Antiherpetic Effects of Gynura procumbens.
The ethanol extract of Gynura procumbens showed virucidal and antireplicative actions against herpes simplex virus HSV-1 and HSV-2. It was further chromatographed on MCI gel CHP20P column giving the extract fractions F1 (water), F2 (water-methanol) F3 (methanol), and F4 (ethyl acetate). All but F1 had virucidal action against both viral types. We reported here the active compounds from F2 and F3. The antiherpetic compounds of F2 was a mixture of dicaffeoylquinic acids with virucidal and antireplicative actions against HSV-2 (IC50 96.0 and 61.0 μ g/mL, resp.) Virucidal compounds of F3 were a mixture of β -sitosterol and stigmasterol (IC50 250.0 μ g/mL against HSV-1), a mixture of β -sitosteryl and stigmasteryl glucosides (IC50 50.0 μ g/mL against HSV-2) and 1, 2-bis-dodecanoyl-3- α -D-glucopyranosyl-sn-glycerol (IC50 of 40.0 μ g/mL against HSV-2). Herbal products containing 1 and 2% of standardized ethanol extract were prepared. Double-blind randomized controlled clinical trial of the products was performed in patients with recurrent herpes labialis. Results showed that the number of patients, whose lesions healed within 7 days and the average healing time of both groups differed insignificantly. Viral culture on D7 indicated a decrease of infected patients from 48.7% to 7.69% in treated group whereas in placebo group the infected patients decreased from 31.25% to 20.00%. The viral reduction in treated group indicated the benefit of the product. Insignificant result might arise from a low number of participated patients and insufficient concentration of plant extract in herbal product.


Endoscopic full-thickness transoral outlet reduction with semicircumferential endoscopic submucosal dissection.
Endoscopic full-thickness transoral outlet reduction (efTOR) is a therapeutic option to reduce a dilated gastrojejunal anastomosis (GJA) after Roux-en-Y gastric bypass (RYGB). Mucosal ablation with argon plasma coagulation (APC) is usually performed to achieve tissue adaptation. However, rupture of sutures before scarring can lead to recurrent dilatation of the GJA. Here, we describe efTOR with a semicircumferential endoscopic submucosal dissection (ESD-efTOR) as an alternative to APC-efTOR. We enrolled 41 patients with comparable baseline characteristics (APC-efTOR 26; ESD-efTOR 15). The main objectives were reduction in the GJA diameter and in ruptured sutures. Technical success, complications, total weight loss (TWL), and percentage of total and excess weight loss (%TWL and %EWL) at 3 and 12 months, were assessed. ESD-efTOR resulted in significantly fewer ruptured sutures (20 % vs. 69 %; P = 0.004) and a greater reduction in the GJA (major 20 % vs. 0 %; minor 54 % vs. 37 %; no reduction 13 % vs. 58 %; P = 0.02) after 3 months. Technical efficacy, examination time, and rate of complications were comparable. ESD-efTOR resulted in a significantly greater reduction in the GJA diameter and a lower risk of ruptured sutures compared with APC-efTOR.


Lanthanum hexaboride hollow cathode for dense plasma production.
A hollow tube cathode using lanthanum hexaboride as the electron emitter has been designed and constructed. Tests in both argon and hydrogen indicate that this cathode is capable of producing over 800 A of electron current continuously, corresponding to over 25 A/cm(2) from the LaB(6). The cathode has been operated for over 300 h and exposed to air more than 100 times with no deterioration in emission. Projected lifetime is in excess of 3500 h for the sintered LaB(6) piece tested in this configuration. Construction details, performance characteristics, and discussions of space charge limits on emission are described.


[Regulation of cooperative properties of alpha-ketoglutarate dehydrogenase by means of thiol-disulfide metabolism].
The redox state of two SH-groups per enzyme subunit has been shown to control the cooperative properties of alpha-ketoglutarate dehydrogenase. These thiols oxidized, alpha-ketoglutarate dehydrogenase does not exhibit any cooperative properties. The enzyme reduction leads to subunit interactions. It has been found that the most effective agent reducing the alpha-ketoglutarate dehydrogenase thiols essential for the cooperativity is dihydrolipoate, one of the intermediates of the overall alpha-ketoglutarate dehydrogenase reaction. The possibility of changing the properties of alpha-ketoglutarate dehydrogenase in the multienzyme complex under the conditions when the lipoic acid integrated into the complex is reduced, has been investigated. Thus, incubation of the alpha-ketoglutarate dehydrogenase complex with NADH has been found to induce the conversion from the non-cooperative form to the cooperative one, presumably through the reduction of lipoic acid bound to the complex in the reaction catalyzed by lipoyl dehydrogenase, the third component of the complex.


Parenting and the best interests of minors.
The treatment decisions of competent adults, especially treatment refusals, are generally respected. In the case of minors something turns on their age, and older minors ought increasingly to make their own decisions. On the other hand, parents decide on behalf of infants and young children. Their right to do so can best be justified in terms of the importance of preserving intimate family relationships, rather than in terms of the child's best interests, although the child's best interests will most often follow from this arrangement. Nevertheless, there are and ought to be legal, ethical, and financial constraints on parental decision making.


The acquisition of medial /t, d/ allophones in bisyllabic contexts.
The acquisition of medial /t, d/ allophones was examined in four children between 2 and 5 years of age, over a period of 38 months. Children labelled pictures designed to elicit a sample of these allophones in iambic ([t]) and trochaic (flap, nasal and lateral release) contexts. Productions were analysed with reference to attainment of target allophones and use of non-target segmental (e.g., [d] or [t] in place of flap) and syllabic variants (e.g., unstressed syllable deletion). All children produced the target [t] allophone in iambic context. Across children, between 10 and 15 variants occurred in trochaic contexts. Nasal and lateral release allophones were never attained. Flap attainment was variable, with significant differences across children and across phonetic contexts. Results suggest a hierarchy of /t, d/ allophone production with reference to prosodic and phonetic contexts. Discussion includes implications of these findings for clinical intervention.


Capturing the impact of individual characteristics on transport accessibility and equity analysis.
Transport accessibility experienced by an individual depends on their needs and abilities, as represented by their individual characteristics, such as age, income and gender. Although important from an equity perspective, the individual component of accessibility is currently ignored in most transport equity studies. This paper evaluates the impact of including individual characteristics into logsum-based accessibility measures for transport equity analysis. Using data from the London Travel Demand Survey (LTDS) 2011-13, two alternate logsum measures of accessibility are specified - with and without individual characteristics. An empirical analysis of spatial, social and economic equity is conducted using both the measures, and the outcomes are compared. The results clearly demonstrate that ignoring individual characteristics in logsum measures of accessibility can lead to unreliable outcomes for social and economic equity analysis, but do not add significant value when aggregated across large geographical zones for spatial equity analysis. Overall, ignoring individual characteristics masks the disparity in distribution of accessibility, as measured by the Gini index. Although not straightforward, the difference between accessibility patterns using the two logsum measures also yields insights into the possible causes of inequity, which can provide actionable inputs to policy makers. The study highlights that personal needs and abilities are often responsible for accessibility variations among individuals and ignoring them can result in a misleading picture of equity, as demonstrated quantitatively in this paper.


Contribution to catalysis and stability of the five cysteines in Escherichia coli aspartate aminotransferase. Preparation and properties of a cysteine-free enzyme.
The five cysteines, at positions 82, 191, 192, 270, and 401, of Escherichia coli aspartate aminotransferase (AATase) were, individually and in some combinations, converted to alanine by site-directed mutagenesis (C82A, C191A, C192A, C270A, C401A). Cys-191, which is conserved in all AATase isozymes, was mutated to serine as well (C191S). A quintuple mutant, with all cysteines converted to alanines (Quint), was also constructed. The effects of these single and multiple mutations were examined by steady-state kinetics and urea denaturation. The thermal stabilities of Quint and of the wild-type enzyme (WT) were determined by differential scanning calorimetry. The mutants had kcat values up to 50% greater than that of WT and KMAsp and KM alpha-KG values up to 1.5- and 3.3-fold higher than that of WT. The mutants C82A and C191A exhibit nearly the same CM in urea denaturation experiments as WT, while the other single mutants and Quint are less stable, with CM differences of up to 0.7 M urea. Quint is also less thermostable than WT, with a delta TM of 3.3-4.4 degrees C. Thus the five cysteine replacements yield small, but significant, changes in catalytic and denaturation parameters, but none of the cysteines was found to be essential. The changes manifested in the mutation of the conserved Cys-191 to alanine are no greater than those observed with the four nonconserved cysteines. We consider the evolutionary implications of these findings.


Prognostic value of lymphocyte-monocyte ratio at diagnosis in Hodgkin lymphoma: a meta-analysis.
Prognoses of most adult Hodgkin lymphoma (HL) patients are excellent; most of them can achieve permanent remission that can be considered cured. However, many are under-treated or over-treated by standard modern therapies. An accurate determination of prognosis may allow clinicians to design personalised treatment according to individual risk of disease progression and survival. Lymphocyte monocyte ratio (LMR) at diagnosis has been investigated as a prognostic biomarker in patients with HL. Our objective with this meta-analysis was to explore the prognostic value of the LMR at diagnosis in adult HL, by investigating the association between LMR and survival outcomes. PUBMED and EMBASE were searched for relevant articles. Survival outcomes that we investigated included overall survival (OS), progression-free survival (PFS), event-free survival (EFS), lymphoma-specific survival (LSS), and time to progression (TTP). No restriction to the language, date, study country, or sample size was applied. Final search of databases was performed on 2 April 2018. We performed random-effects meta-analysis to aggregate and summarise the results from included studies, where four or more studies on a particular outcome were available. A total of eight studies (all retrospective cohort studies) involving 3319 HL patients were selected for analysis. All studies except one reported the effect of LMR on OS; five reported on PFS, three reported on TTP and LSS, respectively, and one reported on EFS. The pooled estimates showed low LMR was associated with poor OS (hazard ratio [HR] 2.67, 95% CI 1.67, 4.26) and PFS (HR 2.19, 95% CI 1.46, 3.29). Subgroup analyses of OS stratified by LMR cut-off values and sample sizes both indicated that low baseline LMR was associated with poorer prognosis. Low LMR at diagnosis was associated with poor OS and PFS in HL. LMR is easy and cheap to determine and has a potential role in daily clinical management. More studies are needed to validate this biomarker and explore its interaction with known prognostic factors.


Zika Virus-Infected Decidual Cells Elicit a Gestational Age-Dependent Innate Immune Response and Exaggerate Trophoblast Zika Permissiveness: Implication for Vertical Transmission.
Vertical transmission of the Zika virus (ZIKV) causes severe fetal defects, but the exact pathogenic mechanism is unclear. We identified up to a 10,480-fold higher expression of viral attachment factors AXL, GAS6, and PROS1 and a 3880-fold increase in ZIKV infectiousness/propagation in human term decidual stromal cells versus trophoblasts. Moreover, levels of viral attachment factors and ZIKV are significantly increased, whereas expression of innate immune response genes are significantly decreased, in human first trimester versus term decidual cells. ZIKV-infected decidual cell supernatants increased cytotrophoblasts infection up to 252-fold compared with directly infected cytotrophoblasts. Tizoxanide treatment efficiently inhibited Zika infection in both maternal and fetal cells. We conclude that ZIKV permissiveness, as well as innate immune responsiveness of human decidual cells, are gestational age dependent, and decidual cells augment ZIKV infection of primary human cytotrophoblast cultures, which are otherwise ZIKV resistant. Human decidual cells may act as reservoirs for trimester-dependent placental transmission of ZIKV, accounting for the higher Zika infection susceptibility and more severe fetal sequelae observed in early versus late pregnancy. Moreover, tizoxanide is a promising agent in preventing perinatal Zika transmission as well as other RNA viruses such as coronavirus.


Novel acyl-coenzyme A:monoacylglycerol acyltransferase plays an important role in hepatic triacylglycerol secretion.
Acyl-CoA:monoacylglycerol acyltransferase (MGAT) plays a predominant role in the resynthesis of triacylglycerol in the small intestine, but its contribution to triacylglycerol synthesis in other tissues, such as the liver, is not clear. In this study, we identified a novel MGAT gene, which is identical with lysophosphatidylglycerol acyltransferase1 (LPGAT1). Mouse LPGAT1 is expressed in a number of tissues and most highly expressed in the liver. Hepatic LPGAT1 expression in diabetic db/db mice is higher than that in the control db/m mouse, which is consistent with increased hepatic MGAT activity in db/db mouse. To elucidate the role of LPGAT1 gene in lipid metabolism in db/db mice, we constructed an adenovirus of short hairpin RNA (shRNA) targeting LPGAT1 to selectively knockdown LPGAT1 gene expression in the liver. Hepatic MGAT activity and LPGAT1 expression in db/db mice infected with LPGAT1 shRNA adenovirus were significantly lower than those in mice infected with the control virus. Notably, treatment with LPGAT1 shRNA adenovirus caused a marked reduction in serum triacylglycerol and cholesterol levels and a significant increase in hepatic cholesterol level. These findings indicate that LPGAT1, a newly identified MGAT enzyme, plays a significant role in hepatic triacylglycerol synthesis and secretion in db/db mice.


Pharmacokinetic and metabolism studies of two novel 1-deaza-7,8-dihydropteridines in mice.
The disposition of two 1-deaza-7,8-dihydropteridines, NSC 269416 and NSC 350386, was studied in mice dosed iv. After dosing with 25 mg/kg of NSC 269416, serum levels fell in two phases with half-lives of 3.1 and 32 min. Highest levels were in liver, kidney, spleen, lungs, and small intestines; little compound was detected in brain, muscle, or fat. Although no metabolites were detected in serum or tissues, four metabolites, but no parent compound, were present in urine. After administration of 7 mg/kg of NSC 350386, serum levels fell with apparent half-lives of 4.3 (alpha-phase) and 49 min (beta-phase). At most times of analysis, liver, kidney, spleen, lung, brain, fat, and small intestines had similar concentrations of the compound. In 24 hr, less than 5% of the dose was excreted into urine unchanged. Analyses of collected urinary products indicated that, in vivo, NSC 350386 was metabolically hydroxylated and conjugated with glucuronic acid and also cleaved, a process involving removal of the ethoxycarbonyl group.


Explanatory pluralism in the medical sciences: theory and practice.
Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise.


Glycaemic hygiene.
Hygiene is the foundation of health. This communication proposes the concept of glycaemic hygiene, defined as "conditions and practices that help to maintain health, and prevent the development of diabetes mellitus and its complications". Glycaemic hygiene is relevant at the level of the person, the physician and the community. Aspects such as personal hygiene, food hygiene, physical activity hygiene, mental/ emotional hygiene and dental hygiene must be optimized to ensure good health individuals. Skin hygiene, vaccine hygiene and environmental hygiene are equally important in diabetes care. Physicians should ensure pharmacological hygiene, language hygiene and information hygiene to foster good diabetes self-care and management.


Membrane therapy using DHA suppresses epidermal growth factor receptor signaling by disrupting nanocluster formation.
Epidermal growth factor receptor (EGFR) signaling drives the formation of many types of cancer, including colon cancer. Docosahexaenoic acid (DHA, 22∶6Δ4,7,10,13,16,19), a chemoprotective long-chain n-3 polyunsaturated fatty acid suppresses EGFR signaling. However, the mechanism underlying this phenotype remains unclear. Therefore, we used super-resolution microscopy techniques to investigate the mechanistic link between EGFR function and DHA-induced alterations to plasma membrane nanodomains. Using isogenic in vitro (YAMC and IMCE mouse colonic cell lines) and in vivo (Drosophila, wild type and Fat-1 mice) models, cellular DHA enrichment via therapeutic nanoparticle delivery, endogenous synthesis, or dietary supplementation reduced EGFR-mediated cell proliferation and downstream Ras/ERK signaling. Phospholipid incorporation of DHA reduced membrane rigidity and the size of EGFR nanoclusters. Similarly, pharmacological reduction of plasma membrane phosphatidic acid (PA), phosphatidylinositol-4,5-bisphosphate (PIP2) or cholesterol was associated with a decrease in EGFR nanocluster size. Furthermore, in DHA-treated cells only the addition of cholesterol, unlike PA or PIP2, restored EGFR nanoscale clustering. These findings reveal that DHA reduces EGFR signaling in part by reshaping EGFR proteolipid nanodomains, supporting the feasibility of using membrane therapy, i.e., dietary/drug-related strategies to target plasma membrane organization, to reduce EGFR signaling and cancer risk.


Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population.
The bile salt export pump (BSEP) encoded by ABCB11 is located in the canalicular membrane of hepatocytes and mediates the secretion of numerous conjugated bile salts into the bile canaliculus. In this study, 28 ABCB11 exons (including non-coding exon 1) and their flanking introns were comprehensively screened for genetic variations in 120 Japanese subjects. Fifty-nine genetic variations, including 19 novel ones, were found: 14 in the coding exons (6 nonsynonymous and 8 synonymous variations), 4 in the 3'-UTR, and 41 in the introns. Three novel nonsynonymous variations, 361C>A (Gln121Lys), 667C>T (Arg223Cys), and 1460G>T (Arg487Leu), were found as heterozygotes and at 0.004 allele frequencies. These data provide fundamental and useful information for genotyping ABCB11 in the Japanese and probably other Asian populations.


[Suicide attempts in the General Hospital and warning signs].
Suicide represents a major public health issue and much research is focusing on the prevention and management of suicidal behavior. The present study aims at the assessment of Warning Signs of Suicide. For this purpose, 100 patients admitted for attempted suicide in Sotiria General Hospital have been included in the study. All patients have been examined through a semi-structured psychiatric interview, the somministration of Beck Depression Inventory (BDI) and the assessment of the following Warning Signs: Internalization, Feeling gloomy, Presence of recent trauma in the patient's history, Change of behavior, Fear, Giving gifts, Depression and Aggression. The results showed that 80% of the sample presented at least two warning signs whereas only 10% of the patients had no warning signs. Moreover, a strong correlation was observed between the total score of depression as assessed with the BDI Scale and the number of Warning Signs. Warning Signs are present with a high percentage in patients who attempt suicide and many authors suggest that they should be included in suicide prevention. Therefore, it is important for all mental health clinicians to integrate the assessment of Warning Signs into their practices and to educate both patients and family members to recognize them.


Improved assessment of functional resectability in repeated hepatectomy by computer-assisted operation planning.
Assessment of the post-resectional functioning liver parenchyma is one of the most important issues in operation planning of liver resections. However, preoperative assessment of the future liver remnant's vascularization is in particular difficult in repeated hepatectomy because of the often altered intrahepatic vascular system after prior vascular dissection. Therefore, in these resections preoperative calculation of the remaining liver parenchyma with unimpaired vascular function is uncertain and imprecise. Based on the case of a 62-year-old woman with a recurrent colorectal liver metastasis in segments VII and VIII after prior left-lateral liver resection (segments II/III) we describe the potential use of computer-assisted operation planning for assessment of functional resectability in repeated hepatectomy.


Adequacy of mortality data and correction of reported deaths from the Proactive Search of Deaths.
The aim of this paper is to propose indicators of adequacy and to estimate correction factors for deaths reported to SIM. In 2014, we carried out a Proactive Search to capture deaths that occurred in 2012 in a sample of municipalities in the regions North and Northeast, and the states of Minas Gerais, Mato Grosso and Goiás. To characterize the coverage of deaths information, we proposed indicators of adequacy by municipality. Correction factors were estimated for individuals one year of age or older and younger than 1 year old. Among the deaths of people aged one year or more, the coverage was above 90% in 12 states. As for infant deaths, the coverage was less than 80% in 7 states. The results of the regression models showed association between the correction factors estimated and the proposed indicators of adequacy. We found very poor death information in 227 municipalities, for which the reported number of infant deaths even after correction, could not reach the minimum expected. Although the progress made in information of vital data in Brazil is recognized, the results show that our greatest challenge is to reach rural and remote municipalities, which do not yet have adequate vital information.


Less is more: optimal recording time for measuring the steady-state accommodative response.
Clinical Relevance Background: Steady-state accommodation is frequently evaluated with open-field autorefractors; however there is no consensus regarding the optimal test duration. Our results allow us to standardise the procedure followed for the assessment of the steady-state accommodative response in clinical and laboratory settings and may be of great relevance in time-constrained situations. The present study aims to determine the optimal recording time to assess the magnitude and variability of the accommodative response with a binocular open-field autorefractor. The steady-state accommodative response of 84 healthy undergraduate students was dynamically measured using the Grand Seiko WAM-5500 autorefractor at 500 cm, 40 cm and 20 cm for 90 s while participants maintained focus on a stationary target. We examined the reliability and level of agreement between four time intervals (the first 10-s, 30-s, 60-s and 90-s) at three accommodative demands (0.2D, 2.5D and 5D). The magnitude of accommodation showed an excellent level of reliability (intraclass correlation coefficient [ICC]> 0.90) for the comparisons between the 90-s, 60-s and 30-s time intervals at the three viewing distances tested. However, when including the 10-s interval, there was a moderate reduction of the reliability indices and an increase of the mean difference between two time intervals (intra-class correlation [ICC] ranging from 0.89 to 0.97; and ESs ranging from 0.16 to 0.42). For the variability of accommodation, we observed an excellent reliability for the comparisons of the 90-s and 60-s measures at the three accommodative demands (ICC: 0.95-0.96), whereas for the rest of comparisons we observed from moderate to good levels of reliability. Our data indicate that of 30-s and 60-s are enough to accurately assess the magnitude and variability of the accommodative response with the WAM-5500 autorefractor, respectively.


Activation of the factor VIIIa-factor IXa enzyme complex of blood coagulation by membranes containing phosphatidyl-L-serine.
Factor IXa, a serine protease of blood coagulation, functions at least 100,000 times more efficiently when bound to factor VIIIa on a phospholipid membrane than when free in solution. We have utilized the catalytic activity of the factor VIIIa-factor IXa complex to report the effect of phospholipid membranes on binding of factor IXa to factor VIIIa and on enzymatic cleavage of the product. The apparent affinity of factor IXa for factor VIIIa was 10-fold lower in the absence of phospholipid membranes with a KD of 46 nM versus 4.3 nM with phospholipid membranes. The Km for activation of factor X by the factor VIIIa-factor IXa complex was 1700 nM in solution, 70-fold higher than the value of 28 nM when bound to membranes containing phosphatidyl-L-serine, phosphatidylethanolamine, and phosphatidylcholine at a ratio of 4:20:76. The largest effect of phosphatidyl-L-serine-containing membranes on the factor VIIIa-factor IXa complex was the accelerated rate of peptide bond cleavage, with the k(cat) increased by 1,500-fold from 0.022 to 33 min-1. Membranes in which phosphatidyl-L-serine was replaced by phosphatidyl-D-serine, phosphatidic acid, or phosphatidylglycerol were at least 10-fold less effective for enhancing the k(cat). Thus, while membranes containing phosphatidyl-L-serine enhance condensation of the enzyme with its cofactor and substrate, their largest effect is activation of the assembled factor VIIIa-factor IXa enzyme complex.


Necrosis affinity evaluation of 131I-hypericin in a rat model of induced necrosis.
Cancers are often with spontaneous or therapeutic necrosis that could be utilized as a generic target for developing new treatments. The purpose of this study was to investigate the biodistribution and pharmacokinetics of radioiodinated hypericin (Hyp), a naturally occurring compound, after intravenous (i.v.) injection in a rat model of liver and muscle necrosis (n = 42), and evaluate its necrosis affinity. Hyp was labeled with (131)I with labeling efficiency >99%. After incubating in solution/rat plasma for 8 days, radiochemical purity of (131)I-Hyp remained 98.1 and 97.1%, respectively, indicating good in vitro stability. SPECT-CT images at 24 h after i.v. injection of (131)I-Hyp in rats with induced liver and muscle necrosis showed obvious tracer absorption in necrotic tissues. Biodistribution studies revealed that the percentage of the injected dose per gram of tissue (%ID/g) evolved from 1.9 %ID/g at 6 h, through a maximum 3.0 %ID/g at 12 h, to 1.0 %ID/g at 192 h in necrotic liver. Pharmacokinetics studies revealed that the terminal elimination half-life, total body clearance and area under the curve of (131)I-Hyp were 32.7 h, 9.2 L/h/kg and 1.6 MBq/L*h, respectively. These results demonstrated that (131)I-Hyp features a long blood circulation in animals and persistent retention in necrotic tissues. Therefore, (131)I-labeled Hyp could be a broad-spectrum anti-tumor agent with a cost much cheaper relative to the biological agents such as monoclonal antibodies.


Click-evoked otoacoustic emissions recorded from untreated congenital hypothyroid newborns.
Thyroid hormone plays an important role in hearing development. Both a genetic or non-genetic hypothyroidism is often associated with congenital hearing loss. The exact incidence of hearing impairment in untreated congenital hypothyroid (CH) patients is unknown. This paper will present the results of measuring of the transient-evoked otoacoustic emissions (TEOAE) in a population of 29 newborns, who tested positive on a screening test for hypothyroidism (CH group) and in 68 well babies (control group) randomly chosen from all the newborns, classified as PASS, included in the Hearing Screening Program of the San Raffaele Hospital in Milan. TEOAE were recorded in all newborns within 1 month after birth and before beginning L-thyroxine treatment with conventional commercial instrumentation. Both temporal and time-frequency analyses of the emitted responses were conducted by means of a wavelet transform. The comparison of the characteristics of the temporal and frequency content of the responses of the two groups (CH and control) showed no statistically significant difference. No correlation was found between outer hair cell dysfunction and hypothyroidism.


Matrix metalloproteinase 8 (collagenase 2) induces the expression of interleukins 6 and 8 in breast cancer cells.
Matrix metalloproteinase 8 (MMP-8) is a tumor-suppressive protease that cleaves numerous substrates, including matrix proteins and chemokines. In particular, MMP-8 proteolytically activates IL-8 and, thereby, regulates neutrophil chemotaxis in vivo. We explored the effects of expression of either a WT or catalytically inactive (E198A) mutant version of MMP-8 in human breast cancer cell lines. Analysis of serum-free conditioned media from three breast cancer cell lines (MCF-7, SK-BR-3, and MDA-MB-231) expressing WT MMP-8 revealed elevated levels of IL-6 and IL-8. This increase was mirrored at the mRNA level and was dependent on MMP-8 catalytic activity. However, sustained expression of WT MMP-8 by breast cancer cells was non-permissive for long-term growth, as shown by reduced colony formation compared with cells expressing either control vector or E198A mutant MMP-8. In long-term culture of transfected MDA-MB-231 cells, expression of WT but not E198A mutant MMP-8 was lost, with IL-6 and IL-8 levels returning to base line. Rare clonal isolates of MDA-MB-231 cells expressing WT MMP-8 were generated, and these showed constitutively high levels of IL-6 and IL-8, although production of the interleukins was no longer dependent upon MMP-8 activity. These studies support a causal connection between MMP-8 activity and the IL-6/IL-8 network, with an acute response to MMP-8 involving induction of the proinflammatory mediators, which may in part serve to compensate for the deleterious effects of MMP-8 on breast cancer cell growth. This axis may be relevant to the recognized ability of MMP-8 to orchestrate the innate immune system in inflammation in vivo.


The effect of skin temperature on performance during a 7.5-km cycling time trial.
Aerobic exercise performance is seriously compromised in the heat. Possibly, a high skin temperature causes a rating of perceived exertion (RPE)-mediated decrease in exercise intensity. The purpose of this study was to determine the effect of skin temperature on power output during a 7.5-km cycling time trial. Thirteen well-trained male subjects performed a 7.5-km cycling time trial at 15°C and 50% relative humidity (CONTROL), with radiative heat stress during the time trial, and with (PRECOOL) or without (HEAT) precooling. Heat stress was applied by infrared heaters positioned in front of the cycle ergometer between 1.5 and 6.0 km. Skin, rectal, and pill temperature, power output, heart rate, and RPE were measured during the trial. Despite the lower mean skin temperature at the start of the time trial for PRECOOL compared to HEAT (-2.1 ± 0.7°C; P < 0.01) and CONTROL (-1.8 ± 0.6°C; P < 0.05), and a greater increase in mean skin temperature during the heat stress period for PRECOOL (4.5 ± 1.0°C) and HEAT (3.9 ± 0.8°C) than for CONTROL (-0.3 ± 0.6°C; P < 0.01), no differences in power output were found between HEAT (273 ± 45 W) and CONTROL (284 ± 43 W; P = 0.11) and between HEAT and PRECOOL (266 ± 50 W; P = 0.47). Power output during the time trial was greater for CONTROL than for PRECOOL (P < 0.05). Additionally, no differences were observed in core temperature measures, HR, and RPE. Skin temperature does not affect the selection and modulation of exercise intensity in a 7.5-km cycling time trial.


Balancing student/trainee learning with the delivery of patient care in the healthcare workplace: a protocol for realist synthesis.
A national survey was recently conducted to explore medical education research priorities in Scotland. The identified themes and underlying priority areas can be linked to current medical education drivers in the UK. The top priority area rated by stakeholders was: 'Understanding how to balance service and training conflicts'. Despite its perceived importance, a preliminary scoping exercise revealed the least activity with respect to published literature reviews. This protocol has therefore been developed so as to understand how patient care, other service demands and student/trainee learning can be simultaneously facilitated within the healthcare workplace. The review will identify key interventions designed to balance patient care and student/trainee learning, to understand how and why such interventions produce their effects. Our research questions seek to address how identified interventions enable balanced patient care-trainee learning within the healthcare workplace, for whom, why and under what circumstances. Pawson's five stages for undertaking a realist review underpin this protocol. These stages may progress in a non-linear fashion due to the iterative nature of the review process. We will: (1) clarify the scope of the review, identifying relevant interventions and existing programme theories, understanding how interventions act to produce their intended outcomes; (2) search journal articles and grey literature for empirical evidence from 1998 (introduction of the European Working Time Directive) on the UK multidisciplinary team working concerning these interventions, theories and outcomes, using databases such as ERIC, Scopus and CINAHL; (3) assess study quality; (4) extract data; and (5) synthesise data, drawing conclusions. A formal ethical review is not required. These findings should provide an important understanding of how workplace-based interventions influence the balance of trainee learning and service provision. They should benefit various stakeholders involved in workplace-based learning interventions, and inform the medical education research agenda in the UK.


Growth of 28 Legionella species on selective culture media: a comparative study.
We compared the growth of 28 Legionella spp. on four manufacturers' buffered charcoal-yeast extract (BCYE) agar media and selective BCYE media that contained polymyxin B, anisomycin, and vancomycin or cefamandole. With BCYE as a "gold standard," growth for Legionella pneumophila was significantly better than for the nonpneumophila species on all media tested. L. pneumophila and 24 other Legionella spp. grew on vancomycin-containing media, while L. santicrucis, L. rubrilucens, and L. erythra grew poorly. In contrast, 11 of 28 species (notably L. micdadei and L. bozemanii) did not grow on cefamandole-containing media and 8 of 28 species only grew marginally. We demonstrated that selective BCYE media that contain vancomycin or cefamandole may not support the growth of all Legionella spp. One commercial manufacturer's media were consistently suboptimal. Laboratories should not rely on a manufacturer's quality control testing in lieu of their own.


Screening for malignant melanoma using instant photography.
To assess the use of instant photography, in addition to clinical grading, as a method of screening for malignant melanoma during routine health examinations. A health screening clinic with an average throughput of about 12,000 patients a year. Suspicious pigmented skin lesions were judged clinically using the revised seven point checklist scoring system. They were then photographed with a Polaroid camera and the prints were graded independently by two consultant dermatologists with a special interest in malignant melanoma. A copy of the print was also given to the patient to keep for observation of any change in the lesion. Over a 45 month period 39,922 patients of both sexes were screened and 1052 skin lesions were clinically assessed and photographed. Fourteen malignant melanomas were diagnosed--all, except one, were thin lesions with a good prognosis. The clinical opinions of non-dermatologists using the revised seven point checklist proved disappointing in screening because of the large number of benign lesions that were given high scores. Photography, on the other hand, detected 11 melanomas and succeeded in separating the majority of banal lesions from potentially malignant ones, thus greatly reducing the need for specialist referral. Nevertheless, three melanomas were missed on purely photographic grading, which emphasises the danger of placing too much reliance solely on a two dimensional image. Finally, the possession of a personal copy of the photograph by the patient proved popular and led to a diagnosis of melanoma in two instances. This procedure merits further study.


Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-α-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes.
Tumor necrosis factor (TNF)-α and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated. The key factors and mechanism of action of TNF-α and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 α (eIF2α) by Western blot and an immunofluorescence assay in 24-hour TNF-α-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation. Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-α-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-α and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2α, a component of the unfolded protein response signaling pathway, was observed in TNF-α or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-α-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2α. These data indicated that AICAR-induced AMPK activation attenuates TNF-α-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2α activity is a novel mechanism of the anti-lipolytic effect of AICAR.


The potential impacts of formyl peptide receptor 1 in inflammatory diseases.
Neutrophils play a critical role in acute and chronic inflammatory diseases. N-formyl peptides, which originate from bacterial peptides or mitochondrial proteins bind with a high binding affinity to formyl peptide receptor 1 (FPR1). N-formyl peptide-FPR1 is involved in the pathogenesis of sterile and infectious inflammatory processes and causes phagocytosis of pathogens or injured cells by neutrophils. Excessive activation of neutrophils by binding of N-formyl peptides is associated with tissue injury requiring drugs that block FPR1-dependent signaling. Here, we review the roles of FPR1 as a critical regulator of inflammatory processes and its involvement in pathological conditions.


Stereotactic body radiotherapy: current strategies and future development.
Stereotactic body radiotherapy (SBRT) has emerged as the standard treatment for medically inoperable early-staged non-small cell lung cancer (NSCLC). The local control rate after SBRT is over 90%. Some forms of tumour motion management and image-guided radiation delivery techniques are the prerequisites for fulfilment of its goal to deliver a high radiation dose to the tumour target without overdosing surrounding normal tissues. In this review, the current strategies of tumour motion management will be discussed, followed by an overview of various image-guided radiotherapy (RT) systems and devices available for clinical practice. Besides medically inoperable stage I NSCLC, SBRT has also been widely adopted for treatment of oligometastasis involving the lungs. Its possible applications in various other cancer illnesses are under extensive exploration. The progress of SBRT is critically technology-dependent. With advancement of technology, the ideal of personalised, effective and yet safe SBRT is already on the horizon.


Preparation from keratin sulfate of substrates for the measurement of 2-acetamido-2-deoxy-D-glucose 6-sulfate sulfatase and (1 goes to 3)-N-acetyl-beta-D-glucosaminidase.
An extract of bacterial cells Pseudomonas sp. IFO-13309 grown on medium containing 0.1% bovine cornea keratan sulfate of low sulfate content degraded exhaustively bovine cornea keratan sulfate to give 2-acetamido-2-deoxy-beta-D-gluco-pyranosyl 6-sulfate-(1 goes to 3)-D-galactose, isolated by gel filtration on Sephadex G-25 and purified by preparative paper chromatography. This was reduced with sodium borotritide to give 2-acetamido-2-deoxy-beta-D-glucopyranosyl 6-sulfate-(1 goes to 3)-D-[1-3H]galactitol, purified by gel filtration on Sephadex G-15, which was an excellent substrate for the measurement of 2-acetamido-2-deoxy-D-glucose 6-sulfate sulfatase. The reduced, radioactive monosulfated disaccharide was desulfated with methanolic 70mM hydrogen chloride and purified by gel filtration on Sephadex G-15 to give O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1 goes to 3)-D-[1-3H]galactitol, which allowed the measurement of (1 goes to 3)-N-acetyl-beta-D-glucosaminidase. This enzyme may participate in the normal degradation of keratan sulfate.


Optimization Algorithms for Joint Power and Sub-Channel Allocation for NOMA-Based Maritime Communications.
This paper investigates resource optimization schemes in a marine communication scenario based on non-orthogonal multiple access (NOMA). According to the offshore environment of the South China Sea, we first establish a Longley-Rice-based channel model. Then, the weighted achievable rate (WAR) is considered as the optimization objective to weigh the information rate and user fairness effectively. Our work introduces an improved joint power and user allocation scheme (RBPUA) based on a single resource block. Taking RBPUA as a basic module, we propose three joint multi-subchannel power and marine user allocation algorithms. The gradient descent algorithm (GRAD) is used as the reference standard for WAR optimization. The multi-choice knapsack algorithm combined with dynamic programming (MCKP-DP) obtains a WAR optimization result almost equal to that of GRAD. These two NOMA-based solutions are able to improve WAR performance by 7.47% compared with OMA. Due to the high computational complexity of the MCKP-DP, we further propose a DP-based fully polynomial-time approximation algorithm (DP-FPTA). The simulation results show that DP-FPTA can reduce the complexity by 84.3% while achieving an approximate optimized performance of 99.55%. This advantage of realizing the trade-off between performance optimization and complexity meets the requirements of practical low-latency systems.


Predictors of nephrological morbidity after coronary artery bypass surgery.
The aim of this study was to analyse the nephrological morbidity after myocardial revascularization. We analysed the pre- per and postoperative data of 3815 patients who underwent a primary isolated coronary bypass grafting between January 1987 and December 1995. Nephrological complications were divided into renal dysfunction and requiring dialysis. The increase in nephrological complications (1.2-4%) is the result of an increase of patients with renal dysfunction. Unifactorial risk analysis identified age, diabetes, hypertension, nephrological pathology, perfusion time, aortic cross-clamp time, emergency operation and perioperative myocardial infarction as risk factors. Multifactorial risk analysis identified age, diabetes, hypertension, nephrological pathology, perfusion time, perioperative myocardial infarction and the cohorts operated upon in 1990-92, 1993-95 as independent risk factors for renal dysfunction, and age, nephrological pathology and perioperative myocardial infarction for those needing dialysis. Several variables have been identified as risk factors for nephrological complications; especially important are pre-existing nephrological pathology and perioperative myocardial infarction.


Theoretical study of excited states of pyrazolate- and pyridinethiolate-bridged dinuclear platinum(II) complexes: relationship between geometries of excited states and phosphorescence spectra.
Dinuclear platinum(II) complexes [Pt(2)(μ-pz)(2)(bpym)(2)](2+) (1; pz = pyrazolate and bpym = 2,2'-bipyrimidine) and [Pt(2)(μ-pyt)(2)(ppy)(2)] (2; pyt = pyridine-2-thiolate and Hppy = 2-phenylpyridine) were theoretically investigated with density functional theory (DFT) to clarify the reasons why the phosphorescence of 1 is not observed in the acetonitrile (CH(3)CN) solution at room temperature (RT) but observed in the solid state at RT and why the phosphorescence of 2 is observed in both the CH(3)CN solution and the solid state at RT. The S(1) and T(1) states of 1 in the CH(3)CN solution are assigned as a metal-metal-to-ligand charge-transfer (MMLCT) excited state. Their geometries are C(2v) symmetrical, in which spin-orbit interaction between the S(1) and T(1) excited states is absent because the direct product of irreducible representations of the singly occupied molecular orbitals (SOMOs) of these excited states and the orbital angular momentum (l) operator involved in the Hamiltonian for spin-orbit interaction does not belong to the a(1) representation. As a result, the S(1) → T(1) intersystem crossing hardly occurs, leading to the absence of T(1) → S(0) phosphorescence in the CH(3)CN solution at RT. In the solid state, the geometry of the S(1) state does not reach the global minimum but stays in the C(1)-symmetrical local minimum. This S(1) excited state is assigned as a mixture of the ligand-centered π-π* excited state and the metal-to-ligand charge-transfer excited state. Spin-orbit interaction between the S(1) and T(1) excited states operates to induce the S(1) → T(1) intersystem crossing because the direct product of the irreducible representations of the SOMOs of these excited states and the l operator belongs to the "a" representation. As a result, T(1) → S(0) phosphorescence occurs in the solid state. In 2, the S(1) and T(1) excited states are assigned as the MMLCT excited state. Their geometries are C(2)-symmetrical in both the CH(3)CN solution and the solid state, in which spin-orbit interaction between the S(1) and T(1) states operates to induce the S(1) → T(1) intersystem crossing because the direct product of the irreducible representations of the SOMOs and the l operator belongs to the "a" representation. Thus, T(1) → S(0) phosphorescence occurs in both the CH(3)CN solution and the solid state at RT, unlike 1.


German Guidelines.
Because of its frequency, diverticular disease is a burden on health care systems. Only few formal guidelines covering all aspects of the disease exist. Here, some selected statements from the German guidelines are given. The guidelines include significant recommendations for the diagnosis and management of diverticular disease. Both diagnosis and management depend definitely on clear definitions of the situation of an individual patient. Therefore, a new classification is proposed that is based on earlier suggestions. An internationally established classification would not only enable better patient care but could also lead to studies with comparable results.


Computed tomography in the elderly: changes over time in a normal population.
The clinical, psychometric, and computed tomographic (CT) status of previously fit elderly volunteers is described at follow-up for up to four years. A number of relationships were found between psychometric and CT scores, but a dementing group could not be determined on the basis of a single scan. However, a subtle reduction in cognition over time was significantly related to CT changes, and occurred in 10%. Larger ventricles were also found in a small sub-group, who developed late-onset depressive disorders; recent bereavement was related to ventricular size. Thus a single CT scan may not be a useful discriminatory test in early dementia, but a repeat demonstrating ventricular enlargement, is likely to be significant. In the elderly, cognitive and CT scan deterioration should not be expected unless a disease process is occurring; this may be indicated by subtle cognitive impairment or by late-onset depressive disorder.


Serum penicillin G levels are lower than expected in adults within two weeks of administration of 1.2 million units.
When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3-4 weeks serum penicillin G levels are less than adequate (below MIC(90) of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections.


Histone Lysine-to-Methionine Mutations Reduce Histone Methylation and Cause Developmental Pleiotropy.
Epigenetic modifications play critical roles in diverse biological processes. Histone Lys-to-Met (K-to-M) mutations act as gain-of-function mutations to inhibit a wide range of histone methyltransferases and are thought to promote tumorigenesis. However, it is largely unknown whether K-to-M mutations impact organismal development. Using Arabidopsis (Arabidopsis thaliana) as a model system, we discovered that a transgene exogenously expressing histone 3 Lys-36 to Met mutation (K36M) acts in a dominant-negative manner to cause global reduction of H3K36 methylation. Remarkably, this dominant repressive activity is dosage-dependent and causes strong developmental perturbations including extreme branching and early flowering by affecting the expression of genes involved in developmental and metabolic processes. Besides the established pathological roles of K-to-M mutations in tumor cells, we demonstrate a physiological outcome for K-to-M induced H3K36 hypomethylation. This study provides evidence for a conserved dominant-negative inhibitory role of histone K-to-M mutation across the plant and animal kingdoms. We also highlight the unique ability of K36M mutations to alter plant developmental processes leading to severe pleiotropic phenotypes. Finally, our data suggests K-to-M mutations may provide a useful strategy for altering epigenetic landscapes in organisms where histone methyltransferases are uncharacterized.


Bacteria-targeted fluorescence imaging of extracted osteosynthesis devices for rapid visualization of fracture-related infections.
Fracture-related infection (FRI) is a serious complication in orthopedic trauma surgery worldwide. Especially, the distinction of infection from sterile inflammation and the detection of low-grade infection are highly challenging. The objective of the present study was to obtain proof-of-principle for the use of bacteria-targeted fluorescence imaging to detect FRI on extracted osteosynthesis devices as a step-up towards real-time image-guided trauma surgery. Extracted osteosynthesis devices from 13 patients, who needed revision surgery after fracture treatment, were incubated with a near-infrared fluorescent tracer composed of the antibiotic vancomycin and the fluorophore IRDye800CW (i.e., vanco-800CW). Subsequently, the devices were imaged, and vanco-800CW fluorescence signals were correlated to the results of microbiological culturing and to bacterial growth upon replica plating of the imaged devices on blood agar. Importantly, compared to culturing, the bacteria-targeted fluorescence imaging of extracted osteosynthesis devices with vanco-800CW allows for a prompt diagnosis of FRI, reducing the time-to-result from days to less than 30 min. Moreover, bacteria-targeted imaging can provide surgeons with real-time visual information on the presence and extent of infection. Here, we present the first clinical application of fluorescence imaging for the detection of FRI. We conclude that imaging with vanco-800CW can provide early, accurate, and real-time visual diagnostic information on FRI in the clinical setting, even in the case of low-grade infections.


Early childhood vaccination levels among urban children--Connecticut, 1990 and 1991.
In the United States, the high incidence of measles among urban preschool-aged children who had not received age-appropriate vaccination has focused attention on the adequacy of and barriers to early childhood vaccinations. To assess early childhood vaccination levels of urban Connecticut children, during fall 1990 and spring 1991, the Connecticut Department of Health Services conducted retrospective surveys of first-grade students in Hartford and New Haven, both with populations greater than 100,000 persons.


The Dynamic Change of Immune Responses Between Acute and Recurrence Stages of Rodent Malaria Infection.
Malaria infections are persistent as frequent recrudescence of the disease may occur following the acute infection stage, but the different immune responses that control the acute and recrudescence stages are still largely unknown. Using single-cell RNA sequencing (scRNA-seq), we showed that the number of Th1 and plasma cells in the spleen was significantly reduced during the recurrence stage compared to the acute stage of Plasmodium chabaudi chabaudi AS (P. chabaudi) infection. Additionally, the ability of both CD4+ T cell responses and B cells to control P. chabaudi recurrence was significantly reduced compared to their roles in the control of acute infection. In contrast, the number of innate immune cells, including red pulp macrophages (RPMs), gamma delta (γδ) T cells, and Dendritic cells (DCs) were significantly increased during the recurrence stage and showed to be critical for P. chabaudi infection recurrence control. Thus, our data strongly suggest the complementary role of innate immune responses in controlling malaria recrudescence when adaptive immune responses are suppressed. These findings shed new light on the development of immune interventions against malaria.


Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients.
Breast conservation has become well-established in the treatment of early mammary carcinoma. However, a standardised treatment modality has not emerged. We have analysed the data from 1,973 patients treated in three consecutive randomised trials by four different radiosurgical procedures: Halsted mastectomy, quadrantectomy plus radiotherapy, lumpectomy plus radiotherapy, and quadrantectomy without radiotherapy, to compare the outcomes of these procedures in terms of local recurrence rate and overall survival. Eligibility criteria were similar in the three trials, and comparability between the four subgroups was excellent. Median follow-up for all patients was 82 months. The annual rates of local recurrence varied markedly according to the treatment. Patients treated with Halsted mastectomy and quadrantectomy plus radiotherapy had low annual rates of local recurrence (0.20 and 0.46, respectively) while both lumpectomy plus radiotherapy and quadrantectomy without radiotherapy had significantly higher rates (2.45 and 3.28, respectively). Patients under 45 years of age had a much higher incidence of local recurrences, while in women over 55 years local recurrences were much less frequent. Overall survival curves were identical in the four groups of patients, so that the three breast conserving radiosurgical procedures had the same survival rates as Halsted mastectomy. However, local recurrence rates were markedly influenced by the treatment method, patient age and specific histological features.


Association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism.
Sudden exposure to high iodide levels may cause thyroid dysfunction. Despite compelling biological plausibility and clinical implication, the association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism has not been rigorously studied. We performed a nested case-control study of patients treated between January 1, 1990, and June 30, 2010, who did not have preexisting hyperthyroidism or hypothyroidism. In parallel analyses, incident hyperthyroid or hypothyroid cases were defined by a change in thyrotropin level from normal (at baseline) to low or high (follow-up measurement). Euthyroid controls were selected using an incidence density sampling approach and were matched to cases on the basis of age, sex, race/ethnicity, estimated glomerular filtration rate, follow-up thyrotropin measurement date, and interval between baseline and the follow-up thyrotropin measurement date. Iodinated contrast media exposure was assessed using claims data for contrast-enhanced computed tomography or cardiac catheterization. In total, 178 and 213 incident hyperthyroid and hypothyroid cases, respectively, were matched to 655 and 779 euthyroid controls, respectively. Iodinated contrast media exposure was associated with incident hyperthyroidism (odds ratio [OR], 1.98; 95% CI, 1.08-3.60), but a statistically significant association with incident hypothyroidism was not observed (OR, 1.58; 95% CI, 0.95-2.62). In prespecified secondary analysis, iodinated contrast media exposure was associated with incident overt hyperthyroidism (follow-up thyrotropin level ≤ 0.1 mIU/L; OR, 2.50; 95% CI, 1.06-5.93) and with incident overt hypothyroidism (follow-up thyrotropin level >10 mIU/L; OR, 3.05; 95% CI, 1.07-8.72). Iodinated contrast media exposure is associated with subsequent development of incident hyperthyroidism and incident overt hypothyroidism.


Comparison of faecal indicator and viral pathogen light and dark disinfection mechanisms in wastewater treatment pond mesocosms.
This study compared light and dark disinfection of faecal bacteria/viral indicator organisms (E. coli and MS2 (fRNA) bacteriophage) and human viruses (Echovirus and Norovirus) in Wastewater Treatment Pond (WTP) mesocosms. Stirred pond mesocosms were operated in either outdoor sunlight-exposed or laboratory dark conditions in two experiments during the austral summer. To investigate wavelength-dependence of sunlight disinfection, three optical filters were used: (1) polyethylene film (light control: transmitting all solar UV and visible wavelengths), (2) acrylic (removing most UVB <315 nm), and (3) polycarbonate (removing both UVB and UVA <400 nm). To assess different dark disinfection processes WTP effluent was treated before spiking with target microbes, by (a) 0.22 μm filtration to remove all but colloidal particles, (b) 0.22 μm filtration followed by heat treatment to destroy enzymes, and (c) addition of Cytochalasin B to supress protozoan grazing. Microbiological stocks containing E. coli, MS2 phage, Echovirus, and Norovirus were spiked into each mesocosm 10 min before the experiments commenced. The light control exposed to all sunlight wavelengths achieved >5-log E. coli and MS2 phage removal (from ~1.0 × 106 to <1 PFU/mL) within 3 h compared with up to 6 h in UV-filtered mesocosms. This result confirms that UVB contributes to inactivation of E. coli and viruses by direct sunlight inactivation. However, the very high attenuation with depth of UVB in WTP water (99% removal in the top 8 cm) suggests that UVB disinfection may be less important than other removal processes averaged over time and full-scale pond depth. Dark removal was appreciably slower than sunlight-mediated inactivation. The dark control typically achieved higher removal of E. coli and viruses than the 0.22 μm filtered (dark) mesocosms. This result suggests that adsorption of E. coli and viruses to WTP particles (e.g., algae and bacteria bio-flocs) is an important mechanism of dark disinfection, while bacteria and virus characteristics (e.g. surface charge) and environmental conditions can influence dark disinfection processes.


Optical and Potentiometric Study of the b- and c-Type Cytochromes in Mushroom Agaricus bisporus Lge Mitochondria.
Differential spectrometry revealed two species for the b-type, as well as for the c-type, cytochromes in mitochondria from Agaricus bisporus Lge. The two b-type components are denoted according to their peak position in the alpha region at room temperature, i.e. b(560) and b(566). The b(556) component present in all the studied higher plant mitochondria was not detected in the system. At 293 K, the c-type cytochromes exhibit a common alpha band with a maximum at 550 nanometers. This band is split at 77 K, with peak positions at 547 nanometers (cytochrome c) and 552 nanometers (cytochrome c(1)).Redox titrations, analyzed according to a new method (Denis, Neau, Blein 1980 Bioelectrochem Bioenerg 7: 757-773), also yielded the resolution of two species of b-type and c-type cytochromes. The b components have midpoint potential values at pH 7.2 and 20 C of E(m1) = 40 +/- 10 millivolts and E(m2) = 175 +/- 10 millivolts. Their calculated individual difference spectra exhibit alpha bands with identical maxima at 561 nanometers, in contrast with optical observations. The midpoint potential values of the resolved c components are 210 +/- 10 millivolts and 292 +/- 5 millivolts at pH 7.2 and 20 C. Their corresponding calculated difference spectra have their alpha band maxima at 553 and 551 nanometers. These two species have been identified respectively with cytochrome c(1) and cytochrome c. The ratio of the maximum optical contributions, c/c(1), is in the range 4/1 to 5/1, in contrast with other results related to yeast or higher plant mitochondria where it amounts to 2/1 or even 1.3/1.


The association of metacognition with emotion recognition and perspective taking in a Russian sample with psychosis.
Schizophrenia may reflect an interactive network of disturbances in cognition. In this study we have examined the relationship between two forms of cognition: metacognition and social cognition among a sample with schizophrenia (n = 41), early episode psychosis (n = 37), and major depression (n = 30) gathered in Moscow, Russia. Metacognition was assessed with the Metacognition Assessment Scale-Abbreviated. Social cognition was assessed with the Ekman 60 Faces Test and the Interpersonal Reactivity Index. Verbal memory and global psychopathology were included as potential covariates. Partial correlations controlling for demographics, neurocognition, and psychopathology revealed greater metacognitive capacity was linked to better facial emotion recognition and perspective taking in the prolonged schizophrenia group. Greater metacognitive capacity in the early psychosis group was linked with greater facial emotion recognition. Metacognition and social cognition were not related to one another in the depression group. Social cognition and metacognition may be uniquely related in psychosis.


Retinoids, eye development, and maturation of visual function.
Vitamin A is known to be critical for the beginning of eye development as well as for photoreception in the functional retina. Hardly anything, however, is known about whether retinoic acid (RA)-regulated gene expression also plays a role in the long intervening period, during which the neurobiological retinal structure takes shape. The eye contains a highly intricate architecture of RA-synthesizing (RALDH) and degrading (CYP26) enzymes. Whereas the RALDHs are integrated in the early molecular mechanisms through which the dorso-ventral retina organization is established, the CYP26 enzymes are not necessary for this process and no molecular targets that match their retinal expression pattern have yet been identified. In this article we describe that CYP26 expression in the mouse is most distinctive during later stages of retina formation. Throughout development CYP26A1 degrades RA in a horizontal region that extends across the retina, but during later embryonic and postnatal retina maturation this function is reinforced by another enzyme, CYP26C1. RA applications at this stage do not affect the RALDHs but cause differential changes in CYP26 expression: Cyp26a1 is up-regulated, but more rapidly by 9-cis than all-trans RA, Cyp26c1 is down-regulated, and Cyp26b1, which is undetectable in the normal mouse retina, is strongly activated in retinal ganglion cells. The dynamic regulation in RA-difference patterns by the CYP26 enzymes may set up spatial constellations for expression of genes involved in formation of retinal specializations for higher acuity vision, which are known to form over a prolonged period late in retina development.


Insulin-like growth factors I and II and their binding proteins in human milk: effect of heat treatment on IGF and IGF binding protein stability.
Insulin-like growth factors (IGF-I and -II) are peptide growth factors that contribute to the growth-promoting properties of human milk. IGFs in extra cellular fluids are associated with high-affinity binding proteins (IGFBPs). In this study, IGF-I and -II, and IGFBPs in human milk were characterized, and the stability of the IGFs and IGFBPs to heat treatment was investigated. IGF-I and -II were quantified by radioimmunoassays of acid-chromatographed samples, and IGFBPs were characterized using Western ligand blotting. The concentration (mean +/- SD) of IGF-I in human milk was 1.5 +/- 0.5 micrograms/L, compared to 2.7 +/- 0.7 micrograms/L for IGF-II. Heat treatment did not significantly affect either IGF-I or -II content. Human milk contains a single, nonglycosylated, IGFBP, with an apparent Mr of 31 k, which was immunoprecititable by an antibody to IGFBP-2. Stability of the IGFBP to heat treatment was assessed and was not significantly affected by heat treatment. Therefore, both IGF-I and -II, and the IGFBP in human milk appear to be stable under heat treatment conditions routinely used for processing banked human milk.


Complete Pathological Response Noted in Explanted Liver After Y90-SIR-Spheres Therapy for Hepatocellular Carcinoma.
In the treatment of hepatocellular carcinoma, achieving complete pathological response (CPR) in explanted liver specimens following any locoregional treatments is associated with reduced recurrence rates and better posttransplant survival compared to the incomplete response. Here, we present the imaging findings of a patient who achieved CPR in the explanted liver following Y-90 SIR-Spheres® therapy.


Genetic association for caries susceptibility among cleft lip and/or palate individuals.
To evaluate the association of the polymorphisms in the TGFB3 gene (rs2268626), and the BMP4 gene (rs17563) with dental caries in two different groups (noncleft group and oral cleft group) from a cleft center located at Rio de Janeiro, Brazil. A total of 486 unrelated children and adolescents with or without caries were evaluated using a cohort design. Data on oral health habits was obtained through a questionnaire and caries data was collected by clinical examination. Genotyping of the selected polymorphisms for TGFB3 and BMP4 were carried out by real-time PCR using the TaqMan assay method from a genomic DNA isolated from buccal epithelial cells of all children and adolescents. No association was found between BMP4 polymorphism and caries among individuals from both groups. For TGFB3 polymorphism, significant differences were observed for allele and genotype frequencies between caries free and caries affected individuals in oral cleft group (p = 0.013 and 0.006 for allele and genotype frequencies respectively). Our findings provide evidence suggesting that TGFB3 may be involved in caries susceptibility in oral cleft group. In the future, the possibility of identifying genes related to caries susceptibility can lead to counseling of the individual that carries gene alterations, with the aim of working on preventive measures for caries as well as bioengineering treatments.


Effects of electrode implantation angle on thalamic stimulation for treatment of tremor.
Introduction. Chronic thalamic stimulation has been confirmed as an effective treatment for tremor. The optimal target has been commonly accepted to be situated within the ventral thalamus, but a standard trajectory of the deep brain stimulation (DBS) electrode has not yet been established. Materials and Methods. A 53-year-old man with an 11-year history of essential tremor was treated by DBS of the thalamus. In this patient, we had a chance to compare the effects of different trajectory angles of the DBS electrode on tremor. Results. Intraoperative stimulation with the DBS electrode temporarily inserted at a high angle to the horizontal plane of the anterior commissure-posterior commissure (AC-PC) line to cover only the nucleus ventralis intermedius (Vim) was not effective. In contrast, stimulation with the DBS electrode permanently implanted at a low angle, covering a wide area extending from the nucleus ventralis oralis (Vo) to the Vim, reduced the tremor. Conclusion. We report on the case of a patient who showed different effects on tremor depending on the trajectory angle of the DBS electrode to the AC-PC line. The insertion trajectory of the DBS electrode may be an important factor for the treatment of tremor.


Studies on synthesis of interleukin-6 and gammaglobulin in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.
Peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) proliferated spontaneously and secreted an elevated level of IgG compared with that of normal controls. However, the levels of interleukin-6 (IL-6) produced by PBMC from patients with SLE with or without pokeweed mitogen (PWM) stimulation showed no significant difference from those of normal controls. The levels of IL-6 secreted spontaneously from PBMC of SLE patients correlated inversely with the percent and the absolute number of CD19 positive cells in PBMC, but not with the levels of IgG and IgM secreted spontaneously from PBMC. There was no significant difference in the levels of IgG produced by PBMC stimulated with IL-6 and also in the levels of IL-6 synthetized by T and B cells between SLE patients and normal controls. These data suggest that IL-6 may not play an important role in the hypergammaglobulinemia in SLE.


Acetyl coenzyme a-glutamate acetyltransferase and N-acetylornithine-glutamate acetyltransferase of chlorella.
The enzymic formation of acetylglutamate has been studied in Chlorella vulgaris extracts. Acetyl CoA and N(2)-acetyl-l-ornithine served as substrates for glutamate acetylation whereas acetylphosphate, N(5)-acetyl-l-ornithine, and N(2)-acetyl-2,4-diamino butyrate were ineffective. Acetyl CoA-glutamate transacetylase and acetylornithine-glutamate transacetylase activities have been purified over 180-fold with no indication of any separation of activities. The acetyl CoA activity was more labile than acetylornithine activity so that preparations having acetylornithine-glutamate transacetylase activity but no acetyl CoA-glutamate transacetylase activity were obtained. The two acetylating activities appear to be properties of one enzyme with one portion more easily denatured.Both acetylating activities had pH optima between 8 and 8.5. The Km value for glutamate was 3 mm for both activities. The Km values were 0.2 mm for acetylornithine and 3.2 mm for acetyl CoA. Arginine inhibited acetyl CoA-glutamate transacetylase (Ki = 0.94 mm) and acetylglutamate phosphokinase (Ki = 0.5 mm) but had no effect on acetylornithine-glutamate transacetylase. The lack of an inhibitory effect of proline on any of the three enzymic activities indicates that acetylglutamate is not a normal intermediate in proline biosynthesis. Growth of Chlorella with arginine as a nitrogen source had no effect on enzyme levels, showing that end-product repression is not a control factor in arginine biosynthesis in Chlorella. In Chlorella, arginine controls its own biosynthesis by inhibiting acetylglutamate phosphokinase and controls the level of acetylated intermediates by inhibiting acetyl CoA-glutamate transacetylase.


Growth and chemotaxis of nematodes reduced upon exposure to Third Fork Creek surface water.
Third Fork Creek is a historically impaired urban stream that flows through the city of Durham, North Carolina. Caenorhabditis elegans (C. elegans) are non-parasitic, soil and aquatic dwelling nematodes that have been used frequently as a biological and ecotoxicity model. We hypothesize that exposure to Third Fork Creek surface water will inhibit the growth and chemotaxis of C. elegans. Using our ring assay model, nematodes were enticed to cross the water samples to reach a bacterial food source which allowed observation of chemotaxis. The total number of nematodes found in the bacterial food source and the middle of the plate with the water source was recorded for 3 days. Our findings suggest a reduction in chemotaxis and growth on day three in nematodes exposed to Third Fork Creek water samples when compared to the control (p value < 0.05). These exploratory data provide meaningful insight to the quality of Third Fork Creek located near a Historically Black University. Further studies are necessary to elucidate the concentrations of the water contaminants and implications for human health. The relevance of this study lies within the model C. elegans that has been used in a plethora of human diseases and exposure research but can be utilized as an environmental indicator of water quality impairment.


The influence of radiotherapy on skin circulation of the breast after subcutaneous mastectomy and immediate reconstruction.
The skin circulation was measured in 43 breast cancer patients following subcutaneous mastectomy and immediate reconstruction with a prosthesis, at least 1 year after radiotherapy (46 Gy) following surgery (19 patients) or if no radiotherapy was given, at least 1 year postoperatively (24 patients). The skin circulation was measured by laser Doppler fluxmetry (LDF) and fluorescein flowmetry within three areas: 2 cm above the border of the areola, within the nipple-areola complex, and 2 cm below the border of the areola. The results show that there was no reduction in skin circulation. On the contrary LDF and fluorescein flowmetry showed in the operated breast an increased circulation in the nipple-areola complex in the irradiated breast compared with the non-irradiated by 26% and 30%, respectively (P < 0.05). The results indicate that radiotherapy following subcutaneous mastectomy and immediate reconstruction with a prosthesis does not lead to long-term reduction in basal skin circulation in the breast.


Conservative treatment of a pathological fracture in a 3-year-old boy with primary hyperoxaluria type I.
Primary hyperoxaluria type I is a rare inherited disease that presents a disturbed metabolism of glyoxylate. Consequently, patients suffer from hyperoxaluria, leading to renal failure and subsequent skeletal calcium oxalate deposition. Areas with high concentrations of calcium oxalate, so-called dense metaphyseal bands, are at risk for pathological fracturing. The primary disease is treated by combined liver-kidney transplantation, although pathological fracturing also occurs in the posttransplant period. In the current case, we present a 3-year-old boy with a pathological fracture of his right femur, 2 years after liver-kidney transplantation. We opted for a conservative regime, leading to good fracture healing. As there are limited data in the literature regarding treatment of fractures in these patients, it is important to notify the outcome of conservative treatment of pathological fractures in patients with primary hyperoxaluria type I.


Using administrative lists to estimate census omissions.
"We present a method for estimating omission rates from censuses. Our method is based on the merger of administrative lists, sampling from these lists, and matching against census rolls. We describe the method, present the results of a test in New York City...in 1980, and evalute the results. We compare our proposed method to other procedures for estimating omission rates."


Acute pain management. Programs in U.S. hospitals and experiences and attitudes among U.S. adults.
The objective of the survey was to assess the status of acute pain management in U.S. hospitals and attitudes of adults in the U.S. toward postoperative pain management, information that has not been previously available. Two telephone questionnaire surveys were conducted U.S. hospital participants, including 100 teaching hospitals (acute care hospitals with a residency program and/or university affiliation), 100 nonteaching (community) hospitals with fewer than 200 beds, and 100 nonteaching (community) hospitals with 200 beds or more were interviewed regarding current and future pain management programs and related topics. Adult participants in 500 U.S. households were interviewed on attitudes and experiences with postoperative pain and its management. Forty-two percent of the hospitals have acute pain management programs, and an additional 13% have plans to establish an acute pain management program. Seventy-seven percent of adults believe that it is necessary to experience some pain after surgery. Fifty-seven percent of those who had surgery cited concern about pain after surgery as their primary fear experienced before surgery. Seventy-seven percent of adults reported pain after surgery, with 80% of these experiencing moderate to extreme pain. Despite a growing trend in pain management, increased professional and public awareness including the establishment of pain management programs and public and patient education is needed to reduce the incidence and severity of postoperative pain.


Occlusion of the carotid artery as presenting symptom of acute promyelocytic leukemia.
In a 44-year-old female acute promyelocytic leukemia (APL) presented with abrupt onset of right hemiplegia and aphasia due to occlusion of the left carotid artery at bifurcatio. There was laboratory evidence of disseminated intravascular coagulation (DIC). Thrombotic complications are unusual in APL, even in cases with evidence of DIC. This report aims at underlying the important implication of a correct timely diagnosis in young patients presenting with stroke.


Intraoperative findings and postoperative results associated with cataract surgery performed after retinal reattachment surgery in dogs-36 cases (41 eyes).
To report intraoperative findings and complications associated with cataract surgery performed after retinal reattachment surgery (RR) via pars plana vitrectomy (PPV) using perfluoro-n-octane (PFO), laser retinopexy, and silicone oil tamponade in dogs. Retrospective record review of dogs that underwent post-RR cataract surgery. Signalment, time between RR and cataract surgery, type of lens extraction, postoperative visual status, and intra- and postoperative complications were recorded. Cataract formation or progression after RR was categorized as early (≤12 months) or late (>12 months). A total of 36 dogs (41 eyes) were included. Average time between RR and cataract surgery was 665 days (median: 546). Early postoperative incidence of cataracts occurred in 19 eyes (46.3%). Types of lens extraction included phacoemulsification with intraocular lens (86.1%, 31/36 dogs), phacoemulsification alone (11.1%, 4/36 dogs), and intracapsular lens extraction (2.8%, 1/36 dogs). Visual improvement occurred in 95.1% of eyes (39/41) immediately postoperatively. Long term, 93.9% of eyes (31/33) maintained vision at 1 month, 85.2% of eyes (23/27) at 3 months, 77.3% of eyes (17/22) at 6 months, and 60% (12/20) at 12 months postoperatively. The most common postoperative complications were glaucoma (29.3%, 12/41 eyes), corneal ulceration (24.4%, 10/36 eyes), fibrin formation (21.9%, 9/41 eyes), and silicone oil migration into the anterior chamber (19.5%, 8/41 eyes). Post-RR cataract surgery should be considered in dogs with vision loss from cataracts after RR. In most eyes, vision was maintained up to 1 year postoperatively.


Experimental and analytical performance evaluation of short circular hydrodynamic journal bearings used in rotary blood pumps.
Rotary blood pumps (RBPs) have demonstrated considerable promise while treating heart failure patients, such that they are being placed at an earlier stage of the disease. These devices may therefore be required to operate for prolonged durations which yields the need for RBPs exhibiting high durability, reliability, and blood compatibility. Noncontacting bearings, utilizing magnetic and/or hydrodynamic suspension techniques, appear to provide a suitable solution to these challenges. Hydrodynamic suspension has the advantage that it does not need feedback control systems. Among various hydrodynamic bearing types, the circular journal bearing has the particular benefit of easy manufacturing. This study presents methods to evaluate the performance of short (length to diameter ratio <1) circular hydrodynamic journal bearings (HJBs) for RBPs. Analytical calculations with specific boundary conditions are presented to predict the rotor's eccentricity under equilibrium states and thus the related performance parameters such as load capacity, power loss, and shear rates. These results and boundary conditions were confirmed experimentally in a specially designed test set-up. The bearing performance was found to correlate to analytical solutions using the full Sommerfeld boundary condition instead of the half Sommerfeld condition conventionally used for such applications. Geometrical and operational parameter variations showed that HJB designs with a short Sommerfeld Number SS >0.02 can provide sufficient fluid film thicknesses and low shear rates. The measurements were further used to evaluate the bearings' stability. The estimation of the stability threshold drawn in relation to a modified stability index and the equilibrium eccentricity of the rotor allows the prediction of stability for short circular HJB designs under full Sommerfeld condition.


Spectral analysis of heart rate variability in evaluation of sympathetic function in elderly subjects.
Plasma concentration of noradrenaline is often used as a measure of sympathetic nervous activity. Recently, the method of spectral analysis of heart rate variability has been introduced to detect autonomic dysfunction. To examine whether spectral analysis of heart rate variability is useful in evaluating sympathetic function, changes in the heart rate variability in the low-frequency spectral band were compared with the change of plasma noradrenaline in response to head-up tilt in elderly hypertensives (n = 13) and diabetics (n = 13). In hypertensive subjects, there was an increase in relative low-frequency power (p = 0.015) and an increase in plasma noradrenaline level (p = 0.040) in response to head-up tilt. Diabetics did not show corresponding changes. There was no change in absolute low-frequency power in either group. It is concluded that spectral analysis of heart rate variability can be useful in evaluating sympathetic function in elderly subjects.


Thyroid hormones in depressive disorders: a reappraisal of clinical utility.
Centuries of clinical observation suggest a connection between thyroid function and behavior. Advances in neuroendocrinology of the hypothalamic-pituitary-thyroid (HPT) axis provide many techniques for examining the role of thyroid function in psychiatric disorders. HPT hypofunctioning may be especially relevant to the pathophysiology of major mood disorders, although the diagnostic specificity and prognostic value of its assessment remain tentative. Evidence that synthesis and actions of thyroid hormones in the brain may not parallel those in the periphery further complicates such assessments. Nevertheless, measures of HPT function show some promise of contributing to the clinical evaluation and treatment of depression. Research findings include an association of subclinical hypothyroidism with unsatisfactory responses to antidepressant treatment, evidence that triiodothyronine and thyroid-stimulating hormone may speed recovery in acute depression, and limited and inconsistent support for the effectiveness of exogenous thyroid hormones to augment antidepressants. Additional systematic and controlled studies comparing various types and doses of thyroid hormones are needed to establish their efficacy and safety. Of special interest would be studies that use contemporary diagnostic methods, assess thyroid function, and employ the newer, safer antidepressants.


Breath Analysis for the In Vivo Detection of Diabetic Ketoacidosis.
Human breath analysis of volatile organic compounds has gained significant attention recently because of its rapid and noninvasive potential to detect various metabolic diseases. The detection of ketones in the breath and blood is key to diagnosing and managing diabetic ketoacidosis (DKA) in patients with type 1 diabetes. It may also be of increasing importance to detect euglycemic ketoacidosis in patients with type 1 or type 2 diabetes or heart failure, treated with sodium-glucose transporter-2 inhibitors (SGLT2-i). The present research evaluates the efficiency of colorimetry for detecting acetone and ethanol in exhaled human breath with the response time, pH effect, temperature effect, concentration effect, and selectivity of dyes. Using the proposed multidye system, we obtained a detection limit of 0.0217 ppm for acetone and 0.029 ppm for ethanol in the detection range of 0.05-50 ppm. A smartphone-assisted unit consisting of a portable colorimetric device was used to detect relative red/green/blue values within 60 s of the interface for practical and real-time application. The developed method could be used for rapid, low-cost detection of ketones in patients with type 1 diabetes and DKA and patients with type 1 or type 2 diabetes or heart failure treated with SGLT2-I and euglycemic ketoacidosis.


Prevalence of Trichomonas vaginalis Among Civilian, Noninstitutionalized Male and Female Population Aged 14 to 59 Years: United States, 2013 to 2016.
Among the US civilian noninstitutionalized population aged 14 to 59 years in 2013 to 2016, prevalence of Trichomonas vaginalis infection in urine was 1.3% overall. Prevalence was 2.1% among females, 0.5% among males, and highest at 9.6% among non-Hispanic black females. Estimate instability limited analysis of factors beyond sex, age, and race/Hispanic ethnicity.


Nasal tactile sensitivity in elderly.
Although older people varied widely in tactile sensitivity, our results show that tactile thresholds increased with age. The aim of this study was to evaluate the effects of aging on nasal tactile sensitivity. A total of 160 healthy patients aged between 50 and 90 years were included. According to their age, patients were divided into groups (A, B, C, D, E, F, G, and H). From the age of 50, each group included subjects with an age range of 5 years (i.e. group A, 50-55 years; group B, 56-60 years, etc.). Each patient's outcome was assessed through the nasal monofilament test: a set of 20 Semmes-Weinstein monofilaments was used to detect nasal sensitivity for both nasal cavities. The sensitivity threshold was recorded as the minimum monofilament size from which patients could detect at least two of three stimuli. In groups D (66-70 years), E (71-75 years), F (76-80 years), G (81-85 years), and H (86-90 years) a significantly (p < 0.05) higher stimulus (171.1 ± 0.34 mg vs 67.7 mg, 167.01 ± 0.31 mg 67.7 mg, 166.54 ± 0.28 mg 67.7 mg, 201.24 ± 0.43 mg 67.7 mg, 165,87 ± 0.27 mg 67.7 mg) was required to trigger a touch response in the monofilament test.


Can We Use mTOR Inhibitors for COVID-19 Therapy?
Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.


Computer-aided volumetry of pulmonary nodules exhibiting ground-glass opacity at MDCT.
The purpose of this study was to investigate the accuracy and reproducibility of results acquired with computer-aided volumetry software during MDCT of pulmonary nodules exhibiting ground-glass opacity. To evaluate the accuracy of computer-aided volumetry software, we performed thin-section helical CT of a chest phantom that included simulated 3-, 5-, 8-, 10-, and 12-mm-diameter ground-glass opacity nodules with attenuation of -800, -630, and -450 HU. Three radiologists measured the volume of the nodules and calculated the relative volume measurement error, which was defined as follows: (measured nodule volume minus assumed nodule volume / assumed nodule volume) x 100. Two radiologists performed two independent measurements of 59 nodules in humans. Intraobserver and interobserver agreement was evaluated with Bland-Altman methods. The relative volume measurement error for simulated ground-glass opacity nodules measuring 3 mm ranged from 51.1% to 85.2% and for nodules measuring 5 mm or more in diameter ranged from -4.1% to 7.1%. In the clinical study, for intraobserver agreement, the 95% limits of agreement were -14.9% and -13.7% and -16.6% to 15.7% for observers A and B. For interobserver agreement, these values were -16.3% to 23.7% for nodules 8 mm in diameter or larger. With computer-aided volumetry of ground-glass opacity nodules, the relative volume measurement error was small for nodules 5 mm in diameter or larger. Intraobserver and interobserver agreement was relatively high for nodules 8 mm in diameter or larger.


Effect of Nanostructuring on the Thermoelectric Properties of β-FeSi2.
Nanostructured β-FeSi2 and β-Fe0.95Co0.05Si2 specimens with a relative density of up to 95% were synthesized by combining a top-down approach and spark plasma sintering. The thermoelectric properties of a 50 nm crystallite size β-FeSi2 sample were compared to those of an annealed one, and for the former a strong decrease in lattice thermal conductivity and an upshift of the maximum Seebeck's coefficient were shown, resulting in an improvement of the figure of merit by a factor of 1.7 at 670 K. For β-Fe0.95Co0.05Si2, one observes that the figure of merit is increased by a factor of 1.2 at 723 K between long time annealed and nanostructured samples mainly due to an increase in the phonon scattering and an increase in the point defects. This results in both a decrease in the thermal conductivity to 3.95 W/mK at 330 K and an increase in the power factor to 0.63 mW/mK2 at 723 K.


[Angiography in the diagnosis of vasculitides].
A review of angiographic findings in vasculitides classified according to Lie is introduced. Angiography is an important investigation in angiitis that affects large, medium and visualizible small vessels. Its importance resides in 1. diagnosis, 2. selection of adequate therapeutic intervention. This work includes the description of angiographic findings in Takayasu's arteritis and Buerger's disease. (Fig. 4, Ref. 26.).


Absence of DNA binding activity of methyl parathion and chlorpyrifos.
We have investigated the characteristics of binding of the organophosphorus insecticides methyl parathion and chlorpyrifos to DNA. Quantitative analysis of our data indicates that if these compounds bind to DNA at all, it is only with weak affinity. Dissociation constants would, according to our analysis, be in excess of 1 mM. Concentrations of methyl parathion and chlorpyrifos in this range are considerably greater that those expected to occur in organisms exposed to sub-lethal amounts of the compounds. Furthermore, the compounds methyl paraoxon and chlorpyrifos oxon, which result from biotransformation of methyl parathion and chlorpyrifos, exhibit similar characteristics (i.e., bind not at all or with weak affinity). These data suggest that direct binding of methyl parathion and chlorpyrifos to DNA is unlikely to be a mechanism through which any genotoxic effects are produced.


Photodynamic therapy: esophagus.
Photodynamic therapy (PDT) is a minimally invasive, organ-preserving therapeutic modality, involving three separate components - light, oxygen and a photosensitizing drug. The principles of PDT are described, and the indications for its use are reviewed. Although a widespread clinical application for PDT has not yet emerged, PDT may establish itself as an endoscopic procedure with few or no side effects in the treatment of Barrett's esophagus (high-grade dysplasia and early carcinoma) and, in selected cases, for the treatment of early squamous cell carcinoma.


Recent Advances in Development of Waste-Based Polymer Materials: A Review.
Limited petroleum sources, suitable law regulations, and higher awareness within society has caused sustainable development of manufacturing and recycling of polymer blends and composites to be gaining increasing attention. This work aims to report recent advances in the manufacturing of environmentally friendly and low-cost polymer materials based on post-production and post-consumer wastes. Sustainable development of three groups of materials: wood polymer composites, polyurethane foams, and rubber recycling products were comprehensively described. Special attention was focused on examples of industrially applicable technologies developed in Poland over the last five years. Moreover, current trends and limitations in the future "green" development of waste-based polymer materials were also discussed.