Effect of soil amendments on antioxidant activity and photosynthetic pigments in pea crops grown in arsenic contaminated soil.
The mechanism of arsenic (As) immobilization in soils is crucial for improving photosynthetic pigments and antioxidants in food crops. The effects of soil amendments with arbuscular mycorrhizal fungi (AMF), biochar (BC), selenium (Se), sulfur (S) and Si-gel on the concentrations of chlorophyll, carotenoid, proline, malondialdehyde (MDA), and the activity of ascorbate peroxidase (APX), guaiacol peroxidase (POD), and catalase (CAT) were studied in BARI pea (Pisum sativum ) under As stress. Soil amendments with AMF, Se, Si-gel and S enhanced chlorophyll a and total chlorophyll contents by 31-35% and 60-75%, respectively. Likewise, CAT activity was increased by 24-46% in BC, AMF, Se, Si-gel and S-treated pea, respectively. APX and POD activity was also found to be enriched with the treatment of BC, AMF and Se. In contrast, the content of MDA and proline was found lower than that of control in peas. These findings indicate that oxidative damage, osmotic stress and cell injury were possibly reduced in As-stressed peas. Particularly, AMF and Se both were comparatively more potential in comparison to BC. Thus, soil amendments with AMF, BC and Se are significantly important for improving antioxidant enzyme activity of food crops grown in soil with elevated As levels.


Angiotensin II, progesterone, and prostaglandins are sequential steps in the pathway to bovine oocyte nuclear maturation.
Oocyte meiotic resumption is triggered by the ovulatory gonadotropin surge; in cattle, angiotensin II (AngII) and prostaglandins (PG) are key mediators of this gonadotropin-induced event. Here, we tested the hypothesis that progesterone (P(4)) is also involved in oocyte meiotic resumption induced by the gonadotropin surge. In Experiment I, P(4) induced nuclear maturation in a dose-dependent manner using a coculture of follicular hemisections and cumulus-oocyte complexes. In the second experiment, using an in vivo model, an injection of mifepristone (MIFE; P(4) receptor antagonist) at the antrum of preovulatory follicles prevented GnRH-induced oocyte meiotic resumption in vivo. In Experiment III (coculture system similar to that of Experiment I), MIFE prevented stimulatory effects of AngII on resumption of meiosis, but saralasin (AngII receptor antagonist) did not inhibit P(4) actions. In Experiments IV and V, fibroblast growth Factor 10 (FGF10; known to suppress steroidogenesis in granulosa cells), blocked AngII-but not P(4)-induced oocyte meiotic resumption. Therefore, we inferred that AngII is upstream to P(4) in a cascade to induce meiotic resumption. Previously, we had reported that AngII acted throughout the PGs pathway to modulate nuclear progression. In Experiment V, indomethacin inhibited resumption of meiosis induced by P(4), providing further support to the AngII-P(4) sequential effect on meiotic resumption. In conclusion, we inferred that AngII, P(4) and PGs are sequential steps in the same pathway that culminates with bovine oocyte maturation.


Causes, evaluation, and management of athletic oligo-/amenorrhea.
Oligomenorrhea and amenorrhea are more common among athletes than among the general population. Although these conditions in athletes are often related to exercise and thinness, they may be caused by serious pathology too. All athletes with menstrual dysfunction deserve thorough evaluation and most need treatment.


Sleep: dozy worms and sleepy flies.
Recent work on quiescent states in Caenorhabditis elegans suggests that worms exhibit behaviours reminiscent of satiety and sleep in mammals. At a molecular level, signalling through the EGF receptor and protein kinase G promotes quiescent states in both worms and flies, suggesting conserved mechanisms for sleep-like behaviours.


Transcriptome and miRNAome analysis reveals components regulating tissue differentiation of bamboo shoots.
Primary thickening determines bamboo yield and wood property. However, little is known about the regulatory networks involved in this process. This study identified a total of 58,652 genes and 150 miRNAs via transcriptome and small RNA sequencing using the underground thickening shoot samples of wild-type (WT) Moso bamboo (Phyllostachys edulis) and a thick wall (TW) variant (P. edulis "Pachyloen") at five developmental stages (WTS1/TWS1-WTS5/TWS5). A total of 14,029 (65.17%) differentially expressed genes and 68 (45.33%) differentially expressed miRNAs were identified from the WT, TW, and WTTW groups. The first two groups were composed of four pairwise combinations, each between two successive stages (WTS2/TWS2_versus_WTS1/TWS1, WTS3/TWS3_versus_WTS2/TWS2, WTS4/TWS4_versus_WTS3/TWS3, and WTS5/TWS5_versus_WTS4/TWS4), and the WTTW group was composed of five combinations, each between two relative stages (TWS1-5_versus_WTS1-5). Additionally, among the phytohormones, zeatin showed more remarkable changes in concentrations than indole-3-acetic acid, gibberellic acid, and abscisic acid throughout the five stages in the WT and the TW groups. Moreover, 125 cleavage sites were identified for 387 miRNA-mRNA pairs via degradome sequencing (P < 0.05). The dual-luciferase reporter assay confirmed that 13 miRNAs bound to 12 targets. Fluorescence in situ hybridization localized miR166 and miR160 in the shoot apical meristem and the procambium of Moso bamboo shoots at the S1 stage. Thus, primary thickening is a complex process regulated by miRNA-gene-phytohormone networks, and the miRNAome and transcriptome dynamics regulate phenotypic plasticity. These findings provide insights into the molecular mechanisms underlying wood formation and properties and propose targets for bamboo breeding.


Construction of Bi/phthalocyanine manganese nanocomposite for trimodal imaging directed photodynamic and photothermal therapy mediated by 808 nm light.
The current conventional photo-therapeutic agents often show low therapy efficacy because of their single treatment model, the limited penetration depth of excitation light and hypoxia in the tumor microenvironment (TME). Herein, a new type of phthalocyanine manganese (MnPcE4) photosensitizer with strong NIR absorption was designed and fabricated for the first time, and was used to modify pure Bi nanomaterials to obtain an intelligent multifunctional Bi/MnPcE4 nanocomposites. The Mn2+ in the Bi/MnPcE4 nanocomposite could catalyze H2O2 to generate O2, thus helping to overcome TME hypoxia and enhancing the photodynamic therapy (PDT) efficacy. Further, the nanocomposites showed excellent T1-weighted MRI performance. Our novel use of a pure metal Bi core, offers lower toxicity, higher CT imaging performance, and a photothermal therapy (PTT) effect triggered by 808 nm near infrared (NIR) laser. Moreover, in vivo fluorescence imaging (in vivo FL) vividly showed that the nanocomposite rapidly accumulates in tumor sites due to the enhanced permeability and retention (EPR) effect and metabolized in the organs. The presence of Bi enables the use of these nanocomposites as a CT contrast agent, and the Mn content enables them to be used in MRI. This triple imaging ability implies that our nanocomposites have a high potential for use in imaging directed tumor therapy.


Susceptibility to beta-lactam antibiotics and production of beta-lactamase in Bacteroides fragilis.
Using the agar dilution technique, 231 strains of Bacteroides fragilis, isolated during a 2-year period from human infections, were identified at subspecies level and were tested for susceptibility to 13 beta-lactam antibiotics. The penicillins were benzylpenicillin, ampicillin, carbenicillin, cloxacillin, and the recently described penicillin derivatives cyclacillin, ticarcillin, and PC-904. The following cephalosporin derivatives were tested: cephaloridine, cephalothin, cephalexin, cefamandole and cefuroxime. The cephamycin C derivative cefoxitin was also included in the study. Cefoxitin was the most effective drug tested since more than 80% of the strains were inhibited by 8 microgram/ml or less, and no strain had a minimal inhibitory concentration (MIC) of more than 64 microgram/ml. There was no marked difference in sensitivity among the subspecies with exception of subspecies vulgatus, which was slightly more sensitive to all antibiotics tested. The size of the inoculum was an important factor for obtaining reproducible results in the sensitivity tests. Increased inocula resulted in markedly higher MICs for cephaloridine and cefuroxime. Production of beta-lactamase was performed on all isolates by a chromogenic cephalosporin substrate and about 90% of the strains were found to be beta-lactamase producers.


Relationship between histamine receptors in the brain and diazepam-induced hyperphagia in rats.
We investigated whether histaminergic neurons in the brain are involved in diazepam-induced hyperphagia in rats. Pretreatment with intracerebroventricular (ICV) injection of either histamine H1-receptor antagonist, pyrilamine (10 and 30 micrograms) or histamine H2-receptor antagonist, famotidine (3 and 10 micrograms) did not affect only diazepam (1 mg/kg, subcutaneous, SC)-induced hyperphagia in nondeprived rats, but also spontaneous feeding in food-deprived rats. In addition, pretreatment with ICV injection of histamine H3-receptor antagonist, thioperamide, and histamine H3-receptor agonist, (R) alpha methylhistamine, enhanced and inhibited diazepam-induced hyperphagia (1 mg/kg, SC) in nondeprived rats, respectively. However, thioperamide and (R) alpha methylhistamine did not affect spontaneous feeding in food-deprived rats. These findings suggest that histaminergic neurons are not directly involved in diazepam-induced hyperphagia in rats. Furthermore, enhancement or inhibition of diazepam-induced hyperphagia by histamine H3-receptor antagonist or agonist may occur via histamine H3-receptors localized in the other neurons in the rat brain.


Motivating operations in appetite research.
Appetite research frequently employs principles derived from behaviour analysis. However, it has yet to utilise the more recent theoretical advances in this field. This paper describes the concept of the motivating operation (MO)--a behaviour analytic formulation of motivation. An MO is an environmental event that (a) establishes or abolishes the reinforcing or punishing effect of another event and (b) evokes or abates behaviours associated with that event. The paper describes both unconditioned and conditioned MOs and the ways in which they may help account for a variety of eating behaviours. It then goes on to highlight the main ways in which the MO account differs from other theories of motivation employed in appetite research. These relate to (1) the ways in which they account for non-regulatory feeding, (2) the extent to which they address cognitive variables and (3) their underlying philosophical assumptions and subsequent relation to intervention.


Transdermal microneedles for the programmable burst release of multiple vaccine payloads.
Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.


Can a sustainability and health scenario provide a realistic challenge to student nurses and provoke changes in practice? An evaluation of a training intervention.
Climate change and limited natural resources will impact on the sustainable supply and disposal of materials used in health care. Healthcare students need opportunities to reflect on the ecological footprint of health services to mitigate against negative effects on service delivery. In order to raise awareness of these issues, there is a need for evidence-based teaching tools which are relevant and meaningful to nursing practice. An evidence-based sustainability skills teaching session was delivered to 293 nursing students from child and adult health disciplines. Following the sessions, evaluation sheets were distributed to the participants, of which 290 responded. The majority of nurses valued both the delivery and the content of the training and some were motivated to complete further study. The evaluation provided valuable information on how to deliver sustainability education and important insights into where more information and support was needed in order to change practice. Embedding sustainability teaching in skill sessions appears to be a realistic way of informing and motivating learners to consider current and best practice. Following training, further evaluation of practice-based behaviour is needed.


CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation.
β-Thalassemias represent a group of genetic disorders caused by human hemoglobin beta (HBB) gene mutations. The radical curative approach is to correct the mutations causing the disease. CRISPR-CAS9 is a novel gene-editing technology that can be used auspiciously for the treatment of these disorders. The study aimed to investigate the utility of CRISPR-CAS9 for gene modification of hematopoietic stem cells in β-thalassemia with IVS-1-110 mutation. We successfully isolated CD34+ cells from peripheral blood of β-thalassemia patients with IVS-1-110 mutation. The cells were transfected with Cas9 endonuclease together with guide RNA to create double-strand breaks and knock out the mutation. The mutation-corrected CD34+ cells were subjected to erythroid differentiation by culturing in complete media containing erythropoietin. CRISPR/Cas-9 is an effective tool for gene therapy that will broaden the spectrum of therapy and potentially improve the outcomes of β-thalassemia.


Diffusion-weighted imaging of ocular melanoma.
Diffusion-weighted imaging (DWI) allows characterization of masses on the basis of their cellular density. We hypothesized that ocular melanoma has a marked diffusion restriction as seen in other malignant tumors. Furthermore, we aimed to assess whether DWI is useful to differentiate ocular melanoma from retinal detachment. The institutional review board approved the prospective study on 44 patients investigated with ocular magnetic resonance imaging including DWI during a 9-month period. A region-of-interest analysis of diffusion-weighted images with b values of 0 and 1000 s/mm was performed to calculate the apparent diffusion coefficient (ADC) of the ocular melanoma and the retinal detachment. Three patients were excluded because DWI was nondiagnostic owing to severe artifacts; in 1 patient, the melanoma was too small for ADC calculation. Therefore, 40 patients were included in the final analysis. Ocular melanomas and detachments were compared with respect to their ADC values. The image quality of DWI was qualitatively scored by 2 readers in consensus on a 3-point scale from 1 (minor artifacts) to 3 (major artifacts). Ocular melanomas showed a marked diffusion restriction, and the mean (SD) ADC was 891 (172) × 10 mm/s. Twenty-nine patients (66%) had retinal detachment. The mean ADC of the ocular melanoma differed significantly (P < 0.001) from the mean ADC of the retinal detachment (1986 [375] × 10 mm/s). The image quality of DWI was rated 1 in 38 patients, 2 in 3 patients, and 3 in 3 patients. Ocular melanoma shows a marked diffusion restriction with an ADC of less than 1000 mm/s, which is in concordance with other malignant tumor entities. Diffusion-weighted imaging helps differentiating ocular tumors from retinal detachment and should therefore be included in the ocular magnetic resonance imaging protocol if an ocular mass is suspected.


Dimensions of Resilience and Their Predictive Utility Among Clients With Anxiety Disorders or Depressive Disorders: A Factor Analytic Study.
The Connor-Davidson Resilience Scale is a commonly used measure of resilience. However, while resilience is considered multidimensional, the specific dimensions embedded within this scale remain equivocal. The aim of this article was to contribute to this debate by analyzing responses from a large sample obtained within a mental health setting. Baseline data from 672 consecutive referrals to a publicly funded outpatient service for adults with anxiety and depression were subjected to exploratory factor analysis. Outcome data from 349 of these participants who had completed treatment were analyzed using confirmatory factor analysis. Both analytical strategies suggested that two dimensions were evident (Adaptability and Tenacity), although comparisons of Adaptability and Tenacity across sociodemographic, diagnostic, psychological distress, and functional impairment variables provided little support for their discriminability. The practical utility to mental health nurses of subcomponents of resilience remains clinically persuasive yet empirically elusive with current instrumentation.


Magnesium sulphate and cervical ripening (a biomechanical double-blind, randomized comparison between a synthetic polyvinyl sponge with and without magnesium sulphate).
Lamicel is a commercially available synthetic polyvinyl sponge impregnated with magnesium sulphate (MgSO4), used to soften and dilate the cervix. To investigate whether magnesium sulphate contributes to the effect of Lamicel, forty-one pregnant nulliparous patients who underwent a first trimester abortion were allocated to three to four hours preoperative treatment with either Lamicel or the same type of tent without magnesium sulphate. The ripening effect on the cervix was measured biomechanically. Lamicel produced a cervical dilatation and ripeness equal to the syntetic tent without MgSO4. The two pretreated groups together showed a significantly (p less than 0.05) more favourable cervix compared to a control group of 40 patient.


Development of semi-defined rice straw-based medium for butanol production and its kinetic study.
Rice straw is one of the potential economic feedstock for biobutanol production through ABE fermentation. However, the rice straw hydrolysate-based fermentation medium needs to be supported with nutritional elements. In this study, an attempt is made to optimize the rice straw hydrolysate-based fermentation medium employing Clostridium acetobutylicum MTCC 481 using Taguchi design of experiments (DOE) statistical model. Initially, a set of 12 nutrient components viz. MgNO3·6H2O, FeNO3, NH4NO3, yeast extract, PABA, biotin, PABA + biotin mixture, CaCl2, KCl, NaCl, MgSO4 and CH3COONa were screened through classical (one-variable-at-a-time) method. Based on the results, four components (PABA, yeast extract, MgSO4 and CH3COONa) were found to have significant impact, and were further subjected to statistical optimization through Taguchi DOE method. These experiments revealed that RSH supported with 3 g L-1 of yeast extract and 4 mg L-1 PABA to RSH was the most optimum fermentation medium. Experiments using 2 L bioreactor with this optimum fermentation medium showed nearly complete utilization of soluble sugars with the production of 8.7 g L-1 of total solvents and 6 g L-1 of butanol. The experimental data were fitted to kinetic models reported in the literature to determine the kinetic parameters of the fermentation process. An interesting result was revealed from this analysis that the under optimized fermentation medium, the kinetic parameters for both shake flask and bioreactor level were similar. This essentially means that effect of scale of operation is rendered insignificant when fermentation medium is under optimum conditions.


Effect of ambient temperature changes on chronic toxoplasmosis in rats.
The effect of excess heat and cold on chronic toxoplasmosis was studied on rats. That was evident from the average increase in body weight, the effect on blood picture, deleterious effect of the pathology recorded in various organs, increased Toxoplasma brain cyst count, long persistence of parasites in the viscera, high antibody titre by I.H.A.T. in infected animals exposed to excess heat and its decrease in animals exposed to excess cold.


[Harm Reduction and Preventive Measures in Berlin's Party Scene].
Substance use patterns and sociodemographic variables of Berlin's party scene were investigated to derive preventive measures and harm reduction services, which meet the needs of the consumers. A questionnaire was used online and in the field among Berlin partygoers (N = 877) and structured interviews (N = 20) were conducted with professionals working in this area, including social workers, emergency medical service, police and club owners and users. A risky consumption pattern was found in 67 % of participants, who also stated need for counseling and a wish for reduction of their substance use. Of all preventive measures, drug checking was requested most often. Substances with the highest prevalence were alcohol, cannabis, amphetamine, MDMA, cocaine and ketamine, whereas methamphetamine and new psychoactive substances were barely stated. There is an urgent need to expand current preventive measures. There is a willingness of the scene to use according services, especially by those who need it the most.


Regulation of sterol synthesis in human lymphocytes: evidence for post-transcriptional control by low density lipoprotein.
The effect of cordycepin (3'-deoxyadenosine), an inhibitor of messenger RNA synthesis, on the induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase mediated by lipid-depleted serum was studied in isolated human lymphocytes. 50 micrograms/ml cordycepin, although inhibiting messenger RNA synthesis by more than 50%, had no inhibitory effect on the two and four-fold induction of hydroxymethylglutaryl-CoA reductase when cells were incubated in a medium containing lipid-depleted serum for 8 and 16 h, respectively. This result suggests that newly synthesises messenger RNA is not required for the effect of lipid-depleted serum on the induction of hydroxymethylglutaryl-CoA reductase in human lymphocytes.


Systemic biomarkers of allogeneic haematopoietic stem cell transplantation outcome-Brief introduction.
Although complex approaches in haematopoietic stem cell transplantation (aHSCT) improved substantially in the last decades, considerable proportion of patients still suffer from life-threatening complications including graft versus host disease (GvHD). Great effort has therefore been dedicated to identification of biomarkers of the aHSCT outcome. Recently, prognostic scores for the prediction of GvHD and non-relapse mortality based on circulating molecules, such as tumour necrosis factor receptor-1, IL-33receptor (ST2) and regenerating islet-derived 3-alpha were proposed and evaluated in multicentre studies. Furthermore, several biomarkers, for example, ST2, represent promising targets for therapeutic intervention in severe GvHD. These results bring us closer to the clinical strategies to effectively control complications following aHSCT, and therefore to the tailored stem cell therapy with higher benefits for the patients.


Invasive alien plants in Croatia as a threat to biodiversity of South-Eastern Europe: distributional patterns and range size.
During the analysis of alien and invasive flora of Europe, as a threat to biodiversity, data for Croatia were missing. The aim of our research was to analyse distributional patterns and range size of all invasive alien plants (64) for the state area (57,000 km(2)). They were detected on 49% of the state territory, averaging five taxa per 35 km(2). The greatest number of invasive plants (>30 per grid cell) was recorded in the major urban centres, increasing in the south-east direction and reflecting positive correlation with temperature and negative with altitude. The most endangered areas are in the Mediterranean region, especially on islands. The number of invasive plants increased with habitat diversity and almost 75% of all sites with invasive plants are located within a few habitats with direct anthropogenic influence. The results should provide a reliable regional and global basis for strategic planning regarding invasive alien plants management.


A fluid mechanical analysis of the velocity, adhesion, and destruction of cancer cells in capillaries during metastasis.
Metastasis, a multistep process by which cancer disseminates through the body, mainly by intravascular routes, constitutes a major problem in cancer. When cancer cells are injected directly into the veins of animals, they are apparently arrested in the vascular bed of the first organ encountered and gradually released over the next 24 h. These interactions with the microvasculature are often associated in some manner with the death of many cancer cells, and are thought to contribute to the inefficiency of the metastatic process. We have made a theoretical analysis of cancer cells deformed into capillaries with respect to their intravascular velocity, adhesion to the vascular endothelium and intravascular destruction, in terms of the dynamics of the thin liquid film separating the surfaces of the blood vessels and cancer cells. Our calculations, which are based on previously reported experimental observations, indicate that the transit of cancer cells through the microvasculature is discontinuous, being interrupted by adhesions between the two. In addition, in some cases cell membrane rupture (and cell death) will occur when the critical membrane tension of the cancer cells is exceeded by the sum of their initial equilibrium membrane tension and the increased tension in the cancer cell membranes caused by friction generated as they move over the intraluminal surfaces of the capillaries. Our calculations on membrane rupture are consistent with previously unexplained observations by Sato and Suzuki relating cancer cell deformability to death on transpulmonary passage, and constitute a novel mechanism for "metastatic inefficiency" in terms of intravascular cancer cell death.


How does Malus crabapple resist ozone? Transcriptomics and metabolomics analyses.
Ozone (O3), an oxidizing toxic air pollutant, is ubiquitous in industrialized and developing countries. To understand the effects of O3 exposure on apple (Malus) and to explore its defense mechanisms, we exposed 'Hongjiu' crabapple to O3 and monitored its responses using physiological, transcriptomics, and metabolomics analyses. Exposure to 300 nL L-1 O3 for 3 h caused obvious damage to the leaves of Malus crabapple, affected chlorophyll and anthocyanin contents, and activated antioxidant enzymes. The gene encoding phospholipase A was highly responsive to O3 in Malus crabapple. McWRKY75 is a key transcription factor in the response to O3 stress, and its transcript levels were positively correlated with those of flavonoid-related structural genes (McC4H, McDFR, and McANR). The ethylene response factors McERF019 and McERF109-like were also up-regulated by O3. Exogenous methyl jasmonate (MeJA) decreased the damaging effects of O3 on crabapple and was most effective at 200 μmol L -1. Treatments with MeJA altered the metabolic pathways of crabapple under O3 stress. In particular, MeJA activated the flavonoid metabolic pathway in Malus, which improved its resistance to O3 stress.


Biological properties and clinical application of propolis. VIII. Experimental observation on the influence of ethanol extract of propolis (EEP) on the regeneration of bone tissue.
Artificially induced bone tissue losses after the application of ethanol extract of propolis (EEP) showed an accelerated rate of ossification. The osteogenetic process was just about half as long as in the control group.


Abnormal fetal cerebral blood flow velocity waveforms as a sign of an aneurysm of the vein of Galen.
A cerebral midline cystic lesion was detected by real-time ultrasound in utero in the absence of other congenital abnormalities. Pulsed Doppler ultrasound assessment of fetal circulation demonstrated normal peripheral and intracardiac hemodynamics associated with decreased cerebral vascular resistance. Furthermore, a markedly turbulent flow pattern was evidenced within the cerebral lesion. The presence of a cerebral arteriovenous malformation with an aneurysm of the vein of Galen was suggested and the provisional diagnosis was later confirmed by computed tomography and carotid angiography performed after birth.


Climate change affects multiple dimensions of well-being through impacts, information and policy responses.
The consequences of climate change and responses to climate change interact with multiple dimensions of human well-being in ways that are emerging or invisible to decision makers. We examine how elements of well-being-health, safety, place, self and belonging-are at risk from climate change. We propose that the material impacts of a changing climate, discourses and information on future and present climate risks, and policy responses to climate change affect all these elements of well-being. We review evidence on the scale and scope of these climate change consequences for well-being and propose policy and research priorities that are oriented towards supporting well-being though a changing climate.


Levonorgestrel intrauterine device use and incident idiopathic intracranial hypertension among commercially insured women.
To estimate the hazard of incident idiopathic intracranial hypertension, a potentially blinding condition, among women using levonorgestrel intrauterine devices (LNG-IUD) compared to copper IUD, as conflicting associations have been reported. This retrospective, longitudinal cohort study identified women ages 18-45 years in a large care network (January 1, 2001, to December 31, 2015) using LNG-IUD, subcutaneous etonogestrel implant, copper IUD, tubal device/surgery, or hysterectomy. Incident idiopathic intracranial hypertension was defined as the first diagnosis code for after 1 year without any codes and following brain imaging or lumbar puncture. Kaplan-Meier analysis estimated time-dependent probabilities of idiopathic intracranial hypertension at 1 and 5 years after incident contraception use, stratified by type. Cox regression estimated the hazard of idiopathic intracranial hypertension associated with LNG-IUD use compared to copper IUD (primary comparison) after adjusting for sociodemographics and factors associated with idiopathic intracranial hypertension (e.g., obesity) or contraception selection. A sensitivity analysis with propensity score-adjusted models was performed. Of 268,280 women, 78,175 (29%) used LNG-IUD, 8715 (3%) etonogestrel implant, 20,275 (8%) copper IUD, 108,216 (40%) hysterectomy, 52,899 (20%) tubal device/surgery, and 208 (0.08%) developed idiopathic intracranial hypertension over a mean follow-up of 2.4 ± 2.4 years. Also, 1-/5-year Kaplan-Meier idiopathic intracranial hypertension probabilities were 0.0004/0.0021 for LNG-IUD and 0.0005/0.0006 for copper IUD users. LNG-IUD use did not show significantly different hazard of idiopathic intracranial hypertension compared to copper IUD (adjusted hazard ratio 1.84 [95% CI 0.88, 3.85]). Sensitivity analyses were similar. We did not observe a significantly increased hazard of idiopathic intracranial hypertension among women using LNG-IUD compared to copper IUDs. The lack of an association between LNG-IUD use and idiopathic intracranial hypertension in this large observational study provides reassurance to women considering initiation or continued use of this highly effective contraceptive method.


Rapid screening of experimental cardiac drugs using atria and a microcomputer.
The authors investigated the use of a programmable digitizer, multiplexer, and laboratory microcomputer as a rapid and accurate means of evaluating potential inotropic or antiarrhythmic drugs using mammalian atrial preparations.


Isolation of rat testis histone TH2B-x, and interaction of TH2B-x antiserum with histones and mononucleosomes.
A method is reported for the isolation of histone TH2B-x from rat testis by affinity chromatography on an agarose-p-chloromercurianilino column. This purified TH2B-x was used to raise antibodies in the rabbit, and the antiserum was assayed by an enzyme-linked double-antibody procedure. At low concentration the antiserum cross-reacts with histone H2B and with histones TH1-x + H1 to the extent of 11-14% of the interaction with TH2B-x. Antiserum preincubated in three successive H2B-coated tubes still retains 80-89% of the original anti-TH2B-x activity when assayed subsequently in TH2B-x-coated tubes, but cross-reaction with H2B is practically zero. The anti-TH2B-x antibodies also interact with tubes coated with mononucleosomes isolated from nuclei of seminiferous epithelial cells (SEC) of rat testis, but the interaction with mononucleosomes from rat liver nuclei is almost zero. The data suggest that in nucleosomes some of the antigenic determinants which are unique to TH2B-x are accessible, while those determinants which are common to H2B and TH2B-x are not accessible for interaction with antibodies. Competition by mononucleosomes, both from rat testis SEC and rat liver (to a lesser degree), in solution is detected by the reduction of binding of enzyme-labeled IgG to TH2B-x-coated tubes. However, an attempted competition by histones TH2B-x or H2B in solution resulted in an increase in the binding of the enzyme-labeled IgG to the mononucleosome-coated tubes. The interpretation of this type of competition assay is complicated by possible interaction of added histones with the coating mononucleosomes, followed by binding of antibodies to the histones. This TH2B-x antibody should be useful in studying changes in structure and function of chromatin during spermatogenesis and in the isolation of TH2B-x mRNA.


Evidence for a Müllerian-inhibiting substance autocrine/paracrine system in adult human endometrium.
To determine if adult human endometrium possesses an intact müllerian-inhibiting substance (MIS) signal transduction system and, if so, whether MIS can modulate endometrial cell viability. Adult human endometrial tissue was subjected to reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. In addition, cultured human endometrial stromal cells were treated with recombinant MIS or transiently transfected with MIS and/or MIS type II receptor (MISRII) expression plasmids to assess for effects upon endometrial cell viability and apoptosis. The MIS in conditioned media was quantified by specific ELISA. Academically affiliated medical center. Reproductive-age women undergoing routine infertility evaluation. Endometrial sampling. Assessment of MIS gene transcription and protein translation in human endometrial tissue in vivo and in vitro. 1) The RT-PCR revealed that adult human endometrium expresses the genes for MIS, MISRII, ALK3, and Smads 1 and 9. 2) Immunohistochemistry reveals that MIS and MISRII protein are expressed in human endometrium. 3) Immunocytochemistry of cultured human endometrial cells reveals that MIS and MISRII protein are primarily restricted to mitosing cells. 4) ELISA reveals that MIS is secreted by human endometrial cells in vitro and that this process is increased by sex steroids. 5) Increasing local MIS concentration in cultured human endometrial stromal cells either by exogenous administration or transient transfection significantly decreases cell viability and increases apoptosis. Adult human endometrium possesses a functional MIS signal transduction system which negatively regulates cellular viability.


Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children.
Morbidity and mortality are high in young children with medulloblastoma who receive craniospinal radiotherapy. We aimed to assess whether adjuvant treatment with protracted chemotherapy alone could replace radiotherapy. We enrolled 79 children aged younger than 5 years who had had surgical resection of medulloblastoma onto a multicentre trial. Patients were treated with combination chemotherapy, which did not include methotrexate, for more than 16 months irrespective of the extent of disease. Early postoperative imaging defined three groups: R0M0 (no residual disease, no metastasis), R1M0 (radiological residual disease alone), and RXM+ (presence of metastases). Patients who did not relapse did not receive radiotherapy. Patients who relapsed or had disease progression received salvage treatment, which consisted of high-dose chemotherapy and stem-cell transplantation followed by local or craniospinal radiotherapy. For children classified as R0M0, the primary endpoint was 5-year overall survival and the secondary endpoint was 5-year progression-free survival. For children classified as R1M0 or RXM+, the primary endpoint was best radiological response and the secondary endpoints were 5-year overall survival and 5-year progression-free survival. Analyses were done by intention to treat. Two of 15 patients classified as RXM+ and four of 17 patients classified as R1M0 had a complete radiological response. 5-year progression-free survival was 29% (95% CI 18-44) in the R0M0 group, 6% (1-27) in the R1M0 group, and 13% (4-38) in the RXM+ group. 5-year overall survival was 73% (59-84) in the R0M0 group, 41% (22-64) in the R1M0 group, and 13% (4-38) in the RXM+ group. In the R0M0 group, 5-year progression-free survival was 41% (26-58) for the 34 patients who underwent gross total resection compared with 0% for the 13 patients who had subtotal resection (relative risk 2.7 [1.3-5.6], p=0.0065). Conventional chemotherapy alone can be used to cure children with non-metastatic medulloblastoma who have gross total resection confirmed by early radiological assessment, but is not sufficient for treatment of those with metastatic or incompletely resected medulloblastoma. Salvage treatment followed by posterior-fossa radiotherapy can effectively treat local relapses or progression.


Effect of food and light schedule on bile flow in the rat.
In the rat after food intake, whether during the dark or light period, bile flow increases. Food intake seems to be a major factor in the circadian rhythm of bile secretion.


A Fibroblastic Reticular Cell Tumour Arising in the Oral Cavity: A Case Report and Review of the Literature.
Tumours of dendritic or histiocytic lineage are amongst the rarest tumours and probably account for < 1% of tumours affecting the lymph nodes or soft tissue. Because several of these entities were poorly recognised until recently, the true incidence is not determined. We present what we believe is the first reported case report of a fibroblastic reticular cell tumour arising in the oral cavity as well as reviewing the current literature regarding this rare subset of tumours. We discuss the clinical and histopathological findings of our reported case and examine the literature regarding this entity. We discuss the key differential diagnoses to consider when making this diagnosis. Histiocytic and dendritic cell derived tumours are exceptionally rare within the head and neck region although a number of these tumours have been reported within the oral cavity. We present what we believe is the first reported case of a fibroblastic reticular cell tumour arising within the oral cavity.


Epidemiologic and molecular analysis of human tularemia, United States, 1964-2004.
Tularemia in the United States is caused by 2 subspecies of Francisella tularensis, subspecies tularensis (type A) and subspecies holarctica (type B). We compared clinical and demographic features of human tularemia cases from 1964 to 2004 from 39 states in which an isolate was recovered and subtyped. Our data indicate that type A and type B infections differ with respect to affected populations, anatomic site of isolation, and geographic distribution. Molecular subtyping with pulsed-field gel electrophoresis further defined 2 subpopulations of type A (type A-east and type A-west) that differ with respect to geographic distribution, disease outcome, and transmission. Our data suggest that type A-west infections are less severe than either type B or type A-east infections. Through a combined epidemiologic and molecular approach to human cases of tularemia, we provide new insights into the disease for future investigation.


Acute Portal Vein Thrombosis, No Longer a Contraindication for Transjugular Intrahepatic Porto-Systemic Shunt (TIPS) Insertion.
Portal vein thrombosis, once considered as a contraindication to transjugular intrahepatic porto-systemic shunt (TIPS) is now considered as an indication. We report a case with clinical and technical success in a patient with Budd Chiari syndrome and acute portal venous thrombosis. Though it is a well-established option, with the best of our knowledge, we could not find a report from India.


The mosquitoes and chaoborids of Glacier and Yellowstone National Parks with new records and Ochlerotatus nevadensis, a new state record for Montana.
The known mosquito fauna of Glacier National Park, Montana, and Yellowstone National Park, Wyoming, is reported with new records, including a list of the species of Chaoboridae known from both parks. Ochlerotatus nevadensis (= Aedes nevadensis) from Glacier National Park is a new record for the state of Montana.


Do contemporary antiretrovirals increase the risk of end-stage liver disease? Signals from patients starting therapy in the North American AIDS Cohort Collaboration on Research and Design.
Despite effective antiretroviral therapy, rates of end-stage liver disease (ESLD) remain high. It is not clear whether contemporary antiretrovirals contribute to the risk of ESLD. We included patients from cohorts with validated ESLD data in the North American AIDS Cohort Collaboration on Research and Design. Patients had to initiate antiretroviral therapy after 1 January 2004 with a nucleos(t)ide backbone of either abacavir/lamivudine or tenofovir/emtricitabine and a contemporary third (anchor) drug. Patients were followed until a first ESLD event, death, end of a cohort's ESLD validation period, loss to follow-up or 31 December 2015. We estimated associations between cumulative exposure to each drug and ESLD using a hierarchical Bayesian survival model with weakly informative prior distributions. Among 10 564 patients included from 12 cohorts, 62 had an ESLD event. Of the nine anchor drugs, boosted protease inhibitors atazanavir and darunavir had the strongest signals for ESLD, with increasing hazard ratios (HR) and narrowing credible intervals (CrI), from a prior HR of 1.5 (95% CrI 0.32-7.1) per 5 year's exposure to posterior HRs respectively of 1.8 (95% CrI 0.82-3.9) and 2.0 (95% CrI 0.86-4.7). Both backbones and efavirenz showed no signal. Hepatitis C coinfection was the most important covariate risk factor (HR 4.4, 95% CrI 2.6-7.0). While contemporary antiretrovirals pose less risk for ESLD than hepatitis coinfection, atazanavir and darunavir had a toxicity signal. We show how hierarchical Bayesian modelling can be used to detect toxicity signals in cohort event monitoring data even with complex treatments and few events.


The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins.
We have determined the DNA sequence of a cloned cDNA that is complementary to the mRNA for the 50 kilodalton (kd) human epidermal keratin. This provides the first amino acid sequence for a cytoskeletal keratin. Comparison of this sequence with those of other keratins reveals an evolutionary relationship between the cytoskeletal and the microfibrillar keratins, but shows no homology to matrix or feather keratins. The 50 kd keratin shares 28%-30% homology with partial sequences of other intermediate filament proteins, which suggests that keratins may be the most distantly related members of this class of fibrous proteins. Our computer analyses predict that the 50 kd keratin contains two long alpha-helical domains separated by a cluster of helix-inhibitory residues in the middle of the protein. These findings indicate that despite major sequence divergence among intermediate filament proteins, they retain sequences compatible with secondary structural features that appear to be common to all of them.


Comparing traditional modeling approaches versus predictive analytics methods for predicting multiple sclerosis relapse.
This study compared traditional statistical methods to different predictive analytics methods on the endpoint of multiple sclerosis (MS) relapse. This is a secondary data analysis on four different MS Centers based on the third year of data, July 2019-June 2020. The parent study is a two-part, 3-year clinical quality improvement prospective study that started in June 2017 and concluded in June 2020, and utilizes a prospective stepped-wedge randomized design. Binary logistic regression was compared with other machine learning models, specifically ridge, least absolute shrinkage and selection operator (LASSO), and random forest. This study used electronic health record data extracted at the individual level and 'rolled up' to the system and population level. Inclusion criteria included participants aged 18 years or older, with MS presenting to any of the four centers, who entered the study in any quarter. Exclusion criteria included cases with missing or incorrectly input data and those who refused to participate in the study. When comparing relapse indices across models, random forest significantly outperformed logistic regression and other machine learning algorithms (ΔperfA =27.1%, ΔperfM =27.5%). However, for ΔperfF, logistic regression and random forest performed relatively the same. Ridge and LASSO outperformed logistic regression (ΔperfM1 =0.9%, ΔperfM2 =9.4%, ΔperfF2=25.8%, respectively). Multiple sclerosis is a complex and costly chronic ("3C") condition that currently has no cure. In a condition like MS, which has an unpredictable course, the use of predictive analytics could help health systems learn better, faster, and to improve more effectively and predict rather than react to emerging health needs for people with MS. Comparing the predictability of relapse across various models with a predictive analytics framework can potentially change how we manage MS care.


Inhibition of polyposis in the small intestine of BALB/c mice by intestinal bacteria.
The incidence of polyposis and the number of polyps per mouse were significantly lower in conventionalized (CVz) mice than in germ-free (GF) mice. There was no significant difference in the average number of polyps between GF and gnotobiotic (GB) mice monoassociated with the various strains of intestinal bacteria. However, the incidence of polyposis and the number of polyps per mouse were significantly lower for mice associated with either chloroform-resistant bacteria (CRB) or fusiform bacteria (FB) than for GF mice. This study demonstrated that polyposis was suppressed by FB and CRB in the small intestine of BALB/c mice.


Mitochondrial tRNA mutations associated with deafness.
Mitochondrial tRNA mutations are one of the important causes of both syndromic and non-syndromic deafness. Of those, syndromic deafness-associated tRNA mutations such as tRNA(Leu(UUR)) 3243A>G are often present in heteroplasmy, while non-syndromic deafness-associated tRNA mutations including tRNA(Ser(UCN)) 7445A>G often occur in homplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary mutations leading to hearing loss. However, other tRNA mutations such as tRNA(Thr) 15927G>A and tRNA(Ser(UCN)) 7444G>A may act in synergy with the primary mitochondrial DNA mutations, modulating the phenotypic manifestation of the primary mitochondrial DNA mutations. Theses tRNA mutations cause structural and functional alteration. A failure in tRNA metabolism caused by these tRNA mutations impaired mitochondrial translation and respiration, thereby causing mitochondrial dysfunctions responsible for deafness. These data offer valuable information for the early diagnosis, management and treatment of maternally inherited deafness.


Novel heterotetranuclear V2Mo2 or V2W2 complexes with 4,4'-di-tert-butyl-2,2'-bipyridine: syntheses, crystal structures, and catalytic activities.
Two novel heterotetranuclear complexes [V(2)O(2)(μ-MeO)(2)(μ-WO(4))(2)(4,4'-(t)Bubpy)(2)] (1) and [V(2)O(2)(μ-MeO)(2)(μ-MoO(4))(2)(4,4'-(t)Bubpy)(2)] (2) were synthesized, and the solid state structures of these complexes were revealed by single crystal X-ray crystallography. The heterotetranuclear complexes 1 and 2 are centrosymmetric building blocks, considered as consisting of two [VO(4,4'-(t)Bubpy)](3+) units bridged by μ-MO(4)(2-) (M = W or Mo) anions connected with methoxy groups. Furthermore, catalytic activities of 1 and 2 in the alcohol oxidation with hydrogen peroxide as terminal oxidants in water as solvent were investigated.


A clinical, pathological and immunohistochemical series of 9 cases of primary cutaneous apocrine carcinomas of the head and neck.
Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region. All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow-up were collected by the clinicians. Nine cases were found, with a mean age of 76 years, ranging in size between 0.3 and 3.5 cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo-papillary and solid-tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP-15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases. In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease. As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow-up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma.


The effects of handling and storage on magnesium based implants--first results.
The present work aimed to investigate the influence of acetone and formalin as well as the duration and type of storage on magnesium based implants by means of microscopic, μ-computed tomographic, scanning electron microscopic, EDX and metallographic investigations. In contrast to storing in acetone, storage in formalin led to an increase in surface to volume ratio, and a decrease of the volume and the density. The various types of storage exerted no differing effects on the implants but with increasing storage duration, a spreading of oxygen rich areas on the surface, increased precipitations and a decrease in grain size could be observed.


Edge enhancement of ECG-gated cardiac images using directional masks.
ECG-gated images were processed by a computer using a nonlinear digital filter and directional masks to improve delineation of cardiac chamber boundaries and identification of the aortic and mitral valve planes. This technique proved to be satisfactory in 30 patients with documented coronary or valvular heart disease.


Detection of 1-O-malylglucose: pelargonidin 3-O-glucose-6''-O-malyltransferase activity in carnation (Dianthus caryophyllus).
Carnations have anthocyanins acylated with malate. Although anthocyanin acyltransferases have been reported in several plant species, anthocyanin malyltransferase (AMalT) activity in carnation has not been identified. Here, an acyl donor substance of AMalT, 1-O-beta-D-malylglucose, was extracted and partially purified from the petals of carnation. This was synthesized chemically to analyze AMalT activity in a crude extract from carnation. Changes in the AMalT activity showed close correlation to the accumulation of pelargonidin 3-malylglucoside (Pel 3-malGlc) during the development of red petals of carnation, but neither AMalT activity nor Pel 3-malGlc accumulation was detectable in roots, stems and leaves.


[Geriatric status of patients over 70 years of age with myocardial infarction and the relationship with the severity of myocardial stress, fibrosis and angiogenesis.]
A prospective study of 92 patients over 70 years old with myocardial infarction was carried out. All patients were diagnosed and determined the severity of geriatric syndromes, including fragility, using specialized scales on the 5th day of hospitalization. The comorbidity was assessed with the calculation of the Charlson Comorbidity Index, levels of NT-proBNP, ST-2, FGF-21, VEGF in blood serum by enzyme immunoassay. In the studied cohort of patients, marked comorbidity, high prevalence of prefragility and fragility in combination with other geriatric syndromes were revealed. Patients over 70 years old with myocardial infarction and fragility showed significantly higher levels of myocardial stress and fibrosis, which is prognostically unfavorable sign for the given group of patients. NT-proBNP and ST-2 levels have significant correlation with major geriatric syndromes and could be the markers of fragility development among elderly and senile patients with myocardial infarction.


Histopathologic factors significantly associated with initial organ-specific metastasis by invasive ductal carcinoma of the breast: a prospective study.
The purpose of this study was to identify histologic factors significantly associated with initial organ-specific metastasis by 1044 invasive ductal carcinomas (IDCs) of the breast with and without adjuvant therapy, separately, according to nodal status and pathologic TNM stage status. The following histologic factors were prospectively analyzed by multivariate analyses for distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy, and for distant organ metastasis, bone metastasis, liver metastasis, and lung metastasis in patients with IDC who received adjuvant therapy: (1) invasive tumor size, (2) histologic grade, (3) tumor necrosis, (4) fibrotic focus (FF), (5) lymphatic invasion, (6) blood vessel invasion, (7) adipose tissue invasion, (8) skin invasion, (9) muscle invasion, (10) age, (11) estrogen (ER)/progesterone (PR) status, and (12) nodal status. The results showed that FF diameter greater than 8 mm and FF fibrosis grade 1 were the factors that most accurately predicted distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy. In patients with IDC who received adjuvant therapy, FF diameter greater than 8 mm was the factor that most accurately predicted bone metastasis, and the presence of tumor necrosis and ER-/PR- were very important predictive factors for metastasis to the lung. Ten or more nodal metastases (N3) were the factor that most accurately predicted liver metastasis. Based on these findings, FF characteristics can be concluded to be the most important histologic factors for predicting metastasis to the bone, the presence of tumor necrosis and ER-/PR- for predicting metastasis to the lung, and N3 for predicting metastasis to the liver.


Utility of cockroach as a model organism in the assessment of toxicological impacts of environmental pollutants.
Environmental pollution is a global concern because of its associated risks to human health and ecosystem. The bio-monitoring of environmental health has attracted much attention in recent years and efforts to minimize environmental contamination as well as to delineate toxicological mechanisms related to toxic exposure are essential to improve the health conditions of both humans and animals. This review aims to substantiate the need and advantages in utilizing cockroaches as a complementary, non-mammalian model to further understand the noxious impact of environmental contaminants on humans and animals. We discuss recent advances in neurotoxicology, immunotoxicology, reproductive and developmental toxicology, environmental forensic entomotoxicology, and environmental toxicology that corroborate the utility of the cockroach (Periplaneta americana, Blaptica dubia, Blattella germanica and Nauphoeta cinerea) in addressing toxicological mechanisms as well as a sensor of environmental pollution. Indeed, recent improvements in behavioural assessment and the detection of potential biomarkers allow for the recognition of phenotypic alterations in cockroaches following exposure to toxic chemicals namely saxitoxin, methylmercury, polychlorinated biphenyls, electromagnetic fields, pharmaceuticals, polycyclic aromatic hydrocarbon, chemical warfare agents and nanoparticles. The review provides a state-of-the-art update on the current utility of cockroach models in various aspects of toxicology as well as discusses the potential limitations and future perspectives.


Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: role of insulin and C-peptide.
Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.


Measurement of soluble transferrin receptor by immunoturbidimetry and immunonephelometry.
To evaluate and compare two new commercially available immunoturbidimetric and immunonephelometric assays for measuring soluble transferrin receptor (sTfR) in serum. To adapt the immunonephelometric assay to an automated chemistry analyzer. Total imprecisions and detection limits were calculated and compared. Fifty-six samples were used for methods comparison. The nephelometric assay was adapted to the Hitachi 911 analyzer. Both methods displayed acceptable imprecisions and detection limits. Their correlation was good but a proportional bias was observed. The adaptation of the nephelometric assay to the Hitachi 911 was successful. These two new immunoassays are analytically acceptable and more practicable than previously developed methods. The differences observed between both methods underscores the need for standardization. The nephelometric assay was easily adaptable to an automated chemistry analyzer.


Association of Estimated Sodium Intake With Adverse Cardiac Structure and Function: From the HyperGEN Study.
The optimal level of sodium intake remains controversial. This study sought to determine whether examination of left ventricular longitudinal strain (LS), circumferential strain, and e' velocity can provide insight into thresholds for the detrimental effects of estimated sodium intake (ESI) on subclinical cardiovascular disease. We performed speckle-tracking analysis on HyperGEN (Hypertension Genetic Epidemiology Network) study echocardiograms with available urinary sodium data (N = 2,996). We evaluated the associations among ESI and LS, circumferential strain, and e' velocity using multivariable-adjusted linear mixed-effects models (to account for relatedness among subjects) with linear splines (spline 1: ESI ≤3.7 g/day, spline 2: ESI >3.7 g/day based on visual inspection of fractional polynomial plots of the association between ESI and indices of strain and e' velocity). We performed mediation analysis to understand the indirect effects of systolic blood pressure and serum aldosterone on the relationship between ESI and strain and e' velocity. Mean age of participants was 49 ± 14 years, 57% were female, 50% were African American, and 54% had hypertension. The median ESI was 3.73 (interquartile range: 3.24, 4.25) g/day. ESI >3.7 g/day was associated with larger left atrial and left ventricular dimensions (p < 0.05). After adjusting for speckle-tracking analyst, image quality, study site, age, sex, smoking status, alcohol use, daily blocks walked, diuretic use, estimated glomerular filtration rate, left ventricular mass, ejection fraction, and wall motion score index, ESI >3.7 g/day was associated with both strain parameters and e' velocity (p < 0.05 for all comparisons), but ESI ≤3.7 g/day was not (p > 0.05 for all comparisons). There were significant interactions by potassium excretion for circumferential strain. Mediation analysis suggested that systolic blood pressure explained 14% and 20% of the indirect effects between ESI and LS and e' velocity, respectively, whereas serum aldosterone explained 19% of the indirect effects between ESI and LS. ESI >3.7 g/day is associated with adverse cardiac remodeling and worse systolic strain and diastolic e' velocity.


Metabolism of PGP peptide after administration via different routes.
Main pathways of degradation of PGP peptide possessing antiulcer and antithrombotic activities were studied after its intraperitoneal, intragastric, and intraintestinal administration. In experiments on rabbits we showed by HPLC that unmodified PGP is released into the blood after administration by all three routes and is detected in the plasma over 3-5 h. PG dipeptide is a more stable PGP metabolite presumably determining (together with tripeptide) its pharmacological properties.


Subclinical leptospirosis may impair athletic performance in racing horses.
The infection by Leptospira in horses, in both its acute disease and subclinical forms, is very common, particularly in endemic regions. Therefore, the objective of this study was to evaluate the effects of subclinical leptospirosis in the athletic performance of racing thoroughbred horses. Athletic performance of 119 racing Thoroughbred horses from Rio de Janeiro, Brazil, was calculated by assigning a point value for the results in racing (performance index (PI)), and serology for leptospirosis was conducted. A total of 85 (71.4 %) horses showed reactive titers (≥ 100), and of which 52 had high titers (34 with 400 and 18 with ≥ 800). Although those animals had high titers against Leptospira, no clinical signs associated with leptospirosis were observed. Seventeen (89.5 %) out of the 19 horses with substandard performance were seroreactive with high titers, in contrast with 35 % of seroreactivity in horses with good athletic performance (P < 0.0001). Additionally, seroreactivity to leptospirosis was more often observed in horses with substandard athletic performance in contrast to those with good performance (P < 0.0001, odds ratio 15.8). The Average PI of this group increased to 133 % after treatment (P < 0.0001). Leptospirosis may impair performance in racing horses, and antibiotic therapy may improve the performance of affected animals.


Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release in neuromuscular synapses.
The beta-amyloid (AB) peptide25-35 contains the functional domain of the AB precursor protein that is both required for neurotrophic effects in normal neural tissues and is involved in the neurotoxic effects in Alzheimer disease. We demonstrated the presence of the amyloid precursor protein/AB peptide in intramuscular axons, presynaptic motor nerve terminals, terminal and myelinating Schwann cells, and the postsynaptic and subsarcolemmal region in the Levator auris longus muscle of adult rats by immunocytochemistry. Using intracellular recording, we investigated possible short-term functional effects of the AB fragment (0.1-10 micromol/L) on acetylcholine release in adult and newborn motor end plates. We found no change in evoked, spontaneous transmitter release or resting membrane potential of the muscle cells. A previous block of the presynaptic muscarinic receptor subtypes and a previous block or stimulation of protein kinase C revealed no masked effect of the peptide on the regulation of transmitter release. The aggregated form of AB peptide25-35, however, interfered acutely with acetylcholine release (quantal content reduction) when synaptic activity was maintained by electric stimulation. The possible relevance of this inhibition of neurotransmission by AB peptide25-35 to the pathogenesis of Alzheimer remains to be determined.


Enhanced spontaneous calcium efflux and decrease of calcium-dependent calcium release from the isolated perfused heart of spontaneously hypertensive rats.
The aim of this study was to clarify the further details of calcium handling in hypertension. By preserving the physiological environment of cell membrane, whole hearts were used for comparison of calcium flux between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Hearts from SHR and WKY rats were perfused with Krebs-Henseleit solution under constant flow and the effluent collected. After labelling of the heart with 45Ca2+ (100 mumol/l), 45Ca2+ binding was found to be saturated, and washing with calcium-free perfusion solution showed two exponential curves for calcium dissociation, indicating a fast (alpha-) and slow (beta-) phase. The half-lives of the beta-phase for both 4- and 8-week-old SHR were significantly shorter than those for age-matched WKY. Also in this phase, infusion of non-radioactive Ca2+ caused a transient dose-dependent release of 45Ca2+. A significant reduction in the amount of 45Ca2+ release induced by 2 mmol/l Ca2+ was observed in both 4- and 8-week-old SHR compared with age-matched WKY rats. Infusion of lanthanum, caffeine, ionomycin (calcium ionophore) and treatment of the hearts with ethyleneglycol-bis-(beta-aminoethylether)-N,N,N,',N'-tetraac etic acid did not alter 45Ca2+ release by non-radioactive Ca2+. From these observations, 45Ca2+ is presumably released from the intracellular calcium pool, and not from extracellular binding sites or sarcoplasmic reticulum. These findings suggest that an abnormal calcium-handling defect (enhanced calcium efflux and reduction of membrane-bound Ca2+) exists under physiological conditions before and after the onset of hypertension, and that this may be a primary characteristic of SHR.


X-Linked Retinitis Pigmentosa Gene Therapy: Preclinical Aspects.
The most common inherited eye disease is retinitis pigmentosa (RP). X-linked RP (XLRP) is one of the most severe types of RP, with a considerable disease burden. Patients with XLRP experience a decrease in their vision and become blind in their 4th decade of life, causing much morbidity after starting a rather normal life. Treatment of XLRP remains challenging, and current treatments are not effective enough in restoring vision. Gene therapy of XLRP, capable of restoring the functional RPGR gene, showed promising results in preclinical studies and clinical trials; however, to date, no approved product has entered the market. The development of a gene therapy product needs through preliminary assessment of the drug in animal models before administration to humans. In this article, we reviewed the genetic pathology of XLRP, along with the preclinical aspects of the XLRP gene therapy, animal models, associated assessments, and future challenges and directions.


Perception of inappropriate cardiopulmonary resuscitation by clinicians working in emergency departments and ambulance services: The REAPPROPRIATE international, multi-centre, cross sectional survey.
Cardiopulmonary resuscitation (CPR) is often started irrespective of comorbidity or cause of arrest. We aimed to determine the prevalence of perception of inappropriate CPR of the last cardiac arrest encountered by clinicians working in emergency departments and out-of-hospital, factors associated with perception, and its relation to patient outcome. A cross-sectional survey was conducted in 288 centres in 24 countries. Factors associated with perception of CPR and outcome were analyzed by Cochran-Mantel-Haenszel tests and conditional logistic models. Of the 4018 participating clinicians, 3150 (78.4%) perceived their last CPR attempt as appropriate, 548 (13.6%) were uncertain about its appropriateness and 320 (8.0%) perceived inappropriateness; survival to hospital discharge was 370/2412 (15.3%), 8/481 (1.7%) and 8/294 (2.7%) respectively. After adjusting for country, team and clinician's characteristics, the prevalence of perception of inappropriate CPR was higher for a non-shockable initial rhythm (OR 3.76 [2.13-6.64]; P < .0001), a non-witnessed arrest (2.68 [1.89-3.79]; P < .0001), in older patients (2.94 [2.18-3.96]; P < .0001, for patients >79 years) and in case of a "poor" first physical impression of the patient (3.45 [2.36-5.05]; P < .0001). In accordance, non-shockable and non-witnessed arrests were both associated with lower survival to hospital discharge (0.33 [0.26-0.41]; P < 0.0001 and 0.25 [0.15-0.41]; P < 0.0001, respectively), as were older patient age (0.25 [0.14-0.44]; P < 0.0001 for patients >79 years) and a "poor" first physical impression (0.26 [0.19-0.35]; P < 0.0001). The perception of inappropriate CPR increased when objective indicators of poor prognosis were present and was associated with a low survival to hospital discharge. Factoring clinical judgment into the decision to (not) attempt CPR may reduce harm inflicted by excessive resuscitation attempts.


Direct Access to α,β-Alkynylamides via Pd-Catalyzed Carbonylation of Terminal Alkynes with Amines Using Chloroform as the CO Surrogate.
We describe the first-time use of a palladium-di(1-adamantyl)-n-butylphosphine catalytic system for the synthesis of alk-2-ynamides from terminal alkynes via aminocarbonylation reaction. This method avoids the direct use of toxic CO gas by utilizing chloroform as an in situ CO source. The aminocarbonylation of both aromatic and aliphatic electron-rich alkyne nucleophiles is reported for the first time. The mild condition provides alk-2-ynamides within 50 min under microwave irradiation at 80 °C.


The incidence of neurologic complications and associated risk factors in elbow surgery: an analysis of 2759 cases.
The purpose of this study was to evaluate the incidence of neurologic complications after elbow surgery and to provide perioperative tips and potential pitfalls for neurologic complications and how to cope with them. A single orthopedic surgeon performed 2759 elbow-related surgical procedures between January 2006 and October 2014. The surgical records and the postoperative follow-up of all 2759 patients were retrospectively reviewed to determine the preoperative diagnosis, the type of procedure, and postoperative neurologic complications. Neurologic complications were very uncommon. Neurologic deficit occurred in 10 of 2759 elbow operations. A neurologic complication occurred 4 distal biceps tendon surgeries (5.3%), 4 elbow arthroscopies (0.4%), 2 ligament reconstructions (0.7%), and 2 total elbow prosthesis (1.4%). A thorough understanding of the 3-dimensional anatomy of the elbow and surrounding nerves is needed to avoid neurologic complications. The neurologic complications we encountered in our series are well within the limits of earlier reports and show that elbow surgery is a relatively safe procedure to perform for a wide variety of indications.


Internal Hernia With Incarceration of the Cecum: A Case Report After Simultaneous Kidney-Pancreas Transplant.
Simultaneous pancreas and kidney (SPK) transplant is the most effective form of managing difficult-to-treat diabetes; however, this does not come without risk. The surgical complications after SPK transplant can be seen in up to 30% of recipients but do not always correlate with a decrease in patient or graft survival. One of the known complications is an internal hernia. Herein, we describe the first case of cecal incarceration in an internal hernia through the defect created by the transplanted ureter and the retroperitoneum in a SPK transplant recipient. Our management entailed the reduction of large bowel and revision of the ureteroneocystostomy to eliminate the potential space that could enable reherniation. Prompt identification of this rare complication with rapid surgical intervention allowed us to avoid serious morbidity or mortality.


Awareness and perspectives of audiologists on assessment and management of misophonia in India.
The assessment and management of misophonia need a team approach, and audiologists are essential team members. However, the role of an audiologist in this condition is not well understood, and there is a lack of awareness even among professionals about their role in the assessment and management of misophonia. The main aim of our study is to document the present level of awareness and knowledge about misophonia assessment and management among audiologists in India. A descriptive cross-sectional study was carried out among audiologists from all over India. Descriptive statistical procedures were measured based on the type of questions being addressed, and a non-parametric chi-square test was done to see the association among variables. The results show a lack of knowledge about misophonia even among audiologists, as only 15.3% of the audiologist reported being confident in handling cases with misophonia. Although the exact assessment and management of misophonia is still the topic of debate, it is clear that audiologists are the team's key members. However, the results clearly show a lack of confidence in handling cases of misophonia among audiologists in India. This result shows the future need for Research in misophonia from an audiological perspective.


Evolution of hominin cranial ontogeny.
Hominin evolution is characterized by two main trends, transition to bipedality and increase in brain size. Fossil evidence shows that both trends had a major impact on the structure and function of the hominin skull. This chapter asks how evolutionary modification of the cranial ontogenetic program led to morphological reorganization of the hominin skull and ultimately to hominin cranial diversity. Three major mechanisms of evolutionary developmental reorganization are proposed: modified prenatal development of the cranial base and face reflects adaptation to bipedality; high rates of neurocranial growth during early postnatal ontogeny are essential to attain large brain sizes; taxon-specific modification of facial development reflects dietary adaptation and-in the genus Homo-a general trend toward neoteny.


Morphologic perfusion patterns and PI-RADSv2.1 in transition zone prostate cancer.
To evaluate morphologic perfusion patterns in transition zone prostate cancer in multiparametric MRI controlled by in-bore MRI-guided prostate biopsy. Two experienced radiologists evaluated MRI perfusion patterns in consensus from 321 biopsy cores from the transition zone in 141 patients. Transition zone cancer was present in 77 cores in 36 patients. Single early-phase perfusion images were evaluated separately for the presence of a transition zone prostate cancer (consensus tumor early perfusion). The proposed criteria for the perfusion pattern (asymmetry, signal strength, and homogeneity) were rated in consensus for each biopsy position in the presence of the T2w images including the markers of the biopsy trace. We analyzed receiver operating characteristic curves for the PI-RADSv2.1 score and the proposed perfusion pattern. A logistic regression model with PI-RADSv2.1 and perfusion patterns in early perfusion imaging improved the model fit significantly compared to a model containing only PI-RADSv2.1 (Likelihood Ratio Test, LR = 14.5, p < .001). The AUC was 0.96 for the multiple regression model compared to 0.92 for the PI-RADSv2.1 alone. The evaluation of homogeneity in single early-enhancement images is not inferior compared to the conventional DCE parameter of PI-RADSv2.1 (AUC 0.84 versus 0.83). Morphologic perfusion patterns significantly improve the diagnostic performance of PI-RADSv2.1 in TZ prostate cancer.


Macrolide resistance in Mycoplasma genitalium from female sex workers in Belgium.
Mycoplasma genitalium is emerging as an aetiological agent of sexually transmitted infections (STIs). Although M. genitalium is commonly treated with azithromycin, macrolide resistance associated with point mutations in the 23S rRNA gene is emerging. In this study, the prevalence of M. genitalium and macrolide resistance in female sex workers (FSW) in Belgium was evaluated by a prospective study conducted between 2015 and 2016. Vaginal swabs were sampled from 303 FSW who underwent testing for M. genitalium along with standard STI screening. All samples positive for M. genitalium were subsequently tested for mutations associated with macrolide resistance. M. genitalium was detected in 10.8% of participants and macrolide resistance-associated mutations (A2058G and A2059G) were found in 6.5% of isolates. M. genitalium is clearly present in FSW in Belgium. In contrast to other reports, for now the occurrence of macrolide resistance appears limited in this specific target population.


[Comparative effectiveness of the sanatorium treatment of patients with bronchopulmonary diseases in the Leningrad health resort zone and at the climatotherapy sanatoria of Yalta and Kislovodsk].
Upon the comparison for Leningrad citizens, CNPD sanatorium treatment in climatic conditions of Leningrad Region was inferior in noway to that in southern climates of Yalta and Kislovodsk resorts as regards to relevant therapeutic response.


Nurses' intentions to leave nursing in Finland.
The shortage of nurses is a problem in many countries. We examined how factors related to wage, work, job satisfaction/dissatisfaction, and workplace or demographic factors were associated with nurses' intentions to switch from health care to non-health-care roles. Wage and share of income from shift work were negatively and statistically significantly related to nurses' intention to leave the health care sector. However, some non-pecuniary variables, such as Possibility for Specialisation gained a positive, statistically significant association with job satisfaction and thereby decreased intention to change work sector. Therefore, not only economic factors influence the labour supply of nurses.


[Improvements in the technical conditions for the evaluation of an elastolytic activity. The role of tryspin as an activator (author's transl)].
An isotopic assay of elastolytic activity is performed; the iodine-125 ions retained inside the elastin framework were removed by appropriate treatment. This acute substrate enables us to study the role of trypsin on elastase activity and facilitates the study of elastase role in atherosclerosis.


Application of Hydromorphone and Ropivacaine in Ultrasound-Guided Brachial Plexus Block of Children.
This research was designed to investigate the effects of hydromorphone combined with ropivacaine anesthesia on brachial plexus block of upper limbs in children. This was a randomized prospective study. A total of 120 children with upper limb fractures were included in this study and treated wtih open reduction and internal fixation (ORIF). The children were randomized into control group and research group. All of them were given a brachial plexus block and anesthetics (control group: 0.2% ropivacaine; research group: additional 5 μg/kg hydromorphone. The time of onset and exercise recovery of the research group increased, and the use times of analgesic drugs decreased, which were significantly different from those of the control group (all P<.05). Hydromorphone can enhance the effectiveness of ropivacaine in blocking the brachial plexus and reduce postoperative pain and the demand for analgesics. Strong postoperative sedation can improve sleep quality and nursing satisfaction.


Management of intrauterine device-associated actinomycosis.
To assess various methods of management of actinomyces-like organisms associated with intrauterine devices. A retrospective chart review of 173 patients with intrauterine device-associated actinomyces- like organisms detected on Pap smear was performed. The patients were managed by IUD removal with or without antibiotic therapy, antibiotic therapy alone, or no treatment at all. The success rate as reflected in negative follow-up smear was 100% for IUD removal combined with antibiotics, 97.4% for IUD removal alone, and 36.8% for antibiotics therapy alone. The best way to manage intrauterine device-associated actinomyces-like organisms is removal of the device with or without antibiotics.


Distribution of the - 13910C>T polymorphism in the general population of Portugal and in subjects with gastrointestinal complaints associated with milk consumption.
The - 13910C>T polymorphism has been associated with lactase persistence (LP) in European populations. To assess - 13910C>T genotypes across Portugal and in adult individuals with unspecific gastrointestinal complaints associated with milk consumption. This study genotyped - 13910C>T in the general population from Northern (n = 64), Central (n = 70) and Southern (n = 65) Portugal and in 40 subjects with gastrointestinal symptoms. Additionally, the concordance was evaluated between breath-hydrogen test and - 13910C>T genotypes in 65 samples. An overall frequency of 0.349 for the LP - 13910*T allele was estimated in the general population, with a noticeable decrease in the South (0.269) compared with North (0.383) and Centre (0.393). Among the symptomatic group, the frequency of the - 13910*T allele (0.363) was not significantly different from the general population. A 94% concordance was found between the breath-hydrogen and the molecular tests. This study suggests that (i) the distribution of the LP polymorphism is not uniform across the country, (ii) genotyping - 13910C>T is a good diagnostic tool for lactase status in the Portuguese population and (iii) self-reported gastrointestinal complaints are not good predictors of the LP status, implying that a significant part of those complaints may not be related to hypolactasia.


Identification and localization of proteins encoded by two DIF-inducible genes of Dictyostelium.
We show that pDd56 and pDd63, two related DIF-inducible genes of Dictyostelium, respectively encode the ST310 and ST430 polypeptides identified by Morrissey, Devine, and Loomis (1984, Dev. Biol. 103, 414-424). We localize the two proteins by immunoelectron microscopy to the extracellular matrix surrounding the stalk cells and the stalk tube. Coupled with their predicted amino acid sequence and biochemical properties, this suggests that they are structural proteins of the stalk.


Lateral asymmetry of the scalp distribution of somatosensory evoked potential amplitude.
Somatosensory potentials evoked by brief low-intensity electrical pulses delivered separately to the left and right index fingers were recorded from the scalp over the posterior half of the contralateral hemisphere in normal human subjects. In two experiments it was found that the scalp areas enclosed by 75 and 90% of maximum-amplitude isopotential contour lines of the early cortically generated complexes were more restricted over the left hemisphere. This asymmetrical evoked potential distribution supports the proposal by Semmes from her observations of brain-damaged patients that elementary somatosensory representation is focal in the left hemisphere and diffuse in the right.


A Swedish version of the Women's Health Questionnaire. A measure of postmenopausal complaints.
We wanted to provide details on the psychometric documentation of the Swedish version of the Women's Health Questionnaire (WHQ), a patient based measure of postmenopausal complaints. The results of two clinical trials in Sweden in which the WHQ had been used as one out of several measurement tools were used to document the reliability, the validity and the responsiveness to change of the WHQ. More than 350 women suffering from postmenopausal complaints were included in the two trials. A factor analysis, using the baseline values of all women in each study, showed that the Swedish version of the WHQ was very close to the English original. The internal consistency reliability was excellent. The clinical validity was confirmed by a significant correlation between change in E2 levels and change in the WHQ during estrogen therapy. A high construct validity was established by the agreement between the WHQ and other quality of life scales. For use in clinical trials the WHQ was sensitive to treatment-induced changes, and added important information to the clinical effect variables.


A hydrophobic ligand-binding protein of the Taenia solium metacestode mediates uptake of the host lipid: implication for the maintenance of parasitic cellular homeostasis.
Parasitic organisms are incapable of de novo fatty acid synthesis due to a down-regulated expression of enzymes involved in the oxygen-dependent pathway. We investigated the uptake of host lipids by a 150-kDa hydrophobic ligand-binding protein (HLBP) of Taenia solium metacestode, an agent causative of neurocysticercosis. The protein was found to be a hetero-oligomeric complex consisting of multiple subunits (M(r) 7, 10, and 15 kDa within pH 8.0-9.7), which may originate from four unique genes of 7- and 10-kDa gene families with 2-3 polymorphic alleles/paralogs. The 15-kDa protein represented glycosylated forms of the 10-kDa. With high binding affinity to lipid analogs, these subunits evidenced high-level sequence identity with other cestode HLBPs and form a novel clade associated with excretory-secretory type HLBP. In vitro experiments with viable worms suggested that the excreted 150-kDa protein might bind to lipids, and participate in the translocation of host lipids across the syncytial membrane. This process was substantially inhibited by the specific anti-150 kDa antibodies. The protein was localized in the parasite syncytium and in the lipid droplets within host granuloma wall, where significant lipase activity was expressed. HLBP-mediated uptake of the host lipid may be critical for the parasite survival and thus could be targeted by chemotherapeutics and/or vaccine.


A rare case of multimetastatic cardiac angiosarcoma.
Cardiac malignant tumors are rare entities with nonspecific clinical presentation and poor prognosis. Here, we report a case of about a 30-year-old man who was admitted for right thoracic pain. Imaging indicated a cardiac malignant tumor, and pathology confirmed the diagnosis. Our case highlights the value of multimodal imaging in the differential diagnosis of a cardiac mass.


[Cytogenetic examination of amniotic fluid specimens in the 2d trimester of pregnancy (personal experience 1981-1989)].
The authors analyze a group of pregnant women examined at the Chair of Biology and Parasitology of the Medical Faculty J. A. Komensky's University between 1981 and the end of August 1989. During this period they cultivated cells from 1755 specimens of amniotic fluid. In the article they evaluate the detection rate of pathological conditions during this period.


Type C retrovirus activation and possible functions in the normal and tumor-bearing host.
The pathological consequences of tumor virus infection, transformation, and tumor development in certain experimental animals is a well-established and accepted fact. More recently, it has been suggested that these viruses may also have a physiological function participating in such processes as cellular differentiation, immune recognition, and embryogenesis. This paper delineates the current information giving some credence to physiological function for type C viruses.


Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.
A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.


Dried Plum's Polyphenolic Compounds and Carbohydrates Contribute to Its Osteoprotective Effects and Exhibit Prebiotic Activity in Estrogen Deficient C57BL/6 Mice.
Evidence of dried plum's benefits on bone continues to emerge. This study investigated the contribution of the fruit's polyphenol (PP) and carbohydrate (CHO) components on a bone model of postmenopausal osteoporosis to explore their prebiotic activity. Osteopenic ovariectomized mice were fed diets supplemented with dried plum, a crude extract of dried plum's polyphenolic compounds, or the PP or CHO fraction of the crude extract. The effects of treatments on the bone phenotype were assessed at 5 and 10 weeks as well as the prebiotic activity of the different components of dried plum. Both the CHO and PP fractions of the extract contributed to the effects on bone with the CHO suppressing bone formation and resorption, and the PP temporally down-regulating formation. The PP and CHO components also altered the gut microbiota and cecal short chain fatty acids. These findings demonstrate that the CHO as well as the PP components of dried plum have potential prebiotic activity, but they have differential roles in mediating the alterations in bone formation and resorption that protect bone in estrogen deficiency.


Underwater endoscopic mucosal resection of a follicular lymphoma: A case report.
Endoscopic resection of a follicular lymphoma (FL) presenting as a gastric subepithelial tumor (SET), along with periodic follow up can be a treatment option because gastrointestinal FL cells tend to reside in the primary site, which may explain its indolent nature. A gastric lesion was found incidentally during a screening endoscopy in 73-year-old woman without any gastrointestinal symptom. The patient was diagnosed with a grade I FL that was 1.4 cm large, at the greater curvature of lower-body. We performed underwater endoscopic mucosal resection (UW-EMR), and there was no serious complication, such as bleeding and perforation. Complete en bloc resection was achieved with UW-EMR. Follow-up endoscopic biopsy after 3 months revealed no residual tumor on the resection site. UW-EMR may be a simple and safe resection method for gastric FL without metastases, that measure >1 cm.


Nutrition management of insulin-dependent diabetes mellitus in adults: review by the diabetes care and education dietetic practice group.
Insulin-dependent diabetes mellitus (IDDM) is a chronic disease in which insulin production from the pancreas is diminished or absent. Insulin-dependent diabetes mellitus is most often diagnosed in childhood, but it also occurs in adults. Treatment requires the use of exogenous insulin coordinated with food intake and physical activity. Management goals for IDDM are to attain metabolic control of glucose and lipid levels and to prevent or delay the onset of medical complications associated with diabetes. Because the type and amount of food consumed directly affect blood glucose levels, meal and snack planning, along with an appropriate insulin regimen and physical activity program, is necessary to achieve management goals. Nutrition assessment, initial education, implementation of a meal plan, and ongoing nutrition education and counseling are part of the process of nutrition management of diabetes. The registered dietitian who has a working knowledge of nutrition and diabetes management serves as an integral part of the diabetes health care team.


Chiral separation of raltitrexed by cyclodextrin-modified micellar electrokinetic chromatography.
A rapid and effective method was developed for the chiral separation of raltitrexed (RD) enantiomers by carboxymethyl-beta-cyclodextrin (CM-beta-CD)-modified micellar electrokinetic chromatography (MEKC). Optimization of conditions including the type and concentration of the chiral selector, concentration of sodium dodecyl sulfate (SDS), pH and concentration of the background electrolyte (BGE), capillary temperature, and applied voltage was investigated. The enantiomers of raltitrexed could be separated with satisfactory resolution and linear response by using 75 mM Tris-phosphate at pH 8.0 containing 30 mM SDS and 8 mM CM-beta-CD as buffer system. Furthermore, the usefulness of this method was demonstrated in a purity test of a real synthetic drug sample.


Telomerase in the human organism.
The intent of this review is to describe what is known and unknown about telomerase in somatic cells of the human organism. First, we consider the telomerase enzyme. Human telomerase ribonucleoproteins undergo at least three stages of cellular biogenesis: accumulation, catalytic activation and recruitment to the telomere. Next, we describe the patterns of telomerase regulation in the human soma. Telomerase activation in some cell types appears to offset proliferation-dependent telomere shortening, delaying but not defeating the inherent mitotic clock. Finally, we elaborate the connection between telomerase misregulation and human disease, in the contexts of inappropriate telomerase activation and telomerase deficiency. We discuss how our current perspectives on telomerase function could be applied to improving human health.


Having a personal weight goal that mismatches healthy weight recommendations increases the likelihood of using unhealthy behaviors among a representative population-based sample of adolescents.
Free living populations adopt practices designed to maintain or influence their weight. These practices include at least two components: a personal weight goal and use of a variety of behaviors to reach this personal weight goal. Personal weight goals can either concur (match) or not concur (mismatch) with recommendations that a health professional might stipulate for achieving a healthy weight status. The variety of behaviors used to achieve a personal weight goal can be thought of as inherently healthy, unhealthy, or disordered. We examined associations between matched vs. mismatched personal weight goals and the frequency of use of different types of weight-related behaviors among adolescents. Measures included whether or not personal weight goals matched or mismatched aims that should be pursued given current weight status and self-reported frequency of use of behaviors from a representative population-based sample of adolescents (n=2, 346, 51% female; 93.3% complete data). Sex-specific multilevel logistic and ordinal regression analyses showed that pursuing a mismatched personal weight goal increases the likelihood of using unhealthy behaviors across sexes. This association is however not significant for healthy and disordered behaviors. We conclude that there is an association between pursuing a mismatched personal weight goal and the use of unhealthy behaviors but not with healthy or disordered behaviors.


Malignant hyperthermia and althesin.
General anaesthesia with Althesin was administered on two occasions to a patient who was identified as susceptible to malignant hyperthermia, in whom there was identified familial subclinical myopathy and once in another patient suffering from arthrogryposis multiplex congenita with a history of fever associated with two previous anaesthetics. In the first patient halothane was administered by accident in association with the Althesin, but no hyperpyrexia occurred. In the second instance nitrous oxide-oxygen and halothane were associated purposely with Althesin. In none of these cases was there any rise in temperature, muscle rigor or elevation of the serum CPK level. This experience corroborates the experimental evidence of Hall, et al.10 and Harrison, who reported that Althesin prevented the onset of hyperthermia, and the clinical reports of Page and Judelman. Althesin can be assumed to be an effective anaesthetic for malignant hyperthermia susceptible patients.