the twins-as-individuals models are consistent with singleton studies, so these results can be applied to the general population.


Selection of antibiotic-resistant pathogens in the community.
In recent years, the importance of the community as a breeding ground for antibiotic-resistant pathogens is being recognized. Prescription of antimicrobial drugs for viral infections, inadequate dosage, use of long-acting macrolides and broad-spectrum antibiotics, and accessibility of over-the-counter antibiotics in many countries are the main drivers of increasing resistance. Education of physicians and the public on the correct use of antibiotics, introduction of rapid and reliable laboratory methods to distinguish between viral and bacterial infections, and offering economic incentives to the pharmaceutical industry to develop new drugs appear to be key issues in the confrontation with this serious public health problem.


Effects of combining inducible nitric oxide synthase inhibitor and radical scavenger during porcine bacteremia.
Complex interactions of nitric oxide and other free radicals have been implicated in the pathogenesis of sepsis and organ dysfunction. We hypothesized that simultaneous inducible nitric oxide synthase inhibition (L-N6-[1-iminoethyl]-lysine [L-NIL]) and neutralization of superoxide (O2-) (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl [Tempol]) would protect from detrimental consequences of long-term, volume-resuscitated, hyperdynamic porcine bacteremia. In this prospective, randomized, controlled experimental study, 16 anesthetized, mechanically ventilated and instrumented pigs were exposed to 24 h of continuous infusion of live Pseudomonas aeruginosa. After 12 h of hyperdynamic sepsis, animals were randomized to receive either vehicle (control, n = 8) or combination of L-NIL and Tempol (n = 8). Systemic and hepatosplanchnic hemodynamics, oxygen exchange, metabolism, ileal mucosal microcirculation and tonometry, oxidative stress and coagulation parameters were assessed before, 12, 18, and 24 h of P. aeruginosa infusion. Combined treatment inhibited sepsis-induced increase in plasma nitrate/nitrite, 8-isoprostane, and thiobarbituric acid reactive species concentrations, prevented hypotension, and reversed hyperdynamic circulation. Despite lower intestinal macrocirculation, combined regimen attenuated the otherwise progressive deterioration in ileal mucosal microcirculation and prevented mucosal acidosis. Treatment substantially attenuated mesenteric and hepatic venous acidosis, preserved sepsis-induced impairment of hepatosplanchnic redox state, and prevented the development of renal dysfunction. Finally, coinfusion of L-NIL and Tempol largely attenuated the sepsis-induced rise in plasma von Willebrand factor and thrombin-antithrombin complexes. Thus, hemodynamic, microcirculatory, metabolic, renal, and coagulation data indicate that combining inducible inhibition with cell permeable O2(-) radical scavenger afforded significant protection in porcine sepsis, thus suggesting an important interactive role of O2(-) and nitric oxide in mediating organ dysfunction.


Cation Exchange and Spontaneous Crystal Repair Resulting in Ultrathin, Planar CdS Nanosheets.
Cation exchange has become a major postsynthetic tool to obtain nanocrystals with a combination of stoichiometry, size, and shape that is challenging to achieve by direct wet-chemical synthesis. Here, we report on the transformation of highly anisotropic, ultrathin, and planar PbS nanosheets into CdS nanosheets of the same dimensions. We monitor the evolution of the Cd-for-Pb exchange by ex-situ TEM, HAADF-STEM, and EDX. We observe that in the early stages of the exchange the sheets show large in-sheet voids that repair spontaneously upon further exchange and annealing, resulting in ultrathin, planar, and crystalline CdS nanosheets. After cation exchange, the nanosheets show broad sub-band gap luminescence, as often observed in CdS nanocrystals. The photoluminescence excitation spectrum reveals the heavy- and light-hole exciton features, with very strong quantum confinement and large electron-hole Coulomb energy, typical for 2D ultrathin Cd-chalcogenide nanosheets.


Autophagy inhibits C2-ceramide-mediated cell death by decreasing the reactive oxygen species levels in SH-SY5Y cells.
Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2. However, only inhibition of ERK1/2 with PD98059 prevented C2-ceramide-induced autophagy, indicating that the ERK1/2 pathway contributes to ceramide-induced autophagy. According to the results of the flow cytometric assays, C2-ceramide-induced cell death was increased by 3-methyadenine (3-MA) and decreased by rapamycin. Furthermore, the generation of reactive oxygen species (ROS) in the cells was increased by 3-MA and decreased by rapamycin. Based on these datas, autophagy protected SH-SY5Y cells from C2-ceramide-induced cell death by decreasing ROS production. Therapeutic strategies that regulate autophagy may be used in the treatment of neurological disorders associated with ceramide-induced cell death.


Clinical Characteristics of and Cancer Incidence in Children Evaluated for Lymphadenoapthy Referred to Pediatric Oncology Clinics.
In our study, we aimed to investigate the clinical characteristics and cancer frequency in patients referred to our pediatric oncology outpatient clinic for lymphadenopathy. The charts of patients admitted to our pediatric oncology outpatient clinics for lymphadenopathy between January 2014, and December 2016 were retrospectively reviewed in this study. Age, gender, duration of complaints, previous therapies, systemic signs and symptoms, lymph node characteristics and laboratory findings were recorded. The frequency of malignancy was calculated. One hundred thirty-four patients (34 girls) with a median age of six years (range four months-17 years) were included in our study. The majority of the patients (98%) had localized lymphadenopathy and the head and neck region was the most common site of involvement (87%). The median long-axis diameter of lymph nodes ranged between 0.5 cm and 5 cm (median 2 cm) by physical examination. Twenty-one patients (15.6%) had lymph node biopsy. Four patients had ruptured epidermal cyst, lymphangioma, pilomatricoma and ectopic thymus. Of the other biopsies, nine patients were diagnosed with reactive LAP, four with lymphadenitis, and four with Hodgkin's disease. The lymphoma patients had lymph node size greater than 2.5 cm and the duration of lymphadenopathy was longer than four weeks. Three out of four patients had systemic clinical findings accompanying lymph node enlargement. Three percent of the patients with lymphadenopathy who were referred for suspected malignancy received a cancer diagnosis. This rate, which is too low for a reference center, suggested that the patients might be referred to the pediatric oncology outpatient clinic without a thorough evaluation in primary health care.


How often do normal persons sneeze and blow the nose?
Rhinitis is defined as an inflammatory disease, but in clinical practice the diagnosis is based on the occurrence of nasal symptoms. As all persons occasionally sneeze and blow the nose, it is necessary to define what is normal. In this study the daily number of sneezes and of nose blowing were recorded in diary-cards over a 14 day period by 80 hospital employees and medical students, who considered themselves not to suffer from rhinitis. The results showed that more than 95% of the normal persons sneezed and blew the nose less than 4 times a day, on average. It is concluded that it is normal to sneeze and blow the nose less than 4 times daily while a higher number can be a sign of rhinitis. It is recommended that counting of sneezes and of nose blowing is used in clinical trials in order to define the study population. Together with an objective measurement of nasal patency this can be useful in defining the effect profile of different types of treatment.


Nonlinear Dendritic Coincidence Detection for Supervised Learning.
Cortical pyramidal neurons have a complex dendritic anatomy, whose function is an active research field. In particular, the segregation between its soma and the apical dendritic tree is believed to play an active role in processing feed-forward sensory information and top-down or feedback signals. In this work, we use a simple two-compartment model accounting for the nonlinear interactions between basal and apical input streams and show that standard unsupervised Hebbian learning rules in the basal compartment allow the neuron to align the feed-forward basal input with the top-down target signal received by the apical compartment. We show that this learning process, termed coincidence detection, is robust against strong distractions in the basal input space and demonstrate its effectiveness in a linear classification task.


The Community Perspective on Potentially Inappropriate Treatment.
Rationale: Medical interventions that prolong life without achieving an effect that the patient can appreciate as a benefit are often considered futile or inappropriate by healthcare providers. In recent years, a multicenter guideline has been released with recommendations on how to resolve conflicts between families and clinicians in these situations and to increase public engagement. Although laypeople are acknowledged as important stakeholders, their perceptions and understanding of the terms "potentially inappropriate" or "futile" treatment have received little formal evaluation.Objectives: To evaluate the community perspective about the meaning of futile treatment.Methods: Six focus groups (two groups each of ages <65, 65-75, and >75 yr) were convened to explore what constitutes futile treatment and who should decide in situations of conflict between doctors and families. Focus group discussions were analyzed using grounded theory.Results: There were 39 participants aged 18 or older with at least one previous hospitalization (personal or by immediate relative). When asked to describe futile or inappropriate treatment, community members found the concept difficult to understand and the terminology inadequate, though when presented with a case describing inappropriate treatment, most participants recognized it as the provision of inappropriate treatment. Several themes emerged regarding participant difficulty with the concept, including inadequate physician-patient communication, lack of public emphasis on end-of-life issues, skepticism that medical treatment can be completely inappropriate, and doubts and fears that medical futility could undermine patient and/or family autonomy. Participants also firmly believed that in situations of conflict families should be the ultimate decision-makers.Conclusions: Public engagement in policy development and discourse around medical futility will first require intense education to familiarize the lay public about use of inappropriate treatment at the end of life.


In vivo kinetics of oxidatively modified HDL.
The kinetics of oxidatively modified high-density lipoprotein (HDL) in vivo were investigated. 125I-labeled oxidized (Ox) HDL and 131I-labeled native (N) HDL were injected simultaneously into control and WHHL rabbits. The fractional catabolic rates of 125I-labeled Ox-HDL were significantly greater than those of 131I-labeled N-HDL in both control (2.52 +/- 0.36/day vs 0.94 +/- 0.02/day) and WHHL rabbits (4.07/day vs 1.32/day). Oxidized HDL was catabolized faster than native HDL and was taken up primarily by the liver, spleen, and kidney.


Wide-angle X-ray solution scattering for protein-ligand binding: multivariate curve resolution with Bayesian confidence intervals.
A new way to use wide-angle x-ray solution scattering to study protein-ligand binding is presented. First, scattering patterns are measured at different protein and ligand concentrations. Multivariate curve resolution based on singular value decomposition and global analysis is applied to estimate the binding affinities and reference patterns (i.e., the scattering patterns of individual components). As validated by simulation, Bayesian confidence intervals provide accurate uncertainty estimates for the binding free energies and reference patterns. Experimental results from several protein-ligand systems demonstrate the feasibility of the approach, which promises to expand the role of wide-angle x-ray scattering as a quantitative biophysical tool.


Clinicopathologic and Molecular Characteristics of and Diagnostic Dilemmas in Invasive Breast Carcinoma with Choriocarcinomatous Pattern apropos a New Case: A Literature Review with New Findings.
Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with β-human chorionic gonadotropin (β-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. Compared to the MC-B patients, the IBC-CP patients were older (p < 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed β-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.


Kruppel-like factor 5 is required for perinatal lung morphogenesis and function.
The transition to air breathing after birth requires both anatomic and biochemical maturation of the lung. Lung morphogenesis is mediated by complex paracrine interactions between respiratory epithelial cells and mesenchymal cells that direct transcriptional programs guiding patterning and cytodifferentiation of the lung. In the present study, transgenic mice were generated in which the Kruppel-like factor 5 gene (Klf5) was conditionally deleted in respiratory epithelial cells in the fetal lung. Lack of KLF5 inhibited maturation of the lung during the saccular stage of development. Klf5(Delta/Delta) mice died of respiratory distress immediately after birth. Abnormalities in lung maturation and morphogenesis were observed in the respiratory epithelium, the bronchiolar smooth muscle, and the pulmonary vasculature. Respiratory epithelial cells of both the conducting and peripheral airways were immature. Surfactant phospholipids were decreased and lamellar bodies, the storage form of surfactant, were rarely found. mRNA microarray analysis demonstrated that KLF5 influenced the expression of genes regulating surfactant lipid and protein homeostasis, vasculogenesis, including Vegfa, and smooth muscle cell differentiation. KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth.


Salivary and serum B-cell activating factor (BAFF) levels after hydroxychloroquine treatment in primary Sjögren's syndrome.
Some evidence implicates a role of hydroxychloroquine (HQ) in the management of Sjögren's syndrome. This study evaluated the effect of HQ on saliva B-cell activating factor (BAFF) levels as well as health related quality of life (QoL) in patients with primary Sjögren's syndrome (pSS). Ten pSS patients who had been treated with HQ for at least 2 years and 15 healthy controls (HC) were included in the study. First, HQ was withdrawn for 12 weeks, then baseline evaluation was performed. Subsequently, HQ was restarted and further evaluations were carried out after 12 and 24 weeks of HQ treatment. Oral infection foci were eliminated by dental and periodontal treatments in both groups before enrollment. BAFF levels were evaluated with ELISA in serum and unstimulated mixed saliva. Salivary flow rates of patients and the control group were measured as well. Oral health quality of life (QoL) was evaluated by an oral health impact profile-14 (OHIP-14) questionnaire. Salivary BAFF levels (median: 12.39 ng/ml) were significantly decreased by using HQ both at 12 (2.78 ng/ml, P = 0.008) and 24 weeks (0.54 ng/ml, P = 0.011). Similarly, decreases in serum BAFF levels (5.23 ng/ml) were seen at 12 and 24 weeks after HQ treatment (2.18 ng/ml, P = 0.008 and 0.0 ng/ml, P = 0.012, respectively). Serum and salivary BAFF levels were significantly lower in healthy controls (0.37 ng/ml and 0.0 ng/ml, resp.) compared to those of pSS before HQ therapy (P = 0.006 and P = 0.001, resp.). Unstimulated salivary flows were similar in patients treated with HQ after 12 (0.38 ml/min) and 24 weeks (0.50 ml/min) (P = 0.51) but higher than the patients' rate at baseline (0.04 ml/min) (P = 0.008). Salivary and serum BAFF levels were lowered in patients with pSS when treated with HQ. In addition, decreased disease activity and increased salivary flows can be achieved with HQ in pSS patients.


In vitro and in vivo repeatability of abdominal diffusion-weighted MRI.
To study the in vitro and in vivo (abdomen) variability of apparent diffusion coefficient (ADC) measurements at 1.5 T using a free-breathing multislice diffusion-weighted (DW) MRI sequence. DW MRI images were obtained using a multislice spin-echo echo-planar imaging sequence with b-values=0, 100, 200, 500, 750 and 1000 s mm(-2). A flood-field phantom was imaged at regular intervals over 100 days, and 10 times on the same day on 2 occasions. 10 healthy volunteers were imaged on two separate occasions. Mono-exponential ADC maps were fitted excluding b=0. Paired analysis was carried out on the liver, spleen, kidney and gallbladder using multiple regions of interest (ROIs) and volumes of interest (VOIs). The in vitro coefficient of variation was 1.3% over 100 days, and 0.5% and 1.0% for both the daily experiments. In vivo, there was no statistical difference in the group mean ADC value between visits for any organ. Using ROIs, the coefficient of reproducibility was 20.0% for the kidney, 21.0% for the gallbladder, 24.7% for the liver and 28.0% for the spleen. For VOIs, values fall to 7.7%, 6.4%, 8.6% and 9.6%, respectively. Good in vitro repeatability of ADC measurements provided a sound basis for in vivo measurement. In vivo variability is higher and when considering single measurements in the abdomen as a whole, only changes in ADC value greater than 23.1% would be statistically significant using a two-dimensional ROI. This value is substantially lower (7.9%) if large three-dimensional VOIs are considered.


Membrane domain formation, interdigitation, and morphological alterations induced by the very long chain asymmetric C24:1 ceramide.
Ceramide (Cer) is involved in the regulation of several biological processes, such as apoptosis and cell signaling. The alterations induced by Cer in the biophysical properties of membranes are thought to be one of the major routes of Cer action. To gain further knowledge about the alterations induced by Cer, membrane reorganization by the very long chain asymmetric nervonoylceramide (NCer) was studied. The application of an established fluorescence multiprobe approach, together with x-ray diffraction, differential scanning calorimetry, and confocal fluorescence microscopy, allowed the characterization of NCer and the determination of the phase diagram of palmitoyloleoylphosphatidylcholine (POPC)/NCer binary mixtures. Nervonoylceramide undergoes a transition from a mixed interdigitated gel phase to a partially interdigitated gel phase at approximately 20 degrees C, and a broad main transition to the fluid phase at approximately 52 degrees C. The solubility of NCer in the fluid POPC is low, driving gel-fluid phase separation, and the binary-phase diagram is characterized by multiple and large coexistence regions between the interdigitated gel phases and the fluid phase. At 37 degrees C, the relevant phases are the fluid and the partially interdigitated gel. Moreover, the formation of NCer interdigitated gel phases leads to strong morphological alterations in the lipid vesicles, driving the formation of cochleate-type tubular structures.


Pathophysiology of stress urinary incontinence.
All cases of stress urinary incontinence (SUI) are not the same; urethral pressures, prolapse conditions, and congenital and acquired sphincteric dysfunction all contribute to SUI pathophysiology. In order to optimally manage SUI, a thorough understanding of the pathophysiology behind the condition is necessary. Unsuccessful treatment of incontinence can result from the procedure itself or from a poor fit between the patient's condition and the treatment chosen. Proper patient evaluation, including videourodynamics and measurement of Valsalva leak point pressure, is key to making the best treatment decisions and obtaining optimal patient outcomes.


Handover checklist: testing a standardization process in an Italian hospital.
This study aimed to standardize and rationalize the handover, a critical and essential moment in common health care practices, through the realization of an efficient and standardized checklist, which could be used daily to ensure complete, thorough and effective handover. The principal purpose of the implementation of the handover is to reduce errors due to superficial and insufficient communication. The "operative group" defined the phases to the realization of the delineated aims: at first, the direct observation and the consequent realization of a handover checklist model and then, the experimental phases (trials). The handover checklist model was used for a month and it was daily and duly completed by the doctors who took part in the trial. To prove the success of the study, three questionnaires were distributed on different occasions. Analyzing the answers to the questionnaires, the importance of the handover has come to light and that for the most part, the doctors consider it an essential and irreplaceable moment in daily health care work. Moreover, it became obvious that the use of the handover checklist guaranteed a considerable improvement in the traditional handover in terms of security, completeness, care continuity and clarity. The handover checklist was completely appreciated by the majority of the participant doctors who agree with the definitive introduction of it in their unit. Our study indicated the consistency of the handover checklist as an instrument to implement the handover and, indirectly, to improve the quality of the care.


Epitope-specific antibody feedback regulation of the humoral immune response against sheep erythrocytes in vitro: specific effects of anti-antigen antibody vs nonspecific T cell activities.
Antibody formed during a 1st in vitro anti-SRBC PFC response had previously been shown to inhibit the formation of PFC when added to a 2nd, freshly established test culture. This effect was to a large extent restricted to test cultures containing B cells sharing VH genes with the B cells producing the initial antibody, and this suggested that anti-SRBC antibody acted via triggering of an anti-idiotypic antibody of TS response. In the present studies this system has been further characterized. First, such antibody feedback occurred in cultures of purified and anti-Lyt2 antiserum and complement-treated surface Ig-positive cells in which TH were substituted for by T-replacing factor. Thus, T cells were not required. Moreover, T cells were always nonspecifically activated in cultures containing FCS. Secondly, anti-idiotypic antibody-like activity was not detected in the sense that generation of inhibitory antibody was never found to be dissociated from generation of anti-SRBC antibody, and LPS-dependent anti-SRBC PFC responses were not inhibited. However, feedback inhibition of SRBC-dependent responses was reversed at increased SRBC concentrations. Thirdly, the feedback mechanism was highly epitope specific, whereas in vitro anti-SRBC PFC responses of different mouse strains (B6 vs BALB/c) were directed to a large extent against different epitopes. These data strongly suggest that VH-restricted inhibitory activity of antibody in this system is a manifestation of epitope specificity of the antibody feedback and not of idiotype specificity, i.e., that anti-SRBC antibody acts via masking of epitopes.


Lifetime of the histone octamer studied by continuous-flow quasielastic light scattering: test of a model for nucleosome transcription.
An instrument for continuous-flow quasielastic light scattering is described that allows the translational diffusion coefficient of macromolecules to be determined as a function of time after the initiation of some time-dependent process by mixing. Control experiments are carried out using the proteins lysozyme and BSA to verify that flow of the solution does not lead to erroneous results. The instrument is used to determine the lifetime of the histone octamer. A solution of octamer that is artificially stabilized in 2.0 M NaCl is rapidly diluted to physiological ionic strength, and the Stokes diameter is determined as a function of the time, delta t, after mixing. We find that the octamers dissociate into their component H2A-H2B heterodimers and H(3)2H4 tetramers on a time scale that is faster than the earliest time point for which data were obtained, 1 s after mixing. This result argues against a simple mechanism for the progression of RNA or DNA polymerase through chromatin.


Neuronal regression during ageing: an ultrastructural study of the human cortex.
Neuronal regression has been ultrastructurally investigated in a neuronal sampling of the ageing human cerebral cortex. Even though the number of specimens examined is limited, there is an indication of an age-related regression involving the intraneuronal "nucleus-ribosome system". Such regressive signs are characterized by the polymorphous outline, invagination, reduced size of the nucleus, and in the nucleolar texture. Recognizable changes in the cytoplasm are, alterations in the density and distribution of free ribosomes and in the structure and organization of the rough endoplasmic reticulum cisternae. Furthermore light cytoplasmic areas, and increased number of microtubules and the gradual congestion of the perikaryon by age pigments are reliable criteria for identifying the sequence of morphologic events that occur during neuronal ageing. The above data provide some insight into the neuronal process and adding to a previous proposed model of neuronal maturation.


A Polymeric Composite Material (rGO/PANI) for Acid Blue 129 Adsorption.
Over the years, polyaniline (PANI) has received enormous attention due to its unique properties. Herein, it was chosen to develop a new polymeric composite material: reduced graphene oxide/polyaniline (rGO/PANI). The composite was prepared by a simple and cost-effective fabrication method of formation by mixing and sonication in various conditions. The obtained materials were characterized and identified using various techniques such as scanning electron microscopy (SEM), Raman and ATR-FTIR spectroscopy, and X-ray diffraction (XRD). The objective of the paper was to confirm its applicability for the removal of contaminants from water. Water could be contaminated by various types of pollutants, e.g., inorganics, heavy metals, and many other industrial compounds, including dyes. We confirmed that the Acid Blue 129 dyes can be substantially removed through adsorption on prepared rGO/PANI. The adsorption kinetic data were modeled using the pseudo-first-order and pseudo-second-order models and the adsorption isotherm model was identified.


Endovascular interventions for hepatic artery complications immediately after pediatric liver transplantation.
Hepatic artery complications after living donor liver transplantation (LDLT) can directly affect both graft and recipient outcomes. For this reason, early diagnosis and treatment are essential. In the past, relaparotomy was generally employed to treat them. Following recent advances in interventional radiology, favorable outcomes have been reported with endovascular treatment. However, there is ongoing discussion regarding the best and safe time for definitive endovascular interventions. We herein report a retrospective analysis for six children with early hepatic artery complication after pediatric LDLT who underwent endovascular treatment as primary therapy at our institution. We evaluate the usefulness of endovascular treatment for hepatic artery complication and its optimal timing. The mean patient age was 11.9 months and mean body weight at LDLT was 6.7 kg. The mean duration between the transplantation and first endovascular treatment was 5.3 days. Five of the six patients were technically successful treated by only endovascular treatment. Of these five patients, two developed biliary complications. Endovascular procedures were performed 10 times in six patients without any complications and nine of the 10 procedures were successful. By selecting optimal devices, our findings suggest that endovascular treatment can be feasible and safe in the earliest time period after pediatric LDLT.


Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB.
Cell cycle dependent phosphorylation of the RB tumor suppressor protein is mediated by a family of G1 cyclin dependent kinases (cdks) and cyclins including the activated cdk4:cyclin D complex. The identification of a cdk4 inhibitor, p16INK4, as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells. We have examined 88 lung cancer lines for p16INK4 protein expression and have observed a striking inverse correlation between the presence of p16INK4 and wildtype RB. We demonstrated that only 6/55 (11%) of small cell lung cancer (SCLC) samples had absent p16INK4 protein, and all 6 belonged to the rare subset of SCLC with wildtype RB expression. Conversely of 48 SCLC samples with absent or mutant RB, all showed detectable levels of p16INK4 protein. In contrast, we observed that 23/33 (70%) of non-SCLC samples had loss of p16INK4. Twenty-two of 26 non-SCLC lines with wildtype RB had absent p16INK4 while 6 of 7 non-SCLC lines with absent or mutant RB had detectable p16INK4. The inverse correlation of RB and p16INK4 expression and the absence of p16INK4 inactivation in RB (-/-) SCLC lines (0/48) confirms a common p16INK4/RB growth suppressor pathway in human cancers and provides evidence that p16INK4, and not an adjacent gene on chromosome 9p, is a specific target for mutational events.


The seventh nationwide tuberculosis prevalence survey in Korea, 1995.
Nationwide random sample survey for tuberculosis prevalence in Korea in 1995. To investigate the prevalence of tuberculosis infection, morbidity and drug resistance, and BCG coverage, and to compare the findings with those of the previous six surveys. The following investigations were performed: tuberculin test, BCG scar screening, chest miniature radiography (70 x 70 mm) for those aged over five years, sputum direct smear, culture and drug susceptibility test, and a questionnaire to obtain history of antituberculosis chemotherapy and symptoms. The coverages of the 1995 survey were as follows: tuberculin 87.0%, radiology 88.4%, bacteriology 98.3%. The observed tuberculin positivity (> or =10 mm in diameter) of subjects aged under 30 was 15.5%. The prevalence of pulmonary tuberculosis per 100000 has decreased in the last 30 years: direct smear positive from 686 to 93, smear and/or culture positive from 940 to 219, active tuberculosis from 5065 to 1032. Rates of drug resistance have also fallen: of those with no previous chemotherapy from 26.2% to 5.8%, of those with history of chemotherapy from 55.2% to 25.0%, and in total from 38.0% to 9.9%. BCG scar prevalence of infants (aged under one year) was 87.7%, and of those under 30 it was 91.8% in 1995. Tuberculosis prevalences and the drug resistance rates have decreased significantly.


Determinants of endogenous ligand specificity divergence among metabotropic glutamate receptors.
To determine the structural origins of diverse ligand response specificities among metabotropic glutamate receptors (mGluRs), we combined computational approaches with mutagenesis and ligand response assays to identify specificity-determining residues in the group I receptor, mGluR1, and the group III receptors, mGluR4 and mGluR7. Among these, mGluR1 responds to L-glutamate effectively, whereas it binds weakly to another endogenous ligand, L-serine-O-phosphate (L-SOP), which antagonizes the effects of L-glutamate. In contrast, mGluR4 has in common with other group III mGluR that it is activated with higher potency and efficacy by L-SOP. mGluR7 differs from mGluR4 and other group III mGluR in that L-glutamate and L-SOP activate it with low potency and efficacy. Enhanced versions of the evolutionary trace (ET) algorithm were used to identify residues that when swapped between mGluR1 and mGluR4 increased the potency of L-SOP inhibition relative to the potency of L-glutamate activation in mGluR1 mutants and others that diminished the potency/efficacy of L-SOP for mGluR4 mutants. In addition, combining ET identified swaps from mGluR4 with one identified by computational docking produced mGluR7 mutants that respond with dramatically enhanced potency/efficacy to L-SOP. These results reveal that an early functional divergence between group I/II and group III involved variation at positions primarily at allosteric sites located outside of binding pockets, whereas a later divergence within group III occurred through sequence variation both at the ligand-binding pocket and at loops near the dimerization interface and interlobe hinge region. They also demonstrate the power of ET for identifying allosteric determinants of evolutionary importance.


Calculation-assisted regioselective functionalization of the imidazo[1,2-a]pyrazine scaffold via zinc and magnesium organometallic intermediates.
Straightforward calculations such as determinations of pKa values and N-basicities have allowed the development of a set of organometallic reactions for the regioselective functionalization of the underexplored fused N-heterocycle imidazo[1,2-a]pyrazine. Thus, regioselective metalations of 6-chloroimidazo[1,2-a]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl·LiCl and TMP2Zn·2MgCl2·2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMP2Zn·2MgCl2·2LiCl as base for the first metalation allowed an alternative regioselective metalation. Nucleophilic additions at position 8 as well as selective Negishi cross-couplings complete the set of methods for selectively decorating this heterocycle of the future.


Effect of bilateral lesions of the solitary tract nucleus on arterial blood pressure in spontaneously hypertensive rats of Okamoto strain.
Bilateral electrolytic lesions of the solitary tract nucleus in control Wistar albino rats as well as in Okamoto rats with spontaneous arterial hypertension caused a considerable rise in the arterial blood pressure. Quantitative comparison of blood pressure rise in normotensive and hypertensive rats demonstrated that the rise in the systolic and mean blood pressure was not significantly different in both groups of animals. However, the rats with spontaneous hypertension reacted, with a greater rise in the diastolic pressure. A characteristic feature observed in the normotensive rats was a high rise in pulse pressure following lesion of the solitary tract nucleus while in the rats with spontaneous hypertension this change was not found. The authors conclude that increased peripheral vascular resistance in the rats with spontaneous hypertension is not due to inhibition or resetting of the baroreceptor reflex.


Solid cryogen: a cooling system for future MgB2 MRI magnet.
An efficient cooling system and the superconducting magnet are essential components of magnetic resonance imaging (MRI) technology. Herein, we report a solid nitrogen (SN2) cooling system as a valuable cryogenic feature, which is targeted for easy usability and stable operation under unreliable power source conditions, in conjunction with a magnesium diboride (MgB2) superconducting magnet. The rationally designed MgB2/SN2 cooling system was first considered by conducting a finite element analysis simulation, and then a demonstrator coil was empirically tested under the same conditions. In the SN2 cooling system design, a wide temperature distribution on the SN2 chamber was observed due to the low thermal conductivity of the stainless steel components. To overcome this temperature distribution, a copper flange was introduced to enhance the temperature uniformity of the SN2 chamber. In the coil testing, an operating current as high as 200 A was applied at 28 K (below the critical current) without any operating or thermal issues. This work was performed to further the development of SN2 cooled MgB2 superconducting coils for MRI applications.


An energy-harvesting scheme employing CuGaSe2 quantum dot-modified ZnO buffer layers for drastic conversion efficiency enhancement in inorganic-organic hybrid solar cells.
We demonstrated a promising route to enhance the performance of inverted organic photovoltaic (OPV) devices by the incorporation of CuGaSe2 (CGS) quantum dots (QDs) into the ZnO buffer layer of P3HT:PCBM-based devices. The modification of QDs provides better band alignment between the organic/cathode interface, improves ZnO crystal quality, and increases photon absorption, leading to more effective carrier transport/collection. By employing this energy-harvesting scheme, short-circuit current density, open-circuit voltage, and fill factor of the OPV device after CGS QD modification are improved by 9.43%, 7.02% and 6.31%, respectively, giving rise to a 23.8% enhancement in the power conversion efficiency.


The role of peripheral nerve surgery in the management of painful chronic wounds: indications and outcomes.
Patients with chronic wounds caused by healing problems often present with chronic pain at the site. Proper wound care with or without appropriate reconstruction usually addresses both the wound and its associated pain. However, wounds occasionally remain painful despite successful reconstruction, particularly when they are complicated by an underlying condition. These patients frequently develop a disabling chronic pain condition despite the application of current treatment modalities. The authors used a novel approach to manage this difficult clinical situation, by addressing the sensory nerve supply to the affected wound region. Five women and two men with intractable chronic pain despite wound reconstruction underwent surgery and were followed for a mean period of 27 months (range, 8 to 40 months). The involved sensory nerve was identified preoperatively by physical examination, confirmed by nerve block, and then surgically excised and implanted into adjacent muscle. Each patient's pain reduction, ambulation status, and quality-of-life improvement were evaluated. The involved nerves included the ilioinguinal, lateral femoral cutaneous, sural, saphenous, superficial peroneal, and deep peroneal nerves, and the genital branch of the genitofemoral nerve. All seven patients reported significant pain reduction (p < 0.0001), improved ambulation (p < 0.0001), and improved quality of life (p < 0.0001), as evaluated at last follow-up (mean, 27 months). This study suggests that an additional treatment modality in the management of chronic wounds can be considered for patients with disabling pain. As an adjunct to other interventions, this novel application of peripheral nerve surgery can critically improve symptoms in selected patients with intractable chronic wound pain.


Serum levels of alpha-fetoprotein, human chorionic gonadotropin and carcinoembryonic antigen in patients with primary intracranial germ cell tumors.
Serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and carcinoembryonic antigen (CEA) were determined by radioimmunoassay in 14 patients with primary intracranial germ cell tumors in the pineal and/or chiasmal region and the relationship between AFP, HCG and CEA levels, tumor histopathology and survival time was studied. In 7 of the 14 patients, elevation of AFP and/or HCG was noted. Histopathological diagnosis of these patients was embryonal carcinoma (1), choriocarcinomas (2) and seminoma (4). Five of the 7 patients died within 2 years after diagnosis in spite of surgery and/or radiation therapy. Seven patients who showed normal AFP and HCG levels consisted of 6 germinomas and one teratoma. Four of the 7 patients remain alive and well more than 5 years after surgery and/or radiation therapy. CEA was above normal in only one patient with a seminoma. Our results suggest that the serum levels of AFP and HCG are useful for predicting tumor histopathology and the prognosis of patients with primary intracranial germ cell tumors.


Heterocyclic compounds based on 3-(4-bromophenyl) azo-5-phenyl-2(3H)-furanone: anti-avian influenza virus (H5N1) activity.
1 3-[2-(4-Bromphenyl)hydrazono]-5-phenyl-furan-2(3H)-one () was used for preparation of some novel pyrazole, pyridazinone, oxadiazole, triazole, thiazolidine and thioxopyrimidine derivatives. Some of the prepared products were tested for anti-avian influenza virus activity and revealed promising antiviral activity against H5N1 virus [A/Chicken/Egypt/1/20 % (H5N1)] by determination of both EC50 and LD50 and confirmed by plaque reduction assay on Madin-Darby canine kidney cells. Compounds 3-[2-(4-bromophenyl)hydrazono]-5-phenylfuran-2(3H)-one (1), 1-(4-bromophenyl)-N-hydroxy-5-phenyl-1H-pyrazole-3-carboxamide (5) and 1-(4-bromophenyl)-N-{2,3-dihydro-4-hydroxy-3-phenyl-6-oxo-2-thioxopyrimidin-1(6H)-yl}-5-phenyl-1H-pyrazole-3-carboxamide (12a) showed the highest effects. Detailed synthesis, spectroscopic data, and antiviral activity of the synthesized compounds are reported.


[Serum free light chains for diagnosis and follow-up of multiple myeloma].
Free light chain (FLC) is widely used to evaluate B-cell proliferative diseases. Herein, we estimated the clinical usefulness of serum FLC in multiple myeloma (MM). Fifty-one patients were enrolled. We performed FLC analysis, protein electrophoresis (PEP), and immunofixation electrophoresis (IFE). FLC was measured using Toshiba 200 FR Neo with FREELITE, and kappa/lambda (kappa/lambda) ratio was calculated. We compared these parameters in 41 patients with increased FLC before and after bortezomib treatment. Complete response (CR) was defined as the disappearance of monoclonal (M) protein in serum and/or urine as measured by IFE. Partial response (PR) was defined as >or=50% reduction of serum M protein. Early objective response (EOR) included both CR and PR. Minimal response (MR) was defined as 25-49% reduction of M protein and stable disease (SD) as <25% reduction. Forty-one (80.4%) of the 51 patients studied revealed increment of FLC and the five patients with no increment revealed an abnormal kappa/lambda ratio. Especially, all of the light chain myeloma and non-secretory myeloma showed increased FLC concentrations. Among the patients with EOR, 72.4% (21/29) showed a normal or subnormal FLC concentration after the first cycle of treatment. Otherwise, PEP and IFE normalized in 24.1% (7/29) and 24.1% (7/29), respectively. The ratio of decreased FLC after the first cycle of treatment was significantly different between EOR and other response groups (MR, SD) (90.6% vs 51.8%, P=0.011). FLC was considered as a good diagnostic method in complement with PEP and IFE in MM, especially in light chain myeloma or non-secretory myeloma. Moreover, FLC is a useful monitoring tool because it reflects therapy results more rapidly owing to a short serum half-life.


Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors.
Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors.


Prognostic significance of interleukin 17 in cancer: a meta-analysis.
The prognostic value of Interleukin 17 (IL-17) in cancer patients is currently under debate and remains inconclusive. We performed a systematic review and meta-analysis to evaluate the role of IL-17 as a prognostic marker in cancer. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were combined to measure the effective value of IL-17 expression on prognosis. Nineteen eligible studies enrolling 2390 patients were identified. We found expression of IL-17 was not significantly correlated with overall survival (OS) in cancer (HR=1.29, 95% Cl: 0.94-1.76; P=0.12). Furthermore, compared to the data from our analysis that high expression of IL-17 predicted poor OS in both non-small cell lung carcinoma (NSCLC) (HR=2.30; 95% CI: 1.45-3.64; P<0.001; I(2)=0%) and hepatocellular carcinoma (HCC) (HR=2.02; 95% CI: 1.44-2.83; P<0.001; I(2)=0%), high expression of IL-17 was associated with favorable OS in esophageal squamous cell carcinoma (ESCC) (HR=0.63; 95% CI: 0.51-0.79; P<0.001; I(2)=0%). This meta-analysis showed that IL-17 has the potential to become a novel prognostic marker in HCC, NSCLC and ESCC. It could potentially help to monitor patients' prognosis and assess therapeutic efficacy in clinical treatment.