Come Together: Molecular Details into the Synergistic Effects of Polymer-Surfactant Adsorption at the Oil/Water Interface.
The synergistic adsorption of polymers with surfactants at the oil/water interface has applications that range from oil remediation to targeted drug delivery. However, the inherent inaccessibility of the buried oil/water interface has challenged the development of a molecular-level understanding of the structure-function relationship of these systems. This study uses vibrational sum frequency spectroscopy to examine the molecular structure, orientation, and electrostatic effects of synergistic adsorption of the surfactant cetrimonium bromide (CTAB) and polymer poly(acrylic acid) (PAA) at a planar oil/water interface. Results demonstrate that coadsorption leads to a high degree of interfacial ordering of both the polymer and the surfactant and a subsequent alteration of the interfacial water bonding and orientation. Complementary zeta potential measurements provide further information about how surface partitioning of a charged polymer and a surfactant relates to their aggregation behavior in a bulk solution. With the CTAB concentration fixed but the PAA concentration variable, hydrophobic interactions result in a modest synergic coadsorption when CTAB is in excess. However, when the PAA carboxylate monomer concentration approaches that of CTAB, the electrostatic interactions between the components change the structure and increase the amount of adsorbed PAA until the interfacial charge is neutralized. This work reveals that the synergic adsorption behavior of this model polyacid/surfactant system arises from a combination of concentration-dependent hydrophobic and electrostatic forces working in tandem.


Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.
Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high-protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus provides essential information for the development of optimal LNAA supplementation as an alternative dietary treatment strategy to optimize neurocognitive outcome in patients with phenylketonuria.


Excess mortality associated with blindness in leprosy patients in Korea.
Vision loss and blindness are potential complications of leprosy. There is little data available to indicate the impact of eye complications on life expectancy and quality of life. We sought to determine the relative risk of death in blind leprosy patients compared to nonblind leprosy patients. A population-based ocular survey of 510 mycobacteriologically negative leprosy patients in rural South Korea, conducted in 1988, formed the study population. After a 7-year period patients were traced to determine their status (alive, dead, lost to follow up). Blind patients showed a 4.8-fold risk of death, even after adjusting for other factors, compared to nonblind patients. Young blind leprosy patients had the highest relative risk of death. Excess mortality was not associated with any specific cause of blindness, ocular pathology, or type of disease. Findings from our study suggest that all leprosy patients with ocular disabilities (including those released from antileprosy treatment) should be targeted to receive eye care to prevent vision loss. Particular emphasis should be placed on young patients.


Selective antitumor activity in vitro from marine algae from Japan coasts.
In vitro selective antitumor activity was tested as a general screening parameter for biologically active substances from a wide range of species of seaweed, 1446 samples of 306 species of marine algae from Japan's coasts. The algae extracts were prepared successively first by phosphate buffered saline (PBS) and then by methanol, and then tested for in vitro selective antitumor activity against murine lymphoid leukemia L1210 cells and for low cytotoxic activity against NIH-3T3 normal cells. Strong cytotoxic activity against L1210 cells was found in 47 species of algae, also showing similar cytotoxicity to mouse NIH-3T3 normal cells. However, four species of green algae showed strong activity specifically against L1210 cells, with low cytotoxicity to normal cells. Such selective activity was conspicuous in two brown and two green algae extracts. In particular, methanol extracts from the green alga, Cladophoropsis vaucheriaeformis, exhibited high viability (86%) to normal cells, showing selective cytotoxicity to tumor cells. This alga extract was no cytocidalic, but cytostatic against L1210 cells. Furthermore, the results of a cytotoxic spectrum test with 9 cell lines including those of L1210 and NIH-3T3 demonstrated that this extract acted strongly only against leukemic cell lines L1210 and P388.


A curious case of 'COVID toes' in pregnancy.
The novel coronavirus of 2019 (COVID-19) can affect multiple organ systems with a wide spectrum of illness severity. Its effect on the respiratory tract is well-documented and has resulted in considerable excess mortality worldwide. However, observed cutaneous manifestations of COVID-19 are rising, ranging from short-lived viral exanthems to vesicular eruptions and urticaria. An unusual subgroup of these manifestations - pseudo-chilblains, also referred to as pernio-like lesions or 'COVID toes' - describes the acral areas of erythema and oedema that can affect young individuals following COVID-19. We present a case associated with pustule and vesicle formation occurring in the context of pregnancy.


A comprehensive linkage map of the pig based on a wild pig-Large White intercross.
A comprehensive linkage map, including 236 linked markers with a total sex-average map length of about 2300 cM, covering nearly all parts of the pig genome has been established. Linkage groups were assigned to approximately all 18 autosomes, the X chromosome and the X/Y pseudoautosomal region. Several new gene assignments were made including the assignment of linkage group U1 (EAK-HPX) to chromosome 9. The linkage map includes 77 types I loci informative for comparative mapping and 72 in situ mapped markers physically anchoring the linkage groups on chromosomes. A highly significant heterogeneity in recombination rates between sexes was observed with a general tendency towards an excess of female recombination. The average ratio of female to male recombination was estimated at 1.4:1 but this parameter varied between chromosomes as well as between regions within chromosomes. An intriguing finding was that blood group loci were overrepresented at the distal ends of linkage groups.


[Voice Handicap Index – efficiency and correlation between physical, functional and emotional aspects and voice disorders].
Voice disorders are a very common medical problem among people whose occupation requires overusing their voice as a working tool. The lack of correct voice projection and phonation training courses is the reason why voice disorders are commonly found throughout society. In order to identify the reasons causing voice disorders, the Voice Handicap Index (VHI) may be used. As an instrument of iterative testing, the VHI allows not only self -assessment of someone's voice, but it is also a very helpful research tool during veri􀏐ication of the effects of voice rehabilitation.


Long-term exposure to ambient ozone and mortality in a population-based cohort of South Korea: Considering for an alternative exposure time metric.
Studies on the health effects of long-term ozone exposure remain limited with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone and mortality in South Korea, using different exposure metrics. We also examined whether heterogeneity between previous studies was due to the different exposure metrics. The study population comprised 179,806 participants from the National Health Insurance Service-National Sample Cohort (2002-2015) residing in seven major cities in South Korea. Several ozone exposure metrics (year-round 24-h, year-round 8-h, warm-season 24-h, and warm-season 8-h) were calculated. Time-varying Cox proportional hazards models were used to estimate the association between ozone and all-cause and cause-specific mortalities. Random-effect meta-analysis and meta-regression analysis were performed to pool the effect estimates of previous studies and examine whether the exposure metric can explain the between-study heterogeneity. The hazard ratios (HRs) per 10 ppb increment in year-round 24-h ozone for all-cause (HR, 1.18; 95% CI, 1.07-1.29) and circulatory (HR, 1.52; 95% CI, 1.25-1.84) mortality were higher than those of the other metrics. Year-round 8-h ozone exhibited the largest association with respiratory mortality (HR, 1.43; 95% CI, 1.04-1.96). A meta-analysis of 29 previous studies and the present study showed the largest HR for all-cause mortality from studies using year-round 8-h exposure (HR, 1.014; 95% CI, 0.994-1.033). The exposure metric was significantly associated with effect estimates in the multivariable meta-regression model. In conclusion, in the population-based cohort in South Korea, we found positive associations between several long-term ozone exposure metrics and mortality. The different ozone exposure metrics exhibited heterogeneous effect estimates. A year-round 24-h average ozone metric also could be considered an alternative long-term standard for ozone.


Physical activity and health outcomes: evidence from Canada.
Health production models include participation in physical activity as an input. We investigate the relationship between participation in physical activity and health using a bivariate probit model. Participation is identified with an exclusion restriction on a variable reflecting sense of belonging to the community. Estimates based on data from Cycle 3.1 of the Canadian Community Health Survey indicate that participation in physical activity reduces the reported incidence of diabetes, high blood pressure, heart disease, asthma, and arthritis as well as being in fair or poor health. Increasing the intensity above the moderate level and frequency of participation in physical activity appears to have a diminishing marginal impact on adverse health outcomes. Our results provide support for guidelines about engaging in exercise regularly to achieve health benefits.


Tolerance to oxidative stress is associated with both oxidative stress response and inherent growth in a fungal wheat pathogen.
Reactive oxygen species are toxic byproducts of aerobic respiration that are also important in mediating a diversity of cellular functions. Reactive oxygen species form an important component of plant defenses to inhibit microbial pathogens during pathogen-plant interactions. Tolerance to oxidative stress is likely to make a significant contribution to the viability and pathogenicity of plant pathogens, but the complex network of oxidative stress responses hinders identification of the genes contributing to this trait. Here, we employed a forward genetic approach to investigate the genetic architecture of oxidative stress tolerance in the fungal wheat pathogen Zymoseptoria tritici. We used quantitative trait locus (QTL) mapping of growth and melanization under axenic conditions in two cross-populations to identify genomic regions associated with tolerance to oxidative stress. We found that QTLs associated with growth under oxidative stress as well as inherent growth can affect oxidative stress tolerance, and we identified two uncharacterized genes in a major QTL associated with this trait. Our data suggest that melanization does not affect tolerance to oxidative stress, which differs from what was found for animal pathogens. This study provides a whole-genome perspective on the genetic basis of oxidative stress tolerance in a plant pathogen.


Topology regulatory elements: From shaping genome architecture to gene regulation.
The importance of 3D genome topology in the control of gene expression is becoming increasingly apparent, while regulatory mechanisms remain incompletely understood. Several recent studies have identified architectural elements that influence developmental gene expression by shaping locus topology. We refer to these elements as topological regulatory elements (TopoREs) to reflect their dual roles in genome organisation and gene expression. Importantly, these elements do not harbour autonomous transcriptional activation capacity, and instead appear to facilitate enhancer-promoter interactions, contributing to robust and precise timing of transcription. We discuss examples of TopoREs from two classes that are either dependent or independent of CTCF binding. Importantly, identification and interpretation of TopoRE function may shed light on multiple aspects of gene regulation, including the relationship between enhancer-promoter proximity and transcription, and enhancer-promoter specificity. Ultimately, understanding TopoRE diversity and function will aid in the interpretation of how human sequence variation can impact transcription and contribute to disease phenotypes.


CD45 limits early Natural Killer cell development.
The clinical development of Natural Killer (NK) cell-mediated immunotherapy marks a milestone in the development of new cancer therapies and has gained traction due to the intrinsic ability of the NK cell to target and kill tumor cells. To fully harness the tumor killing ability of NK cells, we need to improve NK cell persistence and to overcome suppression of NK cell activation in the tumor microenvironment. The trans-membrane, protein tyrosine phosphatase CD45, regulates NK cell homeostasis, with the genetic loss of CD45 in mice resulting in increased numbers of mature NK cells. This suggests that CD45-deficient NK cells might display enhanced persistence following adoptive transfer. However, we demonstrate here that adoptive transfer of CD45-deficiency did not enhance NK cell persistence in mice, and instead, the homeostatic disturbance of NK cells in CD45-deficient mice stemmed from a developmental defect in the progenitor population. The enhanced maturation within the CD45-deficient NK cell compartment was intrinsic to the NK cell lineage, and independent of the developmental defect. CD45 is not a conventional immune checkpoint candidate, as systemic loss is detrimental to T and B cell development, compromising the adaptive immune system. Nonetheless, this study suggests that inhibition of CD45 in progenitor or stem cell populations may improve the yield of in vitro generated NK cells for adoptive therapy.


Clinically isolated syndromes suggestive of multiple sclerosis: an optical coherence tomography study.
Optical coherence tomography (OCT) is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL), which provides an indirect measurement of axonal damage in multiple sclerosis (MS). This study aimed to evaluate RNFL thickness in patients at presentation with clinically isolated syndromes (CIS) suggestive of MS. This was a cross-sectional study. Twenty-four patients with CIS suggestive of MS (8 optic neuritis [ON], 6 spinal cord syndromes, 5 brainstem symptoms and 5 with sensory and other syndromes) were prospectively studied. The main outcome evaluated was RNFL thickness at CIS onset. Secondary objectives were to study the relationship between RNFL thickness and MRI criteria for disease dissemination in space (DIS) as well as the presence of oligoclonal bands in the cerebrospinal fluid. Thirteen patients had decreased RNFL thickness in at least one quadrant. Mean RNFL thickness was 101.67±10.72 µm in retrobulbar ON eyes and 96.93±10.54 in unaffected eyes. Three of the 6 patients with myelitis had at least one abnormal quadrant in one of the two eyes. Eight CIS patients fulfilled DIS MRI criteria. The presence of at least one quadrant of an optic nerve with a RNFL thickness at a P<5% cut-off value had a sensitivity of 75% and a specificity of 56% for predicting DIS MRI. The findings from this study show that axonal damage measured by OCT is present in any type of CIS; even in myelitis forms, not only in ON as seen up to now. OCT can detect axonal damage in very early stages of disease and seems to have high sensitivity and moderate specificity for predicting DIS MRI. Studies with prospective long-term follow-up would be needed to establish the prognostic value of baseline OCT findings.


Catalytic processes in the atmospheres of Earth and venus.
Photochemical processes in planetary atmospheres are strongly influenced by catalytic effects of minor constituents. Catalytic cycles in the atmospheres of Earth and Venus are closely related. For example, chlorine oxides (CIOx) act as catalysts in the two atmospheres. On Earth, they serve to convert odd oxygen (atomic oxygen and ozone) to molecular oxygen. On Venus they have a similar effect, but in addition they accelerate the reactions of atomic and molecular oxygen with carbon monoxide. The latter process occurs by a unique combination of CIOx catalysis and sulfur dioxide photosensitization. The mechanism provides an explanation for the very low extent of carbon dioxide decomposition by sunlight in the Venus atmosphere.


Stimulus preferences and imprinting.
Pekin ducklings were tested with respect to their preference for approaching one of two simultaneously presented, rotating, silent duck decoys, painted in a variety of colors or patterns. Some of the ducklings had not been given any previous visual experience other than that gained in a 20-minute introduction to the empty apparatus; others had previously been given the opportunity to follow one particular decoy for 20 minutes. The decoys could be grouped into three categories: those in the first category were treated as equivalent, that is, so long as the duckling had followed one of these models it would approach either. The decoys of the second category were ones to which "imprinting" occurred, that is, the ducklings showed a decided preference for the model they had originally followed, whichever it was. The third category included models, one of which was always preferred, though the controls showed no such preference. The effects of the imprinting procedure vary with the stimuli presented.


A high frequency of sequence alterations is due to formalin fixation of archival specimens.
Genomic analysis of archival tissues fixed in formalin is of fundamental importance in biomedical research, and numerous studies have used such material. Although the possibility of polymerase chain reaction (PCR)-introduced artifacts is known, the use of direct sequencing has been thought to overcome such problems. Here we report the results from a controlled study, performed in parallel on frozen and formalin-fixed material, where a high frequency of nonreproducible sequence alterations was detected with the use of formalin-fixed tissues. Defined numbers of well-characterized tumor cells were amplified and analyzed by direct DNA sequencing. No nonreproducible sequence alterations were found in frozen tissues. In formalin-fixed material up to one mutation artifact per 500 bases was recorded. The chance of such artificial mutations in formalin-fixed material was inversely correlated with the number of cells used in the PCR-the fewer cells, the more artifacts. A total of 28 artificial mutations were recorded, of which 27 were C-T or G-A transitions. Through confirmational sequencing of independent amplification products artifacts can be distinguished from true mutations. However, because this problem was not acknowledged earlier, the presence of artifacts may have profoundly influenced previously reported mutations in formalin-fixed material, including those inserted into mutation databases.


Effects on Energy Metabolism of Two Guanidine Molecules, (Boc)2 -Creatine and Metformin.
Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc)2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc)2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism. Moreover, (Boc)2 -creatine is able to inhibit the activity of hexokinase with a non-competitive mechanism. Considering that creatine kinase and hexokinase are involved in energy metabolism, we evaluated the effects of (Boc)2 -creatine and metformin on the ATP/AMP ratio and on cellular proliferation in healthy fibroblasts, human breast cancer cells (MDA-MB-468), a human neuroblastoma cell line (SH-SY5Y), a human Hodgkin lymphoma cell line (KMH2). We found that healthy fibroblasts were only partially affected by (Boc)2 -creatine, while both ATP/AMP ratio and viability of the three cancer cell lines were significantly decreased. By inhibiting both creatine kinase and hexokinase, (Boc)2 -creatine appears as a promising new agent in anticancer treatment. Further research is needed to understand what types of cancer cells are most suitable to treatment by this new compound. J. Cell. Biochem. 118: 2700-2711, 2017. © 2017 Wiley Periodicals, Inc.


The impact of a novel franchise clinic network on access to medicines and vaccinations in Kenya: a cross-sectional study.
To study the impact of a new franchise health clinic model (The HealthStore Foundation's CFWShops) on access to vaccinations and treatment for acute illnesses in a nationally representative sample of children in Kenya. The authors used multivariate linear and count regressions to examine associations between receipt of vaccinations or treatment and proximity to a franchise health clinic, adjusting for individual, household and clinic attributes as well as region fixed effects. Demographic and Health Survey data from Kenya, 2008-2009. 6079 Kenyan children younger than 5 years, of whom 2310 reported recent acute illness. Outcomes for all children were number of polio doses received, number of DPT doses received, receipt of BCG vaccine, receipt of measles vaccine and number of total vaccinations received. Outcomes for acutely ill children were receipt of any medical treatment, treatment for fever, treatment for malaria and treatments specifically stocked by CFWShops. Children living within 30 km of a CFWShop received 0.129 (p=0.017) and 0.113 (p=0.025) more DPT and polio doses, respectively; and 0.285 more total vaccinations (p=0.023). Among acutely ill children, CFWShop proximity was associated with significant increases in the probabilities of receiving any medical treatment (0.142; p<0.001), treatment for fever (0.117; p=0.007) and treatments specifically stocked by CFWShops (0.064; p=0.015). Use of CFWShop services was not significantly different for lower-income vis-a-vis higher-income households. The franchise health clinic model could substantially increase access to essential vaccinations and treatments in low-income countries. Moreover, the model's benefits may accrue to lesser- and higher-income households alike.


The 25-kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-I-mediated growth of chick embryo pelvic cartilage in vitro.
Insulin-like growth factor (IGF)-I stimulates the growth of many tissues, including growth plate cartilage. However, the role of IGF-binding proteins in the growth process is controversial. We purified a 25-kDa IGF-binding protein (BP-25) from amniotic fluid. We tested the effect of this BP-25 preparation on both basal and IGF-I-stimulated growth of chick embryo pelvic cartilages maintained in serum-free organ culture. Cartilage wet weight was 4.1 +/- 0.3 mg/cartilage initially; after 3 days, BP-25 inhibited both basal and IGF-I-stimulated growth. Control cartilages weighed 7.4 +/- 0.7 mg/cartilage, while those incubated with 100 nM BP-25 weighed 5.8 +/- 0.5 mg/cartilage (P less than 0.001 vs. control); BP-25 concentrations as low as 0.2 nM significantly inhibited basal cartilage growth. Cartilages incubated with 1.25 nM IGF-I weighed 10.4 +/- 0.8 mg/cartilage (P less than 0.001 vs. control), while those incubated with both 100 nM BP-25 and 1.25 nM IGF-I weighed 8.1 +/- 0.5 mg/cartilage (P less than 0.001 vs. cartilage incubated with IGF-I alone); BP-25 concentrations as low as 0.4 nM significantly inhibited IGF-I-stimulated cartilage growth. BP-25 also inhibited basal and IGF-I-stimulated increases in cartilage dry weight, [3H]thymidine incorporation into DNA, and 35SO4 incorporation into proteoglycan. A second BP-25 preparation, which in the presence of 1% platelet-poor plasma acts synergistically with IGF-I to stimulate DNA synthesis and cell replication of fibroblasts and smooth muscle cells in tissue culture, inhibited IGF-I-stimulated cartilage growth to the same degree as did our BP-25 preparation. In separate experiments, proteins present in serum-free medium conditioned for 3 days by chick cartilages were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and incubated with [125I]IGF-I. This medium was found to contain two IGF-binding proteins; one appeared to be the chick equivalent of BP-25, while the other had a molecular mass similar to that of a poorly characterized human 34-kDa IGF-binding protein. We conclude that purified BP-25 inhibits the growth of chick embryo pelvic cartilage in our serum-free organ culture system. Since conditioned medium from these cartilages contains both IGF-I-like peptides and IGF-binding proteins such as BP-25, we suggest that the IGF-binding proteins present may act to down-regulate the growth-promoting effects of the local IGF peptides.


Temporality and existential mood in Heideggerian phenomenology.
The philosophical perspective of a research methodology should explicitly underpin the decisions the researcher makes throughout the research. It is therefore important to understand the philosophical background and origins of Heideggerian phenomenology when using it as a research methodology. To discuss in detail the main philosophical ideas underpinning Heideggerian phenomenology. Anxiety and boredom are two significant existential moods in Heideggerian phenomenology. Time is the basis of these moods and is an 'originary temporality'. Originary temporality consists of a unified structure that includes the past, present and future. The experience of being human ('dasein') and its care/worry structure are significant features of originary temporality and consequently existential mood. Existential anxiety discloses the threefold characteristics of temporality to the individual, while existential boredom disrupts its unified structure. Both moods highlight the limits of existence to the individual and may culminate in additional distressing moods. It is essential for nurse researchers using Heideggerian phenomenology to understand the philosophical ideas underlining it. The depiction of originary temporality and existential mood illustrated in this article could help nurse researchers embarking on a Heideggerian phenomenological study. The article could also inform researchers new to Heideggerian phenomenological research of the methodology's philosophical background.


Improving the uptake of HIV testing in patients with tuberculosis.
The HIV epidemic has increased the global tuberculosis (TB) burden and focused attention on the need to strengthen links between TB and HIV programmes in order to tackle these public health issues more effectively (World Health Organization (WHO), 2004). HIV testing is now recommended in various healthcare settings and guidelines state that it should include all patients with a diagnosis of active TB (British HIV Association, British Association of Sexual Health and HIV, British Infection Society, 2008; Health Protection Agency (HPA), 2009). This has been shown to standardise HIV testing and improve outcomes as HIV infection will affect the management of active TB and will reduce transmission of the virus within the community (HPA, 2009). The purpose of this study was to determine if a change had occurred after the introduction of nurse-led HIV testing following the results of an audit. The re-audit examined whether a change had occurred in the rate of HIV testing in confirmed active TB cases. The study covered a 12-month period; 31 cases of active TB were identified for inclusion in the study. Patients were offered testing in 90.3% of cases and the results strongly demonstrated that nurse-led HIV testing can improve uptake in both a clinic and community setting.


Structural Diversity of Zirconium Metal-Organic Frameworks and Effect on Adsorption of Toxic Chemicals.
While linkers with various conformations pose challenges in the design and prediction of metal-organic framework (MOF) structures, they ultimately provide great opportunities for the discovery of novel structures thereby enriching structural diversity. Tetratopic carboxylate linkers, for example, have been widely used in the formation of Zr-based MOFs due to the ability to target diverse topologies, providing a promising platform to explore their mechanisms of formation. However, it remains a challenge to control the resulting structures when considering the complex assembly of linkers with unpredicted conformations and diverse Zr6 node connectivities. Herein, we systematically explore how solvents and modulators employed during synthesis influence the resulting topologies of Zr-MOFs, choosing H4TCPB-Br2 (1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene) as a representative tetratopic carboxylate linker. By modulating the reaction conditions, the conformations of the linker and the connectivities of the Zr6 node can be simultaneously tuned, resulting in four types of structures: a new topology (NU-500), she (NU-600), scu (NU-906), and csq (NU-1008). Importantly, we have synthesized the first 5-connected Zr6 node to date with the (4,4,4,5)-connected framework, NU-500. We subsequently performed detailed structural analyses to uncover the relationship between the structures and topologies of these MOFs and demonstrated the crucial role that the flexible linker played to access varied structures by different degrees of linker deformation. Due to a variety of pore structures ranging from micropores to hierarchical micropores and mesopores, the resulting MOFs show drastically different behaviors for the adsorption of n-hexane and dynamic adsorption of 2-chloroethyl ethyl sulfide (CEES) under dry and humid conditions.


S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction.
Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.


[Bacteriologic and serologic studies].
With many infectious eye diseases, the practising ophthalmologist is faced by the question as to whether a serologic or microbiologic work-up pays off in terms of greater diagnostic or therapeutic efficiency. A critical appraisal indicates that on average, they are relatively insignificant, and so some time and money could probably be saved. Important exceptions to the rule are discussed separately.


Circulating Myeloid-Derived Suppressor Cell Subsets in Patients with Colorectal Cancer - Exploratory Analysis of Their Biomarker Potential.
Myeloid-derived suppressor cells (MDSCs) contribute to tumor escape from host immune surveillance and to tumor progression by producing tumor-promoting factors. We focused on clinical and analytical MDSCs-related issues as potential biomarkers and immune regulators involved in tumor progression. We analyzed 10 patients with advanced colorectal carcinoma (CRC) with (M1 subgroup) or without (M0 subgroup) distant metastases at diagnosis. Peripheral blood was collected at diagnosis prior to treatment and subsequently 12 months after therapy initiation. Using multicolor flow cytometry MDSC subsets were evaluated. Monocytic MDSCs (M-MDSCs) were detected as CD45+ CD11b+ CD33+ HLA-DRlow/ CD14+ CD15-, granulocytic MDSCs (CD33hi PMN-MDSC) were detected as CD45+ CD11b+ CD33hi HLA-DRlow/ CD14 CD15+. For analytical and preanalytical studies, random fresh blood specimens predominantly from cancer patients were analyzed. Levels of circulating M-MDSCs were not associated with metastatic disease within advanced CRC patients. Levels of circulating CD33hi PMN-MDSCs were elevated in patients with distant metastases compared to T3 M0 subgroup. Circulating M-MDSCs increased upon treatment initiation in 9 out of 10 patients. CD33hi PMN-MDSCs substantially dropped upon treatment initiation in 5 out of 10 patients and substantially increased in 2 out of 10 patients. Analytical part showed that absolute and relative counts within each MDSC subset are correlated. Coefficient of variation (CV) for repeatability was 6-11% for M-MDSCs and 25-44% for CD33hi PMN-MDSCs. CV for reproducibility was higher with 8-22% for M-MDSCs and 35-79% for CD33hi PMN-MDSCs demonstrating that delay in measurement of MDSCs in whole blood specimen may distort quantification of circulating MDSC subsets. The quantification of MDSC subsets is substantially dependent on the type of specimen examined and its preanalytical processing. Exploratory analysis of M-MDSCs and CD33hi PMN-MDSCs in CRC patients revealed different dynamics of M-MDSC and CD33hi PMN-MDSC subsets in the context anti-cancer treatment. Key words: myeloid-derived suppressor cells - preanalytics - colorectal cancer - flow cytometry - immune monitoring.


Intracellular gold nanoparticles enhance non-invasive radiofrequency thermal destruction of human gastrointestinal cancer cells.
Novel approaches to treat human cancer that are effective with minimal toxicity profiles are needed. We evaluated gold nanoparticles (GNPs) in human hepatocellular and pancreatic cancer cells to determine: 1) absence of intrinsic cytotoxicity of the GNPs and 2) external radiofrequency (RF) field-induced heating of intracellular GNPs to produce thermal destruction of malignant cells. GNPs (5 nm diameter) were added to 2 human cancer cell lines (Panc-1, Hep3B). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and propidium iodide-fluorescence associated cell sorting (PI-FACS) assessed cell proliferation and GNP-related cytotoxicity. Other GNP-treated cells were exposed to a 13.56 MHz RF field for 1, 2, or 5 minutes, and then incubated for 24 hours. PI-FACS measured RF-induced cytotoxicity. GNPs had no impact on cellular proliferation by MTT assay. PI-FACS confirmed that GNPs alone produced no cytotoxicity. A GNP dose-dependent RF-induced cytotoxicity was observed. For Hep3B cells treated with a 67 muM/L dose of GNPs, cytotoxicity at 1, 2 and 5 minutes of RF was 99.0%, 98.5%, and 99.8%. For Panc-1 cells treated at the 67 muM/L dose, cytotoxicity at 1, 2, and 5 minutes of RF was 98.5%, 98.7%, and 96.5%. Lower doses of GNPs were associated with significantly lower rates of RF-induced thermal cytotoxicity for each cell line (P < 0.01). Cells not treated with GNPs but treated with RF for identical time-points had less cytotoxicity (Hep3B: 17.6%, 21%, and 75%; Panc-1: 15.3%, 26.4%, and 39.8%, all P < 0.01). We demonstrate that GNPs 1) have no intrinsic cytotoxicity or anti-proliferative effects in two human cancer cell lines in vitro and 2) GNPs release heat in a focused external RF field. This RF-induced heat release is lethal to cancer cells bearing intracellular GNPs in vitro.


Alcohol and cardio-respiratory deaths in Chinese: a population-based case-control study of 32,462 older Hong Kong adults.
In observational studies moderate alcohol use reduces cardio-respiratory mortality. However observational studies may be biased by many factors including residual confounding by unmeasured differences between moderate alcohol users and other groups or by changes in alcohol use with ill-health and aging. We used two different analytic strategies in an under-studied population, i.e. southern Chinese, to provide an assessment of the specific impact of moderate alcohol use on mortality from ischemic heart disease (IHD) and chronic obstructive pulmonary diseases (COPD). In a population-based case-control study of all adult deaths in Hong Kong Chinese in 1998, we used adjusted logistic regression to compare alcohol use in decedents aged > or = 60 years from IHD (2270) and COPD (1441) with 10,320 living and 9043 dead controls (all non-alcohol related deaths). We also examined whether the association of alcohol use with death from IHD or COPD varied with sex or smoking status. Using living controls and adjusted for age, socio-economic status and lifestyle, occasional and moderate alcohol use were generally associated with lower mortality from IHD and COPD. However, using dead controls the protection of occasional and moderate alcohol use appeared to be limited to ever-smokers for IHD (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.46 to 0.73 for moderate compared to never-use in ever-smokers, but OR 1.07, 95% CI 0.76 to 1.50 in never-smokers), and possibly to men for COPD. High alcohol use was associated with lower IHD mortality and possibly with lower COPD mortality. High levels of alcohol use in an older Chinese population were associated with lower IHD mortality. Moderate alcohol use was less consistently protective against IHD mortality. Alcohol use was associated with lower COPD mortality particularly in men, either due to some yet to be clarified properties of alcohol or as the artefactual result of genetic selection into alcohol use in a Chinese population. Given the increasing use of alcohol in China with economic development, other designs and analytic strategies are needed to assess the impact of alcohol in this population, so that an evidence-based public health policy can be formulated.


Intraventricular ganglioglioma with extensive hemorrhage.
Gangliogliomas represent a rare form of neuroepithelial tumor (up to 1.3% of brain tumors [<xref-ref>1</xref-ref>]), which even more rarely present with hemorrhage or localize intraventricularly. To date, only two cases of ganglioglioma with both of these features have been reported. Our patient is a 23-year-old woman who presented with signs and symptoms of increased intracranial pressure (ICPI), with a post-subtotal resection diagnosis of WHO Grade I ganglioglioma localizing bilaterally to the lateral ventricles. One year following the operation, the tumor showed radiologic evidence of interval hemorrhage, which was verified histopathologically following a second subtotal resection. Greater than 95% of the lesion represented a large hematoma with organization and well-defined fibrous pseudo-capsule, with very scanty fragments of adjacent/peripheral low-grade neuroglial tumor. This case represents a very rare presentation of intraventricular ganglioglioma with extensive hemorrhage. .


Assessment of three frequently used blood glucose monitoring devices in clinical routine.
Self-monitoring of blood glucose plays an important role in the management of diabetes and has been shown to improve metabolic control. The use of blood glucose meters in clinical practice requires sufficient reliability to allow adequate treatment. Direct comparison of different blood glucose meters in clinical practice, independent of the manufactures is scarce. We, therefore, aimed to evaluate three frequently used blood glucose meters in daily clinical practice. Capillary blood glucose was measured simultaneous using the following glucose meters: Contour® (Bayer Diabetes Care, Zürich, Switzerland), Accu-Chek® aviva (Roche Diagnostics, Rotkreuz, Switzerland), Free-Style® lite (Abbott Diabetes Care, Baar, Switzerland). The reference method consisted of the HemoCue® Glucose 201+ System (HemoCue® AB, Ängelholm, Sweden) with plasma conversion. The devices were assessed by comparison of the Mean Absolute Relative Differences (MARD), the Clarke Error Grid Analysis (EGA) and the compliance with the International Organization of Standardization criteria (ISO 15197:2003). Capillary blood samples were obtained from 150 patients. MARD was 10.1 ± 0.65%, 7.0 ± 0.62% and 7.8 ± 0.48% for Contour®, Accu-Chek® and Free-Style®, respectively. EGA showed 99.3% (Contour®), 98.7% (Accu-Chek®) and 100% (Free-Style®) of all measurements in zone A and B (clinically acceptable). The ISO criteria were fulfilled by Accu-Chek® (95.3%) and Free-Style® (96%), but not by Contour® (92%). In the present study the three glucose meters provided good agreement with the reference and reliable results in daily clinical routine. Overall, the Free-Style® and Accu-Chek® device slightly outperformed the Contour® device.


[Syndrome of functional dyspepsia and/or chronic gastritis?].
Definition and prevalence of syndrome of functional dyspepsia (SFD) are discussed along with the brief history of the problem, priority works of V.P. Obraztsov and other authors, current views of SFD etiology and pathogenesis with reference to the role of H. pylori infections. Clinical variants of SFD, their diagnostic criteria and principals of differential diagnostics are described. Special attention is given to the debatable relationship between CFD and chronic gastritis. Nosological and syndromal diagnostics, structure-function relationship, goals and methods of SFD treatment and other matters of dispute are considered.


A model for the coupling of alpha-helix and tertiary contact formation.
Peptides corresponding to excised alpha-helical segments of natural proteins can spontaneously form helices in solution. However, peptide helices are usually substantially less stable in solution than in the structural context of a folded protein, because of the additional interactions possible between helices in a protein. Such interactions can be thought of as coupling helix formation and tertiary contact formation. The relative energetic contributions of the two processes to the total energy of the folded state of a protein is a matter of current debate. To investigate this balance, an extended helix-coil model (XHC) that incorporates both effects has been constructed. The model treats helix formation with the Lifson-Roig formalism, which describes helix initiation and propagation through cooperative local interactions. The model postulates an additional parameter representing participation of a site in a tertiary contact. In the model, greater helix stability can be achieved through combinations of these short-range and long-range interactions. For instance, stronger tertiary contacts can compensate for helices with little intrinsic stability. By varying the strength of the nonlocal interactions, the model can exhibit behavior consistent with a variety of qualitative models describing the relative importance of secondary and tertiary structure. Moreover, the model is explicit in that it can be used to fit experimental data to individual peptide sequences, providing a means to quantify the two contributions on a common energetic basis.


Results of cytogenetic studies of seeds after their extended orbital flight aboard the Salyut orbital scientific station.
Air-dry seeds of Lactuca sativa (lettuce) with a different level of spontaneous mitagenesis were used in these experiments. A part of the seeds was given pre-flight gamma radiation in doses of 1 and 10 krads. Comparison of the results for the in-flight experiments, laboratory and "transport" control showed an increase of cells with chromosome aberrations and an increase of radiobiological effect in irradiated seeds flown aboard the Salyut scientific station. A comparative analysis was made of the cytogenetic changes in seeds after their exposure to different periods of weightlessness during the Cosmos 368, Zond 8 and Salyut missions. The effect of weightlessness of different duration on the development of cytogenetic changes in irradiated and unirradiated seeds is discussed.


Changes of perceived control after kidney transplantation: a prospective study.
The aim of this study was to determine if kidney transplantation is associated with increases of perceived control and how changes of perceived control affect the course of psychological distress until 1 year after transplantation. Low levels of perceived control are associated with reduced well-being among dialysis patients. Prospective longitudinal cohort study. Perceived control (Mastery Scale) and psychological distress (GHQ-12) were prospectively assessed before (T0; n = 470) and three (T1; n = 197), six (T2; n = 210) and twelve (T3; n = 183) months after transplantation. Differences between T1 and T0 perceived control were used to stratify the sample into three groups (control gain, stable control and control loss). Socio-demographic and clinical variables, including complications, were examined as potential correlates and the course of psychological was distress compared across groups. Data were collected between July 2008 - July 2013. Perceived control showed a small increase overall, with 35·1%, 50·0% and 14·9% reporting gain, stable level and loss respectively. Patients with secondary schooling were overrepresented in the control loss group. The course of psychological distress varied across perceived control change groups, with patients in the control gain group experiencing a significant reduction in psychological distress. A considerable number of patients report increased levels of perceived control after transplantation that are associated with a subsequent decrease in psychological distress. Results emphasize the importance of perceived control and could inform interventions to facilitate well-being after kidney transplantation.


Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: a randomized controlled clinical trial.
We evaluated and compared the efficacy of the World Health Organization (WHO) oral rehydration solution (ORS) and 2 different formulations of reduced osmolarity ORSs in infants with persistent diarrhea. Infants with persistent diarrhea (n = 95) were randomized to 1 of the 3 ORSs: WHO-ORS (control, n = 32), a glucose-based reduced osmolarity ORS (RORS-G, n = 30), or a rice-based reduced osmolarity ORS (RORS-R, n = 31) for replacement of ongoing stool losses for up to 7 days. Major outcome measures were stool volume and frequency, ORS intake, and resolution of diarrhea. Although there were variations from one study day to another, the stool volume was approximately 40% less in the reduced osmolarity ORS groups; consequently, these children required less ORS (22% for RORS-G and 27% for RORS-R groups). A higher proportion of children in the RORS-R groups also had resolution of diarrhea during the study period. No children in any of the treatment groups had hyponatremia. Reduced osmolarity ORS is clinically more effective than WHO-ORS and may thus be advantageous for use in the treatment of children with persistent diarrhea.


Design of liposomes to improve delivery of macrophage-augmenting agents to alveolar macrophages.
Factors affecting the localization of liposomes injected i.v. in the lung have been studied to identify the optimal type of liposome for delivery of macrophage-activating agents to the lung to augment the tumoricidal activity of alveolar macrophages (AM). Comparison of pulmonary retention of liposomes of differing size, surface charge, and composition following i.v. injection into inbred mice revealed that large multilamellar (MLV) and reversed-phase-evaporation (REV) liposomes are arrested in the lung more efficiently than are small unilamellar liposomes of identical lipid composition. MLV and REV containing negatively charged amphiphiles arrest in the lung more efficiently than do neutral MLV's or REV's or MULV's and REV's containing positively charged amphiphiles. Comparison of the ability of liposomes containing a variety of negatively charged amphiphiles to localize in the lung established that optimal localization was achieved using MLV and REV prepared from phosphatidylserine (PS) and phosphatidylcholine (PC) (3:7 mol ratio) or PS:PC:lysolecithin (4.95:4.95:0.1 mol ratio). The proportion of these liposomes retained in the lung after i.v. injection was constant over a wide dose range (0.02 to 20 mumol phospholipid per mouse), but hemodilution due to i.v. inoculation of liposomes in volumes exceeding 0.2 ml reduced retention in the lung. Uptake of liposomes by AM was demonstrated by showing that i.v. injection of PS:PC MLV liposomes containing fluorescein-labeled bovine serum albumin resulted in localization of fluorescence within AM recovered by pulmonary lavage. Similarly, AM recovered after i.v. injection of PS:PC MLV liposomes containing lymphokine preparations rich in macrophage-activating factor (MAF) activity exhibited tumoricidal activity. In contrast, macrophages recovered from control animals given injections of unencapsulated MAF or liposomes containing lymphocyte supernatants without MAF activity were devoid of cytotoxic activity. Neutral (PC) MLV liposomes containing MAF, which show only very limited retention in the lung, were ineffective in activating AM in situ. We conclude that negatively charged MLV liposomes (PS:PC, 3:7 mol ratio) localize efficiently in the lung and that macrophage-activating agents encapsulated within such liposomes can successfully activate lung macrophages in situ.


Phenotype masking and streptomycin dependence.
In attempting to define the role of ribosomes in the mechanism of streptomycin dependence, a new phenomenon has been discovered. Analysis of this phenomenon-called phenotypic masking-leads to the conclusion that "streptomycin dependent" mutants are actually "drug dependent" because their dependence is equally satisfied by several drugs. These drugs, some of which are totally unrelated chemically, act on the ribosome and induce misreading in vitro and suppression in vivo.


Neurotopographic considerations in the microsurgical treatment of small acoustic neurinomas.
The authors studied the relationships between tumor size, location, and topographic position relative to the intact facial nerve bundles in acoustic neurinomas to determine the influence of these factors on hearing preservation postoperatively. Consistent topographic relationships were found. Four hundred fifty-two patients with acoustic neurinoma treated via a retrosigmoid approach were analyzed with respect to hearing preservation and facial nerve function. One hundred fifteen tumors were identified as small and were categorized as Grades I and II. Patients with Grade I tumors, that is, purely intracanalicular lesions, all had good hearing preoperatively, defined by a less than 50-dB pure tone average and 50% speech discrimination score. All 14 Grade I tumors were removed, resulting in preservation of the patient's hearing by these criteria. There were no particular topographic anatomical relationships associated with these tumors that affected hearing preservation. Grade II tumors, defined as those protruding into the cerebellopontine angle without contacting the brainstem, were found in 101 patients and were divided by size into two grades: IIA (< 1 cm) and IIB (1-1.8 cm). In 90 patients with Grade IIA tumors, 72 (89%) of 81 who had preserved hearing preoperatively maintained it postoperatively, and in the 11 patients with Grade IIB tumors, six of whom had good hearing preoperatively, four (67%) had preserved hearing postoperatively. Six morphological types were identified based on their neurotopographic relationships to the elements of the vestibulocochlear nerve. Hearing preservation postsurgery by tumor type was as follows: 1A, 92%; 1B, 88%; 1C, 100%; 2A, 83%; 2B, 92%; and 3, 57%. Combined, this represents a hearing preservation rate of 87% after surgical treatment of Grade II acoustic neurinomas. Full nerve function was maintained in 88% of patients with anatomically preserved facial nerves in both Grade I and II tumors. The remaining 12% of patients retained partial function of the facial nerve. Two patients in the series lost anatomical integrity of the nerve due to surgery.


Hepatic Stellate Cell- and Liver Microbiome-Specific Delivery System for Dihydrotanshinone I to Ameliorate Liver Fibrosis.
Liver fibrosis is a major contributor to the morbidity and mortality associated with liver diseases, yet effective treatment options remain limited. Hepatic stellate cells (HSCs) are a promising target for hepatic fibrogenesis due to their pivotal role in disease progression. Our previous research has demonstrated the potential of Dihydrotanshinone I (DHI), a lipophilic component derived from the natural herb Salvia miltiorrhiza Bunge, in treating liver fibrosis by inhibiting the YAP/TEAD2 interaction in HSCs. However, the clinical application of DHI faces challenges due to its poor aqueous solubility and lack of specificity for HSCs. Additionally, recent studies have implicated the impact of liver microbiota, distinct from gut microbiota, on the pathogenesis of liver diseases. In this study, we have developed an HSC- and microbiome-specific delivery system for DHI by conjugating prebiotic-like cyclodextrin (CD) with vitamin A, utilizing PEG2000 as a linker (VAP2000@CD). Our results demonstrate that VAP2000@CD markedly enhances the cellular uptake in human HSC line LX-2 and enhances the deposition of DHI in the fibrotic liver in vivo. Subsequently, intervention with DHI-VAP2000@CD has shown a notable reduction in bile duct-like structure proliferation, collagen accumulation, and the expression of fibrogenesis-associated genes in rats subjected to bile duct ligation. These effects may be attributed to the regulation of the YAP/TEAD2 interaction. Importantly, the DHI-VAP2000@CD intervention has also restored microbial homeostasis in the liver, promoting the amelioration of liver inflammation. Overall, our findings indicate that DHI-VAP2000@CD represents a promising therapeutic approach for liver fibrosis by specifically targeting HSCs and restoring the liver microbial balance.


Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism.
The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.


Myocarditis Attributable to Monkeypox Virus Infection in 2 Patients, United States, 2022.
We report 2 immunocompetent and otherwise healthy adults in the United States who had monkeypox and required hospitalization for viral myocarditis. Both patients were unvaccinated against orthopoxviruses. They had shortness of breath or chest pain and elevated cardiac biomarkers. No immediate complications were observed. They were discharged home after symptoms resolved.


[Polymorphisms of the Arsenite Methyltransferase (As3MT) gene and urinary efficiency of arsenic metabolism in a population in northern Mexico].
The aim of this study was to assess the relationship of the rs11191439 and rs3740393 polymorphisms of the Arsenite Methyltransferase (As3MT) gene with the arsenic urinary excretion profiles in a population in northern Mexico. A crosssectional study was conducted with 102 participants between the ages of 14 and 75 in Comarca Lagunera, Mexico. Speciation of the arsenic urinary metabolites was determined, and DNA was extracted; analysis and amplification of the polymorphisms was made by PCR in real time. A descriptive analysis was carried out and the differences in the urinary arsenic concentrations were assessed according to sex and genotype. The median concentration of arsenic in water was 82 μg/L; the levels of urinary excretion of dimethylarsinic acid (DMA) were higher in women than in the men. The carriers of the CC genetic variant of the As3MT (rs3740393) gene showed higher urinary concentrations of methylarsinic acid (p=0.01) and DMA (p=0.05).


Feasibility and reliability of flow-cytometry (fcm) DNA analysis of fresh and fixed urine samples.
The qualitative results of FCM DNA analysis on fresh and fixed urine specimens (28 and 97, respectively) from 68 normal subjects and 10 patients with a past history of bladder cancer were compared. FCM DNA evaluability was not significantly different in fresh and fixed samples (63% vs 73%, respectively) whereas mean CV was significantly higher (7.3% vs 5.7%, respectively; p=0.04). A double FCM analysis on fresh and fixed urine was also performed in 16 cases. In this subgroup, the percentage of evaluable histograms from fixed urine specimens was slightly higher than that from fresh specimens. Aneuploid cases were found only in the fixed urine samples but the CVs from fresh and fixed cell suspensions did not differ. The absence of inflammatory cells with cytological analysis of the same samples was associated with low percentages of FCM evaluability and higher CVs. The use of fixed samples improves the quality of FCM DNA analysis permitting its use for screening programs.


Current Concepts of Non-Coding RNAs in the Pathogenesis of Non-Clear Cell Renal Cell Carcinoma.
Renal cell carcinoma (RCC) is a relatively rare malignancy of the urinary tract system. RCC is a heterogenous disease in terms of underlying histology and its associated underlying pathobiology, prognosis and treatment schedule. The most prevalent histological RCC subtype is clear-cell renal cell carcinoma (ccRCC), accounting for about 70-80% of all RCCs. Though the pathobiology and treatment schedule for ccRCC are well-established, non-ccRCC subtypes account for 20%-30% of RCC altogether, and their underlying molecular biology and treatment options are poorly defined. The class of non-coding RNAs-molecules that are generally not translated into proteins-are new cancer drivers and suppressors in all types of cancer. Of these, small non-coding microRNAs (miRNAs) contribute to carcinogenesis by regulating posttranscriptional gene silencing. Additionally, a growing body of evidence supports the role of long non-coding RNAs (lncRNAs) in cancer development and progression. Most studies on non-coding RNAs in RCC focus on clear-cell histology, and there is a relatively limited number of studies on non-ccRCC subtypes. The aim of this review is to give an overview of the current knowledge regarding the role of non-coding RNAs (including short and long non-coding RNAs) in non-ccRCC and to highlight possible implications as diagnostic, prognostic and predictive biomarkers.


Monitoring of the physical parameters and evaluation of the chemical composition of river and groundwater in Calabar (Southeastern Nigeria).
A 12-month study was carried to assess the seasonal and tidal effects on the physical parameters of river and groundwater, which constitute the major potable water sources in Calabar (Nigeria). The study also included an evaluation of the chemical composition of the different water bodies and their relationship. The results show that there was a significant seasonal effect on dissolved oxygen (DO) and nitrate in groundwater on one hand, and on temperature, redox potential (Eh), and DO in river water on the other. Also, a significant tidal influence exists on DO in both river-and groundwater. Comparison between groundwater and river water show statistically significant difference in EC, TDS, Eh, DO, Na, Cl and NO(3). The significant differences in EC, TDS, Na and Cl are due to tidal flushing. The difference in Eh is due to geology of the area while, NO(3) is as a result of anthropogenic pollution. The concentrations of ions in the river and groundwater for the different seasons and tidal cycles show an inverse relationship, while the river water is generally more concentrated than the groundwater. Using a binary mixing model, estimates show that the degree of mixing of river water and groundwater is low, with values of between 1.93% and 2.76% respectively, in the western and eastern parts of the study area. The study concludes that tidal flushing, anthropogenic effects and oxygen supply during recharge contribute to the shaping of water chemistry in the area.


Early pregnancy sex steroids and maternal breast cancer: a nested case-control study.
Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); Ptrend = 0.01], and inversely associated with breast cancer diagnosed at age ≥40 [4th vs. 1st quartile OR 0.71 (0.51-1.00); Ptrend = 0.02]. Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER(+)/PR(+) disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER(-)/PR(-) breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor-negative cancers is needed to further characterize this association.


[Anti-inflammatory effect of arglabin and 11,13-dihydro-13-dimethylaminoarglabin hydrochloride].
The sesquiterpene lactone arglabin, as well as its derivative 11,13-Dihydro-13-dimethylaminoarglabin hydrochloride, exhibit antiexudative and antiproliferative properties on the models of acute aseptic inflammation caused by formalin, carrageenan, and histamine, and on the model of proliferative inflammation accompanying cotton-pellet granuloma.


Behavior problems, psychiatric symptoms, and quality of life for older adults with intellectual disability with and without autism.
The evidence base on outcomes associated with autism in older adulthood is limited. The expected increase in the prevalence of older adults with autism highlights the need to describe their profiles and service needs. Adults 50 years or older with an intellectual disability (ID) and the triad of impairments characteristic of autism spectrum disorders (ASD) were compared to peers with ID only, and younger adults with ASD and ID. After accounting for ability differences, older adults with ASD did not differ from those with ID in terms of behavior problems, psychiatric disorder, and quality of life. Any differences in the skills of adults with ASD were associated with decreased adaptive skills, and not the presence of ASD per se.


Socioeconomic inequalities in self-perceived oral health among adults in Chile.
This paper studies the socioeconomic disparities in self-perceived oral health among Chilean adults and in the perceived physical, functional, psychological and social consequences of oral health. In February 2011, 1,413 residents of Metropolitan Area of Santiago, Chile, were interviewed using a standardized questionnaire and examined by dentists for dental status and oral health conditions. Only adults 18 to 60 years old affiliated with the public healthcare system were eligible to participate. We estimate socioeconomic gradients in self-perceived oral health and its distinct dimensions. We use the Heckman two-step procedure to control for selection bias given the non-random nature of the sample. In addition, we use a two-equation ordered response model given the discrete nature of the dependent variable. There is a non-linear socioeconomic gradient in self-perceived oral health even after controlling for oral health status. The gradient is steep at the lower end of the income distribution and constant at mid-income levels. These socioeconomic disparities are also found for the psychological and social dimensions of self-perceived oral health, but not for the functional limitations and physical pain dimensions. The findings are consistent with inequities in the access to oral health services due to insufficient provision in the public sector and costly options in the private sector.


Consumer-directed community care: race/ethnicity and individual differences in preferences for control.
Even though consumer-directed care models are being advocated for use among elder populations, there are few data on the extent of elder interest in participating in the management of community long-term-care services, who they want involved in making these decisions, or their perceptions regarding the relative importance of different service choices. In addition, little is known about how elder preferences for consumer direction may vary by race/ethnicity. With use of a cross-sectional research design, a sample of 731 elders including 200 African American, 200 Chinese, 131 Latino, and 200 White Western European American elders was investigated. New measures were created to assess level of control desired by elders in different areas of community long-term-care service delivery and preference for consumer direction. Multivariate analyses found significant differences between and within race/ethnic groups for preferences for levels of consumer-directed care. Study findings suggest that consumer direction occurs along a continuum, with elders desiring control over some service areas but not others, and the importance of recognizing heterogeneity within racial/ethnic groups regarding consumer-directed care.


Complete Genome Sequence of Streptomyces sp. Strain SHP22-7, a New Species Isolated from Mangrove of Enggano Island, Indonesia.
Streptomyces sp. SHP22-7 is a novel strain isolated from a mangrove sample on Enggano Island, Indonesia. Here, we present the 7.9-Mbp genome sequence of SHP22-7, which will provide insight into its natural compound biosynthetic potential.


Ferulic acid alleviates atopic dermatitis-like symptoms in mice via its potent anti-inflammatory effect.
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the interactions between multiple genetic and environmental factors. The pathogenesis of AD is still not completely clear. Steroid topical therapy has severe side effects for chronic AD symptoms and new therapeutic options are urgently needed. Ferulic acid (FA) is a novel natural dietary polyphenol with anti-oxidative and anti-inflammatory effects.Methods: FA was assessed in BALB/c mice with AD-like lesions resulted from repetitive applications of 2,4-dinitrochlorobenzene (DNCB). Molecular and serological properties of the AD lesions as well as the overall symptomatic score were evaluated.Results: FA ameliorated the overall symptoms of AD, including the severity of skin lesion and incidence of scratching behavior. Systemically, FA markedly decreased DNCB-induced Th2 cytokines and IgE in the peripheral blood. In the local tissue with AD lesions, FA suppressed DNCB-stimulated mRNA production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and IL-31. In THP-1 cells, a human monocyte model, FA dose-dependently suppressed DNCB-elicited up-regulation of CD54 and CD86 at cell surface, secretion of pro-inflammatory cytokines IL-6 and TNF-α, and NFκB signaling activation.Conclusion: Our findings demonstrated that FA could serve as a promising therapeutic agent in AD treatment.


Longitudinal shear wave and transverse dilatational wave in solids.
Dilatation wave involves compression and extension and is known as the curl-free solution of the elastodynamic equation. Shear wave on the contrary does not involve any change in volume and is the divergence-free solution. This letter seeks to examine the elastodynamic Green's function through this definition. By separating the Green's function in divergence-free and curl-free terms, it appears first that, strictly speaking, the longitudinal wave is not a pure dilatation wave and the transverse wave is neither a pure shear wave. Second, not only a longitudinal shear wave but also a transverse dilatational wave exists. These waves are shown to be a part of the solution known as coupling terms. Their special motion is carefully described and illustrated.


Bonding strengths of etched porcelain discs and three different bonding agents.
Forty porcelain disks were resin bonded to etched base metal surfaces to measure tensile bond strengths. One metal surface was bonded to each porcelain surface, making each test specimen "sandwiched", with a porcelain disk between two metal surfaces. The mean bond strength values of the Conclude group was 3017 +/- 869 psi. The mean for the Mar-Bond group was 3747 +/- 693 psi, and the mean for the two Chameleon groups combined was 3172 +/- 544 psi. No two groups were significantly different.


OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.
Pathogenic OPA1 mutations cause autosomal dominant optic atrophy (DOA), a condition characterized by the preferential loss of retinal ganglion cells and progressive optic nerve degeneration. Approximately 20% of affected patients will also develop more severe neuromuscular complications, an important disease subgroup known as DOA(+). Cytochrome c oxidase (COX)-negative fibres and multiple mitochondrial DNA (mtDNA) deletions have been identified in skeletal muscle biopsies from patients manifesting both the pure and syndromal variants, raising the possibility that the accumulation of somatic mtDNA defects contribute to the disease process. In this study, we investigated the mtDNA changes induced by OPA1 mutations in skeletal muscle biopsies from 15 patients with both pure DOA and DOA(+) phenotypes. We observed a 2- to 4-fold increase in mtDNA copy number at the single-fibre level, and patients with DOA(+) features had significantly greater mtDNA proliferation in their COX-negative skeletal muscle fibres compared with patients with isolated optic neuropathy. Low levels of wild-type mtDNA molecules were present in COX-deficient muscle fibres from both pure DOA and DOA(+) patients, implicating haplo-insufficiency as the mechanism responsible for the biochemical defect. Our findings are consistent with the 'maintenance of wild-type' hypothesis, the secondary mtDNA deletions induced by OPA1 mutations triggering a compensatory mitochondrial proliferative response in order to maintain an optimal level of wild-type mtDNA genomes. However, when deletion levels reach a critical level, further mitochondrial proliferation leads to replication of the mutant species at the expense of wild-type mtDNA, resulting in the loss of respiratory chain COX activity.


Structure, functional changes, and proliferative pathology of the human mammary lobule in cancerous breasts.
The mammary glandular tree of 50 human female breasts removed for clinical cancer by radical mastectomy was studied by subgross analysis in whole thin slices, a method that allowed a three-dimensional appraisal of the glandular structures, with removal of interesting or suspicious changes for histology. The glandular tree was more often atrophic (70%) than "adenosic" (righ in mammary lobules, 30%). Many physiopathologic changes were observed, mainly in the lobular area. Abnormal lobules were categorized by type on the basis of size, sensitivity to hormones, stroma, architecture, pattern of epithelial proliferation, cell type, and cell grading. The functional and minor lobular changes (atrophic, sclerotic, hyperplastic, and cystic) were frequent and, as expected, unevenly distributed between adenosic and atrophic breasts. The proliferative lobular changes (including atypical lobules with epithelial proliferation and metaplastic or apocrine lobules with epithelial proliferation) were also frequent but evenly distributed in adenosic (51%) or atrophic (46%) breasts. Intrinsic or extrinsic epithelial proliferation often caused unfolding or lengthening of the lobular structures with deviation of lobular architecture toward ductlike formations. The cells of proliferative changes ranged from typical cells to the anaplastic cells of in situ carcinomas. Independent microscopic foci of infiltrating cancer were found in 20% of either adenosic or atrophic breasts.


Monoclonal antibodies recognizing the nuclear binding sites of the avian oviduct progesterone receptor.
Monoclonal antibodies which block the binding of the avian oviduct progesterone receptor (PR) to nuclear acceptor sites have been prepared. We have previously shown that such acceptor sites consist of complexes of specific nonhistone proteins and DNA. The antigen was a reconstituted, enriched nuclear site for avian oviduct PR formed by reannealing a partially purified acceptor protein to pure hen DNA to reconstitute native-like acceptor sites. These reconstituted acceptor sites were then partially digested with deoxyribonuclease I and injected into BALB/c mice. The spleen cells were fused with NS-1 mouse myeloma cells. Hybridomas were then grown and tested for the ability of their culture media to 1) inhibit PR binding to avian oviduct nucleoacidic protein (NAP) which contains the native-like acceptor sites, but 2) to not inhibit PR binding to pure hen DNA. Three hybridoma clones produced ascites fluids which inhibited PR binding to intact oviduct chromatin and NAP but not to pure hen DNA. Control ascites fluids, prepared against other protein antigens, showed no inhibition of PR binding. The three positive ascites fluids contained low concentrations of immunoglobulin (0.3-0.5 mg/ml). The antibodies did not affect the stability of the receptor and did not interact with PR when analyzed by sucrose density gradient sedimentation. Direct binding of the antibodies to the NAP is shown by an enzyme-linked immunosorbent assay. The monoclonal antibodies display a partial species specificity with regard to the source of NAP in that PR binding to hen oviduct NAP was inhibited by greater than 90%, while PR binding to human uterine NAP was inhibited less than 40% by the antibodies. Further characterization of these candidate antiacceptor site monoclonal antibodies with regard to tissue, species, and steroid receptor specificities are underway.


Inter-organ communication during tissue regeneration.
Tissue regeneration is not simply a local repair event occurring in isolation from the distant, uninjured parts of the body. Rather, evidence indicates that regeneration is a whole-animal process involving coordinated interactions between different organ systems. Here, we review recent studies that reveal how remote uninjured tissues and organ systems respond to and engage in regeneration. We also discuss the need for toolkits and technological advancements to uncover and dissect organ communication during regeneration.


Sleep during the Antarctic winter: preliminary observations on changing the spectral composition of artificial light.
Antarctic Base personnel live for 3 months in winter with no natural sunlight. This project compared sleep, by actigraphy, during periods of increased exposure to white light or blue enriched light in 2003. The primary aim was to help define the optimum spectral composition and intensity of artificial environmental light. Nine men and one woman (33 +/- 7 years, mean +/- SD), wore activity and light monitors continuously from 28.2 to 9.10, and kept sleep diaries. Extra light was provided by light boxes (standard white, 5300 K, or prototype blue enriched, 10,000 K, Philips Lighting), which were turned on in bedrooms and in communal/work areas approximately 08.00-18.00 hours. After a no-treatment control period, 28.2-20.3, sequential 4-5 week periods of first white, then blue light, were imposed with a further control period 19.9-9.10. A limited baseline study in 2002 (no interventions) similarly measured light and activity in seven men and one woman (30 +/- 7 years). Daily light exposure in winter (lux, mean +/- SD) was doubled in 2003 (maximum 1039 +/- 281, average 64 +/- 21), compared to 2002 (572 +/- 276 and 30 +/- 11), P < 0.05 and P < 0.01, with no differences between white and blue light. There were no major differences in sleep between light conditions in 2003. A delay in sleep timing was found in midwinter compared to control (2003, bedtime, P < 0.05, sleep start, P < 0.05, sleep end, P < 0.01) and sleep fragmentation increased (P < 0.05). Sleep efficiency was slightly higher during all blue light periods compared to all white periods (P < 0.05). The use of higher intensity light of suitable spectral composition is proposed.


Ways to improve outcome after cardiopulmonary resuscitation. How to monitor patients, correct dysrhythmias.
Noninvasive monitoring techniques for assessing circulation during CPR include thoracic electrical bioimpedance and measurement of end-tidal carbon dioxide. Many dysrhythmias can be corrected with portable devices, such as automatic external defibrillation pacers, or with automatic implantable cardioverter-defibrillators or external transcutaneous cardiac pacers. Bradycardia is treated, however, only if it is accompanied by hemodynamically significant hypotension or ventricular ectopy. Adenosine may be preferable to verapamil for the management of paroxysmal supraventricular tachycardia. Three consecutive energy discharges are now recommended for the management of ventricular fibrillation.


[New Developments in Compression Treatment].
Patients with peripheral arterial occlusive disease who show an ankle arterial pressure of minimum 60 mmHg can be decongested by use of special padded bandages. Afterwards, medical compression stockings (class 1) with high strength and less elasticity are recommended. Mobile patients seem to benefit from progressive compression therapy with highest pressure above the calf. Compression after uncomplicated interventions of varicose veins or spider veins tends to be modified to a short and excentric compression in patients without risk factors. Valid datas are not available yet. Adaptive compression bandages show pros concerning efficiency, economy and more comfort for patients with edemas or ulcers.


FANCP/SLX4: a Swiss army knife of DNA interstrand crosslink repair.
Fanconi anemia (FA) is a rare genetic disease characterized by congenital abnormalities, bone marrow failure and heightened cancer susceptibility. The FA proteins are known to function in the cellular defense against DNA interstrand crosslinks (ICLs), a process that remains poorly understood. A recent spate of discoveries has led to the identification of one new FA gene, FANCP/SLX4, and two strong candidate FA genes, FAN1 and RAD51C. In this perspective we describe the discovery of FANCP/SLX4 and discuss how these new findings collectively refine our understanding of DNA ICL repair.


Laser induced high temperature thermal-mechanical-oxygen coupling experimental system and method.
In this paper, a thermal-mechanical-oxidation coupling experimental system based on laser heating is developed, containing two modes of Gaussian and flat-top lasers, which has a series of advantages such as high temperature range, rapid heating rate, and convenient observation. The system adopts active illumination and an optical filter to solve the problem where it is difficult for traditional digital-image correlation technology to image clearly under laser heating. A biaxial mechanical test machine is used to simulate the complex load by applying biaxial tension or compression loads on the material. Combined with the radiation temperature measurement and controllable flow field device, the thermal-mechanical-oxygen coupling experiment of high temperature resistant materials under aerobic environment can be carried out. The maximum uniform heat flux output density is 27.2 kW/cm2, and the maximum Gaussian heat flux output density is 105 kW/cm2. The thermal-mechanical-oxygen coupling experimental system and method are of great significance to the development of new high temperature resistant materials and thermal barrier coatings.


The phiX174 protein J mediates DNA packaging and viral attachment to host cells.
Packaging of viral genomes into their respective capsids requires partial neutralization of the highly negatively charged RNA or DNA. Many viruses, including the Microviridae bacteriophages phiX174, G4, and alpha3, have solved this problem by coding for a highly positively charged nucleic acid-binding protein that is packaged along with the genome. The phiX174 DNA-binding protein, J, is 13 amino acid residues longer than the alpha3 and G4 J proteins by virtue of an additional nucleic acid-binding domain at the amino terminus. Chimeric phiX174 particles containing the smaller DNA-binding protein cannot be generated due to procapsid instability during DNA packaging. However, chimeric alpha3 and G4 phages, containing the phiX174 DNA-binding protein in place of the endogenous J protein, assemble and are infectious, but are less dense than the respective wild-type species. In addition, host cell attachment and native gel migration assays indicate surface variations of these viruses that are controlled by the nature of the J protein. The structure of alpha3 packaged with phiX174 J protein was determined to 3.5A resolution and compared with the previously determined structures of phiX174 and alpha3. The structures of the capsid and spike proteins in the chimeric particle remain unchanged within experimental error when compared to the wild-type alpha3 virion proteins. The amino-terminal region of the phiX174 J protein, which is missing from wild-type alpha3 virions, is mostly disordered in the alpha3 chimera. The differences observed between solution properties of wild-type phiX174, wild-type alpha3, and alpha3 chimera, including their ability to attach to host cells, correlates with the degree of order in the amino-terminal domain of the J protein. When ordered, this domain binds to the interior of the viral capsid and, thus, might control the flexibility of the capsid. In addition, the properties of the phiX174 J protein in the chimera and the results of mutational analyses suggest that an evolutionary correlation may exist between the size of the J protein and the stoichiometry of the DNA pilot protein H, required in the initial stages of infection. Hence, the function of the J protein is to facilitate DNA packaging, as well as to mediate surface properties such as cell attachment and infection.


Cardiac rehabilitation effects on quality of life in patients after acute myocardial infarction.
Aim of this study was to investigate the significance of cardiac rehabilitation (CR) on Health Related Quality of Life ( HRQoL) in post acute myocardial infarction (AMI) patients. Methods. A total number off 110 individuals divided in 3 groups was included in the study. Group A consisted of 60 post-AMI pts participating in a CR program. It was a multidisciplinary rehabilitative approach including supervised bike exercise, with parallel education, counselling, psychological and social support, performed 3 times per week for 2 months after AMI . Group B consisted of 40 post-AMI pts not participating in any CR program while the control group C consisted of 10 apparently healthy people. HRQoL was evaluated by the Velasco-Del Barrio questionnaire. Questions on this questionnaire are reffered to 9 categories (health, sleep and rest, emotional behavior, concerns for the future, mobility, social interaction, alertness behavior, communication, work and leisure time). A 5-point scale (1=all of the time, 5=none of the time) and a special (1 to 8) coefficient for each parameter were used for the evaluation of each parameter. The highest score of 220 indicates the poorest QL. Results. Group A pts had better score of HRQoL as compared to Group B (94±3 vs 114±3, p<0.001) and slightly worse than Group C pts (94±4 vs 69±3, p<0.01).Significant difference was found among Group A and B pts regarding the most important evaluated parameters such as symptoms (17±6.8 vs 22±6.5, p<0.001) and social behavior (21±4.2 vs 23±5.5, p<0.0001).Conclusion. It is concluded that participation in a multidisciplinary CR program significantly improves HRQoL in post AMI pts. All these pts must urged to take part in such programs.


Recurrence of Granular Corneal Dystrophy Type 1 After Phototherapeutic Keratectomy, Lamellar Keratoplasty, and Penetrating Keratoplasty in a Single Population.
To describe the recurrence of granular corneal dystrophy type 1 (GCD1) after penetrating keratoplasty (PKP), anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), and phototherapeutic keratectomy (PTK) in a single population. The time required to achieve best-corrected visual acuity (BCVA) after each intervention was also analyzed. Retrospective review of all patients with GCD1 from a single center between 1989 and 2016. Surgical interventions were performed 50 times on 28 eyes of 15 patients. Data were primarily analyzed through Cox regression modeling with clustering and robust log-rank testing. Significant recurrence occurred most rapidly after PTK (median time 2.7 years) and was most delayed after PKP (13.7 years). Significant recurrence occurred at a similar interval after ALK and DALK (3.7 and 3.2 years, respectively). Significant recurrence-free survival was longer for PKP than for ALK, DALK, or PTK (P = 0.04). The time required to obtain BCVA was shorter in the PTK group (median 1.8 months) than in the PKP and DALK groups (median 5.3 and 8.4 months, respectively; P = 0.03 and P = 0.02). All groups achieved a similar median BCVA (20/25-20/30). This series indicates that GCD1 recurrence-free survival is longest after PKP with an associated delay in attaining BCVA. Conversely, PTK provided the fastest visual recovery with shorter recurrence-free survival.


Machine Learning-Based Detection of Parkinson's Disease From Resting-State EEG: A Multi-Center Study.
Resting-state EEG (rs-EEG) has been demonstrated to aid in Parkinson's disease (PD) diagnosis. In particular, the power spectral density (PSD) of low-frequency bands (δ and θ) and high-frequency bands (α and β) has been shown to be significantly different in patients with PD as compared to subjects without PD (non-PD). However, rs-EEG feature extraction and the interpretation thereof can be time-intensive and prone to examiner variability. Machine learning (ML) has the potential to automatize the analysis of rs-EEG recordings and provides a supportive tool for clinicians to ease their workload. In this work, we use rs-EEG recordings of 84 PD and 85 non-PD subjects pooled from four datasets obtained at different centers. We propose an end-to-end pipeline consisting of preprocessing, extraction of PSD features from clinically-validated frequency bands, and feature selection. Following, we assess the classification ability of the features via ML algorithms to stratify between PD and non-PD subjects. Further, we evaluate the effect of feature harmonization, given the multi-center nature of the datasets. Our validation results show, on average, an improvement in PD detection ability (69.6% vs. 75.5% accuracy) by logistic regression when harmonizing the features and performing univariate feature selection (k = 202 features). Our final results show an average global accuracy of 72.2% with balanced accuracy results for all the centers included in the study: 60.6%, 68.7%, 77.7%, and 82.2%, respectively.Clinical relevance- We present an end-to-end pipeline to extract clinically relevant features from rs-EEG recordings that can facilitate the analysis and detection of PD. Further, we provide an ML system that shows a good performance in detecting PD, even in the presence of centers with different acquisition protocols. Our results show the relevance of harmonizing features and provide a good starting point for future studies focusing on rs-EEG analysis and multi-center data.


Analysis of optical gradient profiles during temperature- and salt-dependent swelling of thin responsive hydrogel films.
Surface-attached, cross-linked hydrogel films based on thermoresponsive N-isopropylacrylamide with a dry thickness >1 microm were studied with surface plasmon resonance/optical waveguide mode spectroscopy (SPR/OWS) to monitor temperature-dependent and salt-induced changes of their swelling state. In combination with the reversed Wentzel-Kramers-Brillouin and Bruggeman effective medium approximation and by modeling the hydrogel film as a composite of sublayers with individual complex refractive indices, refractive index/volume fraction gradient profiles perpendicular to the surface are accessible simultaneously with information about local inhomogeneities. Specifically, the imaginary refractive index kappa of each sublayer can be interpreted as a measure for static and dynamic inhomogeneities, which were found to be highest at the volume transition collapse temperature in the layer center. These results indicate that the hydrogel collapse originates rather from the film center than from its boundaries. Upon addition of NaCl to a swollen hydrogel below its transition temperature, comparable optical loss characteristics as for the thermal gel collapse are observed with respect to inhomogeneities. Interestingly, in contrast to the thermally induced layer shrinkage and collapse, swelling increases at intermediate salt concentrations.


Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class I Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor.
A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae ( Fj) differs fundamentally from known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O2-) for activation, but it does not require the O2--supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins. Rather, Fj β directly deploys an oxidized dimanganese cofactor for radical initiation. In treatment with one-electron reductants, the cofactor can undergo cooperative three-electron reduction to the II/II state, in contrast to the quantitative univalent reduction to inactive "met" (III/III) forms seen with I(a-c) βs. This tendency makes Fj β unusually robust, as the II/II form can readily be reactivated. The structure of the protein rationalizes its distinctive traits. A distortion in a core helix of the ferritin-like architecture renders the active site unusually open, introduces a cavity near the cofactor, and positions a subclass-d-specific Lys residue to shepherd O2- to the Mn2II/II cluster. Relative to the positions of the radical tyrosines in the Ia/b proteins, the unreactive Tyr 104 of Fj β is held away from the cofactor by a hydrogen bond with a subclass-d-specific Thr residue. Structural comparisons, considered with its uniquely simple mode of activation, suggest that the Id protein might most closely resemble the primordial RNR-β.