HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community.
Survival of people with HIV-2 and HTLV-1 infection is better than that of HIV-1 infected people, but long-term follow-up data are rare. We compared mortality rates of HIV-1, HIV-2, and HTLV-1 infected subjects with those of retrovirus-uninfected people in a rural community in Guinea-Bissau. In 1990, 1997 and 2007, adult residents (aged ≥15 years) were interviewed, a blood sample was drawn and retroviral status was determined. An annual census was used to ascertain the vital status of all subjects. Cox regression analysis was used to estimate mortality hazard ratios (HR), comparing retrovirus-infected versus uninfected people. A total of 5376 subjects were included; 197 with HIV-1, 424 with HIV-2 and 325 with HTLV-1 infection. The median follow-up time was 10.9 years (range 0.0-20.3). The crude mortality rates were 9.6 per 100 person-years of observation (95% confidence interval 7.1-12.9) for HIV-1, 4.1 (3.4-5.0) for HIV-2, 3.6 (2.9-4.6) for HTLV-1, and 1.6 (1.5-1.8) for retrovirus-negative subjects. The HR comparing the mortality rate of infected to that of uninfected subjects varied significantly with age. The adjusted HR for HIV-1 infection varied from 4.0 in the oldest age group (≥60 years) to 12.7 in the youngest (15-29 years). The HR for HIV-2 infection varied from 1.2 (oldest) to 9.1 (youngest), and for HTLV-1 infection from 1.2 (oldest) to 3.8 (youngest). HTLV-1 infection is associated with significantly increased mortality. The mortality rate of HIV-2 infection, although lower than that of HIV-1 infection, is also increased, especially among young people.


Platelet LGALS3BP as a Mediator of Myeloid Inflammation in Systemic Lupus Erythematosus.
Platelets are mediators of inflammation with immune effector cell properties and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet-associated lectin, galactoside-binding, soluble 3 binding protein (LGALS3BP) as a mediator of inflammation in SLE and as a potential biomarker associated with clinical phenotypes. We performed RNA sequencing on platelets from patients with SLE (n = 54) and on platelets from age-, sex-, and race/ethnicity-matched healthy controls (n = 18) and measured LGALS3BP levels in platelet releasate and in circulating serum. We investigated the association between LGALS3BP levels and the prevalence, disease severity, and clinical phenotypes of SLE and studied platelet-mediated effects on myeloid inflammation. Platelets from patients with SLE exhibited increased expression of LGALS3BP (fold change 4.0, adjusted P = 6.02 × 10-11 ). Platelet-released LGALS3BP levels were highly correlated with circulating LGALS3BP (R = 0.69, P < 0.0001), and circulating LGALS3BP levels were correlated with the severity of disease according to the SLE Disease Activity Index (r = 0.32, P = 0.0006). Specifically, circulating LGALS3BP levels were higher in SLE patients with lupus nephritis than in patients with inactive disease (4.0 μg/ml versus 2.3 μg/ml; P < 0.001). Interferon-α induced LGALS3BP transcription and translation in a megakaryoblastic cell line (MEG-01) in a dose-dependent manner. Recombinant LGALS3BP and platelet releasates from SLE patients enhanced proinflammatory cytokine production by macrophages. Our results support that platelets act as potent effector cells that contribute to the pathogenesis of SLE by secreting proinflammatory LGALS3BP, which also represents a novel biomarker of SLE clinical activity.


Treatment of solitary iliac aneurysms: clinical review of 28 cases.
The clinical characteristics and long-term results of patients with solitary iliac aneurysms (SIAs) were investigated. 28 consecutive patients who underwent repair of SIAs between 1985 and 2004 were reviewed retrospectively, and compared with those of 536 patients who underwent elective repair of an abdominal aortic aneurysm (AAA) during the same period. The incidence of SIAs among all aorto-iliac aneurysms was 5.0%. The 28 patients with SIAs were men with a mean age of 69.1 years. There were a collective total of 42 iliac aneurysms in the 28 patients, with 12 patients having multiple aneurysms. Thirty aneurysms involved the common iliac artery, and 12 involved the internal iliac artery. Twenty-two patients had symptoms, although none of the SIAs ruptured. Four patients had coexistent iliac occlusive disease and two patients had femoral occlusive disease. The 5-and 10-year survival rates of the patients with SIAs were 90.5% and 75.4%, whereas those of the patients with AAAs were 76.3% and 54%, respectively (P = 0.089). Routine imaging is necessary not only to evaluate the SIAs, but also to detect multiple aneurysms or arterial occlusive disease. Close and long-term followup is mandatory for the early detection of the formation of new aneurysms.


Introduction of male circumcision for HIV prevention in Uganda: analysis of the policy process.
Health policy analysis is important for all health policies especially in fields with ever changing evidence-based interventions such as HIV prevention. However, there are few published reports of health policy analysis in sub-Saharan Africa in this field. This study explored the policy process of the introduction of male circumcision (MC) for HIV prevention in Uganda in order to inform the development processes of similar health policies. Desk review of relevant documents was conducted between March and May 2012. Thematic analysis was used to analyse the data. Conceptual frameworks that demonstrate the interrelationship within the policy development processes and influence of actors in the policy development processes guided the analysis. Following the introduction of MC on the national policy agenda in 2007, negotiation and policy formulation preceded its communication and implementation. Policy proponents included academic researchers in the early 2000s and development partners around 2007. Favourable contextual factors that supported the development of the policy included the rising HIV prevalence, adoption of MC for HIV prevention in other sub-Saharan African countries, and expertise on MC. Additionally, the networking capability of proponents facilitated the change in position of non-supportive or neutral actors. Non-supportive and neutral actors in the initial stages of the policy development process included the Ministry of Health, traditional and Muslim leaders, and the Republican President. Using political authority, legitimacy, and charisma, actors who opposed the policy tried to block the policy development process. Researchers' initial disregard of the Ministry of Health in the research process of MC and the missing civil society advocacy arm contributed to delays in the policy development process. This study underscores the importance of securing top political leadership as well as key implementing partners' support in policy development processes. Equally important is the appreciation of the various forms of actors' power and how such power shapes the policy agenda, development process, and content.


Developing children's nursing through action research.
Action research provides an ideal strategy for the integration of theory and practice, as it focuses on the development of theory in practice. Action research is gaining in popularity and acceptance. The collaborative approaches of action research parallel the dominant philosophies of participation and partnership in contemporary children's nursing. Taking the lead in identifying areas of practice for action research is a natural extension of the children's nurse's role as advocate for the child and family. The challenge for the future is to expand the use of action research in children's nursing and to include service users--the children and their families--in the research teams.


Biochar Particles Obtained from Agricultural Carob Waste as a Suitable Filler for Sustainable Biocomposite Formulations.
In the context of sustainable and circular economy, the recovery of biowaste for sustainable biocomposites formulation is a challenging issue. The aim of this work is to give a new life to agricultural carob waste after glucose extraction carried out by a local factory for carob candy production. A pyrolysis process was carried out on bio-waste to produce biofuel and, later, the solid residual fraction of pyrolysis process was used as interesting filler for biocomposites production. In this work, biochar particles (BC) as a pyrolysis product, after fuels recovery of organic biowaste, specifically, pyrolyzed carobs after glucose extraction, were added on poly(butylene-adipate-co-terephthalate), (PBAT), at two different concentrations, i.e., 10 and 20 wt%. The BC have been produced using three pyrolysis processing temperatures (i.e., 280, 340 and 400 °C) to optimize the compositions of produced solid fractions and biofuels. The resulting particles from the pyrolysis process (BC280, BC340 and BC400) were considered as suitable fillers for PBAT. Firstly, the BC particles properties were characterized by elemental composition and spectroscopy analysis, particle size measurements and evaluation of radical scavenging activity and efficiency. Moreover, PBAT/BC composites were subjected to analysis of their rheological and thermal behavior, morphologies and mechanical properties. In addition, accelerated weathering, monitored by both tensile test and spectroscopic analysis, was carried out, and obtained results show that the biochar particles can exert a beneficial effect on photo-oxidation delay of PBAT matrix.


Design of a highly specific and noninvasive biosensor suitable for real-time in vivo imaging of mercury (II) uptake.
Mercury is a ubiquitous pollutant that when absorbed is extremely toxic to a wide variety of biochemical processes. Mercury (II) is a strong, "invisible" poison that is rapidly absorbed by tissues of the intestinal tract, kidneys, and liver upon ingestion. In this study, a novel fluorescence-based biosensor is presented that allows for the direct monitoring of the uptake and distribution of the metal under noninvasive in vivo conditions. With the introduction of a cysteine residue at position 205, located in close proximity to the chromophore, the green fluorescent protein (GFP) from Aequorea victoria was converted into a highly specific biosensor for this metal ion. The mutant protein exhibits a dramatic absorbance and fluorescence change upon mercuration at neutral pH. Absorbance and fluorescence properties with respect to the metal concentration exhibit sigmoidal binding behavior with a detection limit in the low nanomolar range. Time-resolved binding studies indicate rapid subsecond binding of the metal to the protein. The crystal structures obtained of mutant eGFP205C indicate a possible access route of the metal into the core of the protein. To our knowledge, this engineered protein is a first example of a biosensor that allows for noninvasive and real-time imaging of mercury uptake in a living cell. A major advantage is that its expression can be genetically controlled in many organisms to enable unprecedented studies of tissue specific mercury uptake.


Risk factors for invasive Cryptococcus neoformans diseases: a case-control study.
Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study. All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002-2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors. A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio [aOR] = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia. The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.


[The DIC syndrome in severe trauma to the skull and brain].
The article is based on the analysis of the hemocoagulation system in 205 patients (91 with contusion of the brain without compression and 114 with compression). Evaluation of the clinical signs, hemocoagulation disorders, and pathophysiological data revealed 89 (43.4%) cases of the disseminated intravascular coagulation syndrome. Besides other factors, exhaustion of the functioning of the anticoagulation ability of the blood in increased functioning of the coagulation system promoted the development of the syndrome. The syndrome was encountered mostly in the mesencephalobulbar (in 33 among 42 cases) and the diencephalic (in 17 of 37 cases) forms of brain lesions and in subdural hematomas (in 33 among 47 cases). Total mortality was 30.2% (62 among 205), disseminated intravascular coagulation syndrome mortality was 55% (49 among 89 cases).


Comparative Genomics of Two New HF1-like Haloviruses.
Few genomes of the HF1-group of viruses are currently available, and further examples would enhance the understanding of their evolution, improve their gene annotation, and assist in understanding gene function and regulation. Two novel HF1-group haloviruses, Serpecor1 and Hardycor2, were recovered from widely separated hypersaline lakes in Australia. Both are myoviruses with linear dsDNA genomes and infect the haloarchaeon Halorubrum coriense. Both genomes possess long, terminal direct repeat (TDR) sequences (320 bp for Serpecor1 and 306 bp for Hardycor2). The Serpecor1 genome is 74,196 bp in length, 57.0% G+C, and has 126 annotated coding sequences (CDS). Hardycor2 has a genome of 77,342 bp, 55.6% G+C, and 125 annotated CDS. They show high nucleotide sequence similarity to each other (78%) and with HF1 (>75%), and carry similar intergenic repeat (IR) sequences to those originally described in HF1 and HF2. Hardycor2 carries a DNA methyltransferase gene in the same genomic neighborhood as the methyltransferase genes of HF1, HF2 and HRTV-5, but is in the opposite orientation, and the inferred proteins are only distantly related. Comparative genomics allowed us to identify the candidate genes mediating cell attachment. The genomes of Serpecor1 and Hardycor2 encode numerous small proteins carrying one or more CxxC motifs, a signature feature of zinc-finger domain proteins that are known to participate in diverse biomolecular interactions.


Comparison of barium swallow and ultrasound in diagnosis of gastro-oesophageal reflux in children.
Fifty one infants and older children with suspected gastro-oesophageal reflux entered a study comparing the diagnostic accuracy of a standard barium swallow examination with that of ultrasound scanning. All children were examined by both techniques. In 40 cases there was unequivocal agreement between the examinations. Of the remaining patients, four had definite reflux by ultrasonic criteria but showed no evidence of reflux on barium swallow examination, four had positive findings on ultrasound but showed only minimal reflux on barium swallow, and one showed minimal reflux on ultrasound but had a negative barium meal result. In two children the ultrasound study was inconclusive. Ultrasound has an important role in the diagnosis and follow up of patients under the age of 5 years with gastro-oesophageal reflux.


A Flavor Lactone Mimicking AHL Quorum-Sensing Signals Exploits the Broad Affinity of the QsdR Regulator to Stimulate Transcription of the Rhodococcal qsd Operon Involved in Quorum-Quenching and Biocontrol Activities.
In many Gram-negative bacteria, virulence, and social behavior are controlled by quorum-sensing (QS) systems based on the synthesis and perception of N-acyl homoserine lactones (AHLs). Quorum-quenching (QQ) is currently used to disrupt bacterial communication, as a biocontrol strategy for plant crop protection. In this context, the Gram-positive bacterium Rhodococcus erythropolis uses a catabolic pathway to control the virulence of soft-rot pathogens by degrading their AHL signals. This QS signal degradation pathway requires the expression of the qsd operon, encoding the key enzyme QsdA, an intracellular lactonase that can hydrolyze a wide range of substrates. QsdR, a TetR-like family regulator, represses the expression of the qsd operon. During AHL degradation, this repression is released by the binding of the γ-butyrolactone ring of the pathogen signaling molecules to QsdR. We show here that a lactone designed to mimic quorum signals, γ-caprolactone, can act as an effector ligand of QsdR, triggering the synthesis of qsd operon-encoded enzymes. Interaction between γ-caprolactone and QsdR was demonstrated indirectly, by quantitative RT-PCR, molecular docking and transcriptional fusion approaches, and directly, in an electrophoretic mobility shift assay. This broad-affinity regulatory system demonstrates that preventive or curative quenching therapies could be triggered artificially and/or managed in a sustainable way by the addition of γ-caprolactone, a compound better known as cheap food additive. The biostimulation of QQ activity could therefore be used to counteract the lack of consistency observed in some large-scale biocontrol assays.


Diagnostic efficacy of pleural biopsy as compared with that of pleural fluid examination.
Previous studies compared the diagnostic value of pleural fluid cytology versus pleural biopsy. No direct comparison of the procedures including data from a combination of all diagnostic tests performed on each specimen appears to have been done. A total of 385 patients with concurrent pleural biopsy and fluid examination were identified from 1973 to 1986. Clinical records, histologic and cytologic preparations, and microbiologic and chemical data were reviewed. A total of 109 patients had a final diagnosis of malignancy. Cytology was diagnostic in 71% and "suggestive" in an additional 8%. There were no false-positives but, in two patients with pulmonary infarcts, the effusions were reported as "suspicious." Pleural biopsy was positive in 45%, including three cases with negative cytology. In 71 patients with tuberculosis, the pleural biopsy was diagnostic in 49%. A cytologic picture suggesting the diagnosis was present in 68%. Cultures of the biopsy yielded Mycobacterium tuberculosis in 23% of cases, while pleural fluid was positive in 30%. In six cases, the only confirmatory evidence of tuberculosis was pleural culture. In 205 patients, none of the above procedures provided specific diagnoses. A combination of biopsy and fluid examinations improves the diagnostic sensitivity. Pleural biopsy increases the rate of complications and did lead to fatal hemothorax in two patients. These results support the superiority of pleural fluid examination in the diagnosis of malignancy. In addition, they demonstrate the value of pleural fluid examination in the diagnosis of tuberculosis.


Characterization and pharmacodynamic properties of Arnica montana complex.
A dark brown polymeric complex was isolated from flowering parts of medicinal plant Arnica montana L. by hot alkaline extraction followed by neutralization and multi-step extractions with organic solvents. It was recovered in 5.7% yield, on GPC showed two peaks of molecular mass of 9 and 3.5kDa. The compositional analyses of Arnica complex revealed the presence of carbohydrates (26%), uronic acids (12%), phenolics (1.25mM or 213mg of GAE/1g), and low protein content (∼1%). The carbohydrate moiety was rich mainly in rhamnogalacturonan and arabinogalactan. The antitussive tests showed the reduction of the cough efforts by Arnica complex, however, its total antitussive effect was lower compared with that of codeine, the strongest antitussive agent. The bronchodilatory activity of Arnica complex was similar to salbutamol, a classic antiasthmatic drug, and was confirmed by significantly decreased values of specific airways resistance in vivo and by considerably attenuated the amplitude of acetylcholine and histamine-induced contractions in vitro. Arnica complex did not show any cytotoxic effect on mouse fibroblast cultures and human lung cells, up to the dose of 500μg/mL.


Mechanism of Bacillus Calmette-Guérin-induced suppression of metastases in a poorly immunogenic fibrosarcoma.
Bacillus Calmette-Guérin (BCG) reduces the rate of spontaneous pulmonary metastases from a poorly immunogenic fibrosarcoma. To be effective, BCG (1 X 10(6) organisms) must be given in admixture with (1 X 10(6)) tumor cells at the time of transplantation. Reduction of metastasis at this dosage of BCG occurs without a change in the size of the primarytumor or the extent of necrosis within it. Tumors transplanted in admixture with spleen cells from BCG-exposed donors reduced the number of metastases, while spleen cells from normal or tumor-bearing donors had no effect on metastases. Fewer total tumor cells and clumps are collected from the venous effluent of tumors transplanted with BCG than from control tumors. The BCG-treated tumors have more host macrophages intimately associated with the effluent tumor cells then did controls. These data indicate that BCG can inhibit the metastatic potential of a weakly immunogenic fibrosarcoma. The mechanism of this effect appears to be a depression of entry or tumor cells into the tumor vascular channels which may be related to the interaction of tumor cells with BCG-stimulated macrophages.


Coffee diterpenes kahweol acetate and cafestol synergistically inhibit the proliferation and migration of prostate cancer cells.
Coffee inhibits the progression of prostate cancer; however, the direct mechanism through which coffee acts on prostate cancer cells remains unclear. This study aimed to identify the key compounds of coffee that possess anti-cancer effects and to investigate their mechanisms of action. The anti-proliferation and anti-migration effects of six potentially active types of coffee compounds, including kahweol acetate, cafestol, caffeine, caffeic acid, chlorogenic acid, and trigonelline hydrochloride, were evaluated using LNCaP, LNCaP-SF, PC-3, and DU145 human prostate cancer cells. The synergistic effects of these compounds were also investigated. Apoptosis-related and epithelial-mesenchymal transition-related proteins, androgen receptor in whole cell and in nucleus, and chemokines were assessed. A xenograft study of SCID mice was performed to examine the in vivo effect of coffee compounds. Among the evaluated compounds, only kahweol acetate and cafestol inhibited the proliferation and migration of prostate cancer cells in a dose-dependent manner. The combination treatment involving kahweol acetate and cafestol synergistically inhibited proliferation and migration (combination index <1) with the induction of apoptosis, the inhibition of epithelial-mesenchymal transition, and decrease in androgen receptor, resulting in the reduction of nuclear androgen receptor in androgen receptor-positive cells. Moreover, kahweol acetate and cafestol downregulated CCR2 and CCR5 without an increase in their ligands, CCL2 and CCL5. The xenograft study showed that oral administration of kahweol acetate and cafestol significantly inhibited tumor growth. Kahweol acetate and cafestol synergistically inhibit the progression of prostate cancer. These coffee compounds may be novel therapeutic candidates for prostate cancer.


Patients and physician satisfaction of Degarelix in androgen deprivation therapy for advanced hormone-dependent prostate cancer in the Netherlands.
To explore the effectiveness and safety of the gonadotropin-releasing hormone antagonist, Degarelix, for the treatment of advanced hormone-dependent prostate cancer (PCa) in a real-world setting. In this noninterventional study, patients with advanced hormone-dependent PCa were included. Primary endpoints were progression-free survival (PFS) failure defined as either prostate-specific antigen failure, additional therapy related to PCa, or death. Secondary endpoints included patient and physician satisfaction scores, urinary symptoms, and adverse events (AEs). Of 274 patients with PCa, 271 received at least 1 dose of Degarelix. At a median follow-up of 12.2 (interquartile range 6.2-22.0) months, 148 patients (60.2%) had PFS failure. Thirty-five patients (13%) withdrew from the study due to AEs, 23 patients (8.4%) died, and 36 patients (13%) completed 3 years' follow-up. Urinary symptoms significantly decreased over time. In the safety population, 87.8% of patients reported AEs, with injection-site reactions commonly reported. The majority of physicians and patients considered the therapy satisfactory and well tolerated. In this observational study, Degarelix treatment was well accepted by men with advanced hormone-dependent PCa. Compared with phase III studies, a higher proportion of patients had PFS failure, possibly due to the inclusion of men with more advanced disease in the current study, and more men reported AEs.


Genetic Variants in nicotinamide-N-methyltransferase (NNMT) gene are related to the stage of non-alcoholic fatty liver disease diagnosed by controlled attenuation parameter (CAP)-fibroscan.
Various genetic polymorphisms play a key-role in the pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We aimed to study the association between single-nucleotide polymorphisms (SNPs) in NNMT gene, namely rs694539 and the development of different stages of NAFLD diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens®. Transient elastography (FibroScan®) with controlled attenuation parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with liver biopsy) and 80 non-NAFLD controls. The accuracy of CAP and FibroScan for the detection and quantification of hepatic steatosis/fibrosis, respectively, was assessed based on liver biopsy aspect. Genetic variants of NNMT gene rs694539 were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to BMI (kg/m2), among the patients, 17 (21%) were overweight, 56 (69.1%) obese, and 8 (9.9%) morbidly obese. CAP and FibroScan diagnosed steatosis/fibrosis correlated significantly with liver biopsy. There was a significant association between polymorphisms of rs694539-NNMT gene and NAFLD presence and stages. The mutant type (AA-genotype) was found in 33% NAFLD patients versus 1.2% controls (P<0.001), whereas the wild type (GG-genotype) was present in 21% versus 63.8% controls (P<0.001). Moreover, the AA-genotype significantly correlated with the steatosis degree by CAP but not the fibrosis degree by FibroScan. Multivariate regression analysis of all the independent risk factors showed non-significant correlations with the degree of steatosis on CAP. However, by using a stepwise approach, waist circumference showed significance as an independent predictor of NAFLD. Polymorphisms in rs694539-NNMT gene (mutant AA-genotype) could be a genetic risk factor for developing NAFLD and NASH (indicating susceptibility for progression and complications). Individuals with wild type (GG-genotype) are at less risk of NAFLD development. CAP and FibroScan efficiently diagnosed steatosis and fibrosis.


Contra-thermodynamic Olefin Isomerization by Chain-Walking Hydrofunctionalization and Formal Retro-hydrofunctionalization.
We report a contra-thermodynamic isomerization of internal olefins to terminal olefins driven by redox reactions and formation of Si-F bonds. This process involves chain-walking hydrosilylation of internal olefins and subsequent formal retro-hydrosilylation. The process rests upon the high activities of platinum hydrosilylation catalysts for isomerization of metal alkyl intermediates and a new, metal-free process for the conversion of alkylsilanes to alkenes. By this approach, 1,2-disubstituted and trisubstituted olefins are converted to terminal olefins.


The neural basis of aware and unaware forms of memory.
Information regarding the nature of phenomenal awareness in memory comes from a direct comparison of explicit and implicit memory tasks. Explicit memory tasks require conscious awareness of a prior episode, whereas implicit memory tasks do not. This paper reviews evidence regarding the neural basis of aware and unaware forms of memory as obtained from patient studies and functional neuroimaging work. These studies suggest the existence of a memory system centered in the medial temporal and frontal lobes that is dedicated to the storage and retrieval of episodes and several neocortical memory systems that are dedicated to the processing and representation of perceptual and semantic information. Different hypotheses are discussed as to how the phenomenal awareness that accompanies episodic memories may arise within the hippocampal-frontal memory system. These views have in common the notion that various forms of information need to be bound together to be retrievable as an aware memory, and that the hippocampus is critical to this binding function.


High log-scale expansion of functional human natural killer cells from umbilical cord blood CD34-positive cells for adoptive cancer immunotherapy.
Immunotherapy based on natural killer (NK) cell infusions is a potential adjuvant treatment for many cancers. Such therapeutic application in humans requires large numbers of functional NK cells that have been selected and expanded using clinical grade protocols. We established an extremely efficient cytokine-based culture system for ex vivo expansion of NK cells from hematopoietic stem and progenitor cells from umbilical cord blood (UCB). Systematic refinement of this two-step system using a novel clinical grade medium resulted in a therapeutically applicable cell culture protocol. CD56(+)CD3(-) NK cell products could be routinely generated from freshly selected CD34(+) UCB cells with a mean expansion of >15,000 fold and a nearly 100% purity. Moreover, our protocol has the capacity to produce more than 3-log NK cell expansion from frozen CD34(+) UCB cells. These ex vivo-generated cell products contain NK cell subsets differentially expressing NKG2A and killer immunoglobulin-like receptors. Furthermore, UCB-derived CD56(+) NK cells generated by our protocol uniformly express high levels of activating NKG2D and natural cytotoxicity receptors. Functional analysis showed that these ex vivo-generated NK cells efficiently target myeloid leukemia and melanoma tumor cell lines, and mediate cytolysis of primary leukemia cells at low NK-target ratios. Our culture system exemplifies a major breakthrough in producing pure NK cell products from limited numbers of CD34(+) cells for cancer immunotherapy.


Experimental phylogenetics: generation of a known phylogeny.
Although methods of phylogenetic estimation are used routinely in comparative biology, direct tests of these methods are hampered by the lack of known phylogenies. Here a system based on serial propagation of bacteriophage T7 in the presence of a mutagen was used to create the first completely known phylogeny. Restriction-site maps of the terminal lineages were used to infer the evolutionary history of the experimental lines for comparison to the known history and actual ancestors. The five methods used to reconstruct branching pattern all predicted the correct topology but varied in their predictions of branch lengths; one method also predicts ancestral restriction maps and was found to be greater than 98 percent accurate.


Current and emerging biomarkers for ulcerative colitis.
Ulcerative colitis (UC) is a chronic illness requiring lifelong management that could be enhanced by personalizing care using biomarkers. The main biomarker discovery modalities are reviewed, highlighting recent results across the spectrum of applications, including diagnostics (serum anti-αvβ6 antibodies achieving an area under the curve [AUC] = 0.99; serum oncostatin M AUC = 0.94), disease activity assessment (fecal calprotectin and serum trefoil factor 3: AUC > 0.90), prognostication of the need for treatment escalation (whole blood transcriptomic panels and CLEC5A/CDH2 ratio: AUC > 0.90), prediction of treatment response, and early identification of patients with subclinical disease. The use of established biomarkers is discussed, along with new evidence regarding autoantibodies, proteins, proteomic panels, transcriptomic signatures, deoxyribonucleic acid methylation patterns, and UC-specific glycomic and metabolic disturbances. Novel biomarkers will pave the way for optimized UC care. However, validation, simplification, and direct clinical translation of complex models may prove challenging. Currently, few candidates exist to assess key characteristics, such as UC susceptibility, histological disease activity, drug response, and long-term disease behavior. Further research will likely not only reveal new tools to tackle these issues but also contribute to understanding UC pathogenesis mechanisms.


Preventive health behavior among black and white women in urban and rural areas.
The relationship of race to preventive health behavior among women is examined using data from the 1985 National Health Interview Survey. We find that black women are less likely to engage in primary prevention behaviors such as exercising, non-smoking and maintaining a favorable weight. However, black women are more likely to engage in secondary prevention behaviors such as receiving a Pap test or a breast exam. These findings are surprising as they indicate a change in secondary prevention behavior among black women. The racial differences in exercising, maintaining a favorable weight and receiving a Pap test or a breast exam cannot fully be explained by the differing levels of socio-economic status, measured by education and income. However, the higher percentage of smoking among black women is due to their lower levels of education. Urban/rural residence modifies the effect of race on smoking and receiving a Pap test. Black women in urban areas are most likely to be smokers. Almost no difference exists between white women in urban and rural areas concerning their likelihood of receiving a Pap test, we find that black women in urban areas are much more likely to be screened for cervical cancer than black women in rural areas.


Optimal solution of linear inequalities with applications to pattern recognition.
An algorithm for the optimal solution of consistent and inconsistent linear inequalities is presented, where the optimality criterion is the maximization of the number of constraints satisfied. In the terminology of pattern recognition, the algorithm finds a linear decision function which minimizes the number of patterns misclassified. The algorithm is developed as a nonenumerative search procedure based on several new results established in this paper. Bounds on the search are also developed and the method is experimentally evaluated and shown to be computationally superior to other techniques for finding minimum-error solutions.


Narrative verdicts and their impact on mortality statistics in England and Wales.
Annually, there are around 30,000 coroner's inquests held in England and Wales that conclude with a verdict. 'Short form' verdicts such as accident or misadventure; natural causes; suicide; and homicide make up the majority of all verdict conclusions. 'Narrative' verdicts can be used by a coroner or jury, instead of a short form verdict, to express their conclusions as to the cause of death following an inquest. Since 2001 narrative verdicts have been more widely used, with over 3,000 narrative verdicts returned in 2009. In some cases, it can be difficult to code the underlying cause of death from the information provided in the narrative. For some time, the Office for National Statistics (ONS) and other organisations have been concerned about the impact of narrative verdicts on the quality of the statistics on cause of death. Our research investigated the impact of narrative verdicts on trends for deaths attributed to injury and poisoning in England and Wales. The research considered narrative verdicts received by ONS between 2001 and 2009. All available information provided by the coroner from the narrative verdict, together with the underlying cause of death, was used in the analysis. All causes of death where a narrative verdict was returned were investigated. More in-depth analysis of accidental deaths was undertaken, as classification of these deaths by intent is more difficult when the information from the coroner is imprecise. A sensitivity analysis of suicide rates (intentional self-harm and event of undetermined intent) was carried out. This involved using two different scenarios of reclassifying selected proportions of accidental hanging and poisoning deaths, where a narrative verdict was returned, as intentional self-harm. An exercise to measure the consistency of coding cause of death from narrative verdicts was also undertaken. The increasing proportion of narrative verdicts involving injury and poisoning has not significantly affected published mortality rates for suicide (intentional self-harm and injury or poisoning of undetermined intent). However, if the rise in narrative verdicts continues at the same rate, the accurate reporting of injury and poisoning deaths, including suicides, is likely to be affected. The exercise to establish the consistency of coding the cause of death by ONS cause coders showed that the current coding rules were being applied uniformly. The increase in the use of narrative verdicts by coroners has not had a statistically significant impact on published suicide rates in England and Wales and so no revision to these rates is needed. A review of current coding practices and the handling of narrative verdicts will be undertaken by ONS with particular reference to deaths from intentional self-harm. A recommendation has been made to coroners to consider ways of recording narrative verdicts to allow more accurate coding of cause of death. This will ensure that mortality statistics are maintained to the highest standards.List of Tables, 83.


Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.
Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Experimental study of tissue-engineered cartilage allograft with RNAi chondrocytes in vivo.
To determine the effects of RNA interference (RNAi) on chondrocyte proliferation, function, and immunological rejection after allogenic tissue-engineered cartilage transplantation within bone matrix gelatin scaffolds. Seven million rat normal and RNAi chondrocytes were harvested and separately composited with fibrin glue to make the cell suspension, and then transplanted subcutaneously into the back of Sprague Dawley rats after being cultured for 10 days in vitro. Untransplanted animals served as the control group. The allograft and immunological response were examined at 1, 2, 4, 8, and 12 months postoperatively with hematoxylin and eosin histochemical staining, immunohistochemical staining (aggrecan, type II collagen, class I and II major histocompatibility complex), and flow cytometry for peripheral blood cluster of differentiation 4(+) (CD4(+)) and CD8(+) T-cells. There was no infection or death in the rats except one, which died in the first week. Compared to the control group, the RNAi group had fewer eukomonocytes infiltrated, which were only distributed around the graft. The ratio of CD4(+)/CD8(+) T-cells in the RNAi group was significantly lower than the normal one (P<0.05). There were many more positively stained chondrocytes and positively stained areas around the cells in the RNAi group, which were not found in the control group. The aggrecanase-1 and aggrecanase-2 RNAi for chondrocytes decreased the immunological rejection effect.


A bias-free, automated planning tool for technique comparison in radiotherapy - application to nasopharyngeal carcinoma treatments.
In this study a novel, user-independent automated planning technique was developed to objectively compare volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma planning, and to determine which technique offers a greater benefit for parotid-sparing and dose escalation strategies. Ten patients were investigated, with a standard prescription of three dose levels to the target volumes (70, 63, and 56 Gy), using a simultaneous integrated boost in 33 fractions. The automated tool was used to investigate three planning strategies with both IMRT and VMAT: clinically acceptable plan creation, parotid dose sparing, and dose escalation. Clinically acceptable plans were achieved for all patients using both techniques. For parotid sparing, automated planning reduced the mean dose to a greater extent using VMAT rather than IMRT (17.0 Gy and 19.6 Gy, respectively, p < 0.01). For dose escalation to the mean of the main clinical target volume, neither VMAT nor IMRT offered a significant benefit over the other. The OAR-limiting prescriptions for VMAT ranged from 84-98 Gy, compared to 76-110 Gy for IMRT. Employing a user-independent planning technique, it was possible to objectively compare VMAT and IMRT for nasopharyngeal carcinoma treatment strategies. VMAT offers a parotid-sparing improvement, but no significant benefit was observed for dose escalation to the primary target.


An Analysis of Patients with DNA Repair Pathway Mutations Treated with a PARP Inhibitor.
Molecular analysis has revealed four subtypes of pancreatic ductal adenocarcinoma (PDAC). One subtype identified for the presence of DNA damage repair deficiency can be targeted therapeutically with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib. We performed a single institution retrospective analysis of treatment response in patients with PDAC treated with olaparib who have DNA damage repair deficiency mutations. Patients with germline or somatic mutations involving the DNA repair pathway were identified and treated with olaparib. The primary objective was to examine the objective response rate (ORR). The secondary objectives were assessing tolerability, overall survival, and change in cancer antigen 19-9. Quantitative texture analysis (QTA) was evaluated from CT scans to explore imaging biomarkers. Thirteen individuals with metastatic PDAC were treated with Olaparib. The ORR to Olaparib was 23%. Median overall survival (OS) was 16.47 months. Four of seven patients with BRCA mutations had an effect on RAD51 binding, with a median OS of 24.60 months. Exploratory analysis of index lesions using QTA revealed correlations between lesion texture and OS (hepatic lesion tumor texture correlation coefficient [CC], 0.683, p = .042) and time on olaparib (primary pancreatic lesion tumor texture CC, 0.778, p = .023). In individuals with metastatic PDAC who have mutations involved in DNA repair, Olaparib may provide clinical benefit. BRCA mutations affecting RAD51 binding domains translated to improved median OS. QTA of individual tumors may allow for additional information that predicts outcomes to treatment with PARP inhibitors. Pursuing germline and somatic DNA sequencing in individuals with pancreatic ductal adenocarcinoma may yield abnormalities in DNA repair pathways. These individuals may receive benefit with poly (ADP-ribose) polymerase (PARP) inhibition. Radiomics and deep sequencing analysis may yet uncover additional information that may predict outcome to treatment with PARP inhibitors.


Solvation dependence of valence electronic states of water diluted in organic solvents probed by soft X-ray spectroscopy.
Knowledge of hydrogen bonds is important in a wide range of scientific fields. However, information on the electronic state of hydrogen bonded molecules in liquids and solutions is still limited. We applied X-ray emission and absorption spectroscopy to observe the electronic state around oxygen of water and investigate the solvent dependence of occupied and unoccupied valence electronic states of water in acetonitrile, 3-methylpyridine, and ethylenediamine at room temperature under atmospheric pressure. Based on the direct comparison of the spectra, the pronounced variation of the unoccupied 2b2 state of water in acetonitrile and 3-methylpyridine was assigned to the difference of the dipole-dipole interaction and the donor hydrogen bond. For ethylenediamine solution, an enhancement of the peak structure in the post-edge region of X-ray absorption spectra and an evident shoulder structure on the higher energy side of the occupied 1b1 state in X-ray emission spectra were observed. Although ethylenediamine has two amino groups that can form the hydrogen bonds as a proton donor, the obtained results indicate that the amino groups of ethylenediamine also act as a proton acceptor in the hydrogen bond between water molecules. A systematic peak intensity variation of the pre-edge peak corresponding to the lowest unoccupied molecular orbital, 4a1, was also found through the comparison of three organic solvents. Since the peak intensity tends to decrease with increasing number of hydrogen bonds, the results can be interpreted by the covalency of hydrogen bonds.


LDL and HDL lipoprotein subfractions in multiple sclerosis patients with decreased insulin sensitivity.
Increased metabolic and cardiovascular morbidity has been reported in multiple sclerosis (MS) patients. Previously, we have found decreased insulin sensitivity and hyperinsulinemia in a group of newly diagnosed MS patients. We hypothesize that these features may be associated with an altered lipid profile and low, intermediate, or high density lipoprotein (LDL, IDL, HDL) subclasses accelerating atherosclerosis and thus contributing to the cardiovascular risk increase in these patients. In a group of 19 newly diagnosed untreated MS patients with previously found hyperinsulinemia and insulin resistance and a matched group of 19 healthy controls, the lipoprotein subclasses profile was determined. Polyacrylamide gel electrophoresis was used to separate and measure the LDL (large LDL and small dense LDL), HDL (large, intermediate and small), and IDL (A, B and C) subclasses with the Lipoprint© System (Quantimetrix Corporation, Redondo Beach, CA, USA). No difference was found either in the conventional lipid or lipoprotein subclasses profile between the MS patients and healthy controls. We found an inverse association between the level of IDL-B with fasting insulin (r=-0.504, p=0.032), the insulin resistance estimated by homeo-static model assessment - insulin resistance (HOMA-IR) (r=-0.498, p=0.035), insulin response expressed as area under the curve (AUC; r=-0.519, p=0.027), and area above the baseline (AAB; r=-0.476, p=0.045) and positive association with insulin sensitivity estimated by insulin sensitivity index (ISI) Matsuda (r=0.470, 0.048) in MS patients, but not in healthy controls suggesting the first signs in lipoprotein subclasses profile change. Our data indicate that changes in lipoprotein profile and subclasses are preceded by insulin resistance and hyperinsulinemia in patients with newly diagnosed MS.


Stress and Blood Pressure in Dementia Caregivers: The Moderator Role of Mindfulness.
Objective: Dementia caregiving has been described as a chronically stressful situation with adverse cardiovascular effects. Psychological resources such as mindfulness may reduce the impact of stress on caregivers' cardiovascular health. The objective of this study was to analyze the moderating effect of trait mindfulness on the relationship between frequency of disruptive behaviors of the care recipient and blood pressure (BP) in dementia caregivers. Method: Participants were 110 dementia family caregivers. Two hierarchical regressions (for systolic and diastolic BP) were conducted to analyze whether mindfulness moderates the relationship between disruptive behaviors and BP after controlling for known predictors of cardiovascular outcomes. Results: A significant moderator effect of mindfulness was found between the frequency of disruptive behaviors and diastolic BP (β = -.195, p < .05). Among those caregivers reporting low levels of mindfulness, the relationship between frequency of disruptive behaviors and diastolic BP was relatively stronger than among those reporting high mindfulness levels. Conclusions: The results suggest that a high level of trait mindfulness may have protective effect on BP when caregivers face high levels of stress. Clinical Implications: Mindfulness seems to be an important variable with potential for buffering the effects of caregiving stressors on caregivers' blood pressure.


Modulating the Mechanical Properties of Supercrystalline Nanocomposite Materials via Solvent-Ligand Interactions.
Supercrystalline nanocomposite materials with micromechanical properties approaching those of nacre or similar structural biomaterials can be produced by self-assembly of organically modified nanoparticles and further strengthened by cross-linking. The strengthening of these nanocomposites is controlled via thermal treatment, which promotes the formation of covalent bonds between interdigitated ligands on the nanoparticle surface. In this work, it is shown how the extent of the mechanical properties enhancement can be controlled by the solvent used during the self-assembly step. We find that the resulting mechanical properties correlate with the Hansen solubility parameters of the solvents and ligands used for the supercrystal assembly: the hardness and elastic modulus decrease as the Hansen solubility parameter of the solvent approaches the Hansen solubility parameter of the ligands that stabilize the nanoparticles. Moreover, it is shown that self-assembled supercrystals that are subsequently uniaxially pressed can deform up to 6 %. The extent of this deformation is also closely related to the solvent used during the self-assembly step. These results indicate that the conformation and arrangement of the organic ligands on the nanoparticle surface not only control the self-assembly itself but also influence the mechanical properties of the resulting supercrystalline material. The Hansen solubility parameters may therefore serve as a tool to predict what solvents and ligands should be used to obtain supercrystalline materials with good mechanical properties.


[Macula structure and function in retinopathy of prematurity].
Macula structure and function were studied in 64 patients with retinopathy of prematurity (RP) stage I-III aged 8-17 years old using optical coherence tomography (OCT) and electroretinography. Absence of foveolar depression associated with preservation of fovea layers and normal electroretinography indices were showed to be the evidence of differentiation damage and macula underdevelopment due to immaturity and to have no effect on visual acuity. Preserved or pathologic foveolar depression associated with abnormal OCT findings and central retina electrogenesis damage indicate dysfunction and morphological changes of macula due to not macula underdevelopment because of immaturity only but RP either that can lead to depression, visual function.


Cytokeratin 7 negative invasive breast carcinoma: clinicopathological and immunohistochemical analysis of 14 cases with clinical follow-up.
Cytokeratin 7 (CK 7) negative breast tumours are reported to occur rarely. We studied 14 CK 7 negative cases of primary invasive ductal carcinoma (IDC) detected during sentinel lymph node metastases work-up and immunohistochemistry panel in the work-up of metastatic carcinoma of unknown origin. Axillary lymph node metastases were present in seven patients (50%). Oestrogen receptor (ER) was strongly positive in all cases: progesterone receptor in 78%, Her-2/neu in 7% and high proliferation index with Ki-67 >20% was seen in 71% of the cases. Metastatic and/or recurrence were found in 8 of 14 patients (57%) with the mean clinical follow-up of 55 months. Metastatic sites include multiple bones, brain, spinal cord, liver, pancreas, ovary, lung, lymph node other than ipsilateral axillary and skin. 12 of 14 patients received adjuvant chemotherapy. All 14 patients received hormonal therapy and radiation therapy. Morphologically, IDC with neuroendocrine features was noted in 57%. Synaptophysin stain was positive in 57% and chromogranin was positive in 21% of the cases. In conclusion, these CK 7 negative breast carcinomas were ER positive, mostly Her-2/neu negative, had high Ki-67 and frequently showed neuroendocrine differentiation. More than half of these cases had a poor outcome.


Ultrasound estimation of foetal gestational age by transcerebellar diameter in healthy pregnant nigerian women.
Ultrasonography has application in advanced obstetric practice through relatively detailed assessment of foetal anatomy and accurate assessment of gestational age (GA), especially during the first half of pregnancy. Foetal trans-cerebellar diameter (TCD) is an emerging parameter for gestational age determination among Africans. This study was carried out to establish baseline data for TCD at various corresponding gestational ages in Nigerian women, and evaluate the correlation between these two parameters. Four hundred and fifty healthy singleton pregnant women, referred for antenatal scans were prospectively studied, following informed consent. Main inclusion criterion was certain last menstrual dates. A SONOACE χ⁶ ultrasound scanner, with a curvilinear probe and 3.5 MHz transducer, was used to measure the TCD. Data analysis was done and statistical significance set at p ≤ 0.05. TCD of the foetuses studied ranged from 11.9 mm (at 13 weeks) to 59.3mm (at 41 weeks) with a mean value 34.2 ± 14.1mm.There was significant correlation between TCD and menstrual gestational age (r =0.984; p=0.000). TCD has a predictive accuracy of 96.9% with a standard error of ± 10 days. A normogram of foetal TCD throughout gestation is established for Nigerian Africans.


Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole.
We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites. Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4 weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays. 649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79% and 70%, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0 pg/mL, 1.562-183.2 pg/mL, respectively). Considering E2, 8.9% had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug. We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.


Predictive power of UKCAT and other pre-admission measures for performance in a medical school in Glasgow: a cohort study.
The UK Clinical Aptitude Test (UKCAT) and its four subtests are currently used by 24 Medical and Dental Schools in the UK for admissions. This longitudinal study examines the predictive validity of UKCAT for final performance in the undergraduate medical degree programme at one Medical School and compares this with the predictive validity of the selection measures available pre-UKCAT. This was a retrospective observational study of one cohort of students, admitted to Glasgow Medical School in 2007. We examined the associations which UKCAT scores, school science grades and pre-admissions interview scores had with performance indicators, particularly final composite scores that determine students' postgraduate training opportunities and overall ranking (Educational Performance Measure - EPM, and Honours and Commendation - H&C). Analyses were conducted both with and without adjustment for potential socio-demographic confounders (gender, age, ethnicity and area deprivation). Despite its predictive value declining as students progress through the course, UKCAT was associated with the final composite scores. In mutually adjusted analyses (also adjusted for socio-demographic confounders), only UKCAT total showed independent relationships with both EPM (p = 0.005) and H&C (p = 0.004), school science achievements predicted EPM (p = 0.009), and pre-admissions interview score predicted neither. UKCAT showed less socio-demographic variation than did TSS. UKCAT has a modest predictive power for overall course performance at the University of Glasgow Medical School over and above that of school science achievements or pre-admission interview score and we conclude that UKCAT is the most useful predictor of final ranking.


Association between oral cleft and transcobalamin 2 polymorphism in a sample study from Nassiriya, Iraq.
Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene (P = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity.


Intelligence Process vs. Content and Academic Performance: A Trip through a House of Mirrors.
The main purpose of modern intelligence tests has been to predict individual differences in academic performance, first of children, then adolescents, and later extending to adults. From the earliest Binet-Simon scales to current times, most one-on-one omnibus intelligence assessments include both process subtests (e.g., memory, reasoning) and content subtests (e.g., vocabulary, information). As somewhat parallel developments, intelligence theorists have argued about the primacy of the process components or the content components reflecting intelligence, with many modern researchers proposing that process constructs like working memory are the fundamental determinant of individual differences in intelligence. To address whether there is an adequate basis for re-configuring intelligence assessments from content or mixed content and process measures to all-process measures, the question to be answered in this paper is whether intellectual process assessments are more or less valid predictors of academic success, in comparison to content measures. A brief review of the history of intelligence assessment is provided with respect to these issues, and a number of problems and limitations of process measures is discussed. In the final analysis, there is insufficient justification for using process-only measures to the exclusion of content measures, and the limited data available point to the idea that content-dominated measures are more highly predictive of academic success than are process measures.


Inorganic nanoparticles engineered to attack bacteria.
Antibiotics were once the golden bullet to constrain infectious bacteria. However, the rapid and continuing emergence of antibiotic resistance (AR) among infectious microbial pathogens has questioned the future utility of antibiotics. This dilemma has recently fueled the marriage of the disparate fields of nanochemistry and antibiotics. Nanoparticles and other types of nanomaterials have been extensively developed for drug delivery to eukaryotic cells. However, bacteria have very different cellular architectures than eukaryotic cells. This review addresses the chemistry of nanoparticle-based antibiotic carriers, and how their technical capabilities are now being re-engineered to attack, kill, but also non-lethally manipulate the physiologies of bacteria. This review also discusses the surface functionalization of inorganic nanoparticles with small ligand molecules, polymers, and charged moieties to achieve drug loading and controllable release.


Molecularly imprinted nanofilms for endotoxin detection using an surface plasmon resonance sensor.
In this study, a simple, fast, sensitive and selective surface plasmon resonance (SPR) sensor was prepared using molecular imprinting method for endotoxin detection. Endotoxin imprinted and non-imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-(L)-histidine methyl ester) based nanofilms were synthesized on the SPR chip surfaces using ultraviolet polymerization. Endotoxin imprinted and non-imprinted SPR sensors were characterized by using contact angle, atomic force microscopy and ellipsometry. After characterization studies, kinetic studies was carried out in the concentration range of 0.5-100 ng/mL. The limit of detection and quantification were obtained as 0.023 and 0.078 ng/mL, respectively. The response time for the equilibration, adsorption and regeneration was approximately 14 min. The selectivity studies with cholesterol and hemoglobin of endotoxin imprinted SPR sensor were examined. Validation studies were carried out via limulus amebocyte lysate (LAL) in order to demonstrate the applicability of the SPR sensor.


Catastrophic flooding origin of shelf valley systems in the English Channel.
Megaflood events involving sudden discharges of exceptionally large volumes of water are rare, but can significantly affect landscape evolution, continental-scale drainage patterns and climate change. It has been proposed that a significant flood event eroded a network of large ancient valleys on the floor of the English Channel-the narrow seaway between England and France. This hypothesis has remained untested through lack of direct evidence, and alternative non-catastrophist ideas have been entertained for valley formation. Here we analyse a new regional bathymetric map of part of the English Channel derived from high-resolution sonar data, which shows the morphology of the valley in unprecedented detail. We observe a large bedrock-floored valley that contains a distinct assemblage of landforms, including streamlined islands and longitudinal erosional grooves, which are indicative of large-scale subaerial erosion by high-magnitude water discharges. Our observations support the megaflood model, in which breaching of a rock dam at the Dover Strait instigated catastrophic drainage of a large pro-glacial lake in the southern North Sea basin. We suggest that megaflooding provides an explanation for the permanent isolation of Britain from mainland Europe during interglacial high-sea-level stands, and consequently for patterns of early human colonisation of Britain together with the large-scale reorganization of palaeodrainage in northwest Europe.


Music, perceived arousal, and intensity: psychophysiological reactions to Chopin's "Tristesse".
The present study investigates the relation of perceived arousal (continuous self-rating), autonomic nervous system activity (heart rate, heart rate variability) and musical characteristics (sound intensity, musical rhythm) upon listening to a complex musical piece. Twenty amateur musicians listened to two performances of Chopin's "Tristesse" with different rhythmic shapes. Besides conventional statistical methods for analyzing psychophysiological reactions (heart rate, respiration rate) and musical variables, semblance analysis was used. Perceived arousal correlated strongly with sound intensity; heart rate showed only a partial response to changes in sound intensity. Larger changes in heart rate were caused by the version with more rhythmic tension. The low-/high-frequency ratio of heart rate variability increased--whereas the high frequency component decreased--during music listening. We conclude that autonomic nervous system activity can be modulated not only by sound intensity but also by the interpreter's use of rhythmic tension. Semblance analysis enables us to track the subtle correlations between musical and physiological variables.


[Gene therapy to cure HIV infection].
To date, the only intervention that has cured HIV infection has been bone marrow transplants from HIV-resistant donors to HIV-infected recipients. This approach has been used to both cure hematological malignancies and HIV infection, but it cannot be widely adopted due to the high risk of mortality associated with cell transplants between individuals. To overcome this limitation, several approaches have been developed to generate HIV resistance using gene therapy in an infected individual's own cells. With the growing arsenal of effective methods to generate HIV-resistant cells, a safe and effective combination gene therapy approach to cure HIV infection is fast approaching. Here, we review several gene therapy-based methods to generate HIV-resistant cells including the expression of antiviral genes, genome editing, and transcriptional gene silencing. Their varied mechanisms, advantages, and disadvantages are discussed, and perspectives are provided for how they may be combined to design an effective gene therapy for HIV.


Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation.
Canonical and noncanonical nuclear factor kappaB (NF-kappaB) signaling are the two basic pathways responsible for the release of NF-kappaB dimers from their inhibitors. Enhanced NF-kappaB signaling leads to inflammatory and proliferative diseases; thus, inhibitory pathways that limit its activity are critical. Whereas multiple negative feedback mechanisms control canonical NF-kappaB signaling, none has been identified for the noncanonical pathway. Here, we describe a mechanism of negative feedback control of noncanonical NF-kappaB signaling that attenuated the stabilization of NF-kappaB-inducing kinase (NIK), the central regulatory kinase of the noncanonical pathway, induced by B cell-activating factor receptor (BAFF-R) and lymphotoxin beta receptor (LTbetaR). Inhibitor of kappaB (IkappaB) kinase alpha (IKKalpha) was previously thought to lie downstream of NIK in the noncanonical NF-kappaB pathway; we showed that phosphorylation of NIK by IKKalpha destabilized NIK. In the absence of IKKalpha-mediated negative feedback, the abundance of NIK increased after receptor ligation. A form of NIK with mutations in the IKKalpha-targeted serine residues was more stable than wild-type NIK and resulted in increased noncanonical NF-kappaB signaling. Thus, in addition to the regulation of the basal abundance of NIK in unstimulated cells by a complex containing tumor necrosis factor receptor-associated factor (TRAF) and cellular inhibitor of apoptosis (cIAP) proteins, IKKalpha-dependent destabilization of NIK prevents the uncontrolled activity of the noncanonical NF-kappaB pathway after receptor ligation.


[Kidney ultrastructure in experimental lithiasis and nephrocalcinosis].
An experimental electron-microscopic study of the kidneys was carried out in experimental oxamide nephrolithiasis in rabbits and hypervitaminosis D in rats. The most pronounced changes were revealed in the proximal and the distal convoluted tubules. It is suggested that cytosomes and lysosome-like bodies possibly participated in stone formation and nephrocalcinosis. It is supposed that they played an important role in the morphogenesis of nephrolithiasis man.


Ethical quandaries in spiritual healing and herbal medicine: a critical analysis of the morality of traditional medicine advertising in southern African urban societies.
This paper critically examines the morality of advertising by practitioners in spiritual healing and herbal medicine heretofore referred to as traditional medicine, in southern African urban societies. While the subject of traditional medicine has been heavily contested in medical studies in the last few decades, the monumental studies on the subject have emphasised the place of traditional medicine in basic health services. Insignificant attention has been devoted to examine the ethical problems associated with traditional medicine advertising. Critical look at the worthiness of some advertising strategies used by practitioners in traditional medicine in launching their products and services on market thus has been largely ignored. Yet, though advertising is key to helping traditional medicine practitioners' products and services known by prospective customers, this research registers a number of morally negative effects that seem to outweigh the merits that the activity brings to prospective customers. The paper adopts southern African urban societies, and in particular Mozambique, South Africa and Zimbabwe as particular references. The choice of the trio is not accidental, but based on the fact that these countries have in the last few decades been flooded with traditional medicine practitioners/traditional healers from within the continent and from abroad. Most of these practitioners use immoral advertising strategies in communicating to the public the products and services they offer. It is against this background that this paper examines the morality of advertising strategies deployed by practitioners in launching their products and services. To examine the moral worthiness of the advertising strategies used by traditional medical practitioners, I used qualitative analysis of street adverts as well as electronic and print media. From the results obtained through thematic content analysis, the paper concludes that most of the practitioners in traditional medicine lack both business and medical ethics. That said, the paper urges practitioners to seriously consider the morality of their adverts as in most cases they (adverts) do more harm than good. Further to that, the piece recommends the governments of the affected countries to put in place stringent measures to address this mounting problem.


Butyl Benzyl Phthalate Promotes Adipogenesis in 3T3-L1 Cells via the miRNA-34a-5p Signaling Pathway in the Absence of Exogenous Adipogenic Stimuli.
Phthalates, a plasticizer group, are used extensively in many of the products we use every day. Public health concerns are growing as recent studies have implicated butyl benzyl phthalate (BBP) as an obesogen. However, BBP-induced epigenetic regulation during adipogenesis is still unknown. We investigated if BBP altered miR-34a-5p, a key miRNA involved in obesity, and regulated its downstream pathway. Differentiating 3T3-L1 cells were exposed to various doses of BBP without exogenous adipogenic stimuli, tested for adipogenesis markers (PPARγ and aP2), and stained for lipid accumulation with Oil Red O staining. We then measured the expression of miR-34a-5p and its target genes, Nampt and Sirt1, along with another significant epigenetic modulator, Sirt3. Furthermore, using antagomiR, we examined whether miR-34a-5p knockdown decreased adipogenesis. BBP exposure resulted in augmented expression levels of miR-34a-5p with an associated increase in adipogenesis. BBP significantly decreased the Nampt, Sirt1, and Sirt3 gene expression levels. However, a decrease in the protein expression was observed only for Nampt, indicating that miR-34a-5p under BBP exposure may regulate Sirt1/Sirt3 only at the transcriptional level. Interestingly, in the presence of BBP, knockdown of miR-34a-5p decreased adipogenesis in the differentiating 3T3-L1 cells. Furthermore, miR-34a-5p knockdown increased the Nampt protein expression levels as well as NAD+ levels, indicating that miR-34a-5p regulates Nampt during BBP exposure. Additionally, the NAD+-dependent sirtuin activity decreased in BBP-treated cells and increased in miR-34a-5p knockdown cells with BBP treatment. BBP exposure demonstrated the involvement of epigenetic regulation by altering the expression patterns of miR-34a-5p and its target Nampt, which may perturb the energy homeostasis of the differentiating adipocytes by altering NAD+ levels and sirtuin activity, resulting in increased adipogenesis.


Effects of estradiol-17beta and progesterone on mating behavior in female lesser bushbabies (Galago moholi) in captivity.
The effects of ovariectomy, estradiol-17beta, and progesterone on female sexuality were investigated in a prosimian primate, the lesser bushbaby (Galago moholi). Each of eight ovariectomized, adult bushbabies was pair-tested with a male partner in the absence of hormone treatment, during estradiol-17beta (E2) treatment (3.125 microg/0.1 ml), and during E2 + progesterone (0.125 mg/0.1 ml) treatment. Pretreatment females were sexually nonreceptive and nonattractive toward the males. In contrast, E2 treatment elicited vaginal opening, partial or complete epithelial cell cornification, and female receptivity in all females and elicited the complete mating repertoire in seven pairs. Progesterone treatment opposed the facilitatory effects of E2 by inhibiting female receptivity and epithelial cell cornification and inducing vaginal closure. Behaviors were quantified following changes in hormone treatment, vaginal physiology, and the presence or absence of intromission. Female attractiveness (male sexual arousal) was initiated during vaginal swelling and was maintained for the duration of vaginal opening, while female receptivity was manifested exclusively during the period of vaginal opening. Female proceptive behavior was mainly associated with the period of receptivity. This study provided evidence of a strict hormonal regulation of both behavioral and nonbehavioral aspects of female sexuality in a prosimian.


Digital Health Interventions for Cardiac Rehabilitation: Systematic Literature Review.
Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite strong evidence supporting the benefits of cardiac rehabilitation (CR), over 80% of eligible patients do not participate in CR. Digital health technologies (ie, the delivery of care using the internet, wearable devices, and mobile apps) have the potential to address the challenges associated with traditional facility-based CR programs, but little is known about the comprehensiveness of these interventions to serve as digital approaches to CR. Overall, there is a lack of a systematic evaluation of the current literature on digital interventions for CR. The objective of this systematic literature review is to provide an in-depth analysis of the potential of digital health technologies to address the challenges associated with traditional CR. Through this review, we aim to summarize the current literature on digital interventions for CR, identify the key components of CR that have been successfully addressed through digital interventions, and describe the gaps in research that need to be addressed for sustainable and scalable digital CR interventions. Our strategy for identifying the primary literature pertaining to CR with digital solutions (defined as technology employed to deliver remote care beyond the use of the telephone) included a consultation with an expert in the field of digital CR and searches of the PubMed (MEDLINE), Embase, CINAHL, and Cochrane databases for original studies published from January 1990 to October 2018. Our search returned 31 eligible studies, of which 22 were randomized controlled trials. The reviewed CR interventions primarily targeted physical activity counseling (31/31, 100%), baseline assessment (30/31, 97%), and exercise training (27/31, 87%). The most commonly used modalities were smartphones or mobile devices (20/31, 65%), web-based portals (18/31, 58%), and email-SMS (11/31, 35%). Approximately one-third of the studies addressed the CR core components of nutrition counseling, psychological management, and weight management. In contrast, less than a third of the studies addressed other CR core components, including the management of lipids, diabetes, smoking cessation, and blood pressure. Digital technologies have the potential to increase access and participation in CR by mitigating the challenges associated with traditional, facility-based CR. However, previously evaluated interventions primarily focused on physical activity counseling and exercise training. Thus, further research is required with more comprehensive CR interventions and long-term follow-up to understand the clinical impact of digital interventions.


Transabdominal off-pump coronary artery bypass grafting using the right gastroepiploic artery.
: Anastomosis of the right gastroepiploic artery to vessels of the inferior wall of the heart can be performed using a transabdominal approach without sternotomy and without cardiopulmonary bypass. : From July 1999 to December 2004, 18 patients presenting with only right coronary artery disease were operated on by the transabdominal approach using a pedicled right gastroepiploic artery graft. In 14 patients, it was a redo operation. In all redo patients, a patent graft to the anterior wall was present. Median EuroSCORE was 5 (range 1-13). The right descending posterior artery was grafted in 10 patients, the right coronary artery in 8 patients. : There was no hospital mortality and no conversion to sternotomy. Hospital morbidity consisted only of a right pleural hemothorax and a superficial wound infection. No blood transfusion was necessary in 16 (89%) patients. Hospital stay averaged 6 days.Follow-up is complete and averaged 2 years (range 0.5-5.5 years). There was no late mortality. Seventeen patients (94%) were asymptomatic. One patient who experienced return of angina 1 year after the procedure underwent a percutaneous transluminal coronary angioplasty of the right coronary artery. Thirteen patients underwent a stress test at median follow-up of 14 months without signs of myocardial ischemia. : Off-pump coronary bypass grafting using a right gastroepiploic artery by the transabdominal approach is a safe and effective procedure with a low hospital morbidity and excellent follow-up. In redo operations, this technique excludes the risk of damaging patent grafts to the left coronary system.


Administration of melatonin and related indoles prevents exercise-induced cellular oxidative changes in rats.
In an attempt to define the role of the pineal hormone melatonin and two analogues (5-methoxytryptamine, 5MT, and 6-hydroxymelatonin, 6HM) in limiting oxidative stress, the present study investigated the changes in glutathione, lipid peroxidation, and the activity of the antioxidant enzyme glutathione peroxidase after exercise (swimming for 60 min) with or without treatment with the indolamines mentioned. Lipid peroxidation was measured by estimating tissue levels of malondialdehyde and 4-hydroxyalkenals; the experimental animals in these studies were male Sprague-Dawley rats. In the liver, swimming exercise increased the levels of reduced glutathione (GSH) and also significantly increasing oxidized glutathione (GSSG), while decreasing the GSH/GSSG ratio, an index directly related to oxidative stress. When the animals were treated with melatonin, the concentrations of GSH and GSSG were also increased after swimming; however, no reduction in the GSH/GSSG ratio appeared. In the animals treated with 6HM the changes were the same as in those treated with melatonin. In muscle as well, the concentration of GSH and the GSH/GSSG ratio were decreased following 60 min of swimming. Pretreatment of the rats with melatonin prevented these effects. Pretreatment of the rats with both 5MT and 6HM also prevented the changes. Brain GSH/GSSG ratio was not affected by either exercise or indolamine administration. Swimming enhanced lipid peroxidation in the liver, muscle and brain; however, this was prevented in animals treated with melatonin or 6HM before swimming. Glutathione peroxidase was significantly elevated after exercise in the brain but not in the liver and muscle. It is concluded that swimming imposes a severe oxidative stress and suggests that melatonin and, to a lesser degree, 5MT and 6HM confer protection against the oxidative damage associated with swimming for 60 min. This mechanism may be reasonably attributed to their indole structure, which possibly allows these molecules to act as free-radical scavengers.


Long-range three-dimensional active imaging with superresolution depth mapping.
We present a technique to overcome the depth resolution limitation for 3D active imaging. Applying microsecond laser pulses and sensor gate width, a scene of several hundred meters is illuminated and recorded in a single image. The trapezoid-shaped range intensity profile is analyzed to obtain both the reflectivity and the depth of scene. We demonstrate a 3D scene reconstruction in a depth of 650 to 1550 m from only three images with an accuracy of <30 m. This depth accuracy is 10 times better than estimated from the classical resolution limit obtained for depth scanning active imaging with a similar number of images. Therefore, this technique enables superresolution depth mapping with a reduction of image data processing.


The development and evaluation of content validity of the Zambia Spina Bifida Functional Measure: Preliminary studies.
Very little is known on outcome measures for children with spina bifida (SB) in Zambia. If rehabilitation professionals managing children with SB in Zambia and other parts of sub-Saharan Africa are to instigate measuring outcomes routinely, a tool has to be made available. The main objective of this study was to develop an appropriate and culturally sensitive instrument for evaluating the impact of the interventions on children with SB in Zambia. A mixed design method was used for the study. Domains were identified retrospectively and confirmation was done through a systematic review study. Items were generated through semi-structured interviews and focus group discussions. Qualitative data were downloaded, translated into English, transcribed verbatim and presented. These were then placed into categories of the main domains of care deductively through the process of manifest content analysis. Descriptive statistics, alpha coefficient and index of content validity were calculated using SPSS. Self-care, mobility and social function were identified as main domains, while participation and communication were sub-domains. A total of 100 statements were generated and 78 items were selected deductively. An alpha coefficient of 0.98 was computed and experts judged the items. The new functional measure with an acceptable level of content validity titled Zambia Spina Bifida Functional Measure (ZSBFM) was developed. It was designed to evaluate effectiveness of interventions given to children with SB from the age of 6 months to 5 years. Psychometric properties of reliability and construct validity were tested and are reported in another study.


Antibody levels in adult patients with coeliac disease during gluten-free diet: a rapid initial decrease of clinical importance.
Analysis of antibodies against tissue transglutaminase (tTG) has been shown valuable in the diagnosis of coeliac disease (CD) but how quickly serum titres decrease after introduction of a gluten-free diet (GFD) is not known in adults. CD is a well-recognized disorder amongst the general population and many persons try a GFD for fairly vague symptoms before they seek medical advice. Therefore, it is important to determine the time that the serologic tests remain predictive of the disease after the introduction of a GFD. Sera were taken from 22 consecutively biopsy-proven adult patients with CD in connection with the diagnostic biopsy. The patients were followed for 1 year and sera were taken after 1, 3, 6 and 12 months after start of a GFD. Sera were stored at -20 degrees C and analysed for IgA antibodies against gliadin, endomysium and two different commercial tTG assays based on recombinant human tTG (tTGrh) and guinea-pig liver (tTGgp). Twenty patients could be followed during GFD and all antibody titres fell sharply within 1 month after introduction of a GFD and continued to decline during the survey interval. Thirty days after beginning the diet only 58, 84, 74 and 53% of all patients had positive antibody levels of tTGrh, tTGgp, EmA and AGA respectively. As the antibodies used to confirm the diagnosis of CD fall rapidly and continue to decline following the introduction of a GFD, it is important that health care providers carefully inquire about the possibility of self-prescribed diets before patients sought medical attention.


Genetic markers and biochemical evaluation in the winter triticale identification and breeding.
Winter hexaploid triticale lines and cultivars were identified by protein (storage and enzyme) and DNA markers. The locus of B-Amy-2 and Adh-1 were characterized by two alleles, Mdh-1 by 3 alleles, B-Amy-1 and Mdh-2 by 4 alleles and the locus controlling cathodic peroxidase isozymes, a-amylase and esterase by 6, 9 and 12 alleles, respectively. Intra-and intervarietal variation, for the enzyme coding loci, gliadin and glutenine were found. According to the isoenzyme analysis and the grain quality lines 28 and 49 (softness, high amylose content: 28.9-25.6, protein: 11,6- 11,2% and albumin 50-43%) could be marked as genotypes suitable for brewing and were characterized by allele b-Amy-1-b. Genotypes 1420 and 1434 are good for bread making with a hardness index between 52 and 62 and a W value (alveograph) of 110- 120. Allele a-Amy-b is positively correlated with amylose content (r = 0.601) and negatively with protein content (r - 0.490), the correlation of the presence of allele 1-Amy-1-b and amylose content is r- 0.549. Three breeding lines had 40% amylose content in grain and flour. Furthermore, the presence of allele Mdh-1 was associated with a high content of glutenin (r = 0.568), and controlled by genes localized in a single linkage group. Also statistically significant correlations for Mdh-1 -a and Prx-D containing albumin to total protein (%) could observed. It was illustrated that the peroxidase activity and free proline content can be used as resistance markers to abiotic factors.


Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb.
Cholinergic axons and nicotinic receptors are abundant in all layers of the olfactory bulb (OB), the main region of newborn neuron integration in the adult brain. Here, we report that the OB granule cell layer in mice lacking the predominant form of brain high-affinity nicotinic acetylcholine receptors (beta(2)(-/-) mice) displayed nearly 50% more newborn neurons and significantly fewer apoptotic cells than did beta(2)(+/+) mice. Conversely, in vivo chronic nicotine exposure significantly decreased the number of newborn granule cells in beta(2)(+/+) but not beta(2)(-/-) adult mice, confirming that the survival of newborn neurons can be controlled by the activation of beta(2)-containing nicotinic acetylcholine receptors. Unexpectedly, investigating the behavioral consequence of an increased number of granule cells in beta(2)(-/-) mice revealed that these animals have a less robust short-term olfactory memory than their wild-type counterparts. Taken together, these results provide evidence that high-affinity nicotinic receptors are involved in the maturation of adult OB local circuits. They also indicate that an increase in the number of granule cells does not necessarily correlate with better olfactory performance and further highlight the importance of cholinergic afferents for olfactory processing.


[TCOF1 Gene variation in Treacher Collins syndrome and evaluation of speech rehabilitation after bone bridge surgery].
Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome(TCS), the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG(p. A451Gfs*43) and c. 4362_4366del(p. K1457Efs*12), resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance(CAP) score was 6, and the Speech Intelligibility Rating(SIR) score was 4. Assessment using the Meaningful Auditory Integration Scale(MAIS) showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.


Outcomes of Bleb Repair for Delayed Bleb Leaks and Sweating Blebs.
To report the outcomes of bleb repair for delayed onset leaking blebs and sweating blebs following glaucoma filtering surgery. Medical records of 76 eyes of 76 subjects that underwent bleb repair for either leaking bleb or sweating bleb between 1990 and 2015 were reviewed. Complete success was resolution of bleb leak and or hypotony with intraocular pressure ≥5 and ≤21 mm Hg with no antiglaucoma medication. There were 45 eyes with leaking bleb and 31 eyes with sweating bleb that underwent bleb repair by either conjunctival autograft or conjunctival advancement (P=0.11). Before bleb repair, complications like blebitis and hypotony maculopathy were significantly higher in sweating bleb group (13/31) compared with bleb leak group (5/45) (P=0.002). Median follow-up after bleb repair was >2 years in both groups (P=0.69). After repair, eyes in leaking bleb group had higher immediate (P=0.01) and long-term intraocular pressure elevation (P=0.06) compared with sweating bleb group. Complete success probability in sweating bleb group was significantly better (88%, 78%, and 71%) compared with leaking bleb group (54%, 45%, and 40%) at 1, 3, and 6 years, respectively (P=0.01). One eye in each group had blebitis, 2 eyes in leaking bleb group and 1 eye in sweating bleb group needed repeat glaucoma intervention. Higher complication rate before bleb repair in eyes with sweating bleb warrants early bleb repair. Bleb repair helped retain bleb function in majority of the eyes with sweating blebs, strengthening our recommendation.


Using Focus Groups to Explore Evolving Perceptions of Student Pharmacists' Curricular Experiences.
Objective. To explore student pharmacists' shared experiences as they transitioned through the first three years of a Doctor of Pharmacy curriculum, from dependent learners to autonomous contributors. Methods. The researchers used interpretive phenomenology to examine the lived experiences of student pharmacists. Previously gathered focus group data for 309 student pharmacists from the 2015-2016 academic year were explored. A step-wise approach to data analysis was used to perpetuate the natural emergence of themes and alignment with theory. Utilizing Arthur Chickering's Seven Vectors of Identity Development as a lens, the researchers analyzed findings related to self-realization and identification of purpose. Results. The research team identified several themes associated with the teaching and learning process: professionalism, autonomy, and managing the expectations of the curriculum. A connection between the researchers' findings and Chickering's seven vectors was seen as students' comments demonstrated their progress along the vectors over three academic years. Conclusion. This exploration provided a glimpse into the lived experiences of student pharmacists at three different stages in their journey from dependent learners to autonomous contributors. By comparing students in one year with those in the next, the researchers were able to see the evolution that occurred over time as students became self-authored individuals, which is the ideal outcome for pharmacy graduates.