Impact of sugars and sugar taxation on body weight control: A comprehensive literature review.
To conduct a comprehensive literature review in the field of added-sugar consumption on weight gain including the effect of fructose-containing caloric sweeteners and sugar taxation. A search of three databases was conducted in the time period from the inception of the databases to August 2015. Sensitive search strategies were used in order to retrieve systematic reviews (SR) of fructose, sucrose, or sugar-sweetened beverages (SSBs) on weight gain and metabolic adverse effects, conducted on humans and written in English, Spanish, or French. In addition, a review about SSB taxation and weight outcomes was conducted. The search yielded 24 SRs about SSBs and obesity, 23 SRs on fructose or SSBs and metabolic adverse effects, and 24 studies about SSB taxation and weight control. The majority of SRs, especially the most recent ones, with the highest quality and without any disclosed conflict of interest, suggested that the consumption of SSBs is a risk factor for obesity. The effect of fructose-containing caloric sweeteners, on weight gain is mediated by overconsumption of beverages with these sweeteners, leading to an extra provision of energy intake. The tax tool alone on added sugars appears insufficient to curb the obesity epidemic, but it needs to be included in a multicomponent structural strategy.


Splenic injury sustained during body hardening drills and the utility of ultrasound in a prehospital combat medical environment.
This report describes a case of intra-abdominal hemorrhage from body hardening drills in a U.S. soldier during Operation Iraqi Freedom. In body hardening, participants allow themselves to be repeatedly punched and kicked in an effort to impart physical resilience. Portable sonography was used to diagnose hemoperitoneum and to guide the decision for urgent surgical evacuation, ultimately resulting in splenectomy. The case illustrates the risks of body hardening, the medical challenges unique to a prehospital combat environment, and the utility of ultrasound in this setting.


Acute ibuprofen ingestion does not attenuate fatigue during maximal intermittent knee extensor or all-out cycling exercise.
Recent research suggests that acute consumption of pharmacological analgesics can improve exercise performance, but the ergogenic potential of ibuprofen (IBP) administration is poorly understood. This study tested the hypothesis that IBP administration would enhance maximal exercise performance. In one study, 13 physically active males completed 60 × 3-s maximal voluntary contractions (MVCs) of the knee extensors interspersed with 2-s passive recovery periods, on 2 occasions, with the critical torque (CT) estimated as the mean torque over the last 12 contractions (part A). In another study, 16 active males completed two 3-min all-out tests against a fixed resistance on an electronically braked cycle ergometer, with the critical power estimated from the mean power output over the final 30 s of the test (part B). All tests were completed 60 min after ingestion of maltodextrin (placebo, PL) or 400 mg of IBP. Peripheral nerve stimulation was administered at regular intervals and electromyography was measured throughout. For part A, mean torque (IBP: 60% ± 13% of pre-exercise MVC; PL: 58% ± 14% of pre-exercise MVC) and CT (IBP: 41% ± 16% of pre-exercise MVC; PL: 40% ± 15% of pre-exercise MVC) were not different between conditions (P > 0.05). For part B, end-test power output (IBP: 292 ± 28 W; PL: 288 ± 31 W) and work done (IBP: 65.9 ± 5.9 kJ; PL: 65.4 ± 6.4 kJ) during the 3-min all-out cycling tests were not different between conditions (all P > 0.05). For both studies, neuromuscular fatigue declined at a similar rate in both conditions (P > 0.05). In conclusion, acute ingestion of 400 mg of IBP does not improve single-leg or maximal cycling performance in healthy humans.


Toward Reducing hERG Affinities for DAT Inhibitors with a Combined Machine Learning and Molecular Modeling Approach.
Psychostimulant drugs, such as cocaine, inhibit dopamine reuptake via blockading the dopamine transporter (DAT), which is the primary mechanism underpinning their abuse. Atypical DAT inhibitors are dissimilar to cocaine and can block cocaine- or methamphetamine-induced behaviors, supporting their development as part of a treatment regimen for psychostimulant use disorders. When developing these atypical DAT inhibitors as medications, it is necessary to avoid off-target binding that can produce unwanted side effects or toxicities. In particular, the blockade of a potassium channel, human ether-a-go-go (hERG), can lead to potentially lethal ventricular tachycardia. In this study, we established a counter screening platform for DAT and against hERG binding by combining machine learning-based quantitative structure-activity relationship (QSAR) modeling, experimental validation, and molecular modeling and simulations. Our results show that the available data are adequate to establish robust QSAR models, as validated by chemical synthesis and pharmacological evaluation of a validation set of DAT inhibitors. Furthermore, the QSAR models based on subsets of the data according to experimental approaches used have predictive power as well, which opens the door to target specific functional states of a protein. Complementarily, our molecular modeling and simulations identified the structural elements responsible for a pair of DAT inhibitors having opposite binding affinity trends at DAT and hERG, which can be leveraged for rational optimization of lead atypical DAT inhibitors with desired pharmacological properties.


Protective effect of Alstonia scholaris Linn. R. Br. against Bleomycin induced chromosomal damage in cultured human lymphocytes, in vitro.
It is both interesting and necessary to identify and develop nontoxic radioprotective compounds. Bleomycin (BLM), a known radiomimetic drug was used as a clastogen in the present study. The possible protective effects against BLM (15 μg/ml) induced clastogenicity by aqueous and methanolic extracts from Alstonia scholaris bark, stem and leaves were compared. The treatment of bark extracts significantly (p < 0.01) reduced total chromosomal aberrations. Such a reduction was not seen in case of stem and leaf treatments. The dose of 50 μg/ml was fixed for all extracts throughout the study. To understand the mechanism involved with the protective property of bark extracts, sensitive G2 assay was performed. Lymphocyte cultures from 12 healthy volunteers were exposed to aqueous (50 μg/ml) and methanolic (50 μg/ml) extracts of A. scholaris bark alone as well as in combination with Bleomycin under two different growth phases, G0 and G2. There was a statistically significant reduction (p < 0.05) in the total chromatid breaks in all cultures which were exposed at G2 phase as compared to respective cultures exposed at G0 phase. The highest level (p < 0.0001) of reduction in total chromatid breaks was observed in cultures treated with aqueous bark extracts at G2 phase than those at G0 phase. This indicated that there could be certain compound(s) present in aqueous bark extracts which enhance DNA repair capacity. Therefore, the bark of A. scholaris could be further utilized to identify and bring out front line radio protective agents in the market with effective formulations.


The Portal Vein: A Comprehensive Review.
Radiologists are familiar with the appearances of a normal portal vein; variations in its anatomy are commonplace and require careful consideration due to the implications for surgery. These alterations in portal vein anatomy have characteristic appearances that are clearly depicted on CT, MR, and US images. Similarly, there are numerous congenital and acquired disorders of the portal vein that are deleterious to its function and can be diagnosed by using imaging alone. Some of these conditions have subtle imaging features, and some are conspicuous at imaging but poorly understood or underrecognized. The authors examine imaging appearances of the portal vein, first by outlining the classic and variant anatomy and then by describing each of the disorders that impact portal vein function. The imaging appearances of portal vein abnormalities discussed in this review include (a) occlusion from and differentiation between bland thrombus and tumor in vein and the changes associated with resultant hepatic artery buffer response changes, cavernous transformation of the portal vein, and portal biliopathy; (b) ascending thrombophlebitis of the portal vein (pylephlebitis); (c) portal hypertension and its causes and sequelae; (d) the newly described disease entity portosinusoidal vascular disorder; and (e) intra- and extrahepatic shunts of the portal system, both congenital and acquired (including Abernethy malformations), and the associated risks. Current understanding of the pathophysiologic processes of each of these disorders is considered to aid the approach to reporting. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.


Influence of covariates on heterogeneity in Hamilton Anxiety Scale ratings in placebo-controlled trials of benzodiazepines in generalized anxiety disorder: Systematic review and meta-analysis.
Generalized anxiety disorder is a common psychiatric condition that is associated with decreased quality of life and significant disability. Benzodiazepines are anti-anxiety drugs used widely in the treatment of generalized anxiety disorder. This study examines the influence of several variables on benzodiazepine efficacy in generalized anxiety disorder. We performed a systematic review of placebo-controlled randomized controlled trials with benzodiazepines in generalized anxiety disorder. Fifty-eight studies were deemed eligible to include in the meta-analysis. The studies dated from 1977 to 2013 and included over 5400 participants. From each paper, we extracted: benzodiazepine name and dose, dosing regimen, baseline Hamilton Anxiety Scale (HAM-A) score, change in HAM-A score at study endpoint, drop-out rate, year of study publication, diagnostic criteria used, study size, study duration, location, any conflicts of interest and side-effect profile. We then assessed the influence, direct and indirect, of individual variables on the primary outcome (mean difference at endpoint, HAM-A score). Three factors were shown to be associated statistically with change in HAM-A; baseline HAM-A for benzodiazepine arm, baseline HAM-A for the placebo arm, and duration of the study. A higher baseline HAM-A in both arms was associated with a greater mean difference in HAM-A. A shorter study length was also associated with a greater mean difference. The major factors determining benzodiazepine response was baseline anxiety level for the benzodiazepine arm and study duration. In any design of further meta-analyses and clinical trials for generalized anxiety disorder we suggest that these should be considered these as confounding factors.


Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells.
Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect. With cell viability, flow cytometry, PCR and western blot analysis, we demonstrated the efficacious anticancer activity of Res in HCT116 cells. Mechanically, we found that Res greatly upregulates BMP7 in HCT116 cells. Exogenous BMP7 enhances the anticancer effect of Res in HCT116 cells, which was almost reversed by the BMP7 specific antibody. Res does not activate the BMPs/Smads signaling, but decreases the phosphorylation of Akt1/2/3 substantially in HCT116 cells. Exogenous BMP7 enhances the inhibitory effect of Res on the phosphorylation of Akt1/2/3, while BMP7 immunodepletion reverses this effect notably. Res markedly decreases the phosphorylation of PTEN, which can be enhanced by exogenous BMP7 but partly reversed by the BMP7 antibody. Our findings suggested that Res may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating BMP7 to decrease, at least, the phosphorylation of PTEN.


Heterogeneous reactions of ozone and D-limonene on activated carbon.
If released in significant amounts, products formed by reactions between ozone (O3) and volatile organic compounds (VOCs) sorbed on activated carbon (AC) filters could degrade indoor air quality (IAQ). Heterogeneous reactions were investigated in laboratory experiments aimed at characterizing reaction products. Effluent air of AC loaded with limonene and exposed to O3 (5.8 ppm) yielded unreacted limonene (501+/-197 microg/m3), low levels of 4-acetyl-1-methylcyclohexene (AMCH) (20+/-2 microg/m3), and limonene oxides (25+/-7 microg/m3). Most of the O3-limonene products remained on the AC, and most (58%) of the limonene remained unreacted on the AC after exposure to a stoichiometric excess of O3 for 48 h. Thus, in addition to known homogenous reactions, O3-limonene reactions occur heterogeneously on AC but to a much lesser extent. However, the fate of 95% of the depleted limonene was not determined; much of the missing portion was attributed to desorption from the AC, but the formation of other secondary indoor air pollutants is possible. VOC-loaded AC air filters exposed to O3 seem unlikely, however, to constitute a significant emission source of reaction products. More studies are necessary to investigate other pollutants, effects of environmental conditions, and VOC releases from AC that may be enhanced by O3 exposure. Reactions between ozone and certain volatile organic compounds such as limonene (a common ingredient of many consumer products) occurring on the surface of ventilation filters could impact indoor air quality if products are released in significant amounts. This study suggests that although very small amounts of limonene adsorbed on a filter will react with O3, ventilation filters are not likely to be significant sources of ozone oxidation products. More studies are needed to investigate whether ozone exposure enhances desorption of pollutants from ventilation filters and to measure the formation of formaldehyde and other products that are not easily retained by charcoal filters.


Disruption of MET Receptor Tyrosine Kinase, an Autism Risk Factor, Impairs Developmental Synaptic Plasticity in the Hippocampus.
As more genes conferring risks to neurodevelopmental disorders are identified, translating these genetic risk factors into biological mechanisms that impact the trajectory of the developing brain is a critical next step. Here, we report that disrupted signaling mediated MET receptor tyrosine kinase (RTK), an established risk factor for autism spectrum disorders, in the developing hippocampus glutamatergic circuit leads to profound deficits in neural development, synaptic transmission, and plasticity. In cultured hippocampus slices prepared from neonatal mice, pharmacological inhibition of MET kinase activity suppresses dendritic arborization and disrupts normal dendritic spine development. In addition, single-neuron knockdown (RNAi) or overexpression of Met in the developing hippocampal CA1 neurons leads to alterations, opposite in nature, in basal synaptic transmission and long-term plasticity. In forebrain-specific Met conditional knockout mice (Metfx/fx ;emx1cre ), an enhanced long-term potentiation (LTP) and long-term depression (LTD) were observed at early developmental stages (P12-14) at the Schaffer collateral to CA1 synapses compared with wild-type littermates. In contrast, LTP and LTD were markedly reduced at young adult stage (P56-70) during which wild-type mice show robust LTP and LTD. The altered trajectory of synaptic plasticity revealed by this study indicate that temporally regulated MET signaling as an intrinsic, cell autonomous, and pleiotropic mechanism not only critical for neuronal growth and functional maturation, but also for the timing of synaptic plasticity during forebrain glutamatergic circuits development.


The vitamin D status of East Indian Punjabi immigrants to Canada.
1. Serum 25-hydroxyvitamin D (25-OHD), calcium and alkaline phosphatase (EC 22.214.171.124) levels and vitamin D intakes (from 3 d weighed dietary records) were determined in a cohort of fifty-nine male East Indian Punjabi immigrants (37.7 (SD 10.5) years) and fifty-four females (33.3 (SD 7.4) years). 2. Females had somewhat lower mean serum 25-OHD levels (12.3 (SD 5.0) v. 14.2 (SD 5.1) ng/ml, P less than 0.05) and serum Ca levels (88 (SD 8) v. 91 (SD 6) mg/l) than males (P less than 0.05) whereas serum alkaline phosphatase values (males 167 (SD 63), females 169 (SD 43) IU/l) and dietary vitamin D intakes (males 3.5 (SD 1.8), females 3.3 (SD 2.0) micrograms/d) were similar. 3. 22% of the females and 12% of the males had serum 25-OHD levels below 9.0 ng/ml but none had serum 25-OHD levels within the range associated with clinically overt disease. 4. In the males, serum 25-OHD levels were negatively correlated with dietary fibre intakes (g/d; r -0.29; P less than 0.05). 5. Multiple-regression analysis indicated that log serum 25-OHD levels were not related to dietary vitamin D intakes. Instead they were associated with sex and dietary fibre intakes (g/MJ) (F 3.71; P = 0.03). These two variables explained 8% of the variance.


Mimicking Form and Function of Native Small Diameter Vascular Conduits Using Mulberry and Non-mulberry Patterned Silk Films.
Autologous graft replacement as a strategy to treat diseased peripheral small diameter (≤6 mm) blood vessel is often challenged by prior vein harvesting. To address this issue, we fabricated native-tissue mimicking multilayered small diameter vascular graft (SDVG) using mulberry (Bombyx mori) and Indian endemic non-mulberry (Antheraea assama and Philosamia ricini) silk. Patterned silk films were fabricated on microgrooved PDMS mold, casted by soft lithography. The biodegradable patterned film templates with aligned cell sheets were rolled onto an inert mandrel to mimic vascular conduit. The hemocompatible and mechanically strong non-mulberry films with RGD motif supported ∼1.2 folds greater proliferation of vascular cells with aligned anchorage. Elicitation of minimal immune response on subcutaneous implantation of the films in mice was complemented by ∼45% lower TNF α secretion by in vitro macrophage culture post 7 days. Pattern-induced alignment favored the functional contractile phenotype of smooth muscle cells (SMCs), expressing the signature markers-calponin, α-smooth muscle actin (α-SMA), and smooth muscle myosin heavy chain (SM-MHC). Endothelial cells (ECs) exhibited a typical punctuated pattern of von Willebrand factor (vWF). Deposition of collagen and elastin by the SMCs substantiated the aptness of the graft with desired biomechanical attributes. Furthermore, the burst strength of the fabricated conduit was in the range of ∼915-1260 mmHg, a prerequisite to withstand physiological pressure. This novel fabrication approach may eliminate the need of maturation in a pulsatile bioreactor for obtaining functional cellular phenotype. This work is thereby an attestation to the immense prospects of exploring non-mulberry silk for bioengineering a multilayered vascular conduit similar to a native vessel in "form and function", befitting for in vivo transplantation.


[Computerized analysis of cardiovascular activity in the conscious unrestrained rat. Application to the study of a new antihypertensive agent].
A more precise knowledge of cardiovascular activity in rats needs its direct recording for long periods of time, in conscious unrestrained animals. A system has been developed, which allows direct recording of blood pressure (BP) in freely moving rats, by means of a floating catheter chronically inserted in the abdominal aorta, connected to a rotating swivel, and then to a pressure transducer. A mini-computer performs on-line processing of BP curves, and stores the values of 5 cardiovascular parameters on hard disk: systolic, diastolic and mean arterial pressures, heart rate and dp/dt max. Off line processing allows graphic and statistical analysis of the data. Simultaneously recording from two rats is very useful in pharmacology because a treated animal and a control one are studied at the same time and in the same conditions. This methodology was used to evaluate the effects of a chronic treatment (2 mg/kg, ip, during 8 days) and of single injections (0.5 and 3 mg/kg, iv) of a new antihypertensive substance, CM 40441a, in 15 W old males SHR.


Surrounding control of nonlinear multi-agent systems with non-identical agents.
In this paper, the surrounding control problem of a group of non-identical agents is considered, where a team of followers achieves an equidistant distributed formation to surround a team of moving leaders. An adaptive design method is presented for multi-agent systems where the dynamics of agents are supposed to be nonlinear with unknown parameters. First, an estimator for the center of the leaders is introduced. Then, two distributed adaptive controllers based on the estimated center are proposed for each follower. The stability and parameter convergence of the proposed protocols are shown by using algebraic graph theory and Lyapunov theory. Finally, a numerical example is provided to validate the theoretical results.


Smoking and COPD Knowledge in the General Spanish Population: A CONOCEPOC Study.
The objective of this analysis is to evaluate tobacco use and the level of chronic obstructive pulmonary disease (COPD) knowledge among the general adult population in Spain and to compare these results to those obtained in the 2011 survey. A cross-sectional, observational, epidemiological study was conducted by telephone interviews and stratified by sex, age, and setting. The study design was identical to that of the study conducted in 2011. Of a total of 89,601 phone contacts, there were 6534 respondents. The average age was 61.5 years. With respect to smoking, 30.9% reported being former smokers and 14.7% were current smokers, 63.6% of whom reported having attempted to quit. Among the current smokers, 19.7% claimed to use electronic cigarettes, although 88% believe these pose a health risk. No significant differences were found in smoking prevalence or frequency of attempts to quit according to residential setting (rural/urban). The highest prevalence of current smoking in men was recorded in the 55-64 years age range (31.6%), while in women it was from 45 to 54 years (34.6%). Smoking has decreased with respect to 2011, from 21.1% to 16.1% in men and from 17.9% to 13.2% in women, with a clear variability according to region. Of the population surveyed, 32.5% had spontaneous knowledge about COPD, with significant geographic variability. The most frequent sources of information about the disease were social media and the Internet (39.6%), followed by the media (35.2%). The prevalence of tobacco use in adults has considerably decreased and there is greater knowledge about COPD in Spain, although there is significant variability according to region, which could explain the geographic variability in the prevalence of COPD. Strategies are needed to increase COPD education and awareness and to reinforce smoking prevention measures among women.


Evidence for multiple cycles of strand invasion during repair of double-strand gaps in Drosophila.
DNA double-strand breaks (DSBs), a major source of genome instability, are often repaired through homologous recombination pathways. Models for these pathways have been proposed, but the precise mechanisms and the rules governing their use remain unclear. In Drosophila, the synthesis-dependent strand annealing (SDSA) model can explain most DSB repair. To investigate SDSA, we induced DSBs by excision of a P element from the male X chromosome, which produces a 14-kb gap relative to the sister chromatid. In wild-type males, repair synthesis tracts are usually long, resulting in frequent restoration of the P element. However, repair synthesis is often incomplete, resulting in internally deleted P elements. We examined the effects of mutations in spn-A, which encodes the Drosophila Rad51 ortholog. As expected, there is little or no repair synthesis in homozygous spn-A mutants after P excision. However, heterozygosity for spn-A mutations also resulted in dramatic reductions in the lengths of repair synthesis tracts. These findings support a model in which repair DNA synthesis is not highly processive. We discuss a model wherein repair of a double-strand gap requires multiple cycles of strand invasion, synthesis, and dissociation of the nascent strand. After dissociation, the nascent strand may anneal to a complementary single strand, reinvade a template to be extended by additional synthesis, or undergo end joining. This model can explain aborted SDSA repair events and the prevalence of internally deleted transposable elements in genomes.


Consequences of infertility in developing countries.
Infertility affects more than 10% of the world's population. In developing countries, there are severe social, psychological and economic consequences for infertile men and women. All of the cited references are compiled from primary peer-reviewed research articles that were conducted through one-to-one interviews or focus groups in countries of developing regions, such as Africa, Asia and the Middle East. The following paper seeks to raise awareness of the consequences of infertility in developing nations and identify infertility as an under-observed, but significant public health issue. It is proposed that education programmes tailored to each society's specific religious beliefs and grounded traditions must be implemented in order to reverse the social stigma, detrimental psychological effects, and loss of economic security that results from infertility.


BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis.
We have evaluated the role played by BRCA1 in mediating the phenotypic response to a range of chemotherapeutic agents commonly used in cancer treatment. Here we provide evidence that BRCA1 functions as a differential mediator of chemotherapy-induced apoptosis. Specifically, we demonstrate that BRCA1 mediates sensitivity to apoptosis induced by antimicrotubule agents but conversely induces resistance to DNA-damaging agents. These data are supported by a variety of experimental models including cells with inducible expression of BRCA1, siRNA-mediated inactivation of endogenous BRCA1, and reconstitution of BRCA1-deficient cells with wild-type BRCA1. Most notably we demonstrate that BRCA1 induces a 10-1000-fold increase in resistance to a range of DNA-damaging agents, in particular those that give rise to double-strand breaks such as etoposide or bleomycin. In contrast, BRCA1 induces a >1000-fold increase in sensitivity to the spindle poisons, paclitaxel and vinorelbine. Fluorescence-activated cell sorter analysis demonstrated that BRCA1 mediates G(2)/M arrest in response to both antimicrotubule and DNA-damaging agents. However, poly(ADP-ribose) polymerase and caspase-3 cleavage assays indicate that the differential effect mediated by BRCA1 in response to these agents occurs through the inhibition or induction of apoptosis. Therefore, our data suggest that BRCA1 acts as a differential modulator of apoptosis depending on the nature of the cellular insult.


Antenatal depressive symptoms in Jamaica associated with limited perceived partner and other social support: A cross-sectional study.
Antenatal depression is associated with adverse maternal and infant well-being. However, compared to postpartum depression, it has been less frequently explored globally or in Jamaica. This study aimed to determine the prevalence of, and factors associated with, antenatal depressive symptoms among Jamaican women in order to inform policy and build interventions that could improve their management and reduce their negative consequences. This secondary analysis of data from the second Jamaican Birth Cohort Study (JA-Kids Birth Cohort) included 3,517 women enrolled during pregnancy. Information was extracted from interviewer-administered questionnaires which recorded social, demographic, medical and obstetric information during pregnancy. The Edinburgh Postnatal Depression scale (EPDS) was used to screen for depression, with scores ≥13 considered indicative of a high likelihood of depression. Bivariate analysis examined associations between depressive symptoms and: age, income, financial difficulties, perceived social support, perceived partner infidelity, previous child-bearing unions and children with the current partner. Obstetric factors were also explored and included gravidity, prior adverse pregnancy outcome and complications from previous pregnancies. Variables that predicted the likelihood of depression based on an EPDS cut score of 13 were evaluated using logistic regression. One in five participants (19.6%; 95% CI 18.3-20.9%) had a high likelihood of antenatal depression (EPDS ≥13). Significant predictors of high depressive symptom severity included four indicators of poor perceived social and partner support [ORs (95% CI) ranged from: 1.61 (1.07-2.43); p = 0.024 to 3.14(1.69-5.84); p< 0.001], perceived partner infidelity [1.86 (1.36, 2.54); p<0.001], exposure to violence [2.36 (1.66-3.38); p<0.001] and financial difficulties [1.39 (1.07, 1.80); p = 0.013]. Women's perceived social and partner support were strongly associated with depressive symptom severity. Within the Jamaican cultural context of unstable reproductive unions, efforts are needed to involve fathers in the antenatal care process to strategically improve the psychological well-being of new mothers which may positively influence long term developmental outcomes for their babies.


Global action for training in malaria elimination.
The Rethinking Malaria Leadership Forum, held at Harvard Business School in February 2017 with collaboration of the Barcelona Institute for Global Health and the Swiss Tropical and Public Health Institute, identified this training gap as a high priority for both analysis and action. The gap in human resource training for malaria elimination needs to be addressed in order to assure continued progress. This paper identifies major gaps in skills and human resources, suggests institutions that can assist in filling the training gaps, and proposes global actions to implement expanded training for malaria elimination in endemic countries.


Antithrombin III in Sepsis. New evidences and open questions.
Antithrombin III (ATIII) has been found to be a marker for DIC and to be of prognostic significance in septic patients. Several studies have shown that administration of ATIII in patients with sepsis related DIC is effective in shortening the duration of DIC. Despite a meta-analysis of randomized controlled trials have shown a significant reduction in 28-day mortality, a prospective randomized double-blind placebo-controlled trial failed to show a significant improvement in overall survival. However the concomitant use of heparin, which does not seem to have an additional beneficial effect, may have obscured the efficacy of ATIII. More studies are needed to understand mechanism of action of ATIII and better define patient population that may benefit from ATIII.


Purification of Plant Receptor Kinases from Plant Plasma Membranes.
Receptor kinases play a central role in various biological processes, but due to their low abundance and highly hydrophobic and dynamic nature, only a few of them have been functionally characterized, and their partners and ligands remain unidentified. Receptor protein extraction and purification from plant tissues is one of the most challenging steps for the success of various biochemical analyses to characterize their function. Immunoprecipitation is a widely used and selective method for enriching or purifying a specific protein. Here we describe two different optimized protein purification protocols, batch and on-chip immunoprecipitation, which efficiently isolate plant membrane receptor kinases for functional analysis.


Topoisomerase IIα immunoexpression in feline mammary carcinomas: A correlation with Ki67 immunoexpression and the mitotic count.
The aim of the study was to compare the immunohistochemical expression of topoisomerase IIα protein (Topo IIα) with Ki67 expression and mitotic count in feline mammary carcinomas (FMCs). Topo IIα is considered as a proliferation indicator as well as a molecular target of anthracycline chemotherapy. The studied material included 70 FMCs from female cats treated with mastectomy. Primary mouse monoclonal antibodies directed against Topo IIα and Ki67 were used in immunohistochemical reactions. The number of mitotic figures was counted at 400× magnification in a field of 2.37 mm2. Immunohistochemical reaction for Topo IIα occurred in cell nuclei. The Topo IIα index ranged from 6.12% to 54.60% and was positively correlated with the values of the Ki67 index (r = 0.7193) and the mitotic count (r = 0. 2858). This indicates the potential possibility of use of the immunohistochemical expression of Topo IIα to assess the rate of proliferation in FMCs. The wide range of expression of Topo IIα in individual tumorus found in the conducted studies allows us to hypothesize that its assessment could be used as a predictive marker in chemotherapy of FMCs with the use of anthracyclines. However, this requires confirmation in clinical trials.


β-Adrenergic signaling, monoamine oxidase A and antioxidant defence in the myocardium of SHR and SHR-mtBN conplastic rat strains: the effect of chronic hypoxia.
The β-adrenergic signaling pathways and antioxidant defence mechanisms play important roles in maintaining proper heart function. Here, we examined the effect of chronic normobaric hypoxia (CNH, 10% O2, 3 weeks) on myocardial β-adrenergic signaling and selected components of the antioxidant system in spontaneously hypertensive rats (SHR) and in a conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of the more ischemia-resistant Brown Norway strain. Our investigations revealed some intriguing differences between the two strains at the level of β-adrenergic receptors (β-ARs), activity of adenylyl cyclase (AC) and monoamine oxidase A (MAO-A), as well as distinct changes after CNH exposure. The β2-AR/β1-AR ratio was significantly higher in SHR-mtBN than in SHR, apparently due to increased expression of β2-ARs. Adaptation to hypoxia elevated β2-ARs in SHR and decreased the total number of β-ARs in SHR-mtBN. In parallel, the ability of isoprenaline to stimulate AC activity was found to be higher in SHR-mtBN than that in SHR. Interestingly, the activity of MAO-A was notably lower in SHR-mtBN than in SHR, and it was markedly elevated in both strains after exposure to hypoxia. In addition to that, CNH markedly enhanced the expression of catalase and aldehyde dehydrogenase-2 in both strains, and decreased the expression of Cu/Zn superoxide dismutase in SHR. Adaptation to CNH intensified oxidative stress to a similar extent in both strains and elevated the IL-10/TNF-α ratio in SHR-mtBN only. These data indicate that alterations in the mitochondrial genome can result in peculiar changes in myocardial β-adrenergic signaling, MAO-A activity and antioxidant defence and may, thus, affect the adaptive responses to hypoxia.


Toward earlier diagnosis of splenic injury?
A series of patients who were found at operation to have sustained splenic rupture is described and their immediate presenting features are detailed. Signs of peritoneal irritation were not always present and patients were not often 'shocked' when first seen. Helpful early signs included a low haemoglobin and pallor. There is a tendency to underestimate the significance of left quadrant pain in the presence of rib fractures. Peritoneal lavage and ultrasound should be more readily employed. Text book features should not be expected early and this must be taught to junior doctors who work in accident and emergency medicine.


Altered dynamics of alpha-fetoprotein production following pyridoxine and adenosine 5'-triphosphate administration to cirrhotic patients with or without primary hepatomas and to liver-injured and hepatoma-bearing rats.
In 12 cirrhotic patients who developed primary hepatocellular carcinomas during long-term follow-up, surveillance by frequent serum alpha-fetoprotein (AFP) measurements was not useful for their earlier detection. Difficulty was encountered in deciding whether or not hepatomas had already developed in cirrhotic patients with serum AFP levels over 200 ng/ml. Simultaneous injections of pyridoxine and adenosine 5'-triphosphate (ATP) resulted insignificant decreases of elevated serum AFP levels in carbon tetrachloride (CCl4)-injured rats but in 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB)-induced hepatoma-bearing rats. On clinical application of this procedure, it was found that cirrhotic patients without hepatomas could be differentiated from those with primary hepatomas since in the former a clear reduction of AFP levels following the administration of pyridoxine and ATP took place. This may be a new approach to the earlier diagnosis of primary hepatomas in cirrhotic patients with elevated serum AFP levels.


Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment.
To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.


Role of Cation Vacancies in Cu2SnSe3 Thermoelectrics.
In this study, a series of Cu2-xSnSe3 (x = 0.075-0.175) and Cu2Sn1-ySe3 (y = 0.06-0.1) compounds were synthesized by self-propagating high-temperature synthesis combined with plasma-activated sintering. The effects of different cation vacancies (Cu vacancies and Sn vacancies) on the thermoelectric properties are systematically studied. Both Cu vacancies and Sn vacancies enhance the carrier densities and move the Fermi level deeply into the valence band, promoting the multiband from Γ and S points involved in the electrical transport and increasing the effective mass, which is further corroborated by the theoretical calculation. Due to the stronger carrier scattering caused by Cu vacancies, the mobilities of samples with Cu deficiencies reduce leading to decreased power factors. The power factors of samples with Sn deficiencies increase owing to the increased carrier concentration and attaining a maximum power factor of 10.17 μW cm-1 K-2 at 800 K. Besides, the deficiencies of both Cu and Sn strengthen the phonon scattering, and samples with Cu deficiencies obtain lower thermal conductivity than samples with Sn deficiencies due to the lower electronic thermal conductivity. All the samples with cation deficiencies have improved thermoelectric properties. For Cu1.875SnSe3, ZT reaches 0.95 at 800 K, which is 83% higher than those of undoped samples, while for Cu2Sn0.93Se3, ZT reaches 0.87 at 800 K, which is a 67% improvement.


A content analysis of news coverage of the HPV vaccine by U.S. newspapers, January 2002-June 2005.
Genital Human Papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Of the 100 HPV types, HPV type 16 and HPV type 18 have been demonstrated to cause cervical cancer. Two pharmaceutical manufacturers have developed and tested HPV vaccines and are applying to the FDA for licensure. This research describes the content of HPV vaccine information contained in news articles. The Lexis-Nexis database was used to identify 25 articles on HPV that were published in 285 U.S. newspapers from January 1, 2003 to June 17, 2005. The coding schema captured information about the news event and source, as well as HPV and cervical cancer, transmission, vaccine, potential impact of the vaccine, and its relationship to PAP tests. The content analysis revealed that the news coverage of HPV vaccine provides information on the experimental status and efficacy of the vaccine, explains link between HPV and cervical cancer, and reports the manufacturers by name, as well as relies on them for a news source. Detailed information about HPV, however, was frequently missing which could lead to an incomplete picture or lack of understanding of the complexity of HPV and cervical cancer. As a major source of medical information, the media can be particularly important in educating policy makers and the general public about new scientific advances. Public health officials may wish to collaborate with journalists, health educators, healthcare providers, and women's health advocates to ensure that future educational initiatives explain the complexity of the association of HPV and cervical cancer and to stress the importance of continued cervical cancer screening.


Solvable model of spiral wave chimeras.
Spiral waves are ubiquitous in two-dimensional systems of chemical or biological oscillators coupled locally by diffusion. At the center of such spirals is a phase singularity, a topological defect where the oscillator amplitude drops to zero. But if the coupling is nonlocal, a new kind of spiral can occur, with a circular core consisting of desynchronized oscillators running at full amplitude. Here, we provide the first analytical description of such a spiral wave chimera and use perturbation theory to calculate its rotation speed and the size of its incoherent core.


[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].
One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.


Counterion condensation on heparin oligomers.
The electropherogram of native heparin shows a broad distribution of mobilities μ, which truncates abruptly at a notably high μ = 4.7 × 10(-4) cm(2) V(-1) s(-1). This highly skewed mobility distribution is also found for the 20-saccharide chain, which shows from mass spectrometry a more uniform (symmetrical) with respect to sulfation level. Since a partially degraded heparin exhibits oligomer peaks with μ> 5 × 10(-4) cm(2) V(-1) s(-1) (appearing to escape the limitation of the mobility value for native heparin), we examined the electrophoretic behavior of chain-length monodisperse heparin oligomers. Their mobilities varied inversely with the logarithm of the contour length, L, for L from 3 to 10 nm and reached an asymptotic limit for L > 20 nm. The generality of this effect was indicated by similar behavior for oligomers of poly(styrene sulfonate). A recent theory of polyelectrolyte end effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), in which chain termini exhibit reduced counterion condensation was found to quantitatively account for these results. A qualitative explanation for the anomalously high value of μ of native heparin, 10-20% higher than those seen for synthetic polyelectrolytes of higher linear charge density, is suggested on the basis of similar junction effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), which reduce counterion condensation at the interfaces of regions of high and low sulfation. We suggest that these effects should be considered in models for the biofunctionality of the regulated high and low sulfation (NS/NA) domains of heparan sulfate.


Complete hydatidiform mole coexistent with a twin live fetus: clinical course of four cases with complete cytogenetic analysis.
Twin gestations can occur in which one twin is a normal gestation (46 chromosomes: 23 maternal and 23 paternal origin) and in which the other twin is a complete hydatidiform mole (46 chromosomes all of paternal origin). Case reports of four such combined pregnancies that presented to a single institution are provided. All cases had documentation of clinical information, cytogenetic analysis, and fetal and placental pathology. Three of the four pregnancies were terminated for medical indications despite information documenting the presence of a normal fetus. All three of these patients required subsequent chemotherapy. The fourth case was followed conservatively and resulted in the birth of a normal infant at 38 weeks gestation. We speculate that the factors that led to the need for termination of the pregnancy (aggressive growth of trophoblast) may predict the need for further therapy. A true assessment of the antenatal and malignant sequelae risks associated with these rare gestations awaits the collection of a larger series of patients.


DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity.
DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T and NK cells migrate through confined spaces, they develop cell shape and nuclear deformation abnormalities that do not impair chemotaxis but contribute to a distinct form of catastrophic cell death we term cytothripsis. Such defects arise during lymphocyte migration in collagen-dense tissues when DOCK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structures. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells, which in turn impairs control of herpesvirus skin infections. Our results establish that DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin.


Impacts of regular and random noise on the behaviour, growth and development of larval Atlantic cod (Gadus morhua).
Anthropogenic noise impacts behaviour and physiology in many species, but responses could change with repeat exposures. As repeat exposures can vary in regularity, identifying regimes with less impact is important for regulation. We use a 16-day split-brood experiment to compare effects of regular and random acoustic noise (playbacks of recordings of ships), relative to ambient-noise controls, on behaviour, growth and development of larval Atlantic cod (Gadus morhua). Short-term noise caused startle responses in newly hatched fish, irrespective of rearing noise. Two days of both regular and random noise regimes reduced growth, while regular noise led to faster yolk sac use. After 16 days, growth in all three sound treatments converged, although fish exposed to regular noise had lower body width-length ratios. Larvae with lower body width-length ratios were easier to catch in a predator-avoidance experiment. Our results demonstrate that the timing of acoustic disturbances can impact survival-related measures during development. Much current work focuses on sound levels, but future studies should consider the role of noise regularity and its importance for noise management and mitigation measures.


Directed Kinetic Self-Assembly of Mounds on Patterned GaAs (001): Tunable Arrangement, Pattern Amplification and Self-Limiting Growth.
We present results demonstrating directed self-assembly of nanometer-scale mounds during molecular beam epitaxial growth on patterned GaAs (001) surfaces. The mound arrangement is tunable via the growth temperature, with an inverse spacing or spatial frequency which can exceed that of the features of the template. We find that the range of film thickness over which particular mound arrangements persist is finite, due to an evolution of the shape of the mounds which causes their growth to self-limit. A difference in the film thickness at which mounds at different sites self-limit provides a means by which different arrangements can be produced.


Receptor-mediated endocytosis of transferrin and ferritin by guinea-pig reticulocytes. Uptake by a common endocytic pathway.
Earlier studies have shown that transferrin binds to specific receptors on the reticulocyte surface, clusters in coated pits and is then internalized via endocytic vesicles. Guinea-pig reticulocytes also have specific receptors for ferritin. In this paper ferritin and transferrin endocytosis by guinea-pig reticulocytes was studied by electron microscopy using the natural electron density of ferritin and colloidal gold-transferrin (AuTf). At 4 degrees C both ligands bound to the cell surface. At 37 degrees C progressive uptake occurred by endocytosis. AuTf and ferritin clustered in the same coated pits and small intracellular vesicles. After 60 min incubations the ligands colocalized to large multivesicular endosomes (MVE), still membrane-bound. MVE subsequently fused with the plasma membrane and released AuTf, ferritin and inclusions by exocytosis. All endocytic structures labelled with AuTf contained ferritin, but 23 to 35% of ferritin-labelled endocytic structures contained no AuTf. These data suggest that ferritin and transferrin are internalized through the same pathway involving receptors, coated pits and vesicles, but that these proteins are recycled only partly in common.


Urinary epidermal growth factor (EGF) levels and epidermal growth factor receptor (EGF-R) expression in human cerebral tumors. Clinical considerations.
The levels of Epidermal Growth Factor (EGF) in urine samples collected from 58 patients (22 low grade gliomas, 13 anaplastic gliomas, 15 glioblastomas and 8 meningiomas) with cerebral tumors admitted at our Institute during 1994 were determined. EGF levels were measured by a specific RIA method. A preoperative and one or two postoperative determinations were performed. Further samples were collected before and at three weeks after postoperative radiotherapy and/or chemotherapy. EGF-Receptor (EGF-R) was determined by an immunohistochemical method on specimens of the same tumor. Preoperative levels showed a positive correlation with the degree of tumor anaplasia. A decrease of the postoperative levels of EGF was observed in all patients who underwent surgery and the entity of the decrease seemed to be well correlated with the extent of the tumoral resection. A strict correlation between EGF levels fluctuations and clinical and neuroradiological features was documented in patients submitted to radiotherapy and/or chemotherapy. The preliminary results on EGF-R expression suggest the existence of a correlation between EGF levels and the receptor expression. In 4 cases of glioblastoma low preoperative levels were associated to an high receptor expression in 2 cases while in the remainder the receptor was not detectable. An high receptor expression is pathognomonic of meningiomatous tissue, even if is not correlated to the biological behaviour and histological features of the neoplasia. These preliminary data suggest the reliability of EGF levels/EGF-R determination in the diagnosis and follow-up of patients with cerebral tumors particularly for those of glial origin. Our data confirmed the role of the EGF system in the development and growth of human gliomas and meningiomas.


Rational approach to surgical management of complex forms of double outlet right ventricle with modified Fontan operation.
Surgical alternatives to biventricular repair of complex forms of double outlet right ventricle (DORV) remain controversial. The available knowledge of the Fontan operation (FO) for children with this anomaly is limited. The aim of this report is to analyze the results and risk factors of the FO performed as an alternative to the biventricular repair of complex DORV. Between 1980 and 2007, 47 patients with complex forms of DORV underwent a modified FO. Concomitant defects included noncommitted, subpulmonary or multiple ventricular septal defects, anomalies of atrioventricular valves and/or caval veins, and ventricular hypoplasia. Thirty-five of 45 patients (77%) have undergone a hemi-Fontan and 35 patients (77%; 10 children without previous hemi-Fontan) have had a completion FO without mortality or Fontan takedown. Risk factors for adverse outcomes were determined by multivariate analyses. There were no early but six late deaths. The follow-up period ranged from 1 year to 25 years (mean 10.0 +/- 6.5). The actuarial survival was 93% at 1 year, 87% at 10, 15, and 25 years. Multivariate analysis identified preoperative left or common atrioventricular valve insufficiency (P = .001) and decreased left ventricular ejection fraction (<50%) (P = .02) as risk factors for late death and/or morbidity. The only risk factor for a late adverse outcome and poor functional status was increased preoperative pulmonary vascular resistance (>4.0 Woods units/m(2)) (P = .005). FO provides good early- and mid-term results in the treatment of complex forms of DORV. The increased preoperative pulmonary vascular resistance was a significant negative risk factor for adverse outcome in this patient population.


Psychosocial issues associated with genetic testing for breast and ovarian cancer risk: an integrative review.
The identification of the BRCA1/2 genes, and their possible etiologic relationship with various forms of inherited cancer, has been recognized universally as a cornerstone in the search for cancer's genetic link and has made it possible to identify specific individuals and families who harbor a mutation in one of these predisposition genes. Genetic testing for breast and ovarian cancer susceptibility may pose unanticipated psychological and social problems. Because of the recent availability of predisposition genetic testing, research efforts have begun to investigate factors that may influence an individual's intention to undergo testing and the psychosocial sequelae associated with testing. The purpose of this article is to provide an integrative review of the literature that will delineate what is currently known about the psychosocial issues associated with genetic testing for breast and ovarian cancer risk. Important generalizations from the literature include: (a) a positive test for breast cancer susceptibility may ignite a psychological response similar to the diagnosis of breast cancer itself; (b) there is likely a subset of individuals at increased risk for hereditary breast and ovarian cancer who are also at risk for sustained psychosocial problems; (c) available literature challenges a common notion that only individuals with a positive test result will need psychosocial services; and (d) at-risk individuals are basing health care decisions on genetic testing information, thus they are making important decisions under conditions of uncertainty. Clinical issues and directions for future research were highlighted.


A Cell-Adhesive Plasma Polymerized Allylamine Coating Reduces the In Vivo Inflammatory Response Induced by Ti6Al4V Modified with Plasma Immersion Ion Implantation of Copper.
Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film (PPAAm). Thus, this study aimed to examine in vivo local inflammatory reactions for Ti6Al4V implants treated with Cu-PIII (Ti-Cu), alone or with an additional PPAAm film (Ti-Cu-PPAAm), compared to untreated implants (Ti). Successful Cu-PIII and PPAAm treatment was confirmed with X-ray Photoelectron Spectroscopy. Storage of Ti-Cu and Ti-Cu-PPAAm samples in double-distilled water for five days revealed a reduction of Cu release by PPAAm. Subsequently, Ti, Ti-Cu and Ti-Cu-PPAAm samples were simultaneously implanted into the neck musculature of 24 rats. After 7, 14 and 56 days, peri-implant tissue was retrieved from 8 rats/day for morphometric immunohistochemistry of different inflammatory cells. On day 56, Ti-Cu induced significantly stronger reactions compared to Ti (tissue macrophages, antigen-presenting cells, T lymphocytes) and to Ti-Cu-PPAAm (tissue macrophages, T lymphocytes, mast cells). The response for Ti-Cu-PPAAm was comparable with Ti. In conclusion, PPAAm reduced the inflammatory reactions caused by Cu-PIII. Combining both plasma processes could be useful to create antibacterial and tissue compatible Ti-based implants.


Shaping the Lower Jaw Border with Customized Cutting Guides: Development, Validation, and Application in Facial Gender-Affirming Surgery.
Importance: Three-dimensional planning software is not standardized in facial gender-affirming surgery. Objective: To develop and validate surgical planning software to create cutting guides to contour the lower jaw border. Design, Setting, and Participants: A 3-year prospective case series study done in three phases: software development, validation, and surgical guide application. Ethics committee approval was obtained to enroll the patients (Clinical Research Ethics Committee, Hospital Costa del Sol, Marbella, Spain). Main Outcomes and Measures: Validation phase: degree of agreement between the planned and obtained results, modification of cephalometric parameters, and surgical times. Application phase: surgical technique description, complications, and patient-reported outcome measures. Results: The degree of agreement between the planned and obtained results was inframillimetric (0.31 ± 0.70 mm). The guides reduced the mandible to within feminine parameters (p < 0.05). Surgical times decreased by 10.96% with chin ostectomies (p < 0.05) and 23.06% with lower jaw border (angle-to-angle) surgeries (p < 0.001). In the application phase, revision surgery was required for 11 patients out of 260 (4.23%). Conclusions and Relevance: The use of cutting guides on the lower jaw border is effective, helps reach standard feminine parameters, and decreases surgical times.


Performance of "RESIST-3 O.K.N. K-SeT" immunochromatographic assay for the detection of OXA-48 like, KPC, and NDM carbapenemases in Klebsiella pneumoniae in Turkey.
In this study, the performance of the "RESIST-3 O.K.N. K-SeT" (Coris BioConcept, Gembloux, Belgium) immunochromatographic assay was evaluated in 132 Klebsiella pneumoniae comprising 102 carbapenem resistant and 30 carbapenem susceptible isolates. Genotypically known isolates of Gram negative bacteria (n=22) including various species were also tested by the assay as controls. The isolates tested by the immunochromatographic assay and also were run PCR for blaKPC, blaIMP, blaVIM, blaNDM, and blaOXA-48. The rates of blaNDM, blaOXA-48, and blaKPC in carbapenem resistant isolates were found at 52.9%, 39.2%, and 2.0%, respectively. Both blaNDM and blaOXA-48 were found in six (5.9%) isolates. The results of the assay showed 100% concordance with those obtained by PCR in 132K. pneumoniae. The agreement between the two methods was found to be identical at the isolate level. The assay also correctly detected all genotypically known isolates of Escherichia coli, Serratia marcescens, Citrobacter freundii, Enterobacter cloacae, K. pneumoniae carrying blaKPC, blaNDM, and/or blaOXA-48. On the other hand, the assay did not exhibit any cross-reaction in control isolates harboring blaIMP and blaVIM. We conclude that the RESIST-3 O.K.N. K-SeT is a reliable, rapid, and user friendly test and we recommend it for routine diagnostic laboratories.


Superparamagnetic iron oxide enhanced magnetic resonance imaging of rat liver with hepatocellular carcinoma and benign hyperplastic nodule.
The authors assess the potential of a new superparamagnetic iron oxide (SPIO) in grading hepatocellular carcinoma (HCC) histologically and in differentiating HCC from benign hyperplastic nodule (HPN). Nine Wistar rats (with poorly to moderately differentiated HCC, well-differentiated HCC, and HPN) received drinking water containing N-nitrosomorpholine, and were examined by magnetic resonance imaging (4.7 tesla). Spin-echo images (repetition time/echo time, 600/24.5 mseconds) were obtained before and 15 minutes after intravenous administration of 10 mumol Fe/kg of SH U 555A. Poorly to moderately differentiated and well-differentiated HCC showed no significant change in signal-to-noise ratio (SNR) 15 minutes after contrast, whereas HPN showed a significant decrease in SNR. The contrast-to-noise ratio (CNR) between each kind of tumor and adjacent liver parenchyma showed a significant increase at 15 minutes after contrast. The SPIO discussed in this article may help to differentiate HCC from HPN, but it remains difficult to grade hepatocellular carcinoma histologically.


Poly(ADP-ribose) and carcinogenesis.
Poly(ADP-ribose) and poly(ADP-ribose) polymerase (PARP) were discovered about 40 years ago, but their significance was not well elucidated until recently. In the early stage of the history of PARP, the presence of antibodies in the sera of human patients with lupus erythematosus indicated its natural occurrence. PARP, as well as the degrading enzyme, poly(ADP-ribose) glycohydrolase (PARG), are present in most eukaryotes except for yeasts. Studies that used inhibitors of PARP indicated the involvement of PARP and poly(ADP-ribose) in DNA damage repair, and eventually PARP was purified and the gene was cloned. Molecular analysis then revealed various functional domains, such as the one for binding to strand breaks of DNA. Parp-1-deficient and Parg-deficient cells showed, in general, enhanced sensitivity to the lethal effects of ionizing radiation and alkylating agents. Parp-1 knockout mouse embryonic stem cells developed into teratocarcinoma-like tumors when injected subcutaneously into nude mice, these tumors featuring giant cells similar to syncytiotrophoblastic giant cells with hyperploidy. Parp-1 was also found in centrosomes, suggesting that poly(ADP-ribose) and PARP-1 are functionally involved in the maintenance of chromatin structure and the equal distribution of chromosomes into daughter cells. Intriguing findings on the real biological significance continue to be generated, with new light shed on mechanisms of carcinogenesis and pointing to novel cancer treatments. Highlights during the last four decades of studies by laboratories focusing on poly(ADP-ribose)/PARP, including our own, are condensed and summarized in this review.


In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity.
Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation. Plaques were experimentally induced in rabbit (n=11) aortas, and at the day of sacrifice, a pull-back was performed with a thermography catheter. Hot (n=10), cold (n=10), and reference (n=11) regions were dissected and analysed for smooth muscle cell (SMC), lipids (L), collagen (COL), and macrophage (MPhi) cell densities (%); a vulnerability index (VI) was calculated as VI=MPhi+L/(SMC+COL). In addition, accumulation and activity of MMP-2 and MMP-9 were determined with zymography. Ten hot regions were identified with an average temperature of 0.40+/-0.03 degrees C (P<0.05 vs. reference) and 10 cold regions with 0.07+/-0.03 degrees C (P<0.05 vs. hot). In the hot regions, a higher macrophage density (173%), less SMC density (77%), and a higher VI (100%) were identified. In addition, MMP-9 (673%) activity was increased. A detailed regression analysis revealed that MMP-9 predicted hot regions better than macrophage accumulation alone. In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.


Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis.
Mucosal leishmaniasis (ML) is observed only in about 3% of patients with American tegumentary leishmaniasis (ATL) but has a high potential for destructive, disfiguring, and disabling sequelae. Prior reports of clinical and epidemiologic features of ML are limited by small numbers of cases. In this study, we evaluated changes in the demographic features and clinical presentation of ML in an endemic area of Leishmania braziliensis transmission over a period of 20 years. The charts of 327 patients with ML diagnosed between 1995 and 2014 were reviewed. The majority of patients (67%) were male. Age ranged from 8 months to 103 years, with a median age of 38.5 years (interquartile range: 22-58 years). The greatest number of patients was between 19 and 39 years (31%). Over the study period, there was an increase in patients with ML more than 60 years of age, an increase in ML with concomitant cutaneous lesions, a decrease in the period of time between the documentation of cutaneous lesions and the diagnosis of mucosal disease, and an increase in the frequency of patients presenting with stage I and V of ML. Moreover, there was a positive correlation between severity of mucosal disease and both age and the period of time between cutaneous lesion and mucosal disease. Response to therapy of ML remained similar over a period of 20 years. Despite the improvement in medical care during the study period, the prevalence of ML did not change and severe disease continues to be a major challenge for the management of these patients.


Screening of solvent dependent antibacterial activity of Prunus domestica.
Fruit of Prunus domestica was extracted in ethanol. The ethanol extract was further extracted with two solvents ethyl acetate and chloroform. The crude ethanol extract and two fractions (ethyl acetate and chloroform) were screened for their antibacterial activity using the agar well diffusion method .They were tested against nine bacteria; five Gram positive bacteria (Staphylococcus aureus, Streptococcuc intermedius, Bacillus cereus, Bacillus pumilus) and four Gram negative bacteria (Eschrichia coli, Proteus mirabilis Shigella flexneri, Salmonella typhi and Klebsiela pneumoniae). The susceptibility of microorganisms to all three fractions was compared with each other and with standard antibiotic (Ampicillin) Among all fractions ethyl acetate exhibited highest antibacterial activity (average zone of inhibition 34.57mm ± 1.3) while ethyl alcohol exhibited least antibacterial activity (average zone of inhibition 17.42mm ± 3.3). Minimum inhibitory concentration of ethanol, ethyl acetate and chloroform fractions was found in the range of 78 μ g/ml to 2500 μ gl/ml against gram positive and gram negative bacteria.


Antibiotic Use for Febrile Children in a Tertiary Care Hospital's Outpatient Department: A Cross-Sectional Study.
Background Irrational prescription of antibiotics is contributing to the antimicrobial resistance crisis in low and middle-income countries. Antibiotic stewardship programs need to be implemented to rationalize the use of antibiotics, but data on antibiotic prescriptions in pediatric outpatient departments is minimal. This study aimed to determine the frequency of antibiotic prescriptions in febrile children attending the Paediatric Outpatient Department (OPD) at Combined Military Hospital, Lahore, and observe the factors affecting the decision to prescribe antibiotics. Methodology A cross-sectional, descriptive study with non-probability sampling in the Department of Paediatrics at the Combined Military Hospital (CMH), Lahore, was conducted over two years. The confidence limit was 95%, and the anticipated population proportion was 32%. The primary outcome was the proportion of children aged two months to 10 years presenting to the OPD with fever who received antibiotics. Further analysis included the effect of patient-level risk factors on antibiotic prescription, especially in children with respiratory tract infections (RTIs). Results Of the 225 children analyzed, 137 (61%) received antibiotics. Of these antibiotic prescriptions, 123 (90%) were second-line antibiotics. Older age (odds ratio (OR) = 2.3, 1.18-4.46), high fever (OR = 2.48, 1.37-4.5), presenting in autumn and winter seasons (OR = 2.85, 1.53-5.3), ill appearance (OR = 2.71, 1.12-6.55), tachycardia (OR = 4.28, 1.22-15.01), and tachypnea (OR = 4.01, 1.14-14.12) were associated with increased likelihood of antibiotic prescription. Antibiotic prescriptions in children with RTIs were associated with lower RTI (OR = 12.96, 3.49-48.08), probable bacterial infection (OR = 12.37, 4.77-30.05), tachycardia (OR = 10.88, 1.28-92.24), tachypnea (OR = 14.73, 3.14-68.99), and increased work of breathing (OR = 7.8, 2.05-29.56). Conclusions The evidence of the widespread inappropriate use of antibiotics in OPDs, particularly for upper RTIs, highlights the need for an antibiotic stewardship program. Antibiotic overprescription promotes antibiotic resistance, prolonging illness and increasing healthcare costs.


Poly(ADP-ribosyl)ation in mammalian ageing.
Poly(ADP-ribose) polymerases (PARPs) catalyze the post-translational modification of proteins with poly(ADP-ribose). Two PARP isoforms, PARP-1 and PARP-2, display catalytic activity by contact with DNA-strand breaks and are involved in DNA base-excision repair and other repair pathways. A body of correlative data suggests a link between DNA damage-induced poly(ADP-ribosyl)ation and mammalian longevity. Recent research on PARPs and poly(ADP-ribose) yielded several candidate mechanisms through which poly(ADP-ribosyl)ation might act as a factor that limits the rate of ageing.


Physiological and psychological reactions to work in men and women with identical job tasks.
Differences in physiological functioning in the hypothalamus-pituitary-adrenal cortex axis and the autonomic nervous system have been suggested to contribute to many of the health differences that may be observed between men and women as well as being relevant for the development of musculoskeletal pain. To clarify whether men and women with identical work tasks reacted differently when doing work known to induce musculoskeletal pain, ratings and physiological measurements were obtained at work start (15:30) and at the end of the workshift (22:30) on 17 men and 20 women. Men showed a larger decrease in perceived energy levels during the workshift but there were no differences between men and women as regards cortisol, adrenaline, noradrenaline, heart-rate activation, perceived stress, pain and physical exertion. In conclusion, differential physiological activation during the workshift seem to be an unlikely mechanism for explaining gender differences in pain associated with exposure to awkward and repetitive movements.


The rheological properties and emulsifying behavior of polysaccharides sequentially extracted from Amana edulis.
The rheological properties and emulsifying behavior of four polysaccharides (HBSS, CHSS, DASS, and CASS) sequentially extracted from Amana edulis (AEPs) were investigated under various concentrations, temperatures, pH levels, and ionic strengths. The apparent viscosity of the four AEPs solutions at 1% (w/w) concentration were found to be CHSS > DASS > HBSS > CASS. When the AEPs were heated to 100 οC, they showed lower colloidal viscosity, whereas after refrigeration and chilling, higher apparent viscosities were observed. The apparent viscosity of four AEPs at pH 10 or pH 4 was lower than that at pH 7. The apparent viscosity increased at a lower sodium ion concentration and then declined with an increase in ion concentration. The storage modulus (G') and loss modulus (G″) increased with an increase in oscillation frequency. The emulsifying activity and stability were enhanced as the concentration of the four AEPs increased. The emulsifying activity and stability of the AEPs were steady within the pH range of 2-10 and NaCl concentration range of 0-0.4 mol/L. Our results implied that these polysaccharides can be utilized as a novel hydrocolloid source for natural thickeners in the food industry.


Functional enucleation of mouse metaphase II oocytes with etoposide.
Mouse metaphase II (M II) oocytes were exposed to 50 micrograms/microliters etoposide (ETO) before and after parthenogenetic activation with 7% ethanol and they were washed with 0.75 M sucrose. The ETO treated parthenogenetically activated oocytes were cultured or fused to single blastomeres of late 2-cell stage mouse embryo to test their ability to support development in vitro. In parallel untreated parthenogenetically activated oocytes were cultured to serve as control. None of ETO treated oocytes developed beyond the 2-cell stage, whereas 4% of the reconstituted embryos and 35% of control developed to blastocysts. It is concluded that mouse M II oocytes can be functionally enucleated by ETO treatment and can be used for nuclear transfer experiments.


Long-term HIF-1α transcriptional activation is essential for heat-acclimation-mediated cross tolerance: mitochondrial target genes.
An important adaptive feature of heat acclimation (HA) is the induction of cross tolerance against novel stressors (HACT) Reprogramming of gene expression leading to enhanced innate cytoprotective features by attenuating damage and/or enhancing the response of "help" signals plays a pivotal role. Hypoxia-inducible factor-1α (HIF-1α), constitutively upregulated by HA (1 mo, 34°C), is a crucial transcription factor in this program, although its specific role is as yet unknown. By using a rat HA model, we studied the impact of disrupting HIF-1α transcriptional activation [HIF-1α:HIF-1β dimerization blockade by intraperitoneal acriflavine (4 mg/kg)] on its mitochondrial gene targets [phosphoinositide-dependent kinase-1 (PDK1), LON, and cyclooxygenase 4 (COX4) isoforms] in the HA rat heart. Physiological measures of cardiac HACT were infarct size after ischemia-reperfusion and time to rigor contracture during hypoxia in cardiomyocytes. We show that HACT requires transcriptional activation of HIF-1α throughout the course of HA and that this activation is accompanied by two metabolic switches: 1) profound upregulation of PDK1, which reduces pyruvate entry into the mitochondria, consequently increasing glycolytic lactate production; 2) remodeling of the COX4 isoform ratio, inducing hypoxic-tolerant COX4.2 dominance, and optimizing electron transfer and possibly ATP production during the ischemic and hypoxic insults. LON and COX4.2 transcript upregulation accompanied this shift. Loss of HACT despite elevated expression of the cytoprotective protein heat shock protein-72 concomitantly with disrupted HIF-1α dimerization suggests that HIF-1α is essential for HACT. The role of a PDK1 metabolic switch is well known in hypoxia acclimation but not in the HA model and its ischemic setting. Remodeling of COX4 isoforms by environmental acclimation is a novel finding.


Alternative lengthening of telomeres: models, mechanisms and implications.
Unlimited cellular proliferation depends on counteracting the telomere attrition that accompanies DNA replication. In human cancers this usually occurs through upregulation of telomerase activity, but in 10-15% of cancers - including some with particularly poor outcome - it is achieved through a mechanism known as alternative lengthening of telomeres (ALT). ALT, which is dependent on homologous recombination, is therefore an important target for cancer therapy. Although dissection of the mechanism or mechanisms of ALT has been challenging, recent advances have led to the identification of several genes that are required for ALT and the elucidation of the biological significance of some phenotypic markers of ALT. This has enabled development of a rapid assay of ALT activity levels and the construction of molecular models of ALT.


[Occurrence of p-fimbriae in enteropathogenic E coli (EPEC) and in E. coli strains isolated from patients with urinary tract infections].
The aim of this study was to gain knowledge of prevalence of P+ clones among EPEC strains isolated from children with diarrhoea and E. coli strains isolated from urine. Three hundred eighty four E. coli strains isolated from children with diarrhoea were tested. They belonged to 11 serotypes (018, 025, 026, 044, 055, 0111, 0114, 0119, 0124, 0125, and 0128). Nine hundred thirty colonies of E. coli from Mac Conkey's agar plated quantitatively with urine samples of 178 individuals suffering from urinary tract infections were also tested. All strains were assayed by mannose-resistant active haemagglutination test (MRHA) and by slide agglutination using self prepared latex reagent for detection of P fimbriae. Out of 384 E. coli strains tested 122 (31.8%) showed presence of adhesins detected by mannose-resistant active haemagglutination test (MRHA) and in 90 (23.3%) out of all tested strains the presence of P fimbriae was found. The highest percentage of P fimbriae prevalence was found in E. coli belonging to the following serotypes: 018 (in 68.9% strains), 025 (in 29.2% strains), and 0125 (in 25.0% strains). This type of fimbriae was also detected in serotypes 026 (9.1%), 044 (8.7%), 055 (5.6%), and 0119 (in 2 strains out of 5 isolated). Out of 933 colonies of E. coli, isolated from 178 urine samples, 434 (46.5%) colonies gave positive results in MRHA test, including 133 positive in latex test for P fimbriae. These studies showed that for MRHA adhesins, including P fimbriae, a parallel examination of higher number of E. coli was necessary.(ABSTRACT TRUNCATED AT 250 WORDS)


A critical evaluation of the role of Lp(a) in cardiovascular disease: can Lp(a) be useful in risk assessment?
Lp(a) is a structurally complex particle which resembles LDL, but which also contains the distinctive glycoprotein apo(a). Apo(a) is characterized by a variable number of repeated kringle domains, which gives rise to differently-sized Lp(a) isoforms in the population. Although epidemiological studies indicate that elevated Lp(a) concentration and/or small apo(a) isoform sizes increase the risk of coronary heart disease (CHD), a causal role for Lp(a) in CHD remains unproven. This is largely due to the difficulty in establishing a relevant animal model to probe Lp(a) function, and the lack of intervention studies in which Lp(a) concentrations are lowered and outcomes followed. The accumulation of apo(a)/Lp(a) in arterial lesions has provided the rationale for numerous in vitro studies aimed at dissecting its function in this milieu. These studies have resulted in the proposal of numerous proatherogenic, prothrombotic and antifibrinolytic roles for both native and modified apo(a)/Lp(a). Although characterization of Lp(a) in the general population is not presently justified, Lp(a) analysis in patients at risk for CHD may be warranted.


[Advances on antitumor effect of parasites].
Immune response induced by parasites could inhibit tumor growth and promote apoptosis of tumor cells. The investigation into this character will provide new insights on the anti-tumor effect of parasites. The mechanism of parasite immune evasion may provide a reference for tumor research. Furthermore, some anti-parasitic drugs have shown antitumor effect indicating that the development of antitumor drugs may get inspiration from anti-parasitic drug studies.


Low expression of IL6R predicts poor prognosis for lung adenocarcinoma.
Interleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD). In this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Through the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients. In summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.


The influence of fatty acid mixtures on mammalian erythrocyte viability in culture.
Cell culture has been used for many years, mainly using transformed cells, but in some instances normal cells. Generally, the more unsaturated fatty acids were most efficient at limiting cell growth. These fatty acids were usually more efficient at cell growth limitation and cell killing when used with transformed cells, compared to normal controls. Different species of mammals exhibit different capability to metabolise fatty acids, especially polyunsaturated fatty acids. The enzymes for such metabolism are largely cytosolic and mitochondrial, and are not found in erythrocytes. We have maintained erythrocytes from three species (rat, human and cat) in culture and exposed them to mixtures of fatty acids mimicking the composition of seven dietary oils. The mixtures induced varying degrees of erythrocyte death, generally depending on the type and amount of polyunsaturated fatty acids present in, and the concentration of the mixtures. Comparing the three species, the rat cells were generally the most susceptible to the effects of the fatty acids, with either human or cat least susceptible depending on the specific fatty acid mixture. Erythrocytes cannot metabolise fatty acids and hence are not able to remove the mixture dosed, and any effects are most likely to relate to changes in the erythrocyte membrane phosphoglyceride bilayer structure.


Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair.
Receptor interacting protein kinase 3 (RIPK3) induces necroptosis, a type of regulated necrosis, through its kinase domain and receptor interacting protein (RIP) homotypic interaction motif (RHIM). In addition, RIPK3 has been shown to regulate NLRP3 inflammasome and nuclear factor κB (NF-κB) activation. However, the relative contribution of these signaling pathways to RIPK3-dependent inflammation in distinct immune effectors is unknown. To investigate these questions, we generated RIPK3-GFP reporter mice. We found that colonic CD11c+CD11b+CD14+ mononuclear phagocytes (MNPs) expressed the highest level of RIPK3 in the lamina propria. Consequently, deletion of the RIPK3 RHIM in CD11c+ cells alone was sufficient to impair dextran sodium sulfate (DSS)-induced interleukin (IL)-23 and IL-1β expression, leading to severe intestinal inflammation. In contrast, mice expressing kinase inactive RIPK3 were not hypersensitive to DSS. Thus, a key physiological function of RIPK3 is to promote reparative cytokine expression through intestinal CD11c+ MNPs in a kinase- and necroptosis-independent manner.


Human antibody responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine: results from ELISA studies.
Antibody responses after vaccination with three different formulations of a new meningococcal group B outer membrane vesicle (OMV) vaccine have been studied with the ELISA technique using four different antigens. Sera from about 1200 vaccinees participating in steps 1, 2, 3 and 6 of the phase II clinical trials in Norway were analysed. The effects of non-covalently complexing the OMV antigen to group C polysaccharide (C-PS) and of adsorbing OMV (with and without C-PS) to aluminium hydroxide (AH) were studied. All three vaccine formulations were highly immunogenic in humans. Adsorption of the vaccine to AH had a relatively small effect on the immune response, but the results indicated that the booster response was stronger with the adsorbed than with the unadsorbed vaccines. Some increase in the immune response against OMV was also observed by non-covalent complexing OMV with C-PS, particularly after the second dose. In most of the vaccinees the antibody levels were significantly reduced 6 to 12 months after vaccination. Adsorption of the vaccine to AH had no effect on the antibody response against C-PS. Comparison with bactericidal activity of the same sera was done. A highly significant correlation was observed between the bactericidal titres and the levels of IgG antibodies against OMV and class 5C protein, whereas the correlation between antibody levels against lipopolysaccharide and the bactericidal activity was poor.


The feasibility and efficacy of implementing a focused cardiac ultrasound course into a medical school curriculum.
Teaching cardiac ultrasound to medical students in a brief course is a challenge. We aimed to evaluate the feasibility of teaching large groups of medical students the acquisition and interpretation of cardiac ultrasound images using a pocket ultrasound device (PUD) in a short, specially designed course. Thirty-one medical students in their first clinical year participated in the study. All were novices in the use of cardiac ultrasound. The training consisted of 4 hours of frontal lectures and 4 hours of hands-on training. Students were encouraged to use PUD for individual practice. Finally, the students' proficiency in the acquisition of ultrasound images and their ability to recognize normal and pathological states were evaluated. Sixteen of 27 (59%) students were able to demonstrate all main ultrasound views (parasternal, apical, and subcostal views) in a six-minute test. The most obtainable view was the parasternal long-axis view (89%) and the least obtainable was the subcostal view (58%). Ninety-seven percent of students correctly differentiated normal from severely reduced left ventricular function, 100% correctly differentiated a normal right ventricle from a severely hypokinetic one, 100% correctly differentiated a normal mitral valve from a rheumatic one, and 88% correctly differentiated a normal aortic valve from a calcified one, while 95% of them correctly identified the presence of pericardial effusion. Training of medical students in cardiac ultrasound during the first clinical year using a short, focused course is feasible and enables students with modest ability to acquire the main transthoracic ultrasound views and gain proficiency in the diagnosis of a limited number of cardiac pathologies.


Work environment perceptions of staff nurses and aides in home health agencies.
Nurse executives are responsible for ensuring a therapeutic work environment in their organizations. Understanding how staff members perceive their environment is the first step in creating such an environment. In this study, perceptions of the work environment between staff nurses and home health aides in home health agencies were compared. The results suggest that nurse executives need to foster home health aides' job commitment and support for one another and increase opportunities for staff nurses to be innovative and autonomous in their practice.


Observation and ultrafast dynamics of a nonvalence correlation-bound state of an anion.
Nonvalence states of molecular anions play key roles in processes, such as electron mobility, in rare-gas liquids, radiation-induced damage to DNA, and the formation of anions in the interstellar medium. Recently, a class of nonvalence bound anion state has been predicted by theory in which correlation forces are predominantly responsible for binding the excess electron. We present a direct spectroscopic observation of this nonvalence correlation-bound state (CBS) in the para-toluquinone trimer cluster anion. Time-resolved photoelectron velocity map imaging shows that photodetachment of the CBS produces a narrow and highly anisotropic photoelectron distribution, consistent with detachment from an s-like orbital. The CBS is bound by ~50 meV and decays by vibration-mediated autodetachment with a lifetime of 700 ± 100 fs. These states are likely to be common in large and/or polarizable anions and clusters and may act as doorway states in electron attachment processes.


[A case of synchronous resection of double cancers in the lung and stomach through median sternotomy and abdominal incision].
A 72-year-old male was admitted to our clinic for the treatment of early stomach cancer. A chest X-ray film on admission showed a mass in the right lung field. CT scan and transbronchoscopic lung biopsy revealed lung cancer (C-T2N2M0-stage IIIA). Histologically it was poorly differentiated adenocarcinoma, which was different from stomach cancer. We underwent synchronous resection of this double cancer through median sternotomy and abdominal incision. We conducted lobectomy, bilateral mediastinal lymph node dissection, and wedge resection of stomach. Postoperative diagnosis was early lung cancer (p-T2N0M0-stage I) and advanced stomach cancer (A-IIc+IIa advanced t2 (mp) n1H0P0M0-stage II). Postoperative course was stable and the patient was healthy at present. As such, this case report suggests that synchronous double cancers involving the lung and stomach, if both cancer are early stage, should be resected synchronously.


Recent Advances of pH-Induced Charge-Convertible Polymer-Mediated Inorganic Nanoparticles for Biomedical Applications.
The incorporation of functional polymers and inorganic nanoparticles into nanoplatforms has the potential to produce personalized nanomedicine systems for further biomedical applications. Polymers that endow inorganic nanoparticles with unique surface properties for prolonged blood circulation and improved tumor targeting and cellular uptake are especially desired. pH-induced charge-switchable polymers are sensitive to the pH of the tumor environment and maintain a negative or neutral charge in blood circulation, increasing their circulation time and enhancing tumor accumulation via the enhanced permeability and retention effect. This type of polymer further transforms its charge to positive in acidic tumor locations to promote cellular uptake. Furthermore, the combination of pH-induced charge-switchable polymers with various inorganic nanoparticles (e.g., magnetic nanoparticles, gold nanoparticles, quantum dots, and upconversion materials) activates their intrinsic functions in in situ diagnosis and disease therapy. This review briefly overviews the recent progress in the development and application of various pH-induced charge-convertible polymers functionalized with different types of inorganic nanoparticles for different biomedical applications. More importantly, future developments in this field are also discussed.


Heparin-associated thrombocytopenia.
Heparin-associated thrombocytopenia is a relatively common complication of heparin therapy occurring in approximately 5% of the patients who receive this drug. The incidence is higher with bovine heparin then with porcine heparin. Onset of heparin-associated thrombocytopenia usually occurs 6 to 12 days after initiation of treatment and by itself has a low morbidity. Heparin-associated thrombocytopenia plus arterial thrombosis can cause major complications including stroke, heart attack, and death. The incidence of heparin-associated thrombocytopenia plus arterial thrombosis is lower than that for heparin-associated thrombocytopenia alone. The diagnosis of heparin-associated thrombocytopenia remains one of exclusion, but testing for the presence of a heparin-dependent platelet-aggregating factor may prove to be useful. Analysis of the time of onset suggests a strategy for prevention. Oral anticoagulants could be started concomitantly with the heparin so that it could be discontinued in several days. This approach may prevent most episodes of heparin-associated thrombocytopenia.


Ultrastructure and dynamics of selective mitochondrial injury in carcinoma cells after doxycycline photosensitization in vitro.
Mechanisms and intracellular sites of photosensitized damage were investigated in cultured MGH-U1 cells treated with doxycycline (DOTC). Cells were examined by phase-contrast, fluorescence, and electron microscopy at various times (15 minutes to 24 hours) after ultraviolet irradiation (320-400 nm). DOTC localized selectively within the mitochondria, as shown by colocalized fluorescence with rhodamine 123 (R123). Photosensitization at 1 J/sq cm caused striking swelling of the mitochondrial matrix and disruption of the cristae, accompanied by loss of the ability of mitochondria to concentrate R123. These changes progressed during the first hour after irradiation, and then were followed by partial recovery of mitochondrial ultrastructure and function. At no time were other organelles seen to be affected. It appears that this selective, photosensitized alteration was a consequence of localized and partially reversible damage to the mitochondrial inner membrane. In contrast, exposure to 2-6 J/sq cm caused irreversible injury and necrosis.


Different efficacy of inhaled and oral medications in pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is progressive disorder characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death. One of the main therapeutic options for PAH are medications targeting the prostacyclin pathway. Treprostinil is a prostacyclin analogue and selexipag is a selective IP receptor agonist. Treprostinil can be delivered by a variety of routes including oral, inhaled, subcutaneous and intravenous. Selexipag is currently approved as an oral formulation. The impact of the route of delivery and the optimal dosing for transitioning inhaled treprostinil to oral treprostinil or selexipag is unknown. More importantly, given the different selectivity for prostacyclin receptors, it is uncertain whether treprostinil and selexipag can be substituted. We present two patients with PAH who received medications targeting the prostacyclin pathway and were transitioned from inhaled treprostinil to either oral treprostinil or selexipag. In both cases, we noted clinical, functional and hemodynamic deterioration. These cases highlight that the route of delivery (inhaled versus oral) and/or the specific PH medication (treprostinil versus selexipag) matter; therefore close monitoring during transitions is imperative.