The population and reproductive health programme in Brazil 1990-2002: lessons learned.
The story of Brazil's evolution in sexual and reproductive health and rights during the 1990s documents not only a decade of change in the population field, but the powerful role of social movements in a democracy. Between October and December 2002, 23 people were interviewed about where they believe progress has been made in Brazil and where there are still needs in relation to population trends, sexual and reproductive rights, and health policies. This paper contains excerpts from the full report and covers the economic and political background of Brazil; the role of non-governmental and women's organisations in influencing the national agenda; the intersection of national and international agendas on population and development, HIV/AIDS, human rights, racism and other issues; changes in sexual and reproductive health policies; HIV/AIDS policy progress, perhaps most importantly mandatory free treatment for people with HIV/AIDS; recent progress in women's health, especially in relation to antenatal and obstetric services, and services addressing violence against women. Finally it describes the role of policy accountability mechanisms that aim to ensure that the many excellent policies that have been passed since 1990 are implemented in a decentralised health system of national, state and local management and services.


Free radical scavenging of grape pomace extracts from Cabernet sauvingnon (Vitis vinifera).
Pressed grape pomace obtained from the wine production of Cabernet sauvignon (Vitis vinifera) vintage was dried until 9.8% moisture content, ground and submitted to extraction of soluble components from different extraction techniques. Low pressure extractions were performed with ethanol maceration followed by fractionation with n-hexane, dichloromethane, butanol and ethyl acetate. These solvents were furthermore applied for soxhlet extraction. Supercritical fluid extraction (SFE) was also performed to obtain grape pomace extracts by using pure CO2 and CO2 with ethanol as co-solvent in concentrations of 10, 15 and 20%w/w. The operating condition used in high pressure extractions was 150bar and 40 degrees C. The antioxidant activity of the grape pomace extracts was determined considering the free radical scavenging assay using 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and was correlated with the total phenol content determined according to the Folin-Ciocalteu method. The results obtained in DPPH tests indicate the highest antioxidant activity of 96.6+/-0.3%AA, with an IC50 value of 13+/-1, for the extracts obtained with ethyl acetate in solid-liquid extraction. The highest yield values were achieved in soxhlet extraction with ethanol (13.2%w/w) and with butanol (12.2%w/w), and also by SFE with 15% ethanol (9.2%w/w). The lipophilic composition of grape pomace extracts was evaluated by gas chromatography-mass spectrometry with the identification of components like linoleic acid and ethyl linoleate, with important therapeutic activities.


The antimalarial action on Plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress.
The antimalarial activity of qinghaosu (artemisinine) against Plasmodium falciparum in culture was enhanced by increased oxygen tension. Artesunate, a qinghaosu derivative, showed synergistic effects with miconazole, and with doxorubicin, both of which have been suggested to exert their chemotherapeutic effect through increasing the oxidant stress. In contrast, catalase, dithiothreitol and alpha-tocopherol reduced the effectiveness of qinghaosu in vitro. These results suggest that the action of qinghaosu and artesunate might involve increase in oxidant stress on the infected red cells.


Prolyl-4-Hydroxylase 2 Potentially Contributes to Hepatocellular Carcinoma-Associated Erythrocytosis by Maintaining Hepatocyte Nuclear Factor-4α Expression.
Increased red blood cell count (Erythrocytosis) is an important paraneoplastic syndrome of hepatocellular carcinoma (HCC) and is a significant risk factor for lethal lung artery thromboembolism. HCC-associated erythrocytosis is partially caused by the ability of several HCC cells to produce erythropoietin (EPO). Prolyl-4-hydroxylase 2 (PHD2) is an enzyme encoded by the gene EGLN1. The best-known function of PHD2 is to mediate the oxygen-dependent degradation of the labile α-subunit of hypoxia-inducible factor (HIF). However, there is increasing evidence that PHD2 also regulates HIF-independent pathways by interacting with other substrates. In the EPO-producing human HCC cell line HepG2, the expression of PHD2 gene was silenced with siRNA. EPO production was estimated using quantitative PCR and ELISA. In HepG2 cells, PHD2 suppresses the activity of TGF-β1 pathway and consequently maintains the expression of hepatocyte nuclear factor-4α (HNF-4α), an important transcription factor promoting the EPO expression in hepatocytes. PHD2 knockdown caused a marked reduction of EPO production. HIF seemed not to be involved in this biology. Our findings show that PHD2 represents a potential contributing factor for HCC-associated erythrocytosis. Selective inhibition of PHD2 in HCC cells might be considered as a new way to manage erythrocytosis in HCC patients.


1-(2-methoxybenzylidene)-4-phenylthiosemicarbazide as OFF-ON fluorescent chemodosimeter for detection of Cu2+ in acetonitrile-water binary solvents.
A novel fluorescent chemodosimeter, 1-(2-methoxybenzylidene)-4-phenylthiolsemicarbazide, was studied. In 90:10 (v/v) mixture of CH3CN and water binary solution, it exhibits high selectivity toward Cu2+ but very low response toward other competitive cations. The Cu2+ promoting cyclization of the thiosemicarbazide to 1,2,4-triazole-3(4H)-thione ring results in observation of the turn-on fluorescence.


Impact of spatial constraints during seed germination on the evolution of angiosperm cotyledons: a case study from tropical Hydatellaceae (Nymphaeales).
A bipolar embryo with cotyledons is a characteristic feature that appeared early in the evolution of seed plants. Cotyledon number is an important character in angiosperm classification. We explore the links between functional aspects of seed germination and the number and location of the cotyledons, using as a model the early-divergent angiosperm family Hydatellaceae, in which seedlings are superficially monocot-like. • Seedlings of two species of tropical Hydatellaceae were studied using light and scanning electron microscopy. • Seedlings of Trithuria cowieana bear two free cotyledons. Each cotyledon possesses a green, filiform, vascularized blade that resembles subsequent leaves, and a basal, nonvascularized, haustorial outgrowth that remains in close contact with the endosperm. Seedlings of Trithuria konkanensis have two free cotyledonary haustoria inserted close to each other and a leaf blade probably belonging to one of the cotyledons. The cotyledonary node elongates between the haustoria and the leaf blade to form a mesocotyl. • To date, the absence or presence of a cotyledonary tube represents the only known qualitative morphological difference between the two major clades of Hydatellaceae. Cotyledons with a haustorium and leaf blade are unusual at the scale of seed plants and probably evolved due to homeosis. The mesocotyl of T. konkanensis resembles that of grasses and sedges. Seedling diversity in Hydatellaceae and other seed plants is linked with the principal physical and spatial constraint of their embryo structure, with the primary root and shoot apical meristems located at opposite poles, and haustorial cotyledon tips.


Application of liquid-phase microextraction to the analysis of trihalomethanes in water.
A liquid-phase microextraction method for the determination of trihalomethanes (THMs) including chloroform (CHCl3), bromodichloromethane (CHBrCl2), dibromochloromethane (CHBr2Cl) and bromoform (CHBr3) in water samples was developed, with analysis by gas chromatography-electron capture detection (GC-ECD). After the determination of the most suitable solvent and stirring rate for the extraction, several other parameters (solvent drop volume, extraction time and ionic strength of the sample) were optimized using a factorial design to obtain the most relevant variables. The optimized extraction conditions for 5 mL of sample volume in a 10 mL vial were as follows: n-hexane an organic solvent; a solvent drop volume of 2 microL; an extraction time of 5.0 min; a stirring rate of 600 rpm at 25 degrees C; sample ionic strength of 3M sodium chloride. The linear range was 1-75 microg L(-1) for the studied THMs. The limits of detection (LODs) ranged from 0.23 microg L(-1) (for CHBr2Cl) to 0.45 microg L(-1) (for CHCl3). Recoveries of THMs from fortified distilled water were over 70% for a fortification level of 15 microg L(-1), and relative standard deviations of the recoveries were below 5%. Real samples collected from tap water and well water were successfully analyzed using the proposed method. The recovery of spiked water samples was from 73% to 78% with relative standard deviations below 7%.


Stimulation of natriuretic peptide receptor C attenuates accumulation of reactive oxygen species and nitric oxide synthesis in ammonia-treated astrocytes.
Oxidative and nitrosative stress contribute to ammonia-induced astrocytic dysfunction in hepatic encephalopathy. Treatment of cultured astrocytes with 5 mmol/L ammonium chloride ('ammonia') increased the production of reactive oxygen species (ROS), including the toxic NADPH oxidase reaction product, •O(2)(-). Atrial natriuretic peptide (ANP), natriuretic peptide C and a selective natriuretic peptide receptor (NPR)-C ligand, cANP((4-23),) each decreased the total ROS content both in control cells and cells treated with ammonia. However, attenuation of •O(2)(-) accumulation by ANP and cANP((4-23),) was observed in ammonia-treated cells only and the effect of cANP((4-23)) was decreased when the NADPH oxidase-regulatory protein G(iα-2) was blocked with a specific anti-G(iα-2) antibody. Although in contrast to ANP, cANP((4-23)) did not elevate the cGMP content in control astrocytes, it decreased cAMP content and reduced the expression of G(iα-2), the NADPH oxidase-regulatory protein. The results show the presence of functional NPR-C in astrocytes, activation of which (i) attenuates basal ROS production, and (ii) prevents excessive accumulation of the toxic ROS species, •O(2)(-) by ammonia. Ammonia, ANP and cANP((4-23)) added separately, each stimulated formation of NO(x) (nitrates + nitrites) which was associated with up-regulation of the activity [cANP((4-23))] or/and expression (ammonia) of the endothelial isoform of nitric oxide synthase. However, the ammonia-induced increase of NO(x) was not augmented by co-addition of ANP, and was reduced to the control level by co-addition of cANP((4-23)) , indicating that activation of NPR-C may also reduce nitrosative stress. Future hepatic encephalopathy therapy might include the use of cANP((4-23)) or other NPR-C agonists to control oxidative/nitrosative stress induced by ammonia.


In-situ immobilization of arsenic and antimony containing acid mine drainage through chemically forming layered double hydroxides.
Acid mine drainage (AMD) rich in arsenic (As) and antimony (Sb) is considered as a significant environmental challenge internationally. However, simultaneous removal of As and Sb from AMD is still inadequately studied. In this study, a highly effective and simple approach was proposed for mitigating As and Sb-rich AMD, which involves in-situ formation of layered double hydroxides (LDHs). Following the treatment, the residual concentrations of iron (Fe), magnesium (Mg), sulfate, As and Sb in field AMD were decreased from their initial concentrations of 1690, 1524, 2055, 7.8 and 10.6 mg L-1, respectively, to 1.3, 12.4, 623, 0.006 and 0.004 mg L-1, respectively. Chemical formula of the resulting As and Sb-loaded LDHs can be identified as Mg4.226Fe2.024OH2SO4AsSb0.006∙mH2O. The dissolution rates of metal(loid)s in As and Sb-loaded LDH were lower than 1% under strongly acidic and alkaline environments. In presence of the mixed adsorbates, the As immobilization capacity by LDHs was significantly decreased, with an apparent intervention from Sb. However, As did not have a significant effect on the immobilization of Sb by LDH. As was immobilized by LDHs through anion exchange and complexation with -OH groups, while Sb was captured by anion exchange and complexation with [Formula: see text] . Density functional theory (DFT) calculations further proved the above conclusions. This novel approach is effective and can be applied for in-situ AMD treatment from abandoned mines.


Construction of Metatranscriptomic Libraries for 5' End Sequencing of rRNAs for Microbiome Research.
Metatranscriptomic sequencing enables studying community-wide gene expression profiles of microbial samples and getting functional insight on their up- or downregulated pathways. However, shotgun sequencing is not the most efficient way to study expression of ribosomal RNA genes or to compare lot of samples in experimental setups. Here we describe an efficient primer-independent method for processing and barcoding libraries for directional sequencing of the 5' end region of the RNA. When applying size selection of the original RNA, the method forms an optimal solution for the simultaneous analysis of bacterial, archaeal, and eukaryotic rRNA diversity.


Rice transglutaminase gene: Identification, protein expression, functionality, light dependence and specific cell location.
Transglutaminases (TGases), that catalyze post-translational modification of proteins, are scarcely known in plants. As part of a project to characterize transglutaminase genes in new plant species, the identification and characterization of a TGase in rice is presented. Using differential primers, a cDNA (tgo) of 1767bp from genomic rice DNA amplification was obtained. The primers were designed from the rice DNA sequence relatively homologous to the gene encoding active maize chloroplast TGase. Amino acid sequence of the deduced rice TGase protein (TGO) indicated that it contains the enzyme catalytic triad (Cys-His-Asp), three repeats, myristoylation domains and a leucine zipper motif. The TGO recombinant protein was characterized, showing specific activity regulation, and indicating that tgo encoded for an authentic TGase. Substrate preference and Ca(2+) dependent activity were also detected. In the rice plant TGO protein was immunolocalized in the grana chloroplasts, in protein vesicles near them, and in the bulliform cells. Immunoblot analyses, tgo mRNA expression, and TGase activity indicated that TGO expression in rice was light dependent and regulated by the illumination period. This work increases significantly our plant TGase understanding. Its functional role in rice, which is a good model system for C3 plants, is discussed.


Function of amyloid and amyloid protein precursor.
A short review is given of the functions of amyloid (beta/A4) and its precursor protein (APP). The possible relationship between amyloid deposition and dementia is discussed.


[Experimental assessment of adaptive possibilities after chronic prenatal exposure to gamma irradiation at various absorbed doses].
The purpose of the investigation is the study of dose-response relationship at the antenatal exposure of low level ionizing radiation (137Cs, 1.0-1.25; 1.7-1.9 and 2.3-2.5 Gy during 20 days). The decrease of body weight in pregnant females and antenatal embryonic mortality at the doses 2.3-2.5 Gy are revealed. Physical postnatal anomalies with decrease of the adaptation were estimated by the strength endurance after antenatal exposure of gamma-rays at the doses of 1.0-2.5 Gy.


Aesthetic management of severely fluorosed incisors in an adolescent female.
Dental fluorosis is a condition of enamel hypomineralization due to the effects of excessive fluoride on ameloblasts during enamel formation. Delayed degradation of enamel matrix proteins or inhibited protein removal results in impaired and incomplete crystal growth, producing hypomineralized and porous enamel. Severely fluorosed teeth may undergo post-eruptive surface breakdown and post-eruptive dark brown to black staining. A 13 year old girl presented with severely discoloured maxillary central incisors. Initial aesthetic management of these teeth was conservative, including in-office tooth whitening, microabrasion and take-home whitening. Dark brown to black staining of the teeth was reduced successfully without the need for gross mechanical preparation of the enamel. Further improvement of aesthetics was achieved with composite veneers. Conservative treatment options such as tooth whitening and microabrasion can dramatically improve severely discoloured fluorosed teeth. This can provide a satisfactory interim outcome or minimize the removal of discoloured enamel and dentine prior to the provision of composite veneers. The use of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) may enhance remineralization and decrease postoperative sensitivity following tooth whitening and microabrasion procedures in hypomineralized teeth.


Improvement of venous leg ulcers with androgen replacement therapy in a patient with undiagnosed klinefelter syndrome.
Klinefelter syndrome (KS) is the most common genetic form of male hypogonadism. The majority (80-90%) of patients have 47, XXY karyotype while mosaicism is seen in only 10-20% of patients. Leg ulcers may be a presenting symptom of KS with a prevalence of 6-13%. Treatment with testosterone has been reported to improve the ulcers.


CHI3L1 induces autophagy through the JNK pathway in lung cancer cells.
CHI3L1 is closely related to the molecular mechanisms of cancer cell migration, growth, and death. According to recent research, autophagy regulates tumor growth during various stages of cancer development. This study examined the association between CHI3L1 and autophagy in human lung cancer cells. In CHI3L1-overexpressing lung cancer cells, the expression of LC3, an autophagosome marker, and the accumulation of LC3 puncta increased. In contrast, CHI3L1 depletion in lung cancer cells decreased the formation of autophagosomes. Additionally, CHI3L1 overexpression promoted the formation of autophagosomes in various cancer cell lines: it also increased the co-localization of LC3 and the lysosome marker protein LAMP-1, indicating an increase in the production of autolysosomes. In mechanism study, CHI3L1 promotes autophagy via activation of JNK signaling. JNK may be crucial for CHI3L1-induced autophagy since pretreatment with the JNK inhibitor reduced the autophagic effect. Consistent with the in vitro model, the expression of autophagy-related proteins was downregulated in the tumor tissues of CHI3L1-knockout mice. Furthermore, the expression of autophagy-related proteins and CHI3L1 increased in lung cancer tissues compared with normal lung tissues. These findings show that CHI3L1-induced autophagy is triggered by JNK signals and that CHI3L1-induced autophagy could be a novel therapeutic approach to lung cancer.


Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene polymorphisms are associated with human sperm concentration.
Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMT and CHDH gene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT -774G>C and CHDH +432G>T polymorphisms were genotyped. The genotype distribution of the PEMT -774G>C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH +432G>T polymorphism, oligospermic men presented the CHDH 432G/G genotype more frequently than normozoospermic men (62% vs. 42%, P<0.001). The PEMT 774G/G genotype was associated with a higher sperm concentration compared to the PEMT 774G/C and 774C/C genotypes in oligospermic men (12.5 ± 5.6 × 10(6) spermatozoa ml(-1) vs. 8.3 ± 5.2 × 10(6) spermatozoa ml(-1), P<0.002) and normozoospermic men (81.5 ± 55.6 × 10(6) vs. 68.1 ± 44.5 × 10(6) spermatozoa ml(-1), P<0.006). In addition, the CHDH 432G/G genotype was associated with higher sperm concentration compared to CHDH 432G/T and 432T/T genotypes in oligospermic (11.8 ± 5.1 × 10(6) vs. 7.8 ± 5.3 × 10(6) spermatozoa ml(-1), P<0.003) and normozoospermic men (98.6 ± 62.2 × 10(6) vs. 58.8 ± 33.6 × 10(6) spermatozoa ml(-1), P<0.001). In our series, the PEMT -774G>C and CHDH +432G>T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.


The relation between cavitation and platelet aggregation during exposure to high-intensity focused ultrasound.
Our previous study showed that high-intensity focused ultrasound (HIFU) is capable of producing "primary acoustic hemostasis" in the form of ultrasound (US)-induced platelet activation, aggregation and adhesion to a collagen-coated surface. In the current study, 1.1 MHz continuous-wave HIFU was used to investigate the role of cavitation as a mechanism for platelet aggregation in samples of platelet-rich plasma. A 5 MHz passive cavitation detector was used to monitor cavitation activity and laser aggregometry was used to measure platelet aggregation. Using spatial average intensities from 0 to 3350 W/cm2, the effects of HIFU-induced cavitation on platelet aggregation were investigated by enhancing cavitation activity through use of US contrast agents and by limiting cavitation activity through use of an overpressure system. Our results show that increased cavitation activity lowers the intensity threshold to produce platelet aggregation and decreased cavitation activity in the overpressure system raises the intensity threshold for platelet aggregation.


Corneal Transplantation in Disease Affecting Only One Eye: Does It Make a Difference to Habitual Binocular Viewing?
Clarity of the transplanted tissue and restoration of visual acuity are the two primary metrics for evaluating the success of corneal transplantation. Participation of the transplanted eye in habitual binocular viewing is seldom evaluated post-operatively. In unilateral corneal disease, the transplanted eye may remain functionally inactive during binocular viewing due to its suboptimal visual acuity and poor image quality, vis-à-vis the healthy fellow eye. This study prospectively quantified the contribution of the transplanted eye towards habitual binocular viewing in 25 cases with unilateral transplants [40 yrs (IQR: 32-42 yrs) and 25 age-matched controls [30 yrs (25-37 yrs)]. Binocular functions including visual field extent, high-contrast logMAR acuity, suppression threshold and stereoacuity were assessed using standard psychophysical paradigms. Optical quality of all eyes was determined from wavefront aberrometry measurements. Binocular visual field expanded by a median 21% (IQR: 18-29%) compared to the monocular field of cases and controls (p = 0.63). Binocular logMAR acuity [0.0 (0.0-0.0)] almost always followed the fellow eye's acuity [0.00 (0.00 --0.02)] (r = 0.82), independent of the transplanted eye's acuity [0.34 (0.2-0.5)] (r = 0.04). Suppression threshold and stereoacuity were poorer in cases [30.1% (13.5-44.3%); 620.8 arc sec (370.3-988.2 arc sec)] than in controls [79% (63.5-100%); 16.3 arc sec (10.6-25.5 arc sec)] (p<0.001). Higher-order wavefront aberrations of the transplanted eye [0.34 μ (0.21-0.51 μ)] were higher than the fellow eye [0.07 μ (0.05-0.11 μ)] (p<0.001) and their reduction with RGP contact lenses [0.09 μ (0.08-0.12 μ)] significantly improved the suppression threshold [65% (50-72%)] and stereoacuity [56.6 arc sec (47.7-181.6 arc sec)] (p<0.001). In unilateral corneal disease, the transplanted eye does participate in gross binocular viewing but offers limited support to fine levels of binocularity. Improvement in the transplanted eye's optics enhances its participation in binocular viewing. Current metrics of this treatment success can expand to include measures of binocularity to assess the functional benefit of the transplantation process in unilateral corneal disease.


Endoluminal angioplasty of the popliteal artery. Review of 54 consecutive patients.
To determine the results of endoluminal angioplasty for occlusive or stenotic lesions of the popliteal artery. Retrospective study of symptomatic patients having popliteal occlusive lesions treated by endoluminal balloon angioplasty. All patients underwent systematic preoperative and postoperative color duplex scan and preoperative angiography. The principal endpoints were primary and primary assisted patency. Fifty-four percutaneous endoluminal angioplasties of the popliteal artery, including six procedures with stents, were performed in 50 patients. In all cases, the superficial femoral artery was patent and without significant stenosis. Primary patency for the entire cohort was 57.4+/-6.7% at 1 and 2 years. Primary assisted patency was 86.3+/-4.8% at 1 year, and 79.1+/-5.9% at 2 years. The results of angioplasty appeared to be better in patients with intermittent claudication when compared to patients with critical limb ischaemia, (p=0.0006). Angioplasty of single occlusive lesions had a better prognosis than that of multiple occlusive lesions (p=0.01). Results of angioplasty were better at the below-knee and median popliteal artery than at the femoro-popliteal junction or in the above-knee popliteal artery (p=0.03). Tibial run-off and isolated popliteal stenosis versus isolated popliteal thrombosis did not seem to affect primary patency rate. Results of angioplasty of the popliteal artery are acceptable for claudicants, especially those with TASC-A lesions and those with lesions in the distal two thirds of the popliteal artery.


Impact of black carbon on the bioaccessibility of organic contaminants in soil.
The ability of carbonaceous geosorbents (CGs) such as black carbon (BC) to extensively sorb many common environmental contaminants suggests that they potentially possesses qualities useful to the sequestration of harmful xenobiotics within contaminated land. Presently, however, there is limited understanding of the implications for the bioaccessibility, mobility and environmental risk of organic contaminants while sorbed to BC in soil and sediment, in addition to the inherent toxicity of BC itself to terrestrial flora and fauna. We review both the processes involved in and factors influencing BC sorption characteristics, and ultimately consider the impacts BC will have for bioavailability/bioaccessibility, toxicity and risk assessment/remediation of contaminated land. We conclude that while the application of BC is promising, additional work on both their toxicity effects and long-term stability is required before their full potential as a remediation agent can be safely exploited.


The effect of visual targeting on ground reaction force and temporospatial parameters of gait.
Visual targeting has been cited as a confounding factor for gait analysis in which measures of ground reaction force and plantar pressure are obtained. To investigate the effect of visual targeting on temporospatial and kinetic aspects of gait when small targets, such as pressure platforms, have to be used. A within subjects repeated measure design was used to measure step parameters and ground reaction forces of 11 healthy volunteers. Subjects were required to walk over a 10 m walkway at a self-selected pace. A 30x24 cm(2) target area was superimposed over a hidden Kistler force plate (60x90 cm(2)) mounted at the midpoint of the walkway. Step parameters and ground reaction forces were measured with and without the presence of the target. Ground reaction forces were analysed within the time-domain. Subjects used visual control strategies when approaching targets of similar dimensions to a pressure platform. These strategies were manifested by an increase in the variability of the step length onto the target (P<0.05). However, targeting was observed to have no affect on the magnitude, timing and variability of ground reaction forces when measured within the time-domain and averaged over five trials (P>0.05). Visual control strategies employed while walking toward a target area have no affect on ground reaction force parameters when measured within the time-domain. These findings demonstrate that targeting a 30x24 cm(2) target does not affect ground reaction force parameters, when a gait protocol that fine-tunes the start position is employed. The findings are relevant to gait research in which small force or pressure platforms are used to assess gait kinetics.


Pollen allergen skin test and specific IgE reactivity among Filipinos: a community-based study.
Despite the clinical importance of pollen allergens among Filipinos, few studies delve into the sensitization profiles of Filipinos against pollen allergens. This study determined the sensitization profile of Filipinos to pollen using skin prick test (SPT) and pollen-specific ELISA. Pollen from fifteen selected plant sources was collected and extracted for use in sensitization tests. Volunteers were interviewed for their clinical history prior to blood sampling and SPT. The blood samples collected were assessed using Enzyme-Linked Immunosorbent Assay (ELISA). The best panel of pollen allergens for the skin prick test was Mangifera indica (64%), Acacia auriculiformis (28%), Mimosa spp. (25%) Amaranthus spinosus (22%), Lantana camara (20%), Pilea microphylla (16%) and Dichanthium aristatum (15%). Young adults had more sensitizations to pollen than among early childhood and elderly. There were more allergic subjects that have rhinitis (61%) than asthma (42%) and atopic dermatitis (35%). Pollen-specific IgE levels show low percent reactivity as compared to the skin test with Cocos nucifera obtaining the highest IgE reactivity (21%). Pollen allergens from both arboreal and herbaceous plants used in this study yielded positive reactivities for both skin tests and specific IgE tests.


[Creation of an artificial smooth muscle rectal sphincter in children].
A method for creation of the artificial smooth muscle anal sphincter, which was used in 18 children with high forms of anorectal atresia and in 9 children with associated incompetence of the external and internal anal sphincters developed after repeated operations, severe traumas of the perineum and rectum and suppurative processes, has been developed. The effectiveness of the developed method is shown on the basis of clinical, functional and experimental morphologic methods of investigation.


Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases.
In the last few years we have witnessed the emergence of oral chelation which is a new form of therapy for transfusional iron-loaded patients in thalassaemia and other refractory anaemias. The need for a cheap, non-toxic, orally effective iron chelator is paramount because it could potentially save the lives of many thousands of patients. At present, less than 10% of the patients requiring iron chelation therapy worldwide receive the widely used chelating drug desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or INN: Deferiprone), which has so far been taken by over 450 patients in 15 countries, and in some cases daily for over 4 years with very promising results. L1 was shown at 50-100 mg/kg/day to be effective in bringing patients to negative iron balance. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic side effects were mainly encountered at high doses (80-100 mg/kg/day) and include transient agranulocytosis (5 cases), transient musculoskeletal and joint pains (10-20%), gastric intolerance (2-6%) and zinc deficiency (1%). The incidence of these toxic side effects was reduced by using lower doses of 50-75 mg/kg/day. The overall efficacy and toxicity of L1 is comparable to that of DF in animals and humans. Further work is required for identifying susceptible individuals to L1 toxicity, and also optimum dose protocols of L1 which can maximise iron excretion and minimise the incidence of toxic side effects.


Winner of the 2013 Young Investigator Award for the Society for Biomaterials annual meeting and exposition, April 10-13, 2013, Boston, Massachusetts. Osteogenic differentiation of mesenchymal stem cells on demineralized and devitalized biodegradable polymer and extracellular matrix hybrid constructs.
Devitalization and demineralization processing of biodegradable polymer and extracellular matrix (ECM) hybrid constructs was explored for the effect on the retention of ECM components and construct osteogenicity. Hybrid constructs were generated by seeding osteogenically predifferentiated rat mesenchymal stem cells (MSCs) onto electrospun poly(ε-caprolactone) fiber meshes and culturing in osteogenic medium for 12 or 16 days within a flow perfusion bioreactor to create an ECM coating. The resulting constructs were then either devitalized (using a freeze-thaw or a detergent technique), devitalized and demineralized, or left untreated, and subsequently characterized for DNA, glycosaminoglycan, collagen, and calcium content. The osteogenicity of each construct was investigated by culturing MSCs on the hybrid constructs within a flow perfusion bioreactor for 4, 8, and 12 days in osteogenic medium. Histological staining demonstrated that devitalization via the freeze-thaw method retained the thickest coating of ECM components within the constructs. Demineralization and devitalization processing of ECM coated constructs resulted in a decrease in their osteogenicity.


Inhibition of MAC30 exerts antitumor effects in nasopharyngeal carcinoma via affecting the Akt/GSK-3β/β-catenin pathway.
Meningioma-associated protein 30 (MAC30) is a vital modulator of malignant transformation in numerous cancers. Yet, the involvement of MAC30 in nasopharyngeal carcinoma (NPC) is undetermined. This study was devoted to the study of the function of MAC30 in NPC, along with the molecular mechanism of its involvement in disease progression. This study showed an elevated level of MAC30 in NPC tissues and cell lines. MAC30 silencing impeded the proliferation, colony formation, and invasion of NPC cells, while MAC30 upregulation had the opposite effects. MAC30 regulated the Wnt/β-catenin pathway via affecting the protein kinase B (Akt)/glycogen synthase kinase-3β axis. Akt inhibition markedly abrogated the MAC30-mediated activation of the Wnt/β-catenin pathway. Restoration of β-catenin reversed MAC30 silencing-induced tumor-inhibiting effects. Knockdown of MAC30 weakened the tumorigenic potential of NPC cells in vivo. This study elucidates the fact that inhibition of MAC30 produces antitumor effects in NPC via affecting the Akt/Wnt/β-catenin pathway.


Recruitments of trained citizen volunteering for conventional cardiopulmonary resuscitation are necessary to improve the outcome after out-of-hospital cardiac arrests in remote time-distance area: A nationwide population-based study.
To compare the factors associated with survival after out-of-hospital cardiac arrests (OHCAs) among three time-distance areas (defined as interquartile range of time for emergency medical services response to patient's side). From a nationwide, prospectively collected data on 716,608 OHCAs between 2007 and 2012, this study analyzed 193,914 bystander-witnessed OHCAs without pre-hospital physician involvement. Overall neurologically favourable 1-month survival rates were 7.4%, 4.1% and 1.7% for close, intermediate and remote areas, respectively. We classified BCPR by type (compression-only vs. conventional) and by dispatcher-assisted CPR (DA-CPR) (with vs. without); the effects on time-distance area survival were analyzed by BCPR classification. Association of each BCPR classification with survival was affected by time-distance area and arrest aetiology (p<0.05). The survival rates in the remote area were much higher with conventional BCPR than with compression-only BCPR (odds ratio; 95% confidence interval, 1.26; 1.05-1.51) and with BCPR without DA-CPR than with BCPR with DA-CPR (1.54; 1.29-1.82). Accordingly, we classified BCPR into five groups (no BCPR, compression-only with DA-CPR, conventional with DA-CPR, compression-only without DA-CPR, and conventional without DA-CPR) and analyzed for associations with survival, both cardiac and non-cardiac related, in each time-distance area by multivariate logistic regression analysis. In the remote area, conventional BCPR without DA-CPR significantly improved survival after OHCAs of cardiac aetiology, compared with all the other BCPR groups. Other correctable factors associated with survival were short collapse-to-call and call-to-first CPR intervals. Every effort to recruit trained citizens initiating conventional BCPR should be made in remote time-distance areas.


The posterior talocalcaneal ligament: an MRI evaluation.
A wide inter-individual variability in terms of size, orientation and insertion is observed regarding ankle ligaments. The aim of this study is to identify and describe the anatomical features of the posterior talocalcaneal ligament (PTCL) observed through the use of magnetic resonance imaging (MRI) of the ankle. The study was retrospectively carried out on 893 ankle MRI's exams. The exams have all been performed using a 1.5-T (T) MRI. The same scanning protocols and scan planes were carried out in all the exams. The first evaluated parameter was the recognition of the PTCL. Subsequently, in all those cases where the ligament was present, its features such as insertion sites, length, and thickness were evaluated. The PTCL identification was possible in 77 exams (8.6% of the total number). Among these, we were able to identify some variants regarding insertion sites, length, and thickness. The PTCL could be further classified into four categories based on the most common characteristics observed. Our study has identified different characteristics of the PTCL that allow us to further understand the characteristics of the ligament itself. In conclusion, the need for further studies focused on the biomechanical role of the PTCL in the ankle joint appears mandatory.


Maintaining adequate donations and a sustainable blood supply: Lessons learned.
The availability of a safe blood supply is a key component of transfusion medicine. A decade of decreased blood use, decreased payment for products, and a dwindling donor base have placed the sustainability of the US blood supply at risk. A literature review was performed for blood center (BC) and hospital disaster management, chronically transfusion-dependent diseases, and appropriate use of group O-negative red blood cells (RBCs), and the Choosing Wisely campaign. The aim was to identify current practice and to make recommendations for BC and hospital actions. While BCs are better prepared to handle disasters than after the 9/11 attacks, messaging to the public remains difficult, as donors often do not realize that blood transfused during a disaster was likely collected before the event. BCs and transfusion services should participate in drafting disaster response plans. Hospitals should maintain inventories adequate for patients in the event supply is disrupted. Providing specialty products for transfusion-dependent patients can strain collections, lead to increased use of group O RBCs, and create logistical inventory challenges for hospitals. The AABB Choosing Wisely initiative addresses overuse of blood components to optimally use this precious resource. Group O-negative RBCs should be transfused only to patients who truly need them. Collecting and maintaining a blood supply robust enough to handle disasters and transfusion-dependent patients in need of specialty products is challenging. Collaboration of all parties should help to optimize resources, ensure appropriate collections, improve patient care, and ultimately result in a robust, sustainable blood supply.


Effects of Surfactants and Microwave-assisted Pretreatment of Orange Peel on Extracellular Enzymes Production by Aspergillus japonicus PJ01.
The effects of surfactants and microwave pretreatment of orange peel powder (OPP) on the production of pectinase, cellulase, and xylanase by Aspergillus japonicus PJ01 in submerged fermentation were investigated. The results showed that when OPP was pretreated only by microwave (630 W, 9 min, and liquid/solid ratio 5), the activities of exo-pectinase, carboxymethyl cellulase (CMCase), xylanase, and filter paper cellulase (FPase) were increased by 11.8, 20.6, 16.2, and 24.0 %, respectively, and when OPP was pretreated by microwave at the same conditions cited above plus PEG 4000 at the concentration of 3 g/L, the activities of the above four enzymes were enhanced by 40.2, 30.3, 40.4, and 40.0 % after 84-h cultivation, respectively. It is suggested a synergistic effect between microwave and surfactant treatment in enhancing the multiextracellular enzymes production by OPP fermentation of A. japonicus PJ01. Chemical composition and Fourier transform infrared spectroscopy (FTIR) analysis displayed that the microwave pretreatment of OPP led to the decrease of hemicellulose and essential oil contents. Scanning electron microscope (SEM) showed that OPP surface after microwave pretreatment became porous and more susceptible to be invaded by A. japonicus. The results demonstrated that pretreatment of OPP by surfactant PEG 4000 and microwave irradiation as environment-friendly way was cost-effective in enhancing the multienzyme production from agricultural waste orange peel.


Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries.
Our goal in this review is to provide a comprehensive, integrated view of the numerous signaling pathways that are activated by alpha(1)-adrenoceptors and control actin-myosin interactions (i.e., crossbridge cycling and force generation) in mammalian arterial smooth muscle. These signaling pathways may be categorized broadly as leading either to thick (myosin) filament regulation or to thin (actin) filament regulation. Thick filament regulation encompasses both "Ca(2+) activation" and "Ca(2+)-sensitization" as it involves both activation of myosin light chain kinase (MLCK) by Ca(2+)-calmodulin and regulation of myosin light chain phosphatase (MLCP) activity. With respect to Ca(2+) activation, adrenergically induced Ca(2+) transients in individual smooth muscle cells of intact arteries are now being shown by high resolution imaging to be sarcoplasmic reticulum-dependent asynchronous propagating Ca(2+) waves. These waves differ from the spatially uniform increases in [Ca(2+)] previously assumed. Similarly, imaging during adrenergic activation has revealed the dynamic translocation, to membranes and other subcellular sites, of protein kinases (e.g., Ca(2+)-activated protein kinases, PKCs) that are involved in regulation of MLCP and thus in "Ca(2+) sensitization" of contraction. Thin filament regulation includes the possible disinhibition of actin-myosin interactions by phosphorylation of CaD, possibly by mitogen-activated protein (MAP) kinases that are also translocated during adrenergic activation. An hypothesis for the mechanisms of adrenergic activation of small arteries is advanced. This involves asynchronous Ca(2+) waves in individual SMC, synchronous Ca(2+) oscillations (at high levels of adrenergic activation), Ca(2+) sparks, "Ca(2+)-sensitization" by PKC and Rho-associated kinase (ROK), and thin filament mechanisms.


Membrane fluidity regulates development of gonadotrope desensitization to GnRH.
Development of GnRH-mediated gonadotrope desensitization was examined under conditions in which membrane fluidity was altered by temperature and/or chemical means. Cultured pituitary cells were preincubated at temperatures ranging from 4 degrees C to 37 degrees C for 3 h with a desensitizing concentration of GnRH (10(-9) M) or with vehicle alone. Cells were then rinsed and responsiveness assessed by a second 3 h incubation with GnRH at 37 degrees C. As preincubation temperatures decreased from 37 degrees C to 23 degrees C, development of desensitization in gonadotropes was progressively reduced. At 23 degrees C and below, gonadotropes failed to become desensitized to GnRH. Decreases in membrane fluidity occurred over the same temperature range as measured directly by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene incorporated into plasma membrane. When membrane fluidity was increased by incubating cells with the membrane mobilizing agent 2-(2-methoxy-ethoxy)-ethyl-8-(cis-2-n-octylcyclopropyl)-octanoate (A2C), low temperature blockade of GnRH-mediated gonadotrope desensitization was reversed. A2C had no measurable effects on either GnRH receptor binding or number and caused no cytotoxic effects. These studies suggest that development of gonadotropine desensitization to GnRH can be regulated by the state of membrane fluidity.


Schooling and Covid-19: lessons from recent research on EdTech.
The wide-scale global movement of school education to remote instruction due to Covid-19 is unprecedented. The use of educational technology (EdTech) offers an alternative to in-person learning and reinforces social distancing, but there is limited evidence on whether and how EdTech affects academic outcomes. Recently, we conducted two large-scale randomized experiments, involving ~10,000 primary school students in China and Russia, to evaluate the effectiveness of EdTech as a substitute for traditional schooling. In China, we examined whether EdTech improves academic outcomes relative to paper-and-pencil workbook exercises of identical content. We found that EdTech was a perfect substitute for traditional learning. In Russia, we further explored how much EdTech can substitute for traditional learning. We found that EdTech substitutes only to a limited extent. The findings from these large-scale trials indicate that we need to be careful about using EdTech as a full-scale substitute for the traditional instruction received by schoolchildren.


Update on current techniques of myocardial protection.
The spectrum of strategies for myocardial protection has led to the artificial creation of adversarial positions in regard to warm versus cold blood cardioplegia, antegrade versus retrograde delivery, and intermittent versus continuous perfusion. This report reviews the background for the aforementioned methods, that has led to the evolution of an integrated myocardial management technique that combines the advantages of the aforementioned methods to compensate for their individual shortcomings. This approach coordinates the myocardial protective strategies with the continuity of the operation so that the surgical procedure is never interrupted. It provides unimpaired vision, avoids unnecessary ischemia and cardioplegic overdose, allows aortic clamping as soon as cardiopulmonary bypass is started, permits aortic unclamping and discontinuation of bypass shortly after the technical procedure is completed, and minimizes the ration of ischemia and cardiopulmonary bypass. The preliminary results in 1,474 patients from four centers with surgeons participating in the infrastructure of this method are presented.


Studies on the novel anti-staphyloccal compound nematophin.
A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active.


Pediatric residents' career intentions: data from the leading edge of the pediatrician workforce.
To determine factors influencing career choices by pediatric residents and how they may change the future pediatric physician workforce. Societal norms and policy decisions can influence the demographics of residents entering pediatric practice and resident career choices. Although predictors of physician career choice have been identified retrospectively by examining the characteristics of physicians in practice, little work has focused on the job selection factors important to pediatric residents when they make their postresidency career decisions. For 3 consecutive years (1997-1999), the American Academy of Pediatrics surveyed a national sample of 500 third-year residents, totaling 1500 residents. Data on resident characteristics, job selection attitudes, and career decisions were obtained, and trends for the past 3 years were examined. The percentage of residents intending to practice primary care remained constant at around 69% from 1997 through 1999. Female residents, US medical graduates, and residents married to nonphysicians were more likely to report primary care practice as their future clinical goal. These relationships were mediated by higher rates of a primary care practice goal among those who felt geographic location and future colleagues were very important and by lower rates among those who felt acceptable income, teaching opportunities, and research opportunities were very important. Six percent of residents entering general pediatrics were heading to rural locations. With a projected increase in the number of female pediatricians and a decline in international medical graduates, our study suggests that pediatrics may continue to shift toward an increased proportion of general pediatricians. Lifestyle issues are a major factor influencing job choice and must be addressed.


Evaluation of vinburnine in pharmaceuticals by smart spectrophotometric methods; full stability study.
Vinburnine (VNB) is a vinca alkaloid used as a vasodilator to enhance cerebral circulatory insufficiency. It is a cyclic amide containing drug which is expected to be sensitive to hydrolytic degradation. The degradation profile of VNB was studied in this work following ICH recommendations for stability study. The drug was sensitive only to degradation with NaOH with the formation of the carboxylic acid derivative, identified by IR and 1H NMR analyses as 2-((1S,12bS)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizin-1-yl) acetic acid, (DEG). In this study five simple, smart and univariate stability indicating spectrophotometric methods were developed and validated for simultaneous determination of VNB and DEG for the first time. The developed methods include; Dual Wavelength Method (DWM), Dual Wavelength Resolution Method (DWRM), Factorized Absorbance Difference Method (FADM), Advanced Absorbance Subtraction Method (AASM), and Derivative Amplitude Factor Method (DAFM). These methods were capable of determination of VNB and DEG over the ranges of 1-30 and 3-50 µg/mL, respectively. The proposed methods were simple, smart, specific, and could be applied for analyzing synthetic mixtures of VNB and DEG and were successfully applied for determination of the drug in commercially available capsules. The obtained results of these methods were statistically compared with the reported HPLC one using student's-t and F- tests, where no significant difference was observed. Validation of the developed methods was applied according to ICH recommendations and all the results were within the acceptable limits.


Social desirability in the measuring of patient satisfaction after treatment of coloproctologic disorders: on shortcomings of general bipolar satisfaction scales for quality management.
Within the field of medicine, much attention is being paid to quality management, whereby patient satisfaction plays a major role. In order to measure this construct, usually rather general, bipolar rating scales are applied. However, these scales are often susceptible to social desirability biases. Coloproctological patients were asked to complete a questionnaire with ratings of satisfaction and anxiety at two different points of measurement: One group while in treatment (N = 86) and a second group approximately 1 year after their treatment (N = 328). Even when controlling for relevant demographic influences, a clear decrease in intensity of the evaluation ratings is shown when the survey was administered 1 year after release from hospital as compared to during the patients' stay in hospital. For generally formulated scales of patient satisfaction, social desirability constitutes a significant bias. The usual conceptualization of a bipolar continuum of patient satisfaction or dissatisfaction must be renounced. Instead, questionnaires might be constructed in three steps which investigate problem dimensions at a medium level of concreteness. Only in this way can quality management gain credibility and trust within as well as beyond the field of medicine.


Proteoglycans and neoplasia.
There is a growing realization that the whole tumor cell-matrix complex must be investigated in order to fully understand the process of cancer growth and metastasis. Proteoglycans are intrinsic constituents of the cell surface, extracellular matrix, and basement membrane, three logistically and functionally important structures involved in most cellular interactions. Proteoglycans influence the behavior of normal and malignant cells by virtue of their expanded configuration, polyanionic nature and, most of all, by their ability to interact with a variety of cellular products. Consequently, they have been implicated in a number of biological processes including proliferation, recognition, adhesion, and migration. They can serve as links between the extracellular and intracellular environment and thus transduce key biological signals. They can act as receptors for interstitial collagens and other matrix proteins and thus contribute to the organization of pericellular matrix. During neoplastic development there is a profound structural rearrangement of these macromolecules at both the plasma membrane and the pericellular level. Qualitative and quantitative abnormalities in proteoglycan metabolism may contribute to the establishment of some well-known neoplastic properties, including lack of cohesiveness, abnormal assembly of extracellular matrix, abnormal growth, and invasion. The present work will focus on recent advances in our understanding of these complex macromolecules and on some of the alterations associated with the neoplastic phenotype, and will then attempt to elucidate some of the mechanisms regulating these changes.


Role of Hayman technique and its modification in recurrent puerperal uterine inversion.
Acute puerperal uterine inversion is a rare and fatal complication after delivery. The first priority is its rapid management and prevention of postpartum hemorrhage. On rare occasions, there may be recurrence of inversion after reduction. We applied Hayman technique to two cases of recurrent uterine inversion.


Fertility Desires of Adolescent Females: Decreased Desire for Children in Those Identifying as Transgender/Gender Diverse and in Depressed Adolescents.
We aimed to describe fertility desires in healthy adolescent females and to explore associations of fertility desire with conditions and therapies potentially compromising fertility. This was a cross-sectional, anonymous survey. A total of 323 female adolescents aged 13-19 years were recruited from clinic waiting areas at a children's hospital. We oversampled on days when clinics serving adolescents with potential fertility compromise were scheduled. We measured fertility desire by agreement with the statement "I want to have children someday." To measure compromised fertility we asked "In the past year, has a doctor, nurse or other medical professional ever talked to you about the possibility that you may have decreased fertility and may not be able to have your own biological child someday?" To measure depression severity, we used a validated scale, the PHQ-9, scores were dichotomized into no/mild and moderate/severe depression. Mean age was 16.06 ± 1.87 years. Of the 323 participants, 57% identified as Hispanic, 24% as Black, 93.5% as cisgender, 6.5% as transgender/gender diverse, 70% as heterosexual, and 30% as sexual minority. A total of 35% had moderate/severe depression, and 12% had compromised fertility. Overall, 89% wanted children. Fewer transgender/gender diverse than cisgender participants wanted children (67% vs 93%, P < .001), as did fewer with moderate/severe versus no/mild depression (83% vs 93%, P < .05), whereas those with compromised fertility versus those without and heterosexual versus sexual minority participants had similar fertility desires. Transgender/gender diverse identity (odds ratio, 0.33; 95% confidence interval, 0.11-0.97; P < .05) and moderate/severe depression (odds ratio, 0.45; 95% confidence interval, 0.22-0.93; P < .05) were independently associated with lower fertility desire. We found a high overall proportion of female adolescents desiring future children, and only 2 independent predictors of decreased fertility desire, namely, transgender/gender diverse identity and moderate/severe depression.


Risk Reduction Interventions for Human Papillomavirus in Rural Maryland.
Human papillomavirus (HPV) is largely vaccine preventable. The Healthy People 2020 target goal for vaccine administration is 80%. Current United States (U. S.) rates are far lower primarily because of vaccine hesitancy and lack of provider recommendation. Implement a risk reduction initiative to increase HPV vaccine rates in females aged 12-26 in five rural counties in Maryland. A convenience sample from a rural community screened an HPV documentary movie, Questionnaire responses pre- and postscreening were surveyed for impact on vaccine readiness. Postscreening focus group comments were analyzed for common themes. Females aged 12-26 from a University Medical Group Women's Health Center located in rural Maryland were targeted. Chart review of immunization records 90 days pre- and postprovider vaccine recommendation demonstrated impact. Public awareness events have the potential to impact HPV vaccine hesitancy, but this research did not achieve statistical significance. Direct provider to patient recommendations resulted in a 15% increase in HPV immunizations. Education of vaccine-eligible individuals should be undertaken. Providers who recommend administration of the vaccine significantly increase immunization rates.


Inner nuclear layer and olfactory threshold are interlinked and reflect inflammatory activity in multiple sclerosis.
Retinal inner nuclear layer (INL) and olfactory threshold (OT) are associated with inflammatory activity in multiple sclerosis (MS). The study aims to investigate (a) whether there is an association of INL and OT in MS and (b) if changes in INL and OT follow a time pattern in relation to MS relapse. We assessed INL by optical coherence tomography and OT by Sniffin' Sticks in three different cohorts: a cross-sectional MS cohort (n = 260), a longitudinal, 3-year cohort of MS (n = 141) and healthy controls (n = 30), and a longitudinal, 24-weeks cohort with acute MS relapse (n = 28) and stable MS controls (n = 27). Cross-sectionally, INL and OT were strongly correlated with number but not localization of relapse in the previous 12 months and INL correlated with OT. Longitudinally, INL was thicker and OT score was lower short term in times of relapse activity, but not long term and independent of relapse localization. In acute MS relapse, INL and OT were altered compared with stable MS, again, independent of relapse localization resolving over 12-24 weeks with faster approximation to stable MS after escalation of disease-modifying treatment. INL and OT are interlinked markers of short-term inflammatory activity, following a nearly congruent time pattern and independent of relapse localization, possibly reflecting a proinflammatory state within the central nervous system.


Synthesis and caspase-3 inhibitory activity of 8-sulfonyl-1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines.
A convenient synthesis of novel 8-sulfonyl-1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines is described. As key steps to assemble the target molecular scaffold, our method features (a) Pfitzinger reaction of isatin-5-sulfonate 1 with methyl 3-oxo-3-phenylpropanoate, (b) formation of 1-(1H-pyrazol-4-yl)-1H-pyrrole-2,5-dione intermediate 5, and (c) reaction of sulfinic acid 9 with acrylate or methylacrylate leading to the corresponding sulfonyl propionates. Two compounds, ester 11 and morpholide 13, have been identified as potent inhibitors of caspase-3 with IC50 = 6 nM. Our primary data suggest noncompetitive and reversible character of caspase-3 inhibition.


Optimal two-stage genotyping in population-based association studies.
We propose a cost-effective two-stage approach to investigate gene-disease associations when testing a large number of candidate markers using a case-control design. Under this approach, all the markers are genotyped and tested at stage 1 using a subset of affected cases and unaffected controls, and the most promising markers are genotyped on the remaining individuals and tested using all the individuals at stage 2. The sample size at stage 1 is chosen such that the power to detect the true markers of association is 1-beta(1) at significance level alpha(1). The most promising markers are tested at significance level alpha(2) at stage 2. In contrast, a one-stage approach would evaluate and test all the markers on all the cases and controls to identify the markers significantly associated with the disease. The goal is to determine the two-stage parameters (alpha(1), beta(1), alpha(2)) that minimize the cost of the study such that the desired overall significance is alpha and the desired power is close to 1-beta, the power of the one-stage approach. We provide analytic formulae to estimate the two-stage parameters. The properties of the two-stage approach are evaluated under various parametric configurations and compared with those of the corresponding one-stage approach. The optimal two-stage procedure does not depend on the signal of the markers associated with the study. Further, when there is a large number of markers, the optimal procedure is not substantially influenced by the total number of markers associated with the disease. The results show that, compared to a one-stage approach, a two-stage procedure typically halves the cost of the study.


Subject-specific musculoskeletal modeling in the evaluation of shoulder muscle and joint function.
Upper limb muscle force estimation using Hill-type muscle models depends on musculotendon parameter values, which cannot be readily measured non-invasively. Generic and scaled-generic parameters may be quickly and easily employed, but these approaches do not account for an individual subject's joint torque capacity. The objective of the present study was to develop a subject-specific experimental testing and modeling framework to evaluate shoulder muscle and joint function during activities of daily living, and to assess the capacity of generic and scaled-generic musculotendon parameters to predict muscle and joint function. Three-dimensional musculoskeletal models of the shoulders of 6 healthy subjects were developed to calculate muscle and glenohumeral joint loading during abduction, flexion, horizontal flexion, nose touching and reaching using subject-specific, scaled-generic and generic musculotendon parameters. Muscle and glenohumeral joint forces calculated using generic and scaled-generic models were significantly different to those of subject-specific models (p<0.05), and task dependent; however, scaled-generic model calculations of shoulder glenohumeral joint force demonstrated better agreement with those of subject-specific models during abduction and flexion. Muscles in generic musculoskeletal models operated further from the plateau of their force-length curves than those of scaled-generic and subject-specific models, while muscles in subject-specific models operated over a wider region of their force length curves than those of the generic or scaled-generic models, reflecting diversity of subject shoulder strength. The findings of this study suggest that generic and scaled-generic musculotendon parameters may not provide sufficient accuracy in prediction of shoulder muscle and joint loading when compared to models that employ subject-specific parameter-estimation approaches.


Mammalian complex I: a regulable and vulnerable pacemaker in mitochondrial respiratory function.
In this paper the regulatory features of complex I of mammalian and human mitochondria are reviewed. In a variety of mitotic cell-line cultures, activation in vivo of the cAMP cascade, or direct addition of cAMP, promotes the NADH-ubiquinone oxidoreductase activity of complex I and lower the cellular level of ROS. These effects of cAMP are found to be associated with PKA-mediated serine phosphorylation in the conserved C-terminus of the subunit of complex I encoded by the nuclear gene NDUFS4. PKA mediated phosphorylation of this Ser in the C-terminus of the protein promotes its mitochondrial import and maturation. Mass-spectrometry analysis of the phosphorylation pattern of complex I subunits is also reviewed.


[Brachial plexus. Anesthesia and analgesia].
This review explains the different approaches to the brachial plexus (posterior cervical, interscalene, supra- and infraclavicular, and axillary) and their advantages and disadvantages (indications, contraindications, and complications) for surgery and postoperative or chronic pain management. One of the focussed areas of this review is the use of continuous catheter techniques. Information about the most commonly used local anesthetics as well as adjuncts suggested in the literature is summarized. As essential components for the success of those techniques, organizational and documentation requirements are described. In summary, regional techniques for single shot or continuous block of the brachial plexus are an efficient and safe way of providing anesthesia and analgesia for surgery or pain in the region of the shoulder, arm, or hand.


Alteration of HLA-F and HLA I antigen expression in the tumor is associated with survival in patients with esophageal squamous cell carcinoma.
Alteration of human leukocyte antigen (HLA) expression, such as decreased HLA I (HLA-A, -B and -C) antigens and elevated nonclassical HLA I antigens (HLA-E, -F and -G), was reported to have an unfavorable prognosis in various cancers. In our study, HLA-F expression in 105 primary esophageal squamous cell carcinoma (ESCC) lesions and 62 case-matched adjacent normal tissues, and HLA I antigens among 68 cases were analyzed by immunohistochemistry. Data revealed that HLA-F expression was observed in 58.1% (61/105) of the ESCC lesions and in 54.8% (34/62) of the normal esophageal tissues. Among the 62 case-matched samples, HLA-F expression (lesion vs. normal tissue) was upregulated, unchanged and downregulated in 13 (21.0%), 6 (9.6%) and 43 (69.4%) cases, respectively. Patients with HLA-F positive had a worse survival than those with HLA-F negative (p = 0.040). Patients with upregulated HLA-F expression (lesion vs. normal tissue) had significantly worse survival than those with HLA-F unchanged and downregulated (p = 0.010). Furthermore, decreased HLA I expression was observed in 41.2% (28/68) patients and was with worse prognosis in comparison to those with preserved HLA I expression (p = 0.001). Multivariate analysis using Cox's proportional hazards model revealed that upregulated HLA-F expression (p = 0.026) and downregulated HLA I expression (p = 0.013) could be an independent unfavorable prognostic factor. In conclusion, our study provided the evidence that alteration of HLA I and HLA-F antigen expression was associated with survival in patients with ESCC.


Meteorological parameters and the pattern of dermatology clinic attendance through a calendar year: a Sri Lankan experience.
Dermatology clinic attendance at a major hospital depends on many factors. We planned to determine the monthly variations of skin disease presentation and whether there was a correlation between the clinic attendance pattern of skin diseases and meteorological parameters. The dermatology clinic attendance pattern was studied prospectively throughout a calendar year on a monthly basis at the dermatology clinic of the General Hospital, Matara, Sri Lanka. One thousand and twenty-three consecutive dermatology consultations in the private sector were also analyzed for comparison. Meteorological data were obtained from the Government Department of Meteorology. A total of 7419 first visit patients were seen at the general hospital. July and September recorded the highest number (718 each) and April recorded the lowest (426). The lowest relative humidity was in March (75%) and the highest in October (87%). The average maximum temperature ranged from 31.2 degrees C (April) to 29.1 degrees C (August, September). Average rainfall was between 622 mm (October) and 59 mm (June). Of the diseases considered to have a relationship to meteorological parameters, miliaria showed the biggest fluctuation (27 in May to zero in August). Photodermatitis was highest in August. The variation in asteatotic dermatitis patients was minimal. Dermatitis and fungal diseases comprised over 50% of clinic attendance throughout the year in both the state and private sectors. Although there were significant fluctuations in several disease categories in different months, a clear linear correlation between meteorological parameters and the disease presentation pattern could not be established. This could be due to the narrow range of variation in the meteorological parameters in the geographic area and the multiple variables involved in persons presenting to the dermatology clinic.


[The method of the isolated perfused rat heart using the Langendorff model in nutrition research].
The preparation technique and principle of the Langendorff model for the perfusion of isolated rat heart, as well as the assessment of circulatory and metabolic parameters in this model are described, and the role of the model in metabolic and nutrition research is discussed.


The effect of treatment with interferon-gamma on type II collagen-induced arthritis.
We have investigated the effects of recombinant murine interferon-gamma (rIFN-gamma) on type II collagen-induced arthritis (CA) in DBA/l mice. Therapeutic as well as prophylactic treatment with subcutaneous rIFN-gamma, at 10(5) U/mouse six times a week, inhibited the development of CA without any obvious side effects. The accompanying suppression of anti-CII antibody responses may partly explain the inhibition of CA by rIFN-gamma. The possible role of the anti-inflammatory effect of systemic IFN-gamma in the inhibition of CA is discussed.


Mechanical Thrombectomy in Stroke from Infective Endocarditis: Case Report and Review.
To characterize outcomes after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) from infective endocarditis. Case report and review of published cases. We report the case of a 59-year-old woman with fungal endocarditis who developed AIS from a proximal middle cerebral artery (MCA) embolus. She underwent MT, with good outcome. An additional 25 similar cases were identified from 14 publications. Among the 26 cases analyzed (mean [SD] age, 55 [18.7] years, 42% women), the MCA was the most common site of arterial occlusion. Four patients received intravenous tissue plasminogen activator treatment before MT. The median admission NIH Stroke Scale score (NIHSSS) was 15.5 [interquartile range 9.75-19.25] and the median post-procedure NIHSSS was 2 [interquartile range .75-6]. No patient developed symptomatic intracerebral hemorrhage. MT appears to be a safe and effective therapeutic option in infective endocarditis-related AIS with proximal-artery occlusion.


Anguilla anguilla L. antioxidants responses to in situ bleached kraft pulp mill effluent outlet exposure.
This study assesses the antioxidant enzymes activities viz., catalase, glutathione peroxidase, glutathione S-transferase and nonenzymatic antioxidant molecule such as glutathione in Anguilla anguilla L. gill, kidney and liver in response to 8- and 48-h exposure to bleached kraft pulp mill effluent (BKPME). A. anguilla were caged and plunged at three different sites-50 (Site 1), 100 (Site 2) and 2000 m (Site 3) away from the closed BKPME outlet. A significant gill (8 and 48 h) and kidney (48 h) catalase activity decrease was observed at site 2 exposure whereas liver showed a significant increase in catalase activity after 8 and 48 h to site 1 exposure. Glutathione peroxidase (GPX) activity was significantly decreased in gill after 8-h exposure to site 1 and 48-h exposures to sites 1 and 2, respectively. Concerning gill, kidney and liver glutathione S-transferase (GST) activity, a significant gill GST activity decrease after 8 h at site 2 and 48 h at sites 1 and 2 was observed; in kidney, a significant decrease in its activity was observed after 48 h at sites 1 and 2, respectively, whereas in liver, the decrease was significant only at site 2 after 48-h exposure. The in situ BKPME exposure caused a significant total gill and kidney reduced glutathione (GSH) decrease after 8 h at site 2 exposure and after 48 h at site 1 and 2 exposures, respectively. However, a biphasic response was observed in liver, i.e. initial significant increase after 8 h at site 2 followed by a significant decrease after 48 h to the same site exposure. The enzymatic and nonenzymatic antioxidants pattern in gill and kidney, as observed in this study, was different than liver, demonstrating that the liver was more resistant to oxidative damage than gill and kidney. In addition, A. anguilla gill, kidney and liver antioxidants adaptation potentials may serve as a surrogate biomarker to BKPME exposure.


Retracted: Analysis and Research on Audience Satisfaction of Performing Arts Projects in Tourist Scenic Spots Based on the ASCI Model and Big Data.
[This retracts the article DOI: 10.1155/2022/5907900.].


Investigation of Foscan interactions with plasma proteins.
The present study investigates the interaction of the second generation photosensitizer Foscan with plasma albumin and lipoproteins. Spectroscopic studies indicated the presence of monomeric and aggregated Foscan species upon addition to plasma protein solutions. Kinetics of Foscan disaggregation in albumin-enriched solutions were very sensitive to the protein concentration and incubation temperature. Kinetic analysis demonstrated that two types of Foscan aggregated species could be involved in disaggregation: dimers with a rate constant of k1 = (2.30+/-0.15) x 10(-3) s(-1) and higher aggregates with rate constants varying from (0.55+/-0.04) x 10(-3) s(-1) for the lowest to the (0.17+/-0.02) x 10(-3) s(-1) for the highest albumin concentration. Disaggregation considerably increased with the temperature rise from 15 degrees C to 37 degrees C. Compared to albumin, Foscan disaggregation kinetics in the presence of lipoproteins displayed poorer dependency on lipoprotein concentrations and smaller variations in disaggregation rate constants. Gel-filtration chromatography analysis of Foscan in albumin solutions demonstrated the presence of aggregated fraction of free, non-bound to protein Foscan and monomeric Foscan, bound to protein.


Depression, Diabetes Mellitus and Mortality in Older Adults: A National Cohort Study in Taiwan.
Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period. A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups. During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02-3.03), 1.95 (95% CI: 1.63-2.32), and 1.23 (95% CI: 1.09-1.39), respectively. The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.


Synergetic Effect of Ultrasound, the Heterogeneous Fenton Reaction and Photocatalysis by TiO₂ Loaded on Nickel Foam on the Degradation of Pollutants.
The synergistic effect of ultrasound, the heterogeneous Fenton reaction and photocatalysis was studied using a nickel foam (NF)-supporting TiO₂ system and rhodamine B (RhB) as a target. The NF-supporting TiO₂ system was prepared by depositing TiO₂ on the skeleton of NF repeatedly and then calcining it. To optimize the conditions and parameters, the catalytic activity was tested in four systems (ultrasound alone (US), nickel foam (NF), US/NF and NF/US/H₂O₂). The optimal conditions were fixed at 0.1 g/mL NF, initial 5.00 mg/L RhB, 300 W ultrasonic power, pH = 3 and 5.00 mg/L H₂O₂. The effects of the dissolution of nickel from NF and quenching of the Fenton reaction were studied on degradation efficiency. When the heterogeneous Fenton reaction is combined with TiO₂-photocatalysis, the pollutant removal efficiency is enhanced significantly. Through this synergistic effect, 22% and 80% acetochlor was degraded within 10 min and 80 min, respectively.


Structural stability and reversible unfolding of recombinant porcine S100A12.
Porcine S100A12 is a member of the S100 proteins, family of small acidic calcium-binding proteins characterized by the presence of two EF-hand motifs. These proteins are involved in many cellular events such as the regulation of protein phosphorylation, enzymatic activity, protein-protein interaction, Ca2+ homeostasis, inflammatory processes and intermediate filament polymerization. In addition, members of this family bind Zn2+ or Ca2+ with cooperative effect on binding. In this study, the gene sequence encoding porcine S100A12 was obtained by the synthetic gene approach using E. coli codon bias. Additionally, we report a thermodynamic study of the recombinant S100A12 using circular dichroism, fluorescence and isothermal titration calorimetry. The results of urea and temperature induced unfolding and refolding processes indicated a reversible two-state process. Also, the ANS fluorescence studies showed that in presence of divalent ions the protein exposes hydrophobic sites which could facilitate the interaction with other proteins and trigger the physiological responses.


Intrinsic rate of natural increase in Neotropical forest mammals: relationship to phylogeny and diet.
The relationship of diet and phylogeny to the intrinsic rate of population increase (r max) was examined in a sample of 39 mammalian species that live in Neotropical forests. Diets of species did not predict their r max, contrary to published predictions based on associations between basal metabolic rate and diet and between basal metabolic rate and r max. Phylogeny did however, apparently because life history characteristics and susceptibility to predation vary predictably with phylogeny and with one another.


Non-HLA Antibodies and Their Role in Highly Sensitized Patients.
The role of non-HLA antibody is gaining special attention in solid-organ transplantation and in highly sensitized (HS) patients because of its potential involvement in graft loss (GL) and/or antibody-mediated rejection (ABMR). The identification of non-HLA antibodies while listed may provide deeper information about the increased immunologic risk prior to transplant. We aimed to identify non-HLA antibodies pretransplant that could involve GL in HS patients. Nineteen pretransplant samples from HS patients who underwent transplant at the Marqués de Valdecilla University Hospital were studied for both HLA antibodies and a panel of 39 non-HLA antigens analyzed based on Luminex platform. Eleven patient (57.9%) maintained the graft (KT group), whereas 8 (42.1%) had a GL within a median of 30 days. The median fluorescent intensity (MFI) of the 39 non-HLA antigens were compared within the groups, obtaining a statistically significant differences in protein tyrosine phosphatase receptor type N (P < .04) with a MFI mean of 1408 vs 4931 for KT and GL groups, respectively. However, no significant differences were observed in non-HLA MFI between ABMR and non-ABMR KT recipients. The presence of non-HLA antibodies in HS is high. The levels of anti-protein tyrosine phosphatase receptor type N before transplant could indicate a potential risk of GL, although longitudinal studies with large number of cases are needed to define anti-non-HLA profiles of risk of ABMR.


Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women.
In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11-21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL2 and HDL3, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect.


Colocalisation and covariation of c-JUN transcription factor with galanin in primary afferent neurons and with CGRP in spinal motoneurons following transection of rat sciatic nerve.
The expression of galanin (GAL) in L5 dorsal root ganglia (DRG) and calcitonin gene-related peptide (CGRP) in motoneurons (MN) of lumbar spinal cord and their colocalisation with the nuclear c-JUN protein was investigated by immunocytochemistry following transection of rat sciatic nerve. Expression of c-JUN in L5 DRG neurons increased 10 h following transection. Between 24 h and 10 days 64%-72% of all neurons were labelled. After 50 and 150 days, the end of the observation period, 62% and 27%, respectively, of neurons were labelled by c-JUN. Expression of GAL started after 24 h, reached a maximum between 2 and 10 days in 40-50% of all neurons and persisted in 37% up to 50 days. After 150 days, GAL-IR had returned to basal levels. Between 24 h and 150 days, 75%-86% of all GAL positive neurons showed a nuclear c-JUN immunoreactivity, the maximal number was visible between 2 and 10 days. After 30 days, small diameter neurons showed a slightly increased colocalisation of GAL and c-JUN compared to large diameter neurons. In motoneurons (MN) of lumbar spinal cord of untreated rats, c-JUN was predominantly visible in small diameter MN. The number of c-JUN labelled MN raised 15 h following sciatic nerve transection in both small and large diameter MN. It reached its maximum after 2 days and declined after 40 days. CGRP showed basal expression exclusively in large MN. Its expression raised after 20 h, showed a maximum after 48 h and returned to control levels after 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)


Rapid drop in infant blood lead levels during the transition to unleaded gasoline use in Santiago, Chile.
This study was conducted to relate blood lead levels in infants to changes in lead emissions in Santiago, Chile, a heavily polluted setting where leaded gasoline began to be replaced with unleaded gasoline in 1993. Over an 18-mo period, 422 infants had blood lead levels, cotinine, and iron status determined at 12 mo. Blood lead levels fell at an average rate of 0.5 microg/dl every 2 mo, from 8.3 to 5.9 microg/dl, as the city experienced a net fall of 30% in the quantity of leaded gasoline sold. Time progression, car ownership, serum cotinine, and type of housing were significantly associated with a blood lead level > or = 10 microg/dl. In this study, the authors demonstrated that infant blood lead levels, even if relatively low, can drop very rapidly in conjunction with decreases in environmental lead exposure.


Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans.
Recently it was reported that the implantation of octacalcium phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd.


Molecular cloning of the gene that codes for the pyruvate kinase of Bacillus subtilis: primary characterization of a strain carrying this gene insertionally inactivated.
We have cloned and characterized the pykA gene from Bacillus subtilis which codes for a pyruvate kinase (PK) enzyme. This gene has been located downstream a putative phosphofructokinase gene, suggesting that they are part of the same operon. The deduced amino acid sequence of this PK showed a strong similarity to other PKs from different sources; however, as it has been found in other bacilli, the B. subtilis pykA enzyme had an extra C-terminal sequence consisting of about 112 amino acid residues. This gene was insertionally inactivated at the chromosomal level, with an antibiotic resistance marker. The analysis of this mutation in wild type and pts- backgrounds, indicated that B. subtilis has no other pyruvate kinase activity capable of complementing the absence of PykA.


Recent advances on nanomaterials for antibacterial treatment of oral diseases.
An imbalance of bacteria in oral environment can lead to a variety of oral diseases, such as periodontal disease, dental caries, and peri-implant inflammation. In the long term, in view of the increasing bacterial resistance, finding suitable alternatives to traditional antibacterial methods is an important research today. With the development of nanotechnology, antibacterial agents based on nanomaterials have attracted much attention in dental field due to their low cost, stable structures, excellent antibacterial properties and broad antibacterial spectrum. Multifunctional nanomaterials can break through the limitations of single therapy and have the functions of remineralization and osteogenesis on the basis of antibacterial, which has made significant progress in the long-term prevention and treatment of oral diseases. In this review, we have summarized the applications of metal and their oxides, organic and composite nanomaterials in oral field in recent five years. These nanomaterials can not only inactivate oral bacteria, but also achieve more efficient treatment and prevention of oral diseases by improving the properties of the materials themselves, enhancing the precision of targeted delivery of drugs and imparting richer functions. Finally, future challenges and untapped potential are elaborated to demonstrate the future prospects of antibacterial nanomaterials in oral field.


[Disseminated intravascular coagulation in a cow of the breed "Deutsche Rotbunte" with fungal mastitis and abomasal displacement].
This report describes a 7-year-old cow of the breed "Deutsche Rotbunte" which was brought into the clinic because of intense fungal mastitis and left displacement of the abomasum. A disseminated intravascular coagulopathy (DIC) was determined by coagulation assays and verified by necropsy and histopathological examination.


Improving properties of the nucleobase analogs T-705/T-1105 as potential antiviral.
In this minireview we describe our work on the improvement of the nucleobase analogs Favipiravir (T-705) und its non-fluorinated derivative T-1105 as influenza and SARS-CoV-2 active compounds. Both nucleobases were converted into nucleotides and then included in our nucleotide prodrugs technologies cycloSal-monophosphates, DiPPro-nucleoside diphosphates and TriPPPro-nucleoside triphosphates. Particularly the DiPPro-derivatives of T-1105-RDP proved to be very active against influenza viruses. T-1105-derivatives in general were found to be more antivirally active as compared to their T-705 counterpart. This may be due to the low chemical stability of all ribosylated derivatives of T-705. The ribosyltriphosphate derivative of T-1105 was studied for the potential to act as a inhibitor of the SARS-CoV-2 RdRp and was found to be an extremely potent compound causing lethal mutagenesis. The pronucleotide technologies, the chemical synthesis, the biophysical properties and the biological effects of the compounds will be addressed as well.


[Treatment of chronic lupus erythematosus with sulfasalazine in 18 patients: reappraisal].
To evaluate the efficacy and the tolerance of sulfasalazine in the treatment of chronic lupus erythematosus (CLE). We prescribed sulfasalazine (2 g/d) for 18 patients with severe CLE, all of whom had contraindications for or treatment failure with antimalarial drugs and thalidomide. This study analyses their response to treatment, duration of therapy, reasons for stopping, adverse effects, and the influence of the N-acetyltransferase 2 (NAT2) phenotype. We observed 10 complete and 3 partial responses, and 4 patients maintained complete response for at least 7 years. Eight patients experienced adverse effects, and 2 needed to stop treatment (because of photosensitization and development of antinuclear antibodies). All side effects occurred in the first 3 months of treatment. None of the 18 patients developed systemic lupus erythematosus. Of the 10 complete responders, 9 were rapid acetylators (RA), while 4 of the 5 who failed to respond were slow acetylators (SA). Leukopenia and photosensitization were observed in SA patients, while different side effects occurred in RA patients (headaches, diarrhea, moderate increase in liver enzymes and antinuclear antibodies). These findings confirm our earlier reports and demonstrate that sulfasalazine can be used successfully to treat severe CLE. NAT2 genotyping before initiating treatment helps to identify potential responders and avoid side effects. In RA patients, sulfasalazine can be an alternative to thalidomide after antimalarial drugs, whereas in SA patients, it should remain a third-line treatment, to be used only after antimalarials and thalidomide.


Additional Low-Voltage-Area Ablation in Patients With Paroxysmal Atrial Fibrillation: Results of the Randomized Controlled VOLCANO Trial.
Background The efficacy of low-voltage-area (LVA) ablation has not been well determined. This study aimed to investigate the efficacy of LVA ablation in addition to pulmonary vein isolation on rhythm outcomes in patients with paroxysmal atrial fibrillation (AF). Methods and Results VOLCANO (Catheter Ablation Targeting Low-Voltage Areas After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation Patients) trial included paroxysmal AF patients undergoing initial AF ablation. Of 398 patients in whom a left atrial voltage map was obtained after pulmonary vein isolation, 336 (85%) had no LVA (group A). The remaining 62 (15%) patients with LVAs were randomly allocated to undergo LVA ablation (group B, n=30) or not (group C, n=32) in a 1:1 fashion. Primary end point was 1-year AF-recurrence-free survival rate. No adverse events related to LVA ablation occurred. Procedural (124±40 versus 95±33 minutes, P=0.003) and fluoroscopic times (29±11 versus 24±8 minutes, P=0.034) were longer in group B than group C. Patients with LVAs demonstrated lower AF-recurrence-free survival rates (88%) than those without LVA (B, 57%, P<0.0001; C, 53%, P<0.0001). However, LVA ablation in addition to pulmonary vein isolation did not impact AF-recurrence-free survival rate (group B versus C, P=0.67). Conclusions The presence of LVA was a strong predictor of AF recurrence after pulmonary vein isolation in patients with paroxysmal AF. However, LVA ablation had no beneficial impact on 1-year rhythm outcomes. Registration URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023403.


The apical compartment: trafficking pathways, regulators and scaffolding proteins.
Defects in the trafficking of apical membrane proteins in polarized epithelial cells are often associated with diseases, including cystic fibrosis, Liddle's syndrome, nephrogenic diabetes insipidus and Dubin-Johnson syndrome. In recent years, we have learned much about the specialized apical trafficking pathways in polarized cells. Many laboratories have identified signals that direct proteins within these pathways and have defined protein interactions that mediate specific steps in the sorting and stabilization of these proteins. In addition, many cytosolic proteins, including lipid kinases, GTPases, ATPases and scaffolding/adaptor proteins that lack enzymatic activity, regulate the trafficking of proteins through these pathways. Recent advances in the field include the role of small GTPases, unconventional myosins and lipid kinases in apical endocytosis and transcytosis, and the identification of PDZ proteins that regulate apical membrane trafficking of receptors, transporters and ion channels.


Infections associated with the genus Edwardsiella: the role of Edwardsiella tarda in human disease.
The role of the genus Edwardsiella in human illness is reviewed. Of the three recognized species, only Edwardsiella tarda has been demonstrated to be pathogenic for humans. Chief infections associated with this species include bacterial gastroenteritis, wound infections such as cellulitis or gas gangrene associated with trauma to mucosal surfaces, and systemic disease such as septicemia, meningitis, cholecystitis, and osteomyelitis. Risk factors that are associated with E. tarda infections include exposure to aquatic environments or exotic animals (e.g., reptiles or amphibia), preexisting liver disease, conditions leading to iron overload, and dietary habits (e.g., raw fish ingestion). Although studies indicate that this bacterium is susceptible to most commonly prescribed antibiotics, fatal gastrointestinal and extraintestinal infections have been described.


Reversibility of protein-energy malnutrition in a group of chronically-ill elderly outpatients.
Nutritional status was studied in 23 elderly (74 +/- 1 years), malnourished outpatients with non-malignant diseases. The patients' recollections and medical records indicated a gradual weight loss of approximately 25% in the preceding 2-15 years; only a small amount (6%) was lost during the final 6 months. At a re-examination after 3 months, all patients were still malnourished but in general the depletion had decreased. An elevated level of serum orosomucoid (orosomucoid positive) was used as evidence of an on-going inflammatory process. The 14 orosomucoid negative patients displayed a more pronounced improvement in their nutritional status than those who were orosomucoid positive. 15 patients were prescribed a protein and energy enriched formula (40 g protein and 400/1.7 kcal/MJ per day). The orosomucoid positive and orosomucoid negative groups did not differ in number of subjects prescribed supplementation. During the follow-up period the patients that were recommended supplementation showed a more prominent improvement in their nutritional status than the 'non-supplemented' subjects. Discriminant analysis revealed that prescription of oral supplementation and, to a lesser extent, serum orosomucoid concentrations within the reference range favoured nutritional repletion. The most pronounced recovery was registered in orosomucoid negative patients who had been prescribed supplementation.