Dietary chlorogenic acid improves growth performance of weaned pigs through maintaining antioxidant capacity and intestinal digestion and absorption function.
Chlorogenic acid (CGA) is a natural phenolic acid, which is an important component of biologically active dietary phenols isolated from various species. Two experiments were conducted to investigate the effects of CGA on growth performance, antioxidant capacity, nutrient digestibility, diarrhea incidence, intestinal digestion and absorption function, and the expression levels of intestinal digestion and absorption-related genes in weaned pigs. In Exp. 1, 200 weaned pigs were randomly allotted to four dietary treatments and fed with a basal diet or a basal diet supplemented with 250, 500, or 1,000 mg/kg CGA, respectively, in a 14-d trial. Pigs on the 1,000 mg/kg CGA-supplemented group had greater (P < 0.05) G:F compared with those on the control (CON) group. In Exp. 2, 24 weaned pigs were randomly allotted to two groups and fed with a basal diet (CON group) or a basal diet supplemented with 1,000 mg/kg CGA (the optimum does from Exp. 1; CGA group). After a 14-d trial, 8 pigs per treatment were randomly selected to collect serum and intestinal samples. Compared with the CON group, the ADG, G:F, as well as the apparent total tract digestibility of CP, crude fat, and ash were increased (P < 0.05), whereas the diarrhea incidence was decreased (P < 0.05) in the CGA group. Pigs on the CGA group had greater (P < 0.05) serum albumin and IGF-1, and lower (P < 0.05) serum urea nitrogen than pigs on the CON group. Furthermore, dietary CGA supplementation enhanced (P < 0.05) the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the serum, the activity of maltase in the jejunum and ileum, as well as the activities of sucrase and alkaline phosphatase (AKP) in the jejunum. The mRNA levels of sodium glucose transport protein-1 (SGLT1) and zinc transporter-1 (ZNT1) in the duodenum and the mRNA levels of SGLT1, glucose transporter-2 (GLUT2), and divalent metal transporter-1 (DMT1) in the jejunum were upregulated (P < 0.05) in pigs fed the CGA diet. These results suggested that dietary CGA supplementation has the potentials to improve the growth performance and decrease the diarrhea incidence of the weaned pigs, possibly through improving the antioxidant capacity and enhancing the intestinal digestion and absorption function.


A "Corruption of British Science?": The Strategic Defense Initiative and British Technology Policy.
This article shows that the competitive economic forces unleashed by globalization produced new technological choices for policymakers in Britain and throughout the developed world, which increasingly pitted Cold War security rationales against commercial opportunities. Those choices reveal a tension between core tenets of Thatcherism: alignment with U.S. foreign policy objectives and support for corporate interests. Britain's response to the U.S. 1983 Strategic Defense Initiative intensified ideological competition within the ruling Conservative Party about aligning with the United States or the European Union. Prime Minister Margaret Thatcher endorsed British participation in the Strategic Defense Initiative because of supposed national security benefits, promises of economic gains, and suspicion of Britain's further integration in the European common market. This policy failed, as cabinet officials, parliamentarians, researchers, and corporations pursued alternative European arrangements for stimulating technological innovation that did not carry restrictions on intellectual property or limits on the value of research contracts.


Functional characterization of biodegradable nanoparticles as antigen delivery system.
Peptide based vaccines may suffer from limited stability and inefficient delivery to professional antigen-presenting cells (APCs), such as dendritic cells (DCs). In order to overcome such limitations, several types of biodegradable nanoparticles (NPs) have been developed as carrier system for antigens. The present study describes for the first time the extensive biological characterization of cationic NPs made of poly (D,L-lactide-co-glycolide) (PLGA) and polyethylenimine (PLGA/PEI) as delivery system for protein/peptide antigens, with potential in therapeutic cancer vaccine development. Flow cytometry as well as confocal laser scanning microscopy (CLSM) showed that PLGA/PEI NPs are more readily taken up than PLGA NPs by both human CD14(+) monocytes and mouse Hepa 1-6 hepatoma cell line. No signs of toxicity were observed in either cellular setting. Sequential image acquisition by TEM showed an intracellular apical localization for PLGA NPs and a perinuclear localization for PLGA/PEI NPs. Both NPs showed a clathrin-dependent as well as a caveolin-dependent internalization pathway and, once in the cells, they formed multivesicular endosomes (MVE). Finally, an ex vivo priming experiment showed that PLGA/PEI NPs are comparable to PLGA NPs in delivering a non-self antigen (i.e., ovalbumin - OVA) to immature dendritic cells (imDCs), which matured and induced autologous naïve CD4(+) T cells to differentiate to memory (i.e., central memory and effector memory) cells. Such a differentiation was associated with a Th1 phenotype suggesting a downstream activation and amplification of a CD8(+) T cell cytotoxic response. The same OVA antigen in a soluble form was unable to induce maturation of DCs, indicating that both NP formulations provided an intrinsic adjuvanting effect combined to efficient antigen delivery. Our study represents the first report on side-by-side comparison of PLGA and PLGA/PEI NPs as strategy for protein antigen delivery. PLGA/PEI NPs are superior for cellular uptake and antigen delivery as compared to PLGA NPs. Such an evidence suggests their great potential value for vaccine development, including therapeutic cancer vaccines.


ERBB2 Regulates MED24 during Cancer Progression in Mice with Pten and Smad4 Deletion in the Pulmonary Epithelium.
ERBB2 is an oncogenic driver with frequent gene mutations and amplification in human lung tumors and is an attractive target for lung cancer therapy. However, target therapies can be improved by understanding the in vivo mechanisms regulated by ERBB2 during lung tumor development. Here, we generated genetic mouse models to show that Erbb2 loss inhibited lung tumor development induced by deletion of Pten and Smad4. Transcriptome analysis showed that Erbb2 loss suppressed the significant changes of most of the induced genes by ablation of Pten and Smad4. Overlapping with ERBB2-associated human lung cancer genes further identified those ERBB2 downstream players potentially conserved in human and mouse lung tumors. Furthermore, MED24 was identified as a crucial oncogenic target of ERBB2 in lung tumor development. Taken together, ERBB2 is required for the dysregulation of cancer-related genes, such as MED24, during lung tumor development.


Molecular pathways in low grade B-cell lymphoma.
Low grade B-cell non-Hodgkin's lymphomas (B-NHL) represent a markedly heterogeneous group of lymphoproliferative disorders, including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CCL/SLL), lymphoplasmacytoid lymphoma (LPL), follicular lymphoma (FL), mucosa-associated lymphoid tissue lymphoma (MALTL), and splenic lymphoma with villous lymphocytes (SLVL). The molecular pathogenesis of low grade B-NHL is characterized by distinct genetic pathways which selectively associate with each clinicopathologic category. At diagnosis, B-CLL/SLL frequently display deletions of 13q14 and trisomy 12, whereas evolution to Richter's syndrome associates with disruption of p53. LPL carries t(9;14)(p13;q32) in 40-50% of the cases, leading to the deregulated expression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2 independent of the cytologic variant. With time, a fraction of FL cases accumulates mutations of p53 and evolves into a high grade B-NHL. Low grade MALTL are characterized by the frequent occurrence of trisomy 3 and, occasionally, by p53 mutations. SLVL carries p53 mutations in a fraction of cases. The identification of distinct genetic categories among low grade B-NHL may help in the therapeutic stratification of these disorders. In addition, genetic lesions of low grade B-NHL have proved to be a useful molecular marker for monitoring minimal residual disease.


Time- and cell-type specific changes in iron, ferritin, and transferrin in the gerbil hippocampal CA1 region after transient forebrain ischemia.
In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H), and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1-2 days and then increased once again within the CA1 region at 4-7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4-7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.


Treatment of Kaposi sarcoma with vinblastine.
Five cases of Kaposi sarcoma with vinblastine sulfate treatment were compared with 18 cases reported in the literature. Our experience with a low-dosage schedule emphasizes that toxicity is not necessary for a favorable result. Vinblastine seems to be an effective treatment for Kaposi sarcoma and, in selected cases, may supplement radiation therapy or be used alone.


Formation of high affinity IL-2 receptors is dependent on a nonligand binding region of the alpha subunit.
The IL-2R is composed of three subunits, alpha, beta, and gamma, each of which individually contributes to binding IL-2 in the high affinity IL-2R. The molecular mechanism by which the high affinity IL-2R assembles has not been established. Previous studies have shown that human IL-2R subunits form high affinity hybrid IL-2R when mixed with appropriate mouse IL-2R subunits, but the efficiency of this process is not known. In this study, we produced stable cell lines that expressed hybrid human/mouse IL-2R, comprised of heterologous alpha- and beta-chains, to determine the contribution of individual receptor subunits in stabilizing the high affinity IL-2R. Quantitative ligand binding studies and FACS analysis were performed for EL4J cells that expressed hybrid mouse/human IL-2R, and these data were compared with those of cells that expressed homologous mouse IL-2R subunits. EL4J cells that expressed human beta/mouse alpha formed high affinity IL-2R, comparable with cells that express homologous mouse alpha and beta subunits. In contrast, EL4J cells that expressed homologous mouse IL-2R contained an approximately 10-fold higher level of high affinity IL-2R than did EL4J cells that expressed heterologous human alpha/mouse beta IL-2R. This difference was not accounted for by lower levels of human alpha-chains in these cell lines or lower expression of the mouse IL-2R beta or gamma subunits. These results suggest that amino acid sequences within the alpha subunit, distinct from the IL-2 binding site, are important in the assembly and stabilization of the high affinity IL-2R.


Effects of testosterone on renal ornithine decarboxylase and kidney function.
Testosterone injection caused a 2,000% increase in renal ornithine decarboxylase activity in intact male mice. A single injection of testosterone produced the same effect as repeated injections. The response was dose-dependent and could be blocked by actinomycin, diaminopropane, and cadaverine. Cycloheximide and putrescine had no inhibitory effect. Renal ODC response to arginine vasopressin was altered after castration; however, urine specific gravity and serum osmolality were unaffected by changes in renal ornithine decarboxylase activity.


Growth Inhibition Effect and Validation of Stable Expressed Reference Genes for Near-Infrared Photothermal Therapy Mediated by Gold Nanoflower Particles on Human Tongue Carcinoma Tca-8113 Cells.
Compared with surgery, radiotherapy, chemotherapy and other conventional cancer treatments, near-infrared (NIR) photothermal therapy mediated by gold nanoparticles had advantages of non-invasive, safe, non-drug resistance and small side effects. Especially for tongue cancer and other head and neck tumors, NIR gold nanoparticle-mediated photothermal therapy is more conducive to preserve the anatomic and functional integrity of stomatognathic system, improving the life quality of patients. However, the toxic organic phase substances are commonly used in conventional gold nanoparticles preparation process in order to increase the stability of the material which limited its application in the biomedical field. In this study, a new type of gold nanoflower (GNF) particles were synthesized by seeding approach in aqueous phase, with better biocompatibility and free of organic substances. Then, the photo-thermal conversion curve under the irradiation of NIR laser ray were investigated. The absorption peak of prepared GNF particles was 719 nm and they had high efficient photothermal conversion in near-infrared region. Furthermore, we investigated the inhibition effect of NIR photothermal therapy with different laser power mediated by the GNF particles on human tongue carcinoma cells by detecting the relative growth rate, cell cycle, and apoptosis and necrosis. The results showed that NIR photothermal therapy mediated by prepared GNF particles could inhibit proliferation of tongue carcinoma Tca-8113 cells obviously, and the relative growth rate of Tca-8113 cells decreased along with the increasing of GNF concentration and laser power. At last, we validated the expression stabilities of 12 commonly used reference genes (18S, ACTB, ALAS1, GAPDH, TBP, HPRT1, RPL29, HMBS, PPIA, PUM1, GUSB, and B2M) after the above treatment through real-time quantitative polymerase chain reaction (RT-qPCR). Three commonly used software, geNorm, NormFinder, and BestKeeper are used to compare stability between reference genes. The final ranking of the candidate reference genes expression stability was TBP > PPIA > RPL29 > B2M > 18S rRNA > GAPDH > GUSB > ACTB > HPRT1 > ALAS1 > HMBS > PUM1. The combination of TBP + PPIA is best for normalizing the relative quantitation. The results suggested that GNF particles had high photothermal conversion in NIR region and was ideal mediated material for tumor NIR photothermal therapy. NIR photothermal therapy mediated by GNFs could inhibit the growth rate of tongue carcinoma Tca-8113 cells obviously. The recommend reference genes can be used for improving the accuracy of gene expression studies in the molecular mechanism of near-infrared (NIR) photothermal therapy mediated by the gold nanoflower (GNF) particles.


Anti-inflammatory effect of Euphorbia hirta in an adjuvant-induced arthritic murine model.
Despite extensive research into inflammatory diseases to date, no drugs with favourable safety profiles are available for treatment. Euphorbia hirta (E. hirta) is a tree that is locally used as a traditional medicine in Africa and Australia to treat numerous diseases such as hypertension, antipyretic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-arthritic effects of E. hirta in mouse models of adjuvant induced arthritis (AIA). We treated BALB/c mice with (p.o.) E. hirta (25, 50, 100, and 200 mg/kg) daily (13 days) beginning at the onset of AIA. We examined the effect of E. hirta on key mediators of arthritic-inflammation, including pro-inflammatory (IL-2, IFN-γ, and TNF-α) and anti-inflammatory (IL-4 and IL-5) cytokines, T-cell activation markers (CD25/CD69), and co-stimulatory molecules (CD80/CD86). We also examined the inflammatory mediators (PGE2 and LTB4) response. E. hirta-treated mice showed a substantial reduction in the levels of pro-inflammatory cytokines, down regulated cell activation markers and co-stimulatory molecules, and up regulated anti-inflammatory cytokines. E. hirta decreased the levels of inflammatory-mediators in AIA animals. Supplementation with an E. hirta extract may be a promising treatment for arthritic and inflammatory diseases.


Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.
Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.


Polygenic risk scores for schizophrenia are associated with oculomotor endophenotypes.
Schizophrenia is a heterogeneous disorder with substantial heritability. The use of endophenotypes may help clarify its aetiology. Measures from the smooth pursuit and antisaccade eye movement tasks have been identified as endophenotypes for schizophrenia in twin and family studies. However, the genetic basis of the overlap between schizophrenia and these oculomotor markers is largely unknown. Here, we tested whether schizophrenia polygenic risk scores (PRS) were associated with oculomotor performance in the general population. Analyses were based on the data of 2956 participants (aged 30-95) of the Rhineland Study, a community-based cohort study in Bonn, Germany. Genotyping was performed on Omni-2.5 exome arrays. Using summary statistics from a recent meta-analysis based on the two largest schizophrenia genome-wide association studies to date, we quantified genetic risk for schizophrenia by creating PRS at different p value thresholds for genetic markers. We examined associations between PRS and oculomotor performance using multivariable regression models. Higher PRS were associated with higher antisaccade error rate and latency, and lower antisaccade amplitude gain. PRS showed inconsistent patterns of association with smooth pursuit velocity gain and were not associated with saccade rate during smooth pursuit or performance on a prosaccade control task. There is an overlap between genetic determinants of schizophrenia and oculomotor endophenotypes. Our findings suggest that the mechanisms that underlie schizophrenia also affect oculomotor function in the general population.


Interest of Mineralized Plasmatic Matrix in Secondary Autogenous Bone Graft for the Treatment of Alveolar Clefts.
The authors describe a new material termed mineralized plasmatic matrix (MPM), a combination of platelets, fibrin concentrate, and autogenous bone to repair alveolar cleft defects. Autogenous cancellous bone is widely used to this end because such bone affords the functionalities (osteogenesis, osteoinduction, and osteoconduction) required for successful outcomes. To optimize these features, autologous blood products high in platelet concentrations have recently been developed. On the basis of our experience with PRP (platelet-rich plasma) and PRF (platelet-rich fibrin), we developed MPM, which contains platelets and fibrin concentrate in a liquid state; these materials can become bound to bone particles. The filling material is easy to shape and a PRF-type membrane is also generated. Ten patients with cleft lips and alveoli, with or without cleft palates (median, or uni- or bilateral) benefited from secondary bone grafts placed using our new material. We transferred autogenous bone from the iliac crest, an abundant source of cancellous bone associated with a high success rate. The 6-month outcomes of all patients were excellent in terms of both bone graft stability and closure of the oronasal fistulae. The preparation procedure is simple and the technical requirements minimal. Upon further optimization, MPM may serve as a third-generation platelet concentrate with potential applications in various fields.


Community services in the 1990s: are they meeting the needs of caregivers?
The community-based, long-term care system not only sustains the older person in the community but also helps to maintain him or her at the highest level of functioning possible. A broad spectrum of services exists, including personal care, transportation, home-delivered meals, adult day care, and respite care. One hundred sixty-eight primary caregivers were were interviewed regarding awareness of, inquiry into, utilization of, and satisfaction with community services during the caregiving period. The majority of caregivers were aware of and utilized 7 of the 15 services listed, including personal care services, home-delivered meals, rehabilitation services, housekeeping services, nursing services, and information referral services. Nurses remain the key individuals in providing linkages among elderly and their families and community-based services. One of the key roles that nurses can play is to inform caregivers about available community services, to help caregivers recognize the need for these services, to assist them in accessing these services, and to recognize their need for support during this process. Finally, the community nurse can also provide support to the caregiver when institutionalization of the older family member becomes a reality.


Psychedelic Treatments for Substance Use Disorder and Substance Misuse: A Mixed Methods Systematic Review.
Renewed interest in psychedelic substances in the 21st century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use disorder (SUD). This review aimed to assess the effectiveness of psychedelic treatments for people with SUD and those falling below diagnostic thresholds (i.e. substance misuse). We systematically searched 11 databases, trial registries, and psychedelic organization websites for empirical studies examining adults undergoing psychedelic treatment for SUD or substance misuse, published in the English language, between 2000 and 2021. Seven studies investigating treatment using psilocybin, ibogaine, and ayahuasca, alone or adjunct with psychotherapy reported across 10 papers were included. Measures of abstinence, substance use, psychological and psychosocial outcomes, craving, and withdrawal reported positive results, however, this data was scarce among studies examining a wide range of addictions including opioid, nicotine, alcohol, cocaine and unspecified substance. The qualitative synthesis from three studies described subjective experience of psychedelic-assisted treatments enhanced self-awareness, insight, and confidence. At present, there is no sufficient research evidence to suggest effectiveness of any of the psychedelics on any specific substance use disorder or substance misuse. Further research using rigorous effectiveness evaluation methods with larger sample sizes and longer-term follow-up is required.


The compulsive sexual behavior inventory: psychometric properties.
Compulsive sexual behavior (CSB) is a putative clinical syndrome characterized by the experience of sexual urges, sexually arousing fantasies, and sexual behaviors that are recurrent, intense, and a distressful interference in one's daily life. Although the putative phenomenology of CSB has been described in the literature, the lack of a reliable, valid assessment tool has made investigation of prevalence, co-factors, and etiologic factors difficult. This study examined the further development of the Compulsive Sexual Behavior Inventory (CSBI) using a sample of 1,026 Latino men who have sex with men recruited and assessed using web-based technology. The scale showed a two factor structure (control and violence). Further, the CSBI and its subscales showed indications of validity in that those engaging in CSB-type sexual behavior (being drunk or high, feeling lonely or depressed, and feeling driven) had scores indicative of greater CSB. Those with scores above the median had more sexual partners and engaged in more unprotected anal intercourse than those with CSBI scores below the median. Additionally, the instrument showed equivalence when administered in English and Spanish.


[The marketing evaluation of the consumers' preference as regards the use of medicinal and medicinal table mineral waters].
The development of modern technologies in physiotherapy with the use of mineral waters, the expansion of the assortment of the medicinal and medicinal table waters as well as increasing the competitive advantages of domestic products require the more extensive marketing survey of the consumers' preferences in the market of mineral waters. The objective of the present study was the marketing evaluation of the consumers' preference in the segment of medicinal and medicinal table mineral waters in the city of Moscow. The survey involved 697 consumers of medicinal and medicinal table mineral waters. The sampling was carried out by the deterministic quota method. The field research was conducted by means of personal verbal interviews (32%) and the CATI to Web method (phone recruiting and on-line questioning) (68%) with the use of the structured questionnaire. Positioning was carried out making use of the two-dimensional schematic map and scoring assessment on an individual basis with calculation of integrated indicators. The marketing evaluation has demonstrated that the principal motive for purchasing mineral waters in more than 40% of respondents was the treatment and prevention of various diseases including disturbances in the urogenital system as well as digestive and respiratory disorders that appear to be the most frequent reasons for the consumption of mineral waters. The main factors that form the preferences of the consumers as regards the use of a concrete variety of mineral waters were elucidated. Of crucial importance for approximately 40% of the consumers (p<0.01) proved to be their health condition, the medical indications, and the available information about the therapeutic effectiveness of one or another type of mineral waters. Other factors were the quality of mineral water, its cost, the manufacturer and/or place of production, the attractiveness of the packaging, etc. The evaluation of the positioning of the mineral water consumers' preferences made it possible to identify the most preferable products in the group of medicinal mineral waters and in the group of medicinal table mineral waters. The mechanisms governing the formation of the consumers' preferences as regards the use of various mineral waters have been clarified in the course of the present study.


Ultrasound-guided vascular access in adults and children: beyond the internal jugular vein puncture.
Based on our clinical experience and a review of the current literature, this paper describes a large variety of ultrasound-guided vascular puncture techniques used in adults and children far beyond the well described puncture of the internal jugular vein. This includes low or posterior approaches of the internal jugular vein, puncture of the subclavian vein and its variant in children, infraclavicular access to the axillary vein and also more peripheral punctures of the basilic, brachial and cephalic veins. Arterial line placement in the radial, humeral, axillary or femoral are also described as well as the aid of ultrasonography for peripheral insertion of central catheters (PICC Lines). Additional information on ultrasonographic assessment of potentially related complications, like pneumothorax or hemopericardium, will complete this review.


Soft-Tissue Sarcoma following Traumatic Injury: Case Report and Review of the Literature.
Soft-tissue sarcomas (STSs) are a heterogeneous group of tumors, which accounts for 1-2% of adult cancers worldwide. Despite quite a few reports on traumatic events followed by STS formation, the link between the two events remains a point of controversy. In this paper, we present the case of a young patient who had a rhabdomyosarcoma in the lower extremity, which had developed in the same location where the patient was wounded by a gunshot 9 years earlier. X-ray and CT scans clearly showed metal fragments in the area of sarcoma formation. The patient underwent neoadjuvant chemotherapy treatment, to which the tumor was, unfortunately, unresponsive. Therefore, the patient was referred to below-knee amputation of the injured leg. There are several possible etiological factors for sarcoma development in this patient, including tissue damage and inflammation, as well as the presence of metal fragments in the tissue and the limb's exposure to radiation during multiple imaging tests. Here, we will discuss the potential influence wielded by the injury itself, as well as its complications and its medical management on the formation of the sarcoma, in light of the current literature.


Genome amplification and cellular senescence are hallmarks of human placenta development.
Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) β-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM.


Electron-Hole Theory of the Effect of Quantum Nuclei on the X-Ray Absorption Spectra of Liquid Water.
Electron-hole excitation theory is used to unveil the role of nuclear quantum effects on the x-ray absorption spectral signatures of water, whose structure is computed via path-integral molecular dynamics with the MB-pol intermolecular potential model. Compared to spectra generated from the classically modeled water, quantum nuclei introduce important effects on the spectra in terms of both the energies and line shapes. Fluctuations due to delocalized protons influence the short-range ordering of the hydrogen bond network via changes in the intramolecular covalence, which broaden the preedge spectra. For intermediate-range and long-range ordering, quantum nuclei approach the neighboring oxygen atoms more closely than classical protons, promoting an "icelike" spectral feature with the intensities shifted from the main edge to the postedge. Computed spectra are in nearly quantitative agreement with the available experimental data.


Effect of decompression-induced bubble formation on highly trained divers microvascular function.
We previously showed microvascular alteration of both endothelium-dependent and -independent reactivity after a single SCUBA dive. We aimed to study mechanisms involved in this postdive vascular dysfunction. Ten divers each completed three protocols: (1) a SCUBA dive at 400 kPa for 30 min; (2) a 41-min duration of seawater surface head immersed finning exercise to determine the effect of immersion and moderate physical activity; and (3) a simulated 41-min dive breathing 100% oxygen (hyperbaric oxygen [HBO]) at 170 kPa in order to analyze the effect of diving-induced hyperoxia. Bubble grades were monitored with Doppler. Cutaneous microvascular function was assessed by laser Doppler. Endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) reactivity was tested by iontophoresis. Endothelial cell activation was quantified by plasma Von Willebrand factor and nitric oxide (NO). Inactivation of NO by oxidative stress was assessed by plasma nitrotyrosine. Platelet factor 4 (PF4) was assessed in order to determine platelet aggregation. Blood was also analyzed for measurement of platelet count. Cutaneous vascular conductance (CVC) response to ACh delivery was not significantly decreased by the SCUBA protocol (23 ± 9% before vs. 17 ± 7% after; P = 0.122), whereas CVC response to SNP stimulation decreased significantly (23 ± 6% before vs. 10 ± 1% after; P = 0.039). The HBO and immersion protocols did not affect either endothelial-dependent or -independent function. The immersion protocol induced a significant increase in NO (0.07 ± 0.01 vs. 0.12 ± 0.02 μg/mL; P = 0.035). This study highlighted change in microvascular endothelial-independent but not -dependent function in highly trained divers after a single air dive. The results suggest that the effects of decompression on microvascular function may be modified by diving acclimatization.


Chimeric constructs endow the human CFTR Cl- channel with the gating behavior of murine CFTR.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-) channel gated by ATP-driven nucleotide-binding domain (NBD) dimerization. Here we exploit species differences between human and murine CFTR to investigate CFTR channel gating. Using homologous recombination, we constructed human-murine CFTR (hmCFTR) chimeras with sequences from NBD1, NBD2, or the regulatory domain (RD) of human CFTR replaced by the equivalent regions of murine CFTR. The gating behavior of hmRD and human CFTR were indistinguishable, whereas hmNBD1 and hmNBD2 had subtle effects on channel gating, prolonging both burst duration and interburst interval. By contrast, hmNBD1+2, containing both NBDs of murine CFTR, reproduced the gating behavior of the subconductance state of murine CFTR, which has dramatically prolonged channel openings. The CFTR potentiator pyrophosphate (PP(i)) enhanced human, hmRD, and hmNBD1 CFTR Cl(-) currents, but not those of hmNBD2, hmNBD1+2, and murine CFTR. By analyzing the rate-equilibrium free-energy relationships of chimeric channels, we obtained snapshots of the conformation of the NBDs during ATP-driven dimerization. Our data demonstrate that the conformation of NBD1 changes before that of NBD2 during channel opening. This finding suggests that NBD dimerization does not proceed by a symmetric tweezer-like motion, but instead in an asymmetric fashion led by NBD1. We conclude that the NBDs of murine CFTR determine the unique gating behavior of its subconductance state, whereas NBD2 controls channel potentiation by PP(i).


Rutin Promotes Proliferation and Orchestrates Epithelial-Mesenchymal Transition and Angiogenesis in MCF-7 and MDA-MB-231 Breast Cancer Cells.
Rutin has been reported as a potential anti-cancer agent for several decades. This study evaluated the effects of rutin on the proliferation, metastasis, and angiogenesis of MDA-MB-231 and MCF-7 breast cancer cell lines. Increasing concentrations of rutin significantly stimulated the proliferation of MDA-MB-231 and MCF-7 cells compared to controls. Wound scratch assay demonstrated that rutin had an inducing effect on the migration of the cells. In MDA-MB-231 and MCF-7 cells, rutin upregulated MKI67, VIM, CDH2, FN1, and VEGFA and downregulated CDH1 and THBS1 genes. It also increased N-cadherin and VEGFA and decreased E-cadherin and thrombospondin 1 protein expression. Our data indicated that rutin could stimulate proliferation, migration, and pro-angiogenic activity in two different breast cancer cell lines. This phytoestrogen induced invasion and migration of both cell lines by a mechanism involving the EMT process. This suggests that rutin may act as a breast-cancer-promoting phytoestrogen.


Biased gene conversion and GC-content evolution in the coding sequences of reptiles and vertebrates.
Mammalian and avian genomes are characterized by a substantial spatial heterogeneity of GC-content, which is often interpreted as reflecting the effect of local GC-biased gene conversion (gBGC), a meiotic repair bias that favors G and C over A and T alleles in high-recombining genomic regions. Surprisingly, the first fully sequenced nonavian sauropsid (i.e., reptile), the green anole Anolis carolinensis, revealed a highly homogeneous genomic GC-content landscape, suggesting the possibility that gBGC might not be at work in this lineage. Here, we analyze GC-content evolution at third-codon positions (GC3) in 44 vertebrates species, including eight newly sequenced transcriptomes, with a specific focus on nonavian sauropsids. We report that reptiles, including the green anole, have a genome-wide distribution of GC3 similar to that of mammals and birds, and we infer a strong GC3-heterogeneity to be already present in the tetrapod ancestor. We further show that the dynamic of coding sequence GC-content is largely governed by karyotypic features in vertebrates, notably in the green anole, in agreement with the gBGC hypothesis. The discrepancy between third-codon positions and noncoding DNA regarding GC-content dynamics in the green anole could not be explained by the activity of transposable elements or selection on codon usage. This analysis highlights the unique value of third-codon positions as an insertion/deletion-free marker of nucleotide substitution biases that ultimately affect the evolution of proteins.


Changes in microcirculation after ischemic process in rat skeletal muscle.
Laser Doppler flowmetry (LDF) is a good method to investigate tissue microcirculation, but it has many standardization and measuring problems. To exclude these effects, we performed a test using LDF on rat skeletal muscle. In 12 CD outbred anesthetized rats, bilateral femoral vessels and the quadriceps femoris muscle were exposed. The left femoral artery and vein were clamped for 1 h by microvascular clips (ischemic side). On the right side, no other intervention was made (control side). An LDF probe was applied on the medial vastus muscle. Short-term occlusions (2-3 s) were performed before and after the 1-h clamping and on the control side while LDF curves were registered. The halftimes of ascending curves on the ischemic side were significantly elongated vs. the condition before clamping (P = 0.0007) or the control side (P = 0.0017). Microcirculatory changes caused by 1-h ischemia were shown by this simple, quick, and well-reproducible test on rat skeletal muscle.


Impact of early response to sequential high-dose chemotherapy on outcome of patients with advanced myeloma and poor prognostic features.
We report the results of a dose-intense chemotherapy regimen designed to rapidly induce remissions in patients with advanced multiple myeloma (MM). Patients received VAD for 3-6 cycles depending on response kinetics. This was followed by three sequential cycles of cyclophosphamide (CTX) at 3 g/m2 every 15 days with G-CSF support. 71% of these patients had stage IIIa, 23% had renal failure. The median age was 58, median beta-2 microglobulin 4.6 and median albumin was 3.5, indicating poor prognosis. Of 35 patients, 66% achieved a complete response (CR) (SWOG). Six patients (18%) had a partial response. Fifty percent of the patients with renal failure recovered their kidney function. High-dose CTX contributed to tumor-mass reduction particularly in patients presenting with high-tumor burden. Tumor-mass reduction following three pulses of dexamethasone (4 days each) is significantly higher than with one pulse (p < 0.005). While high beta-2 microglobulin and LDH levels (p < 0.05) were associated with poor outcome, patients who responded faster to chemotherapy had a longer survival (p = 0.005). We conclude that this regimen is safe and effective. A rapid response may be useful in selecting patients who may benefit from further high dose chemotherapy and stem cell support.


Characterization of EPPIN's semenogelin I binding site: a contraceptive drug target.
Epididymal protease inhibitor (EPPIN) is found on the surface of spermatozoa and works as a central hub for a sperm surface protein complex (EPPIN protein complex [EPC]) that inhibits sperm motility on the binding of semenogelin I (SEMG1) during ejaculation. Here, we identify EPPIN's amino acids involved in the interactions within the EPC and demonstrate that EPPIN's sequence C102-P133 contains the major binding site for SEMG1. Within the same region, the sequence F117-P133 binds the EPC-associated protein lactotransferrin (LTF). We show that residues Cys102, Tyr107, and Phe117 in the EPPIN C-terminus are required for SEMG1 binding. Additionally, residues Tyr107 and Phe117 are critically involved in the interaction between EPPIN and LTF. Our findings demonstrate that EPPIN is a key player in the protein-protein interactions within the EPC. Target identification is an important step toward the development of a novel male contraceptive, and the functionality of EPPIN's residues Cys102, Tyr107, and Phe117 offers novel opportunities for contraceptive compounds that inhibit sperm motility by targeting this region of the molecule.


Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria.
Sequestration of parasitized erythrocytes in the microcirculation is considered the central pathophysiological process in severe falciparum malaria. Hypovolemia with reduced oxygen delivery and microvascular obstruction have different implications for patient management; however, their relative contributions to disease severity are uncertain. Adult patients (n = 28) with severe Plasmodium falciparum malaria were enrolled in a prospective hemodynamic study. Volume status and oxygen delivery were assessed using transpulmonary thermodilution. Microvascular sequestration was measured using orthogonal polarized spectroscopy. Duration of therapy before study enrollment was correlated with the amount of directly visualized and quantitated microvascular sequestration (P = .03). The amount of sequestration correlated with plasma lactate (r(s )= 0.55; P = .003) and disease severity (r(s )= 0.41; P = .04). In patients who had received artesunate for <10 hours, sequestration was higher in fatal cases than in survivors: median (range) 45% (32-50) vs 15% (0-40); P = .03). Parasite biomass estimated from plasma P. falciparum histidine-rich protein 2 correlated positively with disease severity (r(s )= 0.48; P = .01) and was significantly higher in patients who died (P = .046). There was no relationship between oxygen delivery and disease severity (P = .64) or outcome (P = .74). Vital organ dysfunction in severe malaria results primarily from sequestration of parasitized erythrocytes in the microvasculature rather than reduction in circulating blood volume and oxygen delivery.


Convergent chemical and electrical synaptic inputs from proprioceptive afferents onto an identified intersegmental interneuron in the crayfish.
Synaptic transmission between proprioceptive afferents from a chordotonal organ in the tailfan of the crayfish and an identified ascending interneuron, interneuron A, in the terminal abdominal ganglion was analyzed. Interneuron A is part of a disynaptic pathway from primary afferent neurons to the lateral giant interneuron involved in producing the characteristic ballistic escape behavior of crayfish. Interneuron A received short and long latency excitatory postsynaptic potentials (EPSPs) from chordotonal afferents. Short latency EPSPs occurred with little central synaptic delay, were unchanged by hyperpolarizing current injection of -2 nA, and remained at a constant amplitude when the nervous system was bathed in saline with a low calcium concentration or saline containing the nicotinic antagonist curare. These EPSPs are thus thought to be mediated by electrical transmission. Longer latency potentials were increased in amplitude by hyperpolarizing current injection, reduced in amplitude when the nervous system was bathed in low-calcium saline, and also reduced by bath application of saline containing curare. These potentials are thus thought to be mediated by chemical transmission. The functional significance of the dual modes of transmission at a key synapse in the escape circuitry is discussed.


A method of esophageal electrogram recording for diagnostic atrial and ventricular pacing.
This study evaluates improvement of the electrogram sensed via an esophageal catheter with the sensing electrode adjacent to the stimulating electrode with and without a specialized artifact suppression system. In 100 patients (65 men and 35 women) aged 16-60 years (mean 48 years), esophageal recordings of left atrial activity were obtained during simultaneous transesophageal atrial pacing. Transesophageal ventricular pacing was performed in an additional 34 patients. Without the suppression system, ventricular paced activity, recorded from the esophagus, was not suitable for interpretation. About 10% of the atrial electrogram response could be recorded and evaluated during atrial pacing. With the stimulus artifact suppression system, interpretable recordings were obtained 100% of the time during atrial and ventricular recordings. The method described allows use of transesophageal diagnostic testing where previously only the intracardiac route was possible.


CEP4HFP: Complex Event Processing for Heart Failure Prediction.
This paper presents a novel health analysis approach for heart failure prediction. It is based on the use of complex event processing (CEP) technology, combined with statistical approaches. A CEP engine processes incoming health data by executing threshold-based analysis rules. Instead of having to manually set up thresholds, our novel statistical algorithm automatically computes and updates thresholds according to recorded historical data. Experimental results demonstrate the merits of our approach in terms of speed, precision, and recall.


Where is the wisdom? I--a conceptual history of evidence-based medicine.
Rationale Evidence-based medicine (EBM) has been acclaimed as a major advance in medical science, but criticized as a proposed alternative model for the practice and teaching of medicine. Ambiguity regarding the proper role of the contributions of EBM within the fabric of medicine and health care has contributed to this discrepancy. Aims and objectives We undertook a critical review of the history of the EBM movement, beginning with its origins in the 1970s and continuing through this century. We drew upon the results of an independent project that rationalized the EBM domain from the perspective of educational evaluation and assessment. We considered the content of EBM in relationship to the propositions and promises embodied in advocacy publications. Results EBM emerged in the context of the explosion of biomedical information in the decade preceding public access to the Internet in the mid-1990s and drew upon the independently derived 'information literacy' formula developed by information scientists during the 1980s. The critically important content and achievements of EBM are fully explained within the confines of the information literacy model. The thesis that EBM offers an alternative paradigm for individualized health care, asserted in the advocacy literature, is not supported by published models of evidence-based clinical practice. Conclusion A critical historical review of the origins, content and development of the EBM movement proposes that full integration of the fruits of the movement into routine clinical care remains a conceptual and practical challenge.


Elaboration of the contextual factors of the ICF for Occupational Health Care.
Many work-related items are not included in the current classification of environmental factors from the International Classification of Functioning, Disability and Health (ICF). Furthermore, personal factors are not classified and the ICF only provides a very limited list of examples. These facts make the ICF less useful for occupational health care and for research in the field of occupation and health. The objective of this discussion paper is to introduce an elaboration of contextual factors, focussing on factors that influence work participation. During the last 12 years, we developed two concept lists from the bottom up. These lists are based on our experiences in teaching and research, suggestions from students and other researchers, and factors found in the literature. In the fall of 2015 a scoping literature review was done to check for missing factors in these two concept lists. An elaboration of contextual factors, consisting of a list of work-related environmental factors and a list of personal factors. Important contextual factors that influence work participation are identified. Researchers, teachers, students, occupational and insurance physicians, allied health care professionals, employers, employees, and policy makers are invited to use the elaboration and to make suggestions for improvement. The elaboration and the suggestions received can be used in the ICF revision process. The development of an ICF ontology must be given priority, to give room to this elaboration, which will increase the applicability of the ICF and enable mapping with other terminologies and classifications.


COOP/WONCA charts as a screen for mental disorders in primary care.
Most people with mental disorders receive treatment in primary care. The charts developed by the Dartmouth Primary Care Cooperative Research Network (COOP) and the World Organization of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (WONCA) have not yet been evaluated as a screen for these disorders, using a structured psychiatric interview by an expert or considering diagnoses other than depression. We evaluated the validity and feasibility of the COOP/WONCA Charts as a mental disorders screen by comparing them both with other questionnaires previously validated and with the assessment of a mental health specialist using a structured diagnostic interview. We trained community health workers and nurse assistants working in a collaborative mental health care model to administer the COOP/WONCA Charts, the 20-item Self-Reporting Questionnaire (SRQ-20), and the World Health Organization-Five Well-Being Index (WHO-5) to 120 primary care patients. A psychiatrist blinded to the patients' results on these questionnaires administered the SCID, or Structured Clinical Interview for the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). The area under the receiver operating characteristic curve was at least 0.80 for single items, a 3-item combination, and the total score of the COOP/ WONCA Charts, as well as for the SRQ-20 and the WHO-5, for screening both for all mental disorders and for depressive disorders. The accuracy, sensitivity, specificity, and positive and negative predictive values of these measures ranged between 0.77 and 0.92. Community health workers and nurse assistants rated the understandability, ease of use, and clinical relevance of all 3 questionnaires as satisfactory. One-time assessment of patients with the COOP/WONCA Charts is a valid and feasible option for screening for mental disorders by primary care teams.


Effect of L-deprenyl treatment on electrical activity, Na+, K+ ATPase, and protein kinase C activities in hippocampal subfields (CA1 and CA3) of aged rat brain.
L-deprenyl is considered to protect against age-related cognitive deficits by improving long-term learning/memory in the aged brain. The CA1 and CA3 hippocampal areas are the sites at which initial learning and memory processes occur. Chronic deprenyl treatment significantly augmented the basal electrical firing rate (multiple-unit action potentials), and Na+, K(+)-ATPase and protein kinase C activities of both CA1 and CA3 indicating that the drug increased the excitability of CA1 and CA3. The increase, however, was much greater in CA1 than in CA3 suggesting that deprenyl can improve longer-term learning in aged animals by its excitability-enhancing action in CA1. The drug also countered the ageing-related loss of hippocampal protein kinase C activity.


It's a long way to multimedia: an account of 18 years of pursuing a new media project in physiology.
A teaching-oriented multimedia database authoring system, MILES ( Multimediales Informations- und Lehrsystem), has been in development since 1980 in our department. The hardware consists of a network of personal computers connected to digital and, until recently, audio/video storage devices. The system provides a database capable of handling all kinds of multimedia data and computer programs. User-friendly software provides input, editing, retrieval, and communication; the authoring system allows these components to be organized into structures of complex menus, combined with free database access. More than 12,000 components have been stored, including approximately 3,500 pictures. The paper reports on an extensive field test, in which the system has been applied as a common source for all kinds of materials used in teaching physiology to students of medicine. ResuIts show that the "new media" are powerful instruments for improving teaching and learning. However, they should not be expected to provide the sole basis for education. Their application still faces many problems regarding concepts, efficiency, and acceptance by students and staff.


[Research progress of mechanism and prevention of peritendinous adhesions].
To review the research progress of mechanism and prevention of peritendinous adhesions. Methods Recent literature about peritendinous adhesions was reviewed, and the results from experiments about the mechanism and prevention of peritendinous adhesions were analyzed. The molecular mechanism of peritendinous adhesions is related to overexpressions of transforming growth factor beta 1, early growth response protein 1, matrix metallopeptidase 9, and so on. The present methods of prevention of peritendinous adhesions include drugs, barrier, optimizing rehabilitation, gene therapy, and so on. These methods have achieved good results in experiments, but the clinical applications have not been confirmed yet. It is necessary to pay more attention to the research of mechanism of peritendinous adhesions and methods of its prevention and subsequently to convert them into clinical applications, which is significant to the prevention of peritendinous adhesions in the future.


Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity.
Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in heart failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial DCM is the major form of DCM, with pathogenic variants in LMNA being the second most common form of autosomal dominant DCM. LMNA DCM is a multifactorial and complex disease with no specific treatment thus far. Many studies have demonstrated that perturbing candidates related to various dysregulated pathways ameliorate LMNA DCM. However, it is unknown whether these candidates could serve as potential therapeutic targets especially in long term efficacy. We evaluated 14 potential candidates including Lmna gene products (Lamin A and Lamin C), key signaling pathways (Tgfβ/Smad, mTor and Fgf/Mapk), calcium handling, proliferation regulators and modifiers of LINC complex function in a cardiac specific Lmna DCM model. Positive candidates for improved cardiac function were further assessed by survival analysis. Suppressive roles and mechanisms of these candidates in ameliorating Lmna DCM were dissected by comparing marker gene expression, Tgfβ signaling pathway activation, fibrosis, inflammation, proliferation and DNA damage. Furthermore, transcriptome profiling compared the differences between Lamin A and Lamin C treatment. Cardiac function was restored by several positive candidates (Smad3, Yy1, Bmp7, Ctgf, aYAP1, Sun1, Lamin A, and Lamin C), which significantly correlated with suppression of HF/fibrosis marker expression and cardiac fibrosis in Lmna DCM. Lamin C or Sun1 shRNA administration achieved consistent, prolonged survival which highly correlated with reduced heart inflammation and DNA damage. Importantly, Lamin A treatment improved but could not reproduce long term survival, and Lamin A administration to healthy hearts itself induced DCM. Mechanistically, we identified this lapse as caused by a dose-dependent toxicity of Lamin A, which was independent from its maturation. In vivo candidate evaluation revealed that supplementation of Lamin C or knockdown of Sun1 significantly suppressed Lmna DCM and achieve prolonged survival. Conversely, Lamin A supplementation did not rescue long term survival and may impart detrimental cardiotoxicity risk. This study highlights a potential of advancing Lamin C and Sun1 as therapeutic targets for the treatment of LMNA DCM.


Lawyers' attitudes toward involuntary treatment.
This study examined whether lawyers' attributions of responsibility for mental illnesses affect their decisions about involuntary treatment. A survey that was mailed in 2003 to Illinois lawyers involved in involuntary commitment elicited recommendations for involuntary treatment for characters presented in vignettes. The survey also sought respondents' attributions of personal responsibility for the onset and recurrence of mental illnesses. A total of 89 lawyers responded to the survey, a response rate of 48 percent. Decisions to hospitalize persons with mental illness involuntarily increased significantly with the level of risk of harm and were significantly related to attributions of responsibility for the recurrence of mental illness. Decisions to recommend involuntary medication were not related to attributions of responsibility.


[HISTORY OF GYNECOLOGICAL DISORDERS, OBSTERIC PATHOLOGY AND ANDROGEN LEVELS AS PROGNOSTIC FACTORS AND INDICES OF MYOCARDIAL INJURY AMONG POSTMENOPAUSAL WOMEN WITH ACUTE CORONARY SYNDROME.]
The study ob]ective was assessment of pathogenetic and prognostic significance of gynecologic and obstetrical pathology and the concentrations of sex steroids in adult women with acute coronaty syndrome (ACS). The study group included 120 postmenopausal women with ACS treated in the Clinic of Cardiology, University Hospital "Alexandrovska" between 2011 and 2013. Sex hormones were measured in 57 patients. Enzyme, electrochemiluminescent, enzyme-linked immunologic and immunoturbodimeric methods were used for the examined indices assessment. The history for gynecologic disorders and pregnancy complications was associated with coronaiy atherosclerotic burden (SYNTAX score - 4,6+/-8,8 vs 8,5+/-9,3, p=0,003), gynecologic history only - with lower 17Beta-estradiol levels (139,01+/-167,66 vs 113,51+/-304,1, p=0,004) and coronaly atherosclerosis severity (5,5+/-9,3 vs 8,0+/-10,3, p=0,058). Abnormally high endogenous concentrations of androgens were found among the patients with ACS with ST elevation, STEMI (27,5% vs 77,8%, p=0,004), with significantly more intense acute infiammatoty response (8,7+/-3,21 vs 11,07+/-2,85, p=0,044 3a WBC) and more extensive acute myocardial damage (57,8+/-12,6 vs 45,3 ml, p=O,OO8 for e]ection fraction 33,7+/-37,4 vs 117+/-144,22 U/L, p=0,031 for CPK-MB; 0,89+/-8 18 vs 1,87+/-0,4 ng/ml, p=0,009 for hsTnT). The gynecologic and obstetrical history and hyperandrogenism are related to the extent and severity of coronary atherosclerosis, occurrence of STEMI, more intense acute inflammatory response and myocardial injury among postmenopausal women with ACS.


Post-synthesis, characterization and catalytic properties of fluorine-planted MWW-type titanosilicate.
F-Ti-MWW was post-synthesized by implanting fluorine species into a Ti-MWW framework through an acid treatment process in the presence of ammonium fluoride. The effects of NH4F addition amount, acid treatment temperature and precursor Ti content were investigated on the incorporation of F species, the zeolite structure and the coordination sites of Ti. Fluorine-implanting improved the surface hydrophobicity of the zeolite and altered the electropositivity nearby the tetrahedral Ti sites through forming the SiO3/2F and SiO4/2F(-) units. The negative effect of SiO4/2F(-) units in F-Ti-MWW was eliminated selectively by convenient anion-exchange with various alkali chlorides. F-Ti-MWW containing the SiO3/2F units possessed better catalytic activity and reusability, and a longer catalyst lifetime than conventional Ti-MWW.


Early-onset group B streptococcal disease in African countries and maternal vaccination strategies.
Invasive group B streptococcal (GBS) disease is the commonest perinatally-acquired bacterial infection in newborns; the burden is higher in African countries where intrapartum antibiotic prophylaxis strategies are not feasible. In sub-Saharan Africa, almost one in four newborns with GBS early-onset disease will demise, and one in ten survivors have moderate or severe neurodevelopmental impairment. A maternal GBS vaccine to prevent invasive GBS disease in infancy is a pragmatic and cost-effective preventative strategy for Africa. Hexavalent polysaccharide protein conjugate and Alpha family surface protein vaccines are undergoing phase II clinical trials. Vaccine licensure may be facilitated by demonstrating safety and immunological correlates/thresholds suggestive of protection against invasive GBS disease. This will then be followed by phase IV effectiveness studies to assess the burden of GBS vaccine preventable disease, including the effect on all-cause neonatal infections, neonatal deaths and stillbirths.


Evaluation of two devices for improving thermal control of premature infants in transport.
Two devices, a plastic heat shield and a chemically heated mattress, were evaluated for their ability to reduce the needed air temperature and the power requirements in air servo-controlled transport incubators. A single-walled transporter and a double-walled transporter were evaluated using a heated manikin modeled after a 1000-g baby. The plastic heat shield reduced required transport incubator air temperature by 0.7 degree in the single-walled and 0.5 degree in the double-walled incubator, but did not significantly reduce power consumption. The chemically heated mattress was more effective in reducing power consumption and required air temperature, but it was difficult to stabilize infant temperatures in an incubator without skin servo-control. The transport incubators tested have wide swings in air temperature even during stable operation, rendering them suboptimal to manage small premature infants.


[Menstruation and the woman in Judaism].
Since ancient time subtile cultic regulations have been fundamentals of the habits of jewish people. Women had been affected from these in a considerable degree, consequently pressed into a social exceptional position. The laws of cleanness about behaviour during menstruation have been joined on a large scale. Nevertheless, behind the religious demands are a actual quinding directives of hygiene and timeless ethical principles. The question for prophylactic hints enclosed there cannot be answered.


Hormone-induced aberrations in electromagnetic adhesion signaling as a developmental factor of androgenetic alopecia.
In androgenetic alopecia, overactivation of the androgen hormone cascade in genetically predisposed persons leads to miniaturization of the dermal papilla of the hair follicle and to reduction in the number of papilla cells in the scalp, but the mechanisms explaining this miniaturization have remained unclear. According to our hypothesis, the increase of dihydrotestosterone (DHT) production in the overactive androgen state inhibits cell mitosis in the dermal papilla and contributes to the induction of programmed cell death (apoptosis). Normally, DNA molecules have a negative charge, which doubles in every cell mitosis. In the catagen and telogen phases, the sulphur-rich hair moves upwards, dehydrates and develops an increasing positive charge. In a normal hair-growth cycle, the epithelial column shortens and the secondary germ is formed and it invaginates the dermal papilla by electromagnetic attraction. In the mitotic inhibition state induced by DHT, the negative charge decreases, leading to a weakening of the electromagnetic adhesion forces and weaker electrical attraction between the undifferentiated germ cells and the dermal papilla. Insulin resistance has an additional pathogenic role in the excessive miniaturization of the hair follicle. The vasoactive substances associated with endothelial dysfunction in insulin resistance induce microcirculatory disturbance, perifollicular vasoconstriction and stimulation of smooth muscle cell proliferation in the vascular wall. This leads to microvascular insufficiency and local tissue hypoxia and progressive miniaturization of hair follicles.


Nasal immunization using a mimovirus vaccine based on the Eppin B-cell epitope induced suppressed fertility in mice.
To elicit potent humoral immunity and produce adequate neutralizing antibody especially in the genital tract and eventually to promote its immunogenicity, we designed an Eppin B-cell-dominant-epitope-based mimovirus vaccine with an RGD motif which can be nasally inoculated into male mice. Our results indicate that this immune strategy successfully generated a high antibody response with significantly higher anti-Eppin IgA in the genital tract, and eventually achieve significant inhibition of fertility without any interference with testis function and alteration in structural integrity. The fertility rate of the females mating with the vaccinated males declined and the progeny size was greatly reduced, but the contraceptive efficacy was still far from that of immunocontraceptives for human use. However, the research showed a new contraceptive vaccine construction and inoculation avenue, that is, mimovirus vaccine delivered nasally. Further investigation geared toward improving fertility inhibition efficacy using this inoculation strategy still remains to be explored.


Stiffness and Membrane Anchor Density Modulate DNA-Nanospring-Induced Vesicle Tubulation.
DNA nanotechnology provides an avenue for the construction of rationally designed artificial assemblages with well-defined and tunable architectures. Shaped to mimic natural membrane-deforming proteins and equipped with membrane anchoring molecules, curved DNA nanostructures can reproduce subcellular membrane remodeling events such as vesicle tubulation in vitro. To systematically analyze how structural stiffness and membrane affinity of DNA nanostructures affect the membrane remodeling outcome, here we build DNA-origami curls with varying thickness and amphipathic peptide density, and have them polymerize into nanosprings on the surface of liposomes. We find that modestly reducing rigidity and maximizing the number of membrane anchors not only promote membrane binding and remodeling but also lead to the formation of lipid tubules with better defined diameters, highlighting the ability of programmable DNA-based constructs to controllably deform the membrane.


Molecular epidemiology and clinical severity of Human Bocavirus (HBoV) 1-4 in children with acute gastroenteritis from Pune, Western India.
Although acute gastroenteritis is a major public health problem worldwide, ∼40% of the cases remain undiagnosed for any etiological agent. Human Bocavirus (HBoV) has been detected frequently in feces of diarrhoeic children suggesting its possible etiological involvement in the disease. HBoV has not been reported in association with acute gastroenteritis from India. Fecal samples (n = 418) collected from children (age ≤5 years) hospitalized with acute gastroenteritis, between January 2009 and December 2011, from three local hospitals were examined for presence of HBoV using PCR targeting the partial VP1/VP2 capsid region (∼575 bp) followed by phylogenetic analysis. HBoV was detected in 24/418 (5.7%) cases. Co-infection was observed in 5/24 (21%) cases. HBoV infections occurred in children ≤12 months of age. Peak HBoV activity was observed in monsoon and post monsoon season. All four HBoV genotypes were detected in the study region. Major clinical symptoms of HBoV mono infections included diarrhoea (100%), fever (90%), dehydration (74%), and vomiting (58%). Dehydration was observed in all of the HBoV2-4 cases and in 50% of the HBoV1 cases. Clinical severity varied with genotype (HBoV2 > HBoV1 > HBoV3 > HBoV4). HBoV2 cases recorded severe and very severe infections. The study illustrates prevalence and vast genetic diversity of HBoVs in acute gastroenteritis. It highlights the clinical features of HBoV1-4 infections and sheds light on clinical impact of HBoV genotypes in gastroenteritis. J. Med. Virol. 89:17-23, 2017. © 2016 Wiley Periodicals, Inc.


Apolipoprotein A-I, A-II, and H mRNA and protein accumulation sites in the developing lung in late gestation.
Expression of apolipoprotein A-I (apoA-I), A-II, and H was previously observed at 16 to 50-fold higher levels in the fetal than the adult mouse lung. Here, sites of apoA-I, A-II, and H mRNA and protein accumulation were determined in mouse fetal lungs by in situ hybridization and immunohistochemistry in late gestation. Expression sites vary for the three genes and change for the distal epithelium before the end of the canalicular stage, thus where and when the surge of surfactant synthesis occurs. Messenger of apoH, but not those of apoA-I and A-II, was also observed in the proximal epithelium and smooth muscles surrounding arteries. In contrast to apoC-II protein, none of the three studied apolipoproteins accumulated within secretory granule-like structures. Immunohistochemistry revealed that apoA-I and apoH accumulated mainly in capillaries. Three different positive signals with the anti-apoA-II antibody were found: one transient signal in the nucleus of a portion of mesenchymal cells, a second at lower levels throughout the mesenchyme, and another in capillaries with a specific increase from gestation day 17.5/18.5. Temporal and geographic co-expression of apoAI, AII, and H genes with surfactant production site suggests that the three apolipoproteins are secreted to play roles supporting the lung-specific surfactant lipid-related metabolism.


Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with Down syndrome: description by 3-dimensional ultrasonography and clinical significance.
To determine the frequency and clinical significance of bilateral and unilateral hypoplastic nasal bones for the detection of Down syndrome by 3-dimensional ultrasonography. Thirty-seven volumes of the fetal skull from fetuses with Down syndrome and 37 from fetuses without abnormalities were analyzed by 1 investigator blinded to fetal karyotype. The maximum intensity projection algorithm was used to reconstruct nasal bones. Ossification patterns were identified in anteroposterior and profile views. Sensitivity, false-positive rates (FPRs), and likelihood ratios (LRs) for detection of Down syndrome were calculated. After exclusions (coronal acquisition [n = 11], hand in front of the face [n = 4], poor imaging [n = 2], incomplete follow-up [n = 2], and anomalies detected after delivery [n = 2]), 53 volumes were analyzed (26 fetuses with Down syndrome and 27 without abnormalities; median gestational age, 21 6/7 weeks [interquartile range, 19 6/7-25 2/7 weeks]). Rendered profile views revealed absent nasal bones in 18.9% (10 of 53) of the fetuses, and, among these, 90% (9 of 10) had Down syndrome (sensitivity, 34.6% [9 of 26]; FPR, 3.7% [1 of 27]; LR, 9.3 [95% confidence interval (CI), 1.3-68.7]). Three ossification patterns were identified in anteroposterior views: (1) normally developed, (2) delayed ossification, and (3) absent nasal bones. Sensitivity, FPR, and LR of absent nasal bones for detecting Down syndrome were 34.6% (9 of 26), 3.7% (1 of 27), and 9.0 (95% CI, 1.3-68.7), respectively. Sensitivity, FPR, and LR of delayed ossification for detecting Down syndrome were 42.3% (11 of 26), 22% (6 of 27), and 1.83 (95% CI, 0.8-4.4). Absence of nasal bones is associated with the highest risk of Down syndrome. Delayed ossification is associated with a lower risk of Down syndrome than absent nasal bones. These ossification patterns may be indistinguishable on 2-dimensional ultrasonography.


Obstacles to palliation and end-of-life care in a long-term care facility.
This exploratory study used a set of four obstacle constructs derived from both the existing literature and our earlier work to describe the diverse end-of-life scenarios observed for a group of residents in a long-term care facility. Data from a retrospective chart review and both quantitative and qualitative methods of data collection and analysis were used to examine in-depth the end-of-life experiences of all nursing home residents (N = 41) who died on the nursing care unit of a large continuing care retirement community during an 18-month period. A hierarchy of obstacles to palliation and end-of-life care seems to exist in long-term care settings that begins with the lack of recognition that restorative, rehabilitative, or curative treatment futility has commenced. The next three obstacles in sequence include lack of communication among decision makers, no agreement on a course of care, and failure to implement a timely plan of care. The findings highlight the importance of determining treatment futility as an initial step in the successful delivery of palliative and end-of-life care to residents in long-term care followed by the need for a deliberate and proactive series of actions and care planning processes.


Age-related mechanism and its relationship with secondary metabolism and abscisic acid in Aristotelia chilensis plants subjected to drought stress.
Drought stress is the most important stress factor for plants, being the main cause of agricultural crop loss in the world. Plants have developed complex mechanisms for preventing water loss and oxidative stress such as synthesis of abscisic acid (ABA) and non-enzymatic antioxidant compounds such as anthocyanins, which might help plants to cope with abiotic stress as antioxidants and for scavenging reactive oxygen species. A. chilensis (Mol.) is a pioneer species, colonizing and growing on stressed and disturbed environments. In this research, an integrated analysis of secondary metabolism in Aristotelia chilensis was done to relate ABA effects on anthocyanins biosynthesis, by comparing between young and fully-expanded leaves under drought stress. Plants were subjected to drought stress for 20 days, and physiological, biochemical, and molecular analyses were performed. The relative growth rate and plant water status were reduced in stressed plants, with young leaves significantly more affected than fully-expanded leaves beginning from the 5th day of drought stress. A. chilensis plants increased their ABA and total anthocyanin content and showed upregulation of gene expression when they were subjected to severe drought (day 20), with these effects being higher in fully-expanded leaves. Multivariate analysis indicated a significant positive correlation between transcript levels for NCED1 (9-cis-epoxycarotenoid dioxygenase) and UFGT (UDP glucose: flavonoid-3-O-glucosyltransferase) with ABA and total anthocyanin, respectively. Thus, this research provides a more comprehensive analysis of the mechanisms that allow plants to cope with drought stress. This is highlighted by the differences between young and fully-expanded leaves, showing different sensibility to stress due to their ability to synthesize anthocyanins. In addition, this ability to synthesize different and high amounts of anthocyanins could be related to higher NCED1 and MYB expression and ABA levels, enhancing drought stress tolerance.


Importance of N-Glycosylation for the Expression and Function of Human Organic Anion Transporting Polypeptide 2B1.
Human organic anion transporting polypeptide 2B1 (OATP2B1) is a membrane transporter widely expressed in organs crucial for drug absorption and disposition such as the intestine, liver, and kidney. Evidence indicates that OATP2B1 is a glycoprotein. However, the sites of glycosylation and their contribution to the function and expression of OATP2B1 are largely unknown. In this study, by site-directed mutagenesis, we determined that two of four potential N-glycosylation sites in OATP2B1, N176 and N538, are indeed glycosylated. Functional studies revealed that the transport activities of mutants N176Q and N538Q were greatly reduced as compared to that of wild-type OATP2B1. However, the reduced activity was not due to the impairment of transport function per se but due to the decreased surface expression as the Km and normalized Vmax values of N176Q and N538Q were comparable to those of OATP2B1. Quantitative polymerase chain reaction (PCR) revealed that N176Q and N538Q mutations did not affect the expression of OATP2B1 at a transcriptional level. Immunofluorescence analysis showed that deglycosylated OATP2B1 was largely retained in the endoplasmic reticulum, which may activate the endoplasmic reticulum-associated degradation pathway, and the ubiquitin-proteasome system played a major role in the degradation of OATP2B1. Taken together, OATP2B1 is N-glycosylated, and N-glycosylation is essential for the surface expression of OATP2B1 but not critical for the transport function of OATP2B1 per se.


Antiepileptic drug withdrawal in childhood: does the duration of tapering off matter for seizure recurrence?
There is no consensus on how long the duration of antiepileptic drug withdrawal after seizure control should be. The objective of the present study was to verify if the duration of tapering off matters for seizure recurrence in children with controlled epilepsy. In this prospective study, patients were randomized to taper the antiepileptic drug during a period of 1 or 6 months. Fifty-seven patients met the inclusion criteria; 24 were girls, and ages ranged from 2 to 16 years (mean 9.45 years). There was no difference between the two groups according to age, gender, type of epileptic syndrome, electroencephalogram abnormality, and antiepileptic drug (P > .05). In the 1-month group, seizure recurred in 10 patients, as opposed to 12 patients in the 6-month group. The analysis of seizure recurrence in each group showed no difference (P > .05). We conclude that the duration of antiepileptic drug tapering off does not influence the risk of seizure recurrence in childhood.


Myotonia congenita and regional anaesthesia with peripheral nerve stimulation: a case report.
Myotonia congenita is a rare disorder caused by a defect in the skeletal muscle chloride channel function, which may cause sustained membrane depolarisation. We report a case regarding a 52-year-old man affected by this muscular pathology and scheduled for shoulder surgery that was performed under sedation and peripheral nerve block. The international literature does not elucidate clear preference toward a particular anaesthesia technique, but we believe that in this setting, regional anaesthesia and complete monitoring should be preferentially utilized when possible. In any case, the anaesthesia plan should be prudent and avoid exposure to known dangerous anaesthetics.


Incidence of deep vein thrombosis after major lower limb orthopedic surgery: analysis of a nationwide claim registry.
We aimed to evaluate the nationwide incidence and risk factors for symptomatic deep vein thrombosis (DVT) after major lower limb orthopedic surgeries. The Korean Health Insurance Review and Assessment Service database was used to retrospectively identify International Classification of Disease-10 codes for DVT and operation codes representing hip arthroplasty, knee arthroplasty, and hip fracture surgeries. The age- and gender-adjusted annual incidence of DVT, rates of major lower limb orthopedic surgeries, and the postoperative incidence of DVT according to the surgical procedure were assessed. The age- and gender-adjusted annual incidence of DVT was 70.67 per 100000 persons/year. Compared to patients aged <49 years, the relative risk of DVT was five times higher in patients aged 50-69 and 10 times higher in patients aged >70 years (p<0.001). Females showed a greater relative risk for DVT than males (1.08; p<0.001). The incidence of postoperative DVT, according to the type of surgery, was significantly greater for knee replacement arthroplasty than for other forms of surgery (p<0.002). The relative risk of postoperative DVT was higher in females in knee replacement arthroplasty (1.47) and hip fracture surgery (2.25) groups, although relatively lower in those who underwent hip replacement arthroplasty (0.97). Among major lower limb surgeries, advanced age, female gender, and undergoing a knee replacement arthroplasty were found to be risk factors for developing postoperative DVT. These findings further emphasize the need for orthopedic surgeons to consider the development of DVT after surgery in high-risk patients.


Quantification of Methylenecyclopropyl Compounds and Acyl Conjugates by UPLC-MS/MS in the Study of the Biochemical Effects of the Ingestion of Canned Ackee (Blighia sapida) and Lychee (Litchi chinensis).
Consumption of ackee (Blighia sapida) and lychee (Litchi chinensis) fruit has led to severe poisoning. Considering their expanded agricultural production, toxicological evaluation has become important. Therefore, the biochemical effects of eating 1 g/kg canned ackee, containing 99.2 μmol/kg hypoglycin A, and 5 g/kg canned lychee, containing 1.3 μmol/kg hypoglycin A, were quantified in a self-experiment. Using ultra-high-performance liquid chromatography/mass spectrometry, hypoglycin A, methylenecyclopropylacetyl-glycine, and methylenecyclopropylformyl-glycine, as well as the respective carnitine conjugates, were found in urine after ingesting ackee. Hypoglycin A and its glycine derivative were also present in urine after eating lychee. Excretion of physiological acyl conjugates was significantly increased in the ackee experiment. Ingestion of ackee led to up to 15.1 nmol/L methylenecyclopropylacetyl-glycine and traces of methylenecyclopropylformyl-carnitine in the serum. These compounds were not found in the serum after eating lychee. Hypoglycin A accumulated in the serum in both experiments.


Oxidant-mediated phosphatidylserine exposure and macrophage uptake of activated neutrophils: possible impairment in chronic granulomatous disease.
The removal of neutrophils from inflammatory sites is essential for the resolution of inflammation. Surface changes, including phosphatidylserine exposure, label neutrophils for phagocytosis by macrophages. Here, we demonstrate that externalization of phosphatidylserine and uptake by monocyte-derived macrophages occurred in human neutrophils ingesting Staphylococcus aureus. Both processes were dependent on oxidant production from the neutrophil NADPH oxidase. There was no requirement for myeloperoxidase, and H(2)O(2) was identified as the most likely trigger for PS exposure. We hypothesize that clearance of stimulated neutrophils would be delayed in chronic granulomatous disease (CGD) neutrophils, which lack a functional NADPH oxidase. To explore this possibility, heat-killed S. aureus were injected into the peritoneum of CGD and normal mice. Elevated neutrophil numbers were observed in the inflammatory exudate of the CGD animals, consistent with impaired recognition and clearance.


Scientific Misconduct (Fraud) in Medical Writing.
Scientific misconduct (fraud) in medical writing is an important and not infrequent problem for the scientific community. Although noteworthy examples of fraud surface occasionally in the media, detection of fraud in medical publishing is generally not as straightforward as one might think. National bodies on ethics in science, strict selection criteria, a robust peer-review process, careful statistical validation, and anti-plagiarism and image-fraud detection software contribute to the production of high-quality manuscripts. This article reviews the various types of fraud in medical writing, discusses the related literature, and describes tools journals implement to unmask fraud. [Orthopedics. 2018; 41(2):e176-e183].


Cerebral hemodynamics in orthostatic intolerance with normal head-up tilt test.
Orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS) are well-known causes of orthostatic intolerance (OI). In addition, there are OI patients who are characterized by the symptoms of OI and lack of abnormal findings in head-up tilt (HUT) test. The aim of this study was to determine the cerebral hemodynamic changes in HUT test of OI patients with normal HUT (OINH). Two hundred and sixty-one OI patients and 50 healthy controls were enrolled in this study. All subjects underwent transcranial Doppler test while performing the HUT test. Forty-five patients had OH, 33 patients had POTS, and 183 patients had OINH. Blood pressures, heart rate, cerebral blood flow velocities (CBFVs), end-tidal carbon dioxide (ET-PCO2 ), cerebral critical closing pressure (CCP), cerebral perfusion pressure (CPP), and cerebral vascular resistance (CVR) were measured during HUT test. We compared the hemodynamic parameters of OINH with those of OH, POTS, and healthy controls. Reduced CBFVs, CPP, and ET-PCO2 and elevated CCP were observed in the HUT test of all four groups. CVR was reduced in three OI patients. The drops in systolic CBFV, CPP, and CVR of OINH patients were greater than those of healthy controls. The changes in parameters in the HUT test of OINH group were not different from those of OH and POTS groups except prominent decrements of CPP and CVR in OH group. Our findings suggest that OINH is true OI sharing the common pathomechanism of OH and POTS.


Synthesis, cytotoxicity and antitumour mechanism investigations of polyoxometalate doped silica nanospheres on breast cancer MCF-7 cells.
Polyoxometalates (POMs) have shown the potential anti-bacterial, anti-viral and anti-tumor activities. In order to improve their physiological stability and antitumour activity for medical application, K2Na[AsIIIMo6O21(O2CCH2NH3)3]·6H2O doped silica nanospheres (POM@SiO2) with diameters of ~40 nm have been synthesized by the water-in-oil microemulsion method in this study. The obtained spheres were morphologically uniform nanosized and nearly monodispersed in solution. The nanoparticles had high entrapment efficiency, which was upto 46.2% by the inductively coupled plasma mass spectrometry (ICP-MS) analysis and POMs slowly released from the nanospheres both in the PH 7.4 and 5.5 phosphate buffer saline (PBS) solutions in 60 h. The in vitro MTT assays of particles on MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to that of plain polyoxometalate. The IC50 value of the POM@SiO2 nanoparticles was 40.0 μg/mL at 24 h calculated by the encapsulated POM concentration, which was much lower comparing to that of 2.0 × 104 μg/mL according to the pure POM. And the SiO2 shells showed low inhibitory effect at the corresponding concentration. Confocal images further indicated the cell morphology changes and necrosis. Flow cytometric analysis showed nanoparticles induced the apoptosis by arresting the cells in S phase and western blot analysis indicated they promoted apoptosis by inhibiting the Bcl-2 protein. Moreover, the study of interactions between human serum albumin (HSA) and the nanoparticles indicated the fluorescence quenching was static, and the nanoparticles were likely to bind to HSA and changed its conformation.


Open Reduction and Internal Fixation Versus Radial Head Arthroplasty for Mason III Radial Head Fractures: Appraising the Current Literature Evidence.
Fractures of the radial head are common and account for one-third of elbow fractures. Management has evolved over the past few decades as have the techniques and implants used to treat them. However, no standardized treatment protocol exists because of the complexity with which these fractures may present. The complex, unstable, displaced, and multi-fragmentary fractures, also known as Mason type III fractures, remain one of the most challenging fractures to treat, especially if associated with other elbow injuries. There are various surgical treatment options available, including open reduction and internal fixation or radial head arthroplasty. The purpose of this study was to systematically review the current literature that assessed open reduction and internal fixation compare to radial head replacement to identify the best surgical treatment protocol for the management of Mason type III radial head fracture. All published clinical trials claiming to evaluate or cited elsewhere as being authoritative regarding the surgical treatment of radial head fractures were identified and evaluated. Studies in foreign languages (not in English) were excluded. Based on two randomized controlled trials, this review showed some weak evidence that arthroplasty results in better functional elbow outcomes and lower complication rates as compared to open reduction and internal fixation. There is a scarcity of good quality comparative studies and multicenter randomized controlled trials should be considered.


Jumping on the omega-3 bandwagon: distinguishing the role of long-chain and short-chain omega-3 fatty acids.
Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are almost unanimously recognized for their health benefits, while only limited evidence of any health benefit is currently available specifically for the main precursor of these fatty acids, namely α-linolenic acid (ALA, 18:3n-3). However, both the n-3 LC-PUFA and the short-chain C₁₈ PUFA (i.e., ALA) are commonly referred to as "omega-3" fatty acids, and it is difficult for consumers to recognize this difference. A current gap of many food labelling legislations worldwide allow products containing only ALA and without n-3 LC-PUFA to be marketed as "omega-3 source" and this misleading information can negatively impact the ability of consumers to choose more healthy diets. Within the context of the documented nutritional and health promoting roles of omega-3 fatty acids, we briefly review the different metabolic fates of dietary ALA and n-3 LC-PUFA. We also review food sources rich in n-3 LC-PUFA, some characteristics of LC-PUFA and current industry and regulatory trends. A further objective is to present a case for regulatory bodies to clearly distinguish food products containing only ALA from foods containing n-3 LC-PUFA. Such information, when available, would then avoid misleading information and empower consumers to make a more informed choice in their food purchasing behavior.


Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells.
Nanoparticles (NPs) for targeted therapy are required to have appropriate size, stability, drug loading and release profiles, and efficient targeting ligands. However, many of the existing NPs such as albumin, liposomes, polymers, gold NPs, etc. encounter size limit, toxicity and stability issues when loaded with drugs, fluorophores, and targeting ligands. Furthermore, antibodies are bulky and this can greatly affect the physicochemical properties of the NPs, whereas many small molecule-based targeting ligands lack specificity. Here, we report the utilization of biocompatible, biodegradable, small (∼30 nm) and stable iron oxide NPs (IONPs) for targeted delivery of paclitaxel (PTX) to HER2/neu positive breast cancer cells using an anti-HER2/neu peptide (AHNP) targeting ligand. We demonstrate the uniform size and high stability of these NPs in biological medium, their effective tumour targeting in live mice, as well as their efficient cellular targeting and selective killing in human HER2/neu-positive breast cancer cells.


Leveraging a temperature-tunable, scale-like microstructure to produce multimodal, supersensitive sensors.
The microstructure of a flexible film plays an important role in its sensing capability. Here, we fabricate a temperature-dependent wrinkled single-walled carbon nanotube (SWCNT)/polydimethyl-siloxane (PDMS) film (WSPF) and a wrinkle-dependent scale-like SWCNT/PDMS film (SSPF) successfully, and address the formation and evolution mechanisms of each film. The low elastic modulus and high coefficient of thermal expansion of the PDMS layer combined with the excellent piezoresistive behavior of the SWCNT film motivated us to investigate how the scale-like microstructure of the SSPF could be used to design multimodal-sensing devices with outstanding capabilities. The results show that SSPFs present supersensitive performance in mechanical loading (an effective sensitivity of up to 740.7 kPa-1) and in temperature (a tunable thermal index of up to 29.9 × 103 K). These exceptional properties were demonstrated in practical applications in a programmable flexile pressure sensor, thermal/light monitor or switch, etc., and were further explained through the macroscopic and microscopic piezoresistive behaviors of scale-like SWCNT coatings.


Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection.
Cytolytic T-lymphocyte (CTL) clones against an autologous melanoma (SK-MEL-29) were generated by mixed lymphocyte tumor culture and subsequent cloning of responder lymphocytes at limiting dilutions. These CTL clones lysed autologous melanoma but not autologous Epstein-Barr virus-transformed B cells and none of the allogeneic tumor targets included in the specificity analysis. The lysis of autologous melanoma targets could be inhibited by monoclonal antibodies against monomorphic HLA class I determinants. For proliferation of CTLs, the stimulation with the relevant target antigen on autologous tumor cells was essential. Immunoselection experiments carried out with two CTL clones revealed the existence of melanoma subclones that were resistant to lysis by the CTL clones used for immunoselection but were still lysed by other autologous CTL clones. This analysis allowed us to identify three stable simultaneously expressed antigens on the melanoma cells defined by autologous CTLs.


Quaternary structure of polynucleotide phosphorylase from Escherichia coli: evidence of a complex between two types of polypeptide chains.
A new form of polynucleotide phosphorylase containing alpha and beta subunits was isolated (form B) by purification without preparative electrophoresis; this form was compared to the enzyme obtained by preparative electrophoresis purification (form A). The Stokes radius of these two forms are very different: 6.4 nm for form A and 8.7 - 9.0 nm for form B; on the other hand the sedimentation coefficients are close: 8.9 S and 9.9 S respectively. Such a result suggests that form B is very asymmetric. The apparent molecular weights, calculated from the Stokes radii and from the sedimentation coefficients, are approximately 365000 for form B and 252000 for form A. The latter is homogeneous on polyacrylamide gel, whereas the former yields two components, one of which behaves similarly to form A. Finally, whereas form A is composed of only one type of subunit, alpha, form B contains two types of chains: alpha (Mr 86000 +/- 5000) and beta (Mr 48000 +/- 2000) in stoichiometric proportions. From these results we believe that one should assume for form B the existence of a complex between form A and beta chains; the role of the latter still remains to be specified.