Rats are sensitive to ambiguity.
In the present study, we investigated response decisions made under conditions of incomplete information in rats. In Experiment 1, rats were trained on either a positive patterning (PP; A-, B-, AB+) or a negative patterning (NP; A+, B+, AB-) instrumental lever-press discrimination. Subjects that had learned an NP discrimination responded less to Cue A when Cue B was covered at test. The cover did not, however, affect test responses to Cue A in the PP condition. In Experiment 2, rats received concurrent training on both PP and NP discriminations. After concurrent training, responses to Cue A were different with B covered versus uncovered for both NP and PP discriminations. We discuss possible accounts for why exposure to a nonlinearly soluble discrimination (NP) may have affected sensitivity to cue ambiguity produced by the cover. These results have interesting implications for representational processes engaged in problem solving.


Facile reversibility by design: tuning small molecule capture and activation by single component frustrated Lewis pairs.
A series of single component FLPs has been investigated for small molecule capture, with the finding that through tuning of both the thermodynamics of binding/activation and the degree of preorganization (i.e., ΔS(⧧)) reversibility can be brought about at (or close to) room temperature. Thus, the dimethylxanthene system {(C6H4)2(O)CMe2}(PMes2)(B(C6F5)2): (i) heterolytically cleaves dihydrogen to give an equilibrium mixture of FLP and H2 activation product in solution at room temperature and (ii) reversibly captures nitrous oxide (uptake at room temperature, 1 atm; release at 323 K).


Rapid qualitative antibiotic resistance characterization using VITEK MS.
Development and standardization of simple, timely, and cost-effective antibiotic susceptibility assays are much needed to address the emergence of global resistance. The use of matrix-assisted laser desorption/ionization time of flight mass spectrometry is routine for bacterial identification. This study evaluated 2 assays using the VITEK MS for rapid detection and accurate differentiation of bacterial antibiotic susceptibility. We describe an extraction method and direct-on-target microdroplet growth assay (DOT-MGA). Non-susceptible and susceptible strains of Staphylococcus aureus, Enterococcus species, Escherichia coli, and Klebsiella pneumoniae were tested. The liquid extraction method and DOT-MGA proved to be reliable assays providing consistent differentiation between non-susceptible and susceptible strains. Results from this study support VITEK MS and these assays as rapid and accurate tools to augment traditional susceptibility testing. If implemented clinically, these assays can reduce the cost of patient care and the time to deliver critically needed treatment.


Multifocal Meningiomas Mimicking Metastasis on 18F-Fluciclovine PET/CT.
A 65-year-old male patient with a past medical history of prostate adenocarcinoma presented with biochemical recurrence (prostate-specific antigen level of 5.91 mg/L). 18F-FACBC PET/CT was acquired to evaluate the disease recurrence and metastasis. Multifocal areas of tracer uptake localized to the dural surface of frontal convexities and cavernous sinuses were seen. Subsequent MRI confirmed lesions to be consistent with multifocal meningiomas. Focal intracranial 18F-fluciclovine radiotracer uptake especially at the skull base may present with a diagnostic challenge, and it may be difficult to differentiate between bone metastasis and meningiomas.


A vector stimulator for neurophysiological studies of periodontal mechanosensitive units.
This paper describes a newly designed vector stimulator which can independently stimulate both sides of an animal's canine or incisor teeth to analyse the functional properties of periodontal mechanosensitive (PM) units. The stimulator was designed so as to control and stimulus direction (0 degree-360 degrees) and intensity (0-0.98 N) within the horizontal plane (vector), the rate of application (0.049-490 N/s), and the duration (0-10 s). The stimulator is composed of electromagnetic drivers, a trapezoid-wave generator, and a stimulus monitor. The former is adopted from conventional pen drivers, and the latter two are composed of operational amplifier circuits. The vector stimulator was utilized to apply a stimulus force to the canine teeth of a cat, and the responses of the PM units were recorded in the somatosensory cerebral cortex.


Initial activity and inactivation of alkaline phosphatase in different lots of buffer.
Alkaline phosphatase activities were determined in six lots of 2-amino-2-methyl-1-propanol (AMP) and in six lots of diethanolamine (DEA) buffers without preincubation of the sample. There appeared to be differences between the lot numbers in both cases, resulting in a variation in initial activity. When serum samples are preincubated with buffer a loss of activity was observed in 4 out of the 6 AMP buffers. Four human isoenzymes showed varying inactivation during preincubation with AMP buffer. No loss of activity was observed when the preincubation was done with the six DEA buffers. These results indicate that the purity of the commercially-available buffers is quite unsatisfactory.


Elective induction of labour and maternal request: a national population-based study.
To estimate the rate of elective inductions in France and the proportion of them that were maternally requested, and to study the factors associated with elective inductions that were or were not requested by women. Cross-sectional population-based study. All maternity units in France. About 14 681 women from the 2010 French National Perinatal Survey of a representative sample of births. Inductions were classified as elective based on their indications and maternal and fetal characteristics, collected from medical records. Elective inductions requested by women were identified from the mother's postpartum interviews. Polytomous logistic regression analysis was used to study the determinants of inductions that were or were not maternally requested. Women with spontaneous labour served as the comparison group. Rate of elective inductions. The induction rate was 22.6, 13.9% elective. Among elective inductions, 47.3% were requested by women. The characteristics of mothers, pregnancies, and maternity units were similar in both groups of elective inductions. The main associated factors were parity 2 or more [adjusted odds ratio (OR) 4.7, 95% confidence interval (CI) 3.1-7.2 for maternally requested inductions and aOR of 1.8 (95% CI1.2-2.7) for unrequested inductions, compared with parity 0] and private hospital status [aOR 4.5 95% (CI 3.3-6.0) for maternally requested inductions and aOR 3.7 (95% CI 2.8-4.9) for inductions not requested by the mother]. We found no association between maternal social characteristics and type of elective induction. Parity and organisational factors appear to influence the decision about elective inductions. It would be interesting to determine how obstetricians and women make this decision and for what reasons. About 13.9% of inductions of labour were elective in France, 47.3% of these requested by women.


Systematic and Unsystematic Determinants of Sectoral Risk Default Interconnectedness.
Assessing the financial stability of the banking industry, particularly in credit risk management, has become extremely crucial in times of uncertainty. Given that, this paper aims to investigate the determinants of the interconnectedness of sectoral credit risk default for developing countries. To that purpose, we employ a dynamic credit risk model that considers a variety of macroeconomic indicators, bank-specific variables, and household characteristics. Moreover, the SURE model is used to analyze empirical data. We find the connection between macroeconomic, bank-specific, and household characteristics, and sectoral default risk. The outcomes of macroeconomic factors demonstrate that few macroeconomic determinants significantly influence the sector's default risk. The empirical results of household components reveal that educated households play a substantial role in decreasing sectoral loan defaults interconnectedness and vice versa. While for bank-specific characteristic, we find that greater bank profitability and specialization have substantially reduced loan defaults.


Vestibular rehabilitation by auditory feedback in otolith disorders.
Rehabilitation strategies have been applied successfully over the last few decades to initiate central compensation of the tonus imbalance and to facilitate substitution in different types of peripheral vestibular dysfunction. However, these vestibular rehabilitation strategies are often not successful in patients with isolated otolith disorders. The aim of the present study was therefore to evaluate a specific rehabilitation strategy for patients with an isolated otolith disorder by using an auditory feedback system. Thirteen patients, which suffered from different types of otolith disorders, but no other vestibular pathology and 13 normal controls were included in this study. Vestibular rehabilitation exercises were performed daily over a 2-week period (weekends excluded). During all exercises the patients of the test group (n=13) obtained an acoustic feedback signal when their trunk angle velocity exceeded a preset level while the patients of the control group (n=13) performed the same exercises without auditory feedback. The most effective exercise in the test group was "walking eight tandem steps on a foam support surface". Approximately 85% of the patients showed a significant decrease of trunk sway in this condition. In contrast to these results, patients of the control group showed no significant improvement of postural control after the training. The results indicate that an auditory feedback rehabilitation program with exercises related to the specific neurotological disease could significantly improve the postural control in patients with otolith disorders.


In vitro Effects of Polyphenols on the Peripheral Immune Responses in Nickel-sensitized Patients.
Nickel (Ni) is a metal largely present in the environment and prolonged exposure to it may lead to multiple pathological conditions in human subjects. Among these, the most frequent is allergic contact dermatitis. Peripheral blood mononuclear cells isolated from 25 patients with Ni-dependent contact dermatitis were evaluated in terms of cytokine release and nitric oxide (NO) production in the presence or absence of two doses (3 and 5 µg, respectively) of polyphenols. Polyphenols were able to reduce the increased release of interferon-γ and interleukin (IL)-4, while maintaining the equilibrium between IL-10 and IL-17. At the same time, exaggerated release of NO was reduced by polyphenol supplementation. In view of their anti-inflammatory activities, polyphenols may represent a potential therapeutic tool to treat Ni-sensitized patients.


Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.
The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.


Nitrite biotransformation by mitochondria from the earthworm Eisenia foetida (Savigny).
1. Nitrite oxidase and cytochrome-c oxidase activity catalysed by cytochrome-aa3 were assayed in earthworms and rats. 2. Cytochrome-aa3 and intact mitochondria from the two species were anaerobically incubated in the presence of nitrite; the occurrence of mitochondria-induced nitrite biotransformations was evaluated by monitoring nitrite recovery in incubation medium. Possible nitric oxide production was also tested. 3. The ratio nitrite oxidase/cytochrome-c oxidase activity was much higher in earthworms than in rats. 4. Under anaerobic conditions and in the presence of respiratory substrates, earthworm mitochondria produced a time-dependent loss of nitrite in the incubation medium. On the contrary, rat mitochondria are unable to decrease environmental nitrite concentration. 5. Results support the notion that metabolic properties of earthworm mitochondria can be considered as an adaptation to chronic nitrite exposure, this toxicant being typically present in natural habitats of these worms.


Virus-like particles of porcine bocavirus generated by recombinant baculoviruses can be applied to sero-epidemic studies.
Porcine bocaviruses (PBoVs), new members of the Bocavirus genus, have been identified in swine worldwide. However, the antigenicity and epidemiology of PBoVs are still unclear. Here we used a recombinant baculovirus expression system to express the main capsid protein VP2 of Japan strain JY31b in insect Tn5 cells, and successfully produced the virus-like particles of PBoV (PBoV-LPs). The diameter and densities of the PBoV-LPs were estimated to be 30nm and 1.300g/cm(3), respectively, which were similar to the values for the native virion of PBoV. Antigenic analysis demonstrated that the PBoV-LPs were not cross-reactive with porcine circovirus 2, but were cross-reactive with human bocavirus 1, 2, 3 and 4. An ELISA for detection of anti-PBoV IgG antibodies was established using PBoV-LPs as antigen, which proved to be useful for monitoring PBoV infection in both swine and wild boars. The preliminary epidemiology research showed that 90.7% of pigs and 59.5% of wild boars were positive for the anti-PBoV-IgG, suggesting that both species were also widely infected with PBoV. The seven PBoV strains detected in wild boars separated into four subgroups, demonstrating the genetic diversity of PBoV.


Effects of neurotrophins on embryonic retinal outgrowth.
The neurotrophins brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4 (NT-4), as well as their receptors, are expressed in both the developing and adult visual system. In vitro and in vivo studies suggest that BDNF in particular can enhance the survival of developing and injured retinal ganglion cells. We have previously shown that BDNF secreted by transgenic fibroblasts promotes outgrowth from embryonic retinae when cotransplanted into the cerebral cortex. The roles of NT-3 and NT-4 were investigated in this system along with BDNF, on retinal neuronal outgrowth, both on in vivo retinal transplants and on in vitro retinal explant cultures. Our results confirm that BDNF promotes retinal outgrowth of embryonic retinae both in vivo, and in vitro. NT4 was shown only to promote retinal outgrowth in vitro in the presence of proliferating glia. NT-3 was shown to have no effect on embryonic retinal outgrowth in vivo or in vitro. While other molecules have been proposed to play a role, the present results, together with evidence for BDNF in the developing superior colliculus and receptors on retinal cells, argue for an important role for BDNF in normal retinal neuronal outgrowth, with NT-4 playing a secondary role.


Effect of Digital Noise Reduction of Hearing Aids on Music and Speech Perception.
Although many studies have evaluated the effect of the digital noise reduction (DNR) algorithm of hearing aids (HAs) on speech recognition, there are few studies on the effect of DNR on music perception. Therefore, we aimed to evaluate the effect of DNR on music, in addition to speech perception, using objective and subjective measurements. Sixteen HA users participated in this study (58.00±10.44 years; 3 males and 13 females). The objective assessment of speech and music perception was based on the Korean version of the Clinical Assessment of Music Perception test and word and sentence recognition scores. Meanwhile, for the subjective assessment, the quality rating of speech and music as well as self-reported HA benefits were evaluated. There was no improvement conferred with DNR of HAs on the objective assessment tests of speech and music perception. The pitch discrimination at 262 Hz in the DNR-off condition was better than that in the unaided condition (p=0.024); however, the unaided condition and the DNR-on conditions did not differ. In the Korean music background questionnaire, responses regarding ease of communication were better in the DNR-on condition than in the DNR-off condition (p=0.029). Speech and music perception or sound quality did not improve with the activation of DNR. However, DNR positively influenced the listener's subjective listening comfort. The DNR-off condition in HAs may be beneficial for pitch discrimination at some frequencies.


Infertility and in vitro fertilization: the social worker's role.
The inability to have children may provoke a life crisis for a couple, and infertility treatment itself is usually stressful. After examining the psychosocial impact of infertility and the various options available to infertile couples, this article describes a hospital-based, in vitro fertilization program and the role of the social worker in supporting patients through the course of complicated and anxiety-producing medical procedures.


Ultrasound-guided Injection of the Levator Scapulae Muscle in a Cadaver Model.
Despite the advantages of ultrasound and previous anatomical data on neuromuscular junction locations, to the best of our knowledge, the feasibility and accuracy of precise ultrasound-guided injection techniques into the proposed injection site of botulinum neurotoxin for the levator scapulae muscle have not been assessed in any publication. In the present cadaver-based study, the ultrasound-guided injection technique in the middle and distal portions of the levator scapulae muscle was evaluated to determine whether this method distributes injections properly to the target muscle in fresh cadavers. Cadaveric study. A cadaver laboratory. Twenty fresh cadavers were used. Real-time B-mode ultrasound scanning was performed interfaced with a linear array transducer. A mixture of 0.5 mL of dye and yellow filler was injected transverse in-plane with a 6 cm 21-G. needle. Each specimen was dissected to determine whether the dye was correctly targeted to the middle and distal portions of the levator scapulae muscle and to evaluate the accuracy of the injections and any complications. All 40 injections were successfully injected within the middle and distal portions of the levator scapulae muscle. When dissecting the cadavers, the dye spread was evenly distributed along the muscle fiber. Despite successful injection into the middle and distal portions of the levator scapulae muscle, the usefulness of this technique was not verified in clinical practice. The ultrasound-guided injection technique presented in this study might facilitate precise visualization and localization of the levator scapulae muscle, thereby enhancing the effectiveness and safety of botulinum neurotoxin treatment in cervical dystonia.


Relationship Between Brain Amyloid Deposition and Instrumental Activities of Daily Living in Older Adults: A Longitudinal Study from the Multidomain Alzheimer Prevention Trial.
To examine the evolution of instrumental activity of daily living (IADL) performance according to the presence of brain amyloid deposition. Longitudinal analysis of a randomized controlled trial. Neuroimaging ancillary study from the Multidomain Alzheimer Prevention Trial (MAPT). Community-dwelling individuals aged 70 and older without dementia (N = 269; 60% female, mean age 75±4). Linear mixed models were used to assess the 36-month evolution of the performance of an IADL questionnaire for primary prevention studies in dementia, the Activity of Daily Living Prevention Instrument (ADL-PI), according to the presence of amyloid deposition using florbetapir positron emission tomography (PET) (standardized uptake value≥1.17). Additional analyses were also conducted to examine the changes in specific domains of daily functioning with and without adjustment for age, sex, apolipoprotein E, randomization group, and time between baseline and PET examination. One hundred two (37.9%) participants were amyloid positive. Amyloid-negative participants had statistically significant improvement in ADL-PI total score between baseline and 36 months (p=.04). The difference after 3 years between amyloid-positive and -negative participants was not significant (β=-0.95±0.53 at 36 months, p=.08; adjusted models: β=-1.07±0.56, p=.06). Amyloid-negative participants also improved in memory-related IADLs (p<.001) throughout the study, unlike amyloid-positive participants. Amyloid-positive and -negative older adults are likely to have different trajectories in IADL performance. Future research is needed to better understand the relationship between amyloid plaques and functional limitations.


Efficacy of resuscitative infusion with hemoglobin vesicles in rabbits with massive obstetric hemorrhage.
Hemoglobin vesicles have been developed as artificial oxygen carriers, and they have the potential to serve as a substitute for red blood cell transfusion. This study aimed to evaluate the efficacy of hemoglobin vesicle infusion for the initial treatment instead of red blood cell transfusion in rabbits with massive obstetric hemorrhage. Pregnant New Zealand white rabbits (28th day of pregnancy; normal gestation period, 29-35 days) underwent uncontrolled hemorrhage to induce shock by transecting the right midartery and concomitant vein in the myometrium. Subsequently, rabbits received isovolemic fluid resuscitation through the femoral vein with an equivalent volume of hemorrhage every 5 minutes. Resuscitative infusion regimens included 5% human serum albumin (n=6), stored washed red blood cells with plasma (vol/vol=1:1; n=5), and hemoglobin vesicle with 5% human serum albumin (vol/vol=4:1; n=5). A total of 60 minutes after the start of bleeding, rabbits underwent surgical hemostasis by ligation of the bleeding vessels and then were monitored for survival within 24 hours. During fluid resuscitation, hemoglobin vesicle infusion and red blood cell transfusion maintained a mean arterial pressure of >50 mm Hg and a hemoglobin concentration of >9 g/dL and prevented the elevation of plasma lactate. In contrast, resuscitation with 5% human serum albumin alone could not prevent hemorrhagic shock as evidenced by a low mean arterial pressure (40 mm Hg), a low hemoglobin concentration (2 g/dL), and a marked elevation of plasma lactate. All animals in the red blood cell group and the hemoglobin vesicle group survived more than 8 hours, whereas all animals in the 5% human serum albumin group died within 8 hours. Hemoglobin vesicle infusion may be effective in the initial management of massive obstetric hemorrhage.


Dose-level response rates of mTor inhibition in tuberous sclerosis complex (TSC) related subependymal giant cell astrocytoma (SEGA).
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disease usually diagnosed in childhood. Subependymal giant cell astrocytomas (SEGA) are benign brain lesions occurring in up to 20% of patients with TSC. Treatment with mTOR inhibitors has been proven effective in inducing SEGA shrinkage, but discontinuation results in re-growth. Evidence suggests that mTOR inhibition seems a disease-modifying treatment for TSC beyond inducing SEGA shrinkage; however concerns remain regarding negative long-term effects. Through this retrospective case series, an attempt was made to determine the minimal mTOR inhibitor dose needed to maintain radiological response of SEGA in six pediatric patients treated at The Hospital for Sick Children since 2007. This study reviews medication doses and blood levels as related to SEGA size on MRIs at 3-month intervals. Blood levels were monitored every 3 months and 2 weeks after dose adjustment. Total dose reduction by 25% was considered after SEGA shrinkage was maintained on two consecutive MRIs. All patients demonstrated SEGA shrinkage greater than 50% when treated with mTOR inhibition at therapeutic doses (4-5 mg/m(2)). When sirolimus doses were weaned in two patients by 50%, SEGAs regrew by 84% and 32%. In two patients, responses have been maintained with 30% decrease in sirolimus dose. One patient underwent SEGA resection and one remains on therapeutic dose. Therapeutic dose of mTOR inhibitor is effective in shrinking TSC-related SEGAs. Doses less than 2.5 mg/m(2) were insufficient to maintain response in this limited series.


2-(2-indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling.
We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.


The effect of early stimulation on maternal depression: a cluster randomised controlled trial.
To determine the effect of early childhood stimulation with undernourished children and their mothers on maternal depression. Mothers of 139 undernourished children (weight for age < or =-1.5 z-scores) aged 9-30 months were recruited from 18 government health centres in the parishes of Kingston, St Andrew, and St Catherine, Jamaica. They received weekly home visits by community health aides for one year. Mothers were shown play activities to do with their child using home made materials, and parenting issues were discussed. Frequency of maternal depressive symptoms was assessed by questionnaire. Child development was also measured. Mothers in the intervention group reported a significant reduction in the frequency of depressive symptoms (b = -0.98; 95% CI -1.53 to -0.41). The change was equivalent to 0.43 SD. The number of home visits achieved ranged from 5 to 48. Mothers receiving > or =40 visits and mothers receiving 25-39 visits benefited significantly from the intervention (b = -1.84, 95% CI -2.97 to -0.72, and b = -1.06, 95% CI -2.02 to -0.11, respectively) while mothers receiving <25 visits did not benefit. At follow up, maternal depression was significantly negatively correlated with children's developmental quotient for boys only. A home visiting intervention with mothers of undernourished children, with a primary aim of improving child development, had significant benefits for maternal depression. Higher levels of maternal depression were associated with poorer developmental levels for boys only.


Influence of graft size, histocompatibility,and cryopreservation on reproductive outcome following ovary transplantation in mice.
Transplantation of ovarian tissue is a valuable method to rescue mouse strains with fertility problems and to revitalize archived strains. The purpose of this study was to investigate the effect of (i) different sizes of transplanted ovary pieces on reproductive outcome, (ii) use of immunodeficient recipients to overcome the limitation of histocompatibility, and (iii) to compare different protocols for cryopreservation of ovarian tissue. Halves, quarters, and eights of mouse ovaries were transplanted. Half ovaries from B6 donors were transferred into immunodeficient mice. Halves of ovaries were frozen according to four different protocols, thawed and transferred. Pregnancy rate after transplantation of ovarian tissue was high (90-100%) independent of the transplant size. Although, the average litter size was significantly lower for recipients of quarters and eights (4.4 and 4.6 vs. 6.5), the total number of offspring produced per donor ovary was higher compared with recipients of halves. Pregnancy rate of immunodeficient recipients was 40% (mean 4.7 offspring per litter). All four cryopreservation protocols used were able to preserve functionality of the ovarian tissue. Transplantation of ovarian tissue smaller than halves resulted in reduced litter sizes. The distribution of ovarian tissue of one donor female to 4 or 8 recipients will therefore yield in a higher total number of offspring in a certain time period. The use of immunodeficient recipients is an option for non-histocompatible donors. Cryopreservation of ovarian tissue is generally feasible but the function of frozen-thawed ovary halves after transplantation differs depending on the freezing protocol used.


A general framework to characterize inhibitors of calmodulin: use of calmodulin inhibitors to study the interaction between calmodulin and its calmodulin binding domains.
The prominent role of Ca(2+) in cell physiology is mediated by a whole set of proteins involved in Ca(2+)-signal generation, deciphering and arrest. Among these intracellular proteins, calmodulin (CaM) known as a prototypical calcium sensor, serves as a ubiquitous carrier of the intracellular calcium signal in all eukaryotic cell types. CaM is assumed to be involved in many diseases including Parkinson, Alzheimer, and rheumatoid arthritis. Defects in some of many reaction partners of CaM might be responsible for disease symptoms. Several classes of drugs bind to CaM with unwanted side effects rather than specific therapeutic use. Thus, it may be more promising to concentrate at searching for pharmacological interferences with the CaM target proteins, in order to find tools for dissecting and investigating CaM-regulatory and modulatory functions in cells. In the present study, we have established a screening assay based on fluorescence polarization (FP) to identify a diverse set of small molecules that disrupt the regulatory function of CaM. The FP-based CaM assay consists in the competition of two fluorescent probes and a library of chemical compounds for binding to CaM. Screening of about 5300 compounds (Strasbourg Academic Library) by displacement of the probe yielded 39 compounds in a first step, from which 6 were selected. Those 6 compounds were characterized by means of calorimetry studies and by competitive displacement of two fluorescent probes interacting with CaM. Moreover, those small molecules were tested for their capability to displace 8 different CaM binding domains from CaM. Our results show that these CaM/small molecules interactions are not functionally equivalent. The strategy that has been set up for CaM is a general model for the development and validation of other CaM interactors, to decipher their mode of action, or rationally design more specific CaM antagonists. Moreover, this strategy may be used for other protein binding assays intended to screen for molecules with preferred binding activity. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.


Selective sensing properties and enhanced ferromagnetism in CrI3monolayer via gas adsorption.
Recent fabrication of chromium triiodide (CrI3) monolayers has raised potential prospects of developing two-dimensional (2D) ferromagnetic materials for spintronic device applications. The low Curie temperature has stimulated further interest for improving the ferromagnetic stability of CrI3monolayer. Here, based on density functional theory calculations, we investigated the adsorption energy, charge transfer, electronic and magnetic properties of gases (CO, CO2, N2, NH3, NO, NO2, O2, and SO2) adsorption on the CrI3monolayer. It is found that CrI3is sensitive to the NH3, NO, and NO2adsorption due to the high adsorption energy and large charge transfer. The electrical transport results show that the conductivity of CrI3monolayer is significantly reduced with the adsorption of N-based gases, suggesting that CrI3exhibits superior sensitivity and selectivity toward N-based gases. In addition, the ferromagnetic stability and Curie temperature (TC) of CrI3monolayer can be effectively enhanced by the adsorption of magnetic gases (NO, NO2, O2). This work not only demonstrates that CrI3monolayer can be used as a promising candidate for gas sensing, but also brings further interest to tune the electronic and magnetic properties of 2D ferromagnetic materials via gas adsorption.


Speech sound disorders or differences: Insights from bilingual children speaking two Chinese languages.
The study investigated how Putonghua-Cantonese bilingual children differ from monolinguals in their acquisition of speech sound and phonological patterns. Fifty-four typically developing Putonghua-Cantonese bilingual children aged 3;6-6;0 were recruited from nurseries in the North District of Hong Kong. The Hong Kong Cantonese Articulation Test (Cheung et al., 2006) and a Putonghua picture-naming task (Zhu & Dodd, 2000) were used to elicit single-word samples of both languages. Acquisition of speech sound and phonological patterns exhibited by ≥20% of the children in an age group were compared to the normative data on children who were Cantonese native or Putonghua monolingual speakers. The bilingual children demonstrated smaller sound inventory in both languages and more delayed and atypical phonological processes. The atypical patterns could be explained by phonological interference between Putonghua and Cantonese. The findings serve as a preliminary reference for clinicians in differentiating language difference from true speech sound disorders in Putonghua-Cantonese bilingual children in Hong Kong.


[Anti-pneumococcal vaccine coverage for hospitalized risk patients: Assessment and suggestions for improvements].
Streptococcus pneumoniae can cause invasive infections. Incidence and severity are linked to patients' risk factors. Due to the resistance to leading antibiotics, the anti-pneumococcal vaccination has become a major public health issue. The purpose of this survey was to evaluate the anti-pneumococcal vaccine coverage in a population of adults with risk factors. This was a prospective study that included patients with at least one recommendation for pneumococcal vaccination as indicated by the Weekly Epidemiological Bulletin (BEH), to which three further US recommendations were added (diabetes, obesity and age>65years). One hundred and thirty-four patients with an average age of 70 years were included. The physician could only confirm 68 % of the patients' vaccination status. Vaccination coverage as recommended by the BEH board was 30 % (n=54). All HIV patients were vaccinated (n=2) and the vaccination coverage was 75 % (n=8) for patients treated for autoimmune diseases and only 10 % (n=20) for patients treated with chemotherapy. Patients with no vaccination didn't know the existence of the vaccine or didn't know that vaccination was recommended to them. This study has highlighted a deficit in pneumococcal vaccination coverage and a high level of ignorance of the existence of recommended vaccination. In addition to awareness campaign for patients and caregiver training, the expansion of the vaccine e-book utilization could improve the vaccination status.


Some theoretical results on the observability of repolarization heterogeneity on surface ECG.
Assessing repolarization heterogeneity (RH) from surface ECG recording is an open issue in modern electrocardiography, despite the fact that several indexes measured on the T-wave have been proposed and tested. To understand how RH occurring at myocite level is reflected on T-wave shapes, in this paper we propose a mathematical framework that combines a simple statistical model of cardiac repolarization times with the dominant T-wave formalism. Within this framework we compare different T-wave features such as T-wave amplitude, T-wave amplitude variability or QT intervals and we describe mathematically how they are linked to the spatial and temporal components of repolarization heterogeneity.


Legacy and novel flame retardants in water and sediment from highly industrialized bays of Korea: Occurrence, source tracking, decadal time trend, and ecological risks.
Legacy and novel flame retardants (FRs) such as polybrominated diphenyl ethers (PBDEs), novel BFRs, and organophosphate flame retardants (OPFRs) were measured in water and sediment collected from highly industrialized bays of Korea. Predominant compounds in sediment were BDE 209, DBDPE, and BTBPE for BFRs, and TCPP and TBOEP for OPFRs, respectively. Higher alternative FR concentrations were observed compared to those reported for previous studies. The highest BFR concentrations were found in locations close to industrial complexes, while the OPFR concentrations were highest in locations close to domestic regions and a wastewater treatment plant. Different contamination sources were observed for BFRs and OPFRs. The ratio of DBDPE/BDE 209 in sediment ranged from 0.84 to 28, indicating a shift in consumption of BFRs. A significant decline in PBDEs suggests the effectiveness of domestic and global regulations. Despite this, sedimentary PBDE concentrations may pose adverse health risks to benthic organisms and humans.


Comparison of replicative and non-replicative chromatin assembly pathways in HeLa cell extracts.
It has been reported that chromatin assembly in mammalian cell extracts depends exclusively or preferentially on ongoing DNA replication (Stillman, B. (1986) Cell 45, 555-565). More recently, this view has been challenged demonstrating that, in the same extracts, chromatin can also be formed efficiently in the absence of DNA replication (Gruss et al. (1990) EMBO J. 9, 2911-2922). The experiments, described in this communication, were performed to resolve this apparent contradiction. We found that there are at least two distinct in vitro pathways for chromatin assembly in HeLa cell extracts. The replicative pathway requires a nuclear protein, most likely identical with the chromatin assembly factor, described by Stillman (1986, Cell 45, 555-565), and the free soluble histones present in the cytosol of S phase cells. In contrast, a non-replicative pathway was identified that depends on isolated nuclear histones. As one component of the non-replicative assembly pathway we identified a cytosolic factor that was purified to apparent homogeneity and shown to be an acidic 50 kDa polypeptide. The isolated cytosolic 50 kDa protein efficiently promoted nucleosome assembly as demonstrated by one- and two-dimensional gel electrophoresis of in vitro packaged plasmid DNA.


Habenula Lesions Reveal that Multiple Mechanisms Underlie Dopamine Prediction Errors.
Dopamine (DA) neurons are thought to facilitate learning by signaling reward prediction errors (RPEs), the discrepancy between actual and expected reward. However, how RPEs are calculated remains unknown. It has been hypothesized that DA neurons receive RPE signals from the lateral habenula. Here, we tested how lesions of the habenular complex affect the response of optogenetically identified DA neurons in mice. We found that lesions impaired specific aspects of RPE signaling in DA neurons. The inhibitory responses caused by reward omission were greatly diminished while inhibitory responses to aversive stimuli, such as air puff-predictive cues or air puff, remained unimpaired. Furthermore, we found that after habenula lesions, DA neurons' ability to signal graded levels of positive RPEs became unreliable, yet significant excitatory responses still remained. These results demonstrate that the habenula plays a critical role in DA RPE signaling but suggest that it is not the exclusive source of RPE signals.


Bronchial epithelial cells release inflammatory markers linked to airway inflammation and remodeling in response to TLR5 ligand flagellin.
Flagellin, which is abundant in gram-negative bacteria, including Pseudomonas, is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation. Normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14-16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells. Altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling. These findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling.


Mining and analysis of public sentiment during disaster events: The extreme rainstorm disaster in megacities of China in 2021.
Cities are concentrated areas of population that are vulnerable to the impact of natural disasters. Owing to the impact of climate change and extreme weather incidents in recent years, many cities worldwide have been affected by sudden disasters, especially floods, causing many casualties. Social media plays an important role in the communication and sharing of information when physical communication is limited in emergency situations. However, obtaining and using public sentiment during major disasters to provide support for emergency disaster relief is a popular research topic. In the summer of 2021, China's inland plains experienced extremely serious rainstorms. The rainfall on July 20 in the capital city of Zhengzhou, Henan Province, the most population province in China, reached 201.9 mm/h, causing extremely serious consequences. This case study examines people's sentiment about this event through datamining of Chinese Weibo social media during the extreme rainfall period. The six most concerned types of public response topics and 14 subcategory topics were determined from 2,124,162 Weibo messages. "Asking for help" and "public sentiment" dominated the main topics, reaching almost 66%, with a relatively even distribution of secondary categories, but with "appeal for assistance" taking the top spot. Topics changed cyclically with work and rest, but these areas seemed to lag behind coastal areas in their responses to the storm in the same time. The topics were centred around Zhengzhou and distributed in China's major city clusters, such as the Beijing-Tianjin-Hebei agglomerations, Yangtze River Delta, and Pearl River Delta regions. Community-level disaster relief information was also discovered, which showed that high building power outages, basement flooding, tunnel trapping, and drinking water shortages were common topics in specific inner urban regions. This detailed information will contribute to accurate location-based relief in the future. Based on this lesson, a series of measures for urban flood reduction are proposed, including disaster prevention awareness, infrastructure building, regulation mechanisms, social inclusivity, and media dissemination.


Hybrid 3D printed integrated microdevice for the determination of copper ions in human body fluids.
On-site screening of copper ions in body fluid plays a critical role in monitoring human health, especially in heavy pollution areas. In this study, we have developed a hybrid 3D printed integrated microdevice for the determination of copper ions in human body fluids. A fixed and low volume of sample was detected by using the integrated microdevice without any preprocessing. The hybrid channel enables sample uniform mixing and quantitative dilution with buffer solution by inducing the "horseshoe vortex" phenomenon. The electrolytic microcell based on the flow detection system shows a more effective copper ion reaction ratio and, as a result, a better sensitivity. The simulation of the finite element method (FEM) determined the relevant optimum parameters of the hybrid channel and the microcell. The design, fabrication, and detection procedure of the integrated microdevice are here illustrated. The microdevice presented superior detection properties towards copper ions. The calibration curves covered two linear ranges varying from 20 to 100 ppb and 100 to 400 ppb, respectively. The limit of detection was estimated to be 15 ppb (S/N = 3). The relative standard deviation of the peak current measurements was 2.26%. The designed microdevice was further applied to detect copper ions in practical samples (calf serum sample and synthetic human urine sample) using a standard addition method, and the average recovery was found to be 95-104%. The performance of copper ion detection with the integrated microdevice was consistent with that of the inductively coupled plasma mass spectrometry (ICP-MS) in the same practical samples, demonstrating significant practicality in the test of body fluidics. The portable integrated microdevice is an excellent choice for on-site detection and has a promising prospect in the point-of-care testing (POCT) applications.


Suppression of inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 22(R)-hydroxycholesterol requires de novo protein synthesis in activated macrophages.
Liver X receptors (LXRs) play an important role in lipid metabolism. Recently, a role for these proteins was identified in suppressing the inflammatory response. However, it is not known whether the natural ligands of LXRs, e.g. 22(R)-hydroxycholesterol (22R-HC), can suppress the inflammatory response after the onset of inflammation. We demonstrate here that treatment of Lipopolysaccharide (LPS)-activated RAW264.7 macrophages with 22R-HC markedly suppressed nitric oxide (NO) production and inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression. Additionally, 22R-HC did not affect the DNA binding activity of NF-kappaB, AP-1 and C/EBP(s), important transcriptional factors for iNOS and COX-2 genes expression. Furthermore iNOS and COX-2 mRNA suppression by 22R-HC was diminished by cellular treatment with cycloheximide. These results suggest that 22R-HC suppresses the expression of iNOS and COX-2 genes through de novo protein synthesis of an unidentified protein in LPS-activated macrophages.


Prognostic importance of COX-2 expression in patients with colorectal cancer.
A relationship between cyclooxygenase-2 (COX-2) expression and the pathogenesis of colorectal cancer has been reported in recent studies. Moreover, it has been indicated that COX-2 expression may have a prognostic role in colorectal cancer patients. In this study, we investigated the prognostic significance of COX-2 expression in 83 patients with colorectal cancer. COX-2 expression was assessed using immunohistochemical methods and was evaluated by grading both staining intensity and staining extension. The relationships between COX-2 expression and clinicopathological features of the patients and patient survival were evaluated. There was no relationships between COX-2 expression and tumor size (tm < 3 cm or tm > or = 3 cm), tumor histopathological differentiation (poorly differentiated or moderately + well differentiated), number of metastatic lymph nodes (< 4 or 3 > or = 4), histopathology of the tumor, localization of the tumor (colon or rectum), distant metastasis, and vascular invasion of the tumor. In the multivariate analysis, COX-2 expression was not found as an independent prognostic factor. We demonstrated that COX-2 expression was not correlated with clinicopathological characteristics of colon carcinoma and disease outcome.


Optimal pharmacotherapeutic management of hormone-sensitive metastatic prostate cancer.
The mainstay of initial therapy of metastatic prostate cancer has not changed since 1941 when Huggins and Hodges described the efficacy of castration. The benefit of combining an androgen receptor blocker with medical castration has been debatable despite several large randomized trials and meta-analyses intended to answer the question. Recent phase III trial data with continuous versus intermittent androgen deprivation in newly diagnosed metastatic prostate cancer have established continuous therapy as the preferred approach at the present time. Novel and more potent inhibitors of androgen signaling have been developed in the past 5 years and have been validated in castration-resistant disease. Their role in management of hormone-sensitive metastatic prostate cancer is under evaluation in ongoing studies. As androgen deprivation therapy carries significant long-term toxicities including fatigue and loss of bone and muscle mass, an important element of clinical management is prevention and amelioration of these toxicities.


Left-right symmetry of neuronal cell counts in the nucleus basalis of Meynert of control and of Alzheimer-diseased brains.
The nerve cell counts indicated that the neuronal population of the nucleus basalis of Meynert (nbM) was bilaterally symmetrical in both control and Alzheimer-diseased brains. In addition, the discussion deals with the possibility that a loss of neurons from rostral vs caudal parts of the nbM may occur during different stages of the disease.


Tomoelastography based on multifrequency MR elastography predicts liver function reserve in patients with hepatocellular carcinoma: a prospective study.
Estimating liver function reserve is essential for preoperative surgical planning and predicting post-hepatectomy complications in patients with hepatocellular carcinoma (HCC). We investigated hepatic viscoelasticity quantified by tomoelastography, a multifrequency magnetic resonance elastography technique, to predict liver function reserve. One hundred fifty-six patients with suspected HCC (mean age, 60 ± 1 years; 131 men) underwent preoperative tomoelastography examination between July 2020 and August 2021. Sixty-nine were included in the final analysis, and their 15-min indocyanine green retention rates (ICG-R15s) were obtained to determine liver function reserve. Tomoelastography quantified the shear wave speed (c, m/s), which represents stiffness, and loss angle (φ, rad), which represents fluidity. Both were correlated with the ICG-R15. A prediction model based on logistic regression for major hepatectomy tolerance (ICG-R15 ≥ 14%) was established. Patients were assigned to either the ICG-R15 < 14% (n = 50) or ICG-R15 ≥ 14% (n = 19) group. Liver c (r = 0.617) and φ (r = 0.517) were positively correlated with the ICG-R15 (both p < 0.001). At fibrosis stages F1-2, φ was positively correlated with the ICG-R15 (r = 0.528; p = 0.017), but c was not (p = 0.104). At stages F3-4, c (r = 0.642; p < 0.001) and φ (r = 0.377; p = 0.008) were both positively correlated with the ICG-R15. The optimal cutoffs of c and φ for predicting ICG-R15 ≥ 14% were 2.04 m/s and 0.79 rad, respectively. The area under the receiver operating characteristic curve was higher for c (0.892) than for φ (0.779; p = 0.045). Liver stiffness and fluidity, quantified by tomoelastography, were correlated with liver function and may be used clinically to noninvasively assess liver function reserve and stratify treatments.


Lipoprotein-induced modulation of cyclosporine-A-mediated immunosuppression.
Human serum lipoproteins form complexes with cyclosporine-A and act as a carrier of cyclosporine-A in vivo. We compared the immunosuppressive effects of free cyclosporine-A, a complex composed of cyclosporine-A and lipoproteins, free cyclosporine-A in the presence of each unbound lipoprotein, and each lipoprotein without cyclosporine-A with one another at concentrations comparable with in vivo conditions on PHA-stimulated peripheral blood mononuclear cells. Free cyclosporine-A reduced the proliferation of the PHA-stimulated mononuclear cells to 50% at a concentration of 300 ng ml-1 (SD +/- 30, n = 12) lipoprotein-deficient medium. Cyclosporine-A loaded into VLDL showed a 50% proliferation rate reduction at 60 micrograms VLDL ml-1 (SD +/- 10, n = 12) and 180 ng cyclosporine-A ml-1. In the presence of 100 ng ml-1 cyclosporine-A 180 micrograms ml-1 VLDL (SD +/- 25, n = 12) showed a proliferation rate reduction of 50%. In the same way VLDL without cyclosporine-A induced a reduction to 50% at 740 micrograms ml-1 (SD +/- 30, n = 12). Cyclosporine-A loaded into LDL showed a 50% proliferation rate reduction at 27 micrograms ml-1 LDL (SD +/- 5, n = 12) with 80 ng ml-1 cyclosporine-A. In the presence of 100 ng ml-1, cyclosporine-A 150 micrograms ml-1 LDL (SD +/- 25, n = 12) showed a proliferation rate reduction of 50%. In the same way, LDL without cyclosporine-A induced a reduction to 50% at 950 micrograms ml-1 (SD +/- 50, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)


Correction of interrupted aortic arch.
Twelve consecutive infants with interrupted aortic arch, ventricular septal defect, and persistent ductus arteriosus have had the anomaly repaired without the use of synthetic grafts. In two infants (5 and 9 months) the ductus arteriosus was used for the arch repair. In three patients (mean age 14 days) the left carotid artery was turned down to form the new arch. In the remaining seven (mean age 12 days) a direct anastomosis was achieved, but one of these patients died at operation. Two others in this group also had persistent truncus arteriosus. Five patients have required another operation (two for stenosis of the anastomosis with one death). The 10 survivors (mean follow-up 5 years) are well and support our belief that complete repair without the use of synthetic grafts is the treatment of choice in this rare and difficult group.


Titanium dioxide nanoparticles enhance photocurrent generation of cyanobacteria.
Photosynthetic microorganisms such as cyanobacteria can convert photons into electrons, providing ideal eco-friendly materials for converting solar energy into electricity. However, the electrons are hardly transported outside the cyanobacterial cells due to the insulation feature of the cell wall/membrane. Various nanomaterials have been reported to enhance extracellular electron transfer of heterotrophic electroactive microorganisms, but its effect on intact photosynthetic microorganisms remains unclear. In this study, we investigated the effect of six different nanomaterials on the photocurrent generation of cyanobacterium Synechocystis sp. PCC 6803. Among the nanomaterials tested, titanium dioxide (TiO2) nanoparticles increased the photocurrent generation of Synechocystis sp. PCC 6803 up to four-fold at the optimum concentration of 2 mg/mL. Transmission electron microscopy and scanning electron microscopy showed that TiO2 bound to cyanobacterial cells and likely penetrated inside of cell membrane. Photochemical analyses for photosystems showed that TiO2 blocked the electrons transfer downstream in PS I, implying a possible extracellular electron pathway mediated by TiO2. This study provides an alternative approach for enhancing the photocurrent generation of cyanobacteria, showing the potential of photosynthetic-nanomaterial hybrids.


Role of routine ultrasonography in monitoring the outcome of medical abortion in a clinical setting.
Clinical methods generally used to evaluate the completeness of medical abortion are not accurate. There are no published reports evaluating the role of routine ultrasonography in monitoring the outcome of medical abortion. The purpose of this study was to investigate whether routine transvaginal ultrasonography (TVS) at the follow-up visit after medical abortion can accurately identify women who will require surgical intervention. Retrospective review of medical records and charts of all women undergoing medical abortion in the first trimester of pregnancy between January 1999 and December 2001. Medical abortion was performed using oral mifepristone and a vaginal prostaglandin analog before 63 days gestation. All women had an initial TVS to confirm intrauterine pregnancy and gestational age, and another TVS at the follow-up visit 2-3 weeks later to assess the completeness of abortion. Surgical evacuation of the uterus was allowed as indicated on clinical grounds but not on the basis of ultrasound findings only. A total of 690 women consented to medical abortion during the study period. Eleven of these women were excluded from the study for various reasons. Of the remaining 679 cases, 95% (645/679) had a documented follow-up at the hospital. The pregnancy termination rate among these women was 99.2% (640/645) and TVS identified all five cases of continuing pregnancy at the follow-up. A total of 66 (10.2%) patients had complications. The uterine cavity was empty on TVS at the follow-up visit in 84.8% (547/645) of cases and only 3.1% (17/547) of them required surgical aspiration/curettage due to excessive or prolonged vaginal bleeding. In the remaining 15.2% (98/645) the uterine cavity was not empty, and 43.9% (43/98) of them had a curettage. The risk of requiring a surgical intervention was significantly higher [odds ratio (OR) 24.4; 95% confidence interval (95% CI) 14.9-39.7] when the uterine cavity was not demonstrated to be empty at the follow-up visit 2-3 weeks after medical abortion. However, 59.1% (55/93) of women did not require surgical intervention despite ultrasound evidence of thick endometrial echo-complex. Routine TVS 2-3 weeks after medical abortion appears to be an efficient means of accurately identifying the cases of ongoing pregnancy and diagnosing a complete abortion. Although TVS could be used as an adjunct to clinical examination to diagnose an incomplete expulsion, it does not accurately differentiate those women who require surgical intervention from those who do not.


Effects of relaxation and aversive visual stimulation on dark focus accommodation.
There is evidence that sympathetic innervation induces decreases in accommodation or accommodation amplitude. If so, emotional stress that produces sympathetic activation should induce similar changes in accommodation. In two experiments, dark focus accommodation was assessed following deep relaxation and after subjects looked at gruesome slides. Results showed that stress exposure led to lower dark focus values than did relaxation. Further, the degree to which dark focus was affected depended on subjects' levels of perceived arousal, and on the degree of stressfulness represented by the slides. It was concluded that psychological stress can produce predictable changes in accommodation, changes most parsimoniously understood in terms of autonomic innervation of the ciliary body.


Oral and dental alterations and growth disruption following chemotherapy in long-term survivors of childhood malignancies.
More attention has been focused on the long-term side effects of treatment protocols since impressive advances in childhood cancer treatment have resulted in a growing population of patients. The purpose of this study was to investigate the disturbances of dento-facial development in children who were long-term survivors of childhood malignancies. Fifty-three children (mean age, 10 years + 4 months) in long-term remission underwent oral/dental and radiographic examinations after completion of therapy. Crown and root malformations, gingival/periodontal status, enamel defects, discolorations, decayed and unerupted teeth, premature apexifications, agenesis, maximal interincisal opening and lateral movement of jaws, and soft tissue abnormalities were noted. Caries were evaluated by the decayed-missing-filled teeth (DMFT) index. Forty healthy children (mean age, 12 years + 4 months) belonging to the same age group and socioeconomic community were served as controls. All participants in the study were evaluated in terms of craniofacial development. The data of the study showed that higher prevalence of root malformation, unerupted teeth, and enamel hypoplasia were detected as a consequence of childhood cancer and/or antineoplastic therapy. Although no differences of craniofacial growth and development were observed between groups (P > 0.05), plaque and gingival index scores were statistically higher in the study group (P < 0.05). A range of variations in dental structures is recognized as a side effect of childhood cancer therapy in long-term survivors of pediatric malignancies that may affect their quality of life.


[Rice Bodies Presenting as Intra-Articular Masses in Pediatric Idiopathic Arthritis: A Case Report].
Rice bodies are commonly detected in adults with rheumatoid arthritis and rarely occur in children. An 11-year-old female adolescent who visited our hospital for evaluation of knee pain underwent a MRI scan, which revealed an intra-articular mass. Arthroscopic examination of the mass confirmed conglomerated rice bodies. We report a case of rice bodies that clinically presented as intra-articular masses.


Formulation of traditional Chinese medicine and its application on intestinal flora of constipated rats.
In this study, the self-extracted constipation treatment of traditional Chinese medicine extracts was applied to constipated rats. To explore the mechanism and role of the Chinese medicine for the treatment of constipation, the 16S rRNA sequencing and qRT-PCR technology were used to analyze the intestinal flora. We found that the relative abundance of Firmicutes with constipation was significantly higher accounted for 86.7%, while the gut microbiota was significantly changed after taking a certain dose of Chinese medicine, greatly increased the relative abundance of Lactobacillus accounted for 23.1%, enhanced the symbiotic relationships of Lactobacillus with other intestinal flora. The total copies of intestinal bacteria in the constipated rats decreased after taking the traditional Chinese medicine. Finally, this study results provides a theoretical basis for the treatment and understand the mechanism and effect of traditional Chinese medicine on rate constipation.


The 50th anniversary of gene therapy: beginnings and present realities.
Applying my experience in microbial genetics, especially in the genetic transformation/transduction of Bacilus subtilis bacteria, I decided around 1956 to develop a similar system for eukaryotic, especially human cell cultures. I believed it would permit the development of clinical applications for replacing defective genes to treat or cure some of the genetic diseases.


Vitamin C protects against hypochlorous Acid-induced glutathione depletion and DNA base and protein damage in human vascular smooth muscle cells.
Hypochlorous acid (HOCl), generated by myeloperoxidase released from activated macrophages, is thought to contribute to vascular dysfunction and oxidation of low density lipoproteins (LDLs) in atherogenesis. We have previously shown that HOCl exposure can cause chlorination and oxidation of isolated DNA and that vitamin C protects human arterial smooth muscle cells against oxidized LDL-mediated damage. We report in the present study that vitamin C attenuates HOCl-induced DNA base and protein damage and depletion of intracellular glutathione (GSH) and ATP in human arterial smooth muscle cells. Cells were pretreated in the absence or presence of 100 micromol/L vitamin C (24 hours) and then exposed to HOCl (0 to 500 micromol/L, 0 to 60 minutes) in the absence of vitamin C. Intracellular GSH and ATP levels were depleted by HOCl treatment, and gas chromatography-mass spectroscopy revealed a concentration- and time-dependent increase in DNA base oxidation and protein damage (measured as 3-chlorotyrosine). Pretreatment of smooth muscle cells with vitamin C significantly reduced the extent of HOCl-induced DNA and protein damage and attenuated decreases in intracellular ATP and GSH. Our findings suggest that physiological levels of vitamin C provide an important antioxidant defense against HOCl-mediated injury in atherosclerosis.


Priapism.
Since priapism often leads to impotence immediate therapy should be given with few exceptions (patients with sickle cell disease, neoplasm and infections). A careful history and a search for the etiology are important. The physician should protect himself against legal retribution by obtaining the patient's signature on an informed and witnessed consent to treat.


Sequence analysis and chromosomal localization of human Cap Z. Conserved residues within the actin-binding domain may link Cap Z to gelsolin/severin and profilin protein families.
From a human retinal cDNA library, we have isolated cDNAs that are homologs for the alpha 2 and beta subunits of chicken Cap Z. The derived human alpha subunit shares 95% amino acid identity with the chicken alpha 2 subunit; the beta subunit is 99% identical to the chicken subunit residues 1-243. The remaining portion of the human beta subunit (244-272) diverges significantly with only 8 out of 29 C-terminal amino acids conserved between the two species. This lack of conservation is of particular interest because the chicken C terminus contains an actin-binding domain. Cosedimentation assays with F-actin show that human Cap Z binds actin with an affinity equal that of chicken Cap Z. These results point to the eight shared amino acids as critical for actin binding, three of which are regularly spaced leucines. These apolar residues and one outside the region of divergence align well with those residues of the actin-binding alpha-helix proposed for gelsolin segment 1. The apolar residues as well as three polar amino acids are also conserved in other capping, capping and severing, and monomer-binding proteins. Amino acid substitutions in the chicken beta subunit of the two most highly conserved leucines result in significant decreases in F-actin binding activity. The human alpha 2 gene (CAPZA2) has been mapped to chromosome 7 position q31.2-q31.3 and the beta gene (CAPZB) to chromosome 1 region p36.1.


Anatomical studies and a correlative management of facial skeleton and skull base injuries with bone plate fixation.
Miniplate osteosynthesis is an osteoplastic procedure that achieves secure stabilization of the midface, even following extensive fractures of the midface and the floor of the anterior cranial fossa. This procedure can be considered a satisfactory operative treatment in terms of cosmetic and functional results. Correlative osteology is discussed and clinical experiences are reviewed.


Significance of preoperative serum CA-125 levels in the prediction of lymph node metastasis in epithelial ovarian cancer.
To investigate preoperative serum CA-125 levels as a predictive factor for evaluation of lymph node metastasis in epithelial ovarian cancer. Retrospective study. Medical records at Seoul National University Hospital. Ninety-nine patients with epithelial ovarian cancer between January 2004 and March 2007. The significance of the preoperative serum CA-125 level for the prediction of lymph node metastasis was determined using the receiver operating characteristic (ROC) curve, McNemar's test and logistic regression analysis. Clinical prognostic factors affecting survival were evaluated using the Kaplan-Meier analysis with the log-rank test and Cox's proportional hazard analysis. The ROC curve showed the best cut-off value (535 U/mL) of the preoperative serum CA-125 level with regard to sensitivity (70.0%) and specificity (83.1%). Imaging studies combined with the preoperative serum CA-125 level showed the highest sensitivity (90.0%), whereas imaging studies alone showed the highest specificity (89.8%) for the prediction of lymph node metastasis. FIGO stage III-IV, the preoperative serum CA-125 level (> or =535 U/mL) and lymph node involvement on imaging studies were significant factors for the prediction of lymph node metastasis (p<0.05). Suboptimal debulking surgery and lymph node metastasis were poor prognostic factors for progression-free survival and overall survival, respectively (p<0.05). The preoperative serum CA-125 level (> or =535 U/mL) may be important for the prediction of lymph node metastasis in patients with epithelial ovarian cancer. Furthermore, it can be helpful in selecting patients who should undergo systemic lymphadenectomy for the detection of hidden lymph node metastasis.


Abnormal colour vision is a handicap to playing cricket but not an insurmountable one.
Two studies have reported that abnormal colour vision is under-represented among cricketers, presumably because cricketers with abnormal colour vision have difficulty seeing the red ball against the green grass of the cricket field and the green foliage around it. We have previously reported on the difficulties of five cricketers with abnormal colour vision but we have also reported that one of Australia's finest cricketers was a protanope. This survey was undertaken to confirm the under-representation of abnormal colour vision among cricketers and to ascertain whether those playing tend to be (1) those with a mild colour vision deficiency, (2) bowlers rather than batsman and (3) prefer to field close to the batsman rather than in the outfield. The colour vision of 293 members of seven Melbourne Premier cricket clubs was tested using the Ishihara test. Those who failed were examined further to confirm their abnormal colour vision, to assess its severity with the Farnsworth D15 test and to classify it as either protan or deutan using the Medmont C100 test. A questionnaire about cricketing ability and problems playing cricket was administered. Twenty-six (8.9 per cent) of the cricketers had abnormal colour vision, of whom six played in the First Grade (6.7 per cent of First Grade players). The proportion of cricketers with a severe deficiency was significantly less than expected for the First Grade players. There were only two protans. Bowlers were not over-represented among the colour vision defective cricketers but those preferring to field close to the batsman were significantly over-represented. Abnormal colour vision is a modest handicap to playing cricket, especially at the higher levels of the game. It may impede batting and the ability to field in the outfield.


Determinants of left ventricular mass and presence of metabolic risk factors in normotensive individuals.
Insulin resistance and obesity are recognized as left ventricular (LV) mass determinants independent of blood pressure (BP). Prevalence of LV hypertrophy (LVH) and the relationship between LV mass to body composition and metabolic variables were evaluated in normotensive individuals as participants of a population-based study. LV mass was measured using the second harmonic image by M-mode 2D guided echocardiography in 326 normotensive subjects (mean 47+/-9.4 years). Fasting serum lipids and glucose, BP, body composition and waist circumference (WC) were recorded during a clinic visit. Applying a normalization criterion not related to body weight (g/height raised to the power 2.7) and the cut-off points of 47.7 (men) and 46.6 g/m(2.7) (women), LVH was found in 7.9% of the sample. Univariate analysis showed LV mass (g/m(2.7)) related to age, body mass index (BMI), WC, fat and lean body mass, systolic and diastolic BP, and metabolic variables (cholesterol, HDL-c, triglycerides and glucose). In multivariate analysis only BMI and age-adjusted systolic BP remained as independent predictors of LV mass, explaining 31% and 5% of its variability. Removing BMI from the model, WC, age-adjusted systolic BP and lean mass remained independent predictors, explaining 25.0%, 4.0% and 1.5% of LV mass variability, respectively. After sex stratification, LV mass predictors were WC (8%) and systolic BP (5%) in men and WC (36%) and systolic BP (3%) in women. BMI in general and particularly increased abdominal adiposity (WC as surrogate) seems to account for most of LV mass increase in normotensive individuals, mainly in women.


Isochamaejasmin induces toxic effects on Helicoverpa zea via DNA damage and mitochondria-associated apoptosis.
Stellera chamaejasme L. is a poisonous plant with rich resources and is thus highly valuable in terms of new pesticide development. Isochamaejasmin (ICM), one of the main ingredients in S. chamaejasme has drawn much attention owing to its antitumour properties. However, the toxicity and mode of action of ICM on insects are still not clear. In this article, the larva and neuronal cell (AW1) of Helicoverpa zea were used to clarify the insecticidal activity of ICM as well as its toxic mechanism at the cellular level. The results confirmed that ICM has potential toxicity against H. zea both in vivo and in vitro via time- and dose-dependent manners. Moreover, we found that ICM caused DNA damage and increased the levels of γH2AX and OGG1 in AW1 cells. Results also showed decline in the mitochondrial membrane potential (MMP), upregulation of Bax/Bcl-2 expression resulting in the release of cytochrome c into the cytosol, activation of caspase-3/9, and cleavage of poly ADP-ribose polymerase (PARP) as a result of exposure to ICM. Additionally, a dose-dependent rise in the reactive oxygen species (ROS) levels, accumulation of a lipid peroxidation product, and inactivation of antioxidant enzymes were found in ICM-treated cells. These findings confirmed the insecticidal activity of ICM. Furthermore, the results revealed that ICM could cause DNA damage and induce apoptosis via the mitochondrial pathway in AW1 cells. This study provides the basic information needed to understand the toxicity and mechanisms of action of ICM, which could potentially be used to develop it as a new insecticide.


Direct Chirality Recognition of Single-Crystalline and Single-Walled Transition Metal Oxide Nanotubes on Carbon Nanotube Templates.
Chirality is a significant structural feature for chemistry, biology, physics, and materials science, and especially determines the electrical, mechanical, and optical properties of diverse tubular structures, such as carbon nanotubes (CNTs). To recognize the chirality of nanotubes, templates are introduced as potential tools to obtain crystalline samples with visible chiral fringes under electron microscopes. However, few efforts show optimistic results, and new understanding is desired to control the sample quality with CNT templates. Here, a synthesis strategy of single-crystalline molybdenum trioxide (α-MoO3 ) nanotubes (MONTs) on CNT surfaces is reported to build a 1D van der Waals (vdW) heterostructure. The chirality of the MONTs can be directly "seen" and their structural selectivity is revealed. First, the centralized distribution of the chiral angles of the MONTs indicates a preferential orientation due to the anisotropic bending rigidity of the 2D layers. Then, the interlayer mismatching rejects the radial stacking of α-MoO3 to maintain the single-walled nature. These results provide a spontaneous strategy for the efficient recognition and control of chirality, and open up a new avenue for CNT-based functional 1D vdW heterostructures.


Categorical prevalence and severity of hyperprolactinaemia in two UK cohorts of patients with severe mental illness during treatment with antipsychotics.
Hyperprolactinaemia may be associated with hidden longer-term consequences, such as osteoporosis, bone fractures, pituitary tumours and breast cancer. Prolactin data from clinical trials is not always reported in a categorical manner and does not always allow the risk of hyperprolactinaemia to be evaluated for specific patient cohorts. Patients participating in a physical health management programme in the UK for severe mental illness patients--the Well-being Support Programme--had prolactin measurements made regardless of symptoms. Prolactin data from the complete cohort of 178 patients receiving antipsychotics in Leeds and London are reported. Hyperprolactinaemia was measured in 33.1% but more commonly in females than males (47.3% and 17.6%) and was associated with all antipsychotics except clozapine. The highest prevalence rates were found in amisulpride (n=20) 89%, risperidone long-acting intramuscular injection (LAIM) 67% (n=6) and risperidone (n=30) 55% used as antipsychotic monotherapy. Clinically Significant hyperprolactinaemia (>1000 mIU/L approximately 47 ng/ml) was measured in 15.8% of patients, predominantly in females. Levels >2000 mIU/L approximately 95 ng/ml in 6.2% of the complete cohort. Clinicians may wish to add prolactin measurement to the routine laboratory parameters currently measured for some antipsychotics and should be advised of the potential longer-term consequences of hidden hyperprolactinaemia.


Missed Opportunities in the Outpatient Pediatric Setting to Support Breastfeeding: Results From a Mixed-Methods Study.
Outpatient pediatric providers play a crucial role in the promotion of breastfeeding. We conducted a mixed methods study to measure provider knowledge, attitudes, and current practices around breastfeeding counseling. In New Mexico in 2016 and 2017, we conducted a knowledge, attitudes, and practice survey of outpatient pediatric providers (i.e., nurse practitioners, physicians, and physician assistants) and conducted focus groups with outpatient pediatric providers. Seventy-seven providers responded to the survey, and 17 participated in three focus groups. Fewer than half of providers surveyed reported asking how long mothers plan to breastfeed at initial well-baby examinations. One quarter of participants (28.2%) erroneously reported that hepatitis C was an absolute contraindication to breastfeeding. Just half of respondents had received continuing education within the past 3 years about managing common breastfeeding problems. We identified missed opportunities for outpatient pediatric providers to support breastfeeding and a need for continuing provider education.


Substrate elasticity regulates the behavior of human monocyte-derived macrophages.
Macrophages play a key role in atherosclerosis, cancer, and in the response to implanted medical devices. In each of these situations, the mechanical environment of a macrophage can vary from soft to stiff. However, how stiffness affects macrophage behavior remains uncertain. Using substrates of varying stiffness, we show macrophage phenotype and function depends on substrate stiffness. Notably, the cell area increases slightly from a sphere after 18 h on substrates mimicking healthy arterial stiffness (1-5 kPa), whereas macrophages on stiffer substrates (280 kPa-70 GPa) increased in area by nearly eight-fold. Macrophage migration is random regardless of substrate stiffness. The total average track speed was 7.8 ± 0.5 μm/h, with macrophages traveling fastest on the 280-kPa substrate (12.0 ± 0.5 μm/h) and slowest on the 3-kPa substrate (5.0 ± 0.4 μm/h). In addition F-actin organization in macrophages depends on substrate stiffness. On soft substrates, F-actin is spread uniformly throughout the cytoplasm, whereas on stiff substrates F-actin is functionalized into stress fibers. The proliferation rate of macrophages was faster on stiff substrates. Cells plated on the 280-kPa gel had a significantly shorter doubling time than those plated on the softer substrate. However, the ability of macrophages to phagocytose 1-μm particles did not depend on substrate stiffness. In conclusion, the results herein show macrophages are mechanosensitive; they respond to changes in stiffness by modifying their area, migration speed, actin organization, and proliferation rate. These results are important to understanding how macrophages respond in complex mechanical environments such as an atherosclerotic plaque.


Self-assembled encapsulation systems with pH tunable release property based on reversible covalent bond.
Dynamic diblock polymer PS-r-PEG formed via reversible acylhydrazone connection can be used to construct a pH-responsive self-assembled encapsulation system with high stability and sustained-release property, which shows potential in drug delivery.


Effect of acid lactic bacteria isolated from faeces of healthy dogs on growth parameters and aflatoxin B1 production by Aspergillus species in vitro.
The aim of the present study was to evaluate the inhibitory effect of Enterococcus faecium and Lactococcus lactis subsp. lactis isolated from faeces of healthy dogs on (i) lag phase, (ii) growth rate, and (iii) aflatoxin B1 production by Aspergillus section Flavi on in vitro assays. Thirteen lactic acid bacteria (LAB) isolates were used as antagonist microorganisms. Antagonistic activity was assayed against four potentially aflatoxigenic Aspergillus section Flavi isolates: A. flavus (AF210 and AF281), A. parasiticus (AP245) and A. parasiticus (NRRL 2999). In general, the longest lag phases of Aspergillus isolates were obtained with E. faecium GJ40. Respecting the growth rate, no significant reduction was found in this parameter in the interaction assays with A. flavus and antagonist isolates respecting the control. While in A. parasiticus a significant reduction in growth rate was only observed in the interaction among reference strain and E. faecium MF5 isolate (p < 0.05). In general, AFB1 production was reduced by most of the LAB isolates assayed, except for E. faecium GJ18, GJ20, MF3 and MF4. This study provides the first data about the antiaflatoxigenic activity of autochthonous LAB isolated from dog faeces.


Do count-based differential expression methods perform poorly when genes are expressed in only one condition?
A response to 'Comprehensive evaluation of differential gene expression analysis methods for RNA-seq data' by Rapaport F, Khanin R, Liang Y, Pirun M, Krek A, Zumbo P, Mason CE, Socci ND and Betel D in Genome Biology, 2013, 14:R95.


Idiopathic scoliosis: relations between the Cobb angle and the dynamical strategies when sitting on a seesaw.
The aim of this study was to determine the influence of the severity of the spinal curve on the postural regulation when self-imposed disturbances occur in a seated position in anteroposterior (AP) and mediolateral (ML) orientations. Twelve female adolescents with a right thoracic scoliosis (Cobb = 30.4° ± 9.7) were included in this study. The ground reaction forces (GRF) were studied while the subjects were maintaining their sitting on a seesaw (ML or AP destabilisation). Five conditions were tested: eyes open; with additional loads placed onto the subject's right or left shoulder; or onto the subject's right or left pelvis. We tested the correlation between the Cobb angle and the postural parameters (index of performance and GRF variability) for each condition. When the destabilisation was AP, the Cobb angle was significantly correlated with GRF variability and anterior and concavity index of performance. Two conditions showed higher correlations: stabilisation with the concavity pelvis load (GRF variability) and the open eyes (index of performance). In contrast, whatever the condition tested was, no link was found when the destabilisations were applied in ML direction. The destabilisation in a seated position highlights the influence of the curve severity on the postural organisation. In seated position, the postural control strategies specific to the scoliotic patients were always correlated by severity of curve, especially when the destabilisation is applied in AP directions. This study showed that the unstable seating position can be considered as a pertinent paradigm to help finding a postural clinical index for adolescent idiopathic scoliosis.


A Model of Chloroplast Growth Regulation in Mesophyll Cells.
Chloroplasts regulate their growth to optimize photosynthesis. Quantitative data show that the ratio of total chloroplast area to mesophyll cell area is constant across different cells within a single species and also across species. Wild-type chloroplasts exhibit little scatter around this trend; highly irregularly shaped mutant chloroplasts exhibit more scatter. Here we propose a model motivated by a bacterial quorum-sensing model consisting of a switch-like signaling network that turns off chloroplast growth. We calculated the dependence of the location of the relevant saddle-node bifurcation on the geometry of the chloroplasts. Our model exhibits a linear trend, with linearly growing scatter dependent on chloroplast shape, consistent with the data. When modeled chloroplasts are of a shape that grows with a constant area-to-volume ratio (disks, cylinders), we find a linear trend with minimal scatter. Chloroplasts with area and volume that do not grow proportionally (spheres) exhibit a linear trend with additional scatter.


Newborn screening for G6PD deficiency--why is it important for India?
Neonatal screening, the most important preventive public health programme of the 21st century, is implemented in majority of the developed countries. The Asia-Pacific region has a long history-the late Emeritus Professor Wong Hock Boon in 1965 initiated cord blood G6PD screening in Singapore, which virtually eliminated kernicterus. In India currently there is no government funded neonatal screening programme for the masses, but most private hospitals have started screening for disorders which the pediatrician there thinks is relevant in that part of the country. Indian Council of Medical Research has established a task force to look into these and there have been numerous updates from them including an updated website where a pediatrician or a hospital can download information. The authors present this study, which reveals that G6PD in India is a high priority for public screening.


Stuttering, speech rate, and the metronome effect.
Methodological inadequacies cast doubt on previous investigations of the hypothesis that metronome-paced speech reduces stuttering by slowing the rate of speech. In the present study, 6 stutterers' fluent speech rates were calculated by excluding the time occupied by stutters and pauses. The fluency-enhancing effect of metronome pacing was independent of speech rate.


A rating of perceived exertion scale using facial expressions for conveying exercise intensity for children and young adults.
To design a rating of perceived exertion (RPE) scale using facial expressions and assessed the validity of the scale for both children and young adults. Pearson moment-product correlation analysis was used to assess the correlation among heart rate (HR), RPE and pedaling workload. Fifteen children and 15 young adults participated in the study. Each participant randomly performed 5 pedaling tests with one repetition based on their submaximal acceptable workloads. Under each load condition, participants pedaled on a cycle ergometer for 10min; subsequently, participants completed Borg category ratio (CR10) or facial RPE (FRPE) scale assessments. Participants' heart rates (HR) were used to compare their scores on the Borg CR10 and Facial RPE scales. The results show that both Borg CR10 and FRPE scales reflected different pedaling workload levels. For young adults, HR positively correlated with both RPE scores under the various workload levels (r=0.989 and 0.977, all p<0.005); for children, only FRPE scores were positively correlated with HR (r=0.908, p<0.05). In other words, FRPE scores effectively reflected the HR of children, whereas Borg CR10 scores did not. The children may not understand words as effectively as young adults did, however, they understand facial expressions. The FRPE scale proposed in this study may be available in some special cases because it can assess those who cannot comprehend the written words used for the scale.


Benign peptic ulcers penetrating pericardium and heart: clinicopathological features and factors favoring survival.
Penetration of the pericardium and heart by benign peptic ulcers is rare. Before 1965 it was almost invariably fatal, but about 20% of recently reported cases have survived. We report 4 representative cases and review 91 additional cases from the literature. The ulcers arose in esophagus, hiatus hernias, abdominal stomach, and near anastomoses, and the predominant predisposing factor was previous surgery to the esophagogastric region. Whereas penetrating esophageal ulcers had a slightly better prognosis than gastric lesions, the principal determinant of clinical presentation, findings, and prognosis was the site of cardiac involvement. The clinicopathological features of pericardial, atrial, and ventricular involvement are distinct. We evaluate the different implications of these features for diagnosis, management, and prognosis and make some tentative recommendations regarding diagnostic procedures and treatment. Early diagnosis and prompt surgical intervention are critical to successful treatment of this entity, which may present with predominantly cardiac or gastrointestinal symptomatology.


Rearrangements involving four chromosomes in a child with congenital abnormalities.
This report describes a complex structural rearrangement between chromosomes X and 1 and a 7;13 translocation (together involving six break points) in a child with multiple congenital defects. Both parents showed a normal chromosome complement, suggesting that the changes may have originated either in a gametic nucleus or at a very early stage of zygotic development.


Solid pseudopapillary neoplasm-Case report of a rare pancreatic tumor.
Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor. Most patients are female within the second or third decade of life with only a small minority concerning children. Frequently described as low malignant potential tumors, surgical resection remains the main treatment. The authors present a case of a SPN diagnosed in a 17-year-old Caucasian girl with vomiting and abdominal pain localized to the right upper quadrant. CT scans and MRI scans showed the presence of a well-defined tumor arising from the pancreatic head with 14cm of greater diameter. Pylorus-preserving pancreatoduodenectomy was performed and histopathology confirmed a SPN with complete resection and no evidence of malignancy. SPN are usually found incidentally hence the importance of an accurate radiologic diagnosis. Symptoms may be present such as abdominal pain or vomiting due to compression, namely in large tumors. A surgical approach is usually indicated aiming complete resection, with tumor size not predicting resectability. Solid pseudopapillary tumors of the pancreas are extremely rare and usually have an excellent long-term prognosis after surgical resection.


Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder.
We examined genetic associations with duloxetine response in generalized anxiety disorder (GAD). Three pooled studies in patients with GAD receiving duloxetine 60-120 mg per day (N=164) or placebo (N=95) were used. Associations between 825 single-nucleotide polymorphisms (SNPs) in 61 candidate genes with change in Hamilton Anxiety Scale scores were examined with set-based testing (adjusted for the number of SNPs within each gene); sets with two-sided adjusted P≤0.05 were examined using repeated measure analysis. Follow-up analysis explored associations of these SNPs with change in Hamilton Rating Scale for Depression-Anxiety Subscale in a 6-week study in duloxetine-treated patients with major depressive disorder (MDD) (N=241). Variants in corticotropin-releasing hormone receptor 1 (CRHR1), dopamine receptor D3 (DRD3), nuclear receptor subfamily group C, member 1 (NR3C1) and phosphodiesterase 1A (PDE1A) were associated with duloxetine response in GAD. Only rs4792888 in CRHR1 showed modest evidence of association with duloxetine response in MDD (P=0.029 in GAD, P=0.054 in MDD). In conclusion, CRHR1 variation merits investigation in pathophysiology of anxiety and its treatment response.


Agreement of acute serious events recorded across datasets using linked Australian general practice, hospital, emergency department and death data: implications for research and surveillance.
Understanding the level of recording of acute serious events in general practice electronic health records (EHRs) is critical for making decisions about the suitability of general practice datasets to address research questions and requirements for linking general practice EHRs with other datasets. To examine data source agreement of five serious acute events (myocardial infarction, stroke, venous thromboembolism (VTE), pancreatitis and suicide) recorded in general practice EHRs compared with hospital, emergency department (ED) and mortality data. Data from 61 general practices routinely contributing data to the MedicineInsight database was linked with New South Wales administrative hospital, ED and mortality data. The study population comprised patients with at least three clinical encounters at participating general practices between 2019 and 2020 and at least one record in hospital, ED or mortality data between 2010 and 2020. Agreement was assessed between MedicineInsight diagnostic algorithms for the five events of interest and coded diagnoses in the administrative data. Dates of concordant events were compared. The study included 274,420 general practice patients with at least one record in the administrative data between 2010 and 2020. Across the five acute events, specificity and NPV were excellent (>98%) but sensitivity (13%-51%) and PPV (30%-75%) were low. Sensitivity and PPV were highest for VTE (50.9%) and acute pancreatitis (75.2%), respectively. The majority (roughly 70-80%) of true positive cases were recorded in the EHR within 30 days of administrative records. Large proportions of events identified from administrative data were not detected by diagnostic algorithms applied to general practice EHRs within the specific time period. EHR data extraction and study design only partly explain the low sensitivities/PPVs. Our findings support the use of Australian general practice EHRs linked to hospital, ED and mortality data for robust research on the selected serious acute conditions.


Glucose transporter number, function, and subcellular distribution in rat skeletal muscle after exercise training.
Endurance exercise training can result in increased rates of insulin-stimulated glucose uptake in skeletal muscle; however, this effect may be lost rapidly once training ceases. To examine a mechanism for these changes, the skeletal-muscle glucose transport system of female rats exercise-trained in wheelcages for 6 wk were studied against a group of untrained female rats. The trained rats were studied immediately following and 2 and 5 days after removal from wheelcages; both trained and untrained rats were studied 30 min after insulin (90 nmol/rat, intraperitoneal) or saline injection. The total number of skeletal-muscle plasma-membrane glucose transporters (R0), total muscle-homogenate and plasma-membrane GLUT4 protein, and rates of plasma-membrane vesicle D-facilitated glucose transport were higher in the exercise-trained rats immediately after exercise training and did not decrease significantly during the 5 days after cessation of training. On the other hand, exercise training did not alter microsomal-membrane total glucose-transporter number or GLUT4 protein, nor did training alter GLUT1 protein in total muscle homogenates nor either membrane fraction. The carrier-turnover number, an estimate of average functional activity of glucose transporters in the plasma membrane, was elevated slightly, but not significantly, in the trained muscle. In both the trained and untrained muscle, insulin administration resulted in translocation of glucose transporters from the microsomal-membrane fraction to the plasma membrane and an increase in the carrier-turnover number.(ABSTRACT TRUNCATED AT 250 WORDS)