Clinical Severity on Hospital Admission for COVID-19: An Analysis of Social Determinants of Health From an Early Hot Spot in the Southeastern U.S.
Disparities in COVID-19 infection, illness severity, hospitalization, and death are often attributed to age and comorbidities, which fails to recognize the contribution of social, environmental, and financial factors on health. The purpose of this study was to examine relationships between social determinants of health (SDOH) and COVID-19 severity. This multicenter retrospective study included adult patients hospitalized with COVID-19 in Southwest Georgia, U.S. The primary outcome was the severity of illness among patients on hospital admission for COVID-19. To characterize the effect of biological and genetic factors combined with SDOH on COVID-19, we used a multilevel analysis to examine patient-level and ZIP code-level data to determine the risk of COVID-19 illness severity at admission. Of 392 patients included, 65% presented with moderate or severe COVID-19 compared to 35% with critical disease. Compared to moderate or severe COVID-19, increasing levels of Charlson Comorbidity Index (OR 1.15, 95% CI 1.07-1.24), tobacco use (OR 1.85, 95% CI 1.10-3.11), and unemployment or retired versus employed (OR 1.91, 95% CI 1.04-3.50 and OR 2.17, 95% CI 1.17-4.02, respectively) were associated with increased odds of critical COVID-19 in bivariate models. In the multi-level model, ZIP codes with a higher percentage of Black or African American residents (OR 0.94, 95% CI 0.91-0.97) were associated with decreased odds of critical COVID-19. Differences in SDOH did not lead to significantly higher odds of presenting with severe COVID-19 when accounting for patient-level and ZIP code-level variables.


Response of patients with phenylketonuria in the US to tetrahydrobiopterin.
Tetrahydrobiopterin (BH4) responsive forms of phenylketonuria (PKU) have been recognized since 1999. Subsequent studies have shown that patients with PKU, especially those with mild mutations, respond with lower blood phenylalanine (Phe) concentrations following oral administration of 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4). To determine the incidence of BH4 responding PKU patients in the United States and characterize their phenylalanine hydroxylase (PAH) mutations, a study was undertaken at UTMB in Galveston and the Children's Hospital of Los Angeles on 38 patients with PKU. Patients were screened by a single oral dose of BH4, 10 mg/kg and blood Phe and tyrosine were determined at 0, 4, 8, and 24 h. Twenty-two individuals (58%) responded with marked decrease in blood Phe (>30%) at 24h. Some of the patients that responded favourably were clinically described as having Classical PKU. Blood tyrosine concentrations did not change significantly. Twenty subjects with PKU, responsive and non-responsive to BH4, were enrolled in a second study to evaluate blood Phe response to ascending single doses of BH4 with 10, 20, and 40 mg/kg and to evaluate multiple daily doses, for 7 days each, with 10 and 20 mg/kg BH4. The 7-day trial showed a sustained decrease in blood Phe in 14 of 20 patients taking 20 mg/kg BH4 (70%). Of these 14 patients, 10 (71%) responded with a significant decrease in blood Phe following 10 mg/kg BH4 daily. To understand the mechanism of response to BH4, the kinetics and stability of mutant PAH were studied. We found that mutant PAH responds with increase in the residual enzyme activity following BH4 administration. The increase in activity is multi-factorial caused by increased stability, chaperone effect, and correction of the mutant Km. These studies indicate that BH4 can be of help to patients with PKU, including some considered to have Classical PKU. The PKU population in US is heterogeneous and mutations can be varied so mutations need to be characterized and response to BH4 tested. It is more likely that mutations with residual activity should respond to BH4, therefore the clinical definition of "Classical PKU" should be reconciled with the residual activity of PAH mutations.


Pleated colposuspension: Our modification of Burch colposuspension.
Burch colposuspension is a standard treatment for stress urinary incontinence. However, it is associated with recurrence and urinary retention. We describe a modification of this technique to overcome these problems and evaluate the results in comparison with the standard procedure. A total of 145 patients with isolated stress urinary incontinence (SUI), underwent either our modified pleated colposuspension (PC); n = 97) or standard Burch colposuspension (BC) (n = 48). Description of PC: Three No. 0 non-absorbable sutures were placed in the side-to-side manner at the mid-urethral level with 0.5-1.0 cm distance between them using double bites and were passed through the Cooper's ligament. The patients were followed-up every 6 months for SUI and genital prolapse evaluation. Successful surgery was defined as (1) No self-reported SUI symptoms, (2) Negative Marshall's coughing test (MT), (3) No retreatment for SUI, (4) Absence of urodynamic SUI. In addition, failure was defined as the occurrence of urinary retention, use of catheter on 6-week visit, maximum flow rate >15 ml/s, flow time <60 s, or residual urine <100 ml. Data was compared using Student's paired test and Mantel-Haenzel's χ(2) test. P > 0.05 was considered significant. The mean follow-up after surgery for PC was 102.4 months and for BC was 103.6 months. At last follow-up, data suggesting failure (Stress score ≥7, urge score ≥7, Pad test with weight < 15 g/day and positive MT during lithotomic/upright position) were more frequent in BC group (P > 0.05; P > 0.0; P > 0.01; P > 0.05; P > 0.05, respectively). The incidence of recurrent SUI was 5.2% after PC and almost triple (14.6%) after BC. Residual urine <100 ml and weak stream were more frequent in the BC group (P > 0.05; P > 0.01, respectively). Detrusor over-activity on urodynamic studies, Flow time <60 s, urethral pressure profilometry positive for obstruction had a higher incidence in BC group (P > 0.01; P > 0.001; P > 0.01, respectively). Our modified pleated colposuspension showed improved outcomes when compared with standard Burch colposuspension.


Selective hydrolysis of plasmalogen phospholipids by Ca2+-independent PLA2 in hypoxic ventricular myocytes.
Accelerated phospholipid catabolism occurs early after the onset of myocardial ischemia and is likely to be mediated by the activation of one or more phospholipases in ischemic tissue. We hypothesized that hypoxia increases phospholipase A2 (PLA2) activity in isolated ventricular myocytes, resulting in increased lysophospholipid and arachidonic acid production, contributing to arrhythmogenesis in ischemic heart disease. The majority of ventricular myocyte arachidonic acid was found in plasmalogen phospholipids. Hypoxia increased membrane-associated, Ca2+-independent, plasmalogen-selective PLA2 activity, resulting in increased arachidonic acid release and lysoplasmenylcholine production. Pretreatment with the specific Ca2+-independent PLA2 inhibitor bromoenol lactone blocked hypoxia-induced increases in PLA2 activity, arachidonic acid release, and lysoplasmenylcholine production. Lysoplasmenylcholine produced action potential derangements, including shortening of action potential duration, and induced early and delayed afterdepolarizations in normoxic myocytes. The electrophysiological alterations induced by lysoplasmenylcholine would likely contribute to the initiation of arrhythmogenesis in the ischemic heart.


Comparing outcomes of major models of police responses to mental health emergencies.
The study compared three models of police responses to incidents involving people thought to have mental illnesses to determine how often specialized professionals responded and how often they were able to resolve cases without arrest. Three study sites representing distinct approaches to police handling of incidents involving persons with mental illness were examined-Birmingham, Alabama; and Knoxville and Memphis, Tennessee. At each site, records were examined for approximately 100 police dispatch calls for "emotionally disturbed persons" to examine the extent to which the specially trained professionals responded. To determine differences in case dispositions, records were also examined for 100 incidents at each site that involved a specialized response. Large differences were found across sites in the proportion of calls that resulted in a specialized response-28 percent for Birmingham, 40 percent for Knoxville, and 95 percent for Memphis. One reason for the differences was the availability in Memphis of a crisis drop-off center for persons with mental illness that had a no-refusal policy for police cases. All three programs had relatively low arrest rates when a specialized response was made, 13 percent for Birmingham, 5 percent for Knoxville, and 2 percent for Memphis. Birmingham's program was most likely to resolve an incident on the scene, whereas Knoxville's program predominantly referred individuals to mental health specialists. Our data strongly suggest that collaborations between the criminal justice system, the mental health system, and the advocacy community plus essential services reduce the inappropriate use of U.S. jails to house persons with acute symptoms of mental illness.


Clinical Outcomes of Preserving Bronchial Arteries During Radical Esophagectomy: A Propensity-Score Matched Analysis.
Postoperative pneumonia is a common and major cause of mortality after radical esophagectomy. Intraoperative preservation of the bronchial arteries is often aimed at avoiding tracheobronchial ischemia; however, it is unknown whether this contributes to a reduction in postoperative pneumonia. We enrolled 348 consecutive patients who underwent radical esophagectomy for esophageal cancer at Toranomon Hospital from January 2011 to July 2018. We classified patients into a bronchial artery-resected (BA-R) group (n = 93) and a bronchial artery-preserved (BA-P) group (n = 255) and compared the incidence of postoperative pneumonia between the two groups. A propensity score-matching analysis for bronchial artery preservation versus resection was performed. Overall, 182 patients were matched. Univariate analysis of the propensity score-matched groups showed that Brinkman index ≥ 400, vital capacity (%VC) < 80%, and bronchial artery resection were associated with the development of postoperative pneumonia. Multivariate analysis revealed three significant factors associated with postoperative pneumonia: Brinkman index ≥ 400 [p = 0.006, odds ratio (HR) 3.302, 95% confidence interval (95% CI) 1.399-7.790], %VC < 80% (p = 0.034, HR 6.365, 95% CI 1.151-35.205), and bronchial artery resection (p = 0.034, HR 2.131, 95% CI 1.060-4.282). The incidence of postoperative complications (CD grade III) was higher in the BA-R group (BA-R 42.8% versus BA-P 27.5%, p = 0.030). There was no significant difference in overall survival between the two groups at 5 years (BA-R 63.1% versus BA-P 72.1%, p = 0.130). Preserving the bronchial artery is associated with a decreased incidence of postoperative pneumonia.


Pregnancy Outcomes After Living Liver Donation: A Multi-Institutional Study.
Nearly half of living liver donors in North America are women of child-bearing age. Fetal and maternal outcomes after donation are unknown. We conducted a retrospective cohort study of female living liver donors (aged 18-50 years at donation) from 6 transplant centers. Participants were surveyed about their pregnancies and fertility. Outcomes were compared between predonation and postdonation pregnancies. Generalized estimating equations were clustered on donor and adjusted for age at pregnancy, parity, and pregnancy year. Among the 276 donors surveyed, 151 donors responded (54.7% response rate) and reported 313 pregnancies; 168/199 (68.8%) of the predonation pregnancies and 82/114 (71.9%) of the postdonation pregnancies resulted in live births, whereas 16.6% and 24.6% resulted in miscarriage, respectively. Women with postdonation pregnancies were older (32.0 versus 26.7 years; P < 0.001) and more frequently reported abnormal liver enzymes during pregnancy (3.5% versus 0.0%; P = 0.02) and delivery via cesarean delivery (35.4% versus 19.7%; P = 0.01). On adjusted analysis, there was no difference in cesarean delivery (odds ratio [OR], 2.44; 95% confidence interval [95% CI], 0.98-6.08), miscarriage (OR, 1.59; 95% CI, 0.78-3.24), combined endpoints of pregnancy-induced hypertension and preeclampsia (OR, 1.27; 95% CI, 0.36-4.49), or intrauterine growth restriction and preterm birth (OR, 0.91; 95% CI, 0.19-4.3). Of the 49 women who attempted pregnancy after donation, 11 (22.5%) self-reported infertility; however, 8/11 (72.7%) eventually had live births. Aside from increased reporting of abnormal liver enzymes and cesarean deliveries, there was no significant difference in pregnancy outcomes before and after living liver donation. One-fifth of women who attempt pregnancy after liver donation reported infertility, and although the majority went on to successful live births, further exploration is needed to understand the contributing factors. Future research should continue to monitor this patient-centered outcome across a large cohort of donors.


In Vivo Comparative Study of Radioiodinated Folate Receptor Targeting Albumin Probes for Atherosclerosis Plaque Imaging.
The objective of this study is to compare a series of albumin-based folate radiotracers for the potential imaging of folate receptor (FR) positive macrophages in advanced atherosclerotic plaques. Diversified radioiodinated FR-targeting albumin-binding probes ([131I]IBAbHF, [131I]IBNHF, and [131I]HF) were developed through various strategies. Among the three radiotracers, [131I]IBAbHF and [131I]IBNHF showed excellent in vitro stability (>98%) in saline and PBS 7.4 for 24 h. Also, good stability of [131I]IBNHF in mouse serum albumin was monitored using an HSA ELISA kit. The experiments in Raw264.7 macrophages activated by ox-LDL confirmed the specificity of tracers for FR-β. Biodistribution studies of radiotracers were performed to verify the prolonged blood half-life. Prolonged blood half-lives of [131I]IBAbHF, [131I]HF, and [131I]IBNHF were 17.26 ± 4.29, 6.33 ± 2.64, and 5.50 ± 1.26 h, respectively. SPECT-CT imaging of ApoE-/- mice at different stages was performed to evaluate the progression and monitor the prognosis of AS. Evident [131I]IBNHF uptake in atherosclerotic lesions could be observed along with a low background signal. In summary, we demonstrated a proof-of-concept of albumin-based radioligands for FR-targeting atherosclerosis imaging and found that different incorporation of radioiodinated groups resulted in different pharmacokinetic properties. Among these candidate compounds, [131I]IBNHF would be a satisfactory radiotracer for SPECT imaging of atherosclerosis.


Implementation of service screening with mammography in Sweden: from pilot study to nationwide programme.
Establishment of mammography screening in Sweden has progressed logically from pilot study through clinical trials to service screening. Screening with mammography for early detection of breast cancer has been provided by all Sweden's 26 county councils since 1997. It took 23 years from the initial pilot study through clinical trials to the establishment of mammography service screening throughout Sweden. In the screening rounds completed by 1995-96, and provided by all but one county council, 1040000 women participated, corresponding to 81% of those invited. The national average recall rate was 2.2%, and consequently 23000 women were recalled for additional investigations. Eleven county councils invited women aged 40-74, six invited women aged 50-69, the remaining eight invited women between both these age intervals. Mammography outside screening programmes-clinical mammography-is available throughout Sweden. About 100000 women a year were referred for clinical mammography and about 50% of these were either younger or older than those invited for screening. A negative relation between the use of clinical mammography and participation in the screening programmes was noticed.


Characterization of the CACNA1C-R518C Missense Mutation in the Pathobiology of Long-QT Syndrome Using Human Induced Pluripotent Stem Cell Cardiomyocytes Shows Action Potential Prolongation and L-Type Calcium Channel Perturbation.
The CACNA1C-encoded cardiac L-type calcium channel (Cav1.2) is essential for cardiocyte action potential duration (APD). We previously reported the CACNA1C-p.R518C variant associated with prolonged QT intervals, cardiomyopathy, and sudden cardiac death in several pedigrees. To characterize a patient-derived human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) CACNA1C-p.R518C model, CACNA1C-p.R518C hiPSC-CMs were generated from a 13-year-old man (QTc, >480 ms) with a family history of sudden cardiac death. An isogenic hiPSC-CM gene-corrected control was created using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9). APD and calcium handling were assessed by live cell imaging with Arclight voltage and Fluo-4 calcium indicators, respectively. The APD and L-type calcium channel biophysical properties were further assessed by whole-cell patch clamp technique. The Bazett formula-corrected, Arclight-measured APD90 of CACNA1C-p.R518C hiPSC-CMs was significantly longer (622±11 ms; n=92) than the isogenic control hiPSC-CMs (453±5 ms; n=62; P<0.0001). Patch clamp assessment of CACNA1C-p.R518C hiPSC-CMs paced at 1 Hz confirmed a prolonged APD90 (689±29 ms; n=10) compared with the patient's isogenic control hiPSC-CMs (434±30 ms; n=8; P<0.05). Fluo-4-measured calcium transient decay time suggested calcium mishandling in CACNA1C-p.R518C. Patch clamp analysis revealed increased L-type calcium channel window current, slow decay time at various voltages, and increased late calcium current for CACNA1C-p.R518C hiPSC-CMs when compared with isogenic control hiPSC-CMs. Using patient-specific hiPSC-CM mutant and isogenic control lines, we demonstrate that the CACNA1C-p.R518C variant is the self-sufficient, monogenetic substrate for the patient's long-QT syndrome phenotype. These data further bolster the conclusion that CACNA1C is a bona fide, definite evidence long-QT syndrome susceptibility gene.


Thyroid hormone stimulates the Na(+)-PO4 symporter but not the Na(+)-SO4 symporter in renal brush border.
In our previous studies we established that thyroid hormones [L-thyroxine (T4) or 3,5,3'-triiodothyronine (T3)] elicit an increase in Na(+)-Pi symport in rat and mouse renal brush-border membrane (BBM) vesicles (BBMV), but the Na(+)-coupled symports of other solutes were not influenced. However, a recent report [H. S. Tenenhouse, J. Lee, and N. Harvey. Am. J. Physiol. 261 (Renal Fluid Electrolyte Physiol. 30): F420-F426, 1991]claimed that T3 increases to a similar degree both Na(+)-Pi symport and Na(+)-SO4 symport in murine renal BBM. Adult male rats were fed either normal (0.7% Pi; NPD) or high-phosphate (1.4% Pi; HPD) diet and received T3 (0.2 mg/100 g body wt ip) for 3 days before the kidneys were removed, BBMV were prepared, and the transport rates were determined. Although the Na(+)-Pi symport significantly increased (delta = +35%) in both NPD and HPD rats treated with T3, the Na(+)-35SO4 symport and Na(+)-D-[3H]glucose symports were not influenced by T3. Furthermore, treatment of NPD-fed mice with T3 using a similar protocol as rats resulted in a significant increase (delta = +26%) of Na(+)-(Pi)4 symport, but did not alter Na(+)-SO4 symport or Na(+)-glucose symport. Our findings thus document that T3 regulates selectively the Na(+)-Pi symporter in BBM without having any effect on other major divalent anions, such as SO4.


Association of elevated risk of pancreatic cancer in diabetic patients: A systematic review and meta-analysis.
Pancreatic cancer has a five-year overall survival rate <5%, a situation that has not improved since for 40 years. Diabetes mellitus including type 2 diabetes mellitus (T2D) is a suspected risk factor for the development of pancreatic cancer and nearly 45% of the pancreatic cancer cases are likely to present as new onset diabetes cases; however, the nature of association between T2D and pancreatic cancer is still controversial. In this meta-analysis, we examined the association specifically of T2D with pancreatic cancer and the influence of insulin therapy. PubMed, EMBASE, Scholar, Web of Science and Scopus databases were searched to identify clinical and patient oriented studies that examined the incidence of diabetes in pancreatic cancer patients and vice versa, over the last 10 years. All the authors independently screened the articles, and a collective decision was reached about the studies included in the meta-analysis. Parameters analyzed included, the Incidence of diabetes in pancreatic cancer patients; duration history of T2D in pancreatic cancer patients; influence of insulin therapy in T2D patients on pancreatic cancer incidence. Eleven studies with a total of 14,399 patients, of whom 4,080 were T2D-positive and 9,721 were non-diabetic were included in this meta-analysis. T2D duration history was significantly related to pancreatic cancer incidence and insulin therapy effects. In conclusion, recent-onset T2D is probably a manifestation of pancreatic cancer whereas long-term T2D is likely a risk factor for this cancer. Insulin therapy appears to decrease the incidence of pancreatic cancer.


Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.
Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy.


Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial.
This study reports a phase I immunotherapy trial in 23 women with metastatic breast cancer consisting of eight infusions of anti-CD3 × anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (ATC) in combination with low-dose IL-2 and granulocyte-macrophage colony-stimulating factor to determine safety, maximum tolerated dose (MTD), technical feasibility, T-cell trafficking, immune responses, time to progression, and overall survival (OS). ATC were expanded from leukapheresis product using IL2 and anti-CD3 monoclonal antibody and armed with HER2Bi. In 3+3 dose escalation design, groups of 3 patients received 5, 10, 20, or 40 × 10(9) armed ATC (aATC) per infusion. There were no dose-limiting toxicities and the MTD was not defined. It was technically feasible to grow 160 × 10(9) ATC from a single leukapheresis. aATC persisted in the blood for weeks and trafficked to tumors. Infusions of aATC induced anti-breast cancer responses and increases in immunokines. At 14.5 weeks after enrollment, 13 of 22 (59.1%) evaluable patients had stable disease and 9 of 22 (40.9%) had progressive disease. The median OS was 36.2 months for all patients, 57.4 months for HER2 3+ patients, and 27.4 months for HER2 0-2+ patients. Targeting HER2(+) and HER2(-) tumors with aATC infusions induced antitumor responses, increases in Th1 cytokines, and IL12 serum levels that suggest that aATC infusions vaccinated patients against their own tumors. These results provide a strong rationale for conducting phase II trials.


Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long-term survival in a randomized study.
Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long-term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients. The trial was designed as a randomized, 2-armed study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure (defined as anatomical or minimal). Chemotherapy consisted of cisplatin (100 mg/m2 day 1) and etoposide (120 mg/m2 days 1-3) for 6 cycles. The primary endpoint was overall survival; secondary endpoint was disease-free survival (DFS). One hundred and forty patients entered the study: 70 were assigned to the adjuvant chemotherapy group and 70 to the control group. Groups were homogeneous for conventional risk factors. There was no clinically significant morbidity associated to chemotherapy. Patients were followed for a mean period of 40.31 +/- 30.86 months. A significant difference in overall (p = 0.02) and disease-free (p = 0.0001) survival was observed between patients undergoing adjuvant chemotherapy vs. control group. Adjuvant chemotherapy significantly improved both overall (p = 0.02) and DFS (p = 0.003) of anatomically resected patients, but only the DFS (p = 0.02) of minimally resected patients. Our results confirm that adjuvant chemotherapy may have a real impact on long-term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected.


Prochlorperazine induces central antinociception mediated by the muscarinic system.
The antinociceptive effect of the D(2) antagonist prochlorperazine was examined in the mouse hot-plate and abdominal constriction tests. Prochlorperazine (1-2 mg kg(-1) s.c./i.p.) produced an increase of the pain threshold in the mouse hot-plate test. The antinociception produced by prochlorperazine was prevented by the D(2) selective agonist quinpirole, the unselective muscarinic antagonist atropine, the M(1) selective antagonist pirenzepine, and by the choline uptake inhibitor hemicholinium-3 hydrobromide (HC-3). Moreover, prochlorperazine antinociception was abolished by pretreatment with an aODN against the M(1) receptor subtype, administered at the dose of 2 nmol per single i.c.v. injection. By contrast the analgesic effect of prochlorperazine was not prevented by the opioid antagonist naloxone and the GABA(B) antagonist CGP-35348. Prochlorperazine also elicited a dose-dependent increase in ACh release from rat cerebral cortex. In the antinociceptive dose-range, prochlorperazine did not impair mouse performance evaluated by the rota-rod and hole-board tests. On the basis of the above data, it can be postulated that prochlorperazine exerted an antinociceptive effect mediated by a central cholinergic mechanism.


Seed Discharge in Arceuthobium: A Photographic Study.
Photographs, made at a speed of 5 microseconds, of the ejection of the Arceuthobium seed from its fruit, show that tumbling in the vertical plane begins soon after discharge and that most seeds have turned 90 degrees when they have traveled about 6 centimeters. As the seeds leave the fruit they have a viscous sheath around the trailing end that disintegrates after the seeds have traveled about 2 to 3 centimeters. This viscous material does not act as a rudder as has been postulated.


Familial Alzheimer's disease modelling using induced pluripotent stem cell technology.
Alzheimer's disease (AD) is a progressive neurodegenerative disease in which patients exhibit gradual loss of memory that impairs their ability to learn or carry out daily tasks. Diagnosis of AD is difficult, particularly in early stages of the disease, and largely consists of cognitive assessments, with only one in four patients being correctly diagnosed. Development of novel therapeutics for the treatment of AD has proved to be a lengthy, costly and relatively unproductive process with attrition rates of > 90%. As a result, there are no cures for AD and few treatment options available for patients. Therefore, there is a pressing need for drug discovery platforms that can accurately and reproducibly mimic the AD phenotype and be amenable to high content screening applications. Here, we discuss the use of induced pluripotent stem cells (iPSCs), which can be derived from adult cells, as a method of recapitulation of AD phenotype in vitro. We assess their potential use in high content screening assays and the barriers that exist to realising their full potential in predictive efficacy, toxicology and disease modelling. At present, a number of limitations need to be addressed before the use of iPSC technology can be fully realised in AD therapeutic applications. However, whilst the use of AD-derived iPSCs in drug discovery remains a fledgling field, it is one with immense potential that is likely to reach fruition within the next few years.


Construction of a genetic linkage map in tetraploid species using molecular markers.
This article presents methodology for the construction of a linkage map in an autotetraploid species, using either codominant or dominant molecular markers scored on two parents and their full-sib progeny. The steps of the analysis are as follows: identification of parental genotypes from the parental and offspring phenotypes; testing for independent segregation of markers; partition of markers into linkage groups using cluster analysis; maximum-likelihood estimation of the phase, recombination frequency, and LOD score for all pairs of markers in the same linkage group using the EM algorithm; ordering the markers and estimating distances between them; and reconstructing their linkage phases. The information from different marker configurations about the recombination frequency is examined and found to vary considerably, depending on the number of different alleles, the number of alleles shared by the parents, and the phase of the markers. The methods are applied to a simulated data set and to a small set of SSR and AFLP markers scored in a full-sib population of tetraploid potato.


Design Features for Improving Mobile Health Intervention User Engagement: Systematic Review and Thematic Analysis.
Well-designed mobile health (mHealth) interventions support a positive user experience; however, a high rate of disengagement has been reported as a common concern regarding mHealth interventions. To address this issue, it is necessary to summarize the design features that improve user engagement based on research over the past 10 years, during which time the popularity of mHealth interventions has rapidly increased due to the use of smartphones. The aim of this review was to answer the question "Which design features improve user engagement with mHealth interventions?" by summarizing published literature with the purpose of guiding the design of future mHealth interventions. This review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Databases, namely, PubMed, Web of Science, Cochrane Library, Ovid EMBASE, and Ovid PsycINFO, were searched for English and Chinese language papers published from January 2009 to June 2019. Thematic analysis was undertaken to assess the design features in eligible studies. The Mixed Methods Appraisal Tool was used to assess study quality. A total of 35 articles were included. The investigated mHealth interventions were mainly used in unhealthy lifestyle (n=17) and chronic disease (n=10) prevention programs. Mobile phone apps (n=24) were the most common delivery method. Qualitative (n=22) and mixed methods (n=9) designs were widely represented. We identified the following 7 themes that influenced user engagement: personalization (n=29), reinforcement (n=23), communication (n=20), navigation (n=17), credibility (n=16), message presentation (n=16), and interface aesthetics (n=7). A checklist was developed that contained these 7 design features and 29 corresponding specific implementations derived from the studies. This systematic review and thematic synthesis identified useful design features that make an mHealth intervention more user friendly. We generated a checklist with evidence-based items to enable developers to use our findings easily. Future evaluations should use more robust quantitative approaches to elucidate the relationships between design features and user engagement.


Management of Medullary Thyroid Cancer: Patterns of Recurrence and Outcomes of Reoperative Surgery.
There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center. A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data. In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018). Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control.


Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women.
Lipid responses to a dietary intervention are highly variable between individuals. Part of this variation may be accounted for by individual differences in lipid-regulating genes that interact with diet to induce changes in lipoprotein metabolism. This study determined whether apolipoprotein E (APOE) genotype affects lipid responses to a low-fat, low-cholesterol diet in obese, postmenopausal women. Body weight and lipoprotein lipid responses to a 10-week, dietary intervention (American Heart Association [AHA] Step I) were compared in 61 women with the APOE 2/3 and APOE 3/3 genotype (APOE4-) and 18 women with the APOE 3/4 genotype (APOE4+) of a similar age, body composition, and maximal aerobic capacity. Body weight decreased by 2% in both groups, but changes in body weight correlated only with changes in low-density lipoprotein-cholesterol (LDL-C) (r =.27, P <.05). The dietary intervention decreased total cholesterol and LDL-C to a similar degree in both genotype groups. However, APOE4- women decreased high-density lipoprotein-cholesterol (HDL-C) by 17% +/- 11% and increased triglycerides by 20% +/- 41% in response to the diet, while APOE4+ women had a smaller decrease in HDL-C (-8% +/- 12%) and no change in plasma triglyceride. These group differences were significant for HDL-C (P <.01) and approached significance for triglycerides (P =.08). Moreover, APOE4- women decreased HDL(2)-C by 32% +/- 45%, while APOE4+ women increased HDL(2)-C by 12% +/- 62% (P <.01 between groups). It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the APOE4 allele benefit the most, while the lipid profile could worsen in women without the APOE4 allele.


Accelerating oxygen evolution electrocatalysis of two-dimensional NiFe layered double hydroxide nanosheets via space-confined amorphization.
NiFe layered double hydroxides (LDHs) have received widespread attention due to their unique structures and inherent electrocatalytic activity towards the oxygen evolution reaction (OER). Extensive studies have been reported to further improve the electrocatalytic activity of NiFe-LDHs via various strategies. However, controlling the degree of amorphization and stabilizing the amorphous zone during the electrocatalytic process are still challenging. Here, we report a facile method to synthesize a space-confined amorphous NiFe-LDH (SCA-NiFe-LDH) by selectively etching the surfaces of electrocatalysts. Due to the successful anchoring of amorphous zones onto the basal planes of the two-dimensional NiFe-LDH, the optimized SCA-NiFe-LDH exhibits high electrocatalytic activity with a low overpotential of 190 mV at 10 mA cm-2, a Tafel slope of 31 mV dec-1 and excellent long-term stability. The substantially enhanced OER performance is attributed to the increased amount of active sites and the modified electronic structure of NiFe-LDH after amorphization.


Physical activity monitoring in patients with peripheral arterial occlusive disease.
Physical activity is an important variable to measure in patients with peripheral arterial occlusive disease (PAOD) because of this relationship to cardiovascular disease morbidity and mortality. The purposes of this study were to (1) determine the reliability of measures of daily physical activity in PAOD participants using an accelerometer and a pedometer; and (2) assess the validity of both instruments by comparing them against validated physical activity questionnaires. Forty-three patients with PAOD with a resting ankle/brachial index of 0.63 +/- 0.19 were monitored for 2 consecutive weekdays with an accelerometer and pedometer worn on each hip. The 48-hour monitoring period was repeated approximately 1 week later. The daily physical activity values obtained from the accelerometer were similar between the two testing periods, 352 +/- 248 kcal/day vs. 337 +/- 199 kcal/day; P = 0.61, with a reliability coefficient of r = 0.84. The steps obtained from the pedometer during each 2-day period also were similar, 4615 +/- 2839 steps/day vs. 4498 +/- 2768 steps /day; P = 0.75, with a reliability coefficient of r = 0.86. The physical activity values from the accelerometer moderately correlated with the Minnesota Leisure Time Physical Activity Questionnaire, r = 0.33; P < 0.01, and the NASA/Johnson Space Center Physical Activity Scale, r = 0.44; P < 0.001. Similarly, the relationship between the steps obtained from the pedometer and physical Activity and the Minnesota Leisure Time Physical Activity and NASA/Johnson Space Center Physical Activity Scale questionnaires were significant, r = 0.46 and r = 0.51; P < 0.001, respectively. These findings indicate that an accelerometer and pedometer are two instruments that reliably estimate the physical activity levels of patients with PAOD over 2 consecutive days. Furthermore, the activity questionnaires, suggesting that activity monitoring measures a different component of activities in patients with PAOD with intermittent claudication.


A review of the epidemiology, public health importance, treatment and control of head lice.
Head lice are cosmopolitan and endemic. While they are not responsible for the spread of any disease, they are the cause of considerable social distress. They can infest anybody and do not discriminate between class or cleanliness. Head lice are transmitted primarily by direct contact. The only satisfactory method to clear an infestation is by chemical treatment. The most effective pediculicides to date are those which contain permethrin (Nix) or malathion (Prioderm). Compliance with product instructions eliminates the need for nit removal after treatment. Treatment of inanimate objects and the environment should be discouraged. To obtain effective control of head lice, the whole community needs to be involved. Parents must be encouraged to screen themselves and their children regularly in the home, and to treat themselves only when necessary.


Impact of apo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect.
Plasma lipoprotein(a) [Lp(a)] levels are believed to be controlled predominantly by the apolipoprotein(a) [APO(a)] gene, which encodes the apo(a) glycoprotein, a key constituent of the Lp(a) particle. Previously, it has been accepted that the plasma Lp(a) level is inversely proportional to apo(a) length. To examine this relationship in greater detail, 1500 unrelated, homogeneous (sex, race, age, plasma lipids) subjects were studied, from which 769 were identified with a single-expressing APO(a) allele. A bimodal frequency distribution of apo(a) isoforms was observed. As expected, there was a general inverse relationship between apo(a) isoform size and Lp(a) level. However, when groups with equivalent single-expressing apo(a) isoforms were studied, it was clear that although smaller isoforms were associated on average with higher levels, they were also associated with the greatest variability in level. After logarithmic transformation of Lp(a) data, the overall contribution of the apo(a) length polymorphism was calculated to be 38%. However, in subjects with apo(a) isoforms of </=20 kringle-4 (K-4) repeats, only 9% of the variability in Lp(a) concentration is explicable on the basis of the apo(a) length polymorphism. In those with apo(a) isoforms of >20 K-4 repeats, the corresponding contribution is 10%. We conclude that the contribution of the apo(a) isoform size to the control of plasma Lp(a) level is considerably lower than previously calculated, because the variability in plasma Lp(a) concentration is not uniform across the apo(a) size spectrum.


Neuropathic pain in the community: more under-treated than refractory?
Best current estimates of neuropathic pain prevalence come from studies using screening tools detecting pain with probable neuropathic features; the proportion experiencing significant, long-term neuropathic pain, and the proportion not responding to standard treatment are unknown. These "refractory" cases are the most clinically important to detect, being the most severe, requiring specialist treatment. The aim of this study was to estimate the proportion of neuropathic pain in the population that is "refractory," and to quantify associated clinical and demographic features. We posted self-administered questionnaires to 10,000 adult patients randomly selected from 10 general practitioner practices in 5 UK locations. The questionnaire contained chronic pain identification and severity questions, cause of pain, SF-12, EQ-5D, S-LANSS (Self-administered Leeds Assessment of Neuropathic Signs and Symptoms), PSEQ (Pain Self-Efficacy Questionnaire), use of neuropathic pain medications, and health care utilisation. These data were combined to determine the presence and characteristics of "refractory" neuropathic pain according to the defining features identified by a Delphi survey of international experts. Graded categories of chronic pain with and without neuropathic characteristics were generated, incorporating the refractory criteria. Completed questionnaires were returned by 4451 individuals (response rate 47%); 399 had "chronic pain with neuropathic characteristics" (S-LANSS positive, 8.9% of the study sample); 215 (53.9%) also reported a positive relevant history ("Possible neuropathic pain"); and 98 (4.5% of all Chronic Pain) also reported an "adequate" trial of at least one neuropathic pain drug ("Treated possible neuropathic pain"). The most refractory cases were associated with dramatically poorer physical and mental health, lower pain self-efficacy, higher pain intensity and pain-related disability, and greater health care service use.


Emergence of mcr-1 in Raoultella ornithinolytica and Escherichia coli Isolates from Retail Vegetables in China.
The presence of mcr-1 among Enterobacteriaceae isolates collected from retail vegetables in China between 2015 and 2016 was investigated. Two Raoultella ornithinolytica and seven Escherichia coli strains recovered from lettuce and tomato samples were identified as MCR-1-producers. Similar to isolates from animals and humans, the mcr-1 gene was located on the IncHI2/ST3, IncI2, or IncX4 plasmids. The presence of MCR-1-producing organisms in ready-to-eat food samples represents a serious risk for human health.


Streptococcus anginosus Empyema Induced by Dental Abscess: A Case Report.
Streptococcus anginosus is a gram-positive catalase-negative cocci and commensal flora of the oropharynx and gastrointestinal tract. Streptococcus anginosus is known to be highly virulent and known to cause invasive pyogenic infection which may necessitate emergent surgical treatment. We present a case of a 53-year-old female with dental caries and uncontrolled diabetes mellitus who presented with progressive shortness of breath for 1 week. A computed tomography scan of the chest showed a loculated empyema which was treated with emergent video-assisted thoracoscopic surgery. Pleural fluid culture as well as sputum cultures grew Streptococcus anginosus. The patient was treated intravenous cephalosporins and discharged on oral antibiotics after 14 days with outpatient dental follow-up and improvement of symptoms.


Small-angle multiple scattering and spatial resolution in charged particle tomography.
The formulae for the RMS scattering angle given by small-angle multiple-scattering theory are discussed and a correction to the standard Rossi formula is derived. Values of the correction factor are calculated for protons, alpha-particles and heavy ions; these results show that the correction is important for protons and alpha-particles but negligible for heavy ions with mass number 12-40. The values of the RMS scattering angle and the RMS lateral displacement are calculated for a proton beam passing through water. For protons the correction for energy loss in thick targets is even more important.


A cloning method to identify caspases and their regulators in yeast: identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1.
Site-specific proteases play critical roles in regulating many cellular processes. To identify novel site-specific proteases, their regulators, and substrates, we have designed a general reporter system in Saccharomyces cerevisiae in which a transcription factor is linked to the intracellular domain of a transmembrane protein by protease cleavage sites. Here, we explore the efficacy of this approach by using caspases, a family of aspartate-specific cysteine proteases, as a model. Introduction of an active caspase into cells that express a caspase-cleavable reporter results in the release of the transcription factor from the membrane and subsequent activation of a nuclear reporter. We show that known caspases activate the reporter, that an activator of caspase activity stimulates reporter activation in the presence of an otherwise inactive caspase, and that caspase inhibitors suppress caspase-dependent reporter activity. We also find that, although low or moderate levels of active caspase expression do not compromise yeast cell growth, higher level expression leads to lethality. We have exploited this observation to isolate clones from a Drosophila embryo cDNA library that block DCP-1 caspase-dependent yeast cell death. Among these clones, we identified the known cell death inhibitor DIAP1. We showed, by using bacterially synthesized proteins, that glutathione S-transferase-DIAP1 directly inhibits DCP-1 caspase activity but that it had minimal effect on the activity of a predomainless version of a second Drosophila caspase, drICE.


Can we "apply" the findings of Forster and Lavie (2008)? On the generalizability of attentional capture effects under varying levels of perceptual load.
Perceptual Load theory states that the degree of perceptual load on a display determines the amount of leftover attentional resources that the system can use to process distracting information. An important corollary of this theory is that the amount of perceptual load determines the vulnerability of the attention system to being captured by completely irrelevant stimuli, predicting larger amounts of capture with low perceptual load than with high perceptual load. This prediction was first confirmed by Forster and Lavie (2008). Here, we report 6 experiments that followed up on those earlier results, where we find that in many cases, the opposite pattern is obtained: attentional capture increased with increasing perceptual load. Given the lack of generalizability of the theory to new experimental contexts with fairly minor methodological differences, we conclude that Perceptual Load may not be a useful framework for understanding attentional capture. The theoretical and applied importance of these findings is discussed. In particular, we caution against using this theory in applied tasks and settings because best-use recommendations stemming from this theory regarding strategies to decrease distractibility may in fact produce the opposite effect: an increase in distractibility (with distractibility being indexed by the magnitude of the capture effect). (PsycINFO Database Record


Transcriptome profiling of grapevine seedless segregants during berry development reveals candidate genes associated with berry weight.
Berry size is considered as one of the main selection criteria in table grape breeding programs. However, this is a quantitative and polygenic trait, and its genetic determination is still poorly understood. Considering its economic importance, it is relevant to determine its genetic architecture and elucidate the mechanisms involved in its expression. To approach this issue, an RNA-Seq experiment based on Illumina platform was performed (14 libraries), including seedless segregants with contrasting phenotypes for berry weight at fruit setting (FST) and 6-8 mm berries (B68) phenological stages. A group of 526 differentially expressed (DE) genes were identified, by comparing seedless segregants with contrasting phenotypes for berry weight: 101 genes from the FST stage and 463 from the B68 stage. Also, we integrated differential expression, principal components analysis (PCA), correlations and network co-expression analyses to characterize the transcriptome profiling observed in segregants with contrasting phenotypes for berry weight. After this, 68 DE genes were selected as candidate genes, and seven candidate genes were validated by real time-PCR, confirming their expression profiles. We have carried out the first transcriptome analysis focused on table grape seedless segregants with contrasting phenotypes for berry weight. Our findings contributed to the understanding of the mechanisms involved in berry weight determination. Also, this comparative transcriptome profiling revealed candidate genes for berry weight which could be evaluated as selection tools in table grape breeding programs.


Parabrachial-hypothalamic interactions are required for normal conditioned taste aversions.
Rats with bilateral excitotoxic lesions of the parabrachial nuclei (PBN) fail to acquire a conditioned taste aversion (CTA), yet they retain the ability to express a CTA learned prior to incurring the damage. Rats with bilateral electrolytic lesions of the lateral hypothalamus (LH) also have CTA learning deficits. The PBN have reciprocal neural connections with the LH. This suggests that these CTA deficits may be functionally related. Electrolytic lesions damage fibers of passage, as well as intrinsic neurons. Thus, these LH lesions might also interrupt reciprocal connections between the PBN and other ventral forebrain areas, such as the amygdala and bed nucleus of the stria terminalis. To distinguish the source of the LH-lesion deficit, we tested for CTA first after bilateral excitotoxic lesions of LH and subsequently with a second set of animals that had asymmetric excitotoxic PBN and LH lesions. The rats with bilateral excitotoxic LH lesions showed deficits when acquiring a postlesion CTA. The asymmetrical PBN-LH lesions not only slowed acquisition of a CTA but also sped up extinction. This implies that interaction between the two structures, at minimum, facilitates CTA learning and may have a role in its consolidation.


How do older patients and their GPs evaluate shared decision-making in healthcare?
Older persons represent a growing share of the population, yet very little is known about their specific healthcare needs, problems, and expectations. IMPROVE is an international research project that seeks to improve elderly persons' involvement in their healthcare. This paper analyzes perceptions of patient involvement by elderly patients and their GPs in family medicine in Slovenia. Semi-structured interviews with patients over 70 and their GPs were audio-taped and transcribed. The interviews were analyzed using qualitative content analysis. Specific characteristics of old age must be taken into account in the involvement of older patients. It is important to know the patient's expectations and to communicate clearly with the patient. A trusting relationship between the GP and the patient is a prerequisite for involvement. GPs center involvement on the GP's side. Involvement of the elderly is linked to ethical dilemmas. Understanding the involvement of the elderly focuses more on building a relationship than on making decisions. It is reasonable to educate GPs and GPs' coworkers about caring relationships. Ethical aspects have often been treated in a theoretical manner, whereas empirical practice may be entirely different from theoretical premises. GPs and older patients must learn more about how to address their ethical dilemmas.


Redox cycling and lipid peroxidation: the central role of iron chelates.
Toxicities associated with redox cycling, including lipid peroxidation, are often attributed to the hydroxyl radical through a superoxide-driven, iron-catalyzed Haber-Weiss reaction. However, other cellular reducing agents more prevalent than superoxide, i.e., glutathione, ascorbate, cysteine and certain enzymes, can also reduce chelated iron and thereby initiate lipid peroxidation which is not inhibited by superoxide dismutase. The autoxidation of ferrous chelates yields partially reduced oxygen intermediates similar to those produced during the iron-catalyzed Haber-Weiss reaction. The mechanism of their formation, and the nature of the strong oxidant responsible for the initiation of lipid peroxidation are poorly understood, but are apparently influenced by the chelation of the iron. These conclusions stem from experiments which demonstrated variable amounts of inhibition of lipid peroxidation, dependent on the autoxidation of various ferrous chelates, by added superoxide dismutase or catalase. In addition, certain ferrous chelates are unable to initiate peroxidation of lipids in a liposomal configuration, yet capable of initiating peroxidation of lipids which were dispersed with a detergent. The results of these studies point out the need to isolate and identify the predominant physiological iron chelates for assessment of their ability to participate in redox related toxicities within the cell.


Aminomethylphosphonic acid and glyphosate adsorption onto goethite: a comparative study.
Glyphosate is a non-selective, broad spectrum, post-emergent herbicide widely used in weed control. Aminomethylphosphonic acid (AMPA) is one of the main products of biodegradation of glyphosate in natural systems before its ultimate mineralization and also the breakdown product of more complex phosphonates such as nitrilotris-(methylenephosphonic acid). The adsorption isotherms and surface coverage of AMPA and glyphosate (N-phosphomethylglycine, PMG) in aqueous suspensions of goethite as a function of pH were measured. Electrophoretic mobility curves forthe PMG/goethite system were also determined. The ATR-FTIR interfacial spectra of the surface complexes of AMPA and PMG onto goethite were analyzed as a function of the pH and the surface coverage. The phosphonate moiety of these two ligands coordinates to the iron oxide surface with similar structures as the methylphosphonic acid despite the presence of the amino and/or carboxylate groups of their molecules. Two predominating complexes have been identified where the phosphonate group in PMG or AMPA bonds monodentately or bridges bidentately to the surface of iron oxide in an inner sphere mode, while the carboxylate and amino group are noncoordinated to the surface. The stability constants of the surface complexes (triple bond)FeO-P(O)(OH)--R, (triple bond)FeO--P(O)2--R, and ((triple bond)FeO)2--P(O)--R were calculated using the constant capacitance model.


[Retinal detachment in children and adolescents].
During a 4-year period 22 eyes with rhegmatogenous retinal detachment in children and young adults up to 20 years of age were operated on. This group comprised 6.3 percent of all rhegmatogenous retinal detachments operated on during the same period. In 9 eyes (40.9%) the detachment was due to a direct ocular trauma. In the remaining cases the main etiological factors were: myopia with or without lattice degeneration (5 eyes), retinopathy of prematurity (2 eyes), hereditary vitreoretinal degeneration (1 eye), uveal coloboma (2 eyes), aphakia after congenital cataract (1 eye), sex-linked juvenile retinoschisis (1 eye), and central retinal vein occlusion (1 eye), Conventional surgical procedures using episcleral or intrascleral implants or an encircling band combined with cryotherapy were used. After a follow-up of 7 months to 3.3 years (mean 1.5 years) the retina was flat in 18 cases (82%) and still detached in those with uveal coloboma (2 eyes), hereditary vitreoretinal degeneration (1 eye), and central retinal vein occlusion (1 eye). All traumatic detachments were flat.


Roles And Responsibilities Of The Physical Therapist In Collegiate Athletics: Results Of A National Survey.
Over the past decade, there has been an increased focus on collaboration within collegiate athletics based sports medicine. Specifically, athletic trainers (ATs) and physical therapists (PTs) are working together, often side-by-side, to provide optimal care for the injured athlete. However, the roles and responsibilities of the PT within this model are currently not well described. The purpose of this study was to identify educational training, credentials, roles, and responsibilities of the PT working with collegiate athletes. Cross-sectional survey. An anonymous, descriptive online survey focusing on the demographic and occupational characteristics of PTs providing care for collegiate athletes was created and distributed electronically through the American Academy of Sports Physical Therapy (AASPT), a subgroup within the American Physical Therapy Association (APTA). One hundred forty eligible responses were included. Sixty-four percent (90/140) of the respondents were male; 86% of the respondents (120/140) reported working in the National Collegiate Athletic Association (NCAA) Division I setting. Half (70/140) of respondents were also ATs, and 60% (83/140) were board-certified sports clinical specialists (SCS). All respondents (140/140) provide rehabilitation exercises; nearly all provide sports performance enhancement and manual therapy (97%, 136/140 and 96%, 135/140, respectively). Other identified roles and responsibilities included communication with the athletic training staff, event coverage, and personnel management. The role of the PT within collegiate athletics sports medicine is highly varied; years of experience, certification, credentials, and location of patient care are also variable. PTs working in a collegiate athletics sports medicine setting have many paths to entry and diverse job duties. PTs interested in working in this setting should prioritize developing relevant experience and communication skills. Level 3b.


Common variation at PPARGC1A/B and change in body composition and metabolic traits following preventive interventions: the Diabetes Prevention Program.
PPARGC1A and PPARGCB encode transcriptional coactivators that regulate numerous metabolic processes. We tested associations and treatment (i.e. metformin or lifestyle modification) interactions with metabolic traits in the Diabetes Prevention Program, a randomised controlled trial in persons at high risk of type 2 diabetes. We used Tagger software to select 75 PPARGCA1 and 94 PPARGC1B tag single-nucleotide polymorphisms (SNPs) for analysis. These SNPs were tested for associations with relevant cardiometabolic quantitative traits using generalised linear models. Aggregate genetic effects were tested using the sequence kernel association test. In aggregate, PPARGC1A variation was strongly associated with baseline triacylglycerol concentrations (p = 2.9 × 10(-30)), BMI (p = 2.0 × 10(-5)) and visceral adiposity (p = 1.9 × 10(-4)), as well as with changes in triacylglycerol concentrations (p = 1.7 × 10(-5)) and BMI (p = 9.9 × 10(-5)) from baseline to 1 year. PPARGC1B variation was only associated with baseline subcutaneous adiposity (p = 0.01). In individual SNP analyses, Gly482Ser (rs8192678, PPARGC1A) was associated with accumulation of subcutaneous adiposity and worsening insulin resistance at 1 year (both p < 0.05), while rs2970852 (PPARGC1A) modified the effects of metformin on triacylglycerol levels (p(interaction) = 0.04). These findings provide several novel and other confirmatory insights into the role of PPARGC1A variation with respect to diabetes-related metabolic traits. ClinicalTrials.gov NCT00004992.


Increased levels of interleukin-12 and interleukin-18 in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.
We studied prospectively 43 patients with sarcoidosis and 13 normal subjects. IL-12 and IL-18 levels were measured using ELISA kits. Spirometry and body plethysmography were performed using an Elite DL Medgraphics body box. The sarcoidosis group was characterized by significantly higher median range of the plasma angiotensin-converting enzyme (ACE) concentration (72 vs. 34 U/l, P<0.0001), lymphocyte (34 vs. 14%, P<0.0001), CD4+ cells percentages (59 vs. 36%), and CD4/CD8 ratio (4.2 vs. 1.99, P<0.0001). The BALF IL-12 and IL-18 levels were significantly higher in sarcoidosis patients than in healthy subjects (4.1 pg/ml vs. 3.2 pg/ml; P<0.001 and 11.1 pg/ml vs. 6.15 pg/ml, P<0.0001, respectively). A negative correlation between BALF IL-12 and ACE plasma levels (r=-0.33, P<0.05) within the sarcoidosis group was found. Our data suggest a potential role of IL-12 and IL-18 in a local immunologic response in pulmonary sarcoidosis.


Exploring the connection between self-efficacy and effective diabetes self-management.
The purpose of this study was to review the existing empirical evidence about factors that contribute to effective diabetes self-management as indicated by healthy outcomes in persons with the disease, with a specific focus on self-efficacy, to determine the link between learned self-efficacy and effective diabetes self-management in adults. A systematic review was conducted of the extant literature from 1985-2001 that described factors related to effective self-management of diabetes. The review included theoretical and empirical articles. The search engines included CINAHL, MEDLINE, PUBMED, and COCHRANE. Empirical evidence supports the following factors to improve the education outcomes for adults with diabetes: involve people with diabetes in their own care, guide them in actively learning about the disease, explore their feelings about having the disease, and teach them the skills necessary to adjust their behavior to control their own health outcomes. Thus, the goal for educating people with diabetes is to improve their individual self-efficacy and, accordingly, their self-management ability. Education sessions need to involve fewer lectures and more practical, interactive exercises that focus on developing specific skills. Follow-up contact is a valuable method for helping people make a healthy adjustment to living with diabetes.


Retrospective temporal and spatial mobility of adult Iowa women.
Human exposure assessments require a linkage between toxicant concentrations in occupied spaces and the receptor's mobility pattern. Databases reporting distinct populations' mobility in various parts of the home, time outside the home, and time in another building are scarce. Temporal longitudinal trends in these mobility patterns for specific age and gender groups are nonexistent. This paper describes subgroup trends in the spatial and temporal mobility patterns within the home, outside the home, and in another building for 619 Iowa females that occupied the same home for at least 20 years. The study found that the mean time spent at home for the participants ranged from a low of 69.4% for the 50-59 year age group to a high of 81.6% for the over 80-year-old age group. Participants who lived in either one- or two- story homes with basements spent the majority of their residential occupancy on the first story. Trends across age varied for other subgroups by number of children, education, and urban/rural status. Since all of these trends were nonlinear, they indicate that error exists when assuming a constant, such as a 75% home occupancy factor, which has been advocated by some researchers and agencies. In addition, while aggregate data, such as presented in this report, are more helpful in deriving risk estimates for population subgroups, they cannot supplant good individual-level data for determining risks.


Effect of different soluble dietary fibres on the phenolic profile of blackberry puree subjected to in vitro gastrointestinal digestion and large intestine fermentation.
The aim of this study was to investigate the modulation of polyphenols profile of blackberry purees by soluble dietary fibres (inulin or pectin), during a simulated in vitro gastrointestinal digestion and large intestine fermentation process. Untargeted profiling evidenced that the free phenolic fraction of blackberry puree was characterized mainly by flavonoids, followed by phenolic acids, lignans and other low molecular weight polyphenols, showing clear differences from the bound phenolic fraction detected. This trend could be related to the interactions of dietary fibre and polyphenols, showing synergistic and/or antagonist effect on the bioactivity of polyphenols. On the other hand, in vitro large intestine fermentation of blackberry purees following in vitro gastrointestinal digestion revealed that the highest inclusion level (10% w/w) of soluble dietary fibres was effective in modulating the bioaccessibility of some phenolic classes (mainly phenolic acids, lignans and flavones) characterizing the blackberry puree. In addition, multivariate statistics following metabolomics-based profiling showed that the interaction between fibres and blackberry purees determined a marked modification of both anthocyanins and flavonols during in vitro large intestine fermentation, thus leading to the formation of low-molecular-weight compounds (such as tyrosol, followed by gallic and benzoic acids).


Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) mice.
Epidemiologic studies have shown an association between elevated arsenic levels in drinking water and an increased risk of atherosclerosis and vascular diseases. The studies presented here were performed to evaluate the atherogenic potential of arsenic using a well-established and controlled animal model of human atherosclerosis, mice deficient in apolipoprotein E (ApoE), and in vitro systems including primary human vascular cells. Wild-type and ApoE-deficient mice were exposed to 20 or 100 microg/mL sodium arsenite in drinking water for 24 weeks. As assessed morphometrically, the size of grossly discernible lesions covering the intimal area of aorta were increased significantly in arsenic-treated ApoE-deficient mice compared with nontreated transgenic mice. This effect was not associated with increased levels of serum cholesterol but was accompanied by an accumulation of arsenic in the vessel wall. Introduction of cocoa butter into the diet for 2 weeks resulted in higher serum cholesterol levels and only slight increases in the lesion size in control or arsenic-exposed ApoE-deficient mice. There were no lesions observed in the wild-type C57BL6 mice, resistant to atherosclerosis, whether they received arsenic or control drinking water. In vitro studies, including primary aorta endothelial or smooth muscle cells, were conducted to evaluate whether arsenic induces cellular mechanisms relevant to atherogenesis such as endothelial dysfunction, lipid oxidation, and smooth muscle cell proliferation. Arsenic treatment does not modulate endothelial cell-mediated lipid oxidation or smooth muscle cell proliferation but induced the expression of genes coding inflammatory mediators, including interleukin-8. Induction of endothelial inflammatory activity may play a role in arsenic-related vascular effects.


Toxicity of major cations and anions (Na+, K+, Ca2+, Cl-, and SO4(2-)) to a macrophyte and an alga.
In many freshwater systems around the world, the concentrations of major ions (Na(+), K(+), Ca(2+), Mg(2+), Cl(-), HCO(3)(-), CO(3)(2-), and SO(4)(2-)) are exhibiting increasing trends, approaching the concentrations historically found mainly in estuaries. The objectives of the present study were to determine at what concentrations these salts are toxic to an aquatic plant and a green alga, to investigate two potential mechanisms of toxicity, and to determine the usefulness of conductivity as an indicator of salt toxicity. In a series of laboratory trials, Lemna minor and Pseudokirchneriella subcapitata were exposed to a range of concentrations of five different salts. Conductivity levels that caused 10 or 50% reductions in growth-related traits (EC10 and EC50, respectively) were determined, using conductivity of the test solutions as the independent variable. The EC10 values ranged from 0.44 to 2.67 mS/cm for P. subcapitata and from 1.3 to >19 mS/cm for L. minor. The EC50 values ranged from 1.7 to 5.8 mS/cm for P. subcapitata and from 4.2 to >27 mS/cm for L. minor. For both species the EC values varied dramatically among the salts. Pseudokirchneriella subcapitata was most sensitive to KCl and NaCl, whereas L. minor was most sensitive to Na(2)SO(4). The mechanism of toxicity does not appear to be related to production of reactive oxygen species, nor to reduction in chlorophyll concentrations. Because toxicity was strongly influenced by salt composition, regulation and management of specific ions may be preferable to conductivity.


Toll-Like Receptor 4-Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression.
To investigate the effect of shikonin on (CIA) collagen-induced arthritis and its influence and mechanism on the balance between Th17 cells and Treg cells. Three doses of shikonin were administered orally to mice before the onset of CIA, and celecoxib was used as positive control drug. The arthritis response was monitored visually by macroscopic scoring and hindpaw swelling. Histology of knee was used to assess the occurrence of cartilage destruction and bone erosion. Serum collagen type II (C II) antibody levels associated with CIA were assessed with ELISAs. RT-PCR and quantitative PCR were employed to determine the mRNA expression of cytokines and TLRs in the surface of DCs in the patella with adjacent synovium and spleen in CIA. The expression of cytokines and transcription factors in the peripheral immune organs was tested by Western blotting. Shikonin treatment suppressed the macroscopic score and incidence of arthritis. Swelling of hind paws, cartilage destruction, and serum anti-C II concentration were delayed with shikonin when compared to controls. Shikonin treatment suppressed the arthritis in a dose-dependent manner. Moreover, the expression of Th17 cytokines (IL-17A) was greatly inhibited both in the synovium and spleen in treated groups compared with those in control groups. The mRNA and protein levels of IL-10 and TGF-β, however, were upregulated after shikonin treatment. The expression of Foxp3 in the synovium and spleen was upregulated, and the expression of ROR-γt in the synovium and spleen was downregulated after shikonin treatment through RT-PCR, quantitative PCR, and Western blotting. The DCs in the spleen of shikonin-treated mice had lower expression of TLR4 and MyD88, and the expression of TLR2 and TLR9 in the spleen was not different between the two groups. Shikonin has anti-inflammatory effects on CIA. Shikonin treatment can inhibit Th17 cytokines expression and induce Treg responses through inhibiting the activation of TLR4/MyD88 pathway.


[Morphologic factors influencing the prognosis of squamous-cell cervical cancer].
The role of such morphological factors as depth of invasion, tumor growth pattern, distinct boundary of tumor, presence of tumor emboli in vessels, level of lymphocyte-plasmocyte infiltration and mitotic activity of tumor cells in the course and prognosis of squamous-cell cervical carcinoma has been studied. Invasion depth, tumor pattern, tumor boundary and emboli in the vessels are prognostically relevant in lymph-related dissemination and recurrence of the disease.


Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif.
The heterogeneous ribonucleoprotein A18 (hnRNP A18) is upregulated in hypoxic regions of various solid tumors and promotes tumor growth via the coordination of mRNA transcripts associated with pro-survival genes. Thus, hnRNP A18 represents an important therapeutic target in tumor cells. Presented here is the first X-ray crystal structure to be reported for the RNA-recognition motif of hnRNP A18. By comparing this structure with those of homologous RNA-binding proteins (i.e. hnRNP A1), three residues on one face of an antiparallel β-sheet (Arg48, Phe50 and Phe52) and one residue in an unstructured loop (Arg41) were identified as likely to be involved in protein-nucleic acid interactions. This structure helps to serve as a foundation for biophysical studies of this RNA-binding protein and structure-based drug-design efforts for targeting hnRNP A18 in cancer, such as malignant melanoma, where hnRNP A18 levels are elevated and contribute to disease progression.


The fractal nature of nature: power laws, ecological complexity and biodiversity.
Underlying the diversity of life and the complexity of ecology is order that reflects the operation of fundamental physical and biological processes. Power laws describe empirical scaling relationships that are emergent quantitative features of biodiversity. These features are patterns of structure or dynamics that are self-similar or fractal-like over many orders of magnitude. Power laws allow extrapolation and prediction over a wide range of scales. Some appear to be universal, occurring in virtually all taxa of organisms and types of environments. They offer clues to underlying mechanisms that powerfully constrain biodiversity. We describe recent progress and future prospects for understanding the mechanisms that generate these power laws, and for explaining the diversity of species and complexity of ecosystems in terms of fundamental principles of physical and biological science.


Induction of xanthine oxidase by virus infections in newborn mice.
In the liver tissue of newborn mice, xanthine oxidase activity is very low during the first 7 to 14 days of life. Infection of mice with several different viruses prematurely induced xanthine oxidase activity 2- to 10-fold in the liver tissue. Generally, overt signs of illness appeared after xanthine oxidase induction; however, some viruses induced the enzyme activity without causing morbidity or deaths. The elevated enzyme activity could not be correlated with alteration of either lactate dehydrogenase or glutamate-pyruvate transaminase. Likewise, there were no histological changes in the livers of infected animals when xanthine oxidase levels were abnormally elevated. These observations suggest that measurement of xanthine oxidase may be an effective method for the detection of subclinical or inapparent viral infections in either naturally infected newborn mice or in newborn mice inoculated with suspected virus-containing materials.


Single-cell lysis for visual analysis by electron microscopy.
The stochastic nature of biological systems makes the study of individual cells a necessity in systems biology. Yet, handling and disruption of single cells and the analysis of the relatively low concentrations of their protein components still challenges available techniques. Transmission electron microscopy (TEM) allows for the analysis of proteins at the single-molecule level. Here, we present a system for single-cell lysis under light microscopy observation, followed by rapid uptake of the cell lysate. Eukaryotic cells were grown on conductively coated glass slides and observed by light microscopy. A custom-designed microcapillary electrode was used to target and lyse individual cells with electrical pulses. Nanoliter volumes were subsequently aspirated into the microcapillary and dispensed onto an electron microscopy grid for TEM inspection. We show, that the cell lysis and preparation method conserves protein structures well and is suitable for visual analysis by TEM.


What are the main running-related musculoskeletal injuries? A Systematic Review.
Musculoskeletal injuries occur frequently in runners and despite many studies about running injuries conducted over the past decades it is not clear in the literature what are the main running-related musculoskeletal injuries (RRMIs). The aim of this study is to systematically review studies on the incidence and prevalence of the main specific RRMIs. An electronic database search was conducted using EMBASE (1947 to October 2011), MEDLINE (1966 to October 2011), SPORTDiscus(1975 to October 2011), the Latin American and Caribbean Center on Health Sciences Information (LILACS) [1982 to October 2011] and the Scientific Electronic Library Online (SciELO) [1998 to October 2011] with no limits of date or language of publication. Articles that described the incidence or prevalence rates of RRMIs were considered eligible. Studies that reported only the type of injury, anatomical region or incomplete data that precluded interpretation of the incidence or prevalence rates of RRMIs were excluded. We extracted data regarding bibliometric characteristics, study design, description of the population of runners, RRMI definition, how the data of RRMIs were collected and the name of each RRMI with their rates of incidence or prevalence. Separate analysis for ultra-marathoners was performed. Among 2924 potentially eligible titles, eight studies (pooled n = 3500 runners) were considered eligible for the review. In general, the articles had moderate risk of bias and only one fulfilled less than half of the quality criteria established. A total of 28 RRMIs were found and the main general RRMIs were medial tibial stress syndrome (incidence ranging from 13.6% to 20.0%; prevalence of 9.5%), Achilles tendinopathy (incidence ranging from 9.1% to 10.9%; prevalence ranging from 6.2% to 9.5%) and plantar fasciitis (incidence ranging from 4.5% to 10.0%; prevalence ranging from 5.2% to 17.5%). The main ultra-marathon RRMIs were Achilles tendinopathy (prevalence ranging from 2.0% to 18.5%) and patellofemoral syndrome (prevalence ranging from 7.4% to 15.6%). This systematic review provides evidence that medial tibia stress syndrome, Achilles tendinopathy and plantar fasciitis were the main general RRMIs, while Achilles tendinopathy and patellofemoral syndrome were the most common RRMIs for runners who participated in ultra-marathon races.


[Indications for intestinal ureteroplasty].
Intestinal ureteroplasty was conducted in 81 patient, ageing from 5 to 62 years old. The urodynamics and renal function disorders were caused by existing obstructive megaureter--in 41, refluxing megaureter--in 9, hydronephrosis--in 7, retroperitoneal fibrosis--in 6, traumatic injury of ureter--in 18.


Is There an Association between Norton Scale and Cognitive Impairment in Hip Fractured Elderly Patients?
Geriatric assessment as an integrative part of assessment is a composite of a large number of scales. Sometimes it is difficult to transfer all of them. The Norton Scale Score (NSS) assesses the degree of risk to develop bedsores. In previous studies, a correlation between Norton Scale and function was found. A correlation between Norton Scale and cognitive assessments was not evaluated yet. The aim of this study was to determine if there is an association between Norton Scale Score and cognitive impairment. This association can further facilitate geriatric assessment in frail older patients, especially in older patients with communicative difficulties. We have performed an observational cohort study which included hip fractured older patients consecutively admitted to the rehabilitation ward of the Shmuel Harofe Geriatric Medical Center. The collected data included demographic data and data on chronic illnesses. Results of cognitive status assessment (Mini-Mental State Examination - MMSE) and Norton Scale assessment were received from the computerized patients' charts. We evaluated the association between these 2 scales. The study included 224 consecutive hip fracture patients with a mean age of 81.78 ± 7.19 years. Norton scores at admission, age, education, and previous stroke emerged as the only statistically significant parameters differing between those with cognitive decline and those without it. After adjusting for confounding variables, lower Norton scores at admission (OR 1.303, CI: 1.097-1.548, p = 0.003) were associated with an increased risk finding for cognitive impairment. Our findings suggest that there is an association between Norton Scale Scores and cognitive impairment. Norton score parameters, under certain circumstances, such as speech and other communication difficulties, can be used as a proxy measure for MMSE to indicate cognitive impairment. These findings can be even more helpful in the present time of "COVID-19," when we have to evaluate older patients with facial masks and other defensive suits.


Decreased contrast enhancement on high-resolution vessel wall imaging of unruptured intracranial aneurysms in patients taking aspirin.
Inflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms (UIAs). Animal and human studies have suggested that, due to its antiinflammatory effect, aspirin (ASA) may decrease the risks of growth and rupture of UIAs. High-resolution vessel wall imaging (HR-VWI) has emerged as a noninvasive method to assess vessel wall inflammation and UIA instability. To the authors' knowledge, to date no studies have found a significant correlation between patient use of ASA and contrast enhancement of UIAs on HR-VWI. The University of Iowa HR-VWI Project database was analyzed. This database is a compilation of data on patients with UIAs who prospectively underwent HR-VWI on a 3T Siemens MRI scanner. The presence of aneurysmal wall enhancement was objectively defined using the aneurysm-to-pituitary stalk contrast ratio (CRstalk). This ratio was calculated by measuring the maximal signal intensity in the aneurysmal wall and the pituitary stalk on postcontrast T1-weighted images. Data on aneurysm size, morphology, and location and patient demographics and comorbidities were collected. Use of ASA was defined as daily intake of ≥ 81 mg during the previous 6 months or longer. Univariate and multivariate logistic regression analyses were performed to determine factors independently associated with increased contrast enhancement of UIAs on HR-VWI. In total, 74 patients harboring 96 UIAs were included in the study. The mean patient age was 64.7 ± 12.4 years, and 60 patients (81%) were women. Multivariate analysis showed that age (OR 1.12, 95% CI 1.05-1.19), aneurysm size ≥ 7 mm (OR 21.3, 95% CI 4.88-92.8), and location in the anterior communicating, posterior communicating, and basilar arteries (OR 10.7, 95% CI 2.45-46.5) were significantly associated with increased wall enhancement on HR-VWI. On the other hand, use of ASA was significantly associated with decreased aneurysmal wall enhancement on HR-VWI (OR 0.22, 95% CI 0.06-0.83, p = 0.026). The study results establish a correlation between use of ASA daily for ≥ 6 months and significant decreases in wall enhancement of UIAs on HR-VWI. The findings also demonstrate that detection of wall enhancement using HR-MRI may be a valuable noninvasive method for assessing aneurysmal wall inflammation and UIA instability.


Sexuality and breast cancer: prime time for young patients.
Sexuality and sexual functioning is a cardinal domain of health-related quality of life in breast cancer patients, namely in the younger population. Young women below 40 years of age go through a time in their lives where sexual self-identity has recently matured, their professional obligations are demanding and they bear interpersonal and childbearing expectations, all of which can suffer a devastating turnaround with cancer diagnosis and its physical and psychological aftermath. Although these women's sexuality and directed interventions have remained largely unaddressed so far, concepts are evolving and treatment options are becoming diversified, chiefly on the field of non-hormonal pharmacological therapy of sexual dysfunction. This review will examine the definitions of female sexual dysfunction, the etiology of the disorders in young breast cancer patients, the assessment methods, the non-pharmacological and pharmacological treatment options and the challenges that lie ahead.


A profile of women CEOs/administrators in community and migrant health centers.
Most of the current research on women executives has focused on models in which few women achieve the highest position (e.g. hospital CEOs). This article looks at the nation's Community and Migrant Health Centers where substantial numbers of women hold the highest executive position. A national profile of women Community and Migrant Health Centers (C/MHCs) Chief Executive Officers/Administrators is provided in terms of their personal and work characteristics, as well as their values and beliefs regarding successful C/MHC attributes and important managerial practices. The study compares C/MHC Chief Executive Officers/Administrators based on gender. The study found that 41 percent of the CEO/Administrators were women and that they shared similar values and beliefs about functions/critical managerial factors and managerial characteristics of C/MHCs with their male colleagues. However, the study did find a comparable salary differential of over $11,000 in favor of male Chief Executive Officers/Administrators. The article reviews the literature of female executives in health care and concludes with recommendations for further study using the C/MHCs CEO/Administrators as a model study population.


Development and validation of a novel risk stratification model and a survival rate calculator for diffuse large B-cell lymphoma in the rituximab era: a multi-institutional cohort study.
This study aimed to develop and validate a novel risk stratification model and a web-based survival rate calculator to improve discriminative and predictive accuracy for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. We retrospectively collected pre-treatment data from 873 primary DLBCL patients who received R-CHOP-based immunochemotherapy regimens at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 1, 2005, to December 31, 2018. An independent cohort of 175 DLBCL patients from Fujian Cancer Hospital was used for external validation. Age, ECOG PS, number of extranodal sites, Ann Arbor stage, bulky disease, and LDH levels were screened to develop the nomogram and web-based survival rate calculator. The C-index of the nomogram in the training, internal validation, and external validation cohorts was 0.761, 0.758, and 0.768, respectively. The risk stratification model generated based on the nomogram effectively stratified patients into three distinct risk groups. K-M survival curves demonstrated that the novel risk stratification model exhibited a superior level of predictive accuracy compared to IPI, R-IPI, and NCCN-IPI both in training and two validation cohorts. Additionally, the area under the curve (AUC) value of the novel model (0.763) for predicting 5-year overall survival rates was higher than those of IPI (0.749), R-IPI (0.725), and NCCN-IPI (0.727) in the training cohort. Similar results were observed in both internal and external validation cohort. In conclusion, we have successfully developed and validated a novel risk stratification model and a web-based survival rate calculator that demonstrated superior discriminative and predictive accuracy compared to IPI, R-IPI, and NCCN-IPI in the rituximab era.


Isolation and characterization of conjugation-deficient mutants of Escherichia coli K-12.
Conjugation-deficient mutants (Con-) of Escherichia coli K-12 have been isolated by a variety of indirect selective techniques. Mutants with mutations conferring ampicillin resistance, fosfomycin resistance, an alanine requirement, and a failure of ferment a number of carbohydrates were selected because the impaired functions occur in association with cell wall and cell membrane defects. The integrity of these catalytic or structural elements is postulated to have a role in conjugation. The mutants could be divided into at least six general categories corresponding to their defectiveness in the following postulated recipient cell functions: (i) specific-union formation, (ii) effective-union formation, (iii) deoxyribonucleic acid transfer, (iv) plasmid establishment, (v) plasmid maintenance, and (vi) recombination. The availability of these mutants should contribute to the description of the molecular events involved in each of these conjugation steps and the elucidation of these genetic control over the inheritance of conjugationally transferred deoxyribonucleic acid.


[Alphavirus reproduction in cultures of transplantable human lymphoblastic cells in acute infection].
The results of investigations of acute infection of continuous human B- and T-cells with typical members of the alphavirus group--Semliki Forest, Sindbis, and Venezuelan equine encephalomyelitis viruses, are presented. Virus amplification was shown to pass through the typical phases: eclipse, logarithmic growth, plateau. Infectious virus production per one cell was from 10 to 10,000 PFU in various cultures. Cell infection results in interferon production. Replication of the viruses under study in lymphoblastoid cell cultures is not accompanied by the active cytocidal effect. The regularities determining the sensitivity of lymphoblastoid cells to viruses in general and alphaviruses in particular are discussed. Proceeding from the results of the study of alphavirus replication in human continuous B- and T-cells it is suggested that this system be used as a model for the analysis of antiviral activity of interferon, its inducers, and chemopreparations in special cells. Lymphoblastoid and fibroblast interferon are as active in B-cells and show no antiviral activity in continuous T-cells, as interferon inducer.


[Evidence for the persistence of Epstein-Barr-virus in the parotid gland (author's transl)].
EBV is associated with B-lymphocytes. It is, however, not clear whether spontaneous activation of EBV genomes in carrier lymphocytes, which are present in the lymphocyte rich area of the oropharynx, is responsible for lifelong persistence of antibody-titers directed against EBV related antigens and the shedding of virus into the oropharynx. Alternatively EBV could reside in specific sites of the body and be produced there resembling somehow the situation of Marek's disease virus of chicken. That virus is found in T-lymphocytes and produced and spread from the epithelium of featherfollicles. In situ hybridisations with frozen sections of tonsils and parotid glands reveiled that EBV genomes are present in the tissue of the parotid gland of healthy seropositive persons. The data from in situ hybridisations could be confirmed using stringent reassociationkinetics. It is suggested that spontaneous activation of the lymphocytes is a very rare event and neither the source of virus in the saliva nor the reason for the lifelong persistence of antibodies to EBV related antigens.


Chemical characterization of Citrus limon var. pompia and incorporation in phospholipid vesicles for skin delivery.
The components of pompia, a hybrid Citrus species cultivated only in Sardinia (Italy), were extracted using an environmentally-friendly method and food-grade solvents. Taking into account that only few data are available on pompia composition, the phytochemical fingerprint of its rind extract was obtained by accurate component separation and identification, combining HPLC and mass spectrometry. Different flavones such as naringin (23.77μg/mg), neoeriocitrin (46.53μg/mg) and neohesperidin (44.57μg/mg) were identified. Additionally, the antioxidant activity and phenolic content were confirmed by DPPH and Folin-Ciocalteu assays. The whole extract was incorporated in innovative phospholipid vesicles, namely glycerosomes, hyalurosomes and glycerol containing hyalurosomes, which were prepared using a high ratio of extract/phospholipid (1/3.5w/w). The in vitro biocompatibility of the nanoincorporated extract and its ability to potentiate the aptitude of the extract to counteract oxidative stress in skin cells were evaluated. The vesicles, especially glycerol containing hyalurosomes, were able to prevent oxidative damage and death of both keratinocytes and fibroblasts, promoting their viability.


Urinary Excretion of Yttrium-90 after Radioembolization with Yttrium-90-Labeled Resin-based Microspheres.
In radioembolic therapy (RET) of hepatic malignancies using yttrium-90 (Y)-labeled resin microspheres, radiation protection is primarily concerned with avoiding contamination by radioactive spheres. However, as Y is bound to the microsphere surface by a potentially reversible ion-exchange process, the aim of this study was to assess the extent of the potential excreted activity in urine. After RET with Y-labeled resin-based microspheres, urinary excretion of free Y was prospectively analyzed in 51 interventions (n = 45 patients) by sampling urine over 48 h (two 24-h intervals) consecutively. The measured urinary concentration of Y, normalized to the administered microsphere activity, was a median of 58.5 kBq L GBq (range = 3.5-590.9 kBq L GBq) and 17.8 kBq L GBq (1.8-58.8 kBq L GBq) for the first and second 24-h periods after administration, respectively (p ≤ 0.0001, F = 28.4, result from ANOVA). The total excreted activity significantly decreased (p ≤ 0.0001) from a median of 72.5 kBq in the first 24-h period to a median of 22.1 kBq in the second 24-h period. Urinary excretion of free Y after resin-based RET occurs for a longer period and at a higher activity excretion than previously published, which has to be considered when patients are either hospitalized or return home after RET. Existing approaches for patient hospitalization, especially in temporary radiation protection areas, justified by the previously reported lower excretion rate, should be re-evaluated, and as a consequence, the current product safety information and handling recommendations for Y-labeled resin-based microspheres may need to be revised.


Identification of optimal electrocardiographic criteria for the diagnosis of unrecognized myocardial infarction: a population-based study.
Despite using the same tool (ECG), the proportion of myocardial infarctions that goes unrecognized varies from 20% to 60% in population-based studies. The reasons for such wide variations have not been studied. We sought to evaluate the effect of ECG-MI criteria and study methodology on the prevalence of unrecognized myocardial infarction (UMI) and to identify the optimal ECG-MI criteria for UMI detection in epidemiologic studies. A random population-based sample of 2042 adults, age > or = 45 years, underwent history, medical record abstraction and ECG. Six different ECG-MI criteria and two subjective recognized myocardial infarction (RMI) identification criteria, from different published studies, were applied to the same survey ECG. The operating test characteristics of different criteria were compared with the objective criterion standard of a RMI by Gillum criteria. The UMI proportion estimates varied from 32% to 61% due to variation in ECG-MI criteria, while keeping the study population, MI recognition criteria, and ECG constant. Subjective criteria for MI recognition had limited value (positive predictive value of 44-93%) in picking up RMI. Depending on the ECG abnormality used to define MI, ECG reading had widely varying sensitivity (21-37%; P < 0.0001) with consistently high specificity (92-97%) for detection of RMI. The prevalence estimates of UMI vary widely and are strongly dependent on the ECG-MI and MI recognition criteria. Future studies of UMI should explicitly recognize this variation and select the ECG-MI criteria that match their study aims.