External oxidant-free electrooxidative [3 + 2] annulation between phenol and indole derivatives.
Intermolecular [3 + 2] annulation is one of the most straightforward approaches to construct five membered heterocycles. However, it generally requires the use of functionalized substrates. An ideal reaction approach is to achieve dehydrogenative [3 + 2] annulation under oxidant-free conditions. Here we show an electrooxidative [3 + 2] annulation between phenols and N-acetylindoles under undivided electrolytic conditions. Neither external chemical oxidants nor metal catalysts are required to facilitate the dehydrogenation processes. This reaction protocol provides an environmentally friendly way for the selective synthesis of benzofuroindolines. Various N-acetylindoles bearing different C-3 and C-2 substituents are suitable in this electrochemical transformation, furnishing corresponding benzofuroindolines in up to 99% yield.Electrochemical oxidation provides a green alternative to the use of hazardous chemical oxidants and forcing conditions. Here, the authors show the electrocatalytic cross-coupling of phenols and indoles to generate biologically relevant benzofuroindolines in high yields.


Drug shortages in China: a cross-sectional study.
Drug shortages significantly threaten public health and medical service provision worldwide. Research evidence on the complete picture of drug shortages is currently scant in China. This study aimed to provide a descriptive overview and a reference for alleviating of drug shortages in China. National and provincial lists of drug shortages issued in China from 2018 to 2021 were collected and summarized. The information on essential medicines, medical insurance drugs, emergency drugs, and volume-based purchasing drugs was then matched with a drug shortage list to analyse the characteristics, proportion and incidence of drug shortage on each list based on the analysis of information such as dosage form, shortage frequency, and Anatomical Therapeutic Chemical (ATC) classification of the drugs in shortage. A total of 24 provinces issued drug shortages lists involving 408 drugs from 2018 to 2021. All 58 drugs in the national drug list were included on the provincial drug shortage list. Among all the drugs in shortage, the most significant shortage involved injections, accounting for 45.3% (185/408). Ninety-five drugs (23.3%) were in shortage 5 times (annual shortage > 1 time) or more in the provincial lists, and 199 drugs (48.8%) were on the shortage list only once. In terms of therapeutic property, nearly all categories of drugs had been reported in shortage, among which cardiovascular drugs, nervous system drugs, anti-tumor and immunomodulatory drugs, and blood and hematopoietic organ drugs accounted for more than 10%. There is no significant difference in drug shortage among economic regions. Comparing drugs in shortage and various lists, 81.9% (334/408), 51.0% (208/408) and 67.9% (277/408) fell on the National Medical Insurance Drug List, National Essential Medicines List, and WHO Model List of Essential Medicines, respectively, while the volume-based purchasing drugs accounted for 3.4% (14 drugs). The incidence of drug shortages on NEML, WHO Model List of Essential Medicines and medical insurance category A was significantly higher than that of medical insurance category B and volume-based purchasing drugs (P < 0.05). Of the Emergency Drugs List, 72.0% (36/50) also experienced shortages, significantly higher than all the above categories (P < 0.05). In China, drug shortages were severe and complicated. Drug shortages vary among economic regions but are not significant. In comparison, the national procurement pattern of volume-based drug purchasing may be conducive to alleviating the drug shortage problem. Collaboration of all partners was recommended to ensure the supply of clinically necessary drugs.


Which obesity index is the most useful marker for predicting hepatic steatosis in children and adolescents with obesity? A cross-sectional study using quantitative magnetic resonance imaging.
We aimed to evaluate the relationships between hepatic steatosis and various indices of obesity, and to identify the most useful index for the prediction of hepatic steatosis in children and adolescents with obesity. A total of 226 children and adolescents with a mean body mass index (BMI) z-score of 2.65 and a mean age of 11.4 years were subjected to anthropometric and body composition measurements, laboratory testing, abdominal fat mass assessment, and hepatic fat accumulation by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). The participants were divided into quartiles according to the severity of their hepatic steatosis, and the presence of hepatic steatosis was defined using an MRI-PDFF ≥ 5%. The multivariate ordinal regression analysis showed that the severity of hepatic steatosis was positively associated with BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, fat mass, fat-free mass, visceral adiposity, and abdominal subcutaneous adiposity. Higher activities of liver enzymes and higher concentrations of triglyceride, C-reactive protein, fasting insulin, and leptin were associated with more severe hepatic steatosis, whereas high-density lipoprotein-cholesterol and adiponectin were negatively associated with hepatic steatosis. The indices of obesity with areas under the receiver operating characteristic curves (AUCs) > 0.8 for the prediction of hepatic steatosis were liver enzymes, visceral adipose tissue area, waist-to-hip ratio, and waist-to-height ratio. The severity of hepatic steatosis significantly correlated with various indices of obesity and cardiometabolic markers in children and adolescents with obesity. The indices of abdominal obesity would be the most useful for the prediction of hepatic steatosis.


Evaluation of heart rate variability and night-time blood pressure measurements in patients with idiopathic sudden sensorineural hearing loss.
The aim of this study is to investigate the role of the autonomic nervous system in the etiology of idiopathic sudden sensorineural hearing loss (ISSHL) by measuring heart rate variability (HRV) and night-time blood pressure levels. A total of 58 patients, 31 ISSHL patients (group 1) and 27 healthy volunteers (control group; group 2), were included in this study. Clinical and ambulatory blood pressure measurements and Holter electrocardiography were performed in both groups. After these evaluations, HRV parameters and night-time blood pressure values were determined. Mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) measured at night-time were higher in group 1 compared to group 2 (p < 0.05). Heart rate variability parameters were lower in group 1 than in group 2. In patients with ISSHL, elevated blood pressure at night-time and reduced heart rate variability suggest that autonomic nervous system dysfunction might play a role in the etiopathogenesis of the disease. The measurements of ambulatory blood pressure and heart rate variability can reveal more enlightening data in the determination of the etiology of ISSHL and guiding the treatment.


Going, going, gone...? Implicit and explicit test of conceptual knowledge in a longitudinal study of semantic dementia.
Patients suffering from semantic dementia provide important constraints on theories of the structure and organisation of semantic memory. In this article we report one such patient, AM, whose progressive deterioration of semantics enables us to address the much-debated issue of whether conceptual structure is hierarchically organised. The hierarchical account predicts that brain damage should impair lower levels of the hierarchy (property information) before affecting higher level (category) information (Warrington and Shallice, Q. J. Exp. Psychol. 1975, 27, 635-657). We evaluate this prediction by repeated testing of AM in two studies--a semantic priming task and a verification task--over an 18 month period, contrasting the progressive deterioration of properties (functional and perceptual) and category relations (category co-ordinates and category labels). Properties were preserved longer than category information, arguing against a hierarchical account of semantic memory. In addition, functional properties were most robust to brain damage, supporting our claim that functional information plays a special role in semantic representations (Durrant-Peatfield et al., Proc. 19th Ann. Conf. of the Cognitive Science Society. Erlbaum, Mahwah, NJ, 1997. pp. 193-198. Tyler et al., Cognitive Neuropsychol. 1997, 14, 511-545).


Historical dynamics in ecosystem service bundles.
Managing multiple ecosystem services (ES), including addressing trade-offs between services and preventing ecological surprises, is among the most pressing areas for sustainability research. These challenges require ES research to go beyond the currently common approach of snapshot studies limited to one or two services at a single point in time. We used a spatiotemporal approach to examine changes in nine ES and their relationships from 1971 to 2006 across 131 municipalities in a mixed-use landscape in Quebec, Canada. We show how an approach that incorporates time and space can improve our understanding of ES dynamics. We found an increase in the provision of most services through time; however, provision of ES was not uniformly enhanced at all locations. Instead, each municipality specialized in providing a bundle (set of positively correlated ES) dominated by just a few services. The trajectory of bundle formation was related to changes in agricultural policy and global trends; local biophysical and socioeconomic characteristics explained the bundles' increasing spatial clustering. Relationships between services varied through time, with some provisioning and cultural services shifting from a trade-off or no relationship in 1971 to an apparent synergistic relationship by 2006. By implementing a spatiotemporal perspective on multiple services, we provide clear evidence of the dynamic nature of ES interactions and contribute to identifying processes and drivers behind these changing relationships. Our study raises questions about using snapshots of ES provision at a single point in time to build our understanding of ES relationships in complex and dynamic social-ecological systems.


Cryptogenic emboli in patients with patent foramen ovale or atrial septal defect associated with the use of nonsteroidal anti-inflammatory drugs.
Nonaspirin, nonsteroidal anti-inflammatory drugs (NANSAIDs) have been associated with arterial thromboembolic events in the general population. Our objective was to determine the prevalence of NANSAID use in patients diagnosed with cryptogenic emboli or paradoxical embolic events from a patent foramen ovale (PFO) or atrial septal defect (ASD) compared with a control population with an incidental PFO/ASD and no history of embolic events. We performed a retrospective case-control study of 90 age-matched patients to assess the association of NANSAIDs with cryptogenic arterial embolic events in patients with and without a history of PFO/ASD. Odds ratios (ORs) were obtained by chi2 analysis. Multivariate analysis was conducted with a logistical regression method. Patients with cryptogenic embolic events had a high prevalence of prescription NANSAID use regardless of the presence of a PFO/ASD and were far more likely to have a history of NANSAID use than those with an incidentally discovered PFO/ASD and no history of arterial emboli (OR 4.30, 95% confidence interval 1.14-13.07, p = 0.01). Many patients previously diagnosed with paradoxical emboli may be experiencing the prothrombotic effects of NANSAIDs rather than a paradoxical mechanism for their arterial embolic event.


Medication adherence in patients with chronic non-malignant pain: is there a problem?
Health care providers, treating patients with chronic non-malignant pain, often experience that medication is not as effective as expected. It is important to realize that the effectiveness of a pharmacological treatment can be influenced by the way the medication is taken. Medication adherence is a topic that gains more attention, especially in chronic conditions, because it affects treatment outcome. A systematic review of studies on medication adherence in patients with chronic non-malignant pain was performed to gain insight in the prevalence of the problem, the impact on treatment outcome, influencing variables and interventions. Searching several electronic databases (Medline, CINAHL, Psychinfo and Cochrane), 14 relevant articles were found. The results indicate that medication non-adherence is common in patients with chronic non-malignant pain. Both overuse and underuse of medication occurs. However, due to the scarce literature and important methodological limitations, it is not possible to make firm conclusions concerning the impact on outcome, influencing variables and optimal intervention strategies. This review highlights some important gaps in the adherence literature in a chronic non-malignant pain population and sets the stage for future research.


Minimized extracorporeal circulation system in coronary artery bypass surgery: a 10-year single-center experience with 2243 patients.
Coronary artery bypass grafting (CABG) is the gold standard for the surgical therapy of multivessel coronary artery disease. To reduce the side effects, associated with standard extracorporeal circulation (ECC), a concept of minimal extracorporeal circulation (MECC) was devised in our center. We report on our 10-year experience with the MECC for coronary revascularization. From January 1998 to August 2009, 2243 patients underwent CABG with MECC in our center. In a retrospective observational study, we analyzed indication, preoperative patient co-morbidity, postoperative clinical course, and perioperative outcome of all patients operated on with MECC. Furthermore, the risk factors for mortality in the MECC group were assessed. Patients showed a mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 4.5±0.1%. The mean age of the patients was 66.8±9.1 years. The overall 30-day mortality after CABG with MECC was 2.3%, ranging from 1.1% for elective to 13.0% for emergent patients and was significantly better than standard ECC. Only 15.3% (n=344) of patients with MECC required intra-operative blood transfusion. Postoperative catecholamine support, red blood cell transfusion, need for hemodialysis, release of creatinine kinase, incidence of stroke, and postoperative delirium were low after MECC revascularization. Ejection fraction below 30% (odds ratio (OR): 5.1), emergent operation (OR: 9.4), and high-dose catecholamine therapy (OR: 2.6) were associated predictors for mortality. MECC until now is an established concept and has become an alternative for ECC in routine CABG in our center. The use of the MECC system is associated with low mortality and conversion rate. Excellent survival rates and low transfusion requirements in the perioperative course were achieved.


In vitro susceptibilities of clinical yeast isolates to three antifungal agents determined by the microdilution method.
A comparative evaluation of the in vitro susceptibilities of 597 clinical yeast isolates to amphotericin B, fluconazole, and 5-fluorocytosine (5FC) was conducted. The broth macrodilution reference method of the National Committee for Clinical Laboratory Standards (NCCLS, M27-P) was adapted to the microdilution method. Microdilution endpoints for amphotericin B were scored as the lowest concentration in which a score of 0 (complete absence of growth) was observed and for 5FC and fluconazole as the lowest concentration in which a score of 2 (prominent decrease in turbidity; MIC-2) was observed compared to the growth control. The MIC values were read after 24 and 48 h incubation. A broad range of MIC values was observed with each antifungal agent. Amphotericin B was very active (MIC90 < or = 1.0 microgram/ml) against all of the yeast isolates with the exception of C. lusitaniae (MIC90 > or = 2.0 micrograms/ml). Fluconazole was most active against C. parapsilosis (MIC90 of 1.0 microgram/ml) and least active against C. krusei (MIC90 of 32 micrograms/ml). 5FC was most active against C. albicans, C. parapsilosis, C. tropicalis, and T. glabrata (MIC90 < or = 1.0 microgram/ml) and was least active against C. krusei and C. lusitaniae (MIC90 > or = 16 micrograms/ml). These data indicate that the microdilution method, performed in accordance with M27-P, provides a means of testing larger numbers of yeast isolates against an array of antifungal agents and allows this to be accomplished in a reproducible and standardized manner. Given these results, it appears that the microdilution method may be a useful alternative to the macrodilution reference method for susceptibility testing of yeasts.


Ketones regulate endothelial homeostasis.
In a recent paper in EMBO Molecular Medicine, Weis et al. reveal that cardiac endothelial cells can oxidize ketone bodies, which enhances cell proliferation, migration, and vessel sprouting. Furthermore, increasing ketone body levels with a ketogenic diet can increase endothelial cell proliferation and prevent blood vessel rarefication in hypertrophied mouse hearts. This suggests that increasing endothelial cell ketone oxidation has potential in treating heart failure.


Co-expression of mutant and normal human insulin receptors in COS 7 cells.
In order to assess the interference of the mutant insulin proreceptor on normal receptor function and formation of proreceptor-receptor heterotrimers (alpha beta-proreceptor), COS 7 cells were transfected with the same amount of expression plasmid (pGEM3SV) containing wild-type, a mutant proreceptor cDNA and both, using the DEAE-dextran method. Scatchard analysis of insulin binding data revealed that there was an approx. 50-fold higher receptor concentration in the transfected cells than in untransfected cells. After 0.025% trypsin treatment, insulin binding to the cells expressed with wild-type, proreceptor and both increased by 1-fold, 2.9-fold and 1.5-fold of the untreated cells, respectively. In the presence of 167 nM insulin, the amounts of phosphate incorporated into the 95 kDa protein beta-subunits and 210 kDa proreceptors from co-transfected cells, were identical to those of an in vitro mixture of the wild-type and the mutant receptors. At 10 nM insulin, the proreceptors from co-transfected cells normally autophosphorylated by insulin stimulation, whereas those mixed in vitro did not (73.3 +/- 9.3 vs. 29.6 +/- 2.6% of the maximal effect, n = 4, P < 0.01). However, at a similar concentration of insulin, the phosphate incorporation into Glu-80/Tyr-20 polymers by receptors from co-transfected cells was decreased when compared with a in vitro mixture (9.0 +/- 2.6 vs. 22.5 +/- 6.7% of the maximal effect at 4 nM, n = 6, P < 0.01), although the basal and maximally stimulated phosphate incorporation were comparable among these groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Very low calorie ketogenic diets in overweight and obesity treatment: Effects on anthropometric parameters, body composition, satiety, lipid profile and microbiota.
According to the World Health Organization (WHO) the prevalence of obesity tripled worldwide since 1975. Obesity prevention and treatment is based upon lifestyle changes involving eating habits, physical activity and behaviour therapy. Various dietary patterns have been used as nutritional strategies and, in recent years, interest has been shown in very low calorie ketogenic diets (VLCKD) that provide less than 800 calories (kcal), no more than 20-50 g/day of carbohydrates and 0.8-1.5 g/kg ideal body weight of protein. We conducted a literature review of all clinical trials published between January 2014-November 2019 on people with obesity (PWO) that evaluated VLCKD effects on anthropometric parameters, body composition, satiety, lipid profile and microbiota. Findings from literature showed that VLCKD could be useful to ameliorate the quality of life and sleep of PWO. It leads to a rapid weight loss and results in improvements in body mass index (BMI = kg/m2), waist circumference and fat mass reduction preserving lean body mass and resting metabolic rate. This eating pattern reduced the desire to eat and increased satiety. Little is known regarding the effects of VLCKD on the microbiota of PWO for which it is important to conduct further studies.


Phytochemical Analysis and Assessment of Biological Properties of Essential Oils Obtained from Thyme and Rosmarinus Species.
The plant species Thymus algeriensis (TA); Thymus capitatus (TC) and Rosmarinus officinalis (RO), are widely used in traditional medicine in Tunisia. The bioactivities of their essential oils have also been reported previously. The main objective of this work was to assess the phytochemical composition, the antioxidant activity, cytotoxic potential and the antibacterial, antifungal, of the essential oil (EO) of these plants. Gas Chromatography-Mass Spectrometry (GC-MS) was used to identify and quantify the constituents of the tested EO. Chemical tests, and spectrophotometric methods were used for antioxidant activities and for the screening and quantification of phytochemicals. The cytotoxic potential of the EO was checked using HCT 116 cultures. The extracts were evaluated for their antibacterial potential by the microdilution method. Antifungal activities were tested using the Poisoned food technique against Aspergillus niger and Aspergillus flavus. The EO of tested plants presented several components, mainly monoterpenes and sesquiterpenes. The results revealed that T. capitatus EO is not toxic compared to the other tested samples. Phenolic compounds were detected and this EO showed excellent antioxidant activity presenting dosedependent relationship. Regarding antimicrobial activity, T. capitatus EO, also had the highest inhibition against all tested bacteria and fungi. This study showed the importance of the bioactivities (antioxidant, antimicrobial, and safety potential) of EOs of the plant species TC, RO, and TA used in traditional medicine.


Studies on the erythropoietic effect of plasma from anemic toads both with and without testis.
Injection of plasma from experimentally induced anemic toad with intact testis increases erythropoiesis in starved toads evidenced by the increase of red blood cell, hemoglobin and hematocrit, whereas the plasma of castrated and phenylhydrazine-HCl treated anemic toad failed to do so. It can be suggested that the erythropoiesis stimulating factor (ESF) is produced from the testis of toad and the production of this factor (ESF) was found to increase during anemia in an attempt to correct the anemic condition.


Traffic-derived air pollution compromises skin barrier function and stratum corneum redox status: A population study.
Since air pollution is only one of many environmental stressors that can affect skin, it has been challenging to identify skin appearance or functional features profoundly affected by chronic exposure to traffic-derived air pollution. The current population study focused on taxi drivers working in urban and rural areas in order to take advantage of difference in occupational exposure. The skin conditions of 100 middle-aged male taxi drivers from urban Shanghai and 66 from rural Chongming were measured with facial tape strips were collected for biomarker analyses. Trans-epidermal water loss (TEWL) values before and after tape stripping were considerably higher in urban taxi drivers from Shanghai. Contrary to previous studies, there was no apparent detrimental effect on skin wrinkle or pigmentation from traffic pollution, which might be attributed to the higher than general public level of photo-exposure in this population. At the same time, pollution exposure especially the heavy traffic pollution exposure was found to associate with lower stratum corneum trypsin-like enzyme activity (SCTE), reduced catalase activity and total antioxidant capacity (TAOC) in tape strips. The evidence suggests that traffic-derived air pollution could deteriorate skin's physical and antioxidant barrier, whereas factors like photo-exposure can be overwhelming against appearance aging. Therefore, in addition to photoprotection, skin barrier care should be considered for people with high air pollution exposure.


Functional and morphological organization of the nucleus tractus solitarius in the fictive cough reflex of guinea pigs.
Projection of the superior laryngeal nerve (SLN) afferent fibers into the nucleus tractus solitarius (NTS) was investigated using a fluorescent tracer in guinea pigs. High density of fluorescence was detected in the ipsilateral NTS extending from 0.5 mm caudal to 1.2 mm rostral to the obex. At coronal slices, the fluorescent granules, lines and patches were located in the interstitial, medial and dorsal regions of NTS. Fluorescence was also found in the dorsal region of contralateral commissural NTS. Microstimulation of the rostral NTS, which corresponded to the region showing the strong fluorescence, induced an increase in the inspiratory discharge of phrenic nerve that was immediately followed by a large burst discharge of the iliohypogastric nerve in decerebrate, paralyzed and artificially ventilated guinea pigs. This serial response of the two nerves was identical to that induced by electrical stimulation of the SLN. Intravenous injection of codeine suppressed both NTS and SLN-induced responses. The SLN-induced response was inhibited by microinjection of codeine into the ipsilateral NTS and abolished by lesion of the ipsilateral NTS. These results suggest that the NTS has an integrative function in production of cough reflex and is possible sites of action of central antitussive agents.


Self-assembly of a ibuprofen-peptide conjugate to suppress ocular inflammation.
In the present study, we designed and synthesized a hydrogelator comprised of ibuprofen (IPF) and GFFY peptide linked through a cleavable ester bond. We found that the synthesized hydrogelator could spontaneously self-assemble into a hydrogel under a heating-cooling process. When the hydrogel was acted upon by an esterase, IPF was released in a sustained manner. Moreover, the hydrogel had significantly elevated anti-inflammatory efficacy, compared with IPF, in RAW264.7 macrophages. The hydrogel showed good cytocompatibility, as well as excellent ocular biocompatibility when instilled topically. In vivo results further demonstrated that the hydrogel had therapeutic efficacy comparable to that of a current treatment, sodium diclofenac (DIC) eyedrops, in suppressing ocular inflammation in lipopolysaccharide (LPS) induced uveitis. Our findings illustrated, for the first time, an effective approach for developing supramolecular assemblies as anti-inflammatory ophthalmic therapeutics for eye disorders.


Misdirection - past, present, and the future.
Misdirection refers to the magician's ability to manipulate people's attention, thoughts, and memory. It has been argued that some of the techniques used by magicians to orchestrate people's attention and awareness may provide valuable insights into human cognition. In this paper we review the scientific, as well as some of the magic literature on misdirection. We focus on four main points: (1) the magician's concept of misdirection, (2) the paradigms used to study misdirection scientifically, (3) review of the current scientific findings, and (4) future directions.


HELFIT: Helix fitting by a total least squares method.
The problem of fitting a helix to data arises in analysis of protein structure, in nuclear physics, and in engineering. A continuous helix is described by five parameters: helix axis, helix radius, and helix pitch. One of these helix parameters is frequently predefined in the helix fitting. Other algorithms find only the helix axis or determine separately the helix axis, the helix radius, or the helix pitch. Here we describe a total least squares method, HELFIT, for helix fitting. HELFIT enables one to calculate simultaneously all five of the helix parameters with high accuracy. The minimum number of data points required for the analysis is only four. HELFIT is very insensitive to noise even in short helices. HELFIT also calculates a parameter, p=rmsd/(N-1)(1/2), which estimates the regularity of helical structures independent of the number of data points, where rmsd is the root mean square distance from the best-fit helix to data points and N is the number of data points. It should become a basic tool of structural bioinformatics.


Pulpal and periradicular diagnosis: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section is devoted to clinical classification systems of pulpal and periradicular disease, pulpal diagnostic tests, incomplete crown fractures, transillumination, experimentally produced bony lesions, pulpal clinical correlations with histology, periradicular clinical correlations with histology, and radiographic size of periradicular lesion correlation with histology.


Yield of Imaging Performed as per Indian Society of Pediatric Nephrology Guidelines in Children with Urinary Tract Infection.
To assess yield of imaging performed as per Indian Society of Pediatric Nephrology (ISPN) urinary tract infection (UTI) guideline. Ultrasonography (USG), voiding cystourethrography (VCUG) and dimercaptosuccinic-acid (DMSA) scintigraphy were performed in 183 children (age 0-5y) with first episode (age 0-1y) of UTI or recurrent (age <5y) UTI, as per ISPN recommendations. Significant abnormalities were detected in 110 (63%), with vesicoureteric reflux (VUR) grades 3-5 in 31% and renal scars in 43%. Combined USG and DMSA had a negative predictive value of 94% for significant VUR. ISPN guideline resulted in a high yield of detection of significant abnormalities.


Immunohistochemical localization of collagenous proteins in cartilaginous tumors: characteristic distribution of type IX collagen.
The distinctive tissue localization of collagen types, particularly of type IX collagen in human cartilaginous tumors (10 cases of enchondroma and 15 cases of chondrosarcoma including 3 cases of secondary chondrosarcoma) was examined immunohistochemically using affinity-purified antibodies against types I, II, III, V, VI, and IX collagen, in comparison with that in human fetal cartilage. In fetal cartilage matrix, types II and IX collagen were diffusely distributed, while types I, III, and V collagens were not present. In the matrices of enchondromas and primary chondrosarcomas, types II and IX collagens were also diffusely distributed, but with some areas of irregular type IX collagen deposits. The secondary chondrosarcoma simulated normal fetal cartilage in the distribution pattern of types II and IX collagen, unlike the pattern in primary chondrosarcoma, where types II and IX collagen were decreased and poorly immunostained, whereas non-cartilaginous interstitial collagens (I, III, and V) appeared diffusely in the matrix, increasing with the grade of malignancy. These findings suggest that neoplastic cartilage is characterized initially by an uneven distribution of type IX collagen, prior to any alteration of other types of collagen; the diverse expressions of intercellular components in cartilaginous tumors may be one indicator for malignancy.


Hospital pharmacy practice in Saudi Arabia: Dispensing and administration in the Riyadh region.
There is very little published data assessing hospital pharmacy practice in Saudi Arabia. Hence, a comprehensive survey has been undertaken to evaluate hospital pharmacy services of the Kingdom of Saudi Arabia. Recently, we published the survey results on the prescribing and transcribing steps of the medication use process. This paper focuses on dispensing and administration. A modified-American Society of Health-System Pharmacists (ASHP) survey questionnaire was personally delivered to the pharmacy directors of 48 hospitals in the Riyadh region. Three attempted follow-ups were made within 3 months to non-responders and the surveys were collected upon completion. The survey was conducted using similar methods to those of the ASHP surveys. Twenty-nine hospitals participated in the survey with a response rate of 60.4%. Centralized distribution (74%) is the most commonly used model for inpatient pharmacies. Overall, 21% of hospitals routinely use bar coding technology in medication dispensing. None of the hospitals are using a robotic distribution system to automate the dispensing of unit doses. Automated dispensing cabinets (ADCs) are used by 21% of hospitals as part of their decentralized distribution model. Sixty-one percent of hospital pharmacies have IV admixture preparation area in their facility. In the use of safety technology for medication administration, only one third of hospitals are using electronic medication administration records (eMARs), 7.4% had bar-code-assisted medication administration (BCMA) and 12% had smart infusion pumps. Hospital pharmacies in the Riyadh region are fairly well developed in providing dispensing and administration services. Further improvement can be achieved by increasing the use of new technologies such as bar-code technology, unit dose drug distribution systems, pharmacy-based IV admixture services, smart infusion pumps, and automated medication distribution.


Should determination of the karyotype be systematic for all malformations detected by obstetrical ultrasound?
The aim of this study was to determine whether karyotyping should be performed for every fetal malformation detected in low risk populations. A karyotype was obtained from 428 fetuses examined over a 10-year period after fetal malformation was diagnosed using obstetrical ultrasound. These fetuses were separated into two groups, one with isolated malformations and the other with multiple malformations. The association between each type of malformation and the result of karyotype was evaluated. Forty-eight chromosomal abnormalities were encountered in 428 fetuses (11.2%). The karyotype was abnormal in 32/343 (9.3%) fetuses with isolated malformations and 16/85 (18.8%) fetuses with multiple malformations (p=0.022). The probability of an abnormal karyotype among the group of isolated malformation depended on the anatomical system involved (p<0.001). Our study demonstrated several isolated malformations without chromosomal abnormality (hydronephrosis with high obstruction, unilateral multicystic dysplastic kidney, gastroschisis, intestinal dilatation, meconium peritonitis, cystic adenomatoid malformation, pulmonary sequestration, tumor, vertebral anomaly). Each fetus with multiple malformations needs a chromosomal analysis. Within the group of isolated malformations, our study emphasizes that medical maternal history and the type of malformation need to be taken into account before performing a fetal karyotype.


TEMPOL increases NAD(+) and improves redox imbalance in obese mice.
Continuous energy conversion is controlled by reduction-oxidation (redox) processes. NAD(+) and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS) and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD(+) production in the ascorbic acid-glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD(+)/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD(+)/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity.


Circular dichroism and absorbance properties of nitrotyrosyl chromophores in staphylococcal nuclease and in a model diketopiperazine.
An active derivative of staphylococcal nuclease, in which only tyrosine residue 115 has been nitrated with use of tetranitromethane, has been characterized using absorbance, circular dichroism, and fluorescence spectroscopy. The results show that nitrotyrosine-115 nuclease is indistinguishable from native nuclease with regard to the average secondary structure of the folded polypeptide chain, the susceptibility of the enzyme to heat denaturation, and the local tertiary structure around tryptophan residue 140. Inasmuch as optical properties of nitrotyrosine-115 nuclease from 300 to 500 nm can be unambiguously assigned to nitrotyrosine residue 115 in the active site region, this modified enzyme presents a good model system for studying the circular dichroism properties of this aromatic amino acid in a protein. The spectral properties of nitrotyrosine-115 nuclease have been compared to those of the model compounds, cyclo-(-Gly-Tyr(3NO2)-) and Tyr(3NO2). Circular dichroism spectral changes in nitrotyrosine-115 nuclease due to the binding of deoxythymidine 3',5'-diphosphate and Ca-2+ have been compared to the corresponding nitrotyrosyl-115 absorption spectral changes. This comparison shows that the circular dichroism difference spectrum exhibits an over-all change in the intensity of the observed Cotton effects, whereas the absorption difference spectrum exhibits a blue shift. This finding supports the suggestion that perturbations of aromatic amino acid chromophores in proteins due to ligand binding result in red or blue shifts in absorption difference spectra, but in over-all changes of intensity in circular dichroism difference spectra.


Model-based inference for small area estimation with sampling weights.
Obtaining reliable estimates about health outcomes for areas or domains where only few to no samples are available is the goal of small area estimation (SAE). Often, we rely on health surveys to obtain information about health outcomes. Such surveys are often characterised by a complex design, stratification, and unequal sampling weights as common features. Hierarchical Bayesian models are well recognised in SAE as a spatial smoothing method, but often ignore the sampling weights that reflect the complex sampling design. In this paper, we focus on data obtained from a health survey where the sampling weights of the sampled individuals are the only information available about the design. We develop a predictive model-based approach to estimate the prevalence of a binary outcome for both the sampled and non-sampled individuals, using hierarchical Bayesian models that take into account the sampling weights. A simulation study is carried out to compare the performance of our proposed method with other established methods. The results indicate that our proposed method achieves great reductions in mean squared error when compared with standard approaches. It performs equally well or better when compared with more elaborate methods when there is a relationship between the responses and the sampling weights. The proposed method is applied to estimate asthma prevalence across districts.


The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore.
Necrostatin (Nec-1) protects against ischemia-reperfusion (IR) injury in both brain and heart. We have previously reported in this journal that necrostatin can delay opening of the mitochondrial permeability transition pore (MPTP) in isolated cardiomyocytes. The aim of the present study was to investigate in more detail the role played by the MPTP in necrostatin-mediated cardioprotection employing mice lacking a key component of the MPTP, namely cyclophilin-D. Anaesthetized wild type (WT) and cyclophilin-D knockout (Cyp-D-/-) mice underwent an open-chest procedure involving 30 min of myocardial ischemia and 2 h of reperfusion, with subsequent infarct size assessed by triphenyltetrazolium staining. Nec-1, given at reperfusion, significantly limited infarct size in WT mice (17.7 +/- 3% vs. 54.3 +/- 3%, P < 0.05) but not in Cyp-D-/- mice (28.3 +/- 7% vs. 30.8 +/- 6%, P > 0.05). The data obtained in Cyp-D-/- mice provide further evidence that Nec-1 protects against myocardial IR injury by modulating MPTP opening at reperfusion.


SV40 recombinants carrying a functional RNA splice junction and polyadenylation site from the chromosomal mouse beta maj globin gene.
We have introduced a fragment of the chromosomal mouse beta major globin gene into SV40 and used the resultant hybrid virus to infect cultured monkey kidney cells. The mouse DNA fragment, which contains an intervening sequence and a poly(A) addition site, has been inserted in both possible orientations relative to the SV40 late region promoter. While the fragment is transcribed regardless of orientation, the RNA splice signal and poly(A) addition site are utilized only when the fragment is inserted in the "sense" orientation. Thus genomic mouse signals for both splicing and polyadenylation are recognized across species boundaries. Furthermore, since only an 18 bp segment was included on the 5' border of the intervening sequence, we can define a maximum length for this splice signal.


A national survey on how to improve traditional Chinese medicine learning internationally: Perceptions from both teachers and students.
With the increasing popularity of traditional Chinese medicine (TCM) by the global community, how to teach basic knowledge of TCM to international students and improve the teaching quality are important issues for teachers of TCM. The present study was to analyze the perceptions from both students and teachers on how to improve TCM learning internationally. A cross-sectional national survey was conducted at 23 universities/colleges across China. A structured, self-reported on-line questionnaire was administered to 34 Chinese teachers who taught TCM course in English and to 1016 international undergraduates who were enrolled in the TCM course in China between 2017 and 2021. Thirty-three (97.1%) teachers and 900 (88.6%) undergraduates agreed Chinese culture should be fully integrated into TCM courses. All teachers and 944 (92.9%) undergraduates thought that TCM had important significance in the clinical practice. All teachers and 995 (97.9%) undergraduates agreed that modern research of TCM is valuable. Thirty-three (97.1%) teachers and 959 (94.4%) undergraduates thought comparing traditional medicine in different countries with TCM can help the students better understand TCM. Thirty-two (94.1%) teachers and 962 (94.7%) undergraduates agreed on the use of practical teaching method with case reports. From the perceptions of the undergraduates, the top three beneficial learning styles were practice (34.3%), teacher's lectures (32.5%), case studies (10.4%). The first choice of learning mode was attending to face-to-face teaching (82.3%). The top three interesting contents were acupuncture (75.5%), Chinese herbal medicine (63.8%), and massage (55.0%). To improve TCM learning among international undergraduates majoring in conventional medicine, integration of Chinese culture into TCM course, comparison of traditional medicine in different countries with TCM, application of the teaching method with case reports, and emphasization of clinical practice as well as modern research on TCM should be fully considered.


Activity standardization by means of liquid scintillation counting and determination of the half-life of 89Zr.
A89Zr solution was measured by means of liquid scintillation counting techniques in order to determine the activity concentration. Two methods were used: the CIEMAT/NIST efficiency tracing method with 3H as a tracer, and the triple-to-double coincidence ratio method. The counting efficiencies were computed with a stochastic model. The very detailed investigation showed that a few corrections are particularly important: Asymmetries in the photodetector responses as well as the backscattering of high-energy gamma rays must be taken into account. Corresponding corrections have therefore been applied. In addition, a detailed uncertainty analysis was carried out and the uncertainties compared with those determined by other research groups. The activity concentrations obtained from the two methods agree well and a combined result was used to establish calibration factors for ionization chambers, which are important secondary standardization instruments. The ionization chambers were combined with a new high-precision current measurement device to provide outstanding linearity. Measurement data from one chamber were used to determine the half-life, which was found to be T1/2=(78.373 ± 0.023) h.


Recurrent Klebsiella bacteremia due to chronic strongyloidiasis in the context of cirrhotic hepatopulmonary syndrome.
A woman in her 50s with a medical history of cirrhosis, alcohol use disorder, primary biliary cholangitis and extended spectrum beta lactamase (ESBL) Klebsiella presented with weakness, cough and abdominal pain with positive blood cultures for ESBL Klebsiella, and was treated with intravenous meropenem and patient symptoms improved. Testing for Strongyloides antibodies was positive, so she was treated with ivermectin. Strongyloidiasis-associated Gram-negative rod (GNR) bacteremia are rare conditions; however, it is important to consider an underlying strongyloidiasis in recurrent GNR bacteremia to prevent recurrent hospitalisation and morbidity.


SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function.
The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective autophagy receptor family, are involved in Tax-mediated NF-κB signaling. Here, using a proximity-dependent biotinylation approach (BioID), we identify p62 as a new candidate partner of Tax and confirm the interaction in infected T cells. We then demonstrate that p62 knock-out in MEF cells as well as p62 knock-down in HEK293T cells significantly reduces Tax-mediated NF-κB activity. We further show that although p62 knock-down does not alter NF-κB activation in Jurkat T cells nor in infected T cells, p62 does potentiate Tax-mediated NF-κB activity upon over-expression in Jurkat T cells. We next show that p62 associates with the Tax/IKK signalosome in cells, and identify the 170-206 domain of p62 as sufficient for the direct, ubiquitin-independent interaction with Tax. However, we observe that this domain is dispensable for modulating Tax activity in cells, and functional analysis of p62 mutants indicates that p62 could potentiate Tax activity in cells by facilitating the association of ubiquitin chains with the Tax/IKK signalosome. Altogether, our results identify p62 as a new ubiquitin-dependent modulator of Tax activity on NF-κB, further highlighting the importance of ubiquitin in the signaling activity of the viral Tax oncoprotein.


Lipid lowering agents of natural origin: An account of some promising chemotypes.
The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting naturally occurring compounds and their derivatives as potential hypolipidemic agents. Some of the interesting natural chemotypes that can control the increased levels of plasma lipids and discussed in this review are compactin, lovastatin, gugglesterone, berberine, lupeol, phytol, polyprenol, aegeline, 4-hydroxyisoleucine, α-asarone, resveratrol, esculeoside A, swertiamarin, rutin, saucerneol B, curcumin and a clerodane diterpene.


α-Actinin-4 drives invasiveness by regulating myosin IIB expression and myosin IIA localization.
The mechanisms by which the mechanoresponsive actin crosslinking protein α-actinin-4 (ACTN4) regulates cell motility and invasiveness remain incompletely understood. Here, we show that, in addition to regulating protrusion dynamics and focal adhesion formation, ACTN4 transcriptionally regulates expression of non-muscle myosin IIB (NMM IIB; heavy chain encoded by MYH10), which is essential for mediating nuclear translocation during 3D invasion. We further show that an indirect association between ACTN4 and NMM IIA (heavy chain encoded by MYH9) mediated by a functional F-actin cytoskeleton is essential for retention of NMM IIA at the cell periphery and modulation of focal adhesion dynamics. A protrusion-dependent model of confined migration recapitulating experimental observations predicts a dependence of protrusion forces on the degree of confinement and on the ratio of nucleus to matrix stiffness. Together, our results suggest that ACTN4 is a master regulator of cancer invasion that regulates invasiveness by controlling NMM IIB expression and NMM IIA localization. This article has an associated First Person interview with the first author of the paper.


Early discharge after nonoperative management for splenic injuries: increased patient risk caused by late failure?
With increasing experience and knowledge about nonoperative management of splenic injury (NOMSI), patients are being discharged early and possibly placed at risk for late failure of NOMSI and its associated complications. To evaluate if blunt trauma patients managed by NOMSI can be safely discharged early, because failure after the third day from injury occurs infrequently and is not associated with added morbidity. The medical records of patients who failed NOMSI from January 1993 to December 2005 in an academic level 1 trauma center were reviewed. Patients who failed NOMSI within 3 days (early failure) were compared with patients who failed it after 3 days (late failure) to identify characteristics that may help predict late failure. Primary outcomes were complications and death related to late failure. Of 691 patients admitted with blunt trauma to the spleen, 499 (72%) had NOMSI and 36 (7%) failed it. Early failure was recorded in 26 patients (5%) and late failure in 10 (2%). Late bleeding was the cause of failure in all patients with late failure and occurred in 8 +/- 6 (mean +/- SD) days after admission (4-8 days in 7 patients and 12-22 days in 3). When comparing age, Injury Severity Score, hemotocrit on admission, preoperative blood transfusions, and grade of splenic injury, no differences were found between patients with early and late failure. All but 1 patient with late failure were still in the hospital for associated injuries at the time of failure. No patient died, had delayed diagnosis, or suffered added morbidity because of late failure. Late failure occurs infrequently, unpredictably, and almost always in patients who are still in the hospital for associated injuries. In-hospital observation beyond the third day after injury is not necessary for most patients with splenic injury, who have no other reason to remain hospitalized.


Direct observation of geometric-phase interference in dynamics around a conical intersection.
Conical intersections are ubiquitous in chemistry and physics, often governing processes such as light harvesting, vision, photocatalysis and chemical reactivity. They act as funnels between electronic states of molecules, allowing rapid and efficient relaxation during chemical dynamics. In addition, when a reaction path encircles a conical intersection, the molecular wavefunction experiences a geometric phase, which can affect the outcome of the reaction through quantum-mechanical interference. Past experiments have measured indirect signatures of geometric phases in scattering patterns and spectroscopic observables, but there has been no direct observation of the underlying wavepacket interference. Here we experimentally observe geometric-phase interference in the dynamics of a wavepacket travelling around an engineered conical intersection in a programmable trapped-ion quantum simulator. To achieve this, we develop a technique to reconstruct the two-dimensional wavepacket densities of a trapped ion. Experiments agree with the theoretical model, demonstrating the ability of analogue quantum simulators-such as those realized using trapped ions-to accurately describe nuclear quantum effects.


Myocardial fibrosis in chronic aortic regurgitation: molecular and cellular responses to volume overload.
Myocardial fibrosis is common in patients with chronic aortic regurgitation (AR). Experimentally, fibrosis with disproportionate noncollagen extracellular matrix (ECM) elements precedes and contributes to heart failure in AR. We assessed [3H]-glucosamine and [3H]-proline incorporation in ECM, variations in cardiac fibroblast (CF) gene expression, and synthesis of specific ECM proteins in CF cultured from rabbits with surgically induced chronic AR versus controls. To determine whether these variations are primary responses to AR, normal CF were exposed to mechanical strain that mimicked that of AR. Compared with normal CF, AR CF incorporated more glucosamine (1.8:1, P=0.001) into ECM, showed fibronectin gene upregulation (2.0:1, P=0.02), and synthesized more fibronectin (2:1 by Western blot, P<0.06; 1.5:1 by affinity chromatography, P=0.02). Proline incorporation was unchanged by AR (1.1:1, NS); collagen synthesis was unaffected (type I, 0.9:1; type III, 1.0:1, NS). Normal CF exposed to cyclical mechanical strain during culture showed parallel results: glucosamine incorporation increased with strain (2.1:1, P<0.001), proline incorporation was unaffected (1.1:1, NS), fibronectin gene expression (1.6:1, P=0.07) and fibronectin synthesis (Western analysis, 1.3:1, P<0.01; chromatography, 1.9:1, NS) were upregulated. In AR, CF produce abnormal proportions of noncollagen ECM, specifically fibronectin, with relatively little change in collagen synthesis. At least in part, this is a primary response to strain imposed on CF by AR. Further study must relate these findings to the pathogenesis of heart failure in AR.


Endogenous dopamine and serotonin release from the explanted rat tuberohypophyseal system: effects of electrical stimulation and neurotensin.
Excised blocks of brain tissue encompassing the hypothalamic periventricular nucleus, arcuate nucleus, infundibular stalk and attached pituitary neurointermediate lobe (NIL) were obtained from rats and perifused in vitro. The intact tuberohypophyseal dopaminergic pathway projecting from cell bodies in the hypothalamus to terminations in the pars intermedia and posterior lobes was thus isolated. An electrode placed in the explant delivered electrical pulses at various frequencies to hypothalamic targets. Products released in the immediate vicinity of the NIL were continuously collected and assayed for dopamine and serotonin content. Electrical stimulation of the arcuate nucleus from 1.0 - 10.0 Hz produced a frequency-dependent increase in dopamine, but not serotonin, release from the NIL. Stimulation of the infundibular stalk, however, elevated the release of both neurotransmitters. Addition of neurotensin (0.001 - 1.0 microM) to the bathing media produced a concentration-dependent increase in dopamine, but not serotonin, release. These experiments demonstrate the utility of the tuberohypophyseal explant as a model for use in the study of dopaminergic neuronal function in this neuroendocrine axis.


A study of ΔNp63 expression in lung non-small cell carcinomas.
Distinguishing between lung adenocarcinoma and squamous cell carcinoma is becoming increasingly important, given the different treatment regimens available. Although histologic subdivision between the two is generally not difficult in differentiated tumors, it can be challenging in poorly differentiated tumors and may require a panel of immunohistochemistry stains. The p63 gene encodes two different N-termini (TA and ΔN). ΔNp63 is selectively expressed in squamous cell carcinoma, whereas TAp63 is not restricted only to it. 4A4, a widely used anti-p63 antibody, identifies both isoforms and is expressed in about 15% of adenocarcinomas, and, although generally focal, its expression can be diffuse. In this study, a total of 150 lung adenocarcinomas and 50 squamous cell carcinomas were immunostained by antibodies for p63 (4A4), ΔNp63 (p40), and TTF-1 (8G7G3/1). Twenty-seven adenocarcinomas (18%) were positive for p63 to a variable extent, with diffuse reaction being seen in 13 tumors (8.7%). p63 expression was seen in all subtypes of adenocarcinomas, except for the mucinous type. p40 was negative in all adenocarcinomas. All squamous cell carcinomas were diffusely positive for both p63 and p40. Four of 27 p63-positive adenocarcinomas were negative for TTF-1. p63 expression is not uncommonly seen in adenocarcinomas, whereas ΔNp63 (p40) expression is specific for squamous cell carcinoma, with sensitivity comparable to that of p63 expression. Presence of p63-positive cells in poorly differentiated lung adenocarcinoma may be erroneously interpreted as evidence of squamous cell differentiation. p40 appears to be a more reliable marker for squamous cell carcinoma.


E/Z-Thesinine-O-4'-alpha-rhamnoside, pyrrolizidine conjugates produced by grasses (Poaceae).
Based on direct infusion mass spectrometry we identified a novel alkaloid as a major component of perennial ryegrass (Lolium perenne). Initial mass spectral data suggested it to be a pyrrolizidine conjugate. As this class of alkaloids has not been described before from grasses, we isolated it to elucidate its structure. The isolated alkaloid proved to be a mixture of two stereoisomers. The structures of the two compounds as determined by 1D and 2D NMR spectroscopy, were E-thesinine-O-4'-alpha-rhamnoside (1) and Z-thesinine-O-4'-alpha-rhamnoside (2). These identifications were supported by the characterisation by GC-MS and optical rotation of (+)-isoretronecanol as the necine base released on alkaline hydrolysis of these alkaloids. 1 and 2 together with the aglycone and a hexoside were also detected in tall fescue (Festuca arundinacea). This is the first report of pyrrolizidine alkaloids produced by grasses (Poaceae).


"A Novel Method Using the Petal Pattern for Contouring a Domed Nipple in Tuberous Breasts".
The main cause of domed nipples is increased pressure, which causes the breast tissue to herniate toward the nipple-areola complex. It appears as a characteristic of a tuberous breast rather than occurring alone, and the boundary between the nipple and areolar region is unclear. The authors present a method using petal patterns for the single-stage aesthetic correction of this deformity.


INFLUENCE OF PROLONGED EXERCISE ON THE 24-HOUR FREE TESTOSTERONE - CORTISOL RATIO HORMONAL PROFILE.
This study examined the response of the free testosterone and cortisol ratio (fTC) to prolonged endurance exercise. A trained sportsman performed treadmill exercise at 70% of maximal oxygen uptake to volitional fatigue. Frequent blood samples were collected over 24 hours and analyzed to determine changes in the fTC ratio. Exercise caused an initial increase in the ratio followed by a rapid decline in the immediate recovery from exercise. Approximately 8 hours into recovery from exercise, there was a pronounced and persistent (~6 hours) secondary increase in the ratio. Results suggest that the fTC ratio responds to intensive exercise, but that aspects of the response can be of a delayed nature occurring many hours into recovery. Exercise scientists who wish to monitor this parameter should be aware that the time course by which they choose to conduct their blood sampling could impact upon the interpretation of their data.


Epicardial ventricular pacemaker electrode longevity in children.
While epicardially implanted electrodes remain the most widely used in children for ventricular pacing, their expected longevity remains unknown. The longevity of 126 such electrodes implanted from January 1970 through December 1985 was evaluated in 81 children followed up for 1 to 192 months (median 63). Age at initial implant was 1 day to 18 years. Each child had from 1 to 5 electrodes implanted; 85 electrodes were of the sutureless helical type and 41 were of the suture-fixated type. Electrode failure, defined as loss of capture with a high pacing threshold found at operation or sensing failure, occurred in 38 electrodes from 1 to 157 months postimplant (median 37). Mode of failure was high threshold with high impedance (n = 15), low impedance (n = 6), complete inability to pace (n = 8), sensing failure (n = 2) or high threshold with no measure of impedance (n = 7). Actuarial life table analysis of electrode longevity showed a 88 +/- 3% (standard error of the estimate) survival rate at 6 months with no significant decrease until 53 months (75 +/- 5%, p less than 0.05). There was then a gradual steady decrease to 49 +/- 7% by 101 months. From 101 to 157 months no significant decrease occurred. Survival rate decrease was greatest within the first 6 month period postimplant (-12%). Electrodes surviving to 6 months are highly likely to survive until 53 months. Of those surviving to 53 months, 74% should survive to 120 months.


The Shetland Islands scrapie monitoring and control programme: analysis of the clinical data collected from 772 scrapie suspects 1985-1997.
There were 574 scrapie positive suspects (histopathological scrapie lesions present) and 198 scrapie negative suspects (histopathological scrapie lesions absent). The greatest number of scrapie cases were recorded in sheep of 2, 3 and 4 years of age which represented 17%, 36% and 23% of the scrapie positive suspects, respectively. The sign sensitivities and specificities for the ten recorded signs were, respectively: pruritus (62%, 42%), ataxia (23%, 74%), hyperaesthesia (32%, 74%), wool loss (25%, 73%), fleece discolouration (29%, 85%), bruxism (23%, 69%), nibbling reflex (17%, 58%), head rubbing (47%, 78%), poll rubbing (25%, 83%). These single signs had poor discriminatory values with likelihood ratios close to one (range 0.89-1.21); combinations of the four signs, pruritus, wool loss, ataxia, hyperaesthesia and emaciation were more discriminatory (range 0.30-4.3). This study covered a time period when bovine spongiform encephalopathy (BSE) might have been introduced into the sheep population on the Shetland Islands via contaminated feed. No temporal changes could be detected in the age structure of the affected animals.


Multidetector CT angiography in the follow-up of patients treated with renal artery stents: value of different reformation techniques compared with axial source images.
To evaluate the role of 4 different reformation techniques in comparison with axial images from multidetector computed tomographic angiography (MDCTA) in the follow-up of renal artery stents. Data on 40 patients (20 men; mean age 65 years) who underwent MDCTA as part of their routine follow-up after successful primary stenting of a main renal artery were retrospectively analyzed. Multiplanar reformation (MPR), curved planar reformation (CPR), volume rendering threshold (VRT), and virtual angioscopy (VA) were reviewed by 2 independent observers who were blinded to the results of the axial source images, which served as the gold standard. The stenosis degree was scored as I = 0%, II <50%, III = 51%-75%, IV = 76%-99%, or V = occlusion; a stenosis >50% was considered hemodynamically significant. Five hemodynamically significant stenoses were identified on axial images. The correlation with axial images was perfect for both observers using MPR and CPR (kappa = 1 for each observer); corresponding results were kappa = 0.69 and kappa = 0.64 for VRT and kappa = 0.88 and kappa = 0.83 for VA, respectively. The interobserver correlations were excellent for all reformation techniques (kappa = 0.95 to 1). Compared to axial images, MPR and CPR correlated perfectly with axial images; VA performed surprisingly well, while VRT was affected by artifacts and consequently showed inferior results.


Estimating photosynthetic rate and annual carbon gain in conifers from specific leaf weight and leaf biomass.
Canopy photosynthesis is difficult to measure directly or to predict with complex models demanding knowledge of seasonal variation in environmental and physiological properties of the canopy. Trees in particular offer a challenge with their large, aerodynamically rough and seasonally-changing canopy properties. In this paper we assess the possibility of using specific leaf weight to predict seasonal and annual net photosynthetic rate in deciduous (Larix sp.) and evergreen (Picea abies) conifers.Annual photosynthetic rate and specific leaf weight of different positions of the crown in both species were highly correlated (r 2=0.930). Annual carbon uptake by different segments in a mature P. abies crown was closely related to leaf biomass. The relationship was improved by adjusting the leaf biomass of each segment in regard to its specific leaf weight relative to the maximum found in the canopy. The adjustment accounted for associated differences in photosynthetic activity. This combined structural index (leaf biomassxrelative specific leaf weight) could, when calibrated, predict the total annual carbon uptake by different parts of the crown. If direct measurements of photosynthesis are not available, the combined structural index may still serve as a comparative estimator of annual carbon uptake.


Off-target activity of TNF-alpha inhibitors characterized by protein biochips.
Tumor necrosis factor-alpha inhibitors are widely and successfully used to treat rheumatic diseases. However, significant side effects have been reported. To detect the potential off-target activities of such inhibitors we characterized two therapeutic antibodies (adalimumab, infliximab) and one receptor fusion protein (etanercept) on protein biochips (UNIchip AV-400) containing a printed serial dilution of tumor necrosis factor-alpha and about 384 different human proteins. Etanercept binds to ten proteins (affinity: 20-33% of tumor necrosis factor-alpha recognition), and six of these proteins are related to ribosomal proteins. Interestingly, adalimumab binds to the same six proteins related to ribosomal proteins (affinity: 12-18%) as well as to four proteins crucially involved in ribosomal protein synthesis. Alignment of protein sequences indicates no significant sequence homology between these ten proteins bound by the biological drugs with the highest off-target activities. Taken together, our in vitro results demonstrate that a significant number of proteins are recognized by tumor necrosis factor-alpha inhibitors and are related to ribosome biogenesis.


Addressing high excitation conditions in time-resolved X-ray diffraction experiments and issues of biological relevance.
One of the most important fundamental questions connecting chemistry to biology is how chemistry scales in complexity up to biological systems where there are innumerable possible pathways and competing processes. With the development of ultrabright electron and x-ray sources, it has been possible to literally light up atomic motions to directly observe the reduction in dimensionality in the barrier crossing region to a few key reaction modes. How do these chemical processes further couple to the surrounding protein or macromolecular assembly to drive biological functions? Optical methods to trigger photoactive biological processes are needed to probe this issue on the relevant timescales. However, the excitation conditions have been in the highly nonlinear regime, which questions the biological relevance of the observed structural dynamics.


[Diagnosis of lesions of the ilioinguinal nerve using clinical and electromyographic methods].
On the basis of a study of 11 normals and 19 patients, the clinical and EMG features of iloinguinal nerve lesions are described. In lesions of this nerve there are EMG changes in the internal oblique abdominal muscles, which indicate an involvement into the pathological process of not only of the nerve conductors, but central structures. The EMG method may be recommended as a supplementary one for detecting subclinical forms of the disease, clarification of the diagnosis and determination of the degree of nerve lesions.


Assessment of cervical carotid artery disease. A comparison between the Doppler "Echoflow" and conventional angiography.
Carotid artery disease is an important factor in the aetiology of stroke and cerebrovascular insufficiency. Angiography remains the definitive technique for the investigation of the carotid arteries, but the risk and expense involved has stimulated research into suitable non-invasive techniques. A comparison between a velocity-sensitive, colour-coded Doppler principle ultrasound flowmeter (Echoflow) and conventional angiography was conducted on 52 patients (101 arteries) investigated at Royal Perth Hospital over a 16-month period. An acceptable correlation was found in 78% of cases. Echoflow scanning proved to be particularly accurate in assessing normal arteries. Our results support the use of Echoflow as a first line of investigation, and in aiding the selection of cases requiring further study, although we caution against routine angiography in all patients with positive Echoflow scan results.


Coronary angioplasty to relieve a kinked venous bypass conduit.
An unusual case of kinking of a freshly placed venous bypass conduit was treated by PTCA and catheter traction. This provided translational movement of the conduit with loss of angulation, relief of kinking, and resumption of normal flow.


Open surgical simulation in residency training: a review of its status and a case for its incorporation.
With the increase in minimally invasive approaches to surgical disease and nonoperative management for solid organ injury, the open operative experience of current surgical residents has decreased significantly. This deficit poses a potentially adverse impact on both surgical training and surgical care. Simulation technology, with the potential to foster the development of technical skills in a safe, nonclinical environment, could be used to remedy this problem. In this study, we systematically review the current status of simulation technology in the training of open surgical skills with the aim of clarifying its role and promise in the education of surgical residents. A systematic search of the PubMed database was performed with keywords: "surgical simulation," "skill," "simulat," "surgery," "surgery training," "validity," "surgical trainer," "technical skill," "surgery teach," "skill assessment," and "operative skill." The retrieved studies were screened, and additional studies identified by a manual search of the reference lists of included studies. Thirty-one studies were identified. Most studies used low fidelity bench models designed to train junior residents in more basic surgical skills. Six studies used complex open models to train senior residents in more advanced surgical techniques. "Boot camp" and workshops have been used by some authors for short periods of intense training in a specialized area, with good results. Despite the increasing use of simulation in the technical training of surgical residents, few studies have focused on the use of simulation in the training of open surgical skills. This is particularly true with regard to skills required to competently perform technically challenging open maneuvers under urgent, life-threatening circumstances. In an era marked by a decline in open operative experience, there is a need for simulation-based studies that not only promote and evaluate the acquisition of such less commonly performed techniques but also determine the efficacy with which they can be transferred from a simulated environment to a patient in an operating room.


Effect of automation transparency in the management of multiple unmanned vehicles.
Automated decision aids can undoubtedly benefit system performance, but have the potential to provide incorrect advice, creating the possibility for automation disuse or misuse. This paper examined the extent to which increased automation transparency could improve the accuracy of automation use in a simulation of unmanned vehicle control. Participants were required to assign the best unmanned vehicle to complete missions. An automated recommender system provided advice but was not always reliable. Three levels of automation transparency were manipulated between-participants. Providing transparency regarding the reasoning underlying automated recommendations improved the accuracy of automation use, with no cost to decision time or subjective workload. Higher transparency in the form of projected decision outcome visualizations led to faster decisions, but less accurate automation use and an automation bias. Implications for the design of transparent interfaces to improve human-autonomy teaming outcomes in time-pressured environments are discussed.


InWalker: smart white cane for the blind.
Background/Purpose: Visual impairment is a disability more commonly caused by diseases that lead to several disadvantages to the daily activities amongst those blind. For almost a century since the white cane was first introduced, the cane has remained as the most reliable tool for those affected by blindness.Methods: By using a combination of the capabilities of Internet of Things (IoT) and existing devices, such as mobile phones, an InWalker system is proposed to expand the functionality of the typical white cane, so as to introduce several new features that enhance the safety and confidence amongst people who are blind. As such, this paper explores the existing works and projects to comprehend the motivation and the standard practices for each proposed feature. Each of the strength and drawback has been assessed thoroughly to refine the scope of this project.Results: The proposed project, InWalker, is an intelligent system that has an embedded board system with various sensors to enhance the usability of white cane. The inputs from the sensor are processed on a microcontroller, which then pass the data to a smartphone via Bluetooth for additional features, such as global positioning system (GPS) tracking and SMS services.Conclusions: Based on the initial user testing, the proposed system has successfully fulfilled most of the users' need.Implication for RehabilitationVisual impairment is a disability more commonly caused by diseases that lead to several disadvantages amongst those blind.The white cane has been seen as the most reliable tool for the visual impaired.This tool could be further improved with the integration of additional sensors that works with today's mobile devices.The proposed system, InWalker, is able to improve the overall quality of life among people who are blind through several features: obstacle detection, GPS tracking and a light illumination in dark environments for increased safety.


Effective Treatment of Acute Severe Ulcerative Colitis in Pregnancy Is Associated With Good Maternal and Fetal Outcomes.
Data regarding the management and outcomes of acute severe ulcerative colitis (ASUC) in pregnant patients is sparse, consisting mainly of case reports.1-3 We report on the largest cohort of pregnant patients hospitalized with ASUC and performed a systematic review of the medical literature.


Cholestasis.
Cholestasis can be caused by extrahepatic and intrahepatic pathogenic mechanisms that affect cellular and subcellular functions. The retention of bile results in numerous biochemical abnormalities, some of which are useful as clinical tests. The clinicopathologic findings are often suggestive of the underlying hepatobiliary disorder but are seldom diagnostic.


Long-term recurrences and mortality in patients with noncardiac syncope.
There are no in-depth studies of the long-term outcome of patients with syncope after exclusion of cardiac etiology. We therefore analyzed the long-term outcome of this population. For 147 months, we included all patients with syncope referred to our syncope unit after exclusion of a cardiac cause. We included 589 consecutive patients. There were 313 (53.1%) women, and the median age was 52 [34-66] years. Of these, 405 (68.8%) were diagnosed with vasovagal syncope (VVS), 65 (11%) with orthostatic hypotension syncope (OHS), and 119 (20.2%) with syncope of unknown etiology (SUE). During a median follow-up of 52 [28-89] months, 220 (37.4%) had recurrences (21.7% ≥ 2 recurrences), and 39 died (6.6%). Syncope recurred in 41% of patients with VVS, 35.4% with OHS, and 25.2% with SUE (P=.006). In the Cox multivariate analysis, recurrence was correlated with age (P=.002), female sex (P <.0001), and the number of previous episodes (< 5 vs ≥ 5; P <.0001). Death occurred in 15 (3.5%) patients with VVS, 11 (16.9%) with OHS, and 13 (10.9%) with SUE (P=.001). In the multivariate analysis, death was associated with age (P=.0001), diabetes (P=.007), and diagnosis of OHS (P=.026) and SUE (P=.020). In patients with noncardiac syncope, the recurrence rate after 52 months of follow-up was 37.4% and mortality was 6.6% per year. Recurrence was higher in patients with a neuromedial profile and mortality was higher in patients with a nonneuromedial profile.


Medulloblastomas: a review of 11 cases.
The authors review 11 cases of medulloblastomas, 9 of which were diagnosed and treated in the last 6 years. All were uniformly treated by surgery, radiotherapy and chemotherapy, according to the SIOP protocol. Complications and results are described.


VirtualMicroscopy: ultra-fast interactive microscopy of gigapixel/terapixel images over internet.
As digital imaging technology advances, gigapixel or terapixel super resolution microscopic images become available. We have built a real time virtual microscopy technique for interactive analysis of super high resolution microscopic images over internet on standard desktops, laptops or mobile devices. The presented virtual microscopy technique is demonstrated to perform as fast as using a microscopy locally without any delay to assess gigapixel ultra high resolution image data through wired or wireless internet by a Tablet or a standard PC. More importantly, the presented technology enables analysis of super high resolution microscopic image across sites and time and allows multi-person analysis at the same time, which greatly speed up data analysis process and reduces miscommunication among scientists and doctors. A web site has been created for illustration purposes. (http://www-o.ntust.edu.tw/~cweiwang/VirtualMicroscopy).


P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia.
Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transfer pi (GST-pi) using immunohistochemistry. Expression of P-170 was detected in 36 of 104 patients (35%) and increased GST-pi was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21%), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-170-negative tumours (P < 0.05). However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-pi was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-pi was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors.


Usefulness of Doppler derived end diastolic flow gradient across the patent ductus arteriosus in selecting coils for ductal occlusion.
Transcatheter closure of patent ductus arteriosus (PDA) with coils is accepted as an alternative to surgical ligation. We evaluated whether flow gradient across PDA, obtained by Doppler echocardiography, can aid in selecting coils for percutaneous ductal occlusion. 79 consecutive patients with PDA, who underwent successful percutaneous coil occlusion were retrospectively reviewed. Patients with other structural heart disease and pulmonary hypertension with right-to-left shunt were excluded. Echocardiogram and cardiac catheterization were done in all patients. Gianturco (Occluding Spring Emboli; Cook, Bloomington, IN) non-detachable coils of 0.038 and 0.052-inch core sizes were used for ductal occlusion. Trough diastolic gradient was correlated with the size and the number of coils used. Mean age was 8.6 years (range 1.3 to 27 years); 24 males and 55 females; PDA diameter ranged from 1.3 to 4.5 mm. Number of coils used varied from 1 to 4. Echocardiography measured PDA size was 2.5 ± 0.6 mm and significantly differed from angiographically measured size 2.9 ± 0.6 mm (P = 0.05). End diastolic gradient below 38 mmHg predicted use of multiple coils or coils with larger surface area. End diastolic gradient correlated inversely with total surface area of the coils, which indirectly predicted size and number of coils. Thus, the prediction of the size and the number of coils for PDA occlusion can be assisted by the trough diastolic gradients of PDA.


10-(4-Phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and related compounds: Synthesis, antiproliferative activity and inhibition of tubulin polymerization.
As part of our continuing search for potent inhibitors of tubulin polymerization, two novel series of 42 10-(4-phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and N-benzoylated acridones were synthesized on the basis of a retrosynthetic approach. All newly synthesized compounds were tested for antiproliferative activity and interaction with tubulin. Several analogs potently inhibited tumor cell growth. Among the compounds tested, 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)acridin-9(10H)-one (17c) exhibited excellent growth inhibitory effects on 93 tumor cell lines, with an average GI50 value of 5.4 nM. We were able to show that the strong cytotoxic effects are caused by disruption of tubulin polymerization, as supported by the EBI (N,N'-Ethylenebis(iodoacetamide)) assay and the fact that the most potent inhibitors of cancer cell growth turned out to be the most efficacious tubulin polymerization inhibitors. Potencies were nearly comparable or superior to those of the antimitotic reference compounds. Closely related to this, the most active analogs inhibited cell cycling at the G2/M phase at concentrations down to 30 nM and induced apoptosis in K562 leukemia cells. We believe that our work not only proves the excellent suitability of the acridone scaffold for the design of potent tubulin polymerization inhibitors but also enables synthetic access to further potentially interesting N-acylated acridones.


Fast track biopsy method: a rapid approach to preoperative diagnoses.
It is well known that the use of a microwave oven greatly reduces the time for histoprocessing. Apply the microwave-based histoprocessing method "Fast Track Biopsy" (FTB), previously described for breast needle-core biopsies, to samples of other organs. From 01/09/2008 to 31/12/2008, 125 normal and neoplastic tissue samples (thickness from 0.2 and 1.2 cm) were collected, processed according to the FTB technique, stained with haematoxylin/eosin (H/E) and analysed with tissue-specific immunohistochemical (IHC) markers. The quality of both H/E and IHC stained sections was comparable to that obtained with standard methods. Sample thickness less than 0.5 cm gave better results. the FTB method is suitable for most tissue types, and is thus useful for preoperatory diagnoses.


An experimental examination of the effort-reward imbalance model of occupational stress: Increased financial reward is related to reduced stress physiology.
Effort-reward imbalance in the workplace is linked to a variety of negative health and organisational outcomes, but it has rarely been assessed experimentally. We manipulated reward (while keeping effort constant) in a within-subjects design with female participants (N=60) who were randomly assigned to high and standard reward conditions within a simulated office environment. Self-report, behavioural (task performance), and physiological (heart rate variability, salivary alpha amylase) measures assessed the impact of increased financial reward. Participants reported increased perceptions of reward, performed moderately better on the task, and were less physiologically reactive in the high reward versus the standard condition. These findings highlight the importance of assessing both subjective self-reports of stress together with objective physiological measures of stress, and suggest that increasing monetary rewards has the potential to decrease stress physiological reactivity, and in turn, reduce the risk of ill-health in employees, and may also positively influence task efficacy.


Decrease in sweet taste in rats after gastric bypass surgery.
The literature contains evidence that Roux-en-Y gastric bypass (RYGB) surgery has an effect in humans on taste and preference for carbohydrate-rich foods. This study tested the hypothesis that RYGB affects sweet taste behavior using a rat model. Male Sprague-Dawley rats underwent either RYGB or sham surgery. Then 4 weeks after surgery, the rats were given taste-salient, brief-access lick tests with a series of sucrose concentrations. The RYGB rats, but not the sham rats, lost weight over the 5-week postoperative period. The RYGB rats showed a significant decrease in mean licks for the highest concentration of sucrose (0.25-1.0 mol/l) but not for the low concentrations of sucrose or water. The findings showed that RYGB surgery affected sweet taste behavior in rats, with postsurgical rats having lower sensitivity or avidity for sucrose than sham-treated control rats. This finding is similar to human reports that sweet taste and preferences for high-caloric foods are altered after bypass surgery.


Optically pure γ-butyrolactones and epoxy esters via two stereocentered HKR of 3-substituted epoxy esters: a formal synthesis of (-)-paroxetine, Ro 67-8867 and (+)-eldanolide.
The HKR of racemic anti- or syn-3-substituted epoxy esters catalyzed by a Co(III)salen complex provides ready access to the corresponding enantioenriched 3,4-disubstituted γ-butyrolactones and 3-substituted epoxy esters. This strategy has been successfully employed in the formal synthesis of biologically active 3,4-disubstituted piperidine derivatives, (-)-paroxetine and Ro 67-8867 and a natural product, (+)-eldanolide.


Naïve-like conversion of bovine induced pluripotent stem cells from Sertoli cells.
Feeder cells are essential to derive pluripotent stem cells (PSCs). Mouse embryonic fibroblasts (MEF) are widely used as feeder to generate and culture embryonic stem cells (ESCs) and induced PSCs (iPSCs) in many species. However it may not be suitable for livestock ESCs/iPSCs due to interspecies difference. Previously we derived bovine iPSCs from bovine Sertoli cells using MEF feeder. Here we compared the effects of MEF feeder and bovine embryonic fibroblasts (BEF) feeder on the maintenance of bovine iPSC pluripotency and morphology as well their contributions to the naïve-like conversion, based on a naïve medium (NM). The results showed successful conversion of the primed bovine iPSCs to naïve-like state within 3-4 days both on MEF feeder and BEF feeder in NM (termed as MNM and BNM respectively). These naïve-like iPSCs showed normal karyotype. There were more iPSC colonies under BNM condition than MNM condition. Epigenetically, histone modification H3K4 was upregulated, while H3K27 was downregulated in the naïve-like iPSCs. We further analyzed the naïve markers and differentiation potential both in vitro and in vivo of these cells, which were all reserved throughout the maintenance. Together, bovine naïve-like iPSCs can be generated both on MEF and BEF feeder in NM condition. The BNM condition is able to sustain the pluripotency and differentiation potential of the naïve-like bovine iPSCs, and improve the conversion efficiency.


Alveolar soft-part sarcoma of the female genital tract. Case report with ultrastructural findings.
An alveolar soft-part sarcoma of the uterine cervix observed in a 26-year-old woman is described. One year after extended radical hysterectomy there was no evidence of tumor recurrence. To the best of our knowledge, this is the second reported case of alveolar soft-part sarcoma arising in the female genital tract and the first description of this tumor in the uterine cervix.


Increases in HDL-cholesterol and the HDL/LDL cholesterol ratio during prolonged endurance exercise.
The influence of prolonged, low-intensity exercise (45% VO2max) until exhaustion on plasma lipid levels, in particular high-density lipoprotein cholesterol (HDL-C), and the time sequence associated with changes in these blood constituents was investigated in 10 trained subjects. The exercise consisted of walking on a motor-driven treadmill until exhaustion. Blood samples were drawn before, at 30 and 60 minutes after the beginning of exercise, at each hour thereafter until exhaustion, immediately before exhaustion, and after a 30-minute recovery period. At exhaustion the total cholesterol concentration was significantly elevated by 3% and rose another 3% during the recovery period. The HDL-C level was significantly elevated within two hours after the start of exercise and by exhaustion (about 4.5 hours of exercise) had risen to 52.5 +/- 2.3 mg X dL-1, which represented a 10.8% increase above the pre-exercise concentration (47.4 +/- 1.8 mg X dL-1). The HDL/LDL cholesterol ratio followed a pattern similar to that described for HDL-C. Plasma free fatty acids (FFA) also increased linearly during the exercise period but were not significantly correlated with HDL-C during exercise (r = 0.14). These results suggest that prolonged, low-intensity exercise can acutely improve the lipid profile of humans.


Chemical impurities in [18F]FDG preparations produced by solid-phase 18F-fluorination.
[18F]FDG was produced by solid-phase 18F-fluorination (resin method) and chemical impurities were determined in the [18F]FDG preparations by ion chromatography. The major chemical impurities were D-glucose (90.5 +/- 6.4 microg/mL), 2-chloro-2-deoxy-D-glucose (11.8 +/- 2.7 microg/mL), and D-mannose (1.7 +/- 0.7 microg/mL), which were expected to be present by considering the synthetic routes. An FDG mass (0.5 +/- 0.2 microg/mL) was also detected in the preparations. No notable radiochemical impurities, including 2-[18F]fluoro-2-deoxy-D-mannose, were detected in the [18F]FDG preparations. Thus, the levels of several chemical impurities were determined in the [18F]FDG preparations produced by solid-phase 18F-fluorination.


Genomic profiles of primary and metastatic esophageal adenocarcinoma identified via digital sorting of pure cell populations: results from a case report.
We report on a female patient who underwent primary radical resection for a stage 2B Her-2-positive Barrett's-type esophageal adenocarcinoma (EAC). Despite Her-2 targeted therapy, her disease recurred and required repeated metastectomies. Digital cell sorting and targeted sequencing of cancer sub-clones from EAC and metastases revealed a completely mutated TP53, whereas the sorted stromal cells were wild-type. Her-2 amplification was significantly lower in the metastases when the patient became therapy-resistant. The mechanism of therapy resistance illustrated by this case could only be detected through accurate analysis of tumor sub-populations. Investigating tumor sub-populations of recurrent disease is important for adjusting therapy in recurrent EAC.


An antibody to recombinant crustacean hyperglycaemic hormone of Nephrops norvegicus cross-reacts with neuroendocrine organs of several taxa of malacostracan Crustacea.
The crustacean hyperglycaemic hormones (cHHs) are multifunctional neuropeptides that play a central role in the physiology of crustaceans. A partial cDNA coding for cHH of the Norway lobster, Nephrops norvegicus, was cloned; this cDNA was fused to glutathione- S-transferase (GST) to obtain a recombinant fusion protein that was used to raise a rabbit antiserum and to perform a biological assay. The specificity of the purified antibody was demonstrated by means of Western blotting. To validate the specificity of the purified antibody to the cHH of N. norvegicus and its cross-reactivity with other species, we performed standard immunocytochemistry of the eyestalk on: (1) paraffin sections of the decapod species N. norvegicus, Munida rugosa and Astacus leptodactylus and of the stomatopod Squilla mantis; (2) semithin resin sections of N. norvegicus and Palaemon elegans; (3) ultrathin sections of N. norvegicus sinus gland (transmission electron microscopy studies). The pattern of immunoreactivity shown by N. norvegicus eyestalk sections conforms to distribution, relative amount and ultrastructural features of cHH-containing neurons and nerve endings as reported in the previous literature. In all the crustacean species examined, the antibody marks precisely the X organ-sinus gland complex and unspecific staining is completely lacking. In addition, its specific cross-reaction by immunoprecipitation depletes shrimp eyestalk extract of hyperglycaemic activity in an in vivo bioassay. The results obtained show a cHH-specific molecular recognition despite the fact that the species tested belong to systematic groups increasingly remote in the phylogenetic tree. The antibody could be used for advancing our knowledge on cHH activity in a variety of crustacean species, e.g. for monitoring reproductive and stress conditions.


Reconsolidation and update of morphine-associated contextual memory in mice.
Drug addiction can be viewed as a pathological memory that is constantly retrieved and reconsolidated. Since drug abuse takes place in different contexts, it could be considered that reconsolidation plays a role in memory updating. There is consistent evidence supporting the role of reconsolidation in the strength and maintenance of contextual memories induced by drugs of abuse. However, this role is not well established in memory update. The purpose of the current study was to assess the reconsolidation process over memory update. C57BL6 mice were subjected to a morphine-induced, conditioned place preference (CPP) paradigm. Based on CPP results, animals were divided into distinct experimental groups, according to the contextual characteristics of the re-exposure and a second CPP Test. Re-exposure in the original context was important for memory maintenance and re-exposure under discrete contextual changes resulted in memory updating, although original memory was maintained. Interestingly, cycloheximide, an inhibitor of protein synthesis, had different outcomes in our protocol. When the re-exposure was done under discrete contextual changes, cycloheximide treatment just after re-exposure blocked memory updating, without changes in memory maintenance. When re-exposure was done under the original context, only two subsequent cycloheximide injections (3 and 6h) disrupted later CPP expression. Considering the temporal window of protein synthesis in consolidation and reconsolidation, these findings suggest that re-exposure, according to the contextual characteristics in our protocol, could trigger both phenomena. Furthermore, when new information is present on retrieval, reconsolidation plays a pivotal role in memory updating.


Near-infrared double-illumination optical-resolution photoacoustic microscopy.
Label-free chemical bond imaging is of great importance in biology and medicine. Photoacoustic imaging at the third near-infrared windows (1600-1870 nm, near-infrared-III) provides a stable molecular vibrational imaging tool for lipid-rich tissue owing to the first overtone transition of the CH bond at 1.7 μm. However, lacking high-energy pulsed laser sources at 1.7 μm and the strong water absorption significantly limit the signal-to-noise ratio of the lipid imaging, especially for thin lipid tissues. To circumvent this barrier, we develop near-infrared-III double-illumination optical-resolution photoacoustic microscopy (DIOR-PAM) for improving the sensitivity of label-free lipid imaging. Using the same laser, DIOR-PAM can enhance the sensitivity by nearly 100%, which we prove in the Monte Carlo simulation. We experimentally demonstrated 50% ~ 100% sensitivity enhancements on nonbiological and biological lipid-rich samples.


Synthesis, SAR and antibacterial activity of hybrid chloro, dichloro-phenylthiazolyl-s-triazines.
A series of hybrid novel chloro (1a-9a) and dichloro (10b-18b) phenylthiazolyl-s-triazine were synthesized and subsequently subjected to their antibacterial activity against three gram positive viz. Lactobacillus casei (NCIM-2651); Bacillus cereus (NCIM-2458); Staphylococcus aureus (NCIM-2120) and three gram negative viz Salmonella typhimurium (NCIM-2501); Escherichia coli (NCIM-2065); Klebsiella aerogenes (NCIM-2098). The SAR studies around the lead compound revealed that introduction of electron withdrawing groups and amino (-NH-) and mercapto (-S-) linker bridge seemed more promising towards antibacterial activity. Moreover, the virtual Molinspiration screenings are in compliance with Ghose's rule.