Interaction with single-stranded DNA-binding protein modulates Escherichia coli RadD DNA repair activities.
The bacterial RadD enzyme is important for multiple genome maintenance pathways, including RecA DNA strand exchange and RecA-independent suppression of DNA crossover template switching. However, much remains unknown about the precise roles of RadD. One potential clue into RadD mechanisms is its direct interaction with the single-stranded DNA binding protein (SSB), which coats single-stranded DNA exposed during genome maintenance reactions in cells. Interaction with SSB stimulates the ATPase activity of RadD. To probe the mechanism and importance of RadD-SSB complex formation, we identified a pocket on RadD that is essential for binding SSB. In a mechanism shared with many other SSB-interacting proteins, RadD uses a hydrophobic pocket framed by basic residues to bind the C-terminal end of SSB. We found that RadD variants that substitute acidic residues for basic residues in the SSB binding site impair RadD:SSB complex formation and eliminate SSB stimulation of RadD ATPase activity in vitro. Additionally, mutant Escherichia coli strains carrying charge reversal radD changes display increased sensitivity to DNA damaging agents synergistically with deletions of radA and recG, although the phenotypes of the SSB-binding radD mutants are not as severe as a full radD deletion. This suggests that cellular RadD requires an intact interaction with SSB for full RadD function.


Narrowing the deleted region associated with the 15q21 syndrome.
Interstitial deletions of chromosome 15q, not involving the PWS/AS region, are uncommon and poorly characterized. Few cases defined at the cytogenetic level have been reported with 15q21 deletions and characteristic facial dysmorphisms are present in all them. We report on the molecular characterization by array-CGH of a new patient with a 15q21 deletion and on the redefinition of a second patient previously studied with multicolor banding. The two deletions resulted to be similar and involve about 12 and 8 Mb, respectively. Our study might promote to delineate a better genotype-phenotype correlation associated with 15q21 deletions.


CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis.
Airborne contact dermatitis to cedar pollen is a recently identified disease that generally affects individuals with cedar pollinosis of the nasal and/or ocular symptoms, as well as some patients with atopic dermatitis. To elucidate the pathological mechanisms of cedar pollen dermatitis. We established a mouse model of cedar pollen dermatitis by epicutaneous sensitization with Japanese cedar pollen antigen (Ag). Histologically, there was marked dermal cellular infiltrate, including eosinophils and mast cells, with epidermal thickening. The induction of dermatitis was accompanied by production of cedar pollen-specific IgE. In the lesional skin, IL-13, IL-18, eotaxin/chemokine (C-C motif) ligand (CCL) 11, regulated upon activation, normal T cell expressed and secreted/CCL5, macrophage-derived chemokine/CCL22 and thymus and activation-regulated chemokine/CCL17, but not IL-4 and IFN-gamma, were produced. Mast cell-deficient WBB6F1-W/W(v) mice failed to develop cedar pollen dermatitis, although regional lymph node cells proliferated in response to Cryptomeria japonica (Cry j) 1 and Cry j2 Ags in vitro. Surprisingly, the induction of dermatitis was independent of STAT6/IgE. In contrast, mice deficient in CRTH2, a receptor for prostaglandin D2 (PGD2), showed diminished inflammation. Consistent with this, ramatroban, a CRTH2 antagonist, significantly inhibited inflammatory cell infiltration. These data suggest that PGD2-CRTH2 signalling contributes to inflammation in cedar pollen dermatitis, and unlike cedar pollinosis of the nasal mucosa, STAT6 is not a therapeutic target for treatment.


Collective Cell Sorting Requires Contractile Cortical Waves in Germline Cells.
Encapsulation of germline cells by layers of somatic cells forms the basic unit of female reproduction called primordial follicles in mammals and egg chambers in Drosophila. How germline and somatic tissues are coordinated for the morphogenesis of each separated unit remains poorly understood. Here, using improved live imaging of Drosophila ovaries, we uncovered periodic actomyosin waves at the cortex of germ cells. These contractile waves are associated with pressure release blebs, which project from germ cells into somatic cells. We demonstrate that these cortical activities, together with cadherin-based adhesion, are required to sort each germline cyst as one collective unit. Genetic perturbations of cortical contractility, bleb protrusion, or adhesion between germline and somatic cells induced encapsulation defects resulting from failures to encapsulate any germ cells, or the inclusion of too many germ cells per egg chamber, or even the mechanical split of germline cysts. Live-imaging experiments revealed that reducing contractility or adhesion in the germline reduced the stiffness of germline cysts and their proper anchoring to the somatic cells. Germline cysts can then be squeezed and passively pushed by constricting surrounding somatic cells, resulting in cyst splitting and cyst collisions during encapsulation. Increasing germline cysts activity or blocking somatic cell constriction movements can reveal active forward migration of germline cysts. Our results show that germ cells play an active role in physical coupling with somatic cells to produce the female gamete.


Immune regulation of poly unsaturated fatty acids and free fatty acid receptor 4.
Fatty acid metabolism contributes to energy supply and plays an important role in regulating immunity. Free fatty acids (FFAs) bind to free fatty acid receptors (FFARs) on the cell surface and mediate effects through the intra-cellular FFAR signaling pathways. FFAR4, also known as G-protein coupled receptor 120 (GPR120), has been identified as the primary receptor of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). FFAR4 is a promising target for treating metabolic and inflammatory disorders due to its immune regulatory functions and the discovery of highly selective and efficient agonists. This review summarizes the reported immune regulatory functions of ω-3 PUFAs and FFAR4 in immune cells and immune-related diseases. We also speculate possible involvements of ω-3 PUFAs and FFAR4 in other types of inflammatory disorders.


Vertebrate-tropism of a cressdnavirus lineage implicated by poxvirus gene capture.
Among cressdnaviruses, only the family Circoviridae is recognized to infect vertebrates, while many others have unknown hosts. Detection of virus-to-host horizontal gene transfer is useful for solving such virus-host relationships. Here, we extend this utility to an unusual case of virus-to-virus horizontal transfer, showing multiple ancient captures of cressdnavirus Rep genes by avipoxviruses-large dsDNA pathogens of birds and other saurians. As gene transfers must have occurred during virus coinfections, saurian hosts were implied for the cressdnavirus donor lineage. Surprisingly, phylogenetic analysis revealed that donors were not members of the vertebrate-infecting Circoviridae, instead belonging to a previously unclassified family that we name Draupnirviridae. While draupnirviruses still circulate today, we show that those in the genus Krikovirus infected saurian vertebrates at least 114 Mya, leaving endogenous viral elements inside snake, lizard, and turtle genomes throughout the Cretaceous Period. Endogenous krikovirus elements in some insect genomes and frequent detection in mosquitoes imply that spillover to vertebrates was arthropod mediated, while ancestral draupnirviruses likely infected protists before their emergence in animals. A modern krikovirus sampled from an avipoxvirus-induced lesion shows that their interaction with poxviruses is ongoing. Captured Rep genes in poxvirus genomes often have inactivated catalytic motifs, yet near-total presence across the Avipoxvirus genus, and evidence of both expression and purifying selection on them suggests currently unknown functions.


Membrane function in cystic fibrosis. II. Methionine transport in normal and cystic fibrosis fibroblasts.
Initial rate kinetics of methionine transport, time course of accumulation of methionine, and efflux of accumulated methionine were studied in three normal and four CF human diploid fibroblast strains. The range of apparent Km's was 12.7-32.1 micrometer for the CF strains and 18.3-39.2 micrometer for the normal strains. The range of apparent Vmax's was 6.69-9.22 nmole mg-1 min-1 for the CF strains and 5.59-7.87 nmole mg-1 min-1 for the normal strains. The patterns of accumulation and efflux are quite similar in all the strains studied except for WI-38, which showed somewhat higher efflux and lower accumulation than for others. There was no significant difference in the kinetic parameters of methionine transport between CF and normal skin fibroblasts, and methionine transport will not serve as a marker for cystic fibrosis in cultured fibroblasts.


Is High-Grade Tumor Budding an Independent Prognostic Factor in Stage II Colon Cancer?
Risk factors, including lymphatic, vascular, and perineural invasion, are considered indications for adjuvant treatment in stage II colon cancer. However, tumor budding is not included in the above risk factors. This study aimed to assess the value of tumor budding as a prognostic factor in stage II colon cancer. This is a retrospective cohort study. This study was conducted in a tertiary referral center. This study examined 1390 patients with stage II colon cancer who received curative resection from 2007 to 2013 at an institution. These patients were classified according to tumor budding status: low-grade tumor budding (less than 10 buds) and high-grade tumor budding (10 buds or more). Differences between the 2 groups were corrected by propensity score matching. Disease-free survival and overall survival were the primary end points. Among 1390 patients, 146 (10.5%) had high-grade tumor budding. The high-grade tumor budding group showed adverse histological characteristics such as advanced T stage, histological grade of differentiation, and presence of lymphatic/perineural invasion. After matching, the 5-year disease-free survival rate for the high-grade tumor budding group was significantly lower than for the low-grade group. We also compared survival outcomes according to tumor budding grade for patients who did not have risk factors and did not receive adjuvant treatment. The 5-year overall survival was similar between the 2 groups. However, the 5-year disease-free survival decreased significantly in the high-grade tumor budding group than in the low-grade tumor budding group. This was a retrospective study with a single-center design. High-grade tumor budding is a poor prognostic factor in stage II colon cancer and is considered one of the risk factors for adjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B962 . ANTECEDENTES:Los factores de riesgo, incluida la invasión linfática/vascular/perineural, se consideran indicaciones para el tratamiento adyuvante en el cáncer de colon en estadio II. Sin embargo, la gemación tumoral (desdiferenciación tumoral aislada), no está incluida en los factores de riesgo anteriores.OBJETIVO:El objeto de este estudio fue evaluar el valor de la gemación tumoral como factor pronóstico en el cáncer de colon en estadio II.DISEÑO:Este es un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un centro de referencia terciario.PACIENTES:Este estudio analizó 1390 pacientes con cáncer de colon en estadio II que recibieron una resección curativa entre 2007 y 2013 en una institución.INTERVENCIONES:Estos pacientes se clasificaron según el estado de gemación tumoral: gemación tumoral de bajo grado (<10 yemas) y gemación tumoral de alto grado (≥10 yemas). Las diferencias entre los dos grupos se corrigieron mediante el emparejamiento por puntaje de propensión.PRINCIPALES MEDIDAS DE VALORACIÓN:La supervivencia libre de enfermedad y la supervivencia global fueron los puntos finales primarios.RESULTADOS:Entre 1.390 pacientes, 146 (10,5%) tenían brotes tumorales de alto grado. El grupo de gemación tumoral de alto grado mostró características histológicas adversas como estadio T avanzado, grado histológico de diferenciación y presencia de invasión linfática/perineural. Después del emparejamiento, la tasa de supervivencia libre de enfermedad a cinco años para el grupo de brotes de tumores de alto grado fue significativamente menor que para el grupo de bajo grado. También comparamos los resultados de supervivencia según el grado de gemación del tumor para pacientes que no tenían factores de riesgo y que no recibieron tratamiento adyuvante. La supervivencia global a cinco años fue similar entre los dos grupos. Sin embargo, la supervivencia libre de enfermedad a cinco años disminuyó significativamente en el grupo de brotes de tumores de alto grado que en el grupo de brotes de tumores de bajo grado.LIMITACIONES:Este fue un estudio retrospectivo con un diseño de centro único.CONCLUSIÓNES:La gemación tumoral de alto grado es un factor de mal pronóstico en el cáncer de colon estadio II y se considera uno de los factores de riesgo para el tratamiento adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B962 . (Traducción-Dr. Ingrid Melo ).


Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation.
Histone acetyltransferases (HATs) regulate transcription, chromatin structure and DNA repair. Here, we utilized a novel HAT inhibitor, anacardic acid, to examine the role of HATs in the DNA damage response. Anacardic acid inhibits the Tip60 HAT in vitro, and blocks the Tip60-dependent activation of the ATM and DNA-PKcs protein kinases by DNA damage in vivo. Further, anacardic acid sensitizes human tumor cells to the cytotoxic effects of ionizing radiation. These results demonstrate a central role for HATs such as Tip60 in regulating the DNA damage response. HAT inhibitors provide a novel therapeutic approach for increasing the sensitivity of tumors to radiation therapy.


BRCA1 is required for postreplication repair after UV-induced DNA damage.
BRCA1 contributes to the response to UV irradiation. Utilizing its BRCT motifs, it is recruited during S/G2 to UV-damaged sites in a DNA replication-dependent but nucleotide excision repair (NER)-independent manner. More specifically, at UV-stalled replication forks, it promotes photoproduct excision, suppression of translesion synthesis, and the localization and activation of replication factor C complex (RFC) subunits. The last function, in turn, triggers post-UV checkpoint activation and postreplicative repair. These BRCA1 functions differ from those required for DSBR.


Mental and social health in disasters: relating qualitative social science research and the Sphere standard.
Increasingly, social scientists interested in mental and social health conduct qualitative research to chronicle the experiences of and humanitarian responses to disaster We reviewed the qualitative social science research literature in relation to a significant policy document, the Sphere Handbook, which includes a minimum standard in disaster response addressing "mental and social aspects of health", involving 12 interventions indicators. The reviewed literature in general supports the relevance of the Sphere social health intervention indicators. However, social scientists' chronicles of the diversity and complexity of communities and responses to disaster illustrate that these social interventions cannot be assumed helpful in all settings and times. With respect to Sphere mental health intervention indicators, the research largely ignores the existence and well-being of persons with pre-existing, severe mental disorders in disasters, whose well-being is addressed by the relevant Sphere standard. Instead, many social scientists focus on and question the relevance of posttraumatic stress disorder-focused interventions, which are common after some disasters and which are not specifically covered by the Sphere standard. Overall, social scientists appear to call for a social response that more actively engages the political, social, and economic causes of suffering, and that recognizes the social complexities and flux that accompany disaster. By relating social science research to the Sphere standard for mental and social health, this review informs and illustrates the standard and identifies areas of needed research.


Pancreatitis, gastrointestinal ulceration and haemorrhage and necrotising cystitis following the surgical treatment of degenerative disc disease in a dachshund.
A case of pancreatitis with gastrointestinal ulceration and haemorrhage and necrotising cystitis in a five-and-a-half-year-old dachshund bitch which unexpectedly died six days after dorsolateral fenestration was performed for thoracolumbar degenerative disc disease is described.


Association of low serum iron levels with low-grade inflammation and hyperadiponectinemia in community-living elderly women.
There have been inconsistent reports regarding the relationship between the iron status and coronary vascular diseases (CVD). Recently, low serum iron levels have been shown to be associated with mortality from CVD in women. The relationships between the serum iron levels and traditional and nontraditional risk factors for CVD were examined in 202 community-living elderly Japanese women. The women in the lowest iron tertile had higher high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) levels than the women in the top iron tertile (p<0.01 or less for both). In addition, the women in the lowest tertile had higher serum levels of adiponectin and copper and ratios of serum copper to zinc and lower serum levels of albumin, hemoglobin and hematocrit. Furthermore, the women in the lowest tertile had higher creatinine levels and lower eGFR values, although there were no significant differences in the prevalence of chronic kidney disease between the three tertile groups. In a multiple regression analysis including the levels of hsCRP, TNF-α, adiponectin and serum creatinine and the ratio of serum copper to zinc as independent variables, the levels of hsCRP, TNF-α and adiponectin emerged as independent determinants of the serum iron level (R(2)= 0.106). In the model to which the hemoglobin level was added as an independent variable, the levels of hemoglobin, hsCRP and TNF-α emerged as independent determinants of the serum iron level (R(2)= 0.192). The present study demonstrated that community-living elderly Japanese women with low serum iron levels have nontraditional risk factors for CVD, including low-grade inflammation and higher levels of serum adiponectin.


Identification of cell types in multiplexed in situ images by combining protein expression and spatial information using CELESTA.
Advances in multiplexed in situ imaging are revealing important insights in spatial biology. However, cell type identification remains a major challenge in imaging analysis, with most existing methods involving substantial manual assessment and subjective decisions for thousands of cells. We developed an unsupervised machine learning algorithm, CELESTA, which identifies the cell type of each cell, individually, using the cell's marker expression profile and, when needed, its spatial information. We demonstrate the performance of CELESTA on multiplexed immunofluorescence images of colorectal cancer and head and neck squamous cell carcinoma (HNSCC). Using the cell types identified by CELESTA, we identify tissue architecture associated with lymph node metastasis in HNSCC, and validate our findings in an independent cohort. By coupling our spatial analysis with single-cell RNA-sequencing data on proximal sections of the same specimens, we identify cell-cell crosstalk associated with lymph node metastasis, demonstrating the power of CELESTA to facilitate identification of clinically relevant interactions.


Pretreatment tumor diameter/volume and pelvic lymph node status assessed by magnetic resonance imaging for uterine cervical carcinoma treated with concurrent chemotherapy and radiotherapy.
The aim is to evaluate the prognostic value of tumor diameter, volume and pelvic lymph node status assessed by magnetic resonance imaging (MRI) in patients with uterine cervical carcinoma patients treated with concurrent chemotherapy and radiotherapy. Ninety-eight patients diagnosed with stage IB to IIIB cervical carcinoma were entered into the study. Tumor diameter was evaluated in T2-weighted image. The tumor volume was calculated by the equation (volume = width x length x height x pi/6) as an ellipsoid approximation. Univariate and multivariate analyses were performed to identify the prognostic factors for overall survival (OS), disease-free survival (DFS), pelvic control (PC) and distant metastasis-free survival (DMFS). The 5-year OS, DFS, PC and DMFS rate were 59.8%, 57.3%, 67.9% and 78.8%, respectively. Using univariate analyses, large MRI tumor diameter (4 cm), large tumor volume (30 mL), pelvic enlarged pelvic lymph nodes, large clinical diameter (4 cm) and International Federation of Gynecology and Obstetrics (FigO) stage showed a statistically significantly unfavorable influence on OS and DFS. In multivariate analyses, large tumor volume affected OS, DFS, PC and DMFS, and enlarged pelvic lymph nodes also affected OS. Tumor volume and enlarged pelvic lymph nodes determined by pretreatment MRI examinations were significant prognostic factors for patients with invasive cervical carcinoma treated with concurrent chemotherapy and radiotherapy.


Higher testosterone is associated with increased inflammatory markers in women with SARS-CoV-2 pneumonia: preliminary results from an observational study.
Objective of this study was to assess the association between testosterone (T) levels and biochemical markers in a cohort of female patients admitted for SARS-CoV-2 infection in a respiratory intensive care unit (RICU). A consecutive series of 17 women affected by SARSCoV-2 pneumonia and recovered in the RICU of the Hospital of Mantua were analyzed. Biochemical inflammatory markers as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. TT and cFT were significantly and positively associated with PCT, CRP, and fibrinogen as well as with a worse hospital course. We did not observe any significant association between TT and cFT with LH; conversely, both TT and cFT showed a positive correlation with cortisol. By LOWESS analysis, a linear relationship could be assumed for CRP and fibrinogen, while a threshold effect was apparent in the relationship between TT and procalcitonin, LDH and ferritin. When the TT threshold value of 1 nmol/L was used, significant associations between TT and PCT, LDH or ferritin were observed for values above this value. For LDH and ferritin, this was confirmed also in an age-adjusted model. Similar results were found for the association of cFT with the inflammatory markers with a threshold effect towards LDH and ferritin with increased LDH and ferritin levels for values above cFT 5 pmol/L. Cortisol is associated with serum inflammatory markers with similar trends observed for TT; conversely, the relationship between LH and inflammatory markers had different trends. Opposite to men, in women with SARS-CoV-2 pneumonia, higher TT and cFT are associated with a stronger inflammatory status, probably related to adrenal cortex hyperactivity.


The increased oxygen uptake upon immersion. The raised external pressure could be a causative factor.
The principal cause of the immediate transient elevation in ventilation (VE, L.min-1) and oxygen uptake (VO2, L.min-1), when a human subject is immersed in cold water is considered to be the stimulation of cutaneous cold receptors. The present study demonstrates that the initial VE and VO2 responses are comprised of a thermogenic and a hydrostatic component. The peak values in VE reached (mean +/- SD) 66.8 +/- 22.3, 53.9 +/- 38.1, 32.2 +/- 15.4, 22.5 +/- 3.6, 19.5 +/- 4.6 L.min-1 during the first minute of immersion in 10 degrees, 15 degrees, 20 degrees, 28 degrees and 40 degrees C water, respectively. Similarly, peaks (mean +/- SD) in VO2 of 1.22 +/- 0.25, 1.01 +/- 0.32, 0.98 +/- 0.39, 0.81 +/- 0.09, and 0.78 +/- 0.26 L.O2.min-1, were reached when subjects were immersed in 10 degrees, 15 degrees, 20 degrees, 28 degrees, and 40 degrees C water. It is concluded that the observed increases in VO2 during the first minute of immersion are partly due to the increased hydrostatic pressure causing a shift of venous blood towards the thoracic region, and a transient increase in the uptake of oxygen into the blood.


Association between the gut microbiota and nonalcoholic fatty liver disease: A two-sample Mendelian randomization study.
Increasing studies have shown that there is a significant association between gut microbiota and non-alcoholic fatty liver disease. To show the potential association between gut microbiota and non-alcoholic fatty liver disease, we performed a two-sample Mendelian randomization analysis. We analyzed summary statistics from genome-wide association studies of gut microbiota and non-alcoholic fatty liver disease and conducted Mendelian randomization studies to evaluate relationships between these factors. Of the 211 gut microbiota taxa examined, the inverse variance weighted method identified Lactobacillaceae (OR = 0.83, 95% CI = 0.72 - 0.95, P = 0.007), Christensenellaceae (OR = 0.74, 95% CI = 0.59 - 0.92, P = 0.007), and Intestinibacter (OR = 0.85, 95% CI = 0.73 - 0.99, P = 0.035) were negatively correlated with non-alcoholic fatty liver disease. And Coriobacteriia (OR = 1.22, 95% CI = 1.01 - 1.42, P = 0.038), Actinomycetales (OR = 1.25, 95% CI = 1.02 - 1.53, P = 0.031), Oxalobacteraceae (OR = 1.10, 95% CI = 1.01 - 1.21, P = 0.036), Ruminococcaceae_UCG005 (OR = 1.18, 95% CI = 1.01 - 1.38, P = 0.033) are positively associated with non-alcoholic fatty liver disease. Our study found that the abundance of certain strains was associated with the progression of nonalcoholic fatty liver disease.


Air pressure pulsation solid state fermentation of feruloyl esterase by Aspergillus niger.
Air pressure pulsation solid state fermentation (APP-SSF) was applied to produce feruloyl esterase (FAE) by Aspergillus niger. With the optimization of some variables by orthogonal design, the optimal condition obtained was 0.2 MPa (gauge pressure) of high pressure intensity, 30 min of low pressure duration and 20s of high pressure duration. Based on the optimized condition, the APP-SSF achieved the reasonable enzyme yield of 881 mU/g at 48 h, which was 58% more than that by static solid state fermentation (static SSF) at 72 h. By comparison of two fermentation methods in temperature, O(2) and CO(2) concentration, and respiration intensity, it was concluded that APP-SSF enhanced heat and mass transfer of fermentation system and strengthened the metabolism of microorganisms. The APP-SSF had a greatly positive effect on FAE production by A. niger, by enhancing mass and heat transfer and activating growth and metabolism.


Buprenorphine in opiate withdrawal: a comparison with clonidine.
Clinical efficacy of buprenorphine in controlling withdrawal symptoms was compared against clonidine among 44 opiate dependent males. Subjective and objective withdrawal symptoms were assessed by withdrawal rating scales daily for 10 days. The subjects were randomly assigned to fixed dose schedule of either buprenorphine (0.6-1.2 mg per day, sublingually) or clonidine (0.3-0.9 mg per day, oral) for 10 days. Buprenorphine was found superior to clonidine in alleviating most of the subjective and objective opiate withdrawal symptoms. Subjective symptoms declined earlier among the subjects receiving buprenorphine. No untoward side-effects of buprenorphine were noticed.


Acute lung disease in the immunocompromised host: CT and pathologic examination findings.
To compare findings at computed tomography (CT) and pathologic examination in immuno-compromised patients with acute lung disease. Findings in 33 chest CT scans were compared with findings in pathologic specimens obtained at open lung biopsy (n = 29) or autopsy (n = 4) in 32 patients, aged 17-64 years. Nodules were the main abnormality at CT in 14 cases. Pathologically, the 14 nodules were due to infection (n = 10), bronchiolitis obliterans organizing pneumonia (BOOP) (n = 3), or lymphoma (n = 1). Areas of ground-glass attenuation were the main finding in 15 patients. These areas were a result of BOOP (n = 4), cytotoxic drug reaction (n = 4), infection (n = 4), lymphoma (n = 2), or nondiagnostic biopsy (n = 1). Consolidation was the main finding in four cases, being seen with BOOP (n = 2), infarction due to fungal infection (n = 1), and diffuse pulmonary hemorrhage (n = 1). The pattern at CT accurately reflected the gross morphologic features seen in the pathologic specimens. Nodules were usually inflammatory lesions, often infections, and open lung biopsy usually revealed their specific origin.


A new method for censusing animal populations: The number of Eciton burchelli army ant colonies on Barro Colorado Island, Panama.
A new technique for estimating the size of an animal population is described. This technique is used to provide an up to date estimate of the number of colonies of the army ant Eciton burchelli on Barro Colorado Island, Panama. There have been approximately 50 colonies of this species on Barro Colorado Island for more than thirty years. The relative constancy of this population is contrasted with the great temporal variability of other tropical insect populations.


Evolution of learning in subdivided populations that occupy environmentally heterogeneous sites.
We study the effects of natural selection and migration on the numbers of individual learners and social learners in subdivided populations that occupy environmentally heterogeneous sites. The island model and the circular stepping model each have four classes of globally stable equilibria (fixation of individual learners, polymorphism of individual and social learners, fixation of social learners, and extinction). The linear stepping stone model has an additional class of equilibria, which are characterized by the complete absence of phenotypes adapted to the interior sites. Low and high rates of migration favor social and individual learners, respectively, in all three models. In addition, we use the stepping stone models to study the range expansion of a species, initially confined to one environmentally homogeneous site, into the spatially heterogeneous world. The successive peaks of the transient spatial distributions of the number of individual learners occur at initially empty sites.


Aortic valve replacement: choice between mechanical valves and bioprostheses.
The choice between a mechanical or bioprosthetic valve replacement device is not always clear, although patient age is most often the determining factor. We reviewed our experience with patients undergoing aortic valve replacement (AVR) in order to assess and compare long-term outcomes between patients receiving a mechanical valve and those receiving a bioprosthesis. Three hundred fifty-two patients underwent AVR with or without coronary artery bypass between 1993 and 2004: 189 received a mechanical valve and 163 a bioprosthesis. Events included: late mortality, thrombo-embolic events, stroke, bleeding events, valve thrombosis, endocarditis, reoperation, and coronary catheterization. Patients in the bioprosthesis group were older (71 +/- 11 vs. 65 +/- 13) than in the mechanical group (p < 0.0001). There was no difference in operative mortality (6.8%) or morbidity. Follow-up (61 +/- 40 months) was available in 87%. For mechanical valves and bioprostheses, respectively: 3-, 5-, and 10-year survival was 92%, 86%, and 69% versus 90%, 86%, and 71% (p = n.s.); and event-free survival was 79%, 68%, and 41% versus 79%, 68%, and 44% (p = n.s.). Five patients (3%) in each group required re-replacement of their aortic valve (p = n.s.). Coronary artery disease requiring bypass surgery did not affect long-term survival. Age at operation and renal failure were the only predictors for late mortality. Survival and event-free survival are similar for patients receiving a mechanical or biological aortic valve substitute. Selection of a valve replacement device should be based on life expectancy, patient preference, ability to take anticoagulants, lifestyle, risk of bleeding, and risk of reoperation. Patient age alone should not be the determining factor.


Dental caries at five and twelve years in a South African Indian community: a longitudinal study.
In 1979, 515 of 767 available Indian children born in Lenasia in 1974 were examined and their dental caries status was described. In 1986, 515 of the original 715 were re-examined in order to determine the pattern of dental caries in the primary and permanent dentitions of the same individuals. In contrast to studies in the literature in which treatment records have been used, both investigations were formal epidemiological field studies using calibrated examiners and WHO (1971) caries diagnostic criteria. A firm association was found between caries in the primary and permanent dentitions (r = 0.34).


Epidemiological appraisal of the active role of women in the decline of infant mortality in Spain during the twentieth century.
This paper is concerned with the question of the role which the psycho-cultural development experienced by women in developed countries throughout this century may have played in the decline of infant mortality, taking in Spain between 1900 and 1979 as a basis for observation. We think that, by studying the psycho-cultural development of women, included under the general concept of standard of living, we can take a step forward in explaining such a frequently investigated but nonetheless incompletely understood subject as is that of the marked decline of infant mortality which has taken place in this century in developed countries in general, and in Spain in particular. To this effect, we have attempted to demonstrate the need to consider socio-cultural factors, in addition to the already repeatedly studied economic and biomedical ones; the more so when we take into account the marked decline in infant mortality which occurred in Spain in the 1940s, in which period there was a pronounced stagnation in the economy. To this purpose, we have studied fertility, not only as a gauge of the biological risks which generate a certain reproductive pattern for infant mortality, but also as an indicator of the socio-cultural development of women. Similarly, and through a review of historical documents, we have analysed the role of women in birth control, their incorporation into more qualified jobs, their level of education, their growing awareness of their own situation in society, as well as pertinent legislative changes. All these processes affect the health of children through factors which, although they are very difficult to evaluate and quantify, have previously been described and examined in other studies. Our study has shown the probable relationship between the decline of fertility and the decrease of infant mortality, in view of the fact that there has been a pronounced decrease of parity and fertility in women belonging to the oldest fertile age groups. Similarly, the indications pointed out with respect to the processes mentioned above lead us to infer that in Spain the woman has played a significant role in the decline of infant mortality produced in this century, and especially in the first half of the century. We have embarked on a scantily developed line of investigation, and suggest the need for new studies on the subject.


Quantitative relationship between protonophoric and uncoupling activities of analogs of SF6847 (2,6-di-t-butyl-4-(2',2'-dicyanovinyl)phenol).
Uncoupling activity with rat liver mitochondria and protonophoric activity across the lecithin liposomal membranes were measured for a series of non-classical uncouplers related to the most potent uncoupler known until now, SF6847 (2,6-di-t-butyl-4-(2',2'-dicyanovinyl)phenol). The correlation between uncoupling and protonophoric activities for a number of uncouplers, both non-classical and classical (simply substituted phenols), was examined quantitatively. Correlation was excellent when such factors as the stability of anionic species in the membrane phase and the difference in the pH conditions of the extramembranous aqueous phase were taken into account. Carbonylcyanide m-chlorophenylhydrazone (CCCP) and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), which are structurally different, were correlated in a way that resembled the correlation of phenolic compounds, so we think that the mode of action of weakly acidic uncouplers was the same regardless of the structural type. Our findings were evidence for the shuttle-type mechanism of uncoupling action.


Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing.
Receptors for the Fc region of IgG (FcgammaRIIIa, FcgammaRIIc) and IgM (FcmicroR) were previously described on NK cells. In this work the expression of Fc receptors for IgA (FcalphaR) on human NK cells and the signaling events were investigated. The FcalphaR was demonstrated by flow cytometry using secretory IgA (sIgA) and anti-human IgA antibody. The percentage of NK cells (CD3(-)CD56(+)CD16(+)) expressing FcalphaR ranged between 55.7% and 95.7%, with a mean +/- SD of 75.2+/-11.8. The association constant and the number of (125)I-labeled sIgA ((125)I-sIgA) molecules bound per cell, calculated by Scatchard analysis, were 2 x 10(7) M(-1) and 1.7 x 10(4), respectively. The binding specificity was proved by inhibition experiments. Cold sIgA but not IgA Fab fragments were able to inhibit (125)I-sIgA binding in a concentration-dependent manner. Binding of sIgA to NK cells was neither inhibited by anti-mannose receptor antibody, nor by L-fucose, D-galactose, D-glucose, D-mannose or N-acetyl-D-glucosamine. Pretreatment of NK cells with polymeric IgA inhibited their capacity to kill (51)Cr-labeled K562 target cells by 34.8%, whereas with monomeric IgA only by 13.1%. Ligand-induced clustering of the FcalphaR resulted in activation of tyrosine kinases Lck, Syk and phosphatidylinositol 3-kinase. The present studies support the concept that human NK cells bind preferentially sIgA and polymeric IgA with moderate affinity via FcalphaR, which is different from the FcalphaRI/CD89 and other carbohydrate-recognizing receptors like mannose receptor/CD206. This novel structure mediates signal transduction and cell killing.


Attribution of intentional agency towards robots reduces one's own sense of agency.
In the presence of others, sense of agency (SoA), i.e. the perceived relationship between our own actions and external events, is reduced. The present study aimed at investigating whether the phenomenon of reduced SoA is observed in human-robot interaction, similarly to human-human interaction. To this end, we tested SoA when people interacted with a robot (Experiment 1), with a passive, non-agentic air pump (Experiment 2), or when they interacted with both a robot and a human being (Experiment 3). Participants were asked to rate the perceived control they felt on the outcome of their action while performing a diffusion of responsibility task. Results showed that the intentional agency attributed to the artificial entity differently affect the performance and the perceived SoA on the outcome of the task. Experiment 1 showed that, when participants successfully performed an action, they rated SoA over the outcome as lower in trials in which the robot was also able to act (but did not), compared to when they were performing the task alone. However, this did not occur in Experiment 2, where the artificial entity was an air pump, which had the same influence on the task as the robot, but in a passive manner and thus lacked intentional agency. Results of Experiment 3 showed that SoA was reduced similarly for the human and robot agents, threby indicating that attribution of intentional agency plays a crucial role in reduction of SoA. Together, our results suggest that interacting with robotic agents affects SoA, similarly to interacting with other humans, but differently from interacting with non-agentic mechanical devices. This has important implications for the applied of social robotics, where a subjective decrease in SoA could have negative consequences, such as in robot-assisted care in hospitals.


Isolation of characterization of two sequence-specific endonucleases from the cyanobacterium Synechocystis sp. PCC 6308.
The first two restriction endonucleases to be characterized in the cyanobacterium Synechocystis sp. PCC 6308 are described. SynI, an AvaII isoschizomer, recognizes the base sequence 5-GG[AT]CC-3. SynII, an XmnI isoschizomer, recognizes the sequence 5-GAANNNNTTC-3.


The effect of stimulus level on excitation patterns of individual electrode contacts in cochlear implants.
Spread of excitation (SOE) in cochlear implants (CI) is a measure linked to the specificity of the electrode-neuron interface. The SOE can be estimated objectively by electrically evoked compound action potential (eCAP) measurements, recorded with the forward-masking paradigm in CI recipients. The eCAP amplitude can be plotted as a function of the roving masker, resulting in a spatial forward masking (SFM) curve. The eCAP amplitudes presented in the SFM curves, however, reflect an interaction between a masker and probe stimulus, making the SFM curves less reliable for examining SOE effects at the level of individual electrode contacts. To counter this, our previously published deconvolution method estimates the SOE at the electrode level by deconvolving the SFM curves (Biesheuvel et al., 2016). The aim of this study was to investigate the effect of stimulus level on the SOE of individual electrode contacts by using SFM curves analyzed with our deconvolution method. Following the deconvolution method, theoretical SFM curves were calculated by the convolution of parameterized excitation density profiles (EDP) attributable to masker and probe stimuli. These SFM curves were subsequently fitted to SFM curves from CI recipients by iteratively adjusting the EDPs. We first improved the EDP parameterization to account for stimulus-level effects and validated this updated parameterization by comparing the EDPs to simulated excitation density profiles (sEDP) from our computational model of the human cochlea. Secondly, we analyzed SFM curves recorded with varying probe stimulus level in 24 patients, all implanted with a HiFocus Mid-Scala electrode array. With the deconvolution method extended to account for stimulus level effects, the SFM curves measured with varying probe stimulus levels were converted into EDPs to elucidate the effects of stimulus level on the SOE. The updated EDP parameterization was in good agreement with the sEDPs from the computational model. Using the extended deconvolution method, we found that higher stimulus levels caused significant widening of EDPs (p < 0.001). The stimulus level also affected the EDP amplitude (p < 0.001) and the center of excitation (p < 0.05). Concerning the raw SFM curves, an increase in current level led to higher SFM curve amplitudes (p < 0.001), while the width of the SFM curves did not change significantly (p = 0.62). The extended deconvolution method enabled us to study the effect of stimulus level on excitation areas in an objective way, as the EDP parameterization was in good agreement with sEDPs from our computational model. The analysis of SFM curves provided new insights into the effect of the stimulus level on SOE. We found that the EDPs, and therefore the SOE, mainly became wider when the stimulus level increased. Lastly, the comparison of the EDP parameterization with simulations in our computation model provided new insights about the validity of the deconvolution method.


Long-Term Outcome of Patients With Intractable Chronic Cluster Headache Treated With Injection of Onabotulinum Toxin A Toward the Sphenopalatine Ganglion - An Observational Study.
To investigate long-term outcomes in per-protocol chronic cluster headache patients (n = 7), 18 and 24 months after participation in "Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic cluster headache." Data were collected prospectively through headache diaries, HIT-6, and open questionnaire forms at 18 and 24 months after the first treatment. Patients had access to repeated injections when needed. An overall significant reduction in cluster headache attack frequency per month (57.3 ± 35.6 at baseline vs 12.4 ± 15.2 at month 18 and 24.6 ± 19.2 at month 24) was found. In addition, there was a reduction in attacks with severe and unbearably intensity (50.0 ± 38.3 at baseline vs 10.1 ± 14.7 at month 18 and 16.6 ± 13.7 at month 24) and an increase in attack free days (4.2 ± 5.9 at baseline vs 19.1 ± 9.4 at month 18 and 12.9 ± 8.8 at month 24). Our findings suggest sustained headache relief after repeated onabotulinumtoxinA injections toward the sphenopalatine ganglion in intractable chronic cluster headache. A placebo-controlled trial with long-term follow-up is warranted.


The influence of earthworms (Lumbricidae) on the nitrogen dynamics in the soil litter system of a deciduous forest.
The influence of earthworms (Aporrectodea caliginosa (Savigny) and Lumbricus castaneus (Savigny)) on the rate of nitrogen net mineralization of the soil was studied in the laboratory and in the field. The additional mineralization of nitrogen cause by the burrowing activity of the substrat feeding earthworm A. caliginosa (N L )was directly correlated to the biomass of the lumbricids independently of their number. A rise in temperature caused an exponential increase in N L values. The Q 10 value of this process (2.18) was found to be much higher than that of the nitrogen mineralization without earthworms (Q 10=1.22). At 15°C the N L value caused by A. caliginosa was calculated to be about 250 μg N g-1 fresh body wt d-1. Using the experimentally determined exponential relationship between temperature and N L values, the additional nitrogen mineralization caused by a population of A. caliginosa in a beechwood on limestone was calculated to be 4.23 kg ha-1 a-1.In contrast to A. caliginosa the litter dwelling species L. castaneus lost considerable amounts of biomass (56%) during the 4 week incubation period. Only 1/3 of the nitrogen equivalent to the weight loss of the animals was recovered in the mineral nitrogen pool.The addition of litter (old beech leaf litter, freshly fallen beech and ash leaf litter) had a pronounced effect on both nitrogen net mineralization and N L values of the soil. Presence of old beech leaves caused an increase in both values, wheres the other litter types effected a decrease in nitrogen net mineralization. Fragmented ash litter was found to have the most distinct effect on N L values (-69%) and nitrogen net mineralization (-74%).


A qualitative study on user acceptance of a home-based stroke telerehabilitation system.
Objective: This paper reports a qualitative study of a home-based stroke telerehabilitation system. The telerehabilitation system delivers treatment sessions in the form of daily guided rehabilitation games, exercises, and stroke education in the patient's home. The aims of the current report are to investigate patient perceived benefits of and barriers to using the telerehabilitation system at home.Methods: We used a qualitative study design that involved in-depth semi-structured interviews with 13 participants who were patients in the subacute phase after stroke and had completed a six-week intervention using the home-based telerehabilitation system. Thematic analysis was conducted to analyze the data.Results: Participants mostly reported positive experiences with the telerehabilitation system. Benefits included observed improvements in limb functions, cognitive abilities, and emotional well-being. They also perceived the system easy to use due to the engaging experience and the convenience of conducting sessions at home. Meanwhile, participants pointed out the importance of considering technical support and physical environment at home. Further, family members' support helped them sustain in their rehabilitation. Finally, adjusting difficulty levels and visualizing patients' rehabilitation progress might help them in continued use of the telerehabilitation system.Conclusion: Telerehabilitation systems can be used as an efficient and user-friendly tool to deliver home-based stroke rehabilitation that enhance patients' physical recovery and mental and social-emotional wellbeing. Such systems need to be designed to offer engaging experience, display of recovery progress, and flexibility of schedule and location, with consideration of facilitating and social factors.


Atosiban and nifedipin for the treatment of preterm labor.
To perform a comparison between atosiban (oxytocin antagonist) and nifedipin (calcium channel blocker) for acute treatment of preterm labor and their maternal safety. A randomized controlled trial study was performed on 80 pregnant women with preterm labor, between 26 and 34 weeks of pregnancy, in Akbar Abadi Teaching Hospital in Tehran, Iran. 40 women (the atosiban group) were compared with another 40 women (the nifedipin group) for the drugs' efficacy in delaying delivery for more than 48 h in order to undergo steroid therapy, and for more than 7 days or more, and also to assess their maternal safety. The duration between the drugs' administration and delivery were compared. The statistical analysis was performed using the Statistical Package for Social Science (SPSS). There was no statistically significant difference between the two groups in the treatment of preterm labor. Atosiban was effective in 82.5% of cases, and nifedipin in 75% of the cases (p=1.000), for delaying delivery for 48 h. Atosiban was effective in 75% of the cases, and nifedipin in 65% of the cases, for delaying delivery for more than 7 days. The maternal side effects in the atosiban group were 17.5%, and in the nifedipin group they were 40%, which had a statistically significant difference (p=0.027). The duration between treatment and delivery was 29.03+/-16.12 days in the atosiban group and 22.85+/-13.9 days in the nifedipin group with no statistically significant difference (p=0.79). Atosiban is an effective and safe drug for the acute treatment of preterm labor with minimal side effects, and it can be an option in the treatment of preterm labor, especially in patients with heart disease and multi-fetal pregnancies.


Looking but not seeing: attention, perception, and eye movements in simultanagnosia.
We studied three subjects who reported the apparent "disappearance" of stationary objects from direct view. They had simultanagnosia caused by CT-verified bilateral superior occipital lobe lesions. They had no abnormalities of visual acuity or fields to explain their defect. EOG with computer analysis showed intact motility and scanning. Most important, the subjects reported intermittent disappearance of a light target during EOG-verified fixation--ie, they were looking but not seeing. Results indicate that attention mechanisms that permit sustained awareness of visual targets depend on the superior visual association cortices and are relatively separate from mechanisms that shift gaze and drive visual search.


Fabrication of zirconium (IV)-loaded chitosan/Fe3O4/graphene oxide for efficient removal of alizarin red from aqueous solution.
Zirconium(IV)-loaded chitosan/Fe3O4/graphene oxide (Zr-CMGO) was fabricated and applied to remove alizarin red (AR) from aqueous solution. Characterizations of Zr-CMGO were performed using several techniques. The effects of initial AR pH, coexisted NaCl, contact time and AR concentration were systematically investigated in batch mode. The increased pH had a negative effect on AR adsorption while there was little impact with salinity. Adsorption capacity toward AR reached up to 231 mg/g at 313 K. The kinetic and isotherm analyses indicated that pseudo-second-order kinetic model and Freundlich model could predicted the uptake of AR. In addition, the mechanism of AR adsorption could be mainly complexation, electrostatic force, etc. There is antibacterial activity from test about Zr-CMGO. Furthermore, the two-stage design could be applied for the theoretical support. Based on all results, Zr-CMGO is a novel and selective adsorbent for practical applications.


Neurophysiological and biochemical changes evoked by valproic acid in the central nervous system.
(1) Valproic acid is an anticonvulsant agent widely used in the management of various forms of epilepsy, including absence, myoclonic and tonic-clonic seizures. (2) It also has anticonvulsant potency in a wide variety of animal models of epilepsy. (3) This action is generally thought to be exerted through modulation of the activity of the endogenous inhibitory neurotransmitter, gamma-aminobutyric acid. (4) Evidence that valproic acid interacts with the gamma-aminobutyric acid system is presented. (5) Interactions of valproic acid with other neurotransmitters, i.e. aspartate, glutamate, taurine, serotonin, as well as with cyclic nucleotides and hormones are also considered. (6) Direct effects of valproic acid on excitable membranes and its relationships with analgesia are outlined.


Autonomic system tuning during gesture observation and reproduction.
Gestural communication allows providing information about thoughts and feelings, characterizing face-to-face interactions, also during non-verbal exchanges. In the present study, the autonomic responses and peripheral synchronization mechanisms of two individuals (encoder and decoder) were recorded simultaneously, through the use of biofeedback in hyperscanning, during two different experimental phases consisting in the observation (watching videos of gestures) and reproduction of positive and negative different types of gestures (affective, social and informative) supported by linguistic contexts. Therefore, the main aim of this study was focused on the analysis of simultaneous individuals' peripheral mechanisms during the performing of complex joint action, consisting of the observation (watching videos) and the reproduction of positive and negative social, affective, and informative gestures each supported by a linguistic script. Single-subject and inter-subject correlation analyses were conducted to observe individuals' autonomic responses and physiological synchronization. Single-subject results revealed an increase in emotional arousal, indicated by an increase in electrodermal activity (skin conductance level - SCL and response - SCR), during both the observation (watching videos) and reproduction of negative social and affective gestures contextualized by a linguistic context. Moreover, an increase of emotional engagement, expressed by an increase in heart rate (HR) activity, emerged in the encoder compare to the decoder during gestures reproduction (simulation of gestures). Inter-subject correlation results showed the presence of mirroring mechanisms, indicated by an increase in SCL, SCR, and HR synchronization, during the linguistic contexts and gesture observation (watching videos). Furthermore, an increase in SCL and SCR synchronization emerged during the observation (watching videos) and reproduction of negative social and affective gestures. Therefore, the present study allowed to obtain information on the mirroring mechanisms and physiological synchronization underlying the linguistic and gesture system during non-verbal interaction.


A comparison of the effects of different perfusion regimes on the structure of the isolated human placental lobule.
Isolated lobules of normal term human placentas were perfused using two different procedures. In the first more conventional system, open-circuit perfusion of both the maternal and the fetal circulations with Earle's solution containing dextran was established and maintained for either 30 min or 1 h. In the second series of experiments both circulations were perfused in separate closed circuits with a mixture of fresh autologous fetal blood and Earle's solution for 0, 1, 2 or 3 h. In both series the lobule was then fixed by perfusion through the fetal circulation. Light- and electron-microscopic examination of a set of tissue samples from each perfused lobule showed substantial differences between the effects of these two types of perfusion procedure. Tissue from lobules perfused by the open-circuit blood-free procedure showed patchy but severe cell swelling and vacuolation of the trophoblast after only one hour's perfusion. Particularly striking was swelling and disruption of a large proportion of the mitochondria in all placental cell types. By contrast, placental tissue from the closed-circuit perfusion with blood-containing medium showed little change over a period of two hours, while after three hours it showed oedema and microvillous damage, but no sign of cell swelling and little mitochondrial damage. It is concluded that the viability of the perfused human placental lobule depends on the type of perfusate used, and that the use of a fetal blood-enriched perfusate is of considerable value in maintenance of the preparation as assessed by structural criteria.


Impact of Hyponatremia on Morbidity, Mortality, and Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.
Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of hyponatremia on morbidity and mortality after SAH. We sought to determine the prevalence of hyponatremia after SAH, including in subgroups, as well as its effect on mortality and certain outcome measures, including degree of disability and duration of hospitalization. A search of terms "hyponatremia" and "subarachnoid hemorrhage" was performed on PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Studies were included if they reported prevalence of hyponatremia and if they discussed outcomes such as mortality, duration of stay, functional outcomes (e.g., Glasgow Outcomes Scale), or incidence of complications in patients with aneurysmal SAH. Two independent researchers assessed the titles and abstracts and reviewed articles for inclusion. Thirteen studies met inclusion criteria. The prevalence of at least mild hyponatremia was 859 of 2387 (36%) of patients. Hyponatremia was associated with vasospasm and duration of hospitalization, but it did not influence mortality. Hyponatremia is common after SAH, and there is evidence that it is associated with certain poorer outcomes. Larger, prospective studies are needed to assess these findings and provide further evidence.


Current Neurogenic and Neuroprotective Strategies to Prevent and Treat Neurodegenerative and Neuropsychiatric Disorders.
The adult central nervous system is commonly known to have a very limited regenerative capacity. The presence of functional stem cells in the brain can therefore be seen as a paradox, since in other organs these are known to counterbalance cell loss derived from pathological conditions. This fact has therefore raised the possibility to stimulate neural stem cell differentiation and proliferation or survival by either stem cell replacement therapy or direct administration of neurotrophic factors or other proneurogenic molecules, which in turn has also originated regenerative medicine for the treatment of otherwise incurable neurodegenerative and neuropsychiatric disorders that take a huge toll on society. This may be facilitated by the fact that many of these disorders converge on similar pathophysiological pathways: excitotoxicity, oxidative stress, neuroinflammation, mitochondrial failure, excessive intracellular calcium and apoptosis. This review will therefore focus on the most promising achievements in promoting neuroprotection and neuroregeneration reported to date.


Performance and Behavioural Responses of Group Housed Dairy Calves to Two Different Weaning Methods.
The weaning of dairy calves is a significant stressor which can impact on calf performance and welfare. However, many traditional methods of assessing the effects of stressors can be invasive and impractical for farmers. This study aimed to use a combination of non-invasive monitoring technologies alongside traditional measures of calf performance to examine the impact of two contrasting weaning methods commonly used on dairy farms in the United Kingdom. Ninety group-housed Holstein Friesian calves were allocated to one of two weaning methods: (i) gradual weaning (GW) with volume of milk replacer (MR) stepping down from 36 days of age and complete withdrawal of MR at 57 days of age and (ii) abrupt weaning (AW) with consistent daily volume of milk replacer and complete withdrawal of MR at 50 days of age. Feeding regimes were such that calves from both treatments were offered the same total amount of milk powder. Gradually weaned calves displayed increased solid feed intake at an earlier age when compared with AW calves. Feed conversion efficiency (FCE) was reduced in gradually weaned calves between days 36 and 49. However, there was no difference in live weight (LWT) or average daily gain (ADG) throughout this period. Abrupt weaning at 50 days of age resulted in decreased ADG and FCE between days 50 and 56. However, there were no treatment differences in ADG between days 57 and 62. Live weight tended to be increased by 2.2 kg in GW calves when compared with AW calves at the end of experiment on day 63. Frequency of unrewarded visits to the milk feeder throughout the pre-wean period was consistently increased in GW calves. Daily lying time was reduced in AW compared with GW calves in the days following abrupt weaning (days 50-55). However, these differences did not persist between days 57 and 62. Heart rate variability (HRV) tended to be decreased in GW compared with AW calves in the period following complete withdrawal of milk replacer. Findings from the current study suggest that calves offered the same total amount of milk powder can be weaned either gradually from 36 days of age or abruptly at 50 days of age without significant impact to live weight at 63 days of age. However, both behavioural and physiological data collected using the methods described could suggest that gradual weaning of calves from 36 days of age results in an increase in underlying frustration. This study highlights the potential of using a combination of non-invasive monitoring technologies in assessing calf response to common management practices.


Extracellular vesicles with diagnostic and therapeutic potential for prion diseases.
Prion diseases (PrD) or transmissible spongiform encephalopathies (TSE) are invariably fatal and pathogenic neurodegenerative disorders caused by the self-propagated misfolding of cellular prion protein (PrPC) to the neurotoxic pathogenic form (PrPTSE) via a yet undefined but profoundly complex mechanism. Despite several decades of research on PrD, the basic understanding of where and how PrPC is transformed to the misfolded, aggregation-prone and pathogenic PrPTSE remains elusive. The primary clinical hallmarks of PrD include vacuolation-associated spongiform changes and PrPTSE accumulation in neural tissue together with astrogliosis. The difficulty in unravelling the disease mechanisms has been related to the rare occurrence and long incubation period (over decades) followed by a very short clinical phase (few months). Additional challenge in unravelling the disease is implicated to the unique nature of the agent, its complexity and strain diversity, resulting in the heterogeneity of the clinical manifestations and potentially diverse disease mechanisms. Recent advances in tissue isolation and processing techniques have identified novel means of intercellular communication through extracellular vesicles (EVs) that contribute to PrPTSE transmission in PrD. This review will comprehensively discuss PrPTSE transmission and neurotoxicity, focusing on the role of EVs in disease progression, biomarker discovery and potential therapeutic agents for the treatment of PrD.


Anxiety Disorders in Primary Care.
Investigation for a possible anxiety disorder should be considered in patients with multiple or persistent anxiety symptoms or multiple somatic complaints without a clear somatic etiology. The ideal treatment for anxiety disorders is a combination of pharmacologic and behavioral strategies. As primary care health care evolves, it is expected that the management of mental health disorders (including anxiety disorders) will largely occur in the context of collaborative care models in which patients and primary care clinicians are assisted by trained case managers who help facilitate a more comprehensive, holistic treatment plan between primary care and mental health providers.


Optimization of cancer immunotherapy through pyroptosis: A pyroptosis-related signature predicts survival benefit and potential synergy for immunotherapy in glioma.
Pyroptosis is a critical type of programmed cell death that is strongly associated with the regulation of tumor and immune cell functions. However, the role of pyroptosis in tumor progression and remodeling of the tumor microenvironment in gliomas has not been extensively studied. Thus, in this study, we aimed to establish a comprehensive pyroptosis-related signature and uncover its potential clinical application in gliomas. The TCGA glioma cohort was obtained and divided into training and internal validation cohorts, while the CGGA glioma cohort was used as an external validation cohort. Unsupervised consensus clustering was performed to identify pyroptosis-related expression patterns. A Cox regression analysis was performed to establish a pyroptosis-related risk signature. Real-time quantitative PCR was performed to analyze the expression of signature genes in glioma tissues. Immune infiltration was analyzed and validated by immunohistochemical staining. The expression patterns of signature genes in different cell types were analyzed using single-cell RNA sequencing data. Finally, therapeutic responses to chemotherapy, immunotherapy, and potential small-molecule inhibitors were investigated. Patients with glioma were stratified into clusters 1 and 2 based on the expression patterns of pyroptosis-related genes. Cluster 2 showed a longer overall (P<0.001) and progression-free survival time (P<0.001) than Cluster 1. CD8+ T cell enrichment was observed in Cluster 1. A pyroptosis-related risk signature (PRRS) was then established. The high PRRS group showed a significantly poorer prognosis than the low PRRS group in the training cohort (P<0.001), with validation in the internal and external validation cohorts. Immunohistochemical staining demonstrated that CD8+ T cells were enriched in high PRRS glioma tissues. PRRS genes also showed cell-specific expression in tumor and immune cells. Moreover, the high PRRS risk group showed higher temozolomide sensitivity and increased response to anti-PD1 treatment in a glioblastoma immunotherapy cohort. Finally, Bcl-2 inhibitors were screened as candidates for adjunct immunotherapy of gliomas. The pyroptosis-related signature established in this study can be used to reliably predict clinical outcomes and immunotherapy responses in glioma patients. The correlation between the pyroptosis signature and the tumor immune microenvironment may be used to further guide the sensitization of glioma patients to immunotherapy.


Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.
COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. The study presented was conducted as part of the prospective CoVacSer cohort study. This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.


Introduction of a breast apparent diffusion coefficient category system (ADC-B) derived from a large multicenter MRI database.
To develop an intuitive and generally applicable system for the reporting, assessment, and documentation of ADC to complement standard BI-RADS criteria. This was a multicentric, retrospective analysis of 11 independently conducted institutional review board-approved studies from seven institutions performed between 2007 and 2019. Breast Apparent Diffusion coefficient (ADC-B) categories comprised ADC-B0 (ADC non-diagnostic), ADC-B1 (no enhancing lesion), and ADC-B2-5. The latter was defined by plotting ADC versus cumulative malignancy rates. Statistics comprised ANOVA with post hoc testing and ROC analysis. p values ≤ 0.05 were considered statistically significant. A total of 1625 patients (age: 55.9 years (± 13.8)) with 1736 pathologically verified breast lesions were included. The mean ADC (× 10-3 mm2/s) differed significantly between benign (1.45, SD .40) and malignant lesions (.95, SD .39), and between invasive (.92, SD .22) and in situ carcinomas (1.18, SD .30) (p < .001). The following ADC-B categories were identified: ADC-B0-ADC cannot be assessed; ADC-B1-no contrast-enhancing lesion; ADC-B2-ADC ≥ 1.9 (cumulative malignancy rate < 0.1%); ADC-B3-ADC 1.5 to < 1.9 (0.1-1.7%); ADC-B4-ADC 1.0 to < 1.5 (10-24.5%); and ADC-B5-ADC < 1.0 (> 24.5%). At the latter threshold, a positive predictive value of 95.8% (95% CI 0.94-0.97) for invasive versus non-invasive breast carcinomas was reached. The breast apparent diffusion coefficient system (ADC-B) provides a simple and widely applicable categorization scheme for assessment, documentation, and reporting of apparent diffusion coefficient values in contrast-enhancing breast lesions on MRI. The ADC-B system, based on diverse MRI examinations, is clinically relevant for stratifying breast cancer risk via apparent diffusion coefficient measurements, and complements BI-RADS for improved clinical decision-making and patient outcomes. • The breast apparent diffusion coefficient category system (ADC-B) is a simple tool for the assessment, documentation, and reporting of ADC values in contrast-enhancing breast lesions on MRI. • The categories comprise ADC-B0 for non-diagnostic examinations, ADC-B1 for examinations without an enhancing lesion, and ADC-B2-5 for enhancing lesions with an increasing malignancy rate. • The breast apparent diffusion coefficient category system may be used to complement BI-RADS in clinical decision-making.


Characterization and nutritional value of hydrothermal liquid products from distillers grains.
Hydrothermal liquid products (HLPs) produced by hydrothermal treatment (HTT) contain a large amount of nitrogen, phosphorus and other substances, while the environmental problems caused by arbitrary discharge. This work explored the effects of temperature, reaction time and solid-liquid ratio on the chemistry of HLPs of two different distillers grains, with a focus on nutrient composition. Increased HTT temperature was related to increased HLPs pH, dissolved organic carbon content, and aromaticity, and decreased electrical conductivity. Maximum nutrient extraction efficiencies observed for NH4+-N, NO3--N and PO43- were 92.0, 89.9, and 94.3%, respectively. Response surface methodology showed that the release of nutrient extraction efficiency was the greatest at the hydrothermal treatment of 200 °C for 1 h, and using a solid/liquid ratio of 10%. Comparative studies, the nutritional value of HLPs are appropriate for use as an agricultural fertilizer, and its use as a substitute for synthetic fertilizers could increase the sustainability and profitability of farming.


Suppression of HCT116 Human Colon Cancer Cell Motility by Polymethoxyflavones is Associated with Inhibition of Wnt/β-Catenin Signaling.
Aberrant regulation of the Wnt/β-catenin signaling pathway is one of the major causes of colorectal cancer (CRC). In this study, we examined the effect of polymethoxyflavones present in citrus peels on Wnt/β-catenin signaling in the HCT116 CRC cell line. We found that 5,7,3',4'-tetra-methoxyflavone (TMF) and 7,8,3',4'-TMF inhibited the expression of target genes of Wnt/β-catenin signaling and the transcriptional activities of β-catenin/Tcf and suppressed the motility of HCT116 cells. Because the binding of β-catenin to Tcf-4 was disrupted by 5,7,3',4'-TMF and 7,8,3',4'- TMF, we suggest that they are inhibitors of the Wnt/β-catenin signaling and may have potential applications in CRC prevention.


Photodynamic treatment of yeast cells with the dye toluidine blue: all-or-none loss of plasma membrane barrier properties.
Photodynamic treatment of Kluyveromyces marxianus with the sensitizer Toluidine blue leads to the loss of colony forming capacity. In this paper, the influence of this treatment on the barrier properties of the plasma membrane has been studied. Photodynamic treatment with the dye Toluidine blue resulted in efflux of potassium ions and E260-absorbing material. Moreover, cells became stainable with erythrosine. It is concluded that the permeability change induced by photodynamic treatment proceeds in an all-or-none fashion. Treatment of this yeast strain, with the dye and light, also induced a diminution of the cell volume. This process is most likely not coupled to the cellular potassium content, but rather to the integrity of the vacuole. These data suggest that the vacuole has an important function in the maintenance of cell volume. Finally, it was observed that the loss of cell viability was not induced by the all-or-none loss of barrier properties.


Early regeneration of Calluna heathland under various fertilization treatments.
A sod-cutting and fertilization experiment was performed on a Calluna-dominated heathland in The Netherlands to determine appropriate management regimes for Calluna regeneration, and to further understand the nutrient responses of heathland species. Replicated permanent plots were analysed by multivariate techniques. Sod-cutting alone caused Calluna regeneration from its soil seed bank. A single fertilization at the start of the experiment caused initial vegetation differences which disappeared after a few years as the nutrients were lost from the system, except that one application of nitrogen enhanced the rate of Calluna regeneration. Repeated fertilization caused large differences in the vegetation: repeated nitrogen enhanced several bryophyte species while greatly inhibiting Calluna, repeated phosphate partly inhibited Calluna while greatly favouring several lichen species, and the most striking result of repeated calcium was also an increase in bryophytes, but the species were different from those favoured by nitrogen. Treatments which inhibited Calluna tended to increase species diversity because of the lessened Calluna dominance.


Effect of anti-Helicobacter pylori therapy on outcome of iron-deficiency anemia: a randomized, controlled study.
Helicobacter pylori infection may play a role in iron-deficiency anemia. In 52 patients with iron-deficiency anemia, H. pylori status was determined using rapid urease test and histology. H. pylori -positive patients were randomly assigned to receive anti- H. pylori treatment either immediately (Group I) or after a delay of one month (Group II); in addition, all patients received oral ferrous sulfate for three months. Patients testing negative for H. pylori (Group III) received only oral ferrous sulfate. Hematological parameters were tested every month. Of 52 patients, 32 (61.5%) had H. pylori infection. At the end of one month, median increase in hemoglobin level was lower in Group II than in Groups I and III (1.1 g/dL vs. 3.6 g/dL and 1.9 g/dL, respectively; p=0.025), as were that in serum iron (19 mcg/dL vs. 55.5 mcg/dL and 41 mcg/dL; p=0.019). During the second month, after H. pylori infection in Group II had been treated, median increase in hemoglobin in this group was comparable to those in Groups I and III (3.7 g/dL vs. 2.5 g/dL and 2.5 g/dL. In patients with iron-deficiency anemia, presence of H. pylori infection is associated with a poorer response to oral iron therapy, which improves with treatment for H. pylori infection.


[The E.E.G. in ruptured cerebral aneurysms before operation. Use of carotid compression and the controlled hypotension test (author's transl)].
In 45 cases of ruptured intra-cranial aneurysms the authors studied the standard E.E.G. data under carotid compression and controlled hypotension; the changes observed were analysed and their value assessed for judging the state of the patient's cerebral circulation. A normal resting E.E.G. carries a good prognosis. Carotid compression and controlled hypotension provide a useful assessment of the supply and elasticity of the cerebral vessels; the occurrence of slow waves during controlled hypotension is an alarm signal which often helps in anaesthetic procedure.


A patient with congenitally restrictive strabismus and contralateral secondary muscle enlargement.
To report the case of a congenital restrictive strabismus with a contralateral enlargement of extraocular muscles. The clinical presentation, findings, and postoperative outcomes of a 4 years old boy referred to evaluation for presenting a left eye deviation since birth are detailed. A unilateral congenital restrictive strabismus (congenital hypotropia and esotropia) can be the cause of contralateral secondary enlarged extraocular muscle and It must be included in the differential diagnosis.


Sexual and Gender Minority Persons' Perception of the Female Sexual Function Index.
Patient-reported outcome instruments to assess sexual functioning typically assume that patients are heterosexual and have a single sexual partner, thus they may have limited applicability for sexual and gender minority (SGM) populations as well as for nonpartnered individuals or those with multiple partners. To explore the perceptions of SGM persons regarding the Female Sexual Function Index (FSFI), a commonly used sexual functioning questionnaire. We conducted 2 rounds of cognitive interviews with 27 SGM persons with and without a cancer diagnosis. Interviews were audio-recorded and transcribed. Two researchers independently coded the transcripts using inductive thematic analysis to identify major themes. Themes identified via qualitative analysis. Cognitive debriefing with the participants provided critical insights about the way we ask questions about sexual functioning in the oncology clinic. Three overarching themes arose from the data: (i) Certain aspects of the questionnaire were felt to unnecessarily medicalize sexuality; (ii) FSFI domains were perceived to represent a narrow and heteronormative experience of sexuality focused on penile-vaginal intercourse; (iii) Questionnaire domains emphasizing sexual "performance" were perceived as male-oriented. Questionnaires such as the FSFI that were developed in research studies with specific eligibility criteria need to be adapted to the broader population seen in clinical practice. Strengths of the study include purposive sampling of SGM persons through LGBTQ networks. Our sample included individuals of different sexual orientations, gender identities, marital status, and cancer histories. However, a limitation is that the the majority of the sample was white and college-educated. Other limitations of the study include the potential sampling bias of self-selected participants with a particular interest in the study questions. The findings provide important evidence for the development of a more inclusive sexual function measure, moving away from the traditional heteronormative, cisnormative approach to measuring sexual function. Austria MD, Lynch K, Le T, et al. Sexual and Gender Minority Persons' Perception of the Female Sexual Function Index. J Sex Med 2021;18:2020-2027.


Novel cyclic azo-bridged analogs of gonadotropin-releasing hormone.
Five linear analogs of GnRH containing a p-aminophenylalanine (Pap) residue in their sequence and their six corresponding azo-bridged cyclic derivatives were synthesized. The precyclic peptides were prepared on solid-support, while azo-cyclization was performed in solution by diazotization of the p-aminophenylalanine residue followed by intramolecular coupling of the formed diazo salt with either tyrosine or histidine side chains present in the sequence. All peptides were examined for their binding ability to the GnRH receptor expressed on rat pituitary membranes and for their LH-release activity from dispersed rat pituitary cells. Linear analogs 1 i.e [Pap(5)] GnRH and 3, i.e. [Tyr(3), Pap(5)] GnRH, were found to bind to the GnRH receptors only slightly less avidly than native GnRH. Their cyclization, however, led to a marked reduction in the binding capacity, i.e. from IC(50) of 10(-9) M to the 10(-7) M range, and in biopotency, i.e. LH-release. All other linear and cyclic peptides were found to bind selectively to the GnRH receptor only in the low microM range. Only peptide 1 was found comparable to native GnRH in respect to LH-release activity and thus may potentially be a good agonist of the parent peptide. Peptides 1-4, the most potent GnRH receptor binders, were examined for their conformational properties using CD. Cyclic-azo peptides 2 and 4 were further evaluated by NMR spectroscopy in solution combined with molecular modeling. The structural information obtained explains in part the GnRH-like biological activity observed.


Detection and genotyping of vancomycin-resistant Enterococcus spp. by multiplex polymerase chain reaction in Korean aquatic environmental samples.
The distribution characteristics of Enterococcus spp., which are indicators of fecal pollution, were investigated at 33 sites within the 3 major water systems of Korea. Enterococci were detected at concentrations ranging from 1 to 37 CFU/100mL in 41 of 132 samples (31.1%) from the 3 major water systems. The overall average detected concentration was 1.2 CFU/100mL, while the average concentration for all detection sites was 5.3 CFU/100mL. After optimized multiplex polymerase chain reaction (PCR) was performed with newly developed VanA, VanB, VanC-1, and VanC-2/3 primers, concentrations of vancomycin-resistant Enterococcus spp. (VRE) ranging from 1 to 23 CFU/100mL were detected in 17 of 132 samples (12.9%). Of 216 individual enterococcal colonies, 64 (29.6%) displayed the VanC genotype. The results of a susceptibility test to vancomycin showed that the range of the minimal inhibitory concentration (MIC), an indicator of bacterial resistance, was 4 to 24μg/mL, with the average MIC at 9.2±4.5μg/mL. Of the bacterial isolates, 1 colony with the VanC-1 genotype was identified as E. gallinarum by 16S rDNA sequencing, whereas the other 63 colonies had the VanC-2/3 genotype and were identified as E. casseliflavus. Although these results imply that the major head bays of Korea are not contaminated with the highly vancomycin-resistant VanA- or VanB-type VREs, the misuse of antibiotics should be prohibited to minimize the presence of VREs and to maintain a safe water supply for protecting the health of the general population. Based on the study results, we also recommend the implementation of a continuous, broad-spectrum inspection program for Enterococcus spp. and VRE contamination in the major head bays. Furthermore, the multiplex PCR method described in this study can be used effectively for this purpose.


Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST).
This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan. Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD). A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure. Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136). Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.


Identification of potential biomarkers in malnutrition children with severity by 1H-NMR-based metabolomics: a preliminary study in the Chinese population.
Child malnutrition is a global public health problem, but the underlying pathophysiologic mechanisms with severity remain poorly understood, and the potential biomarkers served to the clinical diagnosis are still not available. This study aimed to identify the serum metabolic characteristics of malnourished children with severity. Fasted overnight serum samples were collected following clinical standard procedures among 275 malnourished and 199 healthy children from the Women and Children's Hospital, Xiamen University Child Health Department from July 2020 to May 2022. Nuclear magnetic resonance (NMR)-based metabolomics strategy was applied to identify the potential serum biomarkers of malnutrition from 275 malnourished children aged 4 to 84 months with mild (Mil, 199 cases), moderate (Mod, 101 cases), and severe (Sev, 7 cases) malnutrition. Ten, fifteen, and fifteen differential metabolites were identified from the Mil, Mod, and Sev malnutrition groups, respectively. Eight common metabolites, including increased acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, and decreased alanine, methionine, and N-acetyl-glycoprotein, could be the potential biomarkers for malnourished children. The altered metabolic pathways were mainly related to energy metabolism and amino acid metabolism via the network-based pathway enrichment. Eight potential biomarkers, including acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, alanine, methionine, and N-acetyl-glycoprotein, could characterize the child malnutrition. Child malnutrition-induced abnormal energy metabolism, impaired nutrition utilization and the reduced nutrient availability, and more metabolic disturbance will appear with the severity. Our results are valuable for further studies on the etiology and pathogenesis of malnutrition for clinical intervention and improvement.


Transcriptional and cell cycle-mediated regulation of myosin heavy chain gene expression during muscle cell differentiation.
The molecular mechanisms regulating the induction of myosin heavy chain (MHC) gene expression during muscle cell differentiation were studied using a MHC cDNA recombinant plasmid. During in vitro L6E9 cell myogenesis, cytoplasmic MHC mRNA content/cell nucleus increases a minimum of 500-fold during the first 6 days of differentiation. Two independent parameters regulating MHC mRNA accumulation were directly measured. (i) Intrinsic (chemical) MHC mRNA stability (t1/2 = 55-60 h) is the same in both myotubes and when first detected in myoblasts. This suggests that the intrinsic stability of the MHC mRNA molecule does not change during myogenesis. (ii) The rate of MHC gene transcription and MHC mRNA synthesis increases approximately 100-fold during myogenesis but is insufficient to account for the entire MHC mRNA accumulation. An additional independent parameter was found to profoundly affect MHC mRNA accumulation. Withdrawal from the cell cycle, as occurs during terminal myogenic differentiation, increases the final accumulation of stable mRNAs, such as MHC, by increasing mRNA effective stability. During L6E9 myogenesis, the transition from mitotically active myoblasts (doubling time = 16 h) to postmitotic myotubes results in a 4-5-fold increase in the effective stability of cytoplasmic MHC mRNA. This cell cycle-mediated effect, combined with the induction of MHC mRNA synthesis, completely accounts for MHC mRNA accumulation. A parallel effect occurs in the total cytoplasmic poly(A)+ mRNA population. The rates of synthesis of each of the two major stability components (t1/2 = 5 and 50 h, respectively) are equally increased 2-3-fold during myogenesis. However, the composition of the cytoplasmic mRNA population changes due to the preferential accumulation of stable mRNAs. We conclude that both transcriptional and cell cycle-mediated regulation of MHC gene expression is necessary, but either alone is not sufficient to produce the differentiated muscle cell phenotype.


Enhanced properties of non-starch polysaccharide and protein hydrocolloids through plasma treatment: A review.
Hydrocolloids are important ingredients in food formulations and their modification can lead to novel ingredients with unique functionalities beyond their nutritional value. Cold plasma is a promising technology for the modification of food biopolymers due to its non-toxic and eco-friendly nature. This review discusses the recent published studies on the effects of cold plasma treatment on non-starch hydrocolloids and their derivatives. It covers the common phenomena that occur during plasma treatment, including ionization, etching effect, surface modification, and ashing effect, and how they contribute to various changes in food biopolymers. The effects of plasma treatment on important properties such as color, crystallinity, chemical structure, rheological behavior, and thermal properties of non-starch hydrocolloids and their derivatives are also discussed. In addition, this review highlights the potential of cold plasma treatment to enhance the functionality of food biopolymers and improve the quality of food products. The mechanisms underlying the effects of plasma treatment on food biopolymers, which can be useful for future research in this area, are also discussed. Overall, this review paper presents a comprehensive overview of the current knowledge in the field of cold plasma treatment of non-starch hydrocolloids and their derivatives and highlights the areas that require further investigation.


Urinary epidermal growth factor/monocyte chemotactic peptide 1 ratio as non-invasive predictor of Mayo clinic imaging classes in autosomal dominant polycystic kidney disease.
Age- and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes. Urinary epidermal growth factor and monocyte chemotactic peptide 1 levels were measured in two independent cohorts (discovery, n = 74 and validation set, n = 177) and healthy controls (n = 59) by immunological assay. Magnetic resonance imaging parameters were used for total kidney volume calculation and the Mayo Clinic Imaging Classification defined slow (1A-1B) and fast progressors (1C-1E). Microarray and quantitative gene expression analysis were used to test epidermal growth factor and monocyte chemotactic peptide 1 gene expression. Baseline ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 correlated with total kidney volume adjusted for height (r = - 0.6, p < 0.001), estimated glomerular filtration rate (r = 0.69 p < 0.001), discriminated between Mayo Clinic Imaging Classes (p < 0.001), and predicted the variation of estimated glomerular filtration rate at 10 years (r = - 0.51, p < 0.001). Conditional Inference Trees identified cut-off levels of the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for slow and fast progressors at > 132 (100% slow) and < 25.76 (89% and 86% fast, according to age), with 94% sensitivity and 66% specificity (p = 6.51E-16). Further, the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 at baseline showed a positive correlation (p = 0.006, r = 0.36) with renal outcome (delta-estimated glomerular filtration rate per year, over a mean follow-up of 4.2 ± 1.2 years). Changes in the urinary epidermal growth factor and monocyte chemotactic peptide 1 were mirrored by gene expression levels in both human kidney cysts (epidermal growth factor: - 5.6-fold, fdr = 0.001; monocyte chemotactic peptide 1: 3.1-fold, fdr = 0.03) and Pkd1 knock-out mouse kidney (Egf: - 14.8-fold, fdr = 2.37E-20, Mcp1: 2.8-fold, fdr = 6.82E-15). The ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 is a non-invasive pathophysiological biomarker that can be used for clinical risk stratification in autosomal dominant polycystic kidney disease.


Aminoacylase I from porcine kidney: identification and characterization of two major protein domains.
The domain structure of hog-kidney aminoacylase I was studied by limited proteolytic digestion with trypsin and characterization of the resulting fragments. In the native enzyme, the sequences from residue 6 to 196 and 307 to 406 are resistant to trypsin and remain tightly bound in nondenaturing solvents, while the intervening sequence (197-306) is efficiently degraded by trypsin. We conclude that the N-terminal half of the molecule and its C-terminal fourth form two independently folded domains. Both contain a peculiar PWW(A,L) sequence motif preceded by several strongly polar residues. We propose that these sequences form surface loops that mediate the membrane association of aminoacyclase I. We further show that the three free cysteine residues and the essential Zn2+ ion reside in the trypsin-resistant domains, while the intervening sequence contains the only disulfide H bond of the protein.


HIV infection among patients with sexually transmitted diseases in rural South Africa.
A cross-sectional study of 360 patients presenting with sexually transmitted diseases (STDs) to a primary care clinic in KwaZulu/Natal, South Africa was done. Prevalence of HIV infection was 42.5%. HIV-infected patients were of similar age to uninfected patients (mean age 25.1 vs 26.1 years), but were less likely to be married (9.2% vs 18.8%; P=0.02). HIV prevalence was highest among young women (47.9% among women aged 15-34 years compared with 33.1% among men of the same age; P=0.03). History of a previous STD in the preceding 3 months was high (40.1% in HIV-infected patients). Similar proportions of the HIV-infected and HIV-uninfected had sought care for the previous illness at private practitioners (16.9%), and primary care clinics (50.0%), and traditional healers (14.6%) or had treated themselves (18.5%). Patients with an STD are at very high risk of HIV infection in this setting. Repeat STDs are frequent and opportunities exist to improve treatment seeking behaviour, to reduce the risk of recurrent STDs, and hence to reduce the incidence of HIV infection.


Effects of the semi-dwarfing sdw1/denso gene in barley.
Recent advances in cereal genomics have made it possible to analyse the architecture of cereal genomes and their expressed components, leading to an increase in our knowledge of those genes that are associated with the key agronomical traits. Presently, use of a dwarfing gene in breeding process is crucial for the development of modern cultivars. In barley, more than 30 types of dwarfs or semi-dwarfs have been hitherto described. However, only a few of them have been successfully used in barley breeding programs. Both breeding and molecular mapping experiments were undertaken to enhance and evaluate the performance of semi-dwarf barley lines. The semi-dwarfing cultivars had improved lodging resistance and a higher harvest index. There have been a lot of investigations that have contributed new information to our basic understanding of the mechanisms underlying growth regulations in barley. This paper reviews semi-dwarfing genes in barley in general and special attention is paid to mapping of the sdw1/denso locus, changes in protein abundance and associations of the semi-dwarfness with gibberellins.


Effects of thyroxine on methionine adenosyltransferase activity in rat cerebral cortex and cerebellum during postnatal development.
Methionine adenosyltransferase (MAT) activity was evaluated in cerebral cortex and cerebellum in controls and in rats treated with thyroxine. In controls the enzyme showed a different pattern in cerebral cortex and cerebellum during neonatal and late suckling periods. Hyperthyroid rats showed a significant increase of the enzyme in cerebral cortex only at the 2nd day of the neonatal period; in cerebellum the developmental pattern of MAT in neonatal period was anticipated temporally by 2-4 days. During the late suckling period thyroxine treatment produced in cerebellum a significant decrease in MAT activity at the 15th day after birth. From these data, we propose that hyperthyroidism may cause precocious induction of MAT both in cerebral cortex and in cerebellum and that the increased availability of S-adenosyl-L-methionine during the neonatal period could be related to its utilization also in polyamine biosynthesis.