Detection and preliminary characterization of two enzymes involved in biosynthesis of platelet-activating factor in mouse oocytes, zygotes and preimplantation embryos: dithiothreitol-insensitive cytidinediphosphocholine: 1-O-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase and acetyl-coenzyme A:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase.
The aim of this study was to determine whether the final enzymes in the two biosynthetic pathways for platelet-activating factor (PAF) (the 'de novo' and the 'membrane remodelling' pathways) are present in mouse embryos, zygotes and oocytes. The enzymes are dithiothreitol-insensitive cytidinediphosphocholine: 1-O-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (cholinephosphotransferase) in the de novo pathway and acetyl-coenzyme A:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase (acetyltransferase) in the membrane remodelling pathway. Activity of both enzymes was detected in the unfertilized oocyte, the zygote and also in the preimplantation embryo (48, 72 and 96 h after the ovulatory injection of hCG). In both cases the activity was destroyed by boiling and increased linearly with incubation time and the concentration of embryo homogenate present, indicating that the reactions were catalysed by enzymes. The product of the reactions was confirmed as PAF using HPLC and structural analyses by enzymatic digestion. Cholinephosphotransferase required Mg2+ and was inhibited by Ca2+, while acetyltransferase required the presence of NaF (a phosphatase inhibitor). The activity of cholinephosphotransferase was similar in unfertilized oocytes and zygotes, and did not change significantly with advancing developmental stage in preimplantation embryos. Acetyltransferase had a significantly lower specific activity (0.078 +/- 0.044 fmol PAF per oocyte per min, mean +/- SEM) in unfertilized oocytes than in zygotes of corresponding age (0.358 +/- 0.097 fmol PAF per zygote per min) (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)


Injectable biomaterials for incontinence and vesico-ureteral reflux: current status and future promise.
Many injectable biomaterials have been produced as bulking agents for compression of urethral sphincter or ureteral orifice for treating adult stress incontinence or vesico-ureteral reflux in pediatrics. The agents being developed include glutaraldehyde crosslinked collagen, dextranomer/hyaluronic acid copolymer, pyrolytic carbon-coated zirconium oxide beads, polydimethyl-siloxane microparticles, polytetrafluoroethylene paste, autologous fats, autologous chondrocytes, and others. Though less invasive nature of these agents has gained their popularity as a quick solution of the disease symptoms, most of such treatments fail to produce good long-term efficacy. The failure is likely caused by the rapid degradation of material implants and the lack of tissue regeneration/integration properties. We thus believe that a good injectable biomaterial for incontinence should possess the following two properties: (1) to resist degradation and to reside in the implantation sites for a long period of time or (2) to enhance tissue regeneration and to establish permanent periurethral or subureteric tissue. Here we report some recent results for supporting this hypothesis.


[Bacteremia: a Spanish multicenter study with 5000 cases. The Hospital Infection Study Group (GEIH)].
Bacteremia is one of the most common nosocomial infections and is still a severe condition that frequently represents a life-threatening problem for the patient. SEPSIS DATA is a software programme developed by the SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) nosocomial infection study group, and it has been designed to collect under common criteria bacteremia cases from Spanish hospitals. In this study, we analyse the results from the first 5,000 cases prospectively collected from 34 hospitals with the following distribution by number of beds: 8 hospitals with less than 200, 15 between 200 and 499.6 between 500 and 999 and 5 with more than 1,000 beds. Male patients (60%), older than 61 years (52%) are the predominant group. Bacteremia acquisition was extra-hospital in 58% of the cases. Most frequent underlying disease was neoplasm (22%) and 9% of the patients had HIV infection. Most frequent bacteremia sources were urinary tract (19.6%), primary (16%) and respiratory tract (15%). Most commonly isolated micro-organisms were E. coli (23%). S. aureus (13%), coagulase-negative Staphylococci (12%) and S. pneumoniae (8%). Microorganisms average time to grow in laboratory was 1.95 days. Origin focus of bacteremia was reported in 30% of the cases. Antibiotic therapy used was active against pathogen isolate in 96% of the cases. Adequate treatment was started empirically from the first day in 76% of the cases. Third generation cephalosporines were the antibiotic group most used (28%). Among the observed complications, 7.68% of the episodes occurred with shock and 2.68% with septic metastasis. Crude mortality until the end of episode was 16.64%.


Unravelling the structural complexity of protein-lipid interactions with neutron reflectometry.
Neutron reflectometry (NR) is a large-facility technique used to examine structure at interfaces. In this brief review an introduction to the utilisation of NR in the study of protein-lipid interactions is given. Cold neutron beams penetrate matter deeply, have low energies, wavelengths in the Ångstrom regime and are sensitive to light elements. High differential hydrogen sensitivity (between protium and deuterium) enables solution and sample isotopic labelling to be utilised to enhance or diminish the scattering signal of individual components within complex biological structures. The combination of these effects means NR can probe buried structures such as those at the solid-liquid interface and encode molecular level structural information on interfacial protein-lipid complexes revealing the relative distribution of components as well as the overall structure. Model biological membrane sample systems can be structurally probed to examine phenomena such as antimicrobial mode of activity, as well as structural and mechanistic properties peripheral/integral proteins within membrane complexes. Here, the example of the antimicrobial protein α1-purothionin binding to a model Gram negative bacterial outer membrane is used to highlight the utilisation of this technique, detailing how changes in the protein/lipid distributions across the membrane before and after the protein interaction can be easily encoded using hydrogen isotope labelling.


Nordihydroguaiaretic acid activates hTRPA1 and modulates behavioral responses to noxious cold in mice.
Nordihydroguaiaretic acid (NDGA) is a major biologically active component of the creosote bush, Larrea tridentate, widely used in unregulated therapies. NDGA is a lipoxygenase inhibitor while a derivative, terameprocol, has been trialed as a chemotherapeutic agent. When investigating fatty acid activation of the human transient receptor potential cation channel subfamily A, member 1 (hTRPA1), we found that NDGA activated the channel. Here we investigate the actions of NDGA and terameprocol at hTRPA1 and the consequences of this for noxious cold sensitivity in mice. hTRPA1 was stably expressed in HEK 293 cells (HEK 293-TRPA1) and channel activity examined by measuring changes in intracellular calcium ([Ca]i) using a fluorescent dye and activation of membrane currents using patch clamp electrophysiology. The effects of local NDGA and terameprocol application on acetone-induced paw flinching were examined in mice. NDGA (pEC50 of 5.4 ± 0.1, maximum change in fluorescence of 385 ± 30%) and terameprocol (pEC50 4.5 ± 0.2, maximum 550 ± 75%) increased [Ca]i in HEK 293-hTRPA1 cells. NDGA also induced an increase in membrane conductance in HEK 293-hTRPA1 cells. These effects were prevented by the TRPA1 antagonist HC-030031, and were dependent on the presence of Cys621, Cys 641, and Cys 665 in hTRPA1. Neither NDGA nor terameprocol alone produced spontaneous pain behaviors in mice after hind paw injection, but both enhanced responses to acetone. NDGA and terameprocol are efficacious activators of TRPA1. NDGA should be used with care to probe lipoxygenase involvement in nociception while TRPA1 activity should be considered when considering use of these drugs in humans.


Application of some chemometric methods in conventional and derivative spectrophotometric analysis of acetaminophen and ascorbic acid.
The multivariate methods, principal component regression (PCR) and partial least squares (PLS) were tested as a calibration procedure for simultaneous ultraviolet spectrophotometric determination of acetaminophen (AC) and ascorbic acid (AA). Determination of these compounds is important because of their pharmacotherapeutic advantages. Due to spectral overlapping of AC and AA, PCR and PLS were used for construction of the calibration sets. The concentration linear range of AC and AA were 1.5-24.2 and 1.8-21.1 microg mL(-1) respectively. The absorption spectra were recorded from 215-310 nm. The minimum root mean square error of prediction (RMSEP) was 1.3507 and 0.4088 for AC and AA, by PLS, 0.7525 and 0.4015 by PCR in original data and 0.9454 and 0.2875, by PLS and 1.0386 and 0.4000 by PCR in derivative data. The procedure allows the simultaneous determination of AC and AA in synthetic mixtures and real sample solutions made up from pharmaceutical products, human serum and urine.


Bis(imino)phenoxide complexes of aluminium.
Reaction of Me(3)Al (one equivalent) with the bis(imino)phenol, [2,6-(ArNCH)(2)-4-MeC(6)H(2)OH] (I)(Ar = 2,6-Pr(i)(2)C(6)H(3)) in toluene at ambient temperature yields the yellow complex [Me(2)Al[2,6-(ArNCH)(2)-4-MeC(6)H(2)O]](1). Interaction of two equivalents of Me(3)Al in refluxing toluene affords the red complex [(Me(2)Al)(2)[2-ArNCH(Me)-6-(ArNCH)-4-MeC(6)H(2)O]](2). Similar interaction (two equivalents, refluxing toluene) of MeAlCl(2) or (i)Bu(3)Al with [2,6-(ArNCH)(2)-4-MeC(6)H(2)OH] affords [ClAl[2,6-(ArNCH)(2)-4-MeC(6)H(2)O](2)](3) or [(i)Bu(2)Al[2,6-(ArNCH)(2)-4-MeC(6)H(2)O]](4), respectively. Hydrolysis of 2 readily affords the iminoaminophenol ligand [2-(ArN=CH)-6-ArNHCH(Me)-4-MeC(6)H(2)OH](II), which reacts further with Me(3)Al to afford [Me(2)Al[2-ArNCH(Me)-6-(ArNCH)-4-MeC(6)H(2)O]](5). An X-ray study on reveals bidentate imino-alkoxide ligation about the distorted aluminium centre, whereas is a binuclear structure with tetrahedral aluminiums ligated by imino-alkoxide and amido-alkoxide ligand fragments, respectively. For and bidentate imino-alkoxide ligation is observed.


Dietary salt intake and blood pressure in a representative Japanese population: baseline analyses of NIPPON DATA80.
The relationship between dietary salt intake and blood pressure (BP) has been rarely investigated in a large population of Japanese. The characteristics of nutrients intake and foods intake in Japanese people with high salt intake have also not investigated well. Data of 10,422 participants (4585 men and 5837 women) aged 30 or older who participated in both the National Survey on Circulatory Disorders and National Nutrition Survey in Japan conducted in 1980 were used. The nutrition surveys were performed with weighing record method for three consecutive days to each household. BP and intakes of nutrients and foods were compared by the quintiles of estimated individual salt intake per day. Analyses of covariance were used to calculate multivariate-adjusted mean BP values by the quintiles. Participants with higher salt intake showed higher intakes of soy beans/legume, fruit, other vegetables, and fish/shellfish. Intakes of protein, potassium, calcium, iron, magnesium, and fiber were higher in higher quintiles of salt intake. In men, adjusted systolic BPs were higher in the higher salt intake quintiles; there was 4.3 mm Hg difference in multivariate-adjusted systolic BP between the lowest quintile (mean salt intake 8.7 g/day) and the highest quintile (mean salt intake 23.5 g/day) (P < 0.001). In women, adjusted mean systolic BPs were not statistically different among the quintile of salt intake. A positive relationship of dietary salt intake to BP was observed, especially in men, in this large-scale representative Japanese population.


Humoral assays of human sera to disrupted and nondisrupted epitopes of human papillomavirus type 1.
The use of different assay systems and the disparity in results obtained has meant that we have little understanding about the role played by the humoral response during human papillomavirus (HPV) infection. Human antibody responses have so far appeared to be largely directed against the major capsid protein, L1. This protein possesses both type-specific and type-common antigenic determinants but it is not known which of these is important in vivo during the natural course of infection. In this study humoral responses of 83 individuals to purified HPV 1 virions were tested in three types of antibody assay. Western blot analysis detected antibodies in only eight of the serum samples, whereas an enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation assay using nondisrupted HPV 1 virions showed positive antibody reactivities for 71 and 64 individuals, respectively. We suggest from these results that the humoral response to L1 is mainly directed against native conformational epitopes present on the whole HPV 1 particle and that type-common epitopes are not largely involved. This was further demonstrated by the fact that when samples were tested in the same ELISA system using disrupted HPV 1 virions as the antigen instead of whole virus particles, the number of positive sera was reduced to 9 out of 83. We further conclude that humoral assays using antigenic material pertaining to disrupted HPV epitopes are of limited use, at least in the case of HPV type 1. There were no obvious correlations between the antibody assay results and clinical histories of wart infection except that a lower number of positive serum reactivities were found among the group of individuals claiming to have no past history of HPV infection.


A new step to the mechanism of the enhancement effect of gold nanoparticles on glucose oxidase.
Quantum size effect was strongly supported by the experiment on correlation between size of gold nanoparticles (below 10 nm) and activity of glucose oxidase attached to them. The attractive enhancement effect of gold nanoparticles on the activity of glucose oxidase was then satisfactorily explained. In this experiment, 2 nm and 6 nm (average diameter) particles were obtained on monolayer matrix. The 2 nm particles proved to be much more able to increase the activity of glucose oxidase.


The influence of superficial dermatophytoses epidemic in India on patients' quality of life.
Superficial dermatophytoses constitute a common and growing problem in India. However, the associated impact on the affected individuals' quality of life (QoL) has rarely been investigated. To assess the quality of life of patients with different dermatophytoses. Among 100 consecutive Indian patients with dermatophytosis, 76% agreed to participate. The diagnosis was established upon the typical clinical manifestation and direct microscopic mycological examination (10% KOH). Dermatology Life Quality Index (DLQI) was utilized to assess QoL impairment. Participants evaluated the presence and intensity of itch during the last 3 days using Numeral Rating Scale (NRS). A combination of tinea corporis and tinea cruris was diagnosed most commonly (52.6%), followed by tinea cruris alone (21%) and tinea corporis alone (13.2%). The mean duration of the disease was assessed as 6.3 ±18.0 months. The mean DLQI score was 8.2 ±5.1 points. A very large and extremely large effect on the DLQI was reported by 26.3% of patients, moderate by 40.8%, whereas small by 29%, with females being more heavily affected than males (9.3 ±5.2 and 7.1 ±4.7 points, respectively) (p = 0.038). Patients with a combination of tinea corporis, tinea cruris and tinea faciei demonstrated the lowest QoL (11.0 ±4.5 points). Additionally, a significant correlation between impairment of QoL and itch intensity (mean NRS score: 6.8 ±1.8 points) (r = 0.37; p < 0.002) was documented. Moreover, there was a trend towards lower QoL in patients who have been previously treated with topical agents containing corticosteroids. Superficial dermatophytoses are associated with a moderate impact on QoL of the affected subjects.


Differential diagnosis and molecular characterization of Theileria spp. in sika deer (Cervus nippon) in Hokkaido, Japan.
Sika deer (Cervus nippon) is widely distributed in Asian countries and is one of the most common wildlife animals in Hokkaido, Japan. Previous studies identified Theileria spp. in sika deer in Japan including Theileria sp. Thrivae belonging to T. cervi group and Theileria sp. sola belonging to T. capreoli group. However, the studies failed to differentiate these two species without sequencing. Therefore, epidemiological information on cervine theileriosis in Hokkaido, Japan is limited. This study differentiated the two Theileria spp. using restriction fragments length polymorphism (RFLP). Based on the PCR-RFLP, Theileria spp. were identified in 103 (88.0%) of 117 samples, and the prevalence of each parasites were 86.3% (n = 101) and 57.3% (n = 67) for Theileria sp. Thrivae and T. capreoli-like, respectively. Phylogenetic analysis based on the 18S rRNA showed a close relationship between Theileria sp. Thrivae and T. cervi in China. In addition, phylogenetic analysis of internal transcribed spacer regions also showed a close relationship between Theileria sp. Thrivae and T. cervi.


Is there evidence to support serum antinuclear antibodies testing in women with recurrent implantation failure undergoing in vitro fertilization?
One of the most challenging aspects of reproductive medicine is the management of recurrent implantation failure. Various investigations, including antinuclear antibodies testing, are performed to seek an explanation and guide treatment. However, is there sufficient evidence or available therapeutic options to support antinuclear antibodies testing? We present a short review on the current literature and an attempt at a systematic review evaluating the association between antinuclear antibodies and recurrent implantation failure to address this question.


Turning I into me: Imagining your future self.
A widely endorsed belief is that perceivers imagine their present selves using a different representational format than imagining their future selves (i.e., near future=first-person; distant future=third-person). But is this really the case? Responding to the paucity of work on this topic, here we considered how temporal distance influences the extent to which individuals direct their attention outward or inward during a brief imaginary episode. Using a non-verbal measure of visual perspective taking (i.e., letter-drawing task) our results confirmed the hypothesized relation between temporal distance and conceptions of the self. Whereas simulations of an event in the near future were dominated by a first-person representation of the self, this switched to a third-person depiction when the event was located in the distant future. Critically, this switch in vantage point was restricted to self-related simulations. The theoretical and practical implications of these findings are considered.


Molecular characterization and expression analysis of Triticum aestivum squamosa-promoter binding protein-box genes involved in ear development.
Wheat (Triticum aestivum L.) is one of the most important crops in the world. Squamosa-promoter binding protein (SBP)-box genes play a critical role in regulating flower and fruit development. In this study, 10 novel SBP-box genes (TaSPL genes) were isolated from wheat ((Triticum aestivum L.) cultivar Yanzhan 4110). Phylogenetic analysis classified the TaSPL genes into five groups (G1-G5). The motif combinations and expression patterns of the TaSPL genes varied among the five groups with each having own distinctive characteristics: TaSPL20/21 in G1 and TaSPL17 in G2 mainly expressed in the shoot apical meristem and the young ear, and their expression levels responded to development of the ear; TaSPL6/15 belonging to G3 were upregulated and TaSPL1/23 in G4 were downregulated during grain development; the gene in G5 (TaSPL3) expressed constitutively. Thus, the consistency of the phylogenetic analysis, motif compositions, and expression patterns of the TaSPL genes revealed specific gene structures and functions. On the other hand, the diverse gene structures and different expression patterns suggested that wheat SBP-box genes have a wide range of functions. The results also suggest a potential role for wheat SBP-box genes in ear development. This study provides a significant beginning of functional analysis of SBP-box genes in wheat.


Health disparities, social injustice, and the culture of nursing.
Nurses are well positioned to challenge institutionalized social injustices that lead to health disparities. The aim of this cross-cultural study was to collect stories of difference and fairness within nursing. The study used a life history methodology informed by feminist theory and critical social theory. Life story interviews were conducted with 26 women nurses of varying racial, cultural, sexual identity, and specialty backgrounds in the United States (n = 13) and Aotearoa New Zealand (n = 13). Participants reported having some understanding of social justice issues. They were asked to reflect on their experience of difference and fairness in their lives and specifically within nursing. Their stories were analyzed using a life history immersion method. Nursing remains attached to the ideological construction of the "White good nurse." Taken-for-granted ideals privilege those who fit in and marginalize those who do not. The nurses experienced discrimination and unfairness, survived by living in two worlds, learned to live in contradiction, and worked surreptitiously for social justice. For nurses to contribute to changing the systems and structures that maintain health disparities, the privilege of not seeing difference and the processes of mainstream violence that support the construction of the "White good nurse" must be challenged. Nurses need skills to deconstruct the marginalizing social processes that sustain inequalities in nursing and healthcare. These hidden realities--racism, sexism, heterosexism, and other forms of discrimination--will then be made visible and open to challenge.


Orally Administered Combination of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin in the Prevention of Postcoital Recurrent Urinary Tract Infections: Analysis of 98 Women in Reproductive Age After 6 Months of Treatment.
The aim of this study is to assess the efficacy of orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin for the prevention of postcoital recurrent urinary tract infection (UTI) in reproductive age women. Ninety-eight consecutive patients in reproductive age affected by UTI were considered for the study. All 98 patients received a combination of HA, CS, curcumin, and quercetin two tablets per diem for the first month and one tablet every day for the next 5 months. We investigate recurrence of UTI with the Urinary Tract Infection Symptoms Assessment and the Pelvic Pain and Urinary Urgency Frequency. The quality of life and sexual function were valued using 36-Item Short Form Survey, Female Sexual Function Index, and the Female Sexual Distress Scale questionnaires. The same investigations were performed at the first visit and after 6 months of treatment. The symptoms associated with UTI significantly decreased after 6 months of treatment, in particular dysuria episodes diminished and number of voiding decreased (P < 0.0001). During the treatment period, only seven patients (7.1%) experienced a UTI recurrence, confirmed by positive urine culture with bacteriuria of greater than 10 colony forming units/mL. The Pelvic Pain and Urinary Urgency Frequency, Female Sexual Function Index, Female Sexual Distress Scale, and 36-Item Short Form Survey showed a statistically significant improvement after 6 months. Oral administration of a combination of HA, CS, curcumin, and quercetin is a valid and well-tolerated nonantibiotic treatment for prevention of postcoital UTI in reproductive age women.


A Comprehensive Examination of the Contaminants in Drinking Water in Public Schools in California, 2017-2022.
Reports of unsafe school drinking water in the United States highlight the importance of ensuring school water is safe for consumption. Our objectives were to describe (1) results from our recent school drinking water sampling of 5 common contaminants, (2) school-level factors associated with exceedances of various water quality standards, and (3) recommendations. We collected and analyzed drinking water samples from at least 3 sources in 83 schools from a representative sample of California public schools from 2017 through 2022. We used multivariate logistic regression to examine school-level factors associated with lead in drinking water exceedances at the American Academy of Pediatrics (AAP) recommendation level (1 part per billion [ppb]) and state action-level exceedances of other contaminants (lead, copper, arsenic, nitrate, and hexavalent chromium). No schools had state action-level violations for arsenic or nitrate; however, 4% had ≥1 tap that exceeded either the proposed 10 ppb action level for hexavalent chromium or the 1300 ppb action level for copper. Of first-draw lead samples, 4% of schools had ≥1 tap that exceeded the California action level of 15 ppb, 18% exceeded the US Food and Drug Administration (FDA) bottled water standard of 5 ppb, and 75% exceeded the AAP 1 ppb recommendation. After turning on the tap and flushing water for 45 seconds, 2%, 10%, and 33% of schools exceeded the same standards, respectively. We found no significant differences in demographic characteristics between schools with and without FDA or AAP exceedances. Enforcing stricter lead action levels (<5 ppb) will markedly increase remediation costs. Continued sampling, testing, and remediation efforts are necessary to ensure drinking water meets safety standards in US schools.


2,4,6-Trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide increases calcium influx in lipopolisaccharide-pre-treated arteries.
It has been demonstrated that 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C (PLC) and stimulates apoptosis in smooth muscle cells, which may increase vascular reactivity. The primary aim of the present study was to evaluate the physiological effects of the direct stimulation of PLC by m-3M3FBS on vascular smooth muscle reactivity in arteries pre-treated with lipopolysaccharides (LPS) as a model of septic shock. Experiments were performed on isolated and perfused tail arteries of Wistar rats. The contraction force in the model was measured by assessing increases in perfusion pressure at a constant flow. Parameters describing the concentration-response curves (CRCs) obtained for phenylephrine and arginine-vasopressin in the presence of LPS confirmed a decrease in vessels reactivity. In comparison with the controls, m-3M3FBS treatment caused a significant increase in LPS-untreated as well as pre-treated arteries. Furthermore, in the presence of m-3M3FBS, calcium influx from intra- as well as extracellular calcium stores was significantly higher for LPS-untreated and pre-treated arteries. The results of the present study suggested that m-3M3FBS significantly increased the reactivity of vascular smooth muscle cells pre-treated with LPS by increasing the calcium influx from intra- and extracellular calcium stores. Further studies investigating this mechanism are required to evaluate whether this pathway may be a potential therapeutic strategy to treat sepsis.


[Mycetoma in northern Argentina].
From 1972 to October 1982 we have observed 39 cases of mycetoma in the Skin Department of the Hospital del Milagro, Salta (Argentina). The diagnosis was based on the clinical aspect, mycological studies and in most cases histopathology was done as well. The mayoritary of the patients were farmers. From the clinical point of view there si a true prevalence of Nocardia Brasiliensis. Most of the mycetomas can be found in the lower limbs. Some of the patients presented quite severe lesions and eight of them had bone involvement. The combination of long action sulphas with sulphonas has been efficient enough in the treatment of mycetomas caused by Nocardia Brasiliensis.


Patient-reported outcome following nonsurgical management of type II odontoid process fractures in adults.
Transverse (type II) odontoid process fracture is among the most commonly encountered cervical spine fractures. Nonsurgical management through external immobilization is occasionally preferred to surgical management but is criticized for its higher rates of failure and lower patient satisfaction. Our aim is to analyze patient-reported outcomes in patients who underwent nonsurgical treatment for type II odontoid fractures. We identified patients >18-year-old who underwent external immobilization as a treatment for isolated type II odontoid fracture between 2007 and 2012. We collected demographic parameters, clinical presentation, mode of injury, imaging studies and modality and duration of treatment (soft collar, halo-vest, or both). Patients were contacted by telephone to participate in a 15-min survey addressing their recovery including their subjective rate of return to preinjury level of functioning. Fifteen patients met the inclusion/exclusion criteria and participated in our survey. Patients were followed up for an average of 19 months after injury. Overall mean age was 61 years. Injury followed a mechanical fall or a road traffic accident in 11 and 4 cases, respectively. External immobilization was achieved by halo vest only in nine patients, soft collar only in two patients (13%), and through a sequential combination in the remaining 4 (27%). This was deployed for a mean of 7.8 months. Radiological studies at the last follow-up showed bony healing (27%), fibrous nonunion (60%), and persistent instability (13%). Patients reported gradual recovery of function throughout the 1st year after injury with levels above 70% of preinjury functioning achieved by 13% of patients at 6 months, 33% at 9 months, and 47% at 12 months. Overall satisfaction with nonsurgical management was 68%. In selected patients with type II odontoid fractures, external immobilization represents a good option with acceptable course of recovery.


Effect of elevated catecholamine levels on cerebral hemodynamics in patients with chronic post-traumatic stress disorder.
The aim of the study was to assess the correlation between the levels of catecholamines and cerebral hemodynamics in patients with chronic post-traumatic stress disorder (PTSD). The study included 50 patients with chronic PTSD hospitalized for psychiatric treatment for the first time, and 50 healthy control subjects. All study subjects were in the 30-50 age group. In PTSD group, determination of vanllylmandelic acid (VMA), an epinephrine and norepinephrine metabolite, in 24-h urine and transcranial Doppler (TCD) sonography of the circle of Willis vasculature were performed on the first day of hospital stay. The same diagnostic procedures were repeated upon the completion of 21-day medicamentous psychiatric treatment. Initial analysis revealed concurrently elevated 24-h VMA in 29 (58.00%) patients and increased values of the mean blood flow velocity (MBFV) in the circle of Willis vasculature in 34 (68.00%) patients, indicating a high correlation of the respective parameters (p = 0.3290). Second analysis performed after 21-day psychiatric treatment showed concurrently elevated 24-h VMA in eight (16.00%) patients and increased MBFV in the circle of Willis vasculature in nine (18.00%) patients, also pointing to a high correlation of the parameters observed (p = 0.7906). In the control group, only two (4.00%) subjects had elevated MBFV in the circle of Willis vessels, whereas the level of 24-h VMA was normal in all control subjects. Study results pointed to a significant association between elevated levels of stress hormones and increased MBFV in the circle of Willis vasculature caused by cerebral vasospasm. Medicamentous psychiatric treatment for PTSD administered for three weeks significantly reduced the proportion of PTSD patients with elevated levels of the catecholamine metabolite and cerebral vasospasm. Study results showed a high correlation between diurnal VMA level and elevated MBFV in the circle of Willis vessels, clearly demonstrating the effect of prolonged elevation of catecholamine levels on cerebral hemodynamics.


The Dirac equation in quantum chemistry: strategies to overcome the current computational problems.
A perspective on the use of the relativistic Dirac equation in quantum chemistry is given. It is demonstrated that many of the computational problems that plague the current implementations of the different electronic structure methods can be overcome by utilizing the locality of the small component wave function and density. Possible applications of such new and more efficient formulations are discussed.


Hypertrophic Obstructive Cardiomyopathy: Comparison of Outcomes After Myectomy or Alcohol Ablation.
The risk of ventricular arrhythmia and heart failure in patients with hypertrophic obstructive cardiomyopathy (HOCM) is much higher than that in the general population. More and more pieces of evidence showed that HOCM is the leading cause of sudden cardiac death in young people. We reported our experience in a study, comparing surgical myectomy, alcohol septal ablation (ASA), and medical therapy. The original cohort included 965 consecutive patients with HOCM. The patients were divided into three groups according to treatment strategies: myectomy group (n = 502), ASA group (n = 138), and medical treatment group (n = 325). The median follow-up duration was 42.99 ± 18.32 months, and the primary endpoints were all-cause mortality and heart transplantation. Both in short- and long-term observations, surgical myectomy reduced the left ventricular outflow tract (LVOT) gradients more effectively (7 days, 16.15 ± 12.07 mmHg vs. 42.33 ± 27.76 mmHg, p < 0.05; 1 year, 14.65 ± 13.18 mmHg vs. 41.17 ± 30.76 mmHg, p < 0.05). Among the three groups, the patients in the medical treatment group were at a higher risk of mortality and cardiac transplantation (vs. the myectomy group, p < 0.001 by log-rank test; vs. the alcohol septal ablation group, p = 0.017 by log-rank test), and the myectomy group shows a lower risk of reaching the primary endpoint than the two other groups. In the multivariate Cox regression analysis, previous atrial fibrillation (AF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and surgical myectomy predicted an HOCM prognosis. However, the impact of surgical myectomy on HOCM prognosis seems to be limited to the <56 years group. The patients with medical treatments seemed to suffer from the highest risk of achieving an all-cause mortality and the endpoint of heart transplantation. In the long-term survival and clinical outcome, myectomy seemed better than alcohol septal ablation, especially the younger patients. Due to the less-controllable degree, periprocedural complication frequency after alcohol septal ablation was higher, compared with myectomy. Furthermore, gradients after myectomy are lower at late follow-up. To sum up, when selecting treatment strategies, the patients should be individually evaluated by a multidisciplinary team of cardiologists and surgeons.


Genetic parameters for somatic cell score, milk yield and type traits in Nigerian Dwarf goats.
This study was conducted to estimate multi-trait genetic parameters for somatic cell score (SCS), milk yield and type traits in Nigerian Dwarf (ND) goats from the United States. Data from 1,041 ND goats in the United States with kiddings in 95 herds were used to estimate multi-trait genetic parameters for SCS, milk (MILK), fat (FAT), and protein (PROT) yields, and 14 type traits. An 18-trait mixed linear animal model for lactation mean SCS (Log2), MILK, FAT, PROT, and 14 type traits was applied. A factor analytic approach (FA1) in ASReml software was used to obtain convergence. Averages for SCS were low (2.85±1.29 Log2), and were 314±110.6, 20.9±7.4, and 14±4.9 kg, respectively, for MILK, FAT, and PROT. Heritabilities for SCS, MILK, FAT, and PROT were 0.32, 0.16, 0.16, and 0.10, respectively. The highest heritabilities for type traits were for stature (0.72), teat diameter (0.49), and rump width (0.48), and the lowest estimates were for dairyness (0.003) and medial suspensory ligament (0.03). Genetic correlations of SCS with MILK, FAT, and PROT were positive but low (0.25, 0.18, and 0.23, respectively). Genetic and phenotypic correlations between MILK, FAT, and PROT were high and positive (≥0.66). Absolute values of genetic correlations involving SCS with type traits were generally low or no different from zero. Most of the phenotypic correlations involving SCS with type traits were low. No serious unfavorable genetic correlations between milk yield traits and SCS or between milk yield traits or SCS and type traits were found. Genetic variation exists in the ND breed for most studied traits. The development of selection programs based on these estimates may help accelerate favorable multitrait genetic changes in this breed.


Best outcomes for Indian children.
The Wisconsin Department of Children and Families and the Midwest Child Welfare Implementation Center are collaborating with Wisconsin's tribes and county child welfare agencies to improve outcomes for Indian children by systemically implementing the Wisconsin Indian Child Welfare Act (WICWA). This groundbreaking collaboration will increase practitioners' understanding of the requirements of WICWA and the need for those requirements, enhance communication and coordination between all stakeholders responsible for the welfare of Indian children in Wisconsin; it is designed to effect the systemic integration of the philosophical underpinnings of WICWA.


Identification and analysis of genomic islands in Burkholderia cenocepacia AU 1054 with emphasis on pathogenicity islands.
Genomic islands (GIs) are genomic regions that reveal evidence of horizontal DNA transfer. They can code for many functions and may augment a bacterium's adaptation to its host or environment. GIs have been identified in strain J2315 of Burkholderia cenocepacia, whereas in strain AU 1054 there has been no published works on such regions according to our text mining and keyword search in Medline. In this study, we identified 21 GIs in AU 1054 by combining two computational tools. Feature analyses suggested that the predictions are highly reliable and hence illustrated the advantage of joint predictions by two independent methods. Based on putative virulence factors, four GIs were further identified as pathogenicity islands (PAIs). Through experiments of gene deletion mutants in live bacteria, two putative PAIs were confirmed, and the virulence factors involved were identified as lipA and copR. The importance of the genes lipA (from PAI 1) and copR (from PAI 2) for bacterial invasion and replication indicates that they are required for the invasive properties of B. cenocepacia and may function as virulence determinants for bacterial pathogenesis and host infection. This approach of in silico prediction of GIs and subsequent identification of potential virulence factors in the putative island regions with final validation using wet experiments could be used as an effective strategy to rapidly discover novel virulence factors in other bacterial species and strains.


Pregnancy and lupus nephritis. A detailed report of six cases with a review of the literature.
The maternal and fetal courses of six pregnancies in 5 patients with histories of systemic lupus erythematosus and lupus nephritis were studied. The immediate and remote effects of these pregnancies on specific parameters of renal function are discussed, and a review of the literature is presented.


[Cross-mapping of terms of the axes time, location, means and client between different versions of ICNP® and CIPESC®].
The ICNP® model of seven axes resulted in the transfer of terms between the axes, conceptual modifications, inclusion and exclusion of terms. This descriptive, bibliographic study, mapped out the terms of the axes "Time", "Location", "Means" and "Client" among Beta-2, 1.0 and 1.1 versions of the ICNP® and CIPESC®. The mapping located the terms of these axes in the different versions of the ICNP® and CIPESC®. It was performed to classify the semantic equivalence of terms and concepts. The result shows that some changes have the objective of reducing ambiguities and redundancies; others do not allow the verification of the criterion for exclusion, inclusion and migration of terms. It is imperative to establish concepts of consensus by the group responsible for building the terminology in order to minimize the misuse or improper use of terms. It is necessary to revise the list of actions in the vocabulary inventory of CIPESC®.


Obesity in young men after famine exposure in utero and early infancy.
In a historical cohort study of 300,000 19-year-old men exposed to the Dutch famine of 1944-45 and examined at military induction, we tested the hypothesis that prenatal and early postnatal nutrition determines subsequent obesity. Outcomes were opposite depending on the time of exposure. During the last trimester of pregnancy and the first months of life, exposure produced significantly lower obesity rates (P less than 0.005). This result is consistent with the inference that nutritional deprivation affected a critical period of development for adipose-tissue cellularity. During the first half of pregnancy, however, exposure resulted in significantly higher obesity rates (P less than 0.0005). This observation is consistent with the inference that nutritional deprivation affected the differentiation of hypothalamic centers regulating food intake and growth, and that subsequent increased food availability produced an accumulation of excess fat in an organism growing to its predetermined maximum size.


Genotypic and Phenotypic Heterogeneity in Alicyclobacillus acidoterrestris: A Contribution to Species Characterization.
Alicyclobacillus acidoterrestris is the main cause of most spoilage problems in fruit juices and acidic products. Since soil borne species often contaminate fruit juices and do not need strict extreme requirements for survival, it is a great concern to investigate whether and how soil species could evolve from their ecological niches in microbial community to new environments as fruit juices. In this study, 23 isolates of thermo-acidophilic, spore-forming bacteria from soil were characterized by cultural and molecular methods. In addition, 2 strains isolated from a spoilage incident in pear juice were typed. Strains phenotyping showed that they could be grouped into 3 different clusters, and some isolates showed identical or quite similar patterns. Analyzing pH and temperature ranges for growth, the majority of strains were able to grow at values described for many species of Alicyclobacillus. Qualitative utilization of lysine, arginine and indole production from tryptophan revealed, for the first time, deamination of lysine and decarboxylation of arginine. Resistance to 5% NaCl as well as the ability to hydrolyze starch and gelatin, nitrate reduction, catalase and oxidase activities confirmed literature evidences. Examining of 16S rRNA, showed that isolates were divided into three blocks represented by effectively soil species and strains that are moving from soil to other possible growing source characterized by parameters that could strongly influence bacterial survival. RAPD PCR technique evidenced a great variability in banding patterns and, although it was not possible to obtain genotypically well-distinguished groups, it was feasible to appreciate genetic similarity between some strains. In conclusion, the investigation of a microbial community entails a combination of metagenomic and classic culture-dependent approaches to expand our knowledge about Alicyclobacillus and to look for new subspecies.


Separation of rotenoids and the determination of rotenone in pesticide formulations by high-performance liquid chromatography.
The rotenoids deguelin, B-dihydrorotenone, dehydrorotenone, rotenone, 6alpha beta, 12alpha beta-rotenolone, and tephrosin were chromatographed on 8-12 mum silica. A mobile phase of chloroform-isooctane (35+65) pumped at a flow rate of 1 ml/min through a 30 cm column was used and the absorbance of the eluate was monitored at 294 nm. Rotenone, B-dihydrorotenone, deguelin, and dehydrorotenone are completely resolved while 6alpha beta, 12alpha beta-rotenolone and tephrosin chromatograph as one peak. This method has potential as a preparative separation technique for rotenoids. Also described is a procedure to quantitatively measure rotenone in pesticide formulations. Samples were extracted with chloroform and chromatographed at a flow of 2.5 ml/min. The method is rapid (rotenone is eluted in 12 min) and reproducible.


Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns.
Asthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year. Serial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods. Trajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations. Trajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.


Plasma monocyte chemoattractant protein-1 as risk marker in type 2 diabetes mellitus and coronary artery disease in North Indians.
The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in chronic inflammation, insulin resistance and atherosclerosis. The present study was designed to explore the relation of plasma levels of MCP-1 to disease pathology in type 2 diabetes and coronary artery disease (CAD) patients. Fasting plasma venous samples were taken from 162 subjects divided into four groups: Patients with type 2 diabetes mellitus and CAD (n=41), type 2 diabetes patients without CAD (n=50), CAD patients with no history of diabetes (n=41) and healthy controls (n=30). Coronary risk factors such as body mass index, percentage body fat, waist/hip ratio, blood pressure and physical activity were measured using standard procedures. Plasma MCP-1 was quantitatively estimated by sandwich enzyme-linked immunoabsorbent assay (ELISA). Significant differences were observed for MCP-1 levels, percent body fat, body mass index, waist/hip ratio, systolic and diastolic blood pressure amongst the groups. MCP-1 concentration was significantly correlated with diabetes duration (p<0.001), body mass index (p<0.01), waist/hip ratio (p<0.01), systolic blood pressure (p<0.01), percentage body fat (p<0.01) and physical activity level (p<0.001). MCP-1 might serve as a marker for CAD, and its association with CAD is mainly driven by traditional coronary risk factors.


Ruptured intercostal artery pseudoaneurysm: a rare cause of acute back pain.
A 63-year-old man with no relevant medical history presented with acute non-traumatic back pain and was found to have a T8 intercostal artery pseudoaneurysm associated with haemomediastinum on CT of the chest. He was taken to angiography with interventional radiology and the aneurysm was coiled without complication.


High incidence of multidrug-resistant Streptococcus pneumoniae in South Korea.
Streptococcus pneumoniae was isolated from patients with bacteremia, meningitis, pneumonia, and otitis media and used to determine susceptibility to various antibiotics. Of 105 isolates, 51% to 83% were resistant to 6 antibiotics (i.e., the percentages of resistance to penicillin, ampicillin, cephalothin, chloramphenicol, tetracycline, and erythromycin were 78%, 67%, 51%, 56%, 83%, and 58%, respectively). Also, 66 of the 105 isolates were multidrug resistant. Seventy-eight percent of multidrug-resistant strains were highly resistant to tetracycline (minimum inhibitory concentration [MIC] > or = 50 micrograms/ml), and 39% of multidrug-resistant strains were also highly resistant to erythromycin (MIC > or = 128 micrograms/ml). However, only 4% of the 105 isolates were resistant to cefotaxime.


Changing breast self-examination behavior.
Breast self-examination instruction was presented to 130 women. Four instructional methods used were: modeling alone, modeling plus guided practice, modeling plus self-monitoring, and modeling plus peer support. Follow-up data were collected at three- and six-month intervals. Data analyses revealed that, although the study population as a whole made statistically significant changes in breast self-examination behavior, no statistically significant outcomes were related to the dependent variables of frequency and knowledge of self-examination and confidence in ability to detect breast abnormalities between subjects in the modeling alone method--which served as the control--and subjects in the other three instructional methods.


Exploration of Multistate Conformational Dynamics upon Ligand Binding of a Monomeric Enzyme Involved in Pyrophosphoryl Transfer.
HPPK (6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase) is a monomeric protein with 158 residues, which undergoes large-scale conformational changes between apo, open, and holo states responding to ligand binding for its function. It has been explored widely as an excellent target for potential antibacterial drug development. However, little is known about how conformational dynamics between the native states influences the substrate recognition and the functionality of enzymatic catalysis. Here, we report a coarse-grained triple-basin structure-based model upon ligand binding to describe such multiple-state system by the molecular dynamics simulation. With our model, we have made theoretical predictions that are in good agreement with the experimental measurements. Our results revealed the intrinsic conformational fluctuations between apo and open states without ligand binding. We found that HPPK can switch to the activated holo state upon the ordered binding of the two ligands (ATP and HP). We uncovered the underlying mechanism by which major induced fit and minor population shift pathways coexist upon ligand binding by quantitative flux analysis. Additionally, we pointed out the structural origin for the conformational changes and identified the key residues as well as contact interactions. We further explored the temperature effect on the conformational distributions and pathway weights. It gave strong support that higher temperatures promote population shift, while the induced fit pathway is always the predominant activation route of the HPPK system. These findings will provide significant insights of the mechanisms of the multistate conformational dynamics of HPPK upon ligand binding.


Thermal engineering of stone increased prehistoric toolmaking skill.
Intentional heat treating of toolstone has been documented to have begun at least by 70 K BP; however, the advantages of such treatment have been debated for decades. There are two schools of thought with regard to its purpose. One, is that it merely reduces the force required for flake propagation. A second is that it also alters flake morphological properties. We systematically tested these hypotheses by generating flakes from cores exposed to three different temperatures (ambient, 300 °C, and 350 °C) using automated propagation procedures that bypassed any human agency. While the force propagation magnitude is altered by heat treatment, the flakes were not. We examined these flakes according to nine measures of morphology. None differed significantly or systematically within the three categories. While our results confirm that heat treatment does reduce the force needed for flake propagation, they also demonstrate that such treatment has no significant effect on major morphological aspects of flake form.


Fine structure of Haemophilus vaginalis.
Haemophilus vaginalis 594 has a trilaminar cell wall, ribosomes, a fibrillar nucleoid, and both convoluted and simple mesosome-like bodies. Polar bulbous enlargements of the cell and multiple cross wall formations may explain its pleomorphism.


Iron loading makes a nonfibrogenic model air pollutant particle fibrogenic in rat tracheal explants.
To examine the potential role of particle iron in fibrogenicity, we loaded nonfibrogenic fine (0.12micro) TiO(2) with increasing amounts of Fe(II)-Fe(III) chloride. Dusts were applied to rat tracheal explants, which were maintained in air organ culture for 1 wk. Iron-loaded dust increased procollagen gene expression and tissue hydroxyproline. The active oxygen species (AOS) scavenger tetramethylthiourea prevented these effects. Iron loading caused nuclear factor (NF)-kappaB activation, decreased levels of total IkappaBalpha, but relatively increased levels of both IkappaBalpha-phosphoserine 32/36 and IkappaBalpha-phosphotyrosine. A citrate extract of iron-loaded dust increased procollagen expression. Gel shift using a probe consisting of the NF-kappaB consensus sequence from the prolyl-4-hydroxylase promoter and adjacent bases showed increased nuclear binding, and RT-PCR examination showed increased prolyl-hydroxylase alpha-chain gene expression after iron loading. We conclude that addition of surface iron can convert a nonreactive model air pollutant particle into a fibrogenic particle via AOS- and NF-kappaB-dependent pathways, probably through two different NF-kappaB activation pathways in two different anatomic compartments. This process may proceed in vivo through iron extracted from the dust into the cytoplasm. NF-kappaB activation may directly increase expression of prolyl hydroxylase, an enzyme involved in collagen synthesis. These findings suggest that air pollutant particles containing significant quantities of transition metals may produce airway wall fibrosis and lead to chronic obstructive pulmonary disease.


A novel technique of submandibular intubation with a camera cable drape: a case report.
Submental or submandibular intubation has been reported to cause fewer complications than tracheostomy. However, the risk of infection is always inherent because oral wounds are exposed to microbial flora and bacteria in the oral cavity. A novel technique of submandibular intubation was devised to reduce infection and injury to the soft tissues. We would like to report a novel safe technique that can be performed in patients requiring submental or submandibular intubation. This is the first report of submandibular intubation using a sterile disposable camera cable drape. This novel technique of submandibular intubation is safer, more sterile, easier, and less invasive than conventional submandibular intubation.


Increased expression of thyroid hormone responsive protein (THRSP) is the result but not the cause of higher intramuscular fat content in cattle.
Thyroid hormone responsive protein (THRSP) is known to be involved in lipogenic processes in rodents. In cattle, THRSP could be a potential molecular marker for intramuscular fat (IMF) deposition since mRNA abundance was frequently found to be increased in skeletal muscle with high IMF content compared to those with low IMF. The aim of this study was to elucidate the background of this differential expression and to evaluate the role of THRSP as candidate for increased IMF content in cattle. By combination of mRNA and protein analyses, we could demonstrate that THRSP is present mainly in nuclei of adipose tissue, in intramuscular fat cells and associated cells, and in cells of the portal triad of liver, whereas muscle cells did not express THRSP. Cell culture analyses revealed furthermore that THRSP is expressed in mature adipocytes rather than in early stages of adipogenesis. Collectively, our data support the putative role of THRSP as transcriptional regulator and demonstrate that an increased expression of THRSP in M. longissimus is a consequence of but not the reason for a higher number of intramuscular adipocytes in cattle with enhanced IMF deposition.


The role of Nod1 signaling in corneal neovascularization.
Corneal neovascularization (CNV) is associated with Chlamydia trachomatis. The minimal components of bacterial cell walls are recognized by nucleotide-binding oligomerization domain-containing protein (Nod), which is important for host defense--a mechanism manifested in human corneal cells. We aimed to examine whether Nod stimulation is associated with CNV. Three groups of mice with alkali-induced CNV were topically treated with tripeptide L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP, a Nod1 agonist), muramyl dipeptide (a Nod2 agonist), or phosphate-buffered saline twice daily for 8 days. The time course responses were quantified using biomicroscopic examinations and immunohistochemistry. Angiogenic factor expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. To confirm the involvement of Nod1 signaling in CNV, RICK (an essential molecule in Nod signaling)-knockout mice treated with Tri-DAP were examined biomicroscopically and immunohistochemically 8 days after injury. According to the biomicroscopic camera images and histology, Tri-DAP and muramyl dipeptide promoted CNV. Significantly, Tri-DAP increased the number and size of the neovascularized areas. The messenger RNA expression level of vascular endothelial growth factor was elevated in the Tri-DAP-treated mice after alkali injury. Compared with wild-type mice, CNV was attenuated in RICK-deficient mice treated with Tri-DAP. These data suggest that Nod1 stimulation is an important inducer of CNV and that Nod1 might be useful in the development of CNV therapies.


Ultrastructural findings in natural canine hepatozoonosis.
The ultrastructure of several stages of Hepatozoon canis found in dogs with clinically and histologically diagnosed infections was determined using transmission electron microscopy. Merozoites, macro- and microschizonts and gamonts were found in spleen, liver, kidneys and lungs. Macro- and micromeronts were characterized by their size and by the presence of intracytoplasmic amylopectin granules. Gamonts, which provide the basis for clinical diagnosis of the disease, were observed within mononuclear cells (monocytes/macrophages); they were butterfly-shaped and exhibited varying electron densities. On the basis of the microscopic observations reported here, it is clear that the life cycle of H. canis is a complex one.


C-reactive protein and radiographic findings of lower respiratory tract infection in infants.
To evaluate the association between C-reactive protein (CRP) and radiological evidence of lower respiratory tract infection (LRTI) in infants. All patients aged less than 4 years who presented with suspected lower respiratory tract infection, who received a peri-presentation chest radiograph and CRP blood measurement over an 18-mo period were included in the study. Age, gender, source of referral, CRP, white cell count, neutrophil count along with the patients' symptoms and radiologist's report were recorded. Three hundred and eleven patients met the inclusion criteria. Abnormal chest radiographs were more common in patients with elevated CRP levels (P < 0.01). Radiologic signs of LRTI were identified in 73.7% of chest radiographs when a patient had a CRP level between 50-99 mg/L. CRP levels were a better predictor of positive chest radiograph findings for those aged greater than I year compared to those 1 year or less. CRP may be used in patients with suspected LRTI diagnosis to select those who are likely to have positive findings on chest radiograph, thus reducing unnecessary chest radiographs.


Biomimetic sensor based on molecularly imprinted polymer with nitroreductase-like activity for metronidazole detection.
The utility of molecularly imprinted polymer (MIP) as electrochemical sensor often suffers from its limited catalytic efficiency. Here, we proposed an alternative approach by combining the concept of MIP with the use of mimetic enzyme. A metronidazole imprinted polymer with nitroreductase-like activity was successfully achieved via an electrochemical method, where melamine served two purposes: functional monomer of MIP and component of mimetic enzyme. During the imprinting process, the redox-active center, which is responsible for catalysis, was introduced into the imprinted cavities. Accordingly, the imprinted polymer, having both catalysis centers and recognition sites, exhibited enhanced electrocatalytic activity and selectivity. The sensing performances of this metronidazole imprinted biomimetic sensor were evaluated in detail. Results revealed that the response to metronidazole was linear in the concentration range of 0.5-1000 μM, and the detection limit was 0.12 μM (S/N=3). In addition, we applied the proposed sensor to detect metronidazole in an injection solution and the results implied its feasibility for practical application.


Circularly polarized chemiluminescence from planar chiral bis(adamantylidene-1,2-dioxetane)s.
Bis(adamantylidene-1,2-dioxetane), upon conjugation to a planar chiral scaffold of [2.2]paracyclophane, gave chemical-triggerable circularly polarized chemiluminescence with a dissymmetry factor of 1.1 × 10-3 scale, to which exciton chirality upon chemiexcitation was assigned as the origin.


Life events, emotional support, and health of older people.
The effects of life events, emotional support, interaction of life events and emotional support, and age on indices of physical and psychological health were examined within a hierarchical multiple-regression design. Fifty older people who were randomly selected from among the residents of a high-rise apartment building provided retrospective data on their life events and emotional support. These same subjects provided more recent data on their functional health, distress arising from chronic health problems, and four indices of morale (agitation, attitude toward own aging, lonely dissatisfaction, and a combined index of the morale dimensions). As expected, significant multivariate effects were demonstrated on all but two measures: distress arising from chronic health problems and attitude toward aging. Examination of the independent contributions to these effects showed variations depending on the health index of focus. Expected moderations of the effects of life events by emotional support effects were not demonstrated. Results are discussed in relationship to previous research and the theoretical expectation that emotional support would moderate the effects of life events on health.


[Difficulties in differential diagnosis of dentin dysplasia. Case report].
In cases of periapical lesions of unknown origin we have to keep in mind the possibility of dentin dysplasia. From the differential diagnostic point of view of differential diagnosis it is important to recognize this disease as it significantly influences the treatment modality. It is an anomaly of unknown etiology that could affect both deciduous and permanent dentition. Dentin dysplasia presentation varies clinically and radiologically. A rare manifestation which affects 1: 100000 patients is spontaneously occurring either as periapical abscess or odontogenic cyst. The affected teeth could become mobile and eventually lost. Dentin dysplasia is a genetic disease which shows autosomal dominant inheritance and characterized by abnormal formation of dentin structure which occurs during tooth development. For this article we have reviewed available literature and PubMed database. Dentin dysplasia increases the risk of early tooth loss and associated with it esthetic and functional disturbances. As a result it can influence the psychological and social status of the patients and affect their quality of life.


Anomalous Hall effect in field-effect structures of (Ga,Mn)As.
The anomalous Hall effect in metal-insulator-semiconductor structures having thin (Ga,Mn)As layers as a channel has been studied in a wide range of Mn and hole densities changed by the gate electric field. Strong and unanticipated temperature dependence, including a change of sign, of the anomalous Hall conductance sigma(xy) has been found in samples with the highest Curie temperatures. For more disordered channels, the scaling relation between sigma(xy) and sigma(xx), similar to the one observed previously for thicker samples, is recovered.


Accuracy of Colon Capsule Endoscopy in Detecting Colorectal Polyps in Individuals with Familial Colorectal Cancer: Could We Avoid Colonoscopies?
Background. Individuals with a family history of colorectal cancer (CRC) have an increased risk of CRC. We evaluated the diagnostic yield of CCE in the detection of lesions and also two different colon preparations. Methods. A prospective multicenter study was designed to assess CCE diagnostic yield in a cohort of asymptomatic individuals with a family history of CRC. CCE and colonoscopy were performed on the same day by 2 endoscopists who were blinded to the results of the other procedure. Results. Fifty-three participants were enrolled. The sensitivity, specificity, PPV, and NPV of CCE for detecting advanced adenomas were 100%, 98%, 67%, and 100%. Sensitivity, specificity, PPV, and NPV of CCE for the diagnosis of individuals with polyps were 87%, 97%, 93%, and 88%, respectively. CCE identify 100% of individuals with significant or advanced lesions. Overall cleanliness was adequate by 60.7% of them. The PEG-ascorbic boost seems to improve colon cleanliness, with similar colonic transit time. Conclusion. CCE is a promising tool, but it has to be considered as an alternative technique in this population in order to reduce the number of colonoscopies performed. More studies are needed to understand appropriate screening follow-up intervals and optimize the bowel preparation regimen.


Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients.
Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer's disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker. Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75-0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82-0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79-0.95, p = 0.07). We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD. NCT01028053 , registered December 9, 2009.


Gold(I)-Catalyzed Enantioselective Desymmetrization of 1,3-Diols through Intramolecular Hydroalkoxylation of Allenes.
A gold(I)-catalyzed enantioselective desymmetrization of 1,3-diols was achieved by intramolecular hydroalkoxylation of allenes. The catalyst system 3-F-dppe(AuCl)2/(R)-C8-TRIPAg proved to be specifically efficient to promote the desymmetrizing cyclization of 2-aryl-1,3-diols, which have proven challenging substrates in previous reports. Multisubstituted tetrahydrofurans were prepared in good yield with good enantioselectivity and diastereoselectivity by this method.


Comment on "Climate legacies drive global soil carbon stocks in terrestrial ecosystems".
Delgado-Baquerizo et al. (Science Advances, 12 April 2017, e1602008) use statistical correlations to infer that paleoclimate (6000 to 22,000 years ago) is a more important driver of current soil organic carbon stocks than the current-day climate. On the other hand, a wealth of radiocarbon measurements indicates that the organic carbon in most topsoils is only a few decades to perhaps a few centuries old. These seemingly incongruous results can perhaps be reconciled by considering that the long-term pedogenic development of a soil strongly influences the physiochemical properties, which lead to stabilization of new carbon entering that soil regardless of current climate.


[Challenging behavior: behavioral phenotypes of some genetic syndromes].
Challenging behavior in individuals with mental retardation (MR) is relatively frequent, and represents a significant obstacle to adaptive skills. The frequency of specific forms and manifestations of challenging behavior can depend on a variety of personal and environmental factors. There are several prominent theoretical models regarding the etiology of challenging behavior and psychopathology in persons with MR: behavioral, developmental, socio-cultural and biological.The biological model emphasizes the physiological, biochemical and genetic factors as the potential source of challenging behavior. The progress in the field of genetics and neuroscience has opened the opportunity to study and discover the neurobiological basis of phenotypic characteristics. Genetic syndromes associated with MR can be followed by a specific set of problems and disorders which constitutes their behavioral phenotype. The aim of this paper was to present challenging behaviors that manifest in the most frequently studied syndromes: Down syndrome, Fragile X syndrome, Williams syndrome, Prader-Willi syndrome and Angelman syndrome. The concept of behavioral phenotype implies a higher probability of manifesting specific developmental characteristics and specific behaviors in individuals with a certain genetic syndrome. Although the specific set of (possible) problems and disorders is distinctive for the described genetic syndromes, the connection between genetics and behavior should be viewed through probabilistic dimension. The probabilistic concept takes into consideration the possibility of intra-syndrome variability in the occurrence, intensity and time onset of behavioral characteristics, at which the higher variability the lower is the specificity of the genetic syndrome. Identifying the specific pattern of behavior can be most important for the process of early diagnosis and prognosis. In addition, having knowledge about behavioral phenotype can be a landmark in the creation of targeted treatment strategies for individuals with a specific genetic syndrome.


Densitometric and local histogram based analysis of computed tomography images in patients with idiopathic pulmonary fibrosis.
Prior studies of clinical prognostication in idiopathic pulmonary fibrosis (IPF) using computed tomography (CT) have often used subjective analyses or have evaluated quantitative measures in isolation. This study examined associations between both densitometric and local histogram based quantitative CT measurements with pulmonary function test (PFT) parameters and mortality. In addition, this study sought to compare risk prediction scores that incorporate quantitative CT measures with previously described systems. Forty six patients with biopsy proven IPF were identified from a registry of patients with interstitial lung disease at Brigham and Women's Hospital in Boston, MA. CT scans for each subject were visually scored using a previously published method. After a semi-automated method was used to segment the lungs from the surrounding tissue, densitometric measurements including the percent high attenuating area, mean lung density, skewness and kurtosis were made for the entirety of each patient's lungs. A separate, automated tool was used to detect and quantify the percent of lung occupied by interstitial lung features. These analyses were used to create clinical and quantitative CT based risk prediction scores, and the performance of these was compared to the performance of clinical and visual analysis based methods. All of the densitometric measures were correlated with forced vital capacity and diffusing capacity, as were the total amount of interstitial change and the percentage of interstitial change that was honeycombing measured using the local histogram method. Higher percent high attenuating area, higher mean lung density, lower skewness, lower kurtosis and a higher percentage of honeycombing were associated with worse transplant free survival. The quantitative CT based risk prediction scores performed similarly to the clinical and visual analysis based methods. Both densitometric and feature based quantitative CT measures correlate with pulmonary function test measures and are associated with transplant free survival. These objective measures may be useful for identifying high risk patients and monitoring disease progression. Further work will be needed to validate these measures and the quantitative imaging based risk prediction scores in other cohorts.


Trypanocidal activity of Meliaceae and Rutaceae plant extracts.
The in vitro trypanocidal activity of 22 extracts and 43 fractions of plants belonging to the families Meliaceae and Rutaceae was evaluated. The extracts from leaves of Conchocarphus heterophyllus and branches of Trichilia ramalhoi were the most active. The trypanocidal activity seems to be increased by fractionation of the extracts. Fractions from C. heterophyllus and Galipea carinata were the most active and a 100% lysis of the parasites was observed for five fractions. From one of them were isolated two flavonoids: flavone and 7-methoxyflavone, which showed weak trypanocidal activity. The results obtained from the extracts and fractions revealed that the order Rutales is a promising source for the search of new drugs for Chagas disease. Phytochemical studies with the other active fractions are underway in order to isolate compounds, which could be associated with observed activities.


Lactating adenoma--cytomorphologic study with review of literature.
Lactating adenoma is an uncommon well-differentiated benign tumor of secretory mammary epithelium that occurs in pregnant and lactating women. Three percent of all breast cancers are diagnosed during pregnancy and need to be differentiated from other breast masses occurring in pregnancy and lactational states. Its origin, though controversial, is believed to be de novo or a variant of pre-existing tubular adenoma or fibroadenoma, that reflects the morphologic changes resulting from the physiologic state of pregnancy. Four pregnant/lactating women presenting with solitary breast masses were aspirated. Spontaneous regression of the mass was observed in two of the four cases, one underwent excision biopsy and one case was lost to follow up. All four cases were diagnosed as lactating adenoma on fine needle aspiration cytology. Cytomorphologic features included cellular aspirates comprising of epithelial cells, scattered and in small groups. The acinar cells had foamy to vacuolated cytoplasm. The nucleus had prominent nucleoli. Background showed abundant foamy material. Biopsy confirmed lactating adenoma in one of the cases. Lactating adenoma needs to be differentiated from other breast masses, including carcinoma, in pregnant or lactating women. Sonographic studies are not diagnostic and surgical biopsies are not recommended as a majority of the lesions are known to regress spontaneously.


A TGF-β-dominant chemoresistant phenotype of hepatoblastoma associated with aflatoxin exposure in children.
Hepatoblastoma (HB) is the most common liver cancer in children, posing a serious threat to children's health. Chemoresistance is the leading cause of mortality in patients with HB. A more explicit definition of the features of chemotherapy resistance in HB represents a fundamental urgent need. We performed an integrative analysis including single-cell RNA sequencing, whole-exome sequencing, and bulk RNA sequencing in 180 HB samples, to reveal genomic features, transcriptomic profiles, and the immune microenvironment of HB. Multicolor immunohistochemistry staining and in vitro experiments were performed for validation. Here, we reported four HB transcriptional subtypes primarily defined by differential expression of transcription factors. Among them, the S2A subtype, characterized by strong expression of progenitor ( MYCN , MIXL1 ) and mesenchymal transcription factors ( TWIST1 , TBX5 ), was defined as a new chemoresistant subtype. The S2A subtype showed increased TGF-β cancer-associated fibroblast and an immunosuppressive microenvironment induced by the upregulated TGF-β of HB. Interestingly, the S2A subtype enriched SBS24 signature and significantly higher serum aflatoxin B1-albumin (AFB1-ALB) level in comparison with other subtypes. Functional assays indicated that aflatoxin promotes HB to upregulate TGF-β. Furthermore, clinical prognostic analysis showed that serum AFB1-ALB is a potential indicator of HB chemoresistance and prognosis. Our studies offer new insights into the relationship between aflatoxin and HB chemoresistance and provide important implications for its diagnosis and treatment.


A review of the function and evolution of the cecal appendix.
Since its initial discovery in the 1500s, the cecal appendix has been an anatomical structure of great intrigue, notorious for its inconvenient tendency to become inflamed and often require surgical intervention. Appendicitis is one of the most common indications for emergency abdominal surgery, costing healthcare systems billions of dollars globally and causing tens of thousands of deaths annually. Yet, recent studies have indicated that the appendix may serve important protective functions in fortifying the body's immune response against invading pathogens and re-inoculating the gut with commensal bacteria after periods of gastrointestinal illness. While the cecal appendix was once believed to be a synapomorphy of hominoids (humans and other great apes), recent studies suggested that it is a recurrent trait found in several other species of primates, rodents, lagomorphs, marsupials, and monotremes. Mapping appendiceal and other gastrointestinal traits across a mammalian consensus phylogeny revealed that the cecal appendix has evolved independently numerous times throughout mammalian evolution, significantly more than would be expected due to chance alone, suggesting that the appendix is adaptively advantageous. However, attempts to identify an overarching ecological, behavioral, dietary, or environmental factor driving some species to evolve an appendix have been largely unsuccessful, indicating that the cecal appendix has a complex and diverse evolutionary history. This review discusses the current understanding of the pathophysiology, evolution, and possible functions of the appendix, both within humans and broadly across the class Mammalia.


Coronary risk factor outcomes following coronary artery bypass surgery.
The coronary risk factor status of patients prior to and following coronary artery bypass surgery (CABG) has been poorly investigated. Two consecutive series of CABG patients were surveyed following CABG. One hundred and thirty patients were assessed immediately following CABG and 530 patients were assessed 12-30 months following CABG. For the long-term post-CABG group, over 80% of those who had ever smoked had ceased. Sixty-four per cent of these males and 50% of females were classified as being overweight. Twenty-five per cent of males and 34% of females reportedly had high serum cholesterol (i.e. greater than or equal to 6.5 mmol/L). Comparing these CABG data with age-adjusted National Heart Foundation Risk Factor Prevalence Survey data, there was a higher prevalence of ex-smokers, overweight, hypertension, and elevated cholesterol. It was concluded that on most coronary risk factors, except for smoking, these CABG patients had a worse profile than the general Australian community. This problem warrants further research and the development of appropriate treatment programs.


Advanced practice nursing: opportunities and challenges.
Planning for the future may not be easy but it is always worthwhile. Resources that can help in making choices include professional organizations such as the Kentucky Coalition of Nurse Practitioners and Nurse Midwives, KNA, American Academy of Nurse Practitioners, American College of Nurse Practitioners, the Internet, and the college and university Schools of Nursing. Taking control of one's destiny is the best gift that can be given to one's self. Increasing options for career development is just one of the benefits of pursuing educational goals. The first step is commitment to goal. Selecting the right specialty, planning how financial obligations will be met and choosing the program that best meets identified needs are steps that will follow. Health care changes are occurring at such a rapid pace the individual nurse may feel caught in a whirlwind without control. Making the choice to seek change will present its own challenges but without change, growth is impossible. For those considering an Advanced Practice role, making the commitment, outlining a plan with each step clearly identified, reliance on a strong support system, and maintaining a vision of the completed goal will lead to success.


Molecular prevalence and genotyping of Chlamydia spp. in wild birds from South Korea.
Wild birds are reservoirs for Chlamydia spp. Of the total 225 samples from wild birds during January to September 2016 in Korea, 4 (1.8%) and 2 (0.9%) showed positive for Chlamydia psittaci and Chlamydia gallinacea, respectively. Phylogenetic analyses and comparisons of sequence identities for outer-membrane protein A (ompA) revealed that Korean C. psittaci fall into three previously known genotypes; genotype E, 1V and 6N, whereas the Korean C. gallinacea were classified as new variants of C. gallinacea. Our study demonstrates that wild birds in South Korea carry at least two Chlamydia species: C. psittaci and C. gallinacea, and provides new information on the epidemiology of avian chlamydiosis in wild birds.


Oxidation of L-cysteine at a fluorosurfactant-modified gold electrode: lower overpotential and higher selectivity.
We describe the oxidation of L-cysteine (CySH) at a fluorosurfactant (i.e., Zonyl FSO)-modified gold electrode (FSO-Au). Significantly reduced anodic overpotential of CySH was observed. The FSO layer inhibited the adsorption of CySH and its oxidation products at the gold electrode surface, and the low coverage of the adsorbed thiol-containing species might account for the more facile electron-transfer kinetics of free CySH at low potentials. An electrochemical impedance spectroscopy study revealed the lower charge-transfer resistance of CySH oxidation at the FSO-Au electrode as compared to that at a bare gold electrode. Interestingly, although the FSO layer facilitated CySH oxidation, the anodic responses of other electroactive biological species such as glucose, uric acid, and ascorbic acid were generally suppressed. Furthermore, the modified electrode was capable of differentiating CySH from other low-molecular-mass biothiols such as homocysteine and glutathione. The unique features of the FSO-Au electrode allowed for the development of a highly selective method of detecting CySH in complex biological matrices. The direct determination of free reduced and total CySH in human urine samples has been successfully carried out without the assistance of any separation techniques.


Follow-up with Callers to the National Suicide Prevention Lifeline: Evaluation of Callers' Perceptions of Care.
Continuity of care for suicidal individuals engaged with a variety of health and mental health care systems has become a national priority, and crisis hotlines are increasingly playing a part in the risk management and continuum of care for these individuals. The current study evaluated a national initiative to have crisis centers in the National Suicide Prevention Lifeline network provide follow-up care to suicidal callers. Data were obtained from 550 callers followed by 41 crisis counselors from 6 centers. Two main data sources provided the information for the current study: a self-report counselor questionnaire on the follow-up activities completed on each clinical follow-up call and a telephone interview with follow-up clients, providing data on their perceptions of the follow-up intervention's effectiveness. The majority of interviewed follow-up clients reported that the intervention stopped them from killing themselves (79.6%) and kept them safe (90.6%). Counselor activities, such as discussing distractors, social contacts to call for help, and reasons for dying, and individual factors, such as baseline suicide risk, were associated with callers' perceptions of the impact of the intervention on their suicide risk. Our findings provide evidence that follow-up calls to suicidal individuals can reduce the perceived risk of future suicidal behavior.


PerPAS: Topology-Based Single Sample Pathway Analysis Method.
Identification of intracellular pathways that play key roles in cancer progression and drug resistance is a prerequisite for developing targeted cancer treatments. The era of personalized medicine calls for computational methods that can function with one sample or a very small set of samples. Developing such methods is challenging because standard statistical approaches pose several limiting assumptions, such as number of samples, that prevent their application when approaches to one. We have developed a novel pathway analysis method called PerPAS to estimate pathway activity at a single sample level by integrating pathway topology and transcriptomics data. In addition, PerPAS is able to identify altered pathways between cancer and control samples as well as to identify key nodes that contribute to the pathway activity. In our case study using breast cancer data, we show that PerPAS can identify highly altered pathways that are associated with patient survival. PerPAS identified four pathways that were associated with patient survival and were successfully validated in three independent breast cancer cohorts. In comparison to two other pathway analysis methods that function at a single sample level, PerPAS had superior performance in both synthetic and breast cancer expression datasets. PerPAS is a free R package (http://csbi.ltdk.helsinki.fi/pub/czliu/perpas/).


Vaccination with recombinant adenovirus expressing multi-stage antigens of Toxoplasma gondii by the mucosal route induces higher systemic cellular and local mucosal immune responses than with other vaccination routes.
Toxoplasmosis caused by Toxoplasma gondii, an obligate intracellular protozoan, is a cause of congenital disease and abortion in humans and animals. Various vaccination strategies against toxoplasmosis in rodent models have been used in the past few decades; however, effective vaccines remain a challenge. A recombinant adenovirus vaccine expressing ubiquitin-conjugated multi-stage antigen segments (Ad-UMAS) derived from different life-cycle stages of T. gondii was constructed previously. Here, we compared the immune responses and protection effects in vaccination of mice with Ad-UMAS by five vaccination routes including intramuscular (i.m.), intravenous (i.v.), subcutaneous (s.c.), intraoral (i.o.), and intranasal (i.n.). Much higher levels of T. gondii-specific IgG and IgA antibodies were detected in the sera of the intraoral and intranasal vaccination groups on day 49 compared with controls (p < 0.05). The percentages of CD8+ T-cells in mice immunized intranasally and intraorally were larger than in mice immunized intramuscularly (p < 0.05). The highest level of IL-2 and IFN-γ was detected in the group with nasal immunization, and splenocyte proliferation activity was significantly enhanced in mice immunized via the oral and nasal routes. Furthermore, the higher survival rate (50%) and lower cyst numbers observed in the intraoral and intranasal groups all indicate that Ad-UMAS is far more effective in protecting mice against T. gondii infection via the mucosal route. Ad-UMAS could be an effective and safe mucosal candidate vaccine to protect animals and humans against T. gondii infection.


Comparison of high-energy photon and electron dosimetry for various dosimetry protocols.
The American Association of Physicists in Medicine Task Group 51 (TG-51) and the International Atomic Energy Agency (IAEA) published a new high-energy photon and electron dosimetry protocol, in 1999 and 2000, respectively. These protocols are based on the use of an ion chamber having an absorbed-dose to water calibration factor with a 60Co beam. These are different from the predecessors, the TG-21 and IAEA TRS-277 protocols, which require a 60Co exposure or air-kerma calibration factor. The purpose of this work is to present the dose comparison between various dosimetry protocols and the AAPM TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams. The absorbed-dose to water calculated according to the Japanese Association of Radiological Physics (JARP), International Atomic Energy Agency Technical Report Series No. 277 (IAEA TRS-277) and No. 398 (IAEA TRS-398) protocols is compared to that calculated using the TG-51 protocol. For various Farmer-type chambers in photon beams, TG-51 is found to predict 0.6-2.1% higher dose than JARP. Similarly, TG-51 is found to be higher by 0.7-1.7% than TRS-277. For electron beams TG-51 is higher than JARP by 1.5-3.8% and TRS-277 by 0.2-1.9%. The reasons for these differences are presented in terms of the cavity-gas calibration factor, Ngas, and a dose conversion factor, Fw, which converts the absorbed-dose to air in the chamber to the absorbed-dose to water. The ratio of cavity-gas calibration factors based on absorbed-dose to water calibration factors, N60Co(D,w), in TG-51 and cavity-gas calibration factors which are equivalent to absorbed-dose to air chamber factors, N(D,air), based on the IAEA TRS-381 protocol is 1.008 on average. However, the estimated uncertainty of the ratio between the two cavity-gas calibration factors is 0.9% (1 s.d.) and consequently, the observed difference of 0.8% is not significant. The absorbed-dose to water and exposure or air-kerma calibration factors are based on standards traceable to the National Institute of Standards and Technology (NIST). In contrast, the absorbed-dose to water determined with TRS-398 is in good agreement with TG-51 within about 0.5% for photon and electron beams.


Effect of Nigella sativa Intake on Oxidative Stress and Inflammation in Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Several studies have shown that the intake of N. sativa has a beneficial effect on metabolic syndrome and related disorders. In this meta-analysis, our primary objective was to assess the impact of Nigella sativa consumption on inflammation and oxidative stress biomarkers among individuals diagnosed with metabolic syndrome and its associated conditions. Our search was conducted on prominent online databases such as Web of Science, Scopus, PubMed, and EMBASE, utilizing relevant keywords until August 2023. This meta-analysis was performed on 16 RCTs comprising 1033 participants. Our results showed that intake of nigella sativa significantly decreased CRP [SMD: -0.60; (95% CI: from -0.96 to -0.23); P = 0.00], TNF-α [SMD: -0.53; (95% CI: from -0.74 to -0.53); P = 0.00]; IL-6 [SMD: -0.54 ; (95% CI: from -1.01 to -0.07); P = 0.02], and MDA: [SMD: -1.28; (95% CI: from -2.11 to -0.46); P = 0.00] levels. In addition, SOD: [SMD: 1.35; (95% CI, from 0.77 to 1.93); P = 0.00] and TAC [SMD: 2.82; (95% CI, from 0.55 to 5.084); P = 0.01] levels significantly increased in the intervention group compared to the placebo group. Our results showed that THE consumption of N. sativa could be associated with improved oxidative stress and inflammation in patients with metabolic syndrome and related disorders.


[Mental capacity of psychiatric patients].
Nearly every society maintains legal norms that define those members of society qualified to participate in social affairs. Mental capacity and legal competence are deemed necessary conditions for legal actions to have legal validity. On Nov. 23, 2009, newly revised adult guardianship provisions came into effect in Taiwan. However, there has been lack of discussion with regard to how assessments of mental capacity and legal competence should be conducted on psychiatric patients. This paper reviewed relevant overseas literature on this subject and followed common practice in separating legal mental capacity into causal and functional components. The causal component predicates the diseases and illnesses that render the disability, while the functional component represents legally substantial impairments in terms of cognition, emotion and behavior. The paper explored functional component contents, including finance management, individual health care, independence in daily life, interpersonal relationships and communing. Findings pointed out that in setting up competence standards, a trade-off between respect for autonomy and beneficence is unavoidable. As Taiwan does not have rich empirical data on competence assessments and decisions, collaboration between the legal and psychiatric professions is recommended to engage in relevant research to enhance legal consistencies and the science of competence assessment.


alpha1,3-Galactosyltransferase gene-knockout miniature swine produce natural cytotoxic anti-Gal antibodies.
The expression of galactose alpha 1,3 galactose (Gal) in pigs has proved a barrier to xenotransplantation. Miniature swine lacking Gal (Gal pigs) have been produced by nuclear transfer/embryo transfer. The tissues of five Gal pigs of SLA dd haplotype (SLA) were tested for the presence of Gal epitopes by staining with the Griffonia simplicifolia IB4 lectin. Their sera were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (Gal) SLA-matched pigs; serum cytotoxicity was also assessed. The cellular responses of PBMC from Gal swine toward Gal SLA-matched PBMC were tested by mixed leukocyte reaction and cell-mediated lympholysis assays. None of the tissues tested showed Gal expression. Sera from all five Gal pigs manifested IgM binding to Gal pig PBMC, and sera from three showed IgG binding. In all five cases, cytotoxicity to Gal cells could be demonstrated, which was lost after treatment of the sera with dithiothreitol, indicating IgM antibody-mediated cytotoxicity. PBMC from Gal swine had no proliferative or cytolytic T-cell response toward Gal SLA-matched PBMC. Gal pigs do not express Gal epitopes and develop anti-Gal antibodies that are cytotoxic to Gal pig cells. The absence of an in vitro cellular immune response between Gal and Gal pigs is related to their identical SLA haplotype and indicates the absence of immunogenicity of Gal in T-cell responses. The model of Gal organ transplantation into a Gal SLA-matched recipient would be a valuable large animal model in the study of accommodation or B-cell tolerance.