Absence of troponin I degradation or altered sarcoplasmic reticulum uptake protein expression after reversible ischemia in swine.
The findings of troponin I (TnI) proteolysis (in isolated rat hearts) and induction of selected sarcoplasmic reticulum (SR) calcium-regulatory genes (after repetitive total coronary occlusions in swine) have given rise to the hypothesis that the time course of functional recovery of stunned myocardium reflects the resynthesis of reversibly damaged proteins. Although stunning occurs after brief total occlusions and prolonged partial occlusions (ie, short-term hibernation), the time course of functional recovery varies from a few hours to several days, suggesting that the severity of protein damage or mechanisms responsible for the dysfunction may differ. To study this, we examined SR gene expression and TnI degradation in stunned myocardium produced by 10-minute total left anterior descending coronary artery (LAD) occlusions (n=4) or 1-hour partial LAD occlusions, in which flow was reduced to approximately 50% of control values for 60 minutes (n=6) in swine. One hour after reperfusion, LAD wall thickening was severely depressed in both models despite normal perfusion and no triphenyltetrazolium chloride evidence of necrosis. Normal myocardium exhibited TnI immunoreactivity at 31 kDa and a weak secondary band at 27 kDa. Irreversible injury or calpain activation in vitro produced a marked increase in the intensity of the 27-kDa band, consistent with TnI degradation. Stunned myocardium demonstrated no change in the 31- or the 27-kDa band, and the percentage of the 27- to 31-kDa band remained constant after 10-minute total occlusions (LAD, 5.9+/-0.9%; normal, 4.9+/-1.6%) and 1-hour partial occlusions (LAD, 8.5+/-1.9%; normal, 7.3+/-1.4%) and in sham controls (LAD, 10.9+/-1.5%; normal, 9.8+/-1.4%). Northern analysis showed no alterations in TnI or SR gene expression, but the stress protein HSP-70 was variably induced. Thus, stunned myocardium occurs without TnI degradation or altered SR gene expression, indicating that additional mechanisms are responsible for the reversible dysfunction after single episodes of regional ischemia in swine.


Cell therapy for diabetes mellitus: an opportunity for stem cells?
Diabetes is a chronic disease characterized by a deficit in beta cell mass and a failure of glucose homeostasis. Both circumstances result in a variety of severe complications and an overall shortened life expectancy. Thus, diabetes represents an attractive candidate for cell therapy. Reversal of diabetes can be achieved through pancreas and islet transplantation, but shortage of donor organs has prompted an intensive search for alternative sources of beta cells. This achievement has stimulated the search for appropriate stem cell sources. Both embryonic and adult stem cells have been used to generate surrogate beta cells or otherwise restore beta cell functioning. In this regard, several studies have reported the generation of insulin-secreting cells from embryonic and adult stem cells that normalized blood glucose values when transplanted into diabetic animal models. Due to beta cell complexity, insulin-producing cells generated from stem cells do not possess all beta cell attributes. This indicates the need for further development of methods for differentiation and selection of completely functional beta cells. While these problems are overcome, diabetic patients may benefit from therapeutic strategies based on autologous stem cell therapies addressing late diabetic complications. In this article, we discuss the recent progress in the generation of insulin-producing cells from embryonic and adult stem cells, together with the challenges for the clinical use of diabetes stem cell therapy.


Role of Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) in the propagation of MPMV vectors by genetic complementation using homologous/heterologous env genes.
To study Mason-Pfizer monkey virus (MPMV) replication over a single round, virus particles were generated that contain a replication-defective vector encoding a dominant selectable marker, the hygromycin B phosphotransferase (hyg) gene. Genetic complementation with a homologous MPMV envelope glycoprotein (Env-gp) or pseudotyping by several heterologous Env-gps from a variety of viruses resulted in infectious MPMV particles containing the replication-defective RNA. Recently, it has been shown that human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) Rev and Rev-responsive element (RRE) functions can be substituted in vitro by a cis-acting sequence, the constitutive transport element (CTE), from simian type D retroviruses like MPMV and simian retrovirus type 1 (SRV-1). To determine whether CTE of MPMV is necessary for MPMV nucleic acid propagation, an MPMV vector that lacked the terminally located CTE was generated. Propagation of this vector was completely abrogated in the absence of CTE, showing the importance of CTE in MPMV replication. Insertion of CTE back into the MPMV genome in the sense orientation rescued replication to wild-type levels. Slot-blot analysis of nuclear versus cytoplasmic RNA fractions revealed that most of the messages were sequestered in the nucleus of cells transfected with the CTE(-) vectors and very little was transported to the cytoplasm. To test whether HIV-1 or SIV RREs could complement CTE function, the HIV-1 or SIV RREs were inserted in the CTE(-) vectors, trans complementation of CTE(-)RRE(+) vectors with Env-and Rev-expression plasmids rescued propagation of the CTE(-) vectors. Computer analysis predicted an RNA secondary structure in MPMV CTE analogous to the HIV-1 and SIV RREs that could form three stable stem loops, the first of which contains a site similar to the Rev-binding domain in the HIV-1 RRE. The presence of a higher-order CTE structure was analyzed by mutational analysis. We conclude that CTE is important in the replication of MPMV and affects the nucleocytoplasmic transport and/or stability of viral messages similar to the Rev/RRE regulatory system of HIV-1 and SIV.


The effects of predator learning, forgetting, and recognition errors on the evolution of warning coloration.
This paper demonstrates that the specifics of predator avoidance learning, information loss, and recognition errors may heavily influence the evolution of aposematism. I establish a mathematical model of the change in frequency over time of bright individuals of a distasteful prey species. Warning color spreads through green beard selection as reformulated by Guilford (1990); bright colored forms gain an advantage due to their phenotypic resemblance to other bright forms, which have been sampled by the predator. I use a general classical conditioning model to examine gradual predator learning and forgetting, and then consider the extreme of one-trial learning and no forgetting over time that may occur with very toxic prey. The advantage of conspicuous coloration under these latter conditions depends upon its role in lowering a constant probability of the prey being misidentified and thus mistakenly attacked by a predator, a rarely emphasized factor in the evolution of warning coloration. This constant probability of mistaken attacks can also be interpreted as a constant probability that forgetting has occurred (forgetting does not increase with time) or a periodic decision by the predator to resample avoided prey. I show that when predators learn and forget gradually, as under the general classical conditioning model, it is very difficult for aposematic coloration to become established unless bright individuals cross an often high threshold frequency through chance factors. In contrast, the conditions expected with highly toxic prey promote the evolution of warning coloration more easily, by means from the fixation of very bright mutations to the fixation of successive mutations each of which causes a small increase in a prey's conspicuousness. The results therefore predict that aposematic coloration may have evolved in a different manner in different predator and prey systems. They also suggest that it may be extremely difficult for warning coloration to evolve in more mildly toxic or distasteful prey outside of a mimicry system.


Staphylococcus aureus infections in Australasian neonatal nurseries.
To study the incidence and outcome of systemic infections with methicillin sensitive (MSSA) and methicillin resistant Staphylococcus aureus (MRSA) infections in Australasian neonatal nurseries. Prospective longitudinal study of systemic infections (clinical sepsis plus positive cultures of blood and/or cerebrospinal fluid) in 17 Australasian neonatal nurseries. The incidence of early onset sepsis with S aureus, mainly MSSA, was 19 cases per 244 718 live births or 0.08 per 1000. From 1992 to 1994, MRSA infections caused only 8% of staphylococcal infections. From 1995 to 1998, there was an outbreak of MRSA infection, in two Melbourne hospitals. The outbreak resolved, after the use of topical mupirocin and improved handwashing. Babies with MRSA sepsis were significantly smaller than babies with MSSA sepsis (mean birth weight 1093 v 1617 g) and more preterm (mean gestation 27.5 v 30.3 weeks). The mortality of MRSA sepsis was 24.6% compared with 9.9% for MSSA infections. The mortality of early onset MSSA sepsis, however, was 39% (seven of 18) compared with 7.3% of late onset MSSA infection presenting more than two days after birth. S aureus is a rare but important cause of early onset sepsis. Late onset MRSA infections carried a higher mortality than late onset MSSA infections, but babies with early onset MSSA sepsis had a particularly high mortality.


Substrate Promotes Productive Gas Binding in the α-Ketoglutarate-Dependent Oxygenase FIH.
The Fe(2+)/α-ketoglutarate (αKG)-dependent oxygenases use molecular oxygen to conduct a wide variety of reactions with important biological implications, such as DNA base excision repair, histone demethylation, and the cellular hypoxia response. These enzymes follow a sequential mechanism in which O2 binds and reacts after the primary substrate binds, making those structural factors that promote productive O2 binding central to their chemistry. A large challenge in this field is to identify strategies that engender productive turnover. Factor inhibiting HIF (FIH) is a Fe(2+)/αKG-dependent oxygenase that forms part of the O2 sensing machinery in human cells by hydroxylating the C-terminal transactivation domain (CTAD) found within the HIF-1α protein. The structure of FIH was determined with the O2 analogue NO bound to Fe, offering the first direct insight into the gas binding geometry in this enzyme. Through a combination of density functional theory calculations, {FeNO}(7) electron paramagnetic resonance spectroscopy, and ultraviolet-visible absorption spectroscopy, we demonstrate that CTAD binding stimulates O2 reactivity by altering the orientation of the bound gas molecule. Although unliganded FIH binds NO with moderate affinity, the bound gas can adopt either of two orientations with similar stability; upon CTAD binding, NO adopts a single preferred orientation that is appropriate for supporting oxidative decarboxylation. Combined with other studies of related enzymes, our data suggest that substrate-induced reorientation of bound O2 is the mechanism utilized by the αKG oxygenases to tightly couple O2 activation to substrate hydroxylation.


Genetic and epigenetic association studies suggest a role of microRNA biogenesis gene exportin-5 (XPO5) in breast tumorigenesis.
Given strong evidence implicating an important role of altered microRNA expression in cancer initiation and progression, the genes responsible for microRNA biogenesis may also play a role in tumorigenesis. Exportin-5 (XPO5) is responsible for exporting pre-miRNAs through the nuclear membrane to the cytoplasm, and is thus critical in miRNA biogenesis. In the current study, we performed both genetic and epigenetic association studies of XPO5 in a case control study of breast cancer. We first genotyped two missense SNPs in XPO5, rs34324334 (S241N) and rs11544382 (M1115T), and further analyzed methylation levels in the XPO5 promoter region for blood DNA samples from a breast cancer case-control study. We found the variant genotypes of rs11544382 to be associated with breast cancer risk (OR=1.59, 95% CI: 1.06 -2.39), compared to the homozygous common genotype. When stratified by menopausal status, the variant alleles of both rs11544382 (OR=1.82, 95% CI: 1.09-3.03) and rs34324334 (OR=1.76, 95% CI: 1.10-2.83) were significantly associated with breast cancer risk in post-menopausal women. The methylation analysis showed that the "high" and combined "high/middle" tertiles of methylation index were associated with reduced risk of breast cancer (OR=0.34, 95% CI:0.15-0.81 and OR=0.47, 95% CI:0.24-0.94, respectively; P(trend)=0.015). These results were corroborated by data from a publicly available tissue array, which showed lower levels of XPO5 expression in healthy controls relative to tumor or adjacent tissues from breast cancer patients with tumor tissue exhibiting the highest expression levels. These findings support the hypothesis that variations in components of the miRNA biogenesis pathway, in this case XPO5, may affect an individual's risk of developing breast cancer.


Identification of the contiguous Paracoccus denitrificans ccmF and ccmH genes: disruption of ccmF, encoding a putative transporter, results in formation of an unstable apocytochrome c and deficiency in siderophore production.
Apocytochrome C550 was detected in the periplasm of a new mutant of Paracoccus denitrificans, HN48, that is pleiotropically lacking c-type cytochromes, produces reduced levels of siderophores and carries a Tn5 insertion in the ccmF gene for which sequence data, along with that for the contiguous ccmH, are reported. A counterpart to the ccmF gene was found in an archaebacterium but could not be located in the yeast genome, whereas mitochondrial haem lyases in the latter were not present in an archaeobacterial or in eubacterial genomes. A topological analysis for CcmF is presented which indicates at least eleven transmembrane helices, suggesting a role as a transporter; evidence against the substrate being haem is presented but sequence similarity with Escherichia coli gamma-aminobutyric acid transporter was identified. Analysis by pulse-chase methodology has shown that, in this and another cytochrome-c-deficient mutant, the apo form of P. denitrificans cytochrome C550 is much less stable than the holo form, directly demonstrating the presence of a periplasmic degradation system in P. denitrificans that removes non-functional proteins. A variety of phenotypes are observed for P. denitrificans mutated in different ccm genes, thus indicating that the stability of the ccm gene products does not require assembly of a complex of all the Ccm proteins.


Evaluating a Longitudinal Cohort of Clinics Engaging in the Family Planning Elevated Contraceptive Access Program: Study Protocol for a Comparative Interrupted Time Series Analysis.
Access to high-quality, comprehensive contraceptive care is an inherent component of reproductive human rights. However, hindrances to specific aspects of contraceptive provision, including availability, accessibility, acceptability, and quality, continue to perpetuate unmet needs. The state of Utah has recently passed a series of contraceptive policies intended to improve contraceptive access. Despite these positive changes to theoretical access, fiscal appropriations to support the implementation of these policies have been minimal, and many individuals still struggle to access contraception. The Family Planning Elevated Contraceptive Access Program (FPE CAP), part of a larger statewide contraceptive initiative, specifically aims to improve contraceptive access within health clinics. This paper describes the study protocol for evaluating the success of FPE CAP. Health clinics apply for membership in the FPE CAP. On acceptance in the program, they receive a cash grant for clinical supplies, equipment, and personnel expenses; reimbursement for contraceptive services and methods for eligible clients; technical support, training, and proctoring on counseling and providing all methods of contraception; method stocking of intrauterine devices and implants; and demand generation activities, including local media campaigns, to inform community members about the FPE CAP and possible eligibility. FPE collects monthly service delivery reports from participating clinics for evaluation purposes. The primary outcomes of FPE CAP are level and trend changes in contraceptive service delivery among individuals earning ≤138% federal poverty level (FPL) following membership in FPE CAP and among FPE CAP clients earning between 139% and 250% FPL (including those ineligible for Medicaid) compared with historical data and control clinics. To assess this, we will conduct comparative interrupted time series analyses assessing the level and trend changes in intervention and control clinics 12 months before the intervention, for the 2-year duration of the intervention, and for the subsequent 12 months following the intervention. We found that the study is adequately powered (>80% power) with our planned number of clinics and the number of months of data available in the study. To date, we have successfully completed the recruitment and enrollment of 8 of the expected 9 health organizations and 4 of the control clinics. Completed health organization enrollment for both intervention and control organizations is expected to be completed in December 2020. The study aims to provide insight into a new approach to contraceptive initiatives by addressing comprehensive aspects of contraceptive care at the health system level. Ongoing state policy changes and implementation components may affect the evaluation outcomes. DERR1-10.2196/18308.


Coordination of PAD4 and HDAC2 in the regulation of p53-target gene expression.
Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53-target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates histone arginine and monomethyl-arginine residues thereby regulating histone Arg methylation. We have recently found that PAD4 serves as a p53 corepressor to regulate histone Arg methylation at the p53-target gene p21/WAF1/CIP1 promoter. However, it has not been tested whether histone Arg citrullination coordinates with other histone modifications to repress transcription. Here, we show that histone deacetylase (HDAC2) and PAD4 interact with p53 through distinct domains and simultaneously associate with the p21 promoter to regulate gene expression. After DNA damage, PAD4 and HDAC2 dissociate from several p53-target gene promoters (for example, p21, GADD45, and PUMA) with a concomitant increase in histone Lys acetylation and Arg methylation at these promoters. Furthermore, PAD4 promoter association and histone Arg modifications are regulated by p53 and HDAC activity. In contrast, HDAC2 promoter association and histone Lys acetylation are affected by p53 and PAD4 activity at minor degrees. Importantly, PAD4 inhibitor Cl-amidine and HDAC inhibitor suberoylanilide hydroxamic acid show additive effects in inducing p21, GADD45, and PUMA expression and inhibiting cancer cell growth in a p53-dependent manner. Our results unveil an important crosstalk between histone deacetylation and citrullination, suggesting that a combination of PAD4 and HDAC2 inhibitors as a potential strategy for cancer treatment.


Trisilver(I) citrate.
Trisilver(I) citrate, 3Ag(+)·C(6)H(5)O(7) (3-), was obtained by evaporation of a saturated aqueous solution of the raw material that had been obtained from sodium dihydrogen citrate and silver nitrate. It features one formula unit in the asymmetric unit. There is an intra-molecular O-H⋯O hydrogen bond between the OH group and one of the terminal carboxyl-ate groups. Different citrate groups are linked via the three Ag(+) ions, yielding a three-dimensional network with rather irregular [AgO(4)] polyhedra.


Comparison Between EPI DWI and PROPELLER DWI in Brain MR Imaging.
EPI DWI is a routinely used sequence in brain imaging but it has limitations when it comes to SNR and artifact reduction. PROPELLER DWI has the benefit of improving image quality compared to EPI DWI. The aim of this study is to compare the EPI DWI sequence in brain MR imaging with the PROPELLER DWI sequence. The objective is to identify which sequence is more beneficial in brain imaging by evaluating image quality and the depiction of pathologies. A total of 101 patients (55 females and 46 males, mean age 56 years) underwent brain MRI examination on a 1.5 T scanner. EPI DWI and PROPELLER DWI sequences were acquired in every exam and were reviewed by 2 radiologists. The images were evaluated by performing a quantitative analysis based on Relative Contrast and a qualitative analysis (overall image quality, conspicuousness of lesions, artifact reduction, etc.). In both the qualitative and quantitative analysis PROPELLER DWI achieved better results than EPI DWI. PROPELLER DWI showed statistical significance in the overall image quality (P < 0.001), the elimination of susceptibility (P < 0.001) and flow pulsation artifacts (P < 0.001), as well as in the contrast between CSF with white (P < 0.001) and grey matter (P < 0.001). Also, PROPELLER DWI presented better delineation of pathologies like ischemic strokes, metastasis, tumors and vasogenic edemas than conventional EPI DWI. PROPELLER DWI was the preferred sequence during the image evaluation. Compared to EPI DWI, PROPELLER DWI managed to reduce susceptibility and flow pulsation whilst achieving higher image quality and lesion delineation and earlier depiction of ischemic strokes than the conventional EPI DWI. PROPELLER DWI may be incorporated in brain MR imaging replacing EPI DWI.


Determination of trace metals in drinking water using solid-phase extraction disks and X-ray fluorescence spectrometry.
A convenient method is described for monitoring Cd, Ni, Cu, and Pb at trace levels in drinking water samples. These metals are preconcentrated on a chelating solid-phase extraction disk and then determined by X-ray fluorescence spectrometry. The method tolerates a wide pH range (pH 6-14) and a large amount of alkaline and alkaline earth elements. The preconcentration factor is well over 1600, assuming a 1 L water sample volume. The limits of detection for Cd, Ni, Cu, and Pb are 3.8, 0.6, 0.4, and 0.3 ng/mL, respectively. These are well below the federal maximum contaminant level values, which are 5, 100, 1300, and 15 ng/mL, respectively. The proposed method has many advantages including ease of operation, multielement capability, nondestructiveness, high sensitivity, and relative cost efficiency. The solid-phase extraction step can be conducted in the field and then the disks can be mailed to a laboratory for the analysis, eliminating the cost of transporting large volumes of water samples. Furthermore, the color of the used extraction disk provides an initial estimate of the degree of contamination for some transition metals (for example, Ni and Cu). Thus, the overall cost for analysis of metals in drinking water can be minimized by implementing the method, and small water supply companies with limited budgets will be better able to comply with the Safe Drinking Water Act.


Clinical and laboratorial evidence of Rickettsia felis infections in Latin America.
After the discovery and initial characterization of Rickettsia felis in 1992 by Azad and cols, and the subsequent first description of a human case of infection in 1994, there have been two communications of human rickettsiosis cases caused by Rickettsia felis in Latin America. The first one was published in 2000 by Zavala-Velazquez and cols in Mexico. In 2001 Raoult and cols described the occurrence of two human cases of Rickettsia felis rickettsiosis in Brazil. In the present discussion these two articles were compared and after the description of the principal signs and symptoms, it was concluded that more studies are needed with descriptions of a greater number of patients to establish the true frequency of the clinical signs and symptoms present in Rickettsia felis rickettsiosis.


Glycosaminoglycans on fibroblasts accelerate thrombin inhibition by protease nexin-1.
Protease nexin-1 (PN-1) is a proteinase inhibitor that is secreted by human fibroblasts in culture. PN-1 inhibits certain regulatory serine proteinases by forming a covalent complex with the catalytic-site serine residue; the complex then binds to the cell surface and is internalized and degraded. The fibroblast surface was recently shown to accelerate the rate of complex-formation between PN-1 and thrombin. The present paper demonstrates that the accelerative activity is primarily due to cell-surface heparan sulphate, with a much smaller contribution from chondroitin sulphate. This conclusion is supported by the effects of purified glycosaminoglycans on the second-order rate constant for the inhibition of thrombin by PN-1. Also, treatment of 35SO4(2-)-labelled cells with heparitin sulphate lyase or chondroitin sulphate ABC lyase demonstrated two discrete pools of 35S-labelled glycosaminoglycans; subsequent treatment of plasma membranes with these glycosidases showed that heparitin sulphate lyase treatment abolished about 80% of the accelerative activity and chondroitin sulphate ABC lyase removed the remaining 20%. These results show that two components are responsible for the acceleration of PN-1-thrombin complex-formation by human fibroblasts. Although dermatan sulphate is also present on fibroblasts, it did not accelerate the inhibition of thrombin by PN-1.


Giant aggressive mesenteric fibromatosis- a case report.
Fibromatosis are rare, accounting for 0.03% of all tumours. Mesenteric fibromatosis is a very rare (8% of all desmoid neoplasm). Aggressive fibromatosis of mesentery is a rare surgical problem affecting 2-4 per million people. Females are more commonly affected than males (Estrogen acts as a growth factor). It is locally invasive and tends to recur but never metastasize. Here, we are discussing about 24-year-old male presented with progressive abdomen distension associated with pain since one month. Abdominal examination showed a firm non-tender intra-abdominal mass, measuring around 15x14 cm size, with intrinsic mobility, which was perpendicular to mesenteric line, all borders were well-made out. CECT abdomen showed features suggestive of GIST . Elective Laparotomy was done and a giant mass arising from mesentery without any infiltration to the surrounding structures was noted. The entire mass was excised and mesentery repaired. Histopathology showed uniform band of spindle shaped cells arranged in fascicles admixed with blood vessels in a collagenous stroma. Immunohistochemistry showed Beta Catenin +ve, CD 117-ve, CD 34 -ve and SMA-ve, which is confirmative of Fibromatosis. Postoperative period was uneventful.


The expression of p53, ki67 and COX-2 in erosive-type oral lichen planus.
Oral lichen planus is a chronic inflammatory disease that affects the oral mucosa and may undergo malignant changes, which can be reflected in the expression of specific proteins that are responsible for maintaining cellular mitosis and apoptosis. The study aimed to investigate the expression of p53, ki67, and COX-2 in erosive lichen planus using immunohistochemistry to correlate these findings with the histological aspects of the disease. Thirty-three biopsies of erosive lichen planus were collected and diagnosed based on histological and clinical criteria. The blocks were processed for immunohistochemistry to assess p53, ki67, and COX-2 expression in the basal layer, suprabasal, and inflammatory infiltrate respectively. The histological analysis of the samples showed no dysplasia or metastasis. P53 stained positively in 80% of the samples, while ki67 was positive in all the cases, ranging from 5% to 85% positivity. COX-2 expression ranged from 0-50% positivity. The highest expression of p53 was observed in 8 cases (24.2%), with a maximum of 5%, and ki67 exhibited the highest expression of 90% in 3 cases (9.1%). COX-2 was negative in 27 cases (81.8%) and positive in 6 cases (18.1%), with the highest expression at 50% in 1 case and 10 % positivity in 4 cases (12.1%). In our study, the markers p53, ki67, and COX-2 proved to be useful for detecting the proliferative, inflammatory, and physiologic states of the keratinocytes. However, they did not demonstrate utility in detecting any malignant transformation.


Novel pseudo-delocalized anions for lithium battery electrolytes.
A novel anion concept of pseudo-delocalized anions, anions with distinct positive and negative charge regions, has been studied by a computer aided synthesis using DFT calculations. With the aim to find safer and better performing lithium salts for lithium battery electrolytes two factors have been evaluated: the cation-anion interaction strength via the dissociation reaction LiAn ⇌ Li(+) + An(-) and the anion oxidative stability via a vertical ionisation from anion to radical. Based on our computational results some of these anions have shown promise to perform well as lithium salts for modern lithium batteries and should be interesting synthetic targets for future research.


Neural adaptation to thin and fat bodies in the fusiform body area and middle occipital gyrus: an fMRI adaptation study.
Visual perception can be strongly biased due to exposure to specific stimuli in the environment, often causing neural adaptation and visual aftereffects. In this study, we investigated whether adaptation to certain body shapes biases the perception of the own body shape. Furthermore, we aimed to evoke neural adaptation to certain body shapes. Participants completed a behavioral experiment (n = 14) to rate manipulated pictures of their own bodies after adaptation to demonstratively thin or fat pictures of their own bodies. The same stimuli were used in a second experiment (n = 16) using functional magnetic resonance imaging (fMRI) adaptation. In the behavioral experiment, after adapting to a thin picture of the own body participants also judged a thinner than actual body picture to be the most realistic and vice versa, resembling a typical aftereffect. The fusiform body area (FBA) and the right middle occipital gyrus (rMOG) show neural adaptation to specific body shapes while the extrastriate body area (EBA) bilaterally does not. The rMOG cluster is highly selective for bodies and perhaps body parts. The findings of the behavioral experiment support the existence of a perceptual body shape aftereffect, resulting from a specific adaptation to thin and fat pictures of one's own body. The fMRI results imply that body shape adaptation occurs in the FBA and the rMOG. The role of the EBA in body shape processing remains unclear. The results are also discussed in the light of clinical body image disturbances.


Developmental differences in episodic memory across school ages: evidence from enacted events performed by self and others.
The aim of this study was to examine action memory as a form of episodic memory among school-aged subjects. Most research on action memory has focused on memory changes in adult populations. This study explored the action memory of children over time. A total of 410 school-aged child participants, comprising 201 girls and 208 boys in four age groups (8, 10, 12, and 14), were included in this study. We studied two forms of action encoding, subject-performed tasks (SPTs) and experimenter-performed tasks (EPTs), which were compared with one verbal encoding task as a control condition. At retrieval, we used three memory tests (free recall, cued recall, and recognition). We observed significant differences in memory performance in children aged 8-14 years with respect to free recall and cued recall but not recognition. The largest memory enhancement was observed for the SPTs in the 8-14-year-old participants under all test conditions. Participants performed equally well on the free recall of SPTs and EPTs, whereas they displayed better performances on the cued recall and recognition of SPTs compared to EPTs. The strategic nature of SPTs and the distinction between item-specific information and relational information are discussed.


Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosus.
Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte-bound complement activation products, erythrocyte-bound C3d (E-C3d) and E-C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE. The levels of E-C3d and E-C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). At baseline, patients with SLE had higher median levels of E-C3d and E-C4d (P < 0.0001) in addition to higher within-patient and between-patient variability in both E-C3d and E-C4d when compared with the 2 non-SLE groups. In a longitudinal analysis of patients with SLE, E-C3d, E-C4d, serum C3, and anti-double-stranded DNA (anti-dsDNA) antibodies were each significantly associated with the SLAM and SELENA-SLEDAI. In a multivariable analysis, E-C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti-dsDNA antibodies; however, E-C3d was associated with the SLAM but not with the SELENA-SLEDAI. Determining the levels of the erythrocyte-bound complement activation products, especially E-C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE.


Dispersion management for controlling image plane in Fourier-domain spectrally encoded endoscopy.
Spectrally encoded endoscopy (SEE) uses single optical fiber and miniature diffractive optics to allow imaging through a miniature probe. Utilizing Fourier-domain interferometry, SEE was shown capable of video-rate three-dimensional imaging, albeit at limited depth of field due to the limited spectral resolution of the detection spectrometer. We show that by using dispersion management at the reference arm of the interferometer, the tilt and curvature of the field of view could be adjusted without modifying the endoscopic probe itself. By controlling the group velocity dispersion, this technique is demonstrated useful for imaging specimen regions which reside outside the system's depth of field. This approach could be used to improve usability, functionality and image quality of SEE without affecting probe size and flexibility.


Episodic aphemia and epileptic focus in nondominant hemisphere: relieved by section of corpus callosum.
A patient had right hemiparesis since infancy. At age 31, she had recurrent right focal motor and sensory seizures. In prolonged focal seizures, she could not speak but retained most other language-related functions. Intracarotid cerebral amytal testing demonstrated right hemisphere speech. Left intracarotid amytal injection stopped a typical attack. Complete section of the corpus callosum abolished the aphemic episodes and reduced the frequency and intensity of the focal seizures. Focal seizure activity in the left nondominant hemisphere appears to have caused restricted functional disturbance in the right dominant hemisphere.


Effects of drought on gene expression in maize reproductive and leaf meristem tissue revealed by RNA-Seq.
Drought stress affects cereals especially during the reproductive stage. The maize (Zea mays) drought transcriptome was studied using RNA-Seq analysis to compare drought-treated and well-watered fertilized ovary and basal leaf meristem tissue. More drought-responsive genes responded in the ovary compared with the leaf meristem. Gene Ontology enrichment analysis revealed a massive decrease in transcript abundance of cell division and cell cycle genes in the drought-stressed ovary only. Among Gene Ontology categories related to carbohydrate metabolism, changes in starch and Suc metabolism-related genes occurred in the ovary, consistent with a decrease in starch levels, and in Suc transporter function, with no comparable changes occurring in the leaf meristem. Abscisic acid (ABA)-related processes responded positively, but only in the ovaries. Related responses suggested the operation of low glucose sensing in drought-stressed ovaries. The data are discussed in the context of the susceptibility of maize kernel to drought stress leading to embryo abortion and the relative robustness of dividing vegetative tissue taken at the same time from the same plant subjected to the same conditions. Our working hypothesis involves signaling events associated with increased ABA levels, decreased glucose levels, disruption of ABA/sugar signaling, activation of programmed cell death/senescence through repression of a phospholipase C-mediated signaling pathway, and arrest of the cell cycle in the stressed ovary at 1 d after pollination. Increased invertase levels in the stressed leaf meristem, on the other hand, resulted in that tissue maintaining hexose levels at an "unstressed" level, and at lower ABA levels, which was correlated with successful resistance to drought stress.


Early evolution of the ossicular chain in Cetacea: into the middle ear gears of a semi-aquatic protocetid whale.
Modifications of the morphology and acoustic properties of the ossicular chain are among the major changes that accompanied the adaptation of Cetacea to the aquatic environment. Thus, data on the middle ear ossicles of early whales are crucial clues to understand the first steps of the emblematic terrestrial/aquatic transition that occurred in that group. Yet, the delicate nature and very small size of these bones make their preservation in the fossil record extremely rare. Due to the scarcity of available data, major questions remain concerning the sound transmission pathways in early non-fully aquatic whales. Virtual reconstruction of a partially complete ossicular chain of an Eocene protocetid whale documents for the first time the three ossicles of a semi-aquatic archaeocete. Contrary to previous hypotheses, these ossicles present different evolutionary patterns, showing that the ossicular chain does not act as a single morphological module. Functional analyses of the different middle ear units highlight a mosaic pattern of terrestrial and aquatic signatures. This integrative anatomical and functional study brings strong evidence that protocetids were adapted to their dual acoustic environment with efficient hearing in both air and water.


Clostridium difficile causing acute renal failure: case presentation and review.
Clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of Clostridium difficile can be found in up to 5% of the general population. Ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with Clostridium difficile-associated diarrhea or colitis. Little is known about acute renal failure as a consequence of Clostridium difficile-associated diarrhea. In this case report, we describe the course of Clostridium difficile-associated diarrhea in an 82-year-old patient developing acute renal failure. Stopping the offending agent and symptomatic therapy brought a rapid improvement of diarrhea and acute renal failure, full recovery was gained 18 d after admission. In a systematic review we looked for links between the two conditions. The link between Clostridium difficile-associated diarrhea and acute renal failure in our patient was most likely volume depletion. However, in experimental studies a direct influence of Clostridium difficile toxins on renal duct cells could be shown. Rapid diagnosis, nonspecific supportive treatment and specific antibiotic treatment, especially in the elderly, may lower excess mortality Clostridium difficile-associated diarrhea and renal failure being possible complications.


Ecological Instability and Children's Classroom Behavior in Kindergarten.
We engage the concept of ecological instability to assess whether children's exposure to frequent change in multiple contexts is associated with teacher reports of students' overall behavior, externalizing behavior, and approach to learning during kindergarten. We operationalize multiple dimensions of children's exposure to repeated change-including the frequency, concurrency, chronicity, timing, and types of changes children experience-in a nationally representative longitudinal cohort of U.S.-born children (Early Childhood Longitudinal Study-Birth Cohort, N ~ 4,750). We focus on early childhood, a period of substantial flux in children's family and neighborhood contexts. Predicted behavior scores differ by approximately one-fifth of a standard deviation for children who experienced high or chronic exposure to ecological change compared with those who experienced little or no change. These findings emphasize the distinctiveness of multidomain ecological instability as a risk factor for healthy development that should be conceptualized differently from the broader concept of normative levels of change in early childhood environments.


Immunization with adenoviral vectors carrying recombinant IL-12 and E7 enhanced the antitumor immunity against human papillomavirus 16-associated tumor.
Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors. Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-gamma production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed. Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-gamma production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells. IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer.


Pathogenesis of preeclampsia: the genetic component.
Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality in the world, causing nearly 40% of births delivered before 35 weeks of gestation. PE begins with inadequate trophoblast invasion early in pregnancy, which produces an increase in oxidative stress contributing to the development of systemic endothelial dysfunction in the later phases of the disease, leading to the characteristic clinical manifestation of PE. Numerous methods have been used to predict the onset of PE with different degrees of efficiency. These methods have used fetal/placental and maternal markers in different stages of pregnancy. From an epidemiological point of view, many studies have shown that PE is a disease with a strong familiar predisposition, which also varies according to geographical, socioeconomic, and racial features, and this information can be used in the prediction process. Large amounts of research have shown a genetic association with a multifactorial polygenic inheritance in the development of this disease. Many biological candidate genes and polymorphisms have been examined in their relation with PE. We will discuss the most important of them, grouped by the different pathogenic mechanisms involved in PE.


Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes.
Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.


Clinical breast examination for asymptomatic women - exploring the evidence.
Clinical breast examination (CBE) is often offered as a component of the well woman check or carried out at the request of an asymptomatic woman. In these cases the examination is a screening procedure, as opposed to a diagnostic CBE in a symptomatic woman. This article examines the evidence for screening CBE. Screening CBE should involve informed consent. A negative examination does not exclude the presence of breast cancer and women should be aware of this. There have been no randomised controlled trials of CBE alone, only trials comparing CBE with mammography for the detection of breast cancer. While there is a low sensitivity (54%) for CBE, the specificity is high (94%). It is unlikely that these figures are discussed with patients. There are different methods of CBE, and these are described in the literature without a firm evidence base as to effectiveness. However, evidence does suggest that practice on models and retraining help improve clinicians' skills.


Results of treatment of cancer of the cervix in Wellington: 1975-9.
A review was undertaken of all patients treated for invasive carcinoma of the cervix in the Wellington region in the period 1975 to 1979. A total of 84 patients were assessed for the results and complications of treatment. Forty-one were stage I, 18 stage II, 18 stage III, and seven stage IV (FIGO staging). Treatment by different combinations of surgery and radiotherapy for each stage are described. Actuarial survival at five years is 54% for all stages. For stage I it is 86%, stage II 54%, and stage III 44%. There were only seven patients in stage IV. Seven patients (8.3%) suffered major complications, mainly gastrointestinal or genitourinary. Most complications occurred in patients treated with a combination of radical surgery followed by high dose external radiotherapy. This treatment should be reserved for selected patients who can be identified as having a very high risk of recurrence in the pelvis after surgery. Invasive cancer of the cervix is a highly treatable disease, with over half the patients surviving free of disease at five years, but screening programmes for early detection are essential.


A phase II trial of telehealth delivery of the Lidcombe Program of Early Stuttering Intervention.
The aims of this study were to evaluate the efficacy of telehealth delivery of the Lidcombe Program of Early Stuttering Intervention, compared with a control group, and to determine the number of children who could be regarded as "responders." A speech-language pathologist provided telehealth delivery of the Lidcombe Program during telephone consultations with parents in their homes, remote from the clinic. The study design was an open plan, parallel group, randomized controlled trial with blinded outcome assessment. Children in the no-treatment control group who were still stuttering after 9 months then received the same treatment. The primary outcome measure was frequency of stuttering, gathered from audiotape recordings of participants' conversational speech in everyday, nontreatment situations, before and after treatment. Analysis of covariance showed a 73% decrease in frequency of stuttering at 9 months after randomization in the treatment group, as compared with the control group (95% confidence interval = 25%-90%, p = .02). Measures of treatment time showed that telehealth delivery of the Lidcombe Program requires around 3 times more resources than standard presentation. Telehealth delivery of the Lidcombe Program is an efficacious treatment for preschool children who cannot receive the standard, clinic-based Lidcombe Program. Avenues for improving efficiency are considered.


Chromosomal basis of dosage compensation in Drosophila. X. Assessment of hyperactivity of the male X in situ.
The results of examination of the template activity of the fixed polytene chromosomes of Drosophila hydei, monitored by 3H-UTP, under in situ assay conditions, upon the use of endogenous Drosophila polymerase, exogenous Escherichia coli RNA polymerase (holoenzyme) and exogenous Drosophila RNA polymerase II (or B) have been presented. Analysis of the data reveals that the transcription patterns with the 3 enzymes are not strictly comparable with the pattern obtained under in vivo conditions. Yet, with each of the 3 conditions of assay, there is a reasonable concordance between the template activity on the single X chromosome of the male and the paired Xs of the female, as observed under in vivo. There is also, in every case, a high positive correlation between the 3H-UMP incorporation into the X chromosome and that into a specific autosome. A site-wise analysis of 3H-UMP labelling under the 3 assay conditions also reveals that for most of the regions, the sites which are highly active in vivo also show high labelling in situ, and the proportionally is maintained in both sexes. These result have been interpreted to have suggested that the hyperactivity of the male X vis-a-vis dosage compensation in Drosophila is primarily a property of the inherent organization of the X chromosome itself and is achieved through modulation in the organization, rather than exclusively through autosomal factor(s), although a secondary level of autosomal regulation has not yet been ruled out.


[Documentation card for hand surgery].
A punched card for documentation of hand surgery cases is presented. It takes into account both malformations as well as the results of injuries and diseases of the hand. In addition, it affords an exact registration of the localization according to region and topography. Treatment methods in complications are likewise documented, so that a combined search by needling the corresponding numbers can be carried out easily and exactly. The system proved to be completely adequate, inexpensive and practical in the course of testing over seven years.


[The double-pentagastrin test for measuring the gastric secretory capacity in patients of an advanced or great age (author's transl)].
For studying the changes in the gastric secretory capacity that are caused by old age, the double-pentagastrin test is recommended; this test serves to examine the gastric secretory reaction by administering twice pentagastrin in a dose of 6 micrograms/kg. With this suggested method it was possible to find out the age-dependent decrease in the functional possibilities of the gastric secretory system. It is demonstrated that these possibilities are determined by the physiological changes in the gastric secretory system and by the peculiarities of its neurohumoral regulation. Observations indicate an increasing sensitivity, with advancing years, of the secretory cells with respect to pentagastrin and a faster exhaustibility of the gastric secretory reaction if stimulated by pentagastrin.


Selective Heavy Atom Effect Forming Photosensitizing Hot Spots in Double-Stranded DNA Matrix.
Triplet exciton formation is essential for photosensitization-based photochemistry and photobiology. The heavy atom effect (HAE), in the form of either external or internal mode, is a basic mechanism for increasing the triplet exciton yield of photosensitizers. Herein, we report a new HAE mode by noncovalent cohosting of heavy atoms and photosensitizers in a double-stranded DNA (dsDNA) matrix. With dsDNA bearing several thymine (T) or cytosine (C) mismatches, heavy atoms (e.g., Hg2+ or Ag+) and dsDNA-staining dyes (photosensitizers) were spatially adjoined in close proximity, thus resulting in enhanced phosphorescence and 1O2 generation from the photosensitizers. The dsDNA-hosted HAE provides highly selective recognition for the heavy atoms, which is not applicable in either the external or the internal mode. Considering the simpleness and efficiency of the spatially adjoined HAE, as well as the functionality of DNA, the proposed HAE mode is appealing for various singlet oxygen- and phosphorescence-related applications.


Central sleep apnea.
A central sleep apnea is the absence of respiratory effect, and, thus, the absence of airflow during sleep. Central hypopnea, a related disorder, is also discussed. The sensory component of central sleep apnea; defects involving the integrative and executive neurons; non-neurologic causes of central sleep apneas, including chronic obstructive pulmonary disease and congestive heart failure; diagnosis; treatment; and other topics are reviewed in detail.


Any novelty in hippocampal formation and memory?
Novel events tend to attract attention and become more effectively encoded in memory than predictable events. The hippocampus and medial-temporal cortical regions, along with regions of the prefrontal cortex, have been associated with enhanced memory for novel events. This review provides an update on recent studies of hippocampal novelty responses in relation to memory. Several different types of novelty have been studied. Stimulus novelty effects have been observed as reduced neural activity in the medial-temporal and prefrontal regions when the same stimulus is repeatedly presented. Contextual novelty effects, the detection of a stimulus or event in an unexpected context, is impaired in patients with hippocampal damage. Single-trial analyses of brain activity show that the hippocampus rapidly habituates to contextually novel situations. Associative novelty, the detection of new arrangements of familiar stimuli, has also been related to the medial-temporal regions. A division of labour among the medial-temporal regions has been proposed such that associative novelty selectively engages the hippocampus, whereas stimulus novelty is mediated by the perirhinal cortex. However, a simple account of when the hippocampus versus other medial-temporal cortical regions is recruited awaits further studies. Increased dopaminergic and cholinergic neurotransmission may account for enhanced memory encoding of novel events, and relate to structural neuronal changes. Interindividual variability in the responsiveness of the hippocampal-novelty system may be genetically mediated, and personality factors can also play a role. A better understanding of such variability can have implications for interventions aimed at supporting memory and for the treatment of drug abuse.


Surveillance of Nosocomial Infections in a Bulgarian Neonatal Intensive Care Unit.
Nosocomial infections (NI) are frequent complications in neonatal intensive care units (NICU) which result in high morbidity and mortality. To determine and analyze the incidence, risk factors and etiologic agents of NI in newborns admitted in the NICU to help plan-ning future surveillance and prevention strategies. A prospective cohort study was carried out at the NICU of St George University Hospital, Plovdiv, Bul-garia from January 1, 2017 to June 31, 2018. The number of neonates included in the study was 507. Descriptive statistics such as count, percent, mean and standard deviation was used. Chi-square test was performed to prove associations. Odds ratios, with 95% confidence intervals, were computed from the results of the binominal logistic regression analyses. Of the 507 hospitalized newborns in NICU, 48 presented with 54 NI. The incidence and the density incidence rates were 9.5% and 7.67 per 1,000 patient-days, respectively. Nosocomial infections were detected in neonates from all birth weight (BW) classes, but it was low BW and premature neonates that were at major risk to acquire them. The most common infection sites were ventilator-asso-ciated pneumonia (VAP) (67.27%), bloodstream infection (23.64%) and conjunctivitis (9.09%). Major pathogens were Gram-negative such as Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa and Acinetobacter baumannii. In the multivariate logistic regression analysis NIs were strongly associated with intubation, presence of a venous catheter, the duration of antibiotic treatment and increased CRP> 10 mg/l. This report highlights the burden of NIs, identifies the major focus for future NI control and prevention programs.


Time and frequency resolved dynamics of ArBr2.
We report the first spectroscopic observation of and vibrational predissociation dynamics for ArBr(2). Measurements are reported for the linear and T-shaped isomers with time and frequency resolution near the Fourier limit of a 15 ps pulse. For the T-shaped isomer, the Ar-Br(2) bond energy D(0) for the B state, nu(')=19, is found to be 200 cm(-1), yielding a D(0)(X) value of 213 cm(-1). Product appearance rates are determined for nu(')=16-25 of the B state of ArBr(2). While the rate generally increases with increasing vibrational quantum number, the trend is not monotonic. Also, obtaining reproducible rates for any given vibrational level requires very careful control of the experimental conditions. The data suggest that ArBr(2) undergoes vibrational predissociation (VP) in the sparse intramolecular vibrational relaxation regime. These observations are consistent with theoretical calculations that show that T-shaped ArBr(2) undergoes VP in the sparse regime, such that lifetimes are strongly dependent on both the vibrational and rotational quantum numbers. As for ArI(2), a linear isomer of ArBr(2) is found to contribute a quasicontinuous background to the excitation spectra. Direct excitation of this continuum results in a very broad product vibrational distribution.


Structure and development of the pitchers from the carnivorous plantNepenthes alata (Nepenthaceae).
The pitchers of the tropical carnivorous plant Nepenthes alata are highly specialized organs for the attraction and capture of insects and absorption of nutrients from them. This study examined the structure and development of these pitchers, with particular focus on the nectaries and digestive glands. Immature pitchers developed at the tips of tendrils and were tightly sealed by a lid structure that opened during the end of pitcher elongation. Opened pitchers exposed a ridged peristome containing large nectaries. Like other members of the genus, a thick coating of epicuticular waxy scales covered the upper one-third of the pitcher. Scattered within this zone were cells resembling a stomatal complex with a protruding ridge. Cross sections showed that this ridge was formed by asymmetric divisions of the epidermal cells and lacked an underlying pore. The basal region of the trap had large multicellular glands that developed from single epidermal cells. These glands were closely associated with underlying vascular traces and provided a mechanism for supplying fluid to closed immature pitchers.


Personal values in human life.
The construct of values is central to many fields in the social sciences and humanities. The last two decades have seen a growing body of psychological research that investigates the content, structure and consequences of personal values in many cultures. Taking a cross-cultural perspective we review, organize and integrate research on personal values, and point to some of the main findings that this research has yielded. Personal values are subjective in nature, and reflect what people think and state about themselves. Consequently, both researchers and laymen sometimes question the usefulness of personal values in influencing action. Yet, self-reported values predict a large variety of attitudes, preferences and overt behaviours. Individuals act in ways that allow them to express their important values and attain the goals underlying them. Thus, understanding personal values means understanding human behaviour.


A prospective latent analyses study of psychiatric comorbidity of DSM-IV bipolar I and II disorders.
To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood. In the Jorvi Bipolar Study (JoBS), 191 secondary-care outpatients and inpatients with DSM-IV bipolar I disorder (BD-I) or bipolar II disorder (BD-II) were evaluated with the Structured Clinical Interview for DSM-IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD-I, 79 BD-II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM-IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM-IV-based scales of substance use and eating disorders. In the SEM, depression and anxiety exhibited strong cross-sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16-0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15-0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001). Depression and anxiety covary strongly cross-sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.


Development and Validation of a Novel At-home Smell Assessment.
Current tools for diagnosis of olfactory dysfunction (OD) are costly, time-consuming, and often require clinician administration. To develop and validate a simple screening assessment for OD using common household items. This fully virtual diagnostic study included adults with self-reported OD from any cause throughout the US. Data were collected from December 2020 to April 2021 and analyzed from May 2021 to July 2021. Participants with self-reported olfactory dysfunction took a survey assessing smell perception of 45 household items and completed the Clinical Global Impression-Severity (CGI-S) smell questionnaire, the University of Pennsylvania Smell Identification Test (UPSIT), and the 36-item Short Form Survey (SF-36). Psychometric and clinimetric analyses were used to consolidate 45 household items into 2 short Novel Anosmia Screening at Leisure (NASAL) assessments, NASAL-7 (range, 0-14; lower score indicating greater anosmia) and NASAL-3 (range, 0-6; lower score indicating greater anosmia). A total of 115 participants were included in the study, with a median (range) age of 42 (19-70) years, 92 (80%) women, and 97 (84%) White individuals. There was a moderate correlation between the UPSIT and NASAL-7 scores and NASAL-3 scores (NASAL-7: ρ = 0.484; NASAL-3: ρ = 0.404). Both NASAL-7 and NASAL-3 had moderate accuracy in identifying participants with anosmia as defined by UPSIT (NASAL-7 area under the receiver operating curve [AUC], 0.706; 95% CI, 0.551-0.862; NASAL-3 AUC, 0.658; 95% CI, 0.503-0.814). Scoring 7 or less on the NASAL-7 had 70% (95% CI, 48%-86%) sensitivity and 53% (95% CI, 43%-63%) specificity in discriminating participants with anosmia from participants without. Scoring 2 or less on the NASAL-3 had 57% (95% CI, 36%-76%) sensitivity and 78% (95% CI, 69%-85%) specificity in discriminating participants with anosmia from participants without. There was moderate agreement between UPSIT-defined OD categories and those defined by NASAL-7 (weighted κ = 0.496; 95% CI, 0.343-0.649) and those defined by NASAL-3 (weighted κ = 0.365; 95% CI, 0.187-0.543). The agreement with self-reported severity of olfactory dysfunction as measured by CGI-S and the NASAL-7 and NASAL-3 was moderate, with a weighted κ of 0.590 (95% CI, 0.474-0.707) for the NASAL-7 and 0.597 (95% CI, 0.481-0.712) for the NASAL-3. The findings of this diagnostic study suggest that NASAL-7 and NASAL-3, inexpensive and brief patient-reported assessments, can be used to identify individuals with OD. As the burden of COVID-19-associated OD increases, these assessments may prove beneficial as screening and diagnostic tools. Future work will explore whether the NASAL assessments are sensitive to change and how much of a change is clinically important.


Nanotechnology for nanomedicine and delivery of drugs.
Nanotechnology is an emerging technology seeking to exploit distinct technological advances controlling the structure of materials at a reduced dimensional scale approaching individual molecules and their aggregates or supramolecular structures. The manipulation and utilization of materials at nanoscale are expected to be critical drivers of economic growth and development in this century. In recent years, nanoscale sciences and engineering have provided new avenues for engineering materials down to molecular scale precision. The resultant materials have been demonstrated to have enhanced properties and applicability; and these materials are expected to be enabling technologies in the successful development and application of nanomedicine. Nanomedicine is defined as the monitoring, repair, construction, and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. Electrospinning is a simple and cost-effective technique, capable of producing continuous fibers of various materials from polymers to ceramics. The electrospinning technique is used for the preparation of nanofibers and macroporous scaffolds intended for drug delivery and tissue engineering. These have special characteristics in terms of fabrication, porosity, variable diameters, topology and mechanical properties. This review summarizes the recent developments in utilizing nanofibers for drug delivery and tissue engineering applications.


Understanding the Efficiency of Aluminum Coagulants Used in Dissolved Air Flotation (DAF).
This paper reports on the efficiency of five aluminum coagulants for the treatment of a paper mill wastewater by dissolved air flotation (DAF). The coagulants studied were: alum, a polyaluminum chloride coagulant of high aluminum content and intermediate basicity (PAC-MB), another with intermediate aluminum content and high basicity (PAC-HB), a polyaluminum nitrate sulfate of intermediate aluminum content and basicity (PANS) and one hybrid coagulant formed by the combination of PANS and a mixture of polyamines (PANS-PA). The influence of Al speciation on contaminants removal and the main flocculation mechanisms involved have been analyzed. High removal of suspended solids together with significant removal of dissolved and colloidal material (COD and silica) were obtained, which is required for extended reuse of this process water. PAC-HB was the best product for removing suspended solids (85%) and soluble silica (50%) with a rather limited COD removal (5%), while PANS-PA obtained high turbidity (90%) and silica removal (45%) together with a significant soluble COD removal (15%). Monomeric Al (Ala, Alm) was more efficient in removing suspended solids and soluble COD than polymeric or colloidal Al (Alc, Alu), but the latter was more efficient in removing soluble silica. Results demonstrated that the main flocculation mechanism varies with the aluminum dosage, being predominantly charge neutralization at low dosages and sweep flocculation at high dosages. The floc strength factor however, was very high and similar for all the coagulants and dosages tested (85-90%), as it was mainly determined by the behavior of the pre-flocculated suspended solids present in wastewater. The reflocculation factor varied from 45 to 75% at the lowest dosages to almost zero at the highest dosages, confirming the transition from charge neutralization to sweep flocculation. The flocs formed by PANS-PA had lower strength than the others and it decreased with the dosage while its reflocculation factor was almost zero, even at low dosages. Due to the polyamines present in this coagulant, its flocculation mechanism is through both charge neutralization and patch formation, especially at low dosages, and sweep flocculation and interparticle bridge formation at high dosages.


Using serum markers in the early diagnosis of myocardial infarction.
Because thrombolytic therapy can save lives and salvage left ventricular function after acute myocardial infarction, rapid and precise diagnosis is essential. Electrocardiographic changes, and the patient's history and physical examination may not confirm the diagnosis of myocardial infarction. Serum markers have specific advantages and disadvantages in confirming this diagnosis. An understanding of the advantages and disadvantages of using serum markers can enhance the clinician's ability to efficiently and accurately triage patients to appropriate care.


External anal sphincter hyperreflexia following spinal transection in the rat.
In the present study, long-term and short-term rat preparations were used to develop a model for investigating external anal sphincter (EAS) reflexes in intact and spinal cord-injured (SCI) rats. In this model, EAS distension with an external probe elicits reflex contractions of the EAS in intact, unanesthetized animals. At 2 h after spinal cord transection, none of the lesioned animals displayed EAS EMG activity. In fact, once distended, the EAS was incapable of maintaining closure of the anal orifice. Over a period of 4 days, spinalized animals developed a hyperreflexia of the EAS response. By 48 h, the rectified, integrated EAS EMG was significantly elevated in comparison with nonlesioned controls (EAS hyperreflexia). In addition, the duration of the EAS EMG bursts in response to sphincter distension had significantly increased. At 6 weeks after injury, the EAS was significantly hyperreflexic as measured by EMG burst duration and burst area. As with intact animals, posttransection EAS reflexes were highly anesthesia sensitive. These studies indicate that (1) brief distension of the anal orifice is sufficient to evoke a physiologically relevant reflexive activation of the EAS in the rat, (2) the 2- to 24-h postinjury areflexia observed in these experiments may be a suitable model for the study of spinal shock, and (3) the observed EAS hyperreflexia after chronic SCI may represent the permanent effects of removing descending inhibitory circuits and segmental plasticity, making this reflex an appropriate measure of defecatory dysfunction after spinal cord injury.


An amyloid β42-dependent deficit in anandamide mobilization is associated with cognitive dysfunction in Alzheimer's disease.
The endocannabinoids and their attending cannabinoid (CB)(1) receptors have been implicated in the control of cognition, but their possible roles in dementias are still unclear. In the present study, we used liquid chromatography/mass spectrometry to conduct an endocannabinoid-targeted lipidomic analysis of postmortem brain samples from 38 Alzheimer's disease (AD) patients and 17 control subjects, matched for age and postmortem interval. The analysis revealed that midfrontal and temporal cortex tissue from AD patients contains, relative to control subjects, significantly lower levels of the endocannabinoid anandamide and its precursor 1-stearoyl, 2-docosahexaenoyl-sn-glycero-phosphoethanolamine-N-arachidonoyl (NArPE). No such difference was observed with the endocannabinoid 2-arachidonoyl-sn-glycerol or 15 additional lipid species. In AD patients, but not in control subjects, statistically detectable positive correlations were found between (1) anandamide content in midfrontal cortex and scores of the Kendrick's Digit Copy test (p = 0.004, r = 0.81; n = 10), which measures speed of information processing; and (2) anandamide content in temporal cortex and scores of the Boston Naming test (p = 0.027, r = 0.52; n = 18), which assesses language facility. Furthermore, anandamide and NArPE levels in midfrontal cortex of the study subjects inversely correlated with levels of the neurotoxic amyloid peptide, amyloid β-protein (Aβ)(42), while showing no association with Aβ(40) levels, amyloid plaque load or tau protein phosphorylation. Finally, high endogenous levels of Aβ(42) in Swedish mutant form of amyloid precursor protein (APP(SWE))/Neuro-2a cells directly reduced anandamide and NArPE concentrations in cells lysates. The results suggest that an Aβ(42)-dependent impairment in brain anandamide mobilization contributes to cognitive dysfunction in AD.


Immunogenic properties of the human gut-associated archaeon Methanomassiliicoccus luminyensis and its susceptibility to antimicrobial peptides.
The methanogenic archaeon Methanomassiliicoccus luminyensis strain B10T was isolated from human feces just a few years ago. Due to its remarkable metabolic properties, particularly the degradation of trimethylamines, this strain was supposed to be used as "Archaebiotic" during metabolic disorders of the human intestine. However, there is still no data published regarding adaptations to the natural habitat of M. luminyensis as it has been shown for the other two reported mucosa-associated methanoarchaea. This study aimed at unraveling susceptibility of M. luminyensis to antimicrobial peptides as well as its immunogenicity. By using the established microtiter plate assay adapted to the anaerobic growth requirements of methanogenic archaea, we demonstrated that M. luminyensis is highly sensitive against LL32, a derivative of human cathelicidin (MIC = 2 μM). However, the strain was highly resistant against the porcine lysin NK-2 (MIC = 10 μM) and the synthetic antilipopolysaccharide peptide (Lpep) (MIC>10 μM) and overall differed from the two other methanoarchaea, Methanobrevibacter smithii and Methanosphaera stadtmanae in respect to AMP sensitivity. Moreover, only weak immunogenic potential of M. luminyensis was demonstrated using peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (moDCs) by determining release of pro-inflammatory cytokines. Overall, our findings clearly demonstrate that the archaeal gut inhabitant M. luminyensis is susceptible to the release of human-derived antimicrobial peptides and exhibits low immunogenicity towards human immune cells in vitro-revealing characteristics of a typical commensal gut microbe.


Association between sperm morphology and sperm count of boar semen.
The number of spermatozoa in the ejaculate is important for its quality and that of the sperm contained in it. The number of ejaculated spermatozoa is also associated with sperm dimensions. The aim of this study was to assess the morphological structure of sperm and the frequency of morphological abnormalities in sperm on the ejaculation performance of boars, measured as the total number sperm per ejaculate. The study was conducted using 648 ejaculates collected from 31 Large White boars and 30 Landrace boars. All ejaculates were analysed for basic physical characteristics and the frequency of sperm with morphological abnormalities. In addition, morphometric measurements of the sperm were made and used to calculate their shape indexes. As a result of our study it was noted that sperm from ejaculates with the most spermatozoa have shorter heads with a smaller area than sperm from ejaculates with a small or intermediate number of spermatozoa. Landrace boars produce semen of better quality, with a smaller percentage of sperm with major abnormalities, and the differences between the breeds increase with the number of spermatozoa in the ejaculate. The sperm from Landrace boars have larger heads and longer flagella than the sperm from Large White boars. The differences in sperm dimensions between breeds decrease as the total number of spermatozoa in the ejaculate increases. The number of spermatozoa in the ejaculate was shown to influence the dimensions of the sperm. The effect of the number of ejaculated sperm on ejaculate characteristics and sperm morphology depends on the breed of the male.


The origin of the eukaryotic cell.
Molecular sequence data are beginning to provide important insights into the evolutionary origin of eukaryotic cells. Global phylogenies of numerous protein sequences indicate that the eukaryotic cell nucleus is a chimera, which has received major contributions from both a Gram-negative eubacterium and an archaebacterium. Recent studies also indicate that the formation of the nuclear envelope and the endoplasmic reticulum was accompanied by duplication of genes for the molecular chaperone proteins (e.g. hsp70, hsp90), which facilitate protein transport across membranes. Based on these observations, it is suggested that the ancestral eukaryotic cell arose by a unique endosymbiotic event involving engulfment of an eocyte archaebacterium by a Gram-negative eubacterial host.


Optimising the assignment of swabs and reagent for PCR testing during a viral epidemic.
Early large-scale swab testing is a fundamental tool for health authorities to assess the prevalence of a virus and enact appropriate mitigation measures during an epidemic. The COVID-19 pandemic has shown that the availability of chemical reagent required to carry out the tests is often a bottleneck in increasing a country's testing capacity. Further, demand is unevenly spread between more affected regions (which require more tests they can perform) and less affected ones (which have spare capacity). These issues hint at the opportunity of increasing test capacity via the optimal allocation of swabs and reagent to laboratories. We prove that this is the case, proposing an Integer Programming formulation to maximise the number of tests a country can perform and validating our approach on both real-life data from Italy and synthetic instances. Our results show that increased inter-regional collaboration and a steadier supply of reagent (i.e., coming from local production sites rather than international shipments) can dramatically increase testing capacity. Accordingly, we propose short-term and long-term recommendations for policy makers and health authorities.


N-heterocyclic amine-directed structures and properties of two Cu(II) diphosphonates.
By introducing the second organic N-heterocyclic ligands 4'-(4-pyridyl)-4,2':6',4''-terpyridine (pyterpy) and 4,4'-bipyridyl (4,4'-bipy), two examples of Cu(II)-diphosphonates, [Cu(3)(HL)(2)(Hpyterpy)(2)]·2H(2)O 1 and [Cu(4)(HL)(2)(4,4'-bipy)(H(2)O)(5)] 2 based on 1-hydroxyethylidenediphosphonic acid (H(5)L = CH(3)C(OH)(PO(3)H(2))(2)), have been hydrothermally obtained and characterized by powder X-ray diffraction, elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions reveal that compound 1 has a one-dimensional fishbone-like chain constructed by anions [Cu(3)(HL)(2)(2-)](n) while simultaneously organic cations [Hpyterpy(+)](n) suspending both sides, and compound 2 exhibits two-dimensional inorganic-organic alternate arrangement layer built from 1-D ladder-like inorganic chain with tetranuclear cluster [Cu(4)O(10)] via 4,4'-bipy linkage. The results of electrochemical measurements indicate half-wave potential of 1 (E(1/2)(1) = 1.01 V) is less than that of 2 (E(1/2)(2) = 1.20 V), indicating a good D-A system in ICT for 1. Moreover fluorescent measurements reveal that emission intensity of 1 centered at 422 nm is larger than that of 2 emitted at 420 nm, caused by intraligand π*-π emission state of organic N-heterocyclic amine (λ(ex) = 233 nm). Magnetism data indicate that compound 1 exhibits ferrimagnetic interactions between metal centers, while compound 2 has antiferromagnetic property.


Late Bilinguals Are Sensitive to Unique Aspects of Second Language Processing: Evidence from Clitic Pronouns Word-Order.
In two self-paced reading experiments we asked whether late, highly proficient, English-Spanish bilinguals are able to process language-specific morpho-syntactic information in their second language (L2). The processing of Spanish clitic pronouns' word order was tested in two sentential constructions. Experiment 1 showed that English-Spanish bilinguals performed similarly to Spanish-English bilinguals and revealed sensitivity to word order violations for a grammatical structure unique to the L2. Experiment 2 replicated the pattern observed for native speakers in Experiment 1 with a group of monolingual Spanish speakers, demonstrating the stability of processing clitic pronouns in the native language. Taken together, the results show that late bilinguals can process aspects of grammar that are encoded in L2-specific linguistic constructions even when the structure is relatively subtle and not affected for native speakers by the presence of a second language.


Pharmacologic modulation by prostaglandin E1 of superoxide anion production by human polymorphonuclear leukocytes.
Inhibition by prostaglandin E1 (PGE1) of superoxide anion (O2-.) production by isolated intact human neutrophils (PMNs) was investigated utilizing initial-velocity enzyme kinetics. Lag time, linearity, rate, and extent of reaction were simultaneously examined. Dose-response data indicate progressive PGE1-induced suppression of O2-. synthesis by activated PMNs with a Ki value of 0.50 and 0.98 mumol/L for initial velocity and extent of reaction, respectively. There were no significant dose-related trends for either lag time or linearity for reactions with PGE1 concentrations less than 10(-6) mol/L; however, at concentrations of 10(-8) mol/L and greater, the length of reaction was progressively shortened. PGE1 inhibition of PMN-induced O2-. production does not involve PMN activation/desensitization since PGE1 itself cannot stimulate O2-. generation. Moreover, PGE1 does not function as a free-radical scavenger. These data indicate the clinical feasibility of utilizing PGE1 to titrate PMN-induced synthesis of active oxygen metabolites, in order to attenuate PMN-associated host autoinjury.


Behaviour of motor unit action potential rate, estimated from surface EMG, as a measure of muscle activation level.
Surface electromyography (EMG) parameters such as root-mean-square value (RMS) are commonly used to assess the muscle activation level that is imposed by the central nervous system (CNS). However, RMS is influenced not only by motor control aspects, but also by peripheral properties of the muscle and recording setup. To assess motor control separately, the number of motor unit action potentials (MUAPs) per second, or MUAP Rate (MR) is a potentially useful measure. MR is the sum of the firing rates of the contributing MUs and as such reflects the two parameters that the CNS uses for motor control: number of MUs and firing rate.MR can be estimated from multi-channel surface EMG recordings. The objective of this study was to explore the behaviour of estimated MR (eMR) in relation to number of active MUs and firing rate. Furthermore, the influence of parameters related to peripheral muscle properties and recording setup (number of fibers per MU, fiber diameter, thickness of the subcutaneous layer, signal-to-noise-ratio) on eMR was compared with their influence on RMS. Physiological parameters were varied in a simulation model that generated multi-channel EMG signals. The behaviour of eMR in simulated conditions was compared with its behaviour in experimental conditions. Experimental data was obtained from the upper trapezius muscle during a shoulder elevation task (20-100 N). The simulations showed strong, monotonously increasing relations between eMR and number of active MUs and firing rate (r(2) > 0.95). Because of unrecognized superimpositions of MUAPs, eMR was substantially lower than the actual MUAP Rate (aMR). The percentage of detected MUAPs decreased with aMR, but the relation between eMR and aMR was rather stable in all simulated conditions. In contrast to RMS, eMR was not affected by number of fibers per MU, fiber diameter and thickness of the subcutaneous layer. Experimental data showed a strong relation between eMR and force (individual second order polynomial regression: 0.96 < r(2) < 0.99). Although the actual number of MUAPs in the signal cannot be accurately extracted with the present method, the stability of the relation between eMR and aMR and its independence of muscle properties make eMR a suitable parameter to assess the input from the CNS to the muscle at low contraction levels non-invasively.


Immune cells and cytokines - their role in cancer-immunotherapy (review).
Conventional cancer therapies such as surgery, chemotherapy and/or radiotherapy, are not always successful in providing long-term survival for cancer patients. One of the major problems with conventional cancer therapies is their inability to eradicate residual/metastatic tumor cells that are resistant to therapy. Therefore, it is necessary to develop new methods for treating such cancer cells in order to improve the clinical outcome of these patients. Despite antitumor effector mechanisms working against cancer cells in the host's body, tumor-cell-induced immunosuppression and or antigenic modulation by the tumor cells often help tumor cells escape host defense mechanisms. Therefore, one approach for treating residual cancer would be to enhance the host's own immunological/antitumor defense mechanisms. Immune cells that have a significant role in mediating antitumor responses include: T lymphocytes; natural killer (NK) cells; macrophages; and B lymphocytes. The ability of these immune cells to effectively destroy malignant cells is carefully governed by chemical mediators in the form of proteins otherwise known as cytokines. Many cytokines (interleukins, interferons, and tumor necrosis factor) have been shown to enhance in vitro and in vivo effector cell antitumor cytotoxic activities. Utilization of cytokines in conjunction with effector cells can also mediate significant antitumor responses in both animal models and cancer patients. One of the major problems associated with systemic treatment with cytokines is the development of dose limiting toxicities. Currently, attempts to reduce this problem include developing techniques to allow for the preferential release of cytokines in proximity to the tumor cell. In this regard, effector cells or tumor cells that have been genetically engineered to secrete cytokine(s) may be useful in localizing an immune response, preferably at the tumor site. Clinical trial using cytokine gene transfected cells for treating cancer are currently under investigation. With the availability of recombinant lymphokines and with our ability to genetically modify effector cells and tumor cells this hopefully will allow us to improve current therapeutic modalities for treating cancer.


The effect of sulphurous air pollutant exposures on symptoms, lung function, exhaled nitric oxide, and nasal epithelial lining fluid antioxidant concentrations in normal and asthmatic adults.
To explore the effects in normal and asthmatic adults of exposure to 200 ppb sulphur dioxide (SO2) and 200 microg/m3 and 2000 microg/m3 aerosols of ammonium bisulphate (AB) and sulphuric acid (SA) (MMD 0.3 microm). Exposures were placebo controlled, for one hour at rest, double blind in random order. DeltaFEV1 was the primary outcome; secondary outcomes included symptoms, ventilation, exhaled nitric oxide (NO) concentrations, and nasal lavage fluid ascorbic (AA) and uric acid (UA) concentrations. There were no significant changes in spirometry or symptoms with any exposure in either group. SO2 exposure was associated with an increased respiratory rate relative to air exposure in the asthmatic group (SO2: 958.9 breaths/hour; air: 906.8 breaths/hour) but the mean volume breathed did not differ significantly (SO2: 318.8 litres; air: 311.4 litres). AB exposures were associated with a significant rise in [NO] in the asthmatic (+1.51 ppb, and +1.39 ppb), but not in the normal group. Mean pre- and post-exposure [AA] tended to be higher in the normal than in the asthmatic group. Within each group, [AA] did not change significantly with any exposure. Post-exposure [UA] were greater than pre-exposure concentrations for all exposures, significantly so in the normal group for all exposures except SO2. There were no significant differences in the mean change in [UA] for any exposure relative to air. The pollutant exposure concentrations employed in this study were generally much greater than ambient. It is unlikely that short lived exposures at lower concentrations would show significant effects, but effects of longer term lower concentration exposures cannot be ruled out.


Biomechanical properties of labral repair: simple versus vertical suture pattern.
The goal of this study was to evaluate contact area and surface pressure as a result of different suture patterns in the treatment of anterior shoulder instability caused by a Bankart lesion. Loads were applied through the humeral head to the glenoid surface in the intact shoulder and after simple suture labral repair (n=10) and vertical mattress labral repair (n=9). Peak contact pressure, mean contact pressure, and contact area were recorded for 0°, 45°, and 90° shoulder abduction, and then the repair was loaded to failure. A significant increase (P<.05) in mean contact pressure and peak contact pressure occurred in both repair groups at 90° abduction. No difference was seen between the 2 repair groups. Total contact area significantly decreased after both repairs at 90° abduction at 220 N force (P<.05). No significant difference occurred in load to failure between the groups. Joint loading properties can be affected by alterations in contact pressure within the glenohumeral joint. In the current study, the authors found no significant difference in contact pressure between the 2 repair groups. However, they found a significant increase in mean contact pressure and peak pressure between the intact specimen and the 2 repair groups. Both simple repair and vertical mattress repair provided similar load to failure for labral repair. Current techniques used to perform Bankart repair may need to be altered to provide the stability of current techniques with more normal glenohumeral joint contact pressure.


Desensitization of patients allergic to penicillin using orally administered beta-lactam antibiotics.
When patients allergic to penicillin develop life-endangering infections that require treatment with beta-lactam antibiotics, they face a fatal infection or the possibility of a fatal allergic reaction. We have approached this situation by using an oral desensitization procedure before full-dose antibiotic therapy. Thirty consecutive patients with histories of allergic reactions to penicillin, positive immediate wheal and flare skin-test reactions to penicillin determinants, and life-threatening infections were studied. Bacterial endocarditis requiring penicillin G therapy led to desensitization of 19 patients, Pseudomonas sepsis of pneumonia requiring treatment led to desensitization of nine subjects, and staphylococcal infections requiring therapy with a penicillinase-resistant penicillin led to desensitization of two patients. Penicillin G or carbenicillin were administered orally, beginning with 100 U or 60 microgram, respectively. At 15-min intervals, progressively doubled doses were given during continuous monitoring for the appearance of allergic reactions. Within 5 hr, full therapeutic doses were administered intravenously. Skin-test reactions disappeared or diminished in all 23 subjects who were retested after desensitization. Full courses of antibiotic therapy and cure of the infections were accomplished in 30 of 30 patients. No deaths, anaphylaxis, or severe acute allergic reactions occurred. Pruritic cutaneous eruptions appeared in nine patients (30%) 6 to 48 hr after the onset of therapy. One patient developed reversible nephritis 3 wk into therapy with penicillin G. The results of this study suggest that oral desensitization is an effective, relatively safe approach to administering beta-lactam antibiotics to penicillin-allergic patients with life-threatening infections.


Do Robotic Surgical Systems Improve Profit Margins? A Cross-Sectional Analysis of California Hospitals.
The aim of this study was to examine the association between ownership of robotic surgical systems and hospital profit margins. This study used hospital annual utilization data, annual financial data, and discharge data for year 2011 from the California Office of Statewide Health Planning and Development. We first performed bivariate analysis to compare mean profit margin by hospital and market characteristics and to examine whether these characteristics differed between hospitals that had one or more robotic surgical systems in 2011 and those that did not. We applied the t test and the F test to compare mean profit margin between two groups and among three or more groups, respectively. We then conducted multilevel logistic regression to determine the association between ownership of robotic surgical systems and having a positive profit margin after controlling for other hospital and market characteristics and accounting for possible correlation among hospitals located within the same market. The study sample included 167 California hospitals with valid financial information. Hospitals with robotic surgical systems tended to report more favorable profit margins. However, multilevel logistic regression showed that this relationship (an association, not causality) became only marginally significant (odds ratio [OR] = 6.2; P = 0.053) after controlling for other hospital characteristics, such as ownership type, teaching status, bed size, and surgical volumes, and market characteristics, such as total number of robotic surgical systems owned by other hospitals in the same market area. As robotic surgical systems become widely disseminated, hospital decision makers should carefully evaluate the financial and clinical implications before making a capital investment in this technology.


Purification of hemopoietic progenitor cells from human marrow using a fucose-binding lectin and cell sorting.
Human peripheral blood granulocytes, but not lymphocytes, erythrocytes, or monocytes, bound the fucose-binding lectin from Lotus tetragonolobus (FBP), and this binding was competitively inhibited by the sugar alpha-L-fucose. The fluorescence-activated cell sorter was used to study the appearance of this receptor on human marrow cells during granulocyte differentiation and to prepare fractions enriched for granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming cells--GM-CFC). Cell binding of fluoresceinated FBP increased for bone marrow cells in the sequence--lymphocytes, blast cells, promyelocytes and myelocytes, monocytes, and polymorphonuclear cells. Selection of cells with appropriate low-angle or high-angle light scatter characteristics achieved a 10-fold or 2-3-fold enrichment of progenitor cells, respectively. By selecting cells with intermediate fluorescence intensity, a further 2-3-fold enrichment for GM-CFC was obtained. Cell sorting using the optimal selection of these three parameters produced up to 36-fold enrichment of the progenitor cells from human bone marrow. The most enriched fraction was composed of 23% progenitor cells (colony- and cluster-forming cells) with a yield of 36%. In populations most highly enriched by GM-CFC, immature cells (blast cells, promyelocytes, and myelocytes) made up 95% of the cells present.


CAHPS in practice: the Iowa demonstration.
This article evaluates the usefulness of the Consumer Assessment of Health Plan Study (CAHPS) surveys and reports in a demonstration and evaluation with three health care purchasers in Iowa. The CAHPS survey detected significant differences between health plans in several domains of health care. Both paper- and Web-based consumer reports were developed and distributed to consumers and stakeholders. There was some agreement on the value of these reports, but areas for improvement were noted.