Pooling Pharyngeal, Anorectal, and Urogenital Samples for Screening Asymptomatic Men Who Have Sex with Men for Chlamydia trachomatis and Neisseria gonorrhoeae.
Screening for Chlamydia trachomatis and Neisseria gonorrhoeae at the pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Combining the three individual-site samples into a single pooled sample could result in significant cost savings, provided there is no significant sensitivity reduction. The aim of this study was to examine the sensitivity of pooled samples for detecting chlamydia and gonorrhea in asymptomatic MSM using a nucleic acid amplification test. Asymptomatic MSM who tested positive for chlamydia or gonorrhoea were invited to participate. Paired samples were obtained from participants prior to administration of treatment. To form the pooled sample, the anorectal swab was agitated in the urine specimen transport tube and then discarded. The pharyngeal swab and 2 ml of urine sample were then added to the tube. The difference in sensitivity between testing of pooled samples and individual-site testing was calculated against an expanded gold standard, where an individual is considered positive if either pooled-sample or individual-site testing returns a positive result. All samples were tested using the Aptima Combo 2 assay. A total of 162 MSM were enrolled in the study. Sensitivities of pooled-sample testing were 86% (94/109; 95% confidence interval [CI], 79 to 92%]) for chlamydia and 91% (73/80; 95% CI, 83 to 96%) for gonorrhea. The sensitivity reduction was significant for chlamydia (P = 0.02) but not for gonorrhea (P = 0.34). Pooling caused 22 infections (15 chlamydia and 7 gonorrhoea) to be missed, and the majority were single-site infections (19/22). Pooling urogenital and extragenital samples from asymptomatic MSM reduced the sensitivity of detection by approximately 10% for chlamydia but not for gonorrhea.


Multiomics study of a heterotardigrade, Echinisicus testudo, suggests the possibility of convergent evolution of abundant heat-soluble proteins in Tardigrada.
Many limno-terrestrial tardigrades can enter an ametabolic state, known as anhydrobiosis, upon desiccation, in which the animals can withstand extreme environments. Through genomics studies, molecular components of anhydrobiosis are beginning to be elucidated, such as the expansion of oxidative stress response genes, loss of stress signaling pathways, and gain of tardigrade-specific heat-soluble protein families designated CAHS and SAHS. However, to date, studies have predominantly investigated the class Eutardigrada, and molecular mechanisms in the remaining class, Heterotardigrada, still remains elusive. To address this gap in the research, we report a multiomics study of the heterotardigrade Echiniscus testudo, one of the most desiccation-tolerant species which is not yet culturable in laboratory conditions. In order to elucidate the molecular basis of anhydrobiosis in E. testudo, we employed a multi-omics strategy encompassing genome sequencing, differential transcriptomics, and proteomics. Using ultra-low input library sequencing protocol from a single specimen, we sequenced and assembled the 153.7 Mbp genome annotated using RNA-Seq data. None of the previously identified tardigrade-specific abundant heat-soluble genes was conserved, while the loss and expansion of existing pathways were partly shared. Furthermore, we identified two families novel abundant heat-soluble proteins, which we named E. testudo Abundant Heat Soluble (EtAHS), that are predicted to contain large stretches of disordered regions. Likewise the AHS families in eutardigrada, EtAHS shows structural changes from random coil to alphahelix as the water content was decreased in vitro. These characteristics of EtAHS proteins are analogous to those of CAHS in eutardigrades, while there is no conservation at the sequence level. Our results suggest that Heterotardigrada have partly shared but distinct anhydrobiosis machinery compared with Eutardigrada, possibly due to convergent evolution within Tardigrada. (276/350).


Evidence for a role of rap1 protein in the regulation of human platelet Ca2+ fluxes.
The relationship between the 22-24 kDa cyclic AMP (cAMP)-dependent phosphoprotein previously described as being involved in the regulation of human platelet membrane Ca2+ transport and a GTP-binding protein of low molecular mass (ras-like protein) was investigated. After isolation of plasma membranes and intracellular membranes, it was found that guanosine 5'-[gamma-thio]triphosphate (GTP[S]) bound to plasma membrane proteins ranging in molecular mass from 22 to 29 kDa, but not to intracellular membranes. The major GTP-binding protein appeared as a 24 kDa protein under reduced conditions and a 22 kDa protein under non-reduced conditions. A similar membrane location and electrophoretic mobility were found for both the cAMP phosphoprotein and the protein recognized by a specific anti-rap1 antibody. The identity between the cAMP phosphoprotein and the rap1 GTP-binding protein was further examined by studying the functional effect of GTP on plasma membrane Ca2+ transport. A maximal GTP[S] concentration of 40 microM was found to: (1) inhibit to the same degree (40%) both Ca(2+)-ATPase activity and the Ca2+ transport function mediated by the Ca(2+)-ATPase; (2) inhibit the phosphorylation of the 22-24 kDa protein by the catalytic subunit of the cAMP-dependent protein kinase (C.Sub.); and (3) abolish the stimulation of Ca2+ uptake induced by C.Sub. It is concluded that the platelet cAMP phosphoprotein is indeed the rap1 GTP-binding protein, and that it regulates plasma membrane Ca2+ transport, thus providing evidence for a new role of a ras-related protein.


[Mechanism of changes in the calcium permeability of the sarcolemma of vascular smooth muscle cells during hypoxia].
In isolated preparations of smooth muscle of the rat portal vein, removal of Ca2+ from perfusate or addition of Ca2+--antagonists as well as hypoxia entailed inhibition of vascular smooth muscle contractile activity. Uptake of 45Ca by vascular smooth muscle cells was diminished in hypoxia. Liposomes filled with Ca2+ or Cr but not ATP prevented the hypoxic relaxation of vascular smooth muscle. One of the main reasons of the decrease of vascular smooth muscle contractility in hypoxia seems to be the disturbance of calcium channel phosphorylation and the decrease of sarcolemma calcium permeability.


Oblique direction reach test: evaluating psychometric properties in stroke population.
Post-stroke individuals are observed to have reduced limits of stability (LOS) in all directions. Functional activities are rarely performed in pure cardinal planes; instead, they are most likely to be performed in an oblique direction. Existing tools are either expensive or sophisticated to assess the LOS in an oblique direction. Therefore, this study's primary objective is to evaluate the intra-rater, inter-rater reliability, and validity of the oblique direction reach test (ODRT) among stroke subjects. A total of 96 first-time stroke patients with age, gender, height, and weight-matched healthy controls aged 18-80 years were recruited for the study. Oblique, forward, and lateral reach distances were assessed using the standard procedure of ODRT, Functional Reach Test (FRT), and Lateral Reach Test (LRT), respectively. Validity was tested by correlating the ODRT distance with the Berg Balance Scale (BBS) Score using Spearman's rank correlation coefficient. Intraclass correlation coefficients (ICCs) and Bland Altman analysis were used to establish inter-rater reliability. ICCs were used to find intra-rater reliability. The Mann-Whitney U test was used to establish the mean difference of the FRT, LRT, and ODRT. Spearman's rank correlation coefficient and linear regression were used to correlate the distance of FRT and LRT with ODRT. A high concurrent validity was found between BBS and ODRT with an r-value of 0.905 (p < 0.001). Inter-rater reliability was high with an ICC of 0.997 (95% CI [0.996-0.998]), and intra-rater reliability was highly significant with an ICC of 0.996 (95% CI [0.994-0.998]). The stroke subjects reached a significantly shorter distance than healthy individuals in FRT, ODRT, and LRT. ODRT was highly correlated with FRT (r = 0.985) and LRT (r = 0.978) (p < 0.001) and had an R2 = 0.987. ODRT is a highly valid and reliable tool that can be used to evaluate balance in stroke patients. Individuals who reached less in the forward and lateral directions showed reduced reach distance in the oblique direction.


An exploratory multi-level attempt to investigate intrapersonal and interpersonal patterns of 20 Athenian families.
The present study is an attempt to explore patterns of family relationships in the context of milieu specific value and role assumptions and to capture the trends in relation to social change. Information collected includes intrapsychic as well as interpersonal material elicited by a combination of tools administered individually and conjointly. The revealed patterns -- extreme emphasis on the future achievement of the child as a shared family goal, the mother's central role which was shown to inhibit constructive processes, the distant marital relationship, and scapegoating of the child because of denied marital difficulties -- are shown to create conflict and tension in all members and render cooperation and decision-making difficult. It is attempted to interpret the above-mentioned patterns in the light of traditional value and role assumptions. The analysis seems to indicate that the adherence to the dysfunctional patterns appears to serve the function of preserving stability of the family in a period of transition.


[Angio-follicular lymph node hyperplasia (Castleman's lymphoma)].
Two patients with angio-follicular lymph node hyperplasia are described, and the literature is reviewed. In one symptom-free man, the chest x-ray showed a tumour of the upper mediastinum the size of a fist (which is known to have been present for 20 years), in another man there was a 4 cm. node in the right hilum, which was shown by computer tomography not to be due to vessels. In each case the tumour was removed. Histologically they proved to be a hyaline-vascular type of angio-follicular lymph node hyperplasia. This is probably an inflammatory-reactive process.


Creating a response space in multiparty classroom settings for students using eye-gaze accessed speech-generating devices.
Conversation Analysis was used to explore how teachers, personal care assistants, and students organized inclusive multiparty classroom interaction when one of the students in the classroom used an eye-gaze accessed speech-generating device (SGD). Scaffolding and collaborative practices that created a response space for the construction of the eye-gaze accessed SGD-mediated turn were identified and analyzed. The participants were two adolescent students with severe cerebral palsy and intellectual disability who relied on eye-gaze accessed SGDs, and their teachers, personal care assistants, and classmates with intellectual disabilities. The data consisted of 2 hr and 40 min of video recordings collected in the participants' classrooms. Three practices were identified (a) the practice of explicit turn allocation organization and the use of display questions, (b) the practice of locally contingent on-screen scaffolding activities, and (c) the practice of dealing with turn competition by classmates. Teacher and assistant practices differed with regard to the student's access to the vocabulary relevant to answering the teacher's question. The practices were found to create a response space for students using SGDs accessed via eye gaze, thereby ensuring their educational inclusion in the classroom.


[Reaction of leukocyte migration inhibition in patients with uveal melanoblastoma].
The paper presents the results of melanoma antigen-mediated reaction of inhibition of leukocyte migration performed in 164 patients (malignant melanoma of the uveal tract-82 and glaucoma and other non-uveal pathology-82 cases). The reaction offers means for identifying cellular immune response to melanoma antigens in uveal melanoma patients. It may be useful in the diagnosis of malignant melanoma of the eye.


Biological effects of selenium compounds with a particular attention to the ontogenetic development.
Selenium is a trace element that is essential for living organism. Its beneficial effect is, however, expressed in a very narrow dosage range: the high and low doses of selenium are connected with pathological manifestations. The toxicity depends on the chemical form of selenium, state of organism, interactions with heavy metals and on the stage of ontogenetic development. Whereas one dose of sodium selenite (20 micromol/kg b.w.) is lethal in adult rats, suckling rats are entirely resistant. However, within one week after administration of the same dose, cataract of eye lens developed. The highest incidence of cataract was observed in 10-day-old animals and it decreased until day 20. From postnatal day 20 to day 40 the rats were resistant to both the lethal and cataractogenic effects of selenium. The incidence of cataract may be suppressed by premature weaning, lower hydration of suckling, change of water soluble/water insoluble lens protein ratio, thyroxine treatment, and by interaction with mercury. By means of its oxidative and reduction properties, selenium is involved in the maintenance of the cell redox homeostasis. Typical example is its possible cardioprotective effect: selenium decreased number of arrhythmias, reduced infarct size and improved the contractile recovery after ischemia/reperfusion injury. Selenium supplementation may thus increase cardiac tolerance to ischemic damage.


Preparation and properties of nexuses and lipid-enriched vesicles from mouse liver plasma membranes.
Extraction of mouse liver plasma membranes with 4% (w/v) N-laurylsarcosinate-tris buffer, pH7.8, solubilized 80-90% of the protein and 60% of the 5'-nucleotidase activity. The membrane residue remaining after extraction was resolved on sucrose gradients into two fractions: a vesicular membrane fraction and a fraction characterized by the presence of large numbers of nexuses in an amorphous background. The vesicular fraction had a phospholipid/protein weight ratio of 7:1, it contained most of the plasma-membrane glycolipids, and polyacrylamide-gel electrophoresis indicated the presence of only five to eight proteins, including two or three glycoproteins. The 5'-nucleotidase and leucine naphthylamidase specific activities were 23- and 6-fold higher respectively than in the plasma membranes. Electron microscopy of thin sections and negatively stained preparations indicated that the nexuses present in the second fraction closely resembled gap junctions present in tissue sections and isolated plasma membranes. The nexus fraction contained a distinctive protein pattern, and of the 20 proteins present about four were identified as glycoproteins by Schiff-periodate staining. Examination of the lipid composition of the fractions by t.l.c. showed that in the nexus fraction, phospholipids and glycolipids were present in small amounts compared with triglycerides and cholesterol. Amino sugar analyses confirmed the t.l.c. results and amino acid analysis showed the fractions to have characteristic protein compositions. A ;reconstituted' membranous fraction prepared by dialysis against MgCl(2) of membrane components soluble in N-laurylsarcosinate-tris buffers, pH7.8, lacked the trilaminar image characteristic of the two other membrane fractions isolated and was devoid of enzyme activities. The results indicate that proteins and glycoproteins play an important role in the structural maintenance of the nexuses isolated from the liver by the present procedure.


Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis.
Premature degradation of mutated cystic fibrosis transmembrane conductance regulator (CFTR) protein causes cystic fibrosis (CF), the commonest Mendelian disease in Caucasians. Despite recent advances in precision medicines for CF patients, many CFTR mutants have not been characterized and the effects of these new therapeutic approaches are still unclear for those mutants. Cells transfected or stably expressing four CFTR transmembrane-domain mutants (G85E, E92K, L1077P, and M1101K) were used to: 1) characterize the mutants according to their protein expression, thermal sensitivity, and degradation pathways; 2) evaluate the effects of correctors in rescuing them; and 3) explore the effects of correctors on CFTR interactions with proteostasis components. All four mutants exhibited lower protein expression than did wild type-CFTR, and they were degraded by proteasomes and aggresomes. At low temperature, only cells expressing the mutants L1077P and M1101K exhibited increased CFTR maturation. Co-administration of C4 and C18 showed the greatest effect, restoring functional expression and partial stability of CFTR bearing E92K, L1077P, or M1101K at the cell surface. However, this treatment was inefficient in rectifying the defect of CFTR bearing G85E. Correctors rescued CFTR mutants by reducing their interactions with proteostasis components associated with protein retention in the endoplasmic reticulum and ubiquitination. Co-administration of C4 and C18 rescued CFTR transmembrane-domain mutants by remodeling the CFTR interactome.


Pain suppression by peripheral nerve stimulation. Part I. Observations with transcutaneous stimuli.
A systematic, strict appraisal was made of 100 patients, after preliminary clinical trials suggested that some patients with pain could be helped by peripheral nerve stimulation. Transcutaneous stimulation of different nerve trunks was done with a special electrical stimulation device with various selected electrical parameters. More than half of the patients experienced some relief; in many, this effect was obtained by stimulating nerves distant from the area of referred pain. Pain relief lasted for varying periods after stimulation. The maximum benefit was noticed after certain specific parameters were reached for each patient. A few patients had response decay, gain or worsening. Results differ to some degree from previous reports. The results seem encouraging for the treatment of certain forms of intractable pain.


The characterization of hippocampal theta-driving neurons - a time-delayed mutual information approach.
Interneurons are important for computation in the brain, in particular, in the information processing involving the generation of theta oscillations in the hippocampus. Yet the functional role of interneurons in the theta generation remains to be elucidated. Here we use time-delayed mutual information to investigate information flow related to a special class of interneurons-theta-driving neurons in the hippocampal CA1 region of the mouse-to characterize the interactions between theta-driving neurons and theta oscillations. For freely behaving mice, our results show that information flows from the activity of theta-driving neurons to the theta wave, and the firing activity of theta-driving neurons shares a substantial amount of information with the theta wave regardless of behavioral states. Via realistic simulations of a CA1 pyramidal neuron, we further demonstrate that theta-driving neurons possess the characteristics of the cholecystokinin-expressing basket cells (CCK-BC). Our results suggest that it is important to take into account the role of CCK-BC in the generation and information processing of theta oscillations.


Cognitive Fatigue Influences Time-On-Task during Bodyweight Resistance Training Exercise.
Prior investigations have shown measurable performance impairments on continuous physical performance tasks when preceded by a cognitively fatiguing task. However, the effect of cognitive fatigue on bodyweight resistance training exercise task performance is unknown. In the current investigation 18 amateur athletes completed a full body exercise task preceded by either a cognitive fatiguing or control intervention. In a randomized repeated measure design, each participant completed the same exercise task preceded by a 52 min cognitively fatiguing intervention (vigilance) or control intervention (video). Data collection sessions were separated by 1 week. Participants rated the fatigue intervention with a significantly higher workload compared to the control intervention (p < 0.001). Additionally, participants self-reported significantly greater energetic arousal for cognitively fatiguing task (p = 0.02). Cognitive fatigue did not significantly impact number of repetitions completed during the exercise task (p = 0.77); however, when cognitively fatigued, participants had decreased percent time-on-task (57%) relative to the no fatigue condition (60%; p = 0.04). RPE significantly changed over time (p < 0.001), but failed to show significant differences between the cognitive fatigue intervention and control intervention (p > 0.05). There was no statistical difference for heart rate or metabolic expenditure as a function of fatigue intervention during exercise. Cognitively fatigued athletes have decreased time-on-task in bodyweight resistance training exercise tasks.


Degraded lands worth protecting: the biological importance of Southeast Asia's repeatedly logged forests.
Southeast Asia is a hotspot of imperiled biodiversity, owing to extensive logging and forest conversion to oil palm agriculture. The degraded forests that remain after multiple rounds of intensive logging are often assumed to be of little conservation value; consequently, there has been no concerted effort to prevent them from being converted to oil palm. However, no study has quantified the biodiversity of repeatedly logged forests. We compare the species richness and composition of birds and dung beetles within unlogged (primary), once-logged and twice-logged forests in Sabah, Borneo. Logging had little effect on the overall richness of birds. Dung beetle richness declined following once-logging but did not decline further after twice-logging. The species composition of bird and dung beetle communities was altered, particularly after the second logging rotation, but globally imperiled bird species (IUCN Red List) did not decline further after twice-logging. Remarkably, over 75 per cent of bird and dung beetle species found in unlogged forest persisted within twice-logged forest. Although twice-logged forests have less biological value than primary and once-logged forests, they clearly provide important habitat for numerous bird and dung beetle species. Preventing these degraded forests from being converted to oil palm should be a priority of policy-makers and conservationists.


A novel ubiquitin-specific protease, UBP43, cloned from leukemia fusion protein AML1-ETO-expressing mice, functions in hematopoietic cell differentiation.
Using PCR-coupled subtractive screening-representational difference analysis, we have cloned a novel gene from AML1-ETO knockin mice. This gene is highly expressed in the yolk sac and fetal liver of the knockin mice. Nucleotide sequence analysis indicates that its cDNA contains an 1,107-bp open reading frame encoding a 368-amino-acid polypeptide. Further protein sequence and protein translation analysis shows that it belongs to a family of ubiquitin-specific proteases (UBP), and its molecular mass is 43 kDa. Therefore, we have named this gene UBP43. Like other ubiquitin proteases, the UBP43 protein has deubiquitinating enzyme activity. Protein ubiquitination has been implicated in many important cellular events. In wild-type adult mice, UBP43 is highly expressed in the thymus and in peritoneal macrophages. Among nine different murine hematopoietic cell lines analyzed, UBP43 expression is detectable only in cell lines related to the monocytic lineage. Furthermore, its expression is regulated during cytokine-induced monocytic cell differentiation. We have investigated its function in the hematopoietic myeloid cell line M1. UBP43 was introduced into M1 cells by retroviral gene transfer, and several high-expressing UBP43 clones were obtained for further study. Morphologic and cell surface marker examination of UBP43/M1 cells reveals that overexpression of UBP43 blocks cytokine-induced terminal differentiation of monocytic cells. These data suggest that UBP43 plays an important role in hematopoiesis by modulating either the ubiquitin-dependent proteolytic pathway or the ubiquitination state of another regulatory factor(s) during myeloid cell differentiation.


Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation.
We sought to describe the effects of continuous intravenous midazolam infusion as therapy for severe bark scorpion (Centruroides exilicauda) envenomation. A retrospective chart review from July 1, 1993, through January 1, 1998, identified all patients treated at a university hospital with International Classification of Diseases, Ninth Revision, codes 989.5 (toxic effect of venom) or E905.2 (scorpion sting causing poisoning). By using standardized collection forms, data were extracted from the medical record of every patient who had a grade III or IV envenomation and was treated with a continuous intravenous midazolam infusion. Our search identified 104 patients; 34 had grade III or IV envenomation. Of these, 33 were treated in the ICU with continuous intravenous midazolam infusion. Median patient age was 4 years (range, 1 to 68 years). Midazolam dosage was adjusted to induce a light sleep state to control agitation and involuntary motor activity. The median amount of midazolam resulting in the first recorded decrease in agitation and involuntary motor activity was 0.30 mg/kg (range, 0.03 to 1.76 mg/kg). This first evidence of clinical improvement was recorded as 1.00 hour (median), with a range of 0.00 to 3.75 hours. The initial midazolam infusion rate was 0.10 mg x kg(-1) x h(-1) (median), with a range of 0.01 to 0.31 mg x kg(-1) x h(-1). The maximal midazolam infusion rate was 0.30 mg x kg(-1) x h(-1) (median), with a range of 0.06 to 1.29 mg x kg(-1) x h(-1). The median time until the maximal midazolam infusion rate was 2.5 hours (range, 0.00 to 8.50 hours). The median duration of infusion was 9. 50 hours (range, 4.25 to 20.50 hours). The median length of stay in the ICU was 15.17 hours (range, 6.0 to 28.0 hours), and 85% of patients were discharged directly home. All patients had resolution of abnormal motor activity and agitation during their midazolam infusion. Transient hypoxemia without evidence of end-organ dysfunction was documented in 4 patients during midazolam therapy. A continuous intravenous midazolam infusion can be a safe, effective, and readily available treatment option for patients with grade III or IV C exilicauda envenomation.


Surgical treatment of incontinence in elderly women.
Careful selection of patients can lead to a modest cure rate in elderly women for incontinence due to urethral sphincter incompetence. This is worth while when considering the few complications encountered during and after the surgical procedure, the independence the patients have achieved and the alternative incomplete cure which would have been afforded by conservative therapy.


A 3-Species Aquatic Community Model for Ecological Risk Assessment Using Basic Ecotoxicity Data.
A simplified ecosystem model, the Aquatic Tritrophic Ecological Risk Assessment Model (A-TERAM), for the ecological risk assessment of chemicals is presented. The A-TERAM comprises a linear grazer food chain with 3 trophic levels (the algae-Daphnia-fish system). The model simulates the seasonal patterns of abundance at each level observed in the field, and it translates the direct toxic effects of chemicals on algae or Daphnia to implications for fish via ecological interactions; thus, the A-TERAM evaluates ecological risk in terms of the annual population growth rate of fish. The model also incorporates toxicokinetics for fish. The minimum input data required for the A-TERAM are basic ecotoxicity endpoints (algal growth inhibition median effect concentration [EC50] or no-observed effect concentration, Daphnia immobility EC50, and fish acute mortality median lethal concentration); however, additional ecotoxicity data (Daphnia reproduction test, fish early life test, and fish reproduction test) are also relevant for improving simulations. Comparisons made across 496 chemicals (255 nonagricultural chemicals and 241 agrochemicals) indicated that the A-TERAM, in comparison with the conventional predicted-effect concentration/predicted-no-effect concentration method, tended to evaluate higher risk to chemicals that are highly bioaccumulative and toxic to fish by 2 orders of magnitude at the largest but lower or comparable risk to chemicals that are toxic only to algae or Daphnia. Environ Toxicol Chem 2020;39:1086-1100. © 2020 SETAC.


Exploratory application of the Ages and Stages (ASQ) child development screening test in a low-income Peruvian shantytown population.
Public health research on child health is increasingly focusing on the long-term impacts of infectious diseases, malnutrition and social deprivation on child development. The objectives of this exploratory study were to (1) implement the Ages and Stages Questionnaires (ASQ) in children aged 3 months to 5 years in a low-income Peruvian population and (2) to correlate outcomes of the ASQ with risk factors such as nutritional status, diarrhoea incidence and wealth index. Primary data collection was carried out in the Pampas de San Juan de Miraflores, a periurban low-income community in Lima, Peru. The study population included 129 children selected through community census data, with a mean age of 22 months (SD 6.8) and with almost equal gender distribution (51% males). A Peruvian psychologist administered the age-appropriate (ASQ2 for participants enrolled in 2009, ASQ3 for participants enrolled in 2010). Results of the ASQ are reported separately for five scales, including Communication, Gross Motor, Fine Motor, Problem Solving and Personal-Social. For each scale, results are reported as normal or suspect, meaning that some milestone attainment was not evident and further evaluation is recommended. Overall, 50 of 129 children (38.7%) had suspect results for at least one of the five scales, with the highest rates of suspect results on the Communication (15.5%) and Problem Solving scales (13.9%). Higher rates of suspect outcomes were seen in older children, both overall (p=0.06) and on Problem Solving (p=0.009), and for some scales there were trends between suspect outcomes and wealth index or undernutrition. The ASQ was successfully applied in a community-based study in a low-income Peruvian population, and with further validation, the ASQ may be an effective tool for identifying at-risk children in resource-poor areas of Latin America.


Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck.
Few epitopes are available for vaccination therapy of patients with squamous cell carcinoma of the head and neck (SCCHN). Using a tumor-specific CTL, aldehyde dehydrogenase 1 family member A1 (ALDH1A1) was identified as a novel tumor antigen in SCCHN. Mass spectral analysis of peptides in tumor-derived lysates was used to determine that the CTL line recognized the HLA-A*0201 (HLA-A2) binding ALDH1A1(88-96) peptide. Expression of ALDH1A1 in established SCCHN cell lines, normal mucosa, and primary keratinocytes was studied by quantitative reverse transcription-PCR and immunostaining. Protein expression was further defined by immunoblot analysis, whereas ALDH1A1 activity was measured using ALDEFLUOR. ALDH1A1(88-96) peptide was identified as an HLA-A2-restricted, naturally presented, CD8(+) T-cell-defined tumor peptide. ALDH1A1(88-96) peptide-specific CD8(+) T cells recognized only HLA-A2(+) SCCHN cell lines, which overexpressed ALDH1A1, as well as targets transfected with ALDH1A1 cDNA. Target recognition was blocked by anti-HLA class I and anti-HLA-A2 antibodies. SCCHN cell lines overexpressing ALDH1 had high enzymatic activity. ALDH1A1 protein was expressed in 12 of 17 SCCHN, and 30 of 40 dysplastic mucosa samples, but not in normal mucosa. ALDH1A1 expression levels in target cells correlated with their recognition by ALDH1A1(88-96) peptide-specific CD8(+) T cells. Our findings identify ALDH1A1, a metabolic antigen, as a potential target for vaccination therapy in the cohort of SCCHN subjects with tumors overexpressing this protein. A smaller cohort of subjects with SCCHN, whose tumors express little to no ALDH1A1, and thus are deficient in conversion of retinal to retinoic acid, could benefit from chemoprevention therapy.


Review article--involvement of gastric APUD cells in chronic renal failure.
Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. Most frequently, alimentary disorders are the first to appear, followed by symptoms from other organs and systems. The gastrointestinal tract is a site of synthesis of many compounds that have hormonal or hormonal-like biological activity. These substances are produced by highly-specialised receptor-effector cells, that are dispersed in the gastrointestinal mucosa and classified as APUD cells. The present review is an attempt to make a synthesis of current opinions and views concerning the effect of homeostatic dysfunction of the kidneys on the morphology and action of APUD cells in the stomach.


Should there be a restriction of optometric treatment?
The restriction of optometric services in third party payment programs is of considerable concern to the profession. Limitations placed on the type and amount of lens prescriptions which can be provided is not in the best interest of the patient. Those outside the profession of optometry must be made aware of the significance of ophthalmic lens prescriptions in terms of total visual performance rather than mere correction of "significant" refractive errors.


Serologic diagnosis of infectious cyclic thrombocytopenia in dogs using an indirect fluorescent antibody test.
An indirect fluorescent antibody test was used for detection of serum antibodies to the platelet-specific rickettsial organism that is the causative agent of infectious cyclic thrombocytopenia (ICT) in dogs. The test converted from negative to positive in 7 of 7 experimentally inoculated dogs. One of 2 attempts to recover the rickettsial agent of ICT from naturally occurring seropositive dogs, by blood inoculation of experimental dogs, was successful. Seemingly, the test did not detect antibodies to Ehrlichia canis, nor did a similar test, using E canis antigen slides, detect antibodies to the rickettsial agent of ICT. The rickettsial agent of ICT has been classified tentatively as E platys. When applied to sera from a group of healthy random-source dogs, the test revealed a relatively low (5%) occurrence of positive reactions. A higher occurrence of positive reactions (35%) was noticed in sera from a group of thrombocytopenic dogs from the University of Florida. A majority of these positive sera were also positive for antibodies to E canis. The highest occurrence of positive reactions was found (greater than 50%) in E canis-positive sera from dogs at the University of Florida, as well as from dogs from 9 other states.


Quantitative Phosphoproteomic and System-Level Analysis of TOR Inhibition Unravel Distinct Organellar Acclimation in Chlamydomonas reinhardtii.
Rapamycin is an inhibitor of the evolutionary conserved Target of Rapamycin (TOR) kinase which promotes and coordinates translation with cell growth and division. In heterotrophic organisms, TOR regulation is based on intra- and extracellular stimuli such as amino acids level and insulin perception. However, how plant TOR pathways have evolved to integrate plastid endosymbiosis is a remaining question. Despite the close association of the TOR signaling with the coordination between protein turn-over and growth, proteome and phosphoproteome acclimation to a rapamycin treatment have not yet been thoroughly investigated in Chlamydomonas reinhardtii. In this study, we have used in vivo label-free phospho-proteomic analysis to profile both protein and phosphorylation changes at 0, 24, and 48 h in Chlamydomonas cells treated with rapamycin. Using multivariate statistics we highlight the impact of TOR inhibition on both the proteome and the phosphoproteome. Two-way ANOVA distinguished differential levels of proteins and phosphoproteins in response either to culture duration and rapamycin treatment or combined effects. Finally, protein-protein interaction networks and functional enrichment analysis underlined the relation between plastid and mitochondrial metabolism. Prominent changes of proteins involved in sulfur, cysteine, and methionine as well as nucleotide metabolism on the one hand, and changes in the TCA cycle on the other highlight the interplay of chloroplast and mitochondria metabolism. Furthermore, TOR inhibition revealed changes in the endomembrane trafficking system. Phosphoproteomics data, on the other hand, highlighted specific differentially regulated phosphorylation sites for calcium-regulated protein kinases as well as ATG7, S6K, and PP2C. To conclude we provide a first combined Chlamydomonas proteomics and phosphoproteomics dataset in response to TOR inhibition, which will support further investigations.


Efficient repair of protein radicals by ascorbate.
Protein radicals were selectively generated by reaction with azide radicals on Trp and Tyr residues in insulin, beta-lactoglobulin, pepsin, chymotrypsin, and bovine serum albumin at rate constants in the range (2.9-19)x10(8) M(-1) s(-1). Monohydrogen ascorbate reduced tryptophanyl radicals in chymotrypsin and pepsin with rate constants in the narrow range of (1.6-1.8)x10(8) M(-1) s(-1), whereas beta-lactoglobulin tryptophanyl radicals reacted almost 10 times slower. The corresponding values for the protein tyrosyl radicals were about an order of magnitude smaller. Comparison of the rate constants of reactions of free and protein-bound tryptophanyl and tyrosyl radicals showed that, in most cases, the location of the radicals in the protein chain did not constitute a major barrier to the reaction with monohydrogen ascorbate. The results suggest that, under physiological concentrations of dioxygen, monohydrogen ascorbate is likely to be a significant target of protein radicals. It seems likely, therefore, that reaction with protein radicals may be responsible for much of the well-documented loss of ascorbate in living organisms subjected to oxidative stress.


Congress, courts, and commerce: upholding the individual mandate to protect the public's health.
Among multiple legal challenges to the Patient Protection and Affordable Care Act (PPACA) is the premise that PPACA's "individual mandate" (requiring all individuals to obtain health insurance by 2014 or face civil penalties) is inviolate of Congress' interstate commerce powers because Congress lacks the power to regulate commercial "inactivity." Several courts initially considering this argument have rejected it, but federal district courts in Virginia and Florida have concurred, leading to numerous appeals and prospective review of the United States Supreme Court. Despite creative arguments, the dispositive constitutional question is not whether Congress' interstate commerce power extends to commercial inactivity. Rather, it is whether Congress may regulate individual decisions with significant economic ramifications in the interests of protecting and promoting the public's health. This article offers a counter-interpretation of the scope of Congress' interstate commerce power to regulate in furtherance of the public's health.


PET study of competition between intravenous cocaine and [11C]raclopride at dopamine receptors in human subjects.
Animal data suggest that the strong euphoriant effects of cocaine are related to the drug's enhancement of available dopamine at the synaptic cleft. The authors' goal was to determine whether this mechanism is the same in humans because the development of putative pharmacological agents for treatment of cocaine dependence depends on this knowledge. Positron emission tomography with [11C]raclopride was used to examine the effects of the intravenous administration of 48 mg of cocaine (a typical "street" dose) on the occupancy of dopamine 2 receptors in the putamen of 11 self-identified intravenous drug abusers. All 11 subjects reported subjective stimulation and euphoria in response to cocaine administration. Radioligand occupancy at dopamine receptors was decreased significantly after cocaine administration, suggesting that higher dopamine concentrations were competing at the receptor site. These results support the concept of dopamine system involvement in human cocaine abuse.


Tetrabutylammonium methacrylate as a novel receptor for selective extraction of sulphonylurea drugs from biological fluids using molecular imprinting.
Glibenclamide (GLIB), an oral antidiabetic medication of the sulphonylurea drug family, was stoichiometrically imprinted using tetrabutylammonium methacrylate as the functional monomer, for the first time in molecular imprinting, and utilising the sulphonylurea affinity for carboxylate anions. Solution association between the drug and the novel functional monomer was studied by 1H-NMR titrations, whereby evidence of sulphonylurea deprotonation followed by the formation of "narcissistic" GLIB dimers was found when tested in CDCl3, while an affinity constant in excess of 105 L mol-1 was measured in DMSO-d6. Detailed analysis of GLIB binding on the subsequently prepared imprinted and non-imprinted polymers confirmed the deactivation of binding sites by exchange of a proton between GLIB and methacrylate, followed by extraction of the tetrabutylammonium counterion from the polymer matrix, resulting in overall reduced binding capacities and affinities by the imprinted material under equilibrium conditions. An optimised MI-SPE protocol, which included a binding site re-activation step, was developed for the extraction of GLIB from blood serum, whereby recoveries of up to 92.4% were obtained with an exceptional sample cleanup.


The presence within single K-562 cells of erythropoietic and granulopoietic differentiation markers.
The continuous cell line K-562, derived from a patient with CML in blast crisis, was examined for markers of granulopoietic (My-1) and erythropoietic (spectrin) differentiation, using specific antibodies detected by indirect immunofluorescence. Both markers were seen, and in 10%--30% of cells, both were present in the same cells. In contrast, the continuous leukemic line HL-60 and KGI contained My-1 only. Controls consisted of colonies in culture containing both granulopoietic and erythropoietic cells (CFU-GEMM). In these, My-1 was seen only in granulopoietic cells and spectrin in erythropoietic cells. The suggestion is advanced that genes coding for differentiation markers are expressed abnormally in K-562.


Metabolic syndrome and daily ambulation in children, adolescents, and young adults.
To compare daily ambulatory measures in children, adolescents, and young adults with and without metabolic syndrome and to assess which metabolic syndrome components, demographic measures, and body composition measures are associated with daily ambulatory measures. Two-hundred fifty subjects between the ages of 10 and 30 yr were assessed on metabolic syndrome components, demographic and clinical measures, body fat percentage, and daily ambulatory strides, durations, and cadences during seven consecutive days. Of the 250 subjects, 45 had metabolic syndrome, as defined by the International Diabetes Federation. Subjects with metabolic syndrome ambulated at a slower daily average cadence than those without metabolic syndrome (13.6 ± 2.2 vs 14.9 ± 3.2 strides per minute; P = 0.012), and they had slower cadences for continuous durations of 60 min (P = 0.006), 30 min (P = 0.005), 20 min (P = 0.003), 5 min (P = 0.002), and 1 min (P = 0.001). However, the total amount of time spent ambulating each day was not different (P = 0.077). After adjustment for metabolic syndrome status, average cadence is linearly associated with body fat percentage (P < 0.001) and fat mass (P < 0.01). Group difference in average cadence was no longer significant after adjusting for body fat percentage (P = 0.683) and fat mass (P = 0.973). Children, adolescents, and young adults with metabolic syndrome ambulate more slowly and take fewer strides throughout the day than those without metabolic syndrome, although the total amount of time spent ambulating is not different. Furthermore, the detrimental influence of metabolic syndrome on ambulatory cadence is primarily a function of body fatness.


Incidence of cytomegalovirus reactivation in patients with inflammatory connective tissue diseases who are under immunosuppressive therapy.
To evaluate the incidence and effect of cytomegalovirus (CMV) reactivation in patients with inflammatory connective tissue diseases (CTD) undergoing immunosuppressive therapy. A total of 18 consecutive CMV seropositive patients undergoing immunosuppressive therapy for inflammatory CTD were enrolled. CMV reactivation was determined by detection of CMV-DNA in peripheral blood leukocytes (PBL) or plasma using quantitative real-time polymerase chain reaction. CMV reactivation was detected in PBL in 7 of 17 evaluable patients (41%), and in plasma in 5 of 17 patients (29%). Patients with detectable CMV-DNA in plasma were exclusively positive for CMV-DNA in PBL. Conclusion. Patients with inflammatory CTD under immunosuppressive therapy are at high risk for CMV reactivation. The clinical significance of such an event and indications for antiviral therapy should be examined further.


Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring.
Exposure of a developing foetus to maternal gestational diabetes (GDM) has been shown to programme future risk of diabetes and obesity. Epigenetic variation in foetal tissue may have a mechanistic role in metabolic disease programming through interaction of the pregnancy environment with gene function. We aimed to identify genome-wide DNA methylation variation in cord blood and placenta from offspring born to mothers with and without GDM. Pregnant women of South Asian origin were studied and foetal tissues sampled at term delivery. The Illumina HumanMethylation450 BeadChip was used to assay genome-wide DNA methylation in placenta and cord blood from 27 GDM exposed and 21 unexposed offspring. We identified 1485 cord blood and 1708 placenta methylation variable positions (MVPs) achieving genome-wide significance (adjusted P-value <0.05) with methylation differences of >5%. MVPs were disproportionately located within first exons. A bioinformatic co-methylation algorithm was used to detect consistent directionality of methylation in 1000 bp window around each MVP was observed at 74% of placenta and 59% of cord blood MVPs. KEGG pathway analysis showed enrichment of pathways involved in endocytosis, MAPK signalling and extracellular triggers to intracellular metabolic processes. Replication studies should integrate genomics and transcriptomics with longitudinal sampling to elucidate stability, determine causality for translation into biomarker and prevention studies.


Reconstruction of pink esthetics: The periodontal way.
Cosmetic procedures involving gingival reconstruction have become an integral part of current periodontal practice. The ability to cover unsightly exposed, sensitive roots and recontour soft tissue recessions have added an esthetic angle to the traditional concept of biological and functional periodontal health. The recession of the gingiva, either localized or generalized, may be associated with one or more surfaces, resulting in attachment loss and root exposure, which can lead to clinical problems such as diminished cosmetic appeal and aesthetic concern. Marginal gingival recession, therefore, can cause major functional and aesthetic problems and should not be viewed as merely a soft tissue defect, but rather as the destruction of both the soft and hard tissue. Treatment proposals for this type of defect have evolved based on the knowledge for healing the gingiva and the attachment system. This case report describes a clinical case of severe Miller Class II gingival recession treated by two stages of surgery that combined a free gingival graft and connective tissue grafting. First, a free gingival graft (FGG) was performed to obtain an adequate keratinized tissue level. Three months later, a connective tissue graft (CTG)was performed to obtain root coverage. The results indicated that the FGG allows for a gain in the keratinized tissue level and the CTG allows for root coverage with decreased recession level after 6 months. Therefore, for this type of specific gingival recession, the combined use of FGG and CTG still serves as a Gold Standard in predictable root coverage.


Scientific output scales with resources. A comparison of US and European universities.
By using a comprehensive dataset of US and European universities, we demonstrate super-linear scaling between university revenues and their volume of publications and (field-normalized) citations. We show that this relationship holds both in the US and in Europe. In terms of resources, our data show that three characteristics differentiate the US system: (1) a significantly higher level of resources for the entire system, (2) a clearer distinction between education-oriented institutions and doctoral universities and (3) a higher concentration of resources among doctoral universities. Accordingly, a group of US universities receive a much larger amount of resources and have a far higher number of publications and citations when compared to their European counterparts. These results demonstrate empirically that international rankings are by and large richness measures and, therefore, can be interpreted only by introducing a measure of resources. Implications for public policies and institutional evaluation are finally discussed.


Small nickel nanoparticle arrays from long chain imidazolium ionic liquids.
A series of six long chain alkyl mono- and bi-cationic imidazolium based salts with bis(trifluoromethylsulfonyl)imide (NTf2(-)) as the anion were synthesized and characterized. The single crystal structure of 1-methyl-3-octadecylimidazolium bis(trifluoromethylsulfonyl)imide could be obtained by X-ray analysis. All these long chain alkyl imidazolium based ILs were applied in the synthesis of nickel nanoparticles via chemical decomposition of an organometallic precursor of nickel. In these media, spontaneous decomposition of Ni(COD)2 (COD = 1,5-cyclooctadiene) in the absence of H2 occurred giving small NPs (≤4 nm) with narrow size distributions. Interestingly, formation of regularly interspaced NP arrays was also observed in long chain ILs. Such array formation could be interesting for potential applications such as carbon nanotube growth.


Association of walkability with obesity in Baltimore City, Maryland.
To investigate the association between walkability and obesity, we studied adults residing in Baltimore City, Maryland, in neighborhoods of varying racial and socioeconomic composition. We conducted a cross-sectional study of 3493 participants from the study Healthy Aging in Neighborhoods of Diversity across the Life Span. We used the Pedestrian Environment Data Scan to measure neighborhood walkability in 34 neighborhoods of diverse racial and socioeconomic composition in which the study participants lived. Confirmatory factor analysis was used to determine walkability scores. Multilevel modeling was used to determine prevalence ratios for the association between walkability and obesity. Among individuals living in predominately White and high-socioeconomic status (SES) neighborhoods, residing in highly walkable neighborhoods was associated with a lower prevalence of obesity when compared with individuals living in poorly walkable neighborhoods, after adjusting for individual-level demographic variables (prevalence ratio-[PR] = 0.58; P = <.001 vs PR = 0.80; P = .004). Prevalence ratios were similar after controlling for the perception of crime, physical activity, and main mode of transportation. The association between walkability and obesity for individuals living in low-SES neighborhoods was not significant after accounting for main mode of transportation (PR = 0.85; P = .060). Future research is needed to determine how differences in associations by neighborhood characteristics may contribute to racial disparities in obesity.


The optimal anti-phospholipase A2 receptor cutoff for the diagnosis of idiopathic membranous nephropathy: a single-center retrospective study.
Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters. A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency. The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate. The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.


Procedural sedation by pediatric hospitalists: analysis of the nature and incidence of complications during ketamine and nitrous oxide sedation.
The goal of this study was to determine the nature and rate of complications during procedural sedation by pediatric hospitalists (PH) using ketamine and nitrous oxide (N2O). This study was a retrospective review and analysis of a quality improvement database for sedations performed by PH at St Louis Children's Hospital from February 2007 to February 2013. Information was obtained on sedations performed and reported in the quality improvement database by PH over this time period using ketamine and N2O. PH performed 8870 sedations from 2007 to 2013, 60.2% using ketamine and 39.8% using N2O. Procedural completion rates were >99%; 0.12% of sedations were not completed due to inadequate sedation, and sedation level was not achieved in 1.71% of sedations. There were no occurrences of death, need for cardiopulmonary resuscitation, unplanned intubation, or emergency anesthesia consultation. The only major complications were 4 unplanned admissions, 2 each with ketamine and N2O. With ketamine, the 2 highest rates of complications were airway repositioning (3.99%) and nausea and/or vomiting (2.98%). With N2O, the 2 highest complication rates were nausea and/or vomiting (8.50%) and airway repositioning (1.10%). Respiratory and cardiovascular events were more frequently encountered with ketamine, whereas nausea/vomiting, sedation level not achieved, and inadequate sedation resulting in procedure not completed occurred more frequently with N2O. PH at St Louis Children's Hospital successfully provided sedation by using ketamine and N2O with low rates of complications for a variety of procedures.


Capture versus suppression of attention by salient singletons: electrophysiological evidence for an automatic attend-to-me signal.
There is considerable controversy about whether salient singletons capture attention in a bottom-up fashion, irrespective of top-down control settings. One possibility is that salient singletons always generate an attention capture signal, but this signal can be actively suppressed to avoid capture. In the present study, we investigated this issue by using event-related potential recordings, focusing on N2pc (N2-posterior-contralateral; a measure of attentional deployment) and Pd (distractor positivity; a measure of attentional suppression). Participants searched for a specific letter within one of two regions, and irrelevant color singletons were sometimes present. We found that the irrelevant singletons did not elicit N2pc but instead elicited Pd; this occurred equally within the attended and unattended regions. These findings suggest that salient singletons may automatically produce an attend-to-me signal, irrespective of top-down control settings, but this signal can be overridden by an active suppression process to prevent the actual capture of attention.


The laboratory heterogeneity of lupus anticoagulants.
Approximately 2% of the patients screened in our laboratories with activated partial thromboplastin times are found to have a lupus anticoagulant. Recognition of lupus anticoagulants has assumed new importance because of a number of associated clinical conditions. Recurrent spontaneous abortions, arterial and venous thrombotic disease, and polyneuropathy have been described in patients with lupus anticoagulants. Although the clinical heterogeneity of these patients has been recognized increasingly, the laboratory identification of the lupus anticoagulant is still confusing and frustrating. In many cases, the diagnosis of this inhibitor is one of exclusion following a series of ambiguous mixing studies and variable factor assays. We studied ten patients with atypical laboratory results. Of particular significance are patients with a time-dependent enhancement of the lupus anticoagulant effect and patients with lupus anticoagulants that manifest a preferential inhibition of the prothrombin time rather than the activated partial thromboplastin time. We also confirmed the sensitivity of the platelet neutralization procedure in the identification of the lupus anticoagulant.


Gut mycobiomes are altered in people with type 2 Diabetes Mellitus and Diabetic Retinopathy.
Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.


Diverticulosis of the appendix: radiographic and clinical features.
We have reported three cases of appendiceal diverticulosis diagnosed by barium enema examination, and reviewed the radiographic and clinical findings. An awareness of this lesion is important, since diverticulitis of the appendix may occur in up to two thirds of patients with DA.


Crosstalk Suppression in Individually Addressed Two-Qubit Gates in a Trapped-Ion Quantum Computer.
Crosstalk between target and neighboring spectator qubits due to spillover of control signals represents a major error source limiting the fidelity of two-qubit entangling gates in quantum computers. We show that in our laser-driven trapped-ion system coherent crosstalk error can be modeled as residual Xσ[over ^]_{ϕ} interaction and can be actively canceled by single-qubit echoing pulses. We propose and demonstrate a crosstalk suppression scheme that eliminates all first-order crosstalk utilizing only local control of target qubits, as opposed to an existing scheme which requires control over all neighboring qubits. We report a two-qubit Bell state fidelity of 99.52(6)% with the echoing pulses applied after collective gates and 99.37(5)% with the echoing pulses applied to each gate in a five-ion chain. This scheme is widely applicable to other platforms with analogous interaction Hamiltonians.


Aliphatic polyester block polymers: renewable, degradable, and sustainable.
Nearly all polymers are derived from nonrenewable fossil resources, and their disposal at their end of use presents significant environmental problems. Nonetheless, polymers are ubiquitous, key components in myriad technologies and are simply indispensible for modern society. An important overarching goal in contemporary polymer research is to develop sustainable alternatives to "petro-polymers" that have competitive performance properties and price, are derived from renewable resources, and may be easily and safely recycled or degraded. Aliphatic polyesters are particularly attractive targets that may be prepared in highly controlled fashion by ring-opening polymerization of bioderived lactones. However, property profiles of polyesters derived from single monomers (homopolymers) can limit their applications, thus demanding alternative strategies. One such strategy is to link distinct polymeric segments in an A-B-A fashion, with A and B chosen to be thermodynamically incompatible so that they can self-organize on a nanometer-length scale and adopt morphologies that endow them with tunable properties. For example, such triblock copolymers can be useful as thermoplastic elastomers, in pressure sensitive adhesive formulations, and as toughening modifiers. Inspired by the tremendous utility of petroleum-derived styrenic triblock copolymers, we aimed to develop syntheses and understand the structure-property profiles of sustainable alternatives, focusing on all renewable and all readily degradable aliphatic polyester triblocks as targets. Building upon oxidation chemistry reported more than a century ago, a constituent of the peppermint plant, (-)-menthol, was converted to the ε-caprolactone derivative menthide. Using a diol initiator and controlled catalysis, menthide was polymerized to yield a low glass transition temperature telechelic polymer (PM) that was then further functionalized using the biomass-derived monomer lactide (LA) to yield fully renewable PLA-PM-PLA triblock copolymers. These new materials were microphase-separated and could be fashioned as high-performing thermoplastic elastomers, with properties comparable to commercial styrenic triblock copolymers. Examination of their hydrolytic degradation (pH 7.4, 37 °C) revealed retention of properties over a significant period, indicating potential utility in biomedical devices. In addition, they were shown to be useful in pressure-sensitive adhesives formulations and as nucleating agents for crystallization of commercially relevant PLA. More recently, new triblocks have been prepared through variation of each of the segments. The natural product α-methylene-γ-butyrolactone (MBL) was used to prepare triblocks with poly(α-methylene-γ-butyrolactone) (PMBL) end blocks, PMBL-PM-PMBL. These materials exibited impressive mechanical properties that were largely retained at 100 °C, thus offering application advantages over triblock copolymers comprising poly(styrene) end blocks. In addition, replacements for PM were explored, including the polymer derived from 6-methyl caprolactone (MCL). In sum, success in the synthesis of fully renewable and degradable ABA triblock copolymers with useful properties was realized. This approach has great promise for the development of new, sustainable polymeric materials as viable alternatives to nonrenewable petroleum-derived polymers in numerous applications.


Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo.
Angiotensin II is a powerful vasoconstrictor and proatherogenic factor. It was recently suggested that the endothelium may influence the actions of angiotensin II by production of, for example, nitric oxide and superoxide. By using venous occlusion plethysmography, forearm blood flow was measured in 26 healthy subjects during intraarterial cumulative infusion of angiotensin II. In 14 subjects, the interaction between angiotensin II and NO was studied by infusion of angiotensin II before and after clamping NO availability at a fixed basal level by using N(G)-monomethyl-L-arginine (L-NMMA) and nitroprusside. During a "free" NO system, blood flow decreased on angiotensin II infusion from 2.70+/-0.30 ml/100 ml forearm/min to 1.38+/-0.15 ml/100 ml forearm/min, whereas during NO-clamp vasoconstriction was significantly enhanced (blood flow from 2.56+/-0.25 to 1.19+/-0.13; p<0.05 saline vs. NO clamp). In 12 other subjects, the interaction between angiotensin II and superoxide was evaluated by comparison of the effects of angiotensin II before and after coinfusion of vitamin C. Angiotensin II-induced vasoconstriction was significantly attenuated by vitamin C at higher dosages of angiotensin (saline, blood flow from 3.08+/-0.33 to 1.12+/-0.09; vitamin C, blood flow from 3.01+/-0.23 to 1.61+/-0.13; p<0.05 saline vs. vitamin C). Vitamin C had no effect on baseline forearm blood flow. In conclusion, this study demonstrates that the constrictor actions of angiotensin II are enhanced during NO clamp and attenuated during vitamin C, suggesting direct angiotensin II-associated stimulation of endothelial NO and of oxygen radicals, respectively, in humans in vivo.


Optimization of multiple-isocenter treatment planning for linac-based stereotactic radiosurgery.
Computer-assisted treatment planning for linac-based radiosurgery is still an open research problem, especially for multiple-isocenter procedures, primarily due to its high complexity and computational requirements. This paper focuses on the optimization of multiple-isocenter treatment planning for linac systems, and addresses several important issues associated with multiple isocenters, such as dose conformality, homogeneity, and optimization of isocenter position and dose. The key idea behind our approach is that the desired dose distribution can be decomposed into a number of fundamental components. In the current paper, an analytical form, the so-called Ellipsoidal Dose Distribution Estimation (EDDE) model, represents each component. We establish ways (arc configurations) to achieve such ellipsoidal doses of arbitrary position, orientation, and size. Since the EDDE model is described by relatively few parameters, it allows very quick estimation of the dose distribution corresponding to a particular isocenter and thus makes the optimization of isocenter position very efficient. It is further used in a framework for optimal treatment planning, in which a number of ellipsoidal dose distributions, each corresponding to a different isocenter, are optimally placed to cover the target while sparing healthy tissue. The general ellipsoidal dose distribution of linac-based radiosurgery is summarized as a mathematical model with the aid of supporting experiments. Comparisons between the EDDE-optimized and clinically implemented plans are made, revealing the superior performance of the former. In addition, a dramatic reduction in planning time is achieved using the EDDE model. The proposed EDDE model is a useful and effective dose model in multiple-isocenter treatment planning for linac-based radiosurgery.


The Circadian Syndrome Is a Significant and Stronger Predictor for Cardiovascular Disease than the Metabolic Syndrome-The NHANES Survey during 2005-2016.
The study aimed to compare the predictive value of the Circadian Syndrome (CircS) and Metabolic Syndrome (MetS) for cardiovascular disease (CVD). We used data of 12,156 adults aged ≥20 years who attended National Health and Nutrition Examination Survey (NHANES) 2005-2016. Mortality was obtained from the registry updated to 2019. The CircS was defined based on components of the MetS, in addition to short sleep and depression. Both the MetS and CircS were directly associated with self-reported history of CVD. The odds ratios for prevalent CVD associated with the CircS and MetS, respectively, were 2.92 (95% confidence interval (CI) 2.21-3.86) and 3.20 (2.38-4.30) in men, and 3.27 (2.34-4.59) and 3.04 (2.15-4.30) in women. The CircS had a better predictive power for prevalent CVD than that of MetS, as indicated by the higher positive predictive value (PPV); in men, the PPV for prevalent CVD with CircS was 23.1% and with MetS 20.9%, and in women these were 17.9% vs. 16.4%, respectively. However, the PPV of the CircS and MetS did not differ for the CVD mortality prediction. Women with CircS alone had a higher risk for both prevalent CVD and CVD mortality than those with MetS alone. In conclusion, the CircS is a significant and stronger predictor for CVD than the MetS in US adults.


Antimutagenic effects of lichen Pseudovernia furfuracea (L.) Zoph. extracts against the mutagenicity of aflatoxin B1 in vitro.
The aim of this study was to investigate the effects of methanol, acetone, n-hexane and ether extracts obtained from Pseudovernia furfuracea on genotoxicity and total antioxidant capacity (TAC) in cultured human blood cells intoxicated with aflatoxin B(1) (AFB(1)). Sister chromatid exchange (SCE) and micronucleus (MN) tests were used for genotoxic influences estimation. In both the test systems, it was observed that P. furfuracea extracts suppressed the mutagenic effects of AFB(1) due to the type of extracts added to the cultures. Furthermore, a significant reduction in plasma TAC was observed after AFB(1) treatment. Interestingly, the methanol and acetone extracts of the lichen recovered AFB(1)-induced TAC inhibition. The order of extracts of anti-genotoxicity efficacy against AFB(1) was methanol, acetone, ether and n-hexane, respectively. In conclusion, P. furfuracea has been shown to modulate the adverse effects of AFB(1) in human blood cells for the first time.


Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology.
The primary objective was to determine clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials. Six tumor markers for colorectal cancer and seven for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used when data were available. Expert consensus was used to inform the recommendations for use of tumor markers when published evidence was insufficient. A computerized literature search was performed using Medline. In addition to reports collected by individual panel members, all articles published in the English-speaking literature from January 1989 to April 1994 were collected for review and distributed to all members of the Panel. Values for use, utility, and levels of evidence were assigned by the expert reviewers and approved by the Panel. Tumor markers were assigned benefit if they had prognostic or predictive value that would lead to the favorable outcomes listed above. Harms considered were inappropriate disease management, and excess cost without definable benefit. Costs were considered but were never the sole determinant of a recommendation. For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) levels be measured preoperatively if it would change surgical management. It is recommended that CEA levels be monitored every 2 to 3 months for > or = 2 years, if resection of liver metastasis would be clinically indicated. The data are insufficient to recommend the routine use of lipid-associated sialic acid (LASA), CA 19-9, DNA index, DNA flow cytometric proliferation analysis, p53 tumor suppressor gene, and ras oncogene. For breast cancer, estrogen receptor and progesterone receptor are recommended to be measured on every primary specimen, but on subsequent specimens only if it would lead to a change in management. The data are insufficient to recommend the routine use of DNA index, DNA flow cytometric proliferation analysis, CA 15-3, CEA, c-erbB-2, p53 or cathepsin-D. In the absence of readily measurable disease, CA 15-3 and CEA levels can be used to document treatment failure. New markers and new evidence will be evaluated by annual update of these guidelines.


Relationship between regional spending on vascular care and amputation rate.
Although lower extremity revascularization is effective in preventing amputation, the relationship between spending on vascular care and regional amputation rates remains unclear. To test the hypothesis that higher regional spending on vascular care is associated with lower amputation rates for patients with severe peripheral arterial disease. Retrospective cohort study of 18,463 US Medicare patients who underwent a major peripheral arterial disease-related amputation during the period between 2003 and 2010. Price-adjusted Medicare spending on revascularization procedures and related vascular care in the year before lower extremity amputation, across hospital referral regions. Correlation coefficient between regional spending on vascular care and regional rates of peripheral arterial disease-related amputation. Among patients who ultimately underwent an amputation, 64% were admitted to the hospital in the year prior to the amputation for revascularization, wound-related care, or both; 36% were admitted only for their amputation. The mean cost of inpatient care in the year before amputation, including costs related to the amputation procedure itself, was $22,405, but it varied from $11,077 (Bismarck, North Dakota) to $42,613 (Salinas, California) (P < .001). Patients in high-spending regions were more likely to undergo vascular procedures as determined by crude analyses (12.0 procedures per 10,000 patients in the lowest quintile of spending and 20.4 procedures per 10,000 patients in the highest quintile of spending; P < .001) and by risk-adjusted analyses (adjusted odds ratio for receiving a vascular procedure in highest quintile of spending, 3.5 [95% CI, 3.2-3.8]; P < .001). Although revascularization was associated with higher spending (R = 0.38, P < .001), higher spending was not associated with lower regional amputation rates (R = 0.10, P = .06). The regions that were most aggressive in the use of endovascular interventions were the regions that were most likely to have high spending (R = 0.42, P = .002) and high amputation rates (R = 0.40, P = .004). Regions that spend the most on vascular care perform the most procedures, especially endovascular interventions, in the year before amputation. However, there is little evidence that higher regional spending is associated with lower amputation rates. This suggests an opportunity to limit costs in vascular care without compromising quality.


Sulfonamide desensitization in solid organ transplant recipients: A protocol-driven approach during the index transplant hospitalization.
Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.


A comparison of gait one year post operation in an RCT of robotic UKA versus traditional Oxford UKA.
Robot-assisted unicompartmental knee surgery has been shown to improve the accuracy of implant alignment. However, little research has been conducted to ascertain if this results in a measureable improvement in knee function post operatively and a more normal gait. The kinematics of 70 OA knees were assessed using motion analysis in an RCT (31 receiving robotic-assisted surgery, and 39 receiving traditional manual surgery) and compared to healthy knees. Statistically significant kinematic differences were seen between the two surgical groups from foot-strike to mid-stance. The robotic-assisted group achieved a higher knee excursion (18.0°, SD 4.9°) compared to the manual group (15.7°, SD 4.1°). There were no significant difference between the healthy group and the robotic assisted group, however there was a significant difference between the healthy group and the manual group (p < 0.001). Hence robotically-assisted knee replacement with Mako Restoris Implants appears to lead not only to better implant alignment but also some kinematic benefits to the user during gait.


Identifying Genes Associated with Alzheimer's Disease Using Gene-Based Polygenic Risk Score.
Except APOE, Alzheimer's disease (AD) associated genes identified in recent large-scale genome-wide association studies (GWAS) had small effects and explained a small portion of heritability. Many AD-associated genes have even smaller effects thereby sub-threshold p-values in large-scale GWAS and remain to be identified. For some AD-associated genes, drug targeting them may have limited efficacies due to their small effect sizes. The purpose of this study is to identify AD-associated genes with sub-threshold p-values and prioritize drugs targeting AD-associated genes that have large efficacies. We developed a gene-based polygenic risk score (PRS) to identify AD genes. It was calculated using SNPs located within genes and having the same directions of effects in different study cohorts to exclude cohort-specific findings and false positives. Gene co-expression modules and protein-protein interaction networks were used to identify AD-associated genes that interact with multiple other genes, as drugs targeting them have large efficacies via co-regulation or interactions. Gene-based PRS identified 389 genes with 164 of them not previously reported as AD-associated. These 389 genes explained 56.12% -97.46% SNP heritability; and they were enriched in brain tissues and 164 biological processes, most of which are related to AD and other neurodegenerative diseases. We prioritized 688 drugs targeting 64 genes that were in the same co-expression modules and/or PPI networks. Gene-based PRS is a cost-effective way to identify AD-associated genes without substantially increasing the sample size. Co-expression modules and PPI networks can be used to identify drugs having large efficacies.


The European Society for Paediatric Nephrology study of pediatric renal care in Europe: comparative analysis 1998-2017.
In 1998, a survey of the European Society for Paediatric Nephrology (ESPN) revealed substantial disparities in pediatric renal care among European countries. Therefore, ESPN aimed at harmonizing renal care in all European countries in the following 20 years. In 2017, we conducted a survey to evaluate the current status of renal health policies for children in Europe. A 33-question web-based survey was designed and sent to presidents or representatives of national societies of pediatric nephrology in 44 European countries. Data was reported from 42 (95.5%) countries. The number of pediatric nephrologists per million child population increased from 1998 to 2017 in 70% of countries. Pediatric dialysis facilities for acute kidney injury and end-stage kidney disease were available in 95% of countries. The availability of pediatric kidney transplantation increased from 55 to 93% of countries. Considerable variation was found in the current availability of allied health professionals, including psychosocial and nutritional support, high-tech diagnostic methods, and treatment with expensive drugs for children with kidney diseases between different European countries. The 20-year follow-up analysis of pediatric renal care services in European countries revealed that pediatric nephrology has become a well-established subspecialty in pediatrics and nephrology in 2017. The ESPN will continue its efforts to further improve pediatric renal care for European children by harmonizing remaining disparities of renal care services.


Virus-induced asthma attack: The importance of allergic inflammation in response to viral antigen in an animal model of asthma.
Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes. We hypothesized that animals with immunologic memory to a respiratory virus would also develop airway hyperresponsiveness in response to a UV-inactivated form of the virus if they have pre-existing allergic airway inflammation. Guinea pigs were ovalbumin-sensitized, infected with live parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re-inoculated 60 days later with live or UV-inactivated PIV. Some animals were either treated with dexamethasone prior to the second viral exposure. Lymphocytes were isolated from parabronchial lymph nodes to confirm immunologic memory to the virus. Airway reactivity was measured and inflammation was assessed using bronchoalveolar lavage and lung histology. The induction of viral immunologic memory was confirmed in infected animals. Allergen sensitized and challenged animals developed airway hyperreactivity with eosinophilic airway inflammation when re-exposed to UV-inactivated PIV, while non-sensitized animals did not. Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment with dexamethasone. We suggest that the response of allergic inflammation to virus antigen is a significant factor causing asthma exacerbation. We propose that this is one mechanism explaining how corticosteroids prevent virus-induced asthma attack.


Pancreatic exocrine function in maturity onset diabetes mellitus.
Exocrine pancreatic function was studied in 14 inpatients with newly diagnosed maturity onset diabetes mellitus. Five patients had clinical and biochemical evidence of pancreatic disease (two carcinoma, three pancreatitis). The other nine patients had no clinical pancreatic disease but all except one had at least one abnormal result of pancreatic function tests. None of this group with idiopathic diabetes mellitus developed any clinical evidence of exocrine pancreatic disease over the next five years. Mild abnormalities of exocrine pancreatic function in newly diagnosed patients with diabetes but without clinical evidence of pancreatic disease do not usually develop into overt pancreatic disease, and are therefore probably clinically unimportant.


Dietary fiber intake and all-cause and cause-specific mortality: An updated systematic review and meta-analysis of prospective cohort studies.
Accumulating evidence supports the effects of dietary fiber on the risk of non-communicable diseases (NCDs). However, there is no updated systematic review and meta-analysis that compares and pools the effect of different types of fiber on mortality. In this systematic review and meta-analysis, all prospective cohort studies that evaluated the relationship between dietary fiber intake and all-cause or cause-specific mortality were included. The PubMed, SCOPUS, and Web of Science databases were searched up to October 2022. Data extraction and quality assessment were performed by two researchers independently. Heterogeneity between studies was assessed using Chi-square based test. Random/fixed effect meta-analysis was used to pool the hazard ratios (HR) or relative risks (RR) and 95 % confidence intervals (CI) for the association between different types of fiber and mortality. This systematic review included 64 eligible studies, with a total sample size of 3512828 subjects, that investigated the association between dietary fiber intake and mortality from all-cause, cardiovascular disease (CVD), and cancer. Random-effect meta-analysis shows that higher consumption of total dietary fiber, significantly decreased the risk of all-cause mortality, CVD-related mortality, and cancer-related mortality by 23, 26 and 22 % (HR:0.77; 95%CI (0.73,0.82), HR:0.74; 95%CI (0.71,0.77) and HR:0.78; 95%CI (0.68,0.87)), respectively. The consumption of insoluble fiber tended to be more effective than soluble fiber intake in reducing the risk of total mortality and mortality due to CVD and cancer. Additionally, dietary fiber from whole grains, cereals, and vegetables was associated with a reduced risk of all-cause mortality, while dietary fiber from nuts and seeds reduced the risk of CVD-related death by 43 % (HR:0.57; 95 % CI (0.38,0.77)). This comprehensive meta-analysis provides additional evidence supporting the protective association between fiber intake and all-cause and cause-specific mortality rates.


Intrathoracic rib: rare rib anomaly, review of the literature and proposal for classification.
Background: Intrathoracic ribs are very rare congenital anomalies, and often discovered incidentally on chest X-ray. Since its first description by Lutz in 1947, approximately 50 cases have been reported in the literature till date. The aim is to review the all reported intrathoracic ribs, summarize their clinical features, and propose a potential classification. Methods: All relevant literatures were searched and reviewed. The terms include intrathoracic rib, intrathoracic bifid rib, trans-thoracic rib and intrathoracic rib anomaly. We have summarized the first finding events, origination, distribution, related anomalies and imaging features of intrathoracic rib, and propose an updated classification. Results: The patients' age at initial finding was from six weeks to 79 years old. Of all, sixty percent was less than 30 years old. There was no difference in gender. Most of them were reported by authors in western countries (85.3%, 58/68), and incidental findings by radiologist and respiratory physician. The intrathoracic rib occurs more frequently on the right side, and is usually single and unilateral. According to the new classification, type I and II was account for 45.6% and 35.3%, respectively. Conclusion: Intrathoracic rib is rare findings in clinical practice. It is useful that radiologists or clinician are familiarized with the imaging appearances of these malformations. These anomalies reflect some disturbances during the embryo development, leading us to propose a potential classification that could contribute to a better understanding of this rib anomaly.


Mammary gland metabolite utilization in response to exogenous glucose or long-chain fatty acids at low and high metabolizable protein levels.
We investigated mammary gland metabolism in lactating dairy cattle in response to energy from glucogenic (glucose; GG) or lipogenic (palm olein; LG) substrates at low (LMP) and high (HMP) metabolizable protein levels. According to a 6 × 6 Latin square design, 6 rumen-fistulated second-lactation Holstein-Friesian dairy cows (97 ± 13 d in milk) were abomasally infused with saline (LMP-C); isoenergetic infusions (digestible energy basis) of 1,319 g/d glucose (LMP-GG), 676 g/d palm olein (LMP-LG), or 844 g/d essential AA (EAA; HMP-C); or isoenergetic infusions of 1,319 g/d glucose + 844 g/d EAA (HMP-GG) or 676 g/d palm olein + 844 g/d EAA (HMP-LG). Each experimental period consisted of 5 d of continuous infusion followed by 2 d of rest. A total mixed ration (42% corn silage, 31% grass silage, and 27% concentrate on a dry matter basis) formulated to meet 100 and 83% of net energy and metabolizable protein requirements, respectively, was fed at 90% of ad libitum intake by individual cow. Arterial and venous blood samples were collected on d 5 of each period. Infusing GG or LG at the HMP level did not affect milk yield or composition differently than at the LMP level. Neither GG nor LG infusion stimulated milk protein or lactose yield, but fat yield tended to decrease with GG and tended to increase with LG. Infusion of GG increased arterial plasma concentrations of glucose and insulin and decreased concentrations of β-hydroxybutyrate (BHB), nonesterified fatty acids, long-chain fatty acids (LCFA), total AA, EAA, and group 2 AA. Infusion of LG increased arterial triacylglycerides (TAG) and LCFA but did not affect EAA concentrations. Compared with the LMP level, the HMP level increased arterial concentrations of BHB, urea, and all EAA groups and decreased the concentration of total non-EAA. Mammary plasma flow increased with GG and was not affected by LG or protein level. Uptake and clearance of total EAA and group 2 AA were affected or tended to be affected by GG × AA interactions, with their uptakes being lower and their clearances higher with GG, but only at the LMP level. Infusion of LG did not affect uptake or clearance of any AA group. The HMP level increased uptake and decreased clearance of all EAA groups and decreased non-EAA uptake. Infusion of GG tended to increase mammary glucose uptake, and tended to decrease BHB uptake only at the LMP level. Infusion of LG increased mammary uptake of TAG and LCFA and increased or tended to increase clearance of TAG and LCFA. We suspect GG increased mammary plasma flow to maintain intramammary energy and AA balance and stimulated lipogenesis in adipose, accounting for depressed arterial BHB and group 2 AA concentrations. Mammary glucose uptake did not cover estimated requirements for lactose and fat synthesis at the HMP level, except during HMP-GG infusion. Results of this study illustrate flexibility in mammary metabolite utilization when absorptive supply of glucogenic, lipogenic, and aminogenic substrate is increased.


Racial Differences and Temporal Obesity Trends in Heart Failure with Preserved Ejection Fraction.
Obesity increases with age, is disproportionately prevalent in black populations, and is associated with heart failure with preserved ejection fraction (HFpEF). An "obesity paradox," or improved survival with obesity, has been reported in patients with HFpEF. The aim of this study was to examine whether racial differences exist in the temporal trends and outcomes associated with obesity among older patients with HFpEF. Community surveillance of acute decompensated heart failure (ADHF) hospitalizations, sampled by stratified design from 2005 to 2014. Atherosclerosis Risk in Communities Study (NC, MS, MD, MN). A total of 10,147 weighted hospitalizations for ADHF (64% female, 74% white, mean age 77 years), with ejection fraction ≥50%. ADHF classified by physician review, HFpEF defined by ejection fraction ≥50%. Body mass index (BMI) calculated from weight at hospital discharge. Obesity defined by BMI ≥30 kg/m2 , class III obesity by BMI ≥40 kg/m2 . When aggregated across 2005-2014, the mean BMI was higher for black compared to white patients (34 vs 30 kg/m2 ; P < .0001), as was prevalence of obesity (56% vs 43%; P < .0001) and class III obesity (24% vs 13%; P < .0001). Over time, the annual mean BMI and prevalence of class III obesity remained stable for black patients, but steadily increased for white patients, with annual rates statistically differing by race (P-interaction = .04 and P = .03, respectively). For both races, a U-shaped adjusted mortality risk was observed across BMI categories, with the highest risk among patients with a BMI ≥40 kg/m2 . Black patients were disproportionately burdened by obesity in this decade-long community surveillance of older hospitalized patients with HFpEF. However, temporal increases in mean BMI and class III obesity prevalence among white patients narrowed the racial difference in recent years. For both races, the worst survival was observed with class III obesity. Effective strategies are needed to manage obesity in patients with HFpEF.


Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses.
To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4+ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4+ T-cell recall responses. Therapeutically, CD4+ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4+ T cells with CaEno1 modulated host CD4+ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4+ T-cell responses.


Association of difficulties in daily physical activities and handgrip strength with cancer diagnoses in 65,980 European older adults.
People with cancer usually report physical deconditioning, which can limit daily activities. Our aim was to analyze associations between daily physical activities and handgrip strength with cancer diagnoses among European older adults. We used data from SHARE (a representative survey of individuals aged 50 years or older) wave 7, residing in 27 European countries and Israel. Participants self-reported difficulties in daily physical activities and cancer diagnoses, and handgrip strength was objectively assessed using a handheld dynamometer. Data were analyzed using binary logistic regression. Overall, 65,980 participants (average age 67.6 years (SD = 9.4)) were analyzed. Having difficulties in any daily physical activity was significantly associated with higher odds of cancer diagnoses. Lower handgrip strength was significantly associated with cancer diagnoses among participants included in the first (adjusted odds ratio (AOR) = 1.27 [95%CI = 1.11-1.45]) and the second third (AOR = 1.15 [95%CI = 1.03-1.28]) when compared with participants from the last third in the final adjusted model. Having difficulties in daily physical activities as well as lower levels of handgrip strength is positively associated with cancer diagnoses. Adults with difficulties lifting or carrying weights over 5 kilos or having difficulties in two or more activities showed critical associations with cancer diagnosis.


Use of profile analysis for the measurement of organ dimensions.
We have developed a method for measurement of organ dimension based on the use of the full width half maximum (FWHM) of profiles taken through an organ. In vitro studies were performed using a large rectangular lucite box filled with water. Five circular lucite phantoms with internal diameters of 1.4-10.2 cm and 1 elliptical phantom with dimensions 9.6 x 4.0 cm were filled with 99mTc-pertechnetate at various concentrations. Phantoms were imaged on a gamma camera at a depth of 5-25 cm in water and the FWHM calculated from horizontal profiles taken across the cylinders. The FWHM showed no variation with 99mTc concentration in the same cylinder. Phantom profiles were deconvolved with a system line spread function measured under similar conditions of scatter and depth. The correction factor to convert the deconvolved profile FWHM to true diameter was independent of cylinder depth and diameter over a range of FWHM 3-10 cm and depth 5-25 cm. The mean value for the correction factor was 1.23 +/- 0.04 for circular phantoms and 1.14 +/- 0.02 for the elliptical phantom. This technique should allow an objective and reproducible estimate of organ dimensions from planar images that is relatively independent of the depth and size of an organ.