Estrogen regulation of protein synthesis in the immature rat uterus: the analysis of proteins released into the medium during in vitro incubation.
Immature rats were treated with estradiol (E2) or other steroids before their uteri were removed and incubated under in vitro conditions in the presence of [35S]methionine. The analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the radiolabeled proteins synthesized and released into the incubation medium demonstrate that E2 regulates the appearance of two proteins. These two proteins have mol wt of 115,000 and 65,000. The concentration of proteins in the medium increases linearly with time, suggesting that they may be secreted. These two proteins were not produced by several other tissues in response to E2 and appear to be specific to the uterus. They also appear to be increased only by estrogens (E2 greater than estrone greater than estriol) and not by other steroids tested. They are increased in response to a single injection within 6 h, and the maximal concentration of proteins occurs approximately 24 h after E2 administration. The protein concentrations have essentially returned to control values by 72 h after hormone injection. The kinetics of the induction is the same for both proteins, suggesting that their increase may be coordinated. Based on the tissue and hormone specificity of the increase in the 115,000- and the 65,000-dalton proteins, they may serve as reliable markers for the study of the uterine response to E2.


[Behavior of the Y and Peruvian strains of Trypanosoma cruzi in mice, after passage through various media].
The behavior of two strains of Trypanosoma cruzi (Y and Peruvian strains) in experimental mouse infection, after being passed through different conditions of maintainance and cultivation was studied. The conditions were: Warren's acellular culture medium, cryopreservation in liquid Nitrogen, passage through the insect vector and direct blood passage from mice to mice. The parameters considered for comparative study were as follows: parasitemia, mortality rate, maximum survival time, morphology of parasites in peripheral blood, tissue tropism and histopathological lesions. Each experimental group consisted of two sub-groups according to the inocula: 10.000 or 50.000 trypomastigotes. The basic characteristics of the strains remained unchanged. These were macrophagotropism, predominance of slender forms of the parasite in early infection and 100 per cent mortality rate in the acute phase of the infection. However, decrease in the virulence was observed when the culture forms were used or when the infection with low inoculum was used (10.00 forms). Therefore the main biological characteristics of the strains tended to remain the same, regardless of the conditions used for maintainance and cultivation.


Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life.
To establish the efficacy of 24-h ambulatory and casual blood pressure (BP) reduction, and the tolerability of once daily felodipine extended release (ER) 2.5 mg and felodipine ER 5 mg as monotherapy. Randomised, double-blind placebo controlled 6 weeks parallel study. From 15 general practices centres (with 19 GPs) in the region of the University of Maastricht, The Netherlands. A total of 129 subjects aged 50-80 years with primary hypertension were screened; 27 men and 61 women with a casual diastolic BP of 100-115 mm Hg and/or a systolic BP of less than 200 mm Hg entered the study. Casual and 24-h ambulatory BP and a subjective symptom assessment (SSA) questionnaire after 6 weeks of therapy. After correlation for placebo response the mean casual systolic/diastolic BP (SBP/DBP) reduction was 10/5 mm Hg (NS) and 12/10 mm Hg (P < 0.05) for felodipine ER 2.5 and 5 mg, respectively. By using 24-h ambulatory BP measurements these reduction were 6/4 mm Hg (NS) and 13/8 mm Hg (P < 0.05), respectively. No significant difference for SBP and DBP was found during the night time between felodipine 2.5 and placebo (-1/0). Felodipine ER 5 mg lowered the BP load significantly during both daytime and night time but felodipine ER 2.5 mg only for DBP during the daytime. There was a significant difference for the number of responders between placebo (28%) vs felodipine ER 2.5 mg (55%) and ER 5.0 mg (59%). Both felodipine dosages and placebo were comparable in (a low) number of adverse events and results of the SSA. During daytime felodipine ER 2.5 mg and 5 mg are effective in BP lowering in elderly hypertensive patients. However, only felodipine ER mg is effective in reducing BP during night time (22.00-7.00). Only felodipine ER 5 mg has a significant reducing effect on BP load during day and night time. Both felodipine ER 2.5 and ER 5.0 have a significant effect on the responder rate. It appeared from this study that compared to placebo, and in contrast with felodipine ER 5 mg, the ER form of felodipine 2.5 mg has no BP lowering effect during night time in elderly patients. To assess the effectivity during night time of felodipine ER 2.5 mg in an individual patient it is recommendable to measure the BP at the end of the dose interval.


Neurologic Injuries in the Athlete's Shoulder.
To review the presentation, evaluation, treatment, and prognosis of various nerve injuries about the shoulder in the athletic population. Included are injuries to the axillary, suprascapular, musculocutaneous, long thoracic, and spinal accessory nerves. This article represents a review of the literature regarding incidence, presentation, and results of treatment of these various nerve injuries. The clinically pertinent anatomy is also presented to better relate mechanism of injury to the occurrence of nerve injury. I searched MEDLINE from 1966 through 1999 and the Journal of Shoulder and Elbow Surgery from 1992 through 1999 for the key words "nerve" and "shoulder." A historical review of treatment results is presented as well as a review of treatment options and the results of studies using modern techniques in the management of nerve injuries. Nerve injuries about the shoulder present as distinct clinical syndromes, although signs and symptoms can be subtle. The athletic trainer and team physician must be able to recognize the presentation of these injuries so that adequate evaluation and prompt treatment can be instituted to maximize the athlete's chance for early return to sport.


Lid-Parallel Conjunctival Folds and Their Ability to Predict Dry Eye.
The observation of lid-parallel conjunctival folds (LIPCOF) is reported to be useful in dry eye diagnoses. Around 70% of the European clinicians use this test in a dry eye clinic. This study investigated the sensitivity and specificity of LIPCOF to predict dry eye. Ocular Surface Disease Index (OSDI) outcome, noninvasive break-up time (NIKBUT) using the Keratograph (Oculus, Wetzlar, Germany), and LIPCOF of 148 randomized selected patient reports (88 females; mean age=37.0±12.9 years) from 3 different sites were analyzed. Subjects were divided into dry eye and non-dry eye groups by OSDI only, named symptomatic dry eye (OSDI scores ≥15) and by a composite score (OSDI scores ≥15 and NIKBUTaverage of ≤9 sec). Lid-parallel conjunctival folds (temporal, nasal, Sum [=temporal+nasal]) were significantly correlated to OSDI and to NIKBUTaverage (Spearman; r>-0.185, P<0.013). NIKBUTaverage (r=-0.322; P<0.001) was significantly correlated to OSDI scores. Based on the OSDI questionnaire, 37.2% of the subjects were symptomatic and 14.7% were positive for dry eye based on the composite score. Lid-parallel conjunctival folds were a significant discriminator between healthy and dry eye subjects (P≤0.001). The areas under the receiver operating characteristic curve for temporal LIPCOF, nasal LIPCOF, and LIPCOF Sum were 0.716, 0.737, and 0.771, respectively, for the symptomatic dry eye group and 0.771, 0.719, and 0.798, respectively, for the composite dry eye group. As LIPCOF demonstrated high predictive ability of dry eye; it appears to be a promising test in the diagnoses of dry eye.


Viedma ripening: a reliable crystallisation method to reach single chirality.
Crystallisation processes have evolved to practical methods that allow isolation of an enantiopure product in high yield. Viedma ripening in particular enables access to enantiopure products in a reliable way, simply through grinding of crystals in a solution. This tutorial review covers the basic principles behind asymmetric crystallisation processes, with an emphasis on Viedma ripening, and shows that to date many novel organic molecules can be obtained in enantiopure solid form.


Hypergammaglobulinemic purpura in systemic autoimmune rheumatic diseases: predictive value of anti-Ro(SSA) and anti-La(SSB) antibodies and treatment with indomethacin and hydroxychloroquine.
To define the clinical manifestations, autoantibody associations, optimal treatment, and prognosis of hypergammaglobulinemic purpura associated with systemic autoimmune rheumatic diseases. Of 303 consecutive patients with systemic autoimmune rheumatic diseases evaluated over 5 years, 17 French Canadian patients with hypergammaglobulinemic purpura with systemic lupus erythematosus (SLE) (n = 12) or another systemic autoimmune rheumatic disease (n = 5) were identified and followed prospectively. Mild secondary Sjörgren's syndrome developed in 9 (53%) patients. Sixteen (94.1%) patients were women. Attacks of hypergammaglobulinemic purpura occurred in the pretibial (76.5%) or perimalleolar (70.5%) areas or the dorsal aspect of the feet (52.9%). Triggering factors included walking, prolonged standing, and alcohol intake. The mean duration of attacks was 6.1 days. Systemic manifestations consistent with a flare of the underlying systemic autoimmune rheumatic diseases accompanied hypergammaglobulinemic purpura attacks in 15 (88%) patients. Arthralgias (n = 13, 86.6%), arthritis (n = 9, 69.2%), and periarthritis were characterstically localized adjacent to the purpura. Anti-Ro antibodies were expressed in all (100%) patients with hypergammaglobulinemic purpura with SLE, but in only 11 (28.9%) of 38 consecutive patients with SLE without hypergammaglobulinemic purpura (P < 0.000001, odds ratio 84, 95% confidence interval 4.6, 1525). The positive predictive values for hypergammaglobulinemic purpura in SLE were: anti-Ro plus anti-La 73%, anti-La 57%, and anti-Ro 52%. The negative predictive value of anti-Ro was 100%. Although 11 (92%) patients with SLE with anti-Ro expressed anti-52 kDa Ro [4 (36.3%) of whom also expressed anti-60 kDa Ro], this frequency was not greater than in anti-Ro positive patients with SLE without hypergammaglobulinemic purpura. The effects of indomethacin or hydroxychloroquine were assessed over 6 months in 8 patients with recurrent incapacitating hypergammaglobulinemic purpura. Complete (n = 4) or partial (n = 4) remission of hypergammaglobulinemic purpura occurred. In 5 additional patients with severe hypergammaglobulinemic purpura, attacks stopped with prednisone 25 to 60 mg daily. The mean duration of hypergammaglobulinemic purpura followup was 5.4 years (range 1-6 years). At last followup, hypergammaglobulinemic purpura had resolved in 11 (64.7%) patients despite persistently abnormal serology. In the absence of anti-Ro antibodies, a presumptive diagnosis of hypergammaglobulinemic purpura secondary to SLE should be questioned. Prednisone should be used only in severe hypergammaglobulinemic purpura. Indomethacin and hydroxychloroquine are of value in the treatment of milder hypergammaglobulinemic purpura.


[Successful preimplantation genetic diagnosis for beta-thalassemia using multiplex nested polymerase chain reaction].
To develop single-cell multiplex nested polymerase chain reaction (PCR) assays for preimplantation genetic diagnosis (PGD) in couples at risk of having child with beta-thalassemia. Primers were designed and synthesized according to the documented mutation sites common among Chinese. Venous blood was collected from 4 pairs of husband and wife, all heterozygotes for beta-thalassemia, and underwent multiple nested PCR. Intraooplasmic sperm injection and mechanical bio psy was used to obtain single blastomere. Multiplex nested PCR was used to detect the CD41-42 mutation and the closely linked polymorphic marker, HumTHO1 gene or CD41-42, CD41-28, IVSII654 mutation and HumTHO1 gene in the single blastomeres from four clinical PGD cycles. The normal embryos with high scores capable of continuing to divide were transplanted into the uteri. The process of gestation was observed. 200 lymphocytes were amplified by nested PCR. The average amplification rate of the most common 16 beta-thalassemia mutations in Chinese population was 91.3% and the average rate of allele drop out for different sites was 17.0% without differences between any 2 sites. During the 4 PGD cycles 33 embryos underwent bioassay with a success rate of 100%. 33 blastomeres were obtained to undergo PCR, of which 30 were successfully amplified with an amplification rate of 90.9%. Explicit diagnosis was obtained in 26 of the 30 embryos: 7 normal homozygotes, 11 heterozygotes, and 8 abnormal or complex heterozygotes. One or more embryos were transferred back into the uteri of the 4 women and clinical pregnancy occurred in one woman. Five weeks after the implantation B-mode ultrasonography showed monocyesis, and in the 17th week of gestational period paracentesis of cord blood showed normal homozygote. At last a normal female infant confirming the PGD result had been born, which was the first reported unaffected pregnancy resulting from PGD using multiplex nested PCR for couples as beta-thalassemia gene carriers. The results of diagnosis for embryo all corresponded to those for blastomere. The average ADO rate of blastomere was 13.3% (4/30). PGD using multiplex nested PCR, as an alternative to prenatal diagnosis, is a reliable and effective way to help couples-carriers of pathogenetic genes to get a healthy baby.


Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome in adolescent and young adult patients.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable treatment option for adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS). The study aim was to evaluate epidemiological data and identify prognostic factors for AYA patients with MDS undergoing allogeneic HSCT. Here, 645 patients were selected from patients enrolled in a multicenter prospective registry for HSCT from 2000 to 2015. The primary endpoint was 3-year overall survival (OS). Survival rates were estimated using the Kaplan-Meier method. Prognostic factors were identified using the multivariable Cox proportional hazards model. The 3-year OS was 71.2% (95% confidence interval [CI]: 67.4-74.6%). In multivariable analysis, active disease status (adjusted hazard ratio: 1.54, 95% CI: 1.09-2.18, p = 0.016), poor cytogenetic risk (1.62, 1.12-2.36, p = 0.011), poor performance status (2.01, 1.13-3.56, p = 0.016), human leukocyte antigen (HLA)-matched unrelated donors (2.23, 1.39-3.59, p < 0.001), HLA-mismatched unrelated donors (2.16, 1.09-4.28, p = 0.027), and cord blood transplantation (2.44, 1.43-4.17, p = 0.001) were significantly associated with poor 3-year OS. In conclusion, in AYA patients with MDS the 3-year OS following allogeneic HSCT was 71.2%. Active disease status, poor cytogenetic risk, poor performance status, and donor sources other than related donors were associated with poor 3-year OS.


Treatment and outcomes of type 2 myocardial infarction and myocardial injury compared with type 1 myocardial infarction.
Type 2 myocardial infarction (MI) is defined by a rise and fall of cardiac biomarkers and evidence of ischemia without unstable coronary artery disease (CAD) because of a mismatch in myocardial oxygen supply and demand. Myocardial injury is similar but does not fulfill the clinical criteria for MI. There is uncertainty in terms of the clinical characteristics, management, and outcomes of type 2 MI and myocardial injury in comparison with type 1 MI. Patients admitted to a Veterans Affairs tertiary care hospital with a rise and fall in cardiac troponin were identified. MI and injury subtypes, presentation, management, and outcomes were determined. Type 1 MI, type 2 MI, and myocardial injury occurred in 137, 146, and 175 patients, respectively. Patients with type 2 MI were older (P=0.02), had lower peak cardiac troponin (P<0.001), and were less likely to receive aspirin and statin at discharge (P<0.001) than type 1 MI survivors. All-cause mortality (median follow-up: 1.8 years) was not different between patient groups (type 1 MI mortality: 29.9%, type 2 MI: 30.8%, myocardial injury: 29.7%; log rank P=0.94). A significant proportion of deaths were attributed to cardiovascular causes in all subgroups (type 1 MI: 34.1%, type 2 MI: 17.8%, myocardial injury: 30.8%). Patients with type 2 MI and myocardial injury were less likely to receive medical therapy for CAD than those with type 1 MI. No differences in all-cause mortality among MI subtypes were observed. Additional studies to determine optimal medical therapy and risk stratification strategies for these high-risk populations are warranted.


Healthcare utilisation prior to suicide in persons with alcohol use disorder: national cohort and nested case-control study.
Alcohol use disorder (AUD) is common and associated with increased risk of suicide. To examine healthcare utilisation prior to suicide in persons with AUD in a large population-based cohort, which may reveal opportunities for prevention. A national cohort study was conducted of 6 947 191 adults in Sweden in 2002, including 256 647 (3.7%) with AUD, with follow-up for suicide through 2015. A nested case-control design examined healthcare utilisation among people with AUD who died by suicide and 10:1 age- and gender-matched controls. In 86.7 million person-years of follow-up, 15 662 (0.2%) persons died by suicide, including 2601 (1.0%) with AUD. Unadjusted and adjusted relative risks for suicide associated with AUD were 8.15 (95% CI 7.86-8.46) and 2.22 (95% CI 2.11-2.34). Of the people with AUD who died by suicide, 39.7% and 75.6% had a healthcare encounter <2 weeks or <3 months before the index date respectively, compared with 6.3% and 25.4% of controls (adjusted prevalence ratio (PR) and difference (PD), <2 weeks: PR = 3.86, 95% CI 3.50-4.25, PD = 26.4, 95% CI 24.2-28.6; <3 months: PR = 2.03, 95% CI 1.94-2.12, PD = 34.9, 95% CI 32.6-37.1). AUD accounted for more healthcare encounters within 2 weeks of suicide among men than women (P = 0.01). Of last encounters, 48.1% were in primary care and 28.9% were in specialty out-patient clinics, mostly for non-psychiatric diagnoses. Suicide among persons with AUD is often shortly preceded by healthcare encounters in primary care or specialty out-patient clinics. Encounters in these settings are important opportunities to identify active suicidality and intervene accordingly in patients with AUD.


Tick-borne encephalitis virus, ticks and humans: short-term and long-term dynamics.
Much public health concern and scientific interest has been kindled by significant increases in incidence of tick-borne encephalitis over the past 1-2 decades. It is the most important vector-borne disease of humans in Europe, for which excellent long-term data allow robust quantitative analyses. Despite the increasing tendency to attribute all increases in vector-borne diseases to climate change, there is no convincing evidence that the appearance of new foci in Sweden, Switzerland, France and Germany during this century, or the upsurge in cases within well recognized endemic regions, is due to the recorded minor extensions of infectious ticks into higher altitudes and latitudes and into winter periods, in response to warmer conditions. Rather, there is now good evidence of greater human exposure to infected ticks through altered socioeconomic circumstances (in addition to higher densities of tick-feeding deer--not reviewed here), so far best quantified for Central and Eastern Europe. Increased awareness of tick-borne encephalitis and understanding of the changing risk factors, including the role of human behaviour, will ensure better personal protection against infection, including vaccination and avoidance of high-risk activities.


Which dimensions of forgiveness mediate and moderate childhood trauma and depression? Insights to prevent suicide risk among university students.
College students who are depressed as a direct or indirect effect of childhood trauma are at risk of suicide. Although forgiveness buffers mental health problems, there are inconsistencies in the results according to the object of forgiveness. This study aimed to examine the role of forgiveness, both as a mediator and as a moderator, for the association between childhood trauma and depression among university students. The sample comprised 398 students from a university in Semarang, Indonesia (M = 18.60, SD = 0.60, male = 26.1%) obtained through cluster random sampling. Measurements used were the Adverse Childhood Experiences (ACEs) questionnaire, Beck Depression Inventory-II (BDI-II) and the Forgiveness Scale which contained the dimensions of self, others, and situations. The path analysis and the investigation of CI result showed that forgiveness mediated the relationship between ACEs and depression. Forgiveness of self and situations were also mediating, but not forgiveness of others. On the other hand, the moderating effect only applied to the forgiveness of others, the effect of which increased positively when the level was high. The result of this study indicates how the addition of ACEs affects lower level of forgiveness, thus explaining the higher level of depression among college students. Only forgiveness of others among the dimensions of forgiveness is not determined by the number of ACEs, but its increase determines the addition of depression level when there are more ACEs. The discussions highlight the mechanism of each dimension, contribution of collectivistic culture, different types of ACEs and limited incidence of ACEs among the general college student population.


Immunogenicity and tolerability of a heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 12 months of age.
The recommended vaccination schedule for the pneumococcal conjugate vaccine (PCV) includes 4 immunizations, according to the national programs in the United States and some European countries. Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses. The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life (a 2+1 dose schedule) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b (Hib) vaccine. A total of 101 healthy Swedish infants were enrolled in an open, nonrandomized, multicenter study. PCV was administered concomitantly with (at separate sites) a diphtheria-tetanus toxoids-acellular pertussis vaccine, inactivated polio vaccine and Hib conjugate vaccine combination at 3, 5 and 12 months of age. IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum samples taken at 3, 6, 12 and 13 months were determined with enzyme immunoassays. Local and systemic reactions were monitored for 3 days after each immunization, and serious adverse reactions were monitored for the whole study period. Two doses of PCV induced satisfactory antibody responses, with the exception of serotypes 6B and 23F. The third dose evoked strong responses for all serotypes, which suggests good immunologic priming with the primary series of 2 doses. The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children. The PCV was well tolerated. The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule. The results suggest that the implementation of a 2+1 dose schedule for PCV should be considered.


How do risk factors for mortality and overall complication rates following laparoscopic and open colectomy differ between inpatient and post-discharge phases of care? A retrospective cohort study from NSQIP.
Risk factors for complications differ between laparoscopic (LC) and open colectomy (OC) patients, given the selection bias between these groups. How risk factors for these outcomes differ between inpatient and post-discharge phases of care requires further study. A retrospective cohort study (2005-2010) using NSQIP data was performed comparing OC and LC patients. Multivariable logistic regression was used to compare covariates associated with mortality and overall complication rates both before and after hospital discharge. Patients in the LC cohort were younger (64.2 vs. 62.5 years; P < 0.0001) with a lower incidence of comorbidities. OC was associated with a higher incidence of mortality compared to LC among inpatients (3.3 vs. 0.61%, P < 0.0001) and following discharge (0.88 vs. 0.29%, P < 0.0001). OC also demonstrated a higher incidence of overall complication rates for both inpatients (22.32 vs. 9.36%, P < 0.0001) and following discharge (8.83 vs. 7.24%, P < 0.0001). Risk factors (P < 0.05) for mortality following LC included age and emergency procedures for inpatients; pre-operative SIRS was associated with mortality occurring after discharge. For the OC cohort, risk for mortality was increased with smoking and contaminated/dirty wounds for inpatients; pre-operative weight loss was associated with death following discharge. Factors associated with increased risk of morbidity following LC included smoking history for inpatients and pre-operative steroid therapy following discharge. Following OC, morbidity was strongly associated with ASA scores for inpatients; pre-operative steroid therapy was a risk factor following discharge. Obesity was strongly associated with non-mortal complications in both cohorts following discharge. (1) LC is associated with a lower incidence of post-operative mortality and complications. (2) Risk factors associated with adverse post-operative outcomes change during the post-operative period; surveillance for these outcomes should be tailored by operative technique and phase of post-operative care (3) Obesity is an underappreciated risk for complications following discharge for both LC and OC.


Socioeconomic Factors Associated With Burnout Among Oncology Trainees.
Burnout in the medical workforce leads to early retirement, absenteeism, career changes, financial losses for medical institutions, and adverse outcomes for patients. Recent literature has explored burnout in different specialties of medicine. This article examines burnout among medical oncology trainees and identifies factors associated with burnout and professional dissatisfaction, including socioeconomic factors. US medical oncology programs were sent a survey that included the Maslach Burnout Index-Human Services Survey as well as demographic, socioeconomic, and program-specific questions tailored to medical oncology fellowship. Primary binary end points included burnout, satisfaction with being a physician, and satisfaction with being a medical oncologist. Binomial logistic models determined associations between various characteristics and end points. Overall, 261 US fellows completed the survey. Seventy percent of international medical graduates reported no educational debt, whereas only 36% of US graduates reported no educational debt. Eighty-two percent of survey respondents reported their mother had at least a bachelor's degree, and 87% of respondents reported their father had at least a bachelor's degree. At least 27% of respondents had symptoms of burnout. Factors inversely associated with burnout on multivariable analysis included having a mother who graduated college (odds ratio [OR], 0.27), reporting an adequate perceived balance between work and personal life (OR, 0.22), feeling that faculty care about educational success (OR, 0.16), and being in the final year of training (OR, 0.45). Having debt ≥ $150,000 (OR, 2.14) was directly associated with burnout. Symptoms of burnout are common among medical oncology fellows and are associated with educational debt and socioeconomic factors.


Ultrasonography and developmental dysplasia of the infant hip.
Hip sonography has been developed, refined, and critiqued for over 18 years. It is now widely accepted as a highly sensitive and useful technique for both the diagnosis and management of developmental dysplasia of the infant hip. Controversy continues surrounding the issue of when and how often hip sonography should be performed. Currently, clinical screening of newborns is the standard of care in the United States, with sonography employed selectively based on clinical findings. Universal ultrasound screening has been used in some countries and is under consideration by many investigators, using a variety of algorithms. This review will focus on recent reports dealing with issues of screening for developmental dysplasia of the infant hip and also will highlight techniques suggested for use in the treatment of development dysplasia of the infant hip.


Optimization of the Surface Activity of Biosurfactant-Surfactant Mixtures.
The impact that rhamnolipid (RL) and sophorolipid (SL) biosurfactants has on solution surface activity when used in conjunction with the commercially important zwitterionic surfactant cocamidopropyl betaine (CAPB) is highlighted for the first time through surface tension and surface rheology measurements on binary and ternary mixtures of these surfactants. It was observed that in both the binary (CAPB/RL) and the ternary (CAPB/RL/SL) mixtures, RL tends to dominate at the air-water interface and primarily control both surface tension and surface elasticity behavior. Significant reduction of surface tension and enhancement of surface elasticity is observed as a result of the competitive adsorbtion/dominance of the RL at the air-water interface and this leads to performance enhancements in terms of foam stability.


A simple template-free approach to TiO2 hollow spheres with enhanced photocatalytic activity.
Mesporous anatase-phase TiO(2) hollow spheres with high photocatalytic activity were prepared by hydrothermal treatment and self-transformation of amorphous TiO(2) solid spheres in an NH(4)F aqueous solution. The prepared samples were characterized by X-ray diffraction, scanning and transmission electron microscopy, X-ray photoelectron spectroscopy, N(2) adsorption-desorption isotherms and UV-vis absorption spectroscopy. The photocatalytic activity was evaluated by photocatalytic oxidation decomposition of acetone in air under UV irradiation. It is found that F(-) plays an essential role in the formation of TiO(2) hollow spheres. F(-) not only induces the hollowing of TiO(2) solid spheres, but also promotes the crystallization of anatase TiO(2) nanocrystals. A possible formation mechanism for the TiO(2) hollow spheres by localized Ostwald ripening or chemically induced self-transformation is proposed based on the experimental observations. Furthermore, the molar ratios of NH(4)F to TiO(2) (R) exhibit a significant influence on the morphology and photocatalytic activity of the TiO(2) samples. The photocatalytic activity of the samples prepared in the presence of NH(4)F is higher than that of TiO(2) sample prepared in pure water and commercial Degussa P25 (P25) powders. Especially, the TiO(2) hollow spheres prepared at R = 1 show the highest photocatalytic activity and the specific rate constant S(k) exceeds that of P25 by a factor of more than two.


Health psychology in the time of COVID-19.
Health Psychology has received numerous papers over the past several months on topics related to the COVID-19 pandemic. Many of them concern depression, anxiety, stress, or other forms of distress in the general population or in health care workers. We have received far fewer papers on COVID-related health behaviors and health communications-factors that have played central roles in the spread of the pandemic and that are major topics in health psychology. Our experience is consistent with the published scientific literature on the pandemic. A Medline search that we conducted in late September yielded over 23,000 English-language articles pertaining to COVID-19. Over 1,400 of them concerned topics that are within the scope of Health Psychology. As shown in Table 1, COVID-related mental disorders comprised the largest category. Many other studies concerned other forms of stress or emotional distress. At least 248 articles addressed the profound ethnic and racial disparities in COVID-19 infection and death rates and in access to health care that are accentuating longstanding health inequities; 22 (9%) of these articles addressed behavioral or psychosocial aspects of COVID-19 health disparities. Thus, the literature on the behavioral and psychosocial aspects of the pandemic has been dominated, so far at least, by research on stress or distress. Fewer reports have been published so far on critical COVID-related health behaviors, health communication, or health disparities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Biologically inspired modelling for the control of upper limb movements: from concept studies to future applications.
Modelling is continuously being deployed to gain knowledge on the mechanisms of motor control. Computational models, simulating the behaviour of complex systems, have often been used in combination with soft computing strategies, thus shifting the rationale of modelling from the description of a behaviour to the understanding of the mechanisms behind it. In this context, computational models are preferred to deterministic schemes because they deal better with complex systems. The literature offers some striking examples of biologically inspired modelling, which perform better than traditional approaches when dealing with both learning and adaptivity mechanisms. Can these theoretical studies be transferred into an application framework? That is, can biologically inspired models be used to implement rehabilitative devices? Some evidences, even if preliminary, are presented here, and support an affirmative answer to the previous question, thus opening new perspectives.


Catalytically inactive phospholipase A2 homologue binds to vascular endothelial growth factor receptor-2 via a C-terminal loop region.
VEGF (vascular endothelial growth factor) regulates neovascularization through binding to its receptor KDR (kinase insert domain-containing receptor; VEGF receptor-2). We recently identified a catalytically inactive PLA(2) (phospholipase A(2)) homologue (KDR-bp) in the venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus) as a third KDR-binding protein, in addition to VEGF(165) and tissue inhibitor of metalloproteinase-3. KDR-bp binds to the extracellular domain of KDR with a K(d) of 10(-8) M, resulting in specific blockade of endothelial cell growth induced by VEGF(165). Inactive PLA(2) homologues are widely distributed in the venoms of Viperidae snakes and are known to act as myotoxins. In the present study, we demonstrated that KDR-binding ability is a common characteristic for inactive PLA(2) homologues in snake venom, but not for active PLA(2)s such as neurotoxic and platelet aggregation-modulating PLA(2)s. To understand better the KDR and KDR-bp interaction, we resolved the binding region of KDR-bp using eight synthetic peptides designed based on the structure of KDR-bp. A synthetic peptide based on the structure of the C-terminal loop region of KDR-bp showed high affinity for KDR, but other peptides did not, suggesting that the C-terminal loop region of KDR-bp is involved in the interaction with KDR. The results of the present study provide insight into the binding of inactive PLA(2) homologues to KDR, and may also assist in the design of novel anti-KDR molecules for anti-angiogenic therapy.


PAST-TENSE GENERATION FROM FORM VERSUS MEANING: BEHAVIOURAL DATA AND SIMULATION EVIDENCE.
The standard task used to study inflectional processing of verbs involves presentation of the stem form from which the participant is asked to generate the past tense. This task reveals a processing disadvantage for irregular relative to regular English verbs, more pronounced for lower-frequency items. Dual- and single-mechanism theories of inflectional morphology are both able to account for this pattern; but the models diverge in their predictions concerning the magnitude of the regularity effect expected when the task involves past-tense generation from meaning. In this study, we asked normal speakers to generate the past tense from either form (verb stem) or meaning (action picture). The robust regularity effect observed in the standard form condition was no longer reliable when participants were required to generate the past tense from meaning. This outcome would appear problematic for dual-mechanism theories to the extent that they assume the process of inflection requires stem retrieval. By contrast, it supports single-mechanism models that consider stem retrieval to be task-dependent. We present a single-mechanism model of verb inflection incorporating distributed phonological and semantic representations that reproduces this task-dependent pattern.


Pathologic examination accurately predicts prognosis in mucinous cystic neoplasms of the pancreas.
The behavior of pancreatic mucinous cystic neoplasms has long been debated. Some authors contend that histologically benign neoplasms can recur and metastasize. We reviewed the gross and microscopic findings and outcomes of 61 mucinous cystic neoplasms diagnosed at The Johns Hopkins Hospital from March 20, 1984 to July 8, 1998. Each neoplasm was placed into one of four categories based on complete histologic examination: invasive mucinous cystadenocarcinoma, mucinous cystic neoplasm with in situ carcinoma, borderline mucinous cystic neoplasm, and mucinous cystadenoma. Neoplasms in the latter three categories were included only if they were entirely resected and completely examined. Patient outcomes were obtained from hospital records and patient and physician follow-up. Twenty (33%) of the patients had invasive mucinous cystadenocarcinomas, and they had 2- and 5-year disease-specific survival rates of 67% and 33% (mean follow-up of survivors, 4.2 years), respectively. Nine (15%) patients had mucinous cystic neoplasms with in situ carcinoma (mean follow-up of survivors, 4.1 years). Five (8.2%) patients had borderline mucinous cystic neoplasms (mean follow-up of survivors, 5.6 years). Twenty-seven (44%) patients had mucinous cystadenomas (mean follow-up of survivors, 5.1 years). No mucinous cystadenoma, borderline mucinous cystic neoplasm, or mucinous cystic neoplasm with in situ carcinoma recurred or metastasized. No patient with the diagnosis of mucinous cystadenoma, borderline mucinous cystic neoplasm, or mucinous cystic neoplasm with in situ carcinoma died of disease. The difference in disease-specific survival rates between patients with invasive mucinous cystadenocarcinomas and those with noninvasive tumors was significant (p < 0.0001, log-rank test). One case, originally showing only benign histology on incisional biopsy, contained foci of invasive carcinoma on complete resection. Completely resected and entirely examined mucinous cystadenomas, borderline mucinous cystic neoplasms, and mucinous cystic neoplasms with in situ carcinoma follow benign courses. Because invasive carcinoma can be focal, failure to study an entire mucinous cystic neoplasm may result in the miscategorization of a malignant neoplasm as benign.


Individualized immunosuppression in transplant patients: potential role of pharmacogenetics.
The immunosuppressive drugs used to prevent the rejection of transplanted organs have a narrow therapeutic index. Under treatment results in episodes of rejection leading to either damage or loss of the organ. Over immunosuppression increases the risk of infection and malignancy as well as drug specific complications including diabetes mellitus and nephrotoxicity. There is wide variation in the drug dose required to achieve target blood concentrations and there is often dissociation between pharmacokinetics and pharmacodynamics. Currently, immunosuppressive drug treatment is individualized based on a clinical assessment of the risk of rejection or toxicity. Therapeutic drug monitoring is routinely employed for several immunosuppressive drugs. Pharmacogenetics has the potential to complement therapeutic drug monitoring but clinical benefit has yet to be demonstrated. Novel biomarker-based approaches to risk stratification and pharmacodynamic monitoring are under development and are ready for clinical trials.


Horizontal Augmentation of Chronic Mandibular Defects by the Guided Bone Regeneration Approach: A Randomized Study in Dogs.
Various biomaterial combinations have been studied focusing on their ability to stabilize blood clots and maintain space under soft tissue to support new bone formation. A popular combination is Deproteinized Bovine Bone Mineral (DBBM) placed with a native collagen membrane (NCM) tacked to native bone. In this study, we compared the outcome of this treatment option to those achieved with three different graft/membrane combinations with respect to total newly occupied area and the mineralized compound inside. After bi-lateral extraction of two mandibular premolars in five adult beagles L-shaped alveolar defects were created. A total of 20 defects healed for 6 weeks resulting in chronic type bone defects. At baseline, four options were randomly allocated to five defects each: a. DBBM + NCM with a four-pin fixation across the ridge; b. DBBM + RCLC (ribose cross-linked collagen membrane); c. DBBM + NPPM (native porcine pericardium membrane); and d. Ca-sulfate (CS) + RCLC membrane. Membranes in b/c/d were not fixed; complete tensionless wound closure was achieved by CAF. Termination after 3 months and sampling followed, and non-decalcified processing and toluidine blue staining were applied. Microscopic images obtained at standardized magnification were histomorphometrically assessed by ImageJ software (NIH). An ANOVA post hoc test was applied; histomorphometric data are presented in this paper as medians and interquartile ranges (IRs). All sites healed uneventfully, all sites were sampled and block separation followed before Technovit embedding. Two central sections per block for each group were included. Two of five specimen were lost due to processing error and were excluded from group b. New bone area was significantly greater for option b. compared to a. (p = 0.001), c. (p = 0.002), and d. (p = 0.046). Residual non-bone graft area was significantly less for option d. compared to a. (p = 0.026) or c. (p = 0.021). We conclude that collagen membranes with a prolonged resorption/barrier profile combined with bone substitutes featuring different degradation profiles sufficiently support new bone formation. Tacking strategy/membrane fixation appears redundant when using these biomaterials.


Age-related differences and the role of augmented visual feedback in learning a bimanual coordination pattern.
The purpose of this study was to investigate the effects of aging and the role of augmented visual information in the acquisition of a new bimanual coordination pattern, namely a 90 degrees relative phase pattern. In a pilot study, younger and older adults received augmented visual feedback in the form of a real-time orthogonal display of both limb movements after every fifth trial. Younger adults acquired this task over three days of practice and retained the task well over periods of one week and one month of no practice while the older adults showed no improvement at all on the task. It was hypothesized that the amount of augmented information was not sufficient for the older adults to overcome the strong tendency to perform natural, intrinsically stable coordination patterns, which consequently prevented them from learning the task. The present study evaluated the age-related role of augmented visual feedback for learning the new pattern. Participants were randomly assigned within age groups to receive either concurrent or terminal visual feedback after every trial in acquisition. In contrast to the pilot study, all of the older adults learned the pattern, although not to the same level as the younger adults. Both younger and older adults benefitted from concurrent visual feedback, but the older adults gained more from the concurrent feedback than the younger adults, relative to terminal feedback conditions. The results suggest that when learning bimanual coordination patterns, older adults are more sensitive to the structure of the practice conditions, particularly the availability of concurrent visual information. This greater sensitivity to the learning environment may reflect a diminished capacity for inhibitory control and a decreased ability to focus attention on the salient aspects of learning the task.


Ngu-ng-gi-la-nha (to exchange) knowledge. How is Aboriginal and Torres Strait Islander people's empowerment being upheld and reported in smoking cessation interventions during pregnancy: a systematic review.
Smoking during pregnancy is a national priority to improve Aboriginal health. Empowerment approaches underpin the priorities set by the government to improve Aboriginal health and wellbeing; however, empowerment is seldom evaluated within interventions for Aboriginal people. Literature was searched to April 2018 and data was extracted using an assessment tool with domains of individual and community empowerment in smoking cessation during pregnancy studies with Aboriginal women. Three interventions were found in published and grey literature. Elements of individual empowerment were embedded in all interventions. Interventions considered barriers for Aboriginal women to quit smoking and areas for capacity building. Interventions used health education resources. There was limited reporting of community empowerment domains. Aboriginal ethics and capacity building was the only criterium addressed by all studies. Interventions are incorporating individual empowerment, but seldom report community empowerment. The development of reporting guidelines or extensions of current guidelines would be beneficial to set a consistently high standard reporting across Aboriginal health interventions, similar to the work conducted to develop the extension of Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Equity (PRISMA-E) for health equity in systematic review reporting. Reporting empowerment domains would reflect the government priority of empowerment to improve Aboriginal health, as well as enhancing knowledge translation into practice.


Nonpharmacological methods: frequency of use and follow-up actions among healthcare staff in the care of older people.
Older people are at risk of developing multi-comorbidity and thus being exposed to multiple treatments and drugs to manage the emerging health complaints. More focus has been put on nonpharmacological alternatives. However, studies revealing the healthcare staff perspective on using nonpharmacological methods (NPMs) in the care of older people are still lacking. Thus, the aim of this study was to map the use of NPMs in daily practices and the follow-up thereof. A population-based survey with questionnaires was performed, included all healthcare professionals (n = 163; nurses and paramedical professionals) working in one district of elderly care in Sweden. The older person's anxiety and worry (76.1%), sleeping problems (53.1%) and pain (41.1%) were the health problems in daily life most likely to trigger use of NPMs. To manage the emerging health problems, interactions (87.1%), diet and nutrition supplements (63.2%) and physical activity were commonly used, particularly by nurses. One third (n = 54) stated that they did not evaluate the NPMs used, with no statistical differences between nurses and paramedical professionals. The present study indicated that NPMs were used in care of older people among nurses and paramedical professionals, but not in a systematic way and often without follow-up.


Methylene as a possible universal footprinting reagent that will include hydrophobic surface areas: overview and feasibility: properties of diazirine as a precursor.
Methylene is one of, if not the, most reactive organic chemical known. It has a very low specificity, which makes it essentially useless for synthesis, but suggests a possible role in protein footprinting with special importance in labeling solvent accessible nonpolar areas, identifying ligand binding sites, and outlining interaction areas on protomers that form homo or hetero oligomers in cellular assemblies. The singlet species is easily and conveniently formed by photolysis of diazirine. The reactions of interest are insertion into C-H bonds and addition to multiple bonds, both forming strong covalent bonds and stable compounds. Reaction with proteins and peptides is reported even in aqueous solutions where the vast majority of the reagent is used up in forming methanol. Species containing up to 5 to 10 extra :CH2 groups are easily detected by electrospray mass spectroscopy. In a mixture of a 14 Kd protein and a noninteracting 1.7 Kd peptide, the distribution of mass peaks in the electrospray spectra was close to that expected from random modification of the estimated solvent accessible area for the two molecules. For analysis at the single residue level, quantitation at labeling levels of one 13CH2 group per 10 to 20 kDa of protein appears to be possible with isotope ratio mass spectroscopy. In the absence of reactive solvents, photolysis of diazirine produces oily polymeric species that contain one or two nitrogen atoms, but not more, and are water soluble.


Causality and persistence in ecological systems: a nonparametric spectral granger causality approach.
Abstract Directionality in coupling, defined as the linkage relating causes to their effects at a later time, can be used to explain the core dynamics of ecological systems by untangling direct and feedback relationships between the different components of the systems. Inferring causality from measured ecological variables sampled through time remains a formidable challenge further made difficult by the action of periodic drivers overlapping the natural dynamics of the system. Periodicity in the drivers can often mask the self-sustained oscillations originating from the autonomous dynamics. While linear and direct causal relationships are commonly addressed in the time domain, using the well-established machinery of Granger causality (G-causality), the presence of periodic forcing requires frequency-based statistics (e.g., the Fourier transform), able to distinguish coupling induced by oscillations in external drivers from genuine endogenous interactions. Recent nonparametric spectral extensions of G-causality to the frequency domain pave the way for the scale-by-scale decomposition of causality, which can improve our ability to link oscillatory behaviors of ecological networks to causal mechanisms. The performance of both spectral G-causality and its conditional extension for multivariate systems is explored in quantifying causal interactions within ecological networks. Through two case studies involving synthetic and actual time series, it is demonstrated that conditional G-causality outperforms standard G-causality in identifying causal links and their concomitant timescales.


Distribution of Basal cell carcinoma and squamous cell carcinoma by facial esthetic unit.
The most common cutaneous malignant masses are basal cell carcinoma (BCC) and squamous cell carcinoma. The predominant site of a malignant mass is the face, which has many opportunities to be exposed to ultraviolet radiation. However the predilection sites of malignant masses have been equivocal due to the use of general regions, rather than anatomical landmarks, in surveys. A facial esthetic unit is an anatomical site classified as an area of similar facial contour characteristics that can be distinguished from other areas. The purpose of this study is to determine widely accepted anatomical landmarks using the esthetic unit. We retrospectively analyzed 118 cases of malignant masses in our clinic from January 2005 to October 2012. We evaluated the patients' age, gender, and predilection site of the malignant mass by esthetic unit through pathology, medical records and patient photographs. We mapped the occurrence site of the malignant mass on schematic drawings of the esthetic units. Most of the malignant masses were BCC. The ratio of males to females was 1:1.41. The frequent predilection site of a malignant mass was on the nasal unit (33.1%), followed by the buccal unit (11.0%). Primary closure was the most common method of repairing a surgical defect (38.9%), followed by a local flap (35.5%). This review described the relationship between clinical characteristics and esthetic units by proposing objective predilection sites for malignant masses, which can be used commonly as a framework in the study of malignant masses by unifying equivocal occurrence sites.


Relationship between the abnormal diastolic vortex structure and impaired left ventricle filling in patients with hyperthyroidism.
Intraventricular hydrodynamics plays an important role in evaluating cardiac function. Relationship between diastolic vortex and left ventricular (LV) filling is still rarely elucidated. The aim of this study was to evaluate the evolution of vortex during diastole in hyperthyroidism (HT) and explore the alteration of hydromechanics characteristics with sensitive indexes.Forty-three patients diagnosed with HT were classified into 2 groups according to whether myocardial damage existed: simple hyperthyroid group (HT1, n = 21) and thyrotoxic cardiomyopathy (HT2, n = 22). Twenty-seven age- and gender-matched healthy volunteers were enrolled as the control group. Offline vector flow mapping (VFM model) was used to analyze the LV diastolic blood flow patterns and fluid dynamics. Hemodynamic parameters, vortex area (A), circulation (C), and intraventricular pressure gradient (ΔP), in different diastolic phases (early, mid, and late) were calculated and analyzed.HT2, with a lower E/A ratio and left ventricular ejection fraction (LVEF), had a larger left atrium diameter (LAD) compared with those of the control group and HT1 (P < .05). Compared with the control group, the vortex size and strength, intraventricular pressure gradient during early and mid-diastole were higher in HT1 and lower in HT2 (P < .05). And in late diastole, the vortex size and strength, intraventricular pressure gradient of HT2 became higher than those of the control group (P < .05). Good correlation could be found between CE and E/A (P < .05), CM and ΔPM (P < .01), CL and FT3 (P < .05).VFM is proven practical for detecting the relationship between the changes of left ventricular diastolic vortex and the abnormal left ventricular filling.


One-dimensional model of a plasma-electrode optical switch driven by one-pulse process.
In this paper, we present a one-dimensional simplified model for the processes of gaseous discharge and charging on the surfaces of KDP crystal for one-pulse process in Plasma-Electrode Pockels Cell (PEPC). The PEPCs are used as large-aperture optical switch in laser drivers for inertial-confinement fusion. The plasma electrodes of the switch are produced by high discharge current, while a high voltage pulse is applied across a thin KDP crystal plate through the helium discharge plasma. The evolvements of discharge current, charging voltage on KDP crystal and the switch efficiency of PEPC are simulated. The model is very useful for the design of PEPC and prediction the behavior of the optical switch.


Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial.
Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.


Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.
An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity. In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew's correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at http://meilerlab.org/q1varpred. Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools.


Oncologic Safety in Autologous Fat Grafting After Breast Conservation Therapy: A Systematic Review and Meta-analysis of the Literature.
Autologous fat grafting (AFG) is often used to reconstruct defects after breast conservation therapy (BCT). However, concerns exist about the possibility of AFG-related recurrence or metastasis. This study aims to evaluate the literature to evaluate oncologic outcomes in patients undergoing AFG at the time of BCT. A systematic review of articles related to AFG based reconstruction at the time of BCT from 1970 to 2021 was performed via PubMed. Patients were grouped based on the presence or lack of AFG usage at the time of BCT, and oncologic outcomes and complications were compared. Of the 146 articles identified, 15 were included. Nine hundred patients underwent BCT alone and 1063 patients underwent BCT with AFG patients. Similar average follow-up time was observed between the groups, 58.7 months (BCT only) and 55.2 months (BCT with AFG). On pooled analysis, no difference was identified in local recurrence 4.8% (43 patients) of the BCT group and 3% (32 patients) in the AFG group (P = 0.8), metastasis 4.8% (43 patients) of the BCT group and 6.9% (73 patients) in the AFG group (P = 0.3), or fat necrosis (P = 0.44). Meta-analysis additionally did not identify any statistically significant odds ratios between the BCT only group and BCT with AFG group when evaluated for total recurrence, local recurrence, metastasis or fat necrosis. The results show no significant difference in cancer recurrence or metastasis in the BCT only group versus BCT and AFG, showing that fat grafting has safe outcomes.


Identification and quantification of oleanolic acid and ursolic acid in Chinese herbs by liquid chromatography-ion trap mass spectrometry.
A rapid and sensitive method for the identification and quantification of ursolic acid (UA) and oleanolic acid (OA) in Chinese herbs is described. The method combines liquid chromatography (LC) with ion trap-mass spectrometry (IT-MS) detection. The UA and OA standard solution were directly infused into IT-MS for collecting MS(n) spectra. The major fragment ions of UA and OA were confirmed by MS(n) at m/z 455, 407, 391, 377 and 363 in negative ion mode, and m/z 457, 439, 411 and 393 in positive mode, respectively. The possible main cleavage pathway of fragment ions was studied. UA and OA provided good signals corresponding to the deprotonated molecular ion [M - H](-). The method is reliable and reproducible, and the detection limit is 5 ng/mL. The method was validated in the concentration range of 0.04-40 μg/mL; intra- and inter-day precisions ranged from 0.78 to 2.15%, and the accuracy was 96.5-108.2% for UA and OA. The mean recovery of UA and OA was 97.1-106.2% with RSD less than 1.86%. An LC-IT-MS method was successfully applied to determine the UA and OA in nine Chinese herbs.


Properties of encapsulated and hand-mixed zinc phosphate dental cement.
Dental cements can be supplied as loose powder and liquid or as encapsulated syringes. This study assessed the compressive strength of a recently marketed zinc phosphate encapsulated cement compared with a hand-mixed system according to the American Dental Association Specification. The mean fracture strength, standard deviations and associated Weibull Moduli (m) of the encapsulated and hand-mixed cements were determined by compressive fracturing 30 cylindrical specimens (height 6.0 +/- 0.1 mm, diameter 4.0 +/- 0.1 mm). Scanning electron microscopy was employed to assess crack growth from indentations and cement morphology. Image analysis was used to investigate the influence of mixing regime on pore distribution within the cement samples. The compressive strength data showed variation in magnitude and reliability ranging from 42 +/- 8 MPa (m = 5.2 +/- 1.0) for the encapsulated cement filled directly from the capsule to 71 +/- 11 MPa (m = 6.3 +/- 1.3) for the hand-mixed cement. The encapsulated cement matrix was extensively porous, consisting of pores between 0.1-0.5 microm diameter, compared with the non-porous hand-mixed cement matrix. Larger pores (over 18 microm diameter) were related to air entrapment in the encapsulated cement on mixing while small pores (0.1-0.5 microm diameter) were indicative of vaporization porosity commonly seen with exothermic reactions.


Palivizumab Prophylaxis for Respiratory Syncytial Virus: Examining the Evidence Around Value.
Respiratory syncytial virus (RSV) infection is the most common cause of lower respiratory tract infection and the leading cause of hospitalization among young children, incurring high annual costs among US children under the age of 5 years. Palivizumab has been found to be effective in reducing hospitalization and preventing serious lower respiratory tract infections in high-risk infants. This paper presents a systematic review of the cost-effectiveness studies of palivizumab and describes the main highlights of a round table discussion with clinical, payer, economic, research method, and other experts. The objectives of the discussion were to (1) review the current state of clinical, epidemiology, and economic data related to severe RSV disease; (2) review new cost-effectiveness estimates of RSV immunoprophylaxis in US preterm infants, including a review of the field's areas of agreement and disagreement; and (3) identify needs for further research.


HPLC Estimation of berberine in Tinospora cordifolia and Tinospora sinensis.
A high-performance liquid chromatographic method for the estimation of berberine in the stem of Tinospora cordifolia (Willd.) Miers. ex Hook.f. and Thoms. and Tinospora sinensis (Lour.) Merrill is described. The dried stems of T. cordifolia and T. sinensis were defatted with petroleum ether (60-80 degrees ). The marc was dried and further extracted with methanol. The concentration of berberine in methanol extract was determined using a C-18 reverse phase column with a mobile phase of acetonitrile:water (10:90 v/v) at a flow rate of 0.6 ml/min and with UV detection at 266 nm. TLC and HPLC comparison of both the species revealed significant variation in the chemical constitution of the two species. This observation becomes important in the context of the use of T. sinensis in place of the genuine drug T. cordifolia.


Dynamic observation of biomechanic properties of sciatic nerve at the suture site in rats following repairing.
To observe the biomechanic properties of the sciatic nerve at the suture site following repairing in rats. The right sciatic nerves of 40 white Sprague-Dawley 300~350 gm rats were exposed, cut and then repaired with 10-0 nylon sutures with four stitches, laced in the epineurium 0, 1, 3, and 6 weeks after operation, the tensile strength of the sciatic nerves were measured, and the data analyzed statistically. The load elongation curves for both the normal unoperated and operated nerves had similar shape. There were significant differences between the tensile strength of the 0th and the 1st, 3rd, and 6th weeks (P < 0.01). No significant difference was found among the 1st, 3rd, and 6th weeks. The tensile strength of the injured nerves recovered 48% of the normal nerve in the 1st week and 54% in 6 weeks after repairing. It may be concluded that the injured nerves can acquire mostly tensile strength stability in 1 week quickly and can maintain this relative tensile strength stability in 6 weeks.


The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate.
Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV-treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV-treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV.


Rationale, design, and goals of the Advanced Cardiovascular Imaging Consortium (ACIC): A Blue Cross Blue Shield of Michigan collaborative quality improvement project.
Coronary computed tomography angiography (CCTA) is an emerging noninvasive anatomical method for evaluation of patients with suspected coronary artery disease (CAD). Multicenter clinical registries are key to efforts to establish the role of CCTA in CAD diagnosis and management. The Advanced Cardiovascular Imaging Consortium (ACIC) is a statewide, multicenter collaborative quality initiative with the intent to establish quality and appropriate use of CCTA in Michigan. The ACIC is sponsored by the Blue Cross Blue Shield of Michigan/Blue Care Network, and its 47 sites include imaging centers that offer CCTA and meet established structure and process standards for participation. Patients enrolled include those with suspected ischemia with or without known CAD, and individuals across the entire spectrum of CAD risk. Patient demographics, history, CCTA scan-related data and findings, and 90-day follow-up data are entered prospectively into a centralized database with strict validation tools and processes. Collaborative quality initiatives include radiation dose reduction and appropriate CCTA use by education and feedback to participating sites and referring physicians. Across a wide range of institutions, the ACIC permits evaluation of "real-world" utilization and effectiveness of CCTA and examines an alternative, nontraditional approach to utilization management wherein physicians and payers collaborate to address the growing problem of cardiac imaging overutilization.


Depression Is Real: Developing a Health Communication Campaign in an Urban African American Community.
Depression is the leading cause of disability in the United States. African Americans are disproportionately affected owing to systemic and sociocultural factors. Stigma, denial, and inadequate knowledge on depression are significant barriers to mental help seeking. Addressing mental health literacy can improve mental health knowledge, management, and outcomes. West Louisville, a predominantly African American community, is of particular interest regarding mental health literacy given existing socioeconomic and health disparities. Boot Camp Translation (BCT), a community-based participatory research (CBPR) approach, enables the translation of medical guidelines into culturally relevant messages. To describe the use of the BCT approach in developing and implementing a culturally tailored health communication campaign designed to measurably increase referral to, and use of, services for depression in West Louisville. Using the BCT approach, a group of academics, community members, and health/public health professionals convened over 6 months to develop and implement a health communication campaign on depression. Process and outcome evaluations were conducted using quantitative and qualitative methods. Our BCT was effective in engaging stakeholders, activating community members, and designing culturally informed health communication materials on depression. Although limited, our evaluation data suggest a modest increase in the evaluation and treatment of depression in West Louisville. BCT offers a structured process for engaging stakeholders in developing culturally tailored health communication campaigns.


The role of CT in functional endoscopic sinus surgery.
The intricate anatomy of the paranasal sinus unit (sinus/nasal cavities and ostia) and its relations to the orbit and anterior cranial fossa make accurate pre-operative evaluation of disease in this region mandatory before undertaking functional endoscopic sinus surgery (FESS). Plain radiography often fails to provide vital information in cases of chronic rhinosinusitis, especially of the ethmoid labyrinth, which is a key area of the paranasal sinus unit. Computerized tomography has significantly enhanced the scope of endoscopic sinus surgery by offering the surgeon hitherto inaccessible information regarding the sinus status. In this article, we review the pros and cons of the two imaging modalities, and present our experience fo 70 CT scans in patients of FESS. We also propose a surgical classification of CT findings. All in all, plain radiographs prove to be of little value for pre-operative assessment in FESS, while CT scans are an essential tool.


Application of molecularly imprinted polymer based matrix solid phase dispersion for determination of fluoroquinolones, tetracyclines and sulfonamides in meat.
In this study, a type of novel mixed-template molecularly imprinted polymer was synthesized that was able to recognize 8 fluoroquinolones, 8 sulfonamides and 4 tetracyclines simultaneously with recoveries higher than 92%. Then the polymer was used to develop a matrix solid phase dispersion method for simultaneous extraction of the 20 drugs in pork followed by determination with ultra performance liquid chromatography. During the experiments, the MMIP amount, washing solvent and elution solvent were optimized respectively. The limits of detection of this method for the 20 drugs in pork were in the range of 0.5-3.0ngg-1, and the intra-day and inter-day recoveries from the fortified blank samples were in the range of 74.5%-102.7%. Therefore, this method could be used as a rapid, simple, specific and sensitive method for multi-determination of the residues of the three classes of drugs in meat.


Hemithyroidectomy, does the indication influence the outcome?
Hemithyroidectomies are mainly performed for two indications, either therapeutically to relieve compression symptoms or diagnostically for suspicious nodule(s). In case of the latter, one could consider the approach to be rather extensive since the majority of patients have no symptoms and will have benign disease. The aim of this study is to investigate the complication rates of diagnostic hemithyroidectomy and to compare it with the complication rates of compressive symptoms hemithyroidectomy. Data from patients who had undergone hemithyroidectomy either for compression symptoms or for excluding malignancy were extracted from a well-established Scandinavian quality register (SQRTPA). The following complications were analyzed: bleedings, wound infections, and paresis of the recurrent laryngeal nerve (RLN). Risk factors for these complications were examined by univariable and multivariable logistic regression. A total of 9677 patients were included, 3871 (40%) underwent surgery to exclude malignancy and 5806 (60%) due to compression symptoms. In the multivariable analysis, the totally excised thyroid weight was an independent risk factor for bleeding. Permanent (6-12 months after the operation) RLN paresis were less common in the excluding malignancy group (p = 0.03). A range of factors interfere and contribute to bleeding, wound infections, and RLN paresis after hemithyroidectomy. In this observational study based on a Scandinavian quality register, the indication "excluding malignancy" for hemithyroidectomy is associated with less permanent RLN paresis than the indication "compression symptoms." Thus, patients undergoing diagnostic hemithyroidectomy can be reassured that this procedure is a safe surgical procedure and does not entail an unjustified risk.


[Evaluation of trap color and position on the capture of cicadellids in Gaultheria phillyreifolia (Ericaceae) affected by phytoplasmas].
Color sticky traps are one of the main alternatives to collect insect vectors, as they are easy to handle and are inexpensive. We aimed to compare the effect of color and height of the traps on the attractiveness to potential cicadellids vectors of plant pathogens. Yellow and green colored stick traps were placed at two different heights in plant of Gaultheria phillyreifolia. Seventeen leafhopper species were identified, with Ribautiana tenerrima Herrich-Shäffer (49%), Carelmapu ramosi Linnavuori & DeLong (33%), Carelmapu aurionitens Linnavuori (5%) and Atanus sp. (6%) being the most common. All these species were significantly attracted by yellow sticky traps. Ribautiana tenerrima was the only species affected by the height of the sticky traps. However, this was also dependent on the sampling season. The phytoplasma vector candidate, C. ramosi, showed two population peaks in early and late summer, which may indicate two different generations. Males of this species were more abundant than females on sticky traps, but were both similarly attracted to yellow sticky traps. No differences were detected in the capture efficiency of both sexes at any height of the traps. The high proportion of C. ramosi captured suggests that the yellow sticky traps can be an important element for monitoring this species.


Hypotension-induced blindness in haemodialysis patients.
Hypotension is a commonly encountered complication in haemodialysis patients and is a significant cause of morbidity and mortality. Bilateral visual loss in dialysis induced hypotension remains poorly recognized as a complication by both renal physicians and ophthalmologists. We report 2 cases of patients on renal dialysis who suffered severe longstanding hypotension with bilateral non-arteritic anterior ischaemic optic neuropathy. Both patients experienced bilateral loss of vision over a short time period. We feel that physicians must be aware of patients complaining of painless visual loss in this high risk group, as control of blood pressure may be the most important factor in prevention of this visually devastating condition.


Blurring the lines in interferon {gamma} receptor deficiency: an infant with near-fatal airway disease.
Deficiencies of the interferon γ (IFN-γ) pathway have become a well-recognized cause of nontuberculous mycobacterial infection. We report here a case of autosomal dominant IFN-γ receptor 1 (IFN-γ-R1) deficiency presenting at the unusually young age of 16 months with a severe clinical course. Mycobacterium avium complex was cultured from bronchial washings of a child who presented with primary endobronchial disease after a 4-month history of rhinorrhea, wheeze, and acute lobar consolidation. A maternal history of multifocal Mycobacterium kansasii osteomyelitis and cutaneous M avium complex led to genetic confirmation of IFN-γ-R1 818del4 deletion (a 4 base pair deletion at nucleotide position 818) in both family members. This case demonstrates the link between mycobacterial disease and IFN-γ pathway deficiency, the diagnosis of which facilitates more accurate therapy and genetic counseling. The case also raises questions about the reported distinct presentation, treatment, and prognosis of autosomal dominant and recessive IFN-γ-R1 phenotypes.


Beyond Valence and Arousal: The Role of Age of Acquisition in Emotion Word Recognition.
Although the age of acquisition (AoA) effect has been established in numerous studies, how emotion word processing is modulated by AoA, along with affective factors, such as valence and arousal, is not well understood. Hence, the influence of age of acquisition (AoA), valence, and arousal on Chinese emotion word recognition was investigated through two experiments. Experiment 1 (N = 30) adopted a valence judgment task to explore the roles of valence and AoA in emotion word recognition, whereas Experiment 2 (N = 30) used a lexical decision task to examine AoA and arousal effects. A mixed linear effects model was used to examine the fixed effects of AoA, arousal, and valence and random effects of participants and items. The findings provided confirmation of the effects of AoA, valence, and arousal. Notably, AoA and valence had independent influences on emotion word recognition, as evidenced by longer reaction times for later-acquired words and negative words compared to early-acquired words and positive words (all ps < 0.05). On the other hand, AoA and arousal demonstrated interdependent effects on emotion word recognition. Specifically, a larger AoA effect was observed for low-arousing words (all ps < 0.05), whereas the influence of AoA on high-arousing words was insignificant. These results underscored the significance of AoA in processing emotion words and highlighted the interplay between AoA and arousal. Additionally, it is plausible to suggest that the AoA effect was primarily perceptual rather than semantic in nature.


51Cr-EDTA absorption blood test: an easy method for assessing small intestinal permeability in dogs.
The 51Cr-EDTA test is a valuable clinical tool for screening intestinal diseases in dogs. The test is performed by calculating the percentage of recovery from urine of a PO-ingested dose of 51Cr-EDTA after 6 or 24 hours. Careful urine collection is a practical limitation of this test in dogs, and our goal was to develop a simpler test that measures 51Cr-EDTA in blood. A 51Cr-EDTA absorption test was simultaneously performed on urine and serum 43 times in healthy Beagle Dogs. Timed blood samples were withdrawn, and urine was collected during a 6-hour period. Percentages of the ingested dose were then calculated in urine and serum. The mean +/- standard deviation (range) percentage in urine after 6 hours was 14.07 +/- 8.72% (3.81-34.18%), whereas results in serum from samples taken at 2, 3, 4, 5, and 6 hours were 0.49 +/- 0.45% (0.02-2.13%), 0.75 +/- 0.52% (0.03-1.89%), 0.82 +/- 0.57% (0.13-2.21%), 0.70 +/- 0.53% (0.12-1.99%), and 0.47 +/- 0.44% (0.11-1.79%), respectively. The results for blood specimens showed good concordance with those for urine, especially for the samples taken at 4 hours (r = 0.89). Moreover, the correlation between urine and blood was better when the sum of the percentages of the recovered analyte from various blood samples was compared with urine. The correlation coefficient when summing 4 blood samples was excellent (r = 0.97) and remained excellent when summing only 2 blood samples taken at 3 and 5 hours (r = 0.95) or at 3 and 4 hours (r = 0.94). We conclude that a serum 51Cr-EDTA test determined by summing successive blood samples provides an easier means of estimating small intestinal permeability in dogs and gives results comparable to those of the 6-hour urine test.


Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women.
To compare ospemifene and raloxifene regarding their effects on hormones, lipids, genital tract, and tolerability in postmenopausal women. A randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) of ospemifene or 60 mg (n = 29) of raloxifene for 3 months. There were no significant differences in the baseline characteristics between study groups. In comparison with raloxifene, follicle-stimulating hormone levels decreased significantly more in the 90-mg ospemifene group and sex hormone-binding globulin levels increased more in all ospemifene groups. Total cholesterol and low-density lipoprotein cholesterol levels decreased more in raloxifene than in ospemifene groups, although the difference in low-density lipoprotein cholesterol between 90-mg ospemifene and raloxifene was not significant. Endometrial thickness did not change in any study group and endometrial biopsies showed atrophy in the majority of subjects at 3 months. All ospemifene groups demonstrated a clear estrogenic effect on the vaginal epithelium, as seen in Pap smears. This was in sharp contrast to the raloxifene group, which had no effect on the vaginal epithelium. Kupperman index decreased in all study groups during treatment. The adverse events were mild, mainly single cases, and no clustering of events was observed. There were no clinically significant abnormal findings in laboratory safety parameters. Ospemifene, at the dose of 90 mg/day, was more estrogenic than raloxifene, as shown by changes in serum follicle-stimulating hormone and sex hormone-binding globulin levels. Neither agent stimulated endometrium, but in contrast to raloxifene, ospemifene had a clear estrogenic effect in the vagina. Further studies with ospemifene are needed in subjects with vaginal atrophy.


[Screening of key genes and pathways of ischemic stroke and prediction of traditional Chinese medicines based on bioinformatics].
The aim of this paper was to explore the key genes and pathogenesis of ischemic stroke(IS) by bioinformatics, and predict the potential traditional Chinese medicines for IS. Based on the gene-chip raw data set of GSE22255 from National Center of Biotechnology Information(NCBI), the article enrolled in 20 patients with ischemic stroke and 20 sex-and age-matched controls, and differentially expressed genes(DEGs) were screened based on R language software. The DAVID tool and R language software were used to perform gene ontology(GO) biological process enrichment analysis and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analysis. The DEGs were imported into STRING to construct a protein-protein interaction network, and the Molecular Complexity Module(MCODE) plug-in of Cytoscape software was used to visualize and analyze the key functional modules. Moreover, the core genes and the medical ontology information retrieval platform(Coremine Medical) were mapped to each other to screen the traditional Chinese medicines and construct drug-active ingredient-target network. Compared with healthy controls, 14 DEGs were obtained, of which 12 genes were up-regulated and 2 genes were down-regulated. DEGs were mainly involved in immune response, inflammatory process, signal transduction, and cell proliferation regulation. The interleukin-17(IL-17), nuclear factor kappaB(NF-κB), tumor necrosis factor(TNF), nucleotide binding oligomerization domain(NOD)-like receptor and other signaling pathways were involved in KEGG pathway enrichment analysis. The key modules of the DEGs-encoding protein interaction network mainly focused on 7 genes of TNF, JUN, recombinant immediate early response 3(IER3), recombinant early growth response protein 1(EGR1), prostaglandin-endoperoxide synthase 2(PTGS2), C-X-C motif chemokine ligand 8(CXCL8) and C-X-C motif chemokine ligand 2(CXCL2), which were involved in biological processes widely such as neuroinflammation and immunity. TNF and JUN were the key nodes in this module, which might become potential biological markers for diagnosis and prognosis evaluation of IS. The potential traditional Chinese medicines for the treatment of IS includes Salviae Miltiorrhizae Radix et Rhizoma, Croci Stigma, Scutellariae Radix, and Cannabis Fructus. The occurrence of stroke was the result of multiple factors. Dysregulation of genes and pathways related to immune regulation and inflammation may be the key link for the development of IS. This study provided research direction and theoretical basis for further exploring the mechanism of action of traditional Chinese medicine in the treatment of IS and searching for potential drug targets.


Computational modeling of a new fluorescent biosensor for caspase proteolytic activity improves dynamic range.
The class of fluorescence resonance energy transfer (FRET) protein biosensors that are useful for measuring protease activity is composed of a tandem fusion of yellow fluorescent protein (YFP), a cleavage recognition sequence, and cyan fluorescent protein (CFP). The dynamic range of these FRET-based protein biosensors is often weak, but applications such as high throughput drug screening require stronger dynamic ranges. Using the biosensor for the caspase-3 protease as an example, here we showed a computational approach to improve the FRET dynamic range based on the atomic structure of caspase-3 bound to its inhibitor. This result was verified from our experiments where the FRET dynamic range improved by at least 60% on average in both in vitro and in vivo contexts. In concept, the same strategy can be applied to improve dynamic range of other FRET-based protein biosensors for protease activity where there exist solved atomic structures for protein complexes.


Utility of B-natriuretic peptide in the evaluation of left ventricular diastolic function and diastolic heart failure.
Heart failure with preserved ejection fraction or diastolic heart failure is an increasingly prevalent disease process today. Natriuretic peptides have been shown to provide diagnostic and prognostic utility in patients with systolic heart failure. Here we review current publications exploring the relationship between B-natriuretic peptide (BNP) and diastolic dysfunction. Investigators have found significant correlations between echocardiographic parameters for diastolic dysfunction and serum BNP levels in diagnosing diastolic heart failure. This relationship is linear with respect to severity of left ventricular dysfunction. Newer echocardiographic modalities like tissue Doppler imaging provide measures of elevated left ventricular filling pressures, which are associated with higher plasma BNP levels. Admission and predischarge BNP levels in patients with decompensated diastolic heart failure have been prognostic with respect to in-hospital mortality, short-term mortality, and hospital readmission. Review of current literature shows that BNP can be useful in providing diagnostic and prognostic data in patients with symptomatic and asymptomatic diastolic dysfunction. These data, combined with other values such as echocardiographic indices and cardiovascular risk factors, can augment the sensitivity and specificity of BNP.


Extracellular Vesicles as Drug Targets and Delivery Vehicles for Cancer Therapy.
Extracellular vesicles (EVs) are particles that are released from cells into the extracellular space both under pathological and normal conditions. It is now well established that cancer cells secrete more EVs compared to non-cancerous cells and that, captivatingly, several proteins that are involved in EV biogenesis and secretion are upregulated in various tumours. Recent studies have revealed that EVs facilitate the interaction between cancer cells and their microenvironment and play a substantial role in the growth of tumours. As EVs are involved in several aspects of cancer progression including angiogenesis, organotropism, pre-metastatic niche formation, fostering of metastasis, and chemoresistance, inhibiting the release of EVs from cancer and the surrounding tumour microenvironment cells has been proposed as an ideal strategy to treat cancer and associated paraneoplastic syndromes. Lately, EVs have shown immense benefits in preclinical settings as a novel drug delivery vehicle. This review provides a brief overview of the role of EVs in various hallmarks of cancer, focusing on (i) strategies to treat cancer by therapeutically targeting the release of tumour-derived EVs and (ii) EVs as valuable drug delivery vehicles. Furthermore, we also outline the drawbacks of the existing anti-cancer treatments and the future prospective of EV-based therapeutics.


Effect of long duration exercise on the ratings of perceived exertion and perceived difficulty of walking and running at the ventilatory threshold.
The purpose of this study was to examine if the relationship between physiological changes classically observed with exercise duration and some subjective workload measures would be affected by the complexity of the locomotion mode (running vs racewalking). The study was conducted on 24 well trained subjects (12 long distance runners and 12 racewalkers) divided in 3 groups (runners, racewalkers and control). Energy cost of locomotion (C), heart rate (HR), minute ventilation (V(E)), lactate concentration [La], ratings of perceived exertion (RPE 6-20 scale) and ratings of perceived difficulty (RPD 1(-1)5 scale) were recorded during 2 10-min submaximal tests on a treadmill before and immediately after a 3 hour exercise (racewalking or running) conducted at the velocity ventilatory threshold (vVT). No significant variations in physiological parameters and perceived measures were observed in G(c). A significant increase (p<0.05) in energy cost of walking (mean: +9.4%) and running (mean: +7.5%) at the end of exercise was observed. A significant interaction of locomotion mode and exercise duration was found on perceived exertion and perceived difficulty. In racewalkers RPD significantly increased with duration whereas no significant effect was found for RPE. Conversely a significant increase in RPE was found after 3 hours in runners without any significant change in RPD. This experiment suggests that, for a complex task, the classical relationship between RPE and metabolic load increase during prolonged exercise could be affected by changes in RPD. In this study, stability in RPE and increase in RPD observed in racewalkers may reflect an attentional focus dissociated from internal sensations and directed toward maintaining the required race walking gait.


The Chinese soft-shelled turtle, Pelodiscus sinensis, decreases nitrogenous excretion, reduces urea synthesis and suppresses ammonia production during emersion.
The objective of this study was to examine the effects of 6 days of emersion on nitrogen metabolism and excretion in the Chinese soft-shelled turtle, Pelodiscus sinensis. Despite having a soft shell with a cutaneous surface that is known to be water permeable, P. sinensis lost only ~2% of body mass and was able to maintain its hematocrit and plasma osmolality, [Na(+)] and [Cl(-)] during 6 days of emersion. During emersion, it ameliorated water loss by reducing urine output, which led to a reduction (by 29-76%) in ammonia excretion. In comparison, there was a more prominent reduction (by 82-99%) in urea excretion during emersion due to a lack of water to flush the buccopharyngeal epithelium, which is known to be the major route of urea excretion. Consequently, emersion resulted in an apparent shift from ureotely to ammonotely in P. sinensis. Although urea concentration increased in several tissues, the excess urea accumulated could only account for 13-22% of the deficit in urea excretion. Hence, it can be concluded that a decrease (~80%) in urea synthesis occurred in P. sinensis during the 6 days of emersion. Indeed, emersion led to significant decreases in the activity of some ornithine-urea cycle enzymes (argininosuccinate synthetase/argininosuccinate lyase and arginase) from the liver of P. sinensis. As a decrease in urea synthesis occurred without the accumulation of ammonia and total free amino acids, it can be deduced that ammonia production through amino acid catabolism was suppressed with a proportional reduction in proteolysis in P. sinensis during emersion. Indeed, calculated results revealed that there could be a prominent decrease (~88%) in ammonia production in turtles after 6 days of emersion. In summary, despite being ureogenic and ureotelic in water, P. sinensis adopted a reduction in ammonia production, instead of increased urea synthesis, as the major strategy to ameliorate ammonia toxicity and problems associated with dehydration during terrestrial exposure.


A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme.
The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.


Characterization of an endo-beta-1,4-glucanase gene induced by auxin in elongating pea epicotyls.
A gene (EGL1) encoding an endo-beta-1,4-D-glucanase (EGase, EC 126.96.36.199) of pea (Pisum sativum) has been cloned and characterized. EGL1 encodes a 486-amino acid polypeptide, including a 24-mer putative signal peptide. The mature protein has a calculated molecular mass of 51.3 kD and an isoelectric point of 9.1. This pea EGase shares significant similarity with EGases from other plant species, but it appears to be distinct from the EGases associated with abscission and fruit ripening. Although EGL1 transcripts are detected in all parts of pea plants, they are relatively abundant in flowers and young pods undergoing rapid growth and most abundant in elongating epicotyls of etiolated seedlings. When epicotyl segments (6 mm long, 4 mm from the apical hook) are incubated in a 5 microM solution of the synthetic auxin analog 2,4-dichlorophenoxyacetic acid, the concentration of EGL1 mRNA increases about 10-fold when the segments elongate most rapidly.