MR-Based Radiomics for Differential Diagnosis between Cystic Pituitary Adenoma and Rathke Cleft Cyst.
It is often tricky to differentiate cystic pituitary adenoma from Rathke cleft cyst with visual inspection because of similar MRI presentations between them. We aimed to design an MR-based radiomics model for improving differential diagnosis between them. Conventional diagnostic MRI data (T1-,T2-, and postcontrast T1-weighted MR images) were obtained from 215 pathologically confirmed patients (105 cases with cystic pituitary adenoma and the other 110 cases with Rathke cleft cyst) and were divided into training (n = 172) and test sets (n = 43). MRI radiomics features were extracted from the imaging data, and semantic imaging features (n = 15) were visually estimated by two radiologists. Four classifiers were used to construct radiomics models through 5-fold crossvalidation after feature selection with least absolute shrinkage and selection operator. An integrated model by combining radiomics and semantic features was further constructed. The diagnostic performance was validated in the test set. Receiver operating characteristic curve was used to evaluate and compare the performance of the models at the background of diagnostic performance by radiologist. In test set, the combined radiomics and semantic model using ANN classifier obtained the best classification performance with an AUC of 0.848 (95% CI: 0.750-0.946), accuracy of 76.7% (95% CI: 64.1-89.4%), sensitivity of 73.9% (95% CI: 56.0-91.9%), and specificity of 80.0% (95% CI: 62.5-97.5%) and performed better than multiparametric model (AUC = 0.792, 95% CI: 0.674-0.910) or semantic model (AUC = 0.823, 95% CI: 0.705-0.941). The two radiologists had an accuracy of 69.8% and 74.4%, respectively, sensitivity of 69.6% and 73.9%, and specificity of 70.0% and 75.0%. The MR-based radiomics model had technical feasibility and good diagnostic performance in the differential diagnosis between cystic pituitary adenoma and Rathke cleft cyst.


The yeast transcription factor Crz1 is activated by light in a Ca2+/calcineurin-dependent and PKA-independent manner.
Light in the visible range can be stressful to non-photosynthetic organisms. The yeast Saccharomyces cerevisiae has earlier been reported to respond to blue light via activation of the stress-regulated transcription factor Msn2p. Environmental changes also induce activation of calcineurin, a Ca(2+)/calmodulin dependent phosphatase, which in turn controls gene transcription by dephosphorylating the transcription factor Crz1p. We investigated the connection between cellular stress caused by blue light and Ca(2+) signalling in yeast by monitoring the nuclear localization dynamics of Crz1p, Msn2p and Msn4p. The three proteins exhibit distinctly different stress responses in relation to light exposure. Msn2p, and to a lesser degree Msn4p, oscillate rapidly between the nucleus and the cytoplasm in an apparently stochastic fashion. Crz1p, in contrast, displays a rapid and permanent nuclear localization induced by illumination, which triggers Crz1p-dependent transcription of its target gene CMK2. Moreover, increased extracellular Ca(2+) levels stimulates the light-induced responses of all three transcription factors, e.g. Crz1p localizes much quicker to the nucleus and a larger fraction of cells exhibits permanent Msn2p nuclear localization at higher Ca(2+) concentration. Studies in mutants lacking Ca(2+) transporters indicate that influx of extracellular Ca(2+) is crucial for the initial stages of light-induced Crz1p nuclear localization, while mobilization of intracellular Ca(2+) stores appears necessary for a sustained response. Importantly, we found that Crz1p nuclear localization is dependent on calcineurin and the carrier protein Nmd5p, while not being affected by increased protein kinase A activity (PKA), which strongly inhibits light-induced nuclear localization of Msn2/4p. We conclude that the two central signalling pathways, cAMP-PKA-Msn2/4 and Ca(2+)-calcineurin-Crz1, are both activated by blue light illumination.


Food Technology Neophobia Scales in cross-national context: Consumers' acceptance of food technologies between Chinese and New Zealand.
An increasing number of novel food technologies have been developed to meet consumers' growing desire for safe and high-quality foods. However, consumers can be cautious of novel food technologies, and their acceptance cannot be guaranteed. Food Technology Neophobia Scales (FTNS) have been proven to be an effective tool to predict consumers' behavior toward novel food technologies in a range of individual countries, but not for cross-national contexts. To fill the gap, this study designed a survey involving 604 Chinese and 614 New Zealand respondents, investigating the influence of consumers' food technology neophobia (FTN) on their acceptance of food technologies. Chinese respondents' FTNS score (50.62) was lower than that of New Zealand respondents (55.02), which was in line with the finding that Chinese respondents' acceptance of all tested food technologies was higher than New Zealand respondents (0.34-0.86 in a Likert-7 scale). Chinese respondents' acceptance was determined by their perception of benefits, whereas New Zealand respondents were influenced by their perception of both benefits and risks. The findings conclude that FTNS is a valid tool to reflect consumers' acceptance of novel food technologies in cross-national contexts, although the influence of FTN varies among consumers from different countries. PRACTICAL APPLICATION: China has the largest food market, and New Zealand is a leading food exporter. Understanding their consumers' acceptance of and attitudes toward food technologies will help food companies implement appropriate strategies in developing and using novel technologies. Because FTNS first was constructed in 2008, it has been applied in Australia, Italy, Canada, Finland, Korea, China, Chile, Brazil, and Uganda; the findings of this study will allow these individual studies on FTNS to better connect, help food companies predict consumer acceptance of food technologies in the global market, and help them identify early adopters of novel food technologies in new food markets.


Activation of phosphoinositide catabolism and DNA synthesis in vascular smooth muscle cells by LDL and positively charged proteins: evidence that effects of LDL are not specifically dependent on the polycationic nature of apo B.
We have investigated whether the polycationic structure of apo B is an important determinant for the recognition of low density lipoprotein (LDL) by putative signalling-coupled/growth receptor(s). Using cultures of human vascular smooth muscle cells (VSMC), the effects of LDL on phosphoinositide (PI) catabolism and DNA synthesis have been compared with those of a variety of proteins which, like apo B, possess a strong positive charge. Using myo-[2-3H]-inositol-prelabelled VSMC, the polycationic proteins protamine and histones II-S, III-S, V-S and VII-S, but not low-molecular weight polyamines (putrescine and spermine), were found to stimulate PI catabolism in a dose- and time-dependent manner. In contrast to LDL which induced rapid, transient increases in inositol tris- and bis-phosphates and a delayed sustained increase in inositol monophosphate, the PI response of VSMC to polycationic proteins was characterized by a potent, sustained increase in inositol bisphosphate and the absence of an inositol trisphosphate transient. Heparin inhibited the PI catabolic response of VSMC to histones and protamine but was without effect on LDL-stimulated PI catabolism. Like LDL, polycationic proteins also stimulated DNA synthesis in VSMC (incorporation of [3H]-thymidine). The data indicate that signalling/growth effects of LDL and positively charged protein occur via distinct mechanisms and that the effects of LDL do not primarily depend upon the polycationic properties of apo B.


Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance.
Glucocorticoid resistance due to mutations in the gene for the glucocorticoid receptor has been suggested to be more common than is thought at present, owing to the relative mildness of its symptoms and the difficulty of its diagnosis. To investigate the prevalence of mutations in the glucocorticoid receptor gene responsible for relative insensitivity to glucocorticoids, we carried out polymerase chain reaction/single-strand conformation analysis of the glucocorticoid receptor gene in a group of 20, otherwise healthy, persons with a reduced response in a dexamethasone suppression test and in 20 controls. We did not find mutations or polymorphisms associated with a reduced sensitivity to glucocorticoids. However, we identified five novel polymorphisms in the gene for the human glucocorticoid receptor, which may be useful in analyzing whether loss of (part of) the glucocorticoid receptor gene plays a role in glucocorticoid-resistant malignancies. Although relative resistance to glucocorticoids seems to be rather frequent in otherwise healthy persons, it is not usually associated with mutations or polymorphisms in the glucocorticoid receptor gene.


The association between skeletal maturation and adrenal androgen levels in obese children and adolescents.
This study aimed to investigate the association between skeletal maturation and adrenal androgen levels in obese children and adolescents. Fifty-three children and adolescents (aged 7-15 years) diagnosed as obese or overweight were investigated. Anthropometric measurements, bone age (BA) determination, serum biochemical analyses, and hormonal measurements were performed. The difference between BA and chronological age (BA-CA, dBACA) was calculated and used to represent the degree of advanced skeletal maturation. Thirty-one subjects were classified into the obese group and 22 subjects into the overweight group. Insulin resistance as calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in the obese group than in the overweight group (4.03±2.20 vs. 2.86±1.11, P=0.026). The skeletal maturation of the obese group was advanced, but the dBACA did not differ between the obese and overweight groups statistically (1.43±1.35 vs. 0.91±1.15, P=0.141). Serum dehydroepiandrosterone sulfate (DHEA-S) levels were significantly higher in subjects with dBACA>1 compared to those with dBACA≤1 (104.3±62.2 vs. 59.6±61.0, P=0.014). Correlation analyses demonstrated that dBACA was positively correlated with body mass index standard deviation scores (r=0.35, P=0.010), fasting insulin (r=0.36, P=0.009), HOMA-IR (r=0.30, P=0.031), and insulin-like growth factor-binding protein-3 (r=0.331, P=0.028). In multivariate linear regression analysis, HOMA-IR (P=0.026) and serum DHEA-S (P=0.032) were positively correlated with the degree of advanced skeletal maturation. Advanced skeletal maturation is associated with increased insulin resistance and elevated DHEA-S levels in obese children and adolescents.


The anti-protozoan drug nifurtimox preferentially inhibits clonogenic tumor cells under hypoxic conditions.
Tumor hypoxia is an independent prognostic indicator of tumor malignant progression and poor patient survival. Therefore, eradication of hypoxic tumor cells is of paramount importance for successful disease control. In this study, we have made a new discovery that nifurtimox, a clinically approved drug to treat Chagas disease caused by the parasitic protozoan trypanosomes, can function as a hypoxia-activated cytotoxin. We have found that nifurtimox preferentially kill clonogenic tumor cells especially under the hypoxic conditions of ≤0.1% O2. Mechanistically, nifurtimox becomes activated after tumor cells enter into a fully hypoxic state, as shown by the stabilization of the Hypoxia-Inducible Factor 1α (HIF-1α). Nifurtimox specifically induces the formation of 53BP1 foci, a hallmark of DNA double-stranded breaks, in hypoxic tumor cells. Hypoxia-dependent activation of nifurtimox involves P450 (cytochrome) oxidoreductase. The anti-protozoan drug nifurtimox holds promise as a new hypoxia-activated cytotoxin with the potential to preferentially eliminates severely hypoxic tumor cells.


The Doppler flow wire in acute myocardial infarction.
Contemporary mechanical reperfusion therapy for acute myocardial infarction is aimed at early and complete restoration of myocardial perfusion. However, successful restoration of epicardial blood flow does not guarantee restoration of flow at the myocardial tissue level. The incidence of inadequate myocardial reperfusion after primary percutaneous coronary intervention (PCI) varies from 15-70%, based upon the diagnostic modality used. The Doppler flow guidewire can be used immediately after primary PCI to identify patients with apparently restored epicardial flow but impaired reperfusion at the myocardial microcirculatory and tissue level. Characteristic findings by intracoronary Doppler flow velocity measurements such as a reduced coronary flow velocity reserve, and, in particular, systolic flow velocity reversal and a short diastolic deceleration time are associated with the presence of microvascular obstruction. Detection of microvascular obstruction by the Doppler flow wire directly after primary PCI can identify patients who may benefit from adjunctive therapy after primary PCI.


State Policies That Treat Prenatal Substance Use As Child Abuse Or Neglect Fail To Achieve Their Intended Goals.
The US is experiencing a complex substance abuse crisis. Not only has opioid overdose mortality increased sharply, by 400 percent from 1999 to 2017, but opioid use during pregnancy contributed to a 300 percent increase in neonatal abstinence syndrome (NAS)-a postnatal drug withdrawal syndrome in infants that is identified at birth-from 1999 to 2013. States have taken myriad policy approaches to combat the opioid crisis and its consequences, and some states have adopted punitive policies toward prenatal substance use. Using data for the period 2000-14 from the State Inpatient Databases of the Healthcare Cost and Utilization Project, this study examined the effect of state-level policies that treat prenatal substance use as child abuse or neglect on the incidence of NAS, maternal narcotic exposure, and substance use treatment admissions for pregnant women. We employed a difference-in-differences approach to estimate the effect of these policies. We did not find evidence that punitive prenatal substance use policies reduced NAS or maternal narcotic exposure at birth; however, we did find evidence that these policies may deter women from seeking substance use treatment during pregnancy. Policy makers might reconsider the efficacy of punitive policies and investigate increasing access to and reducing the cost of treatment for pregnant and parenting women.


Chikungunya outbreaks caused by African genotype, India.
Chikungunya fever is reported in India after 32 years. Immunoglobulin M antibodies and virus isolation confirmed the cause. Phylogenic analysis based on partial sequences of NS4 and E1 genes showed that all earlier isolates (1963-1973) were Asian genotype, whereas the current and Yawat (2000) isolates were African genotype.


Adherence to generic v. brand antidepressant treatment and the key role of health system factors.
One of the major challenges with antidepressant (AD) use is poor adherence and early treatment discontinuation. In addition to socio-demographic and clinical variables, treatment discontinuation may also be related to the capacity of the health system to assure and maintain continuity and intensity of care. Among health system factors that may interfere with adherence to pharmacological treatment, use of generic drugs may play a key role. It has been argued that, although the lower cost of generics may favour persistence on treatment, a widespread a priori scepticism about their effectiveness and safety by doctors and patients may have an opposite effect. This compelling research question has recently been addressed by an observational cohort study that involved 16 778 Medicare fee-for-service beneficiaries who received a new depression diagnosis and initiated generic v. brand AD therapy. The study found that generic initiation was associated with improved adherence. The benefits resulted from the lower out-of-pocket cost associated with generic ADs. In this commentary, we discuss the main findings of this study in view of its methodological strengths and limitations, and we suggest implications for policy.


[A case of papillitis revealing primary syphilis].
Syphilitic ocular manifestations are polymorphous and usually occur during the secondary or tertiary stage of syphilis. We report a case of primary syphilis revealed by papillitis. A 22 year old man presented with blurred vision in the left eye and decreased visual acuity. Fundus examination and fluorescein angiography revealed a papilledema in the left eye and chorioretinitis in the right one. Clinical examination revealed a painless ulceration of the chin. Blood tests were positive for syphilis (positive reaction to the VDRL test and TPHA titer at 1/640) but negative for HIV. After penicillin therapy, the ocular manifestations resolved. Papillitis is a relatively rare ocular manifestation of syphilis. Our case is original because papillitis was the presenting manifestation of the disease and that it was concomitant with the primary chancre. Systematic screening for syphilis should be performed in unexplained ocular inflammation.


Molecular diversity of Uzbekistan's fishes assessed with DNA barcoding.
Uzbekistan is one of two doubly landlocked countries in the world, where all rivers are endorheic basins. Although fish diversity is relatively poor in Uzbekistan, the fish fauna of the region has not yet been fully studied. The aim of this study was to establish a reliable barcoding reference database for fish in Uzbekistan. A total of 666 specimens, belonging to 59 species within 39 genera, 17 families, and 9 orders, were subjected to polymerase chain reaction amplification in the barcode region and sequenced. The length of the 666 barcodes was 682 bp. The average K2P distances within species, genera, and families were 0.22%, 6.33%, and 16.46%, respectively. The average interspecific distance was approximately 28.8 times higher than the mean intraspecific distance. The Barcode Index Number (BIN) discordance report showed that 666 specimens represented 55 BINs, of which five were singletons, 45 were taxonomically concordant, and five were taxonomically discordant. The barcode gap analysis demonstrated that 89.3% of the fish species examined could be discriminated by DNA barcoding. These results provide new insights into fish diversity in the inland waters of Uzbekistan and can provide a basis for the development of further studies on fish fauna.


Frequency and Significance of Hepatic Involvement in New-Onset Giant Cell Arteritis: A Study of 514 Patients.
Abnormalities of liver function in giant cell arteritis (GCA) have long been described1 and are present at the acute phase of the disease in 30% to 60% of cases.2-4 Hepatic involvement is mostly anicteric cholestasis (eg, elevated alkaline phosphatase [ALP] and gamma-glutamyl transferase [GGT]), and, more rarely, cytolytic hepatitis (eg, elevated aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]).


Characterization of the Complete Nucleotide Sequences of IncA/C2 Plasmids Carrying In809-Like Integrons from Enterobacteriaceae Isolates of Wildlife Origin.
A total of 18 Enterobacteriaceae (17 from gulls and 1 from a clinical sample) collected from Australia, carrying IncA/C plasmids with the IMP-encoding In809-like integrons, were studied. Seven plasmids, being representatives of different origins, plasmid sizes, replicon combinations, and resistance genes, were completely sequenced. Plasmid pEc158, identified in a clinical Escherichia coli ST752 isolate, showed extensive similarity to type 2 IncA/C2 plasmids. pEc158 carried none of the blaCMY-2-like region or ARI-B and ARI-A regions, while it contained a hybrid transposon structure. The six remaining plasmids, which were of wildlife origin, were highly similar to each other and probably were fusion derivatives of type 1 and type 2 A/C2 plasmids. The latter plasmids contained an ARI-B region and hybrid transposon structures. In all plasmids, hybrid transposon structures containing In809-like integrons were inserted 3,434 bp downstream of the rhs2 start codon. In all cases, the one outermost 38-bp inverted repeat (IR) of the transposon was associated with the Tn1696 tnp module, while the other outermost 38-bp IR of the transposon was associated with either a Tn6317-like module or a Tn21 mer module. However, the internal structure of the transposon and the resistance genes were different in each plasmid. These findings indicated that, for the specific periods of time and settings, different IncA/C2 plasmid types carrying In809-like elements circulated among isolates of wildlife and clinical origins. Additionally, they provided the basis for speculations regarding the reshuffling of IncA/C2 plasmids with In809-like integrons and confirmed the rapid evolution of IncA/C2 plasmid lineages.


Meteorological factors and respiratory syncytial virus seasonality in subtropical Australia.
Evidence is emerging regarding the influence of meteorological factors on seasonal respiratory syncytial virus outbreaks. Data however, are limited for subtropical regions, especially in the southern hemisphere. We examined whether meteorological data (daily minimum and maximum temperatures, rainfall, relative humidity, dew point, daily global solar exposure) and tourist numbers were associated with the incidence of RSV in children aged <5 years for the Gold Coast region of South-East Queensland, Australia (latitude 28.0°S). RSV cases between 1 July 2007 and 30 June 2016 were identified from the Pathology Queensland Gold Coast Laboratory database. Time-series methods were used to identify seasonal patterns. RSV activity peaked in mid-to-late autumn (April-May), tapering in winter (June-August). While most meteorological variables measured were associated with RSV incidence, rainfall (ρ = 0.40, 95% confidence interval (CI) 0.32-0.48) and humidity (ρ = 0.38, 95% CI 0.29-0.46) 8 weeks earlier had the nearest temporal relationship. Tourist numbers were not correlated with RSV activity. Identifying meteorological conditions associated with seasonal RSV epidemics can improve understanding of virus transmission and assist planning for their impact upon the health sector, including timing of passive RSV immunoprophylaxis for high-risk infants and future public health interventions, such as maternal immunisation with RSV vaccines.


Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells.
The role of the new Myocbacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous meningitis (TBM) has not yet been fully assessed. Here, we conducted a prospective, blinded, observational study to evaluate the diagnostic accuracy of this assay, compared with the conventional tests, for diagnosing TBM. All adult patients with suspected TBM were enrolled at a tertiary care hospital (Seoul, South Korea) during a 12-month period. ELISPOT assays were performed on peripheral mononuclear cells and mononuclear cells from cerebrospinal fluid (CSF). Eighty-nine patients with suspected TBM were enrolled. Of these, 31 (35%) were classified as having TBM (10 confirmed, 6 highly probable, and 15 probable cases), and 55 (62%) were classified as not having active tuberculosis. The remaining 3 (3%) with possible TBM were excluded from the final analysis. The sensitivities and specificities, respectively, of the tested methods for diagnosing TBM were as follows: CSF adenosine deaminase level >5.8 U/L, 89% (95% confidence interval [CI], 69%-98%) and 73% (95% CI, 58%-84%); peripheral mononuclear cells ELISPOT, 71% (95% CI, 51%-86%) and 57% (95% CI, 42%-70%); and CSF mononuclear cells ELISPOT assay, 59% (95% CI, 36%-79%) and 89% (95% CI, 72%-98%). The combined sensitivity of an adenosine deaminase level >5.8 U/L or a positive peripheral mononuclear cells ELISPOT assay result was 94% (95% CI, 79%-99%), conferring a negative likelihood ratio of 0.14 (95% CI, 0.03-0.55) when both test results were negative. ELISPOT assays using peripheral mononuclear cells and CSF mononuclear cells are useful adjuncts to the current tests for diagnosing TBM, particularly when used in combination with the assessment of adenosine deaminase level in CSF.


Multifractal clustering in compressible flows.
A quantitative relationship is found between the multifractal properties of the asymptotic mass distribution in a random dissipative system and the long-time fluctuations of the local stretching rates of the dynamics. It captures analytically the fine aspects of the strongly intermittent clustering of dynamical trajectories. Applied to a simple compressible hydrodynamical model with known stretching-rate statistics, the relation produces a nontrivial spectrum of multifractal dimensions that is confirmed numerically.


Effect of Increasing Amounts of Ammonium Nitrogen Induced by Consecutive Mixture of Poultry Manure and Cattle Slurry on the Microbial Community during Thermophilic Anaerobic Digestion.
Thermophilic anaerobic digestion (TAD) is characterized by higher biogas production rates as a result of assumedly faster microbial metabolic conversion rates compared to mesophilic AD. It was hypothesized that the thermophilic microbiome with its lower diversity than the mesophilic one is more susceptible to disturbances introduced by alterations in the operating factors, as an example, the supply of nitrogen-rich feedstock such as poultry manure (PM). Laboratory scaled TAD experiments using cattle slurry and increasing amounts of PM were carried out to investigate the (in-) stability of the process performance caused by the accumulation of ammonium and ammonia with special emphasis on the microbial community structure and its dynamic variation. The results revealed that the moderate PM addition, i.e., 25% (vol/vol based on volatile substances) PM, resulted in a reorganization of the microbial community structure which was still working sufficiently. With 50% PM application, the microbial community was further stepwise re-organized and was able to compensate for the high cytotoxic ammonia contents only for a short time resulting in consequent process disturbance and final process failure. This study demonstrated the ability of the acclimated thermophilic microbial community to tolerate a certain amount of nitrogen-rich substrate.


Anatomical features of plantar fasciitis in various age cohorts: Based on magnetic resonance imaging.
Due to the lack of further studies on the influence of age factors on plantar fasciitis, this study evaluates the characteristic observation points of magnetic resonance imaging in various age cohorts of patients with plantar fasciitis to help diagnosis. A retrospective analysis of 160 cases of plantar fasciitis patients and normal subjects (who have the disease unrelated to plantar fasciitis) who have undergone an MRI examination in our institution. The two groups were separately divided into young adult subjects (36 to 44 years old), middle age adult subjects (45 to 59 years old), and older adult subjects (60 to 79 years old). Data was gathered regarding plantar fascia thickness, the coronal length of the plantar fascia at the calcaneal origin, the signal intensity of plantar fascia and surrounding structures, and the presence or absence of plantar calcaneal spurs, all of which were assessed objectively by the investigators. There were statistical differences in the thickness of plantar fascia between two groups of three age cohorts (Older adult patients: 0.59 ± 0.09 cm; Middle age adult patients: 0.49 ± 0.09 cm; Young adult patients: 0.47 ± 0.05 cm) (all p < 0.001). In addition, there were also statistical differences in the high signal intensity changes of the plantar fascia and surrounding soft tissues between two groups of three age cohorts (all p < 0.001). In older adult plantar fasciitis patients, with regard to plantar calcaneal spur discovery, there was a statistical difference between the two groups (Chi-square = 12.799. df = 1. p < 0.001). In plantar fasciitis cases where a diagnosis is difficult, abnormalities in the soft tissue surrounding the plantar fascia in patients of low age are noteworthy. In older adult patients, the discovery of plantar calcaneal spurs with abnormal thickening of plantar fascia deserves attention, and abnormal MRI findings are more manifest. But the final diagnosis should be based on the medical history. Level 3.


What factors affect paramedics' involvement of people with dementia in decisions about their care? A qualitative study.
Paramedics are frequently called to people with dementia, but decision making can be challenging due to lack of information or difficulties in assessment. Best-practice dementia care should be holistic and involve people with dementia in decisions as far as possible. To explore how paramedics make decisions when attending people with dementia, with a particular focus on factors that impact on how, and to what degree, paramedics involve people with dementia in these decisions. A generic qualitative research approach was used. Data were collected through semi-structured individual interviews with seven paramedics. The interviews were recorded and transcribed verbatim and subsequently analysed using thematic analysis. Four themes were identified that all touched on challenges to delivering person-centred care. Themes identified were: 1) paramedics' differing approaches to assessing capacity and making best interest decisions; 2) communication and developing a rapport; 3) interconnections with others important to the person with dementia; and 4) the impact of paramedics' values and attitudes. The involvement of people with dementia is sometimes limited by medical, social or clinician-dependent factors. This study highlights how paramedics' values and communication skills influence their interactions with people with dementia. As the paramedic role evolves, there is an opportunity to embed person-centred care in practice and to ensure that education equips paramedics with the skills and ethical frameworks needed to deliver high quality dementia care.


Pd "Kills Two Birds with One Stone" for the Synthesis of Catalyst: Dual Active Sites of Pd Triggers the Kinetics of O2 Electrocatalysis.
Noble metal-based catalyst, despite their exorbitant cost, are the only successful catalyst for bifunctional oxygen electrocatalysis owing to their capability to drive forward the reaction rate kinetically. Therefore, it is desirable to diminish the noble metal loading without any compromise in the catalyst performance. In this study, the aim to achieve two goals with one action via a single-step route to have ultra-low loading of Pd in the catalyst. The Pd is used as a catalyst for C─C bond formation followed by complexation reactions or vice versa, in conventional Suzuki-Miyaura cross-coupling (SMCC) reaction, which yields a Pd-based porous organic polymer. Interestingly, it is found that dispersed Pd nanocluster (PdNC ) is present together with Pd single atom doped into nanocarbon (Pd-NC) matrix in the catalyst (PdNC /Pd-NC800 ) that obtained after pyrolysis of the porous polymer. The catalyst exhibits remarkable bifunctional activity and durability towards oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Further, it is studied that the in situ attenuated total reflection infrared (ATR-IR) spectroscopy at different electrochemical potentials during ORR and OER to observe the reaction intermediates. The homemade zinc-air battery with the catalyst displayed great performance, establishing the significance of PdNC /Pd-NC800 as a bifunctional oxygen electrocatalyst.


Novel T1 Analysis Method to Address Reduced Measurement Accuracy Due to Irregular Heart Rate Variability in Myocardial T1 Mapping Using Polarity-corrected Inversion Time Preparation.
Polarity-corrected inversion time preparation (PCTIP), a myocardial T1 mapping technique, is expected to reduce measurement underestimation in the modified Look-Locker inversion recover method. However, measurement precision is reduced, especially for heart rate variability. We devised an analysis using a recurrence formula to overcome this problem and showed that it improved the measurement accuracy, especially at high heart rates. Therefore, this study aimed to determine the effect of this analysis on the accuracy and precision of T1 measurements for irregular heart rate variability. A PCTIP scan using a 3T MRI scanner was performed in phantom experiment. We generated the simulated R-waves required for electrocardiogram (ECG)-gated acquisition using a signal generator set to 30 combinations. T1 map was generated using the signal train of the PCTIP images by nonlinear curve fitting using conventional and recurrence formulas. Accuracy against reference T1 and precision of heart rate variability were evaluated. To evaluate the fitting accuracy of both analyses, the relative fitting error was calculated. For the longer T1, the fitting error was larger than the short T1, with the conventional analysis showing 10.1±2.0%. The recurrence formula analysis showed a small fitting error less than 1%, which was consistent for all heart rate variability patterns. In the conventional analysis, the accuracy, especially for longer T1, showed a large underestimation of the measurements and poor linearity. However, in the recurrence formula analysis, the accuracy improved at a long T1, and linearity also improved. The Bland-Altman plot showed that it varied greatly depending on the heart rate variability pattern for the longer T1 in the conventional analysis, whereas the recurrence formula analysis suppressed this variation. T1 analysis of PCTIP using the recurrence formula analysis achieved accurate and precise T1 measurements, even for irregular heart rate variability.


Disorders of attention and vigilance.
Attention deficit hyperactivity disorder has gone through multiple name and criterion changes over the last 10 years. It is still viewed as the most common neurobehavioral disorder in the pediatric age group. Diagnostic criteria, as outlined by the DSM III-R, have, as primary diagnostic features of ADHD, inattention, impulsivity, and hyperactivity. There are no diagnostic tests that will absolutely confirm this disorder. Many questionnaires have been devised to help organize and systematize the evaluation. Vision and hearing screening, physical examination, and the neurologic examination are important to exclude other causes for hyperactivity and impulsivity. There are no routine laboratory or specialized tests that are useful in the diagnosis of ADHD. When psychologic testing is deemed necessary, specific areas to study would include discrepancies in the performance and verbal IQ (possibly indicating further testing needed to rule out learning disabilities) and difficulties in the coding portion of the examination, which might point to attentional difficulties. Educational testing can further complete an evaluation when needed. Management of children with ADHD involves multimodal treatment, including educational, behavioral, and possibly pharmacologic intervention. Pharmacotherapy can be a useful adjunct in treating these children. The psycho-stimulants continue to be the first-line medication in treatment, although investigators have studied other drugs. Once the diagnosis has been made and a child has been placed on the multimodal treatment, he should be carefully followed. This disorder does not disappear at the time of puberty, as once was thought, but instead continues to cause problems through adolescence.


Lack of Transmission of Foot-and-Mouth Disease Virus From Persistently Infected Cattle to Naïve Cattle Under Field Conditions in Vietnam.
Foot-and-mouth disease (FMD), caused by FMD virus (FMDV; Aphthovirus, Picornaviridae), is a highly contagious and economically important disease of cloven-hoofed domestic livestock and wildlife species worldwide. Subsequent to the clinical phase of FMD, a large proportion of FMDV-infected ruminants become persistently infected carriers, defined by detection of FMDV in oropharyngeal fluid (OPF) samples 28 days or more post-infection. The goal of this prospective study was to characterize the FMD carrier state in cattle subsequent to natural infection under typical husbandry practices in Vietnam. Ten persistently infected cattle on eight farms in the Long An province in southern Vietnam were monitored by monthly screening of serum and oropharyngeal fluid samples for 12 months. To assess transmission from FMDV carriers, 16 naïve cattle were intentionally brought into direct contact with the persistently infected animals for 6 months, and were monitored by clinical and laboratory methods. The restricted mean duration of the FMD carrier state was 27.7 months, and the rate of decrease of the proportion of carrier animals was 0.03 per month. There was no evidence of transmission to naïve animals throughout the study period. Additionally, there was no detection of FMDV infection or seroconversion in three calves born to carrier animals during the study. The force of infection for carrier-to-contact transmission was 0 per month, with upper 95% confidence limit of 0.064 per month. Phylogenetic analysis of viral protein 1 (VP1) coding sequences obtained from carriers indicated that all viruses recovered in this study belonged to the O/ME-SA/PanAsia lineage, and grouped phylogenetically with temporally and geographically related viruses. Analysis of within-host evolution of FMDV, based upon full-length open reading frame sequences recovered from consecutive samples from one animal, indicated that most of the non-synonymous changes occurred in Lpro, VP2, and VP3 protein coding regions. This study suggests that the duration of FMDV persistent infection in cattle may be longer than previously recognized, but the risk of transmission is low. Additional novel insights are provided into within-host viral evolution under natural conditions in an endemic setting.


Prospects for the development and use of gram-negative bacterial virulence protein secretion inhibitors for prophylaxis and treatment of infectious diseases.
As the breadth and number of bacterial pathogens exhibiting antibiotic resistance is rapidly increasing, our ability to treat new and re-emerging infectious diseases is being threatened. Therefore, the development of new therapeutic strategies, including drugs acting on new targets, is required. In this review, the feasibility of gram-negative bacterial secretion systems for the development of anti-virulence agents and possible arenas for their utility in therapeutic intervention of gram-negative bacterial infections such as gastroenteritis, nosocomial infections, and venereal diseases are discussed.


The production characteristics of volatile organic compounds and their relation to growth status of Staphylococcus aureus in milk environment.
In our previous research, 3-methyl-butanal and 3-methyl-butanoic acid were identified as representative and specific volatile organic compounds released by Staphylococcus aureus in broth. In this study, we explored the production of the 2 volatiles and their correlation to Staph. aureus growth in milk under different conditions. We found significant correlations between the production of 3-methyl-butanoic acid and cell counts of 5 Staph. aureus strains in sterile milk, and there were no obvious differences for its production among 5 tested strains. The intensities of the 2 volatiles were similar and positively correlated with bacterial counts in cultures at 25°C and 37°C despite delayed production of volatiles at 25°C; however, neither compound could be detected at 4°C. The production of 3-methyl-butanoic acid was strongly correlated with growth of Staph. aureus mixed with Streptococcus agalactiae, Escherichia coli O157:H7, and Shigella flexneri, whereas correlations for 3-methyl-butanal were not statistically significant. Compared with the monoculture of Staph. aureus, in mixed cultures, production of 3-methyl-butanal was decreased and that of 3-methyl-butanoic acid was comparatively higher. In pasteurized and raw milks, production of 3-methyl-butanoic acid was correlated with growth of Staph. aureus, and 3-methyl-butanoic acid could be detected when Staph. aureus populations reached 106 to 107 cfu/mL in pasteurized milk and 105 to 106 cfu/mL in raw milk; the correlations for 3-methyl-butanal were not statistically significant. Our results suggest that 3-methyl-butanoic acid is a more suitable marker for high counts of Staph. aureus in milk, whereas 3-methyl-butanal is a transient metabolite and easily depressed by environmental factors.


Radiofrequency ablation of early-stage invasive breast tumors: an overview.
As the management of breast cancer evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising of the noninvasive ablation techniques is radiofrequency ablation, which uses frictional heating that is caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current. Three pilot studies, including an ongoing study at M.D. Anderson Cancer Center, have demonstrated that radiofrequency ablation is effective for the destruction of small primary breast cancers. The most important factorfor successful radiofrequency ablation is accuracy of the ultrasound evaluation, which is used to estimate tumor size, localize the tumor for treatment, and monitor the progress of the ablation. A study in preparation at M.D. Anderson will determine whether the use of radiofrequency ablation alone for the local treatment of primary breast cancer will result in outcomes equivalent to those obtained with breast conservation therapy.


Negative nucleotide ions as sensitive probes for energy specificity in collision-induced fragmentation in mass spectrometry.
The most commonly used fragmentation methods in tandem mass spectrometry (MS/MS) are collision-induced dissociation (CID) and higher energy collisional dissociation (HCD). While in CID the preselected ions in the trap are resonantly (and m/z exclusively) excited, in HCD the entire m/z range experiences the dissociative acceleration. The different excitation is reflected in different fragment distributions. As a test-bed for particularly pronounced fragmentation specificity, here MS/MS experiments on several 4-mer oligonucleotides were conducted employing both collision methods and the results were thoroughly compared. Oligonucleotides are shown to be sensitive probes to subtle changes, especially in the negative ion mode. A detailed analysis of these differences reveals insight into the dissociation mechanics. The differences are represented in heat-maps, which allow for a direct visual inspection of large amounts of data. In these false colour representations the, sometimes subtle, changes in the individual dissociation product distributions become distinct. Another advantage of these graphic plots can be found in the formation of systematic patterns. These patterns reflect trends in dissociation specificity which allow for the formulation of general rules in fragmentation behavior. Instruments equipped with two different excitation schemes for MS/MS are today widely available. Nonetheless, direct comparisons between the individual results are scarcely made. Such comparative studies bear a powerful analytical potential to elucidate fragmentation reaction mechanism.


Do patients with chronic unilateral orofacial pain due to a temporomandibular disorder show increased attending to somatosensory input at the painful side of the jaw?
Patients with chronic orofacial pain due to temporomandibular disorders (TMD) display alterations in somatosensory processing at the jaw, such as amplified perception of tactile stimuli, but the underlying mechanisms remain unclear. This study investigated one possible explanation, namely hypervigilance, and tested if TMD patients with unilateral pain showed increased attending to somatosensory input at the painful side of the jaw. TMD patients with chronic unilateral orofacial pain (n = 20) and matched healthy volunteers (n = 20) performed a temporal order judgment (TOJ) task indicated which one of two tactile stimuli, presented on each side of the jaw, they had perceived first. TOJ methodology allows examining spatial bias in somatosensory processing speed. Furthermore, after each block of trials, the participants rated the perceived intensity of tactile stimuli separately for both sides of the jaw. Finally, questionnaires assessing pain catastrophizing, fear-avoidance beliefs, and pain vigilance, were completed. TMD patients tended to perceive tactile stimuli at the painful jaw side as occurring earlier in time than stimuli at the non-painful side but this effect did not reach conventional levels of significance (p = .07). In the control group, tactile stimuli were perceived as occurring simultaneously. Secondary analyses indicated that the magnitude of spatial bias in the TMD group is positively associated with the extent of fear-avoidance beliefs. Overall, intensity ratings of tactile stimuli were significantly higher in the TMD group than in the control group, but there was no significant difference between the painful and non-painful jaw side in the TMD patients. The hypothesis that TMD patients with chronic unilateral orofacial pain preferentially attend to somatosensory information at the painful side of the jaw was not statistically supported, although lack of power could not be ruled out as a reason for this. The findings are discussed within recent theories of pain-related attention.


Antagonism of Gluconacetobacter diazotrophicus (a sugarcane endosymbiont) against Xanthomonas albilineans (pathogen) studied in alginate-immobilized sugarcane stalk tissues.
Xanthomonas albilineans, a pathogenic bacterium that produces leaf scald disease of sugarcane, secretes a xanthan-like gum that invades both xylem and phloem of the host. Xanthan production has been verified after experimental infection of stalk segments of healthy plants. Moreover, Gluconacetobacter diazotrophicus is a nitrogen-fixing endosymbiont of sugarcane plants that antagonizes with X. albilineans by impeding the production of the bacterial gum. The physiological basis of this antagonism has been studied using tissues of sugarcane stalks previously inoculated with the endosymbiont, then immobilized in calcium alginate and maintained in a culture medium for Gluconacetobacter. Under these conditions, bacteria infecting immobilized tissues are able to secrete to the medium a lysozyme-like bacteriocin that inhibits the growth of X. albilineans.


[When does post-ictal period start in temporal lobe epilepsy? A quantitative EEG perspective].
In partial seizures, from a clinical point of view or even from electroencephalography characterization of post-ictal period can be difficult. The spectral and complex network analysis could lead to a more accurate definition of its limits, as well as to a great understanding of the seizures. Digital EEG recordings from scalp and foramen oval electrodes were used, 32 seizures, from 15 patients with drug-resistant mesial temporal lobe epilepsy (Engel I). We analyzed numerically: the spectral entropy, the different frequency bands and several variables used to characterize the cortical network, density of links, modularity, cluster coefficient and average path length. Variations of for post-ictal versus pre-ictal periods were quantified. The cortical network density of links increased during the post-ictal period of complex seizures matching with an spectral entropy decrease, mainly due to an increase in Delta band activity. This variables reached extreme values around one minute after seizure end, defined by classical electroencephalography. Our results can be explained by the appearance of an 'ending' mechanism that starts in the ictal period, classically defined, and reach their maximum effect during the post-ictal period. These results could be useful to define the post-ictal period start, as the moment with maximum synchrony, which has a highest density of links and a lowest spectral entropy.


Impact of obstructive ventilatory impairment on intraoperative bleeding during laparoscopic hepatectomy.
An animal model of laparoscopic hepatectomy showed that bleeding from the hepatic vein is influenced by airway pressure. However, there are little research reports on how airway pressure leads to risks in clinical practice. The main objective of this study was to investigate the impact of preoperative forced expiratory volume % in 1 s (FEV1.0%) on intraoperative blood loss in laparoscopic hepatectomy. All patients who underwent pure laparoscopic or open hepatectomy from April 2011 to July 2020 were classified into two groups by preoperative spirometry: those with obstructive ventilatory impairment (obstructive group; FEV1.0% < 70%) and those with normal respiratory function (ormal group; FEV1.0% ≥ 70%). Massive blood loss was defined as 400 mL for laparoscopic hepatectomy. In total, 247 and 445 patients underwent pure laparoscopic and open hepatectomy, respectively. Regarding laparoscopic hepatectomy group, blood loss was significantly greater in the obstructive group (122 vs. 100 mL, P = 0.042). Multivariate analysis revealed that high IWATE criteria which classify the surgical difficulty of laparoscopic hepatectomy (≥ 7, odds ratio (OR): 4.50, P = 0.004) and low preoperative FEV1.0% (< 70%, OR: 2.28, P = 0.043) were independent risk factors for blood loss during laparoscopic hepatectomy. In contrast, FEV1.0% did not affect the blood loss (522 vs. 605 mL, P = 0.113) during open hepatectomy. Obstructive ventilatory impairment (low FEV1.0%) may affect the amount of bleeding during laparoscopic hepatectomy.


Microfilariae in fine needle aspirates: a report of 22 cases.
The objective of the study is to document the value of fine needle aspiration cytology (FNAC) in the diagnosis of filariasis at all possible sites in both exfoliative cytologic material and fine needle aspirates. Both unguided and guided FNACs of all foci were studied over a period of two years between 1999 to 2000. Total 22 cases of filariasis were detected which included subcutaneous swellings(7), breast(3), thyroid(3), lymphnodes(3), effusions(3), cervical scrape(1), eyeball(1), sputum(1) and bronchial washing(1). In none of these cases was filariasis considered a diagnostic possibility. Cytologic smears showed eosinophils in 9 cases, oval ova and embryonated eggs in 2 cases. Microfilariae were associated with other diseases in 13 cases, including 6 cases of malignancy. Significant adherence of inflammatory cells and macrophages to microfilariae was present in 6 of the 22 cases. In endemic areas,filariasis should be considered one of the differential diagnosis of a swelling. Thus demonstration and identification of the parasite in cytologic smears played a significant role in the prompt recognition of the disease and institution of specific treatment, thus obviating the more severe manifestations of lymphatic frilariasis.


Fine tuning the purity of blue emission from polydioctylfluorene by end-capping with electron-deficient moieties.
We propose a simple way to achieve pure blue emission and improved device efficiency via capping poly(9,9-dioctylfluorene) (PFO) with electron-deficient moieties (EDMs, such as oxadiazole (OXD) and triazole (TAZ)), which can induce a minor amount of long conjugating length species (regarded as beta phase) to control extents of energy transfer from amorphous matrix to the beta phase. The device efficiency of PFO end-capped with TAZ is higher than that with para-tert-butyl phenyl (TBP) by a factor of 2 (with CsF/Al as cathode), and its electroluminescent spectrum remains stable and with pure blue emission during cyclic operations (C.I.E. color coordinates x = 0.165, y = 0.076, independent of operating voltage and within the limit for pure blue emission x + y < 0.30). The improvement of device efficiency is dependent on the structure of EDM, such as size and planarity. The deep blue emission is originated from the incomplete energy transfer from amorphous matrix to the beta phase induced by the end-cappers.


Genetically modified α-amylase inhibitor peas are not specifically allergenic in mice.
Weevils can devastate food legumes in developing countries, but genetically modified peas (Pisum sativum), chickpeas and cowpeas expressing the gene for alpha-amylase inhibitor-1 (αAI) from the common bean (Phaseolus vulgaris) are completely protected from weevil destruction. αAI is seed-specific, accumulated at high levels and undergoes post-translational modification as it traverses the seed endomembrane system. This modification was thought to be responsible for the reported allergenicity in mice of the transgenic pea but not the bean. Here, we observed that transgenic αAI peas, chickpeas and cowpeas as well as non-transgenic beans were all allergenic in BALB/c mice. Even consuming non-transgenic peas lacking αAI led to an anti-αAI response due to a cross-reactive response to pea lectin. Our data demonstrate that αAI transgenic peas are not more allergenic than beans or non-transgenic peas in mice. This study illustrates the importance of repeat experiments in independent laboratories and the potential for unexpected cross-reactive allergic responses upon consumption of plant products in mice.


Gastric foveolar metaplasia with dysplastic changes in Brunner gland hyperplasia: possible precursor lesions for Brunner gland adenocarcinoma.
Cases of adenocarcinomas developed in Brunner gland hyperplasia (BGH) have been sporadically reported. Herein, we report the morphologic spectrum of hyperplastic changes culminating into dysplasia and carcinoma in 722 cases of BGH listed in our files. Fifteen of these cases showed dysplastic changes, with 8 graded as low-grade dysplasia, 5 as high-grade dysplasia, 11 as atypical hyperplasia, and 2 as invasive carcinoma, although each frequently coexisted in the same tumor. In two carcinomas, one had high-grade dysplasia in the mucosa, and another had only atypical hyperplasia. Interestingly, hyperplastic glands around dysplastic foci were associated with gastric foveolar metaplasia and papillary configuration in 13 cases, 11 of which showed a gradual increase in nuclear atypism in the transition from metaplastic to dysplastic glands. All of the metaplastic gastric glands showed diffuse and strong immunopositivity for gastric foveolar mucin (MUC5AC). Immunohistochemical profiles also supported the concept of a continuous spectrum in carcinogenesis from gastric foveolar hyperplasia through atypical hyperplasia or dysplasia and eventually to frank adenocarcinoma. The results of our study suggest, therefore, that dysplastic and/or carcinomatous change does occur in BGH, that they form the continuous morphologic spectrum, and that papillary foveolar metaplasia may be a precursor lesion in the process of carcinogenesis with a background of BGH.


Unsupervised Noise Reductions for Gravitational Reference Sensors or Accelerometers Based on the Noise2Noise Method.
Onboard electrostatic suspension inertial sensors are important applications for gravity satellites and space gravitational-wave detection missions, and it is important to suppress noise in the measurement signal. Due to the complex coupling between the working space environment and the satellite platform, the process of noise generation is extremely complex, and traditional noise modeling and subtraction methods have certain limitations. With the development of deep learning, applying it to high-precision inertial sensors to improve the signal-to-noise ratio is a practically meaningful task. Since there is a single noise sample and unknown true value in the measured data in orbit, odd-even sub-samplers and periodic sub-samplers are designed to process general signals and periodic signals, and adds reconstruction layers consisting of fully connected layers to the model. Experimental analysis and comparison are conducted based on simulation data, GRACE-FO acceleration data, and Taiji-1 acceleration data. The results show that the deep learning method is superior to traditional data smoothing processing solutions.


Oxytocin and Its Relationship to Body Composition, Bone Mineral Density, and Hip Geometry Across the Weight Spectrum.
Oxytocin (OXT), an anorexigenic hypothalamic hormone anabolic to bone, may reflect energy availability. Basal serum OXT levels are lower in anorexia nervosa (AN, state of energy deficit) than healthy controls (HC) and negatively associated with spine bone mineral density (BMD). Reports are conflicting regarding OXT levels in overweight/obesity (OB, state of energy excess). Relationships between OXT and BMD in OB and hip geometry across the weight spectrum are unknown. To determine whether overnight serum OXT levels are (1) elevated in OB and (2) associated with body composition, BMD, and hip geometry across the weight spectrum. Cross-sectional. Clinical research center. Fifty-nine women, ages 18 to 45 years: amenorrheic AN (N = 16), eumenorrheic HC (N = 24), eumenorrheic OB (N = 19). Serum sampled every 20 minutes from 8 pm to 8 am and pooled for integrated overnight OXT levels. Body composition, BMD, and hip structural analysis measured by dual x-ray absorptiometry. OXT levels were lowest in AN, higher in HC, and highest in OB (P ≤ 0.02). There were positive associations between OXT and (1) body mass index (P = 0.0004); (2) total, visceral, and subcutaneous fat (P ≤ 0.0002); (3) spine and hip BMD Z-scores (P ≤ 0.01); and (4) favorable hip geometry, namely buckling ratio (P ≤ 0.05). In a subset analysis of HC and OB, relationships between OXT and body composition, but not bone parameters, remained significant. These data suggest OXT is a marker of energy availability and may be a mediator of bone density, structure, and strength. OXT pathways may provide targets for obesity and osteoporosis treatment.


Advanced oxidation protein products induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK signaling.
Advanced oxidation protein products (AOPPs) are formed during chronic oxidative stress as a result of reactions between plasma proteins and chlorinated oxidants. Their levels are elevated during various cardiovascular diseases. Because elevated AOPPs serve as independent risk factors for ischemic heart disease, and cardiomyocyte death is a hallmark of ischemic heart disease, we hypothesized that AOPPs will induce cardiomyocyte death. AOPP-modified mouse serum albumin (AOPP-MSA) induced significant death of neonatal mouse cardiomyocytes that was attenuated by knockdown of the receptor for advanced glycation end products, but not CD36. Notably, TRAF3-interacting protein 2 (TRAF3IP2; also known as CIKS or Act1) knockdown blunted AOPP-induced apoptosis. AOPP-MSA stimulated Nox2/Rac1-dependent superoxide generation, TRAF3IP2 expression, and TRAF3IP2-dependent JNK activation. The superoxide anion generating xanthine/xanthine oxidase system and hydrogen peroxide both induced TRAF3IP2 expression. Further, AOPP-MSA induced mitochondrial Bax translocation and release of cytochrome c into cytoplasm. Moreover, AOPP-MSA suppressed antiapoptotic Bcl-2 and Bcl-xL expression. These effects were reversed by TRAF3IP2 knockdown or forced expression of mutant JNK. Similar to its effects in neonatal cardiomyocytes, AOPP-MSA induced adult cardiomyocyte death in part via TRAF3IP2. These results demonstrate for the first time that AOPPs induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK activation in vitro and suggest that AOPPs may contribute to myocardial injury in vivo. Thus TRAF3IP2 may represent a potential therapeutic target in ischemic heart disease.


Regulation of allergic lung inflammation in rats: interaction between estradiol and corticosterone.
One third of asthmatic women report a decreased expiratory peak flow during menses. Since asthma is characterized by lung inflammation and bronchopulmonary hyperresponsiveness, we investigated the role played by estradiol in allergic lung inflammation. Cell migration to the lungs of allergic female rats subjected to oophorectomy (OVx) was compared to that in their sham-operated (sham) control counterparts. Seven days after OVx or sham operation, the rats were sensitized intraperitoneally with ovalbumin (OA, 1 mg/kg) suspended in aluminum hydroxide (day 0). At day 7, a subcutaneous booster of OA was performed and an aerosolized OA challenge was carried out at day 14. One day later (day 15), the rats were killed and cell counts were performed in bronchoalveolar lavages (BAL), in peripheral blood and in bone marrow lavages. After the antigen challenge, OVx rats showed a significant decrease in cell migration to the lung as compared to sham-operated rats. Differential analyses of BAL revealed a reduced number of eosinophils, mononuclear cells and neutrophils. In contrast, in bone marrow as well as in the peripheral blood the numbers of eosinophils, mononuclear cells and neutrophils were increased relative to sham controls. Mast cell numbers were similar in both groups. The estradiol receptor antagonist tamoxifen decreased the allergic lung inflammation in intact rats down to levels similar to those found in untreated OVx rats. In contrast, 17beta-estradiol replacement in OVx rats reestablished the allergic lung inflammation, as observed by an elevated number of eosinophils, mononuclear cells and neutrophils recovered in BAL. Similarly, an elevated number of inflammatory cells were quantified in BAL from allergic OVx rats when corticosterone effects were blocked with metyrapone or RU-486. Our results suggest that estradiol has proinflammatory actions on the allergic lung response, and these actions seem to be mediated, at least in part, by endogenous glucocorticoids.


Passive and Flexible Wireless Electronics Fabricated on Parylene/PDMS Substrate for Stimulation of Human Stem Cell-Derived Cardiomyocytes.
In this paper, we report the development of a wireless, passive, biocompatible, and flexible system for stimulation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMS). Fabricated on a transparent parylene/PDMS substrate, the proposed stimulator enables real-time excitation and characterization of hiPSC-CMs cultured on-board. The device comprises a rectenna operating at 2.35 GHz which receives radio frequency (RF) energy from an external transmitter and converts it into DC voltage to deliver monophasic stimulation. The operation of the stimulator was primarily verified by delivering monophasic voltage pulses through gold electrodes to hiPSC-CMs cultured on the Matrigel-coated substrates. Stimulated hiPSC-CMs beat in accordance with the monophasic pulses when delivered at 0.5, 1, and 2 Hz pulsing frequency, while no significant cell death was observed. The wireless stimulator could generate monophasic pulses with an amplitude of 8 V at a distance of 15 mm. These results demonstrated the proposed wireless stimulator's efficacy for providing electrical stimulation to engineered cardiac tissues. The proposed stimulator will have a wide application in tissue engineering where a fully wireless stimulation of electroconductive cells is needed. The device also has potential to be employed as a cardiac stimulator by delivering external stimulation and regulating the contractions of cardiac tissue.


Performance of the phonatory deviation diagram in monitoring voice quality before and after voice exercise in individuals with Parkinson's Disease.
To assess the performance of the phonatory deviation diagram and its measurements in monitoring voice quality before and after voice exercise in individuals with Parkinson's Disease. Retrospective and documentary study. A sample of 30 subjects was used, 50% male, with a mean age of 62.13 ± 9.05 years. The results of the phonatory deviation diagram were analyzed, in the moments before and after vocal exercise with the pushing technique associated with plosive sounds, considering the area, density, shape and location of the diagram in the quadrants. For comparison purposes, the acoustic parameters of jitter, shimmer, glottal to noise excitation ratio and results of the auditory-perceptual analysis, carried out in previous research, were also considered, in the pre- and post-technical moments. Despite the fact that there was no difference in the distribution of samples in the diagram, after performing the vocal technique, a change in the displacement of the diagram towards the area of normality was identified in the visual qualitative analysis, and there was an association between the general degree of vocal deviation in the analysis auditory perception and the area of the diagram. There was an improvement in the shimmer values after the vocal technique. The displacement of the phonatory deviation diagram towards the area of normality corroborated the results in relation to the general degree of dysphonia, evaluated by the auditory-perceptual analysis and the shimmer results, after the vocal technique. Thus, the diagram shows good performance in monitoring voice quality of individuals with Parkinson's.


Comparing Activity and Participation between Acquired Brain Injury and Spinal-Cord Injury in Community-Dwelling People with Severe Disability Using WHODAS 2.0.
Central-nervous-system (CNS) injuries constitute a significant cause of morbidity (often resulting in long-term disability) and mortality. This cross-sectional study compared the activity and participation of community-dwelling people with severe disability from acquired brain injuries (ABI) (n = 322) and spinal-cord injuries (SCI) (n = 183) to identify risk factors related to disability. Data were collected through a questionnaire survey of community-dwelling people with severe disability attending 65 healthcare centers. The survey included the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) and sociodemographic factors. We categorized a registered grade of disability of 1 or 2 as severe disability. WHODAS 2.0 domain and summary scores were compared between the ABI and SCI groups, and risk factors associated with disability were identified through regression analysis. ABI participants had significantly higher disability in cognition and relationships, whereas patients with SCI had higher disability in mobility (p < 0.05). Onset duration was negatively correlated with cognition, relationships, participation, and summary scores in ABI participants (p < 0.05). Neither group's socioeconomic factors were associated with WHODA 2.0 scores. Understanding the different patterns of disability between SCI and ABI in community-dwelling people with severe disability helps establish future plans for the management of health resources.


Mouse somatic cell nuclear transfer: What has changed and remained unchanged in 25 years.
Somatic cell nuclear transfer (SCNT) is the only reproductive technology used to produce individuals from somatic cells by transferring them to enucleated oocytes. Although more than 25 years have passed since the first mammalian SCNT was reported in sheep, problems such as low birth rates and morphological abnormalities have persisted and limited its practical applications. The mouse is the ideal laboratory animal to unveil these questions due to its established reproductive technologies and extensive knowledge base of its genome and various strains. We investigated the causes of incomplete reprogramming after nuclear transfer of donor somatic cells and found that the loss of imprint in some placenta-specific imprinted genes could induce non-random SCNT abnormalities. By ameliorating aberrantly expressed imprinted genes, we succeeded in increasing the low birth rate and improving morphological abnormalities observed in SCNT fetuses. Furthermore, we sought appropriate mouse strains and cell types as nuclear donors to increase their developmental efficiencies and expand their applications in various fields. Peripheral blood cells are useful as ethical and economical cell species because they can be collected easily, even though SCNT embryos derived from hematopoietic cells show poor developmental abilities after reconstruction. Additionally, it is possible to obtain mice that are reactive to specific antigens of interest by using lymphocytes. Although there are still many limitations to the practical use of SCNT, its utilization is steadily expanding.


Investigation of the Matrix Metalloproteinase-2 Gene in Patients with Non-Syndromic Mitral Valve Prolapse.
Non-syndromic mitral valve prolapse (MVP) is a common degenerative valvulopathy, predisposing to arrhythmia and sudden death. The etiology of MVP is suspected to be under genetic control, as supported by familial cases and its manifestation in genetic syndrome (e.g., Marfan syndrome). One candidate etiological mechanism is a perturbation of the extracellular matrix (ECM) remodeling of the valve. To test this hypothesis, we assessed the role of genetic variants in the matrix metalloproteinase 2 gene (MMP2) known to regulate the ECM turnover by direct degradation of proteins and for which transgenic mice develop MVP. Direct sequencing of exons of MMP2 in 47 unrelated patients and segregation analyses in families did not reveal any causative mutation. We studied eight common single nucleotide polymorphisms (TagSNPs), which summarize the genetic information at the MMP2 locus. The association study in two case controls sets (NCases = 1073 and NControls = 1635) provided suggestive evidence for the association of rs1556888 located downstream MMP2 with the risk of MVP, especially in patients with the fibroelastic defiency form. Our study does not support the contribution of MMP2 rare variation in the etiology to MVP in humans, though further genetic and molecular investigation is required to confirm our current suggestive association of one common variant.


Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders.
Hypercalcaemia is a common metabolic complication of malignant disease often requiring emergency intervention. Although it is more frequently associated with solid tumours, malignancy-associated hypercalcaemia (MAH) is seen in a significant number of patients with blood diseases. Its association with myeloma and adult T-cell leukaemia/lymphoma is well recognized but the incidence of hypercalcaemia in other haematological neoplasms, affecting adults and children, is less clearly defined. Haematologists need to be familiar with the clinical manifestations of, the differential diagnosis to be considered and the most effective management strategies that are currently available for MAH. The key components of management of MAH include aggressive rehydration, specific therapy to inhibit bone resorption and, crucially, treatment of the underlying malignancy. Bisphosphonates have revolutionized the management of MAH over the last 20 years, however the elucidation of molecular pathways implicated in MAH is facilitating the development of more targeted approaches to treatment.


Functional properties of CD19+ B lymphocytes positively selected from buffy coats by immunomagnetic separation.
Here we report that human B lymphocytes can be positively selected directly from buffy coats applying the anti-CD19 antibody AB1 coupled to magnetic beads. This isolation protocol is highly efficient and the isolated cell population is of very high purity and viability. As judged by cell cycle analysis and various parameters for cell activation, the cells are still in a resting state after isolation. Furthermore, different functional assays have shown that the isolation procedure does not interfere with either activation or proliferation/differentiation of CD19 selected cells as compared to negatively isolated cells. As a consequence of cross-linking during the isolation process, the CD19 antigen is temporarily down-regulated as measured by AB1 binding. Despite this decreased expression, monoclonal antibodies to the CD19 antigen nevertheless inhibited anti-mu plus B cell growth factor induced B cell activation as reported also for negatively isolated cells. Taken together, the presented data strongly suggest that B cells isolated through the CD19 antigen can be used in critical functional assays.


Corpectomy of the fifth lumbar vertebra, a challenging procedure.
A retrospective study of 25 consecutive cases undergoing L5 corpectomy and reconstruction. Corpectomy of L5 is a challenging procedure because of the unique biomechanical and anatomic properties of this level. To report the clinical and radiographic outcomes and to stress the technical difficulties encountered with L5 corpectomy, reconstruction of the resulting defect together with posterior stabilization. Between 2003 and 2008 25 consecutive cases (13 females and 12 males, mean age 54.5 y) underwent L5 corpectomy, followed by titanium cage implantation and posterior stabilization. The indications for surgery were fracture (44%), bony destruction by tumor (44%), and spondylodiscitis (12%). The mean amount of intraoperative blood loss was 3.4 L. The cage was implanted through a posterior approach in a single patient with lymphoma. In the remaining 24 patients, an expandable cage was implanted through a ventral approach. Intraoperative complications occurred in 2 patients presenting with fracture. This was in the form of injury to the left common iliac vein in one patient and extensive epidural bleeding reaching 10 L in the other patient. Five patients died within 2 years after surgery: 2 of them were presenting with spondylodiscitis and died later due to sepsis, whereas the remaining 3 patients had advanced malignancy. In the remaining 20 patients, the mean follow-up period was 3.4 years. Local recurrence of infection occurred in 1 patient necessitating change of the cage. Recurrence of metastasis occurred in 2 patients; one of them underwent posterior decompression and the other one was treated successfully with local irradiation. L5 corpectomy is a demanding procedure because of the vascular anatomy at that level. Large amount of blood loss should be expected. In case of complication or recurrence of the pathology, revision surgery is more demanding and necessitates a wide experience.


Production of Chemicals by Klebsiella pneumoniae Using Bamboo Hydrolysate as Feedstock.
Bamboo is an important biomass, and bamboo hydrolysate is used by Klebsiella pneumoniae as a feedstock for chemical production. Here, bamboo powder was pretreated with NaOH and washed to a neutral pH. Cellulase was added to the pretreated bamboo powder to generate the hydrolysate, which contained 30 g/L glucose and 15 g/L xylose and was used as the carbon source to prepare a medium for chemical production. When cultured in microaerobic conditions, 12.7 g/L 2,3-butanediol was produced by wildtype K. pneumoniae. In aerobic conditions, 13.0 g/L R-acetoin was produced by the budC mutant of K. pneumoniae. A mixture of 25.5 g/L 2-ketogluconic acid and 13.6 g/L xylonic acid was produced by the budA mutant of K. pneumoniae in a two-stage, pH-controlled fermentation with high air supplementation. In the first stage of fermentation, the culture was maintained at a neutral pH; after cell growth, the fermentation proceeded to the second stage, during which the culture was allowed to become acidic.


[A case of advanced hepatocellular carcinoma with tumor thrombus treated by transarterial chemoembolization therapy using cisplatin (CDDP) with DSM and SAP-MS].
A 78-year-old woman with advanced HCC had been treated by transarterial chemoembolization with epirubicin, however, tumor progression was not controlled and a tumor thrombus was found in the portal vein trunk. A new treatment method for transarterial chemoembolization using CDDP with DSM and SAP-MS was introduced. Marked regression of hepatic lesions and portal vein tumor thrombus was observed after two sessions. No adverse effect was found. The patient has been controlled without tumor recurrence and elevation of tumor marker for 14 months. A new treatment protocol will be useful for patients with far advanced hepatocellular carcinoma with portal vein tumor thrombus.


Fufang Banmao Capsule, a Traditional Chinese Medicinal Formulation, Enhances the Survival of Patients with Hepatocellular Carcinoma and Vp3-4 Portal Vein Tumor Thrombosis Undergoing Supportive Treatment.
Objectives: Fufang Banmao (FFBM) capsule, a type of Chinese medicinal formulation, has decades of history in treating hepatocellular carcinoma (HCC). This retrospective study aimed to observe the effect of FFBM capsules on the 6-month survival of patients with advanced HCC and Vp3-4 portal vein tumor thrombosis (PVTT) who received supportive therapy alone. Design: In total, 320 HCC/Vp3-4 PVTT patients underwent treatment with supportive therapy, of whom 95 took FFBM capsules and were treated with supportive therapy (FFBM group) and 225 received supportive therapy alone (control group). Comparisons of the 6-month overall survival (OS) rate of the two groups were performed. Propensity score matching (PSM) was used to match the characteristics between individuals in the two groups. A nomogram was built based on independent predictive factors for OS. Results: Cox multivariate analysis revealed that hepatic encephalopathy, aspartate transaminase (AST) and γ-glutamyl transpeptidase levels, Child-Pugh class, prothrombin time, α-fetoprotein level, largest tumor diameter, and use of FFBM capsules were independent predictive factors of OS. Variceal bleeding, alanine transaminase, AST, total bilirubin, and Barcelona Clinic for Liver Cancer stage were different at baseline in the FFBM and control groups. Analysis revealed no significant adverse effects or toxicities relevant to the medications. After PSM (1:1), 95 patient pairs were analyzed as FFBM versus control. The OS probability was remarkably higher for patients in the FFBM group than in those in the control group at 6 months (p < 0.0001). The median survival time was 4 months in the FFBM group and 2.2 months in the control group. Kaplan-Meier analysis showed significant statistical differences in the 6-month OS rates in the patients with total nomogram scores ≥84 (p < 0.0001). Conclusions: Given the satisfying survival outcomes, the results suggested that FFBM capsules should be administered to patients with HCC/Vp3-4 PVTT in the high-risk group (score ≥84). FFBM capsules have the potential for improving patient survival time in those with advanced HCC and Vp3-4 PVTT who receive supportive therapy alone, especially those in the high-risk group (score ≥84).


Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis.
Enterococcus faecalis is an opportunistic pathogen frequently isolated in clinical settings. This organism is intrinsically resistant to several clinically relevant antibiotics and can transfer resistance to other pathogens. Although E. faecalis has emerged as a major nosocomial pathogen, the mechanisms underlying the virulence of this organism remain elusive. We studied the regulation of daughter cell separation during growth and explored the impact of this process on pathogenesis. We demonstrate that the activity of the AtlA peptidoglycan hydrolase, an enzyme dedicated to septum cleavage, is controlled by several mechanisms, including glycosylation and recognition of the peptidoglycan substrate. We show that the long cell chains of E. faecalis mutants are more susceptible to phagocytosis and are no longer able to cause lethality in the zebrafish model of infection. Altogether, this work indicates that control of cell separation during division underpins the pathogenesis of E. faecalis infections and represents a novel enterococcal virulence factor. We propose that inhibition of septum cleavage during division represents an attractive therapeutic strategy to control infections.


Breast cancer and reproductive history from genealogical data.
With the use of data from the Utah State Cancer Registry and Utah genealogical data, an analysis of 236 breast cancer patients and 937 controls matched on year of birth showed that a late age at the birth of the first child was most strongly associated with incidence of breast cancer (relative odds = 2.0; P less than 0.001). A strong interaction was found between age at first delivery (AFD) and age at last delivery (ALD). The association of AFD with breast cancer incidence was strongest for women with an ALD before 35 years of age even after adjustment for partly (relative odds = 4.1; P less than 0.001). Decreased parity was not significantly associated with breast cancer.


Characterizing the breakpoint of stomatal response to vapor pressure deficit in an angiosperm.
Vapor pressure difference between the leaf and atmosphere (VPD) is the most important regulator of daytime transpiration, yet the mechanism driving stomatal responses to an increase in VPD in angiosperms remains unresolved. Here, we sought to characterize the mechanism driving stomatal closure at high VPD in an angiosperm species, particularly testing whether abscisic acid (ABA) biosynthesis could explain the observation of a trigger point for stomatal sensitivity to an increase in VPD. We tracked leaf gas exchange and modelled leaf water potential (Ψl) in leaves exposed to a range of step-increases in VPD in the herbaceous species Senecio minimus Poir. (Asteraceae). We found that mild increases in VPD in this species did not induce stomatal closure because modelled Ψl did not decline below a threshold close to turgor loss point (Ψtlp), but when leaves were exposed to a large increase in VPD, stomata closed while modelled Ψl declined below Ψtlp. Leaf ABA levels were higher in leaves exposed to a step-increase in VPD that caused Ψl to transiently decline below Ψtlp and in which stomata closed compared to leaves in which stomata did not close. We conclude that the stomata of S. minimus are insensitive to VPD until Ψl declines to a threshold that triggers the biosynthesis of ABA and that this mechanism might be common to angiosperms.


A systematic review of the association between breastfeeding and breast cancer.
Breastfeeding is hypothesized to reduce the risk of breast cancer primarily through two mechanisms, differentiation of breast tissue and reduction of the lifetime number of ovulatory cycles, but previous reviews of the association between breastfeeding and breast cancer have not consistently found that breastfeeding reduces risk of breast cancer. Our systematic review yielded 30 case-control studies and 1 cohort study published between 1999 and 2007. Of the 27 studies that assessed the effect of ever breastfeeding compared with never breastfeeding, only 11 found significant protection against breast cancer. Of the 24 studies of the effect of breastfeeding duration, only 13 found a reduced risk of breast cancer with extended lactation. We conclude that no consensus about the relationship between breastfeeding and breast cancer is emerging. Expanded consideration of possible confounders for this relationship is required to determine if breastfeeding is protective and how protection might be conferred.


Inflammatory cytokines and oxidized low density lipoproteins increase endothelial cell expression of membrane type 1-matrix metalloproteinase.
We investigated whether inflammatory cytokines or oxidized low density lipoproteins (Ox-LDL) present in human atheroma modulate extracellular matrix degradation by inducing membrane type 1-matrix metalloproteinase (MT1-MMP) expression. Cultured human endothelial cells (EC) constitutively expressed MT1-MMP mRNA and protein with enzymatic activity. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha, or interleukin-1beta caused a time-dependent increase in the steady-state MT1-MMP mRNA levels within 4 h of exposure, peaking about 4-fold by 6 h, and remaining elevated for 12 h. Increased MT1-MMP mRNA correlated with a 2.5-fold increase in MT1-MMP protein in EC membranes. Ox-LDL also increased MT1-MMP mRNA levels that varied with the duration of exposure and degree of LDL oxidation. The increase in MT1-MMP mRNA occurred within 6 h of exposure to Ox-LDL and peaked over 3-fold by 6 h. Ox-LDL, but not native LDL, increased MT1-MMP protein by 2-fold in EC membranes. A combination of TNF-alpha and Ox-LDL was additive in increasing MT1-MMP expression. Nuclear run-on assays showed that TNF-alpha or Ox-LDL augmented steady-state mRNA levels by increased transcription of the MT1-MMP gene. These findings indicate that activation of EC by inflammatory cytokines and/or Ox-LDL increase MT1-MMP expression. Since MT1-MMP promotes matrix degradation by activating pro-MMP-2, these results suggest a novel mechanism whereby cytokines or Ox-LDL may influence extracellular matrix remodeling.


Analyzing the Unique Needs of International Palliative Care Learners Attending a United States-Based Palliative Care Education and Practice Course.
Background: Many seriously ill patients in need of palliative care (PC) globally never receive it, partly due to a lack of well-trained providers. Objectives: We analyzed feedback from international participants in a U.S.-based PC training course: "Palliative Care Education and Practice" to identify elements of the course that would meet the needs of international learners. Design: This was a qualitative analysis of international course participants' written survey responses. Survey questions were related to anticipated PC practice change, barriers to PC practice change, and course strengths/weaknesses. Results: Key barriers to PC practice change included lack of awareness of PC among local providers, challenges navigating institutional leaders, and a lack of trained providers. Participants requested an increased focus on topics such as resiliency, leadership, and pediatric PC. Conclusions: To address the needs of international learners, PC courses should consider offering a specific track for international participants, as well as an increased focus on topics such as resiliency, leadership development, and pediatric PC.


[Steroid dominance, enzyme activity and morphological appearance of granulosa cells in the largest follicles in cows].
The cyclic nature of the female reproduction process depends to a considerable degree on the unique capacity of ovarial follicles to change their structure and function. The differentiation process during folliculogenesis takes place in all parts of the follicle. Granulosa cells reflect a high degree of structural changes and play an important role in functional maturation of the inert follicle. Changes in the reaction to endocrine and paracrine effects from a unique environment that is inevitably necessary for oocyte growth and ovulation were reached by changes in the biochemical activity and the internal anatomic mutual relation of the follicle (Linder et al., 1976; Hsueh, 1976). This growth process and differentiation depend on gonadotropic stimulation of the follicles and the quantity of receptor sites able to bind them. The aim of this work was compare estradiol 17-beta and progesterone levels in the follicular fluid of the largest follicles with the morphological structure and enzymatic activity of membrana granulosa cells. Ovaries were obtained from 34 SS x LBS randomly chosen cows at the slaughter-house. Follicular fluid to estradiol 17-beta and progesterone level determination was obtained by aspiration of the largest follicles. Estradiol 17-beta and progesterone levels were determined by RIA sets from the URVJT (Institute of Radioecology and Use of Nuclear Techniques) in Kosice, type RIA-test-ESTRA (SI-125-129) and RIAA-test-Prog (SI-125-6), respectively. With the methods used the variation coefficient of intra- and interassay for the estradiol 17-beta of the RIA set were 10.1 and 13.3%, for progesterone of the RIA set these values were 11.4 and 13.7% respectively. Steroid dominance of follicles was determined by the method described by Căllesen et al. (1986), based on the expression of the index of the mutual relation between progesterone levels and estradiol 17-beta was levels. Excisions from the follicular wall were examined under the scanning electron microscope JEOC 1200 Mx at an acceleration voltage of 20 kV. In granulosa cell smears acid phosphatase and non-specific esterase activity were determined by incubation in the incubation media according to Lojda et al. (1979). Steroid levels are given in nmol/l +/- SEM. Mean estradiol 17-beta levels in estrogen dominant follicles were proved to be 2170.0 +/- 1605.3 nmol/l, whereby individual concentrations ranged from 17.0 nmol/l to 10180.0 nmol/l.(ABSTRACT TRUNCATED AT 400 WORDS)


Pfit is a structurally novel Crohn's disease-associated superantigen.
T cell responses to enteric bacteria are important in inflammatory bowel disease. I2, encoded by the pfiT gene of Pseudomonas fluorescens, is a T-cell superantigen associated with human Crohn's disease. Here we report the crystal structure of pfiT at 1.7Å resolution and provide a functional analysis of the interaction of pfiT and its homolog, PA2885, with human class II MHC. Both pfiT and PA2885 bound to mammalian cells and stimulated the proliferation of human lymphocytes. This binding was greatly inhibited by anti-class II MHC HLA-DR antibodies, and to a lesser extent, by anti HLA-DQ and DP antibodies, indicating that the binding was class II MHC-specific. GST-pfiT efficiently precipitated both endogenous and in vitro purified recombinant HLA-DR1 molecules, indicating that pfiT directly interacted with HLA-DR1. Competition studies revealed that pfiT and the superantigen Mycoplasma arthritidis mitogen (MAM) competed for binding to HLA-DR, indicating that their binding sites overlap. Structural analyses established that pfiT belongs to the TetR-family of DNA-binding transcription regulators. The distinct structure of pfiT indicates that it represents a new family of T cell superantigens.


Reactive oxygen scavenger effect of pyrimidines, benzotriazoles and related compounds.
Free radicals and reactive oxygen metabolites have been implicated as important pathologic mediators in many clinical disorders and diseases. An efficient method of detecting the free radical scavenger effect is through xanthine oxidase (XO) inhibition. The inhibition efficiency on XO has been detected as the rate of uric acid production, which has max 295 nm. Sulfasalazine showed potent inhibiting activity on XO (IC50 = 25.11 microM; Ki = 50.88 microM) and induced a mixed-type (non-competitive-uncompetitive) inhibition of the substrate xanthine. 2-mercapto-4(3H)-quinazolinone (16) and 2-mercaptopyrimidine (4) displayed inhibiting activity on XO with IC50 = 98.71 and 136.14 microM, while apparent inhibition constants (Ki) were 158.38 and 62.46 microM, respectively. However benzotriazoles showed weak inhibitory effect. The spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) by electron spin resonance (ESR) detected the presence of O2-* and OH*. It showed that the percentage inhibition for formation of DMPO-OOH for 2-mercapto-pyrimidine and sulfasalazine were 64.78 and 35.09, but for hydroxylation were 49.51, 38.55, 37.29 for 2-mercapto-4(3H)-quinazolinone, sulfasalazine and 2-mercaptopyrimidine at 500 microM, respectively.


Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.
Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period. An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.


Perceptions of women and partners on labor and birth positions: A meta-synthesis.
The risks and benefits of different birthing positions are commonly studied, but both paternal and maternal preferences and experiences of different birth positions are not examined. Therefore, this systematic review aims to explore the perceptions of women and their partners on birthing positions during the first and second stage of labor, so that maternity health care practitioners can provide better quality patient-centered care. Six databases were searched from each database's inception through November 2020. Qualitative or mixed-methods studies exploring perceptions of women and/or their partners on birthing positions were included in the review. Key information and findings of the studies were extracted; qualitative data were meta-summarized, then meta-synthesized using thematic analysis. Seven studies were included, and four themes emerged: (a) Influences on choice and preference; (b) mixed experiences from "pain" to "more in control"; (c) impact on postpartum health; and (d) ways to empower couples in their choice. Women's preferences for birthing positions were influenced by a myriad of personal and socio-cultural beliefs and traditions. Findings suggest a need for health care practitioners to build better rapport and provide more culturally relevant informational support to both women and their birthing partners, so they are better able to make informed decisions on their preferred birthing position.


Use of a clinical audit to promote the quality use of medicines to rural and remote general practitioners.
Very few methods have been shown to change prescribing behaviour. Queensland Rural Medical Support Agency's Quality Use of Medicines (QUM) Program aims to engage rural general practitioners (GPs) in the development of strategies to improve health outcomes in relation to the quality use of medicines. The present paper describes the development of a tool to audit the management of heart failure in rural general practice and to encourage rural GPs to undertake such an audit as a method of continuing medical education. A self-administered retrospective clinical audit of heart failure patients was undertaken by rural and remote GPs. Fourteen doctors undertook the audit, providing data on 270 patient cases. Patient data collected include 30% not receiving adequate angiotensin-converting enzyme inhibitor doses, 45% of patients who may benefit from a beta-blocker and 14% of patients taking a drug known to aggravate heart failure. The majority of participants would review a patient following the audit and 93% confirmed that the audit assisted them in identifying patients whose heart failure management could be enhanced. The clinical audit provided results and a commentary to allow GPs reflective educational opportunities through the dissemination of results and engagement with appropriate educational organisations (e.g. Australian College of Rural and Remote Medicine) to inform the development of educational standards for personal development programs in QUM. Audits must be relevant and practical to meet the learning needs of GPs.


Nuclear organization of RNA polymerase II transcription.
Transcription occurs at distinct nuclear compartments termed transcription factories that are specialized for transcription by 1 of the 3 polymerase complexes (I, II, or III). Protein-coding genes appear to move in and out of RNA polymerase II (RNAPII) compartments as they are expressed and silenced. In addition, transcription factories are sites where several transcription units, either from the same chromosome or different chromosomes, are transcribed. Chromosomes occupy distinct territories in the interphase nucleus with active genes preferentially positioned on the periphery or even looped out of the territory. These chromosome territories have been observed to intermingle in the nucleus, and multiple interactions among different chromosomes have been identified in genome-wide studies. Deep sequencing of the transcriptome and RNAPII associated on DNA obtained by chromatin immunoprecipitation have revealed a plethora of noncoding transcription and intergenic accumulations of RNAPII that must also be considered in models of genome function. The organization of transcription into distinct regions of the nucleus has changed the way we view transcription with the evolving model for silencing or activation of gene expression involving physical relocation of the transcription unit to a silencing or activation compartment, thus, highlighting the need to consider the process of transcription in the 3-dimensional nuclear space.