Fasciola hepatica: a study of the shedding of cercariae from Lymnaea truncatula raised under constant conditions of temperature and photoperiod.
Investigations on the shedding of cercariae of Fasciola hepatica were carried out in Lymnaea truncatula in order to verify the existence of a low-frequency periodicity in the numerical distribution of metacercariae per snail and per day when the snails are raised under controlled conditions. Preadult L. truncatula were thus collected in the field, individually exposed to two miracidia, and subsequently raised until their death under constant temperature (20 degrees C) and photoperiod (12 h/12 h diurnal rhythm). The 102 snails shedding parasites produced 24,325 metacercariae of which 5% were floating cysts. The daily production of cercariae was maximal during the first 30 days of the patent period, subsequently decreased until day 114, and ceased on day 124. No infradian-type rhythm was noted in the daily distribution of mean values. The snails shed their cercariae in one to 14 waves; 20.6% and 15.7% of the snails produced their parasites in four and five periods respectively. The authors suggest that the seven-day periodicity found by Audousset et al. (1989) in the daily distribution of cercariae produced by three colonies of L. truncatula raised in seminatural conditions must be attributed only to the influence of environmental factors.


Detection of Leishmania infantum kinetoplast DNA in laryngeal tissue from an immunocompetent patient.
Mucosal leishmaniasis of the upper respiratory tract is usually associated with the visceral form or is found in immunosuppressed individuals. This report presents a case of isolated mucosal leishmaniasis in an immunocompetent patient, whose diagnosis mainly rested on histology and positive polymerase chain reaction result for Leishmania donovani in the laryngeal tissue. A 59-year-old man, who never lived outside Italy, showed a subglottic mucosal polypoid-like lesion. The typical morphological picture and positive polymerase chain reaction result for L donovani by DNA extracted from laryngeal biopsy specimens allowed the diagnosis of mucosal leishmaniasis. Specific amphotericin B therapy was started, resulting in clinical and endoscopic improvement. Increased knowledge about the histological and molecular tissue analysis of Leishmania enhances the diagnostic testing for mucosal leishmaniasis, as primary mucosal leishmaniasis may occur in both immunosuppresed and immunocompetent patients who travel to or reside in areas endemic for Leishmania.


Treatment of Prolapsing Hemorrhoids in HIV-Infected Patients with Tissue-Selecting Technique.
The aim of this retrospective study was to evaluate the outcome of a tissue-selecting therapy stapler (TST) for prolapsing hemorrhoids in HIV-infected patients. Sixty-two patients with stage III-IV hemorrhoidal prolapse were treated with TST by a single surgeon between June and November 2014. The TST group comprised 32 patients (4 females), and the TST + HIV group comprised 30 HIV-infected patients (3 females). Age, gender, and preoperative examination as well as intraoperative and postoperative features were assessed. There was no marked difference in hemorrhoidal prolapse between the TST and HIV + TST groups, except for patient satisfaction at 12 months. TST is an effective and safe technique for treatment of prolapsing hemorrhoids in HIV-infected patients.


Fetal origin of endocrine dysfunction in the adult: the phthalate model.
Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer with endocrine disrupting properties that is found ubiquitously in the environment as well as in human amniotic fluid, umbilical cord blood, human milk, semen, and saliva. It is used in the industry to add flexibility to polyvinyl chloride-derived plastics and its wide spread use and presence has resulted in constant human exposure through fetal development and postnatal life. Epidemiological studies have suggested an association between phthalate exposures and human reproductive effects in infant and adult populations. The effects of fetal exposure to phthalates on the male reproductive system were unequivocally shown on animal models, principally rodents, in which short term deleterious reproductive effects are well established. By contrast, information on the long term effects of DEHP in utero exposure on gonadal function are scarce, while its potential effects on other organs are just starting to emerge. The present review focuses on these novel findings, which suggest that DEHP exerts more complex and broader disruptive effects on the endocrine system and metabolism than previously thought. This article is part of a Special Issue entitled "CSR 2013".


Presence of B. thailandensis and B. thailandensis expressing B. pseudomallei-like capsular polysaccharide in Thailand, and their associations with serological response to B. pseudomallei.
Burkholderia pseudomallei is an environmental Gram-negative bacillus and the cause of melioidosis. B. thailandensis, some strains of which express a B. pseudomallei-like capsular polysaccharide (BTCV), is also commonly found in the environment in Southeast Asia but is considered non-pathogenic. The aim of the study was to determine the distribution of B. thailandensis and its capsular variant in Thailand and investigate whether its presence is associated with a serological response to B. pseudomallei. We evaluated the presence of B. pseudomallei and B. thailandensis in 61 rice fields in Northeast (n = 21), East (n = 19) and Central (n = 21) Thailand. We found BTCV in rice fields in East and Central but not Northeast Thailand. Fourteen fields were culture positive for B. pseudomallei alone, 8 for B. thailandensis alone, 11 for both B. pseudomallei and B. thailandensis, 6 for both B. thailandensis and BTCV, and 5 for B. pseudomallei, B. thailandensis and BTCV. Serological testing using the indirect hemagglutination assay (IHA) of 96 farmers who worked in the study fields demonstrated that farmers who worked in B. pseudomallei-positive fields had higher IHA titers than those who worked in B. pseudomallei-negative fields (median 1:40 [range: <1:10-1:640] vs. <1:10 [range: <1:10-1:320], p = 0.002). In a multivariable ordered logistic regression model, IHA titers were significantly associated with the presence of B. pseudomallei (aOR = 3.7; 95% CI 1.8-7.8, p = 0.001) but were not associated with presence of B. thailandensis (p = 0.32) or BTCV (p = 0.32). One sequence type (696) was identified for the 27 BTCV isolates tested. This is the first report of BTCV in Thailand. The presence of B. pseudomallei and B. thailandensis in the same field was not uncommon. Our findings suggest that IHA positivity of healthy rice farmers in Thailand is associated with the presence of B. pseudomallei in rice fields rather than B. thailandensis or BTCV.


Sensory processing, participation, and recovery in adults with serious mental illnesses.
People with serious mental illnesses (SMI) have different sensory processing patterns compared to the general population. The purpose of the study was to examine the relationship between different sensory processing patterns and community participation and recovery-oriented outcomes to inform the development of innovative rehabilitation interventions, including those resulting in more accommodating environments. A quasi-experimental, comparative research design was conducted by using data obtained from 95 adults with SMI who received public mental health services. Participants completed a sensory processing profile and measures of community participation, recovery, and quality of life. Comparisons were made between sensory profile categories for each dependent variable using multivariate analyses of variance. The category with more evidence of self-reported low registration and sensory sensitivity than most reported less participation and lower levels of recovery than did their peers with processing patterns in typical ranges. The category with more self-reported sensory sensitivity than most reported lower quality of life. Finally, the category in the "similar" to "more than most" range on self-reported sensory seeking had higher levels of participation and recovery. Assessment of sensory processing patterns in adults with SMI can inform sensory-based interventions that might result in greater community participation and other recovery outcomes. Interventions can include those that seek to enhance person-environment fit by altering the environment, as well as interventions that enhance adaptive sensory responses to external stimuli.


Transcriptome profiling of the nonlactating mammary glands of dairy goats reveals the molecular genetic mechanism of mammary cell remodeling.
The mammary gland redevelops to the prepregnancy state during involution, which shows the mammary cells have the characteristics of remodeling. The rapidity and degree of mammary gland involution vary across species (e.g., between model organism mice and dairy livestock). However, the molecular genetic mechanism of involution and remodeling of goat mammary gland has not yet been clarified. This work investigated the structural changes and transcriptome characteristics of the mammary gland tissue of nonlactating dairy goats during the late lactation (LL), the dry period (DP), and late gestation (LG). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed significant changes in the structure of the nonlactating goat mammary gland, and obvious cell apoptosis occurred at LL and DP. Sequencing identified 1,381 genes that are differentially expressed in mammary gland tissue at the 3 developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism exhibited adaptive transcriptional changes to meet the needs of a new set of mammary gland lactation functions. The significant enrichment of Gene Ontology terms such as humoral immune response, complement activation, and neutrophil-mediated immunity indicates that the innate immune system plays an important role in maintaining the health of degenerative mammary glands and eliminating apoptotic cells. The peroxisome proliferator-activated receptor signaling pathway plays an important regulatory role in lipid metabolism, especially the adaptive changes in expression of genes encoded lipid transport and enzymes, which promote the formation of milk fat during the lactation. The mammary gland development gene module revealed that pregnancy hormone receptors, cell growth factors and their receptors, and genes encoding insulin-like growth factor binding proteins regulate the physiological process of mammary gland involution through adaptive transcriptional changes. Interestingly, ERBB4 was identified as the hub gene of the network that regulates mammary gland growth and development. Overexpression of ERBB4 in mammary epithelial cells cultured in vitro can reduce cell cycle arrest in G1/S phase and apoptosis by regulating the PI3K/Akt signaling pathway and promote the proliferation of mammary epithelial cells. The gene ERBB4 also affects the expression of genes that initiate mammary gland involution and promote mammary gland remodeling. These findings contribute to an in-depth understanding of the molecular mechanisms involved in mammary gland involution and remodeling.


Variability in the Application of Eccentric Force Using Different Rotary Inertia Devices May Influence the Treatment of Tendinopathy.
High intraset variability has been considered as a potential aid in the treatment of tendinopathy by producing forces in variable and unpredictable contexts that allow the athlete to return to sport pain free. The aim of this study was to compare the intraset variability in force profiles between different rotational inertia devices (RIDs) during concentric and eccentric (ECC) phases of movement and between different moments of inertia. Thirty-nine men performed a half-squat incremental test on 2 different RIDs: a horizontal cylinder and a vertical cone-shaped axis. Intraset variabilities in vertical force and velocity were analyzed using average coefficients of variation. RID squat exercise produced force intraset variability. The ECC phase of the movement showed more intraset variability in force output than the concentric phase. ECC vertical cone-shaped shaft showed a higher intraset variability in force than ECC horizontal cylinder-shaped shaft. This study demonstrated that using an RID to provide resistance in squat training of athletes produced a high intraset variability in the application of force.


Active imagination and the analysis of film.
The emotions aroused by the pleasure-generating mechanisms of the cinema are usually benign because they refer to a virtual world. Experiencing affects aroused by fictions can resemble being drawn into a rehearsal for a possible, imagined future that just might (but more likely never will) occur in the individual's life in the real world. Movie-goers, no less than the readers of novels, actively engage with the symbols that film makers inscribe in the screen text. In so doing, they take a measure of control over elements of the fiction. Screened fiction has thus the potential to help the individual grow in self-awareness. Shifting its focus to the work of the film critic, the paper argues that, suitably adapted to the requirements of working with a pre-recorded film or tape, Jung's concept of the active imagination helps us to model, license, limit and endorse the subjective element in textual analysis. Because the method proposed makes it possible formally to recognize that the interpretation of fiction is inevitably integrated with the analyst's personality, interpretation is always a matter of a reader bringing a text into being rather than disinterring a pre-existing object.


Surgical center: challenges and strategies for nurses in managerial activities.
Analyze the challenges and strategies of nurses performing managerial activities in a surgical center. Exploratory, descriptive study with a qualitative approach, involving six nurses by means of the Focus Group Technique, between April and August 2013. Data were submitted to thematic content analysis. The main challenges noted were deficiency of material resources, communication noise, adequacy of personnel downsizing, and relationships with the multidisciplinary team. Key strategies include construction of co-management spaces to promote integration among professionals, conflict resolution and exchange of knowledge. Managerial activities involve the promotion of dialogic moments to coordinate the different processes in the surgical center to provide inputs to expand safety and quality of services provided.


Tris[bis(1-methyl-1H-imidazol-2-yl)methanone-kappa2N3]iron(II) dichloride 5.5-hydrate, cis-bis[bis(1-methyl-1H-imidazol-2-yl)methanone-kappa2N3]dichloroiron(II) (ca 153 K) and di-mu-chloro-bis[[bis(1-methyl-1H-imidazol-2-yl)methanone-kappa2N3]chloroiron(II)] methanol disolvate (ca 300 K).
The first of the title compounds, [Fe(C9H10N4O)3]Cl2.5.5H2O, is the first structurally characterized homoleptic tris[bis(imidazol-2-yl) ketone]-metal complex to be structurally defined. In the second of the title compounds, [FeCl2(C9H10N4O)2], a pair of monodentate donors supplants one of the bidentate ligands. In the third complex, [Fe2Cl4(C9H10N4O)2].2CH3OH, a centrosymmetric binuclear compound with a pair of bridging chloride ligands, the introduction of a third chloro ligand results in five-coordination about each of the metal atoms; the environments of the latter are square pyramidal, with a chloro ligand at the apex and the two bidentate arrays about the base of the pyramid.


Nonfatal maxillocerebral mucormycosis with orbital involvement in a dehydrated infant.
Mucormycosis in infants is exceedingly rare, and over 90% of reported cases have been fatal. A case of a dehydrated three-week-old infant with involvement of the palate, maxilla, orbit, and brain is described with extensive laboratory and radiological investigation. This infant survived after surgical debridement and therapy with amphotericin B.


A comprehensive insight into the potential roles of VDR gene polymorphism in obesity: a systematic review.
Vitamin D receptor (VDR) gene polymorphisms are believed to be involved in the obesity pathogenesis. This study summarises the results of research concerning the association between VDR polymorphisms and obesity. For this survey, the records of common databases were searched until November 2019. Four loci of the VDR gene in four case-controlled and 22 cross-sectional studies were assessed and evaluated. In the case-control studies, no significant association was observed between ApaI and FokI polymorphism with obesity risk. TaqI "T" allele in two studies was related to a higher risk of obesity. One investigation found no relationship between BsmI and obesity, while another article suggested that the "b" allele is more frequently found in obese subjects. The results of cross-sectional studies did not lead to consistent findings. Although the previous studies failed to arrive at conclusive findings, the effects of VDR polymorphism on obesity development cannot be ignored.


Blocking CD226 Promotes Allogeneic Transplant Immune Tolerance and Improves Skin Graft Survival by Increasing the Frequency of Regulatory T Cells in a Murine Model.
Regulatory T cells (Tregs) play key roles in maintaining peripheral tolerance and preventing autoimmune disease. Treg modulation could be helpful in treating malignancies, autoimmune disease, and allergies, as well as to facilitate organ transplantation. Signals transduced by co-stimulatory molecules are essential for Treg differentiation, homeostasis, and function. One well-known active receptor, CD226, also known as DNAM-1 or PTA1, is an adhesion molecule that interacts primarily with CD155 and is involved in Treg differentiation and immune tolerance to transplanted tissue. Anti-CD226 monoclonal antibody (mAb) and truncated recombinant CD226 proteins were employed to manipulate the CD226 signal. Various T cell markers on freshly isolated splenocytes and T lymphocytes were characterized by flow cytometry Cell proliferation was measured by carboxyfluorescein succinimidyl ester dye, mRNA transcripts by q-RT PCR, and protein expression by western blotting. A BALB/c-to-C57BL/6 skin allograft model was used to determine the effects of CD226 blocking treatment. We observed that both intact extracellular domains of CD226 were necessary for functional interaction of the receptor with its ligand CD155, even though one domain was shown to bind CD155 with lower affinity in a solid binding assay. Importantly, CD226 mAb promoted Treg expansion in a mixed lymphocyte culture and inhibited the cytotoxicity of effector cells. In allogeneic skin transplant mice, administering CD226 mAb reduced inflammation and prolonged allogeneic graft survival, with an increase in the frequency of Tregs. Our results reveal the mechanism underlying CD226-CD155 interactions and indicate that CD226 signals can be manipulated to promote Treg expansion. Moreover, we provide new evidence that suggests the therapeutic potential of anti-CD226 with allogeneic transplantation.


Denaturation of uridine phosphorylase from Escherichia coli K-12 by guanidine hydrochloride.
Denaturation of uridine phosphorylase from Escherichia coli K-12 by guanidine hydrochloride results in red shift of the maximum in the protein fluorescence spectrum, dissociation of the hexameric enzyme molecule into monomers, and the loss of the enzymatic activity. The initial rate of the enzyme reactivation after the dilution of the enzyme preincubated with guanidine hydrochloride has the second order with respect to protein. It is assumed that the rate of the reactivation process is limited by the reassociation of monomers possessing low enzymatic activity to dimers followed by the rapid step of hexamer formation.


Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2.
HTLV-1 and HTLV-2 are highly related complex retroviruses that have been studied intensely for nearly three decades because of their association with neoplasia, neuropathology, and/or their capacity to transform primary human T lymphocytes. The study of HTLV also represents an attractive model that has allowed investigators to dissect the mechanism of various cellular processes, several of which may be critical steps in HTLV-mediated pathogenesis. Both HTLV-1 and HTLV-2 can efficiently immortalize and transform T lymphocytes in cell culture and persist in infected individuals or experimental animals. However, the clinical manifestations of these two viruses differ significantly. HTLV-1 is associated with adult T-cell leukemia (ATL) and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast, HTLV-2 is much less pathogenic with reports of only a few cases of variant hairy cell leukemia and neurological disease associated with infection. The limited number of individuals shown to harbor HTLV-2 in association with specific diseases has, to date, precluded convincing epidemiological demonstration of a definitive etiologic role of HTLV-2 in human disease. Therefore, it has become clear that comparative studies designed to elucidate the mechanisms by which HTLV-1 and HTLV-2 determine distinct outcomes are likely to provide fundamental insights into the initiation of multistep leukemogenesis.


HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis.
We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the x-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg(2+) binding hypothesis, together with the x-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC(90) values of ~250-500 ng/mL against S. aureus, 500 ng/mL against Bacillus anthracis, 4 μg/mL against Listeria monocytogenes and Enterococcus faecium, and 1 μg/mL against Streptococcus pyogenes M1, but very little activity against E. coli (DH5α, K12) or human cell lines.


Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays.
Even though it is currently well-established that α-synuclein aggregation is closely associated with the pathological events in Parkinson's disease (PD) and several other neurodegenerative disorders, collectively called synucleinopathies, the mechanistic link between α-synuclein aggregates and the onset and progression of neurodegeneration in these diseases remain unclear. The process of aggregation initiates from a structurally distorted monomer that gradually oligomerizes to generate a repertoire of fibrillar and oligomeric multimers that deposit within diseased cells in the brain. Total α-synuclein has been proposed as a potential biomarker in PD, but most of the studies do not discriminate between distinct α-synuclein conformers. To correlate protein measurements to disease pathology, we have developed a conformation-specific ELISA method that selectively detects fibrillar and oligomeric forms of α-synuclein without cross-reacting with monomers. We have used this assay to determine the levels of aggregated α-synuclein in human and mouse brain tissue as well as in CSF and CSF-derived exosomes from patients with synucleinopathy and control subjects. Our results verify the ability of the new assay to detect aggregated α-synuclein in complex matrices and support the idea that the levels of these conformers are related to the age of onset in PD patients, while CSF analysis showed that these species exist in low abundance in CSF and CSF-derived exosomes. Future studies will be required to fully assess the diagnostic usefulness of this ELISA in synucleinopathies.


Catalytic homogeneous hydrogenation of compounds containing X --> O semipolar bonds (X = N, S, P) with para-hydrogen as a promising route for preparation of para-water.
The quantum-chemical simulation (DFT, PBE, TZ2p basis set) of the mechanism of catalytic hydrogenation of compounds containing R(n)X --> O semipolar bonds (R(n)X = N(2), Me(2)S, C(5)H(5)N, Ph(3)P) on the Wilkinson catalyst (Ph(3)P)(3)RhCl with para-hydrogen showed that this process proceeds with retention of proton nuclear spin correlation, which enables a principal possibility to synthesize para-H(2)O, i.e. the nuclear spin isomer of water with antiparallel proton spins, using this route.


Nerves and Proliferation of Progenitor Cells in Limb Regeneration.
Nerves, in conjunction with the apical epidermal cap (AEC), play an important role in the proliferation of the mesenchymal progenitor cells comprising the blastema of regenerating urodele amphibian limbs. Reinnervation after amputation requires factors supplied by the forming blastema, and neurotrophic factors must be present at or above a quantitative threshold for mitosis of the blastema cells. The AEC forms independently of nerves, but requires nerves to be maintained. Urodele limb buds are independent of nerves for regeneration, but innervation imposes a regenerative requirement for nerve factors on their cells as they differentiate. There are three main ideas on the functional relationship between nerves, AEC, and blastema cells: (1) nerves and AEC produce factors with different roles in maintaining progenitor status and mitosis; (2) the AEC produces the factors that promote blastema cell mitosis, but requires nerves to express them; (3) blastema cells, nerves, and AEC all produce the same factor(s) that additively attain the required threshold for mitosis.


Associations of Abdominal Obesity and New-Onset Atrial Fibrillation in the General Population.
Higher height and weight are known to be associated with higher risk of atrial fibrillation (AF); however, whether the risk of AF is related to abdominal obesity is unclear. We studied 501 690 adults (mean age: 47.6±14.3 years; 250 664 women [50.0%]) without baseline AF in the National Sample Cohort released by the National Health Insurance Service in Korea. Body mass index (underweight defined as <18.5; normal, 18.5 to <25.0; overweight, 25.0 to <30.0; and obese, ≥30.0) and waist circumference (abdominal obesity defined as ≥90 cm for men and ≥80 cm for women) were evaluated. During a mean follow-up of 3.9±1.3 years, 3443 participants (1432 women [41.6%]) developed AF. In multivariable models adjusted for clinical variables, the AF risk of underweight, overweight, and obese individuals increased by 21% (95% confidence interval, 1.01-1.45, P=0.043), 14% (95% confidence interval, 1.06-1.23, P<0.001), and 52% (95% confidence interval, 1.30-1.78, P<0.001), respectively, compared with those with normal body mass index. AF risk with confounder-adjusted hazards for abdominal obesity was 18% (95% confidence interval, 1.10-1.27, P<0.001). The increased AF risk was present in abdominally obese individuals regardless of body mass index except for the obese group. In subgroup analysis, abdominal obesity by waist circumference conferred increased risk of new-onset AF, particularly in participants without comorbidities. Abdominal obesity is an important, potentially modifiable risk factor for AF in nonobese Asian persons. These data suggest that interventions to decrease abdominal obesity may reduce the population burden of AF.


Effect of Triptolide on retinal ganglion cell survival in an optic nerve crush model.
Optic nerve crush model could be used to investigate the mechanism of neuronal survival and axonal regeneration in central nervous system. Triptolide, a Chinese herb extract with anti-inflammatory and immunosuppressive activities, has shown neuron protective functions in nervous system. In this study, we investigated the changes in retinal ganglion cell survival and axonal regeneration after administration of triptolide in optic nerve crush model. Triptolide treatment tended to promote retinal ganglion cell survival rather than optic nerve regeneration as well as inhibit the expression of tumor necrosis factor-α and activation of nuclear factor-kappa B. These findings suggested that intraperitoneal injection of triptolide may be an effective treatment for optic nerve injury and this effect was attributed at least in part to its anti-inflammatory actions.


Isolation, Amino Acid Sequences, and Plausible Functions of the Galacturonic Acid-Binding Egg Lectin of the Sea Hare Aplysia kurodai.
Egg lectins occur in a variety of animals ranging from mollusks to vertebrates. A few examples of molluscan egg lectins have been reported, including that of the sea hare Aplysia kurodai; however, their biological functions in the egg remain unclarified. We report the isolation, determination of primary structure, and possible functions of A.kurodai lectin (AKL) from the egg mass of A. kurodai. We obtained AKL as an inseparable mixture of isoproteins with a relative molecular mass of approximately 32 kDa by affinity purification. The hemagglutinating activity of AKL against rabbit erythrocytes was inhibited most potently by galacturonic acid and moderately by xylose. Nucleotide sequencing of corresponding cDNA obtained by rapid amplification of cDNA ends (RACE) allowed us to deduce complete amino acid sequences. The mature polypeptides consisted of 218- or 219-amino acids with three repeated domains. The amino acid sequence had similarities to hypothetical proteins of Aplysia spp., or domain DUF3011 of uncharacterized bacterial proteins. AKL is the first member of the DUF3011 family whose function, carbohydrate recognition, was revealed. Treatment of the egg with galacturonic acid, an AKL sugar inhibitor, resulted in deformation of the veliger larvae, suggesting that AKL is involved in organogenesis in the developmental stage of A. kurodai.


Deciphering the apoptotic pathway: all roads lead to death.
Research into apoptosis is proceeding at such a fast and ferocious pace that anyone who is not completely engrossed in the field has difficulty keeping track of the constant stream of newly identified proteins involved in the process. Apart from being an enticing concept, the process of cell suicide is an important function with wide-reaching implications. Virologists, biologists, immunologists, physiologists and oncologists alike have had to incorporate this phenomenon into their disciplines. The purpose of this article is to provide a solid background on which to further review recent advances in this exciting field. The Bcl-2 and caspase family homologues are discussed in detail and various models are proposed to explain how they function to regulate and execute the death programme. Finally, the importance of programmed cell death with respect to immune function is explored, emphasizing the targets of viral inhibitors of apoptosis.


A Voice Cloning Method Based on the Improved HiFi-GAN Model.
With the aim of adapting a source Text to Speech (TTS) model to synthesize a personal voice by using a few speech samples from the target speaker, voice cloning provides a specific TTS service. Although the Tacotron 2-based multi-speaker TTS system can implement voice cloning by introducing a d-vector into the speaker encoder, the speaker characteristics described by the d-vector cannot allow for the voice information of the entire utterance. This affects the similarity of voice cloning. As a vocoder, WaveNet sacrifices speech generation speed. To balance the relationship between model parameters, inference speed, and voice quality, a voice cloning method based on improved HiFi-GAN has been proposed in this paper. (1) To improve the feature representation ability of the speaker encoder, the x-vector is used as the embedding vector that can characterize the target speaker. (2) To improve the performance of the HiFi-GAN vocoder, the input Mel spectrum is processed by a competitive multiscale convolution strategy. (3) The one-dimensional depth-wise separable convolution is used to replace all standard one-dimensional convolutions, significantly reducing the model parameters and increasing the inference speed. The improved HiFi-GAN model remarkably reduces the number of vocoder model parameters by about 68.58% and boosts the model's inference speed. The inference speed on the GPU and CPU has increased by 11.84% and 30.99%, respectively. Voice quality has also been marginally improved as MOS increased by 0.13 and PESQ increased by 0.11. The improved HiFi-GAN model exhibits outstanding performance and remarkable compatibility in the voice cloning task. Combined with the x-vector embedding, the proposed model achieves the highest score of all the models and test sets.


Multi-state models for event history analysis.
An introduction to event history analysis via multi-state models in given. Examples include the two-state model for survival analysis, the competing risks and illness-death models, and models for bone marrow transplantation. Statistical model specification via transition intensities and likelihood inference is introduced. Consequences of observational patterns are discussed, and a real example concerning mortality and bleeding episodes in a liver cirrhosis trial is discussed.


Cytokine therapy or structured treatment interruptions in HIV infection: which is best?
Continuous highly active antiretroviral therapy (HAART) is the treatment of choice for HIV patients in order to prevent opportunistic infection or AIDS-related morbidity and mortality. However, new HIV treatment strategies are needed to face the emerging problems related to long-term toxicities and failures of HAART. Moreover, total eradication and complete restoration of immune system function cannot be achieved by HAART alone. Therefore, in an attempt to increase the natural immunity of HIV-infected patients, immune-based therapies have been investigated. This review is intended to provide an update on the use of immune-based therapies, in particular structured treatment interruptions and cytokines, such as IL-2 and IFN-alpha, as potential stimulants of the immune system of patients with HIV-infections and to discuss risks and benefits of each alternative. Ongoing and future clinical trials will provide a rationale for their use in clinical practice and will determine how these strategies can be combined to optimise HAART.


Gene alterations and expression spectrum of SPATA33 in nonobstructive azoospermic Iranian men.
Genetic abnormalities have been considered a significant cause of male infertility. Increased expression of SPATA33 during the first wave of spermatogenesis indicates its possible association with the meiotic process. The aim of the current study was to investigate the genetic variations in the SPATA33 gene and its expression in patients with nonobstructive azoospermia (NOA). A total of 100 Iranian NOA men with idiopathic infertility were taken as the case group. The control group comprised 100 fertile men who had at least one child. The presence of nucleotide variations was analyzed in both groups using the standard polymerase chain reaction (PCR) sequencing technique. For mRNA and protein expression studies, testicular biopsy specimens from 27 patients were subdivided into three groups: nine obstructive azoospermic patients with hypospermatogenesis as control; nine maturation arrest (MA) and nine Sertoli cell-only syndromes (SCOS) as case groups. The expression of SPATA33 at both mRNA and protein levels was compared among these three groups using the reverse transcription PCR technique, the realtime-PCR technique, and immunohistochemistry. Mutation analysis of the SPATA33 gene revealed five nucleotide changes among the population studied. All but one showed no significant differences between the groups. The genotype distributions of rs112536073A > T in the transcription factor binding site region with heterozygote and homozygote genotypes were significantly different ( p < 0.05) between the two groups. More heterozygotes of this polymorphism were observed in patients, whereas more homozygotes were detected in controls. Accordingly, the current study illustrated that alterations in SPATA33 gene, at least those found in this study, may not impair spermatogenesis in patients with NOA. Reduction of gene expression at the level of mRNA in patients with SCOS can be interpreted by the absence of germ cells in the testicular tissue of these patients.


MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1.
Despite improvements in therapeutic approaches for head and neck squamous cell carcinomas (HNSCC), clinical outcome has remained disappointing, with 5-year overall survival rates hovering around 40-50%, underscoring an urgent need to better understand the biological bases of this disease. We chose to address this challenge by studying the role of micro-RNAs (miRNAs) in HNSCC. MiR-193b was identified as an over-expressed miRNA from global miRNA profiling studies previously conducted in our lab, and confirmed in HNSCC cell lines. In vitro knockdown of miR-193b in FaDu cancer cells substantially reduced cell proliferation, migration and invasion, along with suppressed tumour formation in vivo. By integrating in silico prediction algorithms with in vitro experimental mRNA profilings, plus mRNA expression data of clinical specimens, neurofibromin 1 (NF1) was identified to be a target of miR-193b. Concordantly, miR-193b knockdown decreased NF1 transcript and protein levels significantly. Luciferase reporter assays confirmed the direct interaction of miR-193b with NF1. Moreover, p-ERK, a downstream target of NF1 was also suppressed after miR-193b knockdown. FaDu cells treated with a p-ERK inhibitor (U0126) phenocopied the reduced cell proliferation, migration and invasion observed with miR-193b knockdown. Finally, HNSCC patients whose tumours expressed high levels of miR-193b experienced a lower disease-free survival compared to patients with low miR-193b expression. Our findings identified miR-193b as a potentially novel prognostic marker in HNSCC that drives tumour progression via down-regulating NF1, in turn leading to activation of ERK, resulting in proliferation, migration, invasion, and tumour formation.


Regulation of Foxe1 by Thyrotropin and Transforming Growth Factor Beta Depends on the Interplay Between Thyroid-Specific, CREB and SMAD Transcription Factors.
Background: Thyroid follicular cells are characterized by the expression of a specific set of genes necessary for the synthesis and secretion of thyroid hormones, which are in turn regulated by the transcription factors Nkx2-1, Pax8, and Foxe1. Thyroid differentiation is finely tuned by the balance between positive regulatory signals, including thyrotropin (TSH), and by negative regulatory signals, such as transforming growth factor beta (TGF-β), which counteracts the action of TSH. A role for Foxe1 as a mediator of hormonal and growth-factor control of thyroid differentiation has been previously suggested. Therefore, the aim of this work was to study the mechanisms governing Foxe1 expression to define the ligands and signals that regulate one of the important factors in thyroid differentiation. Methods: Expression of Foxe1 was evaluated in rat PCCl3 thyroid follicular cells under different treatments. The mouse Foxe1 promoter was cloned, and site-directed mutagenesis was undertaken to study its transcriptional regulation and to identify response elements. Protein/DNA binding assays were performed to evaluate the binding of different transcription factors, and gene-silencing approaches were used to elucidate their functional roles. Results:In silico analysis of the Foxe1 promoter identified binding sites for Nkx2-1, Pax8, Foxe1, and Smad proteins, as well as cAMP-response element (CRE) sites. It was found that both CRE-binding protein and CRE modulator were necessary for the TSH-mediated induction of Foxe1 expression via the cAMP/PKA signaling pathway. Moreover, transcription of Foxe1 was regulated by Nkx2-1 and Pax8 and by itself, suggesting an autoregulatory mechanism of activation and an important role for thyroid transcription factors. Finally, TGF-β, through Smad proteins, inhibited the TSH-induced Foxe1 expression. Conclusions: This study shows that Foxe1 is the final target of TSH/cAMP and TGF-β regulation that mediates expression of thyroid differentiation genes, and provides evidence of an interplay between CRE-binding proteins, thyroid transcription factors, and Smad proteins in its regulation. Thus, Foxe1 plays an important role in the complex transcriptional network that regulates thyroid follicular cell differentiation.


Assessment of selective mRNA translation in mammalian cells by polysome profiling.
Regulation of protein synthesis represents a key control point in cellular response to stress. In particular, discreet RNA regulatory elements were shown to allow to selective translation of specific mRNAs, which typically encode for proteins required for a particular stress response. Identification of these mRNAs, as well as the characterization of regulatory mechanisms responsible for selective translation has been at the forefront of molecular biology for some time. Polysome profiling is a cornerstone method in these studies. The goal of polysome profiling is to capture mRNA translation by immobilizing actively translating ribosomes on different transcripts and separate the resulting polyribosomes by ultracentrifugation on a sucrose gradient, thus allowing for a distinction between highly translated transcripts and poorly translated ones. These can then be further characterized by traditional biochemical and molecular biology methods. Importantly, combining polysome profiling with high throughput genomic approaches allows for a large scale analysis of translational regulation.


Top Ten Tips Palliative Care Clinicians Should Know About Bereavement and Grief.
Palliative care (PC) focuses on caring for the whole person, from birth to death, while managing symptoms and helping to navigate medical complexities. Care does not stop at the time of death, however, as assisting patients, families, and fellow clinicians through grief and bereavement is within PC's purview. Unfortunately, many clinicians feel unprepared to deal with these topics. In this article, PC and hospice clinicians define and explain bereavement, distinguish normative grief from pathological grief, offer psychometrically sound scales to screen and follow those suffering from grief, and discuss the interaction between grief and bereavement and the physical and mental health of those who are left behind after the death of a loved one.


Fowl adenovirus strains 1/A and 11/D isolated from birds with reovirus infection.
Inclusion body hepatitis (IBH) is, in some cases, a fatal disease affecting fowl by adenovirus strains which are subdivided into 5 species (A-E). In the current study, we investigated sequences from the Loop L1 region of the hexon gene of sequences of adenovirus field stains 1/A and 11/D isolated from a poultry flock co-infected with IBH and avian reoviruses ARVs. In early 2021, an epidemiologic survey highlighted the coinfection adenoviruses with other viruses (orthoreovirus infection) as being particularly deleterious within the poultry industry. Here, we investigated the Loop L1 HVR1-4 region of the hexon gene with relative synonymous codon usage (RSCU) designation and RSCU inclusive of all the mutations. These are the first results that have been presented on fowl adenovirus species A and D with simultaneous reovirus infection in 38-days old broiler chickens in Poland.


Molecular targets for AIDS therapy.
The development of antiretroviral therapy against acquired immunodeficiency syndrome (AIDS) has been an intense research effort since the discovery of the causative agent, human immunodeficiency virus (HIV). A large array of drugs and biologic substances can inhibit HIV replication in vitro. Nucleoside analogs--particularly those belonging to the dideoxynucleoside family--can inhibit reverse transcriptase after anabolic phosphorylation. 3'-Azido-2',3'-dideoxythymidine (AZT) was the first such drug tested in individuals with AIDS, and considerable knowledge of structure-activity relations has emerged for this class of drugs. However, virtually every step in the replication of HIV could serve as a target for a new therapeutic intervention. In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV.


Treatment of dyslipidemia in chronic kidney disease.
Dyslipidemia is a common feature of various renal diseases. This perturbed lipid metabolism results in accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Treatment of dyslipidemia, in addition to normalization of blood pressure and reduction of proteinuria, could provide additional means to retard the progression of chronic renal insufficiency. Possible therapeutic approaches include mainly dietary and life-style modifications, selective use of some technical components of dialysis systems, and the judicious prescriptions of lipid-lowering drugs. Even with relatively normal lipid and lipoprotein profiles statin therapy seems to prevent atherogenesis acceleration. A wide range of therapeutic interventions, targeting the lipid abnormalities that may develop in chronic renal patients and end-stage renal disease (ESRD) are currently available, though still without convincing evidence based on long-term prospective studies which clearly demonstrate a significant reduction in cardiovascular morbidity and mortality of ESRD patients. However, extensive investigations, concerning the best long-term therapeutic strategy for this high-risk population of patients, are still missing.


[Renal angiomyolipoma causing inferior vena cava thrombus and secondary Budd-Chiari's syndrome].
We report one case of renal angiomyolipoma with three characteristics: renal sinus origin, inferior vena cava tumor thrombus reaching the right atrium and Budd-Chiari syndrome. The characteristics of the case are presented and discussed. Renal angiomyolipoma is a benign mesenchymal tumor. It is an uncommon tumor (2-6.4% of all kidney tumors), with a female predominance. Angiomyolipoma most often originate from the renal parenchyma but they can rarely originate from the renal sinus. They can involve the renal vein, the inferior vena cava and even the right atrium as a tumor thrombus. Angiomyolipoma commonly present as an incidental finding on radiographic studies, but the clinical presentation varies from flank pain to fatal pulmonary tumor embolism. The Budd-Chiari syndrome is an extremely rare presentation. Because of the risk of potentially fatal cardiopulmonary embolism and death, surgical treatment (radical nephrectomy plus tumor thrombectomy) of these lesions is indicated even when they are asymptomatic.


Liquid chromatography with diode array detection combined with spectral deconvolution for the analysis of some diterpene esters in Arabica coffee brew.
In this manuscript, the separation of kahweol and cafestol esters from Arabica coffee brews was investigated using liquid chromatography with a diode array detector. When detected in conjunction, cafestol, and kahweol esters were eluted together, but, after optimization, the kahweol esters could be selectively detected by setting the wavelength at 290 nm to allow their quantification. Such an approach was not possible for the cafestol esters, and spectral deconvolution was used to obtain deconvoluted chromatograms. In each of those chromatograms, the four esters were baseline separated allowing for the quantification of the eight targeted compounds. Because kahweol esters could be quantified either using the chromatogram obtained by setting the wavelength at 290 nm or using the deconvoluted chromatogram, those compounds were used to compare the analytical performances. Slightly better limits of detection were obtained using the deconvoluted chromatogram. Identical concentrations were found in a real sample with both approaches. The peak areas in the deconvoluted chromatograms were repeatable (intraday repeatability of 0.8%, interday repeatability of 1.0%). This work demonstrates the accuracy of spectral deconvolution when using liquid chromatography to mathematically separate coeluting compounds using the full spectra recorded by a diode array detector.


Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and Purkinje fibers.
We present systematic numerical studies of the possible effects of the coupling of human endocardial and Purkinje cells at cellular and two-dimensional tissue levels. We find that the autorhythmic-activity frequency of the Purkinje cell in a composite decreases with an increase in the coupling strength; this can even eliminate the autorhythmicity. We observe a delay between the beginning of the action potentials of endocardial and Purkinje cells in a composite; such a delay increases as we decrease the diffusive coupling, and eventually a failure of transmission occurs. An increase in the diffusive coupling decreases the slope of the action-potential-duration-restitution curve of an endocardial cell in a composite. By using a minimal model for the Purkinje network, in which we have a two-dimensional, bilayer tissue, with a layer of Purkinje cells on top of a layer of endocardial cells, we can stabilize spiral-wave turbulence; however, for a sparse distribution of Purkinje-ventricular junctions, at which these two layers are coupled, we can also obtain additional focal activity and many complex transient regimes. We also present additional effects resulting from the coupling of Purkinje and endocardial layers and discuss the relation of our results to the studies performed in anatomically accurate models of the Purkinje network.


Can Boosted Randomness Mimic Learning Algorithms of Geometric Nature? Example of a Simple Algorithm That Converges in Probability to Hard-Margin SVM.
In the light of the general question posed in the title, we write down a very simple randomized learning algorithm, based on boosting, that can be seen as a nonstationary Markov random process. Surprisingly, the decision hyperplanes resulting from this algorithm converge in probability to the exact hard-margin solutions of support vector machines (SVMs). This fact is curious because the hard-margin hyperplane is not a statistical solution, but a purely geometric one-driven by margin maximization and strictly dependent on particular locations of some data points that are placed in the contact region of two classes, namely the support vectors. The proposed algorithm detects support vectors probabilistically, without being aware of their geometric definition. We give proofs of the main convergence theorem and several auxiliary lemmas. The analysis sheds new light on the relation between boosting and SVMs and also on the nature of SVM solutions since they can now be regarded equivalently as limits of certain random trajectories. In the experimental part, correctness of the proposed algorithm is verified against known SVM solvers: libsvm, liblinear, and also against optimization packages: cvxopt (Python) and Wolfram Mathematica.


Characterization of the startup transient electrokinetic flow in rectangular channels of arbitrary dimensions, zeta potential distribution, and time-varying pressure gradient.
The solution to the startup transient EOF in an arbitrary rectangular microchannel is derived analytically and validated experimentally. This full 2D transient solution describes the evolution of the flow through five distinct periods until reaching a final steady state. The derived analytical velocity solution is validated experimentally for different channel sizes and aspect ratios under time-varying pressure gradients. The experiments used a time resolved micro particle image velocimetry technique to calculate the startup transient velocity profiles. The measurements captured the effect of time-varying pressure gradient fields derived in the analytical solutions. This is tested by using small reservoirs at both ends of the channel which allowed a time-varying pressure gradient to develop with a time scale on the order of the transient EOF. Results showed that under these common conditions, the effect of the pressure build up in the reservoirs on the temporal development of the transient startup EOF in the channels cannot be neglected. The measurements also captured the analytical predictions for channel walls made of different materials (i.e., zeta potentials). This was tested in channels that had three PDMS and one quartz wall, resulting in a flow with an asymmetric velocity profile due to variations in the zeta potential between the walls.


Saving the aortic and pulmonary artery valves with total heart replacement.
The natural aortic and pulmonary artery valves can be saved with excision of the ventricles and inflow valves. These valves remain functional and unaltered with implantation of an artificial heart, when pumped for 96 and 122 days. The capacity of the artificial heart to meet the physiological needs of the animal, during exercise and body growth, over 3 and 4 mos has been documented. All of the parameters monitored in 2 experiments for 3 mos (and continuing) and 4 mos clearly demonstrates the efficacy of meeting the cardiac needs with an artificial heart.


Managing hazardous pollutants in Chile: arsenic.
Chile is one of the few countries that faces the environmental challenge posed by extensive arsenic pollution, which exists in the northern part of the country. Chile has worked through various options to appropriately address the environmental challenge of arsenic pollution of water and air. Because of cost and other reasons, copying standards used elsewhere in the world was not an option for Chile. Approximately 1.8 million people, representing about 12% of the total population of the country, live in arsenic-contaminated areas. In these regions, air, water, and soil are contaminated with arsenic from both natural and anthropogenic sources. For long periods, water consumed by the population contained arsenic levels that exceeded values recommended by the World Health Organization. Exposure to airborne arsenic also occurred near several large cities, as a consequence of both natural contamination and the intensive mining activity carried out in those areas. In rural areas, indigenous populations, who lack access to treated water, were also exposed to arsenic by consuming foods grown locally in arsenic-contaminated soils. Health effects in children and adults from arsenic exposure first appeared in the 1950s. Such effects included vascular, respiratory, and skin lesions from intake of high arsenic levels in drinking water. Methods to remove arsenic from water were evaluated, developed, and implemented that allowed significant reductions in exposure at a relatively low cost. Construction and operation of treatment plants to remove arsenic from water first began in the 1970s. Beginning in the 1990s, epidemiological studies showed that the rate of lung and bladder cancer in the arsenic-polluted area was considerably higher than mean cancer rates for the country. Cancer incidence was directly related to arsenic exposure. During the 1990s, international pressure and concern by Chile's Health Ministry prompted action to regulate arsenic emissions from copper smelters. A process began in which emission standards appropriate for Chile were set; this process included careful evaluation of risks versus mitigation costs for abatement options. Such options were developed and implemented. More recently, local communities have pressed for more significant reductions of arsenic in air and water. Considerable experience was gained with the arsenic experience on how to manage this type of hazardous pollutant, in a context of trade-offs among production, jobs, income, and health. In this review article, we cover arsenic levels in Chile's air, water, and soils and discuss health impacts and patterns of exposure. We also describe the process followed to set arsenic regulatory standards, as well as abatement options for air and water and the associated costs.


Reduced response cluster size in early visual areas explains the acuity deficit in amblyopia.
Focal visual stimulation typically results in the activation of a large portion of the early visual cortex. This spread of activity is attributed to long-range lateral interactions. Such long-range interactions may serve to stabilize a visual representation or to simply modulate incoming signals, and any associated dysfunction in long-range activation may reduce sensitivity to visual information in conditions such as amblyopia. We sought to measure the dispersion of cortical activity following local visual stimulation in a group of patients with amblyopia and matched normal. Twenty adult anisometropic amblyopes and 10 normal controls participated in this study. Using a multifocal stimulation, we simultaneously measured cluster sizes to multiple stimulation points in the visual field. We found that the functional MRI (fMRI) response cluster size that corresponded to the fellow eye was significantly larger as opposed to that corresponding to the amblyopic eye and that the fMRI response cluster size at the two more central retinotopic locations correlated with amblyopia acuity deficit. Our results suggest that the amblyopic visual cortex has a diminished long-range communication as evidenced by significantly smaller cluster of activity as measured with fMRI. These results have important implications for models of amblyopia and approaches to treatment.


[New usage for an old drug: acetylcysteine for contrast-induced nephropathy].
Contrast induced nephropathy is the third common cause of hospital-acquired renal failure. The pathophysiology and the mechanism involved in the contrast media induced renal failure are not well understood but it is thought to be the result of direct renal toxicity and medullary ischemia. The only preventive measure proven to reduce such nephropathy is hydration (pre- and post-procedure). However, the above treatment is partially effective. The antioxidant N-acetylcysteine has recently been studied for the prevention of contrast induced nephropathy in several prospective, randomized, placebo-controlled studies among patients with moderate renal insufficiency. Although some discrepancies exist, N-acetylcysteine appears to reduce the risk of contrast-induced nephropathy. N-acetylcysteine has a safety profile and low cost. Taken together, N-acetylcysteine is recommended for the prevention of contrast-induced nephropathy in high-risk patients.


Association between the Type of Workplace and Lung Function in Copper Miners.
The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function.


The effects of tobacco smoking on the short, middle, and long latency responses of the blink reflex in humans.
The three responses (R1, R2, and R3) of the electrically elicited blink reflex (BR) obtained in four normal human subjects were investigated before and after smoking both a filtered and an unfiltered cigarette. The changes observed in the BR were stronger and statistically more significant for the unfiltered than for the filtered cigarette, (p < 0.0001) and were more dramatic in R3 than R1 or R2. The action of nicotine on central pathways located at the interneuronal network of the brainstem, basal ganglia, and C fiber structures involved with this reflex seems to be the most likely mechanism for these findings.


[Rapid propagation of Echinacea angustifolia].
The embryo of Echinacea angustifolia was used for explants to induce shoots and callus on MS medium. The plantlets could produce from embryo directly and the shoots could be induced to form fasciculate buds through the callus differentiation. The green plantlets from embryo or fasciculated buds were used for rooting inducement. The experiment showed that the embryo pre-cultured at 4 degrees C and in dark for 7 days can germinate easier than at other cultural conditions; Treatment with low temperature and dark were favorable for growth of radicle and plumule and development of green plantlets; A single shoot could proliferate rapidly to form fasciculated buds by means of callus induction and differentiation; the optimal medium for growth and proliferate were MS + BA 1.0 mg/L + NAA 0.5 mg/L. With this method, the proliferous coefficient should be achieved 3.05.


Rescue by peripheral blood mononuclear cells in dogs from bone marrow failure after total-body irradiation.
In order to determine the minimum dose of buffy coat cells necessary to achieve hematopoietic rescue following supralethal irradiation, mongrel dogs under general anesthesia were subjected to leukacytapheresis using three different techniques of cell separation. The buffy coats were frozen with dimethylsulfoxide and stored at -196 degrees C until transfused. Sixteen dogs were irradiated with 800 rads and were supported with antibiotics and transfusions of irradiated homologous blood. They were transfused with the frozen and thawed buffy coat cells, and, if they survived, they were followed for 100 days, sacrificed, and their tissues studied. The mean yield of mononuclear cells during leukocytapheresis ranged from 4.1 +/- 2.0 X 10(9) (mean +/- SD) to 6.0 +/- 4.0 X 10(9) for the three leukacytapheresis methods; one technique was not as satisfactory as the other two. Six of the 16 dogs fully recovered with evidence of marrow rescue; however, only one had a dose of mononuclear cells less than 11.1 X 10(9). These data indicate that seven to 17 leukacytapheresis procedures would be required to reconstitute a 70 kilogram patient. These preliminary findings suggest that, because the yields of transplantable cells with current technology are not adequate, the transplantation potential of buffy coat cells exposed to mobilizing agents should be evaluated.


Evolution of a plant gene cluster in Solanaceae and emergence of metabolic diversity.
Plants produce phylogenetically and spatially restricted, as well as structurally diverse specialized metabolites via multistep metabolic pathways. Hallmarks of specialized metabolic evolution include enzymatic promiscuity and recruitment of primary metabolic enzymes and examples of genomic clustering of pathway genes. Solanaceae glandular trichomes produce defensive acylsugars, with sidechains that vary in length across the family. We describe a tomato gene cluster on chromosome 7 involved in medium chain acylsugar accumulation due to trichome specific acyl-CoA synthetase and enoyl-CoA hydratase genes. This cluster co-localizes with a tomato steroidal alkaloid gene cluster and is syntenic to a chromosome 12 region containing another acylsugar pathway gene. We reconstructed the evolutionary events leading to this gene cluster and found that its phylogenetic distribution correlates with medium chain acylsugar accumulation across the Solanaceae. This work reveals insights into the dynamics behind gene cluster evolution and cell-type specific metabolite diversity.


The complete mitochondrial genome of the Alpine black swallowtail, Papilio Maackii (Insecta: Lepidoptera: Papilionidae).
The complete mitochondrial genome (mitogenome) of the swallowtail butterfly Papilio maackii has been completed. It is 15,357 bp in length, and contains the typical complement of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), and 2 ribosomal RNA (rRNA) genes. Two A + T-rich regions are included in this mitogenome. Gene order in P. maackii mitogenome is basically identical to that of the inferred ancestral insect genome, with the exception of translocations of trnM, which is shared by some Papilios.


Efficacy of the proximal balloon flow control method for endovascular coil embolisation as a novel adjunctive technique: A retrospective analysis.
Background and purpose In our previous study, we established the utility of 8-F balloon guide catheters for anterior circulation aneurysms. This study aims to assess the efficacy of the proximal flow control method using 8-F balloon guide catheters for coil deployment into the aneurysms as a novel adjunctive technique for aneurysmal coil embolisation along with local balloon neck remodeling, stent assist and double catheter techniques. Materials and methods We retrospectively analysed patients who underwent endovascular coiling of anterior circulation aneurysms between August 2013 and December 2017. Results Of 206 patients enrolled in this study, the balloon of the guiding catheter was inflated to assist coil deployment in 43 patients (20.9%). In addition, the proximal flow control method found utility in cases with small aneurysms and relatively narrow-necked internal carotid artery. We observed no intraprocedural complications in this study. Conclusion This technique enabled secure coil deployment without navigating another microcatheter or balloon catheter around the aneurysms.


Implications for future studies in humans.
While an environmental link with cancer is widely accepted, its implications are not always understood. Because of the multistage nature of carcinogenesis, it is insufficient to study initiation only at the level of the 'target cell', since events before and after initiation may prove pivotal to neoplastic development. Estimates of the relative contributions of factors causing human cancer are briefly summarized. Tumours related to patterns of life style--including diet and behaviour--and individual susceptibility are discussed. It is in this group of tumours that metabolizing enzymes are probably most significant, especially for weak initiating stimuli, whether extrinsic or intrinsic. There are few epidemiological data available at present but future research can be suggested, to improve the definition in biochemical terms of individual susceptibility and effects of life style.


Factors affecting triple staining of human sperm.
We have previously described a triple stain for evaluating normal acrosome reactions of human sperm. This procedure uses trypan blue to distinguish live and dead sperm, Bismarck brown to stain the sperm's postacrosomal region, and rose Bengal to stain the sperm's acrosome. We have recently found that batches of rose Bengal vary significantly in their ability to produce good staining of the acrosome in this procedure. This appears to be due to variations in the intrinsic pH of rose Bengal solutions and the presence of nondye contaminants in the stain. In this study, we have evaluated acrosomal staining using 6 batches of rose Bengal and report a method for achieving uniform staining quality with each batch. Solutions of rose Bengal (0.8%) are made up in 0.1 M Tris HCl (pH 2.3) buffer and adjusted to pH 5.3 if necessary. For most batches of rose Bengal this promotes precipitation of some of the dye and an unidentified contaminating crystal. The precipitate is removed by centrifugation, and the supernatants have been found to give good to excellent staining of the acrosomes for all batches tested. Solutions of both rose Bengal and Bismarck brown are stable for at least 5 days but their pH values should be monitored daily and adjusted to 5.3 and 1.8 respectively if drifting occurs. We have also observed some variation in the intensity of rose Bengal staining of the acrosome from donor to donor and recommend that staining times in rose Bengal be adjusted for each donor.


Cortical thinning in young psychosis and bipolar patients correlate with common neurocognitive deficits.
People in midlife with established psychosis or bipolar disorder exhibit patterns of cortical thinning across several brain regions. It is unclear whether these patterns are indicative of a continuously active pathological process, residual effects of an earlier illness phase or pre-illness onset developmental risk factors. Here, we investigated whether cortical thinning is evident in younger patients in the early phase of psychosis or bipolar disorder and the relationship between cortical thinning and neurocognitive performance in young people. Magnetic resonance imaging was obtained from a sample of young patients with psychosis (n = 40; mean age 23.5 years), bipolar disorder (n = 73; mean age 21.9 years) or controls (n = 49; mean age 24.2 years). Group differences in cortical thickness were assessed using statistical difference maps, and regions of cortical thinning were correlated with medication dosage and performance on neurocognitive tasks. As initial comparisons using multiple corrections found no differences between the groups, follow-up analysis with a significance threshold of p < 0.001 was performed. As distinct from reported findings in older subjects, young patients with psychosis have less extensive thinning in parietal-temporal areas and do not demonstrate significant thinning in the insula or dorsal lateral prefrontal cortex. Young patients with bipolar disorder exhibit cortical thinning in regions more consistent with those previously reported in paediatric bipolar patients. Although there were some differences in the regions of cortical thinning between the two groups, the shared regions of cortical thinning were correlated with neurocognitive deficits in visual sustained attention, semantic verbal fluency and verbal learning and memory that are commonly reported in young people with either psychosis or bipolar disorder.


[Advance in research of osteoblast adhesion to bioactive materials].
In the research field of bone tissue engineering, the interaction of osteoblast and substrate is pivotal and the adhesion of osteoblast to biomaterials is the basic condition. Firstly, osteoblast must adhere to biomaterials, then it can migrate, proliferate and differentiate. This paper introduces the proteins relating to the adhesion of osteoblast and the influences of relating surface character and modification of biomaterials on the adhesion ability of osteoblast. These could serve as basic data and useful reference for the development of bone tissue engineering and tissue engineering scaffold materials.


Mechanistic studies on protopanaxadiol, Rh2, and ginseng (Panax quinquefolius) extract induced cytotoxicity in intestinal Caco-2 cells.
Certain ginsenosides, also known as triterpene glycosides, have been recently reported to have a characteristic effect on cultured intestinal and leukemia cell growth. Ginsenoside aglycones 20(S)-protopanaxadiol (PD), 20(S)-protopanaxatriol (PT), and ginsenoside Rh2 have been identified as having a strong effect on reducing cell viability. Furthermore, ginsenoside Rh2 is thought to be a rare ginsenoside not found in all ginseng products. Rather, Rh2 has been recently reported to be a breakdown product of thermal processing of North American ginseng. In this study, pure ginsenosides PD, PT, Rh2 standards and an enriched Rh2 fraction derived from ginseng leaf were tested in cultured Caco-2 cells for relative cytotoxic potency. PD and Rh2 LC50 were similar after 24 to 72 h, whereas a drop in PT LC50 occurred later at 48 and 72 h. Furthermore, PD and Rh2 affected membrane integrity as indicated by LDH secretion earlier than PT and the enriched Rh2 fraction (P < or = 0.05). Ginsenoside Rh2 showed the greatest (P < or = 0.05) build up of necrotic cells (18.3 +/- 0.1%) at the respective LC50 after 24 h and PD (21.3 +/- 0.3%) showed the largest effect after 44 h of exposure. The effect on apoptotic cells at 44 h of treatment were significantly different (P < or = 0.05) for Rh2 (21 +/- 0.4%), PD (14.6 +/- 0.1%), enriched Rh2 leaf fraction (9.9 +/- 0.6%), and PT (2.3 +/- 0.1%) treatments. Caco-2 caspase-3 activity was different between ginsenoside exposure; Rh2 (10.6 +/- 0.3 nM pNA) had the greatest (P < or = 0.05) activity followed by the enriched Rh2 leaf fraction (8.3 +/- 0.2 nM pNA), PT (7.3 +/- 0.3 nM pNA). The PD (4.8 +/- 0.04 nM pNA) treatment was similar to untreated cells (4.3 +/- 0.05 nM pNA) in caspase-3 activity. These results show variable bioactive response in cultured intestinal cell to specific ginsenosides and an enriched Rh2 North American ginseng extract which may be explained on basis of hydrophobic/hydrophilic balance.


Catellatospora sichuanensis sp. nov., a novel actinobacterium isolated from soil.
A novel actinobacterium, designated strain H14505T, was isolated from a soil sample collected in Hong Yuan, Sichuan, southwest PR China. The temperature, pH and NaCl ranges for growth were determined to be 15-35 °C (optimum, 28 °C), 6.0-8.0 (optimum, pH 7.0) and 0-2 % (w/v; optimum without NaCl), respectively. The polar lipdis detected for strain H14505T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, glycolipid and four unidentified lipids. The predominant menaquinones of strain H14505T were MK-9(H4) and MK-9(H6), and the prevalent fatty acids (>10 %) were C18 : 1 ω9c, C17 : 1 ω8c, summed feature 5 (anteiso-C18 : 0/ C18 : 2 ω6,9c) and C16 : 0. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences indicated that strain H14505T showed high similarity to Catellatospora vulcania NEAU-JM1T (99.0 %) and Catellatospora paridis NEAU-CL2T (99.0 %), and formed a monophyletic clade within the the genus Catellatospora in the phylogenetic trees. However, the average nucleotide indentity and DNA-DNA hybridization values between strain H14505T and closely related Catellatospora species showed that it belonged to a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of strain H14505T from its closest relatives. Thus, it is proposed that strain H14505T represents a novel species of the genus Catellatospora, for which the name Catellatospora sichuanensis sp. nov. is proposed. The type strain of Catellatospora sichuanensis is H14505T (=JCM 32394T=CICC 11042T).


Biochemical Profile of Heritage and Modern Apple Cultivars and Application of Machine Learning Methods To Predict Usage, Age, and Harvest Season.
The present study represents the first major attempt to characterize the biochemical profile in different tissues of a large selection of apple cultivars sourced from the United Kingdom's National Fruit Collection comprising dessert, ornamental, cider, and culinary apples. Furthermore, advanced machine learning methods were applied with the objective to identify whether the phenolic and sugar composition of an apple cultivar could be used as a biomarker fingerprint to differentiate between heritage and mainstream commercial cultivars as well as govern the separation among primary usage groups and harvest season. A prediction accuracy of >90% was achieved with the random forest method for all three models. The results highlighted the extraordinary phytochemical potency and unique profile of some heritage, cider, and ornamental apple cultivars, especially in comparison to more mainstream apple cultivars. Therefore, these findings could guide future cultivar selection on the basis of health-promoting phytochemical content.


Current practice, demographics, and trends of critical care trained emergency physicians in the United States.
Critical care medicine (CCM) is of growing interest among emergency physicians (EPs), but the number of CCM-trained EPs and their postfellowship practice is unknown. This study's purpose was to conduct a descriptive census survey of EPs who have completed or are currently in a CCM fellowship. The authors created a Web-based survey, and requests to participate were sent to EPs who have completed or are currently in a CCM fellowship. Responses were collected over a 12-month period. Physicians were located via multiple whom electronic mailing lists, including the Emergency Medicine Section of the Society of Critical Care Medicine, Critical Care Section of the American College of Emergency Physicians, and the Emergency Medicine Residents' Association. The authors also contacted CCM fellowship coordinators and used informal networking. Data were collected on emergency medicine (EM) and other residency training; discipline, duration, and year of CCM fellowship; current practice setting; and board certification status, including the European Diploma in Intensive Care (EDIC). A total of 104 physicians completed the survey (97% response rate), of whom 73 had completed fellowship at the time of participation, and 31 of whom were in fellowship training. Of those who completed fellowship, 36/73 (49%) practice both EM and CCM, and 45/73 (62%) practice in academic institutions. Multiple disciplines of fellowship were represented: multidisciplinary (39), surgical (28), internal medicine (16), anesthesia (14), and other (4). Together, the CCM fellowships at the University of Maryland R Adams Cowley Shock Trauma Center and the University of Pittsburgh have trained 42% of all EM-CCM physicians, with 38 other institutions training from one to four fellows each. The number of EPs completing CCM fellowships has risen: from 1974 to 1989, 12 EPs; from 1990 to 1999, 15 EPs; and from 2000 to 2007, 43 EPs. Emergency physicians are entering CCM fellowships in increasing numbers. Almost half of these EPs practice both EM and CCM.


New Developments in Surgery for Endometriosis and Pelvic Pain.
Endometriosis is a common disease affecting reproductive age women. Pain is one of the most common symptoms associated with endometriosis. When medical therapy has failed or in known deeply infiltrating endometriosis, surgical management is warranted. Laparoscopy is the gold standard for diagnosis and treatment of endometriosis. Recent developments in surgery have shown the feasibility of robotic surgery for endometriosis, although these methods have not been shown to be superior to conventional laparoscopy. Enhanced imaging techniques including fluorescence imaging and narrow band imaging have also been studied. However, long-term clinical benefits have yet to be demonstrated.


The radiological evaluation process of the potential live kidney donor assessment programme at al-Shifa Hospital: study and clinical audit.
In 2013, al-Shifa Hospital, the largest hospital in the Gaza Strip, introduced an assessment programme for potential kidney donors on the basis of medical and radiological evaluation. The aims of this study and an associated clinical audit were to examine the final outcome of the potential live kidney donors assessment programme, to review the findings and determine the level of accuracy of the radiological evaluations, to assess the completeness and standard of radiological record keeping, and to evaluate adherence to guidelines. Donor assessment files were retrieved from the kidney transplant database in the renal department of al-Shifa Hospital. Patients who had surgery outside the Gaza Strip were excluded. Delivery of the assessment programme was assessed according to British Transplantation Society guidelines. Radiological investigations were reviewed. The head of the radiological department was interviewed to provide additional information about the approach to assessing donors and current challenges. We retrieved files for 35 potential live kidney donors (mean age 36·82 years [range 23-54]). 32 (91%) donors had a nephrectomy, 33 (94%) donors were directed donors, and the type of donor donation was unknown for two (6%) donors. 24 (69%) donors were women, and 11 (31%) were men. 24 (69%) donors had CT angiography imaging reports as part of their pre-surgical evaluation. Digital access to those reports was limited and inefficient. Radiological assessments of renal parenchymal and renal anatomy and variants were made in 96% of cases. Of the 24 donors whose CT angiography imaging reports were retrieved, the excretory system was assessed in 16 (67%) donors, the presence of nephrolithiasis was assessed in 12 (50%) donors, and parenchymal disease was found in one (4%) donor. The potential live kidney donors assessment programme requires improvement to achieve an organised, consistent, and comprehensive radiological approach to assist clinical decisions, research, and quality assurance. We recommend using the latest radiology management system for an efficient workflow that can provide economical storage and convenient and timely access to images, interpretation, and digital transmission (eg, the Picture Archiving and Communication system). None.


Early auditory experience-induced composition/ratio changes of N-methyl-D-aspartate receptor subunit expression and effects of D-2-amino-5-phosphonovaleric acid chronic blockade in rat auditory cortex.
Auditory function can be affected by many factors, including environment and experience. In this study, we investigated whether early auditory experience mediates the regulation of the composition/ratio changes of the N-methyl-D-aspartic acid (NMDA) receptor subunits during development of the rat auditory cortex. We found that early sound exposure can increase expression of the NMDA receptor subunits and increase the composition/ratios of NMDA receptor subunits during the postnatal critical period. D-2-amino-5-phosphonovaleric acid (D-APV) could block and reverse the auditory experience-mediated changes, and there were marked reductions in expression levels and the composition/ratios of NMDA receptor subunits. These results indicate that the experience-dependent plasticity of the auditory cortex in the critical period during postnatal development has a marked influence on NMDA receptor expression in the rat and that changes in NMDA receptor subunit composition/ratios might mediate the early auditory experience-dependent plasticity crucial to auditory function.


Diversity of Bacterial Urine and Prostate Gland Tissue Cultures in Patients Undergoing Transurethral Prostate Gland Resection.
The objective of this study was to identify the types of bacterial colonization of the prostate gland tissue and urine pre- and postoperatively in patients undergoing a transurethral resection (TUR) of the prostate gland. In addition, clinical symptoms and histopathological findings were included. Forty three patients were investigated. Urine test strips and urine cultures were taken pre- and postoperatively and intraoperatively prostate resection chips were taken for culture. A positive bacterial culture was found in 20 of 43 (46.5%) patients. Preoperatively, a positive bacterial culture was found in 12 patients and postoperatively in 7 patients. Thirteen patients showed a positive culture of the prostate gland tissue. No patient showed the same bacterial isolates in all 3 samples. Postinterventionally, 6 patients of the group with positive bacterial cultures developed complications. From the group of patients without bacterial growth, only one patient developed a postoperative complication. The bacterial colonization in the 3 different cultures showed an inhomogeneous spectrum of bacteria without a reproducible pattern. Nevertheless, it clearly demonstrates that the group with a positive culture is at great risk to develop postoperative complications.


Duration of Pre-Operative Antibiotic Treatment and Culture Results in Patients With Infective Endocarditis.
Bacterial growth in cultures of resected heart valves of patients with infective endocarditis (IE) is influenced by pre-operative antibiotic treatment (preop-AT). This study sought to evaluate the time dependency of valve culture results (positive valve culture [PVC] vs. negative valve culture) on preop-AT. A total of 352 IE episodes in 344 adult patients of our tertiary referral hospital were retrospectively investigated (2005 to 2016). The primary endpoint was PVC results. The study used a logistic additive model adjusted for bacterial species, the McCabe-Jackson classification, and the existence of foreign valve material as covariables. The 231 included IE cases (187 [81%] men, median age 62 years, 153 [66%] native valves) comprised 58 (25%) PVC results and 173 (75%) negative valve culture results. A multivariable analysis adjusted for bacterial species, McCabe-Jackson classification, and valve type resulted in odds ratios for PVC of 6.35 (95% confidence interval [CI]: 1.94 to 20.78; p = 0.002) and 3.93 (95% CI: 1.57 to 9.84; p = 0.003) for Enterococcus spp. and Staphylococcus spp., respectively. Model-based odds ratios for PVC risk reduction in 2-day intervals of preop-AT ranged from 0.64 (95% CI: 0.61 to 0.68) at day 7 to 0.74 (95% CI: 0.70 to 0.78) at day 13 and 0.98 (95% CI: 0.93 to 1.02) at day 21. In IE cases treated with valve surgery, Staphylococcus aureus and Enterococcus spp. were associated with valve culture growth. After 7 days of antibiotic treatment, the additional effect of preop-AT on valve culture results per 2-day interval was minor. Antibiotic treatment beyond 21 days had no influence on culture results.


The location of cemento enamel junction for CAL measurement: A clinical crisis.
We face various problems while measuring the Clinical attachment level (CAL) from Cemento-enamel junction (CEJ). This study aims to record and compare the CEJ location measurements using a xed reference point (FRP) [Custom made stent] before and after ap elevation. A custom made stent and UNC-15 probe were used. Recording of CEJ location was made using a UNC-15 (Hu-Friedy) probe, before (close CEJ) and after (Open CEJ) the reflection of the flap from the lower edge of the stent in those subjects who were indicated for flap surgery, at baseline. We used statistical analysis involving intra-group comparison done by Paired-'t' test. The close and the open CEJ measurements demonstrated a, statistically, non-significant difference. The equi-measurements of close and open CEJ numerical data were remarkably lower than the under and overestimation of measurements. Thus, despite certain disadvantages of stent, the FRP provides a simple solution for CAL measurement. The results of this study confirms the objective of the study and strongly suggests that CAL measurements done without FRP is subjected to great variation and the diagnostic and prognostic interpretation of CAL should be viewed seriously in periodontics.


[Status of resistance of HIV-1 strains in Africa: what is the role of viral surveillance networks?].
The human immunodeficiency virus (HIV-1) epidemic has spread dramatically in sub-Saharan African countries. Implementation of active antiretroviral (ARV) therapy programs is urgently needed. However this emergency situation must not extenuate the importance of preliminary studies on ARV resistance of African HIV-1 isolates. Findings show that genetic mutations underlying the resistance of African strains are generally identical to those observed in HIV-1 subtype B in industrialized countries. However the incidence of some mutations associated with mild resistance to protease inhibitors (PI) appears higher in African isolates. The potential impact of these mutations for development of frank resistance to PI is still unclear. The incidence of high-grade resistance markers in untreated subjects is low. While these results do not compromise use of ARV therapy in Africa, they underline the need to set up local networks for patient follow-up and to carry out epidemiological surveillance of HIV-1 resistance. Success of ARV therapies in Africa will also depend on economic and social programs.


One-Step Preparation of Antifouling Polysulfone Ultrafiltration Membranes via Modification by a Cationic Polyelectrolyte Based on Polyacrylamide.
A novel method for one-step preparation of antifouling ultrafiltration membranes via a non-solvent induced phase separation (NIPS) technique is proposed. It involves using aqueous 0.05-0.3 wt.% solutions of cationic polyelectrolyte based on a copolymer of acrylamide and 2-acryloxyethyltrimethylammonium chloride (Praestol 859) as a coagulant in NIPS. A systematic study of the effect of the cationic polyelectrolyte addition to the coagulant on the structure, performance and antifouling stability of polysulfone membranes was carried out. The methods for membrane characterization involved scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), contact angle and zeta-potential measurements and evaluation of the permeability, rejection and antifouling performance in human serum albumin solution and surface water ultrafiltration. It was revealed that in the presence of cationic polyelectrolyte in the coagulation bath, its concentration has a major influence on the rate of "solvent-non-solvent" exchange and thus also on the rate of phase separation which significantly affects membrane structure. The immobilization of cationic polyelectrolyte macromolecules into the selective layer was confirmed by FTIR spectroscopy. It was revealed that polyelectrolyte macromolecules predominately immobilize on the surface of the selective layer and not on the bottom layer. Membrane modification was found to improve the hydrophilicity of the selective layer, to increase surface roughness and to change zeta-potential which yields the substantial improvement of membrane antifouling stability toward natural organic matter and human serum albumin.


Preparation and properties of formycin analogues methylated on the pyrazolo ring nitrogens and/or the ribose cis-hydroxyls.
1. Diazomethane treatment of formycin A in the presence or absence of SnCl2 as catalyst, was used for the preparation of the 2'-O-methyl, 3'-O-methyl, N1-methyl and N2-methyl derivatives. The four possible dimethylated derivatives, 2'(3")-O,N1(N2)-dimethylformycins, were obtained by controlled treatment of formycin with diazomethane in the presence of SnCl2, and subsequent column chromatography for product isolation. 2. All the foregoing products were characterized and identified by chromatography, ultraviolet absorption spectra, and proton magnetic resonance spectroscopy. Extensive u.v. spectral data, and spectrally determined pK values, for the various derivatives are presented. 3. N2-Methylformycin B was also prepared by enzymatic deamination of the parent N2-methylformycin A. 4. The sequence of elution of N1-methylformycin and N2-methylformycin on a strongly basic ion exchange column suggested that the latter is in the syn conformation. The susceptibility of N2-methylformycin to adenosine deaminase shows that this analogue may adopt the anti conformation on reaction with the enzyme. 5. The active species in the SnCl2-catalysed monomethylation of the 2'(3') cishydroxyls of ribonucleosides by diazomethane was shown to be an organo-tin product of the reaction of SnC2 with diazomethane. This product, not identified, contained no nitrogen or chlorine. 6. A simple column chromatographic procedure is described for the desalting of heterocyclic bases and their nucleosides with pK values for ring protonation down to about 0.


Pak2 Regulation of Nrf2 Serves as a Novel Signaling Nexus Linking ER Stress Response and Oxidative Stress in the Heart.
Endoplasmic Reticulum (ER) stress and oxidative stress have been highly implicated in the pathogenesis of cardiac hypertrophy and heart failure (HF). However, the mechanisms involved in the interplay between these processes in the heart are not fully understood. The present study sought to determine a causative link between Pak2-dependent UPR activation and oxidative stress via Nrf2 regulation under pathological ER stress. We report that sustained ER stress and Pak2 deletion in cardiomyocytes enhance Nrf2 expression. Conversely, AAV9 mediated Pak2 delivery in the heart leads to a significant decrease in Nrf2 levels. Pak2 overexpression enhances the XBP1-Hrd1 UPR axis and ameliorates tunicamycin induced cardiac apoptosis and dysfunction in mice. We found that Pak2 deletion and altered proteostasis render Nrf2 detrimental by switching from its antioxidant role to renin-angiotensin aldosterone system (RAAS) gene regulator. Mechanistically, Pak2 mediated Hrd1 expression targets Nrf2 for ubiquitination and degradation thus preventing its aberrant activation. Moreover, we find a significant increase in Nrf2 with a decrease in Pak2 in human myocardium of dilated heart disease. Using human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we find that Pak2 is able to ameliorate Nrf2 induced RAAS activation under ER stress. These findings demonstrate that Pak2 is a novel Nrf2 regulator in the stressed heart. Activation of XBP1-Hrd1 is attributed to prevent ER stress-induced Nrf2 RAAS component upregulation. This mechanism explains the functional dichotomy of Nrf2 in the stressed heart. Thus, Pak2 regulation of Nrf2 homeostasis may present as a potential therapeutic route to alleviate detrimental ER stress and heart failure.


Evaluations of emamectin benzoate and propiconazole for protecting individual Pinus contorta from mortality attributed to colonization by Dendroctonus ponderosae and associated fungi.
Protection of conifers from bark beetle colonization typically involves applications of liquid formulations of contact insecticides to the tree bole. An evaluation was made of the efficacy of bole injections of emamectin benzoate alone and combined with the fungicide propiconazole for protecting individual lodgepole pine, Pinus contorta Dougl. ex Loud., from mortality attributed to colonization by mountain pine beetle, Dendroctonus ponderosae Hopkins, and progression of associated blue stain fungi. Injections of emamectin benzoate applied in mid-June did not provide adequate levels of tree protection; however, injections of emamectin benzoate + propiconazole applied at the same time were effective for two field seasons. Injections of emamectin benzoate and emamectin benzoate + propiconazole in mid-September provided tree protection the following field season, but unfortunately efficacy could not be determined during a second field season owing to insufficient levels of tree mortality observed in the untreated control, indicative of low D. ponderosae populations. Previous evaluations of emamectin benzoate for protecting P. contorta from mortality attributed to D. ponderosae have failed to demonstrate efficacy, which was later attributed to inadequate distribution of emamectin benzoate following injections applied several weeks before D. ponderosae colonization. The present data indicate that injections of emamectin benzoate applied in late summer or early fall will provide adequate levels of tree protection the following summer, and that, when emamectin benzoate is combined with propiconazole, tree protection is afforded the year that injections are implemented.


LEFT VERSUS RIGHT HEMISPHERE DIFFERENCES IN BRAIN CONNECTIVITY: 4-TESLA HARDI TRACTOGRAPHY IN 569 TWINS.
Diffusion imaging can map anatomical connectivity in the living brain, offering new insights into fundamental questions such as how the left and right brain hemispheres differ. Anatomical brain asymmetries are related to speech and language abilities, but less is known about left/right hemisphere differences in brain wiring. To assess this, we scanned 457 young adults (age 23.4±2.0 SD years) and 112 adolescents (age 12-16) with 4-Tesla 105-gradient high-angular resolution diffusion imaging. We extracted fiber tracts throughout the brain with a Hough transform method. A 70×70 connectivity matrix was created, for each subject, based on the proportion of fibers intersecting 70 cortical regions. We identified significant differences in the proportions of fibers intersecting left and right hemisphere cortical regions. The degree of asymmetry in the connectivity matrices varied with age, as did the asymmetry in network topology measures such as the small-world effect.


Regenerated Cellulose Capsules for Controlled Drug Delivery, Part 2: Modulating Membrane Permeability by Incorporation of Depolymerized Cellulose and Altering Membrane Thickness.
For application of regenerated cellulose (RC) membranes in capsule dosage forms, the methods to modify drug release from these membranes are described. Membranes were fabricated by blending native and depolymerized celluloses dissolved in dimethyl sulfoxide and paraformaldehyde solvent system, prior to casting on molds, precipitation in water, and thermal annealing. The effect of laminating layers of RC to fabricate membranes with increasing thickness was also investigated. Solute diffusion studies using ionic and hydrophobic solutes, as well as large protein molecules, were conducted in side-by-side diffusion cells. Microscopic as well as physiological evaluation of these membranes indicated that pore size, porosity, and water uptake decreased as the fraction of depolymerized cellulose increased in the membranes. Permeability analysis of small ionic and hydrophobic solutes indicated that the solute transport across the hydrated membrane occurs through diffusion in the water-filled pores that are formed in situ. The apparent path for solute diffusion increases as the fraction of depolymerized cellulose increases. Permeability analysis of large protein molecules indicated that the pore sizes and distribution in these membranes is heterogeneous. Increasing the membrane thickness by lamination of RC does not influence porosity but causes formation of dead-end pores because of blocking by subsequent laminate layers.