A comparison of the epidemiology of youth-onset insulin-dependent diabetes mellitus between Japan and the United States (Allegheny County, Pennsylvania).
Children in the United States are almost 20 times more likely to develop insulin-dependent diabetes mellitus (IDDM) than children in Japan. Little is known about the differences between the two countries that might account for this very large difference in risk. The current research compared the characteristics of IDDM in Japan with those of the United States (Allegheny County, Pennsylvania). Seasonality, relationship to socioeconomic status, and age at onset were similar. There was some suggestion of a sex difference. Of interest was that reported recent infections at onset were much higher in the United States. In addition, the risk to first-degree relatives in Japan appeared to be somewhat lower than in the United States, although this may have been the result of differences in ascertainment. These results are discussed in relation to potential factors that might account for the major incidence differences.


The prefusion structure of herpes simplex virus glycoprotein B.
Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins.


Paediatric flexible flat foot: how are we measuring it and are we getting it right? A systematic review.
Flexible flat foot is a normal observation in typically developing children, however, some children with flat feet present with pain and impaired lower limb function. The challenge for health professionals is to identify when foot posture is outside of expected findings and may warrant intervention. Diagnoses of flexible flat foot is often based on radiographic or clinical measures, yet the validity and reliability of these measures for a paediatric population is not clearly understood. The aim of this systematic review was to investigate how paediatric foot posture is defined and measured within the literature, and if the psychometric properties of these measures support any given diagnoses. Electronic databases (MEDLINE, CINAHL, EMBASE, Cochrane, AMED, SportDiscus, PsycINFO, and Web of Science) were systematically searched in January 2017 for empirical studies where participants had diagnosed flexible flat foot and were aged 18 years or younger. Outcomes of interest were the foot posture measures and definitions used. Further articles were sought where cited in relation to the psychometric properties of the measures used. Of the 1101 unique records identified by the searches, 27 studies met the inclusion criteria involving 20 foot posture measures and 40 definitions of paediatric flexible flat foot. A further 18 citations were sought in relation to the psychometric properties of these measures. Three measures were deemed valid and reliable, the FPI-6 > + 6 for children aged three to 15 years, a Staheli arch index of > 1.07 for children aged three to six and ≥ 1.28 for children six to nine, and a Chippaux-Smirak index of > 62.7% in three to seven year olds, > 59% in six to nine year olds and ≥ 40% for children aged nine to 16 years. No further measures were found to be valid for the paediatric population. No universally accepted criteria for diagnosing paediatric flat foot was found within existing literature, and psychometric data for foot posture measures and definitions used was limited. The outcomes of this review indicate that the FPI - 6, Staheli arch index or Chippaux-Smirak index should be the preferred method of paediatric foot posture measurement in future research.


Effects of fabrication errors on the performance of cylindrical diffractive lenses: rigorous boundary-element method and scalar approximation.
The effects of fabrication errors on the performance of collimating finite-thickness cylindrical diffractive lenses with eight discrete levels are investigated with a rigorous boundary-element method and a scalar approach. The photolithographic fabrication errors considered are mask alignment errors, exposure errors (that result in linewidth errors), and etch-depth errors. A cylindrical Gaussian beam of TE or TM polarization is incident upon the resulting lenses. Lenses of F/4, F/2, and F/1.4 are examined. The diffraction efficiencies of the lenses with fabrication errors are generally lower than the error-free lenses with the most severe performance degradation occurring for mask misalignment and exposure errors.


Psychosocial Interventions to Promote Undetectable HIV Viral Loads: A Systematic Review of Randomized Clinical Trials.
Suppressing HIV viral loads to undetectable levels is essential for ending the HIV/AIDS epidemic. We evaluated randomized controlled trials aimed to increase antiretroviral medication adherence and promote undetectable viral loads among people living with HIV through November 22, 2019. We extracted data from 51 eligible interventions and analyzed the results using random effects models to compare intervention effects between groups within each intervention and across interventions. We also evaluated the relation between publication date and treatment effects. Only five interventions increased undetectable viral loads significantly. As a whole, the analyzed interventions were superior to Standard of Care in promoting undetectable viral loads. Interventions published more recently were not more effective in promoting undetectable viral loads. No treatment category consistently produced significant increases in undetectable viral loads. To end the HIV/AIDS epidemic, we should use interventions that can suppress HIV viral loads to undetectable levels.


In vivo monitoring of chlorophyll fluorescence response to low-dose gamma-irradiation in pumpkin (cucurbita pepo) leaves.
The effect of gamma-irradiation on the in vivo-measured chlorophyll fluorescence in a pumpkin leaves (Cucurbita pepo) has been investigated. Plants were grown in the same environment, then divided into several groups and irradiated at ambient conditions at small dose levels (up to 13.4 Gy) with (60)Co gamma-rays. The post-irradiation effect on chlorophyll status in the leaves was examined by measuring chlorophyll fluorescence 2 days (48 h) after exposure. It is undoubtedly found that the value of fluorescence intensity ratio (FIR) at 690 nm and 735 nm (F(690)/F(735)) depends upon the ionizing radiation dose. Even with the smallest dose of 3.35 Gy, ionizing radiation notably altered the fluorescence spectra of leaves. The spectra difference was manifested by decrease of FIR due to changed chlorophyll luminescence, the possible reason for which could be increase of chlorophyll concentration during the recovery process of the plant. The potential implications of these results for plant physiological status monitoring, as well as for pollution detection and assessment, are discussed in brief.


Gene positional changes relative to the nuclear substructure correlate with the proliferating status of hepatocytes during liver regeneration.
In the interphase nucleus the DNA of higher eukaryotes is organised in loops anchored to a proteinaceous substructure variously named but commonly known as the nuclear matrix. Important processes of nuclear physiology, such as replication, transcription and processing of primary transcripts, occur at macromolecular complexes located at discrete sites upon the nuclear substructure. The topological relationships between gene sequences located in the DNA loops and the nuclear substructure appear to be non-random, thus posing the question of whether such relationships remain invariant or change after the critical nuclear transitions associated with cell proliferation and tissue regeneration in vivo. The hepatocytes are cells that preserve a proliferating capacity that is readily displayed after partial ablation of the liver, leading to liver regeneration in experimental animals such as the rat. Using this animal model coupled to a recently developed PCR-based method for mapping the position of specific DNA sequences relative to the nuclear substructure, we provide evidence that transient changes in the topological relationships between specific genes and the nuclear substructure occur during liver regeneration and that such changes correlate with the actual proliferating status of the cells, thus suggesting that specific transitions in the higher-order DNA structure are characteristic of the quiescent (G0) and replicating (S) phases of the cell cycle in vivo.


The clinical features and prognostic implications of PTPN11 mutation in adult patients with acute myeloid leukemia in China.
The clinical significance of protein tyrosine phosphatase nonreceptor type 11 mutation (PTPN11mut ) in acute myeloid leukemia (AML) is underestimated. We collected the data of AML patients with mutated PTPN11 and wild-type PTPN11 (PTPN11wt ) treated at our hospital and analyzed their clinical characteristics and prognosis. Fifty-nine PTPN11mut and 124 PTPN11wt AML patients were included. PTPN11mut was more common in myelomonocytic and monocytic leukemia, and was more likely to co-mutate with KRAS, KMT2C, NRAS, U2AF1, NOTCH1, IKZF1, and USH2A mutations than PTPN11wt . The overall survival for AML patients with PTPN11mut was significantly shorter than that for those with PTPN11wt (p = 0.03). The negative impact of PTPN11mut on overall survival was pronounced in the "favorable" and "intermediate" groups of ELN2017 risk stratification, as well as in the wild-type NPM1 group (p = 0.01, p = 0.01, and p = 0.04). PTPN11mut is associated with distinct clinical and molecular characteristics, and adverse prognosis in AML patients.


Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells.
The glycosyltransferase, ST6Gal-I, adds sialic acid in an α2-6 linkage to the N-glycans of membrane and secreted glycoproteins. Up-regulation of ST6Gal-I occurs in many cancers, including colon carcinoma, and correlates with metastasis and poor prognosis. However, mechanisms by which ST6Gal-I facilitates tumor progression remain poorly understood due to limited knowledge of enzyme substrates. Herein we identify the death receptor, Fas (CD95), as an ST6Gal-I substrate, and show that α2-6 sialylation of Fas confers protection against Fas-mediated apoptosis. Intriguingly, differences in ST6Gal-I activity do not affect the function of DR4 or DR5 death receptors upon treatment with TRAIL, implicating a selective effect of ST6Gal-I on the Fas receptor. Using ST6Gal-I knockdown and forced overexpression colon carcinoma cell models, we find that α2-6 sialylation of Fas prevents apoptosis stimulated by FasL as well as the Fas-activating antibody, CH11, as evidenced by decreased activation of caspases 8 and 3. We also show that α2-6 sialylation of Fas does not alter the binding of CH11, but rather inhibits the capacity of Fas to induce apoptosis by blocking the association of FADD with Fas cytoplasmic tails, an event that initiates death-inducing signaling complex formation. Furthermore, α2-6 sialylation of Fas inhibits Fas internalization, which is required for apoptotic signaling. Although dysregulated Fas activity is a well known mechanism through which tumors evade apoptosis, the current study is the first to link Fas insensitivity to the actions of a specific sialyltransferase. This finding establishes a new paradigm by which death receptor function is impaired for the self-protection of tumors against apoptosis.


Endoscopic Reconstruction of an Oral Feeding Route Using a Rendezvous Approach.
The approach to esophageal obstruction or discontinuity remains challenging and often involves complex reconstructive surgeries. The rendezvous endoscopic technique might be interesting in cases of complete esophageal obstruction. Herein we describe a successful case of endoscopic recanalization of the esophageal lumen in a patient with a long-standing esophageal discontinuity resulting from several surgeries and chemoradiation for a squamous cell carcinoma of the hypopharynx, ending in a major cervical amputation, construction of a neopharynx, and definitive surgical closure of the superior esophagus with a PEG placement. With a rendezvous technique (peroral and through the gastrostomy) and under radiographic guidance, puncture from the neopharynx into the distal esophagus was performed, followed by balloon dilation and covered metal stent placement in order to reconstruct a neoesophagus. Five weeks later, the stent was removed (using a stent-in-stent technique). No complications occurred. The patient has been able to eat soft food and is being kept under regular endoscopic surveillance to control/treat a luminal stenosis of the neoesophagus. This case report illustrates a successful endoscopic treatment of post-surgical complete esophageal obstruction. This approach should be considered in the therapeutic armamentarium of these difficult clinical settings.


Reappraisal of diffusion, solubility, and consumption of oxygen in frog skeletal muscle, with applications to muscle energy balance.
Previously we tested the validity of the one-dimensional diffusion equation for O2 in the excised frog sartorius muscle and used it to measure the diffusion coefficient (D) for O2 in this muscle and the time course of its rate of O2 consumption (Qo2) after a tetanus (Mahler, 1978, 1979, J. Gen. Physiol., 71:533-557, 559-580, 73:159-174). A transverse section of the frog sartorius is in fact well fit by a hemi-ellipse with width divided by maximum thickness averaging 5.1 +/- 0.2. Using the previous techniques with the two-dimensional diffusion equation and this hemi-elliptical boundary yields a value for D that is 30% smaller than reported previously; the revised values at 0, 10, and 22.8 degrees C are 6.2, 7.9, and 10.8 X 10(-6) cm2/s, respectively. After a tetanus at 20 degrees C, Qo2 rose quickly to a peak and then declined exponentially, with a time constant (tau) approximately 15% faster than that reported previously; tau averaged 2.1 min in Rana temporaria and 2.6 min in Rana pipiens. A technique was devised to measure the solubility (alpha) of O2 in intact, respiring muscles, and yielded alpha (muscle)/alpha (H2O) = 1.26 +/- 0.04. With these modifications, the values for O2 consumption obtained with the diffusion method were in agreement with those measured by the direct method of Kushmerick and Paul (1976, J. Physiol. [Lond.]., 254:693-709). Using results from both methods, at 20 degrees C the ratio of phosphorylcreatine split during a tetanus to O2 consumption during recovery ranged from 5.2 to 6.2 mumol/mumol, and postcontractile ATP hydrolysis was estimated to be 13.6 +/- 4.1 (n = 3) nmol/mumol total creatine.


Antibiotic prophylaxis in genitourinary surgery: a comparison of cefotaxime and cefazolin.
In a prospective, single-blind study, the efficacy of cefotaxime and cefazolin in the prevention of postoperative infection was compared in 133 patients admitted for elective genitourinary surgery (over half of whom were undergoing transurethral resection). In regimen 1, cefotaxime was given perioperatively (before, during, and up to two hours after surgery); in regimen 2, cefotaxime was given perioperatively and for 24 hours postoperatively; and in regimen 3, cefazolin was given perioperatively and for 24 hours postoperatively. All doses equaled 1 gm and were given either intramuscularly or by intravenous bolus. All patients had negative urine cultures preoperatively. The criterion for absence of infection was a negative urine culture (less than 10(5) organisms/ml) after surgery. At the final evaluation, 113 of the 133 patients (85%) were free of infection--39 of 45 (86.7%) on regimen 1, 40 of 45 (88.9%) on regimen 2, and 34 of 43 (79.1%) on regimen 3. All 20 patients who had postoperative infections had been catheterized for at least three days. Only 12 patients had temperatures greater than or equal to 101 F two days after surgery, and none had been clinically septic. No side effects other than a mild rash and itching in one patient on regimen 2 were reported. Both cefotaxime regimens were slightly more effective, bacteriologically and clinically, than the standard prophylactic cefazolin regimen. It is concluded that cefotaxime given perioperatively (up to two hours postoperatively) and/or up to 24 hours postoperatively effectively prevents postoperative complications associated with genitourinary surgery.


Scoring system based on BI-RADS lexicon to predict probability of malignancy in suspicious microcalcifications.
To develop a scoring system allowing quantification of the probability of malignancy of suspicious microcalcifications based on Breast Imaging Reporting and Data System (BI-RADS). A total of 163 microcalcification lesions surgically excised in 147 women (aged 28-65 years) were included. Two radiologists independently reviewed each lesion with BI-RADS (4th edition). The interobserver agreement and positive predictive value (PPV) for each descriptor were determined and multivariate analysis was used to develop a scoring system. The scores were compared between benign and malignant lesions and among BI-RADS categories by using the two-sample t-test or the analysis of variance. To assess the discriminative power of the scoring system, the area under the receiver-operating characteristic curve (AUC) and cutoff values for categorization were determined. For the test of the scoring system, the validation data set from a different facility was applied. Interobserver agreement was fair to moderate for distribution, morphology, and category (κ = 0.45, 0.40, and 0.37). PPVs were significantly different among BI-RADS descriptors and categories (P < 0.0001). Of the scoring system developed, the AUC was 0.75. The scores between benign and malignant lesions were significantly different. By means of cutoff values, PPV in category 4a, 4b, 4c, and 5 was 7.0%, 15.0%, 44.8%, and 83.3%, respectively. For the validation data set, the AUC was 0.79 and the PPV in category 4a, 4b, 4c, and 5 was 9.4%, 24.1%, 62.5%, and 80.0%, respectively. In suspicious microcalcifications, our scoring system based on BI-RADS (4th edition) could help to derive a specific final category with good stratification of the probability of malignancy.


Examination of the common cause account in a population-based longitudinal study with narrow age cohort design.
The common cause account suggests that there is a third factor causing aging effects in both sensory and cognitive functioning, hypothesized to be the integrity of the central nervous system [Lindenberger and Baltes; Psychol Aging 1994;9:339-355]. Importantly, the common cause account was developed based on cross-sectional data, which are especially biased by cohort effects. However, cohort effects can be controlled for in narrow age cohort (NAC) designs and by longitudinal examination. Findings from the few longitudinal studies that have studied the relation between age-related changes in sensory and cognitive functions are complex and give only partial support to the common cause account. The present paper examines the common cause account within a longitudinal setting. Our study is unique in the sense that it tests the common cause account within a longitudinal NAC design using data from the Betula project. The participants (n = 1,057) were in the age range of 45-90 years. The findings indicate that the relationship between sensory and memory functioning in both a longitudinal age-heterogeneous and a longitudinal NAC design are much weaker than that detected by an age-heterogeneous cross-sectional design. The demonstrated weak age-associated sensory-cognitive link raises questions regarding the explanatory value of the common cause account and related theoretical accounts for accounting for age-related cognitive changes.


The effect of cannabis on tremor in patients with multiple sclerosis.
Disabling tremor is common in patients with multiple sclerosis (MS). Data from animal model experiments and subjective and small objective studies involving patients suggest that cannabis may be an effective treatment for tremor associated with MS. To our knowledge, there are no published double-blind randomized controlled trials of cannabis as a treatment for tremor in MS patients. The authors conducted a randomized double-blind placebo-controlled crossover trial to examine the effect of oral cannador (cannabis extract) on 14 patients with MS with upper limb tremors. There were eight women and six men, with a mean age of 45 years and mean Expanded Disability Status Scale score of 6.25. Patients were randomly assigned to receive each treatment and the doses escalated over a 2-week period before each assessment. The primary outcome was change on a tremor index, measured using a validated tremor rating scale. The study was powered to detect a functionally significant 50% improvement in the tremor index. Secondary outcomes included accelerometry, an ataxia scale, spiral drawing, finger tapping, and nine-hole pegboard test performance. Analysis of the data showed no significant improvement in any of the objective measures of upper limb tremor with cannabis extract compared to placebo. Finger tapping was faster on placebo compared to cannabis extract (p < 0.02). However, there was a nonsignificant trend for patients to experience more subjective relief from their tremors while on cannabis extract compared to placebo. Cannabis extract does not produce a functionally significant improvement in MS-associated tremor.


Generation of enterocyte-like cells with pharmacokinetic functions from human induced pluripotent stem cells using small-molecule compounds.
The small intestine plays an important role in all aspects of pharmacokinetics, but there is no system for the comprehensive evaluation of small-intestinal pharmacokinetics, including drug metabolism and absorption. In this study, we aimed to construct an intestinal pharmacokinetics evaluation system and to generate pharmacokinetically functional enterocytes from human induced pluripotent stem cells. Using activin A and fibroblast growth factor 2, we differentiated these stem cells into intestinal stem cell-like cells, and the resulting cells were differentiated into enterocytes in a medium containing epidermal growth factor and small-molecule compounds. The differentiated cells expressed intestinal marker genes and drug transporters. The expression of sucrase-isomaltase, an intestine-specific marker, was markedly increased by small-molecule compounds. The cells exhibited activities of drug-metabolizing enzymes expressed in enterocytes, including CYP1A1/2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, UGT, and sulfotransferase. Fluorescence-labeled dipeptide uptake into the cells was observed and was inhibited by ibuprofen, an inhibitor of the intestinal oligopeptide transporter solute carrier 15A1/PEPT1. CYP3A4 mRNA expression level was increased by these compounds and induced by the addition of 1α,25-dihydroxyvitamin D3. CYP3A4/5 activity was also induced by 1α,25-dihydroxyvitamin D3 in cells differentiated in the presence of the compounds. All these results show that we have generated enterocyte-like cells that have pharmacokinetic functions, and we have identified small-molecule compounds that are effective for promoting intestinal differentiation and the gain of pharmacokinetic functions. Our enterocyte-like cells would be useful material for developing a novel evaluation system to predict human intestinal pharmacokinetics.


Equal access, (Un)equal uptake: a longitudinal study of cataract surgery uptake in older people in England.
Uptake of cataract removal is a function of the effectiveness of the healthcare delivery services: services that are inaccessible, inappropriate, or unaffordable will not be utilised by (sub)populations, who consequently live with untreated cataracts. The aim of the study was to identify the relationship between individual wealth inequalities and uptake of cataract surgery in England, having controlled for the effects of potentially confounding variables. The final sample comprised of 2091 respondents from the English Longitudinal Study on Ageing (ELSA) who were diagnosed with cataracts prior to or during the study, aged 50 and over at wave 1, who had not undergone cataract surgery prior to the first survey observation, and had also provided a response in the second wave of the study. The uptake of cataract surgery was measured using the question, have you ever had cataract surgery? Data from waves 1-5 were used to identify those having received treatment during the 8-year observation window of ELSA. Survival analysis techniques were used. Having controlled for the effects of potentially confounding variables, wealth did not make a statistically significant contribution to the overall fit of the Cox proportional hazard model nor were individual parameters statistically significant. Thus, respondents' socioeconomic position was not found to be a significant predictor in the uptake of cataract surgery in the UK. Receiving a recommendation from a medical professional was a key driving factors in the uptake of cataract surgery. Study findings suggest that uptake of cataract surgery among over 50s with a cataracts diagnosis in England do not discriminate on the grounds of individuals' material social position (wealth).


Alcohol intoxication impairs recognition of fear and sadness in others and metacognitive awareness of emotion recognition ability.
Alcohol intoxication is linked to negative social behaviors, but the mechanisms underlying this relationship are poorly understood. We investigated the effects of high-dose alcohol intoxication on the ability to perceive a range of basic emotions (sad, happy, anger, disgust, fear, and surprise) of different intensities, and on self-appraisals of emotion perception ability (i.e., metacognitive judgments). Sixty-four participants consumed either an alcohol or placebo beverage. An emotion recognition task was used to assess emotion perception ability, and participants provided confidence ratings when providing each emotion recognition response. Alcohol-intoxicated individuals demonstrated a reduced ability to detect fear and sadness at moderate-to-high levels of emotion intensity and less overall insight into their ability to recognize emotions. These results provide new insights into the possible difficulties experienced by alcohol-intoxicated individuals in perceiving emotions in others and the limited capacity to monitor their emotion perception abilities, both of which may contribute to inappropriate social responding. (PsycINFO Database Record


Degenerative spondylolisthesis.
This is an interesting group of patients who have in common the roentgenographic finding of degenerative spondylolisthesis. This is a retrospective, uncontrolled review. It would be interesting to have a similar matched group of 132 patients in the same age group without degenerative spondylolisthesis but with marked degenerative changes to compare symptoms, signs, and outcome of treatment. We have not had adequate follow-up on the nonoperative patients and therefore cannot provide data for comparison with the operative group. A total of 51 of our 132 patients had 83 operative procedures. Twenty-five percent, or 13 patients, showed a degenerative spondylolisthesis at L4-5 with a previous history of having undergone a disk excision at the same level. Seven of the 51 patients (14%) developed a progressive slip following surgery. None of these patients had previous fusion. Two patients of the 17 that we operated on primarily (12%) subsequently developed a progressive symptomatic slip. We have concluded from this review that spinal fusion should be performed in conjunction with decompression more frequently in patients with degenerative spondylolisthesis despite the fact that the majority of these patients are over 60 years of age.


Emotional well-being in children with epilepsy: Family factors as mediators and moderators.
Our objective was to examine the relationships of factors associated with children's emotional well-being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors. Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well-being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). The relationships between clinical factors, family factors, and emotional well-being were assessed using multiple regression analyses. Family functioning, family stress, and repertoire of resources that the families had to adapt to stressful events were significantly associated with poor emotional well-being 2 years after diagnosis (p < 0.05) in the multivariable analysis. The effect of parental depressive symptoms was partially mediated by family functioning and family stress (p < 0.01 and p = 0.02, respectively). Family resources acted as a moderator in the relationship between severity of epilepsy and emotional well-being (p < 0.05). Based on our findings, efforts to strengthen the family environment may warrant attention. We suggest that clinicians take a family centered care approach by including families in treatment planning. Family centered care has been shown to improve family well-being and coping and in turn may reduce the impact of clinical factors on emotional well-being to improve long-term health-related quality of life.


Altered praxis network underlying limb kinetic apraxia in Parkinson's disease - an fMRI study.
Parkinson's disease (PD) patients frequently suffer from dexterous deficits impeding activities of daily living. There is controversy whether impaired fine motor skill may stem from limb kinetic apraxia (LKA) rather than bradykinesia. Based on classical models of limb praxis LKA is thought to result when premotor transmission of time-space information of skilled movements to primary motor representations is interrupted. Therefore, using functional magnetic resonance imaging (fMRI) we tested the hypothesis that dexterous deficits in PD are associated with altered activity and connectivity in left parieto-premotor praxis network. Whole-brain analysis of fMRI activity during a task for LKA (coin rotation) showed increased activation of superior and inferior parietal lobule (SPL, IPL) and ventral premotor cortex (vPM) in PD patients compared to controls. For bradykinesia (assessed by finger tapping) a decreased fMRI activity could be detected in patients. Additionally, psychophysical interaction analysis showed increased functional connectivity between IPL and the posterior hippocampi in patients with PD. By contrast, functional connectivity to the right dorsolateral prefrontal cortex was decreased in patients with PD compared to controls. In conclusion, our data demonstrates that dexterous deficits in PD were associated with enhanced fMRI activation of the left praxis network upstream to primary motor areas, mirroring a neural correlate for the behavioral dissociation of LKA and bradykinesia. Furthermore, the findings suggest that patients recruit temporal areas of motor memory as an attempt to compensate for impaired motor skills. Finally, dysexecutive function may contribute to the deficit.


Metastatic disease in uveal melanoma: importance of a genetic profile?
Mutation of SF3B1 has been identified in low-grade uveal melanoma with a good prognosis. In this study, we compare chromosomal aberrations and gene mutations between a primary uveal melanoma and its multiple hepatic and peripancreatic metastases. DNA was isolated from a large primary uveal melanoma after fractionated stereotactic radiotherapy and three distinct metastases (two liver samples and one peripancreatic lymph node) to perform single-nucleotide polymorphism array and fluorescent in-situ hybridization. We analyzed mutations in uveal melanoma target genes BAP1, GNAQ, GNA11, SF3B1, and EIF1AX. The primary tumor showed no abnormalities in chromosome 3, whereas metastases showed deletion of at least 3q12.1-q24 and the BAP1 gene was not mutated. All samples indicated the following consistent chromosomal aberrations: loss of 1p, gain of 6p, and gain of 8q. Subsequently, heterozygous SF3B1 and heterozygous GNA11 mutations were observed. The metastases showed more genetic aberrations than the primary tumor and may therefore represent the genetic status of the tumor before irradiation, whereas the current primary tumor shows presumably irradiation artifacts. An early occurring mutation in GNA11 was observed in all samples. The SF3B1 mutation seems to predispose for late metastatic disease in the absence of a BAP1 mutation.


Cheminformatics in anti-infective agents discovery.
The existing chemical data such as those created by high throughput screening (HTS), structure-activity relationship (SAR) studies are converted into information as a result of storage and registration. Accessibility, manipulation, and data mining of such information make up the knowledge for drug development. Cheminformatics, exploiting the combination of chemical structural knowledge, biological screening, and data mining approaches is used to guide drug discovery and development and would assist by integrating complex series of rational selection of designed compounds with drug-like properties, building smarter focused libraries. This paper presents cheminformatics approaches and tools for designing and data mining of chemical databases and information. Many examples of success in lead identification and optimization in the area of anti-infective therapy have been discussed.


Activation of skeletal alpha-actin gene transcription: the cooperative formation of serum response factor-binding complexes over positive cis-acting promoter serum response elements displaces a negative-acting nuclear factor enriched in replicating myoblasts and nonmyogenic cells.
Three upstream CBAR cis-acting promoter elements, containing the inner core CC(A/T)6GG of the serum response element (SRE), are required for myogenic cell type-restricted expression of the avian skeletal alpha-actin gene (K.L. Chow and R.J. Schwartz, Mol. Cell. Biol. 10:528-538, 1990). These actin SRE elements display differential binding properties with two distinct nuclear proteins, serum response factor (SRF) and another factor described here as F-ACT1. SRF is able to bind to all actin SREs with various affinities. This multisite interaction is marked by cooperative binding events in that the two high-affinity proximal and distal SREs facilitate the weak central-site interaction with SRF, leading to the formation of a higher-order SRF-promoter complex. Functional analyses reveal that undisrupted multiple SRF-DNA interactions are absolutely essential for promoter activity in myogenic cells. F-ACT1, present at higher levels in nonmyogenic cells and replicating myoblasts than in myotubes, binds solely to the proximal SRE, and its binding is mutually exclusive with that of SRF owing to their overlapping base contacts. The cooperative promoter binding by SRF, however, can effectively displace prebound F-ACT1. In addition, an intact F-ACT1 binding site acts as a negative promoter element by restricting developmentally timed expression in myoblasts. F-ACT1 may therefore act as a repressor of skeletal alpha-actin gene transcription. This interplay between F-ACT1 and SRF may constitute a developmental as well as a physiologically regulated mechanism which modulates sarcomeric actin gene expression.


Profiles of Childhood Victimization as Predictors of Sexual Aggression and Intimate Partner Violence Perpetration.
The study utilized a latent profile analysis to evaluate distinct combinations of men's childhood victimization experiences and their communal predictive ability for sexual aggression (SA) and intimate partner violence (IPV) perpetration. Men living in the United States (N = 399) completed assessments of emotional, physical, and sexual childhood victimization, as well as SA and IPV toward women. The results indicated that members of profiles characterized by moderate to high frequencies of childhood victimization-especially sexual victimization-were at increased risk of SA and IPV perpetration. Contrary to expectations, adult- versus peer-perpetrated victimization did not appear to substantially alter risk of perpetration.


Enzymatic synthesis of core 2 O-glycans governs the tissue-trafficking potential of memory CD8+ T cells.
Trafficking of memory CD8+ T cells out of the circulation is essential to provide protective immunity against intracellular pathogens in nonlymphoid tissues. However, the molecular mechanisms that dictate the trafficking potential of diverse memory CD8+ T cell populations are not completely defined. We show that after infection or inflammatory challenge, central memory (TCM) CD8+ T cells rapidly traffic into nonlymphoid tissues, whereas most effector memory cells remain in the circulation. Furthermore, we demonstrate that cellular migration of memory CD8+ T cells into nonlymphoid tissues is driven by interleukin-15 (IL-15)-stimulated enzymatic synthesis of core 2 O-glycans, which generates functional ligands for E- and P-selectins. Given that IL-15-stimulated expression of glycosyltransferase enzymes is largely a feature of TCM CD8+ T cells, this allows TCM to selectively migrate out of the circulation and into nonlymphoid tissues. Collectively, our data indicate that entry of memory CD8+ T cells into inflamed, nonlymphoid tissues is primarily restricted to TCM cells that have the capacity to synthesize core 2 O-glycans.


WEST NILE VIRUS-RELATED TRENDS IN AVIAN MORTALITY IN CALIFORNIA, USA, 2003-12.
West Nile virus (WNV) is an arbovirus transmitted enzootically by Culex mosquitoes among avian hosts. Since 2000, the California Dead Bird Surveillance Program (DBSP) has tracked avian mortality reported by the public on a telephone hotline and website and measured the prevalence of WNV infection in dead birds. We summarize herein WNV prevalence in dead birds tested and variation of WNV transmission over time and space with the use of DBSP data from 2003 to 2012. Prevalence among dead birds was highest in 2004, 2008, and 2012. This pattern was similar to peak WNV infection years for mosquitoes but not to human WNV incidence. Although American Crows (Corvus brachyrhynchos) were most frequently reported and tested, this species ranked third in infection prevalence (44%) after Yellow-billed Magpies (Pica nuttalli; 62%) and Western Scrub-Jays (Aphelocoma californica; 48%). Overall prevalence in American Robin (Turdus migratorius), House Finch (Haemorhous mexicanus), and House Sparrow (Passer domesticus) carcasses ranged from 18% to 22%. Corvid WNV prevalence was highest in South Coast, Bay/Delta, Sacramento, and San Joaquin valleys, and Klamath/North Coast bioregions, overlapping areas of elevated WNV activity in other surveillance measurements. Bioregional analysis revealed the avian species most likely to be reported and found positive in each bioregion. Our results may be useful to WNV surveillance and control efforts and provide insight into bird population trends in California.


Fishing eDNA in One of the World's Largest Rivers: A Case Study of Cross-Sectional and Depth Profile Sampling in the Yangtze.
The world's largest rivers are home to diverse, endemic, and threatened fish species. However, their sheer sizes make large-scale biomonitoring challenging. While environmental DNA (eDNA) metabarcoding has become an established monitoring approach in smaller freshwater ecosystems, its suitability for large rivers may be challenged by the sheer extent of their cross sections (>1 km wide and tens of meters deep). Here, we sampled fish eDNA from multiple vertical layers and horizontal locations from two cross sections of the lower reach of the Yangtze River in China. Over half of the ASVs (amplicon sequence variants) were detected in only a single combination of the vertical layers and horizontal locations, with ∼7% across all combinations. We estimated the need to sample >100 L of water across the cross-sectional profiles to achieve ASV richness saturation, which translates to ∼60 L of water at the species level. No consistent pattern emerged for prioritizing certain depth and horizontal samples, yet we underline the importance of sampling and integrating different layers and locations simultaneously. Our study highlights the significance of spatially stratified sampling and sampling volumes when using eDNA approaches. Specifically, we developed and tested a scalable and broadly applicable strategy that advances the monitoring and conservation of large rivers.


Effect of power ultrasound and Fenton reagents on the biomethane potential from steam-exploded birchwood.
The global demand for non-fossil energy sources is increasing rapidly. As a result, biogas presents a suitable alternative; however, first generation biofuels (e.g., sugar cane) potentially impact food crops globally. Second generation biofuels based on lignocellulose-based biomass are being used more frequently as they do not impact food crops. Furthermore, in Northern Europe, there is a significant interest in utilizing birchwood and paper mill waste for biogas production due to its high availability. The utilization of birchwood for biogas has significantly improved in recent years with the improvement of required pretreatment processes. To date, the most effective and economically feasible pretreatment in an industrial context is the steam explosion of lignocellulose-based biomass. Despite this, there is potential for releasing more digestible components from this biomass by efficiently degrading the lignocellulose components. This research presents another pretreatment that can be applied to steam-exploded wood based on ultrasonication and Fenton reagents. It was observed that by treating the steam exploded birchwood with ultrasonication and mild concentrations of Fenton reagents, an increase in the rate of biogas production was achievable. This would allow the increase in biogas yield of a continuously feed industrial anaerobic digester without increasing the size of the reactor.


"You have to be there": twenty-five years of SCAMC/AMIA symposia.
The AMIA Annual Symposium began life as the Symposium on Computer Applications in Medical Care (SCAMC) in 1977. Inaugurated as a multidisciplinary meeting with multiple sponsors, the Symposium quickly became a force in the development of the field of medical informatics. The authors summarize the 25-year history of the meeting and its proceedings, drawing on information in the printed programs and proceedings and on the personal recollections of some Symposium organizers and attendees. They also present the results of a study of the extent to which Symposium papers have been cited in the journal literature.


Examination of microbial proteome preservation techniques applicable to autonomous environmental sample collection.
Improvements in temporal and spatial sampling frequency have the potential to open new windows into the understanding of marine microbial dynamics. In recent years, efforts have been made to allow automated samplers to collect microbial biomass for DNA/RNA analyses from moored observatories and autonomous underwater vehicles. Measurements of microbial proteins are also of significant interest given their biogeochemical importance as enzymes that catalyze reactions and transporters that interface with the environment. We examined the influence of five preservatives solutions (SDS-extraction buffer, ethanol, trichloroacetic acid, B-PER, and RNAlater) on the proteome integrity of the marine cyanobacterium Synechococcus WH8102 after 4 weeks of storage at room temperature. Four approaches were used to assess degradation: total protein recovery, band integrity on an SDS detergent polyacrylamide electrophoresis (SDS-PAGE) gel, and number of protein identifications and relative abundances by 1-dimensional LC-MS/MS proteomic analyses. Total protein recoveries from the preserved samples were lower than the frozen control due to processing losses, which could be corrected for with internal standardization. The trichloroacetic acid preserved sample showed significant loss of protein band integrity on the SDS-PAGE gel. The RNAlater preserved sample showed the highest number of protein identifications (103% relative to the control; 520 ± 31 identifications in RNAlater versus 504 ± 4 in the control), equivalent to the frozen control. Relative abundances of individual proteins in the RNAlater treatment were quite similar to that of the frozen control (average ratio of 1.01 ± 0.27 for the 50 most abundant proteins), while the SDS-extraction buffer, ethanol, and B-PER all showed significant decreases in both number of identifications and relative abundances of individual proteins. Based on these findings, RNAlater was an effective proteome preservative, although further study is warranted on additional marine microbes.


CT angiography in the evaluation of acute stroke.
To determine the worth of CT angiography of the circle of Willis as a supplement to routine CT in the examination of patients with symptoms of acute stroke in terms of its depiction of the number and distribution of arterial stenoses or occlusions. We also sought to compare the accuracy of CT angiography with MR angiography and/or digital subtraction angiography (DSA). One hundred forty-five patients with symptoms of acute stroke were examined with routine head CT and CT angiography of the circle of Willis. MR angiography was also performed in 27 patients and DSA in 28 patients. CT and MR angiograms and DSAs were reviewed for stenoses or occlusions involving the vessels about the circle of Willis. MR and CT angiograms were also evaluated for image quality, and the corresponding routine CT and MR studies were evaluated for the presence of arterial infarction. CT angiograms were rated good or excellent in 89% of cases whereas MR angiograms were rated good or excellent in 92% of cases. Arterial stenoses or occlusions were present on 43% of CT angiograms, 48% of MR angiograms, and 21% of DSAs. Findings were in agreement in 98% of the vessels analyzed by CT angiography and MR angiography. Similarly, there was overall agreement of findings in 99% of vessels analyzed by CT angiography and DSA. None of the patients had any immediate adverse reactions after administration of intravenous nonionic iodinated contrast material. CT angiography is an accurate and safe method for evaluating arterial stenoses or occlusions in the vessels about the circle of Willis. CT angiography should be used in patients with symptoms of acute stroke for whom evaluation of the intracranial vasculature is desirable.


Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases.
Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0-9 years) and adults (25-54 years) have the highest potential to cause a major zoonotic outbreak.


[Bis-ammonium adamantane derivatives--novel modulators of polyamine binding sites].
Experiments on intact rats and mice showed that the polyamine agonist spermine and the bis-ammonium adamantyl-containing compounds IEM-1460 and IEM-1754 potentiate the NMDA induced analgesia and convulsions and eliminate the analgesic effects of nicotine and kainate. Arcain, a competitive polyamine antagonist, eliminated (at the same dose) the activating and blocking effects of spermine, IEM-1460 and IEM-1754. In small doses, IEM-1754 (similarly to arcain) removed the analgesic effect of NMDA. It is suggested that IEM-1460 (similarly to spermine) is a polyamine agonist, while IEM-1754 is an antagonist/agonist of the polyamine site of NMDA, AMPA/kainate, and nicotinic receptors. The potentiating activity of IEM-1460 is two orders higher as compared to that of spermine.


Assessing the Contributions of Inactivation, Removal, and Transfer of Ebola Virus and Vesicular Stomatitis Virus by Disinfectant Pre-soaked Wipes.
Disinfectant pre-soaked wipes (DPW) containing activated hydrogen peroxide (AHP) or quaternary ammonium compounds (QAC) were tested using ASTM E2967-15 to determine removal, transfer, and inactivation of Ebola virus Makona variant (EBOV/Mak) and vesicular stomatitis virus (VSV) from contaminated stainless steel prototypic environmental surfaces. The infectious virus-contaminated carriers were subjected to wiping in the Wiperator per the standard. Following the use of negative control (J-Cloth)-, AHP-, or QAC-based wipes, recovery of residual infectious virus was assayed. In the case of the J-Cloth wipes (negative control), although removal of virus from inoculated carriers was extensive i.e., ~99% (1.9-3.5 log10) transfer of virus by these wipes to a secondary surface amounted to ≤ 2% (~3.8 log10) of the initial virus load. In the case of each DPW, >6 log10 removal/inactivation of virus was observed, with limited (EBOV/Mak) or no (VSV) virus transfer observed. The efficacy of wipes for decontaminating high-touch environmental surfaces spiked with EBOV/Mak or VSV is discussed. In summary, removal of EBOV/Mak and VSV using wipes was extensive in this study. In the absence of a sufficient concentration and contact time of an appropriate microbicidal active in DPW (such as the AHP- and QAC-based DPW tested), transfer of a low, albeit significant (from an infectious unit/infectious dose perspective), quantity of infectious virus from the inoculated surface to a secondary surface was observed. In the case of Ebola virus, it is essential that a DPW with an appropriate microbicidal active, following the appropriate contact time, be used to prevent unintended transfer of infectious virus to a clean secondary surface (as observed in negative control /J-Cloth). Otherwise, there exists the possibility of dissemination of Ebola virus and the associated risk of transmission of Ebola virus disease.


Prolonged exposure to resistin inhibits glucose uptake in rat skeletal muscles.
To assess the effects and mechanisms of the action of resistin on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells. Rat myoblasts (L6) were cultured and differentiated into myotubes followed by stimulation with single commercial resistin (130 ng/mL, 0-24 h) or cultured supernatant from 293-T cells transfected with resistin-expressing vectors (130 ng/mL, 0-24 h). Liquid scintillation counting was used to quantitate [3H] 2-deoxyglucose uptake. The translocation of insulin-sensitive glucose transporters GLUT4 and GLUT1, synaptosomal-associated protein 23 (SNAP23) and GLUT protein content, as well as the tyrosine phosphorylation status and protein content of insulin receptor substrate (IRS)-1, were assessed by Western blotting. Treatment of L6 myotubes with single resistin or cultured supernatant containing recombinant resistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impaired insulin-stimulated GLUT4 translocation. While SNAP23 protein content was decreased, no effects were noted in GLUT4 or GLUT1 protein content. Resistin also diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels without affecting its protein content. The effects of recombinant resistin from 293-T cells transfected with resistin-expressing vectors were greater than that of single resistin treatment. Resistin regulated IRS-1 function and decreased GLUT4 translocation and glucose uptake in response to insulin. The downregulated expression of SNAP23 may have been partly attributed to the decrease of glucose uptake by resistin treatment. These observations highlight the potential role of resistin in the pathophysiology of type 2 diabetes related to obesity.


Potential Effects of the Coronavirus Disease 2019 (COVID-19) Pandemic on Human Immunodeficiency Virus (HIV) Transmission: A Modeling Study in 32 US Cities.
The degree to which the 2019 novel coronavirus disease (COVID-19) pandemic will affect the US human immunodeficiency virus (HIV) epidemic is unclear. We used the Johns Hopkins Epidemiologic and Economic Model to project HIV infections from 2020 to 2025 in 32 US metropolitan statistical areas (MSAs). We sampled a range of effects of the pandemic on sexual transmission (0-50% reduction), viral suppression among people with HIV (0-40% reduction), HIV testing (0-50% reduction), and pre-exposure prophylaxis use (0-30% reduction), and indexed reductions over time to Google Community Mobility Reports. Simulations projected reported diagnoses would drop in 2020 and rebound in 2021 or 2022, regardless of underlying incidence. If sexual transmission normalized by July 2021 and HIV care normalized by January 2022, we projected 1161 (1%) more infections from 2020 to 2025 across all 32 cities than if COVID-19 had not occurred. Among "optimistic" simulations in which sexual transmission was sharply reduced and viral suppression was maintained we projected 8% lower incidence (95% credible interval: 14% lower to no change). Among "pessimistic" simulations where sexual transmission was largely unchanged but viral suppression fell, we projected 11% higher incidence (1-21% higher). MSA-specific projections are available at www.jheem.org?covid. The effects of COVID-19 on HIV transmission remain uncertain and differ between cities. Reported diagnoses of HIV in 2020-2021 are likely to correlate poorly with underlying incidence. Minimizing disruptions to HIV care is critical to mitigating negative effects of the COVID-19 pandemic on HIV transmission.


Stapled versus handsewn intestinal anastomosis in emergency laparotomy: a systemic review and meta-analysis.
The optimal technique for gastrointestinal anastomosis remains controversial in emergency laparotomy. The aim of this meta-analysis was to compare outcomes of stapled versus handsewn anastomosis after emergency bowel resection. A systematic review was performed for studies comparing outcomes after emergency laparotomy using stapled versus handsewn anastomosis until July 2014 (PROSPERO registry number: CRD42013006183). The primary endpoint was anastomotic failure, a composite measure of leak, abscess and fistula. Odds ratio (OR; with 95% CI) and weighted mean differences were calculated using meta-analytical techniques. Subgroup analysis was conducted for trauma surgery (TS) and emergency general surgery (EGS) cohorts. Risk of bias for each study was calculated using the Newcastle-Ottawa scale for cohort studies, and Cochrane Collaboration's tool for randomized trials. The final analysis included 7 studies of 1,120 patients, with a total of 1,205 anastomoses. There were 5 TS studies and 2 EGS studies. There were no differences in anastomotic failure between handsewn and stapled techniques on an individual anastomosis level (OR, 1.53; 95% CI, 0.97-2.43; P = .070), or on an individual patient level (OR, 1.44; 95% CI, 0.92-2.25; P = .110). There were no differences in the individual rates of anastomotic leak, abscess, fistulae, or postoperative deaths between techniques. Subgroup analysis of EGS and TS studies demonstrated no superior operative technique. Available evidence is sparse and at high risk of bias, and neither stapling nor handsewing is justifiably favored in emergency laparotomy. Surgeons might therefore select the technique of their own choice with caution owing to unresolved uncertainty.


Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II.
Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high density lipoprotein to triglyceride-rich lipoproteins. CETP expression can be transcriptionally activated by liver X receptor (LXR). Etoposide and teniposide are DNA topoisomerase II (Topo II) inhibitors. Etoposide has been reported to inhibit atherosclerosis in rabbits with un-fully elucidated mechanisms. In this study we determined if Topo II activity can influence cholesterol metabolism by regulating hepatic CETP expression. Inhibition of Topo II by etoposide, teniposide, or Topo II siRNA increased CETP expression in human hepatic cell line, HepG2 cells, which was associated with increased CETP secretion and mRNA expression. Meanwhile, inhibition of LXR expression by LXR siRNA attenuated induction of CETP expression by etoposide and teniposide. Etoposide and teniposide induced LXRα expression and LXRα/β nuclear translocation while inhibiting expression of receptor interacting protein 140 (RIP140), an LXR co-repressor. In vivo, administration of teniposide moderately reduced serum lipid profiles, induced CETP expression in the liver, and activated reverse cholesterol transport in CETP transgenic mice. Our study demonstrates a novel function of Topo II inhibitors in cholesterol metabolism by activating hepatic CETP expression and reverse cholesterol transport.


Somatic activity of the mariner transposable element in natural populations of Drosophila simulans.
The characteristics of the mariner transposable element in natural populations of Drosophila simulans from different parts of the world were analysed. The somatic excision rate (estimated from a test-cross with a reference strain), the average number of copies (determined by Southern blots), and the presence of deleted copies (detected by polymerase chain reaction amplification) were estimated for each population. There was a great variability in the somatic excision rate, measured as the percentage of mosaic males, both within and between populations. The population effect was highly significant. The average copy number also varied widely and was correlated with the excision rate. Rare deleted elements were detected by polymerase chain reaction and Southern blots. Percentage of mosaic males increased in strains kept for a long time at low temperature, and the somatic excision rate increased with the latitude of origin of populations. Therefore, these results strongly suggest that temperature could be involved in the regulation of mariner somatic excision in D. simulans.


Survival of airborne bacteria in a high urban concentration of carbon monoxide.
Vegetative cells of Serratia marcescens 8UK, Sarcina lutea, and spores of Bacillus subtilus var. niger were held in aerosols, with and without an urban concentration of CO (85 muliters per liter or ppm), for up to 6 hr at 15 C and a relative humidity (RH) of approximately 0, 25, 50, 75, and 95%. It was found that CO enhanced the death rate of S. marcescens 8UK at least four- to sevenfold at low RH (ca. 1 to 25%), but protected the cells at high RH (ca. 90%). Death rates of S. lutea, with or without added CO, were comparatively low over the entire RH range. However, in the first hour, airborne S. lutea held in CO-containing air were more stable than those in air without added CO (i.e., CO protection). A marked increase in the death rate (up to 70-fold) occurred in the subsequent 5 hr within the RH range of approximately 0 to 75%. Statistical analysis indicated that aerosol decay rates of B. subtilus var. niger spores decreased significantly, when held in a CO-containing as compared to a non-CO-containing atmosphere, in the 0 to 85% RH range. Thus, the data presented indicate that CO in the urban environment may have a protective or lethal effect on airborne bacteria, dependent upon at least the microbial species, aerosol age, and relative humidity. A mechanism for CO death enhancement and protection of airborne S. marcescens 8UK is suggested to involve CO uncoupling of an energy-requiring death mechanism and an energy-requiring maintenance mechanism at high and low RH, respectively.


[Advances in surgical repair of ureteral injury].
Ureteral injury can be classified as iatrogenic or traumatic, which represents a rare but challenging field of reconstructive urology. Due to their close proximity to vital abdominal and pelvic organs, the ureters are highly susceptible to iatrogenic injury, while ureteral injury caused by external trauma is relatively rare. The signs of ureteric injury are difficult to identify initially and often present after a delay. The treatment of ureteral injury, which is depended on the type, location, and degree of injury, the time of diagnosis and the patient's overall clinical condition, ranges from simple endoscopic management to complex surgical reconstruction. And long defect of the ureter presents much greater challenges to urologists. Ureterotomy under endoscopy using laser or cold-knife is available for the treatment of 2-3 cm benign ureteral injuries or strictures. Pyeloplasty is an effective treatment for ureteropelvic junction obstruction and some improved methods showed the possibility of repairing long-segment (10-15 cm) stenosis. Proximal and mid-ureteral injuries or strictures of 2-3 cm long can often be managed by primary ureteroureterostomy. When not feasible due to ureteral defects of longer segment, mobilization of the kidney should be considered, and transureteroureterostomy is alternative if the proximal ureter is of sufficient length. And autotransplantation or nephrectomy is regarded as the last resorts. Most of the injuries or strictures are observed in the distal ureter, below the pelvic brim, and are usually treated with ureteroneocystostomy. A non-refluxing technique together with a ureteral nipple or submucosal tunnel method, is preferable as it minimizes vesico-ureteral reflux and the risk of infection. In order to cover a longer distance, ureteroneocystostomy in combination with a psoas hitch (covering 6-10 cm of defect) or a Boari flap (covering 12-15 cm) is often adopted. Among various ureteral replacement procedures, only intestinal ureteral substitution, which includes ileal ureter, appendiceal interposition and reconfigured colon substitution, has gained wide acceptance when urothelial tissue is insufficient. Ileal ureter can be used to replace the ureter of >15 cm defect and even to replace the entire unbilateral ureter or bilateral ureter. Laparoscopic and robotic-assisted techniques are increasingly being employed for ureteral reconstruction and adopted with encouraging results.


Bragg scattering and Brownian motion dynamics in optically induced crystals of submicron particles.
A set of four confocal laser beams of 1064-nm wavelength is used to prepare optically induced crystals of submicron particles in aqueous solution. Thousands of polystyrene spheres of about 200 nm in diameter are trapped in three dimensions. Bragg scattering patterns obtained with a probe beam of 532-nm wavelength are in agreement with the calculated lattice structure and its polarization dependence. The decay and rise of the Bragg scattering intensity upon switching the lattice off and on reveal the Brownian motion dynamics of the particles in the periodic optical trapping potential. Experimental results agree well with results from trajectory simulations based on the Langevin equation. The results exhibit the interplay between Brownian motion and deterministic forces in an inhomogeneous (near-)periodic optical trapping potential.


Predictors of serum concentrations of polybrominated flame retardants among healthy pregnant women in an urban environment: a cross-sectional study.
Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants commonly used in a wide range of products. Prenatal exposure to PBDEs has been associated with adverse neurodevelopment. Our objective was to characterize predictors of exposure to PBDEs among a multi-ethnic, low-income cohort of pregnant women enrolled from highly urban communities in New York City between years 2009-2010. During the first half of pregnancy we collected 316 maternal serum samples and administered an extensive questionnaire including items on demographics, diet and lifestyle. We measured 12 PBDE congeners in blood samples. Using bivariate and multivariate approaches, we regressed the most commonly detected PBDE congeners (PBDE-47, -99, -100 and -153) against potential demographic, dietary and lifestyle predictor variables. At least one PBDE congener was detected in each serum sample. Our analyses demonstrate unique predictor patterns for PBDE-47, -99, -100 and -153 based on demographic, lifestyle and dietary characteristics of women. Higher education and increased use of household electronics were associated with higher levels of all 4 congeners. Six characteristics were associated with PBDE-153 serum concentrations, more than for any other congener. These include maternal education, household income, body mass index, solid dairy consumption, processed meat consumption and frequent use of household electronics. PBDE exposure in this widespread in this cohort, though levels are lower than previous assessments of US pregnant women. Lower levels may be in response to legislation restricting the production, sale and use of these compounds. In our cohort, we did not observe any individual predictor or a consistent pattern of several predictors representing a significant source of PBDE exposure. These data suggest that legislation and policy may be more effective at reducing exposure than personal lifestyle modifications.


Determination of the Potential Tumor-Suppressive Effects of Gsdme in a Chemically Induced and in a Genetically Modified Intestinal Cancer Mouse Model.
Gasdermin E (GSDME), also known as deafness autosomal dominant 5 (DFNA5) and previously identified to be an inducer of regulated cell death, is frequently epigenetically inactivated in different cancer types, suggesting that GSDME is a tumor suppressor gene. In this study, we aimed to evaluate the tumor-suppressive effects of GSDME in two intestinal cancer mouse models. To mimic the silencing of GSDME by methylation as observed in human cancers, a Gsdme knockout (KO) mouse was developed. The effect of GSDME on tumorigenesis was studied both in a chemically induced and in a genetic intestinal cancer mouse model, as strong evidence shows that GSDME plays a role in human colorectal cancer and representative mouse models for intestinal cancer are available. Azoxymethane (AOM) was used to induce colorectal tumors in the chemically induced intestinal cancer model (n = 100). For the genetic intestinal cancer model, Apc1638N/+ mice were used (n = 37). In both experiments, the number of mice bearing microscopic proliferative lesions, the number and type of lesions per mouse and the histopathological features of the adenocarcinomas were compared between Gsdme KO and wild type (WT) mice. Unfortunately, we found no major differences between Gsdme KO and WT mice, neither for the number of affected mice nor for the multiplicity of proliferative lesions in the mice. However, recent breakthroughs on gasdermin function indicate that GSDME is an executioner of necrotic cell death. Therefore, it is possible that GSDME may be important for creating an inflammatory microenvironment around the tumor. This is in line with the trend towards more severe inflammation in WT compared to Gsdme KO mice, that we observed in our study. We conclude that the effect of GSDME in tumor biology is probably more subtle than previously thought.


[Toxoplasmosis in sick persons].
A screening investigation was conducted designed to identify ill persons presenting with toxoplasmosis with the aid of an intracutaneous test with toxoplasmin and complement-fixing reaction with a dry toxoplasmic antigen. Toxoplasmosis was detected in those persons having lymphadenitis, therapeutical patients, women with aggravated obstetrical history having had spontaneous abortions and having given birth to sick children, patients with sluggish meningoencephalitis presenting with epileptoid and hypothalamic syndrome, polyneuritis, and patients with myopia, chorioretinitis and uveitis. Identification and treatment of toxoplasmic invasion constitutes a valid method of control of spontaneous abortions of toxoplasmic etiology. Detection in a timely fashion of toxoplasmic invasion in pregnant women and preventive treatment with two 5-day cycles of pirimetamin (0.025) twice a day and sulfodimezin (0.5) four times daily with a 10-day interval between the cycles has been found out to prevent toxoplasmosis affliction of the fetus.


Using real-time PCR to specifically detect Burkholderia mallei.
Burkholderia mallei is the causative agent of human and animal glanders and is a category B biothreat agent. Rapid diagnosis of B. mallei and immediate prophylactic treatment are essential for patient survival. The majority of current bacteriological and immunological techniques for identifying B. mallei from clinical samples are time-consuming, and cross-reactivity with closely related organisms (i.e. Burkholderia pseudomallei) is a problem. In this investigation, two B. mallei-specific real-time PCR assays targeting the B. mallei bimA(ma) gene (Burkholderia intracellular motility A; BMAA0749), which encodes a protein involved in actin polymerization, were developed. The PCR primer and probe sets were tested for specificity against a collection of B. mallei and B. pseudomallei isolates obtained from numerous clinical and environmental (B. pseudomallei only) sources. The assays were also tested for cross-reactivity using template DNA from 14 closely related Burkholderia species. The relative limit of detection for the assays was found to be 1 pg or 424 genome equivalents. The authors also analysed the applicability of assays to detect B. mallei within infected BALB/c mouse tissues. Beginning 1 h post aerosol exposure, B. mallei was successfully identified within the lungs, and starting at 24 h post exposure, in the spleen and liver. Surprisingly, B. mallei was not detected in the blood of acutely infected animals. This investigation provides two real-time PCR assays for the rapid and specific identification of B. mallei.


Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry.
Radiotherapy (RT) is an integral part of the interdisciplinary treatment of patients with high-risk neuroblastoma (NB). With the continuous improvements of outcome, the interest in local treatment strategies that reduce treatment-related side effects while achieving optimal oncological results is growing. Proton beam therapy (PBT) represents a promising alternative to conventional photon irradiation with regard to the reduction of treatment burden. Retrospective analysis of children with high or intermediate risk NB receiving PBT of the primary tumor site during first-line therapy between 2015 and 2020 was performed. Data from the prospective in-house registry Standard Protonentherapie WPE - Kinder- (KiProReg) with respect to tumor control and treatment toxicity were analyzed. Adverse events were classified according to CTCAE Version 4 (V4.0) before, during, and after PBT. In total, 44 patients (24 male, 20 female) with high (n = 39) or intermediate risk NB (n = 5) were included in the analysis. Median age was 3.4 years (range, 1.4-9.9 years). PBT doses ranged from 21.0 to 39.6 Gray (Gy) (median 36.0 Gy). Five patients received PBT to the MIBG-avid residual at the primary tumor site at time of PBT according to the NB-2004 protocol. In 39 patients radiation was given to the pre-operative tumor bed with or without an additional boost in case of residual tumor. After a median follow-up (FU) of 27.6 months, eight patients developed progression, either local recurrence (n = 1) or distant metastases (n = 7). Four patients died due to tumor progression. At three years, the estimated local control, distant metastatic free survival, progression free survival, and overall survival was 97.7, 84.1, 81.8, and 90.9%, respectively. During radiation, seven patients experienced higher-grade (CTCAE ≥ °3) hematologic toxicity. No other higher grade acute toxicity occurred. After PBT, one patient developed transient myelitis while receiving immunotherapy. No higher grade long-term toxicity was observed up to date. PBT was a well tolerated and effective local treatment in children with high and intermediate risk NB. The role of RT in an intensive multidisciplinary treatment regimen remains to be studied in the future in order to better define timing, doses, target volumes, and general need for RT in a particularly sensitive cohort of patients.


Solid-state characterization and dissolution properties of bicalutamide-beta-cyclodextrin inclusion complex.
The solid-state properties and dissolution profile of bicalutamide beta-cyclodextrin (betaCD) inclusion complex were investigated. The phase solubility profile of bicalutamide with beta-cyclodextrin was classified as A(L)-type. Stability constant with 1:1 molar ratio was calculated from the phase solubility diagram and the aqueous solubility of bicalutamide was found to be enhanced by 86% for beta-cyclodextrin. Binary systems of bicalutamide with betaCD were prepared by the kneading method. The solid-state properties of the complex were characterized by differential scanning calorimetry, Fourier transformation-infrared spectroscopy and X-ray powder diffractometry. It could be concluded that bicalutamide could form an inclusion complex with beta-cyclodextrin. The dissolution profile of the inclusion complex was determined and compared with those of bicalutamide alone and its physical mixture. The dissolution rate of bicalutamide was significantly increased bycomplexation with betaCD, as compared with pure drug and physical mixture.


Etiological prevalence of epilepsy and epileptic seizures in hospitalized elderly in a Brazilian tertiary center - Salvador - Brazil.
Epilepsy in the elderly has high incidence and prevalence and is often underecognized. To describe etiological prevalence of epilepsy and epileptic seizures in elderly inpatients. Retrospective analysis was performed on elderly patients who had epilepsy or epileptic seizures during hospitalization, from January 2009 to December 2010. One hundred and twenty patients were enrolled. They were divided into two age subgroups (median 75 years) with the purpose to compare etiologies. The most common etiology was ischemic stroke (36.7%), followed by neoplasias (13.3%), hemorrhagic stroke (11.7%), dementias (11.4%) and metabolic disturbances (5.5%). The analysis of etiological association showed that ischemic stroke was predominant in the younger subgroup (45% vs 30%), and dementias in the older one (18.9% vs 3.8%), but with no statistical significance (p = 0.23). This study suggests that epilepsy and epileptic seizures in the elderly inpatients have etiological association with stroke, neoplasias and dementias.


Purification and characterization of extracellular penicillin V acylase from Fusarium sp. SKF 235.
Penicillin V acylase from Fusarium sp. SKF 235 culture filtrate was purified to homogeneity. The enzyme was a glycoprotein and composed of single polypeptide chain with molecular weight of 83,200 Daltons. The pH and temperature optima were 6.5 and 55 degrees C, respectively. The KM for penicillin V was 10 mM but the enzyme was inhibited by penicillin V at concentrations above 50 mM. Products of reaction, 6-aminopenicillanic acid and phenoxyacetic acid inhibited the enzyme competitively and noncompetitively with Ki values of 18 mM and 45 mM, respectively. The enzyme specifically hydrolyzed penicillin V, cephalosporanic acid V and penicillin V sulphoxide. Other phenoxy acetyl amides studied were not hydrolysed. It is proposed that phenoxyacetyl moiety alone is not recognized by the penicillin V acylase and in addition, the beta-lactam structure contributes in formation of enzyme-substrate complex.


SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle.
Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. While reversible acetylation does not impact FBL-mediated pre-rRNA methylation, hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. At the onset of mitosis, nucleolar disassembly is accompanied by hyperacetylation of FBL, loss of H2AQ104me, and repression of polymerase I (Pol I) transcription. Overexpression of an acetylation-deficient, but not an acetylation-mimicking, FBL mutant restores H2AQ104me and transcriptional activity. The results reveal that SIRT7-dependent deacetylation impacts nucleolar activity by an FBL-driven circuitry that mediates cell-cycle-dependent fluctuation of rDNA transcription.


Subcellular localization of the alterations in phosphatidylinositol metabolism following glucose-induced insulin release from rat pancreatic islets.
The subcellular localization of the incorporation of 2-(3H)-myoinositol into lipids has been studied in isolated pancreatic islets of the rat. The recovery of lipid-bound myoinositol increased with time in the nuclear, mitochondrial, microsomal, and secretory granule fractions. The utilization of a filtration technique for the more complete separation of mitochondrial and secretory granule elements permitted us to show that the recovery of lipid-bound 2-(3H)-myoinositol increased most rapidly in the secretory granule fraction. A 30-minute exposure of prelabeled islets to a stimulatory concentration of D-glucose (3.0 mg./ml.) resulted in a statistically significant decrease in the amount of lipid-bound 2-(3H)-myoinositol that was recovered from the secretory granule fraction (p less than 0.001). In contrast, exposure of islets to the elevated glucose concentration had no statistically significant effect on the recovery of lipid-bound radioactivity from other subcellular fractions. Since the majority of lipid-bound radioactivity associated with the secretory granule fraction could be recovered with the presumptive secretory granule membranes, these data suggest that the hydrolysis of phosphatidylinositol that accompanies glucose-induced insulin secretion from the rat pancreatic islet may be localized to the beta granule and, in particular, to its limiting membrane.


Continuous human bone marrow culture: Ia antigen characterization of probable pluripotential stem cells.
The presence of Ia-like antigens on human CFU-C and BFU-e is confirmed and a cell type that lacked immediate capacity for granulocytic colony formation but generated CFU-c after brief incubation in simple suspension culture is identified. This pre-CFU-c, and its immediate progeny, was extremely sensitive to killing by anti-Ia serum with complement. In contrast, anti-Ia serum plus complement treatment of human bone marrow, while eliminating 93%-97% of all CFU-c and BFU-e, did not prevent the rapid regeneration of these progenitor cells and their production for some weeks under the conditions of continuous marrow culture. These studies suggest that the human equivalent of the pluripotential stem cell can replicate for some weeks in culture and generate committed progenitors, such as CFU-c and BFU-e. Furthermore, it would appear that Ia-like antigen is absent on the pluripotential stem cell, is rapidly gained as commitment to the various progenitor cell types occur, and is subsequently lost as these latter undergo differentiation within the marrow.


"Tu" or "Vous?" A European qualitative study of dignity and communication with older people in health and social care settings.
To examine the experiences of communication between older people and health and social care providers in six European countries. Focus groups were carried out with groups of older people (91 focus groups, 391 participants), and health and social care professionals (85 focus groups, 424 participants), in order to gain insights into concepts of good communications. Data collection and analysis continued concurrently according to the method of constant comparison. Different styles of communication between professionals and older people were found to be capable of enhancing or jeopardising dignity. The use of appropriate forms of address, listening, giving people choice, including them, respecting their need for privacy and politeness, and making them feel valued emerged as significant ways to maintain older peoples' sense of self-worth and dignity. Despite being aware of good communication practices, health and social care professionals often failed to implement them. Lack of time, staff, resource scarcity, regulation and bureaucracy were cited as barriers, as was a lack of awareness and effort. The findings have important implications for health and social care professionals when they engage with older people.


Assessment criteria for research misconduct: Taiwanese researchers' perceptions.
Assessing the severity of an instance of research misconduct is undoubtedly challenging, especially when the result of the assessment may be key to suggesting subsequent sanctions. However, only a few references are currently available in the Taiwanese academic context. In a previous study, the present authors developed The Assessment Criteria for Research Misconduct (The Criteria) based on existing international policies and guidelines and reviewed by local research scholars for content validity. The Criteria, with a total of 28 items, were organized into three sections: general criteria for determining case severity, aggravating criteria, and mitigating criteria. In the current study, the authors further conducted a survey and collected data on 277 Taiwanese researchers' perceived importance of each criterion included in The Criteria. The results showed that participants generally agreed with the importance of all criteria. However, the group that lacked case-handling experience attributed significantly greater levels of importance to the criterion of original will (proactive, passive, or coercive) toward participation in misconduct than did the experienced group. In addition, the participants exhibited greater variation in the perceived importance of the mitigating criteria. Finally, the possible utility of The Criteria in real contexts and training materials is suggested in the study.


Molecular design of crown ethers. 21.(1,2) synthesis of novel double-armed benzo-15-crown-5 lariats and their complexation thermodynamics with light lanthanoid nitrates in acetonitrile
Three new disubstituted benzo-15-crown-5 derivatives (3-5) have been synthesized from 4',5'-bis(bromomethyl)benzo-15-crown-5 (2) and the corresponding alkanols in the presence of Na(2)S(2), and their complexation thermodynamics with light lanthanoid(III) nitrates (La-Gd) have been studied in anhydrous acetonitrile at 25 degrees C. Plots of K(S) against the reciprocal ionic diameter of lanthanoid exhibited monotonically declining pattern for the parent benzo-15-crown-5 (1) and 3 but showed a characteristic peak at Ce(3+) for 4 and 5. It is interesting to note that the simple extension of the alkyl side chains in 4 and 5 can alter the cation selectivity profiles of 1 and 3. Possessing two 2-oxapropyl groups, 3 gave a comparable K(S) for La(3+) but a significantly decreased K(S) for Ce(3+) compared with the corresponding values for 1, thus exhibiting an exceptionally high La(3+)/Ce(3+) selectivity of 11. Thermodynamically, the complexation of lanthanoid perchlorates with 1 is absolutely entropy-driven in acetonitrile, while the complexation of lanthanoid nitrates with 3-5 is primarily driven by exothermic enthalpy changes with accompanying moderate entropic gain or small entropic loss.


The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde.
The International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans because there is "sufficient epidemiological evidence that it causes nasopharyngeal cancer in humans". Genes involved in DNA repair and maintenance of genome integrity are critically involved in protecting against mutations that lead to cancer and/or inherited genetic disease. Association studies have recently provided evidence for a link between DNA repair polymorphisms and micronucleus (MN) induction. We used the cytokinesis-block micronucleus (CBMN assay) in peripheral lymphocytes and MN test in buccal cells to investigate the effects of XRCC3 Thr241Met, ADH5 Val309Ile, and Asp353Glu polymorphisms on the frequency of genotoxicity biomarkers in individuals occupationally exposed to formaldehyde (n = 54) and unexposed workers (n = 82). XRCC3 participates in DNA double-strand break/recombination repair, while ADH5 is an important component of cellular metabolism for the elimination of formaldehyde. Exposed workers had significantly higher frequencies (P < 0.01) than controls for all genotoxicity biomarkers evaluated in this study. Moreover, there were significant associations between XRCC3 genotypes and nuclear buds, namely XRCC3 Met/Met (OR = 3.975, CI 1.053-14.998, P = 0.042) and XRCC3 Thr/Met (OR = 5.632, CI 1.673-18.961, P = 0.005) in comparison with XRCC3 Thr/Thr. ADH5 polymorphisms did not show significant effects. This study highlights the importance of integrating genotoxicity biomarkers and genetic polymorphisms in human biomonitoring studies.


The Molecular Phenotype of Kidney Transplants: Insights From the MMDx Project.
This review outlines the molecular disease states in kidney transplant biopsies as documented in the development of the Molecular Microscope Diagnostic System (MMDx). These states include T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), recent parenchymal injury, and irreversible atrophy-fibrosis. The MMDx project, initiated through a Genome Canada grant, is a collaboration involving many centers. MMDx uses genome-wide microarrays to measure transcript expression, interprets the results using ensembles of machine learning algorithms, and generates a report. Experimental studies in mouse models and cell lines were extensively used to annotate molecular features and interpret the biopsy results. Over time, MMDx revealed unexpected aspects of the disease states: for example, AMR is usually C4d-negative and often DSA-negative, and subtle "Minor" AMR-like states are frequent. Parenchymal injury correlates with both reduced glomerular filtration rate and increased risk of graft loss. In kidneys with rejection, injury features, not rejection activity, are the strongest predictors of graft survival. Both TCMR and AMR produce injury, but TCMR induces immediate nephron injury and accelerates atrophy-fibrosis, whereas AMR induces microcirculation and glomerular damage that slowly leads to nephron failure and atrophy-fibrosis. Plasma donor-derived cell-free DNA levels correlate strongly with AMR activity, acute kidney injury, and in a complex way with TCMR activity. Thus, the MMDx project has documented the molecular processes that underlie the clinical and histologic states in kidney transplants, and provides a diagnostic tool that can be used to calibrate biomarkers, optimize histology interpretation, and guide clinical trials.


The Ububele Baby Mat Service - A primary preventative mental health intervention in a culturally diverse setting.
The Ububele Baby Mat Service is a community-based, parent-infant mental health intervention offered at five primary health care clinics in Alexandra Township, in Johannesburg. The aim of the intervention is to promote healthy caregiver-infant attachments. There has been a steady increase in the number of mother-baby dyads making use of the service. This paper aims to explore how the Baby Mat Service and Baby Mat practitioners position and locate themselves in a culturally diverse community setting where multiple meaning systems are drawn on for making sense of health concerns. Two key components of the Baby Mat Service are discussed: i) the presence of an inter-racial therapeutic couple on the mat; and ii) the stance adopted by the Baby Mat practitioners in relation to culturally diverse understandings of a presenting problem. The therapeutic couple engages with culturally-informed frames of reference in an attitude of wondering and tentative thinking ("mhlawumbe" in isiZulu). When a respectfully curious stance was taken by practitioners, it was found to help those accessing the mat to find symbolic meaning in the presenting problem and integrate this with cultural understandings.


Implications of emotion regulation strategies for empathic concern, social attitudes, and helping behavior.
Empathic concern-a sense of caring and compassion in response to the needs of others-is a type of emotional response to the plights and misfortunes of others that predicts positive social attitudes and altruistic interpersonal behaviors. One psychological process that has been posited to facilitate empathic concern is the ability to regulate one's own emotions. However, existing research links some emotion-regulation approaches (e.g., suppression) to social outcomes that would appear at odds with empathic concern, such as decreased interpersonal closeness. In the present research, we tested whether relying on suppression to regulate one's emotions would lead to decreases in empathic concern-and related downstream variables, such as negative social attitudes and unwillingness to engage in altruistic behavior-when learning about another person's misfortune. In Study 1, dispositional and instructionally induced suppression was negatively associated with empathic concern, which led to increased stigmatizing attitudes. By contrast, instructing participants to use another emotion-regulation strategy examined for comparison-reappraisal-did not decrease empathic concern, and dispositional reliance on reappraisal was actually positively associated with empathic concern. In Study 2, the findings of Study 1 regarding the effects of habitual use of reappraisal and suppression were replicated, and reliance on suppression was also found to be associated with reluctance to engage in helping behaviors. These findings are situated within the existing literature and employed to shed new light on the interpersonal consequences of intrapersonal emotion-regulation strategies.


In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration.
To evaluate dominant cell-to-cell paracrine interactions, including those of human annulus fibrosus (AF), nucleus pulposus (NP), and endothelial cells (ECs), in the production of inflammatory mediators and catabolic enzymes, ECs was cultured in soluble factors derived from AF or NP cells (AFCM or NPCM, respectively) and vice versa. We analysed IL-6 and -8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and -3, nerve growth factor (NGF)-β, and brain-derived neurotrophic factors (BDNFs) with qRT-PCR and ELISA. We implement a microfluidic platform to analyse migration properties of AF and NP cells and ECs in 3D cultures. Our results show that IL-1β-stimulated AF cells produced significantly higher levels of IL-6 and -8, VEGF, and MMP-1 than IL-1β-stimulated NP cells. However, production of IL-6 and -8, VEGF, and MMP-3 was significantly higher in NP cells than in AF cells, under the presence of ECs conditioned medium. We observed considerable migration of NP cells co-cultured with ECs through the microfluidic platform. These results suggest that AF cells may play a major role in the initial degeneration of intervertebral disc. Furthermore, it was found that interactions between NP cells and ECs may play a significant role in the development or progression of diseases.


Controlling costs without compromising quality: paying hospitals for total knee replacement.
Unit costs of health services are substantially higher in the United States than in any other developed country in the world, without a correspondingly healthier population. An alternative payment structure, especially for high volume, high cost episodes of care (eg, total knee replacement), is needed to reward high quality care and reduce costs. The National Inpatient Sample of administrative claims data was used to measure risk-adjusted mortality, postoperative length-of-stay, costs of routine care, adverse outcome rates, and excess costs of adverse outcomes for total knee replacements performed between 2002 and 2005. Empirically identified inefficient and ineffective hospitals were then removed to create a reference group of high-performance hospitals. Predictive models for outcomes and costs were recalibrated to the reference hospitals and used to compute risk-adjusted outcomes and costs for all hospitals. Per case predicted costs were computed and compared with observed costs. Of the 688 hospitals with acceptable data, 62 failed to meet effectiveness criteria and 210 were identified as inefficient. The remaining 416 high-performance hospitals had 13.4% fewer risk-adjusted adverse outcomes (4.56%-3.95%; P < 0.001; χ) and 9.9% lower risk-adjusted total costs ($12,773-$11,512; P < 0.001; t test) than all study hospitals. Inefficiency accounted for 96% of excess costs. A payment system based on the demonstrated performance of effective, efficient hospitals can produce sizable cost savings without jeopardizing quality. In this study, 96% of total excess hospital costs resulted from higher routine costs at inefficient hospitals, whereas only 4% was associated with ineffective care.


[Comparative study of two enteral feeding formulas in hospitalized elders: casein versus soybean protein].
To compare the incidence of gastrointestinal side effects of two enteral feeding formulas with changes in the origin of protein (casein and isolated soy protein) in hospitalised elderly patients. A cross sectional survey was done among a sample of elderly patients carrying nasogastric tube admitted to the Reina Sofia General Hospital (Murcia) during a period of 6 months. A formula based on casein or soybean protein was randomly assigned. The variables studied were: age, sex, cause for indication of EN, duration of the EN and maximum amount of EN administered per day. Nutritional status at admission and discharge, mortality and gastrointestinal side effects (diarrhoea, constipation, vomits or regurgitation) were also collected. Statistical analyses were performed with the Student's T and chi 2 tests, with a significance of 95%. Sample conformed by 50 patients over 65 years (48% casein, 52% soybean) without statistically significant differences in age nor cause of indication of the EN. Either there were no differences in the nutritional status at the admission and discharge in both groups. Significant differences were observed in the incidence of diarrhoea (C: 45.83%, S: 7.69%, p = 0.009) and vomits (C: 41.66%, S: 15.38%, p = 0.05). A significant reduction in the incidence of gastrointestinal complications, a reduction in the incidence of ulcers by pressure and less mortality occurred on the group that took formula based on the soybean protein. The individualized nutritional evaluation must be performed routinely when the patient is admitted to the hospital for detection and treatment of early signs of malnutrition.


A nuclear deoxyribonucleic acid analysis of normal and abnormal vulvar epithelium.
Vulvar and groin skin from 21 women with clinical squamous cell carcinoma of the vulva was compared with that from nine patients with vulvar intraepithelial neoplasia. Feulgen-stained nuclear densitometry showed a constancy of Feulgen-deoxyribonucleic acid (DNA) density in normal epithelium and all subepithelial connective tissue nuclei. At three sites--tumor edge, opposite labia, and perineum--there were significant differences in nuclear chromatin content between the two groups and also as compared with normal epithelium.