Hiv and Lymphoma: from Epidemiology to Clinical Management.
Patients infected with human immunodeficiency virus (HIV) are at increased risk for developing both non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common acquired immune deficiency syndrome (AIDS)-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop in the context of AIDS. HIV-associated lymphoma differs from lymphoma in the HIV negative population in that they more often present with advanced disease, systemic symptoms, and extranodal involvement and are frequently associated with oncogenic viruses (Epstein-Barr virus and/or human herpesvirus-8). Before the introduction of cART, most of these patients could not tolerate the treatment strategies routinely employed in the HIV-negative population. The widespread use of cART has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that nowadays can be compared to those seen in non-HIV infected patients. However, a great deal of attention should be paid to opportunistic infections and other infectious complications, cART-chemotherapy interactions, and potential cumulative toxicity. In the context of relatively sparse prospective and randomized trials, the optimal treatment of AIDS-related lymphomas remains a challenge, particularly in patients with severe immunosuppression. This paper will address epidemiology, pathogenesis, and therapeutic strategies in HIV-associated NHL and HL.


Nigrospora oryzae Causing Panicle Branch Rot Disease on Oryza sativa (rice).
The panicle branch, which is the key node for transport of photosynthesis products from source to sink, is vulnerable to many diseases caused by fungal pathogens, such as Magnaporthe oryzae, Cochliobolus miyabeanus. Among these diseases, rice blast is the most important one which causes devastating losses in many regions. In 2019 and 2020, panicle branch rot of rice with a symptom which could be mistaken with rice blast was observed in a paddy field, where is not traditional epidemical region of rice blast, in Fuyang, Zhejiang province. In 2020, similar symptom was also observed in Hubei and Anhui Province. In a paddy field in Fuyang, the symptom appeared on more than 30% investigated panicles. Diseased panicle exhibited brown to black lesions on primary or secondary branches as well as pedicels, however the grain and the neck of spike could not be infected which is the most obvious difference with rice blast. Obviously, the disease can't destroy the entire function of branch and blank grain was rarely observed, so its damage is not comparable with neck blast. Normally, it caused incomplete grain filing commonly leading to 5% - 25% grain weight loss. During the booting stage of rice, local solar irradiation time and temperature were fewer and lower than common years which may be responsible for losses caused by this disease. After surface sterilized, lesion parts cut from infected branches from 25 panicle samples were cultured on 2% water agar at 28℃ for 24-28 h, and fungi were isolated and purified by mycelial tip transferring. Among 31 isolates, 26 showed similar cultural characters. The wool-like mycelia were luxuriant and grew rapidly on PDA spreading the whole 9 cm petri dish in less than a week at 28 ℃. The mycelia were white to ashen at beginning and gradually turned black from center of the plate after 5 days culture at 28 ℃. Hyphae were smooth, branched, septate, hyaline or pale brown. Conidia were single-celled, black, spherical to subspherical, and 10.2 to 14.6 × 12.2 to 15.7 μm (n=50) in dimension and born on tip of hyaline and ampulliform conidiophores. The fungus showed similar morphological characteristics with Nigrospora oryzae (1). ITS sequences of 6 representative strains of the fungus were amplified, sequenced with primer pair, ITS1/ITS4 (2), and submitted into GenBank with an accession number, MW228165. Phylogenetic analysis was conducted with sequences of reference strains (3). The result showed that the fungus obtained in this study was fallen into the same group with N.oryzae. In view of above both morphological and molecular analysis, the strains were finally identified as N. oryzae. Pathogenicity tests were conducted in triplicate with rice panicles in initial heading stage. Fifty panicles were wounded on branches with needles and inoculated by spreading the conidia suspension (10μl, 1 × 106 conidia ml-1) on the wounds. The panicles used as control were treated in same way with 10μl of sterile water. The inoculated and control plants were kept in dark, 25 ℃ and relative humidity of more than 85% for 24 h in culture chamber. Symptoms appeared on 44 of 50 inoculated panicles which were basically similar with those observed in paddy field, while negative controls remained symptomless. The fungi re-isolated from inoculated panicles were also confirmed as N. oryzae by both morphological and molecular analysis. To the best of our knowledge, this is the first report of N. oryzae causing panicle branch rot disease on Oryza sativa (rice). This disease not only cause yield losses and lower milling quality, but could also be mistaken as rice blast incurring unnecessary fungicides spray.


Determination of Cell Doubling Times from the Return-on-Investment Time of Photosynthetic Vesicles Based on Atomic Detail Structural Models.
Cell doubling times of the purple bacterium Rhodobacter sphaeroides during photosynthetic growth are determined experimentally and computationally as a function of illumination. For this purpose, energy conversion processes in an intracytoplasmic membrane vesicle, the chromatophore, are described based on an atomic detail structural model. The cell doubling time and its illumination dependence are computed in terms of the return-on-investment (ROI) time of the chromatophore, determined computationally from the ATP production rate, and the mass ratio of chromatophores in the cell, determined experimentally from whole cell absorbance spectra. The ROI time is defined as the time it takes to produce enough ATP to pay for the construction of another chromatophore. The ROI time of the low light-growth chromatophore is 4.5-2.6 h for a typical illumination range of 10-100 μmol photons m-2 s-1, respectively, with corresponding cell doubling times of 8.2-3.9 h. When energy expenditure is considered as a currency, the benefit-to-cost ratio computed for the chromatophore as an energy harvesting device is 2-8 times greater than for photovoltaic and fossil fuel-based energy solutions and the corresponding ROI times are approximately 3-4 orders of magnitude shorter for the chromatophore than for synthetic systems.


Racing to learn: statistical inference and learning in a single spiking neuron with adaptive kernels.
This paper describes the Synapto-dendritic Kernel Adapting Neuron (SKAN), a simple spiking neuron model that performs statistical inference and unsupervised learning of spatiotemporal spike patterns. SKAN is the first proposed neuron model to investigate the effects of dynamic synapto-dendritic kernels and demonstrate their computational power even at the single neuron scale. The rule-set defining the neuron is simple: there are no complex mathematical operations such as normalization, exponentiation or even multiplication. The functionalities of SKAN emerge from the real-time interaction of simple additive and binary processes. Like a biological neuron, SKAN is robust to signal and parameter noise, and can utilize both in its operations. At the network scale neurons are locked in a race with each other with the fastest neuron to spike effectively "hiding" its learnt pattern from its neighbors. The robustness to noise, high speed, and simple building blocks not only make SKAN an interesting neuron model in computational neuroscience, but also make it ideal for implementation in digital and analog neuromorphic systems which is demonstrated through an implementation in a Field Programmable Gate Array (FPGA). Matlab, Python, and Verilog implementations of SKAN are available at: http://www.uws.edu.au/bioelectronics_neuroscience/bens/reproducible_research.


Using the Tools of Behavioral Neuroscience to Determine the Identity of Different Mouse Strains in a Laboratory Course.
Understanding the neural mechanisms underlying behavior depends on our ability to define and to measure these behaviors in the model animal. We describe an upper-level course which provides students with hands-on experience in the methods of behavioral neuroscience. There are many well-established behavioral tests which are relatively easy for students to conduct that can be used to determine the performance of animals in such tasks as anxiety, motor performance and memory. Laboratory mice bred specifically to exhibit particular behavioral characteristics are readily available from vendors along with well documented behavioral profiles for these strains. We used two albino strains CD1 and BALBc as our model animals. Students were given the task of identifying the strains based on the results of a battery of behavioral tests but were not given information about the mice. These two strains were chosen for their clear differences particularly in tests of anxiety. Students conducted elevated plus maze and zero maze tests, open field test, light-dark exploratory task, rotarod, balance beam test, spatial or novel object learning. Students were able to correctly identify the two strains by comparing their own data with the published literature in the field. The course structure encouraged students to work in teams to design protocols, and then to collect and explore data. Students were enthusiastic about the hands-on laboratory experience and were able to demonstrate an appreciation for and understanding of these methods in behavioral neuroscience.


Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12 cells.
The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+) exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked (*)OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent (*)OH production are critical events in Zn(2+)-induced toxicity in PC12 cells.


Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?
To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.


Measurement of Lingual Cortical Plate Thickness and Lingual Position of Lower Third Molar Roots Using Cone Beam Computed Tomography.
The objective of the study was to determine the potential risk of tooth/root displacement into the soft tissue during the third molar surgery. While performing third molar surgeries, one of the many complications is displacement of the tooth into the soft tissues. This can be due perforation of the lingual cortical bone during surgery or the position of the tooth root which may be close to the lingual bone. Retrospective samples of 251 patients were collected who had undergone cone-beam computed tomography (CBCT) for various reasons. Measurements were performed independently and recorded twice by one surgeon and one radiologist; the average of the two measurements was calculated and evaluated using MyRay CBCT. On the right and the left side, the average distances in males for AL were 3.31 and 2.96 mm, respectively, whereas in females was found to be 3.98 and 3.56 mm which were statistically significant. On the right and left side, the average distances in males for RL were 2.03 and 1.78 mm, respectively, whereas in females, it was 2.41 and 1.99 mm, respectively, with the significant P value in the right side. Despite the sample size being of 251 patients, a large number of root of the third molar (95.62%) were not in contact with lingual cortical bone, but still practitioner should be careful during surgery as there might be the risk for displacement of the tooth. The images used were of impacted molar used in this study and these teeth were not subjected to surgery. Hence, the results can be only correlated theoretically, i.e., there would be a risk of displacement of the tooth during extraction.


The longitudinal study of personality disorders: history, design considerations, and initial findings.
The Longitudinal Study of Personality Disorders (LSPD) began in 1990 and it is the first NIMH-funded prospective multiwave longitudinal study of all DSM-defined personality disorders (PDs). The LSPD, now in its 16th year, has focused on several major issues including: (a) the epidemiology of the PDs; (b) the stability of individual differences and mean levels of PD features over time; (c); patterns of individual growth in PD features over time; (d) the development of a neurobehavioral model that links personality and personality disorder; (e) specification of those neurobehavioral systems predicting change in borderline personality disorder; and (f) illumination of simultaneous growth processes in neurobehavioral systems and PD. The LSPD possesses a number of methodological enhancements designed to increase the validity of the longitudinal findings such as a prospective multiwave design, use of a validated structured interview and well-known self-report instrument for Axis II assessments, double measurement of all major constructs under study, use of blinded interviewers for all interview Axis II assessments, and use of a community sample. The history and context in which the LSPD was developed is reviewed, methodological issues related to the study of PDs are discussed, primary LSPD findings to date are summarized, and future directions of the LSPD are introduced.


[A case of polyarteritis nodosa with bilateral hilar lymphadenopathy].
A 55-year-old male was admitted with non productive cough and fever which had continued for 6 weeks. The patient had symptoms of peripheral neuralgia. Chest X-ray revealed bilateral hilar lymphadenopathy (BHL) and reticular shadows in both lung fields. Other laboratory abnormalities included hematuria, RBC cast, high BUN, leukocytosis and thrombocytosis. Destruction of the internal membrane of arterioles was observed in a livedo reticularis on the right lower extremity. Renal angiography showed irregularity in the diameter, discontinuation and narrowing of peripheral arteries of both kidneys. These findings suggested the existence of "angiitis". These data were compatible with the diagnosis of polyarteritis nodosa (PN). Prednisolone (60 mg/day) administration resulted in the improvement of his symptoms and laboratory findings. A case of PN with lymph node swelling has been reported, however PN with BHL has not yet been reported. This is the first report of PN with BHL.


Analysis of linear free-energy relationships combined with activation parameters assigns a concerted mechanism to alkaline hydrolysis of x-substituted phenyl diphenylphosphinates.
A kinetic study is reported for alkaline hydrolysis of X-substituted phenyl diphenylphosphinates (1 a-i). The Brønsted-type plot for the reactions of 1 a-i is linear over 4.5 pK(a) units with beta(lg)=-0.49, a typical beta(lg) value for reactions which proceed through a concerted mechanism. The Hammett plots correlated with sigma(o) and sigma(-) constants are linear but exhibit many scattered points, while the corresponding Yukawa-Tsuno plot results in excellent linear correlation with rho=1.42 and r=0.35. The r value of 0.35 implies that leaving-group departure is partially advanced at the rate-determining step (RDS). A stepwise mechanism, in which departure of the leaving group from an addition intermediate occurs in the RDS, is excluded since the incoming HO(-) ion is much more basic and a poorer nucleofuge than the leaving aryloxide. A dissociative (D(N) + A(N)) mechanism is also ruled out on the basis of the small beta(lg) value. As the substituent X in the leaving group changes from H to 4-NO(2) and 3,4-(NO(2))(2), DeltaH++ decreases from 11.3 kcal mol(-1) to 9.7 and 8.7 kcal mol(-1), respectively, while DeltaS++ varies from -22.6 cal mol(-1) K(-1) to -21.4 and -20.2 cal mol(-1) K(-1), respectively. Analysis of LFERs combined with the activation parameters assigns a concerted mechanism to the current alkaline hydrolysis of 1 a-i.


Which anti-histamines dermatological specialists select in their therapies for common skin diseases? A practical analysis from multiple clinics.
In the treatment of skin diseases, antihistamines and antiallergic agents are among the most frequently used oral medications, and are available as a wide variety of products. We investigated what criteria dermatological specialists use to select antihistamines and antiallergic agents, as well as the use objectives and expected benefits. The present investigation was conducted in a total of 1448 patients, including 336 patients with urticaria, 944 patients with eczema/dermatitis, and 199 patients with atopic dermatitis, in 6 dermatological clinics and 1 university hospital. A Case Card to record the prescription motives and clinical evaluation was used, and the results were tabulated and analyzed. As a result, it was found that the expected result was obtained in more than 80% of cases prescribed for by dermatologists based on the prescription motives for individual cases.


Keratinization of human keratinocytes in cell culture: the effect of cyclic AMP.
Human keratinocytes in culture were treated with dibutyryl cyclic AMP (DBcAMP) at concentrations of 10(-3) and 10(-4) M, and labeled with [3H]histidine for 48 hours. The proteins of the keratinocytes were serially extracted in 0.25 M sucrose, 0.1 M sodium citrate-citric acid (pH 2.6), 6 M urea-0.1 M Tris-HCl(pH 9.0), and 6 M urea-0.1 M Tris-HCl(pH 9.0) with 1% mercaptoethanol. The incorporation of [3H]histidine into the extract as assayed by DPM of 3H/microgram protein was increased in 0.25 M sucrose extract and Tris-urea extract of the cultures treated with 10(-3) M and 10(-4) M DBcAMP as compared with the control culture. There was no difference between the citrate-buffer extract of the control and that of the DBcAMP-treated cultures. The incorporation of [3H]histidine into the Tris-urea-mercaptoethanol extract was small, and this fraction was thought to be inactive metabolically. It was concluded that dibutyryl cycli AMP stimulated the protein synthesis of the cultured keratinocytes and induced a qualitative change toward accelerating the synthesis of keratinous protein.


Microscopic model for thin film spreading.
A microscopic, driven lattice gas model is proposed for the dynamics and spatiotemporal fluctuations of the precursor film observed in spreading experiments. Matter is transported both by holes and particles, and the distribution of each can be described by driven diffusion with a moving boundary. This picture leads to a stochastic partial differential equation for the shape of the boundary. Explicit analytic results are obtained which agree with the simulations of the lattice gas.


Two reactive site locations and structure-function study of the arrowhead proteinase inhibitors, A and B, using mutagenesis.
The arrowhead (Sagittaria sagittifolia, Linn.) proteinase inhibitor A and B are double-headed and multifunctional, consisting of 179 amino acid residues with three disulfide bridges. Both their primary structures and cDNA sequences have been elucidated [Yang, H. L., Luo, R. S., Wang, L. X., Zhu, D. X., & Chi, C. W. (1992) J. Biochem. 111, 537; Xu, W. F., Tao, W. K., Gong, Z. Z., & Chi, C. W. (1993) J. Biochem. 113, 153; Luo, M. J., Lu, W. Y., & Chi, C. W. (1997) J. Biochem. (in press)]. Though they share 91% homology, they are different in inhibitory activities. Sequence analysis of their full-length cDNAs showed that there are seven extra residues in the C-terminal part which might be cleaved off by proteinase post-processing. To locate the reactive sites and study the structure-function relationship of the two forms A and B, the genes coding for the mature inhibitor B and its extended form were respectively cloned into the secretion expression vector, pVT102U/alpha, and expressed in Saccharomyces cerevisiae strain S-78. Both of the gene products were purified and characterized to have the same inhibitory activities as the natural one. The gene product of the extended form was a mixture with the extended C-terminal part of the inhibitor either completely or partially removed. The two previously predicted reactive site residues, Lys-44 and Arg-76 of inhibitor B, were then respectively substituted with Ala by site-directed mutagenesis and expressed. As compared with the natural inhibitor, each of the mutants could only inhibit one molecule, instead of two molecules of trypsin, and displayed an inhibitory activity against elastase, thus confirming the location of the two reactive sites in the inhibitors. The gene coding for inhibitor A, which for some reason could not be expressed in S. cereviciae, was successfully expressed in the reconstructed plasmid pET-1522bx in Escherichia coli strain BL21 with the expressed product existing in the inclusion body. After denaturation and renaturation, the active inhibitor A was obtained and purified by anhydrotrypsin affinity chromatography. Using site-directed mutagenesis, two residues of inhibitor A, namely, Ser-82 and Leu-87, prominently different from Leu-82 and Arg-87 in inhibitor B, were replaced by these two corresponding residues, respectively. As compared with the natural inhibitor A, its S82L mutant showed a lower inhibitory activity toward trypsin, whereas a higher activity was found in the L87R mutant. Meanwhile, both of their chymotrypsin inhibitory activities became weaker than the natural one. The important accessary role of the residue of position 87 in causing the difference in inhibitory properties between inhibitor A and B was discussed.


Screening of ARX in mental retardation families: Consequences for the strategy of molecular diagnosis.
Mutations in the human ARX gene have been shown to cause nonsyndromic X-linked mental retardation (MRX) as well as syndromic forms such as X-linked lissencephaly with abnormal genitalia (XLAG), Partington syndrome and X-linked infantile spasm. The most common causative mutation, a duplication of 24 bp, was found in families with a variety of phenotypes, but not in the more severe XLAG phenotypes. The aim of the study was to access the frequency of ARX mutations in families with established or putative X-linked mental retardation (XLMR) collected by the European XLMR Consortium. We screened the entire coding region of ARX for mutations in 197 novel XLMR families by denaturing high-performance liquid chromatography, and we identified eight mutations (six c.428_451dup24, one insertion and one novel missense mutation p.P38S). To better define the prevalence of ARX mutations, we included previously reported results of 157 XLMR families. Together, these data showed the relatively high rate (9.5%) of ARX mutations in X-linked MR families and an expectedly low rate in families with affected brother pairs (2.2%). This study confirms that the frequency of ARX mutations is high in XLMR, and the analysis of ARX in MRX should not be limited to duplication.


Ultrasonographic resolution of the vessel wall oedema with modest clinical improvement in a large-vessel vasculitis patient treated with tocilizumab.
We report a 63-year-old man with large-vessel giant cell arteritis with affection of the aorta in its thoracal descendens and abdominal segments, both axillar arteries and the left carotid artery. The diagnosis was confirmed with positive biopsy of the temporal artery. The patient was treated with prednisolone at first and thereafter with methotrexate. Due to a moderate clinical response, tocilizumab at a dose of 8 mg/kg was added 8 weeks after diagnosis. The patient did not improve clinically, and the prednisolone dose could not be tapered rapidly as previously reported in small case series. Nevertheless, the wall oedema determined by ultrasonography in both axillar and left carotid arteries almost disappeared 2 months after tocilizumab initiation. Two months after the last tocilizumab, the patient relapsed clinically. Tocilizumab seems to be an effective therapy with faster resolution of the vessel wall oedema determined by ultrasonography by suppressing Th17-cell activity. But the clinical improvement in our patient has been moderate and short-lived due to persistent Th1 cells activity.


Factors affecting compliance with colorectal cancer screening in France: differences between intention to participate and actual participation.
This study aimed to identify the social, cultural and psychological characteristics influencing behaviour in a cancer mass screening campaign in a French population. The intention to take a screening test and actually doing it was studied, in particular. A self reported-questionnaire was mailed in December 1992 to a random sample of people living in Caen (western France), and aged from 45-74 years. The sample was formed by random selection from electoral registers. The study was population based, in the Caen area, department of Calvados, France. The questionnaire comprised 26 open and close questions. Starting in February 1993, the occult blood screening test (haemoccult IIR) for colorectal cancer was offered by general practitioners (GPs), occupational health doctors and pharmacists in the Caen area to all those aged 45-74 years. From 1 February 1993 to 30 June 1994, the data on the mass screening campaign were centralized and the study population divided into those who took the screening test and those who did not. Of the 1,129 persons contacted, 645 (57.1%) returned the questionnaire. After exclusions, 585 questionnaires were used for analysis. The results show that whether a person will actually take a screening test cannot be predicted from their intention to do so. The sociodemographic and cultural characteristics influencing the intention to take the test differ from those influencing execution of the test. Among the variables tested here, the following four sociodemographic and cultural characteristics were independently predictive of actually taking the screening test for colorectal cancer: compliance with the health insurer's advice; low or medium sociodemographic status, living with a partner (or widowhood); and not knowing someone with cancer. The analysis of the quantitative and qualitative differences between the intention to take the test and actually doing it could elucidate the reasons underlying refusal. Poor screening compliance has multiple causes. A record of intention to take a screening test alone is not appropriate. This type of study should no longer be carried out to determine the mechanisms underlying behaviour towards secondary prevention.


Atomic-scale models of early-stage alkali depletion and SiO2-rich gel formation in bioactive glasses.
Molecular dynamics simulations of Na(+)/H(+)-exchanged 45S5 Bioglass® models reveal that a large fraction of the hydroxyl groups introduced into the proton-exchanged, hydrated glass structure do not initially form covalent bonds with Si and P network formers but remain free and stabilised by the modifier metal cations, whereas substantial Si-OH and P-OH bonding is observed only at higher Na(+)/H(+) exchange levels. The strong affinity between free OH groups and modifier cations in the highly fragmented 45S5 glass structure appears to represent the main driving force for this effect. This suggests an alternative direct route for the formation of a repolymerised silica-rich gel in the early stages of the bioactive mechanism, not considered before, which does not require sequential repeated breakings of Si-O-Si bonds and silanol condensations.


Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer.
Prostate cancer is one of the most commonly diagnosed cancers in men. A number of genomic and clinical studies have led to a better understanding of prostate cancer biology. Still, the care of patients as well as the prediction of disease aggressiveness, recurrence and outcome remain challenging. Here, we showed that expression of the gene ZBTB38 is associated with poor prognosis in localised prostate cancer and could help discriminate aggressive localised prostate tumours from those who can benefit only from observation. Analysis of different prostate cancer cohorts indicates that low expression levels of ZBTB38 associate with increased levels of chromosomal abnormalities and more aggressive pathological features, including higher rate of biochemical recurrence of the disease. Importantly, gene expression profiling of these tumours, complemented with cellular assays on prostate cancer cell lines, unveiled that tumours with low levels of ZBTB38 expression might be targeted by doxorubicin, a compound generating reactive oxygen species. Our study shows that ZBTB38 is involved in prostate cancer pathogenesis and may represent a useful marker to identify high risk and highly rearranged localised prostate cancer susceptible to doxorubicin.


Hydroxychloroquine induces oxidative stress and impairs fracture healing in rats.
The aim of this study was to investigate whether hydroxychloroquine sulfate (HCQS) induced oxidative stress and how it affected the union of bone fractures in an experimental rat model. A total of 48 Wistar albino male rats were used. The rats were divided into six groups. To investigate the effects of oral administration of HCQS at varying doses between the third and sixth weeks, fracture healing processes were evaluated using radiography, histopathology, biochemistry, and dual-energy X-ray absorptiometry. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured to analyze the relationship between HCQS and oxidative stress. Radiographic scores, alkaline phosphatase levels, callus/diaphysis ratio, callus development, and bone mineral density were significantly lower in rats given HCQS at three and six weeks compared to the control group (p<0.005). When oxidative stress parameters were compared among the groups, all antioxidant parameters were statistically significant, indicating that antioxidant systems played a role in peripheral blood, when HCQS was used (p<0.005). Oral HCQS intake impairs the fracture healing process by causing oxidative stress in rats. However, further biomolecular researches are needed to understand the underlying mechanism of these effects.


Rapid detection of hepatitis C virus using recombinase polymerase amplification.
Over 71 million people are infected with hepatitis C virus (HCV) worldwide, and approximately 400,000 global deaths result from complications of untreated chronic HCV. Pan-genomic direct-acting antivirals (DAAs) have recently become widely available and feature high cure rates in less than 12 weeks of treatment. The rollout of DAAs is reliant on diagnostic tests for HCV RNA to identify eligible patients with viremic HCV infections. Current PCR-based HCV RNA assays are restricted to well-resourced central laboratories, and there remains a prevailing clinical need for expanded access to decentralized HCV RNA testing to provide rapid chronic HCV diagnosis and linkage to DAAs in outpatient clinics. This paper reports a rapid, highly accurate, and minimally instrumented assay for HCV RNA detection using reverse transcription recombinase polymerase amplification (RT-RPA). The assay detects all HCV genotypes with a limit of detection of 25 copies per reaction for genotype 1, the most prevalent in the United States and worldwide. The clinical sensitivity and specificity of the RT-RPA assay were both 100% when evaluated using 78 diverse clinical serum specimens. The accuracy, short runtime, and low heating demands of RT-RPA may enable implementation in a point-of-care HCV test to expand global access to effective treatment via rapid chronic HCV diagnosis.


Chronic Thromboembolic Pulmonary Hypertension: Pearls and Pitfalls of Diagnosis.
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by chronic obstruction of major pulmonary arteries by organized thromboembolic material. Untreated CTEPH can result in pulmonary hypertension and eventually right heart failure, yet it is the only form of pulmonary hypertension that is potentially curable with surgical or catheter-based intervention. While early diagnosis is key to increasing the likelihood of successful treatment, CTEPH remains largely underdiagnosed. This article reviews the role of echocardiogram, ventilation/perfusion scan, and other available modalities in the diagnosis of CTEPH.


Fragmentation of cellulose by the major Thermomonospora fusca cellulases, Trichoderma reesei CBHI, and their mixtures.
In this study, the fragmentation activities of Thermomonospora fusca cellulases E(2), E(3), E(5), Trichoderma reesei CBHI, and their mixtures were measured to study synergism in fragmentation. Fragmentation studies revealed that only two pure cellulases, T. fusca E(2) and E(5) had significant fragmentation activity. T. fusca E(3) shows strong synergism in fragmentation both in the production of reducing sugars and in fragmentation with both T. fusca endoglucananses and with T. reesei CBHI. Most mixtures containing CBHI produced higher rates of fragmentation than comparable mixtures containing E(3). The highest rate and extent of reducing sugar formation and the highest fragmentation activity were obtained with a mixture of E(2), E(3), and CBHI.


DLL4/Notch1 and BMP9 Interdependent Signaling Induces Human Endothelial Cell Quiescence via P27KIP1 and Thrombospondin-1.
Bone morphogenetic protein-9 (BMP9)/activin-like kinase-1 and delta-like 4 (DLL4)/Notch promote endothelial quiescence, and we aim to understand mechanistic interactions between the 2 pathways. We identify new targets that contribute to endothelial quiescence and test whether loss of Dll4(+/-) in adult vasculature alters BMP signaling. Human endothelial cells respond synergistically to BMP9 and DLL4 stimulation, showing complete quiescence and induction of HEY1 and HEY2. Canonical BMP9 signaling via activin-like kinase-1-Smad1/5/9 was disrupted by inhibition of Notch signaling, even in the absence of exogenous DLL4. Similarly, DLL4 activity was suppressed when the basal activin-like kinase-1-Smad1/5/9 pathway was inhibited, showing that these pathways are interdependent. BMP9/DLL4 required induction of P27(KIP1) for quiescence, although multiple factors are involved. To understand these mechanisms, we used proteomics data to identify upregulation of thrombospondin-1, which contributes to the quiescence phenotype. To test whether Dll4 regulates BMP/Smad pathways and endothelial cell phenotype in vivo, we characterized the vasculature of Dll4(+/-) mice, analyzing endothelial cells in the lung, heart, and aorta. Together with changes in endothelial structure and vascular morphogenesis, we found that loss of Dll4 was associated with a significant upregulation of pSmad1/5/9 signaling in lung endothelial cells. Because steady-state endothelial cell proliferation rates were not different in the Dll4(+/-) mice, we propose that the upregulation of pSmad1/5/9 signaling compensates to maintain endothelial cell quiescence in these mice. DLL4/Notch and BMP9/activin-like kinase-1 signaling rely on each other's pathways for full activity. This represents an important mechanism of cross talk that enhances endothelial quiescence and sensitively coordinates cellular responsiveness to soluble and cell-tethered ligands.


[When should the pre-operative study of epileptic patients be carried out?].
There is great controversy as to the best moment for the preoperative study of patients with intractable epilepsy. In this study we attempt to give an answer to this question based on a review of the literature and personal experience. First various problems are analyzed: the epilepsy-lesion relationship; kinds of treatment and types of epilepsy: the concept of curative or palliative surgery, surgical syndromes, how long epilepsy has been present and the age of the patient at the time of operation. With these factors in mind we attempt to analyze the clinical situations and determine in each cases the optimum time to carry out any possible surgical treatment as a complement or 'part' of the medical treatment of these patients as a whole.


Electrowetting-actuated optofluidic phase modulator.
In this paper, an optofluidic phase modulator based on electrowetting is presented. The modulator consists of an inner and outer chamber. Two immiscible liquids are filled into the chambers, and a transparent sheet is fixed between the liquid-liquid interface to obtain a flat interface. By applying different voltages to the modulator, the flat interface moves up and down leading to the change of optical path length. Consequently, the variation of the optical path in the proposed modulator exploits the ability to alter the optical phase. To prove the concept, a prototype of the phase modulator is fabricated in experiment, and the ability of phase modulation is detected. Our proposed modulator performs optical phase shift up to ∼6.68 π driven with 150 V. Widespread applications of such an optofluidic phase modulator is foreseeable.


Self-affirmation facilitates cardiovascular recovery following interpersonal evaluation.
Self-affirmation is known to reduce defensive psychological responses to ego threats. The current experiment tested the hypothesis that self-affirmation reduces physiological responses to a form of ego threat-interpersonal evaluation. Participants wrote an essay and received either neutral or insulting evaluative feedback about their essay, ostensibly from another participant. Then participants wrote about a core personal value (self-affirmation) or about a less important value (no self-affirmation). Lastly, participants played a competitive reaction time game that permitted them to blast their purported evaluator with noise. Noise blasts did not vary across conditions, but mean arterial blood pressure increased in response to being evaluated and returned to baseline more quickly following self-affirmation. Further, insulting (versus neutral) evaluative feedback caused a greater increase in heart rate, except among those who self-affirmed following the evaluation manipulation. These results suggest that self-affirmation facilitates the return to baseline cardiovascular activity following interpersonal evaluation.


Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration.
To evaluate the pharmacokinetic and systemic pharmacodynamic properties of inhaled fluticasone propionate (FP). Single doses of 0.25, 0.5, 1.0 and 3.0 mg FP were administered to groups of six healthy subjects. Serum concentration profiles of FP were monitored over 24 h by means of high-performance liquid chromatography/mass spectrometry (HPLC/MS-MS). Systemic pharmacodynamic effects were evaluated by measuring endogenous serum cortisol and circulating white blood cells, and analyzed with previously developed integrated pharmacokinetic/pharmacodynamic (PK/PD) models. FP showed a dose-independent terminal half-life with a mean (SD) of 6.0 (0.7) h. Maximum serum concentrations occurred 1.0 (0.5) h after administration, ranging from 90 pg.ml(-1) for the 0.25 mg dose to 400 pg.ml(-1) for the 3.0 mg dose. This, together with an estimated mean absorption time of nearly 5 h and a known oral bioavailability of less than 1%, indicates prolonged residence at and slow absorption from the lungs. In the investigated dose range, the cumulative systemic effect was dose-dependent for both markers of pharmacodynamic activity. For doses of 0.25, 0.50, 1.0 and 3.0 mg FP, the PK/PD-based cumulative systemic-effect parameters were 159, 186, 257 and 372% .h for lymphocyte suppression, 107, 186, 202 and 348% .h for granulocyte induction and 23.6%, 33.8%, 51.0% and 73.6% for cortisol reduction, respectively. The time courses of lymphocytes, granulocytes and endogenous cortisol could be sufficiently characterized with the applied PK/PD models. The measured in vivo EC50 values, 30 pg.ml(-1) and 7.3 pg.ml(-1) for white blood cells and cortisol, respectively, were in good agreement with predictions based on the in vitro relative receptor affinity of FP. After inhalation, FP follows linear pharmacokinetics and exhibits dose-dependent systemic pharmacodynamic effects that can be described by PK/PD modeling.


New aspects of vulvar cytology.
Smears were taken from vulvar skin in 203 cases (83 normal-appearing, 23 benign, 12 precancerous and 85 malignant conditions). Three cases were analyzed by electron microscopy. The appearance of dyskeratotic cells was regarded as a sign of malignancy; this was supported by ultrastructural study. Smears from normal vulvar skin revealed a high correlation between age and presence of nucleated keratinized squames, which occurred most often in the third and rarely in the eighth decade. Benign conditions showed cellular features like those of the normal vulva. In precancerous lesions, 58% of the smears showed dyskeratotic cells. Malignant conditions showed dyskeratotic cells in 66% of the smears and true cancer cells exclusively in an additional 14%. Our observations indicate that vulvar cytology can be a major diagnostic aid in all suspicious cases, especially in the elderly. Vulvar cytology cannot replace an exact histologic examination, but it can provide a reason for taking a biopsy earlier than might otherwise be the case.


Species identification and vitamin A level in lutjanid fish implicated in vitamin A poisoning.
One outbreak of food poisoning associated with ingestion of the liver of a large lutjanid fish was investigated in this study. The symptoms in three patients primarily included headache, nausea, vomiting, fever, vertigo, and visual disorientation and later included peeling of the skin. The species of fish implicated in this incident was Etelis carbunculus (family Lutjanidae) as determined by direct sequence analysis and PCR plus restriction fragment length polymorphism analysis for detection of the cytochrome b gene. Subsequently, several specimens of E. carbunculus of different body weights were collected, and the level of vitamin A in the muscle and liver was determined by high-performance liquid chromatography. The average level of vitamin A in E. carbunculus muscle was 12 +/- 2 IU/g and that in the liver was 9,844 +/- 7,812 IU/g. Regression models indicate that E. carbunculus with higher body weight and liver weight will have higher levels of vitamin A levels in the liver.


Changes in debrisoquine hydroxylation capacity following liver surgery.
Liver transplantation or the surgical construction of portacaval shunts may radically alter an individual's debrisoquine hydroxylation capacity. Good clinical management should encompass a full awareness of such changing needs and problems in patients who undergo hepatic surgery.


Effects of Cyanidin-3-O-glucoside on Synthetic and Metabolic Activity of Ethanol Stimulated Human Pancreatic Stellate Cells.
Activated pancreatic stellate cells (PSC) play a major role in the development of chronic pancreatitis. Flavonoids (C-3-O-G) theoretically may have potential to suppress activated PSC. The aim of our study was to determine the ability of C-3-O-G to invert synthetic and metabolic activity of alcohol stimulated human pancreatic stellate cells (hPSC). In the present study we demonstrate that treatment with C-3-O-G decreased proliferation rate of ethanol activated hPSC by 51%. Synthesis of extracellular matrix proteins in activated hPSC was markedly inhibited, as shown by reduced levels of collagen I and fibronectin expression. The decrease of secretion of fibronectin by 33% and in collagen I-25% in ethanol activated and C-3-O-G treated hPSC was observed. Moreover, treatment of ethanol activated hPSC with C-3-O-G resulted in the decrease of oxygen consumption rate by 44% and reduced levels of ATP synthesis (i.e. energy production) by 41%. Hence, the effects of C-3-O-G on ethanol activated hPSC may provide new insights for the use of anthocyanins as anti-fibrogenic agents in treatment and/or prevention of pancreatic fibrosis.


Permanent Proplast temporomandibular joint implants: MR imaging of destructive complications.
We studied the radiologic and pathologic changes in 30 patients (34 joints) in which there were locally destructive bone and soft-tissue complications associated with previously inserted permanent temporomandibular joint (TMJ) Proplast-Teflon implants. The cases were selected as representative examples of patients with failed Proplast interpositional arthroplasty, in whom images of the TMJ were obtained with conventional radiography, tomography, and MR, and in whom both surgical and histologic findings were available. Clinical indications for imaging included joint pain, restricted joint motion, crepitus, preauricular swelling, regional lymphadenopathy, malocclusion either acquired or changed since implant surgery, and facial deformity. Surgery was then performed for the purposes of implant retrieval and joint debridement because of destructive soft-tissue and osseous changes observed from the imaging analysis in conjunction with significant clinical signs and symptoms. The pathologic changes, observed 4-54 months after implant surgery, included a destructive foreign-body-type granuloma and avascular necrosis of the mandibular condyle and condylar neck. Our findings suggest that MR is useful in the detection and evaluation of destructive complications that may accompany failed Proplast-Teflon implants in the TMJ. MR is superior to conventional radiography and tomography in detecting soft-tissue lesions and avascular necrosis of bone. Tomography more accurately delineates soft-tissue calcifications and cortical margins of osseous structures.


Preparation and structure of drug-carrying biodegradable microspheres designed for transarterial chemoembolization therapy.
Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 μm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.


Diet micronutrient adequacy of women after 1 year of gastric bypass.
The more effective treatment for severe obesity is bariatric surgery. Gastric bypass is a surgical technique used worldwide; however, as well as other techniques; it has postoperative risks, including nutrient deficiency. To determine the amounts of dietary iron, calcium, vitamin D and vitamin B12 ingested by patients of a public hospital one year after gastric bypass, and compare with the recommendations of the Recommended Dietary Allowances. This was a transverse descriptive study and the sample consisted of 36 women, with at least one year of gastric bypass. Data collected included sociodemographic, anthropometric and diet variables. Dietetic information was collected through a validated food frequency questionnaire. Ingestion of iron, calcium, vitamin D and vitamin B12 was evaluated in comparison with the Recommended Dietary Allowances, as well as correlation of micronutrient ingestion with time of surgery. There was inadequate consumption of iron, calcium and vitamin D. The vitamin B12 intake was considered adequate. There was statistically significant positive correlation between the time of surgery and the ingestion of iron, vitamin B12 and vitamin D. The intake of iron, calcium and vitamin D of women one year after gastric bypass was inadequate, emphasizing the importance of multiprofessional monitoring postoperatively to prevent nutrient deficiencies.


Engaging in an experiential processing mode increases positive emotional response during recall of pleasant autobiographical memories.
It is important to identify effective emotion regulation strategies to increase positive emotion experience in the general population and in clinical conditions characterized by anhedonia. There are indications that engaging in experiential processing (direct awareness of sensory and bodily experience) bolsters positive emotion experience but this has not been extensively tested during memory recall. To further test this notion, 99 community participants recalled two positive autobiographical memories. Prior to the second recall, participants either underwent an experiential, analytical, or distraction induction (n = 33 per condition). Subjective happiness and sadness ratings and heart rate variability (HRV) response were measured during each recall. Greater spontaneous use of experiential processing during the first memory was associated with greater happiness experience, but was unrelated to HRV and sadness experience. Inducing experiential processing increased happiness experience relative to both the analytical and distraction conditions (but had no impact on sadness experience). There was a significant difference in HRV between conditions. The experiential condition led to a trend-significant increase, and the other conditions a non-significant decrease, in HRV from the first to the second memory. These results suggest that engaging in experiential processing is an effective way to up-regulate positive emotion experience during positive memory recall.


Endoscopic transcanal stapedotomy: how I do it.
Current paper presents a surgical technique and preliminary results of the first eight consecutive fully endoscopic transcanal stapedotomies. All eight procedures were performed under local anesthesia by the same surgeon using rigid endoscopes of 3-mm diameter, 14-cm length, 0° and 30°. A posterior tympanomeatal flap was elevated transmeatally with the 0° endoscope and then transposed anteriorly. Stapes fixation was confirmed, the stapes tendon was cut with curved micro-scissors, and the stapes was separated from the incus in the incudo-stapedial joint. The anterior and posterior stapedial crus were carefully fractured, and the superstructure was removed. The hole in the foot-plate was created with a Skeeter microdrill using a 0.5-mm-diameter diamond burr. A platinum/fluoroplastic piston prosthesis (0.4-mm diameter) was placed into this hole and fitted along the long process of the incus. The tympano-meatal flap was repositioned, and the external auditory canal was filled with Gelfoam(®). The chorda tympani nerve was preserved in all cases. A 4.5-mm prosthesis was used in six cases and a 4.75-mm prosthesis in two. Pure tone audiograms demonstrated improved air- and bone-conduction threshold averages across the three speech frequencies (0.5-1.2 kHz) 6 months after surgery (64 vs. 29.8 dB and 30.6 vs. 25.1 dB, respectively). The average postoperative air-bone gap was within 10 dB in six ears and between 10 and 15 dB in the other two ears. Our preliminary results indicate that transcanal fully endoscopic stapedotomy is a feasible and safe technique for surgical management of hearing loss associated with otosclerosis.


Does exaggerated morphology preclude plasticity to cuckoldry in the midshipman fish ( Porichthys notatus)?
In species with more than one male reproductive morph, there typically exists a larger morph with exaggerated secondary sexual characters, and a smaller morph with reduced secondary sexual characters. These "exaggerated" and "reduced" morphologies are commonly thought to represent specializations to alternative behavioral reproductive tactics-large body size and exaggerated secondary sexual characters should both facilitate territoriality, courtship, and pair-spawning; while small body size and reduced secondary sexual characters should facilitate "sneaky" cuckoldry. Given this postulated relationship between morphology and behavior, we examined the relationship between the morphology of exaggerated males and cuckoldry. In a field and aquarium study of the midshipman fish, a fish with both exaggerated and reduced morphs, we demonstrated cuckoldry in some males of the exaggerated morph. Since the "reduced" morphology is thought to be an adaptation towards sneaky cuckoldry, we predicted that, of males with the exaggerated morph, less-exaggerated (smaller) males would be better able to gain proximity to the spawning pair during cuckoldry. In contrast to that prediction, access to the spawning pair during cuckoldry increased with the body size of the cuckolding exaggerated-morph males. This may be related to our observation that exaggerated males often cuckolded aggressively. Thus the "exaggerated" morphology need not preclude adaptive plasticity to cuckoldry, and may even aid it.


Meta-analysis of heparin therapy for preventing venous thromboembolism in acute spinal cord injury.
Venous thromboembolism (VTE) is a frequent complication in patients with acute spinal cord injury (SCI) and may have serious consequences. This study aimed to assess the efficacy and safety of heparin and low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with acute SCI. PubMed, Web of Science, EMBASE and the Cochrane library were searched from January 1980 to August 2016. The primary outcome was the incidence of VTE. Secondary outcomes included the incidences of Deep-vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding. A total of 11 studies including 1605 patients qualified for inclusion. Four studies evaluated the efficacy of heparin treatment compared with placebo or no treatment. There were significant differences between the two treatments, and the summary RR was 0.35 (95% confidence interval (CI) 0.15-0.87; P = 0.02). Seven studies compared low dose unfractionated heparin (LDUH) with LMWH. The incidence of VTE was not significantly different between the two treatments (RR 1.09, 95% CI 0.63-1.89; P = 0.76). There were no differences in the incidence of major bleeding with unfractionated heparin versus LMWH (summary RR 1.32, 95% CI 0.62-2.84; P = 0.47). In this meta-analysis, heparin exhibited protective effects compared with placebo or no treatment with respect to the occurrence of VTE; there were no differences between LMWH and unfractionated heparin with ret to thromboembolism prophylaxis efficacy. LMWH did not reduce the risk of bleeding compared with LDUH.


LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities.
LGP2 is a RIG-I-like receptor (RLR) known to bind and recognize the intermediate double-stranded RNA (dsRNA) during virus infection and to induce type-I interferon (IFN)-related antiviral innate immune responses. Here, we find that LGP2 inhibits Zika virus (ZIKV) and tick-borne encephalitis virus (TBEV) replication independent of IFN induction. Co-immunoprecipitation (Co-IP) and confocal immunofluorescence data suggest that LGP2 likely colocalizes with the replication complex (RC) of ZIKV by interacting with viral RNA-dependent RNA polymerase (RdRP) NS5. We further verify that the regulatory domain (RD) of LGP2 directly interacts with RdRP of NS5 by biolayer interferometry assay. Data from in vitro RdRP assays indicate that LGP2 may inhibit polymerase activities of NS5 at pre-elongation but not elongation stages, while an RNA-binding-defective LGP2 mutant can still inhibit RdRP activities and virus replication. Taken together, our work suggests that LGP2 can inhibit flavivirus replication through direct interaction with NS5 protein and downregulates its polymerase pre-elongation activities, demonstrating a distinct role of LGP2 beyond its function in innate immune responses.


Novel Oral Anticoagulants Compared to Warfarin for Postoperative Atrial Fibrillation After Isolated Coronary Artery Bypass Grafting.
Postoperative atrial fibrillation (POAF) is common after cardiac surgery and contributes to short- and long-term morbidity, particularly thromboembolism. Anticoagulation for sustained or recurrent POAF is suggested to reduce thromboembolism. Novel oral anticoagulants may present a safe alternative to warfarin with further benefits including shorter hospital length of stay and better patient convenience. A retrospective analysis was performed on all isolated cases of coronary artery surgery (CABG) at our institution between January 2015 and December 2018, totalling 960 patients. Rates of POAF were examined with particular focus on preoperative factors, postoperative outcomes, and anticoagulation practices. The incidence of POAF was 31.8% (305 patients) and was higher in older patients (67.6±9.4 yrs vs 63.0±10.7 yrs, p<0.001), those with a history of cerebrovascular disease (14.6% vs 8.7%, p=0.02), those with higher CHADS-VASc scores (2.5±1.3 vs 2.8±1.3, p<0.001) those who had a postoperative return to theatre (2.6% vs 0.8%, p=0.002), and those with new renal failure (4.9% vs 1.8%, p=0.02). Off-pump surgery was associated with lower incidence of POAF (29.8% vs 37.1%, p=0.03). Patients who developed POAF had significantly longer admissions than those without (12.6±10.6 days vs 9.3±16.3 days, p<0.001). In total, 106 patients (11.0%) went home anticoagulated; 77 (72.6%) on warfarin and 29 (27.4% on a NOAC). Readmission for bleeding was higher in patients on anticoagulation (1.0% vs 0.0%, p=0.02), but did not drive readmission for pericardial effusion (0.3% vs 0.6%, p=0.55). No bleeding complications occurred in patients who were discharged on a NOAC. Overall mortality at median of 2 years was 1.8% (17 patients) and no mortality occurred in any patient discharged on anticoagulation. Postoperative atrial fibrillation is a common adverse event and is linked to higher preoperative and postoperative morbidity. Anticoagulation may be safely started in these patients and use of novel anticoagulation does not appear to increase postoperative complications, although overall numbers are low.


Localized Phase Transformation Triggering Lattice Matching of Metal Oxide and Carbonate Hydroxide for Efficient CO2 Photoreduction.
Orderly heterostructured catalysts, which integrate nanomaterials of complementary structures and dimensions into single-entity structures, have hold great promise for sustainability applications. In this work, it is showcased that air as green reagent can trigger in situ localized phase transformation and transform the metal carbonate hydroxide nanowires into ordered heterostructured catalyst. In single-crystal nanowire heterostructure, the in situ generated and nanosized Co3 O4 will be anchored in single-crystal Co6 (CO3 )2 (OH)8 nanowires spontaneously, triggered by the lattice matching between the (220) plane of Co3 O4 and the (001) plane of Co6 (CO3 )2 (OH)8 . The lattice matching allows intimate contact at heterointerface with well-defined orientation and strong interfacial coupling, and thus significantly expedites the transfer of photogenerated electrons from tiny Co3 O4 to catalytically active Co6 (CO3 )2 (OH)8 in single-crystal nanowire, which elevates the catalytic efficiency of metal carbonate catalyst in the CO2 reduction reaction (VCO = 19.46 mmol g-1 h-1 and VH2 = 11.53 mmol g-1 h-1 ). The present findings add to the growing body of knowledge on exploiting Earth-abundant metal-carbonate catalysts, and demonstrate the utility of localized phase transformation in constructing advanced catalysts for energy and environmental sustainability applications.


Mental health problems of homeless children and families: longitudinal study.
To establish the mental health needs of homeless children and families before and after rehousing. Cross sectional, longitudinal study. City of Birmingham. 58 rehoused families with 103 children aged 2-16 years and 21 comparison families of low socioeconomic status in stable housing, with 54 children. Children's mental health problems and level of communication; mothers' mental health problems and social support one year after rehousing. Mental health problems remained significantly higher in rehoused mothers and their children than in the comparison group (mothers 26% v 5%, P = 0.04; children 39% v 11%, P = 0.0003). Homeless mothers continued to have significantly less social support at follow up. Mothers with a history of abuse and poor social integration were more likely to have children with persistent mental health problems. Homeless families have a high level of complex needs that cannot be met by conventional health services and arrangements. Local strategies for rapid rehousing into permanent accommodation, effective social support and health care for parents and children, and protection from violence and intimidation should be developed and implemented.


RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint.
Cytological examination of fine needle aspiration biopsy is the primary means for distinguishing benign from malignant nodules. However, as inconclusive cytology is very frequent, the introduction of molecular markers in the preoperative diagnosis of thyroid nodules has been proposed in recent years. In this article, we review the clinical implications of preoperative detection of rearrangements of the RET gene (RET/papillary thyroid carcinoma (PTC)) in thyroid nodules. The prevalence of RET/PTC in PTC depends on the histological subtypes, geographical factors, radiation exposure, and detection method. Initially, RET/PTC was considered an exclusive PTC hallmark and later it was also found sporadically in benign thyroid lesions. More recently, the very sensitive detection methods, interphase fluorescence in situ hybridization (FISH) and Southern blot on RT-PCR amplicons, demonstrated that the oligoclonal occurrence of RET rearrangement in benign thyroid lesions is not a rare event and suggested that it could be associated with a faster enlargement in benign nodules. For this reason, RET/PTC cannot be considered as an absolute marker of PTC, and its diagnostic application must be limited to assays able to distinguish between clonal and oligoclonal expression. Detection of RET/PTC by quantitative assays will be useful for diagnostic purposes in cytology specimens when a precise cutoff will be fixed in a clinical setting. Until that time, less sensitive RET/PTC detection methods and FISH analysis remain the most appropriate means to refine inconclusive cytology. Future studies with a long follow-up will further clarify the clinical significance of low level of RET rearrangements in benign nodules.


Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease.
Combination therapy with immunomodulators (IMMs) was proposed as a strategy to prevent the development of loss of response (LOR) to anti-tumor necrosis factor (TNF) for patients with inflammatory bowel disease (IBD). However, the effect is unclear in patients already exposed to IMMs. The aim of this study was to evaluate whether combination therapy with IMMs is superior to monotherapy for prevention of LOR to anti-TNF. This was a retrospective study of patients in Seoul National University Bundang Hospital with IBD between January 2009 and October 2018. LOR was defined as clinical deterioration after maintenance of anti-TNF for at least 6 months. We investigated the difference in incidence of LOR to anti-TNF between the monotherapy and combination groups. We additionally assessed factors affecting LOR development to anti-TNF. A total of 116 patients with IBD were included in this study (monotherapy 61 patients; combination 55 patients). Overall, LOR to anti-TNF occurred in 31 patients during the follow-up period. The combination of an anti-TNF agent and IMM showed no significant difference in the incidence of LOR compared to anti-TNF agent monotherapy (hazard ratio [HR], 1.64; 95% confidence interval [CI], 0.786 to 3.148; p = 0.182). Female sex was significantly associated with the development of LOR to anti-TNF (HR, 3.032; 95% CI, 1.467 to 6.268; p = 0.003). Anti-TNF and IMM combination therapy did not prove efficacious in preventing the development of LOR in IBD patients. Female sex was associated with the development of LOR to anti-TNF; further studies are required to confirm these results.


Tubulovesicular transport of horseradish peroxidase in isolated rat hepatocyte couplets: effects of low temperature, cytochalasin B and bile acids.
The transcytotic vesicular pathway in isolated rat hepatocyte couplets was investigated using horseradish peroxidase. Ten to 20 min after horseradish peroxidase labeling, vesicles and tubules containing horseradish peroxidase were observed to be predominantly around the bile canaliculi. In hepatocytes incubated in a 4 degrees C medium for 10 min after horseradish peroxidase labeling, few horseradish peroxidase-containing structures were observed around the bile canaliculi, and the fine reticular immunofluorescence of microtubules was reduced. Cells treated with cytochalasin B (a microfilament inhibitor) showed a fair number of horseradish peroxidase-containing structures around the markedly dilated bile canaliculi and the distribution of microtubules was preserved. Cells labeled by horseradish peroxidase and then incubated for 10 min in a horseradish peroxidase-free medium containing 50 mumol/L of taurocholic acid, ursodeoxycholic acid or tauroursodeoxycholic acid had more tubular structures containing horseradish peroxidase around the bile canaliculi than control cells, whereas 50 mumol/L of taurochenodeoxycholic acid, taurodeoxycholic acid, dehydrocholic acid and taurodehydrocholic acid each failed to increase the number of tubular structures. These findings show that horseradish peroxidase was transported in hepatocyte couplets from the cell periphery to the bile canalicular front through the tubulovesicular pathway, depending on cytoplasmic microtubules. Cytoplasmic microfilaments appeared to play a minor role in this transport. Several specific bile acids such as taurocholic acid, ursodeoxycholic acid and tauroursodeoxycholic acid each promoted the tubular transformation.


Crystal engineering of a versatile building block toward the design of novel inorganic-organic coordination architectures.
Six novel inorganic-organic coordination supramolecular networks based on a versatile linking unit 4-pyridylthioacetate (pyta) and inorganic Co(II), Cu(II), Ag(I), Zn(II), Mn(II) and Pb(II) salts have been prepared in water medium and structurally characterized by single-crystal X-ray diffraction analysis. Reaction of CoCl(2).6H(2)O with Hpyta afforded a neutral mononuclear complex [Co(pyta)(2)(H(2)O)(4)](1), which exhibits a two-dimensional (2-D) layered architecture through intermolecular O-HO interactions. Reaction of CuCl(2.2H(2)O with Hpyta yielded a neutral one-dimensional (1-D) coordination polymer [[Cu(pyta)(2)(H(2)O].0.5H(2)O](n)(2) consisting of rectangle molecular square units, which show a three-dimensional (3-D) supramolecular network through S...S and O-H...O weak interactions. However, when AgNO(3), Zn(OAc)(2).2H(2)O or MnCl(2).4H(2)O salts were used in the above self-assembled processes, the neutral 2-D coordination polymers [Ag(pyta)](n)(3), [[Zn(pyta)(2)].4H(2)O](n)(4) or [[Mn(pyta)(2)(H(2)O)]](n)(5) with different topologies were obtained, respectively. While substituting the transition metal ions used in 1-5 with Pb(OAc)(2).3H(2)O, a one-dimensional coordination polymer [Pb(pyta)(2)](n)(6), which shows a novel 2-fold interpenetrating 2-D supramolecular architecture through weak SS interactions, was isolated. It is interesting to note that the building block pyta anion exhibits different configurations and coordination modes in the solid structures of complexes 1-6. These results indicate that the versatile nature of this flexible ligand, together with the coordination preferences of the metal centers, play a critical role in construction of these novel coordination polymers or supramolecules. The spectral and thermal properties of these new materials have also been investigated.


Desmoplastic fibroma of the calcaneus treated with a microvascular bone graft. Case report.
A calcaneal desmoplastic fibroma in a 24-year-old woman had previously been treated with repeated curettage and bone grafting. Because of a larger recurrence a microvascular bone reconstruction was carried out using an osteofascial radial forearm flap. She could walk without pain in one year. It has not recurred during a five-year follow-up period.


The comparison of placental abruption coupled with and without preeclampsia and/or intrauterine growth restriction in singleton pregnancies.
To compare the clinical features of placental abruption coupled with and without preeclampsia and/or intrauterine growth restriction in singleton pregnancies. A retrospective study of 229 cases of placental abruption was performed and the subjects were collected from Tianjin Central Hospital of Gynecology and Obstetrics between January 2016 and December 2017. The abruption cases were divided into two groups: the abruption with other conditions of ischemic placental disease (IPD group) and the abruption without them (non-IPD group). The clinical features, such as maternal age, gravidity, parity, gestational age at delivery, maternal complications, bleeding volume, fetal gender, sensitivity of ultrasonography, primary symptoms, onset-to-delivery time, mode of delivery, birth weight, and Apgar score at 1 min, were compared between two groups. The primary symptoms in the top three were the central nervous system symptoms involving headache, dizziness or blurred vision (55.0%), decreased fetal movements (13.75%), and abdominal pain (10.0%) in IPD group, while in non-IPD group the top three were vaginal bleeding combined with abdominal pain (31.54%), abdominal pain (22.82%), and vaginal bleeding (16.11%). Compared with non-IPD group, the neonatal outcomes including birth weight, Apgar score at 1 min, and gestation age at delivery were significantly poorer in the IPD group (p < .000, p = .044, and p = .001, respectively). And the sensitivity of ultrasonography was significantly higher in non-IPD group (p = .002). In both preterm and term abruption in IPD group, compared with non-IPD group, it was significantly different in terms of gestation age at delivery, onset-to-delivery time, and birth weight (p < .05). In preterm abruption, IPD group had a significantly higher cesarean section rate than non-IPD group (p = .019). It seemed patients in IPD group had a higher incidence of uterine apoplexy and disseminated intravascular coagulation (DIC), but there was no statistical difference between the two groups in maternal complications including uterine apoplexy, blood transfusion, and DIC (p = .310, p = .585, and p = .121, respectively). It seemed preterm abruption had a poorer maternal prognosis than term abruption in IPD and non-IPD group, but the result had no significant difference (p > .05). Placental abruption complicated with preeclampsia and/or intrauterine growth restriction had a poorer prognosis of newborns, while there was no significant difference in maternal prognosis. And patients with preeclampsia and/or intrauterine growth restriction deserved careful observation during pregnancy, especially when they had central nervous system symptoms of headache, visual changes, or dizziness.


A CASE OF MULTIPLE VISCERAL INJURIES ACCOMPANIED BY RIGHT RENAL PEDICLE INJURY AND LEFT URETERAL DISRUPTION TREATED SUCCESSFULLY BY LEFT URETEROCALICOSTOMY.
We report a 25-year-old male with multiple visceral injuries accompanied by right renal pedicle injury and left ureteral disruption treated successfully by left ureterocalicostomy. He was accidentally crushed by a roller for fishing net hoists while working as a fisherman in May 2011. He was emergently transported to Kurobe City Hospital. He was in shock, but recovered with fluid therapy. CT revealed bilateral hemothorax, liver injury, bowel injury, right renal pedicle injury, left renal injury, and inferior vena cava damage. After bilateral chest drainage, emergent surgery was performed. Laparotomy revealed pancreatic injury, liver injury, disruption of the stomach and jejunum, colonic injury, and retroperitoneal hematoma on the right side. Distal pancreatectomy, hepatorrhaphy, left half resection of the colon, subtotal gastrectomy, and colostomy were performed. However, the bleeding of the right lobe of the liver could not be stopped, and gauze packing on the liver surface was performed for damage control. During the operation, right renal pedicle injury was not treated because the pulsation of the retroperitoneal hematoma was not palpable and the hematoma did not enlarge to the left side across the center; furthermore, his general condition was very poor. After the operation, the patient showed anuria, and hemodialysis was performed twice a week. One week after the operation, removal of the gauze was performed under general anesthesia. The gauze was removed from the liver while sprinkling physiological saline, and there was little bleeding. Tachocomb® (CSL Behring, Tokyo, Japan) was placed on the surface of the liver and a drainage tube was indwelled. Twenty-four days postoperatively, CT revealed left hydronephrosis with right nonfunctioning kidney, and percutaneus left nephrostomy was performed. Antegrade and retrograde pyelograms revealed a left ureteral defect of 8 cm in the upper ureter.The patient was introduced to the Department of Urology of Shinshu University Hospital. Left ureterocalicostomy was performed in January 2012, and the nephrostomy catheter was removed. The temporal colostomy was closed in the Department of Surgery of Kurobe City Hospital in May 2014. He subsequently resumed his normal life.


Body image concerns of reconstructive surgery patients: an underrecognized problem.
This study assessed the body image concerns of reconstructive plastic surgery patients. Forty-three reconstructive surgery patients completed two measures of body image. Responses were compared with a group of patients seeking cosmetic procedures. The two groups did not differ in the degree of dissatisfaction with their overall appearance or dissatisfaction with the specific feature for which they were seeking surgery. Reconstructive patients did consider themselves less healthy and less invested in their appearance than did cosmetic patients. Seven of the reconstructive surgery patients (all scar revision patients) reported a level of dissatisfaction and preoccupation consistent with the psychiatric diagnostic of body dysmorphic disorder. These results underscore the importance of screening for body image dissatisfaction in persons with an objective deformity. Plastic surgeons are in an optimal position to identify body image concerns in these patients and provide appropriate referrals for psychotherapy.


Induction of cell death by pro-oxidant action of Moxa smoke.
Moxa smoke induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in other cell lines. The cytotoxic activity of Moxa smoke was significantly reduced by a popular antioxidant, N-acetyl-L-cysteine (NAC). Moxa smoke showed oxidation potential (measured by NO monitor) and produced carbon radical (measured by ESR spectroscopy). The addition of NAC significantly reduced both the oxidation potential and carbon radical intensity of Moxa smoke. Activity staining of polyacryamide gel electrophoresis of MnSOD revealed the possible modification of the conformation and/or activity of this enzyme at an early stage of HL-60 cell death. These data suggest that Moxa smoke induces cytotoxicity by its pro-oxidant action.


Multigenerational study of chemically induced cytotoxicity and proliferation in cultures of human proximal tubular cells.
Primary cultures of human proximal tubular (hPT) cells are a useful experimental model to study transport, metabolism, cytotoxicity, and effects on gene expression of a diverse array of drugs and environmental chemicals because they are derived directly from the in vivo human kidney. To extend the model to investigate longer-term processes, primary cultures (P0) were passaged for up to four generations (P1-P4). hPT cells retained epithelial morphology and stained positively for cytokeratins through P4, although cell growth and proliferation successively slowed with each passage. Necrotic cell death due to the model oxidants tert-butyl hydroperoxide (tBH) and methyl vinyl ketone (MVK) increased with increasing passage number, whereas that due to the selective nephrotoxicant S-(1,2-dichlorovinyl)-l-cysteine (DCVC) was modest and did not change with passage number. Mitochondrial activity was lower in P2-P4 cells than in either P0 or P1 cells. P1 and P2 cells were most sensitive to DCVC-induced apoptosis. DCVC also increased cell proliferation most prominently in P1 and P2 cells. Modest differences with respect to passage number and response to DCVC exposure were observed in expression of three key proteins (Hsp27, GADD153, p53) involved in stress response. Hence, although there are some modest differences in function with passage, these results support the use of multiple generations of hPT cells as an experimental model.


Motion measurement system of compliant mechanisms using computer micro-vision.
Position sensing is essential to testify the validity of the mechanical design and verify the performance in micromanipulation. A practical system for non-contact micro-motion measurement of compliant nanopositioning stages and micromanipulators is proposed using computer micro-vision. The micro-motion measurement method integrates optical microscopy and an optical flow-based technique, in which the motions of complaint mechanisms are precisely detected and measured. Simulations are carried out to validate the robustness of the proposed method, while the micro-vision system and a laser interferometer measurement system are also built up for a series of experiments. The experimental results demonstrate that the proposed measurement system possesses high stability, extensibility, and precision with 0.06 µm absolute accuracy and 0.05 µm standard deviation.


Observation of locked optical kink-antikink spatial shock waves.
We report the first experimental observation of optical spatial shock-wave pairs. The shock waves consist of two coupled kink and antikink beams that remain locked to each other throughout propagation in a nonlinear diffusion-driven photorefractive crystal. These coupled shock-wave pairs move undistorted at angles that fall outside their original angular sector of propagation.


The underwater environment: cardiopulmonary, thermal, and energetic demands.
Water covers over 75% of the earth, has a wide variety of depths and temperatures, and holds a great deal of the earth's resources. The challenges of the underwater environment are underappreciated and more short term compared with those of space travel. Immersion in water alters the cardio-endocrine-renal axis as there is an immediate translocation of blood to the heart and a slower autotransfusion of fluid from the cells to the vascular compartment. Both of these changes result in an increase in stroke volume and cardiac output. The stretch of the atrium and transient increase in blood pressure cause both endocrine and autonomic changes, which in the short term return plasma volume to control levels and decrease total peripheral resistance and thus regulate blood pressure. The reduced sympathetic nerve activity has effects on arteriolar resistance, resulting in hyperperfusion of some tissues, which for specific tissues is time dependent. The increased central blood volume results in increased pulmonary artery pressure and a decline in vital capacity. The effect of increased hydrostatic pressure due to the depth of submersion does not affect stroke volume; however, a bradycardia results in decreased cardiac output, which is further reduced during breath holding. Hydrostatic compression, however, leads to elastic loading of the chest wall and negative pressure breathing. The depth-dependent increased work of breathing leads to augmented respiratory muscle blood flow. The blood flow is increased to all lung zones with some improvement in the ventilation-perfusion relationship. The cardiac-renal responses are time dependent; however, the increased stroke volume and cardiac output are, during head-out immersion, sustained for at least hours. Changes in water temperature do not affect resting cardiac output; however, maximal cardiac output is reduced, as is peripheral blood flow, which results in reduced maximal exercise performance. In the cold, maximal cardiac output is reduced and skin and muscle are vasoconstricted, resulting in a further reduction in exercise capacity.


[Sports and heat stroke].
We described Characteristic of the heat stroke in the sports activity in Japan. It was common in teenage men, and 15 years old had a peak with a man, the woman. Most patients did not need specific treatment. Many happened from the end of July on the outdoors around 3:00 p.m. in mid-August. There are many in order of baseball, football, tennis, and a basketball. Running and cycling had high severity of illness. Probably, grasp of an environmental condition, suitable sportswear, suitable hydration, and condition management are the best things as preventive measures.


[Not Available].
Description is made of the various stages in the development of the problem. The earliest theories on atherosclerosis are discussed (Lobstein and others). Insofar development of the functional trend is concerned, the science of atherosclerosis is considered in the light of the classic works in the Russian medical literature of the second half of the XIXth century, mainly those of Botkin, Polotebnev etc. The author pays tribute also to the representatives of the French classical school (Euchart etc.). The problem of atherosclerosis is also dealt with in the light of recent advances of biochemistry, as well as in the light of the statements of A. L. Miasnikov on the issue about the relationship between atherosclerosis and hypertonia and his classification of atherosclerosis.


Bedside calculation of energy expenditure does not guarantee adequate caloric prescription in long-term mechanically ventilated critically ill patients: a quality control study.
Nutrition is essential in critically ill patients, but translating caloric prescriptions into adequate caloric intake remains challenging. Caloric prescriptions (P), effective intake (I), and caloric needs (N), calculated with modified Harris-Benedict formulas, were recorded during seven consecutive days in ventilated patients. Adequacy of prescription was estimated by P/N ratio. I/P ratio assessed accuracy of translating a prescription into administered feeding. I/N ratio compared delivered calories with theoretical caloric needs. Fifty patients were prospectively studied in a mixed medicosurgical ICU in a teaching hospital. Basal and total energy expenditure were, respectively, 1361 ± 171 kcal/d and 1649 ± 233 kcal/d. P and I attained 1536 ± 602 kcal/d and 1424 ± 572 kcal/d, respectively. 24.6% prescriptions were accurate, and 24.3% calories were correctly administered. Excessive calories were prescribed in 35.4% of patients, 27.4% being overfed. Caloric needs were underestimated in 40% prescriptions, with 48.3% patients underfed. Calculating caloric requirements by a modified standard formula covered energy needs in only 25% of long-term mechanically ventilated patients, leaving many over- or underfed. Nutritional imbalance mainly resulted from incorrect prescription. Failure of "simple" calculations to direct caloric prescription in these patients suggests systematic use of more reliable methods, for example, indirect calorimetry.


Hypokalemic rhabdomyolysis in a patient with a laparoscopic adjustable gastric banding.
Rhabdomyolysis is an acute skeletal muscle disorder characterized by altered integrity of the cell membranes of muscle fiber cells. It can be related to a variety of factors: muscular trauma, muscle enzyme deficiencies, infections, drugs, toxins, alcohol ingestion, endocrinopathies and electrolyte imbalances such as hypokalemia. We report the case of a 46-year-old woman admitted to the Emergency Department for frequent episodes of vomiting associated with food intake in the last two weeks, general muscular weakness and myalgia. Physical examination on admission was unremarkable, except for a symmetrical and dominantly proximal muscular weakness of all four extremities. Blood pressure was 116/70 mmHg with a sinus bradycardia (53 beats/min) on the electrocardiogram. Laboratory tests showed a metabolic alkalosis with marked hypokalemia (K+= 1.9 mEq/l) and elevation of muscular enzymes (myglobin= 993 ng/ml, troponin T= 0,10 ng/ml e CK= 1113 U/l). No symptoms of recurrent rhabdomyolysis were reported, patient denied alcohol consumption and there was not clinical evidence of hyperthyroidism. A iatrogenic etiology could not be excluded for certain because patient was in therapy with lansoprazole (Naranjo algorithm 3/13) but, revealing medical history that she underwent a laparoscopic adjustable gastric banding for the treatment of a severe obesity, we focused our attention on hypokalemia, due to persistent vomiting. Fasting, administration of metoclopramide and infusion of potassium chloride resulted in steady improvement of clinical conditions and normalization of electrolyte imbalance. At the clinical follow-up of three months, after partial deflation of the gastric banding, the patient was asymptomatic with muscular enzymes and potassium levels in the normal range. Authors discuss the pathophysiologic mechanisms of these alterations.


Magnetic resonance imaging of neuronal function in the spinal cord: spinal FMRI.
A review of the current literature on magnetic resonance imaging of neuronal function in the spinal cord (spinal fMRI) is presented. The unique challenges of spinal fMRI are identified as being the small cross-sectional dimensions of the spinal cord, magnetic field inhomogeneity caused by the bone and cartilage in the spine, and motion of cerebrospinal fluid, blood, adjacent tissues and organs and of the spinal cord itself. Techniques have been developed to overcome or compensate for these challenges and the result is a fMRI method which is distinct from that used for mapping function in the brain. Evidence that the current spinal fMRI method provides accurate and sensitive maps of neuronal function is also discussed. Studies presented in the literature have demonstrated areas of neuronal activity corresponding with spinal cord neuroanatomy as a result of thermal and electrical stimuli and motor tasks with the hands, arms and legs. Signal intensity changes detected in active areas have also been demonstrated to depend on the intensity of the stimuli with both thermal stimulation and a motor task, providing evidence of the correspondence between spinal fMRI results and neuronal activity in the spinal cord.


Nitrogen-Centered Concave Molecules with Double Fused Pentagons.
Distinctive concave compounds bearing a nitrogen core and double fused pentagons were synthesized with a palladium-catalyzed intramolecular coupling of 1-chloro-8 H-indolo[3,2,1- de]acridine as the key step. Structural analysis confirmed the formation of bowl-shaped molecules. Experimental characterizations and theoretical calculations reveal the incorporation of nitrogen is crucial to alleviate the pentagon fusing strain, as well as in property regulation.


The dipsogenic effects of rat relaxin: The effect of photoperiod and the potential role of relaxin on drinking in pregnancy.
Experiments were done to examine whether rat relaxin is dipsogenic and whether such dipsogenic effects of rat relaxin are related to time of injection during the light-dark cycle. Female rats were fitted with a chronic intra-cerebro-ventricular (i.c.v.) cannula. Rat relaxin (2.5, 5, 10, 25, 50, or 100 ng/2 microl in 0.9% saline) was injected into the right lateral ventricle at either morning (0800-1000 h), afternoon (1400-1600 h), or night (2200-2400 h), and water consumption was measured. Relaxin caused a dose-dependent dipsogenesis at doses > or = 5 ng, but the sensitivity and magnitude of the response varied with the photoperiod. Water consumption was smallest (3.5 +/- 0.7 ml at 50 ng) and least sensitive (minimal effective dose at 25 ng) in the afternoon and maximal (17.7 +/- 2.3 ml at 50 ng) and most sensitive (minimal effective dose 5 ng) at night. The latency from injection to drinking was 55.8 +/- 10.4 sec (mean +/- SEM) and did not vary significantly with either the dose or time of day. A second set of experiments was done to examine the effects of neutralizing the central actions of relaxin on drinking behavior in pregnancy. Pregnant rats were injected daily, through a chronically implanted i.c.v. cannula, with either a specific monoclonal antibody raised against rat relaxin from day 12 to day 22 of gestation or with saline as a control. Drinking and eating behavior and weight gain were monitored every 12 h during pregnancy. There was a significant decrease in water consumed at night, but no effect on drinking during the day in relaxin-neutralized rats. These animals also showed a decrease in weight gain during pregnancy compared with controls and gave birth to lighter-weight litters. These data provide evidence that the dipsogenic response to exogenous rat relaxin in female rats varies with time of injection during the light-dark cycle and suggest that relaxin in the brain may have a role in nighttime drinking behavior during the second half of pregnancy.


Dimer formation in immunoglobulin preparations and speculations on the mechanism of action of intravenous immune globulin in autoimmune diseases.
IgG dimers occurring in therapeutic Ig preparations have been characterized as Id-anti-Id, in that the sites of interaction are localized to the distal tips of the Fab arms. The observation that such dimers are prevalent in Ig or Igi.v. prepared from large plasma pools, but absent in preparations from a single individual, supports the notion that the individual immune repertoire is small with respect to the species repertoire. A crude mathematical model that attempts to relate Id-dimer content to the number of donors is presented. This model suggests that Id-pairs may be much more prevalent in Ig than is reflected by the Id-dimer content, inasmuch as the concentrations of the individual Ids and anti-Ids may limit the equilibrium level of dimer. The model further suggests that the antibody diversity in Ig derived from thousands of donors may be representative of the species repertoire; hence, virtually all specificities, including anti-Id specificities, will be included. Because Ig is derived from normal healthy donors, it should be relatively free of pathogenic autoantibodies. However, there is no reason to suspect that anti-Ids to such autoantibodies would not occur, and indeed the presence of such anti-Ids has been demonstrated. Several mechanisms have been proposed by which such anti-Ids might ameliorate autoimmune disease. They may directly inhibit the binding of autoantibody to its target antigen, or they may target for destruction those cells expressing or secreting autoantibody. It may well be that anti-Ids play no role in the mechanism of action of Igi.v. in autoimmune disease. Such appears to have been demonstrated, for example, in the treatment of ITP. There is an obvious need for additional studies in order to elucidate the mechanism of action of Igi.v. in various autoimmune diseases. Experimental animal models of autoimmune disease, such as the mouse model for systemic lupus erythematosus (Mozes et al. 1993), might be very useful in this regard. Finally, it needs to be emphasized that the usefulness of high doses of Igi.v. in many autoimmune diseases remains to be established by controlled clinical trials. Because Igi.v. is a limited resource, and one which cannot be produced through biotechnological advances (at least in the foreseeable future), its widespread use should be restricted to the treatment of diseases for which efficacy has been demonstrated. To do otherwise might deprive appropriate patients of a valuable therapy.


Identification of glutamic acid 646 as a zinc-coordinating residue in endopeptidase-24.11.
Neutral endopeptidase (EC 3.424.11, NEP) is a membrane-bound zinc-metallopeptidase. The substrate specificity and catalytic activity of NEP resemble those of thermolysin, a bacterial zinc-metalloprotease. Comparison of the primary structure of both enzymes suggests that several amino acids present in the active site of thermolysin are also found in NEP. Using site-directed mutagenesis of the cDNA encoding the NEP sequence, we have already shown that His residues 583 and 587 are two of the three zinc ligands. In order to identify the third zinc ligand, we have substituted Val or Asp for Glu616 or Glu646. Val616 NEP showed the same kinetic parameters as the non-mutated NEP. In contrast, the mutant Val646 NEP was almost completely devoid of catalytic activity and unable to bind the tritiated inhibitor [3H]N-[2(R,S)-3-hydroxyaminocarbonyl-2-benzyl-1-oxypropyl]gl ycine, the binding of which is dependent on the presence of the zinc ion. Replacing Glu for Asp at position 646 conserved the negative charge, and the mutant enzyme exhibited the same Km value as the non-mutated enzyme, but kCat was decreased to less than 3% of the value of the non-mutated enzyme. When compared to the non-mutated enzyme Asp646 NEP showed a higher susceptibility to chelating agents, but bound the tritiated inhibitor with the same affinity. Taken together, these observations strongly suggest that Glu646 of NEP is the third zinc-coordinating residue and is equivalent to Glu166 in thermolysin.


Netrin expressed by the ventral ectoderm lineage guides mesoderm migration in epibolic gastrulation of the leech.
Netrin is a remarkably conserved midline landmark, serving as a chemotactic factor that organizes the bilateral neural architecture in the post-gastrula bilaterian embryos. Netrin signal also guides cell migration in many other neural and non-neural organogenesis events in later developmental stages but has never been found to participate in gastrulation - the earliest cell migration in metazoan embryogenesis. Here, we found that the netrin signaling molecules and their receptors are expressed during gastrulation of the leech Helobdella. Intriguingly, Hau-netrin-1 was expressed in the N lineage, which gives rise in part to the ventral midline of ectoderm, at the onset of gastrulation. We demonstrated that the N lineage is required for the entrance of mesoderm into the germinal band and that misexpression of Hau-netrin-1 in early gastrulation prevented mesoderm from entering the germinal band. Together, these results suggested that Hau-netrin-1 secreted by the N lineage guides mesoderm migration during germinal band assembly. Furthermore, ectopic expression of Hau-netrin-1 after the completion of germinal band assembly disrupted the epibolic migration of the germinal bands in a later stage of gastrulation. Thus, Hau-netrin-1 is likely involved in two distinct events in sequential stages of leech gastrulation: the assembly of germinal bands in early gastrulation and their epibolic migration in mid-gastrulation. Given that the leech netrin is expressed in the precursor cells of the ventral midline during gastrulation, we propose that a heterochronic change from the midline netrin expression had taken place in the evolution of a novel mode of gastrulation in the directly developing leech embryos.