Peptidomics coming of age: a review of contributions from a bioinformatics angle.
The term peptidomics for a new promising "omics" field was not introduced until the beginning of 2000. The approach has been proven successful in several domains such as neuroendocrine research and biomarker or drug discovery. This review reports on bioinformatics tools and methodologies within the peptidomics field and the application thereof. Obviously, a plethora of proteomics data analysis tools lends themselves to direct use in peptidomics because the latter is a subfield of the former, at least to a certain extent. Nevertheless, peptidomics-specific tool extensions, inventions, and validation procedures have emerged, and certain tools are more suitable for this subfield than others due to small but important differences in peptidomics sample analysis. This paper focuses on these topics. Furthermore, it gives a comprehensive overview of available online tools tailored to the peptidomics field. To conclude, an ideal pipeline for bioactive peptide identification is presented.


The systemic right ventricle in congenitally corrected transposition of the great arteries is different from the right ventricle in dextro-transposition after atrial switch: a cardiac magnetic resonance study.
Patients with a congenitally corrected transposition of the great arteries show an increasing incidence of cardiac failure with age. In other systemic right ventricles, such as in dextro-transposition after atrial switch, excessive hypertrophy is a potential risk factor for impaired systolic function. In this trial, we sought to compare systemic function and volumes between patients with congenitally corrected transposition and those with dextro-transposition after atrial switch by using cardiac magnetic resonance imaging. A total of 19 patients (nine male) with congenitally corrected transposition and 31 patients (21 male) with dextro-transposition after atrial switch were studied using a 1.5-Tesla scanner. Cine steady-state free-precession sequences in standard orientations were acquired for volumetric and functional imaging. Patient parameters were compared with those of a group of 25 healthy volunteers. Although patients with congenitally corrected transposition were older, they presented with higher right ventricular ejection fractions (p = 0.04) compared with patients with dextro-transposition. Patients with congenitally corrected transposition showed a weak negative correlation between age at examination and systemic ejection fraction (r = −0.18, p = 0.04) but no correlation between right ventricular myocardial mass index and ejection fraction. There was no significant difference in the right ventricular end-diastolic volumes between both patient groups. Although patients with congenitally corrected transposition had a longer pressure load of the systemic right ventricle, ventricular function was better compared with that in patients with dextro-transposition after atrial switch. The results suggest that the systemic ventricles might have partly different physiologies. One difference could be the post-operative situation after atrial switch, which results in impaired atrial contribution to ventricular filling.


Role and molecular mechanism of heterogeneous nuclear ribonucleoprotein K in tumor development and progression.
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the hnRNP family, which exists in the nucleus and the cytoplasm simultaneously. It is a multifunctional protein that can participate in a variety of regulatory progressions of gene expression and signal transduction, such as chromatin remodeling, transcription, RNA alternative splicing and translation. hnRNP K not only directly binds to the kinases, but also recruits the associated factors regarding transcription, splicing and translation to control gene expression, and therefore, it serves as a docking platform for integrating transduction pathways to nucleic acid-directed processes. Numerous studies also show that abnormal expression of hnRNP K is closely associated with the tumor formation. This protein is overexpressed in numerous types of cancer and its aberrant cytoplasmic localization is also associated with a worse prognosis for patients. These results consistently indicate that hnRNP K has a key role in cancer progression. To understand the hnRNP K pathophysiological process in tumor disease, the previous research results regarding the association between hnRNP K and tumors were reviewed.


Casein kinase II catalyzes tyrosine phosphorylation of the yeast nucleolar immunophilin Fpr3.
In the yeast Saccharomyces cerevisiae, the nucleolar immunophilin, Fpr3, is phosphorylated at tyrosine and dephosphorylated by the phosphotyrosine-specific phosphoprotein phosphatase, Ptp1. In Ptp1-deficient cells, Fpr3 contains phospho-Tyr at a single site (Tyr184), but also contains phospho-Ser and phospho-Thr. Ser186 (adjacent to Tyr184) is situated within a canonical site for phosphorylation by casein kinase II (CKII). Yeast cell lysates contain an activity that binds to Fpr3 in vitro and phosphorylates Fpr3 at Ser, Thr, and Tyr; this activity was found to be dependent on expression of functional yeast CKII. Moreover, purified Fpr3 was phosphorylated on Tyr184 in vitro by either purified yeast CKII or purified, bacterially-expressed human CKII. Likewise, phosphorylation of Fpr3 at tyrosine in vivo was markedly enhanced in yeast cells overexpressing a heterologous (Drosophila) CKII, but was undetectable in yeast cells carrying only a temperature-sensitive allele of the endogenous CKII, even when the cells were grown at a permissive temperature. Phosphorylation of Fpr3 at Tyr184 by CKII in vitro lagged behind phosphorylation of Fpr3 at Ser, and was accelerated by pre-phosphorylation of Fpr3 at Ser using CKII. Furthermore, synthetic peptides corresponding to the sequence surrounding Tyr184 that contained P-Ser (or Glu) at position 186 were much more efficient substrates for CKII phosphorylation of Tyr184 than a synthetic peptide containing Ala at position 186. These findings indicate that CKII phosphorylates Fpr3 at tyrosine and serine both in vivo and in vitro and thus possesses dual specificity. These results also indicate that Tyr184 is phosphorylated by CKII via a two-step process, in which phosphorylation at the +2 position provides a negatively-charged specificity determinant that allows subsequent phosphorylation of Tyr184.


A case of acute clival osteomyelitis in a 7-year-old boy secondary to infection of a Thornwaldt cyst.
Clival osteomyelitis is a potentially life-threatening infection that can occur in healthy children. It can be related to congenital anomalies. We report the case of a 7-year-old boy with Streptococcus intermedius and Fusobacterium clival osteomyelitis arising from a Thornwaldt cyst situated in a fossa navicularis magna of the occipital bone. Multidisciplinary management is necessary to ensure rapid improvement and complete healing.


Melting of the Dipalmitoylphosphatidylcholine Monolayer.
Langmuir monolayer self-assembled at the air-water interface represents an excellent model for studying phase transition and lipid polymorphism in two dimensions. Compared with numerous studies of phospholipid phase transitions induced by isothermal compression, there are very scarce reports on two-dimensional phase transitions induced by isobaric heating. This is mainly due to technical difficulties of continuously regulating temperature variations while maintaining a constant surface pressure in a classical Langmuir-type film balance. Here, with technological advances in constrained drop surfactometry and closed-loop axisymmetric drop shape analysis, we studied the isobaric heating process of the dipalmitoylphosphatidylcholine (DPPC) monolayer. It is found that temperature and surface pressure are two equally important intensive properties that jointly determine the phase behavior of the phospholipid monolayer. We have determined a critical point of the DPPC monolayer at a temperature of 44 °C and a surface pressure of 57 mN/m. Beyond this critical point, no phase transition can exist in the DPPC monolayer, either by isothermal compression or by isobaric heating. The melting process of the DPPC monolayer studied here provides novel insights into the understanding of a wide range of physicochemical and biophysical phenomena, such as surface thermodynamics, critical phenomena, and biophysical study of pulmonary surfactants.


Reproduction in feral horses: an eight-year study.
The reproductive rate and foal survival of the free-ranging ponies on Assateague Island National Seashore were studied for 8 years, 1975 to 1982. Most (52%) of the 86 foals were born in May, 13% were born in April, 22.6% in June, 10.4% in July, and less than 1% in August and September. The mean foaling rate was 57.1 +/- 3.9% and the survival rate was 88.3 +/- 3.6%. Forty-eight colts and 55 fillies were born (sex ratio 53% female). Mares less than 3 years old did not foal and the foaling rate of 3-year-old mares was only 23%, that of 4-year-old mares was 46%, that of 5-year-old mares was 53%, and 6-year-old mares was 69%. The relatively poor reproduction rate was believed to be a consequence of the stress of lactating while carrying a foal when forage quality on the island was low. The hypothesis was supported by the higher reproductive rate (74.4 +/- 2.4%) of the ponies in the Chincoteague National Wildlife Refuge on the southern part of the island. Their foals are weaned and sold in July each year. Despite the low reproductive rate on Assateague Island National Seashore , the number of ponies increased from 43 to 80, a 90% increase in the 8-year period or greater than 10%/yr. There were 24 deaths and 8 dispersals from the study area.


Greenlight laser photoselective vaporization vs open simple prostatectomy: long-term functional outcomes after treatment of large volume prostates (> 80 cc).
To compare long-term outcomes between photoselective vaporization (PVP) and Open simple prostatectomy (OSP) for prostates > 80 cc. Men operated either by PVP or OSP for BPH > 80 cc were included in two expert centres. Functional and uroflowmetric outcomes were assessed pre- and postoperatively. Data were collected prospectively in the PVP group and retrospectively in the OSP group and compared at long-term follow-up. Complications and re-intervention rates were used as main outcomes. 332 men underwent surgery: 132 PVP were performed in a fist expert-centre and 200 OSP were performed in a second one with a median follow-up of 54 and 48 months, respectively. Mean Prostate volume was similar between OSP and PVP group (119 vs 116 cc). Major complications were more common in the OSP group (12.5 vs 1.5%, p < 0.001). At long-term follow-up, Qmax was higher and PVR was lower (p < 0.05) in the OSP group. IPSS score was similar between groups (p = 0.45) but the Qol was better in the OSP group (0.9 vs. 1.6; p < 0.05). There were more re-interventions in the PVP group compared to OSP (15.2 vs. 0%, p < 0.005). PVP is a good alternative for prostates > 80 cc particularly for fragile patients as it is associated with a lower complication rate. At long-term follow-up, IPSS was similar between groups, but Qol was better in the OSP group. Patients treated by PVP should be informed that they could require reoperation in 15% of the cases.


A composite dermal filler comprising cross-linked hyaluronic acid and human collagen for tissue reconstruction.
In this study, we developed a composite filler comprising cross-linked hyaluronic acid (HA) and human collagen (COL) derived from the human umbilical cord with the aim of improving its biocompatibility and longevity compared with commercially available fillers. After HA/ COL composite fillers were made in two different ratios (10:1 and 5:1), the physical properties of the fillers were evaluated. The interior morphologies and in vivo weight change of these hydrogels were also characterized at 1-16 weeks after injection into mice. To evaluate their biocompatibility and durability in vivo, we injected the composite fillers into nude mice subcutaneously. The variations of injected gel weight were measured and compared with the commercial dermal fillers (Restylane and TheraFill). The composites showed improved or similar physical properties (complex viscosity of 19-22 × 10(5) cP, and injection force of 10- 12 N) over the commercial dermal fillers. Sixteen weeks following the injection, the ratio of remaining composite filler weight to initial weight (75.5 ± 16.9%; 10:1) was shown to be greater than that of the commercial fillers (43.2 ± 8.1%, Restylane; 12.3 ± 5.3%, TheraFill). In addition, immunohistochemical analysis with angiogenesis-related markers such as isolectin and vWF revealed newly formed blood vessels and cellular influx into the composite filler, which were not observed in the other fillers. These results clearly suggest that the HA/COL composite filler is a superior candidate for soft tissue reconstruction. The filler we developed may be a suitable candidate as an injectable dermal filler for tissue augmentation in humans.


Anti-obesity and anti-diabetic actions of a beta 3-adrenoceptor agonist, BRL 26830A, in yellow KK mice.
The anti-obesity and anti-diabetic actions of BRL 26830A, beta 3-adrenoceptor agonist, (2 mg/kg administered intramuscularly daily for 2 weeks) were evaluated in obese diabetic Yellow KK mice and C57B1 control mice. The following parameters were compared in the treated vs. control animals: brown adipose tissue (BAT) thermogenesis, resting metabolic rate (RMR), insulin receptors in adipocytes, and blood glucose and serum insulin levels during a glucose overloading test. BRL 26830A significantly increased BAT thermogenesis and RMR but it decreased the amount of white adipose tissue without affecting food intake. Those actions contributed to the mitigation of obesity in Yellow KK mice. BRL 26830A also increased the concentration of insulin receptors and decreased the levels of serum insulin and blood glucose during the glucose overloading test in Yellow KK mice. In the glucose overloading test performed one hour after BRL 26830A injection, insulin secretion was significantly increased and the blood glucose level was markedly decreased in both groups. These observations suggest that BRL 26830A possesses anti-obesity and anti-diabetic actions and consequently may be useful for treating obesity as well as non-insulin-dependent diabetes mellitus with obesity.


Revisiting the carboxylic acid dimers in aqueous solution: interplay of hydrogen bonding, hydrophobic interactions, and entropy.
Carboxylic acid dimers are useful model systems for understanding the interplay of hydrogen bonding, hydrophobic effects, and entropy in self-association and assembly. Through extensive sampling with a classical force field and careful free energy analysis, it is demonstrated that both hydrogen bonding and hydrophobic interactions are indeed important for dimerization of carboxylic acids (except formic acid). The dimers are only weakly ordered, and the degree of ordering increases with stronger hydrophobic interactions between longer alkyl chains. Comparison of calculated and experimental dimerization constants reveals a systematic tendency for excessive self-aggregation in current classical force fields. Qualitative and quantitative information on the thermodynamics of hydrogen bonding and hydrophobic interactions derived from these simulations is in excellent agreement with existing results from experiment and theory. These results provide a verification from first principles of previous estimations based on two statistical mechanical hydrophobic theories. We also revisit and clarify the fundamental statistical thermodynamics formalism for calculating absolute binding constants, external entropy, and solvation entropy changes upon association from detailed free energy simulations. This analysis is believed to be useful for a wide range of applications including computational studies of protein-ligand and protein-protein binding.


Trends in end-of-life care and health care spending in women with uterine cancer.
High-intensity care including hospitalizations, chemotherapy, and other interventions at the end of life is costly and often of little value for cancer patients. Little is known about patterns of end-of-life care and resource utilization for women with uterine cancer. We examined the costs and predictors of aggressive end-of-life care for women with uterine cancer. In this observational cohort study the Surveillance, Epidemiology, and End Results-Medicare linked database was used to identify women age ≥65 years who died from uterine cancer from 2000 through 2011. Resource utilization in the last month of life including ≥2 hospital admissions, >1 emergency department visit, ≥1 intensive care unit admission, or use of chemotherapy in the last 14 days of life was examined. High-intensity care was defined as the occurrence of any of the above outcomes. Logistic regression models were developed to identify factors associated with high-intensity care. Total Medicare expenditures in the last month of life are reported. Of the 5873 patients identified, the majority had stage IV cancer (30.2%), were white (79.9%), and had endometrioid tumors (47.6%). High-intensity care was rendered to 42.5% of women. During the last month of life, 15.0% had ≥2 hospital admissions, 9.0% had a hospitalization >14 days, 15.3% had >1 emergency department visits, 18.3% had an intensive care unit admission, and 6.6% received chemotherapy in the last 14 days of life. The percentage of women who received high-intensity care was stable over the study period. Characteristics of younger age, black race, higher number of comorbidities, stage IV disease, residence in the eastern United States, and more recent diagnosis were associated with high-intensity care. The median Medicare payment during the last month of life was $7645. Total per beneficiary Medicare payments remained stable from $9656 (interquartile range $3190-15,890) in 2000 to $9208 (interquartile range $3309-18,554) by 2011. The median health care expenditure was 4 times as high for those who received high-intensity care compared to those who did not (median $16,173 vs $4099). Among women with uterine cancer, high-intensity care is common in the last month of life, associated with substantial monetary expenditures, and does not appear to be decreasing.


[Effect of various perfusion temperature regimens in heart surgery with extracorporeal circulation on glutathione levels and activity of enzymes of glutathione metabolism in erythrocytes].
The level of glutathione and the activity of its exchange enzymes (glutathione reductase, glutathione-S-transferase, glutathione peroxidase), the content of malonic dialdehyde were studied in the red blood levels of 70 patients operated on under hypothermal perfusion for correction of acquired cardiac diseases. The plasma concentrations of myoglobin were also measured. There was a relationship of the time course of changes in the parameters in question to the depth of the body's cooling during surgical interventions. Shallow hypothermia (30-34 degrees C) caused a compensatory increase in the activity of glutathione peroxidase (by more than 30%) and in the concentration of glutathione (by more than 60%) at the cooling stage. Moderate hypothermia (26-29 degrees C) produced no impact on the level of glutathione and the activity of its exchange enzymes while deeper hypothermia (25 degrees C or below) induced decreases in the levels of glutathione (by more than 30 degrees C) and suppressed the activity of all the tested enzymes of its exchange. At the same time there are elevated concentrations of malonic dialdehyde at the warming-up stage and during early postperfusion. Myoglobin washing into plasma occurs under all temperature conditions of perfusion at the warming-up stages and in the early postperfusion period, but it is most profound in deeper hypothermia, which is caused by the toxic effect of oxygen whose plasma solubility increases with lowered temperatures.


Effect of incorporating sodium molybdate in the form of salt lick or in mixed ration on growth and performance of sheep fed palm kernel cake.
The objective of the present experiments are to determine if sheep could safely consume high amount of PKC in their diets and if sheep's consumption of PKC require a chelating agent to tie up the high copper level in PKC to protect it against toxicity. Two experiments were carried out. Experiment 1, with four treatment groups of animals, using from 30 to 100% PKC, mixed with other feed ingredients except minerals. Mineral mixtures were separately mixed with Sodium Molybdate, acting as the chelating agent, and the mineral was offered in separate feed troughs ad.libitum, in the pens for each animal group. Although all groups gave high ADG, the animals in the 100% group had high copper in their blood, which were above4 the normal physiological level at the end of the experimental duration of three months. Three animals from this group died and their liver copper contents were very high. The groups fed up to 72% PKC in their ration did not show any significant elevation of copper or toxicity. Sheep fed similar proportions of ingredients in experiment 2, but with Molybdate incorporated together into all the four similar rations as in experiment 1, did not show any signs of toxicity or elevated blood copper. The animals in all groups produced high ADG. The experiment proved that sheep can take up to 100% PKC in their diet, but a chelating agent must be incorporated into the feed to ensure its sufficient uptake to protect it against toxicity. Giving Molybdate separately from the feed would not ensure sufficient intake of the chelating agent voluntarily. This would result in copper toxicity in the animals.


Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization.
The RNA-binding protein hnRNP A1 is a splicing regulator produced by exclusion of alternative exon 7B from the A1 pre-mRNA. Each intron flanking exon 7B contains a high-affinity A1-binding site. The A1-binding elements promote exon skipping in vivo, activate distal 5' splice site selection in vitro and improve the responsiveness of pre-mRNAs to increases in the concentration of A1. Whereas the glycine-rich C-terminal domain of A1 is not required for binding, it is essential to activate the distal 5' splice site. Because A1 complexes can interact simultaneously with two A1-binding sites, we propose that an interaction between bound A1 proteins facilitates the pairing of distant splice sites. Based on the distribution of putative A1-binding sites in various pre-mRNAs, an A1-mediated change in pre-mRNA conformation may help define the borders of mammalian introns. We also identify an intron element which represses the 3' splice site of exon 7B. The activity of this element is mediated by a factor distinct from A1. Our results suggest that exon 7B skipping results from the concerted action of several intron elements that modulate splice site recognition and pairing.


Mode change of millennial CO2 variability during the last glacial cycle associated with a bipolar marine carbon seesaw.
Important elements of natural climate variations during the last ice age are abrupt temperature increases over Greenland and related warming and cooling periods over Antarctica. Records from Antarctic ice cores have shown that the global carbon cycle also plays a role in these changes. The available data shows that atmospheric CO(2) follows closely temperatures reconstructed from Antarctic ice cores during these variations. Here, we present new high-resolution CO(2) data from Antarctic ice cores, which cover the period between 115,000 and 38,000 y before present. Our measurements show that also smaller Antarctic warming events have an imprint in CO(2) concentrations. Moreover, they indicate that during Marine Isotope Stage (MIS) 5, the peak of millennial CO(2) variations lags the onset of Dansgaard/Oeschger warmings by 250 ± 190 y. During MIS 3, this lag increases significantly to 870 ± 90 y. Considerations of the ocean circulation suggest that the millennial variability associated with the Atlantic Meridional Overturning Circulation (AMOC) undergoes a mode change from MIS 5 to MIS 4 and 3. Ocean carbon inventory estimates imply that during MIS 3 additional carbon is derived from an extended mass of carbon-enriched Antarctic Bottom Water. The absence of such a carbon-enriched water mass in the North Atlantic during MIS 5 can explain the smaller amount of carbon released to the atmosphere after the Antarctic temperature maximum and, hence, the shorter lag. Our new data provides further constraints for transient coupled carbon cycle-climate simulations during the entire last glacial cycle.


Matrix factorization-based data fusion for the prediction of RNA-binding proteins and alternative splicing event associations during epithelial-mesenchymal transition.
The epithelial-mesenchymal transition (EMT) is a cellular-developmental process activated during tumor metastasis. Transcriptional regulatory networks controlling EMT are well studied; however, alternative RNA splicing also plays a critical regulatory role during this process. Unfortunately, a comprehensive understanding of alternative splicing (AS) and the RNA-binding proteins (RBPs) that regulate it during EMT remains largely unknown. Therefore, a great need exists to develop effective computational methods for predicting associations of RBPs and AS events. Dramatically increasing data sources that have direct and indirect information associated with RBPs and AS events have provided an ideal platform for inferring these associations. In this study, we propose a novel method for RBP-AS target prediction based on weighted data fusion with sparse matrix tri-factorization (WDFSMF in short) that simultaneously decomposes heterogeneous data source matrices into low-rank matrices to reveal hidden associations. WDFSMF can select and integrate data sources by assigning different weights to those sources, and these weights can be assigned automatically. In addition, WDFSMF can identify significant RBP complexes regulating AS events and eliminate noise and outliers from the data. Our proposed method achieves an area under the receiver operating characteristic curve (AUC) of $90.78\%$, which shows that WDFSMF can effectively predict RBP-AS event associations with higher accuracy compared with previous methods. Furthermore, this study identifies significant RBPs as complexes for AS events during EMT and provides solid ground for further investigation into RNA regulation during EMT and metastasis. WDFSMF is a general data fusion framework, and as such it can also be adapted to predict associations between other biological entities.


Solitary fibrous tumor of the pancreas: imaging findings.
We report here a case of a pathologically proven solitary fibrous tumor of the pancreas. A 54-year-old man was referred to our hospital for further evaluation of a pancreatic mass that was found incidentally. CT, MR imaging, and endoscopic ultrasonography showed a well-defined, enhancing mass with cystic portions of the pancreas body. MR cholangiopancreatography showed no pancreatic duct dilatation. A solitary fibrous tumor of the pancreas is a very rare lesion.


HMGB1 as a new biomarker of celiac disease in children: A multicenter study.
Despite the availability of specific sierology and point-of-care tests, the phenotypic heterogeneity and the symptoms fluctuation as well as the "open-window" existing among the late and silent forms cause often a delayed celiac disease (CD) diagnosis. Recently, it has been reported that high mobility group box 1 (HMGB1) mediates inflammation and gastrointestinal barrier failure. The aim of this study was to detect serum HMGB1 levels at CD diagnosis and to evaluate the relationship between serum HMGB1 levels and clinical and histologic phenotypes. 49 CD children and 44 healthy children were enrolled. Specific antitissue transglutaminase type 2, antideaminated form of gliadin antibodies, serum HMGB1 levels, and typical histopathological changes in duodenal mucosa were performed in all patients. Mucosal lesions were classified according to Marsh classification. In relation to clinical presentation, we classified patients into: typical, atypical and silent forms. Serum HMGB1 levels were significantly higher in those with CD than those in the healthy control group (P < 0.001). Significant differences in serum HMGB1 levels were detected in children with typical CD form compared to both children with atypical CD form (P < 0.001) and children with silent CD form (P < 0.001). By using the Marsh classification, significant differences were found between subjects with grade 3 B-B1 and 3 C-B2 and villous atrophy, respectively (P < 0.05). On the contrary, no significant differences in serum HMGB1 levels in subgroups of children with grade 3 A compared to grade 3 B-B1 were detected. HMGB1 is upregulated at diagnosis in all CD children, especially in typical form, and reflecting the histologic severity of disease.


A role of dystroglycan in schwannoma cell adhesion to laminin.
Dystroglycan is encoded by a single gene and cleaved into two proteins alpha- and beta-dystroglycan by posttranslational processing. Recently, alpha-dystroglycan was demonstrated to be an extracellular laminin-binding protein anchored to the cell membrane by a transmembrane protein beta-dystroglycan in striated muscle and Schwann cells. However, the biological functions of the dystroglycan-laminin interaction remain obscure, and in particular, it is still unclear if dystroglycan plays a role in cell adhesion. In the present study, we characterized the role of dystroglycan in the adhesion of schwannoma cells to laminin-1. Immunochemical analysis demonstrated that the dystroglycan complex, comprised of alpha- and beta-dystroglycan, was a major laminin-binding protein complex in the surface membrane of rat schwannoma cell line RT4. It also demonstrated the presence of alpha-dystroglycan, but not beta-dystroglycan, in the culture medium, suggesting secretion of alpha-dystroglycan by RT4 cells. RT4 cells cultured on dishes coated with laminin-1 became spindle in shape and adhered to the bottom surface tightly. Monoclonal antibody IIH6 against alpha-dystroglycan was shown previously to inhibit the binding of laminin-1 to alpha-dystroglycan. In the presence of IIH6, but not several other control antibodies in the culture medium, RT4 cells remained round in shape and did not adhere to the bottom surface. The adhesion of RT4 cells to dishes coated with fibronectin was not affected by IIH6. The known inhibitors of the interaction of alpha-dystroglycan with laminin-1, including EDTA, sulfatide, fucoidan, dextran sulfate, heparin, and sialic acid, also perturbed the adhesion of RT4 cells to laminin-1, whereas the reagents which do not inhibit the interaction, including dextran, chondroitin sulfate, dermatan sulfate, and GlcNAc, did not. Altogether, these results support a role for dystroglycan as a major cell adhesion molecule in the surface membrane of RT4 cells.


Computerized Cognitive Behavioral Therapy to Treat Emotional Distress After Stroke: A Feasibility Randomized Controlled Trial.
Depression and anxiety are common complications following stroke. Symptoms could be treatable with psychological therapy, but there is little research on its efficacy. The aim of this study was to investigate (1) the acceptability and feasibility of computerized cognitive behavioral therapy (cCBT) to treat symptoms of depression and anxiety and (2) a trial design for comparing the efficacy of cCBT compared with an active comparator. Of the total 134 people screened for symptoms of depression and anxiety following stroke, 28 were cluster randomized in blocks with an allocation ratio 2:1 to cCBT (n=19) or an active comparator of computerized cognitive remediation therapy (cCRT, n=9). Qualitative and quantitative feedback was sought on the acceptability and feasibility of both interventions, alongside measuring levels of depression, anxiety, and activities of daily living before, immediately after, and 3 months post treatment. Both cCBT and cCRT groups were rated as near equally useful (mean = 6.4 vs 6.5, d=0.05), while cCBT was somewhat less relevant (mean = 5.5 vs 6.5, d=0.45) but somewhat easier to use (mean = 7.0 vs 6.3, d=0.31). Participants tolerated randomization and dropout rates were comparable with similar trials, with only 3 participants discontinuing due to potential adverse effects; however, dropout was higher from the cCBT arm (7/19, 37% vs 1/9, 11% for cCRT). The trial design required small alterations and highlighted that future-related studies should control for participants receiving antidepressant medication, which significantly differed between groups (P=.05). Descriptive statistics of the proposed outcome measures and qualitative feedback about the cCBT intervention are reported. A pragmatic approach is required to deliver computerized interventions to accommodate individual needs. We report a preliminary investigation to inform the development of a full randomized controlled trial for testing the efficacy of computerized interventions for people with long-term neurological conditions such as stroke and conclude that this is a potentially promising way of improving accessibility of psychological support.


Increase in international normalized ratio after smoking cessation in a patient receiving warfarin.
A 58-year-old man who was taking warfarin at a stable dosage was admitted to the hospital with a diagnosis of bacterial meningitis. Although he had previously been a smoker, after this admission, he decided to give up smoking. He was continued on his previous warfarin maintenance dosage when discharged, and his international normalized ratio (INR) soon began to climb substantially. When questioned, the patient reported no diet or lifestyle changes other than his smoking cessation. The patient's INR was stabilized at a warfarin dosage 23% lower than the maintenance dosage before he stopped smoking. This case report illustrates the potential for an interaction between warfarin and cigarette smoking and further suggests that the effect could be significant if a patient starts or stops smoking during warfarin therapy.


Clinical use of pressure-dimension and stress-shortening relations in systole and diastole.
The concept of time-varying elastance is an important one and has clinical relevance for both systole and diastole. The application of this concept to systole has permitted the development of end-systolic pressure-volume (dimension) and stress-shortening analysis as a method of assessing myocardial contractility in patients at risk for congestive cardiomyopathy. The application of the time-varying elastance concept to diastole is particularly relevant to new findings concerning abnormal relaxation in hypertrophic cardiomyopathy and angina pectoris.


Protein a Immunoadsorption May Hamper the Decision to Transplant Due to Interference With CDC Crossmatch Results.
Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers. From 2012 to 2013, we experienced seven patients desensitized using SPA IA, initially presenting negative cytotoxic complement dependent (CDC) T-cell crossmatches but positive B and T cell flowcytometric crossmatch, who despite significant DSA reduction developed weakly positive CDC T-cell crossmatch shortly prior to transplantation. We hypothesised that leached SPA during IA could be the cause, as the complication was not observed in patients who received plasma exchanges. We found that the positive CDC was not donor specific and SPA column material incubated with control serum reproduced a positive CDC T-cell crossmatch. Finally, we detected leached SPA in one of the patient samples using a highly sensitive time-resolved fluorescent assay. In conclusion, the results emphasize the importance of carefully considering CDC crossmatch results subsequent to IA, before a planned transplantation is either postponed or cancelled. J. Clin. Apheresis 32:163-169, 2017. © 2016 Wiley Periodicals, Inc.


Transanal Endoscopic Microsurgery for Patients With Rectal Tumors: A Single Institution's Experience.
The purpose of this study was to look at our complication rates and recurrence rates, as well as the need for further radical surgery, in treating patients with benign and early malignant rectal tumors by using transanal endoscopic microsurgery (TEM). Our study included 130 patients who had undergone TEM for rectal adenomas and early rectal cancer from December 2009 to December 2015 at the Department of Surgical Oncology, National Cancer Institute, Lithuania. Patients underwent digital and endoscopic evaluation with multiple biopsies. For preoperative staging, pelvic magnetic resonance imaging or endorectal ultrasound was performed. We recorded the demographics, operative details, final pathologies, postoperative lengths of hospital stay, postoperative complications, and recurrences. The average tumor size was 2.8 ± 1.5 cm (range, 0.5-8.3 cm). 102 benign (78.5%) and 28 malignant tumors (21.5%) were removed. Of the latter, 23 (82.1%) were pT1 cancers and 5 (17.9%) pT2 cancers. Of the 5 patients with pT2 cancer, 2 underwent adjuvant chemoradiotherapy, 1 underwent an abdominoperineal resection, 1 refused further treatment and 1 was lost to follow up. No intraoperative complications occurred. In 7 patients (5.4%), postoperative complications were observed: urinary retention (4 patients, 3.1%), postoperative hemorrhage (2 patients, 1.5%), and wound dehiscence (1 patient, 0.8%). All complications were treated conservatively. The mean postoperative hospital stay was 2.3 days. TEM in our experience demonstrated low complication and recurrence rates. This technique is recommended for treating patients with a rectal adenoma and early rectal cancer and has good prognosis.


Four methods of brain pattern analyses of fMRI signals associated with wrist extension versus wrist flexion studied for potential use in future motor learning BCI.
In stroke survivors, a treatment-resistant problem is inability to volitionally differentiate upper limb wrist extension versus flexion. When one intends to extend the wrist, the opposite occurs, wrist flexion, rendering the limb non-functional. Conventional therapeutic approaches have had limited success in achieving functional recovery of patients with chronic and severe upper extremity impairments. Functional magnetic resonance imaging (fMRI) neurofeedback is an emerging strategy that has shown potential for stroke rehabilitation. There is a lack of information regarding unique blood-oxygenation-level dependent (BOLD) cortical activations uniquely controlling execution of wrist extension versus uniquely controlling wrist flexion. Therefore, a first step in providing accurate neural feedback and training to the stroke survivor is to determine the feasibility of classifying (or differentiating) brain activity uniquely associated with wrist extension from that of wrist flexion, first in healthy adults. We studied brain signal of 10 healthy adults, who performed wrist extension and wrist flexion during fMRI data acquisition. We selected four types of analyses to study the feasibility of differentiating brain signal driving wrist extension versus wrist flexion, as follows: 1) general linear model (GLM) analysis; 2) support vector machine (SVM) classification; 3) 'Winner Take All'; and 4) Relative Dominance. With these four methods and our data, we found that few voxels were uniquely active during either wrist extension or wrist flexion. SVM resulted in only minimal classification accuracies. There was no significant difference in activation magnitude between wrist extension versus flexion; however, clusters of voxels showed extension signal > flexion signal and other clusters vice versa. Spatial patterns of activation differed among subjects. We encountered a number of obstacles to obtaining clear group results in healthy adults. These obstacles included the following: high variability across healthy adults in all measures studied; close proximity of uniquely active voxels to voxels that were common to both the extension and flexion movements; in general, higher magnitude of signal for the voxels common to both movements versus the magnitude of any given uniquely active voxel for one type of movement. Our results indicate that greater precision in imaging will be required to develop a truly effective method for differentiating wrist extension versus wrist flexion from fMRI data.


Nitrosyl-centered redox and acid-base interconversions in [Ru(Me3[9]aneN3)(bpy)(NO)](3,2,1+). The pKa of HNO for its nitroxyl derivative in aqueous solution.
This work reports the preparation of a new 6-coordinated nitrosyl compound and its use as a model to explore the redox and acid-base properties of the three redox states of bound nitrosyl (formally NO(+), NO(•), NO(-)/HNO) in {RuNO}(6,7,8) species. We prepared the octahedral {RuNO}(6) complex [Ru(Me3[9]aneN3)(bpy)(NO)](3+) (Me3[9]aneN3: 1,4,7-trimethyl-1,4,7-triazacyclononane; bpy = 2,2'-bipyridine), and the related [Ru(Me3[9]aneN3)(bpy)(NO2)](+) nitro derivative. The compounds were characterized by chemical analysis, X-ray diffraction, NMR, IR, and UV-vis spectroscopies, cyclic voltammetry (CV), UV-vis/IR spectroelectrochemistry, and theoretical calculations (DFT, (TD)DFT). The reaction kinetics between the {RuNO}(6) complex and the nucleophile OH(-) is also presented. The incorporation of tridentate and bidentate ligands in the coordination sphere prevents labilization issues associated with the trans effect when attaining the reduced states of the nitrosyl group. This allows for a consistent interpretation of the changes in the main geometrical parameters: Ru-N and N-O distances, Ru-N-O angle, and the νNO frequency and electronic transitions. We explore the redox properties in acetonitrile and aqueous solutions, and provide a potential (E1/2) - pH (Pourbaix) diagram for the three diatomic nitrosyl-bound species, as well as for HNO and NO2(-), including the report of the pKa of the [Ru(Me3[9]aneN3)(bpy)(HNO)](2+) ion, 9.78 ± 0.15 at 25.0 °C.


Fc gamma-receptors on Langerhans' cells and keratinocytes in suspension from normal skin characterized using soluble immune complexes and monoclonal antibodies.
Fc-receptors for IgG (FcR) on epidermal cells in suspension were studied using soluble immune complexes and monoclonal antibodies (MoAbs) against FcR I, FcR II and FcR III using an indirect immunofluorescence technique. The binding of immune complexes demonstrated that most Langerhans' cells (greater than 95%) and a proportion of keratinocytes (25 +/- 6%) expressed functional FcR activity. The reactivity with MoAbs showed that epidermal cells possess different types of FcR. Langerhans' cells reacted only with IV.3 (anti-FcR II/-CDw32). A varying percentage of keratinocytes reacted with 32.2 (anti-FcR I/-CD64) (18 +/- 10%), Leu 11b (anti-FcR III/-CD16) (19 +/- 6%) and B1D6 (against a placental FcR) (35 +/- 8%). Both with immune complexes and MoAbs the staining was strongest along the cell surface, but cytoplasmic staining was also regularly present. The data add further support to the contention that keratinocytes have an immune function. FcR on epidermal cells may play an immunoregulatory role interacting with isotypes and cytokines in the skin. Keratinocyte-produced soluble FcR could also be an immunological mediator.


[Hyponatremia with cisplatin administration in head and neck cancer patients].
Hyponatremia is one of the most common electrolyte disorders encountered in clinical practice of medical anticancer treatment. Cisplatin (CDDP) is a well-known chemotherapeutic agent that associates with hyponatremia. We retrospectively studied clinical features of hyponatremia CDDP administration. The incidence of hyponatremia at the first administration was 64. 1%. The significant risk factors of hyponatremia are body weight less than 60 kg, creatinin clearance less than 60mL/min, and sodium depletion and intake loss due to treatment-induced anorexia, nausea, vomiting and diarrhea. The mechanism of hyponatremia induced by CDDP is thought to be mainly renal salt wasting, and sometimes the syndrome of inappropriate secretion of antidiuretic hormone(SIADH).


e-Health in Scotland: setting a baseline for stakeholder alignment.
Gaining knowledge of nurses' attitudes towards and understanding of various aspects of the Scottish e-Health programme is vital for needed 'stakeholder alignment'. This paper is focused on the Scottish results from a large on-line survey carried out in 2006, across the UK. Key findings, identified through analysis of both qualitative and quantitative data, are discussed. Results suggest that overall there is willingness and enthusiasm to engage and to see the modernisation of the NHS in Scotland underpinned by advanced and effective IT systems. It also shows that nurses have clear ideas about how information technology could help them and their patients in delivering safe care that enhances the visibility of the nursing contribution to care outcomes. It is argued that results help in setting a base-line from which to judge the success or otherwise of the needed e-Health clinical change management programme within clinical settings.


Cyclic GMP mediates SIN-1-induced inhibition of human polymorphonuclear leukocytes.
Different nitrovasodilators were used to assess the role of cyclic GMP in the regulation of polymorphonuclear leukocyte (PMN) function. Molsidomine and its metabolites, 3-morpholinosydnonimine (SIN-1) and N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A) at 0.01-1 mM, inhibited lysosomal enzyme release from PMN stimulated by 30 nM formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). At 1 mM, molsidomine, SIN-1 and SIN-1A decreased beta-glucuronidase release by 19, 37 and 46% of the control, respectively. Glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) showed no effect on beta-glucuronidase release from PMN. At 1 mM, SIN-1A, SIN-1 and SNP in the presence of 0.5 mM isobutylmethylxanthine (IBMX) stimulated cyclic GMP 21-, 9- and 14-fold, respectively, demonstrating a relation between cyclic GMP stimulation and neutrophil inhibition by the molsidomine metabolites. GTN and unmetabolized molsidomine were without effect on cyclic GMP levels. The hypothesis of an inhibitory effect of cyclic GMP on neutrophil function was further supported by the attenuation of SIN-1-induced inhibition of enzyme release by methylene blue (10 microM), an inhibitor of soluble guanylate cyclase. Moreover, 8-bromo cyclic GMP and dibutyryl cyclic GMP, 1 mM, decreased beta-glucuronidase release from FMLP-stimulated PMN by 12 and 44% of the control, respectively. These data demonstrate that cyclic GMP is an inhibitory second messenger in human PMN and suggest that this action of SIN-1 may be of considerable interest under conditions of platelet/PMN activation, e.g. during myocardial ischemia.


Prevalence and determinants of hypertension in the Algerian Sahara.
In-Salah is a city-oasis located in the middle of the Algerian Sahara, a desert area whose drinking water has a high sodium content. No cardiovascular epidemiological studies have ever been conducted in this region. A randomized sample of 635 men and 711 women, aged 40-99 years, was studied. Blood pressure measurements, combined with a clinical questionnaire that included educational and socio-economic data, and standard blood samples for the detection of dyslipidemia and diabetes mellitus, were collected. The mean age was 55 +/- 12 years. The prevalence of hypertension was 44% and was highly influenced by age, sex, skin colour, educational status, obesity and metabolic parameters. The higher prevalence of hypertension among black individuals was independent of socio-economic and educational levels, and of metabolic parameters. The presence of antihypertensive treatment was three times more frequent in women than in men, and there was no difference according to skin colour. Among treated subjects, 25% were well controlled, and this percentage was similar among both black and white individuals. Epidemiological studies in such an emergent population indicate that hypertension is a major public health problem. The high sodium content in drinking water in this region could play a major role in the development of hypertension.


Sustained-release dosage form of phenylpropanolamine hydrochloride (3). Application of factorial design.
In this study a 2(2) factorial design has been applied to the evaluation of dissolution characteristics of phenylpropranolamine hydrochloride (PPA.HCl) from tableted microcapsules. The kinetic model according to the Rosin-Rimmler-Sperling-Bennet-Weillbull (RRSBW) distribution was applied for the parametric representation of the dissolution curves. The effect of two factors; drug particle size and kind of disintegrating agent, on the dissolution rate of PPA.HCl were studied at two levels. The factorial design method proved to be useful for the examination of tableted microcapsules.


Usefulness of Unenhanced MRI and MR Arthrography of the Shoulder in Detection of Unstable Labral Tears.
Shoulder surgeons commonly intervene to repair unstable labral tears (tears that displace with patient movement). Surgeons can detect unstable tears at surgery. It is difficult to be certain if a tear is unstable from a static MR image. This study reports the comparative benefits of using unenhanced MRI and MR arthrography together to detect unstable labral tears. One hundred fifty consecutive unenhanced shoulder MRI and MR arthrography examinations performed on the same patients were reviewed retrospectively by consensus reading of two musculoskeletal radiologists. Both unenhanced MRI and MR arthrography were performed on each patient on the same day. Labral tears were assessed. It was also determined if there was any difference in position of the labral tear between unenhanced MR images and MR arthrograms. A change in position of 4 mm or more between unenhanced MR images and MR arthrograms was considered indicative of an unstable tear. All patients proceeded to arthroscopy. Of these 150 patients, 94 had superior labral anterior-to-posterior (SLAP) tears, 53 had posterior labral tears, and 42 had anterior labral tears on MRI. All lesions described on MRI were described on arthroscopy. Twenty-three SLAP tears, 16 posterior labral tears, and 17 anterior labral tears showed a change in the position of the labral tear when comparing unenhanced MR images versus MR arthrograms of 4 mm or more. All of these labral tears were considered unstable by the surgeon, and all of these patients had surgical tacking performed. The other labral tears showed motion on unenhanced MR images and MR arthrograms of less than 4 mm. All of these tears except for three were considered stable on arthroscopic examination. There were five SLAP tears, three anterior labral tears, and four posterior labral tears seen on arthroscopy that were not seen on unenhanced MRI or MR arthrography. The tears not seen on unenhanced MRI or MR arthrography were considered stable at arthroscopy. In this study, unenhanced MRI and MR arthrography of the shoulder was useful in diagnosing unstable labral tears in 23 patients with SLAP tears, 16 patients with posterior labral tears, and 17 patients with anterior labral tears. This information was useful in surgical planning. Of 133 tears that moved less than 4 mm on unenhanced MR images and MR arthrograms, 130 were considered stable on arthroscopy.


[Deaths from traffic injuries and social inequality in Colombia, 2019Mortalidade por acidentes de trânsito e desigualdades sociais na Colômbia, 2019].
To evaluate the association between social inequalities and deaths from traffic injuries in Colombia in 2019. This ecological study evaluated the association between social inequalities and deaths from traffic injuries among users of the road transport system in Colombia in 2019, based on secondary information sources, using the department level as the administrative and geographic unit of study. A descriptive statistical analysis of health indicators and equity stratifiers was performed. Absolute and relative measures were used to determine social inequality gaps. In 2019, 6 580 people died from road traffic injuries in Colombia. The majority of them (82%) were men. The most critical user condition was being a motorcyclist. The age group with the most victims was approximately 30 years old. Departments with populations between 500 000 and 2 000 000 were the most represented. The most critical equity stratifier was the number of registered motorcycles per 100 000 population. Significant inequality gaps between departments were observed. Inequalities in deaths from road traffic injuries in Colombia were observed. Policies and actions should focus on helping to reduce identified inequities, resulting in better quality of life, well-being, and health for the population.


Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network.
The transcriptional pathways activated downstream of vascular endothelial growth factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand delta-like 4 (DLL4) in endothelial cells, we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction. Transcription of DLL4 coincides with dynamic ERG-dependent recruitment of the transcriptional co-activator p300. Genome-wide gene expression profiling identified a network of VEGF-responsive and ERG-dependent genes, and ERG chromatin immunoprecipitation (ChIP)-seq revealed the presence of conserved ERG-bound putative enhancer elements near these target genes. Functional experiments performed in vitro and in vivo confirm that this network of genes requires ERK, ERG and p300 activity. Finally, genome-editing and transgenic approaches demonstrate that a highly conserved ERG-bound enhancer located upstream of HLX (which encodes a transcription factor implicated in sprouting angiogenesis) is required for its VEGF-mediated induction. Collectively, these findings elucidate a novel transcriptional pathway contributing to VEGF-dependent angiogenesis.


Fetal weight estimation: comparison of two-dimensional US and MR imaging assessments.
To prospectively define fetal density in the second half of pregnancy by using magnetic resonance (MR) imaging and to compare estimates of fetal weight based on ultrasonography (US) and MR imaging with actual birth weight. Written informed consent was obtained for this ethics committee-approved study. In this cross-sectional study between March 2011 and May 2012, fetal density was calculated as actual birth weight at delivery divided by fetal body volume at MR imaging in 188 fetuses between 20 weeks and 2 days and 42 weeks and 1 day of gestational age. Regression analysis was used to investigate the effect of variables, including sex, on fetal density. The US estimate of fetal weight was performed according to Hadlock et al, and the MR estimate of fetal weight was calculated based on the equation developed by Baker et al. US and MR estimates of fetal weight were compared with actual birth weights by using regression analysis. Median fetal density was equal to 1.04 (range, 0.95-1.18). Fetal density was significantly associated with gestational age at delivery but not with fetal sex. In 26.6% of fetuses, the US estimate of fetal weight had a relative error of more than 10%, while a similar relative error for the MR estimate of fetal weight occurred in only 1.1% of fetuses. The limits of agreement were narrower with the MR estimate of fetal weight compared with the US estimate of fetal weight. In the second half of pregnancy, fetal density varies with gestational age. Fetal weight estimates by using fetal MR imaging are better than those by using prenatal US.


Nutritional composition and antinutritional properties of maize ogi cofermented with pigeon pea.
Maize was cofermented with pigeon pea for ogi production and evaluated for nutritional (proximate composition, minerals, vitamins, and amino acid profile analyses) and antinutritional (phytate, tannin, and trypsin inhibitor activity analyses) qualities. White maize and pigeon pea were mixed at ratios of 90:10, 80:20, 70:30, 60:40, and 50:50, respectively, with 100:0 serving as the control. Mixtures were cofermented for 96 hr at 27°C ± 2°C and nutritional, mineral, and antinutritional qualities were analyzed using analysis of variance. Results of proximate analysis showed that the values were significantly difference at p ≤ .05. Maize cofermented with pigeon pea at a ratio of 60:40 had the highest protein (22.79 mg/100 g), fat (19.27 mg/100 g), ash (2.98 mg/100 g), crude fiber (0.73 mg/100 g), and lowest moisture (1.98 mg/100 g) content, and was significantly (p ≤ .05) different from the other ratios. Of all the mixtures analyzed, 60:40 was significantly (p ≤ .05) different and had the highest Vitamin B1, B2, and B3 contents. Amino acid profile results showed that maize cofermented with pigeon pea at a ratio of 60:40 showed the highest contents of lysine (93.95 mg/g), tryptophan (20.38 mg/g), isoleucine (54.78 mg/g), phenylalanine (86.23 mg/g), leucine (109.55 mg/g), and valine (68.29 mg/g), respectively, and was significantly (p ≤ .05) different from the other ratios. Results of antinutritional analysis showed low phytate, tannin, and trypsin inhibitor values in maize cofermented with pigeon pea at a ratio of 60:40 when compared with other ratios. The cofermented maize-pigeon pea product 60:40 had high amino acid profile than the others.


Evidence-Based Supported Employment in the Rural United States: Challenges and Adaptations.
The authors examined how individual placement and support (IPS), an evidence-based model of supported employment, has been successfully adapted in rural communities across the United States. Interviews with 27 key informants in 15 states with successful IPS programs in rural communities identified challenges that IPS workers faced because of rurality and the work-around methods they used to overcome these challenges. The authors conducted a thematic analysis of interviews. Significant challenges to implementing IPS in rural areas included limited availability of public transportation, Internet connectivity, employment opportunities, and workforce. The work-around strategies used by IPS teams differed in relation to local circumstances and cultures, but effective services generally used natural supports for transportation, provided computer access for job applicants, developed relationships with local employers, and hired IPS workers with local knowledge. The adaptations made to IPS in rural areas are specific to local communities but retain core IPS principles.


Carotid Disease and Ageing: A Literature Review on the Pathogenesis of Vascular Senescence in Older Subjects.
Aging is a natural process that affects all systems of the human organism, leading to its inability to adapt to environmental changes. Advancing age has been correlated with various pathological conditions, especially cardiovascular and cerebrovascular diseases. Carotid artery (CA) is mainly affected by age-induced functional and morphological alterations causing atheromatous disease. The evolvement of biomedical sciences has allowed the elucidation of many aspects of this condition. Symptomatic carotid disease (CD) derives from critical luminar stenosis or eruption of an atheromatous plaque due to structural modifications of the vessels, such as carotid intima-media thickening. At a histologic level, the aforementioned changes are mediated by elastin fragmentation, collagen deposition, immune cell infiltration, and accumulation of cytokines and vasoconstrictors. Underlying mechanisms include chronic inflammation and oxidative stress, dysregulation of cellular homeostatic systems, and senescence. Thus, there is an imbalance in components of the vessel wall, which fails to counteract exterior stress stimuli. Consequently, arterial relaxation is impaired and atherosclerotic lesions progress. This is a review of current evidence regarding the relationship of aging with vascular senescence and CD. A deeper understanding of these mechanisms can contribute to the production of efficient prevention methods and targeted therapeutic strategies.


[Pulmonary function in patients with infiltrative pulmonary tuberculosis].
Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, pulmonary residual volume (PRV), R(aw), R(in),, R(ex), DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 103 patients with infiltrative pulmonary tuberculosis. Pulmonary dysfunction was detected in 83.5% of the patients. Changes were found in lung volumes and capacities in 63.1%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 60.2 and 41.7%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC and FVC, and decreased and increased TGV and TLC; impaired bronchial patency presented as decreased PEF, MEF25, MEF50, MEF75, FEV1/VC% and increased R(aw) R(in), and R(ex); pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, DLCO-SS, and PaO2 and decreased and increased PaCO2. The magnitude of the observed functional changes was generally slight. Significant disorders were observed rarely and very pronounced ones were exceptional.


Distribution of HLA class II alleles and haplotypes in Mexican Mestizo population: comparison with other populations.
We describe the analysis of the Major Histocompatibility Complex (MHC) class II polymorphism in Mexican Mestizo population. The study provides the HLA-DRB1, DQA1 and DQB1 allele frequencies in 99 Mexican Mestizos. DNA from these individuals was typed by PCR followed by hybridization using sequence specific oligonucleotides (PCR-SSO). The relationship with other worldwide populations was studied by using HLA data from 69 different populations and calculating neighbor-joining dendrograms and correspondence multidimensional values. The highest frequencies were for DRB1*0802 (allele frequency = 0.151), DRB1*0701 (allele frequency = 0.111) and DRB1*0407 (allele frequency = 0.106). Among the eight DQA1 alleles detected, the most frequent were DQA1*03011 (allele frequency = 0.257), DQA1*0501 (allele frequency = 0.227) and DQA1*0401 (allele frequency = 0.166). Twelve DQB1 alleles were found and four of them, DQB1*0302 (allele frequency = 0.237), DQB1*0301 (allele frequency = 0.176), DQB1*0201 (allele frequency = 0.166) and DQB1*0402 (allele frequency = 0.166) showed the highest frequencies. The haplotype DRB1*0802-DQA1*0401-DQB1*0402 (0.151) predominated clearly, followed by DRB1*0701-DQA1*0201-DQB1*0201 (0.111) and DRB1*0407-DQA1*03011-DQB1*0302 (0.101). Both genetic distances and correspondence analyses showed that Mexicans clustered with Amerindian population. These results suggest that the Mexican Mestizo population be principally characterized by haplotypes presents in Amerindian and Caucasian populations with a low frequency of Black haplotypes. In summary, the HLA class II haplotype frequencies demonstrated the tri-racial component existing in Mexican Mestizos.


Diagnostic ultrasound in pregnancy and low birthweight.
Diagnostic ultrasound has been used increasingly in obstetric practice over the past decade. To date, adverse effects of ultrasound on the fetus have not been reported, but studies have been done on small sample sizes. This study looks specifically at the association of ultrasound exposure during pregnancy and the risk of low birthweight in the offspring. A validation case-control study was also performed based on information from a sample of medical charts. With a database of more than 13,000 pregnancies, there was no indication of an adverse effect of ultrasound performed during the first two trimesters of pregnancy.


Venous and arterial gas embolism associated with positive pressure ventilation.
We report a 53-year-old woman with ARDS who required positive pressure ventilation with positive end-expiratory pressure. She sustained an acute right ventricular myocardial infarction associated with cardiovascular instability. The next day she sustained a fatal cerebral arterial gas embolism. Intravascular gas was documented within the cerebral, coronary, and pulmonary arterial circulations. Clinicians need to be aware of venous and arterial gas embolism as a complication of mechanical ventilation.


Seasonal Patterns: Bovine Trypanosomosis, Glossina pallidipes Density, and Infection in Rift Valleys of Gamo Zone, Southern Ethiopia.
Bovine trypanosomosis is a parasitic disease causing serious economic losses in livestock productivity and agricultural development. The disease has been reported in different parts of Ethiopia. However, seasonal pattern of trypanosomosis, tsetse fly apparent density, and infection are very limited in the southern rift valley of the country, particularly in Gamo Zone. Therefore, the objective of this cross-sectional study design was to estimate seasonal prevalence of bovine trypanosomosis, assessing tsetse fly apparent density and its infection by trypanosomes. For the parasitological study, a total of 600 cattle (300 in each season) were sampled and assayed using the buffy coat technique. A total of 80 standard NGU traps were deployed around the watering and grazing areas for the entomological survey. An overall prevalence of trypanosomosis was 10.17% (61/600), of which 7.33% (22/300) and 13% (39/300) accounted for the dry and wet seasons, respectively. The prevalence of trypanosomosis was significantly higher during the wet season (OR = 2.47; p < 0.05), in black coat color (OR = 7.2, p < 0.05), and poor body-conditioned (OR = 3.15; p < 0.05) animals. Two species of trypanosomes, Trypanosoma congolense, 68.85% (42/61), and Trypanosoma vivax, 31.15% (19/61), were circulating in the area. The mean PCV value in infected animals (22.56 ± 4.61) was significantly lower than in non-infected animals (25.3 ± 4.75). Entomological result indicated that Glossina pallidipes (G. pallidipes) was the only species of tsetse found in the study area. Totally, 3,789 flies were caught of which 81.42% (3,085/3,789) belong to G. pallidipes and 18.58% (704/3,789) were other biting flies. The overall apparent density of G. pallidipes was 12.85 flies/trap/day (FTD). Relatively higher G. pallidipes/trap/day were caught in the wet season (13.64 F/T/D) than in the dry season (12.07F/T/D). Of the flies caught, 342 G. pallidipes were randomly selected and dissected. The overall proportion of G. pallidipes infection was 18.42% (63/342) of which 12.28% (21/171) and 24.56% (42/171) were accounted in the dry and wet seasons, respectively. Infection in G. pallidipes was significantly higher during the wet season (OR = 2.32; p < 0.05) and in park grazing areas (OR = 2.45; p < 0.05). In conclusion, trypanosomosis is the major challenge for cattle productivity in the district. So this study warrants the need for strengthening the vector and parasite control interventions in the area.


A new standardized phytoextract from red orange and lemon wastes (red orange and lemon extract) reduces basophil degranulation and activation.
Citrus fruits are rich sources of bioactive compounds and their consumption is associated to health-promoting effects. Citrus processing wastes contain bioflavonoids and other high added value compounds. The aim of this study was to evaluate the antiallergic properties of a new phytoextract obtained by citrus wastes and peels. Blood orange and lemon processing wastes were used to produce a Red orange and Lemon Extract (RLE). Blood samples from 30 allergic donors were collected and used to evaluate the basophil activation (CD203c) and degranulation (CD63) by stimulation trough allergen with and without the RLE. Reduced basophil expression of CD203c and CD63 were observed in RLE + Allergen treated samples, with -20.21% of CD203c expression (p < 0.0001) and -54.11% of CD63 expression (p < 0.0001), compared to Allergen treated samples. The RLE evidenced a good antiallergic activity, mainly acting on basophils degranulation, and therefore reducing the key event of pro-inflammatory mediators release after allergic stimuli.


Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review.
The aim of this review was to recommend training strategies that improve the functional capacity in physically frail older adults based on scientific literature, focusing specially in supervised exercise programs that improved muscle strength, fall risk, balance, and gait ability. Scielo, Science Citation Index, MEDLINE, Scopus, Sport Discus, and ScienceDirect databases were searched from 1990 to 2012. Studies must have mentioned the effects of exercise training on at least one of the following four parameters: Incidence of falls, gait, balance, and lower-body strength. Twenty studies that investigated the effects of multi-component exercise training (10), resistance training (6), endurance training (1), and balance training (3) were included in the present revision. Ten trials investigated the effects of exercise on the incidence of falls in elderly with physical frailty. Seven of them have found a fewer falls incidence after physical training when compared with the control group. Eleven trials investigated the effects of exercise intervention on the gait ability. Six of them showed enhancements in the gait ability. Ten trials investigated the effects of exercise intervention on the balance performance and seven of them demonstrated enhanced balance. Thirteen trials investigated the effects of exercise intervention on the muscle strength and nine of them showed increases in the muscle strength. The multi-component exercise intervention composed by strength, endurance and balance training seems to be the best strategy to improve rate of falls, gait ability, balance, and strength performance in physically frail older adults.


Physical activity patterns of college students with and without high school physical education.
The purpose of this study was to examine differences in physical activity patterns of high school graduates in Texas who completed physical education class credit during high school and those who did not but who were varsity athletes. A questionnaire was designed and tested for reliability prior to being administered to 201 college students. Analysis indicated that participants who completed high school physical education class credit do not currently participate in regular physical activity as much as those who were not required to complete such credit. Conversely, athletes who did not participate in physical education reported currently engaging in more cardiovascular exercise and team sports than the physical education students during high school.


X-ray and dielectric measurements of the smectic- A -hexatic- B transitionin bulk and confined geometries.
We report x-ray and dielectric measurements on a liquid crystal exhibiting a smectic- A -hexatic- B (Sm- A -Hex- B ) transition in bulk and confined geometries. The confined geometry experiments have been performed by filling the compound, n -butyl 4(') - n -hexyloxybiphenyl-4-carboxylate, into Anopore membranes with 20 nm pore size. The surprising result seen in the x-ray studies on both the bulk and the Anopore samples is the presence of unusually strong second harmonic reflection arising from the smectic layers in both the Sm- A and Hex- B phases. In fact, the third harmonic reflection is also observed in the entire temperature range of the Hex- B phase and close to the transition in the Sm- A phase of the bulk sample, with the ratio of I(2qo) / I(qo), and I(3qo) / I(qo) being approximately 1/40 and 1/470, respectively (here I(qo), I(2qo), and I(3qo) correspond to the peak intensities of the first, second, and third harmonic reflections). These features point to the fact that the layering is much better defined in this system, unlike the usual description of pure sinusoidal mass density wave with a typical value of 10(-4) for I(2qo) / I(qo). Another notable feature observed is that whereas the extent of positional correlations of the molecules within the smectic layer, is comparable in the Sm- A phase of the bulk and Anopore samples, the correlations are reduced in the Hex- B phase. In the bulk as well as the Anopore case, the critical behavior of the positional correlations is found to be well described by a power-law expression with the exponent alpha being slightly larger for the Anopore sample. It is also seen that the weak first order nature of the transition seen in the bulk, gets weakened further, perhaps becoming second order. Despite such significant differences between the bulk and Anopore samples, the dynamics associated with the director fluctuations is only slightly influenced by confinement.


Alliance Rupture and Resolution in Dialectical Behavior Therapy for Borderline Personality Disorder.
The aim of this exploratory study was to investigate alliance rupture and resolution processes in the early sessions of a sample of clients who underwent 1 year of standard dialectical behavior therapy (DBT) for borderline personality disorder (BPD). Participants were three recovered and three unrecovered clients drawn from the DBT arm of a randomized controlled trial that compared the clinical and cost-effectiveness of DBT and general psychiatric management. Alliance rupture and resolution processes were coded using the observer-based Rupture Resolution Rating Scale. Unrecovered clients evidenced a higher frequency of withdrawal ruptures than recovered clients. Withdrawal ruptures tended to persist for unrecovered clients despite the degree of resolution in the prior session, unlike for recovered clients, for whom the probability of withdrawal ruptures decreased as the degree of resolution increased. This study suggests that alliance rupture and resolution processes in early treatment differ between recovered and unrecovered clients in DBT for BPD.


The effect of prophylactic antibiotics on risk factors for endomyometritis in adolescent patients undergoing cesarean section.
The efficacy of ticarcillin and its effect on the known risk factors for endomyometritis and the prevention of postcesarean infection was studied in adolescents. Patients were randomly given the antibiotic or a placebo. The patients who received prophylactic ticarcillin had one-half the endomyometritis rate as the placebo group. Four or more vaginal examinations during labor were associated with a high incidence of endomyometritis. This was reduced by 35% with prophylaxis. When membranes were ruptured for more than 8 hours before cesarean section, the endomyometritis rate was 86% in the placebo group, as compared to 28% in the prophylactic-treated group. A similar effect occurred in the high-risk length of labor group. Ticarcillin appears to be effective in reducing the incidence of postcesarean endomyometritis in adolescent patients. The critical risk factors, in order of importance, were the number of pelvic examinations performed during labor, the length of time between rupture of membranes and cesarean section, and the length of labor before cesarean section.


Hemolytic activity of phosphorite and apatite dusts in vitro.
An examination was performed to assess the hemolytic activity of phosphorite and apatite dust in vitro by a method used by Potts et al. (1978). After evaluation of dispersion, a certain contents of elements was established, using a spectrometer of X-ray fluorescence. Phosphorite dusts caused 50.4% of hemolyse that is about 5 times more than those caused by dust of apatites. The mean hemolysis index for phosphorite dust was 0.799 and for apatite dust 0.142. Thus, phosphorites are much more toxic to a human being than apatites. A higher level of hemolytical activity in phosphorite dust as compared to apatite one can be explained by significant difference in the contents of certain elements, SiO2, in particular. The mean SiO2 level in samples containing phosphorites was 6.3 +/- 0.1% compared to samples of apatites (3.8 +/- 0.09%).


Nicotianamine: A Key Player in Metal Homeostasis and Hyperaccumulation in Plants.
Nicotianamine (NA) is a low-molecular-weight N-containing metal-binding ligand, whose accumulation in plant organs changes under metal deficiency or excess. Although NA biosynthesis can be induced in vivo by various metals, this non-proteinogenic amino acid is mainly involved in the detoxification and transport of iron, zinc, nickel, copper and manganese. This review summarizes the current knowledge on NA biosynthesis and its regulation, considers the mechanisms of NA secretion by plant roots, as well as the mechanisms of intracellular transport of NA and its complexes with metals, and its role in radial and long-distance metal transport. Its role in metal tolerance is also discussed. The NA contents in excluders, storing metals primarily in roots, and in hyperaccumulators, accumulating metals mainly in shoots, are compared. The available data suggest that NA plays an important role in maintaining metal homeostasis and hyperaccumulation mechanisms. The study of metal-binding compounds is of interdisciplinary significance, not only regarding their effects on metal toxicity in plants, but also in connection with the development of biofortification approaches to increase the metal contents, primarily of iron and zinc, in agricultural plants, since the deficiency of these elements in food crops seriously affects human health.


Effects of nebulised magnesium sulphate on inflammation and function of the guinea-pig airway.
Magnesium sulphate is a potential treatment for acute severe asthma. However, the mechanisms and dose-response relationships are poorly understood. The first objective of this study was to examine whether inhaled magnesium sulphate exerts bronchodilator activity measured as bronchoprotection against histamine-induced bronchoconstriction in conscious guinea-pigs alone and combined with salbutamol. Secondly, we examined whether inhaled magnesium sulphate inhibits airways inflammation and function in models of neutrophilic and eosinophilic lung inflammation induced, respectively, by inhaled lipopolysaccharide or the inhaled antigen, ovalbumin (OVA). Airway function was measured in conscious guinea-pigs as specific airway conductance (sGaw) by whole-body plethysmography. Anti-inflammatory activity was measured against lung inflammatory cell influx induced by OVA inhalation in OVA-sensitised animals or by lipopolysaccharide (LPS) exposure of non-sensitised animals. Airway function (sGaw) was measured over 24h after OVA exposure. Airway hyperresponsiveness to inhaled histamine and inflammatory cells in bronchoalveolar lavage fluid were recorded 24h after OVA or LPS challenge. Histamine-induced bronchoconstriction was inhibited by inhaled magnesium sulphate or salbutamol alone and in combination, they produced synergistic bronchoprotection. LPS-induced neutrophil influx was inhibited by 6 days pretreatment with magnesium sulphate. Early and late asthmatic responses in OVA sensitised and challenged animals were attenuated by magnesium sulphate. Lung inflammatory cells were increased by OVA, macrophages being significantly reduced by magnesium sulphate. Nebulised magnesium sulphate protects against histamine-induced bronchoconstriction in conscious guinea-pigs and exerts anti-inflammatory activity against pulmonary inflammation induced by allergen (OVA) or LPS. These properties of magnesium sulphate explain its beneficial actions in acute asthma.


Do People Know What They're Like in the Moment?
Knowing yourself requires knowing not only what you are like in general (trait self-knowledge) but also how your personality fluctuates from moment to moment (state self-knowledge). We examined this latter form of self-knowledge. Participants (248 people; 2,938 observations) wore the Electronically Activated Recorder (EAR), an unobtrusive audio recorder, and completed experience-sampling self-reports of their personality states four times each day for 1 week. We estimated state self-knowledge by comparing self-reported personality states with consensual observer ratings of personality states coded from the EAR files, which formed the criterion for what participants were "actually" like in the moment. People had self-insight into their momentary extraversion, conscientiousness, and likely neuroticism, suggesting that people can accurately detect fluctuations in some aspects of their personality. However, the evidence for self-insight was weaker for agreeableness. This apparent self-ignorance may be partly responsible for interpersonal problems and for blind spots in trait self-knowledge.


Standardized cloning vectors for protein production and generation of large gene libraries in Escherichia coli.
Here, we modified the multiple cloning sites from commonly used expression vectors to create a new suite of cloning plasmids that simplify and speed up cloning procedures in Escherichia coli. Each of our standardized plasmids contains two BsaI restriction sites, allowing for highly efficient cloning of genes and bringing their expression under control of either a T7 (pET21a_BsaI, pET28a_BsaI, and pMAL-c5T_BsaI) or T5 promoter (pUR22 and pUR23). Another plasmid in our suite (pTNA_BsaI) allows for generation of large gene libraries containing >108 variants, which can be constitutively expressed in selection experiments using metabolic complementation of auxotrophic E. coli strains. Coupling restriction and ligation with the BsaI restriction enzyme minimizes hands-on time, while the need for only three different primers to clone a target gene into the six different vectors keeps overall cloning costs low.


Production of Curcuminoids in Engineered Escherichia coli.
Curcumin, a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa, possesses diverse pharmacological properties, including anti-inflammatory, antioxidant, antiproliferative, and antiangiogenic activities. Two curcuminoids (dicinnamoylmethane and bisdemethoxycurcumin) were synthesized from glucose in Escherichia coli. PAL (phenylalanine ammonia lyase) or TAL (tyrosine ammonia lyase), along with Os4CL (p-coumaroyl-CoA ligase) and CUS (curcumin synthase) genes, were introduced into E. coli, and each strain produced dicinnamoylmethane or bisdemethoxycurcumin, respectively. In order to increase the production of curcuminoids in E. coli, the shikimic acid biosynthesis pathway, which increases the substrates for curcuminoid biosynthesis, was engineered. Using the engineered strains, the production of bisdemethoxycurcumin increased from 0.32 to 4.63 mg/l, and that of dicinnamoylmethane from 1.24 to 6.95 mg/l.


c-erbB-2 gene product-like expression in urothelial carcinomas of the human bladder. Its value as a prognostic indicator in superficial tumors.
54 transitional cell carcinomas and 8 mucosal biopsies of the human bladder were stained with monoclonal 3B5 antibody, using three stage peroxidase technique. The antibody is raised against intracytoplasmic domain of the human c-erbB-2 gene product. 37 (69%) carcinomas and 1 specimen with hyperplastic-dysplastic changes, showed positive staining. There was good correlation between c-erbB-2 protein expression and extent of tumor invasion. Correlation with clinical course showed that it was also a good predictor of superficial tumors.


Primary hyperparathyroidism--an Indian study.
Twenty eight patients of sporadic primary hyperparathyroidism seen over a period of 10 years were studied. There were 18 females and 10 males with a mean age of 35.9 years. Bone involvement was the commonest clinical presentation (90%) followed by renal involvement (65%) and more than half the patients (54%) had involvement of both the skeletal and renal systems. The tumor was clinically palapable in six patients. Thalliumtechnetium subtraction scan had a sensitivity of 87% followed by computerised tomography (70%), and ultrasound (65%) in diagnosing parathyroid pathology. All the patients underwent surgical excision of the abnormal gland (S). Adenomas constituted the single largest group (90%). Histologically, only 32% of the patients had chief cell morphology. Clear cell (32%) mixed cell, and oxyphil cell (7.2%) types accounted for the remaining adenomas. Majority of the patients (82%) had symptomatic postoperative hypocalcemia requiring intravenous calcium with or without vitamin D supplementation. In contrast to western reports most of our patients were young, presented late with florid bone and renal disease and had large palpable tumors.


An update on the AHCPR guideline implementation.
Publication in 1992 of national Clinical Practice Guidelines for Urinary Incontinence in Adults by the US Department of Health and Human Services, Agency for Health Care Policy and Research (AHCPR) brought together in one document, for the first time, all the relevant material on the diagnosis and treatment of urinary incontinence. These guidelines also provided data about the effectiveness of various treatment options. Dissemination has been enhanced through massive distribution to professional and lay groups as well as making copies available at no charge by telephone (1-800-358-9295). Because of the volume of new research on incontinence, the guidelines are now being revised and updated with publication expected in 1995. This guideline is especially relevant for nursing because nurses are often the first, and may be the only, health professional with whom patients will discuss this embarrassing problem.


How does Zika virus cause microcephaly?
The re-emergence of Zika virus (ZIKV), a mosquito-borne and sexually transmitted flavivirus circulating in >70 countries and territories, poses a significant global threat to public health due to its ability to cause severe developmental defects in the human brain, such as microcephaly. Since the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern, remarkable progress has been made to gain insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection. Here we review the current knowledge and progress in understanding the impact of ZIKV exposure on the mammalian brain development and discuss potential underlying mechanisms.


Evaluation of a score for the prehospital distinction between cerebrovascular disease and stroke mimic patients.
Patients with a sudden onset of focal neurological deficits consistent with stroke, who turn out to have alternative conditions, have been labeled stroke mimics. We assessed a recently validated telemedicine-based stroke mimic score (TeleStroke mimic score; TM-score) and individual patient characteristics with regard to its discriminative value between cerebrovascular disease and stroke mimic patients in the in-person, pre-hospital setting. We evaluated patients cared for in a mobile stroke unit in Berlin, Germany. We investigated whether the TM-score (comprising six parameters), Face Arm Speech Time test, and individual patient characteristics were able to differentiate cerebrovascular disease from stroke mimic patients. We included 423 patients (299 (70.7%) cerebrovascular disease and 124 (29.3%) stroke mimic) in the final analysis. A TM-score > 30 indicated a high probability of a cerebrovascular disease and a score ≤15 of a stroke mimic. The TM-score performed well to identify stroke mimics (area under the curve of 0.74 under receiver-operating characteristic curve analysis). The cerebrovascular disease patients were older (74.8 vs. 69.8 years, p = 0.001), had more often severe strokes (NIHSS > 14 25.8% vs. 11.3%, p = 0.001), presented more often with weakness of the face (70.9% vs. 42.7%, p = 0.001) or arm (60.9% vs. 33.9%, p = 0.001), dysarthria (59.5% vs. 40.3%, p < 0.001), history of atrial fibrillation (38.1% vs. 21.0%, p = 0.001), arterial hypertension (78.9% vs. 53.2%, p < 0.001), and less often with seizure (0.7% vs. 21.0%, p < 0.001). The TM-score and certain patient characteristics can help paramedics and emergency physicians in the field to identify stroke mimic patients and select the most appropriate hospital destination.


Orthoplastic surgical collaboration is required to optimise the treatment of severe limb injuries: A multi-centre, prospective cohort study.
Open fractures are severe, complex, limb-threatening and high-energy injuries, often involving lesions of both bone and soft tissues. Traditionally, treatment has been piecemeal by orthopaedic and plastic surgeons. This study aimed to prospectively investigate whether combining orthopaedic and plastic surgery in treating these injuries is more effective than the conventional orthopaedic care. A prospective multi-centre cohort study was conducted. Differences in the type of approach to severe limb trauma allowed a comparison between combined orthoplastic and traditional exclusively orthopaedic treatment. Time for fracture and soft tissue healing and the recovery of limb function were the main outcome measures studied. All patients suffering from a severe open tibial fracture were prospectively included between January 2012 and December 2013 and followed until December 2014. Recruiting units were as follows: (1) an established orthoplastic centre, (2) a unit without experience in the orthoplastic approach and (3) a unit where the orthoplastic approach has been recently introduced in a developing country (Pakistan). A total of 160 patients were included in the study. Of these, 70% were treated with an orthoplastic approach, whereas 30% were treated by an orthopaedic team. All outcome measures were statistically improved by the orthoplastic approach. A coordinated, combined pathway to both the bony and the soft tissue components of open tibial fractures through orthoplastic surgery can be successfully delivered with attention to important timelines to achieve better patient outcomes in different socio-economic settings.


Emergency medical services providers' perspective of end-of-life decision making for people with intellectual disabilities.
Emergency medical services (EMS) providers are often called to rapidly determine and act upon patients' wishes for end-of-life care. People with intellectual disabilities are living increasingly longer with complex conditions leading to international calls for person-centred advance care planning. Yet, best estimates suggest that very few people with intellectual disabilities document their wishes. This exploratory-descriptive study incorporated mixed methods to analyse data collected consecutively (surveys, n = 239; interviews, n = 48) with EMS providers from five agencies. Data were subjected to a sequential quantitative-qualitative analysis applying a critical discourse analysis framework. Findings indicate that 62.7% had treated a person with intellectual disability who had medical orders directing end-of-life care. Three themes (provider familiarity, organizational processes, sociocultural context) offer insights about how medical orders inform EMS providers during calls involving people with intellectual disabilities. Multiple contexts influence how wishes are documented and care provided to people with intellectual disabilities near life's end.


Hepatitis D Virus-Specific CD8+ T Cells Have a Memory-Like Phenotype Associated With Viral Immune Escape in Patients With Chronic Hepatitis D Virus Infection.
Hepatitis D virus (HDV) superinfection of patients with chronic HBV infection results in rapid progression to liver cirrhosis. Little is known about HDV-specific T cells and how they contribute to the antiviral immune response and liver disease pathogenesis. We isolated peripheral blood mononuclear cells from 28 patients with chronic HDV and HBV infection, identified HDV-specific CD8+ T-cell epitopes, and characterized HDV-specific CD8+ T cells. We associated these with HDV sequence variations and clinical features of patients. We identified 6 CD8+ T-cell epitopes; several were restricted by multiple HLA class I alleles. HDV-specific CD8+ T cells were as frequent as HBV-specific CD8+ T cells but were less frequent than T cells with specificity for cytomegalovirus, Epstein-Barr virus, or influenza virus. The ex vivo frequency of activated HDV-specific CD8+ T cells correlated with transaminase activity. CD8+ T-cell production of interferon gamma after stimulation with HDV peptides correlated inversely with HDV titer. HDV-specific CD8+ T cells did not express the terminal differentiation marker CD57, and fewer HDV-specific than Epstein-Barr virus-specific CD8+ T cells were 2B4+CD160+PD1+, a characteristic of exhausted cells. Approximately half of the HDV-specific CD8+ T cells had a memory-like PD1+CD127+TCF1hiT-betlow phenotype, which associated with HDV sequence variants with reduced HLA binding and reduced T-cell activation. CD8+ T cells isolated from patients with chronic HDV and HBV infection recognize HDV epitopes presented by multiple HLA molecules. The subset of activated HDV-specific CD8+ T cells targets conserved epitopes and likely contributes to disease progression. The subset of memory-like HDV-specific CD8+ T cells is functional but unable to clear HDV because of the presence of escape variants. ClinicalTrials.gov, Numbers: NCT02511431, NCT00023322, NCT01495585, and NCT00001971. GenBank accession, Number: MK333199-333226.


Pseudoptosis Correction With the 270° Pedicle Reduction Mammoplasty: An Anatomic and Clinical Study.
Background: Reduction mammoplasty techniques have evolved considerably. Today, aesthetically pleasing results and preservation of nipple sensation and vascularity are emphasized. Achieving the aforementioned goals for the patient with pseudoptosis remains challenging. Objective: We present 270° pedicle reduction mammoplasty as a safe and direct technique for treatment of pseudoptosis to reduce size and improve breast shape. Methods: Circumareolar subcutaneous dissection of 10 breasts (5 cadavers) was performed to identify the nerves from the chest wall to the nipple. The trajectory of the nerves to the nipple was identified and dissected to their origin of penetration of the chest fascia. This information provides the basis for lateral chest wall tissue preservation for preserved nipple-areolar innervation, which is incorporated into this technique. Retrospective review of a single surgeon's experience with the 270° pedicle technique for reduction mammoplasty over a 1-year period was performed. Results: Anatomic dissection identified 3 to 5 branches of the fourth intercostal nerve to primarily innervate the nipple on 8 of 10 breast dissections. Accessory innervation from the fifth intercostal nerve provided lateral branches to the nipple in 5 of 10 specimens. Five patients underwent reduction mammoplasty with the 270° pedicle technique. No complications were identified. Excellent aesthetic outcomes were achieved on the basis of patient-reported satisfaction and the surgeon's judgment. All patients demonstrated normal nipple sensation at postoperative follow-up. Follow-up at 1 year did not demonstrate recurrence of ptosis/pseudoptosis or change in nipple position. Conclusions: The 270° technique for pedicle reduction mammoplasty yields aesthetically pleasing results and symptomatic relief from macromastia and preserves nipple sensation.


Surgical removal of an intracardiac sewing needle in a 13-month-old Chinese girl: report of a case.
Abstract Introduction: Sewing needles, albeit a rare case of penetrating cardiac injury, are highly lethal, especially in children, because it is difficult to diagnose and treat. We herein present the case of a 13-month-old girl who was injured by a sewing needle inserted in the myocardium, which probably is the first report from mainland China.Case presentation: The 13-month-old girl was referred to our hospital with a range of symptoms, such as convulsions, diarrhea, and cough. Chest X-ray and echocardiogram revealed a needle located below the aortic valve, passing through the ventricular septum and aortic root. Surgical removal of the needle was performed under extracorporeal circulation. No hemorrhage or arrhythmia was seen, so the operation was ended, and the patient was discharged 8 days after the surgery. Conclusion: An early diagnosis and intervention proved to be life-saving for this penetrating cardiac injury. Hopefully, this case could provide a reference for the treatment of similar situations.