Unusual bone marrow hyperplasia in a case of thalassemia intermedia.
A case of beta thalassemia intermedia is described. Beside the typical hematologic picture and extramedullary erythropoiesis in the liver always present in such a clinical form, atypical masses due to foci of erythropoiesis were found at paravertebral, parasternal and subcostal sites. The size of these masses caused problems in differential diagnosis; they have been solved by computerized axial tomography.


Cardiovascular and metabolic comorbidities in patients with obstructive sleep apnoea syndrome.
The purpose of this study was to evaluate the correlation between severity of obstructive sleep apnoea syndrome (OSAS), cardiovascular disease and metabolic syndrome. We recruited 1185 patients with OSAS who underwent a complete ENT examination, including nasolaryngeal fibre optic endoscopy with Müller's manoeuvre, overnight cardio-respiratory monitoring, Epworth Sleepiness Scale (ESS) to measure daytime sleepiness, body mass index (BMI), measurement of blood pressure and blood tests.SUBSEQUENTLY, SUBJECTS WERE DIVIDED INTO THREE SUBGROUPS ACCORDING TO THE APNOEA HYPOPNOEA INDEX (AHI): mild OSAS (AHI 5-15), moderate OSAS (AHI 15-30) and severe OSAS (AHI > 30). In the sample collected, 347 (262 males and 85 females) of 1185 patients suffered from mild OSAS, 363 (269 males and 94 females) from moderate OSAS and 475 (330 males and 145 females) from severe OSAS. In the group suffering from mild OSAS, we found: 127 patients affected by hypertension, 48 with diabetes, 11 with dyslipidaemia and 32 with metabolic syndrome. In the group with moderate OSAS there were 157 patients with hypertension, 63 with diabetes, 72 with dyslipidaemia and 47 with metabolic syndrome. In the group suffering from severe OSAS there were 244 patients with hypertension, 138 with diabetes, 47 with dyslipidaemia and 90 with metabolic syndrome. For data analysis, we used the Spearman correlation test adjusted according to Sidak between the dependent variable AHI and the independent variables BMI, ESS, average SO2 (SO(2med)), hypertension, diabetes mellitus, dyslipidaemia and metabolic syndrome. The results show different patterns of correlation in terms of statistical significance: BMI ρ(s) = 0.26, SO(2med) ρ(s) = -0:51, hypertension ρ(s) = -0.05, dyslipidaemia ρ(s) = 0.22 for women, and BMI ρ(s) = 0.53, ESS ρ(s) = 0.28, SO(2med) ρ(s) = -0.50, hypertension ρ(s) = 0.17, diabetes mellitus ρ(s) = 0.28 and metabolic syndrome ρ(s) = 0.26 for men. The results of the study confirm the existence of a statistically significant correlation between the severity of OSAS and BMI, ESS, average SO2, hypertension, diabetes mellitus, dyslipidaemia and metabolic syndrome.


Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member of the TNF receptor-associated factor family.
An immunohistochemical approach was used to explore the in vivo expression of TNF receptor-associated factor 3 (TRAF-3), a putative signaling protein that binds to the cytosolic domains of CD30, CD40, and lymphotoxin-beta receptors. TRAF-3 immunostaining was detected in many types of cells throughout the human body. TRAF-3 immunostaining was only rarely present in thymocytes but was found in the thymic epithelioreticular cells. Lymphocytes in the bone marrow were also typically TRAF-3 immunonegative, whereas myeloid progenitor cells and megakaryocytes were often TRAF-3 positive. Peripheral blood lymphocytes were mostly TRAF-3 immunonegative, while granulocytes were TRAF-3 immunopositive. Monocytes were strongly immunostained for TRAF-3, but macrophages in nodes typically contained little or no TRAF-3 immunoreactivity. Some lymphocytes within the germinal centers of secondary lymphoid follicles in normal and reactive nodes were TRAF-3 immunopositive, as were occasional interfollicular lymphocytes in the T cell regions of these organs, but most lymphocytes appeared to be TRAF-3 immunonegative or stained only weakly. Plasma cells, however, were strongly TRAF-3 positive. Stimulation of PBLs with anti-CD3 Ab induced marked increases in the steady state levels of TRAF-3 protein in vitro as determined by immunoblotting, while levels of TRAF-2 were unchanged, implying a dynamic regulation of TRAF-3 expression. The findings establish for the first time the cell type- and differentiation-specific patterns of expression of a member of the TRAF family of proteins.


[Effects of tetrandrine on hypertensive responses induced by electric stimulation and alpha-adrenoceptor agonists in pithed rats].
Tetrandrine (Tet) 5 mg.kg-1 i.v. inhibited the pressor action of norepinephrine (NE) release induced by electric stimulation (10 V, 0.5-16 Hz) of spinal cord T11-L2. However, Tet 5 mg.kg-1 ia did not obviously attenuate the hypertensive responses to NE 0.51-16.91 micrograms.kg-1 i.v., indicating that Tet did not affect the alpha 1-adrenoceptors-mediated vasoconstriction. Tet 5 mg.kg-1 ia decreased the pressor responses to NE 0.05 and 0.17 micrograms.kg-1 i.v. and markedly reduced the dose-dependent hypertensive responses to B-HT920 i.v., a selective alpha 2-adrenoceptor agonist, proving that Tet reduced alpha 2-adrenoceptors-mediated vasoconstriction.


Land use in life cycle assessment: global characterization factors based on regional and global potential species extinction.
Land use is one of the main drivers of biodiversity loss. However, many life cycle assessment studies do not yet assess this effect because of the lack of reliable and operational methods. Here, we present an approach to modeling the impacts of regional land use on plants, mammals, birds, amphibians, and reptiles. Our global analysis calculates the total potential damage caused by all land uses within each WWF ecoregion and allocates this total damage to different types of land use per ecoregion. We use an adapted (matrix-calibrated) species-area relationship to model the potential regional extinction of nonendemic species caused by reversible land use and land use change impacts. The potential global extinction of endemic species is used to assess irreversible, permanent impacts. Model uncertainty is assessed using Monte Carlo simulations. The impacts of land use on biodiversity varied strongly across ecoregions, showing the highest values in regions where most natural habitat had been converted in the past. The approach is thus retrospective and was able to highlight the impacts in highly disturbed regions. However, we also illustrate how it can be applied to prospective assessments using scenarios of future land use. Uncertainties, modeling choices, and validity are discussed.


[Bronchial arteries: anatomical and clinical studies and strategies in surgical approach].
One of the most important and controversial aspects of thoracic surgery is due to the topographical and surgical anatomy of the vascular structures involving the mediastinum. The knowledge of the so-called "vascular time", in fact, allows to face more complicated surgical situations, typical of the most specialistic thoracic surgery. The bronchial arteries represent a paradigm of what we have just stated. The study of their anatomy (number, position, origin, distribution and relationships with the mediastinal structures) is of relevant importance, not only for the interest the bronchial vascular tree arises in tracheo-bronchial surgery and in pulmonary transplantology, but also for the knowledge of the pathogenesis of some processes regarding pulmonary and pleural pathologies. The aim of this paper is to evaluate the real clinical interest of bronchial arteries, with an analytic study of the anatomy of vessels, and with the possibility to show the most frequent and characteristic anomalies involving the origin and course of these arteries.


Insights from 36 years' follow up of a patient with the Ross operation.
Pulmonary autograft replacement of the aortic valve has been shown to have many potential advantages over other forms of aortic valve replacement. However, there is still a paucity of studies that provide new information about the possible behavior of the two valves and the cardiac and extracardiac responses in the very long-term. Here, a patient is presented who underwent this operation 36 years ago, together with detailed anatomical and physiological documentation. This case report serves to illustrate several important features relating to the late behavior of the two valves, the response of the two ventricles, and the 'quality of life' of the patient.


A Comparative Morphometric Study on Odontobuthus bidentatus and Odontobuthus doriae (Scorpionida: Buthidae) in Iran.
Scorpions are one of the most venomous animals which cause serious public health problems. The sting of scorpions can sometimes be fatal depending on the scorpion species involved. So far, sixty-six (66) scorpion species have been identified in Iran. Annually, about 40-50000 cases of scorpionism are reported in Iran. Odontobuthus doriae and O. bidentatus are among the most medically important scorpion species in Iran, and they are very similar to each other in coloration, carination, and trichobotrial patterns. This morphometric study aimed to compare some of the important morphological characteristics in order to identify the key differences between these two species. A total of 45 morphological characters were measured using calipers and stereomicroscope, and 55 morphological characters and ratios (relative of length to width ratio of morphological characters of scorpions) were analyzed. The independent sample t-test in SPSS software (version 24) was used for the statistical analyses in this study. The mean total length, carapace width, length of fixed and moveable fingers, and chelicerae length of O. doriae were greater than those of O. bidentatus in our study area. The morphological measurements displayed a clear distinction between O. doriae and O. bidentatus in our study area; therefore, they can be used as morphological identification keys for distinguishing between these two species.


Predicting growth-no growth of Listeria monocytogenes on vacuum-packaged ready-to-eat meats.
Compliance with U.S. Department of Agriculture (USDA) composition-based labeling standards often has been regarded as evidence of the shelf stability of ready-to-eat (RTE) meats. However, the USDA now requires further proof of shelf stability. Our previous work included development of equations for predicting the probability of Staphylococcus aureus growth based on the pH and a(w) of an RTE product. In the present study, we evaluated the growth-no-growth during 21 degrees C storage of Listeria monocytogenes on 39 vacuum-packaged commercial RTE meat products with a wide range of pH (4.6 to 6.5), a(w) (0.47 to 0.98), and percent water-phase salt (%WPS; 2.9 to 34.0). Pieces of each product were inoculated with a five-strain cocktail of L. monocytogenes and vacuum packaged, and L. monocytogenes levels were determined immediately after inoculation and after storage at 21 degrees C for up to 5 weeks. L. monocytogenes grew on 13 of 14 products labeled "keep refrigerated" but not on any of the 25 products sold as shelf stable. Using bias reduction logistic regression data analysis, the probability of L. monocytogenes growth (Pr) could be predicted as a function of pH and a(w): Pr = exp[-59.58 + (4.67 x pH) + (35.05 x a(w))]/{1 + exp[-59.58 + (4.67 x pH) + (35.05 x a(w))]}. Pr also could be predicted as a function of pH and %WPS: Pr = exp[-20.52 + (4.10 x pH) - (0.51 x %WPS)]/{1 + exp[-20.52 + (4.10 x pH) - (0.51 x %WPS)]}. The equations accurately predicted L. monocytogenes growth (Pr values of 0.68 to 0.99) or no growth (Pr values of <0.01 to 0.26) and with our equations for predicting S. aureus growth will be useful for evaluating RTE meat shelf stability.


Hodgkin Lymphoma Mimicking Osteomyelitis.
Hodgkin lymphoma with symptomatic osseous involvement can have a similar presentation to osteomyelitis. Common findings in symptoms, laboratory workup, and imaging can make it very difficult to distinguish between the two diseases. Excisional biopsy should be pursued if fine-needle biopsy is equivocal and suspicion of lymphoma is high. We report a case of a 40-year-old man who presented with a history of marine animal sting on his neck and later developed erythema in the area, chest pain, constitutional symptoms, adenopathy, and imaging classic for sternal osteomyelitis. Fortunately, initial biopsy prompted the possibility of lymphoma, and further workup was initiated, which confirmed Hodgkin lymphoma. This case is a good reminder that malignancies and infections can share many common features, and keeping a broad differential diagnosis can be lifesaving. Proper staging and risk stratification of Hodgkin lymphoma help determine the optimal treatment.


A new method to synthesize multiple gRNA libraries and functional mapping of mammalian H3K4me3 regions.
Genetic screening based on the clustered regularly interspaced palindromic repeat (CRISPR) system has been indicated to be a powerful tool for identifying regulatory genes or cis-elements. However, when applying CRISPR screens to pinpoint functional elements at particular loci, a large number of guide RNA (gRNA) spacers may be required to achieve saturated coverage. Here, we present a controlled template-dependent elongation (CTDE) method relying on reversible terminators to synthesize gRNA libraries with genomic regions of interest. By applying this approach to H3K4me3 chromatin immunoprecipitation (ChIP)-derived DNA of mammalian cells, mega-sized gRNA libraries were synthesized in a tissue-specific manner, with which we conducted screening experiments to annotate essential sites for cell proliferation. Additionally, we confirmed that an essential site within the intron of LINC00339 regulates its own mRNA and that LINC00339 is a novel regulator of the cell cycle that maintains HepG2 proliferation. The CTDE method has the potential to be automated with high efficiency at low cost, and will be widely used to identify functional elements in mammalian genomes.


Pentacarbonyl(di-2-pyridylamine)tungsten(0).
In the title molecular complex, (I), the W atom is in an octahedral environment with four equatorial carbonyl ligands and a fifth in an axial position trans to the monodentate dipyridylamine ligand. The long dimension of this last bisects the angle between two of the equatorial carbonyl groups and while the non-bonded pyridyl N atom is directed away from the W atom, the bridging amine group is directed towards it. Thus, in addition to the N atom to which it is attached, the amino H has two nearest neighbour C atoms of equatorial carbonyl groups but does not participate in hydrogen bonding in any real or usual sense. The W-C bond distance for the axial carbonyl group is notably less than those of the equatorial groups.


Orally administered grass pollen.
In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.


The First Reported Case of Elizabethkingia anophelis From Nepal.
Elizabethkingia anophelis, a gram-negative bacillus belonging to the Flavobacteriaceae family, is found in various environmental sources and has been associated with community and hospital outbreaks. Correct identification is crucial, guided by advanced genomic techniques, i.e., matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system with an updated database. The case fatality rate, ranging from 24 to 60%, underscores the need for timely recognition and appropriate management. Additionally, Elizabethkingia presents a challenge due to its recent discovery, misidentification history, and drug resistance. Here, we present a case of fatal infection in a 30-year-old male, who presented with pneumonia. It gradually progressed and ultimately proved fatal underscoring the virulence of the pathogen involved. It was a diagnostic challenge as it likely is the first reported instance of Elizabethkingia anophelis infection from Nepal.


Characterization of In Vitro Resistance Development to the Novel Echinocandin CD101 in Candida Species.
CD101 is a novel echinocandin with a long half-life undergoing clinical development for treatment of candidemia/invasive candidiasis and vulvovaginal candidiasis. The potential for and mechanisms underlying the development of resistance to CD101 in Candida species were investigated by using spontaneous resistance and serial passage selection methodologies. Four Candida spp. (C. albicans, C. glabrata, C. parapsilosis, and C. krusei) were chosen for resistance characterization with CD101, anidulafungin, and caspofungin. The frequency of spontaneous, single-step mutations conferring reduced susceptibility to CD101 at 1× the agar growth inhibition concentration was low across all species, with median frequencies ranging from 1.35 × 10(-8) to 3.86 × 10(-9), similar to ranges generated for anidulafungin and caspofungin. Serial passage of Candida spp. on agar plates containing drug gradients demonstrated a low potential for resistance development, with passage 20 CD101-selected strains possessing increases in MICs equivalent to or lower than those for the majority of strains generated under selection with anidulafungin and caspofungin. A total of 12 fks "hot spot" mutations were identified, typically in strains with the highest MIC shifts. Cross-resistance was broadly observed among the 3 echinocandins evaluated, with no CD101-selected mutants (with or without fks hot spot mutations) exhibiting reduced susceptibility to CD101 but not also to anidulafungin and/or caspofungin. Consistent with currently approved echinocandins, CD101 demonstrates a low potential for resistance development, which could be further enhanced in vivo by the high maximum concentration of drug in serum (Cmax)/area under the concentration-time curve (AUC) plasma drug exposure achieved with once-weekly dosing of CD101.


Acellular pertussis vaccines and complement killing of Bordetella pertussis.
Antibody-dependent complement killing of Bordetella pertussis after immunization with a three-component acellular pertussis vaccine was characterized. Postimmunization activity was unchanged for about half of the adult vaccine recipients. The responses of the other individuals were complex, with evidence of both beneficial and antagonistic responses occurring, sometimes in the same individual.


[Anatomy of the development of the digestive tract and shape of the external body during the embryonic period of the goat (Capra hircus)].
The purpose of this work has been to establish the pattern of prenatal growth and normal development of the digestive tract and annex glands during goat embryonic stages. 21 embryos with ages ranging from 14 to 34 days (1.69 to 5.90 cm CR) as determined by registering the mating time, were obtained by cesarean section. This material was histologically processed to obtain complete serial sections of the stomatodaeum, foregut, midgut, hindgut and cloaca. In this work, it is chronologically described the morphogenesis and histogenesis of the mouth, hypophysis, pharynx and its derivatives, stomach, intestine, liver, pancreas and cloaca. The results obtained establish chronological comparisons with the development of the lamb and gives information on the unitary origin of the gastric compartments in ruminants.


Borderline or Schizotypal? Differential Psychodynamic Assessment in Severe Personality Disorders.
Considerable overlap in symptoms between patients with borderline personality disorder (BPD) and schizotypal personality disorder (STPD) complicates personality diagnostics. Yet very little is known about the level of psychodynamic functioning of both personality disorders. Psychodynamic assessment procedures may specify personality characteristics relevant for differential diagnosis and treatment planning. In this cross-sectional study we explored the differences and similarities in level of personality functioning and psychodynamic features of patients with severe BPD or STPD. In total, 25 patients with BPD and 13 patients with STPD were compared regarding their level of personality functioning (General Assessment of Personality Disorder), current quasipsychotic features (Schizotypal Personality Questionnaire), and psychodynamic functioning [Developmental Profile (DP) interview and Developmental Profile Inventory (DPI) questionnaire]. Both groups of patients showed equally severe impairments in the level of personality functioning and the presence of current quasipsychotic features. As assessed by the DP interview, significant differential psychodynamic patterns were found on the primitive levels of functioning. Moreover, subjects with BPD had significantly higher scores on the adaptive developmental levels. However, the self-questionnaire DPI was not able to elucidate all of these differences. In conclusion, our study found significant differences in psychodynamic functioning between patients with BPD and STPD as assessed with the DP interview. In complicated diagnostic cases, personality assessment by psychodynamic interviewing can enhance subtle but essential differentiation between BPD and STPD.


Site-specific skeletal response to long-term weight training seems to be attributable to principal loading modality: a pQCT study of female weightlifters.
Physical training may be able to improve bone strength through site-specific changes in the composition, size and structure of the bone without notable increases in volumetric density. To address this possibility specifically, we compared 14 competitive female weightlifters with 14 female physical therapy students. Peripheral quantitative computed tomographic scans (pQCT) were taken from the distal radius, radial shaft, distal femur, and tibial midshaft of the dominant limb. Analysis of covariance (ANCOVA) was used to estimate the intergroup differences, using body weight and age as covariates. Cortical density did not differ between the weightlifters and controls at any site, whereas trabecular density was greater in the weightlifters, the benefit being 10% (P = 0.186) at the distal radius and 11% (P = 0.040) at the distal femur compared with the controls. Weightlifters' cortical cross-sectional area was 38% (P = 0.029) larger at the distal radius, 26% larger (P = 0.001) at the radial shaft, and 9% larger at the tibial midshaft (P = 0.034). Consequently, the weightlifters' forearm bone strength indices were also significantly higher, the intergroup difference being 41% (P = 0.001) at the distal radius and 43% (P = 0.004) at the radial shaft. Thus, the observed intergroup difference at the distal radius was mainly due to enlarged bone, particularly its cortex, rather than higher volumetric bone density. Findings at the radial shaft were similar. In contrast, weightlifters' trabecular tissue at the distal femur was denser but the bone per se was not clearly bigger than that of the controls' (intergroup difference 5%, P = 0.117). We suggest that bones subjected to exceptionally high bending-loading (distal radius and radial shaft) are larger than their normal counterparts while at sites experiencing axial, compressive-loading (e.g., distal femur), a denser trabecular structure (more load-carrying area) may be sufficient and any substantial enlargement in bone size may not be necessary.


Eight-year trend analysis of malaria prevalence in Kombolcha, South Wollo, north-central Ethiopia: a retrospective study.
Malaria is one of the most serious public health problems in the world, and is a major public health problem in Ethiopia. Over the past years, the disease has been consistently reported as the first leading cause of outpatient visits, hospitalization and death in health facilities across the country. This study aimed to assess malaria prevalence trend in the Kombolcha Health Centre. A retrospective study was carried out in the Kombolcha Health Centre, north-central Ethiopia. Malaria cases reported from 2009 to 2016 were carefully reviewed from the laboratory record books. Interventions that had been taken in each year were collected from the district health bureau and head of Kombolcha Health Centre using checklists. A total of 27,492 blood films were examined from malaria-suspected patients in the Kombolcha Health Centre from 2009 to 2016. Malaria was confirmed and reported in 2066 (7.52%) of the examined blood films with 258 mean annual cases of. Minimum and maximum cases were reported in 2009 and 2010, respectively. Plasmodium falciparum and P. vivax accounted 60.2% and 35.5% of the cases, respectively. Male patients were more affected (n = 1407; 68.1%) than female ones (n = 659; 31.89%). The highest malaria prevalence (n = 1440; 69.69%) was seen in the 15-45 years age group, followed by those 5-14 years old (n = 303; 14.67%), and finally patients under five years old (n = 217; 10.5%). Malaria cases were at a peak in spring and reduced in the winter season. Although the current malaria control strategies are effective in decreasing the morbidity and mortality, malaria is still among major public health problems in Ethiopia. Plasmodium falciparum is the dominant species in the study area. However, in recent years P. vivax cases are increasing, indicating that attention should also be given to this species. The efficacy of chloroquine for P. vivax should be evaluated in the study area. Control activities should be continued and scale up.


Vein of Galen Arteriovenous Malformation in a Neonate.
The vein of Galen is the most common type of arteriovenous malformation in the fetus and neonate. Most vein of Galen arteriovenous malformations (VGAMs) are diagnosed in the neonatal period, with the remainder being identified in early childhood, typically via computed tomography scan. The VGAM is found in five different patterns where the vein of Galen and straight sinus extending to the torcula Herophili are dilated. This dilation can lead to significant compression of the posterior fossa structures. Clinically, the infant with this malformation can present with seizures or most commonly, high output cardiac failure. It is important, however, to keep a broad differential diagnosis as more prevalent neonatal conditions arise similarly. These conditions can include developmental delay, cerebral palsy, epilepsy, superior vena cava syndrome, hemangioendothelioma, and other arteriovenous fistulae. Treatment begins with early diagnosis and testing of initial sequelae. This is often accomplished in consultation with different pediatric subspecialists, particularly neurologists and cardiologists. The mainstay of therapy is with neurosurgical intervention. Although the mortality of a fetus or neonate with VGAM is very high, prognosis is dependent on the size of the malformation, age at diagnosis, and successful neurosurgical outcome.


Cryptic species in lichen-forming fungi.
This contribution provides a synopsis of the presentations and discussions during the SIG session on cryptic speciation in lichen-forming fungi held during IMC9. In several cases, a re-examination of morphology against the background of molecular phylogenetic evidence revealed, sometimes subtle, morphological and/or chemical characters, supporting the distinction of particular clades at species level. However, there are also examples of cryptic species in which no morphological characters could be identified to distinguish between lineages. Several cases were presented in which distinct lineages are correlated with biogeographical patterns. When and how to name cryptic species was debated, and the use of terms such as "complex" or "aggregate" commended where the taxa formed part of a single lineage.


Comparison of Spectral Analysis of Gamma Band Activity During Actual and Imagined Movements as a Cognitive Tool.
Background. Imagined motor movement is a cognitive process in which a subject imagines a movement without doing it, which activates similar brain regions as during actual motor movement. Brain gamma band activity (GBA) is linked to cognitive functions such as perception, attention, memory, awareness, synaptic plasticity, motor control, and Imagination. Motor imagery can be used in sports to improve performance, raising the possibility of using it as a rehabilitation method through brain plasticity through mirror neurons. Method. A comparative observational study was conducted on 56 healthy male subjects after obtaining clearance from the Ethics Committee. EEG recordings for GBA were taken for resting, real, and imaginary motor movements and compared. The power spectrum of gamma waves was analyzed using the Kruskal-Wallis test; a p-value <.05 was considered significant. Results. The brain gamma rhythm amplitude was statistically increased during both actual and imaginary motor movement compared to baseline (resting stage) in most of the regions of the brain except the occipital region. There was no significant difference in GBA between real and imaginary movements. Conclusions. Increased gamma rhythm amplitude during both actual and imaginary motor movement than baseline (resting stage) indicating raised brain cognitive activity during both types of movements. There was no potential difference between real and imaginary movements suggesting that the real movement can be replaced by the imaginary movement to enhance work performance through mirror therapy.


Seroprevalence of Toxoplasmosis with ELISA and Rapid Diagnostic Test among Residents in Gyodong-do, Inchon city, Korea: A Four-Year Follow-up.
ELISA has been used for the diagnosis of toxoplasmosis, but it is being gradually replaced by a rapid diagnostic test (RDT). We compared and analyzed ELISA and RDT results using the sera collected during 4 consecutive years from residents of Gyodong-do (Island), Incheon-city, Korea. Sera from 921, 993, 940, and 838 adult residents were collected on a yearly basis (2010-2013). ELISA was performed by using a crude extract of T. gondii RH strain antigen and IgG/IgM RDT mounted with recombinant fragment of major surface antigen (SAG1), GST-linker-SAG1A, were applied to the sera. Comparison between groups was analyzed by the Student's t-test. The positive seroprevalence surged from 14.7% (135/921, 2010), 23.1% (231/993, 2011), 23.6% (222/940, 2012), and 32.1% (269/838, 2013) by ELISA. In contrast, RDT showed a more moderate increasing trend from 21.7% (200/921, 2010), 25.5% (253/993, 2011), 28.9% (272/940, 2012) and 33.1% (277/838, 2013). Discrepancies between ELISA and RDT were noted near the cut-off value. At the OD 0.15-0.24 range, RDT could detect 16.1% (169/1051) more positives, which suggests an early or acute toxoplasmosis, but at the OD 0.25-0.34 range, ELISA could detect 35.9% (92/256) more positives of possible chronic infections. Over the OD > 0.35 ELISA and RDT agreed in the majority of the cases. This surge in seroprevalence may be caused by the organic agriculture in addition to eating behavior or increase in pets among Koreans. These facts may be applied on a full-scale national survey using RDT to supplement ELISA to define the characteristics of the infection.


The evolutionary origin of near-death experiences: a systematic investigation.
Near-death experiences are known from all parts of the world, various times and numerous cultural backgrounds. This universality suggests that near-death experiences may have a biological origin and purpose. Adhering to a preregistered protocol, we investigate the hypothesis that thanatosis, aka death-feigning, a last-resort defense mechanism in animals, is the evolutionary origin of near-death experiences. We first show that thanatosis is a highly preserved survival strategy occurring at all major nodes in a cladogram ranging from insects to humans. We then show that humans under attack by animal, human and 'modern' predators can experience both thanatosis and near-death experiences, and we further show that the phenomenology and the effects of the two overlap. In summary, we build a line of evidence suggesting that thanatosis is the evolutionary foundation of near-death experiences and that their shared biological purpose is the benefit of survival. We propose that the acquisition of language enabled humans to transform these events from relatively stereotyped death-feigning under predatory attacks into the rich perceptions that form near-death experiences and extend to non-predatory situations.


Identification of a conserved HLA-A2-restricted decapeptide from the IE1 protein (pUL123) of human cytomegalovirus.
Control of human cytomegalovirus (HCMV) infection is predominantly mediated by cytolytic CD8+ T lymphocytes (CTL). Among the roughly 200 HCMV-encoded polypeptides, the tegument protein pp65 (ppUL83) and the nonstructural IE1 protein are considered to be dominant CTL targets. Yet the importance of CTL against IE1 for protective immunity against HCMV reactivation and disease has remained elusive. Analyses have been difficult, as all MHC class I presented peptides of IE1 defined so far are located in parts of the protein that are variable between viral strains. In this study a conserved decameric peptide from IE1 (P6, IE1(354-363)) that bound to HLA-A2 was identified. Using peptide-pulsed, HLA-matched stimulator cells, CTL lines which recognized P6 after exogenous loading as well as after endogenous processing could repeatedly be generated. However, memory CTL directed against P6 were not readily detectable by ex vivo ELISPOT analysis in peripheral blood mononuclear cells of healthy seropositive individuals, indicating that this peptide represents a quantitatively subdominant determinant during latent HCMV infection. Using the conserved HLA-A2 presented peptide P6 will enable more detailed studies on the role of IE1-specific CTL in patients suffering from various HCMV-related disease conditions and investigation of the role of such cells for immune control of HCMV. Since IE1 is the first viral protein to be expressed after reactivation from latency, P6 may also serve as an important component of a future recombinant HCMV vaccine.


Independent Modular Filter for Embolic Protection in Carotid Stenting.
Embolic protection during carotid artery stenting reduces the rate of thromboembolic events. The Wirion Embolic Protection System is used to deploy an independent distal filter using any 0.014″ guidewire. WISE study (Wirion Study Europe) evaluated the safety and performance of Wirion Embolic Protection System in patients undergoing carotid artery stenting. A prospective, multicenter, nonrandomized, open-label, single-arm study of carotid artery stenting in high surgical risk patients was performed. The primary end point, a composite of death, stroke, and myocardial infarction at 30 days, was compared with performance goal derived from historical controls. Secondary end points were components of the primary end point and the device, angiographic, procedural, and clinical success rates. Preplanned interim analysis was performed on the first 120 patients. At interim analysis, the primary end point was significantly lower for the Wirion Embolic Protection System group, compared with historical data (3.3% versus 6.3%, respectively; P value =0.0008). Analysis of primary end point components in the WISE group, compared with the historical control group, shows numerically lower mortality (0% versus 1.7%, respectively; P=0.21), stroke (2.5% versus 4.6%, respectively; P=0.18), and myocardial infarction (0.8% versus 1.5%, respectively; P=0.50). Device, angiographic, procedural, and clinical success was achieved in 99.2%, 99.1%, 98.3%, and 96.6% of cases, respectively. The data suggest that independent modular filter use in carotid artery stenting in high surgical risk patients is safe and effective. The outcomes suggest that use of an independent modular filter may be associated with a lower rate of embolic complications associated with carotid stent placement. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01783639.


Molecular cloning of Reteplase and its expression in E. coli using tac promoter.
This study aimed to clone and express the reteplase cDNA, a thrombolytic agent used for the treatment of acute myocardial infarction and stroke, in E. coli, utilizing tac promoter for its expression. Reteplase cDNA was amplified by polymerase chain reaction (PCR) with designed primers. The product was then cloned into pTZ57R plasmid. The cloned cDNA was digested out and ligated into pGEX-5x-1 expression vector. The presence of the insert was confirmed by restriction digestion. By using 0.2, 0.5 and 1 mM isopropyl beta-D thiogalactopyranoside (IPTG), expression of reteplase was induced in E. coli TOP10 cells and analyzed by SDS-PAGE. Electrophoresis of PCR product and also double digested recombinant pTZ57R plasmid, also, pGEX-5x-1 vector, showed a 1068bp band of reteplase. SDS-PAGE analysis showed a 60 KDa band of protein product induced with different concentrations of IPTG. In the present study, reteplase cDNA was successfully cloned and expressed using tac promoter. This vector will be used for the optimization of the expression of reteplase in E. coli.


Diagnostic uses of angiotensin-converting enzyme inhibitors in renovascular hypertension.
The response to angiotensin-converting enzyme inhibitors (ACEIs) can be of considerable help in the diagnosis of human renovascular hypertension (RVH) in three settings. First, a particularly dramatic antihypertensive response or a decline in glomerular filtration rate (GFR), as indexed by a rise in serum creatinine or blood urea nitrogen concentrations, are useful clues to the presence of renovascular hypertension. Second, an exaggerated rise in plasma renin activity (PRA) after short-term captopril administration is a very promising screening test for this condition. Third, ACEI-induced changes in single-kidney hemodynamics (assessed by renography) may be helpful in confirming the diagnosis and offers the prospect of localizing the ischemic kidney.


Midwifery Students' Perceptions of Spirituality and Spiritual Care: An Example from Western Turkey.
This cross-sectional study aimed to explore Turkish midwifery students' perceptions of spirituality and spiritual care and to investigate the factors affecting them. Data were collected from 271 students of the Midwifery Department of the High School of Health of a state university in the west of Turkey using the Spirituality and Spiritual Care Rating Scale. A significant difference was found between belief in the need for spiritual care and the practice of spiritual care during midwifery training and the total score on the Spirituality and Spiritual Care Rating Scale, but no significant difference was found between the students' year of class, whether they had heard about spiritual care, and their state of knowledge concerning spiritual care. An increase in awareness, knowledge and skills relating to spirituality and spiritual care on the part of midwifery students, who are the midwives of the future, will allow students to provide spiritual care to their patients after they qualify. For this reason, the education program of midwifery students should be seen from a holistic standpoint in order to develop spiritual care.


Expression of pro-inflammatory interleukin-8 is reduced by ayurvedic decoctions.
Eleven decoctions, obtained from indian plants widely used in ayurvedic medicine, have been investigated as a possible source of molecules exhibiting biological activity on the interaction between DNA and NF-kB, a transcription factor involved in the expression of proinflammatory genes. Cystic fibrosis (CF) cell line stimulated by TNF-α has been used as inflammatory cellular model to determinate interleukin-8 (IL-8), one of the most relevant pro-inflammatory mediator in CF regulated by the NF-kB. The chemical characterization of these 11 decoctions by spectrophotometric analysis and NMR fingerprinting highlighted that sugars and polyphenols seemed to be the main compounds. Our results demonstrated that Azadirachta indica, Terminalia bellerica, Terminalia chebula, Hemidesmus indicus, Emblica officinalis and Swertia chirata are the most active decoctions in inhibiting NF-kB/DNA interactions by EMSA assay and in reducing pro-inflammatory IL- 8 expression in CF cells at IC50 concentrations by Real-Time and Bio-plex analyses. Finally, we observed the increase of all inhibitory activities with the rise of total polyphenols, procyanidins and flavonoids, except for the levels of IL-8 mRNA accumulation, that were as high as flavonoid content grown up by the statistical multivariate analyses. In conclusion, these six decoctions might be interesting to explore new anti-inflammatory treatments for diseases, such as CF.


Exploring rare cellular activity in more than one million cells by a transscale scope.
In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.


Exome sequencing and case-control analyses identify RCC1 as a candidate breast cancer susceptibility gene.
Breast cancer is a genetic disease but the known genes explain a minority of cases. To elucidate the molecular basis of breast cancer in the Tunisian population, we performed exome sequencing on six BRCA1/BRCA2 mutation-negative patients with familial breast cancer and identified a novel frameshift mutation in RCC1, encoding the Regulator of Chromosome Condensation 1. Subsequent genotyping detected the 19-bp deletion in additional 5 out of 153 (3%) breast cancer patients but in none of 400 female controls (p = 0.0015). The deletion was enriched in patients with a positive family history (5%, p = 0.0009) and co-segregated with breast cancer in the initial pedigree. The mutant allele was lost in 4/6 breast tumors from mutation carriers which may be consistent with the hypothesis that RCC1 dysfunction provides a selective disadvantage at the stage of tumor progression. In summary, we propose RCC1 as a likely breast cancer susceptibility gene in the Tunisian population.


CarboGrove: a resource of glycan-binding specificities through analyzed glycan-array datasets from all platforms.
Glycan arrays continue to be the primary resource for determining the glycan-binding specificity of proteins. The volume and diversity of glycan-array data are increasing, but no common method and resource exist to analyze, integrate, and use the available data. To meet this need, we developed a resource of analyzed glycan-array data called CarboGrove. Using the ability to process and interpret data from any type of glycan array, we populated the database with the results from 35 types of glycan arrays, 13 glycan families, 5 experimental methods, and 19 laboratories or companies. In meta-analyses of glycan-binding proteins, we observed glycan-binding specificities that were not uncovered from single sources. In addition, we confirmed the ability to efficiently optimize selections of glycan-binding proteins to be used in experiments for discriminating between closely related motifs. Through descriptive reports and a programmatically accessible Application Programming Interface, CarboGrove yields unprecedented access to the wealth of glycan-array data being produced and powerful capabilities for both experimentalists and bioinformaticians.


New dark energy constraints from supernovae, microwave background, and galaxy clustering.
Using supernova, cosmic microwave background, and galaxy clustering data, we make the most accurate measurements to date of the dark energy density rho(X) as a function of cosmic time, constraining it in a rather model-independent way, assuming a flat universe. We find that Einstein's simplest scenario, where rho(X)(z) is constant, remains consistent with these new tight constraints and that a big crunch or big rip is more than 50 Gyr away for a broader class of models allowing such cataclysmic events. We discuss popular pitfalls and hidden priors.


The yeast La protein is required for the 3' endonucleolytic cleavage that matures tRNA precursors.
Although the La autoantigen binds to the 3' ends of all nascent polymerase III transcripts, its function in vivo has long been unclear. Although S. cerevisiae cells lacking the La protein homolog Lhp1p are viable, cells containing a mutation that disrupts the anticodon stem of tRNA(Ser)CGA require Lhp1p for growth. We demonstrate that for the wild-type pre-tRNA(Ser)CGA and other pre-tRNAs, Lhp1p is required for the normal endonucleolytic removal of the 3' trailer sequence. In cells lacking Lhp1p, the 3' trailer is removed by exonuclease(s). Although maturation of the mutant pre-tRNA(Ser)CGA requires Lhp1p, introduction of a second mutation that restores base pairing eliminates the requirement. We propose that binding by Lhp1p stabilizes pre-tRNAs in conformations that allow the 3' endonucleolytic cleavage to occur.


Preparation and Photocatalytic Activity of Potassium- Incorporated Titanium Oxide Nanostructures Produced by the Wet Corrosion Process Using Various Titanium Alloys.
Nanostructured potassium-incorporated Ti-based oxides have attracted much attention because the incorporated potassium can influence their structural and physico-chemical properties. With the aim of tuning the structural and physical properties, we have demonstrated the wet corrosion process (WCP) as a simple method for nanostructure fabrication using various Ti-based materials, namely Ti-6Al-4V alloy (TAV), Ti-Ni (TN) alloy and pure Ti, which have 90%, 50% and 100% initial Ti content, respectively. We have systematically investigated the relationship between the Ti content in the initial metal and the precise condition of WCP to control the structural and physical properties of the resulting nanostructures. The WCP treatment involved various concentrations of KOH solutions. The precise conditions for producing K-incorporated nanostructured titanium oxide films (nTOFs) were strongly dependent on the Ti content of the initial metal. Ti and TAV yielded one-dimensional nanowires of K-incorporated nTOFs after treatment with 10 mol/L-KOH solution, whereas TN required a higher concentration (20 mol/L-KOH solution) to produce comparable nanostructures. The obtained nanostructures revealed a blue-shift in UV absorption spectra due to the quantum confinement effects. A significant enhancement of the photocatalytic activity was observed via the chromomeric change and the intermediate formation of methylene blue molecules under UV irradiation. This study demonstrates the WCP as a simple, versatile and scalable method for the production of nanostructured K-incorporated nTOFs to be used as high-performance photocatalysts for environmental and energy applications.


Emergence of electronic home monitoring in chronic heart failure: rationale, feasibility, and early results with the HomMed Sentry-Observer system.
Electronic home monitoring for chronic heart failure is emerging as an available option to add to our armamentarium as a vital part of the multidisciplinary care process. This investigation describes the early clinical results of a multicenter study that suggests that important trends in medical resource utilization may be attained by the use of this modality. (c)2000 by CHF, Inc.


Circulating vitamin D concentration and risk of prostate cancer: a dose-response meta-analysis of prospective studies.
Though many studies have been performed to elucidate the association between circulating vitamin D and prostate cancer, no conclusive result is available. We carried out a dose-response meta-analysis to quantitatively examine the association of circulating 25-hydroxyvitamin D (25[OH]D) concentration with prostate cancer. Only prospective studies examining the associations of circulating 25[OH]D concentration with prostate cancer were eligible for the meta-analysis. A random-effect meta-analysis was done first, to calculate the summary relative risk (RR) and 95% confidence intervals (CIs) comparing the higher concentration with the lower concentration of 25[OH]D. A dose-response meta-analysis using random-effects model was then carried out to evaluate the nonlinearity and calculate the summary RR caused per 10 ng/mL increment. Nineteen prospective cohort or nested case-control studies were included. Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer (RR =1.15, 95% CI 1.06-1.24). No nonlinear relationship was found between 25[OH]D concentration and risk of prostate cancer (P=0.654). Dose-response meta-analysis showed that the summary RR caused per 10 ng/mL increment in circulating 25[OH]D concentration was 1.04 (95% CI 1.02-1.06). Subgroup analysis also found a modest dose-response relationship. Funnel plot and Egger's test did not detect publication bias. The findings suggest that highest 25[OH]D concentration is correlated with elevated risk of prostate cancer and a modest dose-response effect exists in this association; however, more studies are needed.


Aortic Valve Area and Strain Measurements by Cardiac MRI and Transthoracic Echocardiography in Severe Aortic Stenosis with Normal Left Ventricular Function.
Transthoracic echocardiography (TTE) is the recommended imaging technique for the evaluation of patients with aortic stenosis (AS). However, in cases with inconclusive findings, cardiac magnetic resonance (CMR) planimetry is used to grade AS severity. This study aimed to compare the results derived from TTE and CMR in patients with severe AS with normal left ventricular (LV) function. In a prospective study, 20 patients with severe AS were recruited and data derived from TTE and CMR modalities were compared with the archived records of 28 age- and sex-matched healthy controls. The data included aortic valve area (AVA), MRI-derived biventricular global strains, and TTE-derived global longitudinal strain (GLS). SPSS software was used to analyze the data with independent samples t test, intraclass correlation coefficient (ICC), and Pearson correlation. P<0.05 was considered statistically significant. An excellent agreement was found in AVA values derived from CMR and TTE with an average ICC of 0.932 (95% CI=0.829-0.973). There was a significant difference in LV-GLS, LV global radial strain (GRS), right ventricular (RV) GRS, and RV global circumferential strain between the groups. A good correlation was found between CMR- and TTE-derived GLS with an average ICC of 0.721 (95% C=0.255-0.896). The mean aortic valve pressure gradient in TTE had a significant inverse linear correlation with LV-GRS in CMR (r=-0.537). All P values were <0.05. There was a good agreement between AVA and strain values derived from cardiac MRI and TTE. The myocardial strain was impaired in patients with severe AS and normal LV function and correlated with disease severity.


Molecular foundations of prion strain diversity.
Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical properties, form aggregates with characteristic morphologies and preferentially seed certain brain regions, causing markedly different disease phenotypes. Strain diversity is determined by protein structure, post-translational modifications and the presence of extracellular matrix components, with single amino acid substitutions or altered protein glycosylation exerting dramatic effects. Here, we review recent advances in the study of prion strains and discuss how a deeper knowledge of the molecular origins of strain heterogeneity is providing a foundation for the development of anti-prion therapeutics.


Interaction of petroleum-relevant organosulfur compounds with TiO2(110).
The interaction of two sets of structurally related molecules, thiophenol/thioanisole, and thiophene/tetrahydrothiophene, with vacuum-annealed and ion-bombarded TiO(2)(110) surfaces has been studied using a combination of temperature-programmed reaction spectroscopy (TPRS) and X-ray photoelectron spectroscopy (XPS). All thioethers studied were observed to adsorb and desorb from both surfaces without producing reaction products, while thiophenol, the only species studied containing a S-H bond, reacted with both surfaces. Approximately 25% of surface bound thiophenol decomposed over the vacuum-annealed surface. On the bombarded surface, thiophenol both decomposed into surface-bound C(x)H(y)/S fragments, and reacted to form benzene, which desorbed from the surface at 400 K. We propose that phenylthiolate formation on the bombarded surface leads to the observed production of benzene. These results highlight the importance of defects in the reactivity of titania, and lay the foundation for the study of larger, refractory sulfur compounds present in fuel.


A broadband polygonal cloak for acoustic wave designed with linear coordinate transformation.
Previous acoustic cloaks designed with transformation acoustics always involve inhomogeneous material. In this paper, a design of acoustic polygonal cloak is proposed using linear polygonal transformation method. The designed acoustic polygonal cloak has homogeneous and anisotropic parameters, which is much easier to realize in practice. Furthermore, a possible acoustic metamaterial structure to realize the cloak is proposed. Simulation results on the real structure show that the metamaterial acoustic cloak is effective to reduce the scattering of the object.


Determination of the pKa and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)-2H-3,1-benzoxazin-2-one (DMP 266).
The solubility of a nonnucleoside reverse transcriptase inhibitor, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl )- 2H-3,1-benzoxazin-2-one (DMP 266), was investigated as a function of pH. A dramatic increase in the aqueous solubility was observed at pH > or = 10, which was consistent with going from a neutral to a charged species. The ionization of the proton positioned on the carbamate functionality was confirmed spectrophotometrically (pKa = 10.1). The spectrophotometric result was in excellent agreement with that obtained from the solubility studies (pKa = 10.2). The ionization behavior of DMP 266 represents a unique case in which the pKa for a carbamate functional group is quite low. The anomalous pKa value may be attributed to stabilization of the negatively charged species through inductive effects, which originate from the surrounding substituents and delocalization of the negative charge via resonance effects.


[Influence of the family situation on the form of expression of neuroses].
In this research were investigated the conditions of the family environment and the contact with the parents in 3 different groups of children and adolescents who presented respectively conversion neurosis, other types of neurosis and behavior disorders of the aggressive type. The analysis of the results obtained indicated a positive correlation between the tendency to manifest emotional conflicts under the form of conversion symptoms and the course of childhood in a family inadequate environment, with the absence of one or both parents. This fact was not found in the two other groups.


[Peritonitis caused by a giant trichobezoar ventriculi--a case report].
Bezoars are the most common foreign bodies of gastrointestinal tract. They contain swallowed hair, different fibres, seeds, nut shells, sweets or drugs. Clinical manifestations vary, depending on the location and size of bezoar, from "no symptoms" to "acute abdomen" syndrome. In this case report, the authors describe a giant trichobezoar from the stomach of an 18-year-old girl, who had been admitted to the gynecological department with syndromes suggesting an ovarian cyst torsion. The preoperative diagnosis was not confirmed and a giant trichobezoar was found and removed during the surgery.


A 3D analysis of mechanically stressed dentin-adhesive-composite interfaces using X-ray micro-CT.
Dentin bonding systems (DBS) have been developed in order to bond restorative materials (i.e. composite) to tooth tissues when function and integrity have to be re-established. Adhesion to dentin results from the penetration of DBS into the demineralised substrate constituted by a conditioned collagen network. The long-term stability of a restored tooth is mainly affected by the seal of the restorative material on the dental structures. Although leakage through the dentin-DBS interface has been widely reported, 3D investigation technique and accurate non-destructive measurements of leakage as functions of mechanical cycling have never been provided. To address these issues, the properties of the material interface are analysed using micro-tensile static and dynamic tests, assisted by the finite element modelling and by the X-ray computed micro-tomography. The dual energy absorption technique, with the synchrotron beam light, has been developed to investigate, in a non-destructive manner, the effect of mechanical cycling on leakage of a silver nitrate staining solution at the dentin-DBS interface. The effect of the pulpal roof on the stress distribution in the coronal dentin-DBS-composite interface has been investigated and the level at which the state of stress can be assumed to be uniform within acceptable limits has been defined. The tensile static and dynamic results suggest that the adhesive strength for the multi-step DBS resulted significantly higher than the other investigated DBS. Imaging results indicate that 3D leakage occurs radially at the dentin-adhesive interface through the interface itself rather than through the unconditioned dentin bulk; moreover, the dynamic tensile loading allows a more diffuse staining penetration.


Where antibiotic resistance mutations meet quorum-sensing.
We do not need to rehearse the grim story of the global rise of antibiotic resistant microbes. But what if it were possible to control the rate with which antibiotic resistance evolves by de novo mutation? It seems that some bacteria may already do exactly that: they modify the rate at which they mutate to antibiotic resistance dependent on their biological environment. In our recent study [Krašovec, et al. Nat. Commun. (2014), 5, 3742] we find that this modification depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress). Specifically, the wild-type strains of Escherichia coli we used will, in minimal glucose media, modify their rate of mutation to rifampicin resistance according to the density of wild-type cells. Intriguingly, the higher the density, the lower the mutation rate (Figure 1). Why this novel density-dependent 'mutation rate plasticity' (DD-MRP) occurs is a question at several levels. Answers are currently fragmentary, but involve the quorum-sensing gene luxS and its role in the activated methyl cycle.


Programmed deep brain stimulation synchronizes VTA gamma band field potential and alleviates depressive-like behavior in rats.
Deep brain stimulation (DBS) significantly alleviates symptoms in various neurological disorders. Current research focuses on developing programmed stimulation protocols for customization to individual symptoms. However, the therapeutic mechanism of action of programmed DBS (pDBS) is poorly understood. We previously demonstrated that pDBS in the ventral tegmental area (VTA) normalizes molecular and behavioral abnormalities in the Flinders Sensitive Line (FSL) rat model for depression. Herein, we examined the effect of a short-duration, low-frequency DBS template on local field potential (LFP) synchronization patterns along the anterior-posterior axis of the VTA of FSL rats, and correlation of this effect with depressive-like behavior, as compared with non-programmed, continuous low-frequency DBS (npDBS). We used the wavelet phase coherence (WPC) measure for effective representation of time and frequency of LFP patterns, and the forced swim test to measure immobility (despair). Baseline WPC values were lower in FSLs as compared with SD controls, at the low and high gamma frequency range (above 30 Hz). Baseline immobility scores for FSL rats were higher than those of SD rats, while pDBS, and not npDBS, significantly reduced FSL immobility scores to control SD levels, up to day 14. pDBS also significantly increased the change (between baseline and day 14) in WPC values, in beta, low gamma and high gamma frequency ranges. The change in high gamma (60-100 Hz) WPC values correlated with improvement in depressive-like behavior. Our results suggest that programmed DBS of the VTA increases interaction among local neuronal populations, an effect that may underlie the normalization of depressive-like behavior.


The outcomes of treatment of giant cell tumor of bone around the knee.
Giant cell tumor of bone has been characterized as an aggressive benign bone tumor and commonly occurs at the distal femur and the proximal tibia. The recommended treatment has ranged from intralesional curettage to wide excision and the decision depends on severity of the tumor extent, rate of local recurrence,functional and morbidity outcomes. To compare extended curettage and wide excision in Grade II-III giant cell tumor of bone around the knee with regard to their effectiveness in tumor control and complication. There were 54 patients with a giant cell tumor which involved the distal femur or proximal tibia who had been managed consecutively at Siriraj Hospital between 1994-2009. The lesion of all patients were staged according to the system of Campanacci et al. There were 21 males and 33 females with mean age of 34 years. Thirty-five tumors located at distal femur and 19 located at proximal tibia. Fourteen patients had a Grade II lesion and 40 had a Grade III lesion. Thirty patients received extended curettage whereas other 24 patients had a wide excision. Fisher's exact analysis was used for statistical analysis for the outcome of tumor recurrence in each surgery. The mean follow-up time was 59 months. There were 7 (23.3 percent) local recurrences in the extended curettage group and 2 (8.3 percent) in the wide excision group. Most recurrences occurred within one year postoperatively. There was no statistical difference for the outcome of tumor recurrence in each group (p = 0.270). All patients with tumor recurrence were successfully treated with re-curettage, except for 3 patients who was treated by above-knee amputation. The functional analysis was excellence in the extended curettage group (94 percent) and good in the wide excision group (77.6 percent) according to the Musculoskeletal Tumor Society functional classification. The authors believe that using extended curettage was not significantly different in percentage of local recurrence when compared with wide excision for Campanacci's Grade II-III of giant cell tumor of bone. Even better function was found in extended curettage group, the choice of surgical treatment should be considered in individual patient which depends on the extent of bone destruction and risk of tumor recurrence.


Role of methionyl-transfer ribonucleic acid in the regulation of methionyl-transfer ribonucleic acid synthetase of Escherichia coli K-12.
A decrease in the in vivo acylation level of methionine transfer ribonucleic acid (tRNAmet) induced by methioninyl adenylate led to a specific derepression of methionyl-transfer ribonucleic acid (tRNA) synthetase formation. This derepression required de novo protein synthesis and was reflected by overproduction of unaltered enzyme. Two different strains of Escherichia coli K-12 that have normal levels of methionyl-tRNA synthetase were examined and the derepression of methionyl-tRNA synthetase was observed in both. Moreover, for one of these strains, the relation between the level of methionyl-tRNA synthetase and deacylation level of tRNAmet was established; under the growth conditions used, when more than 25% of tRNAmet was deacylated, methionyl-tRNA synthetase formation was derepressed and the level of derepression became proportional to the amount of tRNAmet deacylated. Concomitantly, the enzyme was subject to specific inactivation as a consequence of which the true de novo rate of derepression of the formation of this enzyme was higher than that determined by measurements of enzyme activity. These studies were extended to strains AB311 and ed2, which had a constitutive enhanced level of methionyl-tRNA synthetase. In these strains no derepression of enzyme formation was observed on reducing the acylation level of tRNAmet by use of methioninyl adenylate.


Conversion of Cellulose into Amphiphilic Alkyl Glycosides Catalyzed by Aquivion, a Perfluorosulfonic Acid Polymer.
The perfluorosulfonic acid (PFSA) Aquivion PW98 is an amphiphilic solid superacid which is shown to catalyze the conversion of cellulose into amphiphilic alkyl glycosides (AAGs) in 85 % yield (with 97 % selectivity). The process involves a mechanocatalytic depolymerization of cellulose followed by a direct glycosylation with n-dodecanol. In comparison to H2 SO4 and solid acid catalysts commonly employed in cellulose processing, Aquivion PFSA PW98 is not only recyclable but also exhibits superior catalytic performances in terms of yield, selectivity, and reactor productivity.


Anthracene/phenothiazine π-conjugated sensitizers for dye-sensitized solar cells using redox mediator in organic and water-based solvents.
Metal-free dyes (MD1 to MD5) containing an anthracene/phenothiazine unit in the spacer have been synthesized. The conversion efficiency (7.13 %) of the dye-sensitized solar cell using MD3 as the sensitizer reached approximately 85 % of the N719-based standard cell (8.47 %). The cell efficiency (8.42 %) of MD3-based dye-sensitized solar cells (DSSCs) with addition of chenodeoxycholic acid is comparable with that of N719-based standard cell. The MD3 water-based DSSCs using a dual-TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl)/iodide electrolyte exhibited very promising cell performance of 4.96 % with an excellent Voc of 0.77 V.


Geometrical analysis of third-order aberrations for a solid immersion lens.
This paper gives a treatment for finding 3rd order aberrations in solid-immersion lenses (SIL) using spherical-aberration as the basis for a polynomial power expansion of the wavefront. Unlike previous work, the treatment is general for any incident and lens media, for any lens thickness, and any chief-ray specification. Using this treatment, a tolerance analysis is given with particular discussion on thickness tolerance and limitations on field of view. Major findings include very tight thickness tolerance for high-index hyperhemisphere SILs and a thickness tolerance window for hemispheres skewed to values less than the radius of curvature of the lens.


Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure): Clinical and Prognostic Associations.
A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215.


Factors associated with the formation of SARS-CoV-2 case-clusters in Danish schools: a nationwide register-based observational study.
A register-based retrospective observational study was conducted to describe SARS-CoV-2 cases and case-clusters in schoolchildren of Danish primary and lower secondary schools and identify which factors were associated with the occurrence of case-clusters in schools. The study period was the autumn school semester 2021. Clusters were defined as three or more cases in a school-class level within 14 days. Descriptive analysis was carried out and multivariable logistic regression analysis was performed to determine which factors were associated with case introductions (i.e., primary case) being linked to a cluster. More cases and clusters were identified in lower than in higher class levels. Out of 21,497 cases introduced into a school, 41.6% started a cluster. A higher assumed immunity level in a class level was significantly reducing the odds of a case introduction being linked to a cluster (e.g., assumed immunity of ≥80% vs <20%: OR: 0.28; 95%CI: 0.17-0.44). A previous infection (in the primary case) had a protective effect (OR: 0.58; 95%CI: 0.33-0.99). This study suggests that most cases appearing in schools did not induce clusters, but that once cluster occur sizes can be large. It further indicates that vaccination of children markedly reduces the risk of secondary infections.


Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example.
An emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions. After nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence. A paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies. A productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world.


High-voltage electron microscopy of extracellular fibrillogenesis.
High-voltage electron microscopy was employed to observe developing extracellular connective tissue elements in the cervical perinotochordal and perivertebral regions in the chick embryo from 2 through 15 days' incubation. During days 2 and 3, small (10 nm) and large (18-20 nm) microfibrils surrounded the notochord, becoming evident around fibroblast-like cells in day 4. Amorphous material, globular granules and microfibrillar bundles were present at this time. Microfibrillar length increased as did the total population of microfibrils. At four days microfibrils 3-5 nm in diameter arose in all directions from globular granules. During day 9 and thereafter to day 15, microfibrillar diameters increased. This growth formed unit collagenous fibrils 30 nm in diameter or greater. Axial periodicity became evident at day 14. Small microfibrils appear to be composed largely of glycoproteins and do not contain a significant amount of collagen. The globular granules and associated filaments are probably proteoglycans. The amorphous material is believed to provide molecular collagen to developing fibrils. Large microfibrils and unit collagenous fibrils contain significant amounts of molecular collagen.


Site of action of indomethacin on implantation in the rabbit.
Blastocysts recovered from oil- or indomethacin-treated donor rabbits between 5 1/2 and 6 days after insemination and hCG injection were transferred to oil- or indomethacin-treated recipients between 135 and 147 h after hCG injection. Indomethacin treatment of donor rabbits (10 mg/kg s.c.) given every 6 h during the day before transfer had no effect on subsequent implantation of the blastocysts. However, indomethacin treatment of the recipients (10 mg/kg s.c. every 6 h from 120 to 168 h after hCG) prevented implantation of all transferred blastocysts, although 6 of the 8 rabbits died between Days 9 and 16 of (pseudo)pregnancy. Restriction of the indomethacin treatment of the recipients to only 3 injections of 10 mg/kg s.c. between 128 and 140 h after hCG injection had no effect on the implantation of the transferred blastocysts. It is concluded that indomethacin exerts its inhibitory influence on implantation via an action on the endometrium rather than on the blastocyst.


Association between the development of the body axis and the craniofacial skeleton studied by immunohistochemical analyses using collagen II, Pax9, Pax1, and Noggin antibodies.
Immunohistochemical analyses on the axial skeleton from wild type mice. In the clinic, we have previously observed cervical spine defects associated with deviations in the posterior part of the occipital bone and with morphologic and functional variations in the craniofacial skeleton. As examples, cervical spine fusions occurred frequently in patients with mandibular overjet and even more frequently and more caudally in the cervical spine in patients with sleep apnoea. The aims of the present study were to elucidate this association between the spine and the cranium by comparing gene expression domains of important developmental genes known to be involved in vertebral column formation with gene expression in the craniofacial region. This is the first study looking specifically on gene expression in the basilar part of the occipital bone that is formed around the cranial part of the notochord, thus connecting the spine and the craniofacial skeleton. The material consisted of 4 mouse embryos p.c. day 13.5, NMRI wild-type mice, from the same litter. The body axis, the cranial base, and the craniofacial area were studied by immunohistochemical analyses using Collagen II, Pax9, Pax1, and Noggin antibodies. Pax1 expression was highly similar in the posterior part of the occipital bone and in the vertebral column, indicating that the basilar part of the occipital bone from a developmental standpoint can be considered the uppermost vertebra. Pax9 and Noggin expression domains were in accordance with those described previously. The present study supports that the basilar part of the occipital bone may be regulated by similar developmental mechanisms as the vertebral column and may thus be regarded the uppermost vertebra. Thus, the clinically observed association between the cervical column and the craniofacial area has been proved by immunohistochemical methods.


The second victim requires more than Medice Cura Te Ipsum.
Burnout has attained epidemic proportions in all reaches of society. Only recently, has its impact in healthcare become a burning platform. Second victim syndrome, a consequence of an unforeseen adverse event, often precipitated by an error, can lead to a post-traumatic stress-like reaction, that is unique to healthcare workers. Often, the second victim suffers in silence, forced to rely on resilience. Peer support has been demonstrated to be beneficial in assisting healthcare workers in recovering from both burnout and second victim syndrome. Institutions and organizations must be more influential and responsive in supporting physicians and other healthcare workers in need.


Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.
Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.


Verbal learning and visuomotor attention in Alzheimer's disease and geriatric depression.
We compared the verbal learning and visuomotor attention of 34 Alzheimer's patients and 18 depressive patients. Verbal learning was assessed using The Hopkins Verbal Learning Test--Revised (HVLT--R); visuomotor attention was assessed using the Trail Making Test (TMT). The Alzheimer's patients had significantly lower scores on immediate and delayed recall of a word list. There was a nonsignificant trend in this group toward a fewer number of true positives and a greater number of false positives. Alzheimer's patients were significantly slower on Trails A, with a nonsignificant trend toward slower performance on Trails B. No difference was observed in accuracy of attentional processing. The results are discussed in terms of other factors, such as stage of cognitive decline, which might have influenced the findings.


Drug resistance phenotypes and genotypes in Mexico in representative gram-negative species: Results from the infivar network.
This report presents phenotypic and genetic data on the prevalence and characteristics of extended-spectrum β-lactamases (ESBLs) and representative carbapenemases-producing Gram-negative species in Mexico. A total of 52 centers participated, 43 hospital-based laboratories and 9 external laboratories. The distribution of antimicrobial resistance data for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, Acinetobacter baumannii complex, and Pseudomonas aeruginosa in selected clinical specimens from January 1 to March 31, 2020 was analyzed using the WHONET 5.6 platform. The following clinical isolates recovered from selected specimens were included: carbapenem-resistant Enterobacteriaceae, ESBL or carbapenem-resistant E. coli, and K. pneumoniae, carbapenem-resistant A. baumannii complex, and P. aeruginosa. Strains were genotyped to detect ESBL and/or carbapenemase-encoding genes. Among blood isolates, A. baumannii complex showed more than 68% resistance for all antibiotics tested, and among Enterobacteria, E. cloacae complex showed higher resistance to carbapenems. A. baumannii complex showed a higher resistance pattern for respiratory specimens, with only amikacin having a resistance lower than 70%. Among K. pneumoniae isolates, blaTEM, blaSHV, and blaCTX were detected in 68.79%, 72.3%, and 91.9% of isolates, respectively. Among E. coli isolates, blaTEM, blaSHV, and blaCTX were detected in 20.8%, 4.53%, and 85.7% isolates, respectively. For both species, the most frequent genotype was blaCTX-M-15. Among Enterobacteriaceae, the most frequently detected carbapenemase-encoding gene was blaNDM-1 (81.5%), followed by blaOXA-232 (14.8%) and blaoxa-181(7.4%), in A. baumannii was blaOXA-24 (76%) and in P. aeruginosa, was blaIMP (25.3%), followed by blaGES and blaVIM (13.1% each). Our study reports that NDM-1 is the most frequent carbapenemase-encoding gene in Mexico in Enterobacteriaceae with the circulation of the oxacillinase genes 181 and 232. KPC, in contrast to other countries in Latin America and the USA, is a rare occurrence. Additionally, a high circulation of ESBL blaCTX-M-15 exists in both E. coli and K. pneumoniae.


Ocean temperature impact on ice shelf extent in the eastern Antarctic Peninsula.
The recent thinning and retreat of Antarctic ice shelves has been attributed to both atmosphere and ocean warming. However, the lack of continuous, multi-year direct observations as well as limitations of climate and ice shelf models prevent a precise assessment on how the ocean forcing affects the fluctuations of a grounded and floating ice cap. Here we show that a +0.3-1.5 °C increase in subsurface ocean temperature (50-400 m) in the northeastern Antarctic Peninsula has driven to major collapse and recession of the regional ice shelf during both the instrumental period and the last 9000 years. Our projections following the representative concentration pathway 8.5 emission scenario from the Fifth Assessment Report of the Intergovernmental Panel on Climate Change reveal a +0.3 °C subsurface ocean temperature warming within the coming decades that will undoubtedly accelerate ice shelf melting, including the southernmost sector of the eastern Antarctic Peninsula.


Bovine spongiform encephalopathy (BSE) and its epidemiology.
Since the recognition of BSE in 1986, over 180,000 cattle in the UK have developed the disease and 1-3 million are likely to have been infected with the BSE agent, most of which were slaughtered for human consumption before developing signs of the disease. The origin of the first case of BSE is unknown, but the epidemic was caused by the recycling of processed waste parts of cattle, some of which were infected with the BSE agent, to other cattle in feed. Control measures have resulted in the consistent decline of the epidemic in the UK since 1992. Cattle and feed exported from the UK have seeded smaller epidemics in other European countries, where control measures were applied later. If the control measures now in place to protect public and animal health are well enforced, the epidemic in cattle should be largely under control and any remaining risk to humans through the consumption of beef should be very small.


INTRASPECIFIC VARIATION IN SEX ALLOCATION IN A SIMULTANEOUS HERMAPHRODITE: THE EFFECT OF INDIVIDUAL SIZE.
Within a population of simultaneous hermaphrodites, individuals may vary in both their current reproductive investment (biomass invested in gonads) and in how they allocate that investment between male and female function. In the chalk bass, Serranus tortugarum, estimates of both reproductive allocation and reproductive success as a male and a female can be made for individuals of different sizes. As individuals increase in size, their investment in gamete production increases, and there is a shift in allocation to a stronger female bias. Spawning frequency as a female in pair spawnings and as a male in both pair spawning and streaking (an alternative mating tactic) does not vary with individual size. As a result, larger individuals should release more sperm or eggs per spawn. Size-assortative pair spawning in this species leads to larger individuals having higher potential returns in total male reproductive success than smaller individuals, which should lead to increases in absolute levels of sperm production in larger individuals when individuals compete for fertilizations through sperm competition. However, smaller individuals contribute a smaller proportion of the sperm released in spawns with multiple spawners and thus are under more intense sperm competition than larger individuals, which should select for increases in male allocation in smaller individuals, all else equal. A local-mate-competition (LMC) model predicts that these factors select for increasing absolute male and female investment with individual size but a relative shift to more female-biased allocation as individual size increases. These predictions are supported by gonadal data. The predictions of average male allocation from the quantitative LMC model were 21.6% and 25.7%, whereas the collections averaged 21.3%. This close agreement of both the mean male allocation and its relative shift with individual size between model and data support the hypothesis that size-specific shifts in sex allocation in this species represent an adaptive response to patterns of mating success and sperm competition.


What surface of the intestinal epithelium is effectively available to permeating drugs?
A mathematical model is presented which examines the extent to which the intestinal epithelium is accessed by drug molecules. Morphological information from the literature for the jejunum, ileum, and colon of the rat and for human jejunum was incorporated. Perturbation theory was used to derive the limiting cases for total access to the entire epithelial surface, for transport by diffusion and by diffusion with convection, respectively. A parameter gamma = square root of (Ph2)/(Db) was identified to provide a measure of the ability of drug molecules to access the entire epithelial surface down to the crypt wells, where P is the cell permeability, D the aqueous diffusion coefficient, h the channel depth between the villi, and b is half the width of the idealized intervillous channel. When gamma << 1, diffusion is not a limitation and the entire surface is fully utilized for absorption of drug. This condition arises with drugs of low permeability and is more likely to be met with colonic than small intestinal epithelium. When gamma >/= 1, diffusion becomes a limitation and then not all of the epithelial surface is functionally accessible to drug molecules, a condition most likely to prevail with drugs of high permeability traversing the jejunum. Furthermore, water flux per se is predicted to have relatively little influence on enhancing surface accessibility. This simple, but quantitative approach showed that the ranking order of permeability jejunum >ileum> colon for low permeable drugs can at least in part be explained by the differences in surface amplification between these different epithelial regions. The analysis also indicates that for highly permeable drugs extreme caution should be exercised in extrapolating permeability measurements in vitro across various preparations and to events in vivo.


[A case of superior mesenteric artery syndrome after left nephrectomy].
Postoperative superior mesenteric artery syndrome is a rare complication of left nephrectomy. We treated a case of superior mesenteric artery syndrome that occurred 7 days after radical left nephrectomy for renal cell carcinoma. The patient was a 54-year-old Japanese man who presented with gross hematuria. Abdominal computed tomography showed a 3.8 x 3.8 x 5 cm heterogeneous cystic mass in the left kidney. Transperitoneal left radical nephrectomy was performed because renal cell carcinoma was suspected. The patient resumed oral intake 3 days after surgery, but he began vomiting repeatedly from the 7th day after surgery. Gastroduodenography showed an abrupt vertical linear obstruction of the third portion of the duodenum. Superior mesenteric artery syndrome was diagnosed. Conservative therapy (indwelling nasogastric tube, intravenous hyperalimentation and postural changes) was effective.


Emerging Bottom-Up Strategies for the Synthesis of Graphene Nanoribbons and Related Structures.
The solution-phase synthesis is one of the most promising strategies for the preparation of well-defined graphene nanoribbons (GNRs) in large scale. To prepare high quality, defect-free GNRs, cycloaromatization reactions need to be very efficient, proceed without side reaction and mild enough to accommodate the presence of various functional groups. In this Minireview, we present the latest synthetic approaches for the synthesis of GNRs and related structures, including alkyne benzannulation, photochemical cyclodehydrohalogenation, Mallory and Pd- and Ni-catalyzed reactions.


Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies.
Health-related quality of life (HRQoL) in common variable immunodeficiency diseases (CVID) was evaluated by different tools, which were mainly used to compare different schedules of immunoglobulins administration in cross-sectional or short-term longitudinal studies. We assessed the HRQoL and psychological status of CVID patients in a longitudinal study over a 6-year period by a generic, non-disease-specific instrument (SF-36), and by a General Health Questionnaire (GHQ-12) for the risk of depression/anxiety. At baseline, 96 patients were enrolled. After 1 year, a second assessment was performed on 92 patients and, after 6 years, a third assessment was performed on 66 patients. Eighteen patients died during the study time. HRQoL was low, with mental health scales less affected than physical scales. A decline in the score on SF-36 scales was observed between the first and the third assessment for the Physical Functioning, Body Pain, General Health, Social Functioning, and Role-Emotional scales. The General Health scale showed a lower score in these patients, when compared to patients with other chronic diseases. Approximately one-third of the patients were at risk of anxiety/depression at all observation times, a percentage that reached two thirds of the patients, considering only the group of females. Over the 6 years of the study, the health condition of 11/66 patients worsened, passing from "GHQ-negative" to "GHQ-positive"; their score on SF-36 scales also decreased. A decrement of one point in each of the Physical Functioning, Vitality, Social Functioning, and Mental Health SF-36 scales increased the risk of developing anxiety/depression from three to five percent. A negative variation of the Physical Functioning score increased the risk of psychological distress. In a survival analysis with dichotomized variables, Physical Functioning scores <50 were associated with a relative risk (RR) of 4.4, whereas Social Functioning scores <37.5 were associated with a RR of 10.0. In our study, it was the clinical condition, as opposed to the different treatment strategies with immunoglobulins, which had a major role on the deterioration of HRQoL. Moreover, in a quality-of-life evaluation, disorders such as anxiety/depression should be assessed, as they yet often go unrecognized. Our results might be helpful in the interpretation of currently available data on quality of life in CVID patients.


Effects of risperidone on cytokine profile in drug-naïve first-episode psychosis.
There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder. The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls. We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms. In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.


Off-label drug use in hospitalized children: a prospective observational study at Gondar University Referral Hospital, Northwestern Ethiopia.
Most of the medications which are currently used for the treatment of childhood diseases are either not licensed or being prescribed outside the terms of the product license (off-label prescribing). This study aimed at determining the extent of unlicensed and off-label drug uses and associated factors in children hospitalized in Gondar University Referral Hospital, Northwest Ethiopia. An institution-based prospective cross-sectional study was employed from April 15 to July 15, 2016. A total of 243 pediatric patients admitted to Gondar university referral hospital were included in the study using simple random sampling method. Data were collected using structured questionnaire, and the data collected were entered and analyzed using Statistical Packages for Social Sciences (SPSS) version 20. From the total of 800 drugs prescribed, 607 (75.8%) were off-label. Off-label medicine use was frequently observed in antimicrobials (60.6%) followed by central nervous system drugs (14.3%). The extent off-label prescribing was highest in age group of 6-13 years (30%). Inappropriate dosing and frequency (42.3%) were the most common reason for off-label medicine use. Having other variables controlled, age group and undergoing surgical procedure remained to be significant predictors of off-label prescribing in the multivariate regression analysis. Implementing evidence-based approach in prescribing by generating more quality literatures on the safety profile and effectiveness of off-label would improve the injudicious use of drugs in pediatric population.