Activity-dependent neurotransmitter respecification.
For many years it has been assumed that the identity of the transmitters expressed by neurons is stable and unchanging. Recent work, however, shows that electrical activity can respecify neurotransmitter expression during development and in the mature nervous system, and an understanding is emerging of the molecular mechanisms underlying activity-dependent transmitter respecification. Changes in postsynaptic neurotransmitter receptor expression accompany and match changes in transmitter specification, thus enabling synaptic transmission. The functional roles of neurotransmitter respecification are beginning to be understood and appear to involve homeostatic synaptic regulation, which in turn influences behaviour. Activation of this novel form of plasticity by sensorimotor stimuli may provide clinical benefits.


Effects of root exudates of bivalent transgenic cotton (Bt+CpTI) plants on antioxidant proteins and growth of conventional cotton (Xinluhan 33).
A greenhouse experiment was conducted to assess the adverse impact of transgenic cotton on ecosystem and environment via effect of transgenic Bt+CpTI cotton root exudates on growth and antioxidant activity of conventional parental cotton. Results showed elevated reductive and oxidative species activities in the leaves of conventional parental cotton seedlings treated with varying concentrations of transgenic cotton root exudates. Compared to control, 14.9% to 39.9% increase in catalase, 8.8% to 114% increase in for peroxidase, 21.3% to 59.7% increase in phenylalanine ammonia-lyase and 5.8 to 19.5 fold in ascorbate specific peroxidase was observed. However, biomass and height of conventional cotton seedlings were not affected by any concentration of transgenic cotton root exudates. These results suggested that cultivation of transgenic Bt+CpTI cotton plants poses little risk to conventional parental cotton based on their root interactions.


Evaluating thermal resource partitioning : By sympatric lizards Anolis cooki and A. cristatellus: a field test using null hypotheses.
The field thermal biology of sympatric Anolis cooki and A. cristatellus were evaluated in January and in August in desert scrub forest at Playa de Tamarindo near Guanica, Puerto Rico. Data on randomly positioned copper models of lizards, each equipped with a built-in thermocouple, established null hypotheses about basking frequency and operative temperatures (T e) against which the behavior and body temperatures (T b) of live lizards were evaluated. Both species exhibited non-random hourly basking rates (more marked in cristatellus than in cooki), and cristatellus was virtually inactive during the warm mid-day hours. The relationship between lizards' T b and randomly sampled T e differed between the species: cristatellus's mean T b was 2° to 3° C lower than randomly sampled mean T e in both months, whereas cooki's mean T b was slightly higher than mean T e in January and slightly lower in August. Although cooki's mean T b was higher than that of cristatellus in both months, the T b's of the two species overlapped substantially over an annual cycle. Given the similarities in their field active T b and the low thermal heterogeneity among microsites at Playa de Tamarindo, these species appear not to partition the thermal environment there in a coarse-grained way. Instead, the relatively small differences in their field active T b probably result from small differences in their use of similar microhabitats within their mutually exclusive territories. Thermal resource partitioning by territorial animals is unlikely unless thermal heterogeneity is coarse-grained in relation to territory size.


Anesthetic Management for Open Thoracoabdominal and Abdominal Aortic Aneurysm Repair.
Open thoracoabdominal and abdominal aortic aneurysm repairs are some of the most challenging cases for anesthesiologists because of the potential for rapid blood loss combined with clamping and reperfusion, potential use of left heart bypass, the potential need for lung isolation, and potential placement and management of a spinal drain. In addition, patients often present with other significant comorbidities and a detailed understanding of the disease process, the complex physiology throughout the case, and the intricacies of organ protection are critical.


Pubertal BMI change and adult-onset asthma in men: Population-based cohort study in Sweden.
The role of pubertal BMI change in adult-onset concomitant asthma and allergic rhinitis is unknown. We investigated the association of childhood and young adult BMI, and pubertal BMI changes with adult-onset asthma, allergic rhinitis, and concomitant asthma and rhinitis in Swedish men. The BMI Epidemiology Study in Gothenburg, Sweden, comprised of height and weight measures taken from school health records (6.5-9.5 years) and during military conscription (17.5-22 years) for all men born 1945-1961 (n = 37 652). Age-adjusted childhood BMI centred at 8 years and young adult BMI at 20 years were linked to high quality data on asthma and allergic rhinitis diagnoses from the Swedish National Patient Register. High BMI (4th quartile vs the two median quartiles) at 8 years was associated with increased risk of concomitant asthma and allergic rhinitis (HR 1.45; 95% CI 1.00-2.11). Overweight (HR 1.45; 95% CI 1.12-1.89) and obesity (HR 1.95; 95% CI 1.08-3.54) at 20 years were associated with increased risk of asthma without concomitant allergic rhinitis as main or auxiliary diagnosis. Pubertal BMI change showed a non-linear association, so that both low (1st quartile vs the two median quartiles) and high pubertal BMI changes were associated with increased risk of asthma (low: HR 1.36; 95% CI 1.11-1.68; high: HR 1.32; 95% CI 1.07-1.63) and asthma without concomitant allergic rhinitis (low: HR 1.33; 95% CI 1.04-1.69; high: HR 1.36; 95% CI 1.07-1.74) as a main diagnosis. Both low and high pubertal BMI changes are predictors of adult-onset asthma in men, particularly asthma without concomitant allergic rhinitis. Primary prevention of adult-onset asthma requires monitoring of changes in BMI during puberty.


Angiotensin II type 2 receptor-interacting protein prevents vascular senescence.
Angiotensin II type 2 (AT(2)) receptor-interacting protein (ATIP), which interacts with the C-terminal tail of the AT(2) receptor, regulates the functions of the AT(2) receptor. We have reported that AT(2) receptor stimulation attenuated vascular senescence. Therefore, we examined the possible negative role of ATIP in regulating vascular senescence. We generated ATIP-transgenic (Tg) mice, and cultured vascular smooth muscle cells (VSMCs). Persistent angiotensin II stimulation induced increases in SA-β-gal-positive cells and the level of a DNA damage marker, 8-OHdG in VSMC, whereas these effects of angiotensin II were attenuated in VSMC prepared from ATIP-Tg mice. Angiotensin II treatment also upregulated the expression of methyl methanesulfonate-sensitive 2 (MMS2), a DNA repair factor, and Src homology 2 domain-containing protein-tyrosine phosphatase 1 (SHP-1) activity, whereas these effects of angiotensin II were further enhanced in ATIP-Tg VSMC. In vivo, x-ray irradiation to mice caused increases in SA-β-gal-positive area and 8-OHdG level in the thoracic aorta; however, these effects were reduced in ATIP-Tg mice, with a significant increase in MMS2 expression. These results suggest that ATIP could inhibit VSMC senescence, involving MMS2 expression and SHP-1 activity. ATIP might be a new therapeutic molecule to treat vascular aging and age-related vascular diseases.


Phenylalanine hydroxylase from the sponge Geodia cydonium: implication for allorecognition and evolution of aromatic amino acid hydroxylases.
The prophenoloxidase activating system is a defense system, frequently reported both in protostomes and in deuterostomes. The final product of the phenoloxidase activity is melanin which is ubiquitously present throughout the metazoan kingdom. The melanin synthesis pathway starts with the amino acid [aa] phenylalanine which is converted to tyrosine by the phenylalanine hydroxylase [PAH]. We show that after allo-transplantation in the marine sponge Geodia cydonium PAH is upregulated in the grafts. Enzyme determination studies revealed that PAH activity increases by three-fold two d after transplantation and reaches its maximum after 3d (by 3.7-fold). This finding was supported by determining the steady-state level of the mRNA for PAH. Furthermore the cDNA, encoding this enzyme was isolated from G. cydonium. Its deduced aa sequence encodes a protein of 51 kDa. Alignment studies indicate that the sponge PAH shares the consensus pattern as well as one characteristic pterin-binding site with the biopterin-dependent aromatic amino acid hydroxylases. Phylogenetic analysis of sponge PAH shows that all metazoan PAH fall in one group with the sponge PAH as the oldest member. The related classes of enzymes, the tyrosine hydroxylases and the tryptophan hydroxylases are statistically significantly separated from PAH; the tyrosine hydroxylase diverged as the first class from the common ancestor, a process which was calculated to have occurred 500 million years ago. It is concluded that in the sponge model system G. cydonium allogeneic rejection involves an upregulation of PAH, an enzyme initiating the pathway to melanin synthesis.


HER-2/neu assessment in primary chemotherapy treated breast carcinoma: no evidence of gene profile changing.
HER-2/neu protein expression and gene amplification were analyzed in a series of 85 consecutive breast carcinoma patients entered into an adriamicin/taxol primary chemotherapy trial followed by surgery, 45 of whom underwent pre-treatment fine needle aspirate (FNA). Dual color FISH (fluorescent in situ hybridization) assay revealed high-level HER-2/neu gene amplification in the immunocytochemistry (ICC) indicated 3+ cases and no, low or moderate amplification in the ICC 2+ group, consistent with previous findings in untreated patients series. Results obtained with the ICC assay CB 11 showed higher overall concordance with FISH than did the Herceptest ICC assay, but CB 11 was less accurate than Herceptest in terms of selecting patients suitable for Herceptin treatment, which is currently restricted to ICC 3+/FISH amplified patients. The only ICC 3+ low-level amplified case (non-amplified according the two more stringent criteria applied) was found with the CB 11 assay. Comparison between pre-treatment smears and post-treatment sections by FISH revealed no significant changes in the HER-2/neu gene profile. In the clinical setting these findings point to the usefulness of HER-2/neu assessment in chemotherapy-treated patients, when pre-treatment material is unavailable.


Resynchronization of previously timed-inseminated beef heifers with progestins.
The objective was to determine the efficacy of a previously used CIDR or melengestrol acetate (MGA; 0.5mg/head/day) for resynchronization of estrus in beef heifers not pregnant to timed-AI (TAI). In three experiments and a field trial, heifers were reinseminated 6-12 h after first detection of estrus. Pregnancy diagnosis was done from approximately 25-43 days after either TAI or reinsemination. In Experiment 1, 79 heifers received a once-used CIDR from 13 to 20 days after TAI and 80 heifers were untreated controls. For these two groups, there were 34 and 35 heifers, respectively, not pregnant to TAI; median +/- S.E. intervals from TAI to onset of estrus were 22 +/- 0.2 days versus 20 +/- 0.6 days (P < 0.001); estrus rates were 70.6% versus 85.7% (P = 0.1); conception rates were 62.5% versus 76.7% (P < 0.3); and pregnancy rates were 44.1% versus 65.7% (P = 0.07), for CIDR and untreated (control) groups, respectively. In Experiment 2, heifers (n = 651) were TAI (Day 0) and 13 days later randomly assigned to one of seven groups (n = 93 per group) to receive a once-used CIDR (three groups; Days 13-20), MGA (three groups; Days 13-19), or no treatment (control group). Groups given a CIDR or MGA also received: no further treatment (CIDR or MGA alone); 1.5mg estradiol-17beta (E-17beta) and 50 mg progesterone (P4) in 2 mL canola oil on Day 13; or E-17beta and P4 on Day 13 and 0.5 mg E-17beta on Day 21 (24 h after CIDR removal or 48 h after the last feeding of MGA). Pregnancy rate to TAI was lowest (P < 0.05) for the group given a CIDR plus E-17beta and P4 on Day 13 and E-17beta on Day 21. Variability in return to estrus was greater (P < 0.001) in the control and MGA groups than in CIDR groups. Conception and pregnancy rates in heifers given a CIDR (65.1 and 61.4%) were higher (P<0.01) than those fed MGA (49.6 and 40.4%), but not different from controls (62.2 and 54.9%, respectively). In Experiment 3, 616 heifers received a once- or twice-used CIDR for 7 days, beginning 13+/-1 days after TAI, with or without a concurrent injection of 150 mg of P4 (2 x 2 factorial design). Pregnancy rate to TAI was 47.2%. In heifers that returned to estrus, there was no significant difference between a once- or twice-used CIDR for rates of estrus (68.8%, P < 0.3), conception (65.9%, P < 0.6) and pregnancy (45.3%, P < 0.8). Injecting progesterone at CIDR insertion increased the median interval from CIDR removal to onset of estrus (P < 0.05) and reduced rates of estrus (63.8% versus 73.8%, P<0.05), conception (60.5% versus 70.6%, P = 0.1) and pregnancy (38.6% versus 52.2%, P < 0.02). In a field trial, 983 heifers received a once-used CIDR for 7 days, beginning 13 +/- 1 days after TAI. Pregnancy rate to TAI was 55.2%. The median (and mode) of the interval from CIDR removal to estrus was 2.5 days. Estrus, conception and pregnancy rates were 78.2, 70.3 and 55.0% (overall pregnancy rate to TAI and rebreeding, 78.7%). In summary, a once- or twice-used CIDR for 7 days, starting 13 +/- 1 days after TAI resulted in the majority of nonpregnant heifers detected in estrus over a 4-day interval, with acceptable conception rates; however, injecting progesterone at CIDR insertion significantly reduced both estrus and pregnancy rates, and estradiol treatment after CIDR removal was associated with a decreased pregnancy rate to TAI. Fertility was higher in heifers resynchronized with a once-used CIDR than with MGA.


A recipe for specificity.
Water molecules and DNA conformation are now recognized as ingredients which can influence both the affinity and specificity of protein/DNA complexes.


Mixed epithelial and stromal tumor of the kidney in a 12-year-old girl.
Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare kidney neoplasm that almost exclusively occurs in perimenopausal women, and long-term estrogen replacement is relevant to its pathogenesis. Herein is described an atypical case of MESTK uncovered in a 12-year-old premenarcheal girl without a history of prior estrogen use. On surgical specimen it was found that the well-circumscribed tumor measuring 14 cm arose from the lower pole of the right kidney, showing solid and fibrous-cystic areas. Microscopically, it was composed both of epithelial structures similar to renal tubules and stroma comprising non-specific spindle cells. Some intratumoral tubules showed affinities to distal-nephron-specific lectins, and those immunoreactive for proximal-tubule-specific CD15 were also present. In addition, primitive ductal structures were reactive both for CD15 and lectins, but immature epithelial elements typical of nephroblastoma were absent. Spindle cells were positive for actin, desmin and vimentin, and expressed progesterone and estrogen receptors. The tumor was comparable with MESTK, although some epithelia were associated with the immunophenotype of proximal tubules. The patient was free of disease postoperatively for 40 months. In the present case, remnants of the primitive periductal mesenchyme might be promoted to neoplastic cells by a sex-steroid surge during puberty.


Characteristics of Platelet Lysate Compared to Autologous and Allogeneic Serum Eye Drops.
Platelet lysate produced from platelet apheresis components has been proposed as an alternative to serum eye drops in the treatment of ocular surface disease. This study compared the effects of platelet lysate and serum on growth factor, cytokine and nanoparticle concentrations, and corneal epithelial cell proliferation. The concentration of growth factors, cytokines, and nanoparticles in platelet lysates manufactured from either fresh or expired platelet apheresis concentrations collected with Trima or Haemonetics technology was characterized and compared with those of allogeneic, autologous, and fetal calf serum. The ability to promote corneal epithelial cell proliferation and wound healing was tested in vitro. Platelet lysate enriched the amount of transforming growth factor β1, platelet-derived growth factor -AB and -BB, fibroblast growth factor, and epidermal growth factor compared with the two sera groups. The concentrations of insulin-like growth factor 1, hepatocyte growth factor, and fibronectin were significantly lower than in sera. There were no differences in nanoparticle concentrations. There was no significant difference in corneal epithelial cell proliferation. Platelet lysates were comparable to fetal calf serum in accelerating corneal epithelial wound healing in vitro. Fresh and expired platelet lysates from the Trima and Haemonetics systems had higher growth factor concentrations than sera. The ability of platelet lysates to promote corneal epithelial cell proliferation and wound healing was equivalent to sera. Platelet lysates may serve as an efficient and reliable source of human growth factors for the treatment of ocular surface diseases.


Quantitative parameters in novel spectral computed tomography for assessing gastric cancer and cell proliferation.
To investigate the diagnostic ability of novel spectral CT-derived parameters for gastric cancer histological types and Ki-67 expression. A total of 72 patients with histologically proven gastric cancer (GC) were retrospectively included in this study. All patients underwent dual-phase enhanced abdominal spectral CT. The arterial (AP) and venous phase (VP) slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (NIC), effective atomic number (Zeff) and iodine-no-water concentration were retrospectively compared between patients with low and high Ki-67 expression levels and with different histological types in GC patients. The ROI was outlined independently by two senior physicians, and the average of three measurements at the largest level was taken. In addition, interobserver reproducibility was assessed by Bland-Altman analysis. Correlations between quantitative parameters and Ki-67 expression levels were assessed by Spearman's correlation coefficients. The values between the mucinous group and nonmucinous carcinoma group were significantly different in both phases. The IC, NIC, and iodine-no-water concentration in the VP were significantly different among the Ki-67_L, Ki-67_M, and Ki-67_H groups. Spearman rank correlation analysis demonstrated a positive correlation between Ki-67 expression levels and IC, NIC, and iodine-no-water concentration in the VP, with correlation coefficients of 0.304, 0.424, and 0.322, respectively. Quantitative spectral parameters can discriminate between low and high Ki-67 expression and different histological types in GC. The NIC, IC and iodine-no-water concentration can be useful parameters for evaluating of Ki-67 expression levels.


HIV infection and AIDS 1: the evolving epidemiology.
This is the first of a two-part unit on HIV and Aids. This part reviews the global epidemiology of the HIV/Aids pandemic.


Brain segmentation and trigeminal projections in the lamprey; with reference to vertebrate brain evolution.
Vertebrate brains exhibit remarkable diversity in each animal group, reflecting evolutionary changes at the molecular-level developmental program of the nervous system that vertebrates have experienced. We focused on the developmental morphological plan of the brain to understand the evolutionary scenario that led to the above diversity. By comparing the organization of the brain of non-vertebrate chordates, cyclostomes and gnathostomes, a step-wise modification of brain patterning programs becomes apparent. Furthermore, by labeling the lamprey oral region, the somatotopic projections of the trigeminal nerve that enter into the hindbrain become visible. Finally, by combining the knowledge on rhombomere segments and neuronal projections, the evolutionary relationship between somatotopy and brain segmentation are discussed.


Austrian experiences with redo antireflux surgery.
From 1996, the entire number of fundoplications performed in Austria increased dramatically, favoring the laparoscopic technique. Despite good results, some patients experience failure of antireflux surgery and therefore require redo surgery if medical therapy fails to control symptoms. The aim of the study was to describe the refundoplication policy in Austria with evaluation of the postoperative results. A questionnaire was sent to all Austrian surgical departments at the beginning of 2003 with questions about redo fundoplications (number, techniques, intraoperative complications, history, migration of patients, preoperative workup, mortality, and postoperative long-term complaints). It also included questions about primary fundoplications (number, technique, postoperative symptoms). Out of 4,504 primary fundoplications performed in Austria since 1990, 3,952 have been carried out laparoscopically. In a median of 31 months after the primary operation, 225 refundoplications have been performed, laparoscopically in the majority of patients. The Nissen and the partial posterior fundoplication were the preferred techniques. The conversion rate in these was 10.8%, mainly because of adhesions and lacerations of the spleen, the stomach, and the esophagus. The mortality rate after primary fundoplications was 0.04%, whereas the rate after refundoplications was 0.4%, all resulting from an open approach. Laparoscopic refundoplications are widely accepted as a treatment option after failed primary antireflux surgery in Austria. However, the conversion rate is 6 times higher and the mortality rate is 10 times higher than for primary antireflux surgery. Therefore, redo fundoplications should be performed only in departments with large experience.


Evaluation of an automated thermodynamic treatment (LipiFlow®) system for meibomian gland dysfunction: a prospective, randomized, observer-masked trial.
To compare the effectiveness of a single LipiFlow(®) treatment with combined lid warming and massage in patients with meibomian gland dysfunction (MGD). In this prospective, randomized, crossover, observer-masked clinical trial, subjects were randomized to receive either a single 12-min LipiFlow-LipiFlow Thermal Pulsation (LTP) system treatment or to perform combined twice-daily lid warming and massage for 3 months. All subjects were examined before, and 1 and 3 months after initiation of treatments. Investigated parameters included subjective symptoms, lipid layer thickness, meibomian gland assessment, tear break-up time, tear osmolarity, corneal and conjunctival staining, Schirmer test values, and tear meniscus height. A total of 31 subjects completed the 3-month follow-up. At 1 and 3 months, patients in the LipiFlow treatment group had a significant reduction in Ocular Surface Disease Index (OSDI) scores compared with those in the lid-margin hygiene group. Both treatments produced a significant improvement in expressible meibomian glands compared to the baseline parameters, but no significant difference was noted between the two groups. The other investigated objective parameters did not show a significant difference. Results of our study show that a single LipiFlow treatment is as least as effective as a 3-month, twice-daily lid margin hygiene regimen for MGD. However, the present study was observer-masked only, and therefore a placebo effect may have confounded any improvements in subjective symptoms and other parameters in both groups.


Synthesis and anticancer studies of Michael adducts and Heck arylation products of sesquiterpene lactones, zaluzanin D and zaluzanin C from Vernonia arborea.
Sesquiterpene lactones containing α-methylene-γ-lactones, zaluzanin D 1 and zaluzanin C 2 were isolated from the leaves of Vernonia arborea. Several diverse Michael adducts (3-22) and Heck arylation analogs (23-34) of 1 have been synthesized by reacting with various amines and aryl iodides, respectively and were assayed for their in vitro anticancer activities against human breast cancer cell lines MCF7 and MDA-MB-231. Among all the synthesized analogs, Michael adducts 9 and 10 showed better anticancer activities as compared to 1. However, among these compounds, only 10 has minimal cytotoxic effect on normal breast epithelial MCF10A cells. Our detailed mechanistic studies reveal that compounds 9 and 10 execute their antiproliferative activity through induction of apoptosis and thereby inhibit the cancer cells proliferation and compound 10 could be a lead compound for designing potential anti-cancer compound.


Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes.
Several ETS transcription factors are involved in the pathogenesis of human cancers by different mechanisms. As gene copy number gain/amplification is an alternative mechanism of oncogenic activation and 1q gain is the most common copy number change in breast carcinoma, we investigated how that genomic change impacts in the expression of the three 1q ETS family members ETV3, ELK4, and ELF3. We have first evaluated 141 breast carcinomas for genome-wide copy number changes by chromosomal CGH and showed that 1q21 and 1q32 were the two chromosome bands with most frequent genomic copy number gains. Second, we confirmed by FISH with locus-specific BAC clones that cases showing 1q gain/amplification by CGH showed copy number increase of the ETS genes ETV3 (located in 1q21~23), ELF3, and ELK4 (both in 1q32). Third, gene expression levels of the three 1q ETS genes, as well as their potential targets MYC and CRISP3, were evaluated by quantitative real-time PCR. We here show for the first time that the most common genomic copy number gains in breast cancer, 1q21 and 1q32, are associated with overexpression of the ETS transcription factors ETV3 and ELF3 (but not ELK4) at these loci irrespective of molecular subtypes. Among the three 1q ETS genes, ELF3 has a relevant role in breast carcinogenesis and is also the most likely target of the 1q copy number increase. The basal-like molecular subtype presented the worst prognosis regarding disease-specific survival, but no additional prognostic value was found for 1q copy number status or ELF3 expression. In addition, we show that there is a correlation between the expression of the oncogene MYC, irrespectively of copy number gain at its loci in 8q24, and the expression of both the transcriptional repressor ETV3 and the androgen respondent ELK4.


Novel usage of the cryoballoon catheter to achieve large area atrial substrate modification in persistent and long-standing persistent atrial fibrillation.
The cryoballoon catheter has proven to be both safe and effective when used for pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). More recently, the cryoballoon catheter has demonstrated the ability to create durable, transmural, and large areas of PV ablation. However, persistent and long-standing persistent AF can require additional cardiac substrate modification(s) before a patient is returned to normal sinus rhythm. Yet, no study has reported the techniques necessary to achieve extra-PV lesion sets using the cryoballoon catheter. Cryoballoon ablation was completed in 225 patients with varying degrees of AF disease. In several cases, the balloon was used for more than PV isolation. This study examines the 11 anatomical cardiac locations where extra-PV lesion sets were utilized. This study demonstrates that these extra-PV ablations can be done safely with the balloon catheter (3.6 % total complication rate). The 12-month efficacy (freedom from all atrial arrhythmia) using these techniques was 88 % in 88 patients with paroxysmal AF, 71 % in 75 patients with persistent AF, and 55 % in 62 patients with long-standing persistent AF. While using this protocol, mean procedure time was 2.2 ± 0.6 h, and average fluoroscopy time was 4.2 ± 2.2 min. The cryoballoon catheter can be used to make effective and safe extra-PV lesions. However, these techniques will need to be validated in more multi-center studies with review of complication rates and long-term freedom from AF.


The Role of Families in Adolescent and Young Adults' PrEP Use.
While pre-exposure prophylaxis (PrEP) is a key HIV prevention tool for adolescents and young adults (AYAs), its initiation and sustained use is shaped by AYAs' unique social contexts, including family. We explored the role of families in AYAs' PrEP use through qualitative in-depth interview (IDI) data from iPrevent, an end-user study designed to identify factors that could optimize PrEP adherence among South African youth (18-24 years old). These data were collected using a semi structured guide and were analysed using an inductive approach. Several themes describing family influence on AYAs' PrEP use emerged including family support; family attitude towards PrEP; and the family's ability to obviate PrEP disclosure challenges. In addition, dimensions of family closeness, categorized as 'close', 'in-between' and 'loose-knit,' appeared important in contextualizing family influence on AYAs' PrEP use. We found that family remains a proximal and fundamental social system in which AYA are socialized and greater family engagement could aid PrEP implementation in this priority population.


Primary squamous cell carcinoma of the stomach.
Primary squamous cell carcinoma (SCC) of the stomach is extremely rare; only 32 cases are found in the Japanese literature. The pathogenesis of this neoplasm remains obscure and controversial. Furthermore, the optimal treatment, including adjuvant chemotherapy, remains unclear. We report herein a case of SCC of the stomach in a 70-year-old male with amazing effectiveness of neoadjuvant chemotherapy, low-dose FP chemotherapy. To our knowledge, no case of this disease has ever been reported that was given neoadjuvant chemotherapy and histologically showed its effectiveness. Our case demonstrated a striking effectiveness of chemotherapy in the neoplasm both radiologically and histologically.


Machine part data with part-of relations and part dissimilarities for planted partition generation.
Identifying relationships between entities in data is a central topic across various industries and businesses, from social networks to supply chain and heavy manufacturing industries. In this paper we present data from a database of machinery represented in terms of machine parts. The machine parts are originally organised in tree structures where the vertices are machine part types, and the edges are "part-of" relations. Hence, each tree represents a type of machinery broken down into its machine part constituent types. The data we present is the union over these trees, making up a directed acyclic graph describing the type hierarchy of the machine parts. The motivation for publishing the dataset is the following real-world industry problem: Each tree represents a mechanical design, and over time some designs have been copy-pasted with minor modifications. The new instances have been given new identifiers with no reference to where from they were copied. In hindsight, it is desirable to recover the copy-paste links to for interchange between essentially identical designs. However, telling which parts are copies of which other parts has turned out to be difficult. In particular, the metadata has a tendency of displaying higher similarities within a composite part than between a part and its copy. Due to non-disclosure, we cannot provide the metadata, but we provide element wise dissimilarities that are generated based on the metadata using classical methods such as Jaccard similarity on description texts, material types etc. The dissimilarities are obtained from a data science project in the company owning the data, trying to tackle the very problem of recovering the copy-paste links. Availability of labeled data on this data set is limited, so based on our in-depth knowledge of the problem domain, we present a data synthesisation method that can generate arbitrarily large problem instances of the copy-paste problem based on the sample data, that provides a realistic representation of the real world problem. The problems are presented as planted partitions of vertices of directed acyclic graphs with vertex dissimilarities, and thus constitutes a typical classification problem along the lines of graph- or network clustering. The type of industry data we present is usually company confidential, bound by intellectual property rights, and generally not available to scientists. We therefore publish this anonymised dataset to offer real world sample data and generated problem instances for researchers that are interested in this type of classification problems, and on which theories and algorithms can be tested. The data and the problem generation methodology are backed by a Python implementation, providing both data access and an API for parameterised problem generation. The data is also available as raw files.


Effect of mts1 (S100A4) expression on the progression of human breast cancer cells.
The mts1 (S100A4) gene, encoding a Ca(2+)-binding protein of the S-100 subfamily, is involved in the control of tumor metastasis in some murine tumor cell lines. To further analyze its role, we transfected hormone-responsive human breast cancer MCF-7 cells with the mts1 gene under the control of a strong constitutive promoter. All of the 3 tested clones (MCF-7/mts1) producing Mts1 protein acquired an ability for hormone-independent growth in nude mice. Tumors derived from mts1 transfectants revealed local invasiveness into surrounding muscle and adipose tissues and metastasized to regional lymph nodes and lungs, characteristics which are rarely observed with parental MCF-7 cells. Electron-microscopic analysis of MCF-7/mts1 cells demonstrated structural changes in anchoring junctions, particularly in intermediate filament attachment site (desmosomes). The mts1-transfected clones expressed estrogen receptor, and their growth in tissue culture was both estrogen- and anti-estrogen responsive. Changes in regulation of the estrogen-dependent proteins progesterone receptor and cathepsin D were observed in some of the transfected clones. Our results indicate that mts1 expression in human breast cancer cells induces several changes characteristic of malignant phenotype and tumor progression.


[Combination of AD5-10 and epirubicin in treating rheumatoid arthritis].
To investigate the mechanism of anti-death receptor 5-10 (AD5-10) combined with epirubicin in treating rheumatoid arthritis (RA). We detected the cell viability of the fibroblast-like synoviocytes (FLS) from RA patients with MTT. The expression level of apoptosis signaling pathways protein, p53, and p21 were evaluated with Western blot. We found that epirubicin, at different doses, could enhance the effect of AD5-10 on FLS, promoting the apoptosis of FLS. The expression levels of caspase-3, -8, -9, c-FLIP, Bcl-2, p53, and p21 in the FLS changed after epirubicin treatment. Epirubicin may coordinate with AD5-10 in inducing FLS apoptosis through affecting the levels of p53, p21, c-FLIP, and Bcl-2.


Retroperitoneal fibrosis presenting as colonic dysfunction: CT diagnosis.
In a patient who presented with pelvic pain and changed bowel habits, barium enema and sigmoidoscopic examinations demonstrated a nonspecific asymmetric narrowing of the colon at the rectosigmoid junction with normal mucosal appearance. Computed tomography revealed the etiology to be retroperitoneal fibrosis with pelvic extension and entrapment of the colon at this level. The importance of CT in diagnosis of this unusual manifestation of retroperitoneal fibrosis is discussed.


Purification and characterization of the isozymes of phosphoenolpyruvate carboxykinase from rabbit liver.
Procedures are described for the purification of the mitochondrial and cytosolic isozymes of phosphoenolpyruvate carboxykinase from rabbit liver. Examination of the purified isozymes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated apparent homogeneity and identical molecular weights of approximately 65,000. Gel filtration chromatography of the native isozymes, however, yielded apparent molecular weights of 68,000 and 56,000 for the cytosolic and mitochondrial isozymes, respectively. The isoelectric points as determined by chromatofocusing were 5.8 for the mitochondrial isozyme and 5.0 for the cytosolic isozyme. The purified isozymes were readily separable on ion-exchange columns, with the cytosolic isozyme showing the greater affinity. A minor amount of cross-reactivity was apparent when each isozyme was immunotitrated with polyclonal antibodies raised in goat against the opposite isozyme. Peptide maps obtained by high pressure liquid chromatography of both tryptic digests and cyanogen bromide digests of the isozymes showed that many of the peaks were not coincident, suggesting that differences in the sequences are found throughout the primary structures of the isozymes.


Application of Auricular Cartilage-Skin Graft in the Reconstruction of Unilateral Cleft Lip Nasal Deformity.
Autologous cartilage grafts are increasingly used in the treatment of cleft lip nasal deformity, but nasal alar retraction caused by lining defects often occurs after surgery. We designed a new graft to treat unilateral cleft lip nasal deformity while avoiding nasal alar retraction. Nineteen patients in our hospital underwent unilateral cleft lip nasal deformity repair surgery with an auricular cartilage-skin graft. The effect of surgery was evaluated in four aspects: satisfaction with postoperative appearance, nasal aesthetic subunit indices, position of the nasal alar rim and three-dimensional spatial difference. Overall satisfaction with each index was above 90%. The nasal tip angle and nasolabial angle of patients were significantly smaller after surgery than before surgery (P < 0.01). The height of the nostril on the affected side and the length of the nasal columella were greater after surgery than before surgery (P < 0.01). The spatial differences in soft tissue between the unaffected side and the affected side after surgery were significantly smaller than before surgery (P < 0.01). According to the follow-up results of 1-2 years, there were no significant retraction of the nasal alar rim (P > 0.05) and no obvious auricular deformity. All patients had a noticeable improvement in their nasal appearance. The auricular cartilage-skin graft, which can not only improve the appearance of the nose but also avoid nasal alar retraction, is an ideal graft to cure unilateral cleft lip nasal deformity. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Claroideoglomus etunicatum affects the structural and functional genes of the rhizosphere microbial community to help maize resist Cd and La stresses.
Arbuscular mycorrhizal fungi (AMF) and plant rhizosphere microbes reportedly enhance plant tolerance to abiotic stresses and promote plant growth in contaminated soils. The co-contamination of soil by heavy metals (e.g., Cd) and rare earth elements (e.g., La) represents a severe environmental problem. Although the influence of AMF in the phytoremediation of contaminated soils is well documented, the underlying interactive mechanisms between AMF and rhizosphere microbes are still unclear. We conducted a greenhouse pot experiment to evaluate the effects of AMF (Claroideoglomus etunicatum) on maize growth, nutrient and metal uptake, rhizosphere microbial community, and functional genes in soils with separate and combined applications of Cd and La. The purpose of this experiment was to explore the mechanism of AMF affecting plant growth and metal uptake via interactions with rhizosphere microbes. We found that C. etunicatum (i) significantly enhanced plant nutritional level and biomass and decreased metal concentration in the co-contaminated soil; (ii) significantly altered the structure of maize rhizosphere bacterial and fungal communities; (iii) strongly enriched the abundance of carbohydrate metabolism genes, ammonia and nitrate production genes, IAA (indole-3-acetic acid) and ACC deaminase (1-aminocyclopropane-1-carboxylate) genes, and slightly altered the abundance of P-related functional genes; (iv) regulated the abundance of microbial quorum sensing system and metal membrane transporter genes, thereby improving the stability and adaptability of the rhizosphere microbial community. This study provides evidence of AMF improving plant growth and resistance to Cd and La stresses by regulating plant rhizosphere microbial communities and aids our understanding of the underlying mechanisms.


Symmetric double-well potential model and its application to vibronic spectra: studies of inversion modes of ammonia and nitrogen-vacancy defect centers in diamond.
In this paper, we have studied the vibronic transitions between two symmetric double-well potentials by proposing a model Hamiltonian consisting of a harmonic oscillator and a parturition described by a Gaussian function that leads to a double minima potential with a barrier between the two energy minima. Making use of the contour integral form of Hermite polynomials, we present a new formula that can calculate Franck-Condon factors of the system rigorously. The simulated vibronic spectra of ammonia and the negatively charged nitrogen-vacancy center in diamond are presented as an application of the formula.


Obligate cavity-roosting as a constraint on dispersal of green (red-billed) woodhoopoes: consequences for philopatry and the likelihood of inbreeding.
I studied and compared life histories and dispersal patterns of two populations of green (red-billed) woodhoopoes Phoeniculus purpureus, occupying different habitats (with widely different vegetation, topography and climate), over a period of eight years (258 "flock years") in the eastern Cape Province, South Africa. The birds are obligate cavity-roosters, and I performed an experiment in which several woodhoopoe territories were established after the introduction of artificial roost sites in an area which previously supported no woodhoopoes. The evidence supports the hypothesis that roost cavities are critical in determining the limits to woodhoopoe distribution. Group size, dispersal frequency and dispersal distance differed significantly between the two study sites. I suggest that where cavities are in short supply and unevenly distributed, long-distance scouting forays are undertaken at a high probability of not finding a safe roost site to sleep in. This may result in an increased probability of predation, or physiological conditions with which an individual in poor body condition cannot cope. I propose that among woodhoopoes a stay-and-foray dispersal strategy is preferred to a depart-and-search strategy for a number of reasons. First, there is no within-group competition for limiting resources, since roost cavities do not provide a situation in which within-group conflict could arise. Second, I show that competition for breeding vacancies is more severe at the inland than at the coastal site, further borne out by the fact that, compared to coastal birds, inland ones are proportionally more likely to attain breeding status in the natal group than elsewhere. Finally, I propose that such environmentally-induced differential dispersal patterns between the two study sites have indirectly affected the frequency with which apparent inbreeding occurs, and I suggest that since incestuous pairings are relatively common, the either have no deleterious consequences for breeder fitness, or the potential costs of inbreeding are counterbalanced by the risks associated with dispersal.


Protective effect of an oral infection with herpes simplex virus type 1 against subsequent genital infection with herpes simplex virus type 2.
The problem of whether oral Herpes simplex virus type 1 (HSV-1) infection provides protection against subsequent genital infection by Herpes simplex virus type 2 (HSV-2) was investigated. Mice were used as models. Following conditions in man, both the oral and genital infections applied were noninjurious. Mice infected orally with HSV-1 were weakly protected against virus 'take' following vaginal challenge with HSV-2. Genital 'takes' were found in 67% of the immunized mice, as compared with 83% of the controls (protection rate 20%, P = 0.002). The course of genital infection in the immunized mice, however, was relatively mild: Lethality decreased from 97% in the controls to 35% in the immunized mice (protection rate 63%, P less than 0.001). Furthermore, local and neurologic symptoms occurred less frequently. Attempts to isolate the virus from homogenized brain and spinal cord of immunized mice that died after genital challenge with HSV-2 failed in most cases. Also virus could not be recovered from the liver of infected mice, irrespective of the experimental group.


Synthesis and monoamine transporter affinity of 3-aryl substituted trop-2-enes.
A series of new 3-aryl-tropanes have been synthesized, and their affinities and selectivities were evaluated for monoamine transporters. (1RS)-3-(Fluoren-2-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene exhibited the highest affinity for the human serotonin transporter (IC(50)=14.5nM). It is also 52-fold and 230-fold selective over human dopamine and norepinephrine transporters, respectively.


Realization of anti-SN2' selective allylation of 4-cyclopentene-1,3-diol monoester with aryl- and alkenyl-zinc reagents.
Anti-SN2' mode of allylation of the monoester of 4-cyclopentene-1,3-diol with aryl and alkenyl anions was achieved, for the first time, with the MeOCH2CO2- group as a leaving group to which R-ZnBr and CuCl (as a catalyst) were best fitted. The aryl groups successfully installed were Ph, o- and p-MeC6H4, o-MOMOC6H4, o-MeOC6H4, and p-F-C6H4, while cis and trans alkenyl groups were attached with retention of the olefinic stereochemistries.


Risk Factors for the Incident Decline of Physical Performance in Older Men: The Prospective Strambo Study.
Risk factors of physical performance decline in older men remain uncertain. We assessed risk factors of incident physical performance deterioration in older men followed up prospectively. In a cohort of 821 men aged 60-87, physical performance was assessed by four tests (five chair stands, standing with closed eyes, forward and backward tandem walk) at baseline, 4 and 8 years. Various predictive biological measurements were performed at baseline. Serum creatinine/ cystatin C (Cr/CysC) ratio was used as an index of muscle mass. In multivariate models, higher age, higher fat mass index (FMI = fat mass/height2), low physical activity, prior stroke and fracture were associated with poor physical performance at baseline. Higher age, low physical activity, low calcium intake, prior non-vertebral fractures, low apparent free testosterone concentration and poor health status were associated with higher risk of loss to follow-up. Low grip strength, Parkinson's disease and stroke were associated with higher risk of incident inability to do five chair stands. Low Cr/CysC ratio and high FMI were associated with high risk of incident inability to perform forward and backward tandem walk. Sarcopenic obesity (co-occurrence of lower tertile of Cr/CysC and upper tertile of FMI) was associated with higher risk of incident inability to perform forward (OR = 3.31, 95% CI 1.88-5.84, p < 0.001) and backward tandem walk and of incident inability to perform more than one test (OR = 5.82, 95% CI 1.29-26.27, p < 0.001). In conclusion, sarcopenic obesity and poor health are associated with higher risk of incident severe decline of physical performance.


Appearance of secretory IgM and IgA antibodies to Escherichia coli in saliva during early infancy and childhood.
Unstimulated whole saliva was collected from 203 uninfected individuals at various ages from birth until adulthood. Levels of specific antibodies against Escherichia coli O antigens of secretory IgA, secretory IgM and IgG, as well as total amounts of SIgA, were determined using ELISA. Levels of SIgA antibodies found in adults were approached by the age of 12 months, but high levels could be attained earlier, presumably in response to antigenic exposure at the mucosal level. During the first few months of life, secretory IgM antibodies appeared in the saliva, possibly compensating for the relative lack of IgA.


The Use of Force Plate Vertical Jump Scans to Identify Special Warfare Trainees at Risk for Musculoskeletal Injury: A Large Cohort Study.
Vertical jump scans from commercially available force plate systems are increasingly used in military settings to screen for musculoskeletal injury (MSKI) risk. However, to date, no studies have determined the ability of these tools to identify tactical athletes at elevated risk for MSKI. To (1) determine associations between scores from a force plate vertical jump test and the likelihood of experiencing an MSKI and to (2) establish the test-retest reliability of the output scores from the force plate system used. Cohort study; Level of evidence, 3. A total of 823 male Air Force Special Warfare trainees underwent force plate vertical jump screenings before entering an 8-week training course at US Air Force Special Warfare Training Wing. MSKI data were collected for the 8-week surveillance period for each trainee. Logistic regression analyses were used to identify associations between baseline force plate jump scores and the likelihood of MSKI (any region) or a lower extremity MSKI (significance level, P = .05). The test-retest portion of the study collected force plate output scores from 12 trainees performing 3 trials of the standard test procedures. The reliability of 5 output scores was assessed with intraclass correlation coefficients (ICCs) using a single rater. All force plate output scores demonstrated excellent test-retest reliability (ICC >0.90). Overall 308 (36.4%) trainees had an MSKI during the surveillance period. However, no significant associations were found between the proprietary force plate vertical jump scan output scores and the likelihood of experiencing either an MSKI or a lower extremity MSKI. Output scores from this commercially available force plate system did not identify Air Force Special Warfare trainees at elevated risk of experiencing an MSKI.


Enzyme changes in rat small intestine during pregnancy and lactation.
Small fluctuations in the activity of a number of important enzymes have been found during the intestinal hyperplasia and hypertrophy of pregnancy and lactation. The pattern of change differs between the enzymes studied, and for individual enzymes often varies between the jejunum and ileum. These results suggest that there must be a complex response to the signals that trigger hyperplasia in the mucosal epithelium.


Nutritional composition and in vitro digestibility of two Plantain Cultivars (Musa Paradisiaca spp.) in Puerto Rico.
Plantain is a basic component in the Puerto Ricans' diet and one of the most economically important crops on the Island. Maricongo crops, the predominant cultivar, do not satisfy the demand for fresh and processed products. The objective of this study was to evaluate the nutritional composition and in vitro digestibility of Maiden and FHIA 20 plantains in stages 1 and 5 and compare these data to Maricongo. Estimated glycemic indexes (eGI) of cultivars under conventional cooking processes (i.e., boiling, fried, baked, and steamed) were performed as well. Baked Maricongo stood out because of its lowest rapidly available glucose value (22.06%), constituting a healthier and the first cooking alternative. eGI values were classified as medium and high, where frying and baking processes presented medium values, and boiling displayed the greatest eGI for both stages. In terms of nutritional profile, this research concludes that Maiden could constitute an option to substitute or supplement Maricongo.


Physicochemical and histological analysis of an experimental endodontic repair material containing 45S5 bioactive glass.
This study aimed to evaluate the maximum compressive strength, the modulus of elasticity, pH variation, ionic release, radiopacity and biological response of an experimental endodontic repair cement based on 45S5 Bioglass®. An in vitro and in vivo study with an experimental endodontic repair cement containing 45S5 bioactive glass was conducted. There were three endodontic repair cement groups: 45S5 bioactive glass-based (BioG), zinc oxide-based (ZnO), and mineral trioxide aggregate (MTA). In vitro tests were used to evaluate their physicochemical properties: compressive strength, modulus of elasticity, radiopacity, pH variation, and the ionic release of Ca+ and PO4. An animal model was used to evaluate the bone tissue response to endodontic repair cement. Statistical analysis included the unpaired t-test, one-way ANOVA and Tukey's test. BioG showed the lowest compressive strength and ZnO showed the highest radiopacity among the groups, respectively (p < 0.05). There were no significant differences in the modulus of elasticity among the groups. BioG and MTA maintained an alkaline pH during the 7 days of evaluation, both at pH 4 and in a pH 7 buffered solutions. PO4 was elevated in BioG, peaking at 7 days (p < 0.05). Histological analysis showed less intense inflammatory reactions and new bone formation in MTA. BioG showed inflammatory reactions that decreased over time. These findings suggest that the BioG experimental cement had good physicochemical characteristics and biocompatibility required for bioactive endodontic repair cement.


SalK/SalR, a two-component signal transduction system, is essential for full virulence of highly invasive Streptococcus suis serotype 2.
Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant. These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.


Synthesis, characterization and adsorption properties of magnetite/reduced graphene oxide nanocomposites.
Three kinds of magnetite/reduced graphene oxide (MRGO) nanocomposites were prepared by solvothermal, hydrothermal and co-precipitation methods. The as-prepared nanocomposites were characterized and compared by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and zeta potential. The results showed that MRGO made by different methods differed in surface functional groups, crystal structure, particle sizes, surface morphology and surface charge. Due to their unlike features, these nanocomposites displayed dissimilar performances when they were used to adsorb drugs, dyes and metal ions. The MRGO prepared by the co-precipitation method showed special adsorption ability to negative ions, but those synthesized by the solvothermal method obtained the best extraction ability and reusability to the others and showed a good prospective in magnetic solid-phase extraction. Therefore, it is highly recommended to use the right preparation method before application in order to attain the best extraction performance.


Transcriptome Analysis to Identify Human Spermatogonial Cells from Sertoli Cell-Only Testes.
We sought to determine whether gene products from spermatogenic cells could be detected in Sertoli cell-only testes. Transcriptome analysis using next generation sequencing was performed using human testicular samples. This study enrolled 20 men with nonobstructive azoospermia with a histological diagnosis of Sertoli cell-only and no germ cells on in vitro fertilization analysis and 5 with obstructive azoospermia and histologically normal spermatogenesis. Individual differences in the transcriptome of obstructive azoospermia testicular tissues generated on the Illumina® platform were compared as the number of fragments per kilobase of exon per million mapped sequence reads. We confirmed mRNA expression and targeted gene product localization by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively. Using next generation sequencing we analyzed 5,666 of the 23,003 screened genes. As representative markers of immature germ cells, UTF1, CD9, DDX4, EPCAM, GFRA1, KIT, LIN28, DMRT, GPR125, UCHL1 and NANOG transcripts were detected in 13 Sertoli cell-only samples (65%). Reverse transcriptase-polymerase chain reaction showed significant mRNA expression of UTF1, CD9, DDX4 and KIT in Sertoli cell-only samples. Immunostaining revealed the localization of DDX4-positive cells, presumably spermatogonia, in 9 Sertoli cell-only samples (45%). These cells lacked proliferative cell nuclear antigen expression. A number of Sertoli cell-only testes contain immature germ cells (spermatogonia and spermatogenic stem cells) with various gene expression profiles. Sertoli cell-only is a heterogeneous pathophysiology which may be corrected by medical treatment or regenerative technologies.


Clinical, cognitive and neural correlates of self-monitoring deficits in schizophrenia: an update.
An area of recent interest in schizophrenia research is to investigate specific neural and cognitive abnormalities associated with symptoms of this disorder. To establish clinical, cognitive and neural correlates of self-monitoring deficits in schizophrenia, which according to various theoretical models can account for the first-rank symptoms of this disorder. Relevant data were identified from PubMed and PsycInfo searches up to July 2006 using combinations of keywords including 'self-monitoring', 'symptoms', 'self-agency', 'neuropsychological', 'cognitive', 'brain activity', 'PET' and 'fMRI'. Self-monitoring deficit is most consistently observed in patients with schizophrenia with auditory hallucinations and passivity experiences. This deficit may not be schizophrenia specific. At present, there are insufficient direct data to reach meaningful conclusions about the cognitive correlates of this deficit. Functional neuroimaging studies in patients with schizophrenia with auditory hallucinations point to defective engagement of the neural regions known to be involved in self-monitoring in healthy people. Further multimodal studies using validated cognitive and clinical measures, self-monitoring paradigms and appropriate imaging tools to analyze patients with schizophrenia with and without self-monitoring deficits are required to increase our understanding of this topic.


Male-female response profile differences on the WAIS-R in clients suffering from borderline personality disorders.
One hundred nineteen clients diagnosed with borderline personality disorders participated in a correlational study using standard intelligence and achievement measures. We expected to confirm the presence of an organic subtype that might help clinicians who work with this group of clients (average IQ = 79.3). We found gender differences that tended to support previous research on male-female differences. In general, the data supported the presence of an organic subtype. Analyses of arrest history and additional differential diagnoses showed this category of client relatively free of dependency concerns but manifesting signs of an anxiety disorder.


Self-protective whole body motion for humanoid robots based on synergy of global reaction and local reflex.
This paper describes a self-protective whole body motor controller to enable life-long learning of humanoid robots. In order to reduce the damages on robots caused by physical interaction such as obstacle collision, we introduce self-protective behaviors based on the adaptive coordination of full-body global reactions and local limb reflexes. Global reactions aim at adaptive whole-body movements to prepare for harmful situations. The system incrementally learns a more effective association of the states and global reactions. Local reflexes based on a force-torque sensing function to reduce the impact load on the limbs independently of high-level motor intention. We examined the proposed method with a robot simulator in various conditions. We then applied the systems on a real humanoid robot.


Molecular bases for the selection of the chromophore of animal rhodopsins.
The functions of microbial and animal rhodopsins are triggered by the isomerization of their all-trans and 11-cis retinal chromophores, respectively. To lay the molecular basis driving the evolutionary transition from the all-trans to the 11-cis chromophore, multiconfigurational quantum chemistry is used to compare the isomerization mechanisms of the sensory rhodopsin from the cyanobacterium Anabaena PCC 7120 (ASR) and of the bovine rhodopsin (Rh). It is found that, despite their evolutionary distance, these eubacterial and vertebrate rhodopsins start to isomerize via distinct implementations of the same bicycle-pedal mechanism originally proposed by Warshel [Warshel A (1976) Nature 260:678-683]. However, by following the electronic structure changes of ASR (featuring the all-trans chromophore) during the isomerization, we find that ASR enters a region of degeneracy between the first and second excited states not found in Rh (featuring the 11-cis chromophore). We show that such degeneracy is modulated by the preorganized structure of the chromophore and by the position of the reactive double bond. It is argued that the optimization of the electronic properties of the chromophore, which affects the photoisomerization efficiency and the thermal isomerization barrier, provided a key factor for the emergence of the striking amino acid sequence divergence observed between the microbial and animal rhodopsins.


Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (ARGENTA).
To establish the influence of genotypic resistance-guided treatment decisions and patient-reported adherence on the virological and immunological responses in patients failing a potent antiretroviral regimen in a randomized, controlled trial in a tertiary care infectious diseases department. A total of 174 patients with virological failure were randomly assigned to receive standard of care (SOC) or additional genotypic resistance information (G). Adherence was measured by a self-administered questionnaire. Primary endpoints were the proportion with HIV-RNA < 500 copies/ml at 3 and 6 months by intention-to-treat analysis. Secondary endpoints were changes from baseline HIV-RNA levels and CD4 cell counts. At entry, 25% had failed three or more highly active antiretroviral therapy (HAART) regimens and 41% three drug classes; there were more resistance mutations in G. In 127 evaluable questionnaires, 43% reported last missed dose during the previous week. At 3 months, 11 of 89 patients (12%) in SOC and 23 of 85 (27%) in G had HIV-RNA < 500 copies/ml (OR 2.63, 95% CI 1.12-6.26); the relative proportions were 17 and 21% at 6 months. CD4 cell changes did not differ between arms. Six month CD4 cell changes were +62 in adherent and -13 cells/microl in non-adherent patients (P < 0.01). Being assigned to G, good adherence, previous history of virological success, fewer experienced HAART regimens and lower baseline viral load were independently predictive of 3 month virological success. The virological benefit of genotype-guided treatment decisions in heavily pre-exposed patients was short term. Patients adherence and residual treatment options influenced outcomes.


Analysis and deliberation as a mechanism to assess changes in preferences for indicators of sustainable forest management: a case study in Puebla, Mexico.
The purpose of this study was to assess changes in forest owners' preferences regarding indicators of sustainable forest management. The analysis and deliberation framework served as a platform upon which to explore these changes in a rural community in Puebla, Mexico. Sixty-two indicators were selected from existing sets to design a five-point Likert survey instrument. The instrument was administered three times: early in the study to capture the forest owners' preferences before intervention (baseline); following an educational meeting in which the participants learned of three alternative forest management plans (analysis); and following a community meeting in which the forest owners deliberated to choose one of the alternatives (deliberation). As forest owners were exposed to knowledge (analysis) and deliberation, their preferences for the indicators changed significantly. An examination of the instrument demonstrated how the indicators increased or decreased in importance. Social and economic indicators tended to be ranked differently following analysis and again following deliberation because of the commitment to pursue a forest management plan that would benefit the community without jeopardizing stakeholder values. The ecological indicators directly associated with forest structure gained relevance following the analysis meeting. The deliberation process elucidated the importance of forest administration and professional help. Forest owners' preferences were reflected by the selection of the management plan that included good science and accommodated community values. The forest owners changed their preferences in response to new knowledge, management objectives, and their commitment to safeguarding the future condition of the forest. Analysis and deliberation is a participatory forum that facilities communication and learning and allows stakeholders to share values; thus, it serves as a mechanism for forest planning.


Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability.
Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.


The Importance of PPE and Regular Testing in Health Care Facilities.
Nearly 30% of health workers with COVID-19 didn't know they had it.


Coexistence of left main and right coronary artery ostial stenosis: demographic and angiographic features.
This study was designed to evaluate ostial left main coronary artery (LMCA) stenosis and investigate concomitant stenotic lesions of LMCA and right coronary arteries (RCA) and their demographic and angiographic features. We evaluated 11,283 patients who underwent coronary angiography. Patients were placed into four groups according to having ostial or nonostial LMCA or RCA stenosis. Significant LMCA stenosis was observed in 242 (8.3%) of the patients, and only 68 (28.1%) of them had significant ostial LMCA stenosis. There was a significant correlation between ostial stenosis of LMCA and RCA (p = 0.03). The frequency of female gender was greater in ostial LMCA and ostial RCA stenosis groups compared with the other groups (p = 0.01). Ostial LMCA and RCA stenosis were related significantly. Both female predominance and coexistence of ostial LMCA and RCA stenosis might have suggest a different pathological ground for this disease.


The current status of drug development of hypoxic cell radiosensitizers and their potential role in gynecologic oncology.
Both laboratory and clinical data suggest that hypoxia contributes to the failure of radiotherapy to achieve local control of bulky gynecologic tumors. As part of a Phase I trial of hypoxic cell radiosensitizers, 19 women at Stanford University with advanced (n = 6) or recurrent (n = 13) pelvic neoplasms were treated with radiotherapy plus desmethylmisonidazole. Complete or partial response occurred in 42% of patients with some patients achieving local control for over 1 year. It is unknown if the sensitizer added to the results of radiotherapy alone. A Phase I trial of a theoretically superior sensitizer, SR-2508, is soon to begin. It is anticipated that the dose-limiting neurotoxicity seen with misonidazole and desmethylmisonidazole will either be eliminated or will occur at a much higher total dose of drug. Many patients with gynecologic tumors could potentially benefit from participation in the new drug trials.


Effects of acute and chronic administration of acebutolol on the right ventricular effective refractory period in conscious dogs.
beta-Adrenergic blocking drugs are effective in reducing sudden cardiac death after acute myocardial infarction but the precise mechanism of this effect is unclear. We investigated the acute and chronic effects of acebutolol, a beta-adrenergic blocker, on electrocardiographic parameters, diastolic excitability threshold (DET), and right ventricular effective refractory period (RVERP) in chronically instrumented conscious dogs. These parameters were determined during spontaneous sinus rhythm and at a fixed pacing rate (200 beats/min). Acebutolol (0.5, 1, and 5 mg/kg i.v.) decreased the heart rate (HR) (by 23, 26, and 24%, respectively) without effects on any electrocardiographic parameters or on the DET. The maximal increases in ERP were 4.7, 7, and 7.8%, respectively, during pacing and 8.5, 13.3, and 10.3%, respectively, during sinus rhythm. Acebutolol, 10 mg/kg/day P.O. for 6 weeks, reduced the HR from the third day onward without altering the PR, QRS, QT, or QTc intervals or the DET. The increase in ERP was significant from the third day (14%) during pacing and from the seventh day (15.5%) during sinus rhythm. The degree of prolongation of the ERP subsequently remained stable during the 6 weeks of treatment. The ERP returned to the baseline value 7 days after acebutolol withdrawal. This increase in ERP, which was more marked during chronic oral treatment, could contribute to the documented protective effect of the beta-blocking drugs against sudden cardiac death after myocardial infarction.


Efficacy of covert closed-circuit television monitoring of the hand hygiene compliance of health care workers caring for patients infected with multidrug-resistant organisms in an intensive care unit.
To compare covert closed-circuit television (CCTV) monitoring to standard overt observation in assessing the hand hygiene (HH) conduct of health care workers (HCWs) caring for patients infected with multidrug-resistant organisms (MDROs). This was a cross-sectional study in a general intensive care unit of a 1,000-bed university hospital. Forty-six general intensive care unit HCWs (staff physicians, registered nurses, and auxiliary workers) caring for contact isolation MDRO-infected patients. The study incorporated the following 3 phases: phase 1, establishment of interrater reliability between 2 simultaneous observers using the overt observation method; phase 2, establishment of interrater reliability between 2 simultaneous observers using the CCTV method; and phase 3, simultaneous monitoring of HH by both methods to evaluate the suitability of CCTV as an alternative to direct observation of the HH conduct of HCWs caring for MDRO-infected patients. Overall, 1,104 opportunities to perform HH were documented during 49 observation sessions. The compliance rate observed by the overt method (37.3%) was significantly higher than that observed when only the covert method was used (26.5%). However, simultaneous overt-covert observations were found to have intraclass correlation coefficients of >0.85. Covert CCTV observation of HCW HH compliance appears to provide a truer and more realistic picture than overt observation, probably because of its ability to neutralize the Hawthorne effect of overt observation. The high intraclass correlation coefficients between covert observation and overt observation supports this conclusion.


Activity of partially purified protein chain initiation factors from the livers of dimethylnitrosamine-treated rats.
Partially purified polypeptide chain initiation factors were prepared from the 0.5 M KCl wash of rat liver microsomes. Their activities in connection with dimethylnitrosamine (DMNA)-induced inhibition of protein synthesis were studied by use of the following reactions: (1) poly(U)-directed binding of Phe-tRNA to ribosomes, (2) formation of a GTP-dependent ternary initiation complex with Met-tRNAf, (3) binding of Met-tRNAf to 40-S ribosomal subunits, (4) assembly of a Met-tRNAf containing 80-S ribosomal initiation complex and (5) ribosome-dependent GTPase activity. The inhibition of protein synthesis with DMNA was not associated with a loss of factor activity in any of these reactions. In the binding of Met-tRNAf to 40-S subunits there was a noticeable increase, probably related to the stability of the resulting complex. The Met-tRNA deacylase activity was also increased.


Composition-driven symptom phrase recognition for Chinese medical consultation corpora.
Symptom phrase recognition is essential to improve the use of unstructured medical consultation corpora for the development of automated question answering systems. A majority of previous works typically require enough manually annotated training data or as complete a symptom dictionary as possible. However, when applied to real scenarios, they will face a dilemma due to the scarcity of the annotated textual resources and the diversity of the spoken language expressions. In this paper, we propose a composition-driven method to recognize the symptom phrases from Chinese medical consultation corpora without any annotations. The basic idea is to directly learn models that capture the composition, i.e., the arrangement of the symptom components (semantic units of words). We introduce an automatic annotation strategy for the standard symptom phrases which are collected from multiple data sources. In particular, we combine the position information and the interaction scores between symptom components to characterize the symptom phrases. Equipped with such models, we are allowed to robustly extract symptom phrases that are not seen before. Without any manual annotations, our method achieves strong positive results on symptom phrase recognition tasks. Experiments also show that our method enjoys great potential with access to plenty of corpora. Compositionality offers a feasible solution for extracting information from unstructured free text with scarce labels.


Neural structure of a sensory decoder for motor control.
The transformation of sensory input to motor output is often conceived as a decoder operating on neural representations. We seek a mechanistic understanding of sensory decoding by mimicking neural circuitry in the decoder's design. The results of a simple experiment shape our approach. Changing the size of a target for smooth pursuit eye movements changes the relationship between the variance and mean of the evoked behavior in a way that contradicts the regime of "signal-dependent noise" and defies traditional decoding approaches. A theoretical analysis leads us to propose a circuit for pursuit that includes multiple parallel pathways and multiple sources of variation. Behavioral and neural responses with biomimetic statistics emerge from a biologically-motivated circuit model with noise in the pathway that is dedicated to flexibly adjusting the strength of visual-motor transmission. Our results demonstrate the power of re-imagining decoding as processing through the parallel pathways of neural systems.


Molecular docking and antimalarial evaluation of novel N-(4-aminobenzoyl)-l-glutamic acid conjugated 1,3,5-triazine derivatives as Pf-DHFR inhibitors.
Malaria has been a source of concern for humans for millennia; therefore in the present study we have utilized in-silico approach to generate diverse anti-malarial hit. Towards this, Molinspiration cheminformatics and Biovia Discovery Studio (DS) 2020 were used to conduct molecular modelling studies on 120 designed compounds. Furthermore, the TOPKAT module was used to evaluate the toxicity of the screened compounds. The CDOCKER docking technology was used to investigate protein-ligand docking against the Pf-DHFR-TS protein (PDB ID: 1J3I and 1J3K). These compounds were synthesized using a conventional and microwave-assisted nucleophilic substitution reaction, and they were characterized using a variety of physicochemical and spectroscopic methods. Among the ten compounds tested, Df3 had the highest antimalarial activity against the chloroquine-resistant (Dd2) strain, with an IC50 value of 9.54 μg mL-1 and further demonstrate, molecular dynamics (MD) simulation studies and estimation of MM-PBSA-based free binding energies of docked complexes with 1J3I and 1J3K were carried out. The discovery of a novel class of Pf-DHFR inhibitors can be accomplished using this hybrid scaffold. The online version contains supplementary material available at 10.1007/s13205-022-03400-2.


Naso- and oropharyngeal dimensions in children with obstructive sleep apnea.
Sixty children (3-11 years) were evaluated to determine variations in naso- and oropharyngeal dimensions associated with tonsil and adenoid hypertrophy. The subjects were grouped according to tonsil size and a clinical history of chronic upper airway obstruction. Intraoperative measurements included oropharyngeal diameter, length of the hard and soft palates, width and arch of the hard palate, nasopharyngeal volume, as well as tonsil and adenoid weights and volumes. A significantly larger oropharyngeal diameter was found in children with small, non-obstructing tonsils (P less than 0.01). Children with large, non-obstructing tonsils had a similar oropharyngeal diameter to those children with large, obstructing tonsils. However, tonsil volume, not weight, was increased in the children with large obstructing tonsils as compared to those with large non-obstructing tonsils and small non-obstructing tonsils (P less than 0.04). A shorter soft palate was associated with larger, obstructing tonsils (P less than 0.004). The length of the hard palate was similar in all patients, however, a trend towards a higher arched palate was seen in patients with larger, obstructing tonsils. The distance from the soft palate to the posterior pharyngeal wall was greater in obstructed patients with adenotonsillar hypertrophy (P less than 0.003). In patients requiring adenoidectomy, the nasopharyngeal volume prior to adenoidectomy was significantly smaller in patients with obstructive symptoms (P less than 0.001). Postadenoidectomy, no significant difference was found in the nasopharynx volume amongst all subjects. These data indicate that subtle differences in oropharyngeal dimensions exist which along with increased lymphoid tissue volume, lead to the development of obstructive symptoms. Etiologic considerations are discussed.


Pediatric flecainide toxicity from a double dose.
A 23-month-old boy was brought to the emergency department of an adult and pediatric tertiary care center 1 hour after an inadvertent "double dose" of 120 mg flecainide (9.2 mg/kg). His electrocardiogram revealed sinus rhythm with a terminal R wave in aVR greater than 7 mm, a bifascicular block, and prolonged QRS and QTc intervals. A dramatic improvement in the bifascicular block and terminal R wave occurred after the administration of sodium bicarbonate. He was discharged after 36 hours with no complications. This case demonstrates that flecainide can cause significant cardiac conduction disturbances in doses much lower than previously described. All supratherapeutic ingestions should be assessed in hospital.


Data needs and models for the opioid epidemic.
The evolving nature of the opioid epidemic and continued increases in overdose deaths highlight a need for fundamental change in the collection and use of surveillance data to link them to implementation of effective service, treatment, and prevention approaches. Yet at present, the quality and timeliness of US surveillance data often limits data-driven approaches. We review current information needs, summarize limitations of existing data, propose complementary surveillance resources, and provide examples of promising approaches designed to meet the needs of data end-users. We conclude that there is a need for an approach that focuses on the needs of data end-users, such as public health systems leaders, policy makers, public, nonprofit and prepaid healthcare systems, and other systems, such as the justice system. Such an approach, which may require investments in new infrastructure, should prioritize improvements in data timeliness, sample representativeness, database linkage, and increased flexibility to adapt to shifts in the environment, while preserving the privacy of survey participants. Use of simulations, distributed research and data networks, alternative data sources, such as wastewater or digital data collection and use of blockchain technology, are some of promising avenues toward an improved and more user-centered surveillance system.


Deoxyglucose kinetics in a rat brain tumor.
Accurate quantitation of local glucose metabolic rates (LMRglc) of abnormal tissues such as brain tumors with the 2-deoxyglucose (DG) method requires knowledge of the tissue rate constants and lumped constant. The deoxyglucose rate constants were measured in an experimental intracerebral glioma in 24 awake rats with a dual tracer [(3H)-DG and (14C)-DG] method. Tissue time points were obtained at 2, 5, 10, 18, 30, 60, 90, and 180 min after injection by decapitation and liquid scintillation counting. Blood samples were obtained at 1 min intervals initially and at longer intervals later. The rate constants were estimated with parameter estimation. LMRglc was calculated from the rate constants, assuming a lumped constant of 0.5. K1 for normal cerebrum was found to be 0.258 ml/g/min, and k2-k4 were 0.406, 0.075, and 0.0103 min-1; LMRglc = 65.1 mumol/100 g/min. The corresponding values for the glioma were 0.108, 0.126, 0.040, and 0.0019 with LMRglc = 41.7. The considerably lower k4 in the glioma was reflected in persistent higher activity in the glioma at longer times. Thus, tissue activity alone cannot be used to assess relative glucose metabolic rates in abnormal tissues such as gliomas, particularly at late times after injection.


Skin temperature changes in paradoxical sleep in man in the cold.
Mean skin temperature (Tsk) calculated from seven sites and rectal temperature (Tre) were recorded every minute for a total of 88 man-nights in eight young men sleeping at night in both cold (during the Artic winter) and neutral (laboratory) environments, and were related to the EEG stages of sleep, especially to paradoxical sleep (PS). In the neutral environment, Tre was always above 36 degrees C and Tsk increased during PS. In the cold conditions, during PS, Tsk increased when Tre was high, and decreased when Tre was below 36 degrees C. It was concluded that, although it is not known why a core temperature of about 36 degrees C is the critical point of change in the direction of Tsk variations during PS, the direction in which Tsk will vary during PS is dependent on the core temperature at the time.


Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.
Tuberous sclerosis complex (TSC) is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR) pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD) was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/-) CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/-) hippocampal slices. We also report that adult TSC2(+/-) mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.


Surgical Boot Camps Increases Confidence for Residents Transitioning to Senior Responsibilities.
Surgical boot camps enhance the confidence of medical students and surgical interns. The impact of boot camps on the confidence of post-graduate year (PGY) 2 residents is unknown. We hypothesized that a postinternship boot camp would improve the confidence of PGY-2 residents in managing their newfound responsibilities. We also hypothesized that the effect of a tailored high-impact boot camp would persist over time. A 2-hour boot camp at our simulation center was implemented for PGY-2 residents in 2016 and 2017. Confidence in handling boot camp scenarios was measured on a 1 to 5 Likert scale before and after the boot camp. Three-month follow-up was assessed in the 2017 cohort. Thirty-one PGY-2 residents (n = 16 in 2016, n = 15 in 2017) completed the boot camp. Residents reported increased confidence in placing central lines (p < 0.001), placing chest tubes (p = 0.01), managing emergency airways (p < 0.001), running a code (p = 0.03), and fulfilling the role of in-house senior resident (p < 0.001). Three-month follow-up in 2017 (n = 10) demonstrated no difference in confidence compared to postboot camp results. Boot camps can durably improve confidence in skills expected of PGY-2 residents assuming in-house senior resident responsibilities.


Fundamentals of High-Resolution Ultrasound in Breast Implant Screening for Plastic Surgeons.
This article introduces the plastic surgeon to the basics of high-resolution ultrasound (HRUS) for screening breast implants. It describes how HRUS has become an accepted alternative to MRI for screening and diagnosis, and how plastic surgeons should use this new technology for the benefit of their patients and their practices. Basic principles, technology, and nomenclature are presented. Key steps to obtaining diagnostic images of breast implants are reviewed, including typical artifacts and sources of error. Imaging examples are presented. The article ends with a review and a step-by-step guide for plastic surgeons looking to use the technology.


Temporal sequence of interleukin 1 alpha-mediated stimulation and inhibition of bone formation by isolated fetal rat calvaria cells in vitro.
Cytokines released at sites of inflammation and infection may alter normal bone remodeling processes resulting in pathologic bone destruction or bone formation. Interleukin 1, an inflammatory mediator, has been shown to stimulate as well as inhibit parameters associated with bone formation. In this study we have examined temporal aspects of the biphasic effects of recombinant interleukin 1 alpha (IL 1 alpha) on the differentiation of osteoprogenitor cells into bone-forming osteoblasts (bone nodules) in vitro. A dose-dependent stimulation of bone formation over a concentration range of 0.5 to 50 U/mL (1.4 x 10(-12) to 1.4 x 10(-10) M) was observed when preconfluent, primary cultures of fetal rat calvaria (RC) cells were pulsed with IL 1 alpha for 72 to 96 hr from the beginning of the culture period. This was correlated with a stimulation of cell proliferation and alkaline phosphatase activity measured during the late log phase of growth. In contrast, continuous exposure to IL 1 alpha or exposure to IL 1 alpha after confluency resulted in inhibition of bone nodule formation and alkaline phosphatase activity. IL 1 alpha-stimulated prostaglandin E2 (PGE2) production until the RC cells became multilayered, but the addition of the cyclooxygenase inhibitor indomethacin had no effect in reducing the IL 1 alpha-mediated stimulation of cell proliferation or bone nodule formation. However, in cultures continuously exposed to IL 1 alpha, added indomethacin partially reduced the inhibition of bone formation, suggesting that prostaglandin production may play a role in the inhibitory effects of IL 1 alpha on bone formation.


A white-box model for real-time simulation of acid-base balance in blood plasma.
Maintaining an optimal acid base is important for the patient. The theory underlying acid-base balance can be challenging for clinicians and educators. These considerations justify creating simulations that include realistic changes to the partial pressure of carbon dioxide, pH, and bicarbonate ion concentration in a range of conditions. Our explanatory simulation application requires a model that derives these variables from total carbon dioxide content and runs in real time. The presented model is derived from the Stewart model, which is based on physical and chemical principles, and takes into account the effects of weak acids and strong ions on the acid-base balance. An inventive code procedure allows for efficient computation. The simulation results match target data for a broad range of clinically and educationally relevant disturbances of the acid-base balance. The model code meets the real-time goals of the application and can be applied in other educational simulations. Python model source code is made available.


Monoclonal antibodies specific for the different subunits of asymmetric acetylcholinesterase from chick muscle.
The asymmetric (20S) acetylcholinesterase (AChE, EC 126.96.36.199) from 1-day-old chick muscle, purified on a column on which was immobilised a monoclonal antibody (mAb) to chick brain AChE, was used to immunise mice. Eight mAbs against the muscle enzyme were hence isolated and characterised. Five antibodies (4A8, 1C1, 10B7, 7G8, and 8H11) recognise a 110-kilodalton (kDa) subunit with AChE catalytic activity, one antibody (7D11) recognises a 72-kDa subunit with pseudocholinesterase or butyrylcholinesterase (BuChE, EC 220.127.116.11) catalytic activity, and two antibodies (6B6 and 7D7) react with the 58-kDa collagenous tail unit. Those three polypeptides can be recognised together in the 20S enzyme used, which is a hybrid AChE/BuChE oligomer. Antibodies 6B6 and 7D7 are specific for asymmetric AChE. Four of the mAbs recognising the 110-kDa subunit were reactive with it in immunoblots. Sucrose density gradient analysis of the antibody-enzyme complexes showed that the anti-110-kDa subunit mAbs cross-link multiple 20S AChE molecules to form large aggregates. In contrast, there is only a 2-3S increase in the sedimentation constant with the mAbs specific for the 72-kDa or for the 58-kDa subunit, suggesting that those subunits are more inaccessible in the structure to intermolecular cross-linking. The 4A8, 10B7, 7D11, and 7D7 mAbs showed cross-reactivity to the corresponding enzyme from quail muscle; however, none of the eight mAbs reacted with either enzyme type from mammalian muscle or from Torpedo electric organ. All eight antibodies showed immunocytochemical localisation of the AChE form at the neuromuscular junctions of chicken twitch muscles.


Perception of implicit relationships between personality traits by schizotypic college subjects: a pilot study.
The perception of trait relationships was measured in both schizotypic and control college subjects (N = 46) by use of a similarity rating method. Schizotypic and control subjects were selected on the basis of their scores on four scales of schizotypy: Physical Anhedonia, Perceptual Aberration, Intense Ambivalence, and Somatic Symptoms. Schizotypes as a group were more variable in their ratings of trait relationships than were controls. When each scale was considered separately, only perceptual aberrators as a group were as consistent in their ratings of trait relationships as control subjects. These findings support the hypothesis that schizotypes fail to share the semantic trait structure accepted by most normal subjects and may be a possible explanation for previous findings of social deficits in schizotypes.


Colour and flicker thresholds for high frequency increments.
Previous investigators have elicited spectral sensitivity functions for the chromatic and achromatic systems by manipulating the stimulus spatiotemporal parameters. An alternative strategy for obtaining these two functions is to use a single set of stimulus parameters and vary the threshold criterion. This can be accomplished by determining colour and flicker thresholds for a high frequency train of increments. In the current study, spectral sensitivity functions, based on colour and flicker thresholds, were determined for increments presented at 25 Hz. The colour and flicker threshold functions are similar in form to those previously published for the chromatic and achromatic systems. The existence of distinct threshold functions for colour and flicker are interpreted in the context of parvo and magno pathways. Potential clinical applications of this model are discussed.


Lipid transfer between human plasma low-density lipoprotein and a triolein/phospholipid microemulsion catalyzed by insect hemolymph lipid transfer particle.
Lipid transfer between human plasma low-density lipoprotein (LDL) and an LDL-size microemulsion of triolein and phosphatidylcholine stabilized with human apolipoprotein A-I was catalyzed by the lipid transfer particle from hemolymph of the tobacco hornworm (Manduca sexta). Net transfer of phospholipid and triacylglycerol from the emulsion to LDL was observed and the apparent initial rates of transfer were dependent on the amount of catalyst. Net transfer of phospholipid mass was twice as much as that of triacylglycerol with respect to both the initial rate and the final equilibrium state. The final amount of net transfer of both lipids was dependent upon the initial ratio of LDL: microemulsion present in the incubation mixture up to 1:1 on the basis of phospholipid. The microemulsion lipid composition was maximally altered from an initial weight ratio of 1.09 +/- 0.08 (phospholipid/triolein) to 0.90 +/- 0.03 by this reaction. Further increase of LDL in the incubation caused neither further net transfer nor further change in the lipid composition of the microemulsion. The catalyst neither affected spontaneous transfer of free cholesterol between the emulsion and LDL nor enhanced cholesteryl ester transfer in this reaction system. As a result of the facilitated reaction, LDL gained a significant amount of phospholipid and triacylglycerol causing up to an 8% increase in core lipids and 14% in phospholipid. Some free cholesterol is recovered in the emulsions via spontaneous exchange. Transfer or exchange of apolipoproteins during the course of facilitated lipid transfer did not occur.