Comparison between selective distal splenorenal shunt and small diameter H-graft portosystemic shunt.
Although most commonly performed portal decompressive procedures control bleeding effectively, postoperative morbidity and mortality remains a serious problem in these patients. Both distal splenorenal shunts (DSRS) and small-diameter portacaval H-grafts (PCHG) are reported to produce decreased rates of postoperative encephalopathy. We prospectively evaluated 69 patients in whom 27 PCHG and 45 DSRS were performed over a seven-year interval. There were no significant preoperative differences between these groups. Operative mortality was 12.9% overall. DSRS was associated with decreased intraoperative blood transfusions and operative time. Postoperatively, DSRS was associated with significantly less encephalopathy, other postoperative complications, and ascites. Recurrent variceal bleeding was seen in three patients treated with PCHG and two patients with DSRS. We conclude that both DSRS and PCHG are effective in preventing recurrent variceal bleeding, but DSRS remains our procedure of choice because of its decreased rates of postoperative complications.


The optimal structure for psychoanalytic education today: a feasible proposal?
Our psychoanalytic training system, close to a century old, has been subjected to increasing criticism, starting shortly after its creation, for failing to properly fulfill its avowed purposes. The most intense critiques have centered around the authoritarian power lodged in a self-selected training analyst elite, the inadequate development of a psychoanalytic research tradition, and the isolation of our educational structure from cognate disciplines concerned with human mental life, owing to its private and part-time nature, apart from the university with its spectrum of biological and human sciences. Efforts to reform this system, including the establishment of psychoanalytic institutes within medical school departments of psychiatry, and the further call for their autonomous placement within the university at large, with full-time students and faculty, have been only partially successful and have not become widespread. The values of the newly emerging multifaceted psychoanalytic center as the best currently achievable fundamental reform are presented.


Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain.
There is no effective therapy for ischemic stroke following the acute stage. Neural transplantation offers a potential option for repairing the ischemic lesion. However, this strategy is hindered by the poor survival of the neural precursor cells (NPCs) that are transplanted into the inflammatory ischemic core. Here, a chemical cocktail consisting of fibrinogen and maraviroc is developed to promote the survival of the transplanted NPCs in the ischemic core of the mouse cerebral cortex. The grafted NPCs survive in the presence of the cocktail but not fibrinogen or maraviroc alone at day 7. The surviving NPCs divide and differentiate to mature neurons by day 30, reconstituting the infarct cortex with vascularization. Molecular analysis in vivo and in vitro shows that blocking the activation of CCR5 on the NPCs protects the NPCs from apoptosis induced by pro-inflammatory factors, revealing the underlying protective effect of the cocktail for NPCs. The findings open an avenue to enable survival of the transplanted NPCs under the inflammatory neurological conditions like stroke.


B cell-helping functions of gut microbial metabolites.
Commensal microflora profoundly affects the host immune system. It has long been observed that commensal bacteria enhance antibody production in the host by producing antigens for B cell receptors (BCR) and ligands for Toll-like receptors (TLR). We recently reported that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production (Kim et al. Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host & Microbe. 2016; 20(2):202-14). The B-cell helping function of SCFAs and its implication in the host immune system are discussed in this article.


Ocular implications of long-term prednisone therapy in children.
We compared 23 patients (ages 4 to 18 years) who were receiving long-term oral prednisone therapy with 31 normal controls (ages 7 to 16 years). Indications for corticosteroid treatment included renal transplant in 11 patients, nephrotic syndrome in 7, glomerulonephritis in 4, and vasculitis without renal disease in 1. The mean duration of prednisone therapy was 5.0 +/- 3.5 years, and the mean dose at the time of examination was 0.29 +/- 0.18 mg/kg/day. Mean intraocular pressure was 16.0 +/- 3.0 mm Hg (range, 12 to 25 mm Hg) in the prednisone group and 15.4 +/- 2.1 mm Hg (range, 12 to 20 mm Hg) in the control group. The difference between the means was 0.6 mm Hg (P = 0.35). Posterior subcapsular cataracts were present in seven (30%) of the prednisone patients, but in none of the controls (P = .001). None of the cataracts were visually significant. We found no evidence that pediatric patients on long-term, low-dose prednisone have higher intraocular pressures (IOPs) than normal children, although they are more likely to develop posterior subcapsular cataracts.


Effects of the amino-terminal portion of human growth hormone on glucose clearance and metabolism in normal, diabetic, hypophysectomized, and diabetic-hypophysectomized rats.
A naturally occurring pituitary peptide, human (h) GH-(1-43) potentiates insulin action. The present study has compared the effects of acute (30-60 min) and chronic (3-6 days) injections of synthetic hGH-(1-43), hGH, and insulin in normal, diabetic, hypophysectomized, and diabetic-hypophysectomized rats. Male rats (150-250 g) received injections of saline, insulin (50-200 mU), hGH (200 micrograms), or hGH-(1-43) (200-400 micrograms) with or without insulin. Hormone and glucose were injected simultaneously for glucose tolerance tests. Basal and insulin-stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue were measured in vitro after in vivo treatments; insulin release by isolated pancreatic islets was determined in vitro. Acute injections of hGH-(1-43) with insulin dramatically increased glucose clearance in diabetic (P less than 0.05) and hypophysectomized (P less than 0.01) rats. In diabetic-hypophysectomized rats acute injections of hGH-(1-43) significantly lowered the elevated basal blood glucose level (P less than 0.025) and stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue (P less than 0.05); it did not increase the glucose clearance rate during glucose administration. Chronic treatment of diabetic rats with hGH-(1-43) did not lower the elevated blood glucose level significantly, but it stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue; the oxidation was further stimulated by treatment with insulin. Chronic injections of hGH-(1-43) slightly lowered blood glucose levels in hypophysectomized rats (P less than 0.025) despite a diminished release in vitro of insulin from pancreatic islets (P less than 0.05). Therefore, these experiments show hGH-(1-43) to be an insulin potentiator that increases insulin-stimulated glucose clearance and glucose oxidation without an increase in insulin secretion, and they suggest that the peptide may have a physiological role in regulating carbohydrate metabolism.


Haemopoietic microenvironments in vitro: ultrastructural aspects.
Haemopoietically active long-term bone marrow cultures from several species have been investigated ultrastructurally. Human, tree shrew and mouse cultures generally support granulopoiesis, although recently it has been possible to convert a granulopoietic mouse culture to extensive erythropoiesis. The haemopoietic products of the cultures include granulocytes (neutrophil and basophil), mast cells, monocytes, megakaryocytes and all stages of the erythrocytic series. Plasmacytes and occasional lymphocytes have been observed in small numbers in human cultures (possible indicating retention rather than formation). The stromal elements of the adherent layer of these cultures include endothelial cells, reticulum cells, fat cells and fibroblasts. The adherent layers are responsible for the inductive microenvironment within the cultures, and show features specific for the line of differentiation. In the granulocytic cultures there is close association between developing fat cells (reticulum cells) and granulocyte precursors. Endothelial cell monolayers cover large regions of these cultures, and the areas beneath this monolayer are rich in early granulocytes. Mature granulocytes and monocytes migrate through the endothelial layer, demonstrating in vitro "transmural passage". Cultures stimulated for erythropoiesis show a considerable reduction in fat cells, in endothelial cell cover and in the numbers of classical monocytes. Erythropoiesis appears to be promoted by a close association of the entire erythrocytic series with monocytic cells, forming "erythroblastic islets" in vitro. A possible pathway of intracellular communication between differentiating haemopoietic cells and the stromal cells in their microenvironment is suggested.


Ultraviolet A phototest positivity is associated with higher free erythrocyte protoporphyrin IX concentration and lower transferrin saturation values in erythropoietic protoporphyria.
Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis hallmarked by early-onset photosensitivity and mainly due to defective ferrochelatase activity leading to increased erythrocyte protoporphyrin IX (PPIX) levels. Evidence regarding the relationship between erythrocyte PPIX concentration and photosensitivity is limited. To investigate the relationship between free erythrocyte PPIX (FEP) concentration; routine laboratory tests, particularly iron metabolism biomarkers; and ultraviolet (UV) A/visible light phototesting findings, 20 genetically confirmed EPP and one XLPP treatment-naive patients were included in our study. They underwent UVA and visible light phototesting. On the same day, blood samples were collected for measurement of FEP, serum iron, transferrin, transferrin saturation, and ferritin, 25-hydroxyvitamin D, and liver enzyme levels. Median FEP concentration at the time of phototesting was 57.50 (IQR: 34.58-102.70) μg/g of Hb. UVA and visible light phototesting were positive in 9 (42.9%) and 8 (38.1%) patients, respectively. Median FEP concentration was significantly higher in UVA phototest-positive patients than in those negative (64.37 [IQR: 57.45-121.82] vs 45.35 [IQR: 24.53-74.61] μg/g of Hb, respectively; P = .04486). Similarly, UVA photosensitive individuals had significantly lower median serum iron levels (61.5 [IQR: 33.5-84] μg/dL vs 109 [IQR: 63.25-154] μg/dL, respectively; P = .01862) and transferrin saturation values (15.005 [IQR: 7.0775-18.41] % vs 29.645 [IQR: 17.8225-34.3575] %; P = .0109) than those negative. Our study demonstrates that UVA phototest positivity is associated with higher FEP concentration and lower transferrin saturation and serum iron concentration in EPP.


Central V1b receptor antagonism in lactating rats: impairment of maternal care but not of maternal aggression.
Maternal behaviour in rodents is mediated by the central oxytocin and vasopressin systems, amongst others. The role of vasopressin, acting via the V1a receptor (V1aR), on maternal care and maternal aggression has recently been described. However, a potential involvement of the V1b receptor (V1bR) in maternal behaviour has only been demonstrated in knockout mice. The present study aimed to examine the effects of central pharmacological manipulation of the V1bR on maternal behaviour in lactating Wistar rats. On pregnancy day 18, female rats were implanted with a guide cannula targeting the lateral ventricle. After parturition, dams received an acute central infusion of a specific V1bR agonist (d[Leu4,Lys8]VP) or V1bR antagonist (SSR149415) once daily, followed by observations of maternal care [lactation day (LD) 1], maternal motivation in the pup retrieval test (LD 2), anxiety-related behaviour on the elevated plus-maze (LD 3) and maternal aggression in the maternal defence test followed by maternal care monitoring (LD 4). Our data demonstrate that, under nonstress conditions, the V1bR antagonist decreased the occurrence of both nursing and mother-pup interaction, whereas the V1bR agonist did not affect either parameter. Under stress conditions (i.e. after the maternal defence test), mother-pup interaction was decreased by infusion of the V1bR antagonist. During the maternal defence test, neither treatment affected aggressive or non-aggressive behaviour. Finally, neither treatment altered maternal motivation or anxiety. In conclusion, central V1bR antagonism modulates aspects of maternal care but not of maternal aggression or maternal motivation in lactating rats. These findings further extend our knowledge on the vasopressin system as a vital mediator of maternal behaviour.


Granulocytic sarcoma presenting as bleeding gastric polyp.
Granulocytic sarcoma may develop before, after or at the time of presentation of acute myeloid leukemia. We report an unusual case in which the first manifestation of leukemic conversion of myelodysplastic syndrome was bleeding from a polypoid gastric granulocytic sarcoma.


Catecholamines modulate protein turnover in cultured, quiescent rabbit cardiac myocytes.
When rabbit ventricular myocytes were cultured for 1 wk and then exposed to alpha- and/or beta-adrenergic agonists, such nonbeating heart cell preparations disclosed increased protein-to-DNA ratios and elevated RNA content, indicative of cellular hypertrophy. Norepinephrine, isoproterenol, and phenylephrine provoked hypertrophy with norepinephrine eliciting a greater response than isoproterenol or phenylephrine. Specific alpha- and beta-antagonists blocked growth by inhibiting catecholamine-induced changes in protein turnover. Each catecholamine enhanced the fractional rate of protein synthesis within 48 h; however, changes in growth rates appeared to be modulated, in part, by alterations in protein degradation. Even though rates of total protein and actin synthesis resembled values measured in vivo, myosin heavy chain fractional rate of synthesis was only 22% of in vivo levels. Double label immunofluorescence microscopy further illustrated that catecholamine treatment accelerated myofibrillar disruption in these quiescent heart cells. These observations suggested that in the absence of beating, neurohumoral modulation of contractile protein turnover was not associated with the maintenance of myofibrillar integrity even though catecholamines induced cellular hypertrophy.


Infrared frequency combs and supercontinua for multiplex high sensitivity spectroscopy.
An infrared high-brightness light source based on supercontinuum generation through a SF6 photonic crystal fiber seeded by a Cr(4+):YAG femtosecond oscillator is developed for high resolution multiplex spectroscopy in the 1.5 μm region. Moreover, a multiplex high resolution approach based on a Cr(4+):YAG frequency comb enables to probe large spectral domains, with simultaneous sensitive measurement of the absorption and the dispersion associated with all individual spectral features.


Altered growth and phenotype in clonal mycN transfectants of the SK-N-SH neuroblastoma cell line.
We have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed out-growth of autocrine cells with evidence of an advanced malignant phenotype in a mycN-transfected clonal cell line derived from the single-copy mycN neuroblastoma, SK-N-SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class-I molecules. Clones with high levels of mycN expression had a Schwann/glial-like phenotype with higher surface HLA class-I display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage-independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.


Self-Organized Velocity Pulses of Dense Colloidal Suspensions in Microchannel Flow.
We present a numerical study of dense colloidal suspensions in a pressure-driven microchannel flow in two dimensions. The colloids are modeled as elastic and frictional spheres suspended in a Newtonian fluid, which we simulate using the method of multiparticle collision dynamics. The model reproduces periodic velocity and density pulse trains, traveling upstream in the microchannel, which are found in experiments conducted by Isa et al. [Phys. Rev. Lett. 102, 058302 (2009)PRLTAO0031-900710.1103/PhysRevLett.102.058302]. We show that colloid-wall friction and the resultant force chains are crucial for the formation of these pulses. With an increasing colloid density, first solitary jams occur, which become periodic pulse trains at intermediate densities and unstable solitary pulses at high densities. We formulate a phenomenological continuum model and show how these spatiotemporal flow and density profiles can be understood as homoclinic and periodic orbits in traveling-wave equations.


SARS-CoV-2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids.
The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates.


[Amoxicillin in tonsillectomy: preliminary data on the evaluation of serum and tissue concentrations].
Amoxicillin was administered to 50 patients with chronic recurrent tonsillitis waiting for tonsillectomy. Group A (N=16) received 2.2 g of amoxicillin plus clavulanic acid with intravenous injection 10 minutes before tonsillectomy Group B (N=34) was treated with 3 doses of amoxicillin-clavulanic acid administered orally the day before surgery, plus one oral administration 2 hours before tonsillectomy. Antibiotic doses were established on patient's weight using maximum suggested. The measures were, estimated in serum and in tonsils using High Performance Liquid Chromatography, (HPLC). The data show better efficacy of intravenous administration than oral administration.


Ultrastructure of the human intra-articular disc of the temporomandibular joint.
The ultrastructural appearance of the human intra-articular disc (IAD) was investigated in three discs that had been surgically removed due to disease from three female patients aged 47, 50, and 54 years of age. Regions of the IAD were selected from central areas that appeared to be least affected by disease. Sections were fixed in 2.5 per cent glutaraldehyde in 0.1 M phosphate buffer, pH 7.3 immediately after surgery. The regions examined showed no obvious signs of inflammation. The cells showed moderate amounts of the intracellular organelles associated with protein synthesis and secretion, and possessed considerable amounts of microfilamentous material, thus resembling those described in other mammals. Despite the large number of cells examined, only one cell showed evidence of a chondrocyte-like morphology in that it possessed an incomplete pericellular zone of microfilamentous material separating the cell membrane from the adjacent collagen bundles of the extracellular matrix (ECM). Thus, on morphological grounds, fibrocartilage was virtually non-existent in the specimens examined. The mean collagen fibril diameter was 43.9 nm and the fibril diameter distribution was not unimodal. Although the majority of fibrils had a relatively small diameter, two of the three specimens possessed many fibrils with diameters of over 100 nm, this being consistent with tissue subjected to tension. The mean area of a fibre bundle occupied by collagen (as opposed to the ground substance) was approximately 56 per cent.


Leopard and spotted hyena densities in the Lake Mburo National Park, southwestern Uganda.
Robust measures of animal densities are necessary for effective wildlife management. Leopards (Panthera pardus) and spotted hyenas (Crocuta Crocuta) are higher order predators that are data deficient across much of their East African range and in Uganda, excepting for one peer-reviewed study on hyenas, there are presently no credible population estimates for these species. A lack of information on the population status and even baseline densities of these species has ramifications as leopards are drawcards for the photo-tourism industry, and along with hyenas are often responsible for livestock depredations from pastoralist communities. Leopards are also sometimes hunted for sport. Establishing baseline density estimates for these species is urgently needed not only for population monitoring purposes, but in the design of sustainable management offtakes, and in assessing certain conservation interventions like financial compensation for livestock depredation. Accordingly, we ran a single-season survey of these carnivores in the Lake Mburo National Park of south-western Uganda using 60 remote camera traps distributed in a paired format at 30 locations. We analysed hyena and leopard detections under a Bayesian spatially explicit capture-recapture (SECR) modelling framework to estimate their densities. This small national park (370 km2) is surrounded by Bahima pastoralist communities with high densities of cattle on the park edge (with regular park incursions). Leopard densities were estimated at 6.31 individuals/100 km2 (posterior SD = 1.47, 95% CI [3.75-9.20]), and spotted hyena densities were 10.99 individuals/100 km2, but with wide confidence intervals (posterior SD = 3.35, 95% CI [5.63-17.37]). Leopard and spotted hyena abundance within the boundaries of the national park were 24.87 (posterior SD 7.78) and 39.07 individuals (posterior = SD 13.51) respectively. Leopard densities were on the middle end of SECR studies published in the peer-reviewed literature over the last 5 years while spotted hyena densities were some of the first reported in the literature using SECR, and similar to a study in Botswana which reported 11.80 spotted hyenas/100 km2. Densities were not noticeably lower at the park edge, and in the southwest of our study site, despite repeated cattle incursions into these areas. We postulate that the relatively high densities of both species in the region could be owed to impala Aepyceros melampus densities ranging from 16.6-25.6 impala/km2. Another, potential explanatory variable (albeit a speculative one) is the absence of interspecific competition from African lions (Panthera leo), which became functionally extinct (there is only one male lion present) in the park nearly two decades ago. This study provides the first robust population estimate of these species anywhere in Uganda and suggests leopards and spotted hyenas continue to persist in the highly modified landscape of Lake Mburo National Park.


The National Sleep Foundation's Sleep Health Index.
A validated survey instrument to assess general sleep health would be a useful research tool, particularly when objective measures of sleep are not feasible. Thus, the National Sleep Foundation spearheaded the development of the Sleep Health Index (SHI). The development of the SHI began with a task force of experts who identified key sleep domains and questions. An initial draft of the survey was created and questions were refined using cognitive testing and pretesting. The resulting 28-question survey was administered via random-sample telephone interviews to nationally representative samples of adults in 2014 (n=1253) and 2015 (n=1250). These data were combined to create the index. A factor analysis linked 14 questions to 3 discrete domains: sleep quality, sleep duration, and disordered sleep. These were assembled as sub-indices, then combined to form the overall SHI, with scores ranging from 0 to 100 (higher score reflects better sleep health). Americans earned an overall SHI score of 76/100, with sub-index scores of 81/100 in disordered sleep, 79/100 in sleep duration, and 68/100 in sleep quality. In regression analyses, the strongest independent predictors of sleep health were self-reported stress (β=-0.26) and overall health (β=0.26), which were also the strongest predictors of sleep quality (β=-0.32 and β=0.27 respectively). The current 12-item SHI is a valid, reliable research tool that robustly measures 3 separate but related elements of sleep health-duration, quality, and disorders-and assesses the sleep health status of adults in the United States.


Changes in the athletic profile of elite college American football players.
The purpose of this study was to compare positional anthropometric and National Football League (NFL) Combine performance levels in elite college American football players over the 3-year period from 1999 to 2001 to the 3-year period from 2008 to 2010. The sample included 15 offensive and defensive positions, and only those players invited to the combine and subsequently drafted in the same year (n = 1,712) were included in the study. Data from 10 combine physical tests were examined, including weight; height; the 9.1-, 18.3-, and 36.6-m sprints; the vertical and horizontal jumps; the 18.3-m shuttle run; the 3-cone drill; and the 102.1-kg bench press for maximum repetitions. Independent samples t-tests detected differences for each of the 15 positions (p < 0.05). There were no discernible trends in height and weight over the period in question, whereas players in the more recent group significantly improved performance in straight sprinting, the 3-cone drill, and the horizontal jump. Findings suggest that these tests better reflect characteristics such as explosiveness and first-step quickness as compared with the 18.3-m shuttle and the vertical jump, and that such characteristics have become more highly sought after by NFL coaches and scouts. The results of the present research suggest that the position-specific profiles changed over a relatively short period of time. Coaches and practitioners will be able to use the findings of this research to better prepare athletes for entry into the NFL.


Regulation of allergic reaction by aerobic Corynebacterium equi extract, CEF. I. Antigen-nonspecific suppression of reaginic antibody response in mice.
The effect of a water-soluble fraction (CEF) that was prepared from an extract of Corynebacterium equi on primary reaginic antibody formation was studied in Balb/c mice. Mice were immunized with a hapten carrier (DNP-OVA) and received intraperitoneal injections of CEF 7 and 2 days prior to, or 2 and 7 days after the immunization. PCA titers of both antihapten (DNP) and anticarrier (OVA) antibodies of IgE class were reduced significantly by the CEF treatment. Evidence was presented in adoptive transfer experiments that the number of IgE-producing cells in the CEF-treated mice was lower than that of controls. Suppression of IgG1 anti-DNP antibody formation was also achieved by the CEF treatment. Formation of IgG1 anti-OVA antibodies, however, was not suppressed significantly by the treatment. The suppressive activities of CEF were shown to be dose-dependent, but timing of CEF administration did not appear critical.


First-principles study of ferromagnetism in epitaxial Si-Mn thin films on Si(001).
Density-functional theory calculations are employed to investigate both the epitaxial growth and the magnetic properties of thin Mn and MnSi films on Si(001). For single Mn adatoms, we find a preference for the second-layer interstitial site. While a monolayer Mn film is energetically unfavorable, a capping-Si layer significantly enhances the thermodynamic stability and induces a change from antiferromagnetic to ferromagnetic order. For higher Mn coverage, a sandwiched Si-Mn thin film (with CsCl-like crystal structure) is found to be the most stable epitaxial structure. We attribute the strong ferromagnetic intralayer coupling in these films to Mn 3d-Si 3s3p exchange.


Orthodontic implications of protein undernutrition in mandibular growth. A cephalometric study in growing rats.
The present experimental work analyzes the development of different mandibular units and its likely impact on the direction of mandibular displacement during facial development, and the relation between the mesiodistal dimension of the first, second, and third molars and the length of the mandibular corpus in a model of protein undernutrition with muscular atrophy in growing rats. Sixteen Wistar rats weaned at the age of 21 days were assigned to one of the following groups: control (fed a regular hard diet ad libitum) and experimental (fed a diet lacking in protein, corn flour, ad libitum). All the animals were euthanized five weeks after the onset of the experiment. Following resection of the mandibles, the mandibles were hemisected at the symphysis and fixed in 10% formalin. Remaining soft tissue was removed. Metallic landmarks were placed in the mental and mandibular foramens of one hemimandible of each rat. The hemimandibles were radiographed. The cephalometric study was performed on paper tracings of the projected image of the radiographs. Both groups exhibited a slight increase in body weight (b.w) throughout the first ten days of the experiment. After this point, the undernourished group showed no further increase in b.w., and exhibited significantly lower b.w. than controls at the end of the experiment. The cephalometric study showed that the length of the mandible as a whole, and of the condylar and angular processes was significantly lower in the undernourished group. In addition, significant differences in the vertical relation between the angular process to the mandibular corpus, the convexity of the angular process, and the ratio between total molar width (from the first to the third molar) and the length of the mandibular corpus were observed.


Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan: a randomized phase 2 trial by the Cancer and Leukemia Group B (CALGB 19803).
The Cancer and Leukemia Group B evaluated oral topotecan administered at 2 schedules and doses for myelodysplastic syndrome (MDS). Patients with previously untreated primary or therapy-related MDS were eligible. Patients with refractory anemia (RA), RA with ringed sideroblasts, or refractory cytopenia with multilineage dysplasia (RCMD) were eligible only if they were dependent on erythrocyte transfusion, had a platelet count<50,000/microL, or had an absolute neutrophil count<1000/microL with a recent infection that required antibiotics. Patients were randomized to receive oral topotecan either at a dose of 1.2 mg/m2 twice daily for 5 days (Arm A) or once daily for 10 days (Arm B) repeated every 21 days for at least 2 cycles. Responding patients continued until they developed disease progression or unacceptable toxicity or until they had received 2 cycles beyond a complete response. Ninety patients received treatment, including 46 patients on Arm A and 44 patients on Arm B. Partial responses with improvement in all 3 cell lines occurred in 6 patients (7%), and hematologic improvement (in 1 or 2 cell lines) was observed in 21 patients (23%), for an overall response rate of 30%. Response duration was longer on Arm A (23 months vs 14 months; P=.02). Seven of 14 patients with chronic myelomonocytic leukemia responded. There were 8 treatment-related deaths from infection (6 deaths) and bleeding (2 deaths). Diarrhea was the most frequent nonhematologic toxicity (grade 3, 11%; grade 4, 2%; grading determined according to the National Cancer Institute Comman Toxicity Criteria v.2.0). Oral topotecan in the dose and schedules evaluated in this trial demonstrated only a modest response rate with a troublesome toxicity profile in the treatment of MDS.


Development of biomedical 5-fluorouracil nanoplatforms for colon cancer chemotherapy: Influence of process and formulation parameters.
In the present investigation solvent displacement or nanoprecipitation, and emulsion/solvent evaporation methods were utilized to optimize poly(D,L-lactide-co-glycolide) nanoparticles for the vehiculization of the 5-fluorouracil. Formulation components from both the aqueous and organic phases, as well as, operating conditions were varied. Particles were characterized in terms of particle size and morphology, electrical properties, rheology, drug loading, stability, and drug release. Furthermore, in vitro cytotoxicity on human colon cells and different colon carcinoma cells was evaluated. Four types of nanoparticles were selected for drug loading, revealing differences between variables. Low viscosity values and their Newtonian behavior could assure the suitability of the nanoformulation for the intravenous route of administration. The greatest drug entrapment efficiency and best stability was achieved when the chemotherapeutic agent was incorporated into the internal aqueous phase of particles prepared by double emulsion/solvent evaporation. However, a more sustained drug release at pH 7.4 was possible when 5-fluorouracil was added to the external aqueous phase. These were the nanoformulations reporting the greatest antiproliferative efficacy compared with the free drug. The nanocarrier can optimize the antitumor activity of 5-fluorouracil, thus being a potential nanotool against colon cancer.


Interferon-gamma, mitomycin C, and cycloheximide as regulatory agents of MHC class II-associated invariant chain expression.
The murine and human major histocompatibility complex class II-associated invariant chain genes are expressed in mature B cells and in antigen-presenting cells. Several pre-B cell lines and fibroblasts do not naturally contain invariant chain mRNA. Expression is inducible, however, by interferons and other agents interfering with proliferation. Mitomycin C induces the transcription of the gene in pre-B cells, but not in fibroblasts. Interferon-gamma acts in both types of cells. Cycloheximide inhibits the induction of the invariant chain mRNA by interferon-gamma, suggesting that protein synthesis is required. In fact, cycloheximide itself increases the transcriptional rate at the invariant chain gene, suggesting the existence of a labile repressor or an indirect action through cycloheximide arrest of the cell cycle. Lipopolysaccharide (LPS) activation of B lymphocytes causes a rapid decrease of the invariant chain mRNA level and of the amount of invariant chain protein due to rapid turnover. Also class II alpha and beta mRNA expression decreases after LPS treatment. The decrease of invariant chain protein is accompanied by increased surface expression of alpha and beta. The murine invariant chain gene transfected into human fibroblasts is regulated by the same agents and the same dose of agents as is the endogenous gene. The differentiation marker invariant chain thus seems to be transcribed from a gene that is accessible to regulation even in nonlymphoid cells and the expression of which is linked to states of nonproliferation. The sequence responsible for these responses is contained within the cloned genomic fragment and is conserved between mouse and man.


Attachment and Depressive Symptoms in Adolescence: The Mediatory Role of Emotion Awareness.
Attachment seems to influence depression through emotion regulation. However, no study has yet examined the mediatory role of emotion awareness, a particular subset of emotion regulation abilities, in the relationship between attachment and depressive problems in early and middle adolescence. The aim of this study is to examine the direct and indirect effects of attachment on depressive symptoms in adolescence, considering the mediatory role of emotion awareness dimensions. A sample of adolescents (n = 223) filled up self-report questionnaires on attachment, emotion awareness and depression. Serial mediation models suggest direct effects on depression: negative for secure attachment and positive for anxious/ambivalent attachment. Anxious/ambivalent attachment has a positive indirect effect through lower differentiation of emotions. Both secure and anxious/ambivalent attachment have indirect positive effects on depression through the sequence of bodily unawareness and differentiation of emotions. Differentiating emotions has a central role in mediating the relationship between attachment and depressive symptoms, and the lack of bodily awareness of emotions contributes to such mediation.


High-resolution spectroscopy of Lambda16N by electroproduction.
An experimental study of the (16)O(e,e'K(+))(Lambda)(16)N reaction has been performed at Jefferson Lab. A thin film of falling water was used as a target. This permitted a simultaneous measurement of the p(e,e'K(+))Lambda, Sigma(0) exclusive reactions and a precise calibration of the energy scale. A ground-state binding energy of 13.76+/-0.16 MeV was obtained for (Lambda)(16)N with better precision than previous measurements on the mirror hypernucleus (Lambda)(16)O. Precise energies have been determined for peaks arising from a Lambda in s and p orbits coupled to the p(1/2) and p(3/2) hole states of the (15)N core nucleus.


Update on the antitumor activity of alpha interferon.
Alpha interferons have shown significant antitumor activity against B-cell malignancies (especially hairy cell leukemia), and chronic myelogenous leukemia. They are also useful against malignant carcinoid tumors, renal cell carcinoma, and Kaposi's sarcoma. Alpha interferons are less effective against lung, liver, ovary, breast, and colon carcinoma. Side effects vary in severity according to type of interferon, route of administration, schedule, and dose. In general, tolerance and compliance are excellent with doses of one to nine million units per day.


Power's Presence in Nurse Education.
The notion of power has long been discussed in literature. There continues to exist a vast number of ideas as to what power really is and means. The author here discusses some early notions of power from the philosophical literature where there is debate as to whether power is innate or earned and bestowed upon persons. The potential for power as well as powers need for support from others is then examined in light of the nursing educational arena. Parse's humanbecoming school of thought also enlightens beliefs on power through the teaching-learning model as well as within the third principle of humanbecoming. These humanbecoming aspects are discussed regarding their presence or role in nursing academia. The column concludes with the notion that possibly the most important power possessed by all is the power to choose.


A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge.
Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 103 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 106 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate.IMPORTANCE A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform.


Endoscopic Submucosal Dissection Using a Novel Versatile Knife: An Animal Feasibility Study (with Video).
In order to reduce the procedure time and the number of accessory changes during endoscopic submucosal dissection (ESD), we developed a novel versatile knife, which has the combined advantages of several conventional knives. The aim of this study was to compare the efficacy, safety, and histological quality of ESD performed using this novel versatile knife and a combination of several conventional knives. This was an in vivo animal study comparing two different modalities of ESD in mini-pigs. Completion time of each resection was documented, and the resected specimens were retrieved and evaluated for completeness. To assess the quality control of the procedures and adverse events, detailed histopathological examinations were performed. A total of 18 specimens were dissected by ESD safely and easily (nine specimens using the new versatile knife; nine specimens by mixing conventional knives). All resections were completed as en bloc resections. There was no significant difference in procedure time between the 2 modalities (456 seconds vs. 355 seconds, p=0.258) and cutting speed (1.983 mm(2)/sec vs. 1.57 mm(2)/sec, p=1.000). The rate of adverse events and histological quality did not statistically differ between the modalities. ESD with a versatile knife appeared to be an easy, safe, and technically efficient method.


Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD.
Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages. Using nuclear magnetic resonance (NMR) serum samples of 210 NAFLD cases and control individuals diagnosed with liver U/S, our untargeted metabolomics enquiry provided a sex distinct metabolic bouquet. Increased levels of alanine, histidine and tyrosine are associated with severity of NAFLD in both men and women. Moreover, higher serum concentrations of valine, aspartic acid and mannose were positively associated with the progression of NAFLD among the male subjects, while a negative association was observed with the levels of creatine, phosphorylcholine and acetic acid. On the other hand, glucose was positively associated with the progression of NAFLD among the female subjects, while levels of threonine were negatively related. Fluctuations in ketone bodies acetoacetate and acetone were also observed among the female subjects probing a significant reduction in the circulatory levels of the former in NAFLD cases. A complex glycine response to hepatic steatosis of the female subjects deserves further investigation. Results of this study aspire to address the paucity of data on sex differences regarding NAFLD pathogenesis. Targeted circulatory metabolome measurements could be used as diagnostic markers for the distinct stages of NAFLD in each sex and eventually aid in the development of novel sex-related therapeutic options.


Paclitaxel as first-line treatment for metastatic breast cancer. The Taxol Investigational Trials Group, Australia and New Zealand.
When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line therapy for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14, intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for six cycles (6 months). Patients whose disease progressed or relapsed were recommended to receive second-line epirubicin. Accrual has been completed with 208 patients randomized, but a preplanned interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by a linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months for paclitaxel-treated patients and 6.4 months for those given CMFP, with median survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4 neutropenia occurred in 64% of patients treated with paclitaxel and in 63% treated with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses. Nine percent of the patients had major infections with CMFP, but none were seen with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel-treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results on paclitaxel treatment as compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides comparable control of metastatic cancer to CMFP combination therapy when used as front-line treatment.


Hybrid optoelectronic system for wideband complex-valued Fourier transform measurements.
A hybrid optoelectronic system for Fourier transform measurements of temporal signals is described. The magnitude and phase of the signal transform are system outputs. High resolution spectral analysis operation is accomplished by proper spatially dependent phase corrections equivalent to aperture synthesis. Configurations for 1-D and 2-D input data formats are discussed. The system can process signals with continuous spectral content as well as narrow spectral lines.


Probe selection and expression index computation of Affymetrix Exon Arrays.
There is great current interest in developing microarray platforms for measuring mRNA abundance at both gene level and exon level. The Affymetrix Exon Array is a new high-density gene expression microarray platform, with over six million probes targeting all annotated and predicted exons in a genome. An important question for the analysis of exon array data is how to compute overall gene expression indexes. Because of the complexity of the design of exon array probes, this problem is different in nature from summarizing gene-level expression from traditional 3' expression arrays. In this manuscript, we use exon array data from 11 human tissues to study methods for computing gene-level expression. We showed that for most genes there is a subset of exon array probes having highly correlated intensities across multiple samples. We suggest that these probes could be used as reliable indicators of overall gene expression levels. We developed a probe selection algorithm to select such a subset of highly correlated probes for each gene, and computed gene expression indexes using the selected probes. Our results demonstrate that probe selection improves gene expression estimates from exon arrays. The selected probes can be used in future analyses of other exon array datasets to compute gene expression indexes.


Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B.
HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNα treatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of in vitro and in vivo experiments. GWAS results indicated a significant association between the rs7519753 C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p = 4.85 × 10-8, odds ratio = 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753 C allele (p = 2.90 × 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p = 0.035). In vitro and in vivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. The rs7519753 C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753 C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.


Novel anastomotic method enables aortofemoral bypass for patients with porcelain aorta.
Porcelain aorta is an indication for axillofemoral bypass. However, the procedure has definitive flaws. We present a new method for achievement of aortofemoral bypass. The portion of the distal aorta for anastomosis is wrapped with a double polytetrafluoroethylene mesh and fixed to the adventitia with continuous sutures. The adventitia of the anastomotic site is cut over the mesh until the calcified surface is disclosed. Margins of the mesh and the peeled adventitia are fixed along the anastomotic margin with continuous sutures. After the aorta and distal arteries are occluded with balloon catheters, an opening on the bared calcification is made with an airdrill and enlarged with a laminectomy rongeur. The anastomosis is performed between a graft and the mesh-reinforced adventitia with continuous sutures. Over 6 years, this method has been applied to nine patients with porcelain aorta who are diabetic or undergoing dialysis. The indications were disabling claudication in three patients and limb salvage in six patients. No anastomotic complications or operative deaths were seen, and satisfactory mid-term results were obtained, with follow-up ranging from 3 to 62 months after surgery. One patient died of coronary heart disease 3 years after surgery, but the grafts retained a good function. This method is safe and effective, and more liberal application of this method may help improve outcome and quality of life.


Acute myocardial injury in patients with COVID-19: Possible mechanisms and clinical implications.
Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs, but also the cardiovascular system, having a major impact on patients' outcomes. Myocardial injury (MI) occurs in the context of coronavirus infectious disease 2019 (COVID-19) and is associated with a higher risk of severe clinical outcome and mortality. COVID-19-related MI can have various clinical manifestations, of which the main ones are myocarditis, stress cardiomyopathy, acute coronary syndrome, and pulmonary embolism. The exact mechanisms of how MI occurs in these patients are not yet fully known. Direct injury, through direct viral myocardial invasion, and indirect injury, through interaction with angiotensin I converting enzyme 2, increased inflammation, and thrombocyte and endothelial dysfunction, could be involved in acute MI in patients with COVID-19. A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies. The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.


Efficacy of β-Lactam-plus-Macrolide Combination Therapy in a Mouse Model of Lethal Pneumococcal Pneumonia.
Community-acquired pneumonia is a common disease with considerable morbidity and mortality, for which Streptococcus pneumoniae is accepted as a leading cause. Although β-lactam-plus-macrolide combination therapy for this disease is recommended in several guidelines, the clinical efficacy of this strategy against pneumococcal pneumonia remains controversial. In this study, we examined the effects of β-lactam-plus-macrolide combination therapy on lethal mouse pneumococcal pneumonia and explored the mechanisms of action in vitro and in vivo We investigated survival, lung bacterial burden, and cellular host responses in bronchoalveolar lavage fluids obtained from mice infected with pneumonia and treated with ceftriaxone, azithromycin, or both in combination. Although in vitro synergy was not observed, significant survival benefits were demonstrated with combination treatment. Lung neutrophil influx was significantly lower in the ceftriaxone-plus-azithromycin-treated group than in the ceftriaxone-treated group, whereas no differences in the lung bacterial burden were observed on day 3 between the ceftriaxone-plus-azithromycin-treated group and the ceftriaxone-treated group. Notably, the analysis of cell surface markers in the ceftriaxone-plus-azithromycin combination group exhibited upregulation of presumed immune checkpoint ligand CD86 and major histocompatibility complex class II in neutrophils and CD11b-positive CD11c-positive (CD11b(+) CD11c(+)) macrophages and dendritic cells, as well as downregulation of immune checkpoint receptors cytotoxic-T lymphocyte-associated antigen 4 and programmed death 1 in T helper and T regulatory cells. Our data demonstrate that the survival benefits of ceftriaxone-plus-azithromycin therapy occur through modulation of immune checkpoints in mouse pneumococcal pneumonia. In addition, immune checkpoint molecules may be a novel target class for future macrolide research.


Bipolar Coping Strategies of Nurses in Facing the COVID-19 Pandemic: A Meta-synthesis Review.
Nurses on the front line of facing the COVID-19 pandemic have applied many coping strategies to adapt to their experienced physical and psychosocial challenges. This review aimed to identify coping strategies of nurses in the face of Covid-19. In this meta-synthesis review, qualitative articles related to the coping strategies published in English in the Google Scholar, PubMed, Web of Science, ScienceDirect, and CINAHL databases were selected and analyzed. The review of selected articles showed nurses have used various coping strategies that can be categorized into one main theme, two themes, and ten sub-themes. The theme of efficient coping strategies includes the sub-themes of spiritual-religious coping, protective coping (protection of family members and colleagues), supportive coping by obtaining support from family, friends, colleagues, society, and government organizations, committed coping, positive mind coping, emotional coping, operational coping, and fun coping. The theme of inefficient coping strategies includes the sub-themes of avoidance and risky behaviors. The strategies lead to the synthesis of bipolar coping strategies of nurses during the COVID-19 pandemic. Therefore, healthcare policymakers should emphasize using efficient strategies and avoiding inefficient ones.


Hippocampal CA1 circuitry dynamically gates direct cortical inputs preferentially at theta frequencies.
Hippocampal CA1 pyramidal neurons receive intrahippocampal and extrahipppocampal inputs during theta cycle, whose relative timing and magnitude regulate the probability of CA1 pyramidal cell spiking. Extrahippocampal inputs, giving rise to the primary theta dipole in CA1 stratum lacunosum moleculare, are conveyed by the temporoammonic pathway. The temporoammonic pathway impinging onto the CA1 distal apical dendritic tuft is the most electrotonically distant from the perisomatic region yet is critical in regulating CA1 place cell activity during theta cycles. How does local hippocampal circuitry regulate the integration of this essential, but electrotonically distant, input within the theta period? Using whole-cell somatic recording and voltage-sensitive dye imaging with simultaneous dendritic recording of CA1 pyramidal cell responses, we demonstrate that temporoammonic EPSPs are normally compartmentalized to the apical dendritic tuft by feedforward inhibition. However, when this input is preceded at a one-half theta cycle interval by proximally targeted Schaffer collateral activity, temporoammonic EPSPs propagate to the soma through a joint, codependent mechanism involving activation of Schaffer-specific NMDA receptors and presynaptic inhibition of GABAergic terminals. These afferent interactions, tuned for synaptic inputs arriving one-half theta interval apart, are in turn modulated by feedback inhibition initiated via axon collaterals of pyramidal cells. Therefore, CA1 circuit integration of excitatory inputs endows the CA1 principal cell with a novel property: the ability to function as a temporally specific "AND" gate that provides for sequence-dependent readout of distal inputs.


Droplet and Particle Generation on Centrifugal Microfluidic Platforms: A Review.
The use of multiphase flows in microfluidics to carry dispersed phase material (droplets, particles, bubbles, or fibers) has many applications. In this review paper, we focus on such flows on centrifugal microfluidic platforms and present different methods of dispersed phase material generation. These methods are classified into three specific categories, i.e., step emulsification, crossflow, and dispenser nozzle. Previous works on these topics are discussed and related parameters and specifications, including the size, material, production rate, and rotational speed are explicitly mentioned. In addition, the associated theories and important dimensionless numbers are presented. Finally, we discuss the commercialization of these devices and show a comparison to unveil the pros and cons of the different methods so that researchers can select the centrifugal droplet/particle generation method which better suits their needs.


Feedback and training tool to improve provision of preventive care by physicians using EMRs: a randomised control trial.
Electronic medical records (EMRs) have the potential to improve the provision of preventive care by allowing general practitioners (GPs) to track and recall eligible patients and record testing for feedback on their service provision. This study evaluates the effect of an educational intervention and feedback tool designed to teach GPs how to use their EMRs to improve their provision of preventive care. A randomised controlled trial comparing rates of mammography, Papanicolaou tests, faecal occult blood tests and albumin creatinine ratios one-year pre- and post-intervention was conducted. Nine primary care practices (PCPs) representing over 30 000 patients were paired by practice size and experience of GPs, and randomly allocated to intervention or control groups. Physicians at the four intervention practices received a two-hour feedback session on their current level of preventive care and training to generate eligible patient lists for preventive services from their EMR database. One-year post-intervention results provided no evidence of a difference. The intervention was not a significant predictor of the one-year postintervention test rates for any of the four tests. On average, the intervention practices increased postintervention test rates on all tests by 16.8%, and control practices increased by 22.3%. The non-significant results may be due to a variety of reasons, including the level of intensity of the educational intervention, the cointervention of a government programme which provided incentives to GPs meeting specific targets for preventive care testing or the level of recording of tests performed in the EMR.


Comparison of sexual and drug use behaviors between female sex workers in Tijuana and Ciudad Juarez, Mexico.
Female sex workers (FSWs) have been documented to have high rates of sexually transmitted diseases and HIV in many parts of the world. However, little work has been done to characterize the prevalence of these infections along the U.S.-Mexican border, where sexual tourism and culturally sanctioned sex work among nationals is widespread. The objective of this study was to compare differences in background characteristics, HIV risk behaviors, drug use, and sexually transmitted infection/HIV prevalence between FSWs who participated in a behavioral risk intervention in two U.S.-Mexican border cities. Baseline data were collected from March 2004 through September 2005. Data from 295 FSWs were compared between Tijuana and Ciudad (Cd.) Juarez. Among 155 FSWs in Tijuana and 140 in Cd. Juarez, HIV seroprevalence was 4.8% and 4.9%, respectively. FSWs in Cd. Juarez were more likely to test positive for active syphilis (31.3%) compared with Tijuana (11.8%) but did not differ in terms of the prevalence of gonorrhea and chlamydia. FSWs in both sites reported high levels of unprotected sex and use of drugs; however, FSWs in Cd. Juarez were more likely than those in Tijuana to ever have injected drugs (75% vs. 25%, p <.001). Heroin and cocaine use and injection drug use were significantly more common in Cd. Juarez, whereas methamphetamine use was more common in Tijuana. Injection of vitamins was common in both cities. Logistic regression analyses suggested that being younger, working in Cd. Juarez, and using heroin or cocaine were independently associated with active syphilis infection. In Tijuana, methamphetamine use was strongly associated with active syphilis infection. These preliminary results suggest that risk profiles for HIV/sexually transmitted infection among FSWs in these two Mexico-U.S. border cities differ, suggesting a need to tailor interventions to the specific needs in each city.


[Rifampicin diffusion in non-infected human bone (author's transl)].
Rifampicin levels in serum, cortical bone and spongious bone were measured by a biological assay in 13 non-infected patients undergoing total replacement of the hip. Samples were collected after 24-72 hours rifampicin administration (daily oral dose: 600 mg). The mean level was 0.67 +/- 0.48 microgram/g in cortical bone and 3.35 +/- 0.72 microgram/g in spongious bone. Rifampicin diffusion was also assessed in normal bone from crista iliaca needle biopsy specimens in 7 patients treated for osteitis or septic arthritis. Bone and serum levels did not appear linearly correlated but, in any case, bone levels were much higher than MIC for Staphylococcus aureus which is usually involved in bone and joint infections.


Comparative bioavailability study with two sodium valproate tablet formulations administered under fasting conditions in healthy subjects.
To assess the bioequivalence of two sodium valproate formulations in healthy subjects of both sexes. The study was conducted using an open, randomized, two-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 96-hour period. Plasma concentrations of valproate were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC/MS) with negative ion electrospray ionization. From the sodium valproate plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained Cmax, AUC, tmax, Ke, and T1/2. The geometric mean with corresponding 90% confidence interval for test/reference percent ratios were 104.43% (90% CI 100.42 - 108.61%) for Cmax, 98.11% (90% CI = 94.66 - 101.70%) for AUClast, and 96.71% (90% CI = 92.97 - 100.60%) for AUC0-inf. Since the 90% CI for Cmax and AUClast ratios were all inside the 80 - 125% interval proposed by the US Food and Drug Administration Agency (FDA), it was concluded that the new sodium valproate formulation (epilenil 500-mg coated tablet) without food elaborated by Biolab Sanus Farmaceutica Ltda is bioequivalent to depakene formulation for both the rate and the extent of absorption.


FDM 3D Printing of Polymers Containing Natural Fillers: A Review of their Mechanical Properties.
As biodegradable thermoplastics are more and more penetrating the market of filaments for fused deposition modeling (FDM) 3D printing, fillers in the form of natural fibers are convenient: They have the clear advantage of reducing cost, yet retaining the filament biodegradability characteristics. In plastics that are processed through standard techniques (e.g., extrusion or injection molding), natural fibers have a mild reinforcing function, improving stiffness and strength, it is thus interesting to evaluate whether the same holds true also in the case of FDM produced components. The results analyzed in this review show that the mechanical properties of the most common materials, i.e., acrylonitrile-butadiene-styrene (ABS) and PLA, do not benefit from biofillers, while other less widely used polymers, such as the polyolefins, are found to become more performant. Much research has been devoted to studying the effect of additive formulation and processing parameters on the mechanical properties of biofilled 3D printed specimens. The results look promising due to the relevant number of articles published in this field in the last few years. This notwithstanding, not all aspects have been explored and more could potentially be obtained through modifications of the usual FDM techniques and the devices that have been used so far.


The role of self-control in early escalation of substance use: a time-varying analysis.
This research tested predictions about the role of temperament and self-control in early substance use (tobacco, alcohol, and marijuana). A sample of 1,526 participants was assessed in 6th grade (mean age = 11.5 years) and followed with yearly assessments through 9th grade. Latent growth models showed temperament dimensions were related to early substance use, and their effects were mediated through generalized self-control ability. Time-varying effects indicated rate of growth in substance use was higher among participants who showed increases in poor self-control and lower among participants who showed increases in good self-control. Results in self-report data were corroborated by independent teacher ratings. Findings are discussed with reference to epigenetic models of protection and vulnerability.


Haematological indices are modulated in juvenile carp, Cyprinus carpio L., exposed to microcystins produced by cyanobacterial water bloom.
This study evaluated the influence of toxic cyanobacterial water blooms on the blood indices of the common carp, Cyprinus carpio L. Experimental fish were exposed to a natural population of cyanobacterial water blooms (mainly Microcystis aeruginosa and M. ichthyoblabe), which contained microcystins [total concentration 133-284 μg g⁻¹ (DW), concentration in water 2.8-7.4 μg L⁻¹]. Haematological indices showed marked changes in fish exposed to the cyanobacterial population in comparison with the control group. Statistical evaluation of the influence of cyanobacterial water blooms on biochemical indices of the juvenile carp showed a distinct decrease in albumin, alanine aminotransferase, total bilirubin, calcium, cholesterol, glucose, phosphorus and iron when compared to controls. Values of red blood counts [haemoglobin, haematocrit (PCV), mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration] and lactate were significantly increased compared to controls. After exposure to cyanobacterial water bloom, the carp were kept in clean water to monitor the persistence of biochemical indices. The influence of cyanobacterial populations on calcium, cholesterol, glucose, lactate, phosphorus and PCV persisted up to 28 days after conclusion of the experiment. Duration of exposure, toxicity and density of cyanobacterial water blooms had an important impact on individual haematological indices.


Detection of a Mammographically Occult Breast Cancer with a Challenging Clinical History.
Screening mammography has helped to identify countless incidences of breast cancer since its adoption in the 1960s. Over time, the screening guidelines and techniques have been refined to better detect malignancies and to avoid false positive results. However, weaknesses remain in mammography and represent an opportunity for improvement. The interference of natural breast tissue and glands can obscure the presence of occult breast malignancies. Additionally, the inability to differentiate breast tissue on the basis of depth, and the compounding of breast densities that occurs as a consequence of two-dimensional imaging, are setbacks when it comes to relying on mammography. User error and bias can also misguide the proper detection of underlying cancers during the radiological interpretation process. The following case represents a combination of these factors and others that culminated in a missed diagnosis of invasive ductal carcinoma in a young woman suffering from mastitis of the contralateral breast.


Effects of Site Preparation for Pine Forest/Switchgrass Intercropping on Water Quality.
A study was initiated to investigate the sustainability effects of intercropping switchgrass ( L.) in a loblolly pine ( L.) plantation. This forest-based biofuel system could possibly provide biomass from the perennial energy grass while maintaining the economics and environmental benefits of a forest managed for sawtimber. Operations necessary for successful switchgrass establishment and growth, such as site preparation, planting, fertilizing, mowing and baling, may affect hydrology and nutrient runoff. The objectives of this study were (i) to characterize the temporal effects of management on nutrient concentrations and loadings and (ii) to use pretreatment data to predict those treatment effects. The study watersheds (∼25 ha each) in the North Carolina Atlantic Coastal Plain were a pine/switchgrass intercropped site (D1), a midrotation thinned pine site with natural understory (D2), and a switchgrass-only site (D3). Rainfall, drainage, water table elevation, nitrogen (total Kjedahl N, NH-N, and NO-N), and phosphate were monitored for the 2007-2008 pretreatment and the 2009-2012 treatment periods. From 2010 to 2011 in site D1, the average NO-N concentration effects decreased from 0.18 to -0.09 mg L, and loads effects decreased from 0.86 to 0.49 kg ha. During the same period in site D3, the average NO-N concentration effects increased from 0.03 to 0.09 mg L, and loads effects increased from -0.26 to 1.24 kg ha. This study shows the importance of considering water quality effects associated with intensive management operations required for switchgrass establishment or other novel forest-based biofuel systems.


Severe abdominal pain and diarrhea - unusual multiple myeloma presentation with a severe prognosis: a case report.
Multiple myeloma is a hematologic disease with high mortality rates all over the world. The diagnosis has always been challenging since the first case was reported in 1844. For that reason the diagnostic criteria have evolved over years to include the features of the disease more comprehensively. Unusual presentations are infrequent and a diagnostic challenge. For this reason we report this rare case in which diarrhea and abdominal pain were the initial presenting symptoms of multiple myeloma with a plasmacytoma. An 87-year-old Hispanic man with a past medical history of hypertension, diabetes, and constipation, presented to an emergency department complaining of severe generalized abdominal pain and profuse diarrhea for 3 days. A physical examination revealed generalized pallor and dehydration but no signs of abdominal peritoneal irritation. Laboratory tests revealed neutrophilia and an elevated total protein. He received intravenously administered fluids and antibiotics. His abdominal pain became localized in the infraumbilical area and a small mass was palpated on the right lower quadrant on subsequent examination. An abdominal computed tomography scan showed a tumor lesion surrounded by fluid collection and a computed tomography-guided biopsy of the lesion confirmed it to be a plasmacytoma. A bone marrow biopsy revealed plasmatic cell augmentation but his beta-2 microglobulin levels were inconclusive. The diagnosis of multiple myeloma was finally confirmed with urine immunofixation. Bortezomib was initiated to decrease disease progression, but unfortunately 4 days later he developed acute pulmonary edema, had a cardiac arrest, and died. This case illustrates the protean initial manifestations of multiple myeloma and the importance of an accurate diagnosis. Our patient's initial presentation with gastrointestinal complaints is rare and the plasmacytoma location is even rarer, providing a challenging diagnostic problem. Prompt recognition of multiple myeloma is critical to institute appropriate therapy and prevention of disease progression.


Association of ALOX12 and ALOX15 gene polymorphisms with age at menarche and natural menopause in Chinese women.
Lipoxygenase (LOX) is one of the major metabolic enzymes for arachidonic acid, which has been reported to be associated with many postmenopausal and many hormone-related diseases. In rats, selective inhibition of the LOX pathway led to defective ovulation. However, little is known about the association of the LOX-related genes with menstruation in women. In this study, we investigated the possible association of two key gene (ALOX12 and ALOX15) polymorphisms with age of menarche and menopause in Chinese women. Six tagging single nucleotide polymorphisms (SNPs) of ALOX12 and five SNPs of ALOX15 were genotyped. The association of single SNPs and haplotypes in two candidate genes and age at menarche (AAM) variation was tested in 401 Chinese nuclear families using the quantitative transmissing disequilibrium test. Furthermore, the association between these SNPs and haplotypes and age at natural menopause (AANM) in 710 postmenopausal Chinese women was measured. Using family- and population-based statistical procedures, significant association was found between SNPs rs312462 in ALOX12 and AAM in nuclear families (P = 0.043), and three SNPs (rs2292350, rs312470, and rs312462) in ALOX12 were significantly associated with AANM in postmenopausal women (P = 0.012, P = 0.045, and P = 0.033, respectively). Haplotype analyses corroborated our single SNP results (P = 0.030). However, we failed to find a significant association between ALOX15 gene polymorphisms and AAM as well as AANM (P > 0.05). Our present results suggest that genetic variations in ALOX12 are associated with both the onset and cessation of menstruation in Chinese women living in Shanghai.


Changes in anxiety in abstinence correlate with the state of the nigrostriatal system in the rat hippocampus.
Opiate dependence results from impairments of neuronal plasticity, i.e., so-called aberrant neuroplasticity, formation of which involves long-term structural-functional rearrangements persisting even during drug abstinence. Nitric oxide (NO) is involved both in mediating the effects of opiates and in the mechanisms of some types of neuroplasticity, so NO may potentially take part in the development of psychopathological processes on opiate withdrawal. The present study addressed measures of the nitrergic system (nitric oxide synthase (NOS) activity and nitrite and nitrate (NO (x) (-) ) concentrations) in areas of the rat brain; anxiety was also assessed, in terms of behavioral measures in the elevated plus maze, during morphine withdrawal. NOS activity was found to increase by day 3, while the NO (x) (-) concentration was increased by day 6 of withdrawal, these changes being seen only in the hippocampus. At six days after morphine withdrawal, rats showed more entries into the open arms of the elevated plus maze and remained in these arms longer. Correlations were found between measures of the NO system in the hippocampus and the behavior of the animals in the maze. These results suggest that changes in the activity of the nitrergic system in the hippocampus represent one of the molecular mechanisms impairing the behavior of animals in abstinence.


Patient concerns about accessing sexual and reproductive health services outside of primary care: A survey in rural and urban settings in the Pacific Northwest.
While primary care providers are a major source of sexual and reproductive health (SRH) services in the United States, particularly in rural areas, not all primary care settings offer a full range of SRH services. We aimed to understand primary care patient concerns regarding accessing SRH services, including abortion care, outside of their primary care clinic and if those concerns differed by urban or rural setting. An anonymous survey was distributed over a 2-week period between December 2019 to March 2020 to all adult patients in four primary care clinics in Idaho, Washington, and Wyoming. The survey assessed patient concerns regarding accessing SRH services outside of their primary care clinic and their willingness to travel to access SRH services. The overall response rate was 69% (745/1086). Over 85% of respondents identified at least one concern to seeking SRH services outside of a primary care setting, with cost, insurance coverage, length of wait time, and lack of an established relationship being the most frequently reported concerns. A majority of respondents were willing to travel a maximum of 1 hour for most SRH services. Respondents from rural-serving clinics were significantly more likely to be willing to travel longer amounts of time for medication abortion, aspiration abortion, and intrauterine device placement. Our findings highlight that a majority of both urban and rural primary care patients have concerns regarding accessing SRH services outside of their primary care clinic and are unwilling to travel more than 1 hour to access most SRH services. A majority of primary care patients have concerns regarding accessing SRH services outside of primary care settings. Health care policy changes should aim to strengthen the SRH services available in primary care settings to alleviate the burdens primary care patients face in accessing SRH services outside of their primary care clinic, particularly for rural populations.


[Survey of coping style and mental health status of patients with lumbar intervertebral disc herniation].
To investigate the correlation between the coping style and mental health of patients with lumbar intervertebral disc herniation. The simplified coping style questionnaire and SCL-90 were used to conduct a survey of 106 patients with lumbar intervertebral disc herniation, and the scores were compared with the national norms. The patients had a positive coping style score of 1.51-/+0.58 and negative coping style score of 1.13-/+0.58. The SCL-90 scores were significantly higher than the national norms. A significant correlation was found between the negative coping style and mental health of the patients. Negative coping style is an important factor influencing the mental health of patients with lumbar intervertebral disc herniation.


Suicidal behavior and stress generation in adolescents.
Stress generation has potential to account for recurrent suicidal behavior. The current study represents a first step toward evaluating this possibility in a sample of adolescent psychiatric inpatients (n = 99; 79.80% female) followed over six months. At index admission, participants completed baseline measures of depressive symptom severity, suicidal ideation, lifetime history of suicide attempts, and negative life events using a contextual threat life stress interview. Negative life events since baseline were assessed at the follow-up assessment. Consistent with the stress generation hypothesis, lifetime number of suicide attempts prospectively predicted higher rates of dependent, but not independent, stress. Bayesian analyses also yielded substantial support for an association with overall dependent stress, but provided more modest support for specificity to this form of life stress relative to independent stress. Implications of these findings and directions for future research further clarifying the role of stress generation in suicidal behavior are discussed.


GenoMass--a computer software for automated identification of oligonucleotide DNA adducts from LC-MS analysis of DNA digests.
In the investigation of oligonucleotides, DNA and their adducts by LC-MS, a myriad of data are generated that make manual data processing quite difficult. This paper describes a 'reversed pseudo-combinatorial' approach for fragment identification and the software implementation of this approach. Combinatorial isomer libraries are generated in silico to represent the digestion products of oligonucleotides, DNA or DNA adducts of various sizes. The software automatically calculates ion masses of each isomeric segment of the library, searches for them in complicated LC-MS data, lists their intensities and plots extracted ion chromatograms (EIC). This customized new data analysis tool has enabled a study of the enzymatic behavior of a nuclease system in the digestion of normal and adducted DNA, and in the recognition of oligomers containing a carcinogen bound to a nucleobase. The software program potentially can be further expanded to postulate unknown DNA sequences and recognize the adduction sites.


Fear Extinction Recall Modulates Human Frontomedial Theta and Amygdala Activity.
Human functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) studies, as well as animal studies, indicate that the amygdala and frontomedial brain regions are critically involved in conditioned fear and that frontomedial oscillations in the theta range (4-8 Hz) may support communication between these brain regions. However, few studies have used a multimodal approach to probe interactions among these key regions in humans. Here, our goal was to bridge the gap between prior human fMRI, EEG, and animal findings. Using simultaneous EEG-fMRI recordings 24 h after fear conditioning and extinction, conditioned stimuli presented (CS+E, CS-E) and not presented during extinction (CS+N, CS-N) were compared to identify effects specific to extinction versus fear recall. Differential (CS+ vs. CS-) electrodermal, frontomedial theta (EEG) and amygdala responses (fMRI) were reduced for extinguished versus nonextinguished stimuli. Importantly, effects on theta power covaried with effects on amygdala activation. Fear and extinction recall as indicated by theta explained 60% of the variance for the analogous effect in the right amygdala. Our findings show for the first time the interplay of amygdala and frontomedial theta activity during fear and extinction recall in humans and provide insight into neural circuits consistently linked with top-down amygdala modulation in rodents.


Are the ACOSOG Z0011 Trial Findings Being Applied to Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy?
In 2010, the ACOSOG Z0011 trial showed equivalent survival and recurrence between sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for those with a tumor positive sentinel node (SN). We examined national trends in axillary surgery following neoadjuvant chemotherapy (NAC) for clinically node positive disease in the years prior to and after the Z0011 trial publication. 12,063 women with cT1-4N1M0 invasive breast cancer who underwent NAC from 2006 to 2013 and had 1-3 positive nodes on pathology were selected from the National Cancer Data Base. We defined SLNB as 1-4 nodes and ALND as ≥10 nodes examined. 2,704 women (22.4%) underwent SLNB alone and 9,359 (77.6%) underwent ALND. The rate of SLNB increased from 25.6% in 2006 to 33.3% in 2012 in patients that underwent lumpectomy (p < 0.01) and increased from 20.6% to 22.8% in patients that underwent mastectomy (p = 0.25). Patients treated at Community centers (30.4% versus 19.2% at Academic centers) and those with less positive nodes (32.2% for 1 positive node versus 10.1% for 3 positive nodes, p < 0.01) were more likely to have SLNB alone compared to ALND. On multivariate analysis, treatment with lumpectomy (OR 1.46, CI 1.28-1.67), lower number of positive nodes (OR 3.98, CI 3.29-4.82) and lobular subtype (OR 1.82, CI 1.42-2.34) were independent predictors of receiving SLNB alone after NAC. Approximately 22% of patients with cN1 breast cancer underwent SLNB alone for pN1 disease after NAC. Ongoing clinical trials will determine if recurrence and survival rates are equivalent between SLNB and ALND groups.


The association of school connectedness and bullying involvement with multiple screen-time behaviours among youth in two Canadian provinces: a COMPASS study.
Screen time, a proxy for sedentary behaviours, has emerged as a critical health determinant among youth in contemporary societies, where most aspects of youth life involve access to screen-time devices. An understudied approach to reducing screen time among youth is bullying reduction. This study aims to understand the association between bullying perpetration, victimization, youth perception of the school environment and multiple screen-time behaviours. A total of 44,861 youth aged between 13 and 18 years in two Canadian provinces completed a validated questionnaire that collected student data on health behaviours and outcomes, including multiple screen-time behaviours, bullying perpetration and victimization, and school connectedness. The outcome variables were total screen time, time spent watching television, playing video games, internet surfing, and communication- based screen-time behaviours. Using a random intercept, the final models were built using PROC MIXED in SAS 9.4. These models were adjusted for age, ethnicity, weekly disposable income, daylight hours, and weather variables. Compared to youth who reported non-involvement in bullying, youth who were bullies, victims, or both bullies and victims spent on average more minutes per day in front of screens across all screen time categories. Youth who felt happy and safe at school, and who perceived their teachers as being fair, reported lower levels of multiple screen-time behaviours. With non-involvement in bullying showing a strong negative association with multiple screen-time behaviours, school policies to address bullying and screen time through school connectedness could offer a novel approach in minimizing these harmful behaviours.


Pharmacogenomics of immunosuppressive drug metabolism.
The immunosuppressants are potent and toxic drugs with narrow therapeutic ranges. The pharmacokinetic variability of these drugs has made establishing appropriate dosing difficult. Currently, therapeutic drug monitoring is an important adjunct to achieving the precarious balance between efficacy and toxicity. However, pharmacogenomic analysis has the potential to improve dosing strategies. Several of the drugs in this category are metabolized through complex pathways, which have the potential to be affected by genetic traits. The current literature has addressed several genes and polymorphisms in relation to these drugs. Polymorphisms related to the coding of P-glycoprotein (coded by the MDR-1 gene) and cytochrome P450 3A enzymes have been the main focus of research. These gene products are involved in regulating the absorption and metabolism of the principal immunosuppessants. Two polymorphisms (C3435T and G2677[A/T]) of the MDR-1 gene have been shown to influence the bioavailability and toxicity of tacrolimus and cyclosporin. Phase I metabolism of these drugs has been shown to be affected by two polymorphisms (CYP3A5*1 and CYP3AP1*1), related to cytochrome P450 3A5 expression, rather than cytochrome P450 3A4. The current literature has shown disparity as to which are the most important polymorphisms affecting the metabolism of immunosuppressants. Although pharmacogenomics has the potential to allow improvements in devising optimal dosing regimes, it has not yet offered any definitive solutions to the problems of dosing, because the process of elucidating the complex influence of genetics on drug metabolism is only starting to be unravelled.


[Expression of CREB/Bcl-2 in bone marrow mononuclear cells of children with acute leukemia].
To study the expression and role of cyclic-AMP response binding protein (CREB) and Bcl-2 in children with acute leukemia. Ninety-two children with acute leukemia (leukemia group) and 30 children with non-hematologic malignancies (control group) were enrolled. The mRNA and protein expression of CREB and Bcl-2 in bone marrow mononuclear cells were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot. The mRNA and protein expression of CREB and Bcl-2 in the leukemia group was significantly higher than that in the control group (p<0.01). There were no significant differences in the expression of CREB and Bcl-2 between acute lymphoblastic leukemia and acute myeloid leukemia subgroups. At the initial diagnosis, the mRNA and protein expression of CREB and Bcl-2 in children with extramedullary infiltration was higher than that in children without (p<0.05). In the leukemia group, the mRNA and protein expression of CREB and Bcl-2 in the complete remission subgroup was significantly lower than that in the non-complete remission subgroup (p<0.01). High mRNA expression of CREB and Bcl-2 in the leukemia group was positively correlated with peripheral blood leucocyte counts (r=0.62, 0.71 respectively, p<0.05). There was a positive correlation between mRNA and protein expression of CREB and Bcl-2 (r=0.75, 0.68 respectively; p<0.05). The expression of CREB and Bcl-2 may be correlated with the pathogenesis and clinical prognosis of childhood leukemia, however, their expression may not be associated with the classification of acute leukemia.


Correlations between magnetic resonance imaging-based hippocampal sclerosis and depth electrode investigation in epilepsy of the mesiotemporal lobe.
Quantitative analysis of hippocampal formations (HF) by magnetic resonance imaging (MRI) was correlated with depth electrode recordings in 18 patients with partial epilepsy. All had seizures of mesiotemporal origin. Electrodes explored three HF segments: amygdala and HF head and anterior and posterior HF body. Corresponding HF measurements were made on coronal MRI sequences, and atrophy was quantified by one global and three segmental indexes of asymmetry per patient. HF from which seizure originated showed global atrophy in 15 patients. Segmental analysis demonstrated discrete tissue damage in 1 patient; thus, 16 patients (88%) had significant hippocampal atrophy ipsilateral to the mesial focus. The existence of more pronounced atrophy in segments giving rise to ictal onset than in segments without ictal onset was not statistically significant. Nevertheless, in posterior HF, all segments (four) with seizure onset were atrophied and none of the nonatrophied posterior segments (four) were at seizure origin. These findings confirm that MRI-detected hippocampal atrophy is a powerful indicator of a mesiotemporal focus and strongly contributes to consideration of resective surgery without intracerebral EEG monitoring. Study of the distribution of maximal tissue damage may add some information, and help surgeons decide on the posterior extent of hippocampus removal. As illustrated by 3 patients who had multiple sites of seizure onset, however, the presence of this marker should not be interpreted systematically as evidence of pure mesiotemporal epilepsy.


Aliphatic Sulfonyl Fluoride Synthesis via Decarboxylative Fluorosulfonylation of Hypervalent Iodine(III) Carboxylates.
We disclose herein a photocatalytic decarboxylative fluorosulfonylation reaction of various hypervalent iodine(III) carboxylates in combination with 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct as a sulfonyl source and KHF2 as a desirable fluorine source via a radical sulfur dioxide insertion and fluorination strategy. A one-pot photocatalytic decarboxylative fluorosulfonylation reaction of various carboxylic acids mediated by PhI(OAc)2 was realized, as well. Notably, this transformation can be performed under heating conditions without the need for catalysts.


Development of novel real-time TaqMan(®) PCR assays for the species and sex identification of otter (Lutra lutra) and their application to noninvasive genetic monitoring.
Developing strategies to maintain biodiversity requires baseline information on the current status of each individual species. The development of genetic techniques and their application to noninvasively collected samples have the potential to yield information on the structure of elusive animal populations and so are important tools in conservation management. Using DNA isolated from faecal samples can be challenging owing to low quantity and quality. This study, however, presents the development of novel real-time polymerase chain reaction assays using fluorescently labelled TaqMan(®) MGB probes enabling species and sex identification of Eurasian otter (Lutra lutra) spraints (faeces). These assays can also be used in determining an optimum microsatellite panel and can be employed as cost-saving screening tools for downstream genetic testing including microsatellite genotyping and haplotype analysis. The techniques are shown to work efficiently with L. lutra DNA isolated from tissue, hair, spraint, blood and anal jelly samples.


Staphylococcus aureus lipoteichoic acid triggers inflammation in the lactating bovine mammary gland.
The response of the bovine mammary gland to lipoteichoic acid (LTA), which is a major pathogen-associated molecular pattern of Gram-positive bacteria, was investigated by infusing purified Staphylococcus aureus LTA in the lumen of the gland. LTA was able to induce clinical mastitis at the dose of 100 microg/quarter, and a subclinical inflammatory response at 10 microg/quarter. The induced inflammation was characterized by a prompt and massive influx of neutrophils in milk. LTA proved to induce strongly the secretion of the chemokines CXCL1, CXCL2, CXCL3 and CXCL8, which target mainly neutrophils. The complement-derived chemoattractant C5a was generated in milk only with the highest dose of LTA (100 microg). The pro-inflammatory cytokine IL-1beta was induced in milk, but there was very little if any TNF-alpha and no IFN-gamma. The re-assessment of CXCL8 concentrations in milk whey of quarters previously challenged with S. aureus, by using an ELISA designed for bovine CXCL8, showed that this chemokine was induced in milk, contradicting previous reports. Overall, S. aureus LTA elicited mammary inflammatory responses that shared several attributes with S. aureus mastitis. Purified LTA looks promising as a convenient tool to investigate the inflammatory and immune responses of the mammary gland to S. aureus.