Orthostatic stress response during the menstrual cycle is unaltered in formerly preeclamptic women with low plasma volume.
Plasma volume (PV) varies with the menstrual cycle not only in healthy parous controls (CON) but also in formerly preeclamptic women with a subnormal PV (LPV). It is unknown whether formerly preeclamptic women with LPV are more susceptible to orthostatic stress than healthy controls. In this study, the authors compared autonomic responses to acute (standing from supine position) and gradual (menstrual cycle) orthostatic stress between LPV and CON. In 11 LPV (PV<or= 49 mL/kg lean body mass) and 7 CON, beat-to-beat blood pressure (BP) and heart rate (HR) were measured in supine position and after an orthostatic stress test, during the follicular phase (FP) and luteal phase (LP) of the menstrual cycle. Spectral analysis (fast Fourier transform) was performed on beat-to-beat signals to quantify the magnitude of the spontaneous BP and pulse interval (PI) fluctuations. The absolute powers within the low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.4 Hz) ranges of BP and PI were used as estimates for sympathetic and parasympathetic activity, respectively. Baroreflex sensitivity was calculated as the transfer function gain from low-frequency systolic BP to PI. Differences between groups, menstrual phase, and response to standing were compared by analysis of variance. Basal BP was comparable in both study groups. However, basal PI and spontaneous baroreflex sensitivity were lower in LPV than in CON. The autonomic responses to acute and gradual orthostatic stress were similar in the 2 groups, irrespective of the phase of the menstrual cycle. The cardiovascular response to acute and gradual orthostatic stress in both FP and LP is comparable in LPV and CON.


Binocular correlation of ocular aberration dynamics.
Fluctuations in accommodation have been shown to be correlated in the two eyes of the same subject. However, the dynamic correlation of higher-order aberrations in the frequency domain has not been studied previously. A binocular Shack-Hartmann wavefront sensor is used to measure the ocular wavefront aberrations concurrently in both eyes of six subjects at a sampling rate of 20.5 Hz. Coherence function analysis shows that the inter-ocular correlation between aberrations depends on subject, Zernike mode and frequency. For each subject, the coherence values are generally low across the resolvable frequency range (mean 0.11), indicating poor dynamic correlation between the aberrations of the two eyes. Further analysis showed that phase consistency dominates the coherence values. Monocular and binocular viewing conditions showed similar power spectral density functions.


A Supersonic Underwater Discharge as a High-Power Ultrasound Source.
A supersonic underwater discharge system, driven by a pulsed power generator with 235 ns voltage rise time, was developed to be used as a powerful ultrasound source. The article presents details of the system's components and the various diagnostic methods used, together with the main findings obtained during the first experimental campaign. The system generated a peak pressure of 184 kPa at 1-m distance, with an efficiency of energy conversion from electrical to acoustic estimated as 0.8%. The pressure profile was found to display a resemblance to the radiation pattern generated by a dipole antenna. Using an ultrahigh-speed camera, a study of the interelectrode discharge revealed details of the prebreakdown streamer dynamics and an estimate for the lifetime of the postbreakdown plasma column. The way forward includes testing the system at a very high repetition rate.


Transurethral procedures in the treatment of benign prostatic hyperplasia: A systematic review and meta-analysis of effectiveness and complications.
With the progress of surgical techniques and instruments, various minimally invasive surgical therapies were developed to treat benign prostatic hyperplasisa (BPH). However, the efficacy and safety of different transurethral procedures for the treatment of BPH are still undefined. A systematic search was performed for all randomized controlled trials (RCTs), which compared the transurethral procedures for BPH from 1995 to 2016. The clinical baseline characteristics, International Prostate Symptom Score (IPSS), quality of life (QoL), postvoid residual (PVR), maximum flow rate (Qmax), short-term and long-term complications were analyzed using RevMan and ADDIS software. Eighty-eight randomly controlled trials and fifteen procedures were included in the network meta-analysis. HoLEP greatly inproved PVR. TmLRP had the best efficacy in improving QoL score. Diode laser vaporization of prostate was superior in improving IPSS and Qmax. Diode laser through vaporization required the shortest time in catheterization, while Nd:YAG was the longest procedure. For the hospitalization time, TUR was the longest and HoLEP was the shortest. TmLRP was related to the lowest postoperative hemoglobin decrease. TmLEP had the least rates of occurrence of hematuria, reoperation and erectile dysfunction. HoLEP was the best choice to reduce the incidence of recatheterization, urinary retention, urinary tract infection, stress urinary incontinence and retrograde ejaculation. The complications such as blood transfusion, urethral stricture, bladder neck contracture were relatively rare in the patients who underwent diode laser vaporization of prostate. Compared with other transurethral procedures, thulium, holmium and diode lasers were associated with better efficacy and fewer complications.


Management of wounds of exposed or infected knee prostheses.
Skin damage after total knee arthroplasty may jeopardise the functional benefit of the prosthesis. In such cases standard treatment is aimed at avoiding arthrodesis, sometimes replacing the implant and, in exceptional cases, amputation. In most cases early and adequate coverage of the soft tissue defect may make it possible to salvage the prosthesis. Ten patients with skin damage after total knee arthroplasty were treated by debridement of the wound, which was then covered with a pedicled gastrocnemius muscle flap. This was supported by local irrigation and systemic antibiotics. Seven patients were reviewed after a mean follow-up of 28 months (range 14-59). Six patients kept their prostheses and one had a relapse caused by infection at 22 months, which required removal of the prosthesis and secondary arthrodesis. The gastrocnemius muscle flap provides good quality coverage, permits early mobilisation and fast rehabilitation, and reduces the rate of arthrodesis after failure of total knee arthroplasty.


Variation in patterns of health care before suicide: A population case-control study.
The United States has experienced a significant rise in suicide. As decision makers identify how to address this national concern, healthcare systems have been identified as an optimal location for prevention. To compare variation in patterns of healthcare use, by health setting, between individuals who died by suicide and the general population. Case-Control Study. Eight healthcare systems across the United States. 2674 individuals who died by suicide between 2000 and 2013 along with 267,400 individuals matched on time-period of health plan membership and health system affiliation. Healthcare use in the emergency room, inpatient hospital, primary care, and outpatient specialty setting measured using electronic health record data during the 7-, 30-, 60-, 90-, 180-, and 365-day time periods before suicide and matched index date for controls. Healthcare use was more common across all healthcare settings for individuals who died by suicide. Nearly 30% of individuals had a healthcare visit in the 7-days before suicide (6.5% emergency, 16.3% outpatient specialty, and 9.5% primary care), over half within 30 days, and >90% within 365 days. Those who died by suicide averaged 16.7 healthcare visits during the year. The relative risk of suicide was greatest for individuals who received care in the inpatient setting (aOR = 6.23). There was both a large relative risk (aOR = 3.08) and absolute utilization rate (43.8%) in the emergency room before suicide. Participant race/ethnicity was not available. The sample did not include uninsured individuals. This study provides important data about how care utilization differs for those who die by suicide compared to the general population and can inform decision makers on targeting of suicide prevention activities within health systems.


Acquired camptothecin resistance of human breast cancer MCF-7/C4 cells with normal topoisomerase I and elevated DNA repair.
A camptothecin (CPT)-resistant cell line (MCF-7/C4) was established from MCF-7 cells by mutagenic treatment with methylmethanesulfonate and selection with CPT. MCF-7/C4 is 30-fold resistant to CPT and is cross-resistant to UV and cis-dichlorodiammineplatinum(II) but not to VP-16 or ionizing radiation. Topoisomerase I (top1)-mediated cleavable complexes in the presence of CPT, measured by oligonucleotide assay and by alkaline elution, were similar in both cell lines. Other top1 parameters such as top1 protein, RNA levels, and DNA relaxation were also similar in both cell lines. Thus, CPT resistance is not due to alterations in top1 activity but is caused by changes in the downstream pathways from the top1-induced damage. Both cell lines had similar doubling time (22 hr), but MCF-7/C4 cells showed reduced S-phase fraction in the absence of CPT and reduced G2 delay after CPT treatment. p53, GADD45, and p21WAF1/CIP1 were induced similarly by CPT in both cell lines. The overall repair capacity estimated by the ability of cells to reactivate UV-damaged pSV-CAT plasmid was increased in MCF-7/C4 cells. These observations suggest that enhanced DNA repair is one of the factors involved in CPT resistance.


The potential role of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) is primarily a motor disorder, but its pathogenesis is multifactorial. Although gastric acid secretion is usually normal in GERD patients, treatment with proton pump inhibitors (PPIs) has become the standard of care, despite increasing awareness of their shortcomings. In this article, a new class of antisecretory drugs (namely potassium-competitive acid blockers, P-CABs), developed to overcome these limitations, is discussed. P-CABs block the K exchange channel of the proton pump, resulting in rapid, competitive, reversible inhibition of acid secretion. These drugs offer a more rapid elevation of intragastric pH than PPIs, while maintaining similar antisecretory effect, the duration of which is dependent on half-life and can be prolonged with extended release formulations. Thus, P-CABs offer advances in the treatment of GERD including rapid heartburn relief, faster and more reliable healing of severe grades of erosive esophagitis, as a consequence of better control of nighttime acid secretion than PPIs. P-CABs overcome many of the drawbacks of PPIs. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett's esophagus.


Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats.
Transient forebrain ischemia results in a 24- to 72-hour delayed loss of CA1 neurons. Previous work has not assessed whether insult durations can vary the degree and maturation rate of CA1 injury and whether there are different ultrastructural features of death after brief or severe ischemia. We also tested whether known cytoprotective drugs achieve permanent or transient neuroprotection. In the first experiment, ischemia was induced for 5, 15, or 30 minutes with the use of the 4-vessel occlusion rat model with 1- to 28-day survival. Others subjected to 5 or 15 minutes of ischemia and allowed to survive for 14 or 7 days, respectively, were examined with electron microscopy. Finally, we determined whether NBQX (30 mg/kg x3 at 0 or 6 hours after ischemia), an AMPA antagonist, and SNX-111 (5 mg/kg at 6 hours after ischemia), an N-type Ca2+ channel antagonist, provided enduring CA1 protection against 10 minutes of ischemia. CA1 damage was not detected at 24 hours. Thirty minutes of ischemia produced 47% and 84% CA1 damage at 2 and 3 days, respectively. A 15-minute occlusion yielded 11%, 74%, and 86% loss at 2, 3, and 7 days, respectively. Five minutes of ischemia produced an even slower progression with 24%, 52%, and 59% loss at 3, 7, and 14 days, respectively. Ultrastructural examination after 5 and 15 minutes of ischemia revealed necrosis with no morphological evidence of apoptosis. Both NBQX (P<0.021) and SNX-111 (P<0.001) significantly reduced CA1 death at 7 days (</=35%) but not at 28 days (>/=80%) compared with saline treatment ( approximately 79%). Brief forebrain ischemia results in a slower progression of CA1 loss than more severe insults. Nonetheless, neuronal injury had necrotic, not apoptotic, morphology. NBQX and SNX-111 only postponed CA1 injury.


Properties of uracil transport by vegetative mycelium of Trichoderma viride.
The transport of radioactively labelled uracil into submerged mycelium of T. viride was measured by means of a membrane filtration technique. It was found to be time-dependent (up to 90 min) and concentration-dependent (up to 8 mmol l-1). Its concentration dependence was biphasic and consisted from the saturatable part (at the uracil concentration below 0.2 mmol l-1) with KM = 0.08 +/- 0.02 mmol l-1 and Vmax = 1.74 +/- 0.3 nmol (mg dry wt.)-1 h-1, and from the region at higher uracil concentration which showed only a weak saturatability with the substrate. The transport measured in the saturatable part of the curve was also pH- and temperature-dependent. The optimal pH was between 5.4 and 6.4 and the optimal temperature was at 37 degrees C. The activation energy of 54 kJ mol-1 and the temperature quotient of Q10 = 2.1 could be calculated from the temperature dependence. The entry of uracil was in part inhibited by nucleobases and their analogues, nucleosides, nucleotides and amino acids. The inhibitors had similar inhibitory efficiency about 50% at 0.2 mmol l-1. 3,3',4',5-tetrachlorosalicylanilide (TCS), the uncoupling agent, significantly inhibited the uracil transport, but its inhibitory efficiency decreased upon increasing the uracil concentration. Ionophore antibiotics valinomycin and monensin also inhibited the uracil transport. Inhibitors of RNA-polymerase, rifamycin and rifampicin were without effect. The results suggest that at low uracil concentrations (below 0.2 mmol l-1), its transport is mediated by a carrier and is driven by the electrochemical potential of protons. At higher uracil concentrations, the transport may be driven by the concentration difference of uracil with the contribution of the protonmotive force. It is feasible that inhibitors of uracil transport tested exert their inhibition by the dissipation of the driving force rather than by the direct competition with the substrate-binding site.


The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites.
The paraxial mesoderm of the somites of the vertebrate embryo contains the precursors of the axial skeleton, skeletal muscles and dermis. The Meox1 and Meox2 homeobox genes are expressed in the somites and their derivatives during embryogenesis. Mice homozygous for a null mutation in Meox1 display relatively mild defects in sclerotome derived vertebral and rib bones, whereas absence of Meox2 function leads to defective differentiation and morphogenesis of the limb muscles. By contrast, mice carrying null mutations for both Meox genes display a dramatic and wide-ranging synthetic phenotype associated with extremely disrupted somite morphogenesis, patterning and differentiation. Mutant animals lack an axial skeleton and skeletal muscles are severely deficient. Our results demonstrate that Meox1 and Meox2 genes function together and upstream of several genetic hierarchies that are required for the development of somites. In particular, our studies place Meox gene function upstream of Pax genes in the regulation of chondrogenic and myogenic differentiation of paraxial mesoderm.


An investigation into the expectations of mothers of children with cochlear implants.
The process of implantation is fraught with expectations. To ensure continued parental commitment and motivation, it is important to have insight into expectations and the factors that influence them. This study investigated the expectations of mothers whose children used a cochlear implant, and the influence that satisfaction with outcomes had on expectations over time. A qualitative research methodology was used. In-depth interviews were undertaken with eight mothers of pre-school children. The data were analysed according to a detailed qualitative analysis procedure. Findings revealed changing expectations over time, based either on hope or knowledge. Many variables influenced expectations, including response to deafness, anxiety and performance outcomes. Theoretical and clinical implications include the dynamic nature of expectations and the impact these have on counselling.


Step by step: a proof of concept study of C-Mill gait adaptability training in the chronic phase after stroke.
To evaluate the concept of C-Mill gait adaptability training. Pre- and post-intervention assessments. Sixteen community-dwelling persons in the chronic phase after stroke (mean age 54.8 years). Participants received 10 sessions (1 h per session, for 5-6 weeks) of gait adaptability training on an instrumented treadmill augmented with visual targets and obstacles (C-Mill). Pre- and post-intervention assessments included: (i) clinical assessments of balance and gait: 10-m walking test, Timed Up-and-Go test, Berg Balance Scale, obstacle sub-task of the Emory Functional Ambulation Profile, and the Trunk Impairment Scale; (ii) physical activity level, assessed with a pedometer; (iii) success rate of accurate step adjustments towards a displacing target, assessed with an instrumented Target-Stepping Task; (iv) participant's experience with the training. All clinical assessments improved significantly after training (all p < 0.05), except for the Trunk Impairment Scale (p = 0.584). Physical activity increased by 19.6% (p < 0.05). Improvements in Target-Stepping Task success rates depended on the specific testing condition (time × body support × step direction, χ2(1) = 3.884, p < 0.05). All participants appreciated the training. The concept of C-Mill gait adaptability training in the chronic phase after stroke is promising and warrants future research involving a randomized controlled trial.


BDNFVal66met polymorphism: a potential bridge between depression and thrombosis.
Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk factor for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which phenocopies psychiatric-related symptoms found in humans, we investigated the impact of this SNP on thrombosis. BDNFMet/Met mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyperreactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-type (WT) mice showed differential expression of proteins involved in the coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection. Interestingly, transfection with BDNFMet construct induced a prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using resveratrol and/or CAY10591, prevented thrombus formation and restored the physiological levels of coagulation and of platelet markers in BDNFMet/Met mice and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory phenotype in WT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans. Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNFMet/Met mice recapitulate well the features occurring in the anxiety/depression condition. Furthermore, our data suggest that the BDNFVal66Met polymorphism contribute to the individual propensity for arterial thrombosis related to AMI.


Functional characterization of TLR4 +3725 G/C polymorphism and association with protection against overweight.
Subclinical low-grade systemic inflammation has been associated with obesity, insulin resistance and metabolic syndrome (MS). Recent studies have highlighted the role of gut microbiota in these disorders. The toll-like receptor 4 (TLR4) plays a key role in the innate immune response activation. We studied two polymorphisms (+3725G/C and 11350G/C) in the 3' untranslated region (3'UTR) of the TLR4 gene that may alter its expression and their association with metabolic disorders related to systemic inflammation. We cloned the 3'UTR into a luciferase reporter system and compared wild-type 3'UTR (WT) and +3725C variant (MUT) constructs luciferase activities. MUT construct reduced the reporter gene activity by 30% compared to WT (P = 0.0001). To evaluate the association between these polymorphisms with biochemical and clinical overweight related variables, we conducted a population cross-sectional study in 966 men of Argentine general population. Considering smoking as a confounding variable that causes systemic inflammation, we studied these possible effects in both, smokers and nonsmokers. The 11350G/C polymorphism was not detected in our sample whereas the CC genotype of +3725 polymorphism was associated with lean subjects (p = 0.011) and higher Adiponectin levels (p = 0.021). Subjects without any NCEP/ATP III MS component were associated with this genotype as well (p = 0.001). These results were strengthened in nonsmokers, in which CC genotype was associated with lean subjects (p = 0.003) and compared with G carriers showed significantly lower BMI (25.53 vs. 28.60 kg/m2; p = 0.023) and waist circumference (89.27 vs. 97.51 cm; p = 0.025). None of these associations were found in smokers. These results showed that +3725C variant has a functional effect down-regulating gene expression and it could be considered as a predictive factor against overweight, particularly in nonsmokers. Considering the role of TLR4 in inflammation, these findings would suggest that the presence of +3725C variant could predict a lower prevalence of chronic metabolic disorders.


Myelopathy in Behçet's disease: The Bagel Sign.
To describe the clinical and distinctive imaging features of myelopathy associated with Behçet's disease (BD). We evaluated the records of patients meeting the following criteria: (1) fulfillment of the International Study Group criteria for BD; (2) clinically suggestive of myelopathy; (3) simultaneous spinal cord and brain magnetic resonance images (MRIs) within 1 month of acute worsening of myelopathy; and (4) follow-up duration ≥ 1 year after initial MRI evaluation. Patients not fulfilling all inclusion criteria and having MRIs with poor quality or missing sequences were excluded. In 11 patients (9 men, 2 women), we studied 14 MRIs during distinct myelopathy episodes and nine follow-up MRIs. Two distinct MRI patterns of spinal cord involvement were described according to T2-weighted (T2W) axial images: (1) "Bagel Sign" pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and (2) "Motor Neuron" pattern: a symmetric involvement of the anterior horn cells. Bagel Sign was present in 13 of 14 myelopathy episodes whereas Motor Neuron pattern was observed in 1 of 14 MRIs. Of the 13 MRIs with Bagel Sign long myelopathy (n = 9), both long and short myelopathy (n = 2) and short myelopathy (n = 2) was observed. All patterns cleared with some residual lesions after steroid use and immunomodulation with associated clinical recovery in patients. The signal characteristics of the Bagel Sign potentially represent venous engorgement and/or acute blood products within the spinal cord. To our knowledge, Bagel Sign has not been observed in other forms of longitudinal myelopathy outside of BD, including neuromyelitis optica. Ann Neurol 2017;82:288-298.


Molecules Acting on CB1 Receptor and their Effects on Morphine Withdrawal In Vitro.
Several pharmacological studies indicate that CB1 cannabinoid receptors (CB1Rs) are present in guinea pig ileum (GPI) and their activation reduce the acetylcholine (Ach) release. Dependence can be induced and measured in vitro by using GPI and the contraction due to opioid withdrawal is caused by acetylcholine release.Design of molecules acting on the CB1Rs are widely studied and the large availaibility of CB1Rs agonists and antagonists provides powerful tools to determine the role of these receptors in mediating some of physiological and pharmacological effects in the myenteric neurones.Given the relationship between CB1Rs/Opioid Withdrawal/Ach system, in the present paper we have designed six new CB1Rs agonists named A-F and evaluated their role in mediating morphine withdrawal in GPI. Also, a comparative study was performed by using the CB1Rs synthetic cannabinoid WIN 55,212-2 and CP 55,940. The results of our experiments indicate that both WIN 55,212-2 and CP 55,940 (1x10(-8)-5x10(-8)-1x10(-7) M) were able to reduce morphine withdrawal in a concentration-dependent manner. Very similar results were obtained with the new CB1Rs agonists (A-F) used at same concentrations. The results of our experiments indicate that CB1Rs are involved in the control of morphine withdrawal in vitro thus confirming an important functional interaction between the cannabinoid and opioid system.


Management of acute cerebellar infarction: one institution's experience.
The management of cerebellar infarctions is controversial. The aim of this study was to determine which patients require surgical treatment and which surgical procedure should be performed when a patient with a cerebellar infarction exhibits progressive neurological deterioration. A total of 44 patients (24 male and 20 female patients; average age, 56 yr) were treated at our institution for cerebellar infarctions in the past 8 years. Twenty-five patients received conservative treatment; two patients who were deeply comatose received no treatment. The remaining 17 patients underwent emergency surgery. Of those 17 patients, 8 underwent external ventricular drainage alone, 5 underwent external ventricular drainage as the first treatment plus secondary suboccipital craniectomy, and 4 underwent suboccipital craniectomy, with removal of necrotic tissue, as the first treatment. Of the 25 conservatively treated patients, 20 experienced good outcomes, 4 experienced moderate outcomes, and 1 died as a result of pulmonary embolism. Of the 17 surgically treated patients, 10 experienced good functional recoveries (7 treated with external ventricular drainage only and 3 treated with drainage followed by suboccipital craniectomy) and 3 survived with mild neurological deficits (one patient underwent ventriculostomy, one suboccipital craniectomy plus external ventricular drainage, and one suboccipital craniectomy only). The overall mortality rate was 13.6% (6 of 44 patients). For patients with worsening levels of consciousness and radiologically evident ventricular enlargement, we recommend external ventricular drainage. We reserve surgical resection of necrotic tissue for patients whose clinical status worsens despite ventriculostomy, those for whom worsening is accompanied by signs of brainstem compression, and those with tight posterior fossae.


Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source.
Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.


Ultrasensitive electrochemical detection and inhibition evaluation of DNA methyltransferase based on cascade strand displacement amplification.
An electrochemical sensing approach for ultrasensitive DNA methyltransferase (MTase) activity assay is proposed. After specific cleavage reaction in the presence of a methylated state, strand displacement polymerization (SDP) is initiated in the solution. The product of upstream SDP further triggers downstream SDP, which enriches abundant electrochemical species at the electrode. The whole process is quite convenient with shared enzymes. Due to the cascade signal amplification, ultrahigh sensitivity is promised. Inhibitor screening results are also demonstrated to be good. Besides, target MTase can be accurately determined in human serum samples, confirming excellent practical utility. This work provides a reliable approach for the analysis of MTase activity, which is of vital importance for related biological studies and clinical applications.


Systematic assessment of prescribed medications and short-term risk of myocardial infarction - a pharmacopeia-wide association study from Norway and Sweden.
Wholesale, unbiased assessment of Scandinavian electronic health-care databases offer a unique opportunity to reveal potentially important undiscovered drug side effects. We examined the short-term risk of acute myocardial infarction (AMI) associated with drugs prescribed in Norway or Sweden. We identified 24,584 and 97,068 AMI patients via the patient- and the cause-of-death registers and linked to prescription databases in Norway (2004-2014) and Sweden (2005-2014), respectively. A case-crossover design was used to compare the drugs dispensed 1-7 days before the date of AMI diagnosis with 15-21 days' time -window for all the drug individually while controlling the receipt of other drugs. A BOLASSO approach was used to select drugs that acutely either increase or decrease the apparent risk of AMI. We found 48 drugs to be associated with AMI in both countries. Some antithrombotics, antibiotics, opioid analgesics, adrenergics, proton-pump inhibitors, nitroglycerin, diazepam, metoclopramide, acetylcysteine were associated with higher risk for AMI; whereas angiotensin-II-antagonists, calcium-channel blockers, angiotensin-converting-enzyme inhibitors, serotonin-specific reuptake inhibitors, allopurinol, mometasone, metformin, simvastatin, levothyroxine were inversely associated. The results were generally robust in different sensitivity analyses. This study confirms previous findings for certain drugs. Based on the known effects or indications, some other associations could be anticipated. However, inverse associations of hydroxocobalamin, levothyroxine and mometasone were unexpected and needs further investigation. This pharmacopeia-wide association study demonstrates the feasibility of a systematic, unbiased approach to pharmacological triggers of AMI and other diseases with acute, identifiable onsets.


An echolocation visualization and interface system for dolphin research.
The present study describes the development and testing of a tool for dolphin research. This tool was able to visualize the dolphin echolocation signals as well as function as an acoustically operated "touch screen." The system consisted of a matrix of hydrophones attached to a semitransparent screen, which was lowered in front of an underwater acrylic panel in a dolphin pool. When a dolphin aimed its sonar beam at the screen, the hydrophones measured the received sound pressure levels. These hydrophone signals were then transferred to a computer where they were translated into a video image that corresponds to the dynamic sound pressure variations in the sonar beam and the location of the beam axis. There was a continuous projection of the image back onto the hydrophone matrix screen, giving the dolphin an immediate visual feedback to its sonar output. The system offers a whole new experimental methodology in dolphin research and since it is software-based, many different kinds of scientific questions can be addressed. The results were promising and motivate further development of the system and studies of sonar and cognitive abilities of dolphins.


[Correlation between receptor status and results of treatment in endometrial carcinoma].
In the course of immunohistochemical assay of estrogen (ER), progesterone (PR) and oncoprotein HER-2/neu receptors, PR+ expression was identified in 52% of 50 patients with endometrial carcinoma. A direct correlation between ER and PR levels (i = 0.7) was established (ER+/PR(+)--26.0%; ER-/PR(-)--42.0%; ER-/PR(+)--26.0%; ER+/PR(-)--6.0%). In the ER+/PR+ and--ER-/PR+ groups, adjuvant therapy with progestins was carried out (3-year-survival--95.3% (p < 0.05)); recurrence rate--8.0%. Inverse correlations were characteristic of ER and HER-2/neu (i = -0.4) and PR and HER-2/neu (i = -0.114). Adjuvant polychemotherapy was administered in 12.2% of cases of HER-2/neu over-expression. That group revealed a drop in 3-year survival from 85.5 to 41.7% and relapse in half of the patients.


Neuroprotective Effect of Nanodiamond in Alzheimer's Disease Rat Model: a Pivotal Role for Modulating NF-κB and STAT3 Signaling.
Current therapeutic approaches of Alzheimer's disease (AD) are symptomatic and of modest efficacy, and there is no available effective cure or prevention of AD; hence, the need arise to search for neuroprotective agents to combat AD. The current study aimed at investigating the neuroprotective effect of nanodiamond (ND), adamantine-based nanoparticles, in aluminum-induced cognitive impairment in rats, an experimental model of AD. AD was induced by aluminum chloride (17 mg/kg, p.o. for 6 weeks) and confirmed by Morris water maze and Y-maze behavioral tests. Biochemical and histological analyses of the hippocampus were also performed. Aluminum-treated rats showed behavioral, biochemical, and histological changes similar to those associated with AD. ND improved learning and memory and reversed histological alterations. At the molecular levels, ND mitigated the increase of hippocampal beta-amyloid (Aβ42) and beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) together with down-regulation of phosphorylated tau protein. It also modulated the excitatory glutamate neurotransmitter level. Furthermore, ND boosted the brain-derived neurotrophic factor (BDNF) and mitochondrial transcription factor-A (TFAM), suppressed the proinflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and curbed oxidative stress by hampering of inducible nitric oxide synthase (iNOS). Moreover, ND augmented the hippocampal levels of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and B cell leukemia/lymphoma-2 (Bcl-2) anti-apoptotic protein while diminished nuclear factor-kappaB (NF-κB) and caspase-3 (casp-3) expression. These findings indicate the protective effect of ND against memory deficits and AD-like pathological aberrations probably via modulating NF-kB and STAT3 signaling, effects mediated likely by modulating N-methyl-D-aspartate (NMDA) receptors.


Incidence and risk of fatal myocardial infarction and stroke events in rheumatoid arthritis patients. A systematic review of the literature.
There is substantial evidence of excess cardiovascular morbidity and mortality in rheumatoid arthritis (RA) patients, but the related studies showed important variations in the estimation of the risk. We conducted a meta-analysis to evaluate more accurately the incidence of cardiovascular events, and the excess of cardiovascular risk in a population of RA patients. The authors searched for observational studies accounting for the number of myocardial infarction or stroke events, using Medline, and congress abstracts published until February 2006. The populations studied were adults and RA diagnosis was based on the American College of Rheumatology (ACR) criteria. We calculated the incidence of myocardial infarction and cerebrovascular fatal events in RA patients and estimated the cardiovascular risk increase for RA patients compared with the control group. 17 publications and abstracts were identified, 15 were selected for the meta-analysis (two publications were excluded because of the lack of person-years information). The incidence of fatal myocardial infarction was 13.3 for 1000 RA patients-year (IC95%=[13-13.6]). The incidence of fatal cerebrovascular accident was 4.5 for 1000 RA patients-year (IC95%=[4.3-4.7]). Risk of myocardial ischemia in RA patients was about 1.63 compared to the general population (OR=1.63, IC95%=[1.34-2]). No excess was found for the risk of stroke event in RA patients. RA patients were reported to present an excess risk of fatal myocardial infarction compared to the general population. The prevention of cardiovascular complications, including management of cardiovascular risk factors and control of systemic inflammation, should be taken into account by the rheumatologist.


When Doctors strike: Making Sense of Professional Organizing in Kenya.
Little is known about how the health professions organize in low- and middle-income countries (LMICs). This is particularly troubling as health worker strikes in LMICs appear to be growing more frequent and severe. While some research has been conducted on the impact of strikes, little has explored their social etiology. This article draws on theory from organization and management studies to situate strike behavior in a historical process of sensemaking in Kenya. In this way, doctors seek to expand pragmatic, moral, and cognitive forms of legitimacy in response to sociopolitical change. During the first period (1963-2000), the legacy of colonial biomedicine shaped medical professionalism and tensions with a changing state following independence. The next period (2000-2010) was marked by the rise of corporate medicine as an organized form of resistance to state control. The most recent period (2010-2015) saw a new constitution and devolution of health services cause a fractured medical community to strike as a form of symbolic resistance in its quest for legitimacy. In this way, strike behavior is positioned as a form of legitimation among doctors competing over the identity of medicine in Kenya and is complicating the path to universal health coverage.


Acute kidney injury in China.
China has a large population and bears a heavy burden of kidney diseases. Acute kidney injury (AKI) is increasingly prevalent in China and is associated with severe morbidity and mortality. The inadequacies of early diagnosis and management remain the major challenges to Chinese nephrologists. There is an urgent need for a nationwide, or even a global effort to increase an awareness of the devastating effects of AKI, to develop professional preventive strategies, as well as to achieve early diagnosis and early intervention. In this article, we review the increasing incidence of AKI and complexity behind prevention and management, focusing on differences in various clinical settings in China.


Translation and linguistic validation of the Allergy-CONTROL-ScoreTM for use in Japan.
Symptom and medication scores are recommended to measure the primary outcome on allergies. The Allergy Control Score was proved to be a valid and reliable instrument to assess allergy severity in clinical trials and may be used in observational studies of respiratory allergic diseases in many countries. We translated the Allergy Control Score and adapted it for use in Japan. We translated the original English version into Japanese according to the Mapi approach to linguistic validation: conceptual definition, forward translation by two native Japanese speakers, reconciliation, back-translation by an independent translator, review in consultation with original developer, and pilot testing on 12 patients of an allergy clinic and 3 volunteers with seasonal/non-seasonal allergic rhinitis and/or asthma. Two of the ten back-translated items needed slight modifications and some words were revised. In the pilot test, the average time required to complete the questionnaire was 55 seconds for the section on symptoms and 25 seconds for the section on medication. All participants were able to self-complete the questionnaire. By applying the Mapi approach to linguistic validation, we ensured a close match between the Japanese and English versions of the Allergy Control Score. The Allergy Control Score Japanese version is accessible and acceptable to persons with respiratory allergic symptoms in Japan.


Factors associated with primary graft failure after heart transplantation.
Primary graft failure (PGF) is the most common cause of short-term mortality after cardiac transplantation. The low prevalence of PGF has limited efforts at identifying risk factors for its development. The purpose of this study was to evaluate risk factors associated with PGF after heart transplantation. Deidentified data were obtained from United Network for Organ Sharing. Analysis included heart transplant recipients more than or equal to 18 years transplanted between January 1, 1999, and December 31, 2007 (n=16,716). PGF was studied from the perspective of "hard outcomes" including death or retransplantation within 90 days of transplant due to graft failure, not related to rejection or infection. Multivariate regression analysis was performed (backward, remove P>0.15) to assess the simultaneous effect of multiple variables on PGF. The odds ratio and 95% confidence interval were reported for each factor. Among the 414 heart transplants complicated by PGF, 354 (85.5%) recipients died and 60 (14.5%) were retransplanted. PGF accounted for 23.4% (n=364) of all deaths (n=1555) in the first 90 days posttransplant. Categories of pretransplant variables associated with PGF included: ischemic time, donor gender, donor age, multiorgan donation, center volume, extracorporeal membrane oxygenation, mechanical circulatory support, etiology of heart failure, and reoperative heart transplant. The area under the receiver operative characteristic curve for the multivariate model was 0.764 (0.733-0.796). Pretransplant recipient and donor characteristics are associated with PGF. Identification of risk factors may aid in understanding the mechanisms underlying PGF and in matching recipients with donors in efforts to diminish the high mortality associated with this complication.


In Vitro and In Vivo Interactions of TOR Inhibitor AZD8055 and Azoles against Pathogenic Fungi.
In the present study, in vitro and in vivo interactions of TOR inhibitor AZD8055 and azoles, including itraconazole, voriconazole, posaconazole and fluconazole, against a variety of pathogenic fungi were investigated. A total of 69 isolates were studied via broth microdilution checkerboard technique, including 23 isolates of Aspergillus spp., 20 isolates of Candida spp., 9 isolates of Cryptococcus neoformans complex, and 17 isolates of Exophiala dermatitidis. The results revealed that AZD8055 individually did not exert any significant antifungal activity. However, synergistic effects between AZD8055 and itraconazole, voriconazole or posaconazole were observed in 23 (33%), 13 (19%) and 57 (83%) isolates, respectively, including azole-resistant A. fumigatus strains and Candida spp., potentiating the efficacy of azoles. The combination effect of AZD8055 and fluconazole was investigated against non-auris Candida spp. and C. neoformans complex. Synergism between AZD8055 and fluconazole was observed in six strains (60%) of Candida spp., resulting in reversion of fluconazole resistance. Synergistic combinations resulted in 4-fold to 256-fold reduction of effective MICs of AZD8055 and azoles. No antagonism was observed. In vivo effects of AZD8055-azole combinations were evaluated by survival assay in Galleria mellonella model infected with A. fumigatus strain AF002, E. dermatitidis strain BMU00038, C. auris strain 383, C. albicans strain R15, and C. neoformans complex strain Z2. AZD8055 acted synergistically with azoles and significantly increased larvae survival (P < 0.05). In summary, the results suggested that AZD8055 combined with azoles may help to enhance the antifungal susceptibilities of azoles against pathogenic fungi and had the potential to overcome azole resistance issues. IMPORTANCE Limited options of antifungals and the emergence of drug resistance in fungal pathogens has been a multifaceted clinical challenge. Combination therapy represents a valuable alternative to antifungal monotherapy. The target of rapamycin (TOR), a conserved serine/threonine kinase from yeast to humans, participates in a signaling pathway that governs cell growth and proliferation in response to nutrient availability, growth factors, and environmental stimuli. AZD8055 is an orally bioavailable, potent, and selective TOR kinase inhibitor that binds to the ATP binding cleft of TOR kinase and inhibits both TORC1 and TORC2. Synergism between AZD8055 and azoles suggested that the concomitant application of AZD8055 and azoles may help to enhance azole therapeutic efficacy and impede azole resistance. TOR inhibitor with fungal specific target is promising to be served as combination regimen with azoles.


New sandwich-type polymeric potassium-dicyanoargentate(I) complex: synthesis, characterization and enzymatic activity.
Coordination compounds containing dicyanoargentate(I) have remarkable biological potential due to their therapeutic antibacterial, antifungal, antibiofilm, and anticancer properties. In this study, a new dicyanoargentate(I)-based complex was synthesized and characterized by various procedures (elemental, thermal, FT-IR for complex) involving crystal analysis of the complex. In addition, the biological activity of this new compound on the acetylcholinesterase (AChE) enzyme, an important enzyme for the nervous system, was investigated. When the infrared (IR) spectrum of the complex is examined, the OH vibration peak resulting from H2O molecules in the structure at 3948-3337 cm-1 and at 2138 cm-1, along with a CN peak coordinated to Ag, can be seen, indicating that the mass remaining in the thermal degradation of the complex at 1000 ◦ C is the weight corresponding to the metal mixture consisting of K+Ag (calc.: 68.06). The crystal method revealed that the complex has a sandwich-like, polymeric chemical structure with layers formed by K+ cations and [Ag(CN)2H2O]- anions. Therefore, the AChE enzyme has potential therapeutic uses in improving ACh levels in brain cells, in reducing various side effects, and in improving cognitive impairment, especially in advanced Alzheimer's disease patients. In this study, the activity of this newly synthesized complex on AChE was also investigated. As a result of this research, [Ag(CN)2(H2O)K] had 0.0282 ± 0.010 μM Ki values against AChE. The compound was therefore a good inhibitor for the AChE enzyme. This type of compound can be used for the development of novel anticholinesterase drugs.


Comparison of the acceptance of progressive addition multifocal vs. a standard multifocal lens design.
An evaluation of the relative influence of the optical features of two forms of multifocal lenses, one of progressive power form and one of standard flat-top 25 bifocal form, is made upon a number of subjects. A comparison of acceptance was made with special emphasis on testing of intermediate range of vision and breadth of the near field. The progressive form of multifocal correction were overwhelmingly preferred over flat-top 25 bifocals. A preference was found for the optical advantage of acceptable vision at all distances over the disadvantages of narrower field afforded by the progressive multifocal design.


[Primary coronary fistulas. Angiographic study of 21 cases].
A retrospective study of 21 cases of congenital primary coronary fistulae and a review of the literature underline the exceptional features of 2 of our cases and recall the main features of coronary fistulae. Coronary angiography (18 cases) or aortography (3 cases) confirmed the diagnosis in our 21 cases. Six of them involved the right coronary artery, 12 the left one, and 3 the two coronary arteries. Seven of them involved the right heart (2 right atrium, 5 right ventricle), 11 the main pulmonary artery, 2 the left heart (the left ventricle in both cases), and the last case was a coronaro-bronchial fistula. Our series comprised 11 men and 10 women; the mean age was 33 (range: 4 days to 67 years of age). The main presenting features were: murmur (7 cases), angina (7 cases), angina (7 cases), Stage II or III dyspnoea (5 cases). Clinical examination showed a systolic-diastolic murmur in 12 cases and a systolic murmur in one case. The chest X ray showed signs of left to-right shunt in 6 cases. The right heart catheterisation of 16 of the 19 left-to-right shunts confirmed the shunt in 9 cases. The 7 cases of coronaro-right cardiac fistulae drained directly (4 cases), by aneurysmal dilatation with diaphragm (3 cases); the 2 cases of coronaro-left-ventricular fistulae drained via microfistulae; the 11 cases of proximal coronaro-pulmonary fistulae drained mostly by an angiomatous plexus (9 cases).(ABSTRACT TRUNCATED AT 250 WORDS)


Maternal vitamin D status as a critical determinant in gestational diabetes.
To synthesize published research to determine the evidence for the association between maternal vitamin D status during pregnancy and the development of gestational diabetes mellitus (GDM). Literature searches were conducted for data based articles that examined maternal vitamin D during pregnancy, GDM, glucose tolerance, and insulin resistance using the PubMed, CINAHL, and SCOPUS data bases and reference lists from reviewed papers. Primary research studies published in the English language between 1999 and 2011 reporting findings regarding the association of vitamin D with glucose homeostasis during pregnancy and GDM. Study characteristics and findings related to vitamin D status determinants, gestational timing, and measures of glucose homeostasis and insulin resistance. Six data based articles met the criteria for study inclusion. Study findings comprised solely Level-2 evidence for the association of maternal vitamin D deficiency and risk of GDM. The majority of studies (66%) were conducted between 24 and 30 weeks gestation. Five (83%) studies reported an inverse relationship between circulating vitamin D levels and markers of glucose homeostasis associated with gestational diabetes or an increased risk for GDM associated with reduced maternal levels of vitamin D. In one study, researchers did not identify an association between vitamin D and GDM but did identify an association between higher vitamin D levels and lower fasting glucose and insulin levels. Maternal vitamin D deficiency and insufficiency is prevalent among gravid women and is associated with markers of altered glucose homeostasis. These findings underscore the need for mechanistic and clinical studies to determine optimal vitamin D status in pregnancy for reduction in the risk for GDM with implications for vitamin D supplementation as a potential target for GDM prevention.


Effectiveness and Ethics of Incentives for Research Participation: 2 Randomized Clinical Trials.
Incentivizing research participation is controversial and variably regulated because of uncertainty regarding whether financial incentives serve as undue inducements by diminishing peoples' sensitivity to research risks or unjust inducements by preferentially increasing enrollment among underserved individuals. To determine whether incentives improve enrollment in real randomized clinical trials (RCTs) or serve as undue or unjust inducements. Two RCTs of incentives that were embedded in 2 parent RCTs, 1 comparing smoking cessation interventions (conducted at smoking cessation clinics in 2 health systems) and 1 evaluating an ambulation intervention (conducted across wards of the Hospital of the University of Pennsylvania) included all persons eligible for the parent trials who did not have prior knowledge of the incentives trials. Recruitment occurred from September 2017 to August 2019 for the smoking trial and January 2018 through May 2019 for the ambulation trial; data were analyzed from January 2020 to July 2020. Patients were randomly assigned to incentives of $0, $200, or $500 for participating in the smoking cessation trial and $0, $100, or $300 for the ambulation trial. The primary outcome of each incentive trial was the proportion of people assigned to each recruitment strategy that consented to participate. Each trial was powered to test the hypotheses that incentives served neither as undue inducements (based on the interaction between incentive size and perceived research risk, as measured using a 10-point scale, on the primary outcome), nor unjust inducements (based on the interaction between incentive size and participants' self-reported income). Noninferiority methods were used to test whether the data were compatible with these 2 effects of incentives and superiority methods to compare the primary and other secondary outcomes. There were a total of 654 participants (327 women [50.0%]; mean [SD] age, 50.6 [12.1] years; 394 Black/African American [60.2%], 214 White [32.7%], and 24 multiracial individuals [3.7%]) in the smoking trial, and 642 participants (364 women [56.7%]; mean [SD] age, 46.7 [15.6] years; 224 Black/African American [34.9%], 335 White [52.2%], and 5 multiracial individuals [0.8%]) in the ambulation trial. Incentives significantly increased consent rates among those in the smoking trial in 47 of 216 (21.8%), 78 of 217 (35.9%), and 104 of 221 (47.1%) in the $0, $200, and $500 groups, respectively (adjusted odds ratio [aOR] for each increase in incentive, 1.70; 95% CI, 1.34-2.17; P < .001). Incentives did not increase consent among those in the ambulation trial: 98 of 216 (45.4%), 102 of 212 (48.1%), and 92 of 214 (43.0%) in the $0, $100, and $300 groups, respectively (aOR, 0.88; 95% CI, 0.64-1.22; P = .45). In neither trial was there evidence of undue or unjust inducement (upper confidence limits of ORs for undue inducement, 1.15 and 0.99; P < .001 showing noninferiority; upper confidence limits of ORs for unjust inducement, 1.21 and 1.26; P = .01 and P < .001, respectively). There were no significant effects of incentive size on the secondary outcomes in either trial, including time spent reviewing the risk sections of consent forms, perceived research risks, trial understanding, perceived coercion, or therapeutic misconceptions. In these 2 randomized clinical trials, financial incentives increased trial enrollment in 1 of 2 trials and did not produce undue or unjust inducement or other unintended consequences in either trial. ClinicalTrials.gov Identifier: NCT02697799.


Clinical correlation of brachial artery flow-mediated dilation in patients with systemic sclerosis.
To investigate the clinical significance of flow-mediated dilation (FMD) in systemic sclerosis (SSc). Thirty-three SSc patients and 12 healthy controls were studied. Ultrasound assessment of the brachial artery FMD was performed on all subjects. The results were expressed as the percentage of increase in brachial artery diameter following hyperemia. Limited cutaneous SSc (lcSSc) patients had significantly lower FMD values than healthy controls (5.3 ± 2.7 versus 7.7 ± 2.0 %, p < 0.05), while the values in diffuse cutaneous SSc (dcSSc) patients (6.7 ± 4.0 %) were comparable to those in lcSSc patients and healthy controls. Although FMD values did not correlate with any clinical features in dcSSc patients, there was an inverse correlation between FMD values and disease duration in lcSSc patients (r = -0.64, p < 0.05). Furthermore, lcSSc patients with decreased FMD values showed significantly higher prevalence of digital ulcers and elevated right ventricular systolic pressure than those with normal values (for each; 75 versus 10 %, p < 0.05). The FMD values represent the severity of vascular damages, which progress along with disease duration and lead to digital ulcers and pulmonary arterial hypertension, in lcSSc patients.


High avidity melanoma-reactive cytotoxic T lymphocytes are efficiently induced from peripheral blood lymphocytes on stimulation by peptide-pulsed melanoma cells.
To design an efficient procedure to expand high avidity melanoma reactive T cells and to perform immunotherapies, we compared conditions of peripheral blood lymphocyte (PBL) stimulation by Melan-A/MART-1 peptides. Avidity of induced CTLs was evaluated by measuring their lysis and cytokine secretion to peptide-pulsed transporter-associated protein-deficient cells and to melanoma cells. In side-by-side experiments, we show that melanoma cells, either allogeneic or autologous, induced the growth of high avidity Melan-A-reactive CTLs from all donors, whereas essentially low avidity T cells were induced by peptide-pulsed PBLs. We also show that at least two cytokines, interleukin-6 and interleukin-2, were required to promote the growth of high avidity CTLs. Once sorted by tetramer labeling or cloning, the specificity and reactivity to tumor cells of peptide-specific T cells induced by allogeneic melanoma cells were confirmed. We then describe a relatively simple and efficient procedure that allowed us to obtain systematically high amounts (in the range of billion) of high avidity Melan-A/ MART-1-specific T cells from the PBLs of HLA-A2 melanoma patients and healthy donors in 3 months. Because this antigen is expressed by most melanoma tumors, this procedure should be useful for checking the efficiency of adoptive immunotherapy of melanoma tumors and using functionally well-defined Melan-A/MART-1-specific CTLs in a large group of patients.


A Bayesian Approach to Integrated Ecological and Human Health Risk Assessment for the South River, Virginia Mercury-Contaminated Site.
We conducted a regional-scale integrated ecological and human health risk assessment by applying the relative risk model with Bayesian networks (BN-RRM) to a case study of the South River, Virginia mercury-contaminated site. Risk to four ecological services of the South River (human health, water quality, recreation, and the recreational fishery) was evaluated using a multiple stressor-multiple endpoint approach. These four ecological services were selected as endpoints based on stakeholder feedback and prioritized management goals for the river. The BN-RRM approach allowed for the calculation of relative risk to 14 biotic, human health, recreation, and water quality endpoints from chemical and ecological stressors in five risk regions of the South River. Results indicated that water quality and the recreational fishery were the ecological services at highest risk in the South River. Human health risk for users of the South River was low relative to the risk to other endpoints. Risk to recreation in the South River was moderate with little spatial variability among the five risk regions. Sensitivity and uncertainty analysis identified stressors and other parameters that influence risk for each endpoint in each risk region. This research demonstrates a probabilistic approach to integrated ecological and human health risk assessment that considers the effects of chemical and ecological stressors across the landscape.


Endogenous Lipid Pneumonia in a Ferret (Mustela putorius furo).
A 1-year-old female ferret was presented with an acute history of severe respiratory distress. Abnormal clinical signs noted during the initial physical examination were hypothermia, dehydration, pale mucous membranes, tachypnea, and severe dyspnea. Thoracic radiographs revealed pleural effusion, an enlarged cardiac silhouette, and areas of lung consolidation. Both blood and thoracic fluid were hyperproteinemic and hypergammaglobulinemic. Antibiotic, corticosteroid, and diuretic supportive treatment provided temporary improvement. After the initial positive response to treatment, the ferret's condition progressively deteriorated until the owners decided to euthanize the patient 15 days after initial presentation. Gross necropsy results revealed 5 mL of serosanguinous fluid within the thoracic cavity, cardiomegaly, and consolidated lungs that had a patchy, pale golden tissue pattern. The histologic diagnosis was endogenous lipid pneumonia. Findings suggest that endogenous lipid pneumonia can be associated with severe respiratory disease in ferrets.


Quantification of gaping, bruising, and blood spots in salmon fillets using image analysis.
An image analysis method was developed to quantify the gaping, bruising, and blood spots of red salmon (Oncorhynchus nerka) fillets. Images of 15 fillets with various levels of gaping were taken either with a dSLR camera, or with a video camera. Also, the same fillets were recorded using the same camera both under regular illumination, and under polarized illumination. In either case, light at an angle was used to highlight the gapes in the flesh. An image analysis method was developed that can adaptively apply an L*threshold value to the image depending on the average color of the fillet, and quantify the resulting percent of the fillet area that has an L* value less than or equal to L*threshold. Polarized lighting changed the color by eliminating artifacts resulting from reflections. It is recommended to use polarized light for this purpose. Both cameras could be used adequately to quantify defects. The proper setting of the L*threshold value depended on the camera and on the polarized light. No correlation could be found between the average L* value of the fillets and the L*threshold value. It was possible to quantify the gaping, bruising, and blood spots on the salmon fillets using this method, which can be the first step toward the automation of this operation. Gaping, bruising, and blood spots can be recognized and quantified by analyzing images of salmon fillets. Polarized light is recommended to eliminate color artifacts caused by reflected light. This can be used to automate the detection of these defects.


An Nd³⁺-sensitized upconversion nanophosphor modified with a cyanine dye for the ratiometric upconversion luminescence bioimaging of hypochlorite.
Excessive or misplaced production of ClO(-) in living systems is usually associated with many human diseases. Therefore, it is of great importance to develop an effective and sensitive method to detect ClO(-) in living systems. Herein, we designed an 808 nm excited upconversion luminescence nanosystem, composed of the Nd(3+)-sensitized core-shell upconversion nanophosphor NaYF4:30%Yb,1%Nd,0.5%Er@NaYF4:20%Nd, which serves as an energy donor, and the ClO(-)-responsive cyanine dye hCy3, which acts as an energy acceptor, for ratiometric upconversion luminescence (UCL) monitoring of ClO(-). The detection limit of ClO(-) for this nanoprobe in aqueous solution is 27 ppb and the nanoprobe was successfully used to detect the ClO(-) in the living cells by ratiometric upconversion luminescence. Importantly, the nanoprobe realized the detection of ClO(-) in a mouse model of arthritis, which produced an excess of ROS, under 808 nm irradiation in vivo. The excitation laser efficiently reduced the heating effect, compared to the commonly used 980 nm laser for upconversion systems.


Transgene integration, organization and interaction in plants.
It has been appreciated for many years that the structure of a transgene locus can have a major influence on the level and stability of transgene expression. Until recently, however, it has been common practice to discard plant lines with poor or unstable expression levels in favor of those with practical uses. In the last few years, an increasing number of experiments have been carried out with the primary aim of characterizing transgene loci and studying the fundamental links between locus structure and expression. Cereals have been at the forefront of this research because molecular, genetic and cytogenetic analysis can be carried out in parallel to examine transgene loci in detail. This review discusses what is known about the structure and organization of transgene loci in cereals, both at the molecular and cytogenetic levels. In the latter case, important links are beginning to be revealed between higher order locus organization, nuclear architecture, chromatin structure and transgene expression.


Perinatal echovirus infection: insights from a literature review of 61 cases of serious infection and 16 outbreaks in nurseries.
A review of literature published before June 1985 revealed 61 reported cases of neonatal echovirus infection at a nonmucosal site, including 43 cases (70%) due to echovirus 11. Onset of disease occurred between the third and fifth days of life in 63% of cases, indicating that most infections are acquired in the immediate perinatal period rather than in utero. Mortality was higher in infants with severe hepatitis (83%) than in infants with infection of the central nervous system (19%). Acute illness occurred within one week before delivery in 68% of the mothers of nonnosocomially infected infants. There was a trend (P = .11) towards a higher mortality rate for infants born by cesarian section than for those delivered vaginally. In the 11 nosocomially acquired cases, the onset of infection was later and the mortality rate lower. In 16 outbreaks in nurseries, 206 infants developed illness attributed to echovirus infection. Attack rates of clinical disease were 22%-52% and illness was generally mild. In four outbreaks, six index cases were identified as infants who had acquired infection from their mothers; five of these infants had severe disease and three died. The 24 infants subsequently infected by nosocomial spread in these outbreaks had milder disease; three (12%) died. Thus, whereas acute illness in the mother before birth often precedes neonatal echovirus infection and infections transmitted vertically from mother to infant may be severe, postnatal transmission of the same serotype results in milder disease.


The interagency strategic plan for research and development of blood products and related technologies for trauma care and emergency preparedness 2015-2020.
Intensive blood use is expected to occur at levels, which will overwhelm blood supplies as they exist with current capabilities and technologies, both in civilian mass casualty events and military battlefield trauma. New technologies are needed for trauma care, and specifically to provide safer, more effective, and more logistically supportable blood products to treat patients with, or at risk of developing, acquired bleeding disorders resulting from trauma, acute radiation exposure, or other causes. Three of the primary agencies with major research and development programs related to blood products, the Biomedical Advanced Research and Development Authority (BARDA), the Department of Defense (DoD), and the National Heart, Lung, and Blood Institute are uniquely positioned to partner in addressing these issues, which have significant implications for each respective agency, as well as for the US population. Providing leadership, coordination, and oversight for the Food and Drug Administration's national and global health security, counterterrorism, and emerging threats portfolios, the US Food and Drug Administration Office of Counterterrorism and Emerging Threats serves in a critical advisory and facilitative role regarding development and availability of blood products. This plan is informed by the 2012 PHEMCE Strategy (US Department of Health and Human Services, 2012), the 2007 "Shaping the Future of Research" Strategic Plan for the National Heart, Lung, and Blood Institute, the 2011 BARDA Strategic Plan, the DoD Combat Casualty Care Research Program: Policy Review, the 2015 DoD Hemorrhage and Resuscitation Research and Development Strategic Plan, and more than 30 participants from other agencies who participated in planning.


A community-based participatory planning process and multilevel intervention design: toward eliminating cardiovascular health inequities.
The elimination of persistent health inequities requires the engagement of multiple perspectives, resources, and skills. Community-based participatory research (CBPR) is one approach to developing action strategies that promote health equity by addressing contextual as well as individual-level factors, and that can contribute to addressing more fundamental factors linked to health inequity. Yet many questions remain about how to implement participatory processes that engage local insights and expertise, are informed by the existing public health knowledge base, and build support across multiple sectors to implement solutions. This article describes a CBPR approach used to conduct a community assessment and action planning process, culminating in development of a multilevel intervention to address inequalities in cardiovascular disease in Detroit, Michigan. The authors consider implications for future efforts to engage communities in developing strategies toward eliminating health inequities.


Clinical and microbiological outcomes, by causative pathogen, in the ASPECT-NP randomized, controlled, Phase 3 trial comparing ceftolozane/tazobactam and meropenem for treatment of hospital-acquired/ventilator-associated bacterial pneumonia.
In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated. Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7-14 days after the end of therapy) in the microbiological ITT (mITT) population. The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: -4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: -18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: -4.51 to 19.38], respectively, were also comparable. In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.


Caregiver water safety knowledge and views of toddler water competency.
Drowning is the leading cause of death for toddlers. When caregivers are knowledgeable about water safety, they can provide the best protection against drowning. The aim of this study is to survey caregivers of toddlers to better understand factors associated with water safety knowledge, attitudes about pool supervision, and toddler water competency skills. An online survey of 650 parents/caregivers of 1-4-year-old toddlers asked about the caregiver's water safety and swimming background and views on pool supervision. Surveys included a true/false section of ten basic water safety knowledge questions. Caregivers also reported on toddler swim lesson history and whether their toddler could perform six standard water competency skills. Linear regression identified factors predictive of water safety knowledge. On average, caregivers selected the correct answer on six out of ten water safety knowledge questions. Water safety knowledge was predicted by the relationship of the caregiver to the toddler, gender, race, education, prior CPR training, caregiver swim capability, and reported pool supervision style. On average, caregivers reported that their toddler could perform half of the water competency skills. The majority of the toddlers had taken swimming lessons. One third of caregivers believed that after a toddler has had swimming lessons, they don't need to be watched as closely when they are in a pool. Findings suggest that water safety knowledge is poor and that there are misconceptions about toddler supervision needs. Efforts are needed to improve water safety knowledge and to change perceptions about supervision among caregivers of toddlers.


Gold nanoparticle/polymer nanocomposite for highly sensitive drug-DNA interaction.
The interaction of the anticancer drug mitomycin C (MC) and DNA immobilized on gold a nanoparticle/polyvinylferrocenium (AuNP/PVF(+)) coated electrode is presented. This is the first attempt to prepare a biocompatible nanoparticle/redox polymer composite in a one-step and easy electropolymerization procedure and then use the coated electrode for MC-DNA interaction. The prepared electrode exhibits high sensitivity for the investigation of drug-DNA interaction.


Detection of the cardiac function by fractal dimension analysis.
Nonlinearity in circulation control attracts attention because nonlinearity is thought to be essential in the function of the living body. Many investigators have pointed out that the analysis of heart rate variability in particular is important in the analysis of autonomic nerve and cardiac function evaluation. Heart rate variability shows nonlinear behavior. However, until the present, many reports have been premised on linearity; linear correlation by frequency analysis has been used by many studies. However, in terms of this methodology, there is a problem applying it to the nonlinear living body. Therefore, fractal and chaos methodology has been used. The ascertainment of cardiac function has become important in allowing the clinical stage of a ventricular assist system to be successful. The purpose of this study was cardiac function evaluation by a methodology that was premised on nonlinearity. Chaos and fractal theory was used as a nonlinear dynamic theory. As a methodology of measurement, the volume of the left ventricle was used rather than an electrocardiogram, the waveform of arterial blood pressure. The volume was measured using acoustic quantification (AQ) ultrasonic echocardiography. Using these methodologies, the time series of many patients were analyzed. For example, drug administration was attempted in this study, and it was found that some drugs like ACE inhibitors showed a significant effect upon nonlinear dynamics in the cardiovascular system. The result, which attempted cardiac function evaluation by these various methodologies, is reported.


Bayesian hierarchical models for high-dimensional mediation analysis with coordinated selection of correlated mediators.
We consider Bayesian high-dimensional mediation analysis to identify among a large set of correlated potential mediators the active ones that mediate the effect from an exposure variable to an outcome of interest. Correlations among mediators are commonly observed in modern data analysis; examples include the activated voxels within connected regions in brain image data, regulatory signals driven by gene networks in genome data, and correlated exposure data from the same source. When correlations are present among active mediators, mediation analysis that fails to account for such correlation can be suboptimal and may lead to a loss of power in identifying active mediators. Building upon a recent high-dimensional mediation analysis framework, we propose two Bayesian hierarchical models, one with a Gaussian mixture prior that enables correlated mediator selection and the other with a Potts mixture prior that accounts for the correlation among active mediators in mediation analysis. We develop efficient sampling algorithms for both methods. Various simulations demonstrate that our methods enable effective identification of correlated active mediators, which could be missed by using existing methods that assume prior independence among active mediators. The proposed methods are applied to the LIFECODES birth cohort and the Multi-Ethnic Study of Atherosclerosis (MESA) and identified new active mediators with important biological implications.


Salinarimonas ramus sp. nov. and Tessaracoccus oleiagri sp. nov., isolated from a crude oil-contaminated saline soil.
Four bacterial strains, SL014B-41A4(T), SL014B-20A1(T), SL014B-76A1 and SL014B-79A, isolated from a crude oil-contaminated saline soil of Shengli Oilfield, China, were investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SL014B-41A4(T) belonged to the genus Salinarimonas in the order Rhizobiales, with the highest sequence similarity with Salinarimonas rosea YIM YD3(T) (98.3 %). The DNA-DNA relatedness of strain SL014B-41A4(T) to S. rosea YIM YD3(T) was 27.03 ± 3.0 %. Strain SL014B-41A4(T) was Gram-negative staining, facultatively anaerobic and produced deep red pigment in artificial seawater medium. Cells of strain SL014B-41A4(T) were rod-shaped (0.6-4.0 × 1.25-25 µm), motile with a single polar flagellum and often formed branches. The strain contained Q-10 as the predominant respiratory ubiquinone and C(18 : 1)ω7c (57.5 %), C(16 : 0) (16.4 %) and 10-methyl C(19 : 0) (9.1 %) as the major fatty acids. Strains SL014B-20A1(T), SL014B-76A1 and SL014B-79A were actinobacteria and belonged to the genus Tessaracoccus in the family Propionibacteriaceae of the order Actinomycetales with the highest 16S rRNA gene sequence similarities with Tessaracoccus flavescens SST-39(T) (96.4 %), Tessaracoccus lubricantis KISS-17Se(T) (96.2 %) and Tessaracoccus bendigoensis Ben 106(T) (94.7 %). Strains SL014B-20A1(T), SL014B-76A1 and SL014B-79A were Gram-positive staining, facultatively anaerobic, non-endospore-forming, non-motile, acid-fast and oval to rod-shaped (0.48 × 0.5-1.0 µm). These three novel strains had ll-diaminopimelic acid (DAP) as the diagnostic diamino acid in the cell-wall peptidoglycan, MK-9(H(4)) as the only menaquinone and anteiso-C(15 : 0) (67.11-76.14 %) as the major cellular fatty acid. The G+C contents of the genomic DNA of strain SL014B-41A4(T) and strains SL014B-20A1(T), SL014B-76A1 and SL014B-79A were 67.68 mol% and 65.65-67.17 mol%, respectively. Based on phenotypic and genotypic characteristics, strain SL014B-41A4(T) represents a novel species of the genus Salinarimonas, for which the name Salinarimonas ramus is proposed, with strain SL014B-41A4(T) ( = DSM 22962(T) = CGMCC 1.9161(T)) as the type strain. Strains SL014B-20A1(T), SL014B-76A1 and SL014B-79A represent a novel species of the genus Tessaracoccus, for which the name Tessaracoccus oleiagri is proposed, with strain SL014B-20A1(T) ( = DSM 22955(T) = CGMCC 1.9159(T)) as the type strain.


HPV Infection-Associated Cancers: Next-Generation Technology for Diagnosis and Treatment.
Disease caused by human papillomavirus (HPV) remains common, despite preventive vaccines and screening strategies. Globally, HPVs cause one third of infection-associated cancers. The indolent clinical course of the precursor intraepithelial lesions provides an opportunity to understand immunologic obstacles posed by the microenvironment of incipient disease, and how they might be overcome. Results from recent therapeutic HPV vaccine clinical trials suggest that relevant immune responses may be sequestered at the lesion site and are difficult to detect in the circulation. In this Cancer Immunology at the Crossroads article, we outline the current understanding of the risk, diagnosis, and treatment of HPV infection-associated cancers and suggest that quantitative tissue-based endpoints should be included whenever possible in the evaluation of immune-based therapies.


Is vancomycine still a choice for chronic osteomyelitis empirical therapy in iran?
Pyogenic bacteria and especially Staphylococcus aurous (S. aurous) are the most common cause of chronic osteomyelitis. Not only treatment protocol of chronic osteomyelitis occasionally is amiss but also this malady responds to treatment difficultly. This study investigates antibiotic resistance pattern of S. aurous isolated from Iranian patients who suffer from chronic osteomyelitis by two methods: disk diffusion (Kirby bauyer) and E-test (Epsilometer test) to find Vancomycin susceptibility and MIC (Minimum inhibitory concentration). One hundred and thirty one patients who suffer from chronic osteomyelitis which have been referred to both governmental and private hospitals at 2010 were tried out for culturing of osteomyelitis site (sites). Antibiotic susceptibility and MIC of isolated bacteria were investigated by Kirby bauyer and E-test respectively. Samples were collected from bone (73.4%), surrounding tissue (14.6%) and wound discharge (12%). S. aureus was isolated from 49.6% of the samples. According to disc diffusion, methicillin resistance S. aureus (MRSA) was 75% and Vancomycin resistance S. aurous (VRSA) was 0% and based on MIC, MRSA was 68.5% and VRSA was 0%. According to MIC experiments, maximum sensitivity was against to Vancomycin (90.2%) and ciprofloxacin (54.4%) respectively but based on disc diffusion, maximum sensitivity was against to Vancomycin (97.7%) and ciprofloxacin (43.2%), respectively (P = 0.001). E-test (9.8%) in comparison with Disc diffusion (2.3%) showed higher percent of intermediate susceptibility to Vancomycin (P = 0.017). Comparison of antibiograms and MICs showed that Kirby bauyer technique especially for detection of VISA strains is not reliable comparison with E-test. Already VRSA strains have not detected in Iranian chronic osteomyelitis, Thus Vancomycin is the first choice for chronic osteomyelitis empirical therapy in Iran yet.


CIRPLAST: Cleft Lip and Palate Missions in Peru.
The author presents a 20-year experience leading cleft lip and palate surgical volunteer missions in Peru for CIRPLAST, a nonprofit volunteer plastic surgery goodwill program that has provided free surgery for patients with cleft lip and palate deformities in remote areas of Peru. Surgical procedures were performed by the author, together with a group of experienced plastic surgeons, under the auspices of the Peruvian Plastic Surgery Society, and local health authorities. CIRPLAST missions are scheduled annually in different locations around Peru. Selected patients for surgery after adequate screening are photographed, and their cleft deformity is recorded. Scheduled patients or their parents, when they are minors, sign an informed consent form. Patients operated on in any given day are examined and photographed 1 day after surgery, before discharge. Between 30 and 35 patients are operated on at each mission site. About 2 weeks after the mission, patients are checked and photographed, and the outcome of surgery is recorded. Complications that may occur are recorded and treated by the CIRPLAST team as soon as possible. Almost all operations are performed under general endotracheal anesthesia coupled by local anesthesia containing a vasoconstrictor, to reduce bleeding and facilitate tissue dissection. All wounds of the lip and palate are closed with absorbable sutures, to avoid the need for suture removal. After cleft lip surgery, patients go to the recovery room for monitoring by nurses until they recover completely. A total of 6108 cleft lip and palate repairs, primary and secondary, were performed by CIRPLAST in 141 missions, between May 12, 1994, and October 15, 2014. The medical records of the 5162 patients (84.5%) who returned for follow-up (ranging from 12 days to 9 years) were reviewed retrospectively. Between 45% and 70% of the patients operated on a mission have returned for early follow-up and some the following year. There were 3176 males (51.9%) and 2932 females (48.1%). The incidence of isolated lip clefts was 1546 patients (25.3%); of isolated palate clefts, 2223 patients (36.4%); and combined defects, 2339 patients (38.3%). Of the 5162 patients who returned for follow-up, 377 patients (7.3%) had complications. Lip wound dehiscence was present in 58 patients (15.4). Palate fistula formation in 33 patients (8.8%): 24 (6.4%) after primary palate closure, and 9 (2.4%) after previous fistula closure. Infection occurred in 37 cleft lip patients (9.8%). Hypertrophic lip scars were seen in 56 patients (14.9%). Bleeding occurred in the recovery room after palatoplasty in 48 patients (12.7%), and in most cases, it was contained by applying pressure. No blood transfusions were used. Residual deformities of varying degree of the nose and/or lip occurred in 145 patients (38.5%). All required reoperation for correction. There were no intraoperative deaths in this series. During the past 20 years, the CIRPLAST team has offered free surgery with good outcomes and few complications, to more than 6000 cleft lip and/or palate patients in remote areas of Peru.


Vitamin D deficiency is an independent predictor of anemia in end-stage heart failure.
Both, anemia and vitamin D deficiency are prevalent in patients with heart failure. According to recent evidence, vitamin D may stimulate erythropoiesis. We measured circulating 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH](2)D) and hemoglobin (Hb) in a cross-sectional study in 364 end-stage heart failure patients awaiting cardiac transplantation, of whom 52.6% met the criteria for anemia (Hb < 13 g/dl in males and <12 g/dl in females). None of the patients were on erythrocyte-stimulating agents. Of the study cohort, 87.8% had 25(OH)D concentrations below 50 nmol/l. The mean Hb concentrations were significantly reduced in the lower tertiles of 25(OH)D and 1,25(OH)(2)D (P < 0.001). In multivariate-adjusted logistic regression analyses, the odds ratios for anemia of the lowest tertile of 25(OH)D (<18 nmol/l) and 1,25(OH)(2)D (<40 pmol/l) were 2.69 (1.46-5.00) and 4.08 (2.18-7.62) compared with their respective highest tertile (>32 nmol/l and >70 pmol/l). Patients with severe dual deficiency of 25(OH)D and 1,25(OH)(2)D had an odds ratio for anemia of 9.87 (95% CI 3.59-27.1) compared with patients in the highest tertile for both vitamin D metabolites. Circulating 1,25(OH)(2)D was directly related to circulating 25(OH)D levels and kidney function (P < 0.001), and inversely associated with C-reactive protein (P = 0.020). Our data demonstrate that vitamin D deficiency is independently associated with low Hb values and anemia in end-stage heart failure. Circulating 1,25(OH)(2)D is a better predictor of anemia than circulating 25(OH)D. Prospective randomized studies with administration of vitamin D (metabolites) will have to clarify if the association of vitamin D deficiency with anemia is causal.


The attrition rate of students in master's level nurse anesthesia programs.
This survey was conducted in October 1990. Survey forms were sent to all nurse anesthesia programs offering master's degrees. The purpose of the study was to determine the dropout rate of students who did not complete their programs during the period from 1985 to 1990. Directors were asked to rate their satisfaction to determine if students were more likely to leave because of clinical or academic difficulties or for personal reasons. The time frame and the circumstances surrounding the students' departures were also examined. The attrition rate of programs ranged from 0-25% (mean = 8.2%). More than half the students left for personal reasons. The remainder were almost equally divided between clinical and academic reasons. In fact, many directors had difficulty distinguishing between these two causes. Most students left during the first 12 months of their program, and more than half of them were not encouraged to resign. A large majority (78%) of directors found their program's attrition rate to be very acceptable.


Cellulose nanocrystals/ZnO as a bifunctional reinforcing nanocomposite for poly(vinyl alcohol)/chitosan blend films: fabrication, characterization and properties.
In this study, cellulose nanocrystals/zinc oxide (CNCs/ZnO) nanocomposites were dispersed as bifunctional nano-sized fillers into poly(vinyl alcohol) (PVA) and chitosan (Cs) blend by a solvent casting method to prepare PVA/Cs/CNCs/ZnO bio-nanocomposites films. The morphology, thermal, mechanical and UV-vis absorption properties, as well antimicrobial effects of the bio-nanocomposite films were investigated. It demonstrated that CNCs/ZnO were compatible with PVA/Cs and dispersed homogeneously in the polymer blend matrix. CNCs/ZnO improved tensile strength and modulus of PVA/Cs significantly. Tensile strength and modulus of bio-nanocomposite films increased from 55.0 to 153.2 MPa and from 395 to 932 MPa, respectively with increasing nano-sized filler amount from 0 to 5.0 wt %. The thermal stability of PVA/Cs was also enhanced at 1.0 wt % CNCs/ZnO loading. UV light can be efficiently absorbed by incorporating ZnO nanoparticles into a PVA/Cs matrix, signifying that these bio-nanocomposite films show good UV-shielding effects. Moreover, the biocomposites films showed antibacterial activity toward the bacterial species Salmonella choleraesuis and Staphylococcus aureus. The improved physical properties obtained by incorporating CNCs/ZnO can be useful in variety uses.


Clinical risk factors for the development of late-onset circulatory collapse in premature infants.
Very low birth weight (VLBW) infants may be at risk for late-onset circulatory collapse (LCC) where otherwise stable infants develop hypotension resistant to vasoactive agents. The risk factors for LCC development are poorly defined, and it has been theorized that it may be in part due to withdrawal from exogenous prenatal steroids. The goal of this study was to define the clinical characteristics of LCC and investigate its association with antenatal steroid administration. This is a retrospective cohort study of infants born ≤1500 g. LCC was retrospectively diagnosed in infants requiring glucocorticoids for circulatory instability at >1 week of life. Demographic and clinical characteristics were compared between groups using Mann-Whitney test. Three hundred and ten infants were included; 19 (6.1%) developed LCC. Infants with LCC were born at a median 4.6 weeks' lower gestation, 509 g lower birth weight than those without LCC. There was no difference in antenatal steroid delivery between the groups. LCC occurs in a distinct subset of VLBW infants, suggesting the need for monitoring in this high-risk population. Antenatal steroids did not significantly increase the risk of LCC development in this study. Late-onset circulatory collapse (LCC) is a life-threatening clinical entity occurring in around 6% in VLBW infants and is likely underdiagnosed in the United States. Targeting specific demographic characteristics such as birth weight (<1000 g) and gestational age at birth (<26 weeks) may allow for early identification of high-risk infants, allowing close monitoring and prompt treatment of LCC. No significant association was found between antenatal steroid administration and LCC development, suggesting that the theoretical risks of antenatal steroids on the fetal HPA axis does not outweigh the benefits of antenatal steroids in fetal lung maturity. To date, no studies characterizing LCC have originated outside of Asia. Therefore, providing a description of LCC in a U.S.-based cohort will provide insight into both its prevalence and presentation to inform clinicians about this potentially devastating disorder and foster early diagnosis and treatment. This study validates LCC characteristics and prevalence previously outlined by Asian studies in a single-center U.S.-based cohort while also identifying potential risk factors for LCC development. This manuscript will provide education for U.S. physicians about the risk factors and clinical presentation of LCC to facilitate early diagnosis and treatment, potentially decreasing neonatal mortality. With prompt recognition and treatment of LCC, infants may have decreased exposure to vasoactive medications that have significant systemic effects.


Influence of renal function on the hemodynamic and clinical responses to long-term captopril therapy in severe chronic heart failure.
To evaluate the influence of renal function on the efficacy of converting-enzyme inhibition in patients with severe chronic heart failure, we measured the long-term hemodynamic and clinical responses to captopril in 101 consecutive patients with heart failure grouped according to pretreatment serum creatinine concentration (group I, less than 1.4 mg/dL; group II, 1.4 to 2.8 mg/dL; and group III, greater than 2.8 mg/dL). After 1 to 3 months of treatment, patients with preserved renal function (group I) had greater increases in stroke volume index and greater decreases in left ventricular filling pressure and systemic vascular resistance than did patients with renal impairment (groups II and III) (p less than 0.05). Clinical improvement paralleled these hemodynamic benefits; only 2 of 12 patients with severe renal insufficiency (group III) improved clinically compared with 29 of 40 patients with preserved renal function (group I) and 29 of 49 patients with mild-to-moderate renal impairment (group II), (p less than 0.005). Therapy-limiting rash and dysgeusia occurred most frequently in patients with renal impairment. Our findings support an important role for the kidneys in mediating the beneficial actions of captopril in patients with severe congestive heart failure.


A record sheet for pressure sore risk assessment.
Pressure sore risk assessment should be used to inform practice. Differences exist in methods of using risk assessment scales. Nurses need a way of recording risk factors quickly and easily in a format which indicates what action should be taken.


Clinical and genetic characterization of an autosomal dominant nephropathy.
Autosomal dominant familial nephropathies with adult onset, no macroscopic cysts, and progressive deterioration include medullary cystic disease (ADMCKD) as well as other less specific entities. We studied a kindred of Jewish ancestry in which 15 members (both male and female) have suffered from chronic renal failure. The first evidence of renal involvement was observed between 18 and 38 years. It included hypertension followed by progressive renal insufficiency. No polyuria, anemia, gout, hematuria, nor proteinuria were seen. An average of 4.5 years elapsed from diagnosis to end-stage renal disease. Renal pathology at early stages of the disease showed extensive tubulointerstitial fibrosis and global glomerulosclerosis. Linkage analysis was performed at the two known loci of ADMCKD, on Chromosomes 1 and 16. Linkage to the chromosome 16 locus was excluded. However, linkage to the chromosome 1q21 locus of ADMCKD was established with a maximum two-point LOD score of 3.82 to D1S394. The disease interval could be narrowed to about 9 cM/7.4 Mb between D1S1156 and D1S2635. Multiple-point linkage analysis revealed a maximum LOD of 4.21, with a broad peak from markers D1S2858 and D1S2624. This report establishes linkage between a familial nephropathy characterized by hypertension and progressive renal failure to the locus described for ADMCKD, a disease classically associated with macroscopic corticomedullary cysts, salt-losing tubulointerstitial nephropathy, and anemia. This finding broadens the clinical spectrum of ADMCKD positioned on chromosome 1q21 locus.