Reality negotiation in non-depressed and depressed persons.
Non-depressed and depressed persons were hypothesized to input and recall self-referential information that was consistent with their self theories. Non-depressed and depressed persons were compared. Non-depressed (14) and depressed (14) students chose between positive or negative audio statements, and then recalled the statements. Non-depressed relative to depressed participants: (i) listened more to the positive than the negative tapes; and (ii) fabricated (i.e. incorrectly recalled) less negative messages. Partial support is given to reality negotiation processes.


Impact of neoadjuvant chemotherapy on nodal regression and survival in oesophageal adenocarcinoma.
The prognostic value of lymph node regression (LNR) following neoadjuvant chemotherapy (nCT) for oesophageal and gastro-oeosphageal adenocarcinoma remains unclear. This study aimed to characterise the long-term survival outcomes of LNR in patients having resectional surgery after nCT. This study included patients undergoing oesophagectomy or extended total gastrectomy for oesophageal and junctional tumours (Siewert types 1,2,3) at the Queen Elizabeth Hospital Birmingham from 2012 to 2018. Lymph nodes retrieved at surgery were examined for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive with either partial or no response. This study identified 183 patients who received nCT, of which 71% (130/183) had positive lymph nodes. Of these 130 patients, 44% (57/130) had a lymph node response and 56% (73/130) did not. The remaining 53 patients (29.0%) had negative lymph nodes with no evidence of tumour. Lymph node responders had a significant survival benefit compared to patients without lymph node response, but shorter than those with negative lymph nodes (median: 27 vs 18 vs NR months, p < 0·001). On multivariable analysis, lymph node responders had an improved overall (Hazard ratio (HR): 0.86, 95% CI: 0.80-0.92, p < 0.001) and recurrence-free (HR: 0.90, 95% CI: 0.82-0.98, p = 0.030) survival. Lymph node regression is an important prognostic factor, warranting closer evaluation over primary tumour response to help with planning further adjuvant therapy in these patients.


A novel role for the Bombyx Slbo homologue, BmC/EBP, in insect choriogenesis.
One previously unidentified cDNA clone coding for a C/EBP factor, BmC/EBP, was isolated from Bombyx mori follicular cells. This is the first time that a C/EBP factor has been isolated and characterized in Lepidoptera. We provide information concerning structural features and developmental specificity, as well as in vitro interaction properties with chorion gene promoter modules. BmC/EBP was capable of effectively recognizing homologous binding sites from chorion gene promoters derived from flies and other moths, despite significant diversity of chorion structure, gene organization, and gene expression profiles. We propose that the relative concentration of BmC/EBP, in relation to its differential binding affinity for promoter cis-elements, results in activation or repression of silkmoth chorion gene expression.


Ixodidin, a novel antimicrobial peptide from the hemocytes of the cattle tick Boophilus microplus with inhibitory activity against serine proteinases.
The presence of an effective immune response in the hemocoel of arthropods is essential for survival as it prevents the invasion of pathogens throughout the animal body. Antimicrobial peptides (AMPs) play an important role in this response by rapidly killing invading microorganisms. In this study, a novel cysteine-rich AMP has been isolated and characterized from the hemocytes of the cattle tick, Boophilus microplus. In addition to growth inhibition of Escherichia coli and Micrococcus luteus, the newly described AMP, designated ixodidin (derived from the Family Ixodidae), was found to exert proteolytic inhibitory activity against two exogenous serine proteinases, elastase and chymotrypsin. This is the first report of a molecule of an arachnid that has been shown to inhibit bacterial growth and proteinase activity.


Start-up of an UASB-septic tank for community on-site treatment of strong domestic sewage.
Two community on-site UASB-septic tanks were operated in parallel over a six months period under two different hydraulic retention times (HRT) of 2 days for R1 and 4 days for R2 at mean sewage temperature of 24 degrees C. The sewage was characterised by a high COD(tot) concentration of 1189 mg/L, with a large fraction of COD(sus), viz. 54%. The achieved removal efficiencies in R1 and R2 for COD(tot), COD(sus), BOD5 and TSS were "56%, 87%, 59% and 81%" and "58%, 90%, 60% and 82%" for both systems, respectively. R2 achieved a marginal but significant (p<0.05) better removal efficiencies of those parameters as compared to R1. The COD(col) and COD(dis) removals in R1 and R2 were respectively 31% and 20%, and 34% and 22%. The sludge accumulation was very low suggesting that the desludging frequency will be of several years. Accordingly, the reactor can be adequately designed at 2 days HRT.


Comprehensive Environmental Assessment Index of Ecological Footprint.
This paper aims to contribute to the growing body of research literature on assessing environmental efficiency by introducing a new key performance indicator (KPIs) in more complete and dependable aspects of ecological footprint indices. For this purpose, the DEA model considering three inputs (energy consumption, labor force, and capital stock), one desirable output (GDP), and different undesirable outputs (CO2 emissions, ecological footprint indicators) are applied to 27 OECD countries from 2000 to 2017. According to the results, Norway, Luxemburg, and United Kingdom are the most environmentally efficient countries in terms of environmental efficiency and ecological footprint efficiency. On the other hand, the lowest environmental and ecological footprint efficiencies were in countries like Lithuania, Slovak, Czech, Estonia, and the USA. In addition, these nations fare poorly regarding their carbon footprint and farmland efficiency. In further detail, Lithuania, South Korea, Portugal, and Spain have a critical status in fishing ground efficiency, while the forest area efficiency is very acute in Estonia, Latvia, Lithuania, and Czech.


Osteopontin and bone metabolism: a histology and scintigraphy study in rats.
Osteopontin (OPN) is one of the major non-collagen proteins in extracellular bone matrix. To elucidate the function of OPN in bone metabolism, a cellular defect was created in parietal bone and tibia of 12 rats. In Group 1, the left defects were filled with OPN-coated hydroxyapatite (OPN-H). In Group 2, the right defects were filled with non-coated hydroxyapatite (N-H). In both groups, the contra lateral defects were used as control defects. In Group 3, OPN-H was inserted in the left defects and N-H in the right defects. Bone metabolism was measured by (45)Ca and technetium-99m methylene diphosphonate scintigraphy for 4 weeks. Scintigraphy did not show any significant differences in bone metabolism between the defects filled with OPN-H and N-H. A higher bone metabolism was measured between the parietal defects filled with OPN-H or N-H in comparison with the parietal control defects. This difference, however, was not significant and was less for tibia defects. Histological observation (7th week) shows less inflammatory cells at the tibia defects filled with OPN-H compared to the tibia defects filled with N-H. This study did not show any acceleration or inhibition of bone metabolism in parietal or tibia bone in rats, but there is some evidence that OPN might influence inflammatory cells in bone matrix.


Combined hepatic and gastric artery aneurysms: a case report and review of the literature.
A patient is presented who was successfully managed with metasynchronous rupture of a hepatic and a left gastric artery aneurysm. The subject of visceral artery, hepatic artery, and gastric artery aneurysms is reviewed. The role and limitations of modern interventional radiologic procedures in treating this entity is illustrated.


Inflammatory cell and cytokine patterns in patients with chronic polyarthritis and temporomandibular joint involvement.
To investigate the occurrence of selected markers for inflammatory cells and cytokines in patients with chronic polyarthritis (CPA) and temporomandibular joint (TMJ) involvement. Eleven patients (11 joints) with CPA and TMJ disorder were included in the study. Synovial specimens were obtained during TMJ open surgery and these were subjected to immunohistochemistry on frozen sections post-fixed with paraformaldehyde and with the cell membranes permeabilized by saponin. In all patients, the cytokines IL-1alpha, IL-1beta, IL-1ra, TNFalpha, IFNgamma, IL2, and TGFbeta were investigated using specific antibodies. The occurrence of macrophages and T-lymphocytes was investigated using immunohistochemistry with monoclonal antibodies against antigens CD68 and CD45RO, respectively. In addition, PCNA was used as a marker for cell proliferation. Staining of IL-1alpha, IL-1, and TGF was seen in all 11 specimens, IFN? in 1, TNFalpha in 4, and IL-2 in none. CD45RO-positive T cells were detected in 7 specimens, CD68-positive macrophages in 6, and cell proliferation seen with PCNA was noted in 8. The predominant cytokines of TMJ CPA were IL-1alpha, IL-1beta, and TGFbeta, and there appeared to be no differences between the subgroups (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) involved. Moreover, the cytokine pattern of TMJ CPA patients seemed to differ from patients with osteoarthritis, as shown in our previous study. The main difference was the absence of IFNgamma and TNFalpha in TMJ CPA patients and a stronger TGFbeta and IL-1alpha expression.


Correction to: Measuring quality of life in children with spinal muscular atrophy: a systematic literature review.
In the original publication of the article, the co-author name "Stefan Boes" has been mistakenly missed out. This has been updated in this correction.


Methods to Study the Biogenesis of Mitoribosomal Proteins in Yeast.
The biogenesis of mitoribosomes is an intricate process that relies on the coordinated synthesis of nuclear-encoded mitoribosomal proteins (MRPs) in the cytosol, their translocation across mitochondrial membranes, the transcription of rRNA molecules in the matrix as well as the assembly of the roughly 80 different constituents of the mitoribosome. Numerous chaperones, translocases, processing peptidases, and assembly factors of the cytosol and in mitochondria support this complex reaction. The budding yeast Saccharomyces cerevisiae served as a powerful model organism to unravel the different steps by which MRPs are imported into mitochondria, fold into their native structures, and assemble into functional ribosomes.In this chapter, we provide established protocols to study these different processes experimentally. In particular, we describe methods to purify mitochondria from yeast cells, to import radiolabeled MRPs into isolated mitochondria, and to elucidate the assembly reaction of MRPs by immunoprecipitation. These protocols and the list of dos and don'ts will enable beginners and experienced scientists to study the import and assembly of MRPs.


Severe head injury: should expected outcome influence resuscitation and first-day decisions?
An early 'prognosis' based on initial findings can influence clinical decisions. To evaluate the quality of first-day outcome prediction based on either clinical or neuroradiological information, we prospectively examined 100 consecutive severely head-injured patients from the surgical intensive care unit. The prognoses were always made by the same experienced neurosurgeon and neuroradiologist according to a contracted Glasgow Outcome Scale (GOS). Every patient's outcome was predicted according to a three-class GOS within 24 h after injury. Correct 'first-day' prognoses were made in 59 and 56% of the cases by the neuroradiologist and neurosurgeon, respectively. In those instances where the prognoses made by the clinician and the radiologist coincided, the prognoses were correct for 73% of the patients. Based on accepted criteria, the neuroradiologist tended to overpredict favorable outcomes and missed many of the unfavorable outcomes (dead or vegetative) whereas the clinician overestimated unfavorable outcomes. Our study showed that outcome prognosis of patients with severe head injury has limited accuracy when made within 24 h after the injury, although an improvement in accuracy occurred when there was agreement between clinical and radiological predictions. Even with sophisticated clinical and radiological technologies, it is not possible to predict outcome on the first day after the accident with sufficient accuracy to guide early management.


Scaling behavior in crackle sound during lung inflation.
During slow inflation of lung lobes, we measure a sequence of short explosive transient sound waves called "crackles," each consisting of an initial spike followed by ringing. The crackle time series is irregular and intermittent, with the number of spikes of size s following a power law, n(s) proportional, variants(-alpha), with alpha=2.77+/-0.05. We develop a model of crackle wave generation and propagation in a tree structure that combines the avalanchelike opening of airway segments with the wave propagation of crackles in a tree structure. The agreement between experiments and simulations suggests that (i) the irregularities are a consequence of structural heterogeneity in the lung, (ii) the intermittent behavior is due to the avalanchelike opening, and (iii) the scaling is a result of successive attenuations acting on the sound spikes as they propagate through a cascade of bifurcations along the airway tree.


Use of a rapid immunochromatographic test for early diagnosis of dengue virus infection.
Acute serum samples collected from 92 patients were analysed for the presence of immunoglobulin M and G antibodies against dengue viruses using a rapid immunochromatographic (IC) test. Of 52 patients with dengue virus infection diagnosed using a standard hemagglutination inhibition test, 41 patients demonstrated dengue virus infection using the IC test. Half of the serum samples collected on day 3 after the onset of fever were positive for dengue antibodies, and all were positive on day 6 after symptom onset. In comparison with the hemagglutination inhibition test, the rapid IC test showed 79% sensitivity and 95% specificity. The efficiency of the test was 86%. The IC test showed good agreement with the hemagglutination inhibition test (k=0.72). The IC test is quick to perform and provides early diagnosis of dengue virus infection.


[Serological survey in a Sahelian country, the Niger. Sampling problems and results of the serosurveillance of rinderpest].
A survey on Rinderpest serology was conducted in Niger with a sample of 2815 sera. The authors present the sampling method and resulting bias. The analysis of the sera is discussed according to the following factors: sex, age, vaccination status and geographic origin of the sera.


Histamine secretion in leukocyte incubates of patients with allergic hyperreactivity induced by somatostatin-14 and somatostatin-28.
Somatostatin is a potent histamine secretagogue found not only in rat mast cells but also in human leukocyte preparations. In concentrations greater than or equal to 5 mumol/l, somatostatin-14 induces histamine release, which correlates with the basophilic blood cell count, as shown in samples from allergic patients suffering from slight basophilia. Somatostatin-14 is twice as effective as somatostatin-28 on a molar basis, and acylating the tetradecapeptide with N-hydroxysuccinimidyl-p-hydroxy-phenyl-propionate decreases significantly the potency of histamine release.


Cost effectiveness of hepatitis C-related interventions targeting substance users and other high-risk groups: a systematic review.
In developed countries, injection drug users have the highest prevalence and incidence of hepatitis C virus (HCV) infection. Clinicians and policy makers have several options for reducing morbidity and mortality related to HCV infection, including preventing new infections, screening high-risk populations, and optimizing uptake and delivery of antiviral therapy. Cost-effectiveness analyses provide an estimate of the value for money associated with adopting healthcare interventions. Our objective was to determine the cost effectiveness of hepatitis C interventions (prevention, screening, treatment) targeting substance users and other groups with a high proportion of substance users. We conducted a systematic search of MEDLINE, EMBASE, CINAHL, HealthSTAR and EconLit, and the grey literature. Studies were critically appraised using the Drummond and Jefferson, Neumann et al. and Philips et al. checklists. We developed and applied a quality appraisal instrument specific to cost-effectiveness analyses of HCV interventions. In addition, we summarized cost-effectiveness estimates using a single currency and year ($US, year 2009 values). Twenty-one economic evaluations were included, which addressed prevention (three), screening (ten) and treatment (eight). The quality of the analyses varied greatly. A significant proportion did not incorporate important aspects of HCV natural history, disease costs and antiviral therapy. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (less costly and more effective) to $US603,352 per QALY. However, many ICERs were less than $US100,000 per QALY. Screening and treatment interventions involving pegylated interferon and ribavirin were generally cost effective at the $US100,000 per QALY threshold, with the exception of some subgroups, such as immune compromised patients with genotype 1 infections. No clear consensus emerged from the studies demonstrating that prevention, screening or treatment provides better value for money as each approach can be economically attractive in certain subgroups. More high-quality economic evaluations of preventing, identifying and treating HCV infection in substance users are needed.


An autopsy study to clarify characteristics of local recurrence after extended pancreatectomy with intraoperative radiation therapy in patients with pancreatic cancer.
Local relapses frequently occur even after curative resection of pancreatic cancer. To control local recurrence, we adopted extended radical resection combined with intraoperative radiation therapy. A retrospective review was conducted on 41 patients who underwent extended radical pancreatectomy combined with intraoperative radiation therapy for pancreatic cancer. Fourteen patients underwent autopsies. We took en bloc specimens of the abdominal aorta with surrounding connective tissue to evaluate histological characteristics of local status at autopsies. Autopsies disclosed microscopic local recurrence in five (36%) of the 14 patients, although no evidence of local relapse was observed in either follow-up images or macroscopic findings at autopsy. Of the three patients with R1 resection, two had no local recurrence microscopically at autopsy. Histological features of local recurrence in autopsy samples showed small numbers of cancer cells surrounded by thick connective tissue without mass formation. The autopsy study revealed that a characteristic of local recurrence after this treatment was tiny cancer cells scattered in dense connective tissue; these cells were undetected by follow-up imaging.


Indirect DNA Sequence Readout by LAGLIDADG Homing Endonucleases.
In this issue of Structure, Lambert et al. (2016) describe extensive structural and functional work on meganucleases, the group of homing endonucleases most commonly adapted to genome engineering applications. The data are of interest to structural biologists, evolutionary biologists, protein designers, and genome engineers.


Objective evaluation of anterior knee laxity; comparison of the KT-1000 and GNRB® arthrometers.
Accurate measurement of laxity after anterior cruciate ligament (ACL) rupture is usually performed with the KT-1000 arthrometer, and reproducibility and reliability are discussed. A new arthrometer, the GNRB(®), has been recently developed in an attempt to improve intra- and inter-examiner reproducibility. The aim of this diagnostic study was to evaluate the intra- and inter-examiner reproducibility of the GNRB(®) and the KT-1000. Three protocols were designed to evaluate and compare the two arthrometers. Fifteen physiotherapists conducted tests on 15 subjects with healthy knees. The intra- and inter-reproducibility of the two tests were compared by analysis of variance and the F-test. Measure reproducibility was significantly worst with the KT-1000 than with the GNRB(®) (machine effect, P < 0.001) regardless of operator experience. There was no significant difference between experienced and inexperienced examiners with the GNRB(®) (no 'examiners effect'). Regardless of the machine, there was a 'side effect' with healthy knees. This clinical study demonstrates the superior intra- and inter-examiner reproducibility of the GNRB(®) over the KT-1000. There appears to be some technological advantages to using the GNRB(®) including pressure control of the patella, accuracy of the displacement transducer, control of the load on the calf, and control of hamstring activity. Diagnostic study, Level I.


Mental health delivery through rural primary care-development and evaluation of a training programme.
There is a growing consensus of opinion (WHO 1975) that in developing countries, doctors and para-medical staff of the existing health care cadres should, after a short course of problem oriented training, deliver basic mental health care. This paper describes the development and evaluation of such a training programme.


Bacterial leaching of metal sulfides proceeds by two indirect mechanisms via thiosulfate or via polysulfides and sulfur
The acid-insoluble metal sulfides FeS2, MoS2, and WS2 are chemically attacked by iron(III) hexahydrate ions, generating thiosulfate, which is oxidized to sulfuric acid. Other metal sulfides are attacked by iron(III) ions and by protons, resulting in the formation of elemental sulfur via intermediary polysulfides. Sulfur is biooxidized to sulfuric acid. This explains leaching of metal sulfides by Thiobacillus thiooxidans.


Diethylaminoethyl chitosan-hyaluronic acid polyelectrolyte complexes.
Polysaccharide-based polyelectrolyte complexes (PECs) are of great interest for the development of drug delivery systems, as they are easily prepared and exhibit a wide range of colloidal properties. The water-soluble diethylaminoethyl chitosan (DEAE-CS) was synthesized with various degrees of substitution (DS), ranging from 26 to 113%. Analysis of the substitution pattern of DEAE-CS by different NMR techniques revealed N- and O-substitution, as well as quaternization of the tertiary amino group of the DEAE substituent; the fraction of quaternary amino groups increased with the DS. Unlike the tertiary amino groups, the quaternary amino groups did not support increases in the ζ-potential of DEAE-CS with the DS and the complexation with hyaluronic acid (HA). The influence of the PEC composition, DS of DEAE-CS, and mixing order on the size and polydispersity of PEC nanoparticles was investigated by dynamic and static light scattering. Internal disordered heterogeneous PEC nanoparticles were formed by the aggregates of several primary PECs. Disordered and structurally heterogeneous spherical complexes were formed (Rg/Rh = 1.0 ± 0.3). The obtained PECs were metastable and their properties were influenced by mixing order. The high molecular weight component (HA), being a minor component, was more exposed on the surface than was the low molecular weight DEAE-CS.


Identification of four novel HLA-DQA1 alleles: HLA-DQA1*01:01:02:04, 01:04:01:05, 03:03:01:19 and 05:01:01:08.
Four novel HLA-DQA1 alleles, -DQA1*01:01:02:04, -DQA1*01:04:01:05, -DQA1*03:03:01:19 and -DQA1*05:01:01:08, characterized in Spanish individuals.


Adaptive model-based Magnetic Resonance.
Conventional sequences are static in nature, fixing measurement parameters in advance in anticipation of a wide range of expected tissue parameter values. We set out to design and benchmark a new, personalized approach-termed adaptive MR-in which incoming subject data is used to update and fine-tune the pulse sequence parameters in real time. We implemented an adaptive, real-time multi-echo (MTE) experiment for estimating T2 s. Our approach combined a Bayesian framework with model-based reconstruction. It maintained and continuously updated a prior distribution of the desired tissue parameters, including T2 , which was used to guide the selection of sequence parameters in real time. Computer simulations predicted accelerations between 1.7- and 3.3-fold for adaptive multi-echo sequences relative to static ones. These predictions were corroborated in phantom experiments. In healthy volunteers, our adaptive framework accelerated the measurement of T2 for n-acetyl-aspartate by a factor of 2.5. Adaptive pulse sequences that alter their excitations in real time could provide substantial reductions in acquisition times. Given the generality of our proposed framework, our results motivate further research into other adaptive model-based approaches to MRI and MRS.


Chemotactic effects of the complement-derived peptides C3a, C3ai and C5a (classical anaphylatoxin) on rabbit and guinea-pig polymorphonuclear leukocytes.
The complement-derived peptides C3a, C3ai and C5a (= classical anaphylatoxin) were purified from hog serum and examined for chemotactic activity on rabbit and guinea-pig polymorphonuclear leukocytes (PMN) with the Boyden chamber technique (with filters of 3,0 micrometer pore size). When media containing albumin or serum were used all peptides induced chemotaxis of both cell species. Only C3a showed a pronounced species dependence in that it was much more active on rabbit than on guinea-pig PMN. No gross differences were found between the influence of 0.5% BSA and 10% heated (56 degree, 30 min) homologous serum added to the medium. In the absence of protein chemotaxis did not occur.


Effect of orthostatic changes on urokinase excretion.
The effects of orthostatic changes on the excretion of urokinase were studied in healthy normal volunteers. Urokinase excretion rose (average +69%) significantly (p less than .005) while urine volume fell (average-59%) significantly (p less than .001) after the subjects had been standing. There was no difference between men and women nor was there an apparent diurnal variation in urokinase excretion of recumbent subjects. A relationship between urokinase excretion and sympathetic nervous system activity is suggested.


An Efficient Method to Evaluate Intermolecular Interaction Energies in Large Systems Using Overlapping Multicenter ONIOM and the Fragment Molecular Orbital Method.
We propose an approach based on the overlapping multicenter ONIOM to evaluate intermolecular interaction energies in large systems and demonstrate its accuracy on several representative systems in the complete basis set limit at the MP2 and CCSD(T) level of theory. In the application to the intermolecular interaction energy between insulin dimer and 4'-hydroxyacetanilide at the MP2/CBS level, we use the fragment molecular orbital method for the calculation of the entire complex assigned to the lowest layer in three-layer ONIOM. The developed method is shown to be efficient and accurate in the evaluation of the protein-ligand interaction energies.


Observation of slow down of polystyrene nanogels diffusivities in contact with swollen polystyrene brushes.
The diffusion of dilute colloids in contact with swollen polymer brushes has been studied by evanescent wave dynamic light scattering. Two polystyrene nanogels with 16 nm and 42 nm radius were put into contact with three polystyrene brushes with varying grafting densities. Partial penetration of the nanogels within the brushes was revealed by the evanescent wave penetration depth-dependent scattering intensities. The experimental short-time diffusion coefficients of the penetrating particles were measured and found to strongly slow down as the nanoparticles get deeper into the brushes. The slow down is much more marked for the smaller (16 nm) nanogels, suggesting a size exclusion type of mechanism and the existence of a characteristic length scale present in the outer part of the brush.


Pregnancy and its complications following cardiac valve prostheses.
Approximately 100 cases of pregnancy in women with cardiac valve prostheses have been reported in the world's medical literature. In most instances, the need for continuous anticoagulation therapy constituted a major concern in the obstetric management of these high-risk pregnancies, particularly since coumarin has been implicated as causing an increased frequency of fetal wastage or birth defects (or both). Of all women who received cardiac valve prostheses at the Mayo Clinic between 1965 and 1975, 23 conceived 40 times after the procedure. Fetal wastage was more than doubled in women receiving coumarin therapy at conception and during the first trimester, as compared with that in women not receiving coumarin therapy. Fetal wastage exceeded 80% in women with multiple-valve prostheses who received coumarin therapy throughout early pregnancy. There were no serious maternal sequelae in any of the women. One infant of a mother receiving anticoagulation therapy had mild nasal hypoplasia, but there were no other congenital anomalies in which coumarin had been previously implicated.


Spermatozoon ultrastructure of Platichthys flesus.
The ultrastructure of the spermatozoon of Platichthys flesus (flounder) has been determined. The cell is of the primitive type and lacks an acrosome. The bullet-shaped, homogeneously electron-dense nucleus has a deep, caudal articular fossa containing proximal and distal centrioles. Both centrioles are embedded in pericentriolar material which is intimately associated with the nuclear envelope. Around the proximal centriole the material is organised into a dense ring which bears nine fibres associated with the triplets, and a large fibrous body, all connected to the nuclear envelope. Connections exist also between the pericentriolar material of the proximal and distal centrioles. The material around the distal centriole is organised into a complex collar. The anterior surfaces of eight spherical mitochondria lie within shallow depressions of the nuclear caudal surface. They form a ring surrounding the posterior opening of the articular fossa and the proximal region of the 9 + 2 flagellar axoneme.


Unchanging dilemmas in American medical education.
The author reviews "the lietmotiv of unresolved dilemmas" in American medical education: the problems of determining the premedical and medical school curricula and of selecting medical students. She offers suggestions for each area, but cautions that there are no simple answers.


Influences of microclimatic conditions and water relations on seasonal leaf dimorphism of Prosopis glandulosa var. torreyana in the Sonoran Desert, California.
Seasonal measurements of microclimatic conditions were compared to seasonal indices of leaf structural components and plant water relations in Prosopis glandulosa var. torryana. P. glandulosa had two short periods of leaf production which resulted in two distinct even aged cohorts of leaves. The two leaf cohorts (summer, winter) were concurrent in the summer and fall, contrasting to previous studies on other species in which one leaf form replaces a previous leaf type. The structural characteristics of these two cohorts differed significantly in two replicate year cycles. The leaves of the spring cohort were larger in weight and area but similar to the summer cohort in specific leaf weight and leaflet number. The second growth period leaves constituted only a small proportion of the total plant leaf area. The dimorphism between the two cohorts was best associated with plant water relations and not energy load. Second growth period leaves maintained turgor to greater water deficits but lost turgor at higher leaf water potentials. Seasonal osmotic adjustment occurred for first growth period leaves but not second growth period leaves. The small leaves produced during the hot climate were most likely the result of low turgor potential during development rather than an adaptation to tolerate stressful environments.


Management of fractures in field settings.
Limb fractures are common in farm animals, are most commonly found in young stock, and often occur subsequent to trauma during dystocia or handling. Cattle are excellent patients for treatment of orthopedic injuries because they spend a majority of time lying down, have a tremendous potential for bone healing, are more resistant than other animals to contralateral limb breakdown and stress laminitis, and usually do not resist having orthopedic devices on their limbs. This article describes management of fractures, especially for cattle, in field settings; explains how the principles of external skeletal fixation are adapted for cattle; discusses the application of external skeletal fixation to individual bones, and reviews potential complications in the use of external skeletal fixation.


Effect of tamsulosin on the number and intensity of ureteral colic in patients with lower ureteral calculus.
We aimed to objectively determine whether tamsulosin as an alpha(1)-blocker was effective in patients who had ureterolithiasis located in the lower part of the ureter. Sixty patients with lower ureteral calculi (juxtavesical or intramural portion) were included in the present study. Conservative treatment, such as hydration and tenoxicam as a non-steroidal anti-inflammatory drug, was given to group 1 (30 patients). Group 2 (30 patients) was given tamsulosin (0.4 mg daily) in addition to the conservative treatment. All patients were followed up and questioned about the numbers and intensity of ureteral colic, and the rates of spontaneous passage after the procedure. Spontaneous passage was observed in 22 of the 30 patients in group 1 (73.3%) and 26 of the 30 patients in group 2 (86.6%). The difference within groups 1 and 2 was not significant (P=0.196). The difference between both groups was not statistically significant either, with the stone diameter being 6 mm (P=0.635) or >6 mm (P=0.407). As group 1 patients were passing their stones, they had more ureteral colic episodes than group 2 patients. This difference was statistically significant and correlated well with the administration of tamsulosin (P=0.038). Group 1 patients reported higher scores according to a visual analog scale than group 2 patients. Also, this difference was statistically significant (P=0.000). We think that the treatment of alpha(1)-blockers decreased the number of ureteral colic episodes and the intensity of pain during spontaneous passage at the lower ureteral calculi. Also, it will be beneficial to patients' quality of life.


[Does the pharmacological class effect between the different luteinizing hormone releasing hormone analogues used in the treatment of prostate cancer have to be assumed?].
Evidence-based medicine is transforming clinical practice because of its progressive implantation. We considered studying whether LHRH analogues are agents of the same pharmacological class, i.e., whether they have the same clinical effect, using the approach to evidence-based medicine. PubMed was used as the main source of search. We have reviewed the evidence on the alleged «drug class effect» between analogues and the existing bibliographic support for their use in various medical indications. An evidence level and degree of recommendation have been assigned to each conclusion based on the «Scottish Intercollegiate Guidelines Network». There are no studies designed to answer the question of a class effect between LHRH analogues or agonists. Reviews and meta-analyses have been performed on many other issues related to therapeutic management either with analogues, alone or in combination with surgery or radiation therapy. Direct comparisons do not allow for obtain definitive conclusions: Indirect evidence is obtained from randomized studies comparing the different LHRH analogues to other treatments used to obtain androgen deprivation. Other issues related to pharmacokinetics and pharmacodynamics supporting either the existence or non-existence of class effect were evaluated. The current available evidence is not enough to support a presumed «drug class effect» among the various analogues in the treatment of prostate carcinoma.


Isolated adrenocorticotropic hormone deficiency secondary to hypothalamic deficit of corticotropin releasing hormone.
A 42-year-old man and a 51-year-old woman with a positive history of weakness and gastrointestinal complaints were shown to have low basal plasma cortisol and ACTH levels, and low daily urinary excretion of free cortisol. An empty sella was found in patient no. 1, while patient no. 2 was hypothyroid. Both patients showed a normal plasma cortisol response to ACTH and an increment in plasma ACTH and lipotropin levels after ovine CRH (oCRH), lysine vasopressin (LVP) and oCRH-LVP stimulation tests. These studies clearly report an isolated idiopathic ACTH deficiency due to a deficit in CRH in two adult subjects.


WT1 protein expression in slowly proliferating myeloid leukemic cell lines is scarce throughout the cell cycle with a minimum in G0/G1 phase.
Wilms' tumor gene 1 (WT1) is overexpressed in various hematological malignancies and has been proposed as a target for minimal residual disease (MRD) detection and for immunotherapy. Although WT1 is known as a key molecule for tumor cell proliferation, the expression pattern of WT1 in leukemic cells in dependency of proliferation has not yet been investigated. Furthermore, WT1 expression was mostly studied by reverse transcriptase PCR and the expression of WT1 protein has not been extensively studied. Here, we analyzed WT1 protein expression in the human myeloid leukemia cell lines K562 and HL-60 by indirect immunofluorescence and flow cytometry. Both cell lines exhibited varying nuclear WT1 immunoreactivity pointing to a cell cycle-dependent and/or proliferation-dependent WT1 expression. In rapidly proliferating cells high levels of WT1 protein were detected by flow cytometry. A reduced proliferation rate was associated with a low WT1 protein expression and an accumulation of cells in G(0)/G(1) phase. During G(0)/G(1) phase cells expressed WT1 at a lower level than in S or G(2)/M phase. Moreover, WT1 expression was diminished in all cell cycle phases in slowly proliferating cells. We conclude that WT1 protein expression is dependent on the cell cycle phase as well as on the proliferation rate. This finding might be relevant for MRD studies and immunotherapeutic strategies targeting WT1.


Insights of arsenic (III/V) adsorption and electrosorption mechanism onto multi synergistic (redox-photoelectrochemical-ROS) aluminum substituted copper ferrite impregnated rGO.
The understanding of mechanistic insights in environmental remediation and mitigation systems is attracting larger attention, in recent days. Here in, aluminium substituted copper ferrite impregnated rGO hybrid (CAF-rGO) is verified to understand the adsorption/electrosorption mechanism of arsenic in aqueous systems. Near-surface study (XPS: As 3d, Cu 2p, Fe 2p, Al 2p, O 1s, C 1s) proposes redox, and ligand exchange reactions between contaminant, and CAF-rGO. Adsorption capacities are observed around 128.8 mg g-1 [As(III)], 153.5 mg g-1 [As(V)] with Freundlich model isotherms. Kinetics study follows the PSO model with influence of solar light (> 420 nm). Cyclic voltammetry (CV) analysis in different molarity conditions observed with signals around +0.1 and -0.6 V confirm the redox abilities, and N2/O2 purged environments understood that electrosorption occurred through both reduction and sorption. Electrosorption study with pH variation shows the effect of protonation on the redox activity of individual arsenic species. Consistent signal around -0.6 ± 0.05 V in all the CV plots (i.e., Molarity, Environment, pH) recommends the usage of CAF-rGO for arsenic mitigation. Possible influence of photo-current (∼40 μA/cm2 at ∼ 0 V) towards As(III/V) decontamination is understood though photoelectrochemical analysis. Impedance plot shows low-resistance and better diffusion of arsenic oxy-anions during light irradiation. Synergistic nature of CAF-rGO generates reactive oxygen species (i.e., ●OH/●O2-/1O2) in mitigating highly toxic As(III) species is also detailed in the present work.


A rare case of bowel intussusception due to adenocarcinomatous polyp in a 14 year-old child: case report.
Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. It is an uncommon condition in children older than 2 years and causes intestinal obstruction. On the contrary of adult intussusception, childhood intussusception does not usually happen on a lead point of a malignant organic lesion. A 14-year-old male presented with complaints of heavy, bilious emesis and periumbilical colicky pain. Ultrasonography showed a dilated intestinal loop with absent bowel movement. CT scan revealed two masses in the abdomen. We performed an exploratory laparotomy that revealed invaginated intestines and showed a polyp near the area of interest. Necrotic segments and the polyp were removed and examined pathologically. Pathology showed adenocarcinoma in the polyp. After surgery, the general condition of the patient was normal and no complications occurred. Intussusception mainly occurs during infancy and early childhood. Mostly it is an idiopathic ileo-colic invagination. In our case, the patient had a jejuno-jejunal intussusception in his late childhood, and the lead point was an adenocarcinomatous polyp, which is rare in children. Amongst the many types of treatment, we chose surgical resection because of patient's age.


Pathophysiological Insight into Fatty Acid-Binding Protein-4: Multifaced Roles in Reproduction, Pregnancy, and Offspring Health.
Fatty acid-binding protein-4 (FABP4), commonly known as adipocyte-fatty acid-binding protein (A-FABP), is a pleiotropic adipokine that broadly affects immunity and metabolism. It has been increasingly recognized that FABP4 dysfunction is associated with various metabolic syndromes, including obesity, diabetes, cardiovascular diseases, and metabolic inflammation. However, its explicit roles within the context of women's reproduction and pregnancy remain to be investigated. In this review, we collate recent studies probing the influence of FABP4 on female reproduction, pregnancy, and even fetal health. Elevated circulating FABP4 levels have been found to correlate with impaired reproductive function in women, such as polycystic ovary syndrome and endometriosis. Throughout pregnancy, FABP4 affects maternal-fetal interface homeostasis by affecting both glycolipid metabolism and immune tolerance, leading to adverse pregnancy outcomes, including miscarriage, gestational obesity, gestational diabetes, and preeclampsia. Moreover, maternal FABP4 levels exhibit a substantial linkage with the metabolic health of offspring. Herein, we discuss the emerging significance and potential application of FABP4 in reproduction and pregnancy health and delve into its underlying mechanism at molecular levels.


Genetic association between CD95 rs2234767 polymorphism and cervical cancer risk: a meta analysis.
CD95 rs2234767 polymorphism in the promotor region of CD95 gene has been implicated in several studies of cervical cancer. However, the results have not been conclusively established. The main aim of this study was to deal with the controversy with respect to the correlation between CD95 rs2234767 polymorphism and risk of cervical cancer through a meta-analysis. Association studies that pertain to CD95 rs2234767 polymorphism and risk of cervical cancer were identified up to May 26, 2014. ORs and 95% CIs were calculated assuming AA versus GG, AA + AG versus GG, AA versus AG + GG, A versus G and AG versus GG genetic models. A total of 5 case-control studies were included in this meta-analysis. Overall, no significant effect modification of cervical cancer risk was revealed either at the genotypic or the allelic level for CD95 rs2234767 polymorphism. This null association persisted in the stratified analysis of Asian population. These findings revealed that CD95 rs2234767 polymorphism may not act as a causative agent of cervical cancer. Further evidence is needed to confirm our findings.


Prediction of genomic breeding values based on pre-selected SNPs using ssGBLUP, WssGBLUP and BayesB for Edwardsiellosis resistance in Japanese flounder.
Edwardsiella tarda causes acute symptoms with ascites in Japanese flounder (Paralichthys olivaceus) and is a major problem for China's aquaculture sector. Genomic selection (GS) has been widely adopted in breeding industries because it shortens generation intervals and results in the selection of individuals that have great breeding potential with high accuracy. Based on an artificial challenge test and re-sequenced data of 1099 flounders, the aims of this study were to estimate the genetic parameters of resistance to E. tarda in Japanese flounder and to evaluate the accuracy of single-step GBLUP (ssGBLUP), weighted ssGBLUP (WssGBLUP), and BayesB for improving resistance to E. tarda by using three subsets of pre-selected single nucleotide polymorphisms (SNPs). In addition, SNPs that are associated with this trait were identified using a single-SNP genome-wide association study (GWAS) and WssGBLUP. We estimated a heritability of 0.13 ± 0.02 for resistance to E. tarda in Japanese flounder. One million SNPs at fixed intervals were selected from 4,978,724 SNPs that passed quality controls. GWAS identified significant SNPs on chromosomes 14 and 24. WssGBLUP revealed that the putative quantitative trait loci on chromosomes 1 and 14 contained SNPs that explained more than 1% of the genetic variance. Three 50 k-SNP subsets were pre-selected based on different criteria. Compared with pedigree-based prediction (ABLUP), the three genomic methods evaluated resulted in at least 7.7% greater accuracy of predictions. The accuracy of these genomic prediction methods was almost unchanged when pre-selected trait-related SNPs were used for prediction. Resistance to E. tarda in Japanese flounder has a low heritability. GWAS and WssGBLUP revealed that the genetic architecture of this trait is polygenic. Genomic prediction of breeding values performed better than ABLUP. It is feasible to implement genomic selection to increase resistance to E. tarda in Japanese flounder with 50 k SNPs. Based on the criteria used here, pre-selection of SNPs was not beneficial and other criteria for pre-selection should be considered.


Abolition of reactive hyperemia in the dog heart following alpha adrenergic blockade and its reversal by vasopressin.
The local intracoronary application of the alpha adrenergic blocking agents phenoxybenzamine or dibenamine, in open chest anesthetized dogs, regularly resulted in maximal coronary vasodilatation thus abolishing reactive hyperemia. Infusion of vasopression or angiotensin returned coronary flow to near control levels and restored reactive hyperemia. It is thus concluded that although alpha blocking agents can relax coronary vessel smooth muscle, reactive hyperemia does not appear to be mediated through the inhibition of alpha adrenergic constrictor tone.


A fucoidan-gelatin wound dressing accelerates wound healing by enhancing antibacterial and anti-inflammatory activities.
Microbial infections and the slow regression of inflammation are major impediments to wound healing. Herein, a tilapia fish skin gelatin-fucose gum-tannic acid (Gel&Fuc-TA) hydrogel wound dressing (Gel&Fuc-TA) was designed to promote wound healing by mixing and reacting tannic acid (TA) with tilapia fish skin gelatin (Gel) and fucoidan (Fuc). Gel&Fuc-TA hydrogel has a good network structure as well as swelling and release properties, and shows excellent antibacterial, antioxidant, cell compatibility, and hemostatic properties. Gel&Fuc-TA hydrogel can promote the expression of vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (CD-31), and alpha-smooth muscle actin (α-SMA), enhance collagen deposition, and accelerate wound repair. Gel&Fuc-TA hydrogel can change the wound microbiome, reduce wound microbiome colonization, and decrease the expression of microbiome-related proinflammatory factors, such as lipopolysaccharide (LPS), Toll-like receptor 2 (TLR2), and Toll-like receptor 4 (TLR4). Gel&Fuc-TA hydrogel effectively regulates the conversion of wound macrophages to the M2 (anti-inflammatory phenotype) phenotype, decreases the expression of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), and increases the expression of arginase-1 (Arg-1), interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), thereby reducing the inflammatory response. In summary, Gel&Fuc-TA hydrogel prepared using a rational green cross-linking reaction can effectively accelerate wound healing.


Variation in the expression of insulin-like growth factor-1 in human pulp tissue according to the root-development stage.
Insulin-like growth factor-1 (IGF-1) plays an important role in cell proliferation and differentiation. It actively participates during odontogenesis and mineralization of dental hard tissues. The purpose of this study is to use a radioimmunoassay (RIA) to determine whether there are differences in the expression of IGF-1 in human pulp from teeth having incomplete or complete root development. Twenty-six pulp samples were obtained from freshly extracted human third molars, half of them from teeth with incomplete root development. All of the samples were processed and labeled using an IGF-1 RIA kit. Results showed IGF-1 presence in all human pulp samples with a statistically significant higher expression in pulps having complete root development. The present findings are consistent with the hypothesis that IGF-1 contributes toward forming and mineralizing dental tissues in teeth with incomplete root development as well as in pulp-repairing process in teeth with complete root development.


Ankylosing spondylitis presenting as juxta-articular masses in females.
Juxta-articular inflammatory masses, sternomanubrial or sternoclavicular, were noted in two women who were subsequently found to have ankylosing spondylitis. The differential diagnosis of juxta-articular masses should include systemic rheumatic disorders as well as tumor or infection.


Can an old dog learn (and want to experience) new tricks? Cognitive training increases openness to experience in older adults.
The present study investigated whether an intervention aimed to increase cognitive ability in older adults also changes the personality trait of openness to experience. Older adults completed a 16-week program in inductive reasoning training supplemented by weekly crossword and Sudoku puzzles. Changes in openness to experience were modeled across four assessments over 30 weeks using latent growth curve models. Results indicate that participants in the intervention condition increased in the trait of openness compared with a waitlist control group. The study is one of the first to demonstrate that personality traits can change through nonpsychopharmocological interventions.


Effect of apomorphine, piribedil and haloperidol on adrenal ornithine decarboxylase activity of the rat.
The administration of the dopaminergic drugs, apomorphine and piribedil to rats resulted in an increase in the activity of ornithine decarboxylase of the adrenal medulla and cortex. Pretreatment of the rats with the dopamine-receptor antagonist haloperidol caused a partial blockade of the apomorphine-induced effect at 4 hr in both medulla and cortex. At 6 hr, however, haloperidol did not block the effect of apomorphine and produced an increase in ornithine decarboxylase activity of both structures when administered alone. Hypophysectomy abolished the cortical ornithine decarboxylase response to apomorphine and haloperidol and the medullary response to haloperidol. The results suggest that the response of cortical ornithine decarboxylase activity to apomorphine and haloperidol is entirely mediated by the hypophysis and that the effect of apomorphine and the antagonistic action of haloperidol towards apomorphine in regard to the induction of adrenal medullary ornithine decarboxylase must be taking place at some central site independent of the hypothalamic-hypophyseal system.


[Radiology and pregnancy : Part 2: clinical recommendations].
In spite of a growing number of radiological scans in pregnant women there is still a high level of uncertainty concerning radiation exposure to the fetus. At the same time, the risk of fetal radiation injury is frequently overestimated. This entails an avoidable fear in the pregnant patient and may delay urgently required imaging and thus lead to an increased risk for maternal and fetal health. As a consequence, radiological scans in pregnant patients do not only require a thorough medical check but also a careful estimate of the specific radiation exposure to the fetus. The previous first part of the article described the legal requirements in Germany, the technical exposure and pharmacological risks for the pregnant woman and the fetus. The current second article focuses on the risk analysis for examinations with ionizing radiation and will provide recommendations for typical indications for maternal and fetal imaging.


Chinese hamster ovary cells produce sufficient recombinant insulin-like growth factor I to support growth in serum-free medium. Serum-free growth of IGF-I-producing CHO cells.
Insulin-like growth factor I has similar mitogenic effects to insulin, a growth factor required by most cells in culture, and it can replace insulin in serum-free formulations for some cells. Chinese Hamster Ovary cells grow well in serum-free medium with insulin and transferrin as the only exogenous growth factors. An alternative approach to addition of exogenous growth factors to serum-free medium is transfection of host cells with growth factor-encoding genes, permitting autocrine growth. Taking this approach, we constructed an IGF-I heterologous gene driven by the cytomegalovirus promoter, introduced it into Chinese Hamster Ovary cells and examined the growth characteristics of Insulin-like growth factor I-expressing clonal cells in the absence of the exogenous factor. The transfected cells secreted up to 500 ng/10(6) cells/day of mature Insulin-like growth factor I into the conditioned medium and as a result they grew autonomously in serum-free medium containing transferrin as the only added growth factor. This growth-stimulating effect, observed under both small and large scale culture conditions, was maximal since no further improvement was observed in the presence of exogenous insulin.


Cardiovascular responses to acute myocardial ischaemia in morphine-dependent rats.
1. The cardiovascular responses to acute myocardial ischaemia were studied in opiate-dependent animals before and after 2 weeks morphine withdrawal. 2. Rats were treated with morphine sulphate in drinking water for 2, 3 or 5 weeks. The development of morphine tolerance and dependence was verified by the tail-immersion test for analgesia and the naloxone-precipitated withdrawal syndrome, respectively. 3. Acute left coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate and ventricular tachycardia or fibrillation in anaesthetized naive rats. 4. Chronic morphine treatment did not alter the haemodynamic responses to coronary artery ligation. However, a significantly lowered incidence, and prolonged time of onset, of ventricular arrhythmias was found in 3 and 5 week morphine-treated rats. This phenomenon did not occur in animals receiving morphine for 2 weeks and in a 3 week morphine-treated group which was subsequently withdrawn for 2 weeks. 5. It is suggested that the decreased occurrence of early ventricular arrhythmias resulting from acute myocardial ischaemia in chronic morphine-treated rats may be related to the degree of opiate tolerance and dependence.


Role of Pharmacogenomics in the Efficacy and Safety of Thiopurines in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
Thiopurines' toxicity often leads to dose reduction or discontinuation. This systematic review aims to synthesize the evidence on the effect of genotype-based dosing of thiopurines on treatment efficacy and safety in inflammatory bowel disease (objective #1), and the association between genotype status and the efficacy and safety profile (objective #2). The Cochrane Library, MEDLINE, and EMBASE were searched in August 2021. A total of 80 studies (19,859 individuals) were included. Meta-analyses for mortality, different types of adverse events (AEs), withdrawal due to AE, change in disease activity and clinical remission were performed following mainly a fixed-effects model. PROSPERO registration: CRD42020148130. Genotype-based dosing was associated to a significantly lower incidence of hematologic AEs (risk ratio=0.71; 95% CI: 0.56-0.90; I2 : 47%; 4 randomized controlled trials; moderate quality), which may be attributable to nudix hydrolase 15 (NUDT15) testing more than to thiopurine methyltransferase (TPMT) genotyping. No differences were found in other outcomes. Mutations in TPMT and NUDT15 genes were associated to a higher probability of serious AEs [odds ratio (OR) TPMT=4.98; OR NUDT15=11.44], hematologic AEs (OR TPMT=3.18), and serious hematologic AEs (OR TPMT=7.88; OR NUDT15=12.83). TPMT was also associated with a higher risk of withdrawals due to AEs (OR=3.38), and NUDT15 with gastrointestinal AEs (OR=2.04). Mutations in the ITPA gene did not lead to significant differences. Evidence of an association between other genes and clinical outcomes is still scarce. Mutations in TPMT and NUDT15 genes predispose patients to suffer thiopurine-induced toxicity, and genotype-guided treatment has been shown to contribute to the prevention of thiopurine-induced toxicity, especially in the case of NUDT15 in Asians.


A novel vitamin D-regulated immediate-early gene, IEX-1, alters cellular growth and apoptosis.
1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) inhibits the expression of an immediate-early gene, IEX-1, which is involved in the regulation of cellular growth and apoptosis in a variety of cells. 1alpha,25(OH)2D3 alters the subcellular localization of IEX-1 by causing an efflux of IEX-1 from the nucleus, and the sterol decreases the expression of IEX-1 messenger RNA in cells via a novel DR3 repeat-type DNA response element.


Speed bump-induced spinal column injury.
Compression fracture of the vertebral body is common, especially in older adults. Injuries to the spinal column are one of the most frequent injuries by accidents and falls from heights. Vertebral fracture associated with minor trauma, however, is a rare occasion. Five cases were injured in the inner city buses after passing onto speed bumps are presented. On presentation, four patients complained of severe pain in the thoracolumbar region, while in the other patient, physical examination revealed pain and tenderness on the neck. No neurologic deficit was noted except for one patient with tenderness on thoracic spines. Examination of the thoracolumbar X-ray and computed tomography displayed compression fractures in four patients. Other laboratory data obtained on admission were within normal limits. Posterior instrumentation was applied to three patients. All patients recovered well except for the one with cervical fracture. Drivers should be strongly warned and educated on the potential hazards of traversing past such bumps in roads too fast and such barriers should be built regarding tested standards.


An Unusual Case of Infantile Hepatic Steatosis Caused by Coconut-Based Infant Formula.
We report a 5-month-old African American male with hepatic steatosis secondary to chronic and exclusive homemade coconut milk formula ingestion. Findings resolved with discontinuation.


Molecular mechanisms of Holliday junction branch migration catalyzed by an asymmetric RuvB hexamer.
The Holliday junction (HJ) is a DNA intermediate of homologous recombination, involved in many fundamental physiological processes. RuvB, an ATPase motor protein, drives branch migration of the Holliday junction with a mechanism that had yet to be elucidated. Here we report two cryo-EM structures of RuvB, providing a comprehensive understanding of HJ branch migration. RuvB assembles into a spiral staircase, ring-like hexamer, encircling dsDNA. Four protomers of RuvB contact the DNA backbone with a translocation step size of 2 nucleotides. The variation of nucleotide-binding states in RuvB supports a sequential model for ATP hydrolysis and nucleotide recycling, which occur at separate, singular positions. RuvB's asymmetric assembly also explains the 6:4 stoichiometry between the RuvB/RuvA complex, which coordinates HJ migration in bacteria. Taken together, we provide a mechanistic understanding of HJ branch migration facilitated by RuvB, which may be universally shared by prokaryotic and eukaryotic organisms.


Hyperbolic material enhanced scattering nanoscopy for label-free super-resolution imaging.
Fluorescence super-resolution microscopy has, over the last two decades, been extensively developed to access deep-subwavelength nanoscales optically. Label-free super-resolution technologies however have only achieved a slight improvement compared to the diffraction limit. In this context, we demonstrate a label-free imaging method, i.e., hyperbolic material enhanced scattering (HMES) nanoscopy, which breaks the diffraction limit by tailoring the light-matter interaction between the specimens and a hyperbolic material substrate. By exciting the highly confined evanescent hyperbolic polariton modes with dark-field detection, HMES nanoscopy successfully shows a high-contrast scattering image with a spatial resolution around 80 nm. Considering the wavelength at 532 nm and detection optics with a 0.6 numerical aperture (NA) objective lens, this value represents a 5.5-fold resolution improvement beyond the diffraction limit. HMES provides capabilities for super-resolution imaging where fluorescence is not available or challenging to apply.


Ten human cases of Fibricola seoulensis infection and mixed one with Stellantchasmus and Metagonimus.
Ten soldiers of the Korean Army were found to have F. seoulensis ova in their faeces. These men were treated with praziquantel and the worms passed after purging were successfully collected in one case: 59 F. seoulensis, 68 Metagonimus and 2 Stellantchasmus falcatus were collected. 2 men were also infected with Clonorchis sinensis. All the cases of fibricoliasis had eaten raw or undercooked snake meat or frogs during survival training. All were egg-negative 2-6 months after treatment.


Treatment of advanced uterine sarcoma with adriamycin.
Between 1971 and 1979, 39 patients with clearly measurable metastatic or advanced recurrent sarcoma of uterine origin were treated with Adriamycin, either alone or in combination with other chemotherapeutic drugs. The median survival was 7.2 months. No patient lived beyond 32 months from the start of chemotherapy. The response rate was 10.3% (10.3% partial responses and no complete responses). The median duration of a partial response was 4 months. There was no difference between the median survival of the responders and nonresponders.


A Phase IB/IIA Study of Allogeneic, Bone Marrow-derived, Mesenchymal Stem Cells for the Treatment of Refractory Ileal-anal Anastomosis and Peripouch Fistulas in the Setting of Crohn's Disease of the Pouch.
Mesenchymal stem cells [MSCs] have been used for the treatment of perianal Crohn's fistulising disease by direction injection. No studies to date have included patients with an ileal pouch-anal anastomosis [IPAA] in situ. A phase IB/IIA, randomised, control trial of bone marrow-derived, allogeneic MSCs via direct injection to treat adult patients with a peripouch fistula[s] was conducted; 75 million MSCs were administered with a 22 G needle, with repeat injection at 3 months if complete clinical and radiographic healing was not achieved. Adverse and serious adverse events at post-procedure Day 1, Week 2, Week 6, Month 3, Month 6, and Month 12 were assessed. Clinical healing, radiographic healing per pelvic magnetic resonance imaging [MRI], and patient-reported outcomes were assessed at the same time points. A total of 22 patients were enrolled and treated; 16 were treated and six were controls. There were no adverse or serious adverse events related to MSC therapy. At 6 months, 31% of the treatment group and 20% of the control had complete clinical and radiographic healing. When stratifying the treatment group into perianal [n = 7] and ano-vaginal [n = 8] fistulas, 6-month healing in the treatment groups was 57% and 0%, respectively. The perianal Crohn's disease activity index [PCDAI], Wexner incontinence score, and van Assche score all significantly decreased in treatment patients at 6 months; only the PCDAI decreased in the control group. Bone marrow-derived, allogeneic MSCs offer a safe and effective alternative treatment approach for peripouch fistulas in the setting of a Crohn's like phenotype of the pouch [ClinicalTrials.gov Identifier: NCT04519684.].


The inositol 5-phosphatase SHIP-1 and adaptors Dok-1 and 2 play central roles in CD4-mediated inhibitory signaling.
CD4 functions to enhance the sensitivity of T cells to antigenic peptide/MHC class II. However, if aggregated in isolation, e.g. in the absence of T cell receptor (TCR), CD4 can transduce yet undefined signals that lead to T cell unresponsiveness to antigen and apoptosis. In Human Immunodeficiency Virus-1 (HIV-1) disease, CD4(+) T cell loss can result from gp120-induced CD4 signaling in uninfected cells. We show here that CD4 aggregation leads to Lck-dependent phosphorylation of the RasGAP adaptors Downstream of kinase-1/2 (Dok-1/2) and the inositol 5-phosphatase-1 (SHIP-1) and association of the two molecules. Studies using SHIP-1 shRNA, knockout mice and decoy inhibitors further indicate that CD4-mediated inhibition of TCR-mediated T cell activation is SHIP-1 and Dok-1/2 dependent, and involves SHIP-1 hydrolysis of Phosphatidylinositol 3,4,5-trisphosophate (PI(3,4,5)P3) needed for TCR signaling. Our studies provide evidence for a novel mechanism by which ill-timed CD4-mediated signals activated by ligands such as HIV-1 gp120 lead to disarmament of the immune system.


Neuroscience Training for the 21st Century.
The field of neuroscience is enjoying a rapid expansion in scope, coupled with a remarkable broadening of conceptual approaches, scientific tools, and clinical applications. This growth poses new challenges for academic training programs as they prepare young neuroscientists for a more complex, competitive, and diverse career landscape. Multiple stakeholders, including academia, federal funding agencies, industry, scientific societies, private foundations, and other public and private sector contributors, need to be actively engaged in supporting this broad training effort. A renewed commitment to a more forward-looking, flexible yet integrative training vision offers opportunities for a bright future for young neuroscientists as they assume the role of vanguard of the enterprise that enriches our understanding of the brain.


Methodologic and clinical validation of the TIMI myocardial perfusion grade in acute myocardial infarction.
Improved microvascular perfusion using the TIMI myocardial perfusion grade (TMPG) has been related to reduced in hospital, 30-day and 2-year mortality following thrombolytic administration. We sought to validate this measure using the more quantitative technique of digital subtraction angiography (DSA) and to correlate TMPG with ST segment resolution. DSA was used to analyze films from the LIMIT AMI acute myocardial infarction trial of front loaded r-tPA and rhuMAb CD18. Dye kinetics were also characterized using DSA in 88 arteries from patients without acute coronary syndromes in the absence of an obstructive lesion. Compared to normal patients, microvascular perfusion was reduced in acute myocardial infarction patients on DSA as demonstrated by a reduction in peak Gray (brightness) (p < 0.0001), the rate of rise in Gray/sec (p < 0.0001), the blush circumference (p < 0.0001), and the rate of growth in circumference (cm/sec) (p < 0.0001). However, while DSA perfusion was impaired overall in the setting of acute myocardial infarction, TMPG grade 3 in the setting of acute myocardial infarction did not differ from that in normal patients when studied quantitatively as shown by similar rates of growth in brightness and circumference (p = NS). ST resolution and the TMPG were significantly associated (p = 0.04). Compared to normal patients, acute myocardial infarction reduces the peak brightness of the myocardium, the rate of rise in brightness, the circumference of blush and the rate of growth in circumference as assessed using digital subtraction angiography. However, acute myocardial infarction patients with TMPG 3 had rates of growth in brightness and circumference that were nearly identical to normal patients. Thus, DSA validates that TMPG 3 is associated with normal kinetics of myocardial perfusion, and this likely accounts for the low (0.7%) 30 day mortality observed among those patients with TFG 3 and TMPG 3.


Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension.
Excess and ectopic smooth muscle cells (SMCs) are central to cardiovascular disease pathogenesis, but underlying mechanisms are poorly defined. For instance, pulmonary hypertension (PH) or elevated pulmonary artery blood pressure is a devastating disease with distal extension of smooth muscle to normally unmuscularized pulmonary arterioles. We identify novel SMC progenitors that are located at the pulmonary arteriole muscular-unmuscular border and express both SMC markers and the undifferentiated mesenchyme marker platelet-derived growth factor receptor-β (PDGFR-β). We term these cells "primed" because in hypoxia-induced PH, they express the pluripotency factor Kruppel-like factor 4 (KLF4), and in each arteriole, one of them migrates distally, dedifferentiates, and clonally expands, giving rise to the distal SMCs. Furthermore, hypoxia-induced expression of the ligand PDGF-B regulates primed cell KLF4 expression, and enhanced PDGF-B and KLF4 levels are required for distal arteriole muscularization and PH. Finally, in PH patients, KLF4 is markedly up-regulated in pulmonary arteriole smooth muscle, especially in proliferating SMCs. In sum, we have identified a pool of SMC progenitors that are critical for the pathogenesis of PH, and perhaps other vascular disorders, and therapeutic strategies targeting this cell type promise to have profound implications.


An automated insertion tool for cochlear implants with integrated force sensing capability.
Minimally invasive cochlear implantation and residual hearing preservation require both the surgical approach to the cochlea as well as the implant insertion to be performed in an atraumatic fashion. Considering the geometric limitations of this approach, specialized instrumentation is required to insert the electrode while preserving intracochlear membranes carrying the sensory hair cells. An automated insertion tool for cochlear implants, which is capable of sensing insertion forces with a theoretical resolution of 30 μN, is presented. In contrast to previous designs, the custom force sensor is integrated in the insertion mechanism. Moreover, a test bench for insertion studies under constant and reproducible boundary conditions is proposed. It is used to experimentally validate the force sensing insertion tool, which is achieved by comparing the acquired forces to a ground truth measurement. The results of insertion studies on both an acrylic cochlear phantom and temporal bone specimen are given and discussed. Results reveal that friction, occurring between the electrode carrier and the inside of the insertion tool guide tube, is likely to affect the force output of the proposed sensor. An appropriate method to compensate for these disturbances is presented and experimentally validated. Using the proposed approach to friction identification, a mean accuracy of (4.0±3.2) mN is observed. The force information provided by the proposed, automated insertion tool can be used to detect complications during electrode insertion. However, in order to obtain accurate results, an identification of frictional forces prior to insertion is mandatory. The insertion tool is capable of automatically executing the appropriate trajectories.


Microalbuminuria is associated with high prevalence of anemia in renal transplant recipients.
Prevalence of anemia is higher in diabetic patients with microalbuminuria than those with normoalbuminuria despite the absence of significant renal impairment. The aim of this study was to investigate whether there was a relationship between microalbuminuria and anemia in renal transplant recipients (RTRs). Twenty-eight RTRs with microalbuminuria and 21 control RTRs with normoalbuminuria were classified based on urinary albumin creatinine ratios (UACR) of 0.03-0.3 versus <0.03, respectively. Anemia was defined as a hemoglobin level <13 g/dL for men and <12 g/dL for women. Anemia was observed in 13 (46.4%) microalbuminuric and 4 (19%) normoalbuminuric patients (P = 0.044). Hemoglobin level was significantly lower in the microalbuminuric than the normoalbuminuric group (13.3 ± 1.3 g/dL vs 14.4 ± 1.9 g/dL, respectively; P = .018). Although creatinine clearance was significantly higher among the normoalbuminuric group (84 ± 30 mL/min vs 65 ± 22 mL/min, respectively; P = .017), mean creatinine clearance in microalbuminuric group was >60 mL/min, the threshold value for anemia due to erythropoietin (EPO) deficiency. In contrast, there was no significant difference between the 2 groups for age, gender, donor source, and transplant duration. Anemia was frequent among RTRs displaying microalbuminuria, which may reflect EPO deficiency due to the tubulointerstitial injury of chronic allograft nephropathy. The EPO deficiency may begin before significant deterioration in excretory function of the kidney.


Hetero Diels-Alder reactions of nitrosoamidines: an efficient method for the synthesis of functionalized guanidines.
Hetero Diels-Alder reactions of transient nitrosoamidines are reported. Transient nitrosoamidines are formed by oxidation of protected N-hydroxylguanidines and are trapped in situ by 1,3-dienes to give [4 + 2] cycloadducts in good yields and regioselectivity. The resultant cycloadducts are versatile intermediates for the formation of functionalized guanidines. [reaction: see text]


Immunoglobulin isotype in the murine response to polysaccharide antigens.
Murine antisera specific for the alpha (1 leads to 3) and alpha (1 leads to 6)-linked glucosyl determinants of dextran, as well as for meningococcal polysaccharide group C, have been examined for the distribution of their immunoglobulin classes and subclasses. Whereas the thymus-independent anti-alpha (1 leads to 3) dextran response in BALB/c mice was found to be IgM greater than IgG3 greater than IgA, thus corresponding to previously published work, neither the alpha (1 leads to 6) response in its thymus-dependent or-independent form, nor the response to purified meningococcal polysaccharide, corresponded to this pattern. No preference for any of the IgG subclasses appeared for these antigens when given as thymus-independent carbohydrates. On the other hand, thymus-dependent forms of alpha (1 leads to 6) dextran showed an IgG1 greater than IgG3 greater than IgG2 pattern.


Bone assessment around the delayed dental implant with and without preformed anatomical caps: A 1-year retrospective case-control study.
To investigate the amount of first-year peri‑implant bone loss and the development of the papillae when delayed dental implants loaded with anatomic cover screw and those underwent conventional healing protocol were compared. Edentulous healed sites had undergone delayed implants placement. In the anatomical cap group, patients were treated with a guided tissue healing, tooth-like cross-linkable acrylic resin caps had been immediately screwed on dental implants. The marginal loss of the alveolar bone height 1 year after surgery and Jemt's papillae index were obtained. Non-parametric statistics were performed with a level of significance of 1% RESULTS: Forty patients were included in the present retrospective analysis. After a follow-up of 1 year, none of the 40 included implants showed a failure. The Jemt's papilla index was 1.76±0.44 and 1.34±0.50 respectively for guided tissue healing and conventional healing group, without any significant difference. Within the first year of survey a bone loss of -1.27±0.26 mm for conventional healing treatment showed a statistically significant difference (p-value<0.0001) when it was compared to the negligible of the other group (-0.06±0.31 mm). A guided healing procedure with preformed caps seemed to give better outcomes regarding marginal bone loss and papilla index than those of conventional abutments.


Impact of Universal Hepatitis B Vaccination on Prevalence, Infection-Associated Morbidity and Mortality, and Circulation of Immune Escape Variants in Russia.
6,217 sera samples collected from volunteers in six epidemiologically different regions of Russia were tested for serological and molecular markers of HBV infection. A mathematical model developed by the U.S. Centers for Disease Control and Prevention was used to estimate the effect of vaccination and birth dose coverage on the incidence of HB and adverse outcomes of infection. Prevalence of HBsAg in the study population varied from 1.2% to 8.2%; anti-HBc detection rates were 13.0-46.2%. HBsAg detection rates in epidemiologically significant cohorts were 0.6-10.5% in women of childbearing age; 0-2.4% in children ≤5 years old; 1.9-8.1% in adults ≥30 years old. Mathematical modeling demonstrated that the current 96.1-99.6% level of birth dose coverage increased the effectiveness of vaccination 10-21 times compared to 50% and 0% birth dose coverage scenarios. HBV DNA was detected in 63 sera samples. The frequency of amino acid substitutions in HBsAg was 38% (24/63). Only in 3% (2/63) the mutations were within the a-determinant of HBsAg (M133T and G145S, one case each). None of the identified mutations eluded HBsAg detection, since all these samples tested positive for HBsAg by commercial ELISA. Despite a significant decline in acute HB incidence after the introduction of universal vaccination, many undiagnosed potential sources of infection remain. Low prevalence of HBV immune escape variants is a favorable predictor of vaccine effectiveness in the future.


Personality, stress, and injuries in professional ballet dancers.
Twenty-nine soloist and principal dancers (mean age, 29.08 years) from America's two most celebrated ballet companies were administered questionnaires measuring personality (API), occupational stress (OES), strain (PSQ), and coping mechanisms (PRQ), and injury patterns. The results revealed that male dancers demonstrated significantly more negative personality traits and psychological distress than female dancers or men in the general population. In addition, physical stress and personality traits, characteristic of the "overachiever," distinguished injured dancers. It is suggested that classical ballet's emphasis on the ballerina may be at odds with a masculine identity in male dancers. Furthermore, the qualities that lead to success in this profession may contribute to injuries if carried to an extreme.


The electrical properties of isolated microtubules.
This study examines the electrical properties of isolated brain microtubules (MTs), which are long hollow cylinders assembled from αβ-tubulin dimers that form cytoskeletal structures engaged in several functions. MTs are implicated in sensory functions in cilia and flagella and cellular activities that range from cell motility, vesicular traffic, and neuronal processes to cell division in the centrosomes and centrioles. We determined the electrical properties of the MTs with the loose patch clamp technique in either the presence or absence of the MT stabilizer Paclitaxel. We observed electrical oscillations at different holding potentials that responded accordingly in amplitude and polarity. At zero mV in symmetrical ionic conditions, a single MT radiated an electrical power of 10-17 W. The spectral analysis of the time records disclosed a single fundamental peak at 39 Hz in the Paclitaxel-stabilized MTs. However, a richer oscillatory response and two mean conductances were observed in the non-Paclitaxel MTs. The findings evidence that the brain MTs are electrical oscillators that behave as "ionic-based" transistors to generate, propagate, and amplify electrical signals.


Substituted trifluoroketones as potent, selective inhibitors of mammalian carboxylesterases.
A series of substituted trifluoroketones were tested as inhibitors of mammalian liver microsomal carboxylesterase(s) hydrolyzing a variety of substrates including malathion, diethylsuccinate (DES) and p-nitrophenyl acetate (p-NpAc). The trifluoroketones used were very potent "transition state" inhibitors of crude mouse and human liver microsomal carboxylesterases as well as commercial porcine liver carboxylesterase (Sigma EC 184.108.40.206 Type I). These enzymes were found to differ in their sensitivity to the inhibitors employed, and some compounds caused dramatic activation of the hydrolysis of DES. In some but not all cases, a thioether beta to the carbonyl increased the inhibitory potency of the compound. Structure-activity relationships also were evaluated among aliphatic versus substituted and unsubstituted aromatic trifluoroketones. Kinetic parameters [i.e. Km, Vmax and (T1/2)e] for the mouse liver microsomes and the porcine carboxylesterase hydrolyzing DES were determined. Apparent high- and low-affinity forms were observed with each preparation. 3-Nonylthio-1,1,1-trifluoropropan-2-one was synthesized by the reaction of the corresponding thiol with 3-bromo-1,1,1-trifluoroacetone, and apparent synergism was observed when it was coadministered i.p. with malathion to mice.


Editorial: Analyzing Treatment and Prescribing in Large Administrative Datasets With a Lens on Equity.
In this issue of the Journal, Bushnell and colleagues1 present findings from their analysis of a commercial insurance administrative dataset, examining the ways that antipsychotics are used in young children (aged 2-7 years) in the United States. From 2009 to 2017, they find that the use of antipsychotics decreased and there was a shift toward use of medications in alignment with evidence-based standards. The most common conditions for use of antipsychotics included pervasive developmental disorders, externalizing disorders, and attention-deficit/hyperactivity disorder. More troubling were the findings that less than half of young children on antipsychotics had a visit with a psychiatrist, and only a third of children had evidence of a minimum dose of psychotherapy. These findings deserve attention and should be a cause for strengthening the use of existing treatment guidelines for preschool and younger children. They should also prompt enhanced advocacy to expand access to evidence-based mental health care for children that includes high-quality psychiatric assessment, treatment, and psychotherapy. The latter includes increasing the number of child and adolescent psychiatrists who focus on preschool-aged and younger children.


Enhanced activity of demineralised bone matrix augmented with xenogeneic bone morphogenetic protein complex in rats.
Demineralised bone matrix (DBM) is an allograft material widely used as a bone filler and bone graft substitute. DBM contains bone morphogenetic proteins (BMPs), which induce and regulate bone formation during embryogenesis and in postnatal life. To investigate the osteoinductivity of DBM augmented with xenogeneic BMP-complex at different doses. Rat DBM was augmented with BMP-complex purified from porcine diaphyseal bone. Dorsal subcutaneous implantation of 25 mg rat allogeneic DBM augmented with 0, 3, 6 and 12 mg BMP-complex per gram of DBM resulted in dose dependant up-regulation of bone formation on day 21, as scored histologically and biochemically. Allogeneic DBM can be augmented with xenogeneically sourced BMP-complex to improve DBM performance in vivo. This work demonstrates the potential of BMP-complex augmented DBM to induce new bone formation with improved parameters of bone formation.


Chronic ankle instability modifies proximal lower extremity biomechanics during sports maneuvers that may increase the risk of ACL injury: A systematic review.
The biomechanical changes in the lower extremity caused by chronic ankle instability (CAI) are not restricted to the ankle joint, but also affect the proximal joints, increasing the risk of joint injury. This study aimed to systematically review the research on CAI and lower extremity angle and movements during side-cutting, stop jumping, and landing tasks, to provide a systematic and basic theoretical basis for preventing lower extremity injury. Literature published from exception to April 2022 were searched in the PubMed, Web of Science, and SPORTDiscus databases using the keywords of "chronic ankle instability," "side-cut," "stop jump," and "landing." Only studies that compared participants with chronic ankle instability with healthy participants and assessed lower extremity kinetics or kinematics during side-cutting, stop jumping, or landing were included. The risk of bias assessment was conducted using a modified version of the Newcastle-Ottawa checklist. After title, abstract, and full text screening, 32 studies were included and the average score of the quality evaluation was 7 points (range 6-8). Among them five studies were related to the side-cut task, three studies were the stop-jump task, and twenty-four studies were related to landing. Although the results of many studies are inconsistent, participants with CAI exhibit altered lower extremity proximal joint movement strategies during side cut, stop jump, and landings, however, such alterations may increase the risk of anterior cruciate ligament injury.


Identifying Mutations of the Tetratricopeptide Repeat Domain 37 (TTC37) Gene in Infants With Intractable Diarrhea and a Comparison of Asian and Non-Asian Phenotype and Genotype: A Global Case-report Study of a Well-Defined Syndrome With Immunodeficiency.
Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare, autosomal recessive and severe bowel disorder mainly caused by mutations in the tetratricopeptide repeat domain 37 (TTC37) gene which act as heterotetrameric cofactors to enhance aberrant mRNAs decay. The phenotype and immune profiles of SD/THE overlap those of primary immunodeficiency diseases (PIDs). Neonates with intractable diarrhea underwent immunologic assessments including immunoglobulin levels, lymphocyte subsets, lymphocyte proliferation, superoxide production, and IL-10 signaling function. Candidate genes for PIDs predisposing to inflammatory bowel disease were sequencing in this study. Two neonates, born to nonconsanguineous parents, suffered from intractable diarrhea, recurrent infections, and massive hematemesis from esopharyngeal varices due to liver cirrhosis or accompanying Trichorrhexis nodosa that developed with age and thus guided the diagnosis of SD/THE compatible to TTC37 mutations (homozygous DelK1155H, Fs*2; heterozygous Y1169Ter and InsA1143, Fs*3). Their immunologic evaluation showed normal mitogen-stimulated lymphocyte proliferation, superoxide production, and IL-10 signaling, but low IgG levels, undetectable antibody to hepatitis B surface antigen and decreased antigen-stimulated lymphocyte proliferation. A PubMed search for bi-allelic TTC37 mutations and phenotypes were recorded in 14 Asian and 12 non-Asian cases. They had similar presentations of infantile onset refractory diarrhea, facial dysmorphism, hair anomalies, low IgG, low birth weight, and consanguinity. A higher incidence of heart anomalies (8/14 vs 2/12; P = 0.0344, Chi-square), nonsense mutations (19 in 28 alleles), and hot-spot mutations (W936Ter, 2779-2G>A, and Y1169Ter) were found in the Asian compared with the non-Asian patients. Despite immunoglobulin therapy in 20 of the patients, 4 died from liver cirrhosis and 1 died from sepsis. Patients of all ethnicities with SD/THE with the characteristic triad of T nodosa, hepatic cirrhosis, and intractable enteropathy have low IgG, poor vaccine response and/or decreased antigen-stimulated lymphocyte proliferation. This is now better classified into the subgroup of "well-defined syndromes with immunodeficiency" (the update termed as "combined immunodeficiencies with associated or syndromic features") than "predominantly antibody deficiencies" in the update PIDs classification, and requires optimal interventions.


Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines.
Monoclonal antibody YHD-06 generated by immunization with GM2 reacted with gangliosides with GM2-determinant, i.e., GM2, GalNAc-GM1b and GalNAc-GD1a, among which GalNAc-GD1a was characterized as an antigen of autoimmune peripheral neuropathies including Guillain-Barré syndrome. When glycolipids were examined by TLC-immunostaining with YHD-06 in seven human cervical carcinoma-derived cell lines, GM2 was found in all cell lines, amounting to 15.5 % to 57.5 % of total gangliosides. Whereas GalNAc-GD1a was present in three cell lines, amounting to 5.4-17.5 % of total gangliosides, and GalNAc-GM1b in four cell lines in amounts of less than 2 %. The elevated amounts of gangliosides with GM2 determinant were closely correlated with the relative intensities of gene expression of GalNAc transferase, this being characteristic of cervical carcinoma-derived cells. However, in tissues from patients with several histological types of cervical carcinomas, GM3 was ubiquitously expressed in amounts of more than 66 % of total gangliosides, GM2 was expressed in only five of 15 tissues, and both GalNAc-GM1b and GalNAc-GD1a were not even detected in trace amounts. Since GM1 was detected in all tissues in amounts of less than 0.06 μg/mg dried tissue, all cervical carcinoma tissues were revealed to exhibit GM2 synthesis, indicating that enhanced synthesis of gangliosides with GM2 determinant is a characteristic of cultivated cells in vitro. Similarly, although I(3)SO3-GalCer was not present in the squamous cell carcinoma (SCC) tissues, SCC-derived cells selectively expressed II(3)SO3-LacCer. Since enhanced synthesis of GM2 has been reported in SV-40 virus-transfected fibroblasts, papilloma virus might be involved in the expression of GM2 in cervical carcinoma-derived cells.


Outcomes of early ileocolectomy after percutaneous drainage for perforated ileocolic Crohn's disease.
The optimal treatment for an intra-abdominal abscess/infection secondary to perforating ileocolic Crohn's disease (PCD) is unclear. Forty-seven consecutive PCD patients treated via an institutional protocol of ileocolectomy after a 7-day period of percutaneous abscess drainage were retrospectively compared with 160 consecutive patients who underwent an elective ileocolectomy for Crohn's disease (ECD) between 1992 and 2014. Outcomes were compared using univariate analysis and propensity score matching. Univariate analysis demonstrated significant differences in ileostomy rates (PCD: 48.9% vs ECD: 18.8%; P = .001), 30-day readmissions (PCD: 38.3% vs ECD: 18.8%; P = .01), and overall 30-day postoperative complications (PCD: 29.8% vs ECD: 15%; P = .03). After matching, a statistically significant difference was retained in ileostomy rates (P = .02) and 30-day readmissions (P = .01). Early operative intervention after percutaneous drainage in perforating CD may be associated with a high incidence of diversions and readmissions.


Jasmonic acid-amino acid conjugation enzyme assays.
Jasmonic acid (JA) is activated for signaling by its conjugation to isoleucine (Ile) through an amide linkage. The Arabidopsis thaliana JASMONIC ACID RESISTANT1 (JAR1) enzyme carries out this Mg-ATP-dependent reaction in two steps, adenylation of the free carboxyl of JA, followed by condensation of the activated group to Ile. This chapter details the protocols used to detect and quantify the enzymatic activity obtained from a glutathione-S-transferase:JAR1 fusion protein produced in Escherichia coli, including an isotope exchange assay for the adenylation step and assays for the complete reaction that involve the high-performance liquid chromatography quantitation of adenosine monophosphate, a stoichiometric by-product of the reaction, and detection of the conjugation product by thin-layer chromatography or gas -chromatography/mass spectrometry.


Huwentoxin-V, a novel insecticidal peptide toxin from the spider Selenocosmia huwena, and a natural mutant of the toxin: indicates the key amino acid residues related to the biological activity.
A neurotoxin peptide (named Huwentoxin-V) was purified from the venom of the Chinese bird spider Selenocosmia huwena by a combination of ion exchange chromatography and reverse phase HPLC. HWTX-V has 35 amino acid residues, and is in perfect agreement with the molecular mass 4111.4 Da identified by mass spectrometry. A natural mutant of the toxin (called mHuwentoxin-V) was also isolated from the venom. mHWTX-V was only truncated two amino acid residues from the C-terminus of HWTX-V, and its molecular weight is 3877.1 Da determined by mass spectrometry. The six cysteine residues in each sequence of the two peptides suggest three disulfide bridges, the present of which was demonstrated by mass spectrometry after dithiothreiotol reduce and S-carboxymethylation. The primary structure of the two toxins exhibits sequence identity with other spider toxins such as ProTx-I (64%), SGTx (57%), SNX-482 (55%), and Hanatoxin (54%). HWTX-V can reversibly paralyze locusts and cockroaches for several hours with a ED50 value as 16 +/- 5 microg/g to locusts, and a larger dose of the toxin can cause death. However, mHWTX-V shows no significant effect on locusts and cockroaches. The structure-activity relationship indicates that the residues Phe34 and Ser35 in the C-terminus of HWTX-V are the key residues of the biological activity.


New therapies towards a better glycemic control in youths with type 1 diabetes.
Type 1 diabetes (T1D) is the most frequent form of diabetes in pediatric age, affecting more than 1.5 million people younger than age 20 years worldwide. Early and intensive control of diabetes provides continued protection against both microvascular and macrovascular complications, enhances growth, and ensures normal pubertal development. In the absence of definitive reversal therapy for this disease, achieving and maintaining the recommended glycemic targets is crucial. In the last 30 years, enormous progress has been made using technology to better treat T1D. In spite of this progress, the majority of children, adolescents and young adults do not reach the recommended targets for glycemic control and assume a considerable burden each day. The development of promising new therapeutic advances, such as more physiologic insulin analogues, pioneering diabetes technology including continuous glucose monitoring and closed loop systems as well as new adjuvant drugs, anticipate a new paradigm in T1D management over the next few years. This review presents insights into current management of T1D in youths.


Comparative study of aggression - Dangerousness on patients with paranoid schizophrenia: Focus on demographic data, PANSS, drug use and aggressiveness.
This cross sectional study aimed to compare the differences in psychopathology of Greek homicide and homicide attempters, patients with schizophrenia, with non violent individuals, suffering from schizophrenia. The study compared three Groups of 220 men, diagnosed with schizophrenia: (a) Group Α (Schizophrenia - No violence, (b) Group Β (Schizophrenia - with violence or violent crime), (c) Group C (Schizophrenia - not guilty by reason of insanity - violent crime). Several psychometric tools were used, such as M.I.N·I (Mini-International Neuropsychiatric Interview), PANSS scale (Positive and Negative Symptoms Scale). Most subjects suffered from paranoid schizophrenia. On factors such as demographic characteristics (i.e. current occupational status, living status), statistically significant findings were shown for Groups B and C vs Group A. Predisposing psychosocial factors, such as family conflicts and aggressiveness against family, were found to be statistically significant in differentiating violent versus nonviolent individuals with psychosis. They differed significantly in factors like history of juvenile delinquency, but also in the type of aggressiveness in general. These differences were confirmed on PANSS scale. In conclusion, the longer the history of aggressiveness is presented, the greater the chances are of individuals falling into Group C and it is possible to spend several years from the onset of the disease until the moment of crime.


Aminohydroxyacetone synthons: versatile intermediates for the organocatalytic asymmetric aldol reaction.
A practical method for the synthesis of 1,3-aminohydroxyacetone synthons was developed, and their utility in the organocatalytic asymmetric aldol reaction was demonstrated in a short synthesis of aza-sugars.